Background:In this study,we aimed to validate and test the reliability of the Yonsei lifestyle profile(YLP)in assessing multifaceted health lifestyle levels in a study population from the United States.Methods:The YLP...Background:In this study,we aimed to validate and test the reliability of the Yonsei lifestyle profile(YLP)in assessing multifaceted health lifestyle levels in a study population from the United States.Methods:The YLP-English version and health-promoting lifestyle profile II were administered to 100 individuals living in the United States.Concurrent validity was analyzed using Pearson's correlation coefficient,and discriminant validity was examined by comparing sex and age differences through t-tests and multiple variance analysis.Internal consistency was assessed using Cronbach'sαfor each sub-factor.Results:The YLP-English Version demonstrated concurrent validity with the Health-Promoting Lifestyle Profile II,showing consistent correlations for the total score(0.3,p<0.01)and frequency sub-factors(0.25-0.69,p<0.01).Among the satisfaction sub-factors,only nutrition showed a weak negative correlation(-0.19,p<0.01);all others were nonsignificant.Discriminant validity revealed no significant sex differences,but physical activity frequency varied across age groups.Internal consistency was high(Cronbach'sα=0.80-0.86).Conclusion:In this study,we validated the YLP-English version as a reliable instrument for assessing health-related lifestyle behaviors.The YLP uniquely captures both lifestyle frequency and satisfaction,offering a comprehensive perspective on health behaviors.Although this tool is currently most applicable in population-level studies,future research should establish clinical thresholds to enhance its utility in individualized health assessments and interventions.展开更多
Background:Childhood environmental unpredictability(CEU)is crucial to personal development,profoundly influence physical and psychological growth particularly,and psychopathy is recognized as a dark personality trait....Background:Childhood environmental unpredictability(CEU)is crucial to personal development,profoundly influence physical and psychological growth particularly,and psychopathy is recognized as a dark personality trait.The aim of this study is to investigate the effects of insecure attachment and life history strategy(LHS)on the relationship between CEU and psychopathy by establishing a sequential mediation model based on evolutionary life history theory and cognitive-affective personality system.Methods:A group of 532 undergraduates completed the measurements for CEU,insecure attachment,LHS,and psychopathy,and Bootstrap mediation test through SPSS 25.0 and PROCESS macro tool was used to examine the relationship among these variables.Results:The results revealed positive relations between CEU and insecure attachment(β=0.87,p<0.001),CEU and LHS(β=0.11,p<0.001),and CEU and psychopathy(β=0.14,p<0.001).Insecure attachment was also positively associated with LHS(β=0.62,p<0.001)and psychopathy(β=0.04,p<0.001).In addition,LHS was significantly associated with psychopathy(β=0.08,p<0.001).The relationship between CEU and psychopathy is mediated independently and sequentially by insecure attachment and LHS.Conclusion:The current research shows the relationship between CEU and psychopathy,as well as the mechanism of insecure attachment and life history strategy as mediators.展开更多
Somatic cell nuclear transfer(SCNT)has been successfully employed across various mammalian species,yet cloned animals consistently exhibit low pregnancy rates,primarily due to placental abnormalities such as hyperplas...Somatic cell nuclear transfer(SCNT)has been successfully employed across various mammalian species,yet cloned animals consistently exhibit low pregnancy rates,primarily due to placental abnormalities such as hyperplasia and hypertrophy.This study investigated the involvement of the Hippo signaling pathway in aberrant placentaldevelopmentinSCNT-inducedbovine pregnancies.SCNT-derived cattle exhibited placental hypertrophy,including enlarged abdominal circumference and altered placental cotyledon morphology.RNA sequencing analysis indicated significant dysregulation of Hippo signaling pathway genes in SCNT placentas.Coexpression of YAP1 and CCND1 was observed in cloned blastocysts,placental tissues,and bovine placental mesenchymal stem cells(bPMSCs).Manipulation of YAP1expression demonstrated the capacity to regulate bPMSC proliferation.Experimental assays confirmed the direct binding of YAP1 to CCND1,which subsequently promoted CCND1 expression in bPMSCs.Furthermore,inhibition of CDK6,a downstream target of CCND1,attenuated SCNT bPMSC proliferation.This study identified YAP1 as a key regulatory component within the Hippo signaling pathway that drives placental hyperplasia in cloned cattle through up-regulation of CCND1-CDK6 expression,facilitating cell cycle progression.These findings offer potential avenues for enhancing cloning efficiency,with implications for evolutionary biology and the conservation of valuable germplasm resources.展开更多
Soil organic carbon(SOC)plays a crucial role in mangrove blue carbon formation,yet the differences in microbemediated underlying SOC sequestration between introduced and native mangroves remain unclear.Here,we compare...Soil organic carbon(SOC)plays a crucial role in mangrove blue carbon formation,yet the differences in microbemediated underlying SOC sequestration between introduced and native mangroves remain unclear.Here,we compared the SOC pool,including recalcitrant organic carbon(ROC)and labile carbon pools,as well as three residual carbon sources(amino sugars,lignin phenols,and lipids)in sediments between mangroves of introduced Sonneratia apetala and native Kandelia obovata,and further connected them with microbial life strategies and C metabolism capability.The results showed that SOC accumulation in S.apetala(SA)sediment was about 30%-50% of that in K.obovata(KO)sediment.ROC was the dominant form of SOC in long-term sequestration(76%-83%),while lignin phenols,amino sugars,and lipids were important sources of ROC.In S.apetala sediments,the ROC content was positively correlated with amino sugars,resulting from the more r-strategist microbes that can rapidly convert plant-derived carbon into microbial biomass,which is subsequently transformed into microbial necromass.In contrast,in K.obovata sediments,ROC content showed a stronger positive correlation with the concentrations of lignin phenols and lipids.More K-strategist fungi in the topsoil of K.obovata increased enzyme activities,while more K-strategist bacteria in the subsoil enhanced carbon utilization capacity,thereby increasing lignin phenols and lipids from plant residues in both soil layers.Meanwhile,higher Ca^(2+)concentrations in K.obovata sediments protected three residual carbons from further microbe decomposition.This study provides valuable insights into the molecular mechanisms of SOC sequestration mediated by microbial life strategies in mangrove ecosystems.展开更多
Ulva prolifera green tides are becoming aworldwide environmental problem,especially in the Yellow Sea,China.However,the effects of the occurrence of U.prolifera green tides on the community organization and stability ...Ulva prolifera green tides are becoming aworldwide environmental problem,especially in the Yellow Sea,China.However,the effects of the occurrence of U.prolifera green tides on the community organization and stability of surrounding microbiomes have still not been de-termined.Here,the prokaryotic microbial community network stability and assembly char-acteristics were systematically analyzed and compared between the green tide and non-green tide periods.U.prolifera blooms weaken the community complexity and robustness of surrounding microbiomes,increasing fragmentation and decreasing diversity.Bacteria and archaea exhibited distinct community distributions and assembly patterns under the influ-ence of green tides,and bacterial communities were more sensitive to outbreaks of green tides.The bacterial communities exhibited a greater niche breadth and a lower phyloge-netic distance during the occurrence of U.prolifera green tides compared to those during the non-green tide period while archaeal communities remained unchanged,suggesting that the bacterial communities underwent stronger homogeneous selection and more sensitive to green tide blooms than the archaeal communities.Piecewise structural equation model analysis revealed that the different responses of major prokaryotic microbial groups,such as Cyanobacteria,to environmental variables during green tides,were influenced by the variations in pH and nitrate during green tides and correlated with the salinity gradient during the non-green tide period.This study elucidates the response of the adaptability,associations,and stability of surrounding microbiomes to outbreaks of U.prolifera green tides.展开更多
Understanding how species diverge and adapt is fundamental to unraveling biodiversity.While environmental impacts on species evolution are well-documented,the roles of intrinsic life-history traits remain underexplore...Understanding how species diverge and adapt is fundamental to unraveling biodiversity.While environmental impacts on species evolution are well-documented,the roles of intrinsic life-history traits remain underexplored.The Qinghai-Xizang Plateau,with its harsh conditions and unique biodiversity,offers a natural laboratory for such investigations.Here,we examine two sympatric small mammals—the solitary,low-dispersal plateau zokor(Eospalax baileyi)and the social,high-dispersal plateau pika(Ochotona curzoniae)—to elucidate how life-history traits shape population structures and adaptive strategies.Through whole-genome sequencing and cardiac-blood phenotype analyses,we reveal striking differences in their evolutionary trajectories.Despite enduring similar environmental pressures,plateau zokor populations exhibit pronounced genetic subdivisions,high inbreeding,and distinct local adaptations.In contrast,plateau pika populations display genetic panmixia,widespread diversity,and adaptive uniformity.Demographic inference highlights that plateau zokors experienced severe population bottlenecks and restricted gene flow during glacial periods,underscoring the impact of dispersal capacity on evolutionary outcomes.Our findings demonstrate that intrinsic biological traits,particularly dispersal ability,fundamentally influence genetic architecture,population connectivity,and local adaptation.This study not only provides empirical evidence of how life-history traits shape evolutionary dynamics but also offers a framework for integrating intrinsic and extrinsic factors in understanding biodiversity formation.展开更多
Understanding the molecular relevance of metabolic rate(MR)is crucial for unveiling the mechanisms driving the evolution of animals.In this study,we investigated the association between mitochondrial DNA characteristi...Understanding the molecular relevance of metabolic rate(MR)is crucial for unveiling the mechanisms driving the evolution of animals.In this study,we investigated the association between mitochondrial DNA characteristics and both resting and maximal MRs in conjunction with life-history traits among 139 species of teleost fish,We gathered fish MR data from various sources and procured sequences of 13 mitochondrial protein-encoding genes.We calculated the absolute substitution rate for entire nucleotide sequences and 4-fold degenerate sites of each gene,along with encoding amino acid sequences.Using the phylogenetic comparative method,we then explored the associations between MR and mitochondrial DNA absolute substitution rate.Additionally,we screened MR-associated single nucleotide variants in mitochondrial DNA.The findings indicate no positive correlation between MRs and any substitution rate values of both combined sequences and individual mitochondrial protein-coding genes,refuting the MR hypothesis.Instead,both maximum body size and longevity correlated negatively with molecular substitution rates,suggesting their influences on both mutation and fixation within mitochondrial genes in fish.Results also revealed significant correlations between base variation at ATP6_169 and both resting MR and maximum MR,identifying the unique ATP6_169G in Scombridae fish,which results in an extremely low isoelectric point(pl)value of the ATP6 protein.Considering its functional significance,the ATP6_169G in Scombridae fish might link to their lifestyle characterized by fast locomotion and high metabolic demands alongside a slower molecular evolutionary rate.展开更多
BACKGROUND Rotavirus(RV),a primary cause of diarrhea-related mortality in 2021,has been shown to damage intestinal epithelial cells while upregulating intestinal stem cells(ISCs)activities.ISCs within the crypt niche ...BACKGROUND Rotavirus(RV),a primary cause of diarrhea-related mortality in 2021,has been shown to damage intestinal epithelial cells while upregulating intestinal stem cells(ISCs)activities.ISCs within the crypt niche drive the continuous self-renewal of intestinal epithelium,preserving its barrier functions.Paneth cells secrete antimicrobial peptide and signaling molecules within the intestine crypt,thereby playing a crucial role in intestinal immune defense and providing ISCs functional support.However,the regulatory function of Paneth cells under pathological conditions,such as RV infection,remains unclear.AIM To determine the impact of RV infection on Paneth cells and how Paneth cells regulate ISCs during intestinal injury repair.METHODS We constructed a reference genome for the RV enteric cytopathogenic human orphan virus strain and reanalyzed published single-cell RNA sequencing data to investigate Paneth cell responses to RV-induced intestinal injury.We derived Paneth-ISC communication networks using CellChat,tracked ISC differentiation with pseudotime analysis,and validated our findings in leucine-rich repeat-containing G protein-coupled receptor 5-enhanced green fluorescent protein-internal ribosomal entry site-Cre recombinase estrogen receptor variant 2 mice and organoids via immunofluorescence,flow cytometry,and reverse transcription quantitative polymerase chain reaction.RESULTS We found that RV directly infects Paneth cells,leading to a reduction in mature Paneth cells and an increase in kallikrein 1-high immature Paneth cells.Paneth-ISC communication was significantly enhanced.In particular,the bone morphogenic protein 7(BMP7)-activin A receptor type 2B/BMP receptor type 1A-Smad pathway was upregulated post-infection,suggesting that Paneth cells suppress excessive ISC proliferation.Functional validation confirmed activation of this pathway.CONCLUSION Paneth cells regulate ISC proliferation during RV infection by activating BMP7 signaling,limiting excessive stem cell expansion and preserving crypt homeostasis for effective epithelial repair.展开更多
Although p21-activated kinase 2(PAK2)is an essential serine/threonine protein kinase,its role in the progression of lung squamous cell carcinoma(LUSC)has yet to be fully understood.We analyzed PAK2 mRNA levels,DNA cop...Although p21-activated kinase 2(PAK2)is an essential serine/threonine protein kinase,its role in the progression of lung squamous cell carcinoma(LUSC)has yet to be fully understood.We analyzed PAK2 mRNA levels,DNA copy numbers,and protein levels by quantitative reverse transcription-PCR and immunohistochemical staining in both human LUSC tissues and adjacent normal tissues.Then,we performed colony formation assays,cell counting kit-8 assays,Matrigel invasion assays,wound healing assays,and xenograft models in nude mice to investigate the functions of PAK2 in LUSC progression.We demonstrated that PAK2 mRNA levels,DNA copy numbers,and protein levels were upregulated in human LUSC tissues,compared with adjacent normal tissues.Additionally,higher PAK2 expression was associated with poorer prognosis in LUSC patients.In the in vitro study,we found that PAK2 promoted cell growth,migration,invasion,epithelialmesenchymal transition,and cell morphology regulation in LUSC cells.Mechanistically,PAK2 promoted tumor cell proliferation,migration,and invasion by regulating actin dynamics through the LIMK1/cofilin signaling pathway.Our findings indicate that the PAK2/LIMK1/cofilin signaling pathway may serve as a potential clinical marker and therapeutic target for LUSC.展开更多
Human bocavirus 1(HBoV1;family:Parvoviridae)causes a wide spectrum of respiratory diseases in children and gastroenteritis in adults.A lack of sensitive cell lines and efficient animal models hinders research on HBoV,...Human bocavirus 1(HBoV1;family:Parvoviridae)causes a wide spectrum of respiratory diseases in children and gastroenteritis in adults.A lack of sensitive cell lines and efficient animal models hinders research on HBoV,including the development of anti-HBoV drugs or vaccines.Although the construction of a wild-type HBoV1 infectious clone has been reported,generating HBoV1 infectious clone carrying foreign reporter genes with suitable insertion sites in its genome while retaining replicative ability remains challenging.Here,HBoV1 infectious clones harboring the 11-amino-acid HiBiT tag at five distinct insertion sites were constructed and evaluated.Only the recombinant HBoV1 carrying the HiBiT tag in the N-terminus of the NS1 protein(HBoV1-HiBiTNS1)displayed comparable characteristics to wild-type HBoV1 as determined via the analysis of viral DNA copy number,NanoLuc activity,viral protein expression,and the formation of replication intermediates.Notably,the replication kinetics of HBoV1-HiBiTNS1 could be examined by monitoring NanoLuc activity,which was noted to be correlated with the viral DNA level.Additionally,we successfully applied HiBiT-tagged HBoV1 for the evaluation of antiviral drug activity and identified ivermectin(EC50=2.27μM)as a potent anti-HBoV1 replication drug.Overall,our study demonstrated that the HBoV1-HiBiTNS1 reporter can serve as a convenient platform for screening candidate drugs targeting HBoV1 replication and may also be useful for investigating the life cycle of the virus.展开更多
Background:The maturation of the immune system is critical during early life,as it involves the differentiation,maturation,and establishment of immune tolerance of immune cells.This process is influenced not only by g...Background:The maturation of the immune system is critical during early life,as it involves the differentiation,maturation,and establishment of immune tolerance of immune cells.This process is influenced not only by genetic factors but also by en-vironmental factors,particularly the symbiotic microbiota.Bifidobacterium animalis subsp.lactis(BB-12),originally found in dairy products,is widely used in infant for-mula and dietary supplements.However,its role and mechanisms in immune develop-ment during early life remain unclear.Methods:Using GF mice as the experimental model,B.animalis subsp.lactis BB-12 was administered via gavage during early life.In the juvenile stage,changes in T-cell subsets in the spleen,thymus,and gut intraepithelial lymphocytes(IEL)were assessed using spectral flow cytometry.Additionally,targeted metabolomics analysis of trypto-phan metabolism and short-chain fatty acid pathways in colonic tissue was conducted to explore how B.animalis subsp.lactis BB-12 influences the immune system through gut microbiota metabolism.Results:BB-12 effectively modulates the gut immune microenvironment,leading to beneficial changes in T-cell subsets in key immune tissues such as the spleen,thymus,and gut IELs.Metabolomics analysis further supports these findings by showing that BB-12 intervention greatly increased the production of tryptophan derivatives and acetic acid in the colon of GF mice.Conclusion:The findings provide theoretical evidence for the role of B.animalis subsp.lactis in immune system development and support its application in dietary supple-ments,suggesting potential as a component for infant immune health and in prevent-ing immune-related diseases.展开更多
BACKGROUND Proteins play a central role in regulating biological functions,and various pathways regulate their synthesis and secretion.Endoplasmic reticulum-associated protein degradation(ERAD)is crucial for monitorin...BACKGROUND Proteins play a central role in regulating biological functions,and various pathways regulate their synthesis and secretion.Endoplasmic reticulum-associated protein degradation(ERAD)is crucial for monitoring protein synthesis and processing unfolded or misfolded proteins in actively growing tumor cells.However,the role of the multiple ERAD complexes in liver cancer remains unclear.AIM To elucidate the effects of SEL1L-mediated ERAD on Huh7 and explore the underlying mechanisms in vivo and in vitro.METHODS Huh7 cells were treated with ERAD inhibitor to identify ERAD’s role.Cell counting kit-8,5-ethynyl-2’-deoxyuridine and colony formation experiments were performed.Apoptosis level and migration ability were assessed using fluorescence activated cell sorting and Transwell assay,respectively.Huh7 SEL1L knockout cell line was established via clustered regularly interspaced short palindromic repeats,proliferation,apoptosis,and migration were assessed through previous experiments.The role of SEL1L in vivo and the downstream target of SEL1L were identified using Xenograft and mass spectrometry,respectively.RESULTS The ERAD inhibitor suppressed cell proliferation and migration and promoted apoptosis.SEL1L-HRD1 significantly influenced Huh7 cell growth.SEL1L knockout suppressed tumor cell proliferation and migration and enhanced apoptosis.Mass spectrometry revealed EXT2 is a primary substrate of ERAD.SEL1L knockout significantly increased the protein expression of EXT2.Furthermore,EXT2 knockdown partially restored the effect of SEL1L knockout.CONCLUSION ERAD inhibition suppressed the proliferation and migration of Huh7 and promoted its apoptosis.EXT2 plays an important role and ERAD might be a potential treatment for Huh7 hepatocellular carcinoma.展开更多
Objective This study aimed to explore the interplay between the life-course body mass index(BMI)trajectories and insulin resistance(IR)on incident diabetes.Methods This longitudinal cohort included 2,336 participants ...Objective This study aimed to explore the interplay between the life-course body mass index(BMI)trajectories and insulin resistance(IR)on incident diabetes.Methods This longitudinal cohort included 2,336 participants who had BMI repeatedly measured 3–8times between 1989 and 2009,as well as glucose and insulin measured in 2009.BMI trajectories were identified using a latent class growth mixed model.The interplay between BMI trajectories and IR on diabetes was explored using the four-way effect decomposition method.Logistic regression and mediation models were used to estimate the interaction and mediation effects,respectively.Results Three distinct BMI trajectory groups were identified:low-stable(n=1,625),mediumincreasing(n=613),and high-increasing(n=98).Both interaction and mediation effects of BMI trajectories and IR on incident diabetes were significant(P<0.05).The proportion of incident diabetes was higher in the IR-obesity than in the insulin-sensitivity(IS)obesity group(18.9%vs.5.8%,P<0.001).After adjusting for covariates,the odds ratios(95%confidence intervals)of the IR,IS-obesity,and IRobesity groups vs.the normal group were 3.22(2.05,5.16),2.05(1.00,3.97),and 7.98(5.19,12.62),respectively.IR mediated 10.7%of the total effect of BMI trajectories on incident diabetes(P<0.001).Conclusion We found strong interactions and weak mediation effects of IR on the relationship between life-course BMI trajectories and incident diabetes.IS-obesity is associated with a lower risk of incident diabetes than IR-obesity.展开更多
In this editorial,we examine a paper by Koizumi et al,on the role of peroxisome proliferator-activated receptor(PPAR)agonists in alcoholic liver disease(ALD).The study determined whether elafibranor protected the inte...In this editorial,we examine a paper by Koizumi et al,on the role of peroxisome proliferator-activated receptor(PPAR)agonists in alcoholic liver disease(ALD).The study determined whether elafibranor protected the intestinal barrier and reduced liver fibrosis in a mouse model of ALD.The study also underlines the role of PPARs in intestinal barrier function and lipid homeostasis,which are both affected by ALD.Effective therapies are necessary for ALD because it is a critical health issue that affects people worldwide.This editorial analyzes the possibility of PPAR agonists as treatments for ALD.As key factors of inflammation and metabolism,PPARs offer multiple methods for managing the complex etiology of ALD.We assess the abilities of PPARα,PPARγ,and PPARβ/δagonists to prevent steatosis,inflammation,and fibrosis due to liver diseases.Recent research carried out in preclinical and clinical settings has shown that PPAR agonists can reduce the severity of liver disease.This editorial discusses the data analyzed and the obstacles,advantages,and mechanisms of action of PPAR agonists for ALD.Further research is needed to understand the efficacy,safety,and mechanisms of PPAR agonists for treating ALD.展开更多
Background:A greater prevalence of arrhythmias has been described in endurance athletes,but it remains unclear whether this risk persists after detraining.We aimed to evaluate the prevalence of arrhythmias and their r...Background:A greater prevalence of arrhythmias has been described in endurance athletes,but it remains unclear whether this risk persists after detraining.We aimed to evaluate the prevalence of arrhythmias and their relationship with cardiac remodeling in lifelong and retired master endurance athletes compared to non-athletic controls.Methods:We performed a cross-sectional analysis of observational studies that used echocardiography and cardiac magnetic resonance to detail cardiac structure and function,and Holter monitors to identify atrial and ventricular arrhythmias in 185 endurance athletes and 81 non-athletic controls aged≥40 years.Athletes were categorized as active lifelong(n=144)or retired(n=41)based on hours per week of high-intensity endurance exercise within 5 years of enrollment and validated by percentage of predicted maximal oxygen consumption(VO_(2max)).Athletes with overt cardiomyopathies,channelopathies,pre-excitation,and/or myocardial infarction were excluded.Results:Lifelong athletes(median age=55 years(interquartile range(IQR):46-62),79%male)were significantly fitter than retired athletes(median age=66 years(IQR:58-71),95%male)and controls(median age=53 years(IQR:48-60),96%male),respectively(predicted VO_(2max):131%±18%vs.99%±14%vs.98%±15%,p<0.001).Compared to controls,athletes in our cohort had a higher prevalence of atrial fibrillation((AF):32%vs.0%,p<0.001)and non-sustained ventricular tachycardia((NSVT):9%vs.1%,p=0.007).There was no difference in prevalence of any arrhythmia between lifelong and retired athletes.Lifelong athletes had larger ventricular volumes than retired athletes,who had ventricular volumes similar to controls(left ventricular end-diastolic volume indexed to body surface area(LVEDVi):101±20 m L/m^(2)vs.86±16 mL/m^(2)vs.94±18 mL/m^(2),p<0.001;right ventricular end-diastolic volume indexed to body surface area(RVEDVi):117±23 mL/m^(2)vs.101±19 mL/m^(2)vs.100±19 mL/m^(2),p<0.001).Athletes had more scar(40%vs.18%,p=0.002)and larger left atria(median volume=45m L/m^(2)(IQR:38-52)vs.31 mL/m^(2)(IQR:25-38),p<0.001)than controls,with no difference in atrial volumes and non-ischaemic scar between the athlete groups.Conclusion:Master endurance athletes have a higher prevalence of AF and NSVT than non-athletic controls.Whereas ventricular remodeling tends to reverse with detraining,the propensity to arrhythmias persists regardless of whether they are actively exercising or retired.展开更多
Mutations in the microrchidia CW-type zinc finger protein 2(MORC2)gene are the causative agent of Charcot-Marie-Tooth disease type 2Z(CMT2Z),and the hotspot mutation p.S87L is associated with a more seve re spinal mus...Mutations in the microrchidia CW-type zinc finger protein 2(MORC2)gene are the causative agent of Charcot-Marie-Tooth disease type 2Z(CMT2Z),and the hotspot mutation p.S87L is associated with a more seve re spinal muscular atrophy-like clinical phenotype.The aims of this study were to determine the mechanism of the severe phenotype caused by the MORC2 p.S87L mutation and to explore potential treatment strategies.Epithelial cells were isolated from urine samples from a spinal muscular atrophy(SMA)-like patient[MORC2 p.S87L),a CMT2Z patient[MORC2 p.Q400R),and a healthy control and induced to generate pluripotent stem cells,which were then differentiated into motor neuron precursor cells.Next-generation RNA sequencing followed by KEGG pathway enrichment analysis revealed that differentially expressed genes involved in the PI3K/Akt and MAP K/ERK signaling pathways were enriched in the p.S87L SMA-like patient group and were significantly downregulated in induced pluripotent stem cells.Reduced proliferation was observed in the induced pluripotent stem cells and motor neuron precursor cells derived from the p.S87L SMA-like patient group compared with the CMT2Z patient group and the healthy control.G0/G1 phase cell cycle arrest was observed in induced pluripotent stem cells derived from the p.S87L SMA-like patient.MORC2 p.S87Lspecific antisense oligonucleotides(p.S87L-ASO-targeting)showed significant efficacy in improving cell prolife ration and activating the PI3K/Akt and MAP K/ERK pathways in induced pluripotent stem cells.Howeve r,p.S87L-ASO-ta rgeting did not rescue prolife ration of motor neuron precursor cells.These findings suggest that downregulation of the PI3K/Akt and MAP K/ERK signaling pathways leading to reduced cell proliferation and G0/G1 phase cell cycle arrest in induced pluripotent stem cells might be the underlying mechanism of the severe p.S87L SMA-like phenotype.p.S87L-ASO-targeting treatment can alleviate disordered cell proliferation in the early stage of pluripotent stem cell induction.展开更多
Automatically detecting Ulva prolifera(U.prolifera)in rainy and cloudy weather using remote sensing imagery has been a long-standing problem.Here,we address this challenge by combining high-resolution Synthetic Apertu...Automatically detecting Ulva prolifera(U.prolifera)in rainy and cloudy weather using remote sensing imagery has been a long-standing problem.Here,we address this challenge by combining high-resolution Synthetic Aperture Radar(SAR)imagery with the machine learning,and detect the U.prolifera of the South Yellow Sea of China(SYS)in 2021.The findings indicate that the Random Forest model can accurately and robustly detect U.prolifera,even in the presence of complex ocean backgrounds and speckle noise.Visual inspection confirmed that the method successfully identified the majority of pixels containing U.prolifera without misidentifying noise pixels or seawater pixels as U.prolifera.Additionally,the method demonstrated consistent performance across different im-ages,with an average Area Under Curve(AUC)of 0.930(+0.028).The analysis yielded an overall accuracy of over 96%,with an average Kappa coefficient of 0.941(+0.038).Compared to the traditional thresholding method,Random Forest model has a lower estimation error of 14.81%.Practical application indicates that this method can be used in the detection of unprecedented U.prolifera in 2021 to derive continuous spatiotemporal changes.This study provides a potential new method to detect U.prolifera and enhances our under-standing of macroalgal outbreaks in the marine environment.展开更多
Stylonema alsidii(Zandardini)Drew f.ramosum Zheng et Li is a common species in the genus Stylonema,but there are limited reports on morphological taxonomy and a lack of studies on life history and the regulation of ea...Stylonema alsidii(Zandardini)Drew f.ramosum Zheng et Li is a common species in the genus Stylonema,but there are limited reports on morphological taxonomy and a lack of studies on life history and the regulation of early development.The early development,discoid formation,and erect thallus growth of Stylonema alsidii f.ramosum were observed under laboratory conditions.In addition,the influence of main environmental factors such as temperature and light intensity on its development was briefly studied,and various stages of its life history were observed.The result shows:(1)there are two reproductive modes:asexual reproduction and sexual reproduction;(2)the morphology of this species varies in different degrees under laboratory culture conditions;(3)sexual reproduction and asexual reproduction can coexist under suitable conditions.Five pathways of life history were inferred from experimental phenomena.Mature sporophytes form mature gametophytes by producing initially isolated or initially attached monospore,and mature gametophytes form mature sporophytes by fertilization of eggs and sperms.The sexual and asexual reproduction processes of Stylonema alsidii f.ramosum were reported for the first time,and this is also the first report on sexual reproduction in the genus Stylonema.展开更多
As a cell proliferation regulator involved in wide biological processes in plants,GRF-INTERACTING FACTOR(GIF)controls different tissues development.However,whether GIF participates in fruit development remains unclear...As a cell proliferation regulator involved in wide biological processes in plants,GRF-INTERACTING FACTOR(GIF)controls different tissues development.However,whether GIF participates in fruit development remains unclear.According to transcriptome data,we identified PbGIF1was highly expressed during fruit development in cytokinins induced parthenocarpy pear.In the present study,the biofunction of PbGIF1 was initially verified.Overexpression of PbGIF1 promoted fruit size of transgenic tomato.The size of flesh fruit was not affected by cell expansion but the cell proliferation was promoted by overexpressing Pb GIF1.The accelerated cell proliferation process was also observed in PbGIF1-overexpressed transgenic pear fruit calli.The transcriptional regulation of cytokinins on PbGIF1 was further confirmed by exogenous CPPU treatments in pear fruitlets.To investigate the underlying mechanism,the cytokinins-responded factor,PbRR1,was further focused on.The results of Yeast-one-hybrid assay suggested that PbRR1 can bind to the promoter sequence of PbGIF1.The transcriptional activation of PbRR1 on PbGIF1 was also confirmed by Dual-Luciferase assays.Taken together,the results showed that cytokinins control pear fruit development via the transcriptional activation of PbGIF1 by PbRR1.展开更多
基金supported by the Ministry of Education of the Republic of Korea and the National Research Foundation of Republic of Korea(NRF-2021S1A3A2A02096338).
文摘Background:In this study,we aimed to validate and test the reliability of the Yonsei lifestyle profile(YLP)in assessing multifaceted health lifestyle levels in a study population from the United States.Methods:The YLP-English version and health-promoting lifestyle profile II were administered to 100 individuals living in the United States.Concurrent validity was analyzed using Pearson's correlation coefficient,and discriminant validity was examined by comparing sex and age differences through t-tests and multiple variance analysis.Internal consistency was assessed using Cronbach'sαfor each sub-factor.Results:The YLP-English Version demonstrated concurrent validity with the Health-Promoting Lifestyle Profile II,showing consistent correlations for the total score(0.3,p<0.01)and frequency sub-factors(0.25-0.69,p<0.01).Among the satisfaction sub-factors,only nutrition showed a weak negative correlation(-0.19,p<0.01);all others were nonsignificant.Discriminant validity revealed no significant sex differences,but physical activity frequency varied across age groups.Internal consistency was high(Cronbach'sα=0.80-0.86).Conclusion:In this study,we validated the YLP-English version as a reliable instrument for assessing health-related lifestyle behaviors.The YLP uniquely captures both lifestyle frequency and satisfaction,offering a comprehensive perspective on health behaviors.Although this tool is currently most applicable in population-level studies,future research should establish clinical thresholds to enhance its utility in individualized health assessments and interventions.
基金supported by the Guangdong Basic and Applied Basic Research Foundation(2020A1515110608)Department of Education of Guangdong Province-Guangdong Province General University Youth Innovative Talent Project(2019KQNCX039).
文摘Background:Childhood environmental unpredictability(CEU)is crucial to personal development,profoundly influence physical and psychological growth particularly,and psychopathy is recognized as a dark personality trait.The aim of this study is to investigate the effects of insecure attachment and life history strategy(LHS)on the relationship between CEU and psychopathy by establishing a sequential mediation model based on evolutionary life history theory and cognitive-affective personality system.Methods:A group of 532 undergraduates completed the measurements for CEU,insecure attachment,LHS,and psychopathy,and Bootstrap mediation test through SPSS 25.0 and PROCESS macro tool was used to examine the relationship among these variables.Results:The results revealed positive relations between CEU and insecure attachment(β=0.87,p<0.001),CEU and LHS(β=0.11,p<0.001),and CEU and psychopathy(β=0.14,p<0.001).Insecure attachment was also positively associated with LHS(β=0.62,p<0.001)and psychopathy(β=0.04,p<0.001).In addition,LHS was significantly associated with psychopathy(β=0.08,p<0.001).The relationship between CEU and psychopathy is mediated independently and sequentially by insecure attachment and LHS.Conclusion:The current research shows the relationship between CEU and psychopathy,as well as the mechanism of insecure attachment and life history strategy as mediators.
基金supported by the National Natural Science Foundation of China (32060755)Natural Science Foundation of Inner Mongolia (2024MS03001)+7 种基金Inner Mongolia Autonomous Region Open Competition Projects (2022JBGS0018)Program for Young Talents of Science and Technology in Universities of Inner Mongolia Autonomous Region (NJYT23090)Inner Mongolia Autonomous Region Science and Technology Leading Team (2022LJRC0006)Inner Mongolia Autonomous Region Science and Technology Major Project (2021ZD0009)Major Agricultural Science and Technology Project of the Ministry of Agriculture and Rural Affairs (NK2022130203)Central Government Guides Local Science and Technology Development Funds (2022ZY0212)Inner Mongolia Autonomous Region High-level Talent Support ProgramInner Mongolia University Chief Scientist Program。
文摘Somatic cell nuclear transfer(SCNT)has been successfully employed across various mammalian species,yet cloned animals consistently exhibit low pregnancy rates,primarily due to placental abnormalities such as hyperplasia and hypertrophy.This study investigated the involvement of the Hippo signaling pathway in aberrant placentaldevelopmentinSCNT-inducedbovine pregnancies.SCNT-derived cattle exhibited placental hypertrophy,including enlarged abdominal circumference and altered placental cotyledon morphology.RNA sequencing analysis indicated significant dysregulation of Hippo signaling pathway genes in SCNT placentas.Coexpression of YAP1 and CCND1 was observed in cloned blastocysts,placental tissues,and bovine placental mesenchymal stem cells(bPMSCs).Manipulation of YAP1expression demonstrated the capacity to regulate bPMSC proliferation.Experimental assays confirmed the direct binding of YAP1 to CCND1,which subsequently promoted CCND1 expression in bPMSCs.Furthermore,inhibition of CDK6,a downstream target of CCND1,attenuated SCNT bPMSC proliferation.This study identified YAP1 as a key regulatory component within the Hippo signaling pathway that drives placental hyperplasia in cloned cattle through up-regulation of CCND1-CDK6 expression,facilitating cell cycle progression.These findings offer potential avenues for enhancing cloning efficiency,with implications for evolutionary biology and the conservation of valuable germplasm resources.
基金supported by grants from the National Natural Science Foundation of China(Nos.42076117 and 32160051)the Guangdong Basic and Applied Basic Research Foundation(Nos.2023A1515012772,2024A1515011721,and 2024A1515012249).
文摘Soil organic carbon(SOC)plays a crucial role in mangrove blue carbon formation,yet the differences in microbemediated underlying SOC sequestration between introduced and native mangroves remain unclear.Here,we compared the SOC pool,including recalcitrant organic carbon(ROC)and labile carbon pools,as well as three residual carbon sources(amino sugars,lignin phenols,and lipids)in sediments between mangroves of introduced Sonneratia apetala and native Kandelia obovata,and further connected them with microbial life strategies and C metabolism capability.The results showed that SOC accumulation in S.apetala(SA)sediment was about 30%-50% of that in K.obovata(KO)sediment.ROC was the dominant form of SOC in long-term sequestration(76%-83%),while lignin phenols,amino sugars,and lipids were important sources of ROC.In S.apetala sediments,the ROC content was positively correlated with amino sugars,resulting from the more r-strategist microbes that can rapidly convert plant-derived carbon into microbial biomass,which is subsequently transformed into microbial necromass.In contrast,in K.obovata sediments,ROC content showed a stronger positive correlation with the concentrations of lignin phenols and lipids.More K-strategist fungi in the topsoil of K.obovata increased enzyme activities,while more K-strategist bacteria in the subsoil enhanced carbon utilization capacity,thereby increasing lignin phenols and lipids from plant residues in both soil layers.Meanwhile,higher Ca^(2+)concentrations in K.obovata sediments protected three residual carbons from further microbe decomposition.This study provides valuable insights into the molecular mechanisms of SOC sequestration mediated by microbial life strategies in mangrove ecosystems.
基金supported by the National Key Research and Development Program of China(No.2022YFC2807500)Laoshan Laboratory(No.LSKJ202203201)+1 种基金the National Natural Science Foundation of China(Nos.42206147,42120104006 and 42176111)the Natural Science Foundation of Shandong Province(Nos.ZR2022QD046,ZR2021QD051).
文摘Ulva prolifera green tides are becoming aworldwide environmental problem,especially in the Yellow Sea,China.However,the effects of the occurrence of U.prolifera green tides on the community organization and stability of surrounding microbiomes have still not been de-termined.Here,the prokaryotic microbial community network stability and assembly char-acteristics were systematically analyzed and compared between the green tide and non-green tide periods.U.prolifera blooms weaken the community complexity and robustness of surrounding microbiomes,increasing fragmentation and decreasing diversity.Bacteria and archaea exhibited distinct community distributions and assembly patterns under the influ-ence of green tides,and bacterial communities were more sensitive to outbreaks of green tides.The bacterial communities exhibited a greater niche breadth and a lower phyloge-netic distance during the occurrence of U.prolifera green tides compared to those during the non-green tide period while archaeal communities remained unchanged,suggesting that the bacterial communities underwent stronger homogeneous selection and more sensitive to green tide blooms than the archaeal communities.Piecewise structural equation model analysis revealed that the different responses of major prokaryotic microbial groups,such as Cyanobacteria,to environmental variables during green tides,were influenced by the variations in pH and nitrate during green tides and correlated with the salinity gradient during the non-green tide period.This study elucidates the response of the adaptability,associations,and stability of surrounding microbiomes to outbreaks of U.prolifera green tides.
基金supported by the Second Tibetan Plateau Scientific Expedition and Research(STEP)Program(2019QZKK05010900 and 2019QZKK05010405)the National Natural Science Foundation of China(32100339 and 32200350)+3 种基金Yunnan Revitalization Talent Support Program Top team(202405AS350022)supported by the Youth Innovation Promotion Association,Chinese Academy of Sciencessupported by Yunnan Fundamental Research Projects(202201AU070208)supported by Yunnan Revitalization Talent Support Program Yunling Scholar Project(XML)。
文摘Understanding how species diverge and adapt is fundamental to unraveling biodiversity.While environmental impacts on species evolution are well-documented,the roles of intrinsic life-history traits remain underexplored.The Qinghai-Xizang Plateau,with its harsh conditions and unique biodiversity,offers a natural laboratory for such investigations.Here,we examine two sympatric small mammals—the solitary,low-dispersal plateau zokor(Eospalax baileyi)and the social,high-dispersal plateau pika(Ochotona curzoniae)—to elucidate how life-history traits shape population structures and adaptive strategies.Through whole-genome sequencing and cardiac-blood phenotype analyses,we reveal striking differences in their evolutionary trajectories.Despite enduring similar environmental pressures,plateau zokor populations exhibit pronounced genetic subdivisions,high inbreeding,and distinct local adaptations.In contrast,plateau pika populations display genetic panmixia,widespread diversity,and adaptive uniformity.Demographic inference highlights that plateau zokors experienced severe population bottlenecks and restricted gene flow during glacial periods,underscoring the impact of dispersal capacity on evolutionary outcomes.Our findings demonstrate that intrinsic biological traits,particularly dispersal ability,fundamentally influence genetic architecture,population connectivity,and local adaptation.This study not only provides empirical evidence of how life-history traits shape evolutionary dynamics but also offers a framework for integrating intrinsic and extrinsic factors in understanding biodiversity formation.
基金supported by the National Natural Science Foundation of China[Grant No.:32070438].
文摘Understanding the molecular relevance of metabolic rate(MR)is crucial for unveiling the mechanisms driving the evolution of animals.In this study,we investigated the association between mitochondrial DNA characteristics and both resting and maximal MRs in conjunction with life-history traits among 139 species of teleost fish,We gathered fish MR data from various sources and procured sequences of 13 mitochondrial protein-encoding genes.We calculated the absolute substitution rate for entire nucleotide sequences and 4-fold degenerate sites of each gene,along with encoding amino acid sequences.Using the phylogenetic comparative method,we then explored the associations between MR and mitochondrial DNA absolute substitution rate.Additionally,we screened MR-associated single nucleotide variants in mitochondrial DNA.The findings indicate no positive correlation between MRs and any substitution rate values of both combined sequences and individual mitochondrial protein-coding genes,refuting the MR hypothesis.Instead,both maximum body size and longevity correlated negatively with molecular substitution rates,suggesting their influences on both mutation and fixation within mitochondrial genes in fish.Results also revealed significant correlations between base variation at ATP6_169 and both resting MR and maximum MR,identifying the unique ATP6_169G in Scombridae fish,which results in an extremely low isoelectric point(pl)value of the ATP6 protein.Considering its functional significance,the ATP6_169G in Scombridae fish might link to their lifestyle characterized by fast locomotion and high metabolic demands alongside a slower molecular evolutionary rate.
文摘BACKGROUND Rotavirus(RV),a primary cause of diarrhea-related mortality in 2021,has been shown to damage intestinal epithelial cells while upregulating intestinal stem cells(ISCs)activities.ISCs within the crypt niche drive the continuous self-renewal of intestinal epithelium,preserving its barrier functions.Paneth cells secrete antimicrobial peptide and signaling molecules within the intestine crypt,thereby playing a crucial role in intestinal immune defense and providing ISCs functional support.However,the regulatory function of Paneth cells under pathological conditions,such as RV infection,remains unclear.AIM To determine the impact of RV infection on Paneth cells and how Paneth cells regulate ISCs during intestinal injury repair.METHODS We constructed a reference genome for the RV enteric cytopathogenic human orphan virus strain and reanalyzed published single-cell RNA sequencing data to investigate Paneth cell responses to RV-induced intestinal injury.We derived Paneth-ISC communication networks using CellChat,tracked ISC differentiation with pseudotime analysis,and validated our findings in leucine-rich repeat-containing G protein-coupled receptor 5-enhanced green fluorescent protein-internal ribosomal entry site-Cre recombinase estrogen receptor variant 2 mice and organoids via immunofluorescence,flow cytometry,and reverse transcription quantitative polymerase chain reaction.RESULTS We found that RV directly infects Paneth cells,leading to a reduction in mature Paneth cells and an increase in kallikrein 1-high immature Paneth cells.Paneth-ISC communication was significantly enhanced.In particular,the bone morphogenic protein 7(BMP7)-activin A receptor type 2B/BMP receptor type 1A-Smad pathway was upregulated post-infection,suggesting that Paneth cells suppress excessive ISC proliferation.Functional validation confirmed activation of this pathway.CONCLUSION Paneth cells regulate ISC proliferation during RV infection by activating BMP7 signaling,limiting excessive stem cell expansion and preserving crypt homeostasis for effective epithelial repair.
基金National Natural Science Foundation of China(Grant No.32300615)Nanjing Medical Science and Technique Development Foundation(Grant No.JQX19010)。
文摘Although p21-activated kinase 2(PAK2)is an essential serine/threonine protein kinase,its role in the progression of lung squamous cell carcinoma(LUSC)has yet to be fully understood.We analyzed PAK2 mRNA levels,DNA copy numbers,and protein levels by quantitative reverse transcription-PCR and immunohistochemical staining in both human LUSC tissues and adjacent normal tissues.Then,we performed colony formation assays,cell counting kit-8 assays,Matrigel invasion assays,wound healing assays,and xenograft models in nude mice to investigate the functions of PAK2 in LUSC progression.We demonstrated that PAK2 mRNA levels,DNA copy numbers,and protein levels were upregulated in human LUSC tissues,compared with adjacent normal tissues.Additionally,higher PAK2 expression was associated with poorer prognosis in LUSC patients.In the in vitro study,we found that PAK2 promoted cell growth,migration,invasion,epithelialmesenchymal transition,and cell morphology regulation in LUSC cells.Mechanistically,PAK2 promoted tumor cell proliferation,migration,and invasion by regulating actin dynamics through the LIMK1/cofilin signaling pathway.Our findings indicate that the PAK2/LIMK1/cofilin signaling pathway may serve as a potential clinical marker and therapeutic target for LUSC.
基金supported by the Guangzhou National Laboratory(SRPG22-002 to X.W.Chen)the Pearl River Talent Recruitment Program(2019CX01Y422 to X.W.Chen)+1 种基金the Natural Science Foundation of Guangdong Province(2025A1515011018 to J.L.Tang)the Basic and Applied Basic Research Projects of Guangzhou Basic Research Program(2025A04J5492 to J.L.Tang,2023A04J0161 to Q.Yang).
文摘Human bocavirus 1(HBoV1;family:Parvoviridae)causes a wide spectrum of respiratory diseases in children and gastroenteritis in adults.A lack of sensitive cell lines and efficient animal models hinders research on HBoV,including the development of anti-HBoV drugs or vaccines.Although the construction of a wild-type HBoV1 infectious clone has been reported,generating HBoV1 infectious clone carrying foreign reporter genes with suitable insertion sites in its genome while retaining replicative ability remains challenging.Here,HBoV1 infectious clones harboring the 11-amino-acid HiBiT tag at five distinct insertion sites were constructed and evaluated.Only the recombinant HBoV1 carrying the HiBiT tag in the N-terminus of the NS1 protein(HBoV1-HiBiTNS1)displayed comparable characteristics to wild-type HBoV1 as determined via the analysis of viral DNA copy number,NanoLuc activity,viral protein expression,and the formation of replication intermediates.Notably,the replication kinetics of HBoV1-HiBiTNS1 could be examined by monitoring NanoLuc activity,which was noted to be correlated with the viral DNA level.Additionally,we successfully applied HiBiT-tagged HBoV1 for the evaluation of antiviral drug activity and identified ivermectin(EC50=2.27μM)as a potent anti-HBoV1 replication drug.Overall,our study demonstrated that the HBoV1-HiBiTNS1 reporter can serve as a convenient platform for screening candidate drugs targeting HBoV1 replication and may also be useful for investigating the life cycle of the virus.
基金supported by the National Key R&D Programs of China(2022YFF0710701,2022YFF0710702)Guangzhou Key Research and Development Program(202206010157)+2 种基金Guangzhou Joint Fund for Key Laboratory(202201020381)Medical Joint Fund of Jinan University(YXJC202204)Open Research Project of the Key Laboratory of Viral Pathogenesis and Infection Prevention and Control of the Ministry of Education(2023VPPC-R02).
文摘Background:The maturation of the immune system is critical during early life,as it involves the differentiation,maturation,and establishment of immune tolerance of immune cells.This process is influenced not only by genetic factors but also by en-vironmental factors,particularly the symbiotic microbiota.Bifidobacterium animalis subsp.lactis(BB-12),originally found in dairy products,is widely used in infant for-mula and dietary supplements.However,its role and mechanisms in immune develop-ment during early life remain unclear.Methods:Using GF mice as the experimental model,B.animalis subsp.lactis BB-12 was administered via gavage during early life.In the juvenile stage,changes in T-cell subsets in the spleen,thymus,and gut intraepithelial lymphocytes(IEL)were assessed using spectral flow cytometry.Additionally,targeted metabolomics analysis of trypto-phan metabolism and short-chain fatty acid pathways in colonic tissue was conducted to explore how B.animalis subsp.lactis BB-12 influences the immune system through gut microbiota metabolism.Results:BB-12 effectively modulates the gut immune microenvironment,leading to beneficial changes in T-cell subsets in key immune tissues such as the spleen,thymus,and gut IELs.Metabolomics analysis further supports these findings by showing that BB-12 intervention greatly increased the production of tryptophan derivatives and acetic acid in the colon of GF mice.Conclusion:The findings provide theoretical evidence for the role of B.animalis subsp.lactis in immune system development and support its application in dietary supple-ments,suggesting potential as a component for infant immune health and in prevent-ing immune-related diseases.
基金Supported by the National Natural Science Foundation of China,No.82241219,No.82127808 and No.81921004The Shenzhen Science and Technology Program,No.JCYJ20210324120813037.
文摘BACKGROUND Proteins play a central role in regulating biological functions,and various pathways regulate their synthesis and secretion.Endoplasmic reticulum-associated protein degradation(ERAD)is crucial for monitoring protein synthesis and processing unfolded or misfolded proteins in actively growing tumor cells.However,the role of the multiple ERAD complexes in liver cancer remains unclear.AIM To elucidate the effects of SEL1L-mediated ERAD on Huh7 and explore the underlying mechanisms in vivo and in vitro.METHODS Huh7 cells were treated with ERAD inhibitor to identify ERAD’s role.Cell counting kit-8,5-ethynyl-2’-deoxyuridine and colony formation experiments were performed.Apoptosis level and migration ability were assessed using fluorescence activated cell sorting and Transwell assay,respectively.Huh7 SEL1L knockout cell line was established via clustered regularly interspaced short palindromic repeats,proliferation,apoptosis,and migration were assessed through previous experiments.The role of SEL1L in vivo and the downstream target of SEL1L were identified using Xenograft and mass spectrometry,respectively.RESULTS The ERAD inhibitor suppressed cell proliferation and migration and promoted apoptosis.SEL1L-HRD1 significantly influenced Huh7 cell growth.SEL1L knockout suppressed tumor cell proliferation and migration and enhanced apoptosis.Mass spectrometry revealed EXT2 is a primary substrate of ERAD.SEL1L knockout significantly increased the protein expression of EXT2.Furthermore,EXT2 knockdown partially restored the effect of SEL1L knockout.CONCLUSION ERAD inhibition suppressed the proliferation and migration of Huh7 and promoted its apoptosis.EXT2 plays an important role and ERAD might be a potential treatment for Huh7 hepatocellular carcinoma.
基金supported by Grant 82222064 from the National Natural Science Foundation of Chinathe Shandong University Distinguished Young Scholars。
文摘Objective This study aimed to explore the interplay between the life-course body mass index(BMI)trajectories and insulin resistance(IR)on incident diabetes.Methods This longitudinal cohort included 2,336 participants who had BMI repeatedly measured 3–8times between 1989 and 2009,as well as glucose and insulin measured in 2009.BMI trajectories were identified using a latent class growth mixed model.The interplay between BMI trajectories and IR on diabetes was explored using the four-way effect decomposition method.Logistic regression and mediation models were used to estimate the interaction and mediation effects,respectively.Results Three distinct BMI trajectory groups were identified:low-stable(n=1,625),mediumincreasing(n=613),and high-increasing(n=98).Both interaction and mediation effects of BMI trajectories and IR on incident diabetes were significant(P<0.05).The proportion of incident diabetes was higher in the IR-obesity than in the insulin-sensitivity(IS)obesity group(18.9%vs.5.8%,P<0.001).After adjusting for covariates,the odds ratios(95%confidence intervals)of the IR,IS-obesity,and IRobesity groups vs.the normal group were 3.22(2.05,5.16),2.05(1.00,3.97),and 7.98(5.19,12.62),respectively.IR mediated 10.7%of the total effect of BMI trajectories on incident diabetes(P<0.001).Conclusion We found strong interactions and weak mediation effects of IR on the relationship between life-course BMI trajectories and incident diabetes.IS-obesity is associated with a lower risk of incident diabetes than IR-obesity.
文摘In this editorial,we examine a paper by Koizumi et al,on the role of peroxisome proliferator-activated receptor(PPAR)agonists in alcoholic liver disease(ALD).The study determined whether elafibranor protected the intestinal barrier and reduced liver fibrosis in a mouse model of ALD.The study also underlines the role of PPARs in intestinal barrier function and lipid homeostasis,which are both affected by ALD.Effective therapies are necessary for ALD because it is a critical health issue that affects people worldwide.This editorial analyzes the possibility of PPAR agonists as treatments for ALD.As key factors of inflammation and metabolism,PPARs offer multiple methods for managing the complex etiology of ALD.We assess the abilities of PPARα,PPARγ,and PPARβ/δagonists to prevent steatosis,inflammation,and fibrosis due to liver diseases.Recent research carried out in preclinical and clinical settings has shown that PPAR agonists can reduce the severity of liver disease.This editorial discusses the data analyzed and the obstacles,advantages,and mechanisms of action of PPAR agonists for ALD.Further research is needed to understand the efficacy,safety,and mechanisms of PPAR agonists for treating ALD.
基金funded by the National Health and Medical Research Council of Australia(Grant No.APP1130353)supported by a Royal Australian College of Physicians Research Entry Scholarship(Grant No.2023RES00039)+4 种基金The National Health and Medical Research Council Postgraduate Scholarship(Grant No.2031119)a Heart Foundation PhD Scholarship(Grant No.107659)supported through an Australian Government Research Training Program Scholarshipsupported as a postdoctoral clinical researcher by the Fund for Scientific Research Flanderssupported by a National Health and Medical Research Council of Australia Investigator Grant(Grant No.APP 2027105)。
文摘Background:A greater prevalence of arrhythmias has been described in endurance athletes,but it remains unclear whether this risk persists after detraining.We aimed to evaluate the prevalence of arrhythmias and their relationship with cardiac remodeling in lifelong and retired master endurance athletes compared to non-athletic controls.Methods:We performed a cross-sectional analysis of observational studies that used echocardiography and cardiac magnetic resonance to detail cardiac structure and function,and Holter monitors to identify atrial and ventricular arrhythmias in 185 endurance athletes and 81 non-athletic controls aged≥40 years.Athletes were categorized as active lifelong(n=144)or retired(n=41)based on hours per week of high-intensity endurance exercise within 5 years of enrollment and validated by percentage of predicted maximal oxygen consumption(VO_(2max)).Athletes with overt cardiomyopathies,channelopathies,pre-excitation,and/or myocardial infarction were excluded.Results:Lifelong athletes(median age=55 years(interquartile range(IQR):46-62),79%male)were significantly fitter than retired athletes(median age=66 years(IQR:58-71),95%male)and controls(median age=53 years(IQR:48-60),96%male),respectively(predicted VO_(2max):131%±18%vs.99%±14%vs.98%±15%,p<0.001).Compared to controls,athletes in our cohort had a higher prevalence of atrial fibrillation((AF):32%vs.0%,p<0.001)and non-sustained ventricular tachycardia((NSVT):9%vs.1%,p=0.007).There was no difference in prevalence of any arrhythmia between lifelong and retired athletes.Lifelong athletes had larger ventricular volumes than retired athletes,who had ventricular volumes similar to controls(left ventricular end-diastolic volume indexed to body surface area(LVEDVi):101±20 m L/m^(2)vs.86±16 mL/m^(2)vs.94±18 mL/m^(2),p<0.001;right ventricular end-diastolic volume indexed to body surface area(RVEDVi):117±23 mL/m^(2)vs.101±19 mL/m^(2)vs.100±19 mL/m^(2),p<0.001).Athletes had more scar(40%vs.18%,p=0.002)and larger left atria(median volume=45m L/m^(2)(IQR:38-52)vs.31 mL/m^(2)(IQR:25-38),p<0.001)than controls,with no difference in atrial volumes and non-ischaemic scar between the athlete groups.Conclusion:Master endurance athletes have a higher prevalence of AF and NSVT than non-athletic controls.Whereas ventricular remodeling tends to reverse with detraining,the propensity to arrhythmias persists regardless of whether they are actively exercising or retired.
基金supported by the National Natural Science Foundation of China,Nos.82171172(to RZ)and 81771366(to RZ)Fundamental Research Funds for the Central Universities of Central South University,Nos.2021zzts1095(to SZ)and 2022zzts0832(to HY)。
文摘Mutations in the microrchidia CW-type zinc finger protein 2(MORC2)gene are the causative agent of Charcot-Marie-Tooth disease type 2Z(CMT2Z),and the hotspot mutation p.S87L is associated with a more seve re spinal muscular atrophy-like clinical phenotype.The aims of this study were to determine the mechanism of the severe phenotype caused by the MORC2 p.S87L mutation and to explore potential treatment strategies.Epithelial cells were isolated from urine samples from a spinal muscular atrophy(SMA)-like patient[MORC2 p.S87L),a CMT2Z patient[MORC2 p.Q400R),and a healthy control and induced to generate pluripotent stem cells,which were then differentiated into motor neuron precursor cells.Next-generation RNA sequencing followed by KEGG pathway enrichment analysis revealed that differentially expressed genes involved in the PI3K/Akt and MAP K/ERK signaling pathways were enriched in the p.S87L SMA-like patient group and were significantly downregulated in induced pluripotent stem cells.Reduced proliferation was observed in the induced pluripotent stem cells and motor neuron precursor cells derived from the p.S87L SMA-like patient group compared with the CMT2Z patient group and the healthy control.G0/G1 phase cell cycle arrest was observed in induced pluripotent stem cells derived from the p.S87L SMA-like patient.MORC2 p.S87Lspecific antisense oligonucleotides(p.S87L-ASO-targeting)showed significant efficacy in improving cell prolife ration and activating the PI3K/Akt and MAP K/ERK pathways in induced pluripotent stem cells.Howeve r,p.S87L-ASO-ta rgeting did not rescue prolife ration of motor neuron precursor cells.These findings suggest that downregulation of the PI3K/Akt and MAP K/ERK signaling pathways leading to reduced cell proliferation and G0/G1 phase cell cycle arrest in induced pluripotent stem cells might be the underlying mechanism of the severe p.S87L SMA-like phenotype.p.S87L-ASO-targeting treatment can alleviate disordered cell proliferation in the early stage of pluripotent stem cell induction.
基金Under the auspices of National Natural Science Foundation of China(No.42071385)National Science and Technology Major Project of High Resolution Earth Observation System(No.79-Y50-G18-9001-22/23)。
文摘Automatically detecting Ulva prolifera(U.prolifera)in rainy and cloudy weather using remote sensing imagery has been a long-standing problem.Here,we address this challenge by combining high-resolution Synthetic Aperture Radar(SAR)imagery with the machine learning,and detect the U.prolifera of the South Yellow Sea of China(SYS)in 2021.The findings indicate that the Random Forest model can accurately and robustly detect U.prolifera,even in the presence of complex ocean backgrounds and speckle noise.Visual inspection confirmed that the method successfully identified the majority of pixels containing U.prolifera without misidentifying noise pixels or seawater pixels as U.prolifera.Additionally,the method demonstrated consistent performance across different im-ages,with an average Area Under Curve(AUC)of 0.930(+0.028).The analysis yielded an overall accuracy of over 96%,with an average Kappa coefficient of 0.941(+0.038).Compared to the traditional thresholding method,Random Forest model has a lower estimation error of 14.81%.Practical application indicates that this method can be used in the detection of unprecedented U.prolifera in 2021 to derive continuous spatiotemporal changes.This study provides a potential new method to detect U.prolifera and enhances our under-standing of macroalgal outbreaks in the marine environment.
基金Supported by the National Natural Science Foundation of China(Nos.31970216,32270219)。
文摘Stylonema alsidii(Zandardini)Drew f.ramosum Zheng et Li is a common species in the genus Stylonema,but there are limited reports on morphological taxonomy and a lack of studies on life history and the regulation of early development.The early development,discoid formation,and erect thallus growth of Stylonema alsidii f.ramosum were observed under laboratory conditions.In addition,the influence of main environmental factors such as temperature and light intensity on its development was briefly studied,and various stages of its life history were observed.The result shows:(1)there are two reproductive modes:asexual reproduction and sexual reproduction;(2)the morphology of this species varies in different degrees under laboratory culture conditions;(3)sexual reproduction and asexual reproduction can coexist under suitable conditions.Five pathways of life history were inferred from experimental phenomena.Mature sporophytes form mature gametophytes by producing initially isolated or initially attached monospore,and mature gametophytes form mature sporophytes by fertilization of eggs and sperms.The sexual and asexual reproduction processes of Stylonema alsidii f.ramosum were reported for the first time,and this is also the first report on sexual reproduction in the genus Stylonema.
基金supported by the China Agriculture Research System of MOF and MARA。
文摘As a cell proliferation regulator involved in wide biological processes in plants,GRF-INTERACTING FACTOR(GIF)controls different tissues development.However,whether GIF participates in fruit development remains unclear.According to transcriptome data,we identified PbGIF1was highly expressed during fruit development in cytokinins induced parthenocarpy pear.In the present study,the biofunction of PbGIF1 was initially verified.Overexpression of PbGIF1 promoted fruit size of transgenic tomato.The size of flesh fruit was not affected by cell expansion but the cell proliferation was promoted by overexpressing Pb GIF1.The accelerated cell proliferation process was also observed in PbGIF1-overexpressed transgenic pear fruit calli.The transcriptional regulation of cytokinins on PbGIF1 was further confirmed by exogenous CPPU treatments in pear fruitlets.To investigate the underlying mechanism,the cytokinins-responded factor,PbRR1,was further focused on.The results of Yeast-one-hybrid assay suggested that PbRR1 can bind to the promoter sequence of PbGIF1.The transcriptional activation of PbRR1 on PbGIF1 was also confirmed by Dual-Luciferase assays.Taken together,the results showed that cytokinins control pear fruit development via the transcriptional activation of PbGIF1 by PbRR1.
