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
Atherosclerotic cardiovascular disease remains the leading cause of global mortality,with low-density lipoprotein cholesterol established as a primary causal risk factor.Despite widespread implementation of statin the...Atherosclerotic cardiovascular disease remains the leading cause of global mortality,with low-density lipoprotein cholesterol established as a primary causal risk factor.Despite widespread implementation of statin therapy,substantial interindividual variability in treatment response persists,necessitating precision medicine approaches to optimize therapeutic outcomes.This comprehensive narrative review synthesizes current understanding of pharmacogenomic determinants influencing lipid-lowering therapy efficacy,examines mechanisms underlying residual cardiovascular risk,and evaluates emerging therapeutic modalities targeting previously unexploited pathways in lipid metabolism.Genetic variants in key genes including 3-hydroxy-3-methylglutaryl-CoA reductase,apolipoprotein E,low-density lipoprotein receptor,and proprotein convertase subtilisin/kexin type 9 demonstrate significant associations with differential treatment responses,with specific polymorphisms conferring enhanced efficacy or increased intolerance risk.Beyond traditional statin therapy,novel therapeutic approaches targeting proprotein convertase subtilisin/kexin type 9,angiopoietin-like protein 3,apolipoprotein C-Ⅲ,and ATP citrate lyase offer substantial low-density lipoprotein cholesterol reductions of 50-80%,while RNA-based therapies including antisense oligonucleotides and small interfering RNA provide precise molecular targeting capabilities.Despite intensive lipid-lowering interventions,residual cardiovascular risk persists through four principal mechanisms:triglyceride-rich lipoproteins,lipoprotein(a),inflammatory processes,and suboptimal treatment adherence.Integration of pharmacogenomic insights with emerging therapeutic modalities enables personalized risk stratification and treatment selection,representing a paradigm shift toward precision medicine in cardiovascular disease prevention and management.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
This systematic review synthesizes empirical research on external risk factors for adolescent smartphone addiction.Scopus and Web of Science were searched for English peer-reviewed empirical articles from 2008 onward;...This systematic review synthesizes empirical research on external risk factors for adolescent smartphone addiction.Scopus and Web of Science were searched for English peer-reviewed empirical articles from 2008 onward;28 met inclusion criteria(excluding non-adolescents,generic internet addiction,non-empirical work,or non-English).Thematic synthesis organized findings into three external risk domains—family,school,and peers—considering cultural/contextual mechanisms.Family dynamics(parental phubbing,harsh parenting,dysfunction),school stressors,and adverse peer relationships were identified as accumulating,direct and indirect contributors to smartphone addiction.These operate within a techno-ecological framework,where digital technologies amplify vulnerabilities and create new pathways for maladaptive use.Evidence favors an ecological,multi-level perspective.Future research should use longitudinal designs,standardize measures across cultures,and examine understudied regions—especially Africa—to guide culturally sensitive interventions.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
BACKGROUND:Acute pain is a sudden experience secondary to injuries and varies in perception among individuals.In trauma patients,it can negatively aff ect respiratory function,immune response,and wound healing,making ...BACKGROUND:Acute pain is a sudden experience secondary to injuries and varies in perception among individuals.In trauma patients,it can negatively aff ect respiratory function,immune response,and wound healing,making it a signifi cant public health concern.This study is to determine the prevalence and factors associated with acute pain among emergency trauma patients.METHODS:A multicenter cross-sectional study was conducted.Data were collected via interviewer-administered questionnaires and patient chart review.The data were analyzed via the statistical package for social science version 25.Bivariable and multivariable logistic regression analyses were used.Variables with a P-value<0.05 were considered statistically signifi cant.RESULTS:A total of 397 patients were included in the study,for a response rate of 96.8%.The prevalence of pain during admission was 91.9%(95%confi dence intervals[95%CIs]:88.8%-94.4%).Blunt trauma(adjusted odds ratio[aOR]=2.82;95%CI:1.23-6.45),analgesia before admission to the emergency department(aOR=2.71;95%CI:1.16-6.36),documentation of pain severity in the chart(aOR=2.71;95%CI:1.16-6.36),analgesia provided within two hours after admission(aOR=7.60;95%CI:2.79-20.68),use of non-pharmacological pain management methods(aOR=3.09;95%CI:1.35-7.08)and availability of analgesia(aOR=3.95;95%CI:1.36-11.43)were associated with acute pain experience.CONCLUSION:The prevalence of acute pain among emergency trauma patients was high in the study area.Analgesia should be administered prior to admission,and non-pharmacological pain management should be implemented.Moreover,training on pain assessment and management should be provided for healthcare providers in the emergency department.展开更多
The interplay between gut microbiota and host health has attracted significant interest in the animal science community.Maintaining gut microbiota homeostasis by supplementing probiotics to treat clinical conditions l...The interplay between gut microbiota and host health has attracted significant interest in the animal science community.Maintaining gut microbiota homeostasis by supplementing probiotics to treat clinical conditions like calf diarrhea is an emerging area of research nowadays because of increased concerns regarding antimicrobial resistance(AMR)and drug residues in animal products.Probiotics reduce the incidence of calf diarrhea by increasing the gut microbiota diversity and richness with more commensal bacteria such as Lactobacillus and Bifidobacterium that produce antimicrobial compounds,as well as modulating the immune response by increasing cytokines,Interleukin-2(IL-2),IL-4,IL-6,IL-10,and reducing tumor necrosis factor-α(TNF-α),by increasing production of antibodies,especially immunoglobulin E(Ig E),also Ig G,differentiating naive Th lymphocytes(Tho)into Th1,hence stimulate innate immunity and prime the adaptive immune response.Specific probiotic strains of bacteria and yeast(Saccharomyces cerevisiae)derived probiotics maintain the integrity of the intestinal barrier.In this review,data are being organized to address the role of probiotics in treating calf diarrhea by modulating gut microbiota and stimulating an immune response against notorious pathogens,to present animal and veterinary scientists and nutritionists with a new concept to treat infectious diseases from the perspective of the gut microbiota,increasing animal health,performance,and welfare.In conclusion,health status and gut microbiome are strongly interlinked.Research data indicated a significant reduction in the incidence of diarrhea after probiotic administration.If interrelations between probiotics and existing gut microbiota are explored more quantitatively,novel antibiotic substitutes can emerge in the future.展开更多
Reinforced concrete(RC)columns are often subjected to off-central explosion due to the uncertainty of blast locations.However,few studies have focused on the dynamic response of RC columns under offcentral explosions....Reinforced concrete(RC)columns are often subjected to off-central explosion due to the uncertainty of blast locations.However,few studies have focused on the dynamic response of RC columns under offcentral explosions.A field blast experiment was conducted under close-in explosion with varying detonation offset distances(0 m,0.5 m,and 1 m),the overpressure load and dynamic responses of the full-scale RC columns were measured.Compared with the centrally detonated condition,a relative offset distance of 1.67 decreases the maximum and residual deflections of the RC column by 16.8%and 21.4%,respectively,while increasing the maximum and residual support rotations by 24.7%and 17.8%.Based on the experimental results,a theoretical model was proposed that considers the detonation location and charge mass,boundary conditions,axial compression ratio and material properties.The theoretical model exhibited good agreement with the experimental results,with prediction errors below 10%for both maximum and residual deflection.The effects of parameters were analyzed,and it indicated that an increase in offset distance results in decreased maximum and residual deflections but an increased support angle,thereby exacerbating damage.Higher axial load ratio,span-depth ratio,and longitudinal reinforcement ratio reduce both deflections and support angle.Additionally,a rapid method to predict the maximum and residual deflection of RC columns under off-central blast loading was also proposed based on the Generalized Regression Neural Network(GRNN).Eleven features which related to the RC column properties and the blast characteristics were used in the training process of GRNN,and accurate predictions were achieved with prediction errors within 20%.This study fills the gap in predicting the dynamic response of RC columns under off-central explosion,providing valuable references for blast-resistant design.展开更多
With the continuous progress of automatic driving technology,automatic driving technology standards are gradually affecting the determination of criminal responsibility for traffic accidents in China.At present,the ch...With the continuous progress of automatic driving technology,automatic driving technology standards are gradually affecting the determination of criminal responsibility for traffic accidents in China.At present,the characteristics and tendency of China's automatic driving technology standards present the situation of high policy relevance coexisting with low normative binding,professionalism coexist with barriers,forefront coexist with ambiguity.Therefore,challenges are presented both theoretically and practically on the determination of criminal responsibility based on automatic driving technology standard..In this regard,the misunderstanding should be clarified in theory:The legal order under the automatic driving technology standard has constitutionality and systematic,and there is a balance between the frontier of automatic driving technology development and the lagging of criminal law.The automatic driving technology risk level system should be built to clarify the boundary of the effectiveness of criminal law norms,seeking fora breakthrough in the application of the establishment of a comprehensive judgment system of the risks and accidents and the system of evidence to prove the system,which clarifies the determination of criminal responsibility under the automatic driving technology standard.This essay hopes to pursue breakthroughs in the application-to establish a comprehensive judgment system of risks and accidents as well as an evidence proof system,so as to clarify the determination of criminal responsibility under automatic driving technology standards.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
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.
文摘Atherosclerotic cardiovascular disease remains the leading cause of global mortality,with low-density lipoprotein cholesterol established as a primary causal risk factor.Despite widespread implementation of statin therapy,substantial interindividual variability in treatment response persists,necessitating precision medicine approaches to optimize therapeutic outcomes.This comprehensive narrative review synthesizes current understanding of pharmacogenomic determinants influencing lipid-lowering therapy efficacy,examines mechanisms underlying residual cardiovascular risk,and evaluates emerging therapeutic modalities targeting previously unexploited pathways in lipid metabolism.Genetic variants in key genes including 3-hydroxy-3-methylglutaryl-CoA reductase,apolipoprotein E,low-density lipoprotein receptor,and proprotein convertase subtilisin/kexin type 9 demonstrate significant associations with differential treatment responses,with specific polymorphisms conferring enhanced efficacy or increased intolerance risk.Beyond traditional statin therapy,novel therapeutic approaches targeting proprotein convertase subtilisin/kexin type 9,angiopoietin-like protein 3,apolipoprotein C-Ⅲ,and ATP citrate lyase offer substantial low-density lipoprotein cholesterol reductions of 50-80%,while RNA-based therapies including antisense oligonucleotides and small interfering RNA provide precise molecular targeting capabilities.Despite intensive lipid-lowering interventions,residual cardiovascular risk persists through four principal mechanisms:triglyceride-rich lipoproteins,lipoprotein(a),inflammatory processes,and suboptimal treatment adherence.Integration of pharmacogenomic insights with emerging therapeutic modalities enables personalized risk stratification and treatment selection,representing a paradigm shift toward precision medicine in cardiovascular disease prevention and management.
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 the 2025 Fujian Provincial Social Science Foundation Project(FJ2025C074).
文摘This systematic review synthesizes empirical research on external risk factors for adolescent smartphone addiction.Scopus and Web of Science were searched for English peer-reviewed empirical articles from 2008 onward;28 met inclusion criteria(excluding non-adolescents,generic internet addiction,non-empirical work,or non-English).Thematic synthesis organized findings into three external risk domains—family,school,and peers—considering cultural/contextual mechanisms.Family dynamics(parental phubbing,harsh parenting,dysfunction),school stressors,and adverse peer relationships were identified as accumulating,direct and indirect contributors to smartphone addiction.These operate within a techno-ecological framework,where digital technologies amplify vulnerabilities and create new pathways for maladaptive use.Evidence favors an ecological,multi-level perspective.Future research should use longitudinal designs,standardize measures across cultures,and examine understudied regions—especially Africa—to guide culturally sensitive interventions.
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BACKGROUND:Acute pain is a sudden experience secondary to injuries and varies in perception among individuals.In trauma patients,it can negatively aff ect respiratory function,immune response,and wound healing,making it a signifi cant public health concern.This study is to determine the prevalence and factors associated with acute pain among emergency trauma patients.METHODS:A multicenter cross-sectional study was conducted.Data were collected via interviewer-administered questionnaires and patient chart review.The data were analyzed via the statistical package for social science version 25.Bivariable and multivariable logistic regression analyses were used.Variables with a P-value<0.05 were considered statistically signifi cant.RESULTS:A total of 397 patients were included in the study,for a response rate of 96.8%.The prevalence of pain during admission was 91.9%(95%confi dence intervals[95%CIs]:88.8%-94.4%).Blunt trauma(adjusted odds ratio[aOR]=2.82;95%CI:1.23-6.45),analgesia before admission to the emergency department(aOR=2.71;95%CI:1.16-6.36),documentation of pain severity in the chart(aOR=2.71;95%CI:1.16-6.36),analgesia provided within two hours after admission(aOR=7.60;95%CI:2.79-20.68),use of non-pharmacological pain management methods(aOR=3.09;95%CI:1.35-7.08)and availability of analgesia(aOR=3.95;95%CI:1.36-11.43)were associated with acute pain experience.CONCLUSION:The prevalence of acute pain among emergency trauma patients was high in the study area.Analgesia should be administered prior to admission,and non-pharmacological pain management should be implemented.Moreover,training on pain assessment and management should be provided for healthcare providers in the emergency department.
基金financial support from the Postdoctoral Fellowship Program of China Postdoctoral Science Foundation(GZC20230718)。
文摘The interplay between gut microbiota and host health has attracted significant interest in the animal science community.Maintaining gut microbiota homeostasis by supplementing probiotics to treat clinical conditions like calf diarrhea is an emerging area of research nowadays because of increased concerns regarding antimicrobial resistance(AMR)and drug residues in animal products.Probiotics reduce the incidence of calf diarrhea by increasing the gut microbiota diversity and richness with more commensal bacteria such as Lactobacillus and Bifidobacterium that produce antimicrobial compounds,as well as modulating the immune response by increasing cytokines,Interleukin-2(IL-2),IL-4,IL-6,IL-10,and reducing tumor necrosis factor-α(TNF-α),by increasing production of antibodies,especially immunoglobulin E(Ig E),also Ig G,differentiating naive Th lymphocytes(Tho)into Th1,hence stimulate innate immunity and prime the adaptive immune response.Specific probiotic strains of bacteria and yeast(Saccharomyces cerevisiae)derived probiotics maintain the integrity of the intestinal barrier.In this review,data are being organized to address the role of probiotics in treating calf diarrhea by modulating gut microbiota and stimulating an immune response against notorious pathogens,to present animal and veterinary scientists and nutritionists with a new concept to treat infectious diseases from the perspective of the gut microbiota,increasing animal health,performance,and welfare.In conclusion,health status and gut microbiome are strongly interlinked.Research data indicated a significant reduction in the incidence of diarrhea after probiotic administration.If interrelations between probiotics and existing gut microbiota are explored more quantitatively,novel antibiotic substitutes can emerge in the future.
基金financially supported by the National Natural Science Foundation of China(Grants No.12472399)。
文摘Reinforced concrete(RC)columns are often subjected to off-central explosion due to the uncertainty of blast locations.However,few studies have focused on the dynamic response of RC columns under offcentral explosions.A field blast experiment was conducted under close-in explosion with varying detonation offset distances(0 m,0.5 m,and 1 m),the overpressure load and dynamic responses of the full-scale RC columns were measured.Compared with the centrally detonated condition,a relative offset distance of 1.67 decreases the maximum and residual deflections of the RC column by 16.8%and 21.4%,respectively,while increasing the maximum and residual support rotations by 24.7%and 17.8%.Based on the experimental results,a theoretical model was proposed that considers the detonation location and charge mass,boundary conditions,axial compression ratio and material properties.The theoretical model exhibited good agreement with the experimental results,with prediction errors below 10%for both maximum and residual deflection.The effects of parameters were analyzed,and it indicated that an increase in offset distance results in decreased maximum and residual deflections but an increased support angle,thereby exacerbating damage.Higher axial load ratio,span-depth ratio,and longitudinal reinforcement ratio reduce both deflections and support angle.Additionally,a rapid method to predict the maximum and residual deflection of RC columns under off-central blast loading was also proposed based on the Generalized Regression Neural Network(GRNN).Eleven features which related to the RC column properties and the blast characteristics were used in the training process of GRNN,and accurate predictions were achieved with prediction errors within 20%.This study fills the gap in predicting the dynamic response of RC columns under off-central explosion,providing valuable references for blast-resistant design.
基金The National Social Science Foundation Youth Project of China:Research on the collaborative govemance path of administrative law and criminal law against dangerous driving behaviors in the digital-intelligent society(25CFX108)。
文摘With the continuous progress of automatic driving technology,automatic driving technology standards are gradually affecting the determination of criminal responsibility for traffic accidents in China.At present,the characteristics and tendency of China's automatic driving technology standards present the situation of high policy relevance coexisting with low normative binding,professionalism coexist with barriers,forefront coexist with ambiguity.Therefore,challenges are presented both theoretically and practically on the determination of criminal responsibility based on automatic driving technology standard..In this regard,the misunderstanding should be clarified in theory:The legal order under the automatic driving technology standard has constitutionality and systematic,and there is a balance between the frontier of automatic driving technology development and the lagging of criminal law.The automatic driving technology risk level system should be built to clarify the boundary of the effectiveness of criminal law norms,seeking fora breakthrough in the application of the establishment of a comprehensive judgment system of the risks and accidents and the system of evidence to prove the system,which clarifies the determination of criminal responsibility under the automatic driving technology standard.This essay hopes to pursue breakthroughs in the application-to establish a comprehensive judgment system of risks and accidents as well as an evidence proof system,so as to clarify the determination of criminal responsibility under automatic driving technology standards.
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.
