The transcriptional cascade and regulatory loop play crucial roles in regulating plant-specialized metabolite biosynthesis.Capsaicinoids are unique to the genus Capsicum and confer a pungent flavor to its fruits.Howev...The transcriptional cascade and regulatory loop play crucial roles in regulating plant-specialized metabolite biosynthesis.Capsaicinoids are unique to the genus Capsicum and confer a pungent flavor to its fruits.However,the transcriptional regulation of capsaicinoid biosynthesis remains largely unknown.In this study,two AP2/ERF transcription factors(TFs),CaERF102 and CaERF111,were characterized for their role in the capsaicinoid biosynthesis process.Expression analysis of two ERFs and capsaicinoid biosynthetic genes(CBGs)suggested that they were associated with capsaicinoid biosynthesis.Both ERFs encode nuclear-localized proteins and function as transcriptional activators through their C-terminal activation motifs.The two ERF TFs participated in capsaicinoid biosynthesis by directly activating the promoters of key CBGs,and this activation was significantly enhanced when CaMYC2 was co-expressed.Moreover,CaERF102 and CaERF111 were found to interact with CaMYC2.This study helps elucidate the AP2/ERF TF regulatory network that governs capsaicinoid biosynthesis in Capsicum species.展开更多
BACKGROUND Gastric cancer is a malignant tumor with high morbidity and mortality worldwide.Neoadjuvant chemotherapy(NAC),defined as chemotherapy administered before the primary treatment(usually surgery)to reduce tumo...BACKGROUND Gastric cancer is a malignant tumor with high morbidity and mortality worldwide.Neoadjuvant chemotherapy(NAC),defined as chemotherapy administered before the primary treatment(usually surgery)to reduce tumor size and control micrometastases,has emerged as a crucial therapeutic strategy for locally advanced gastric cancer.Pathological complete response(pCR),characterized by the absence of viable tumor cells in the resected specimen after neoadjuvant treatment,is recognized as a strong predictor of favorable prognosis.However,the factors influencing the achievement of pCR remain incompletely understood.AIM To identify and analyze the predictive factors associated with achieving pCR after NAC in gastric cancer patients,thereby providing evidence-based guidance for clinical decision-making.METHODS A retrospective analysis was performed on 215 patients from Shandong Cancer Hospital and Tai’an Central Hospital with locally advanced gastric cancer who underwent NAC followed by radical surgery at our hospital between January 2015 and December 2023.Comprehensive clinical and pathological data were collected,including age,gender,tumor location,Lauren classification,clinical staging,chemotherapy regimens,number of chemotherapy cycles,and baseline hematological indicators.The baseline hematological indicators included neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio,albumin level,carcinoembryonic antigen(CEA),and carbohydrate antigen 19-9.Univariate and multivariate logistic regression analyses were employed to determine the independent predictive factors for pCR.RESULTS Among 215 gastric cancer patients,41(19.1%)achieved pCR after NAC.Multivariate analysis identified five independent predictive factors for pCR:Lauren intestinal type[odds ratio(OR)=3.28],lower clinical T stage(OR=2.75),CEA decrease≥70%after NAC(OR=3.42),pre-treatment NLR<2.5(OR=2.13),and≥4 chemotherapy cycles(OR=2.87).The fluorouracil,leucovorin,oxaliplatin,docetaxel regimen achieved the highest pCR rate(27.5%),and oxaliplatin-containing regimens were superior to cisplatin-containing regimens(22.3%vs 12.7%,P=0.034).Patients with both low NLR and platelet-to-lymphocyte ratio had the highest pCR rate(33.8%),while those with both high inflammatory markers had the lowest rate(10.7%).Earlier clinical stage disease(cT3N+vs cT4N+:28.6%vs 13.0%)and lower lymph node burden were associated with higher pCR rates.CONCLUSION The achievement of pCR after NAC in gastric cancer patients is closely associated with Lauren intestinal type,lower clinical T stage,a significant decrease in CEA after chemotherapy,low pre-treatment NLR,and an adequate number of chemotherapy cycles.展开更多
BACKGROUND Dental implants are widely used to replace missing teeth.Currently,clinicians assess osseointegration success by measuring the implant’s stability within the bone and monitoring the marginal tissue height....BACKGROUND Dental implants are widely used to replace missing teeth.Currently,clinicians assess osseointegration success by measuring the implant’s stability within the bone and monitoring the marginal tissue height.Diabetes,especially type 2 diabetes mellitus(T2DM),has been reported to impair implant healing,drastically reducing implant success rates.AIM To analyze the high-risk factors for inflammatory response and prognosis after dental implantation in patients with T2DM,and provide strong evidence for reducing the incidence of postimplant peri-implantitis(PI).METHODS We performed a retrospective review of 146 patients with T2DM who had dental implants placed at Tianjin Fifth Central Hospital,between September 2021 and September 2023,which was regarded as the observation group.Moreover,60 ageand gender-matched individuals with normal blood glucose levels served as the control group.The general information,postoperative periodontal indices,and levels of inflammatory factors were comprehensively analyzed and compared.Furthermore,the incidence of postimplant PI was counted,and multivariate logistic regression was used to identify the determinants of postimplant PI.RESULTS In terms of the periodontal indices,the probing depth,modified sulcus bleeding index,and marginal bone loss in the observation cohorts began to increase significantly at 6 months and 3 months,respectively,after the completion of dental implant restoration.The T2DM cases demonstrated significantly elevated counts of leukocytes,lymphocytes,and neutrophils compared to the controls at 24 hours postoperatively.Moreover,the TNF-α,IL-1β,and IL-6 concentrations started to increase significantly in the gingival crevicular fluid 3 months after the completion of dental implant restoration in both cohorts,with the observation group exhibiting higher levels than the controls at each time point.63 out of the 146 cases developed PI.Multivariate logistic regression analysis indicated that high glycosylated hemoglobin levels,smoking,daily tooth-brushing frequency of less than once,and the anterior tooth as the implant site independently contributed to postimplant PI in T2DM cases,while a tooth-brushing duration of≥3 minutes was a protective factor.CONCLUSION Patients with T2DM are at risk of developing PI following dental implantation.Clinically,it is necessary to enhance the identification of risk factors for postimplant PI,improve risk prediction,prevention,and control,and formulate targeted intervention countermeasures to reduce the occurrence of postimplant PI.展开更多
Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in s...Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in spinal cord injury.Previous studies have shown that microglia can promote neuronal survival by phagocytosing dead cells and debris and by releasing neuroprotective and anti-inflammatory factors.However,excessive activation of microglia can lead to persistent inflammation and contribute to the formation of glial scars,which hinder axonal regeneration.Despite this,the precise role and mechanisms of microglia during the acute phase of spinal cord injury remain controversial and poorly understood.To elucidate the role of microglia in spinal cord injury,we employed the colony-stimulating factor 1 receptor inhibitor PLX5622 to deplete microglia.We observed that sustained depletion of microglia resulted in an expansion of the lesion area,downregulation of brain-derived neurotrophic factor,and impaired functional recovery after spinal cord injury.Next,we generated a transgenic mouse line with conditional overexpression of brain-derived neurotrophic factor specifically in microglia.We found that brain-derived neurotrophic factor overexpression in microglia increased angiogenesis and blood flow following spinal cord injury and facilitated the recovery of hindlimb motor function.Additionally,brain-derived neurotrophic factor overexpression in microglia reduced inflammation and neuronal apoptosis during the acute phase of spinal cord injury.Furthermore,through using specific transgenic mouse lines,TMEM119,and the colony-stimulating factor 1 receptor inhibitor PLX73086,we demonstrated that the neuroprotective effects were predominantly due to brain-derived neurotrophic factor overexpression in microglia rather than macrophages.In conclusion,our findings suggest the critical role of microglia in the formation of protective glial scars.Depleting microglia is detrimental to recovery of spinal cord injury,whereas targeting brain-derived neurotrophic factor overexpression in microglia represents a promising and novel therapeutic strategy to enhance motor function recovery in patients with spinal cord injury.展开更多
Magnolol,a compound extracted from Magnolia officinalis,demonstrates potential efficacy in addressing metabolic dysfunction and cardiovascular diseases.Its biological activities encompass anti-inflammatory,antioxidant...Magnolol,a compound extracted from Magnolia officinalis,demonstrates potential efficacy in addressing metabolic dysfunction and cardiovascular diseases.Its biological activities encompass anti-inflammatory,antioxidant,anticoagulant,and anti-diabetic effects.Growth/differentiation factor-15(GDF-15),a member of the transforming growth factorβsuperfamily,is considered a potential therapeutic target for metabolic disorders.This study investigated the impact of magnolol on GDF-15 production and its underlying mechanism.The research examined the pharmacological effect of magnolol on GDF-15 expression in vitro and in vivo,and determined the involvement of endoplasmic reticulum(ER)stress signaling in this process.Luciferase reporter assays,chromatin immunoprecipitation,and in vitro DNA binding assays were employed to examine the regulation of GDF-15 by activating transcription factor 4(ATF4),CCAAT enhancer binding proteinγ(CEBPG),and CCCTC-binding factor(CTCF).The study also investigated the effect of magnolol and ATF4 on the activity of a putative enhancer located in the intron of the GDF-15 gene,as well as the influence of single nucleotide polymorphisms(SNPs)on magnolol and ATF4-induced transcription activity.Results demonstrated that magnolol triggers GDF-15 production in endothelial cells(ECs),hepatoma cell line G2(HepG2)and hepatoma cell line 3B(Hep3B)cell lines,and primary mouse hepatocytes.The cooperative binding of ATF4 and CEBPG upstream of the GDF-15 gene or the E1944285 enhancer located in the intron led to full-power transcription of the GDF-15 gene.SNP alleles were found to impact the magnolol and ATF4-induced transcription activity of GDF-15.In high-fat diet ApoE^(-/-)mice,administration of magnolol induced GDF-15 production and partially suppressed appetite through GDF-15.These findings suggest that magnolol regulates GDF-15 expression through priming of promoter and enhancer activity,indicating its potential as a drug for the treatment of metabolic disorders.展开更多
Background The association of systemic inflammatory response index(SIRI)with prognosis of coronary artery disease(CAD)patients has never been investigated in a large sample with long-term follow-up.This study aimed to...Background The association of systemic inflammatory response index(SIRI)with prognosis of coronary artery disease(CAD)patients has never been investigated in a large sample with long-term follow-up.This study aimed to explore the association of SIRI with all-cause and cause-specific mortality in a nationally representative sample of CAD patients from United States.Methods A total of 3386 participants with CAD from the National Health and Nutrition Examination Survey(NHANES)1999-2018 were included in this study.Cox proportional hazards model,restricted cubic spline(RCS),and receiver operating characteristic curve(ROC)were performed to investigate the association of SIRI with all-cause and cause-specific mortality.Piecewise linear regression and sensitivity analyses were also performed.Results During a median follow-up of 7.7 years,1454 all-cause mortality occurred.After adjusting for confounding factors,higher lnSIRI was significantly associated with higher risk of all-cause(HR=1.16,95%CI:1.09-1.23)and CVD mortality(HR=1.17,95%CI:1.05-1.30)but not cancer mortality(HR=1.17,95%CI:0.99-1.38).The associations of SIRI with all-cause and CVD mortality were detected as J-shaped with threshold values of 1.05935 and 1.122946 for SIRI,respectively.ROC curves showed that lnSIRI had robust predictive effect both in short and long terms.Conclusions SIRI was independently associated with all-cause and CVD mortality,and the dose-response relationship was Jshaped.SIRI might serve as a valid predictor for all-cause and CVD mortality both in the short and long terms.展开更多
Pulpitis is a common infective oral disease in clinical situations.The regulatory mechanisms of immune defense in pulpitis are still being investigated.Osteomodulin(OMD)is a small leucine-rich proteoglycan family memb...Pulpitis is a common infective oral disease in clinical situations.The regulatory mechanisms of immune defense in pulpitis are still being investigated.Osteomodulin(OMD)is a small leucine-rich proteoglycan family member distributed in bones and teeth.It is a bioactive protein that promotes osteogenesis and suppresses the apoptosis of human dental pulp stem cells(hDPSCs).In this study,the role of OMD in pulpitis and the OMD-induced regulatory mechanism were investigated.The OMD expression in normal and inflamed human pulp tissues was detected via immunofluorescence staining.Intriguingly,the OMD expression decreased in the inflammatory infiltration area of pulpitis specimens.The cellular experiments demonstrated that recombined human OMD could resist the detrimental effects of lipopolysaccharide(LPS)-induced inflammation.A conditional Omd knockout mouse model with pulpal inflammation was established.LPS-induced inflammatory impairment significantly increased in conditional Omd knockout mice,whereas OMD administration exhibited a protective effect against pulpitis.Mechanistically,the transcriptome alterations of OMD overexpression showed significant enrichment in the nuclear factor-κB(NF-κB)signaling pathway.Interleukin-1 receptor 1(IL1R1),a vital membrane receptor activating the NF-κB pathway,was significantly downregulated in OMD-overexpressing hDPSCs.Additionally,the interaction between OMD and IL1R1 was verified using co-immunoprecipitation and molecular docking.In vivo,excessive pulpal inflammation in Omd-deficient mice was rescued using an IL1R antagonist.Overall,OMD played a protective role in the inflammatory response via the IL1R1/NF-κB signaling pathway.OMD may optimize the immunomodulatory functions of hDPSCs and can be used for regenerative endodontics.展开更多
Extensive transcriptomic reprogramming is triggered by biotic and abiotic stresses in plants,with coordinated regulation mediated through multiple transcription factor families,such as WRKY,MYB,NAC,and BBX proteins.Am...Extensive transcriptomic reprogramming is triggered by biotic and abiotic stresses in plants,with coordinated regulation mediated through multiple transcription factor families,such as WRKY,MYB,NAC,and BBX proteins.Among these,B-box(BBX)proteins represent a distinct class of zinc finger transcription factors characterized by the presence of conserved B-box domains.They serve as central regulators in plant photomorphogenesis and developmental processes.Accumulating genetic and biochemical evidence demonstrates that BBX family members orchestrate plant responses to biotic and abiotic stresses through multifaceted molecular mechanisms,including the regulation of reactive oxygen species(ROS)homeostasis,enhancement of anthocyanin biosynthesis,and modulation of hormonal signaling pathways.This review systematically summarizes recent advances in the identification of BBX family genes in different plant species.Furthermore,their emerging roles in mediating plant stress responses are elucidated,with molecularmechanisms being comprehensively analyzed at both transcriptional and post-translational levels.However,to fully harness the potential of BBX genes in crop improvement,a deeper understanding of their functional mechanisms including BBX-mediated hormonal crosstalk networks,growth-defense trade-offs,and more extensive field performance data remains essential.These insights provide a theoretical foundation for developing climate-resilient crop varieties through targeted genetic improvement strategies.展开更多
Microorganisms actively participate in biogeochemical cycling processes and play a crucial role in maintaining the dynamic balance of hot spring ecosystems.However,the distribution of microbial functional genes and th...Microorganisms actively participate in biogeochemical cycling processes and play a crucial role in maintaining the dynamic balance of hot spring ecosystems.However,the distribution of microbial functional genes and their influencing factors in hot springs remain largely unclear.Therefore,this study investigated the microbial functional genes and their potential for controlling biogeochemical cycles(C,N,S,and P) in the hot Springs of Tengchong,China,using the Geochip method,a functional gene microarray technology.The examined hot springs have very different microbial functional genes.A total of 22 736 gene probe signals were identified,belonging to 567 functional genes and associated with 15 ecological functions,mainly involving stress response,carbon cycle,nitrogen cycle,sulfur cycle,phosphorus cycle and energy processes.The amyA,narG,dsrA and ppx genes were most abundant in carbon,nitrogen,sulfur and phosphorus cycles,respectively,and were significantly correlated with pH,temperature and SO_(4)^(2-).The diversity and abundance of detected gene probes were negatively correlated with temperature.The α-diversity(i.e.,Shannon index) was high at low temperature and low pH.Molecular functional interactions revealed by the gene connectivity levels were negatively correlated with temperature,pH and SO_(4)^(2-).These results suggested that the abundance,diversity and interactions of microbial functional genes were significantly influenced by geochemical parameters.-In addition,some genera possessed functional genes related to carbon,nitrogen,sulfur,and phosphorus cycles and can synergistically control the biogeochemical cycles of carbon,nitrogen,sulfur and phosphorus.These findings provide new insights into the functional potentials of microorganisms to participate in biogeochemical cycles and their responses to environmental factors in hot springs.展开更多
BACKGROUND The pathogenesis of primary biliary cholangitis(PBC)remains unclear.Ursodeoxycholic acid(UDCA)is the only first-line clinical treatment,but approximately 40%of patients exhibit a poor response.AIM To identi...BACKGROUND The pathogenesis of primary biliary cholangitis(PBC)remains unclear.Ursodeoxycholic acid(UDCA)is the only first-line clinical treatment,but approximately 40%of patients exhibit a poor response.AIM To identify novel biomarkers for PBC to predict the efficacy of UDCA and enhance treatment.METHODS Microarray expression profiling datasets were downloaded from the Gene Expression Omnibus and analyzed to identify differentially expressed genes between PBC patients and healthy controls.Immunohistochemistry was performed to validate key genes in liver tissues of the participants.Logistic regression was employed to evaluate prognostic risk factors,receiver operating characteristic curves were used to assess predictive performance,and correlations between key genes and clinicopathological characteristics were analyzed.RESULTS By bioinformatic analysis,13 genes primarily associated with the progression of PBC were identified,and tumor necrosis factor alpha-induced protein 3(TNFAIP3)was selected for further investigation.Then expression of TNFAIP3 in PBC patients was significantly elevated compared to healthy controls on immunohistochemistry(P<0.0001).Multivariate Cox regression analysis indicated that both TNFAIP3 and fatigue were independent risk factors for response to UDCA in PBC patients(P<0.05).The area under the curve for TNFAIP3 and fatigue were 0.691 and 0.704,respectively,while their combination showed a significantly higher area under the curve of 0.848.The expression of TNFAIP3 was also correlated with age,albumin,total bilirubin,alkaline phosphatase and splenomegaly(P<0.05).CONCLUSION TNFAIP3 and fatigue are independent risk factors for response to UDCA in Chinese patients with PBC.TNFAIP3 may be a potential biomarker or therapeutic target for PBC.These findings offer new insights into the pathogenesis of PBC.展开更多
In this editorial,we comment on the article by Zhang et al recently published in the World Journal of Gastroenterology.The manuscript elucidates significant novel mechanisms underlying hepatocellular carcinoma(HCC)pro...In this editorial,we comment on the article by Zhang et al recently published in the World Journal of Gastroenterology.The manuscript elucidates significant novel mechanisms underlying hepatocellular carcinoma(HCC)progression.HCC is currently considered one of the major causes of global cancer-associated deaths,underscoring the critical need for novel therapeutic targets.Growing evidence underlines the role of the lipid raft protein flotillin-1(FLOT1)in cancer,whose dysregulation drives tumor cell growth and survival.However,the regulatory role of FLOT1 on Golgi apparatus function in HCC is unknown.In this study,Zhang et al elucidated a pivotal mechanism by which FLOT1 promotes HCC progression through activation of transcription factor E3-mediated Golgi stress response.The study reveals that FLOT1 inhibits the mechanistic target of rapamycin complexes 1 and 2 by ubiquitination,facilitating transcription factor E3 dephosphorylation,nuclear translocation,and subsequent upregulation of Golgi stress-associated genes,thereby leading to enhanced HCC cell growth and invasive capacity.These findings obtained in vitro/in vivo highlight the interplay between FLOT1 and Golgi homeostasis in HCC.Targeting FLOT1 may offer a new strategy for the treatment of HCC.展开更多
BACKGROUND Ischemic stroke is one of the leading global causes of disability and death.Despite advances in modern medical technology that improve acute treatment and rehabilitation measures,post-stroke anxiety and dep...BACKGROUND Ischemic stroke is one of the leading global causes of disability and death.Despite advances in modern medical technology that improve acute treatment and rehabilitation measures,post-stroke anxiety and depression(PSD)do not receive sufficient attention.AIM To systematically evaluate risk factors and early identification markers for PSD for more precise screening and intervention strategies in clinical practice.METHODS This retrospective study analyzed clinical data from 112 patients with ischemic stroke admitted between January 2022 and December 2024.Based on assessments using the Hamilton Rating Scale for Anxiety(HAMA)and Hamilton Rating Scale for Depression(HAMD)at 2 weeks(±3 days)post-stroke,patients were classified into the PSD group(HAMA≥7 and/or HAMD≥7)and the non-PSD group(HAMA<7 and HAMD<7).Observation indicators included psychological assessment,demographic and clinical characteristics,stroke-related clinical indicators,neuroimaging assessments,and laboratory biomarkers.Multivariate logistic regression analysis was used to identify independent risk factors for PSD,and receiver operating characteristic curve analysis was used to evaluate the diagnostic value of potential biomarkers.RESULTS Of the 112 patients,46(41.1%)were diagnosed with PSD.Multivariate analysis identified five independent risk factors:Female gender[Odds ratio(OR)=2.32,95%confidence interval(CI):1.56-3.45],history of mental disorders prior to stroke(OR=3.17,95%CI:1.89-5.32),infarct location in the frontal lobe or limbic system(OR=2.86,95%CI:1.73-4.71),stroke severity with National Institutes of Health Stroke Scale≥8 at admission(OR=2.54,95%CI:1.62-3.99),and low social support(Social Support Rating Scale<35,OR=2.18,95%CI:1.42-3.36).Subgroup analysis showed that depression patients more commonly had left hemisphere lesions(68.4%vs 45.2%),while anxiety patients more frequently presented with right hemisphere lesions(59.5%vs 39.5%).The PSD group exhibited larger infarct volumes(8.7 cm^(3) vs 5.3 cm^(3)),more severe white matter hyperintensities,and more pronounced frontal lobe atrophy.Analysis of inflammatory markers showed significantly elevated levels of interleukin-6(7.8 pg/mL vs 4.5 pg/mL)and tumor necrosis factor-alpha(15.6 pg/mL vs 9.8 pg/mL)in the PSD group,while hypothalamicpituitary-adrenal axis function assessment revealed higher cortisol levels(386.5±92.3 nmol/L vs 328.7±75.6 nmol/L)and flattened diurnal rhythm in the PSD group.CONCLUSION PSD is a complex neuropsychiatric consequence of stroke involving disruption of the frontal-limbic circuitry,neuroinflammatory responses,and dysfunction of the hypothalamic-pituitary-adrenal axis.展开更多
Strokes include both ischemic stroke,which is mediated by a blockade or reduction in the blood supply to the brain,and hemorrhagic stroke,which comprises intracerebral hemorrhage and subarachnoid hemorrhage and is cha...Strokes include both ischemic stroke,which is mediated by a blockade or reduction in the blood supply to the brain,and hemorrhagic stroke,which comprises intracerebral hemorrhage and subarachnoid hemorrhage and is characterized by bleeding within the brain.Stroke is a lifethreatening cerebrovascular condition characterized by intricate pathophysiological mechanisms,including oxidative stress,inflammation,mitochondrial dysfunction,and neuronal injury.Critical transcription factors,such as nuclear factor erythroid 2-related factor 2 and nuclear factor kappa B,play central roles in the progression of stroke.Nuclear factor erythroid 2-related factor 2 is sensitive to changes in the cellular redox status and is crucial in protecting cells against oxidative damage,inflammatory responses,and cytotoxic agents.It plays a significant role in post-stroke neuroprotection and repair by influencing mitochondrial function,endoplasmic reticulum stress,and lysosomal activity and regulating metabolic pathways and cytokine expression.Conversely,nuclear factor-kappa B is closely associated with mitochondrial dysfunction,the generation of reactive oxygen species,oxidative stress exacerbation,and inflammation.Nuclear factor-kappa B contributes to neuronal injury,apoptosis,and immune responses following stroke by modulating cell adhesion molecules and inflammatory mediators.The interplay between these pathways,potentially involving crosstalk among various organelles,significantly influences stroke pathophysiology.Advancements in single-cell sequencing and spatial transcriptomics have greatly improved our understanding of stroke pathogenesis and offer new opportunities for the development of targeted,individualized,cell typespecific treatments.In this review,we discuss the mechanisms underlying the involvement of nuclear factor erythroid 2-related factor 2 and nuclear factor-kappa B in both ischemic and hemorrhagic stroke,with an emphasis on their roles in oxidative stress,inflammation,and neuroprotection.展开更多
Nerve trauma commonly results in chronic neuropathic pain. This is by triggering the release of proinflammatory mediators from local and invading cells that induce inflammation and nociceptive neuron hyperexcitability...Nerve trauma commonly results in chronic neuropathic pain. This is by triggering the release of proinflammatory mediators from local and invading cells that induce inflammation and nociceptive neuron hyperexcitability. Even without apparent inflammation, injury sites are associated with increased inflammatory markers. This review focuses on how it might be possible to reduce neuropathic pain by reducing inflammation. Physiologically, pain is resolved by a combination of the out-migration of pro-inflammatory cells from the injury site, the down-regulation of the genes underlying the inflammation, up-regulating genes for anti-inflammatory mediators, and reducing nociceptive neuron hyperexcitability. While various techniques reduce chronic neuropathic pain, the best are effective on < 50% of patients, no technique reliably or permanently eliminates neuropathic pain. This is because most techniques are predominantly aimed at reducing pain, not inflammation. In addition, while single factors reduce pain, increasing evidence indicates significant and longer-lasting pain relief requires multiple factors acting simultaneously. Therefore, it is not surprising that extensive data indicate that the application of platelet-rich plasma provides more significant and longer-lasting pain suppression than other techniques, although its analgesia is neither complete nor permanent. However, several case reports indicate that platelet-rich plasma can induce permanent neuropathic pain elimination when the platelet concentration is significantly increased and is applied to longer nerve lengths. This review examines the primary triggers of the development and maintenance of neuropathic pain and techniques that reduce chronic neuropathic pain. The application of plateletrich plasma holds great promise for providing complete and permanent chronic neuropathic pain elimination.展开更多
BACKGROUND Post-transplant tertiary hyperparathyroidism(PT-tHPT)is a well-recognized complication following kidney transplantation,characterized by persistent excessive secretion of parathyroid hormone(PTH)despite imp...BACKGROUND Post-transplant tertiary hyperparathyroidism(PT-tHPT)is a well-recognized complication following kidney transplantation,characterized by persistent excessive secretion of parathyroid hormone(PTH)despite improved renal function.It is potentially associated with an increased risk of cardiovascular events,renal osteodystrophy,pathologic fractures,graft loss,and mortality.AIM To evaluate the incidence,risk factors,and outcomes of PT-tHPT amongst kidney transplant recipients.METHODS A total of 887 transplant recipients who underwent transplantation between 2000 and 2020 were evaluated.Univariable and multivariable logistic regression was performed to determine the predictors of tertiary hyperparathyroidism.Graft and recipient outcomes were assessed using multivariable Cox regression.A separate multivariable Cox regression was performed to determine the effect of treatment strategies on outcomes.RESULTS PT-tHPT,defined as elevated PTH(>65 ng/L)and persistent hypercalcemia(>2.60 mmol/L),was diagnosed in 14%of recipients.Risk factors for PT-tHPT included older age[odds ratio(OR)=1.36,P<0.001],Asian ethnicity(OR=0.33,P=0.006),total ischemia time(OR=1.03,P=0.048 per hour),pre-transplant serum calcium(OR=1.38,P<0.001)per decile increase,pre-transplant PTH level(OR=1.31,P<0.001)per decile increase,longer dialysis duration(OR=1.12,P=0.002)per year,history of acute rejection(OR=2.37,P=0.012),and slope of estimated glomerular filtration rate change(OR=0.91,P=0.001).There were a 3.4-fold higher risk of death-censored graft loss and a 1.9-fold greater risk of recipient death with PT-tHPT.The three treatment strategies of conservative management,calcimimetic and parathyroidectomy did not significantly change the graft or patient outcome.CONCLUSION Pretransplant elevated calcium and PTH levels,older age and dialysis duration are associated with PT-tHPT.While PT-tHPT significantly affects graft and recipient survival,the treatment strategies did not affect survival.展开更多
BACKGROUND Sorafenib has been the conventional treatment for advanced hepatocellular carcinoma(HCC)since 2008.While radiological complete responses are extremely rare,improved supportive care and multidisciplinary app...BACKGROUND Sorafenib has been the conventional treatment for advanced hepatocellular carcinoma(HCC)since 2008.While radiological complete responses are extremely rare,improved supportive care and multidisciplinary approaches in clinical practice may explain the recent increase in case reports and retrospective series documenting such responses.CASE SUMMARY This case series describes 3 patients with advanced HCC who achieved durable complete responses using first-line sorafenib therapy,even in the presence of portal vein thrombosis or extrahepatic spread,and highlights the potential for sustained remission in selected patients.Dermatologic toxicity and non-viral etiology may correlate with favorable outcomes;however,reliable predictive biomarkers for sorafenib response are lacking.CONCLUSION Future research into the etiology and molecular differences in HCC is necessary to develop more personalized therapy options.展开更多
Understanding water chemistry in karst regions is crucial for improving global water resource management and deepening our knowledge of the biogeochemical cycles shaping these sensitive environments.Despite advance-me...Understanding water chemistry in karst regions is crucial for improving global water resource management and deepening our knowledge of the biogeochemical cycles shaping these sensitive environments.Despite advance-ments in karst hydrology,significant gaps remain in long-term trends,underlying processes,and quantitative effects of environmental changes.This is especially true in areas like the Wujiang River(WJ)in China,where human activities such as reservoir construction and land use/cover changes have accelerated hydrochemical changes.We combined recent and historical monitoring data to provide a detailed analysis of the spatial and temporal characteristics,evolution,and controlling factors of major ions in WJ.These findings are important for local water management and contribute to global efforts to manage similar karst systems facing human-induced pressures.Our research shows clear seasonal differences in solute concentrations,with higher levels during the dry season.WJ’s water is rich in calcium,with Ca-HCO_(3) ion pairs being the most common.Reservoir monitor-ing stations show much higher levels of NO_(3)^(−)and SO_(4)^(2−)compared to river-type stations,likely due to longer hydraulic retention time and increased acid deposition.The study confirms the significant role of pH and water temperature in rock weathering processes.Land use/cover changes were identified as the primary drivers of solute variations(46.37%),followed by lithology(13.92%)and temperature(8.35%).Over the past two decades,in-tense carbonate weathering has been observed,especially during wet seasons.Among karstic provinces,Guizhou Province stands out with the highest ion concentrations,indicative of its extensive karst coverage and heightened weathering processes.展开更多
Landslides pose a formidable natural hazard across the Qinghai-Tibet Plateau(QTP),endangering both ecosystems and human life.Identifying the driving factors behind landslides and accurately assessing susceptibility ar...Landslides pose a formidable natural hazard across the Qinghai-Tibet Plateau(QTP),endangering both ecosystems and human life.Identifying the driving factors behind landslides and accurately assessing susceptibility are key to mitigating disaster risk.This study integrated multi-source historical landslide data with 15 predictive factors and used several machine learning models—Random Forest(RF),Gradient Boosting Regression Trees(GBRT),Extreme Gradient Boosting(XGBoost),and Categorical Boosting(CatBoost)—to generate susceptibility maps.The Shapley additive explanation(SHAP)method was applied to quantify factor importance and explore their nonlinear effects.The results showed that:(1)CatBoost was the best-performing model(CA=0.938,AUC=0.980)in assessing landslide susceptibility,with altitude emerging as the most significant factor,followed by distance to roads and earthquake sites,precipitation,and slope;(2)the SHAP method revealed critical nonlinear thresholds,demonstrating that historical landslides were concentrated at mid-altitudes(1400-4000 m)and decreased markedly above 4000 m,with a parallel reduction in probability beyond 700 m from roads;and(3)landslide-prone areas,comprising 13%of the QTP,were concentrated in the southeastern and northeastern parts of the plateau.By integrating machine learning and SHAP analysis,this study revealed landslide hazard-prone areas and their driving factors,providing insights to support disaster management strategies and sustainable regional planning.展开更多
Drought stress significantly impedes apple growth,development,and yield,leading to substantial economic losses within the global apple industry.Malus prunifolia(Mp),a commonly utilized apple rootstock,has shown promis...Drought stress significantly impedes apple growth,development,and yield,leading to substantial economic losses within the global apple industry.Malus prunifolia(Mp),a commonly utilized apple rootstock,has shown promise in augmenting cultivated apple resistance to abiotic stress.Although Alfin-like(ALs)proteins have demonstrated pivotal roles in dicotyledonous plants'response to abiotic stresses,knowledge about AL genes in apple rootstocks is limited,and their functions remain largely elusive.In this study,we identified and characterized 10 MpAL gene members in the apple rootstock genome,confirming their localization within the nucleus.Our investigation revealed the significant regulation of MpALs'expression under drought and abscisic acid(ABA)stresses in M.prunifolia.In this study,one of the members,MpAL1,was selected for further exploration in Arabidopsis and apple to explore its potential function in response to drought and ABA stresses.The results showed that overexpression-MpAL1 transgenic apple calli grew significantly better than WT and MpAL1-RNAi lines,which regulates the accumulation of H_(2)O_(2)and O_(2).-levels.Additionally,transgenic Arabidopsis plants overexpressing MpAL1 exhibited positively regulating antioxidant enzymes activities under stress treatments.Further study showed that silencing MpAL1 in apple plants showed obvious chlorosis in leaves,and accumulation of reactive oxygen species under drought stress.Moreover,our detailed analysis established that MpAL1 regulates several drought and ABA-responsive genes,exerting an influence on their expression in transgenic apple.Collectively,our findings identify MpAL1 as a positive regulator that increases drought stress in apple,shedding light on its potential significance in bolstering drought resistance in this fruit crop.展开更多
BACKGROUND Aseptic loosening remains the leading cause of revision in primary total hip arthroplasty(pTHA).However,the literature demonstrates significant variability regarding the relative contributions of different ...BACKGROUND Aseptic loosening remains the leading cause of revision in primary total hip arthroplasty(pTHA).However,the literature demonstrates significant variability regarding the relative contributions of different factors.AIM To investigate the key determinants of aseptic loosening,we performed a systematic review and meta-analysis.METHODS A comprehensive search of PubMed,Web of Science,EMBASE,and the Cochrane Library was conducted,encompassing studies from database inception to January 1,2025.Meta-analyses were performed to evaluate factors associated with aseptic loosening following pTHA.Inclusion and exclusion criteria were systematically applied at each stage to ensure methodological transparency and reproducibility.Study quality was assessed using standardized categories.Pooled odds ratio(OR)with corresponding 95%confidence interval were calculated with random-or fixed-effects models to generate reliability estimates,and study heterogeneity was visualized using forest plots.Ten factors,categorized into patient-,surgeon-,and device-related domains,were reviewed and meta-analyzed.Funnel plot analysis demonstrated a relatively symmetrical distribution,suggesting minimal publication bias.RESULTS A meta-analysis of 20 studies(520789 participants)found a pooled prevalence of 1.96%.Significant risk factors for aseptic loosening after pTHA included elevated body mass index(OR=1.116,P<0.001),higher Charlson comorbidity index(OR=1.378,P<0.001),prosthesis-related factors(OR=1.497,P<0.001),and adverse lifestyles(OR=2.198,P=0.037).Protective factors were non-white race(OR=0.445,P<0.001)and favorable genetics(OR=0.723,P<0.001).Male sex increased risk(OR=1.232,P=0.016),while age and anatomy were not significant.Surgical expertise showed a slight protective effect(OR=1.048,P<0.001).A comprehensive understanding of the modifiable and non-modifiable factors contributing to aseptic loosening after pTHA requires consideration of patient-related factors,surgical expertise,and prosthesis characteristics.CONCLUSION The identification of these factors is critical for risk mitigation.High-risk patients should receive targeted counseling regarding individualized profiles.Further studies are warranted to establish clearer causal relationships and identify additional contributing factors.展开更多
基金funded by the National Natural Science Foundation of China(Grant Nos.32202502,U21A20230,32070331,32102380 and 32072580)National Key Research and Development Program(Grant No.2018YFD1000800)+3 种基金the Key-Area Research and Development Program of Guangdong Province(Grant No.2022B0202080001)the Special Fund for Seed Industry of Guangdong Province Rural Revitalization Strategy(Grant No.2022-NPY00-024)Tibet Autonomous Region of Lhasa City Science and Technology Project(Grant No.LSKJ202310)the Science and Technology Project of Bijie City(Grant No.BKK2022-3)。
文摘The transcriptional cascade and regulatory loop play crucial roles in regulating plant-specialized metabolite biosynthesis.Capsaicinoids are unique to the genus Capsicum and confer a pungent flavor to its fruits.However,the transcriptional regulation of capsaicinoid biosynthesis remains largely unknown.In this study,two AP2/ERF transcription factors(TFs),CaERF102 and CaERF111,were characterized for their role in the capsaicinoid biosynthesis process.Expression analysis of two ERFs and capsaicinoid biosynthetic genes(CBGs)suggested that they were associated with capsaicinoid biosynthesis.Both ERFs encode nuclear-localized proteins and function as transcriptional activators through their C-terminal activation motifs.The two ERF TFs participated in capsaicinoid biosynthesis by directly activating the promoters of key CBGs,and this activation was significantly enhanced when CaMYC2 was co-expressed.Moreover,CaERF102 and CaERF111 were found to interact with CaMYC2.This study helps elucidate the AP2/ERF TF regulatory network that governs capsaicinoid biosynthesis in Capsicum species.
文摘BACKGROUND Gastric cancer is a malignant tumor with high morbidity and mortality worldwide.Neoadjuvant chemotherapy(NAC),defined as chemotherapy administered before the primary treatment(usually surgery)to reduce tumor size and control micrometastases,has emerged as a crucial therapeutic strategy for locally advanced gastric cancer.Pathological complete response(pCR),characterized by the absence of viable tumor cells in the resected specimen after neoadjuvant treatment,is recognized as a strong predictor of favorable prognosis.However,the factors influencing the achievement of pCR remain incompletely understood.AIM To identify and analyze the predictive factors associated with achieving pCR after NAC in gastric cancer patients,thereby providing evidence-based guidance for clinical decision-making.METHODS A retrospective analysis was performed on 215 patients from Shandong Cancer Hospital and Tai’an Central Hospital with locally advanced gastric cancer who underwent NAC followed by radical surgery at our hospital between January 2015 and December 2023.Comprehensive clinical and pathological data were collected,including age,gender,tumor location,Lauren classification,clinical staging,chemotherapy regimens,number of chemotherapy cycles,and baseline hematological indicators.The baseline hematological indicators included neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio,albumin level,carcinoembryonic antigen(CEA),and carbohydrate antigen 19-9.Univariate and multivariate logistic regression analyses were employed to determine the independent predictive factors for pCR.RESULTS Among 215 gastric cancer patients,41(19.1%)achieved pCR after NAC.Multivariate analysis identified five independent predictive factors for pCR:Lauren intestinal type[odds ratio(OR)=3.28],lower clinical T stage(OR=2.75),CEA decrease≥70%after NAC(OR=3.42),pre-treatment NLR<2.5(OR=2.13),and≥4 chemotherapy cycles(OR=2.87).The fluorouracil,leucovorin,oxaliplatin,docetaxel regimen achieved the highest pCR rate(27.5%),and oxaliplatin-containing regimens were superior to cisplatin-containing regimens(22.3%vs 12.7%,P=0.034).Patients with both low NLR and platelet-to-lymphocyte ratio had the highest pCR rate(33.8%),while those with both high inflammatory markers had the lowest rate(10.7%).Earlier clinical stage disease(cT3N+vs cT4N+:28.6%vs 13.0%)and lower lymph node burden were associated with higher pCR rates.CONCLUSION The achievement of pCR after NAC in gastric cancer patients is closely associated with Lauren intestinal type,lower clinical T stage,a significant decrease in CEA after chemotherapy,low pre-treatment NLR,and an adequate number of chemotherapy cycles.
基金Supported by Tianjin Municipality Health Science and Technology Project,No.TJWJ2023MS052.
文摘BACKGROUND Dental implants are widely used to replace missing teeth.Currently,clinicians assess osseointegration success by measuring the implant’s stability within the bone and monitoring the marginal tissue height.Diabetes,especially type 2 diabetes mellitus(T2DM),has been reported to impair implant healing,drastically reducing implant success rates.AIM To analyze the high-risk factors for inflammatory response and prognosis after dental implantation in patients with T2DM,and provide strong evidence for reducing the incidence of postimplant peri-implantitis(PI).METHODS We performed a retrospective review of 146 patients with T2DM who had dental implants placed at Tianjin Fifth Central Hospital,between September 2021 and September 2023,which was regarded as the observation group.Moreover,60 ageand gender-matched individuals with normal blood glucose levels served as the control group.The general information,postoperative periodontal indices,and levels of inflammatory factors were comprehensively analyzed and compared.Furthermore,the incidence of postimplant PI was counted,and multivariate logistic regression was used to identify the determinants of postimplant PI.RESULTS In terms of the periodontal indices,the probing depth,modified sulcus bleeding index,and marginal bone loss in the observation cohorts began to increase significantly at 6 months and 3 months,respectively,after the completion of dental implant restoration.The T2DM cases demonstrated significantly elevated counts of leukocytes,lymphocytes,and neutrophils compared to the controls at 24 hours postoperatively.Moreover,the TNF-α,IL-1β,and IL-6 concentrations started to increase significantly in the gingival crevicular fluid 3 months after the completion of dental implant restoration in both cohorts,with the observation group exhibiting higher levels than the controls at each time point.63 out of the 146 cases developed PI.Multivariate logistic regression analysis indicated that high glycosylated hemoglobin levels,smoking,daily tooth-brushing frequency of less than once,and the anterior tooth as the implant site independently contributed to postimplant PI in T2DM cases,while a tooth-brushing duration of≥3 minutes was a protective factor.CONCLUSION Patients with T2DM are at risk of developing PI following dental implantation.Clinically,it is necessary to enhance the identification of risk factors for postimplant PI,improve risk prediction,prevention,and control,and formulate targeted intervention countermeasures to reduce the occurrence of postimplant PI.
基金supported by the National Natural Science Foundation of China,Nos.82072165 and 82272256(both to XM)the Key Project of Xiangyang Central Hospital,No.2023YZ03(to RM)。
文摘Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in spinal cord injury.Previous studies have shown that microglia can promote neuronal survival by phagocytosing dead cells and debris and by releasing neuroprotective and anti-inflammatory factors.However,excessive activation of microglia can lead to persistent inflammation and contribute to the formation of glial scars,which hinder axonal regeneration.Despite this,the precise role and mechanisms of microglia during the acute phase of spinal cord injury remain controversial and poorly understood.To elucidate the role of microglia in spinal cord injury,we employed the colony-stimulating factor 1 receptor inhibitor PLX5622 to deplete microglia.We observed that sustained depletion of microglia resulted in an expansion of the lesion area,downregulation of brain-derived neurotrophic factor,and impaired functional recovery after spinal cord injury.Next,we generated a transgenic mouse line with conditional overexpression of brain-derived neurotrophic factor specifically in microglia.We found that brain-derived neurotrophic factor overexpression in microglia increased angiogenesis and blood flow following spinal cord injury and facilitated the recovery of hindlimb motor function.Additionally,brain-derived neurotrophic factor overexpression in microglia reduced inflammation and neuronal apoptosis during the acute phase of spinal cord injury.Furthermore,through using specific transgenic mouse lines,TMEM119,and the colony-stimulating factor 1 receptor inhibitor PLX73086,we demonstrated that the neuroprotective effects were predominantly due to brain-derived neurotrophic factor overexpression in microglia rather than macrophages.In conclusion,our findings suggest the critical role of microglia in the formation of protective glial scars.Depleting microglia is detrimental to recovery of spinal cord injury,whereas targeting brain-derived neurotrophic factor overexpression in microglia represents a promising and novel therapeutic strategy to enhance motor function recovery in patients with spinal cord injury.
基金supported by the National Natural Science Foundation of China(Nos.82171552 and 82170479)the Natural Science Foundation of Shanghai Ctiy(No.21ZR1457500)the Science and Technology Bureau of Shanghai Putuo District(No.ptkwws202102).
文摘Magnolol,a compound extracted from Magnolia officinalis,demonstrates potential efficacy in addressing metabolic dysfunction and cardiovascular diseases.Its biological activities encompass anti-inflammatory,antioxidant,anticoagulant,and anti-diabetic effects.Growth/differentiation factor-15(GDF-15),a member of the transforming growth factorβsuperfamily,is considered a potential therapeutic target for metabolic disorders.This study investigated the impact of magnolol on GDF-15 production and its underlying mechanism.The research examined the pharmacological effect of magnolol on GDF-15 expression in vitro and in vivo,and determined the involvement of endoplasmic reticulum(ER)stress signaling in this process.Luciferase reporter assays,chromatin immunoprecipitation,and in vitro DNA binding assays were employed to examine the regulation of GDF-15 by activating transcription factor 4(ATF4),CCAAT enhancer binding proteinγ(CEBPG),and CCCTC-binding factor(CTCF).The study also investigated the effect of magnolol and ATF4 on the activity of a putative enhancer located in the intron of the GDF-15 gene,as well as the influence of single nucleotide polymorphisms(SNPs)on magnolol and ATF4-induced transcription activity.Results demonstrated that magnolol triggers GDF-15 production in endothelial cells(ECs),hepatoma cell line G2(HepG2)and hepatoma cell line 3B(Hep3B)cell lines,and primary mouse hepatocytes.The cooperative binding of ATF4 and CEBPG upstream of the GDF-15 gene or the E1944285 enhancer located in the intron led to full-power transcription of the GDF-15 gene.SNP alleles were found to impact the magnolol and ATF4-induced transcription activity of GDF-15.In high-fat diet ApoE^(-/-)mice,administration of magnolol induced GDF-15 production and partially suppressed appetite through GDF-15.These findings suggest that magnolol regulates GDF-15 expression through priming of promoter and enhancer activity,indicating its potential as a drug for the treatment of metabolic disorders.
基金National Key Research and Development Program of China(2022YFC2503500 and 2022YFC2503504)。
文摘Background The association of systemic inflammatory response index(SIRI)with prognosis of coronary artery disease(CAD)patients has never been investigated in a large sample with long-term follow-up.This study aimed to explore the association of SIRI with all-cause and cause-specific mortality in a nationally representative sample of CAD patients from United States.Methods A total of 3386 participants with CAD from the National Health and Nutrition Examination Survey(NHANES)1999-2018 were included in this study.Cox proportional hazards model,restricted cubic spline(RCS),and receiver operating characteristic curve(ROC)were performed to investigate the association of SIRI with all-cause and cause-specific mortality.Piecewise linear regression and sensitivity analyses were also performed.Results During a median follow-up of 7.7 years,1454 all-cause mortality occurred.After adjusting for confounding factors,higher lnSIRI was significantly associated with higher risk of all-cause(HR=1.16,95%CI:1.09-1.23)and CVD mortality(HR=1.17,95%CI:1.05-1.30)but not cancer mortality(HR=1.17,95%CI:0.99-1.38).The associations of SIRI with all-cause and CVD mortality were detected as J-shaped with threshold values of 1.05935 and 1.122946 for SIRI,respectively.ROC curves showed that lnSIRI had robust predictive effect both in short and long terms.Conclusions SIRI was independently associated with all-cause and CVD mortality,and the dose-response relationship was Jshaped.SIRI might serve as a valid predictor for all-cause and CVD mortality both in the short and long terms.
基金supported by grants from the National Natural Science Foundation of China (82071104)Science and Technology Commission of Shanghai Municipality (23XD1434200/22Y21901000)+9 种基金Shanghai Hospital Development Center(SHDC12022120)National Clinical Research Center for Oral Diseases (NCRCO2021-omics-07)Shanghai Clinical Research Center for Oral Diseases (19MC1910600)Major and Key Cultivation Projects of Ninth People’s Hospital affiliated to Shanghai Jiao Tong University School of Medicine (JYZP006)Shanghai’s Top Priority Research Center (2022ZZ01017)CAMS Innovation Fund for Medical Sciences (2019-I2M-5-037)Fundamental research program funding of Ninth People’s Hospital affiliated to Shanghai Jiao Tong University School of Medicine(JYZZ237)Eastern Talent Plan Leading Project (BJZH2024001)partly supported by the Shanghai Ninth People’s Hospital affiliated with Shanghai Jiao Tong University,School of Medicine(JYJC202223)Shanghai Key Laboratory of Translational Medicine on Ear and Nose diseases (14DZ2260300)
文摘Pulpitis is a common infective oral disease in clinical situations.The regulatory mechanisms of immune defense in pulpitis are still being investigated.Osteomodulin(OMD)is a small leucine-rich proteoglycan family member distributed in bones and teeth.It is a bioactive protein that promotes osteogenesis and suppresses the apoptosis of human dental pulp stem cells(hDPSCs).In this study,the role of OMD in pulpitis and the OMD-induced regulatory mechanism were investigated.The OMD expression in normal and inflamed human pulp tissues was detected via immunofluorescence staining.Intriguingly,the OMD expression decreased in the inflammatory infiltration area of pulpitis specimens.The cellular experiments demonstrated that recombined human OMD could resist the detrimental effects of lipopolysaccharide(LPS)-induced inflammation.A conditional Omd knockout mouse model with pulpal inflammation was established.LPS-induced inflammatory impairment significantly increased in conditional Omd knockout mice,whereas OMD administration exhibited a protective effect against pulpitis.Mechanistically,the transcriptome alterations of OMD overexpression showed significant enrichment in the nuclear factor-κB(NF-κB)signaling pathway.Interleukin-1 receptor 1(IL1R1),a vital membrane receptor activating the NF-κB pathway,was significantly downregulated in OMD-overexpressing hDPSCs.Additionally,the interaction between OMD and IL1R1 was verified using co-immunoprecipitation and molecular docking.In vivo,excessive pulpal inflammation in Omd-deficient mice was rescued using an IL1R antagonist.Overall,OMD played a protective role in the inflammatory response via the IL1R1/NF-κB signaling pathway.OMD may optimize the immunomodulatory functions of hDPSCs and can be used for regenerative endodontics.
基金National Natural Science Foundation of China(grant No.32301870 and 32572302 to Chen Lin)Natural Science Foundation of Jiangsu Province(grant No.BK20230568 to Chen Lin)+3 种基金the Jiangsu Provincial Agricultural Science and Technology Independent Innovation Fund(grant No.CX(24)3124 to Chen Lin)Outstanding Ph.D.Program in Yangzhou(grant No.YZLYJFJH2022YXBS147 to Chen Lin)the General Project of Basic Scientific Research to colleges and universities in Jiangsu Province(grant No.22KJB210019 to Chen Lin)the Priority Academic Program Development of Jiangsu Higher Education Institutions is greatly acknowledged.
文摘Extensive transcriptomic reprogramming is triggered by biotic and abiotic stresses in plants,with coordinated regulation mediated through multiple transcription factor families,such as WRKY,MYB,NAC,and BBX proteins.Among these,B-box(BBX)proteins represent a distinct class of zinc finger transcription factors characterized by the presence of conserved B-box domains.They serve as central regulators in plant photomorphogenesis and developmental processes.Accumulating genetic and biochemical evidence demonstrates that BBX family members orchestrate plant responses to biotic and abiotic stresses through multifaceted molecular mechanisms,including the regulation of reactive oxygen species(ROS)homeostasis,enhancement of anthocyanin biosynthesis,and modulation of hormonal signaling pathways.This review systematically summarizes recent advances in the identification of BBX family genes in different plant species.Furthermore,their emerging roles in mediating plant stress responses are elucidated,with molecularmechanisms being comprehensively analyzed at both transcriptional and post-translational levels.However,to fully harness the potential of BBX genes in crop improvement,a deeper understanding of their functional mechanisms including BBX-mediated hormonal crosstalk networks,growth-defense trade-offs,and more extensive field performance data remains essential.These insights provide a theoretical foundation for developing climate-resilient crop varieties through targeted genetic improvement strategies.
基金supported by grants from the National Natural Science Foundation of China(Nos.42172339,91951205)。
文摘Microorganisms actively participate in biogeochemical cycling processes and play a crucial role in maintaining the dynamic balance of hot spring ecosystems.However,the distribution of microbial functional genes and their influencing factors in hot springs remain largely unclear.Therefore,this study investigated the microbial functional genes and their potential for controlling biogeochemical cycles(C,N,S,and P) in the hot Springs of Tengchong,China,using the Geochip method,a functional gene microarray technology.The examined hot springs have very different microbial functional genes.A total of 22 736 gene probe signals were identified,belonging to 567 functional genes and associated with 15 ecological functions,mainly involving stress response,carbon cycle,nitrogen cycle,sulfur cycle,phosphorus cycle and energy processes.The amyA,narG,dsrA and ppx genes were most abundant in carbon,nitrogen,sulfur and phosphorus cycles,respectively,and were significantly correlated with pH,temperature and SO_(4)^(2-).The diversity and abundance of detected gene probes were negatively correlated with temperature.The α-diversity(i.e.,Shannon index) was high at low temperature and low pH.Molecular functional interactions revealed by the gene connectivity levels were negatively correlated with temperature,pH and SO_(4)^(2-).These results suggested that the abundance,diversity and interactions of microbial functional genes were significantly influenced by geochemical parameters.-In addition,some genera possessed functional genes related to carbon,nitrogen,sulfur,and phosphorus cycles and can synergistically control the biogeochemical cycles of carbon,nitrogen,sulfur and phosphorus.These findings provide new insights into the functional potentials of microorganisms to participate in biogeochemical cycles and their responses to environmental factors in hot springs.
基金Supported by the National Natural Science Foundation of China,No.81671600 and No.81241094Natural Science Foundation of Shandong Province,China,No.ZR2016HM13 and No.ZR2023MH066Qingdao Medical and Health Scientific Research Project,China,No.2024-WJKY160.
文摘BACKGROUND The pathogenesis of primary biliary cholangitis(PBC)remains unclear.Ursodeoxycholic acid(UDCA)is the only first-line clinical treatment,but approximately 40%of patients exhibit a poor response.AIM To identify novel biomarkers for PBC to predict the efficacy of UDCA and enhance treatment.METHODS Microarray expression profiling datasets were downloaded from the Gene Expression Omnibus and analyzed to identify differentially expressed genes between PBC patients and healthy controls.Immunohistochemistry was performed to validate key genes in liver tissues of the participants.Logistic regression was employed to evaluate prognostic risk factors,receiver operating characteristic curves were used to assess predictive performance,and correlations between key genes and clinicopathological characteristics were analyzed.RESULTS By bioinformatic analysis,13 genes primarily associated with the progression of PBC were identified,and tumor necrosis factor alpha-induced protein 3(TNFAIP3)was selected for further investigation.Then expression of TNFAIP3 in PBC patients was significantly elevated compared to healthy controls on immunohistochemistry(P<0.0001).Multivariate Cox regression analysis indicated that both TNFAIP3 and fatigue were independent risk factors for response to UDCA in PBC patients(P<0.05).The area under the curve for TNFAIP3 and fatigue were 0.691 and 0.704,respectively,while their combination showed a significantly higher area under the curve of 0.848.The expression of TNFAIP3 was also correlated with age,albumin,total bilirubin,alkaline phosphatase and splenomegaly(P<0.05).CONCLUSION TNFAIP3 and fatigue are independent risk factors for response to UDCA in Chinese patients with PBC.TNFAIP3 may be a potential biomarker or therapeutic target for PBC.These findings offer new insights into the pathogenesis of PBC.
基金Supported by Italian Association for Cancer Research(AIRC),No.21956Italian Ministry of Health-5×1000 funds 2023.
文摘In this editorial,we comment on the article by Zhang et al recently published in the World Journal of Gastroenterology.The manuscript elucidates significant novel mechanisms underlying hepatocellular carcinoma(HCC)progression.HCC is currently considered one of the major causes of global cancer-associated deaths,underscoring the critical need for novel therapeutic targets.Growing evidence underlines the role of the lipid raft protein flotillin-1(FLOT1)in cancer,whose dysregulation drives tumor cell growth and survival.However,the regulatory role of FLOT1 on Golgi apparatus function in HCC is unknown.In this study,Zhang et al elucidated a pivotal mechanism by which FLOT1 promotes HCC progression through activation of transcription factor E3-mediated Golgi stress response.The study reveals that FLOT1 inhibits the mechanistic target of rapamycin complexes 1 and 2 by ubiquitination,facilitating transcription factor E3 dephosphorylation,nuclear translocation,and subsequent upregulation of Golgi stress-associated genes,thereby leading to enhanced HCC cell growth and invasive capacity.These findings obtained in vitro/in vivo highlight the interplay between FLOT1 and Golgi homeostasis in HCC.Targeting FLOT1 may offer a new strategy for the treatment of HCC.
文摘BACKGROUND Ischemic stroke is one of the leading global causes of disability and death.Despite advances in modern medical technology that improve acute treatment and rehabilitation measures,post-stroke anxiety and depression(PSD)do not receive sufficient attention.AIM To systematically evaluate risk factors and early identification markers for PSD for more precise screening and intervention strategies in clinical practice.METHODS This retrospective study analyzed clinical data from 112 patients with ischemic stroke admitted between January 2022 and December 2024.Based on assessments using the Hamilton Rating Scale for Anxiety(HAMA)and Hamilton Rating Scale for Depression(HAMD)at 2 weeks(±3 days)post-stroke,patients were classified into the PSD group(HAMA≥7 and/or HAMD≥7)and the non-PSD group(HAMA<7 and HAMD<7).Observation indicators included psychological assessment,demographic and clinical characteristics,stroke-related clinical indicators,neuroimaging assessments,and laboratory biomarkers.Multivariate logistic regression analysis was used to identify independent risk factors for PSD,and receiver operating characteristic curve analysis was used to evaluate the diagnostic value of potential biomarkers.RESULTS Of the 112 patients,46(41.1%)were diagnosed with PSD.Multivariate analysis identified five independent risk factors:Female gender[Odds ratio(OR)=2.32,95%confidence interval(CI):1.56-3.45],history of mental disorders prior to stroke(OR=3.17,95%CI:1.89-5.32),infarct location in the frontal lobe or limbic system(OR=2.86,95%CI:1.73-4.71),stroke severity with National Institutes of Health Stroke Scale≥8 at admission(OR=2.54,95%CI:1.62-3.99),and low social support(Social Support Rating Scale<35,OR=2.18,95%CI:1.42-3.36).Subgroup analysis showed that depression patients more commonly had left hemisphere lesions(68.4%vs 45.2%),while anxiety patients more frequently presented with right hemisphere lesions(59.5%vs 39.5%).The PSD group exhibited larger infarct volumes(8.7 cm^(3) vs 5.3 cm^(3)),more severe white matter hyperintensities,and more pronounced frontal lobe atrophy.Analysis of inflammatory markers showed significantly elevated levels of interleukin-6(7.8 pg/mL vs 4.5 pg/mL)and tumor necrosis factor-alpha(15.6 pg/mL vs 9.8 pg/mL)in the PSD group,while hypothalamicpituitary-adrenal axis function assessment revealed higher cortisol levels(386.5±92.3 nmol/L vs 328.7±75.6 nmol/L)and flattened diurnal rhythm in the PSD group.CONCLUSION PSD is a complex neuropsychiatric consequence of stroke involving disruption of the frontal-limbic circuitry,neuroinflammatory responses,and dysfunction of the hypothalamic-pituitary-adrenal axis.
基金supported by grants from the Zhejiang Provincial TCM Science and Technology Plan Project,No.2023ZL156(to YH)Ningbo Top Medical and Health Research Program,No.2022020304(to XG)+1 种基金the Natural Science Foundation of Ningbo,No.2023J019(to YH)Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province,No.2022E10026(to YH)。
文摘Strokes include both ischemic stroke,which is mediated by a blockade or reduction in the blood supply to the brain,and hemorrhagic stroke,which comprises intracerebral hemorrhage and subarachnoid hemorrhage and is characterized by bleeding within the brain.Stroke is a lifethreatening cerebrovascular condition characterized by intricate pathophysiological mechanisms,including oxidative stress,inflammation,mitochondrial dysfunction,and neuronal injury.Critical transcription factors,such as nuclear factor erythroid 2-related factor 2 and nuclear factor kappa B,play central roles in the progression of stroke.Nuclear factor erythroid 2-related factor 2 is sensitive to changes in the cellular redox status and is crucial in protecting cells against oxidative damage,inflammatory responses,and cytotoxic agents.It plays a significant role in post-stroke neuroprotection and repair by influencing mitochondrial function,endoplasmic reticulum stress,and lysosomal activity and regulating metabolic pathways and cytokine expression.Conversely,nuclear factor-kappa B is closely associated with mitochondrial dysfunction,the generation of reactive oxygen species,oxidative stress exacerbation,and inflammation.Nuclear factor-kappa B contributes to neuronal injury,apoptosis,and immune responses following stroke by modulating cell adhesion molecules and inflammatory mediators.The interplay between these pathways,potentially involving crosstalk among various organelles,significantly influences stroke pathophysiology.Advancements in single-cell sequencing and spatial transcriptomics have greatly improved our understanding of stroke pathogenesis and offer new opportunities for the development of targeted,individualized,cell typespecific treatments.In this review,we discuss the mechanisms underlying the involvement of nuclear factor erythroid 2-related factor 2 and nuclear factor-kappa B in both ischemic and hemorrhagic stroke,with an emphasis on their roles in oxidative stress,inflammation,and neuroprotection.
文摘Nerve trauma commonly results in chronic neuropathic pain. This is by triggering the release of proinflammatory mediators from local and invading cells that induce inflammation and nociceptive neuron hyperexcitability. Even without apparent inflammation, injury sites are associated with increased inflammatory markers. This review focuses on how it might be possible to reduce neuropathic pain by reducing inflammation. Physiologically, pain is resolved by a combination of the out-migration of pro-inflammatory cells from the injury site, the down-regulation of the genes underlying the inflammation, up-regulating genes for anti-inflammatory mediators, and reducing nociceptive neuron hyperexcitability. While various techniques reduce chronic neuropathic pain, the best are effective on < 50% of patients, no technique reliably or permanently eliminates neuropathic pain. This is because most techniques are predominantly aimed at reducing pain, not inflammation. In addition, while single factors reduce pain, increasing evidence indicates significant and longer-lasting pain relief requires multiple factors acting simultaneously. Therefore, it is not surprising that extensive data indicate that the application of platelet-rich plasma provides more significant and longer-lasting pain suppression than other techniques, although its analgesia is neither complete nor permanent. However, several case reports indicate that platelet-rich plasma can induce permanent neuropathic pain elimination when the platelet concentration is significantly increased and is applied to longer nerve lengths. This review examines the primary triggers of the development and maintenance of neuropathic pain and techniques that reduce chronic neuropathic pain. The application of plateletrich plasma holds great promise for providing complete and permanent chronic neuropathic pain elimination.
文摘BACKGROUND Post-transplant tertiary hyperparathyroidism(PT-tHPT)is a well-recognized complication following kidney transplantation,characterized by persistent excessive secretion of parathyroid hormone(PTH)despite improved renal function.It is potentially associated with an increased risk of cardiovascular events,renal osteodystrophy,pathologic fractures,graft loss,and mortality.AIM To evaluate the incidence,risk factors,and outcomes of PT-tHPT amongst kidney transplant recipients.METHODS A total of 887 transplant recipients who underwent transplantation between 2000 and 2020 were evaluated.Univariable and multivariable logistic regression was performed to determine the predictors of tertiary hyperparathyroidism.Graft and recipient outcomes were assessed using multivariable Cox regression.A separate multivariable Cox regression was performed to determine the effect of treatment strategies on outcomes.RESULTS PT-tHPT,defined as elevated PTH(>65 ng/L)and persistent hypercalcemia(>2.60 mmol/L),was diagnosed in 14%of recipients.Risk factors for PT-tHPT included older age[odds ratio(OR)=1.36,P<0.001],Asian ethnicity(OR=0.33,P=0.006),total ischemia time(OR=1.03,P=0.048 per hour),pre-transplant serum calcium(OR=1.38,P<0.001)per decile increase,pre-transplant PTH level(OR=1.31,P<0.001)per decile increase,longer dialysis duration(OR=1.12,P=0.002)per year,history of acute rejection(OR=2.37,P=0.012),and slope of estimated glomerular filtration rate change(OR=0.91,P=0.001).There were a 3.4-fold higher risk of death-censored graft loss and a 1.9-fold greater risk of recipient death with PT-tHPT.The three treatment strategies of conservative management,calcimimetic and parathyroidectomy did not significantly change the graft or patient outcome.CONCLUSION Pretransplant elevated calcium and PTH levels,older age and dialysis duration are associated with PT-tHPT.While PT-tHPT significantly affects graft and recipient survival,the treatment strategies did not affect survival.
文摘BACKGROUND Sorafenib has been the conventional treatment for advanced hepatocellular carcinoma(HCC)since 2008.While radiological complete responses are extremely rare,improved supportive care and multidisciplinary approaches in clinical practice may explain the recent increase in case reports and retrospective series documenting such responses.CASE SUMMARY This case series describes 3 patients with advanced HCC who achieved durable complete responses using first-line sorafenib therapy,even in the presence of portal vein thrombosis or extrahepatic spread,and highlights the potential for sustained remission in selected patients.Dermatologic toxicity and non-viral etiology may correlate with favorable outcomes;however,reliable predictive biomarkers for sorafenib response are lacking.CONCLUSION Future research into the etiology and molecular differences in HCC is necessary to develop more personalized therapy options.
基金supported by Guangdong Basic and Applied Basic Research Foundation(Nos.2023A1515110824 and 2025A1515011839)Shenzhen Science and Technology Program(No.RCBS20231211090638066).
文摘Understanding water chemistry in karst regions is crucial for improving global water resource management and deepening our knowledge of the biogeochemical cycles shaping these sensitive environments.Despite advance-ments in karst hydrology,significant gaps remain in long-term trends,underlying processes,and quantitative effects of environmental changes.This is especially true in areas like the Wujiang River(WJ)in China,where human activities such as reservoir construction and land use/cover changes have accelerated hydrochemical changes.We combined recent and historical monitoring data to provide a detailed analysis of the spatial and temporal characteristics,evolution,and controlling factors of major ions in WJ.These findings are important for local water management and contribute to global efforts to manage similar karst systems facing human-induced pressures.Our research shows clear seasonal differences in solute concentrations,with higher levels during the dry season.WJ’s water is rich in calcium,with Ca-HCO_(3) ion pairs being the most common.Reservoir monitor-ing stations show much higher levels of NO_(3)^(−)and SO_(4)^(2−)compared to river-type stations,likely due to longer hydraulic retention time and increased acid deposition.The study confirms the significant role of pH and water temperature in rock weathering processes.Land use/cover changes were identified as the primary drivers of solute variations(46.37%),followed by lithology(13.92%)and temperature(8.35%).Over the past two decades,in-tense carbonate weathering has been observed,especially during wet seasons.Among karstic provinces,Guizhou Province stands out with the highest ion concentrations,indicative of its extensive karst coverage and heightened weathering processes.
基金The National Key Research and Development Program of China,No.2023YFC3206601。
文摘Landslides pose a formidable natural hazard across the Qinghai-Tibet Plateau(QTP),endangering both ecosystems and human life.Identifying the driving factors behind landslides and accurately assessing susceptibility are key to mitigating disaster risk.This study integrated multi-source historical landslide data with 15 predictive factors and used several machine learning models—Random Forest(RF),Gradient Boosting Regression Trees(GBRT),Extreme Gradient Boosting(XGBoost),and Categorical Boosting(CatBoost)—to generate susceptibility maps.The Shapley additive explanation(SHAP)method was applied to quantify factor importance and explore their nonlinear effects.The results showed that:(1)CatBoost was the best-performing model(CA=0.938,AUC=0.980)in assessing landslide susceptibility,with altitude emerging as the most significant factor,followed by distance to roads and earthquake sites,precipitation,and slope;(2)the SHAP method revealed critical nonlinear thresholds,demonstrating that historical landslides were concentrated at mid-altitudes(1400-4000 m)and decreased markedly above 4000 m,with a parallel reduction in probability beyond 700 m from roads;and(3)landslide-prone areas,comprising 13%of the QTP,were concentrated in the southeastern and northeastern parts of the plateau.By integrating machine learning and SHAP analysis,this study revealed landslide hazard-prone areas and their driving factors,providing insights to support disaster management strategies and sustainable regional planning.
基金supported by the National Natural Science Foundation of China(Grant Nos.32102311 and 32102338)the China Postdoctoral Science Foundation(Grant No.2021M690129).
文摘Drought stress significantly impedes apple growth,development,and yield,leading to substantial economic losses within the global apple industry.Malus prunifolia(Mp),a commonly utilized apple rootstock,has shown promise in augmenting cultivated apple resistance to abiotic stress.Although Alfin-like(ALs)proteins have demonstrated pivotal roles in dicotyledonous plants'response to abiotic stresses,knowledge about AL genes in apple rootstocks is limited,and their functions remain largely elusive.In this study,we identified and characterized 10 MpAL gene members in the apple rootstock genome,confirming their localization within the nucleus.Our investigation revealed the significant regulation of MpALs'expression under drought and abscisic acid(ABA)stresses in M.prunifolia.In this study,one of the members,MpAL1,was selected for further exploration in Arabidopsis and apple to explore its potential function in response to drought and ABA stresses.The results showed that overexpression-MpAL1 transgenic apple calli grew significantly better than WT and MpAL1-RNAi lines,which regulates the accumulation of H_(2)O_(2)and O_(2).-levels.Additionally,transgenic Arabidopsis plants overexpressing MpAL1 exhibited positively regulating antioxidant enzymes activities under stress treatments.Further study showed that silencing MpAL1 in apple plants showed obvious chlorosis in leaves,and accumulation of reactive oxygen species under drought stress.Moreover,our detailed analysis established that MpAL1 regulates several drought and ABA-responsive genes,exerting an influence on their expression in transgenic apple.Collectively,our findings identify MpAL1 as a positive regulator that increases drought stress in apple,shedding light on its potential significance in bolstering drought resistance in this fruit crop.
基金Supported by the National Natural Science Foundation of China,No.82402789Beijing Jishuitan Hospital Youcai Plan,No.KYYC202402+2 种基金Beijing Jishuitan Research Funding,No.HL202402and Beijing Natural Science Foundation,No.L232062No.L222063.
文摘BACKGROUND Aseptic loosening remains the leading cause of revision in primary total hip arthroplasty(pTHA).However,the literature demonstrates significant variability regarding the relative contributions of different factors.AIM To investigate the key determinants of aseptic loosening,we performed a systematic review and meta-analysis.METHODS A comprehensive search of PubMed,Web of Science,EMBASE,and the Cochrane Library was conducted,encompassing studies from database inception to January 1,2025.Meta-analyses were performed to evaluate factors associated with aseptic loosening following pTHA.Inclusion and exclusion criteria were systematically applied at each stage to ensure methodological transparency and reproducibility.Study quality was assessed using standardized categories.Pooled odds ratio(OR)with corresponding 95%confidence interval were calculated with random-or fixed-effects models to generate reliability estimates,and study heterogeneity was visualized using forest plots.Ten factors,categorized into patient-,surgeon-,and device-related domains,were reviewed and meta-analyzed.Funnel plot analysis demonstrated a relatively symmetrical distribution,suggesting minimal publication bias.RESULTS A meta-analysis of 20 studies(520789 participants)found a pooled prevalence of 1.96%.Significant risk factors for aseptic loosening after pTHA included elevated body mass index(OR=1.116,P<0.001),higher Charlson comorbidity index(OR=1.378,P<0.001),prosthesis-related factors(OR=1.497,P<0.001),and adverse lifestyles(OR=2.198,P=0.037).Protective factors were non-white race(OR=0.445,P<0.001)and favorable genetics(OR=0.723,P<0.001).Male sex increased risk(OR=1.232,P=0.016),while age and anatomy were not significant.Surgical expertise showed a slight protective effect(OR=1.048,P<0.001).A comprehensive understanding of the modifiable and non-modifiable factors contributing to aseptic loosening after pTHA requires consideration of patient-related factors,surgical expertise,and prosthesis characteristics.CONCLUSION The identification of these factors is critical for risk mitigation.High-risk patients should receive targeted counseling regarding individualized profiles.Further studies are warranted to establish clearer causal relationships and identify additional contributing factors.
