Objective Previous Mendelian randomization(MR)studies have suggested an association between the gut microbiome and metabolic-associated fatty liver disease(MAFLD).However,the reliance on 16S rRNA sequencing data has l...Objective Previous Mendelian randomization(MR)studies have suggested an association between the gut microbiome and metabolic-associated fatty liver disease(MAFLD).However,the reliance on 16S rRNA sequencing data has led to inconsistent findings and limited species-level insights.To address this,we conducted a de novo MR analysis using species-level shotgun metagenomic data,combined it with a meta-analysis to consolidate the existing evidence,and explored metabolite-mediated pathways.Methods Bidirectional MR analyses were performed between 883 gut microbiota taxa(derived from shotgun metagenomic genome-wide association study)and MAFLD.Published MR studies(up to December 1,2024)were identified using PubMed,Embase,Web of Science,and the Cochrane Library for meta-analysis.Multivariable MR(MVMR)and mediation analyses were applied to assess the mediating effects of 1,400 blood metabolites.Results The de novo MR identified 25 MAFLD-associated microbial taxa.Integration with 7 published studies revealed 34 causal taxa,including 10 at the species level.Among the 1,400 metabolites,53 showed causal links with MAFLD.MVMR and mediation analyses identified deoxycholate as a mediator of the effect of Bifidobacterium on MAFLD risk(22.06%mediation proportion).Conclusion This study elucidated the connections between species-level gut microbiota and MAFLD,highlighting the interplay between microbiota,metabolites,and disease pathogenesis.These findings provide novel insights into the potential therapeutic targets for MAFLD.展开更多
Background:Antipsychotic-induced movement disorders(AIMDs)are prevalent side effects of antipsychotics,particularly during the acute phase of treatment.This study aimed to elucidate the genetic mechanisms underlying A...Background:Antipsychotic-induced movement disorders(AIMDs)are prevalent side effects of antipsychotics,particularly during the acute phase of treatment.This study aimed to elucidate the genetic mechanisms underlying AIMDs using a genome-wide association study(GWAS).Methods:GWASs on AIMDs were conducted in three independent cohorts:a discovery cohort of 3067 patients(2016 subjects were reserved after quality control),a validation cohort of 277 patients,and a multi-ancestry validation cohort of 766 patients.Subsequent post-GWAS analyses included gene-based analyses,transcriptome-wide association studies(TWASs),and polygenic risk score(PRS)profiling.Results:Our study identified two loci located in RAB44 gene(rs116249243,P=5.98×10^(-9);rs117097482,P=1.17×10^(-8))associated with extrapyramidal symptoms(EPSs),1 locus(rs6826172,P=5.56×10^(-9))related to akathisia,and 76 loci linked to involuntary movements(11 genes were mapped).Risk loci located in CNTNAP2,LUZP2,TMEM167A,and RAB44 genes were successfully replicated in the validation cohort,whereas the locus located in RAB44 was also replicated in the multi-ancestry cohort.Gene-based analyses indicated that XRCC4 and PAIP2B reached significance at the genome-wide level in involuntary movements.Tissue expression analysis revealed that involuntary movement-related genes are predominantly expressed in the substantia nigra.Additionally,the TWAS suggested a causal relationship between XRCC4 and involuntary movement.The PRSs derived from the discovery cohort significantly predicted AIMDs in the validation cohort,with area under the receiver operating characteristic curve(AUC)values from 0.60 to 0.80.Conclusions:Our findings highlight the role of substantia nigra related gene polymorphisms in AIMDs.This study provides novel insights into the pathogenesis of AIMDs and supports the potential for personalized treatment approaches for schizophrenia.展开更多
The published article titled“MicroRNA-148a Acts as a Tumor Suppressor in Osteosarcoma via Targeting Rho-Associated Coiled-Coil Kinase”has been retracted from Oncology Research,Vol.25,No.8,2017,pp.1231–1243.DOI:10.3...The published article titled“MicroRNA-148a Acts as a Tumor Suppressor in Osteosarcoma via Targeting Rho-Associated Coiled-Coil Kinase”has been retracted from Oncology Research,Vol.25,No.8,2017,pp.1231–1243.DOI:10.3727/096504017X14850134190255 URL:https://www.techscience.com/or/v25n8/56908 Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed experiments were intended to have been shown,although the areas immediately surrounding this area featured comparatively different distributions of cells.In addition,the western blots in this article were presented with atypical,unusually shaped and possibly anomalous protein bands in many cases.展开更多
Astrocytes,a major class of glial cells,have emerged as crucial regulators of synaptic function,neuronal homeostasis,and cognitive processes(Cabral-Miranda et al.,2024).These star-shaped cells not only provide structu...Astrocytes,a major class of glial cells,have emerged as crucial regulators of synaptic function,neuronal homeostasis,and cognitive processes(Cabral-Miranda et al.,2024).These star-shaped cells not only provide structural and metabolic support to neurons but also actively participate in modulating synaptic transmission,neurovascular coupling,and inflammatory responses in the brain.展开更多
Aging is a universal biological process characterized by the progressive decline in cellular and tissue function,representing the main risk factor for the development of most chronic human diseases.At the cellular lev...Aging is a universal biological process characterized by the progressive decline in cellular and tissue function,representing the main risk factor for the development of most chronic human diseases.At the cellular level,one hallmark of aging is the accumulation of senescent cells—non-dividing yet metabolically active cells that adopt a unique phenotype,including the senescence-associated secretory phenotype(SASP)(Wang et al.,2024).展开更多
MASLD in China:an under-recognized public health problem Epidemic characteristics of metabolic dysfunction-associated steatotic liver disease(MASLD)in China As one of the most common chronic non-infectious liver disea...MASLD in China:an under-recognized public health problem Epidemic characteristics of metabolic dysfunction-associated steatotic liver disease(MASLD)in China As one of the most common chronic non-infectious liver diseases,metabolic dysfunction-associated steatotic liver disease(MASLD),previously known as non-alcoholic fatty liver disease(NAFLD),affects one quarter of the world’s population,is closely related to diabetes and obesity[1,2].展开更多
The cultivation of grapes is severely impacted by the emergence of downy mildew (DM) disease which negatively affects quality and yield possibly resulting in heavy losses. Due to certain shortcomings in the usage of f...The cultivation of grapes is severely impacted by the emergence of downy mildew (DM) disease which negatively affects quality and yield possibly resulting in heavy losses. Due to certain shortcomings in the usage of fungicides and the development of new cultivars by plant breeding, marker assisted selection (MAS) will be an efficient alternative method to introduce desired genes into the cultivated varieties in a short time period. The Simple sequence repeats (SSR) markers seem to be the most popular genetic marker of choice for MAS. In the present study, we identified 14 new SSR markers in <i>RPV1</i> locus that are associated with downy mildew resistance in grapes. The characterization of the identified markers was carried out on the basis of various parameters such as types of repeat motifs, number of repeats, different classes and structure of microsatellites. Additionally, SSR genotyping in 56 different grape accessions was done to determine the susceptibility or resistance of these accessions to DM.展开更多
Salt stress is a major problem in most of the rice growing areas in the world. A major QTLSaltol associated with salt tolerance at the seedling stage has been mapped on chromosome 1 in rice.This study aimed to charact...Salt stress is a major problem in most of the rice growing areas in the world. A major QTLSaltol associated with salt tolerance at the seedling stage has been mapped on chromosome 1 in rice.This study aimed to characterize the haplotype diversity at Saltol and additional QTLs associated withsalt tolerance. Salt tolerance at the seedling stage was assessed in 54 rice genotypes in the scale of 1to 9 score at EC = 10 dSm^-1 under controlled environmental conditions. Seven new breeding linesincluding three KMR3/O. rufipogon introgression lines showed similar salt tolerant ability as FL478 andcan be good sources of new genes/alleles for salt tolerance. Simple sequence repeat （SSR） markerRM289 showed only two alleles and RM8094 showed seven alleles. Polymorphic information contentvalue varied from 0.55 for RM289 to 0.99 for RM8094 and RM493. Based on 14 SSR markers, the 54lines were clearly separated into two major clusters. Fourteen haplotypes were identified based onSaltol linked markers with FL478 as the reference. Alleles of RM8094 and RM3412 can discriminatebetween the salt tolerant and susceptible genotypes clearly and hence can be useful in marker-assistedselection at the seedling stage. Other markers RM10720 on chromosome 1 and RM149 and RM264 onchromosome 8 can also distinguish tolerant and susceptible lines but with lesser stringency.展开更多
Objective Junctophilin-2(JPH2)is an essential structural protein that maintains junctional membrane complexes(JMCs)in cardiomyocytes by tethering the plasma membrane to the sarcoplasmic reticulum,thereby facilitating ...Objective Junctophilin-2(JPH2)is an essential structural protein that maintains junctional membrane complexes(JMCs)in cardiomyocytes by tethering the plasma membrane to the sarcoplasmic reticulum,thereby facilitating excitationcontraction(E-C)coupling.Mutations in JPH2 have been associated with hypertrophic cardiomyopathy(HCM),but the molecular mechanisms governing its membrane-binding properties and the functional relevance of its membrane occupation and recognition nexus(MORN)repeat motifs remain incompletely understood.This study aimed to elucidate the structural basis of JPH2 membrane association and its implications for HCM pathogenesis.Methods A recombinant N-terminal fragment of mouse JPH2(residues 1-440),encompassing the MORN repeats and an adjacent helical region,was purified under near-physiological buffer conditions.X-ray crystallography was employed to determine the structure of the JPH2 MORN-Helix domain.Sequence conservation analysis across species and junctophilin isoforms was performed to assess the evolutionary conservation of key structural features.Functional membrane-binding assays were conducted using liposome co-sedimentation and cell-based localization studies in COS7 and HeLa cells.In addition,site-directed mutagenesis targeting positively charged residues and known HCM-associated mutations,including R347C,was used to evaluate their effects on membrane interaction and subcellular localization.Results The crystal structure of the mouse JPH2 MORN-Helix domain was resolved at 2.6Å,revealing a compact,elongated architecture consisting of multiple tandem MORN motifs arranged in a curved configuration,forming a continuous hydrophobic core stabilized by alternating aromatic residues.A C-terminalα-helix further reinforced structural integrity.Conservation analysis identified the inner groove of the MORN array as a highly conserved surface,suggesting its role as a protein-binding interface.A flexible linker segment enriched in positively charged residues,located adjacent to the MORN motifs,was found to mediate direct electrostatic interactions with negatively charged phospholipid membranes.Functional assays demonstrated that mutation of these basic residues impaired membrane association,while the HCM-linked R347C mutation completely abolished membrane localization in cellular assays,despite preserving the overall MORN-Helix fold in structural modeling.Conclusion This study provides structural insight into the membrane-binding mechanism of the cardiomyocyte-specific protein JPH2,highlighting the dual roles of its MORN-Helix domain in membrane anchoring and protein interactions.The findings clarify the structural basis for membrane targeting via a positively charged linker and demonstrate that disruption of this interaction—such as that caused by the R347C mutation—likely contributes to HCM pathogenesis.These results not only enhance current understanding of JPH2 function in cardiac E-C coupling but also offer a structural framework for future investigations into the assembly and regulation of JMCs in both physiological and disease contexts.展开更多
This article reviews the study,“Fanlian huazhuo formula alleviates high-fat-dietinduced nonalcoholic fatty liver disease by modulating autophagy and lipid synthesis signaling pathway”published in the World Journal o...This article reviews the study,“Fanlian huazhuo formula alleviates high-fat-dietinduced nonalcoholic fatty liver disease by modulating autophagy and lipid synthesis signaling pathway”published in the World Journal of Gastroenterology.The study explores the therapeutic potential of Fanlian Huazhuo formula(FLHZF)in treating metabolic-associated steatotic liver disease(MASLD),demonstrating that FLHZF reduces lipid accumulation,oxidative stress,and liver injury in MASLD models by modulating key signaling pathways involved in lipid metabolism and autophagy.This editorial emphasizes the potential of FLHZF as a treatment for MASLD and calls for further research to verify its clinical efficacy.展开更多
Introduction: Foot amputation in a diabetic patient is a real public health problem due to its functional and psychological repercussions. The objective was to study the factors associated with amputation in patients ...Introduction: Foot amputation in a diabetic patient is a real public health problem due to its functional and psychological repercussions. The objective was to study the factors associated with amputation in patients monitored for a diabetic foot in the internal medicine hospitalization of the Abass Ndao University Hospital Center (CHU) in Dakar. Methods: This was a retrospective, descriptive and analytical study conducted from the records of hospitalized patients over a 24-month period. The analysis included a descriptive phase, followed by a bivariate phase completed by logistic modeling following a descending procedure. Results: Of 1499 hospitalized patients, 224 cases had diabetic foot (14.9%). Among the cases of diabetic foot, 198 patients met the inclusion criteria. Their mean age was 61.7 ± 11.3 years, the sex ratio (M/F) was 1.2. Other associated cardiovascular risk factors were high blood pressure (54.0% 107 cases), and smoking (10.9% 21 cases). A history of lower limb amputation was found in 21.2% (42 cases). It was type 2 diabetes in 184 cases (92.9%) and the mean blood sugar was 2.7 ± 1.3 g/l. Chronic complications included neuropathy in 112 cases (78.3%), arteriopathy in 172 cases (86.9%), and chronic kidney disease in 167 cases (84.4%). The mean consultation time was 47.6 days. The main lesions were gangrene (64.6%), ulcer (24.7%), phlegmon (5.6%), and necrotizing fasciitis (5.1%). According to the University of Texas classification, patients presented with a stage D lesion (86.4%), grade 3 (51.0%). The hospital prevalence of amputation was 57.6% (114 cases), including major amputation in 55.1% (109 cases). The mortality rate was 36.4% (72 cases). Risk factors for amputation were peripheral arterial disease (ORa = 4.96 [1.33 - 18.43] p = 0.017), foot gangrene (Ora = 3.16 [1.24 - 8.04] p = 0.016) and Texas classification grade 3 (ORa = 17.49 [1.67 - 190] p = 0.019). Conclusion: The prevalence of foot and amputations remains a health problem. Reducing amputations will necessarily require strengthening prevention through education and early monitoring of diabetic patients.展开更多
Introduction: Uterine rupture is certainly one of the most serious, as it immediately jeopardises the vital prognosis of the mother and foetus. It is a common obstetric tragedy in our delivery rooms in countries with ...Introduction: Uterine rupture is certainly one of the most serious, as it immediately jeopardises the vital prognosis of the mother and foetus. It is a common obstetric tragedy in our delivery rooms in countries with limited resources, reflecting the poor quality of obstetric care and, consequently, an unmet obstetric need. Methods: This was a descriptive and analytical cross-sectional study with prospective data collection over a four-year period from 1 January 2020 to 31 December 2023 at the University Hospital Centre (CHU) of Bouaké, in the Obstetrics and Gynaecology Department. The variables studied were epidemiological characteristics, therapeutic aspects and factors associated with maternal. Results: The prevalence of uterine rupture was 0.63%. The average age was 32, with patients aged 35 and over accounting for 33.68%, married 44.21% and 70% not in education. Patients with uterine rupture had been evacuated in 85.26% of cases. Uterine rupture was diagnosed in 97.89% of cases during labour. Maternal lethality due to rupture was 15.79%. The causes of maternal death were dominated by haemorrhagic shock (53.33%). Factors statistically associated with death were age ≥ 35 years (OR: 3.14), duration of labour ≥ 12 hours (OR: 5.8), multiparity (OR: 19.04), admission delay beyond 2 hours (OR: 4.36), haemoglobin level ≤ 7 g/dl (OR: 36.84), coma or obnubilation (OR: 71.82), haemorrhagic shock (OR: 243.94) and occurrence of post-operative complications (OR: 76.45). Conclusion: The frequency of uterine rupture remains significant in the department (0.63%), with maternal mortality still high (15.79%). The key to reducing uterine rupture and its consequences lies in timely referral and early, appropriate management.展开更多
Background and Objectives: Post-operative complications (POC) are new pathological phenomena occurring in the post-operative period and worsening the previous situation through their morbidity and mortality. Our aim w...Background and Objectives: Post-operative complications (POC) are new pathological phenomena occurring in the post-operative period and worsening the previous situation through their morbidity and mortality. Our aim was to determine the prevalence and preoperative factors associated with early POC at University Clinics of Kisangani (CUKIS). Methods: This was a cross-sectional study conducted in the CUKIS, Department of Surgery from 1 January 2014 to 31 December 2023. The target population consisted of all patients who had undergone full post-operative follow-up. A logistic regression model using RStudio version 4.4.0 software was used to determine the factors predicting early postoperative complications. Results: The prevalence of early POC was estimated at 35%, with surgical site infection the most frequent POC at 45.3%. After multivariate analysis using logistic regression, the social category of widow(er)s, transfer, previous laparotomy, acute generalised peritonitis, preoperative length of stay of more than 10 days and ASA score 2 and 5 were significant risk factors associated with the occurrence of POC in the preoperative period. Conclusion: Certain factors can predict the occurrence of POC. Knowledge of these factors can help practitioners to take useful measures before each surgical operation on a patient with these factors, with a view to preventing or managing POC.展开更多
In this study,we searched for dispersed repeats(DRs)in the rice(Oryza sativa)genome using the iterative procedure(IP)method.The results revealed that the O.sativa genome contained 79 DR families,comprising 992739 DNA ...In this study,we searched for dispersed repeats(DRs)in the rice(Oryza sativa)genome using the iterative procedure(IP)method.The results revealed that the O.sativa genome contained 79 DR families,comprising 992739 DNA repeats,of which 496762 and 495977 were identified on the forward and reverse DNA strands,respectively.The detected DRs were,on average,374 bp in length and occupied 66.4%of the O.sativa genome.Totally 61%of DRs,identified by the IP method,overlapped with previously annotated dispersed repeats(ADRs)detected using the Extensive De Novo TE Annotator(EDTA)pipeline.展开更多
Short tandem repeats(STRs)modulate gene expression and contribute to trait variation.However,a systematic evaluation of the genomic characteristics of STRs has not been conducted,and their influence on gene expression...Short tandem repeats(STRs)modulate gene expression and contribute to trait variation.However,a systematic evaluation of the genomic characteristics of STRs has not been conducted,and their influence on gene expression in rice remains unclear.Here,we construct a map of 137,629 polymorphic STRs in the rice(Oryza sativa L.)genome using a population-scale resequencing dataset.A genome-wide survey encompassing 4726 accessions shows that the occurrence frequency,mutational patterns,chromosomal distribution,and functional properties of STRs are correlated with the sequences and lengths of repeat motifs.Leveraging a transcriptome dataset from 127 rice accessions,we identify 44,672 expression STRs(eSTRs)by modeling gene expression in response to the length variation of STRs.These eSTRs are notably enriched in the regulatory regions of genes with active transcriptional signatures.Population analysis identifies numerous STRs that have undergone genetic divergence among different rice groups and 1726 tagged STRs that may be associated with agronomic traits.By editing the(ACT)_(7) STR in OsFD1 promoter,we further experimentally validate its role in regulating gene expression and phenotype.Our study highlights the contribution of STRs to transcriptional regulation in plants and establishes the foundation for their potential use as alternative targets for genetic improvement.展开更多
Digital sculpture is the product of the cross-integration of art and technology,and its development is accompanied by the two-way interaction between technological innovation and artistic concepts.Based on this,this p...Digital sculpture is the product of the cross-integration of art and technology,and its development is accompanied by the two-way interaction between technological innovation and artistic concepts.Based on this,this paper mainly analyzes the remolding of artistic creation logic by technical tools and the expansion of technical application boundary by artistic expression,and further reveals the dynamic balance relationship between the two in symbiosis,hoping to help understand the accompanying mechanism of art and technology in the digital age.展开更多
The potential of induced pluripotent stem cells(iPSCs)for modeling and treating metabolic associated fatty liver disease(MAFLD)and metabolic associated steatohepatitis(MASH)is emerging.MAFLD is a growing global health...The potential of induced pluripotent stem cells(iPSCs)for modeling and treating metabolic associated fatty liver disease(MAFLD)and metabolic associated steatohepatitis(MASH)is emerging.MAFLD is a growing global health concern,currently with limited treatment options.While primary mesenchymal stem cells hold promise,iPSCs offer a versatile alternative due to their ability to differentiate into various cell types,including iPSC-derived mesenchymal stem cells.However,challenges remain,including optimizing differentiation protocols,ensuring cell safety,and addressing potential tumorigenicity risks.In addition,iPSCs offer the possibility to generate complex cellular models,including three-dimensional organoid models,which are closer representations of the human disease than animal models.Those models would also be valuable for drug discovery and personalized medicine approaches.Overall,iPSCs and their derivatives offer new perspectives for advancing MAFLD/MASH research and developing novel therapeutic strategies.Further research is needed to overcome current limitations and translate this potential into effective clinical applications.展开更多
With the prevalence of obesity,metabolic dysfunction-associated steatotic liver disease(MASLD)has become the most common chronic liver disease worldwide and can cause a series of serious complications.The pathogenesis...With the prevalence of obesity,metabolic dysfunction-associated steatotic liver disease(MASLD)has become the most common chronic liver disease worldwide and can cause a series of serious complications.The pathogenesis of MASLD is complex,characterized by oxidative stress,impaired mitochondrial function and lipid metabolism,and cellular inflammation.Mitochondrial biology and function are central to the physiology of the liver.It has been suggested that mitochondrial oxidative stress plays a crucial role in MASLD progression.Excessive oxidative stress response is an important trigger for the occurrence and development of MASLD.In this review,we aim to focus on the recent advances in understanding mitochondrial oxidative stress-related mechanisms in the progression of MASLD.The in-depth elaboration of its related mechanisms is hoped to help find effective methods for treating MASLD.展开更多
Hydrogen doping in associated gas combustion presents a promising strategy for mitigating carbon emissions from typically flared or vented gases.To support this idea,this study employed Chemkin Pro to model the lamina...Hydrogen doping in associated gas combustion presents a promising strategy for mitigating carbon emissions from typically flared or vented gases.To support this idea,this study employed Chemkin Pro to model the laminar premixed combustion of associated gases and conducted a sensitivity analysis of key combustion factors.The results demonstrated that increasing the hydrogen-doping ratio accelerated flame propagation and reduced combustion product accumulation time,while also elevating flame instability and inducing cracks or folds on the flame front at higher ratios.Notably,flame speed exhibited a 40%increase per 10%rise in the hydrogen-doping ratio,which directly enhanced combustion efficiency.Flame temperature peaked at an equivalence ratio of 1,whereas flame speed enhancement was maximized at a ratio of 1.3.Higher premix temperatures increased flame speed,and elevated combustion pressures raised flame temperature(stabilizing above 1 atm),with flame speed peaking at 0.06 atm.Critically,hydrogen doping below 15%minimally altered flame morphology,but 30%doping caused significant flame retraction toward the nozzle,which increased the flashback risk and raised NOx emissions by nearly one third.These findings provide insights for optimizing hydrogen-doped combustion processes to balance efficiency gains while ensuring operational safety and emission control.展开更多
Background: Recurrent spontaneous abortion (RSA) is defined as the occurrence of three or more consecutive spontaneous abortion prior to 20 weeks from the last menstrual period. It affects approximately 1% to 2% of wo...Background: Recurrent spontaneous abortion (RSA) is defined as the occurrence of three or more consecutive spontaneous abortion prior to 20 weeks from the last menstrual period. It affects approximately 1% to 2% of women, and about 40% - 80% of RSA are still remained unexplained. In recent years, a lot of studies suggest that RSA is caused by the immune factors. T helper 1(Th1)-type immunity is associated with unsuccessful pregnancy especially in women with RSA, while Th2-type immunity is associated with pregnancy success. Interleukin (IL)-2 may influence Th1/Th2 immune responsiveness and has been implicated association with RSA. Aim: The aim of this study was to investigate the association of the interleukin 2 (IL-2) promoter polymorphisms at the site ‐330 A/C (rs2069762) with RSA. Methods: The study group comprised 189 women with RSA, and the control group consisted of 187 healthy pregnant women. Gene polymorphisms were detected by the technique of polymerase chain reaction restriction fragment length polymorphism. Results: The frequency of genotype ‐330C/C was significant higher (χ2 = 7.266, p = 0.007, OR = 0.362, 95% CI = 0.169 - 0.777) in the control group than in the patient group. And the frequency of the -330Aallele was significant higher (χ2 = 11.862, p = 0.001, OR = 1.741, 95% CI = 1.268 - 2.389) in the patient group than in the control group. Conclusions: This study indicated that the IL-2-330Aallele may be considered as a risk factor for RSA. C→A mutation is may associated with RSA in Ningxia Han people.展开更多
基金supported by grants from the National Natural Science Foundation of China(82270924)the CAMS Innovation Fund for Medical Sciences(CIFMS 2021-I2M-1-016)the National High Level Hospital Clinical Research Funding(2022-PUMCH-C-014,2025-PUMCH-C-041).
文摘Objective Previous Mendelian randomization(MR)studies have suggested an association between the gut microbiome and metabolic-associated fatty liver disease(MAFLD).However,the reliance on 16S rRNA sequencing data has led to inconsistent findings and limited species-level insights.To address this,we conducted a de novo MR analysis using species-level shotgun metagenomic data,combined it with a meta-analysis to consolidate the existing evidence,and explored metabolite-mediated pathways.Methods Bidirectional MR analyses were performed between 883 gut microbiota taxa(derived from shotgun metagenomic genome-wide association study)and MAFLD.Published MR studies(up to December 1,2024)were identified using PubMed,Embase,Web of Science,and the Cochrane Library for meta-analysis.Multivariable MR(MVMR)and mediation analyses were applied to assess the mediating effects of 1,400 blood metabolites.Results The de novo MR identified 25 MAFLD-associated microbial taxa.Integration with 7 published studies revealed 34 causal taxa,including 10 at the species level.Among the 1,400 metabolites,53 showed causal links with MAFLD.MVMR and mediation analyses identified deoxycholate as a mediator of the effect of Bifidobacterium on MAFLD risk(22.06%mediation proportion).Conclusion This study elucidated the connections between species-level gut microbiota and MAFLD,highlighting the interplay between microbiota,metabolites,and disease pathogenesis.These findings provide novel insights into the potential therapeutic targets for MAFLD.
基金supported by the National Natural Science Foundation of China(82330042,82441005 and 82301687)the National Key R&D Program of China(2023YFE0119400)+9 种基金the Capital’s Funds for Health Improvement and Research(2024-1-4111)the STI2030-Major Projects-2021ZD0200702Fundamental Research Funds for the Central Universities(Peking University Medicine Fund for world’s leading discipline or discipline cluster development,BMU2022DJXK007)the Beijing Municipal Health Commission Research Ward Programme(3rd batch)Beijing Nova Program(20230484425)the Beijing Municipal Science&Technology Commission,Administrative Commission of Zhongguancun Science Park(Z221100003522010)the China Postdoctoral Science Foundation(2024M760141 and 2022M720302)the National Postdoctoral Program for Innovative Talents(BX20240029)the Beijing Natural Science Foundation(7254462)the Peking University Medicine Sailing Program for Young Scholars’Scientific&Technological Innovation,the Fundamental Research Funds for the Central Universities(BMU2025YFJHPY044 and BMU2025YFJHPY046).
文摘Background:Antipsychotic-induced movement disorders(AIMDs)are prevalent side effects of antipsychotics,particularly during the acute phase of treatment.This study aimed to elucidate the genetic mechanisms underlying AIMDs using a genome-wide association study(GWAS).Methods:GWASs on AIMDs were conducted in three independent cohorts:a discovery cohort of 3067 patients(2016 subjects were reserved after quality control),a validation cohort of 277 patients,and a multi-ancestry validation cohort of 766 patients.Subsequent post-GWAS analyses included gene-based analyses,transcriptome-wide association studies(TWASs),and polygenic risk score(PRS)profiling.Results:Our study identified two loci located in RAB44 gene(rs116249243,P=5.98×10^(-9);rs117097482,P=1.17×10^(-8))associated with extrapyramidal symptoms(EPSs),1 locus(rs6826172,P=5.56×10^(-9))related to akathisia,and 76 loci linked to involuntary movements(11 genes were mapped).Risk loci located in CNTNAP2,LUZP2,TMEM167A,and RAB44 genes were successfully replicated in the validation cohort,whereas the locus located in RAB44 was also replicated in the multi-ancestry cohort.Gene-based analyses indicated that XRCC4 and PAIP2B reached significance at the genome-wide level in involuntary movements.Tissue expression analysis revealed that involuntary movement-related genes are predominantly expressed in the substantia nigra.Additionally,the TWAS suggested a causal relationship between XRCC4 and involuntary movement.The PRSs derived from the discovery cohort significantly predicted AIMDs in the validation cohort,with area under the receiver operating characteristic curve(AUC)values from 0.60 to 0.80.Conclusions:Our findings highlight the role of substantia nigra related gene polymorphisms in AIMDs.This study provides novel insights into the pathogenesis of AIMDs and supports the potential for personalized treatment approaches for schizophrenia.
文摘The published article titled“MicroRNA-148a Acts as a Tumor Suppressor in Osteosarcoma via Targeting Rho-Associated Coiled-Coil Kinase”has been retracted from Oncology Research,Vol.25,No.8,2017,pp.1231–1243.DOI:10.3727/096504017X14850134190255 URL:https://www.techscience.com/or/v25n8/56908 Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed experiments were intended to have been shown,although the areas immediately surrounding this area featured comparatively different distributions of cells.In addition,the western blots in this article were presented with atypical,unusually shaped and possibly anomalous protein bands in many cases.
文摘Astrocytes,a major class of glial cells,have emerged as crucial regulators of synaptic function,neuronal homeostasis,and cognitive processes(Cabral-Miranda et al.,2024).These star-shaped cells not only provide structural and metabolic support to neurons but also actively participate in modulating synaptic transmission,neurovascular coupling,and inflammatory responses in the brain.
基金NIH NIA1RO1AG061879 and 5PO1AG066591(to LME)FONDAP Program 15150012,ECOS-A NID(ECOS230034)the US Army Medical Research Acquisition Activity(USAMRAA)AL2201415(to CH)。
文摘Aging is a universal biological process characterized by the progressive decline in cellular and tissue function,representing the main risk factor for the development of most chronic human diseases.At the cellular level,one hallmark of aging is the accumulation of senescent cells—non-dividing yet metabolically active cells that adopt a unique phenotype,including the senescence-associated secretory phenotype(SASP)(Wang et al.,2024).
基金funded by the Program of China Scholarships Council(No.202206785007)“Four New”Experimental Teaching Curriculum Reform Project of Jinan University in China(SYJG202235),the Teaching QualityTeaching Reform Project of Undergraduate University of Guangdong in China(2020).
文摘MASLD in China:an under-recognized public health problem Epidemic characteristics of metabolic dysfunction-associated steatotic liver disease(MASLD)in China As one of the most common chronic non-infectious liver diseases,metabolic dysfunction-associated steatotic liver disease(MASLD),previously known as non-alcoholic fatty liver disease(NAFLD),affects one quarter of the world’s population,is closely related to diabetes and obesity[1,2].
文摘The cultivation of grapes is severely impacted by the emergence of downy mildew (DM) disease which negatively affects quality and yield possibly resulting in heavy losses. Due to certain shortcomings in the usage of fungicides and the development of new cultivars by plant breeding, marker assisted selection (MAS) will be an efficient alternative method to introduce desired genes into the cultivated varieties in a short time period. The Simple sequence repeats (SSR) markers seem to be the most popular genetic marker of choice for MAS. In the present study, we identified 14 new SSR markers in <i>RPV1</i> locus that are associated with downy mildew resistance in grapes. The characterization of the identified markers was carried out on the basis of various parameters such as types of repeat motifs, number of repeats, different classes and structure of microsatellites. Additionally, SSR genotyping in 56 different grape accessions was done to determine the susceptibility or resistance of these accessions to DM.
基金Financial support of Department of Biotechnology,Government of India[Grant Nos.BT/AB/FG-2(PH-II)2009 and BT/PR13357/AGR/02/695/2009]
文摘Salt stress is a major problem in most of the rice growing areas in the world. A major QTLSaltol associated with salt tolerance at the seedling stage has been mapped on chromosome 1 in rice.This study aimed to characterize the haplotype diversity at Saltol and additional QTLs associated withsalt tolerance. Salt tolerance at the seedling stage was assessed in 54 rice genotypes in the scale of 1to 9 score at EC = 10 dSm^-1 under controlled environmental conditions. Seven new breeding linesincluding three KMR3/O. rufipogon introgression lines showed similar salt tolerant ability as FL478 andcan be good sources of new genes/alleles for salt tolerance. Simple sequence repeat （SSR） markerRM289 showed only two alleles and RM8094 showed seven alleles. Polymorphic information contentvalue varied from 0.55 for RM289 to 0.99 for RM8094 and RM493. Based on 14 SSR markers, the 54lines were clearly separated into two major clusters. Fourteen haplotypes were identified based onSaltol linked markers with FL478 as the reference. Alleles of RM8094 and RM3412 can discriminatebetween the salt tolerant and susceptible genotypes clearly and hence can be useful in marker-assistedselection at the seedling stage. Other markers RM10720 on chromosome 1 and RM149 and RM264 onchromosome 8 can also distinguish tolerant and susceptible lines but with lesser stringency.
文摘Objective Junctophilin-2(JPH2)is an essential structural protein that maintains junctional membrane complexes(JMCs)in cardiomyocytes by tethering the plasma membrane to the sarcoplasmic reticulum,thereby facilitating excitationcontraction(E-C)coupling.Mutations in JPH2 have been associated with hypertrophic cardiomyopathy(HCM),but the molecular mechanisms governing its membrane-binding properties and the functional relevance of its membrane occupation and recognition nexus(MORN)repeat motifs remain incompletely understood.This study aimed to elucidate the structural basis of JPH2 membrane association and its implications for HCM pathogenesis.Methods A recombinant N-terminal fragment of mouse JPH2(residues 1-440),encompassing the MORN repeats and an adjacent helical region,was purified under near-physiological buffer conditions.X-ray crystallography was employed to determine the structure of the JPH2 MORN-Helix domain.Sequence conservation analysis across species and junctophilin isoforms was performed to assess the evolutionary conservation of key structural features.Functional membrane-binding assays were conducted using liposome co-sedimentation and cell-based localization studies in COS7 and HeLa cells.In addition,site-directed mutagenesis targeting positively charged residues and known HCM-associated mutations,including R347C,was used to evaluate their effects on membrane interaction and subcellular localization.Results The crystal structure of the mouse JPH2 MORN-Helix domain was resolved at 2.6Å,revealing a compact,elongated architecture consisting of multiple tandem MORN motifs arranged in a curved configuration,forming a continuous hydrophobic core stabilized by alternating aromatic residues.A C-terminalα-helix further reinforced structural integrity.Conservation analysis identified the inner groove of the MORN array as a highly conserved surface,suggesting its role as a protein-binding interface.A flexible linker segment enriched in positively charged residues,located adjacent to the MORN motifs,was found to mediate direct electrostatic interactions with negatively charged phospholipid membranes.Functional assays demonstrated that mutation of these basic residues impaired membrane association,while the HCM-linked R347C mutation completely abolished membrane localization in cellular assays,despite preserving the overall MORN-Helix fold in structural modeling.Conclusion This study provides structural insight into the membrane-binding mechanism of the cardiomyocyte-specific protein JPH2,highlighting the dual roles of its MORN-Helix domain in membrane anchoring and protein interactions.The findings clarify the structural basis for membrane targeting via a positively charged linker and demonstrate that disruption of this interaction—such as that caused by the R347C mutation—likely contributes to HCM pathogenesis.These results not only enhance current understanding of JPH2 function in cardiac E-C coupling but also offer a structural framework for future investigations into the assembly and regulation of JMCs in both physiological and disease contexts.
文摘This article reviews the study,“Fanlian huazhuo formula alleviates high-fat-dietinduced nonalcoholic fatty liver disease by modulating autophagy and lipid synthesis signaling pathway”published in the World Journal of Gastroenterology.The study explores the therapeutic potential of Fanlian Huazhuo formula(FLHZF)in treating metabolic-associated steatotic liver disease(MASLD),demonstrating that FLHZF reduces lipid accumulation,oxidative stress,and liver injury in MASLD models by modulating key signaling pathways involved in lipid metabolism and autophagy.This editorial emphasizes the potential of FLHZF as a treatment for MASLD and calls for further research to verify its clinical efficacy.
文摘Introduction: Foot amputation in a diabetic patient is a real public health problem due to its functional and psychological repercussions. The objective was to study the factors associated with amputation in patients monitored for a diabetic foot in the internal medicine hospitalization of the Abass Ndao University Hospital Center (CHU) in Dakar. Methods: This was a retrospective, descriptive and analytical study conducted from the records of hospitalized patients over a 24-month period. The analysis included a descriptive phase, followed by a bivariate phase completed by logistic modeling following a descending procedure. Results: Of 1499 hospitalized patients, 224 cases had diabetic foot (14.9%). Among the cases of diabetic foot, 198 patients met the inclusion criteria. Their mean age was 61.7 ± 11.3 years, the sex ratio (M/F) was 1.2. Other associated cardiovascular risk factors were high blood pressure (54.0% 107 cases), and smoking (10.9% 21 cases). A history of lower limb amputation was found in 21.2% (42 cases). It was type 2 diabetes in 184 cases (92.9%) and the mean blood sugar was 2.7 ± 1.3 g/l. Chronic complications included neuropathy in 112 cases (78.3%), arteriopathy in 172 cases (86.9%), and chronic kidney disease in 167 cases (84.4%). The mean consultation time was 47.6 days. The main lesions were gangrene (64.6%), ulcer (24.7%), phlegmon (5.6%), and necrotizing fasciitis (5.1%). According to the University of Texas classification, patients presented with a stage D lesion (86.4%), grade 3 (51.0%). The hospital prevalence of amputation was 57.6% (114 cases), including major amputation in 55.1% (109 cases). The mortality rate was 36.4% (72 cases). Risk factors for amputation were peripheral arterial disease (ORa = 4.96 [1.33 - 18.43] p = 0.017), foot gangrene (Ora = 3.16 [1.24 - 8.04] p = 0.016) and Texas classification grade 3 (ORa = 17.49 [1.67 - 190] p = 0.019). Conclusion: The prevalence of foot and amputations remains a health problem. Reducing amputations will necessarily require strengthening prevention through education and early monitoring of diabetic patients.
文摘Introduction: Uterine rupture is certainly one of the most serious, as it immediately jeopardises the vital prognosis of the mother and foetus. It is a common obstetric tragedy in our delivery rooms in countries with limited resources, reflecting the poor quality of obstetric care and, consequently, an unmet obstetric need. Methods: This was a descriptive and analytical cross-sectional study with prospective data collection over a four-year period from 1 January 2020 to 31 December 2023 at the University Hospital Centre (CHU) of Bouaké, in the Obstetrics and Gynaecology Department. The variables studied were epidemiological characteristics, therapeutic aspects and factors associated with maternal. Results: The prevalence of uterine rupture was 0.63%. The average age was 32, with patients aged 35 and over accounting for 33.68%, married 44.21% and 70% not in education. Patients with uterine rupture had been evacuated in 85.26% of cases. Uterine rupture was diagnosed in 97.89% of cases during labour. Maternal lethality due to rupture was 15.79%. The causes of maternal death were dominated by haemorrhagic shock (53.33%). Factors statistically associated with death were age ≥ 35 years (OR: 3.14), duration of labour ≥ 12 hours (OR: 5.8), multiparity (OR: 19.04), admission delay beyond 2 hours (OR: 4.36), haemoglobin level ≤ 7 g/dl (OR: 36.84), coma or obnubilation (OR: 71.82), haemorrhagic shock (OR: 243.94) and occurrence of post-operative complications (OR: 76.45). Conclusion: The frequency of uterine rupture remains significant in the department (0.63%), with maternal mortality still high (15.79%). The key to reducing uterine rupture and its consequences lies in timely referral and early, appropriate management.
文摘Background and Objectives: Post-operative complications (POC) are new pathological phenomena occurring in the post-operative period and worsening the previous situation through their morbidity and mortality. Our aim was to determine the prevalence and preoperative factors associated with early POC at University Clinics of Kisangani (CUKIS). Methods: This was a cross-sectional study conducted in the CUKIS, Department of Surgery from 1 January 2014 to 31 December 2023. The target population consisted of all patients who had undergone full post-operative follow-up. A logistic regression model using RStudio version 4.4.0 software was used to determine the factors predicting early postoperative complications. Results: The prevalence of early POC was estimated at 35%, with surgical site infection the most frequent POC at 45.3%. After multivariate analysis using logistic regression, the social category of widow(er)s, transfer, previous laparotomy, acute generalised peritonitis, preoperative length of stay of more than 10 days and ASA score 2 and 5 were significant risk factors associated with the occurrence of POC in the preoperative period. Conclusion: Certain factors can predict the occurrence of POC. Knowledge of these factors can help practitioners to take useful measures before each surgical operation on a patient with these factors, with a view to preventing or managing POC.
基金supported by the Russian Science Foundation,Russia(Grant No.24-24-00031).
文摘In this study,we searched for dispersed repeats(DRs)in the rice(Oryza sativa)genome using the iterative procedure(IP)method.The results revealed that the O.sativa genome contained 79 DR families,comprising 992739 DNA repeats,of which 496762 and 495977 were identified on the forward and reverse DNA strands,respectively.The detected DRs were,on average,374 bp in length and occupied 66.4%of the O.sativa genome.Totally 61%of DRs,identified by the IP method,overlapped with previously annotated dispersed repeats(ADRs)detected using the Extensive De Novo TE Annotator(EDTA)pipeline.
基金supported by the National Natural Science Foundation of China(32172010)the Major Program of Guangdong Basic and Applied Basic Research(2019B030302006).
文摘Short tandem repeats(STRs)modulate gene expression and contribute to trait variation.However,a systematic evaluation of the genomic characteristics of STRs has not been conducted,and their influence on gene expression in rice remains unclear.Here,we construct a map of 137,629 polymorphic STRs in the rice(Oryza sativa L.)genome using a population-scale resequencing dataset.A genome-wide survey encompassing 4726 accessions shows that the occurrence frequency,mutational patterns,chromosomal distribution,and functional properties of STRs are correlated with the sequences and lengths of repeat motifs.Leveraging a transcriptome dataset from 127 rice accessions,we identify 44,672 expression STRs(eSTRs)by modeling gene expression in response to the length variation of STRs.These eSTRs are notably enriched in the regulatory regions of genes with active transcriptional signatures.Population analysis identifies numerous STRs that have undergone genetic divergence among different rice groups and 1726 tagged STRs that may be associated with agronomic traits.By editing the(ACT)_(7) STR in OsFD1 promoter,we further experimentally validate its role in regulating gene expression and phenotype.Our study highlights the contribution of STRs to transcriptional regulation in plants and establishes the foundation for their potential use as alternative targets for genetic improvement.
文摘Digital sculpture is the product of the cross-integration of art and technology,and its development is accompanied by the two-way interaction between technological innovation and artistic concepts.Based on this,this paper mainly analyzes the remolding of artistic creation logic by technical tools and the expansion of technical application boundary by artistic expression,and further reveals the dynamic balance relationship between the two in symbiosis,hoping to help understand the accompanying mechanism of art and technology in the digital age.
基金American Heart Association Award,No.24IVPHA1288417and FCT Fellowships,No.2022.13253.BDANA.
文摘The potential of induced pluripotent stem cells(iPSCs)for modeling and treating metabolic associated fatty liver disease(MAFLD)and metabolic associated steatohepatitis(MASH)is emerging.MAFLD is a growing global health concern,currently with limited treatment options.While primary mesenchymal stem cells hold promise,iPSCs offer a versatile alternative due to their ability to differentiate into various cell types,including iPSC-derived mesenchymal stem cells.However,challenges remain,including optimizing differentiation protocols,ensuring cell safety,and addressing potential tumorigenicity risks.In addition,iPSCs offer the possibility to generate complex cellular models,including three-dimensional organoid models,which are closer representations of the human disease than animal models.Those models would also be valuable for drug discovery and personalized medicine approaches.Overall,iPSCs and their derivatives offer new perspectives for advancing MAFLD/MASH research and developing novel therapeutic strategies.Further research is needed to overcome current limitations and translate this potential into effective clinical applications.
基金supported by grants from the Top Medical Expert Team of Wuxi Taihu Talent Plan(Grant Nos.DJTD202106,GDTD202105 and YXTD202101)Medical Key Discipline Program of Wuxi Health Commission(Grant Nos.ZDXK2021007 and CXTD2021005)+1 种基金Top Talent Support Program for Young and MiddleAged People of Wuxi Health Committee(Grant No.BJ2023090)Scientific Research Program of Wuxi Health Commission(Grant Nos.Z20210 and M202208).
文摘With the prevalence of obesity,metabolic dysfunction-associated steatotic liver disease(MASLD)has become the most common chronic liver disease worldwide and can cause a series of serious complications.The pathogenesis of MASLD is complex,characterized by oxidative stress,impaired mitochondrial function and lipid metabolism,and cellular inflammation.Mitochondrial biology and function are central to the physiology of the liver.It has been suggested that mitochondrial oxidative stress plays a crucial role in MASLD progression.Excessive oxidative stress response is an important trigger for the occurrence and development of MASLD.In this review,we aim to focus on the recent advances in understanding mitochondrial oxidative stress-related mechanisms in the progression of MASLD.The in-depth elaboration of its related mechanisms is hoped to help find effective methods for treating MASLD.
基金supported by the China Postdoctoral Science Foundation(Grant No.2022M723497).
文摘Hydrogen doping in associated gas combustion presents a promising strategy for mitigating carbon emissions from typically flared or vented gases.To support this idea,this study employed Chemkin Pro to model the laminar premixed combustion of associated gases and conducted a sensitivity analysis of key combustion factors.The results demonstrated that increasing the hydrogen-doping ratio accelerated flame propagation and reduced combustion product accumulation time,while also elevating flame instability and inducing cracks or folds on the flame front at higher ratios.Notably,flame speed exhibited a 40%increase per 10%rise in the hydrogen-doping ratio,which directly enhanced combustion efficiency.Flame temperature peaked at an equivalence ratio of 1,whereas flame speed enhancement was maximized at a ratio of 1.3.Higher premix temperatures increased flame speed,and elevated combustion pressures raised flame temperature(stabilizing above 1 atm),with flame speed peaking at 0.06 atm.Critically,hydrogen doping below 15%minimally altered flame morphology,but 30%doping caused significant flame retraction toward the nozzle,which increased the flashback risk and raised NOx emissions by nearly one third.These findings provide insights for optimizing hydrogen-doped combustion processes to balance efficiency gains while ensuring operational safety and emission control.
文摘Background: Recurrent spontaneous abortion (RSA) is defined as the occurrence of three or more consecutive spontaneous abortion prior to 20 weeks from the last menstrual period. It affects approximately 1% to 2% of women, and about 40% - 80% of RSA are still remained unexplained. In recent years, a lot of studies suggest that RSA is caused by the immune factors. T helper 1(Th1)-type immunity is associated with unsuccessful pregnancy especially in women with RSA, while Th2-type immunity is associated with pregnancy success. Interleukin (IL)-2 may influence Th1/Th2 immune responsiveness and has been implicated association with RSA. Aim: The aim of this study was to investigate the association of the interleukin 2 (IL-2) promoter polymorphisms at the site ‐330 A/C (rs2069762) with RSA. Methods: The study group comprised 189 women with RSA, and the control group consisted of 187 healthy pregnant women. Gene polymorphisms were detected by the technique of polymerase chain reaction restriction fragment length polymorphism. Results: The frequency of genotype ‐330C/C was significant higher (χ2 = 7.266, p = 0.007, OR = 0.362, 95% CI = 0.169 - 0.777) in the control group than in the patient group. And the frequency of the -330Aallele was significant higher (χ2 = 11.862, p = 0.001, OR = 1.741, 95% CI = 1.268 - 2.389) in the patient group than in the control group. Conclusions: This study indicated that the IL-2-330Aallele may be considered as a risk factor for RSA. C→A mutation is may associated with RSA in Ningxia Han people.
