Background:Wenqing Yin(WQY)is a classic prescription used to treat skin diseases like atopic dermatitis(AD)in China,and the aim of this study is to investigate the therapeutic effects and molecular mechanisms of WQY o...Background:Wenqing Yin(WQY)is a classic prescription used to treat skin diseases like atopic dermatitis(AD)in China,and the aim of this study is to investigate the therapeutic effects and molecular mechanisms of WQY on AD.Methods:The DNFB-induced mouse models of AD were established to investigate the therapeutic effects of WQY on AD.The symptoms of AD in the ears and backs of the mice were assessed,while inflammatory factors in the ear were quantified using quantitative real-time-polymerase chain reaction(qRT-PCR),and the percentages of CD4^(+)and CD8^(+)cells in the spleen were analyzed through flow cytometry.The compounds in WQY were identified using ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)analysis and the key targets and pathways of WQY to treat AD were predicted by network pharmacology.Subsequently,the key genes were tested and verified by qRT-PCR,and the potential active components and target proteins were verified by molecular docking.Results:WQY relieved the AD symptoms and histopathological injuries in the ear and back skin of mice with AD.Meanwhile,WQY significantly reduced the levels of inflammatory factors IL-6 and IL-1βin ear tissue,as well as the ratio of CD4^(+)/CD8^(+)cells in spleen.Additionally,a total of 142 compounds were identified from the water extract of WQY by UPLC-Orbitrap-MS/MS.39 key targets related to AD were screened out by network pharmacology methods.The KEGG analysis indicated that the effects of WQY were primarily mediated through pathways associated with Toll-like receptor signaling and T cell receptor signaling.Moreover,the results of qRT-PCR demonstrated that WQY significantly reduced the mRNA expressions of IL-4,IL-10,GATA3 and FOXP3,and molecular docking simulation verified that the active components of WQY had excellent binding abilities with IL-4,IL-10,GATA3 and FOXP3 proteins.Conclusion:The present study demonstrated that WQY effectively relieved AD symptoms in mice,decreased the inflammatory factors levels,regulated the balance of CD4^(+)and CD8^(+)cells,and the mechanism may be associated with the suppression of Th2 and Treg cell immune responses.展开更多
Under solvothermal conditions,1,4‑naphthalenedicarboxylic acid(H_(2)ndc)and 9,9′‑dihexyl‑2,7‑di(pyridin‑4‑yl)fluorene(hfdp)reacted with Co^(2+)ions and Cd^(2+)ions to form two coordination polymers,[Co(hfdp)(ndc)(H2O...Under solvothermal conditions,1,4‑naphthalenedicarboxylic acid(H_(2)ndc)and 9,9′‑dihexyl‑2,7‑di(pyridin‑4‑yl)fluorene(hfdp)reacted with Co^(2+)ions and Cd^(2+)ions to form two coordination polymers,[Co(hfdp)(ndc)(H2O)]·DMA}n(1)and{[Cd(hfdp)(ndc)(H_(2)O)]·DMA}_(n)(2),respectively(DMA=N,N‑dimethylacetamide).Single‑crystal X‑ray diffraction analyses showed that both complexes 1 and 2 contain similar structures.Topological analysis indicates that complexes 1 and 2 have a{44·62}planar structure.In addition,both complexes reveal good thermal stability and fluorescence sensing performance.They exhibited good sensitivity and selectivity towards 2,4,6‑trinitrophenol(TNP)by fluorescent quenching.The limits of detection of 1 and 2 for TNP were 0.107 and 0.327μmol·L^(-1),respectively.CCDC:2475515,1;2475516,2.展开更多
Neurodegenerative diseases are a group of illnesses characterized by the gradual deterioration of the central nervous system,leading to a decline in patients'cognitive,motor,and emotional abilities.Neuroinflammati...Neurodegenerative diseases are a group of illnesses characterized by the gradual deterioration of the central nervous system,leading to a decline in patients'cognitive,motor,and emotional abilities.Neuroinflammation plays a significant role in the progression of these diseases.However,there is limited research on therapeutic approaches to specifically target neuroinflammation.The role of T lymphocytes,which are crucial mediators of the adaptive immune response,in neurodegenerative diseases has been increasingly recognized.This review focuses on the involvement of T lymphocytes in the neuroinflammation associated with neurodegenerative diseases.The pathogenesis of neurodegenerative diseases is complex,involving multiple mechanisms and pathways that contribute to the gradual degeneration of neurons,and T cells are a key component of these processes.One of the primary factors driving neuroinflammation in neurodegenerative diseases is the infiltration of T cells and other neuroimmune cells,including microglia,astrocytes,B cells,and natural killer cells.Different subsets of CD4~+T cells,such as Th1,Th2,Th17,and regulatory T cells,can differentiate into various cell types and perform distinct roles within the neuroinflammatory environment of neurodegenerative diseases.Additionally,CD8~+T cells,which can directly regulate immune responses and kill target cells,also play several important roles in neurodegenerative diseases.Clinical trials investigating targeted T cell therapies for neurodegenerative diseases have shown that,while some patients respond positively,others may not respond as well and may even experience adverse effects.Targeting T cells precisely is challenging due to the complexity of immune responses in the central nervous system,which can lead to undesirable side effects.However,with new insights into the pathophysiology of neurodegenerative diseases,there is hope for the establishment of a solid theoretical foundation upon which innovative treatment strategies that target T cells can be developed in the future.展开更多
Objective To investigate the microbial mechanisms of Banxia Xiexin Decoction(半夏泻心汤,BXXXD)in the treatment of esophageal precancerous lesions.Methods A total of 30 specific pathogen-free(SPF)grade female C57BL/6J ...Objective To investigate the microbial mechanisms of Banxia Xiexin Decoction(半夏泻心汤,BXXXD)in the treatment of esophageal precancerous lesions.Methods A total of 30 specific pathogen-free(SPF)grade female C57BL/6J mice were randomly assigned to a control group(n=6)and a 4-nitroquinoline 1-oxide(4-NQO)-exposed group(n=24).Esophageal precancerous lesions were induced by providing the 4-NQO-exposed group with 4-NQO in drinking water(100μg/mL)for 17 consecutive weeks,whereas control group received sterile drinking water.After model establishment,the mice in 4-NQOexposed group were further randomized into model group and three BXXXD-treated groups:low-dose(BXXXD-L,3.7 g/kg),medium-dose(BXXXD-M,7.4 g/kg),and high-dose(BXXXDH,14.8 g/kg)groups(n=6 per group).During the subsequent intervention period,mice in control and model groups were gavaged with sterile water,while mice in BXXXD groups were gavaged once daily with the corresponding dose of BXXXD aqueous extract for 4 weeks.Histopathological changes in esophageal tissues were observed by hematoxylin and eosin(HE)staining.The fecal and esophageal microbiota were profiled via 16S rDNA high-throughput sequencing to evaluate bacterial diversity,community structure,and co-occurrence networks.BXXXD chemical fingerprints were analyzed using ultra-high-performance liquid chromatography coupled with quadrupole QExactive Orbitrap mass spectrometry(UHPLCQE-MS).Serum short-chain fatty acids(SCFA)level was quantified by targeted metabolomics using gas chromatography-mass spectrometry(GC-MS).Transcriptomic analysis of esophageal tissues was performed to assess gene expression profiles.Results Compared with model group,BXXXD-M group exhibited reduced mucosal hyperplasia and more orderly epithelial cell arrangement,with superior therapeutic effects in comparison with both BXXXD-L and BXXXD-H groups(P<0.01).Microbiota analysis revealed that BXXXD increased the abundance of beneficial Enterococcus and reduced pathogenic Escherichia-Shigella in the esophagus.In the gut,BXXXD elevated the relative abundance of beneficial taxa,including Lactobacillus,Dubosiella,Bacteroides,and Faecalibacterium.Targeted metabolomics showed that BXXXD significantly reduced total serum SCFA level(P<0.01).Transcriptomic analysis indicated that BXXXD downregulated the expression of genes associated with the progression,migration,and invasion of esophageal cancer,which were identified as kallikrein-related peptidase 6(Klk6),defensin beta 4(Defb4),family with sequence similarity 3 member B(Fam3b),carboxypeptidase A4(Cpa4),serum amyloid A1(Saa1),and chitinase-like 1(Chil1)(P<0.05).Conclusion BXXXD may reduce the expression levels of esophageal cancer-related genes and improve esophageal precancerous lesions through modulation of the gut microbiota and metabolites.展开更多
Antibiotics are widespread in aquatic environments due to their extensive use in human healthcare and ani-mal husbandry.However,research on the occurrence and bioaccumulation of antibiotics in aquatic organisms within...Antibiotics are widespread in aquatic environments due to their extensive use in human healthcare and ani-mal husbandry.However,research on the occurrence and bioaccumulation of antibiotics in aquatic organisms within shallow wetland lakes remains limited.This study investigated the occurrence and bioaccumulation of ten commonly used antibiotics in the Baiyang Lake,northern China’s largest shallow wetland lake.The results indicated that sulfonamides and fluoroquinolones were the predominant antibiotics in surface water,whereas fluoroquinolones and macrolides were more prevalent in sediment.Fluoroquinolones demonstrated significant potential for bioaccumulation in targeted aquatic organisms,including both animals and plants(Carassius au-ratus and Phragmites australis).The bioaccumulation of antibiotics in Carassius auratus was correlated with their solubility,whereas in Phragmites australis,this was associated with their octanol-water partition coefficients and molecular weights.Ecological risk assessment indicated that most antibiotics posed minimal to low risk levels.However,four antibiotics were exceptions:clarithromycin(12.5%)and sulfamethoxazole(6.25%)presented a high risk in surface water samples,while norfloxacin(25.0%)and ciprofloxacin(25.0%)posed a high risk in sediment samples.Norfloxacin,ciprofloxacin,and roxithromycin were identified as key indicator antibiotics for enhancing the local monitoring and control of antibiotic contamination based on four criteria:(1)high con-centrations,(2)frequent detection,(3)capacity for bioaccumulation,and(4)ecological risk levels.This study contributes to a deeper understanding of the status of antibiotic contamination,bioaccumulation characteristics,and ecological risk in Baiyang Lake,thereby supporting efforts to monitor and regulate antibiotic pollution.展开更多
Catalpa bungei,a fast-growing timber tree,is threatened by the lepidopteran pest Omphisa plagialis.Previous studies in our laboratory successfully generated transgenic C.bungei lines overexpressing Cry genes(Cry1Ab,Cr...Catalpa bungei,a fast-growing timber tree,is threatened by the lepidopteran pest Omphisa plagialis.Previous studies in our laboratory successfully generated transgenic C.bungei lines overexpressing Cry genes(Cry1Ab,Cry2A,and Cry9-2)that exhibited resistance to O.plagialis,but their potential impact on soil bacterial communities remains unclear.In this study,we analyzed nine transgenic C.bungei lines(three independent lines for each Cry gene)to characterize their rhizosphere bacterial communities using high-throughput sequencing of the 16S ribosomal DNA(rDNA)V4-V5 regions.A total of 628 amplicon sequence variants(ASVs)were shared among all transgenic and wild-type(WT)lines,forming a stable core microbiome dominated by Proteobacteria,Bacteroidota,Acidobacteriota,and Actinobacteriota.Alpha diversity showed no significant differences,while beta diversity revealed minor but distinct compositional shifts.Cry1Ab lines exhibited higher abundances of fast-growing taxa,particularly Proteobacteria and Bacteroidota;Cry2A lines displayed intermediate profiles,whereas Cry9-2 lines were nearly indistinguishable from WT communities.Linear discriminant analysis of the effect size revealed significant enrichment of taxa such as Burkholderiaceae and Ralstonia in the Cry1Ab rhizosphere,in contrast to the higher abundance of Chloroflexi in the WT.Functional predictions indicated consistent metabolic pathways across all treatments,suggesting strong ecological redundancy.This study demonstrates minimal impact on rhizosphere microbial communities in transgenic C.bungei plants.The Cry9-2 construct exhibited superior environmental stability,whereas the Cry1Ab construct caused only slight but ecologically acceptable shifts.These findings support the ecological safety of Bt-transgenic C.bungei and identify Cry9-2 as a particularly favorable candidate for forestry applications.This comparative evaluation of three Cry genes in a tree species provides a framework for future gene-specific biosafety assessments in woody plants.展开更多
RNA binding proteins(RBPs) are a crucial class of proteins that interact with RNA and play a key role in various biological process.Deficiencies or abnormalities of RBPs are closely linked to the occurrence and progre...RNA binding proteins(RBPs) are a crucial class of proteins that interact with RNA and play a key role in various biological process.Deficiencies or abnormalities of RBPs are closely linked to the occurrence and progression of numerous diseases,making RBPs potential therapeutic targets.However,the limited tissue penetration of 254 nm UV irradiation makes it difficult to efficiently crosslink weak and dynamic RNA-protein interactions in mammal tissues.Additionally,RNA degradation in metal catalyzed click reaction further hinders the enrichment of RNA-protein complexes(RPCs).Due to these inherent limitations,globally profiling the RNA binding proteome in mammal organs has long been a challenge.Herein,we proposed a novel method,which utilized a dual crosslinking with formaldehyde and 254 nm UV irradiation,metabolic labeling and metal-free thiol-yne click reaction to enable large-scale enrichment and identification of RBPs in mouse liver,called FTYc_UV.In this method,formaldehyde is first used to crosslink the crude RNA-protein complexes(cRPCs) in situ to address the problem of poor tissue penetration of 254 nm UV irradiation.Furthermore,this method integrates metabolic labeling with a metal-free thiol-yne click reaction to achieve non-destructive RNA tagging.After specifically RNA-RBPs crosslinking by 254 nm UV irradiation in tissue lysates,formaldehyde decrosslinking is employed to remove non-specific proteins,leading to effective enrichment of RPCs from mouse liver and thereby overcoming the poor specificity of formaldehyde crosslinking.Application of FTYc_UV in mouse liver successfully identified over 1600 RBPs covering approximately 75 % of previously reported RBPs.Furthermore,420 candidate RBPs,including 151metabolic enzymes,were also obtained,demonstrating the sensitivity of FTYc_UV and the potential of this method for in-depth exploration of RNA-protein interactions in biological and clinical research.展开更多
Objective Patients with atherosclerotic cardiovascular disease(ASCVD)following percutaneous coronary intervention(PCI)are classified as very-high-risk individuals in cardiovascular disease(CVD)risk stratification.The ...Objective Patients with atherosclerotic cardiovascular disease(ASCVD)following percutaneous coronary intervention(PCI)are classified as very-high-risk individuals in cardiovascular disease(CVD)risk stratification.The distribution pattern of traditional Chinese medicine(TCM)syndromes in this patient population,as well as its association with blood lipid profiles and clinical prognosis,remains unclear.The present prospective cohort study aims to investigate these correlations,thereby providing insights to enrich the research fields.Methods We enrolled consecutive patients with ASCVD who underwent PCI at the Integrated Cardiology Unit of China-Japan Friendship Hospital between September 1,2020 and December 31,2022.Demographics and clinical characteristics,signs and symptoms defining each TCM syndrome,and fasting venous blood samples were collected at baseline and follow up or upon major adverse cardiovascular events(MACEs).We analyzed the correlation between TCM syndromes,blood lipid profiles,and MACEs,and developed a new joint prognostic model incorporating both TCM syndromes and blood lipids using logistic regression.The analyses were based on detailed baseline and one-year follow-up data.Results A per-protocol analysis was performed on 586 patients with complete data ultimately.During the one-year follow-up,174 patients(29.69%)experienced a MACE.We performed statistical analyses on comorbidities,medication,and biochemical indicators across groups defined by TCM syndrome differentiation.When comparing different TCM syndromes,no significant differences were found in age,body mass index(BMI),history of revascularization,comorbidities,family history of CVD,smoking or drinking,or statin intensity(P>0.05).Patients with intertwined phlegm and blood stasis syndrome exhibited significantly higher levels of total cholesterol(TC,5.27±1.18 mmol/L,P<0.001),triglyceride(TG,1.96±1.33 mmol/L,P=0.008),low-density lipoprotein cholesterol(LDL-C,3.35±0.79 mmol/L,P<0.001),and high-density lipoprotein cholesterol(HDL-C,1.24±0.81 mmol/L,P<0.001)compared with those with other TCM syndromes combined.A multivariable logistic regression model was constructed to predict MACEs.The model included TCM syndrome type[with intertwined phlegm and blood stasis as a predictor,adjusted odds ratio(OR)=1.413,95%confidence interval(CI):0.517–3.864,P=0.501],age(adjusted OR=0.97,95%CI:0.955–1.001,P=0.057),male gender(adjusted OR=0.698,95%CI:0.416–1.170,P=0.173),TC(adjusted OR=1.004,95%CI:0.513–1.965,P=0.990),and LDL-C(adjusted OR=5.825,95%CI:2.214–15.326,P<0.001).This model demonstrated good discriminatory ability for MACEs in post-PCI ASCVD patients[the area under the receiver operating characteristic(ROC)curve(AUC)=0.865,95%CI:0.816–0.914].Conclusion The intertwined phlegm and blood stasis TCM syndrome is associated with a distinct atherogenic lipid profile characterized by elevated levels of TC and LDL-C.The prognostic model that incorporates this TCM syndrome type along with conventional lipid parameters(TC and LDL-C)shows good discriminatory ability for predicting MACEs in ASCVD patients after PCI,underscoring the potential clinical utility of integrating TCM syndrome differentiation into CVD risk assessment.展开更多
Ischemic stroke remains a leading cause of disability and death,with mesenchymal stem cell-derived exosomes emerging as a promising therapeutic avenue.However,the optimal timing and underlying therapeutic mechanisms o...Ischemic stroke remains a leading cause of disability and death,with mesenchymal stem cell-derived exosomes emerging as a promising therapeutic avenue.However,the optimal timing and underlying therapeutic mechanisms of exosome treatment require further elucidation.In this study,we used a murine model of middle cerebral artery occlusion to investigate the therapeutic efficacy of human umbilical cord mesenchymal stem cell-derived exosomes administered intravenously at an early(6 hours)or delayed(3 days)time point post-ischemia.Compared with delayed treatment,early administration of exosomes resulted in significantly superior efficacy,as evidenced by improved neurological function scores and reduced infarct volumes.Transcriptomic analysis of brain tissues from mice receiving early exosome treatment revealed marked downregulation of inflammation-related genes,including Ccl2,Ccl5,Cxcl10,Il-1β,Il-6,Itgam,Itgax,and Tnf-α.Metabolomic profiling of these brain tissues further identified modulation of key metabolites,including trimethylamine N-oxide,glutathione,1-stearoyl-rac-glycerol,and phosphatidylcholine,suggesting that alteration of metabolic pathways contributes to the therapeutic effect.Integrated transcriptomic and metabolomic analysis pinpointed significant modulation of pathways involving metabolism of eicosapentaenoic acid,lysine,propanoate,and tyrosine.These findings suggest that umbilical cord mesenchymal stem cell-derived exosomes,particularly when administered early post-ischemia,exert their neuroprotective effects by broadly suppressing inflammatory pathways and modulating key metabolic processes in the ischemic brain,highlighting their potential as a therapeutic intervention for ischemic stroke.展开更多
OBJECTIVE:To examine the differences in cognitive processing between patients with mild cognitive impairment(MCI)of different Traditional Chinese Medicine(TCM)syndrome types to provide evidence supporting the TCM typi...OBJECTIVE:To examine the differences in cognitive processing between patients with mild cognitive impairment(MCI)of different Traditional Chinese Medicine(TCM)syndrome types to provide evidence supporting the TCM typing of MCI.METHODS:Participants were screened using a battery of scales for spleen and kidney deficiency(SKD)/liver Qi stagnation(LQS)-type MCI or those without syndrome or normal control(NC).Following sex,age,and educational matching,behavioral and electroencephalographic data were recorded using the verbal N-back experimental paradigm.The data were then analyzed and compared with respect to the reaction time and correctness of the participants in each group,as well as the amplitude and latency of the event-related potential(ERP)components of P2,N2,and P3.RESULTS:There were no statistically significant differences in the accuracy or reaction times of the behavioral data of the groups.Regarding ERP data,the SKD group had a shorter P2 latency than the LQS and NC groups,while the latter two groups did not differ statistically.The SKD group had a shorter N2 latency than the NC group,while the SKD group did not differ from the LQS group.The SKD and LQS groups had a shorter P3 latency than the NC group.CONCLUSION:Our study offers objective evidence of the distinction between the types of TCM syndrome.Different types of TCM syndromes produce different disease mechanisms,resulting in brain damage with different presentations of cognitive impairment and cognitive processing characteristics.展开更多
The major aim of stroke therapy is to stimulate brain repair and improve behavioral recovery after cerebral ischemia.One option is to stimulate endogenous neurogenesis in the subventricular zone and direct the newly f...The major aim of stroke therapy is to stimulate brain repair and improve behavioral recovery after cerebral ischemia.One option is to stimulate endogenous neurogenesis in the subventricular zone and direct the newly formed neurons to the damaged area.However,only a small percentage of these neurons survive,and many do not reach the damaged area,possibly because the corpus callosum impedes the migration of subventricular zone-derived stem cells into the lesioned cortex.A second major obstacle to stem cell therapy is the strong inflammatory reaction induced by cerebral ischemia,whereby the associated phagocytic activity of brain macrophages removes both therapeutic cells and/or cell-based drug carriers.To address these issues,neurogenesis was electrically stimulated in the subventricular zone,followed by isolation of proliferating cells,including newly formed neurons,which were subsequently mixed with a nutritional hydrogel.This mixture was then transferred to the stroke cavity of day 14 post-stroke mice.We found that the performance of the treated animals improved in behavioral tests,including novel object,open field,hole board,grooming,and“time-to-feel”adhesive tape tests.Furthermore,immunostaining revealed that the stem cell marker nestin,the neuroepithelial marker Mash1,and the immature neuronal marker doublecortin-positive cells survived in the transplanted area for 2 weeks,possibly due to reduced phagocytic activity and supportive angiogenesis.These results clearly indicate that the transplantation of committed subventricular zone stem cells combined with a protective nutritional gel directly into the infarct cavity after the peak of stroke-induced neuroinflammation represents a feasible approach to improve neurorestoration after cerebral ischemia.展开更多
Background:In recent decades,the global incidence of dengue fever has been stead-ily increasing,with continuous geographical expansion.Researchers have successfully modeled most clinical symptoms of human dengue fever...Background:In recent decades,the global incidence of dengue fever has been stead-ily increasing,with continuous geographical expansion.Researchers have successfully modeled most clinical symptoms of human dengue fever using interferon type I(IFN-I)or combined IFN-I/II receptor knockout mice infected with dengue virus(DENV).However,this model requires further optimization to better support related studies.Methods:This study aimed to establish a stable dengue infection model by evaluating the effects of different genetic backgrounds and injection routes on DENV infection in interferon receptor knockout mice.We first infected various strains of interferon receptor-deficient mice with DENV and compared their susceptibility based on clini-cal symptoms,viremia levels,organ indices,histopathological findings,and vascular leakage markers.Subsequently,we selected the most susceptible strain to further investigate the impact of different injection methods on infection outcomes.Results:We found that BALB/c background mice with type 1 interferon recep-tor knockout(IFNAR)had the most obvious symptoms.Subsequently,we selected IFNAR−/−BALB/c mice to further explore the effects of different injection methods on dengue virus infection.The results showed that the intraperitoneal injection group had the most severe clinical symptoms,the longest duration of viremia,and the most obvious degree of organ damage.Conclusion:Through systematic screening and optimization,we established a robust animal model of dengue virus infection via intraperitoneal injection in IFNAR−/−BALB/c mice.This model offers a valuable tool for future dengue research.展开更多
OBJECTIVE:To study the anaphylaxis of Qingkailing injection(QI) and its components.METHODS:Experimental anaphylactoid and allergic reactions were used.Changes in the behaviors of Beagles and serum levels of histamine,...OBJECTIVE:To study the anaphylaxis of Qingkailing injection(QI) and its components.METHODS:Experimental anaphylactoid and allergic reactions were used.Changes in the behaviors of Beagles and serum levels of histamine,immunoglobulin(Ig)E,IgG,IgM,eosinophil cationic protein(ECP),and interleukin(IL)-4,as well as blood pressure,after injecting QI and its components on the forelimb veins of Beagles were observed.RESULTS:According to comprehensive determination of abnormal behavior scores and changes in serum levels of histamine,IgE,IgG,IgM,ECP,and IL-4,as well as in blood pressure,radix isatidis and hyodeoxycholic acid caused anaphylactoid reactions,and honeysuckle,radix isatidis,hydrolysate,cholic acid and Gardenia jasminoides caused allergic reactions.The anaphylaxis of QI involved anaphylactoid and allergic reactions.CONCLUSION:QI and its components need to be refined further to improve the safety,efficacy,and quality of its use in clinical settings.展开更多
Thermochemical sulfate reduction(TSR)is an important organic-inorganic reaction that occurs within sedimentary basins and alters the original chemical compositions and isotopic structures of hydrocarbons in natural ga...Thermochemical sulfate reduction(TSR)is an important organic-inorganic reaction that occurs within sedimentary basins and alters the original chemical compositions and isotopic structures of hydrocarbons in natural gases.We used the GC-Py-GC-IRMS method to study TSR and obtained a novel finding related to intramolecular carbon isotope fractionation in natural propane.The results show that theΔC-T(δ^(13)C_(central)-13 C_(terminal))andδ^(13)C_(central)values significantly increased to 44.7‰and 11.9‰,respectively,with increasing TSR alteration.In contrast,the 13 C_(terminal)values of propane remained largely unaltered by the TSR reaction.This difference in position-specific isotope fractionation can be attributed to the central carbon’s reactivity being higher than that of terminal carbon during TSR.In sum,the results indicate that theδ^(13)C_(terminal)values of propane can serve as robust indicators for source rock identification of natural gas altered by post-generation reactions such as TSR and anaerobic microbial oxidation.展开更多
Objective:To determine the potential molecular mechanisms underlying the therapeutic effect of curcumin on hepatocellular carcinoma(HCC)by network pharmacology and experimental in vitro validation.Methods:The predicti...Objective:To determine the potential molecular mechanisms underlying the therapeutic effect of curcumin on hepatocellular carcinoma(HCC)by network pharmacology and experimental in vitro validation.Methods:The predictive targets of curcumin or HCC were collected from several databases.the identified overlapping targets were crossed with Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses using the Database for Annotation,Visualization,and Integrated Discovery(DAVID)platform.Two of the candidate pathways were selected to conduct an experimental verification.The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium(MTT)assay was used to determine the effect of curcumin on the viability of Hep G2 and LO2 cells.The apoptosis and autophagy of Hep G2 cells were respectively detected by flow cytometry and transmission electron microscopy.Besides,western blot and real-time polymerase chain reaction(PCR)were employed to verify the p53 apoptotic pathway and adenosine 5’-monophosphate(AMP)-activated protein kinase(AMPK)autophagy pathway.Hep G2 cells were pretreated with pifithrin-α(PFT-α)and GSK690693 for further investigation.Results:The 167 pathways analyzed by KEGG included apoptosis,autophagy,p53,and AMPK pathways.The GO enrichment analysis demonstrated that curcumin was involved in cellular response to drug,regulation of apoptotic pathway,and so on.The in vitro experiments also confirmed that curcumin can inhibit the growth of Hep G2 cells by promoting the apoptosis of p53 pathway and autophagy through the AMPK pathway.Furthermore,the protein and messenger RNA(m RNA)of the two pathways were downregulated in the inhibitor-pretreated group compared with the experimental group.The damage-regulated autophagy modulator(DRAM)in the PFT-α-pretreated group was downregulated,and p62 in the GSK690693-pretreated group was upregulated.Conclusions:Curcumin can treat HCC through the p53 apoptotic pathway and the AMPK/Unc-51-like kinase 1(ULK1)autophagy pathway,in which the mutual transformation of autophagy and apoptosis may occur through DRAM and p62.展开更多
BACKGROUND Acute pancreatitis(AP)is a pancreatic inflammatory disorder that is commonly complicated by extrapancreatic organ dysfunction.Dachengqi decoction(DCQD)has a potential role in protecting the extrapancreatic ...BACKGROUND Acute pancreatitis(AP)is a pancreatic inflammatory disorder that is commonly complicated by extrapancreatic organ dysfunction.Dachengqi decoction(DCQD)has a potential role in protecting the extrapancreatic organs,but the optimal oral administration time remains unclear.AIM To screen the appropriate oral administration time of DCQD for the protection of extrapancreatic organs based on the pharmacokinetics and pharmacodynamics of AP rats.METHODS This study consisted of two parts.In the first part,24 rats were divided into a sham-operated group and three model groups.The four groups were intragastrically administered with DCQD(10 g/kg)at 4 h,4 h,12 h,and 24 h postoperatively,respectively.Tail vein blood was taken at nine time points after administration,and then the rats were euthanized and the extrapancreatic organ tissues were immediately collected.Finally,the concentrations of the major DCQD components in all samples were detected.In the second part,84 rats were divided into a sham-operated group,as well as 4 h,12 h,and 24 h treatment groups and corresponding control groups(4 h,12 h,and 24 h control groups).Rats in the treatment groups were intragastrically administered with DCQD(10 g/kg)at 4 h,12 h,and 24 h postoperatively,respectively,and rats in the control groups were administered with normal saline at the same time points.Then,six rats from each group were euthanized at 4 h and 24 h after administration.Serum amylase and inflammatory mediators,and pathological scores of extrapancreatic organ tissues were evaluated.RESULTS For part one,the pharmacokinetic parameters(C max,T max,T 1/2,and AUC 0→t)of the major DCQD components and the tissue distribution of most DCQD components were better when administering DCQD at the later(12 h and 24 h)time points.For part two,delayed administration of DCQD resulted in lower IL-6 and amylase levels and relatively higher IL-10 levels,and pathological injury of extrapancreatic organ tissues was slightly less at 4 h after administration,while the results were similar between the treatment and corresponding control groups at 24 h after administration.CONCLUSION Delayed administration of DCQD might reduce pancreatic exocrine secretions and ameliorate pathological injury in the extrapancreatic organs of AP rats,demonstrating that the late time is the optimal dosing time.展开更多
Copper ions are essential for cellular function but can induce cytotoxic effects when dysregulated.This review explores the multifaceted role of copper in cancer metabolism with a focus on the novel concept of cupropt...Copper ions are essential for cellular function but can induce cytotoxic effects when dysregulated.This review explores the multifaceted role of copper in cancer metabolism with a focus on the novel concept of cuproptosis,a regulated form of cell death triggered by copper accumulation.The mechanisms underlying copper homeostasis are detailed,including dietary absorption,systemic distribution,and intracellular utilization.Key transporters,such as copper transporter 1(CTR1)and ATPase copper transporting alpha/b(ATP7A/B),are highlighted.Cancer cells often exhibit elevated copper levels,supporting proliferation and metastasis through pro-tumorigenic pathways.Recent studies have shown that disrupting copper homeostasis can induce cuproptosis,which is characterized by the aggregation of lipoylated mitochondrial proteins and disruption of iron-sulfur cluster biogenesis.Advances in copper-based nanotechnology have enabled targeted delivery of copper to tumors,enhancing therapeutic efficacy through synergistic effects with reactive oxygen species(ROS)generation and immunomodulation.However,the hypoxic tumor microenvironment poses significant challenges by upregulating copper-sequestering proteins and downregulating key cuproptosis mediators.Future directions include integrating multi-omics approaches to identify novel therapeutic targets and developing combination therapies to overcome hypoxia-induced resistance.This review provides a comprehensive overview of copper metabolism in cancer,emphasizing the potential of cuproptosis induction as a powerful strategy for oncologic intervention.展开更多
AIM:To investigate whether butyrate or glutamine enemas could diminish inflammation in experimental diversion colitis.METHODS:Wistar specific pathogen-free rats were submitted to a Hartmann's end colostomy and tre...AIM:To investigate whether butyrate or glutamine enemas could diminish inflammation in experimental diversion colitis.METHODS:Wistar specific pathogen-free rats were submitted to a Hartmann's end colostomy and treated with enemas containing glutamine,butyrate,or saline.Enemas were administered twice a week in the excluded segment of the colon from 4 to 12 wk after the surgical procedure.Follow-up colonoscopy was performed every 4 wk for 12 wk.The effect of treatment was evaluated using video-endoscopic and histologic scores and measuring interleukin-1β,tumor necrosis factor-alpha,and transforming growth factor beta production in organ cultures by enzyme linked immunosorbent assay.RESULTS:Colonoscopies of the diverted segment showed mucosa with hyperemia,increased number of vessels,bleeding and mucus discharge.Treatment with either glutamine or butyrate induced significant reductions in both colonoscopic(P < 0.02) and histological scores(P < 0.01) and restored the densities of collagen fibers in tissue(P = 0.015;P = 0.001),the number of goblet cells(P = 0.021;P = 0.029),and the rate of apoptosis within the epithelium(P = 0.043;P = 0.011) to normal values.The high levels of cytokines in colon explants from rats with diversion colitis significantly decreased to normal values after treatment with butyrate or glutamine.CONCLUSION:The improvement of experimental diversion colitis following glutamine or butyrate enemas highlights the importance of specific luminal nutrients in the homeostasis of the colonic mucosa and supports their utilization for the treatment of human diversion colitis.展开更多
The acceleration of LMXB 4U 1820-30 derived from its orbital-period derivative P_(b)was supposed to be the evidence for an Intermediate-mass black hole(IMBH)in the Galactic globular cluster(GC)NGC 6624.However,we find...The acceleration of LMXB 4U 1820-30 derived from its orbital-period derivative P_(b)was supposed to be the evidence for an Intermediate-mass black hole(IMBH)in the Galactic globular cluster(GC)NGC 6624.However,we find that the anomalous P_(b)is mainly due to the gravitational wave emission,rather than the acceleration in cluster potential.Using the standard structure models of GCs,we simulate acceleration distributions for pulsars in the central region of the cluster.By fitting the acceleration of J1823-3021 A with the simulated distribution profiles(maximum values),it is suggested that an IMBH with mass M■950_(-350)^(+550)M_(⊙) may reside in the cluster center.We further show that the second period derivative P of J1823-3021 A is probably due to the gravitational perturbation of a nearby star.展开更多
In view of the key role of undergraduate experimental teaching reform in cultivating high-quality talents with both innovative spirit and practical ability,this paper deeply discusses multi-dimensional reform strategi...In view of the key role of undergraduate experimental teaching reform in cultivating high-quality talents with both innovative spirit and practical ability,this paper deeply discusses multi-dimensional reform strategies.Specifically,the teaching mode of"double teachers for every student"is innovatively introduced,and scientific research projects are deeply integrated into undergraduate experimental teaching,aiming at realizing the modern development of teaching content and the diversified expansion of teaching methods.By designing and applying the undergraduate experimental teaching platform for intelligent limb rehabilitation training based on the concept of"medical-engineering interdisciplinary crossing",it not only builds a bridge for students to contact cutting-edge scientific research and strengthen practical skills,but also provides valuable ideas and practical models for the innovation of undergraduate experimental teaching.In the future,with the continuous optimization and upgrading of platform functions,it is expected to provide students with a richer and richer learning experience and comprehensively promote students'overall quality.展开更多
基金supported by grants from the National Natural Science Foundation of China(82004252)the Project of Administration of Traditional Chinese Medicine of Guangdong Province(202405112017596500)the Basic and Applied Basic Research Foundation of Guangzhou Municipal Science and Technology Bureau(202102020533).
文摘Background:Wenqing Yin(WQY)is a classic prescription used to treat skin diseases like atopic dermatitis(AD)in China,and the aim of this study is to investigate the therapeutic effects and molecular mechanisms of WQY on AD.Methods:The DNFB-induced mouse models of AD were established to investigate the therapeutic effects of WQY on AD.The symptoms of AD in the ears and backs of the mice were assessed,while inflammatory factors in the ear were quantified using quantitative real-time-polymerase chain reaction(qRT-PCR),and the percentages of CD4^(+)and CD8^(+)cells in the spleen were analyzed through flow cytometry.The compounds in WQY were identified using ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)analysis and the key targets and pathways of WQY to treat AD were predicted by network pharmacology.Subsequently,the key genes were tested and verified by qRT-PCR,and the potential active components and target proteins were verified by molecular docking.Results:WQY relieved the AD symptoms and histopathological injuries in the ear and back skin of mice with AD.Meanwhile,WQY significantly reduced the levels of inflammatory factors IL-6 and IL-1βin ear tissue,as well as the ratio of CD4^(+)/CD8^(+)cells in spleen.Additionally,a total of 142 compounds were identified from the water extract of WQY by UPLC-Orbitrap-MS/MS.39 key targets related to AD were screened out by network pharmacology methods.The KEGG analysis indicated that the effects of WQY were primarily mediated through pathways associated with Toll-like receptor signaling and T cell receptor signaling.Moreover,the results of qRT-PCR demonstrated that WQY significantly reduced the mRNA expressions of IL-4,IL-10,GATA3 and FOXP3,and molecular docking simulation verified that the active components of WQY had excellent binding abilities with IL-4,IL-10,GATA3 and FOXP3 proteins.Conclusion:The present study demonstrated that WQY effectively relieved AD symptoms in mice,decreased the inflammatory factors levels,regulated the balance of CD4^(+)and CD8^(+)cells,and the mechanism may be associated with the suppression of Th2 and Treg cell immune responses.
文摘Under solvothermal conditions,1,4‑naphthalenedicarboxylic acid(H_(2)ndc)and 9,9′‑dihexyl‑2,7‑di(pyridin‑4‑yl)fluorene(hfdp)reacted with Co^(2+)ions and Cd^(2+)ions to form two coordination polymers,[Co(hfdp)(ndc)(H2O)]·DMA}n(1)and{[Cd(hfdp)(ndc)(H_(2)O)]·DMA}_(n)(2),respectively(DMA=N,N‑dimethylacetamide).Single‑crystal X‑ray diffraction analyses showed that both complexes 1 and 2 contain similar structures.Topological analysis indicates that complexes 1 and 2 have a{44·62}planar structure.In addition,both complexes reveal good thermal stability and fluorescence sensing performance.They exhibited good sensitivity and selectivity towards 2,4,6‑trinitrophenol(TNP)by fluorescent quenching.The limits of detection of 1 and 2 for TNP were 0.107 and 0.327μmol·L^(-1),respectively.CCDC:2475515,1;2475516,2.
基金supported by Yunnan Provincial Science and Technology Department,Nos.202403AC100007(to NZ),202301AY070001-239(to JY)Yunnan Revitalization Talent Support Program,Nos.2019-069(to ZY)and 2019-300(to JY)+1 种基金the National Natural Science Foundation of China,Nos.32260196(to JY)a grant from Kunming Medical University,No.2024S085(to KL)。
文摘Neurodegenerative diseases are a group of illnesses characterized by the gradual deterioration of the central nervous system,leading to a decline in patients'cognitive,motor,and emotional abilities.Neuroinflammation plays a significant role in the progression of these diseases.However,there is limited research on therapeutic approaches to specifically target neuroinflammation.The role of T lymphocytes,which are crucial mediators of the adaptive immune response,in neurodegenerative diseases has been increasingly recognized.This review focuses on the involvement of T lymphocytes in the neuroinflammation associated with neurodegenerative diseases.The pathogenesis of neurodegenerative diseases is complex,involving multiple mechanisms and pathways that contribute to the gradual degeneration of neurons,and T cells are a key component of these processes.One of the primary factors driving neuroinflammation in neurodegenerative diseases is the infiltration of T cells and other neuroimmune cells,including microglia,astrocytes,B cells,and natural killer cells.Different subsets of CD4~+T cells,such as Th1,Th2,Th17,and regulatory T cells,can differentiate into various cell types and perform distinct roles within the neuroinflammatory environment of neurodegenerative diseases.Additionally,CD8~+T cells,which can directly regulate immune responses and kill target cells,also play several important roles in neurodegenerative diseases.Clinical trials investigating targeted T cell therapies for neurodegenerative diseases have shown that,while some patients respond positively,others may not respond as well and may even experience adverse effects.Targeting T cells precisely is challenging due to the complexity of immune responses in the central nervous system,which can lead to undesirable side effects.However,with new insights into the pathophysiology of neurodegenerative diseases,there is hope for the establishment of a solid theoretical foundation upon which innovative treatment strategies that target T cells can be developed in the future.
基金National Natural Science Foundation of China(82274369).
文摘Objective To investigate the microbial mechanisms of Banxia Xiexin Decoction(半夏泻心汤,BXXXD)in the treatment of esophageal precancerous lesions.Methods A total of 30 specific pathogen-free(SPF)grade female C57BL/6J mice were randomly assigned to a control group(n=6)and a 4-nitroquinoline 1-oxide(4-NQO)-exposed group(n=24).Esophageal precancerous lesions were induced by providing the 4-NQO-exposed group with 4-NQO in drinking water(100μg/mL)for 17 consecutive weeks,whereas control group received sterile drinking water.After model establishment,the mice in 4-NQOexposed group were further randomized into model group and three BXXXD-treated groups:low-dose(BXXXD-L,3.7 g/kg),medium-dose(BXXXD-M,7.4 g/kg),and high-dose(BXXXDH,14.8 g/kg)groups(n=6 per group).During the subsequent intervention period,mice in control and model groups were gavaged with sterile water,while mice in BXXXD groups were gavaged once daily with the corresponding dose of BXXXD aqueous extract for 4 weeks.Histopathological changes in esophageal tissues were observed by hematoxylin and eosin(HE)staining.The fecal and esophageal microbiota were profiled via 16S rDNA high-throughput sequencing to evaluate bacterial diversity,community structure,and co-occurrence networks.BXXXD chemical fingerprints were analyzed using ultra-high-performance liquid chromatography coupled with quadrupole QExactive Orbitrap mass spectrometry(UHPLCQE-MS).Serum short-chain fatty acids(SCFA)level was quantified by targeted metabolomics using gas chromatography-mass spectrometry(GC-MS).Transcriptomic analysis of esophageal tissues was performed to assess gene expression profiles.Results Compared with model group,BXXXD-M group exhibited reduced mucosal hyperplasia and more orderly epithelial cell arrangement,with superior therapeutic effects in comparison with both BXXXD-L and BXXXD-H groups(P<0.01).Microbiota analysis revealed that BXXXD increased the abundance of beneficial Enterococcus and reduced pathogenic Escherichia-Shigella in the esophagus.In the gut,BXXXD elevated the relative abundance of beneficial taxa,including Lactobacillus,Dubosiella,Bacteroides,and Faecalibacterium.Targeted metabolomics showed that BXXXD significantly reduced total serum SCFA level(P<0.01).Transcriptomic analysis indicated that BXXXD downregulated the expression of genes associated with the progression,migration,and invasion of esophageal cancer,which were identified as kallikrein-related peptidase 6(Klk6),defensin beta 4(Defb4),family with sequence similarity 3 member B(Fam3b),carboxypeptidase A4(Cpa4),serum amyloid A1(Saa1),and chitinase-like 1(Chil1)(P<0.05).Conclusion BXXXD may reduce the expression levels of esophageal cancer-related genes and improve esophageal precancerous lesions through modulation of the gut microbiota and metabolites.
基金supported by Hebei Natural Science Foundation(No.JZX2023018)Hebei Natural Science Foundation(No.C2022201042)the 100 Foreign Experts Plans of Hebei Province(No.606080123001).
文摘Antibiotics are widespread in aquatic environments due to their extensive use in human healthcare and ani-mal husbandry.However,research on the occurrence and bioaccumulation of antibiotics in aquatic organisms within shallow wetland lakes remains limited.This study investigated the occurrence and bioaccumulation of ten commonly used antibiotics in the Baiyang Lake,northern China’s largest shallow wetland lake.The results indicated that sulfonamides and fluoroquinolones were the predominant antibiotics in surface water,whereas fluoroquinolones and macrolides were more prevalent in sediment.Fluoroquinolones demonstrated significant potential for bioaccumulation in targeted aquatic organisms,including both animals and plants(Carassius au-ratus and Phragmites australis).The bioaccumulation of antibiotics in Carassius auratus was correlated with their solubility,whereas in Phragmites australis,this was associated with their octanol-water partition coefficients and molecular weights.Ecological risk assessment indicated that most antibiotics posed minimal to low risk levels.However,four antibiotics were exceptions:clarithromycin(12.5%)and sulfamethoxazole(6.25%)presented a high risk in surface water samples,while norfloxacin(25.0%)and ciprofloxacin(25.0%)posed a high risk in sediment samples.Norfloxacin,ciprofloxacin,and roxithromycin were identified as key indicator antibiotics for enhancing the local monitoring and control of antibiotic contamination based on four criteria:(1)high con-centrations,(2)frequent detection,(3)capacity for bioaccumulation,and(4)ecological risk levels.This study contributes to a deeper understanding of the status of antibiotic contamination,bioaccumulation characteristics,and ecological risk in Baiyang Lake,thereby supporting efforts to monitor and regulate antibiotic pollution.
基金funded by the Chinese Academy of Forestry-Special funds for basic scientific research service expenses of the central level public welfare research institutes(Grant No.CAFYBB2020QD001)the National Natural Science Foundation of China(Grant Nos.32101550,32271917)+1 种基金Jiangsu Agricultural Science and Technology Innovation Fund(Grant No.CX(24)3052)National Forestry and Grassland Administration’s Center for Science and Technology Development Projects(Grant No.KJZXSA202202).
文摘Catalpa bungei,a fast-growing timber tree,is threatened by the lepidopteran pest Omphisa plagialis.Previous studies in our laboratory successfully generated transgenic C.bungei lines overexpressing Cry genes(Cry1Ab,Cry2A,and Cry9-2)that exhibited resistance to O.plagialis,but their potential impact on soil bacterial communities remains unclear.In this study,we analyzed nine transgenic C.bungei lines(three independent lines for each Cry gene)to characterize their rhizosphere bacterial communities using high-throughput sequencing of the 16S ribosomal DNA(rDNA)V4-V5 regions.A total of 628 amplicon sequence variants(ASVs)were shared among all transgenic and wild-type(WT)lines,forming a stable core microbiome dominated by Proteobacteria,Bacteroidota,Acidobacteriota,and Actinobacteriota.Alpha diversity showed no significant differences,while beta diversity revealed minor but distinct compositional shifts.Cry1Ab lines exhibited higher abundances of fast-growing taxa,particularly Proteobacteria and Bacteroidota;Cry2A lines displayed intermediate profiles,whereas Cry9-2 lines were nearly indistinguishable from WT communities.Linear discriminant analysis of the effect size revealed significant enrichment of taxa such as Burkholderiaceae and Ralstonia in the Cry1Ab rhizosphere,in contrast to the higher abundance of Chloroflexi in the WT.Functional predictions indicated consistent metabolic pathways across all treatments,suggesting strong ecological redundancy.This study demonstrates minimal impact on rhizosphere microbial communities in transgenic C.bungei plants.The Cry9-2 construct exhibited superior environmental stability,whereas the Cry1Ab construct caused only slight but ecologically acceptable shifts.These findings support the ecological safety of Bt-transgenic C.bungei and identify Cry9-2 as a particularly favorable candidate for forestry applications.This comparative evaluation of three Cry genes in a tree species provides a framework for future gene-specific biosafety assessments in woody plants.
基金financial support from the National Key R&D Program of China (No.2021YFA1302604)Scientific and technological innovation project of China Academy of Chinese Medical Sciences (No.CI2021B017)China Postdoctoral Science Foundation (No.2023T160727)。
文摘RNA binding proteins(RBPs) are a crucial class of proteins that interact with RNA and play a key role in various biological process.Deficiencies or abnormalities of RBPs are closely linked to the occurrence and progression of numerous diseases,making RBPs potential therapeutic targets.However,the limited tissue penetration of 254 nm UV irradiation makes it difficult to efficiently crosslink weak and dynamic RNA-protein interactions in mammal tissues.Additionally,RNA degradation in metal catalyzed click reaction further hinders the enrichment of RNA-protein complexes(RPCs).Due to these inherent limitations,globally profiling the RNA binding proteome in mammal organs has long been a challenge.Herein,we proposed a novel method,which utilized a dual crosslinking with formaldehyde and 254 nm UV irradiation,metabolic labeling and metal-free thiol-yne click reaction to enable large-scale enrichment and identification of RBPs in mouse liver,called FTYc_UV.In this method,formaldehyde is first used to crosslink the crude RNA-protein complexes(cRPCs) in situ to address the problem of poor tissue penetration of 254 nm UV irradiation.Furthermore,this method integrates metabolic labeling with a metal-free thiol-yne click reaction to achieve non-destructive RNA tagging.After specifically RNA-RBPs crosslinking by 254 nm UV irradiation in tissue lysates,formaldehyde decrosslinking is employed to remove non-specific proteins,leading to effective enrichment of RPCs from mouse liver and thereby overcoming the poor specificity of formaldehyde crosslinking.Application of FTYc_UV in mouse liver successfully identified over 1600 RBPs covering approximately 75 % of previously reported RBPs.Furthermore,420 candidate RBPs,including 151metabolic enzymes,were also obtained,demonstrating the sensitivity of FTYc_UV and the potential of this method for in-depth exploration of RNA-protein interactions in biological and clinical research.
基金Capital Health Development Scientific Research Project(2020-2-4064)National Key Research and Development Program of China(2018YFC2002502).
文摘Objective Patients with atherosclerotic cardiovascular disease(ASCVD)following percutaneous coronary intervention(PCI)are classified as very-high-risk individuals in cardiovascular disease(CVD)risk stratification.The distribution pattern of traditional Chinese medicine(TCM)syndromes in this patient population,as well as its association with blood lipid profiles and clinical prognosis,remains unclear.The present prospective cohort study aims to investigate these correlations,thereby providing insights to enrich the research fields.Methods We enrolled consecutive patients with ASCVD who underwent PCI at the Integrated Cardiology Unit of China-Japan Friendship Hospital between September 1,2020 and December 31,2022.Demographics and clinical characteristics,signs and symptoms defining each TCM syndrome,and fasting venous blood samples were collected at baseline and follow up or upon major adverse cardiovascular events(MACEs).We analyzed the correlation between TCM syndromes,blood lipid profiles,and MACEs,and developed a new joint prognostic model incorporating both TCM syndromes and blood lipids using logistic regression.The analyses were based on detailed baseline and one-year follow-up data.Results A per-protocol analysis was performed on 586 patients with complete data ultimately.During the one-year follow-up,174 patients(29.69%)experienced a MACE.We performed statistical analyses on comorbidities,medication,and biochemical indicators across groups defined by TCM syndrome differentiation.When comparing different TCM syndromes,no significant differences were found in age,body mass index(BMI),history of revascularization,comorbidities,family history of CVD,smoking or drinking,or statin intensity(P>0.05).Patients with intertwined phlegm and blood stasis syndrome exhibited significantly higher levels of total cholesterol(TC,5.27±1.18 mmol/L,P<0.001),triglyceride(TG,1.96±1.33 mmol/L,P=0.008),low-density lipoprotein cholesterol(LDL-C,3.35±0.79 mmol/L,P<0.001),and high-density lipoprotein cholesterol(HDL-C,1.24±0.81 mmol/L,P<0.001)compared with those with other TCM syndromes combined.A multivariable logistic regression model was constructed to predict MACEs.The model included TCM syndrome type[with intertwined phlegm and blood stasis as a predictor,adjusted odds ratio(OR)=1.413,95%confidence interval(CI):0.517–3.864,P=0.501],age(adjusted OR=0.97,95%CI:0.955–1.001,P=0.057),male gender(adjusted OR=0.698,95%CI:0.416–1.170,P=0.173),TC(adjusted OR=1.004,95%CI:0.513–1.965,P=0.990),and LDL-C(adjusted OR=5.825,95%CI:2.214–15.326,P<0.001).This model demonstrated good discriminatory ability for MACEs in post-PCI ASCVD patients[the area under the receiver operating characteristic(ROC)curve(AUC)=0.865,95%CI:0.816–0.914].Conclusion The intertwined phlegm and blood stasis TCM syndrome is associated with a distinct atherogenic lipid profile characterized by elevated levels of TC and LDL-C.The prognostic model that incorporates this TCM syndrome type along with conventional lipid parameters(TC and LDL-C)shows good discriminatory ability for predicting MACEs in ASCVD patients after PCI,underscoring the potential clinical utility of integrating TCM syndrome differentiation into CVD risk assessment.
基金supported by the National Key R&D Program of China,Nos.2021YFA1101703/2021YFA1101700(to YD).
文摘Ischemic stroke remains a leading cause of disability and death,with mesenchymal stem cell-derived exosomes emerging as a promising therapeutic avenue.However,the optimal timing and underlying therapeutic mechanisms of exosome treatment require further elucidation.In this study,we used a murine model of middle cerebral artery occlusion to investigate the therapeutic efficacy of human umbilical cord mesenchymal stem cell-derived exosomes administered intravenously at an early(6 hours)or delayed(3 days)time point post-ischemia.Compared with delayed treatment,early administration of exosomes resulted in significantly superior efficacy,as evidenced by improved neurological function scores and reduced infarct volumes.Transcriptomic analysis of brain tissues from mice receiving early exosome treatment revealed marked downregulation of inflammation-related genes,including Ccl2,Ccl5,Cxcl10,Il-1β,Il-6,Itgam,Itgax,and Tnf-α.Metabolomic profiling of these brain tissues further identified modulation of key metabolites,including trimethylamine N-oxide,glutathione,1-stearoyl-rac-glycerol,and phosphatidylcholine,suggesting that alteration of metabolic pathways contributes to the therapeutic effect.Integrated transcriptomic and metabolomic analysis pinpointed significant modulation of pathways involving metabolism of eicosapentaenoic acid,lysine,propanoate,and tyrosine.These findings suggest that umbilical cord mesenchymal stem cell-derived exosomes,particularly when administered early post-ischemia,exert their neuroprotective effects by broadly suppressing inflammatory pathways and modulating key metabolic processes in the ischemic brain,highlighting their potential as a therapeutic intervention for ischemic stroke.
基金Supported by National Natural Science Foundation of China-funded Project:Study on Mechanism of“Smoothing The Liver Therapy”on Working Memory of the Patients with Mild Cognitive Impairment Caused by Negative Emotion Regulation(No.81473556)Effects and Mechanism of Liver’s Failing to Facilitate the Coursing of Qi on Decline Process of Cognitive Function of Normal People and Patients with MCI(No.81873208)。
文摘OBJECTIVE:To examine the differences in cognitive processing between patients with mild cognitive impairment(MCI)of different Traditional Chinese Medicine(TCM)syndrome types to provide evidence supporting the TCM typing of MCI.METHODS:Participants were screened using a battery of scales for spleen and kidney deficiency(SKD)/liver Qi stagnation(LQS)-type MCI or those without syndrome or normal control(NC).Following sex,age,and educational matching,behavioral and electroencephalographic data were recorded using the verbal N-back experimental paradigm.The data were then analyzed and compared with respect to the reaction time and correctness of the participants in each group,as well as the amplitude and latency of the event-related potential(ERP)components of P2,N2,and P3.RESULTS:There were no statistically significant differences in the accuracy or reaction times of the behavioral data of the groups.Regarding ERP data,the SKD group had a shorter P2 latency than the LQS and NC groups,while the latter two groups did not differ statistically.The SKD group had a shorter N2 latency than the NC group,while the SKD group did not differ from the LQS group.The SKD and LQS groups had a shorter P3 latency than the NC group.CONCLUSION:Our study offers objective evidence of the distinction between the types of TCM syndrome.Different types of TCM syndromes produce different disease mechanisms,resulting in brain damage with different presentations of cognitive impairment and cognitive processing characteristics.
基金supported by European Union Funding Programme,PNRR,No. 760058(to DMH)the UEFISCDI Project,No. PN-III-P4-IDPCE-2020-059(to APW)
文摘The major aim of stroke therapy is to stimulate brain repair and improve behavioral recovery after cerebral ischemia.One option is to stimulate endogenous neurogenesis in the subventricular zone and direct the newly formed neurons to the damaged area.However,only a small percentage of these neurons survive,and many do not reach the damaged area,possibly because the corpus callosum impedes the migration of subventricular zone-derived stem cells into the lesioned cortex.A second major obstacle to stem cell therapy is the strong inflammatory reaction induced by cerebral ischemia,whereby the associated phagocytic activity of brain macrophages removes both therapeutic cells and/or cell-based drug carriers.To address these issues,neurogenesis was electrically stimulated in the subventricular zone,followed by isolation of proliferating cells,including newly formed neurons,which were subsequently mixed with a nutritional hydrogel.This mixture was then transferred to the stroke cavity of day 14 post-stroke mice.We found that the performance of the treated animals improved in behavioral tests,including novel object,open field,hole board,grooming,and“time-to-feel”adhesive tape tests.Furthermore,immunostaining revealed that the stem cell marker nestin,the neuroepithelial marker Mash1,and the immature neuronal marker doublecortin-positive cells survived in the transplanted area for 2 weeks,possibly due to reduced phagocytic activity and supportive angiogenesis.These results clearly indicate that the transplantation of committed subventricular zone stem cells combined with a protective nutritional gel directly into the infarct cavity after the peak of stroke-induced neuroinflammation represents a feasible approach to improve neurorestoration after cerebral ischemia.
基金Guangdong Province Medical Research Fund Project,Grant/Award Number:B2024112The Scientific Research Special Project of the Joint Construction Project of High-level Hospitals between Guangzhou University of Chinese Medicine and the Scientific Research Fund Project,Grant/Award Number:GZYZS2024G09+2 种基金Special Project of the Research Platform of Guangdong Provincial Department of Traditional Chinese Medicine,Grant/Award Number:20254040the Project of the Incubation Program for the Science and Technology Development of Chinese Medicine Guangdong Laboratory/Hengqin Laboratory,Grant/Award Number:HQL2024PZ043Guangdong Province Natural Science Foundation-Guangzhou-South China Joint Youth Fund Project,Grant/Award Number:2023A1515110849。
文摘Background:In recent decades,the global incidence of dengue fever has been stead-ily increasing,with continuous geographical expansion.Researchers have successfully modeled most clinical symptoms of human dengue fever using interferon type I(IFN-I)or combined IFN-I/II receptor knockout mice infected with dengue virus(DENV).However,this model requires further optimization to better support related studies.Methods:This study aimed to establish a stable dengue infection model by evaluating the effects of different genetic backgrounds and injection routes on DENV infection in interferon receptor knockout mice.We first infected various strains of interferon receptor-deficient mice with DENV and compared their susceptibility based on clini-cal symptoms,viremia levels,organ indices,histopathological findings,and vascular leakage markers.Subsequently,we selected the most susceptible strain to further investigate the impact of different injection methods on infection outcomes.Results:We found that BALB/c background mice with type 1 interferon recep-tor knockout(IFNAR)had the most obvious symptoms.Subsequently,we selected IFNAR−/−BALB/c mice to further explore the effects of different injection methods on dengue virus infection.The results showed that the intraperitoneal injection group had the most severe clinical symptoms,the longest duration of viremia,and the most obvious degree of organ damage.Conclusion:Through systematic screening and optimization,we established a robust animal model of dengue virus infection via intraperitoneal injection in IFNAR−/−BALB/c mice.This model offers a valuable tool for future dengue research.
基金Supported by National Science and Technology Major Projects(No.2010ZX09502-002)
文摘OBJECTIVE:To study the anaphylaxis of Qingkailing injection(QI) and its components.METHODS:Experimental anaphylactoid and allergic reactions were used.Changes in the behaviors of Beagles and serum levels of histamine,immunoglobulin(Ig)E,IgG,IgM,eosinophil cationic protein(ECP),and interleukin(IL)-4,as well as blood pressure,after injecting QI and its components on the forelimb veins of Beagles were observed.RESULTS:According to comprehensive determination of abnormal behavior scores and changes in serum levels of histamine,IgE,IgG,IgM,ECP,and IL-4,as well as in blood pressure,radix isatidis and hyodeoxycholic acid caused anaphylactoid reactions,and honeysuckle,radix isatidis,hydrolysate,cholic acid and Gardenia jasminoides caused allergic reactions.The anaphylaxis of QI involved anaphylactoid and allergic reactions.CONCLUSION:QI and its components need to be refined further to improve the safety,efficacy,and quality of its use in clinical settings.
基金supported by the Helium Enrichment and Detection in Natural Gas Reservoirs Related to Oil and Gas Fields project(Grant No.2025ZD1010500)the Deep Earth Probe and Mineral Resources Exploration―National Science and Technology Major Project.-。
文摘Thermochemical sulfate reduction(TSR)is an important organic-inorganic reaction that occurs within sedimentary basins and alters the original chemical compositions and isotopic structures of hydrocarbons in natural gases.We used the GC-Py-GC-IRMS method to study TSR and obtained a novel finding related to intramolecular carbon isotope fractionation in natural propane.The results show that theΔC-T(δ^(13)C_(central)-13 C_(terminal))andδ^(13)C_(central)values significantly increased to 44.7‰and 11.9‰,respectively,with increasing TSR alteration.In contrast,the 13 C_(terminal)values of propane remained largely unaltered by the TSR reaction.This difference in position-specific isotope fractionation can be attributed to the central carbon’s reactivity being higher than that of terminal carbon during TSR.In sum,the results indicate that theδ^(13)C_(terminal)values of propane can serve as robust indicators for source rock identification of natural gas altered by post-generation reactions such as TSR and anaerobic microbial oxidation.
基金supported by the General Project of Shaanxi Science and Technology Plan(No.2021JM-472)the Key Laboratory Project of Education Department of Shaanxi Province(Nos.21JS014 and 21JS007)+1 种基金the Subject Innovation Team of Shaanxi University of Chinese Medicine(No.2019YL14)the Postgraduate Student’s Innovation Project of Shaanxi University of Chinese Medicine(No.2021-09),China。
文摘Objective:To determine the potential molecular mechanisms underlying the therapeutic effect of curcumin on hepatocellular carcinoma(HCC)by network pharmacology and experimental in vitro validation.Methods:The predictive targets of curcumin or HCC were collected from several databases.the identified overlapping targets were crossed with Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses using the Database for Annotation,Visualization,and Integrated Discovery(DAVID)platform.Two of the candidate pathways were selected to conduct an experimental verification.The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium(MTT)assay was used to determine the effect of curcumin on the viability of Hep G2 and LO2 cells.The apoptosis and autophagy of Hep G2 cells were respectively detected by flow cytometry and transmission electron microscopy.Besides,western blot and real-time polymerase chain reaction(PCR)were employed to verify the p53 apoptotic pathway and adenosine 5’-monophosphate(AMP)-activated protein kinase(AMPK)autophagy pathway.Hep G2 cells were pretreated with pifithrin-α(PFT-α)and GSK690693 for further investigation.Results:The 167 pathways analyzed by KEGG included apoptosis,autophagy,p53,and AMPK pathways.The GO enrichment analysis demonstrated that curcumin was involved in cellular response to drug,regulation of apoptotic pathway,and so on.The in vitro experiments also confirmed that curcumin can inhibit the growth of Hep G2 cells by promoting the apoptosis of p53 pathway and autophagy through the AMPK pathway.Furthermore,the protein and messenger RNA(m RNA)of the two pathways were downregulated in the inhibitor-pretreated group compared with the experimental group.The damage-regulated autophagy modulator(DRAM)in the PFT-α-pretreated group was downregulated,and p62 in the GSK690693-pretreated group was upregulated.Conclusions:Curcumin can treat HCC through the p53 apoptotic pathway and the AMPK/Unc-51-like kinase 1(ULK1)autophagy pathway,in which the mutual transformation of autophagy and apoptosis may occur through DRAM and p62.
基金Supported by the National Natural Science Foundation of China,No.81603480 and No.81573857.
文摘BACKGROUND Acute pancreatitis(AP)is a pancreatic inflammatory disorder that is commonly complicated by extrapancreatic organ dysfunction.Dachengqi decoction(DCQD)has a potential role in protecting the extrapancreatic organs,but the optimal oral administration time remains unclear.AIM To screen the appropriate oral administration time of DCQD for the protection of extrapancreatic organs based on the pharmacokinetics and pharmacodynamics of AP rats.METHODS This study consisted of two parts.In the first part,24 rats were divided into a sham-operated group and three model groups.The four groups were intragastrically administered with DCQD(10 g/kg)at 4 h,4 h,12 h,and 24 h postoperatively,respectively.Tail vein blood was taken at nine time points after administration,and then the rats were euthanized and the extrapancreatic organ tissues were immediately collected.Finally,the concentrations of the major DCQD components in all samples were detected.In the second part,84 rats were divided into a sham-operated group,as well as 4 h,12 h,and 24 h treatment groups and corresponding control groups(4 h,12 h,and 24 h control groups).Rats in the treatment groups were intragastrically administered with DCQD(10 g/kg)at 4 h,12 h,and 24 h postoperatively,respectively,and rats in the control groups were administered with normal saline at the same time points.Then,six rats from each group were euthanized at 4 h and 24 h after administration.Serum amylase and inflammatory mediators,and pathological scores of extrapancreatic organ tissues were evaluated.RESULTS For part one,the pharmacokinetic parameters(C max,T max,T 1/2,and AUC 0→t)of the major DCQD components and the tissue distribution of most DCQD components were better when administering DCQD at the later(12 h and 24 h)time points.For part two,delayed administration of DCQD resulted in lower IL-6 and amylase levels and relatively higher IL-10 levels,and pathological injury of extrapancreatic organ tissues was slightly less at 4 h after administration,while the results were similar between the treatment and corresponding control groups at 24 h after administration.CONCLUSION Delayed administration of DCQD might reduce pancreatic exocrine secretions and ameliorate pathological injury in the extrapancreatic organs of AP rats,demonstrating that the late time is the optimal dosing time.
基金supported by the National Natural Science Foundation of China(Grant Nos.82303206,82372749,and 82072951)Science and Technology Commission of Shanghai Municipality(Grant Nos.20Y11914300 and 22Y21900100)+2 种基金Shanghai Anticancer Association(Grant No.SACAAX202213)Major Research Projects of Taizhou Clinical Medical College(Grant No.TZKY20230308)Natural Science Foundation in University of Jiangsu Province(Grant No.BK20231261).
文摘Copper ions are essential for cellular function but can induce cytotoxic effects when dysregulated.This review explores the multifaceted role of copper in cancer metabolism with a focus on the novel concept of cuproptosis,a regulated form of cell death triggered by copper accumulation.The mechanisms underlying copper homeostasis are detailed,including dietary absorption,systemic distribution,and intracellular utilization.Key transporters,such as copper transporter 1(CTR1)and ATPase copper transporting alpha/b(ATP7A/B),are highlighted.Cancer cells often exhibit elevated copper levels,supporting proliferation and metastasis through pro-tumorigenic pathways.Recent studies have shown that disrupting copper homeostasis can induce cuproptosis,which is characterized by the aggregation of lipoylated mitochondrial proteins and disruption of iron-sulfur cluster biogenesis.Advances in copper-based nanotechnology have enabled targeted delivery of copper to tumors,enhancing therapeutic efficacy through synergistic effects with reactive oxygen species(ROS)generation and immunomodulation.However,the hypoxic tumor microenvironment poses significant challenges by upregulating copper-sequestering proteins and downregulating key cuproptosis mediators.Future directions include integrating multi-omics approaches to identify novel therapeutic targets and developing combination therapies to overcome hypoxia-induced resistance.This review provides a comprehensive overview of copper metabolism in cancer,emphasizing the potential of cuproptosis induction as a powerful strategy for oncologic intervention.
基金Supported by Grants from the Brazilian Research CouncilFundao de Amparo à Pesquisa do Estado do Rio de Janeiro
文摘AIM:To investigate whether butyrate or glutamine enemas could diminish inflammation in experimental diversion colitis.METHODS:Wistar specific pathogen-free rats were submitted to a Hartmann's end colostomy and treated with enemas containing glutamine,butyrate,or saline.Enemas were administered twice a week in the excluded segment of the colon from 4 to 12 wk after the surgical procedure.Follow-up colonoscopy was performed every 4 wk for 12 wk.The effect of treatment was evaluated using video-endoscopic and histologic scores and measuring interleukin-1β,tumor necrosis factor-alpha,and transforming growth factor beta production in organ cultures by enzyme linked immunosorbent assay.RESULTS:Colonoscopies of the diverted segment showed mucosa with hyperemia,increased number of vessels,bleeding and mucus discharge.Treatment with either glutamine or butyrate induced significant reductions in both colonoscopic(P < 0.02) and histological scores(P < 0.01) and restored the densities of collagen fibers in tissue(P = 0.015;P = 0.001),the number of goblet cells(P = 0.021;P = 0.029),and the rate of apoptosis within the epithelium(P = 0.043;P = 0.011) to normal values.The high levels of cytokines in colon explants from rats with diversion colitis significantly decreased to normal values after treatment with butyrate or glutamine.CONCLUSION:The improvement of experimental diversion colitis following glutamine or butyrate enemas highlights the importance of specific luminal nutrients in the homeostasis of the colonic mucosa and supports their utilization for the treatment of human diversion colitis.
基金supported by the National Natural Science Foundation of China under Grant Nos.11803009 and 11603009the Natural Science Foundation of Fujian Province under Grant Nos.2018J05006,2018J01416 and 2016J05013。
文摘The acceleration of LMXB 4U 1820-30 derived from its orbital-period derivative P_(b)was supposed to be the evidence for an Intermediate-mass black hole(IMBH)in the Galactic globular cluster(GC)NGC 6624.However,we find that the anomalous P_(b)is mainly due to the gravitational wave emission,rather than the acceleration in cluster potential.Using the standard structure models of GCs,we simulate acceleration distributions for pulsars in the central region of the cluster.By fitting the acceleration of J1823-3021 A with the simulated distribution profiles(maximum values),it is suggested that an IMBH with mass M■950_(-350)^(+550)M_(⊙) may reside in the cluster center.We further show that the second period derivative P of J1823-3021 A is probably due to the gravitational perturbation of a nearby star.
基金Supported by Undergraduate Teaching Research and Reform Project of University of Shanghai for Science and Technology in 2024(JGXM24281)University-Level First-Class Undergraduate Course Construction Project of University of Shanghai for Science and Technology in 2024(YLKC202424394).
文摘In view of the key role of undergraduate experimental teaching reform in cultivating high-quality talents with both innovative spirit and practical ability,this paper deeply discusses multi-dimensional reform strategies.Specifically,the teaching mode of"double teachers for every student"is innovatively introduced,and scientific research projects are deeply integrated into undergraduate experimental teaching,aiming at realizing the modern development of teaching content and the diversified expansion of teaching methods.By designing and applying the undergraduate experimental teaching platform for intelligent limb rehabilitation training based on the concept of"medical-engineering interdisciplinary crossing",it not only builds a bridge for students to contact cutting-edge scientific research and strengthen practical skills,but also provides valuable ideas and practical models for the innovation of undergraduate experimental teaching.In the future,with the continuous optimization and upgrading of platform functions,it is expected to provide students with a richer and richer learning experience and comprehensively promote students'overall quality.
