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
A lactating dairy cow mammary epithelial cell(DCMEC)model is useful for studying milk synthesis and lactation in the dairy cow mammary gland.However,the cells can only maintain their original characteristics for a lim...A lactating dairy cow mammary epithelial cell(DCMEC)model is useful for studying milk synthesis and lactation in the dairy cow mammary gland.However,the cells can only maintain their original characteristics for a limited period in vitro.Thus,the proliferative capacity and lactation pattern of subcultured DCMECs need to be characterized.In the present study,subcultured DCMECs appeared to proliferate without changes in morphology or growth pattern up to the 12th passage.Subculturing had no obvious effect on the lactation capacity of the subcultured DCMEC up to the 10th passage in vitro.These results indicated that the DCMEC line could be subpassaged up to 10 times and still maintain its original milk synthesis characteristics.Moreover,DCMECs were frozen using different methods,and the method of placing the vials in the foam box was determined after cryopreservation with the best adherence of 91.2%.This method was recommended for long-term cryopreservation for DCMECs.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
Objective Telomere length is a key aging biomarker,but its sex-specific impact on individualized life expectancy remains uncertain.This study explores sex differences in leukocyte telomere length(LTL)and individualize...Objective Telomere length is a key aging biomarker,but its sex-specific impact on individualized life expectancy remains uncertain.This study explores sex differences in leukocyte telomere length(LTL)and individualized expected years of life lost(YLL).Methods A prospective cohort of 445,399 participants(203,731 males and 241,668 females)from the UK Biobank was analyzed.LTL values were log-transformed,and YLL was calculated using life tables.Multiple linear regression was applied to examine sex-specific associations.Results In males,each standard deviation(S.D.)increase in LTL was linked to a 0.965-year decrease in YLL(95%CI:–1.025,–0.900;P<0.001).In females,longer LTL was related to a 0.102-year increase in YLL(95%CI:0.057,0.146;P<0.001).Among postmenopausal females,LTL showed a protective effect similar to that in males(0.387-year decrease,95%CI:−0.446,–0.328;P<0.001),while premenopausal females exhibited a detrimental association(0.705-year increase,95%CI:0.625,0.785;P<0.001).Comparable trends were observed across major aging-related diseases,pointing to a consistent biological pattern.Conclusion The influence of LTL on life expectancy varies significantly by sex,with protective associations seen in males and postmenopausal females.This suggests hormonal involvement in telomere dynamics.The results support integrating sex-specific perspectives into aging and telomere research and clinical practice.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
Alzheimer’s disease(AD)is a degenerative disease of the central nervous system.It results in cognitive dysfunction due to the loss of functional neurons and a deficit of new neurons,which can lead to death in severe ...Alzheimer’s disease(AD)is a degenerative disease of the central nervous system.It results in cognitive dysfunction due to the loss of functional neurons and a deficit of new neurons,which can lead to death in severe cases.Repairing damaged neurons by promoting hippocampal neurogenesis has become therapeutic modality to combat neurodegenerative diseases.The novel isoflavone alkaloid LY01,found in the edible fruits of Sophora alopecuroides L.,has various neuroprotective effects.However,the molecular mechanism by which it promotes the proliferation of endogenous neural stem cells(NSCs)is not yet precisely known.The effects of LY01 were investigated in vivo and in vitro.In vivo experiments showed that LY01 could counteract the toxic damage of amyloid β-protein(Aβ),enhance the learning ability and memory capacity of 5×FAD mice,and improve the morphology of neurons in the hippocampal region.In vitro experiments showed that LY01 was effective against antioxidant damage,improved the cell morphology of C17.2 mouse NSCs after hydrogen peroxide injury,and increased cell viability.Both in vitro and in vivo experiments promoted NSC proliferation by upregulating the mRNA and protein levels of the critical genes of the Wnt/β-catenin pathway,which increased levels of doublecortin to facilitate new neuronal generation.This indicates that the ability of LY01 to counteract Aβ toxicity and alleviate oxidative damage in early AD is associated with activation of the Wnt/β-catenin signaling pathway to promote NSC proliferation and thus repair damaged neurons.展开更多
Background:This study investigated the phenolic profile,antioxidant capacity,antibacterial effect,and antihemolytic activity of nettle leaves from two understudied Algerian species,Urtica pilulifera and Urtica urens.M...Background:This study investigated the phenolic profile,antioxidant capacity,antibacterial effect,and antihemolytic activity of nettle leaves from two understudied Algerian species,Urtica pilulifera and Urtica urens.Methods:Urtica pilulifera and Urtica urens leaves extracts were prepared by maceration using methanol and distilled water respectively.Their phytochemical analysis(total phenolic content,flavonoids,hydrolysable and condensed tannins)was determined.The chemical profle of these extracts was performed using ultra-high-performance liquid chromatography diode array detection tandem mass spectrometry.Antioxidant activity(using the 2,2-diphenyl-1-picrylhydrazyl free radical scavenging method),antibacterial activity(using disk diffusion method),and antihemolytic activity were carried out.Results:Results reveal high levels of flavonoids,tannins,alkaloids,and terpenoids.Several classes of compounds were identified in the extracts.Phenolic acid and other acids and their derivatives and flavonoids were detected in the extracts,with 4-O-caffeoyl-quinic acid and 5-O-caffeoyl-quinic acid being the main constituents in both extracts.Caffeic acid was also the main constituent present only in U.urens extract.For antioxidant activity of the methanolic extract of U.pilulifera and the aqueous extract of U.urens,the percentage inhibition value(82.76%and 59.06%)and the half-maximum inhibitory concentration(IC_(50))value(302 and 423μg/mL),respectively,were obtained.Antibacterial activity of nettle extracts(10 mg/mL)demonstrated the sensitivity of pathogenic strain susceptibility.The strongest antibacterial effect on tested strains was found in the aqueous extract of U.urens against Staphylococcus aureus(21±0.41 mm)compared to the methanolic extract of U.pilulifera(16±0.40 mm).The antihemolytic activity in the methanolic and aqueous extracts was 76.26%and 60.67%,respectively.The methanolic extract exhibited exceptional antihemolytic effect,with an IC_(50)value of 327μg/mL,whereas the aqueous extract had an IC_(50)value of 412μg/mL.Conclusions:The study confirms the presence of bioactive substances in the nettle species,including flavonoids and tannins,which possess antioxidant,antibacterial,and antihemolytic properties,and can be processed into food and pharmaceutical products.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
Psoriasis is a common inflammatory skin disease with characterization of epidermal hyperplasia and sustained skin inflammation.Long noncoding RNAs(lncRNAs),which contain more than 200 nucleotide-long transcripts,are e...Psoriasis is a common inflammatory skin disease with characterization of epidermal hyperplasia and sustained skin inflammation.Long noncoding RNAs(lncRNAs),which contain more than 200 nucleotide-long transcripts,are emerging as the crux of epigenetic regulators in multiple biological processes and diseases.However,how lncRNAs contribute to the etiology of psoriasis remains to be elucidated.For the first time,this study revealed that SNHG15,which was elevated in cytokines-stimulated keratinocytes and psoriasis lesions,promoted keratinocytes hyperproliferation.Mechanistically,SNHG15 fueled epithelial pathology through activation of STAT3/Cyclin D1 axis.Intriguingly,activation of STAT3 enhanced SNHG15 transcription to form a positive feed-back modulatory loop and consequently augmented the skin lesions in psoriasis.Furthermore,knock down the expression of SNHG15 can counteract the IMQ-induced keratinocytes hyperproliferation in vivo.Taken together,our findings uncover that SNHG15 facilitates epidermal hyperplasia via STAT3/Cyclin D1 axis,which might provide a novel therapeutic avenue for psoriasis treatment.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 Small bowel adenocarcinoma(SBA)is a rare malignant tumor of gastrointestinal tract.Currently,there is no standard treatment approach for late-stage SBA,which lead to poor outcome and prognosis.Rapamycin is ...BACKGROUND Small bowel adenocarcinoma(SBA)is a rare malignant tumor of gastrointestinal tract.Currently,there is no standard treatment approach for late-stage SBA,which lead to poor outcome and prognosis.Rapamycin is an immunosuppressive agent that has been reported to inhibit the proliferation of tumor cells.However,whether rapamycin inhibit the growth of SBA remains to be investigated.AIM To observe the inhibitory effect of rapamycin on small intestinal adenocarcinoma cells.METHODS Methylthiazolyldiphenyl-tetrazolium bromide assay,colony formation assay,cell cycle analysis,and glycolysis assay were used to observe the phenotypic changes of rapamycin-treated HUTU 80 cells.RNA sequencing and untargeted ultra-high performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS)metabolomics were also used to find the potential targets of action of rapamycin in inhibiting HUTU 80 cells prolif-eration,and validate potential targets by quantitative polymerase chain reaction and western blotting.The construction of a subcutaneous HUTU 80 xenograft in BALB/c nude mice was used to explore the tumor suppre-ssion effect of rapamycin.RESULTS Rapamycin inhibited HUTU 80 cell proliferation in vitro and in vivo.Rapamycin inhibited the migration,invasion,and glycolysis of HUTU 80 cells,and induced cell cycle arrest.RNA sequencing and untargeted UHPLC-MS/MS metabolomic analysis indicated that the mechanism of rapamycin action was linked to the hypoxia-inducible factor(HIF)-1αsignaling pathway and the related gluconeogenesis/glycolysis pathways.Subsequent experiments found that rapamycin downregulated the messenger RNA expression of HIF-1αand its downstream target genes,LDHA,PDK1 and VEGF.Additionally,rapamycin inhibited expression of phosphorylated mammalian target of rapamycin(mTOR),phosphorylated-70 kDa ribosomal protein S6 kinase(p70S6k),phosphorylated eukaryotic translation initiation factor 4E-binding protein 1(4E-BP1)and HIF-1αproteins in vitro and in vivo.CONCLUSION Downregulation of mTOR/p70S6k/4E-BP1/HIF-1αsignaling pathway activation,leading to decreased glycolysis and cell cycle arrest,may be the pivotal mechanism by which rapamycin inhibits SBA.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
Life-history traits represent evolutionary adaptations that mediate responses to external environments.Analyzing variation in these traits provides valuable insights into macroecological processes and supports the dev...Life-history traits represent evolutionary adaptations that mediate responses to external environments.Analyzing variation in these traits provides valuable insights into macroecological processes and supports the development of effective conservation and restoration strategies.However,large-scale biogeographic patterns in life-history trait diversity among terrestrial vertebrates remain insufficiently characterized,and the processes shaping these patterns are not well understood.This study integrated life-history and spatial distribution data for 2334 terrestrial vertebrate species in China,including 398 amphibians,211 reptiles,541 mammals,and 1184 birds,to evaluate spatial patterns of trait diversity and identify underlying drivers.Assemblages in South and Southwest China exhibited high species richness,substantial assemblage-level evolutionary distinctiveness,expanded trait volumes,and elevated trait densities compared to null expectations,indicating roles as both evolutionary museums and cradles.In contrast,assemblages on the Tibetan Plateau showed expanded trait volumes but low trait densities,reflecting niche expansion among limited taxa.These findings emphasize the importance of niche packing before assemblages reach environmental carrying limits.Assemblages with high evolutionary distinctiveness tended to display high trait volumes and low trait densities,suggesting a consistent relationship between phylogenetic structure and functional diversification.Among the four groups,amphibians showed the highest sensitivity to environmental variation,highlighting the need for focused conservation efforts.Overall,this study revealed pronounced spatial heterogeneity in trait diversity across China,shaped by species richness,evolutionary distinctiveness,and environmental variation,providing valuable insights for refining conservation priorities for terrestrial vertebrate taxa.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 National Natural Science Foundation of China(31601141)。
文摘A lactating dairy cow mammary epithelial cell(DCMEC)model is useful for studying milk synthesis and lactation in the dairy cow mammary gland.However,the cells can only maintain their original characteristics for a limited period in vitro.Thus,the proliferative capacity and lactation pattern of subcultured DCMECs need to be characterized.In the present study,subcultured DCMECs appeared to proliferate without changes in morphology or growth pattern up to the 12th passage.Subculturing had no obvious effect on the lactation capacity of the subcultured DCMEC up to the 10th passage in vitro.These results indicated that the DCMEC line could be subpassaged up to 10 times and still maintain its original milk synthesis characteristics.Moreover,DCMECs were frozen using different methods,and the method of placing the vials in the foam box was determined after cryopreservation with the best adherence of 91.2%.This method was recommended for long-term cryopreservation for DCMECs.
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(82192903,82192904)the National Science and Technology Major Projects of China(2023ZD0510103)。
文摘Objective Telomere length is a key aging biomarker,but its sex-specific impact on individualized life expectancy remains uncertain.This study explores sex differences in leukocyte telomere length(LTL)and individualized expected years of life lost(YLL).Methods A prospective cohort of 445,399 participants(203,731 males and 241,668 females)from the UK Biobank was analyzed.LTL values were log-transformed,and YLL was calculated using life tables.Multiple linear regression was applied to examine sex-specific associations.Results In males,each standard deviation(S.D.)increase in LTL was linked to a 0.965-year decrease in YLL(95%CI:–1.025,–0.900;P<0.001).In females,longer LTL was related to a 0.102-year increase in YLL(95%CI:0.057,0.146;P<0.001).Among postmenopausal females,LTL showed a protective effect similar to that in males(0.387-year decrease,95%CI:−0.446,–0.328;P<0.001),while premenopausal females exhibited a detrimental association(0.705-year increase,95%CI:0.625,0.785;P<0.001).Comparable trends were observed across major aging-related diseases,pointing to a consistent biological pattern.Conclusion The influence of LTL on life expectancy varies significantly by sex,with protective associations seen in males and postmenopausal females.This suggests hormonal involvement in telomere dynamics.The results support integrating sex-specific perspectives into aging and telomere research and clinical practice.
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.
基金supported by the National Nature Science Foundation of China(82174085)Natural Science Foundation of Inner Mongolia Autonomous Region(2019MS08032).
文摘Alzheimer’s disease(AD)is a degenerative disease of the central nervous system.It results in cognitive dysfunction due to the loss of functional neurons and a deficit of new neurons,which can lead to death in severe cases.Repairing damaged neurons by promoting hippocampal neurogenesis has become therapeutic modality to combat neurodegenerative diseases.The novel isoflavone alkaloid LY01,found in the edible fruits of Sophora alopecuroides L.,has various neuroprotective effects.However,the molecular mechanism by which it promotes the proliferation of endogenous neural stem cells(NSCs)is not yet precisely known.The effects of LY01 were investigated in vivo and in vitro.In vivo experiments showed that LY01 could counteract the toxic damage of amyloid β-protein(Aβ),enhance the learning ability and memory capacity of 5×FAD mice,and improve the morphology of neurons in the hippocampal region.In vitro experiments showed that LY01 was effective against antioxidant damage,improved the cell morphology of C17.2 mouse NSCs after hydrogen peroxide injury,and increased cell viability.Both in vitro and in vivo experiments promoted NSC proliferation by upregulating the mRNA and protein levels of the critical genes of the Wnt/β-catenin pathway,which increased levels of doublecortin to facilitate new neuronal generation.This indicates that the ability of LY01 to counteract Aβ toxicity and alleviate oxidative damage in early AD is associated with activation of the Wnt/β-catenin signaling pathway to promote NSC proliferation and thus repair damaged neurons.
基金Ministry of Science,Technological Development and Innovations of the Republic of Serbia,Grant/Award Number:451-03-137/2025-03/200133。
文摘Background:This study investigated the phenolic profile,antioxidant capacity,antibacterial effect,and antihemolytic activity of nettle leaves from two understudied Algerian species,Urtica pilulifera and Urtica urens.Methods:Urtica pilulifera and Urtica urens leaves extracts were prepared by maceration using methanol and distilled water respectively.Their phytochemical analysis(total phenolic content,flavonoids,hydrolysable and condensed tannins)was determined.The chemical profle of these extracts was performed using ultra-high-performance liquid chromatography diode array detection tandem mass spectrometry.Antioxidant activity(using the 2,2-diphenyl-1-picrylhydrazyl free radical scavenging method),antibacterial activity(using disk diffusion method),and antihemolytic activity were carried out.Results:Results reveal high levels of flavonoids,tannins,alkaloids,and terpenoids.Several classes of compounds were identified in the extracts.Phenolic acid and other acids and their derivatives and flavonoids were detected in the extracts,with 4-O-caffeoyl-quinic acid and 5-O-caffeoyl-quinic acid being the main constituents in both extracts.Caffeic acid was also the main constituent present only in U.urens extract.For antioxidant activity of the methanolic extract of U.pilulifera and the aqueous extract of U.urens,the percentage inhibition value(82.76%and 59.06%)and the half-maximum inhibitory concentration(IC_(50))value(302 and 423μg/mL),respectively,were obtained.Antibacterial activity of nettle extracts(10 mg/mL)demonstrated the sensitivity of pathogenic strain susceptibility.The strongest antibacterial effect on tested strains was found in the aqueous extract of U.urens against Staphylococcus aureus(21±0.41 mm)compared to the methanolic extract of U.pilulifera(16±0.40 mm).The antihemolytic activity in the methanolic and aqueous extracts was 76.26%and 60.67%,respectively.The methanolic extract exhibited exceptional antihemolytic effect,with an IC_(50)value of 327μg/mL,whereas the aqueous extract had an IC_(50)value of 412μg/mL.Conclusions:The study confirms the presence of bioactive substances in the nettle species,including flavonoids and tannins,which possess antioxidant,antibacterial,and antihemolytic properties,and can be processed into food and pharmaceutical products.
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supported by the Natural Science Foundation of Guangdong Province(2024A1515030148,China)the Joint Funding Project of Municipal Schools(Colleges)of Science and Technology Program of Guangzhou(No.202102010192,China)+4 种基金the Specific Fund of“Young Talents Program”of Guangdong College of Traditional Chinese Medicine(SZ2022QN10,China)Young Elite Scientists Sponsorship Program by China Association of Chinese Medicine(2022-QNRC2-B07,China)Specific Fund of State Key Laboratory of Dampness Syndrome of Chinese Medicine(SZ2021ZZ23,China)the Specific Research Fund for TCM Science and Technology of Guangdong Provincial Hospital of Chinese Medicine(YN2024HL04 and YN2024GZRPY072,China)the Sanming Project of Medicine in Shenzhen(No.SZZYSM202106008,China).
文摘Psoriasis is a common inflammatory skin disease with characterization of epidermal hyperplasia and sustained skin inflammation.Long noncoding RNAs(lncRNAs),which contain more than 200 nucleotide-long transcripts,are emerging as the crux of epigenetic regulators in multiple biological processes and diseases.However,how lncRNAs contribute to the etiology of psoriasis remains to be elucidated.For the first time,this study revealed that SNHG15,which was elevated in cytokines-stimulated keratinocytes and psoriasis lesions,promoted keratinocytes hyperproliferation.Mechanistically,SNHG15 fueled epithelial pathology through activation of STAT3/Cyclin D1 axis.Intriguingly,activation of STAT3 enhanced SNHG15 transcription to form a positive feed-back modulatory loop and consequently augmented the skin lesions in psoriasis.Furthermore,knock down the expression of SNHG15 can counteract the IMQ-induced keratinocytes hyperproliferation in vivo.Taken together,our findings uncover that SNHG15 facilitates epidermal hyperplasia via STAT3/Cyclin D1 axis,which might provide a novel therapeutic avenue for psoriasis treatment.
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 Natural Science Foundation of China,No.81660270Hainan Provincial Natural Science Foundation of China,No.823RC497+2 种基金Project of Nanhai Series of Talent Cultivation Program,No.20192031Key Discipline Project of Pathophysiology at Hainan Medical University,No.05The Open Project Fund for Provincial Key Disciplines of Basic Medicine at Hainan Medical University,Hainan Medical College Talent Research Start up Fund,No.RZ300006194.
文摘BACKGROUND Small bowel adenocarcinoma(SBA)is a rare malignant tumor of gastrointestinal tract.Currently,there is no standard treatment approach for late-stage SBA,which lead to poor outcome and prognosis.Rapamycin is an immunosuppressive agent that has been reported to inhibit the proliferation of tumor cells.However,whether rapamycin inhibit the growth of SBA remains to be investigated.AIM To observe the inhibitory effect of rapamycin on small intestinal adenocarcinoma cells.METHODS Methylthiazolyldiphenyl-tetrazolium bromide assay,colony formation assay,cell cycle analysis,and glycolysis assay were used to observe the phenotypic changes of rapamycin-treated HUTU 80 cells.RNA sequencing and untargeted ultra-high performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS)metabolomics were also used to find the potential targets of action of rapamycin in inhibiting HUTU 80 cells prolif-eration,and validate potential targets by quantitative polymerase chain reaction and western blotting.The construction of a subcutaneous HUTU 80 xenograft in BALB/c nude mice was used to explore the tumor suppre-ssion effect of rapamycin.RESULTS Rapamycin inhibited HUTU 80 cell proliferation in vitro and in vivo.Rapamycin inhibited the migration,invasion,and glycolysis of HUTU 80 cells,and induced cell cycle arrest.RNA sequencing and untargeted UHPLC-MS/MS metabolomic analysis indicated that the mechanism of rapamycin action was linked to the hypoxia-inducible factor(HIF)-1αsignaling pathway and the related gluconeogenesis/glycolysis pathways.Subsequent experiments found that rapamycin downregulated the messenger RNA expression of HIF-1αand its downstream target genes,LDHA,PDK1 and VEGF.Additionally,rapamycin inhibited expression of phosphorylated mammalian target of rapamycin(mTOR),phosphorylated-70 kDa ribosomal protein S6 kinase(p70S6k),phosphorylated eukaryotic translation initiation factor 4E-binding protein 1(4E-BP1)and HIF-1αproteins in vitro and in vivo.CONCLUSION Downregulation of mTOR/p70S6k/4E-BP1/HIF-1αsignaling pathway activation,leading to decreased glycolysis and cell cycle arrest,may be the pivotal mechanism by which rapamycin inhibits SBA.
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 the National Key Program of Research and Development,Ministry of Science and Technology(2022YFF1301401,2022YFF0802300)National Natural Science Foundation of China(32370553)+3 种基金Second Tibetan Plateau Scientific Expedition and Research Program(STEP,2019QZKK0501)China Biodiversity Observation Networks(Sino BON)Fundamental Research Funds for the Central Universities(SWU-KR24004)Scientific Research Innovation Project of Graduate Student of Southwest University(SWUB23080)。
文摘Life-history traits represent evolutionary adaptations that mediate responses to external environments.Analyzing variation in these traits provides valuable insights into macroecological processes and supports the development of effective conservation and restoration strategies.However,large-scale biogeographic patterns in life-history trait diversity among terrestrial vertebrates remain insufficiently characterized,and the processes shaping these patterns are not well understood.This study integrated life-history and spatial distribution data for 2334 terrestrial vertebrate species in China,including 398 amphibians,211 reptiles,541 mammals,and 1184 birds,to evaluate spatial patterns of trait diversity and identify underlying drivers.Assemblages in South and Southwest China exhibited high species richness,substantial assemblage-level evolutionary distinctiveness,expanded trait volumes,and elevated trait densities compared to null expectations,indicating roles as both evolutionary museums and cradles.In contrast,assemblages on the Tibetan Plateau showed expanded trait volumes but low trait densities,reflecting niche expansion among limited taxa.These findings emphasize the importance of niche packing before assemblages reach environmental carrying limits.Assemblages with high evolutionary distinctiveness tended to display high trait volumes and low trait densities,suggesting a consistent relationship between phylogenetic structure and functional diversification.Among the four groups,amphibians showed the highest sensitivity to environmental variation,highlighting the need for focused conservation efforts.Overall,this study revealed pronounced spatial heterogeneity in trait diversity across China,shaped by species richness,evolutionary distinctiveness,and environmental variation,providing valuable insights for refining conservation priorities for terrestrial vertebrate taxa.
