Chondrocyte senescence is a critical pathological hallmark of osteoarthritis(OA).Aberrant mechanical stress is considered a pivotal determinant in chondrocyte aging;however,the precise underlying mechanism remains elu...Chondrocyte senescence is a critical pathological hallmark of osteoarthritis(OA).Aberrant mechanical stress is considered a pivotal determinant in chondrocyte aging;however,the precise underlying mechanism remains elusive.Our findings demonstrate that SPI1 plays a significant role in counteracting chondrocyte senescence and inhibiting OA progression.SPI1 binds to the PERK promoter,thereby promoting its transcriptional activity.Importantly,PERK,rather than GCN2,facilitates eIF2αphosphorylation,activating the mitochondrial unfolded protein response(UPRmt)and impeding chondrocyte senescence.Deficiency of SPI1 in mechanical overload-induced mice leads to diminished UPRmt activation and accelerated OA progression.Intra-articular injection of adenovirus vectors overexpressing SPI1 and PERK effectively mitigates cartilage degeneration.In summary,our study elucidates the crucial regulatory role of SPI1 in the pathogenesis of chondrocyte senescence by activating UPRmt signaling through PERK,which may present a novel therapeutic target for treating OA.展开更多
Intercropping has been widely used in arid and semi-arid regions because of its high yield,stable productivity,and efficient utilization of resources.However,in recent years,the high yield of traditional intercropping...Intercropping has been widely used in arid and semi-arid regions because of its high yield,stable productivity,and efficient utilization of resources.However,in recent years,the high yield of traditional intercropping is mainly attributed to the large amount of purchased resources such as water and fertilizer,plastic film,and mechanical power.These lead to a decline in cultivated land quality and exacerbate intercrops'premature root and canopy senescence.So,the application of traditional intercropping faces major challenges in crop production.This paper analyzes the manifestations,occurrence mechanisms,and agronomic regulatory pathways of crop senescence.The physiological and ecological characteristics of intercropping to delay root and canopy senescence of crops are reviewed in this paper.The main agronomic regulatory pathways of intercropping to delay root and canopy senescence of crops are based on above-and blow-ground interactions,including collocation of crop varieties,spatial arrangement,water and fertilizer management,and tillage and mulch practices.Future research fields of intercropping to delay root and canopy senescence should focus on the aspects of selecting and breeding special varieties,application of molecular biology techniques,and developing or applying models to predict and evaluate the root and canopy senescence process of intercrops.Comprehensive analysis and evaluation of different research results could provide a basis for enhancing intercropping delay root and canopy senescence through adopting innovative technologies for regulating the physio-ecological characteristics of intercrops.This would support developing and adopting high-yield,efficient,and sustainable intercropping systems in arid and semi-arid areas with high population density,limited land,and abundant light and heat resources.展开更多
Stem cells play a crucial role in maintaining tissue regenerative capacity and homeostasis.However,mechanisms associated with stem cell senescence require further investigation.In this study,we conducted a proteomic a...Stem cells play a crucial role in maintaining tissue regenerative capacity and homeostasis.However,mechanisms associated with stem cell senescence require further investigation.In this study,we conducted a proteomic analysis of human dental pulp stem cells(HDPSCs)obtained from individuals of various ages.Our findings showed that the expression of NUP62 was decreased in aged HDPSCs.We discovered that NUP62 alleviated senescence-associated phenotypes and enhanced differentiation potential both in vitro and in vivo.Conversely,the knocking down of NUP62 expression aggravated the senescence-associated phenotypes and impaired the proliferation and migration capacity of HDPSCs.Through RNA-sequence and decoding the epigenomic landscapes remodeled induced by NUP62 overexpression,we found that NUP62 helps alleviate senescence in HDPSCs by enhancing the nuclear transport of the transcription factor E2F1.This,in turn,stimulates the transcription of the epigenetic enzyme NSD2.Finally,the overexpression of NUP62 influences the H3K36me2 and H3K36me3 modifications of anti-aging genes(HMGA1,HMGA2,and SIRT6).Our results demonstrated that NUP62 regulates the fate of HDPSCs via NSD2-dependent epigenetic reprogramming.展开更多
To determine the effects of preharvest arginine spraying on the nutritional level of broccoli and the mechanism of action of arginine in improving the storage quality of broccoli,arginine spraying(5 mmol/L)was conduct...To determine the effects of preharvest arginine spraying on the nutritional level of broccoli and the mechanism of action of arginine in improving the storage quality of broccoli,arginine spraying(5 mmol/L)was conducted at 0,1,3,and 5 days before harvest.The appearance,respiration rate,mass-loss rate,electrolyte leakage,glucosinolate,ascorbic acid,total phenol,total flavonoid,total sugar and sucrose contents,and sucrose phosphate synthase(SPS),invertase(INV),sucrose synthase synthesis(SSS)and cleavage(SSC)activities of broccoli samples were observed after 0,2,4,6,8,and 10 days of storage.The results showed that spraying arginine at 5 days preharvest(5-ARG)helped to inhibit broccoli respiration during storage,delay electrolyte leakage,and maintain broccoli color.Furthermore,during the growth stage,total sugar accumulation was higher in the 5-ARG group.In addition,during the storage period,sucrose synthesis was accelerated,while sucrose cleavage was inhibited,resulting in more sucrose retention in postharvest broccoli.In conclusion,5-ARG resulted in the accumulation of more nutrients during the growth process and effectively delayed the quality decline during storage,thereby prolonging the shelf life of broccoli.Therefore,this study provides a theoretical basis for improving postharvest storage characteristics of broccoli through preharvest treatments.展开更多
Objective The nucleolar protein PES1(Pescadillo homolog 1)plays critical roles in ribosome biogenesis and cell cycle regulation,yet its involvement in cellular senescence remains poorly understood.This study aimed to ...Objective The nucleolar protein PES1(Pescadillo homolog 1)plays critical roles in ribosome biogenesis and cell cycle regulation,yet its involvement in cellular senescence remains poorly understood.This study aimed to comprehensively investigate the functional consequences of PES1 suppression in cellular senescence and elucidate the molecular mechanisms underlying its regulatory role.Methods Initially,we assessed PES1 expression patterns in two distinct senescence models:replicative senescent mouse embryonic fibroblasts(MEFs)and doxorubicin-induced senescent human hepatocellular carcinoma HepG2 cells.Subsequently,PES1 expression was specifically downregulated using siRNA-mediated knockdown in these cell lines as well as additional relevant cell types.Cellular proliferation and senescence were assessed by EdU incorporation and SA-β-gal staining assays,respectively.The expression of senescence-associated proteins(p53,p21,and Rb)and SASP factors(IL-6,IL-1β,and IL-8)were analyzed by Western blot or qPCR.Furthermore,Northern blot and immunofluorescence were employed to evaluate pre-rRNA processing and nucleolar morphology.Results PES1 expression was significantly downregulated in senescent MEFs and HepG2 cells.PES1 knockdown resulted in decreased EdU-positive cells and increased SA-β-gal-positive cells,indicating proliferation inhibition and senescence induction.Mechanistically,PES1 suppression activated the p53-p21 pathway without affecting Rb expression,while upregulating IL-6,IL-1β,and IL-8 production.Notably,PES1 depletion impaired pre-rRNA maturation and induced nucleolar stress,as evidenced by aberrant nucleolar morphology.Conclusion Our findings demonstrate that PES1 deficiency triggers nucleolar stress and promotes p53-dependent(but Rb-independent)cellular senescence,highlighting its crucial role in maintaining nucleolar homeostasis and regulating senescence-associated pathways.展开更多
Cellular senescence and its senescence-associated secretory phenotype(SASP)represent a pivotal role in the development of skeletal diseases.Targeted elimination or rejuvenation of senescent cells has shown potential a...Cellular senescence and its senescence-associated secretory phenotype(SASP)represent a pivotal role in the development of skeletal diseases.Targeted elimination or rejuvenation of senescent cells has shown potential as a therapeutic strategy to reverse age-related skeletal senescence and promote bone regeneration.Meanwhile,other age-related mechanisms,involving altered cellular functions,impaired intercellular crosstalk,disturbed tissue microenvironment,and decreased regenerative capacity,synergistically contribute to the pathogenesis.In this review,we outline the cellular senescence and other age-related mechanisms in developing skeletal diseases,including osteoporosis,intervertebral disc degeneration,osteoarthritis,rheumatoid arthritis,bone tumors and ankylosing spondylitis,with the aim of comprehensively understanding their detrimental effects on the aged skeleton and screening the potential targets for anti-aging therapy within the skeletal system.展开更多
Aging is considered the main risk factor for the development of several diseases,including the leading neurodegenerative disorders.While the cellular features of aging are complex and multifaceted,neuronal senescence ...Aging is considered the main risk factor for the development of several diseases,including the leading neurodegenerative disorders.While the cellular features of aging are complex and multifaceted,neuronal senescence has emerged as a major contributor and driver of this process in the mammalian cell.Cellular senescence is a programmed response to stress and irreparable damage,which drives the cell into an apoptosis-resistant,non-proliferative state.Senescent cells can also deleteriously affect neighboring,non-senescent cells.Senescence is a complex and multifaceted process associated with a wide range of cellular events,including the secretion of pro-inflammatory molecules and the arrest of the cell cycle.展开更多
Intervertebral disc degeneration(IDD)is a progressive and dynamic process in which the senescence-associated secretory phenotype(SASP)of nucleus pulposus cells(NPC)plays a significant role.While impaired chaperone-med...Intervertebral disc degeneration(IDD)is a progressive and dynamic process in which the senescence-associated secretory phenotype(SASP)of nucleus pulposus cells(NPC)plays a significant role.While impaired chaperone-mediated autophagy(CMA)has been associated with inflammation and cellular senescence,its specific involvement in the self-perpetuating feedback loop of NPC senescence remains poorly understood.Through LAMP2A knockout in NPC,we identified a significant upregulation of DYRK1A,a core mediator of premature senescence in Down syndrome.Subsequent validation established DYRK1A as the critical driver of premature senescence in CMA-deficient NPC.Combinatorial transcription factor analysis revealed that under IL1B stimulation or CMA inhibition,elevated DYRK1A promoted FOXC1 phosphorylation and nuclear translocation,initiating transcriptional activation of cell cycle arrest.Intriguingly,CMA impairment concurrently enhanced glutamine metabolic flux in senescent NPC,thereby augmenting their survival fitness.Transcriptomic profiling demonstrated that CMA reactivation in senescent NPC facilitated fate transition from senescence to apoptosis,mediated by decreased glutamine flux via GLUL degradation.Therefore,CMA exerts protective effects against IDD by maintaining equilibrium between premature senescence and senolysis.This study elucidates CMA’s regulatory role in SASP-mediated senescence amplification circuits,providing novel therapeutic insights for IDD and other age-related pathologies.展开更多
Diabetic kidney disease(DKD)has emerged as one of the leading causes of chronic kidney disease and end-stage renal disease worldwide.In the progression of DKD,renal tubular injury plays a pivotal role,with stress-indu...Diabetic kidney disease(DKD)has emerged as one of the leading causes of chronic kidney disease and end-stage renal disease worldwide.In the progression of DKD,renal tubular injury plays a pivotal role,with stress-induced senescence of renal tubular epithelial cells(RTECs)being a critical cellular event contributing to tubular damage in DKD.Recent studies have revealed that multiple mechanisms,including oxidative stress,mitochondrial autophagy,endoplasmic reticulum stress,and epigenetic modifications,can induce stress-induced senescence in RTECs,thereby driving the progression of DKD.In recent years,research has demonstrated that traditional Chinese medicine(TCM)can regulate these mechanisms through multiple targets and key pathways,inhibiting stress-induced senescence in RTECs and ameliorating the progression of DKD.TCM has been widely applied in clinical practice with proven efficacy.This article systematically summarizes the concept of cellular senescence,delves into the relationship between stress-induced senescence of RTECs and DKD,analyzes the mechanisms underlying the formation of stress-induced senescence in RTECs within the context of DKD,and reviews the research progress of TCM in anti-senescence treatment for DKD.The aim is to provide a reference for future research and the development of novel therapeutic strategies.展开更多
1.HOU J,DU Y,SHAO Y,et al.Identification,Albanol B inhibits glioblastoma progression by inducing senescence and apoptosis via the RNF6/p27 signaling axis.Phytomedicine.DOI:10.1016/j.phymed.2025.157056.(2025)[题目]Alba...1.HOU J,DU Y,SHAO Y,et al.Identification,Albanol B inhibits glioblastoma progression by inducing senescence and apoptosis via the RNF6/p27 signaling axis.Phytomedicine.DOI:10.1016/j.phymed.2025.157056.(2025)[题目]Albanol B通过RNF6/p27信号轴诱导细胞衰老与凋亡,从而抑制胶质母细胞瘤进展。展开更多
Healthy aging is a common goal for humanity and society,and one key to achieving it is the rejuvenation of senescent resident stem cells and empowerment of aging organ regeneration.However,the mechanistic understandin...Healthy aging is a common goal for humanity and society,and one key to achieving it is the rejuvenation of senescent resident stem cells and empowerment of aging organ regeneration.However,the mechanistic understandings of stem cell senescence and the potential strategies to counteract it remain elusive.Here,we reveal that the aging bone microenvironment impairs the Golgi apparatus thus diminishing mesenchymal stem cell(MSC)function and regeneration.Interestingly,replenishment of cell aggregates-derived extracellular vesicles(CA-EVs)rescues Golgi dysfunction and empowers senescent MSCs through the Golgi regulatory protein Syntaxin 5.Importantly,in vivo administration of CA-EVs significantly enhanced the bone defect repair rate and improved bone mass in aging mice,suggesting their therapeutic value for treating age-related osteoporosis and promoting bone regeneration.Collectively,our findings provide insights into Golgi regulation in stem cell senescence and bone aging,which further highlight CA-EVs as a potential rejuvenative approach for aging bone regeneration.展开更多
Senescent macrophages have emerged as dynamic cells within the tumor microenvironment that significantly promote tumor progression through complex cellular and molecular functional alterations. This review explores th...Senescent macrophages have emerged as dynamic cells within the tumor microenvironment that significantly promote tumor progression through complex cellular and molecular functional alterations. This review explores the multifaceted roles of macrophage senescence in cancer, and establishes links between senescent macrophages and tumor progression from multiple perspectives, on the basis of the first comprehensive analysis of the molecular mechanisms and pathways involved. By systematically examining the diverse changes in senescent macrophages, this review integrates and analyzes their effects on tumors, thus offering a comprehensive and novel theoretical foundation, and practical insights for cancer treatment. Notably, by integrating current molecular research and therapeutic advancements, we summarize novel therapeutic strategies targeting senescent macrophages, including senolytics, senescence modulators, and cutting-edge immunotherapies, thereby highlighting the potential of senescent macrophages as a therapeutic target and introducing new opportunities for cancer treatment.展开更多
BACKGROUND Acute liver failure(ALF)is a loss of liver function due to a severe hepatic insult.Studies utilizing the azoxymethane(AOM)mouse model of ALF,which also generates hepatic encephalopathy,have primarily focuse...BACKGROUND Acute liver failure(ALF)is a loss of liver function due to a severe hepatic insult.Studies utilizing the azoxymethane(AOM)mouse model of ALF,which also generates hepatic encephalopathy,have primarily focused on development of neurological deficits.However,the molecular processes that generate liver damage have not been fully characterized.Therefore,a more comprehensive characterization of the hepatic consequences of AOM toxicity is needed to better understand this disease model.AIM To identify molecular pathology contributing to hepatic injury during the progression of AOM-induced ALF.METHODS C57BL/6 mice were injected with AOM to produce ALF and hepatic encephalopathy.Tissue was collected at defined stages of neurological decline up to coma.Liver injury,CYP2E1 expression,oxidative stress,inflammation,apoptosis,necroptosis,and hepatocellular senescence were assessed.RESULTS Increased hepatic necrosis and exacerbated liver injury were observed after AOM injection as mice progressed towards coma.CYP2E1 expression decreased in AOM-treated mice as liver injury progressed.Malondialdehyde,myeloperoxidase and other measures of oxidative stress were significantly increased during AOM-induced ALF.Hepatic CCL2 and tumor necrosis factorαexpression increased as AOM-induced liver injury progressed.Mixed lineage kinase domain-like protein phosphorylation was increased early during the progression of AOM-induced liver injury.Measures of apoptosis and cellular senescence all increased as the time course of AOM progressed.CONCLUSION These data support that necrosis,oxidative stress,inflammation,apoptosis,and senescence were elevated in AOMtreated mice,with inflammation being the earliest significant change.展开更多
There is still no effective treatment for pancreatic cancer,one of the deadliest malignancies among the gastrointestinal diseases.Jiang et al demonstrated the presence of senescent cancer-associated fibroblasts(CAFs)i...There is still no effective treatment for pancreatic cancer,one of the deadliest malignancies among the gastrointestinal diseases.Jiang et al demonstrated the presence of senescent cancer-associated fibroblasts(CAFs)in pancreatic cancer tissues,supporting the use of CAFs as potential anti-cancer targets.The study indicated that a natural plant-derived compound resveratrol can reverse senescent CAF phenotype and decrease the growth,migration,and invasiveness of pancreatic cancer cells.Notably,the study indicated that resveratrol might be involved in regulating epithelial-to-mesenchymal transition in the tumor microenvironment.This editorial shares insights on the future investigation of resveratrol signaling in cancer cells and the tumor microenvironment,and discusses resveratrol-based treatment perspectives.展开更多
BACKGROUND Extracellular vesicles derived from mesenchymal stromal cells(MSC-EVs)can be used for anti-aging therapy and treating various aging-related diseases.However,the clinical application of MSC-EVs is still limi...BACKGROUND Extracellular vesicles derived from mesenchymal stromal cells(MSC-EVs)can be used for anti-aging therapy and treating various aging-related diseases.However,the clinical application of MSC-EVs is still limited,mainly due to insufficient in-formation on the preparation process,quality,and mechanism of action of MSC-EVs.To study the biological effects of MSC-EVs in regulating cellular senescence.METHODS In this study,we developed a clinical-grade production process for MSC-EVs and defined the release criteria for products suitable for human use.To support the clinical use of our product as a therapeutic agent,we performed efficacy assays to evaluate the anti-aging capacity of MSC-EVs in vitro and in vivo.RESULTS The functional analysis results revealed that MSC-EVs significantly reduced the levels of senescence-associatedβ-galactosidase,matrix metallopeptidase 1,P21,and interleukin-1βand increased the level of collagen I in a naturally aged cell model of human dermal fibroblasts.Similarly,treatment with MSC-EVs effectively improved D-gal-induced subacute aging in mice,aging-related histopathological changes,oxidative stress,and aging-related gene expression.CONCLUSION These findings indicate that MSC-EVs can partially alleviate D-gal-induced senescence by reducing oxidative stress and regulating metabolism.Overall,these findings strongly suggest that MSC-EVs hold promise for aging therapy.展开更多
Drought is one of the important stress factors affecting the growth and development processes of wheat in China's arid zones, which severely limits the yield. This study examined the impact of deficit irrigation o...Drought is one of the important stress factors affecting the growth and development processes of wheat in China's arid zones, which severely limits the yield. This study examined the impact of deficit irrigation on the flag leaf protection system and yield of drip-irrigated spring wheat during the growth stages in arid zones. In addition, this study aimed to determine the optimal water supply mode for efficient production under drip irrigation conditions and to provide technical support for water-saving and high-yield cultivation of drip-irrigated wheat. The experiment was conducted with a split plot design using the water-sensitive variety Xinchun 22(XC22) and the drought-tolerant variety Xinchun 6(XC6) as the main plots, while a fully irrigated control(CK, 75–80% FC, where FC is field water holding capacity), mild deficit(T1, 60–65% FC) and moderate deficit(T2, 45–50% FC) at the tillering stage, and mild deficit(J1, 60–65% FC) and moderate deficit(J2, 45–50% FC) at the jointing stage were used as the subplots. Systematic studies were conducted on the regulatory effects of deficit irrigation during the tillering and jointing stages on protective substances, membrane lipid metabolism, endogenous hormones in the flag leaf, and yield of spring wheat. Compared with treatments T2 and J2, treatments T1 and J1 were beneficial for increasing the activities of superoxide dismutase(SOD), peroxidase(POD), and catalase(CAT), the levels of proline(Pro), indole-3-acetic acid(IAA), and zeatin riboside(ZR), and the ratios IAA/abscisic acid(ABA), ZR/ABA, IAA/ZR, and(IAA+ZR)/ABA, while reducing the levels of hydrogen peroxide(H2O2), superoxide anion radicals(O2–·), malondialdehyde(MDA), phosphatidic acid(PA), free fatty acids(FFA), ABA, phospholipase D(PLD), and lipoxygenase(LOX), alleviating flag leaf senescence, and increasing yield. Under treatment T1, the SOD, POD, CAT, and Pro levels of flag leaves in XC6 were 11.14, 8.08, 12.98, and 3.66% higher than those of treatment CK, and under treatment J1, they were 6.43, 4.49, 7.36, and 2.50% higher than those of treatment CK. Under treatment T1 in XC6, the IAA, ZR level of the flag leaf, spike number, grains per spike, 1,000-grain weight and yield were 10.50, 5.79, 3.10, 8.84, 3.78, and 10.52% higher than those of treatment CK, and under treatment J1, they were 5.36, 3.94, 2.40, 3.72, 1.37, and 4.46% higher than those of treatment CK. Compared with XC22, XC6 was more conducive to the improvement of flag leaf protective substances, IAA, ZR, dry matter weight, yield components and yield. The correlation analysis showed significant positive correlations between IAA and ZR with SOD, POD, CAT, proline, and yield. IAA and ZR promoted the enhancement of protective enzyme activities, thereby clearing reactive oxygen species to cope with the oxidative stress caused by drought and achieve the effect of delaying senescence. Principal component analysis showed that yield components and dry matter weight, had direct effects on yield. Mild deficiency during the tillering stage without water stress in other stages could effectively optimize yield components, not only achieving high yield while increasing protective substances, but also reducing the reactive oxygen species content. This strategy can be recommended as a water-saving and high-yield production mode for drip irrigation of spring wheat in Xinjiang, China.展开更多
Decabromodiphenyl ether(BDE-209)has been recognized for its adverse effects on the male reproductive system.The specific negative effects and underlying mechanisms through which BDE-209 impacts the reproductive functi...Decabromodiphenyl ether(BDE-209)has been recognized for its adverse effects on the male reproductive system.The specific negative effects and underlying mechanisms through which BDE-209 impacts the reproductive function of offspring are not yet fully understood.The present study classified institute of cancer research(ICR)mice into control and BDE-209 treatment groups,administering doses of 0 and 75 mg/(kg·day),respectively.After 50 days of exposure,normal female mice were co-housed with the male mice,and their male offspring were sacrificed at 2 and 12 months of age.Paternal BDE-209 exposure reduced both sperm quantity and quality in offspring.Furthermore,exposure to BDE-209 resulted in DNA damage and the upregulation of the cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)DNA-sensing and inflammatory signaling pathways.The activation resulted in Z-DNA binding protein 1(ZBP1)binding to the mitochondrial antiviral signaling protein(MAVS),subsequently activating mitochondrial apoptosis in the testes.The activation of the cGAS-STING pathway inhibited mitophagy,leading to senescence in the testes of male offspring.In vitro studies indicated that the cGAS inhibitor RU320521(RU.521)effectively reversed the cGAS-STING pathway activation,alleviated the mitophagy inhibition,and decreased apoptosis and senescence in mouse spermatocyte line GC-2spd cells treated with BDE-209.The results showed that paternal BDE-209 exposure might disrupt spermatogenesis in mouse offspring by activating the cGAS-STING pathway and inhibiting mitophagy.This study provides essential data on the toxicity of BDE-209 to male reproduction and have important scientific and practical implications for maintaining biodiversity and population health in general.展开更多
Senescence,a crucial developmental process in the life cycle of plants,involves programmed destruction of cellular components of leaves.The onset of senescence is synchronized with other developmental processes for su...Senescence,a crucial developmental process in the life cycle of plants,involves programmed destruction of cellular components of leaves.The onset of senescence is synchronized with other developmental processes for successful reproduction since senescence eventually leads to cell death.Arabinosyltransferase FASCIATED AND BRANCHED 2(FAB2)is known to control meristem proliferation.Here,we show that FAB2 could inhibit premature leaf senescence in tomato plants.Both chemically mutagenized and CRISPR-generated fab2 mutants exhibited excessively accelerated senescence,which resulted in sterility.Transcriptome analysis revealed that FAB2 extended leaf longevity by suppressing transcription of genes highly expressed in mature leaves.Transcription of FAB2 was increased in younger leaves,potentially inhibiting premature leaf senescence.The precocious senescence of fab2 mutants was in contrast to fasciated inflorescence(fin)mutants,which carried mutations in a hydroxyproline O-arabinosyltransferase gene,leading to meristem overproliferation.Our observations indicate that complex genetic hierarchy in the cascade of tomato arabinosyltransferases could control different aspects of developmental processes such as stem cell proliferation and senescence.展开更多
Non-destructive time-series assessment of chlorophyll content in flag-leaf(FLC)accurately mimics the senescence rate and the identification of genetic loci associated with senescence provides valuable knowledge to imp...Non-destructive time-series assessment of chlorophyll content in flag-leaf(FLC)accurately mimics the senescence rate and the identification of genetic loci associated with senescence provides valuable knowledge to improve yield stability under stressed environments.In this study,we employed both unmanned aerial vehicles(UAVs)equipped with red–green–blue(RGB)camera and ground-based SPAD-502 instrument to conduct temporal phenotyping of senescence.A total of 262 recombinant inbred lines derived from the cross of Zhongmai 578/Jimai 22 were evaluated for senescence-related traits across three environments,spanning from heading to 35 d post-anthesis.The manual senescence rate(MSR)was quantified using the FLC and the active accumulated temperature,and UAV derived vegetation index were utilized to assess the stay-green rate(USG)facilitating the identification of senescent and stay-green lines.Results indicated that higher senescence rates significantly impacted grain yield,primarily by influencing thousand-kernel weight,and plant height.Quantitative trait loci(QTL)mapping for FLC,USG,and MSR using the 50K SNP array identified 38 stable loci associated with RGB-based vegetation indices and senescence-related traits:among which 19 loci related to senescence traits from UAV and FLC were consistently detected across at least two growth stages,with nine loci likely representing novel QTL.This study highlights the potential of UAV-based high-throughput phenotyping and phenology in identifying critical loci associated with senescence rates in wheat,validating the relationship between senescence rates and yield-related traits in wheat,offering valuable opportunities for gene discovery and significant applications in breeding programs.展开更多
Developing and identifying effective medications and targets for treating hepatic fibrosis is an urgent priority.Our previous research demonstrated the efficacy of artesunate(ART)in alleviating liver fibrosis by elimi...Developing and identifying effective medications and targets for treating hepatic fibrosis is an urgent priority.Our previous research demonstrated the efficacy of artesunate(ART)in alleviating liver fibrosis by eliminating activated hepatic stellate cells(HSCs).However,the underlying mechanism remains unclear despite these findings.Notably,endocytic adaptor protein(NUMB)has significant implications for treating hepatic diseases,but current research primarily focuses on liver regeneration and hepatocellular carcinoma.The precise function of NUMB in liver fibrosis,particularly its ability to regulate HSCs,requires further investigation.This study aims to elucidate the role of NUMB in the anti-hepatic fibrosis action of ART in HSCs.We observed that the expression level of NUMB significantly decreased in activated HSCs compared to quiescent HSCs,exhibiting a negative correlation with the progression of liver fibrosis.Additionally,ART induced senescence in activated HSCs through the NUMB/P53 tumor suppressor(P53)axis.We identified NUMB as a crucial regulator of senescence in activated HSCs and as a mediator of ART in determining cell fate.This research examines the specific target of ART in eliminating activated HSCs,providing both theoretical and experimental evidence for the treatment of liver fibrosis.展开更多
基金supported by the Anhui Provincial Natural Science Foundation(Grant No.2308085MH250)the Natural Science Research Project of Anhui Educational Committee(Grant No.2023AH053327)the Scientific Research Fund Project of Anhui Medical University(2020xkj039).
文摘Chondrocyte senescence is a critical pathological hallmark of osteoarthritis(OA).Aberrant mechanical stress is considered a pivotal determinant in chondrocyte aging;however,the precise underlying mechanism remains elusive.Our findings demonstrate that SPI1 plays a significant role in counteracting chondrocyte senescence and inhibiting OA progression.SPI1 binds to the PERK promoter,thereby promoting its transcriptional activity.Importantly,PERK,rather than GCN2,facilitates eIF2αphosphorylation,activating the mitochondrial unfolded protein response(UPRmt)and impeding chondrocyte senescence.Deficiency of SPI1 in mechanical overload-induced mice leads to diminished UPRmt activation and accelerated OA progression.Intra-articular injection of adenovirus vectors overexpressing SPI1 and PERK effectively mitigates cartilage degeneration.In summary,our study elucidates the crucial regulatory role of SPI1 in the pathogenesis of chondrocyte senescence by activating UPRmt signaling through PERK,which may present a novel therapeutic target for treating OA.
基金supported by the National Natural Science Foundation of China(32101857 and U21A20218)the China Agricultural University Corresponding Support Research Joint Fund(GSAU-DKZY-2024-001)+1 种基金the Science and Technology Program in Gansu Province,China(24ZDNA008and23JRRA1407)the Fuxi Young Talents Fund of Gansu Agricultural University,China(Gaufx-03Y10).
文摘Intercropping has been widely used in arid and semi-arid regions because of its high yield,stable productivity,and efficient utilization of resources.However,in recent years,the high yield of traditional intercropping is mainly attributed to the large amount of purchased resources such as water and fertilizer,plastic film,and mechanical power.These lead to a decline in cultivated land quality and exacerbate intercrops'premature root and canopy senescence.So,the application of traditional intercropping faces major challenges in crop production.This paper analyzes the manifestations,occurrence mechanisms,and agronomic regulatory pathways of crop senescence.The physiological and ecological characteristics of intercropping to delay root and canopy senescence of crops are reviewed in this paper.The main agronomic regulatory pathways of intercropping to delay root and canopy senescence of crops are based on above-and blow-ground interactions,including collocation of crop varieties,spatial arrangement,water and fertilizer management,and tillage and mulch practices.Future research fields of intercropping to delay root and canopy senescence should focus on the aspects of selecting and breeding special varieties,application of molecular biology techniques,and developing or applying models to predict and evaluate the root and canopy senescence process of intercrops.Comprehensive analysis and evaluation of different research results could provide a basis for enhancing intercropping delay root and canopy senescence through adopting innovative technologies for regulating the physio-ecological characteristics of intercrops.This would support developing and adopting high-yield,efficient,and sustainable intercropping systems in arid and semi-arid areas with high population density,limited land,and abundant light and heat resources.
基金supported by the National Natural Science Foundation of China(32171347)the Foundation of Leading Talents from Shanghai Health Commission(2022XD038)+1 种基金Training Program for Research Physicians in Innovation,the Funda-mental Research Funds for the Central Universities(YG2023QNA23)Transforma-tion from shanghai hospital development center(SHDC2022CRD002).
文摘Stem cells play a crucial role in maintaining tissue regenerative capacity and homeostasis.However,mechanisms associated with stem cell senescence require further investigation.In this study,we conducted a proteomic analysis of human dental pulp stem cells(HDPSCs)obtained from individuals of various ages.Our findings showed that the expression of NUP62 was decreased in aged HDPSCs.We discovered that NUP62 alleviated senescence-associated phenotypes and enhanced differentiation potential both in vitro and in vivo.Conversely,the knocking down of NUP62 expression aggravated the senescence-associated phenotypes and impaired the proliferation and migration capacity of HDPSCs.Through RNA-sequence and decoding the epigenomic landscapes remodeled induced by NUP62 overexpression,we found that NUP62 helps alleviate senescence in HDPSCs by enhancing the nuclear transport of the transcription factor E2F1.This,in turn,stimulates the transcription of the epigenetic enzyme NSD2.Finally,the overexpression of NUP62 influences the H3K36me2 and H3K36me3 modifications of anti-aging genes(HMGA1,HMGA2,and SIRT6).Our results demonstrated that NUP62 regulates the fate of HDPSCs via NSD2-dependent epigenetic reprogramming.
文摘To determine the effects of preharvest arginine spraying on the nutritional level of broccoli and the mechanism of action of arginine in improving the storage quality of broccoli,arginine spraying(5 mmol/L)was conducted at 0,1,3,and 5 days before harvest.The appearance,respiration rate,mass-loss rate,electrolyte leakage,glucosinolate,ascorbic acid,total phenol,total flavonoid,total sugar and sucrose contents,and sucrose phosphate synthase(SPS),invertase(INV),sucrose synthase synthesis(SSS)and cleavage(SSC)activities of broccoli samples were observed after 0,2,4,6,8,and 10 days of storage.The results showed that spraying arginine at 5 days preharvest(5-ARG)helped to inhibit broccoli respiration during storage,delay electrolyte leakage,and maintain broccoli color.Furthermore,during the growth stage,total sugar accumulation was higher in the 5-ARG group.In addition,during the storage period,sucrose synthesis was accelerated,while sucrose cleavage was inhibited,resulting in more sucrose retention in postharvest broccoli.In conclusion,5-ARG resulted in the accumulation of more nutrients during the growth process and effectively delayed the quality decline during storage,thereby prolonging the shelf life of broccoli.Therefore,this study provides a theoretical basis for improving postharvest storage characteristics of broccoli through preharvest treatments.
文摘Objective The nucleolar protein PES1(Pescadillo homolog 1)plays critical roles in ribosome biogenesis and cell cycle regulation,yet its involvement in cellular senescence remains poorly understood.This study aimed to comprehensively investigate the functional consequences of PES1 suppression in cellular senescence and elucidate the molecular mechanisms underlying its regulatory role.Methods Initially,we assessed PES1 expression patterns in two distinct senescence models:replicative senescent mouse embryonic fibroblasts(MEFs)and doxorubicin-induced senescent human hepatocellular carcinoma HepG2 cells.Subsequently,PES1 expression was specifically downregulated using siRNA-mediated knockdown in these cell lines as well as additional relevant cell types.Cellular proliferation and senescence were assessed by EdU incorporation and SA-β-gal staining assays,respectively.The expression of senescence-associated proteins(p53,p21,and Rb)and SASP factors(IL-6,IL-1β,and IL-8)were analyzed by Western blot or qPCR.Furthermore,Northern blot and immunofluorescence were employed to evaluate pre-rRNA processing and nucleolar morphology.Results PES1 expression was significantly downregulated in senescent MEFs and HepG2 cells.PES1 knockdown resulted in decreased EdU-positive cells and increased SA-β-gal-positive cells,indicating proliferation inhibition and senescence induction.Mechanistically,PES1 suppression activated the p53-p21 pathway without affecting Rb expression,while upregulating IL-6,IL-1β,and IL-8 production.Notably,PES1 depletion impaired pre-rRNA maturation and induced nucleolar stress,as evidenced by aberrant nucleolar morphology.Conclusion Our findings demonstrate that PES1 deficiency triggers nucleolar stress and promotes p53-dependent(but Rb-independent)cellular senescence,highlighting its crucial role in maintaining nucleolar homeostasis and regulating senescence-associated pathways.
基金supported by the National Natural Science Foundation of China(82172468,82372436)Outstanding Youth Fund of Jiangsu Province(BK2024047)+1 种基金China Postdoctoral Science Foundation(2023T160553)Postgraduate Research&Practice Innovation Program of Jiangsu Province(SJCX22-1819).
文摘Cellular senescence and its senescence-associated secretory phenotype(SASP)represent a pivotal role in the development of skeletal diseases.Targeted elimination or rejuvenation of senescent cells has shown potential as a therapeutic strategy to reverse age-related skeletal senescence and promote bone regeneration.Meanwhile,other age-related mechanisms,involving altered cellular functions,impaired intercellular crosstalk,disturbed tissue microenvironment,and decreased regenerative capacity,synergistically contribute to the pathogenesis.In this review,we outline the cellular senescence and other age-related mechanisms in developing skeletal diseases,including osteoporosis,intervertebral disc degeneration,osteoarthritis,rheumatoid arthritis,bone tumors and ankylosing spondylitis,with the aim of comprehensively understanding their detrimental effects on the aged skeleton and screening the potential targets for anti-aging therapy within the skeletal system.
文摘Aging is considered the main risk factor for the development of several diseases,including the leading neurodegenerative disorders.While the cellular features of aging are complex and multifaceted,neuronal senescence has emerged as a major contributor and driver of this process in the mammalian cell.Cellular senescence is a programmed response to stress and irreparable damage,which drives the cell into an apoptosis-resistant,non-proliferative state.Senescent cells can also deleteriously affect neighboring,non-senescent cells.Senescence is a complex and multifaceted process associated with a wide range of cellular events,including the secretion of pro-inflammatory molecules and the arrest of the cell cycle.
基金supported by the National Natural Science Foundation of China (NSFC) (No.82172497)
文摘Intervertebral disc degeneration(IDD)is a progressive and dynamic process in which the senescence-associated secretory phenotype(SASP)of nucleus pulposus cells(NPC)plays a significant role.While impaired chaperone-mediated autophagy(CMA)has been associated with inflammation and cellular senescence,its specific involvement in the self-perpetuating feedback loop of NPC senescence remains poorly understood.Through LAMP2A knockout in NPC,we identified a significant upregulation of DYRK1A,a core mediator of premature senescence in Down syndrome.Subsequent validation established DYRK1A as the critical driver of premature senescence in CMA-deficient NPC.Combinatorial transcription factor analysis revealed that under IL1B stimulation or CMA inhibition,elevated DYRK1A promoted FOXC1 phosphorylation and nuclear translocation,initiating transcriptional activation of cell cycle arrest.Intriguingly,CMA impairment concurrently enhanced glutamine metabolic flux in senescent NPC,thereby augmenting their survival fitness.Transcriptomic profiling demonstrated that CMA reactivation in senescent NPC facilitated fate transition from senescence to apoptosis,mediated by decreased glutamine flux via GLUL degradation.Therefore,CMA exerts protective effects against IDD by maintaining equilibrium between premature senescence and senolysis.This study elucidates CMA’s regulatory role in SASP-mediated senescence amplification circuits,providing novel therapeutic insights for IDD and other age-related pathologies.
基金supported by the Hebei Natural Science Foundation(Grant No.H2022110019).
文摘Diabetic kidney disease(DKD)has emerged as one of the leading causes of chronic kidney disease and end-stage renal disease worldwide.In the progression of DKD,renal tubular injury plays a pivotal role,with stress-induced senescence of renal tubular epithelial cells(RTECs)being a critical cellular event contributing to tubular damage in DKD.Recent studies have revealed that multiple mechanisms,including oxidative stress,mitochondrial autophagy,endoplasmic reticulum stress,and epigenetic modifications,can induce stress-induced senescence in RTECs,thereby driving the progression of DKD.In recent years,research has demonstrated that traditional Chinese medicine(TCM)can regulate these mechanisms through multiple targets and key pathways,inhibiting stress-induced senescence in RTECs and ameliorating the progression of DKD.TCM has been widely applied in clinical practice with proven efficacy.This article systematically summarizes the concept of cellular senescence,delves into the relationship between stress-induced senescence of RTECs and DKD,analyzes the mechanisms underlying the formation of stress-induced senescence in RTECs within the context of DKD,and reviews the research progress of TCM in anti-senescence treatment for DKD.The aim is to provide a reference for future research and the development of novel therapeutic strategies.
文摘1.HOU J,DU Y,SHAO Y,et al.Identification,Albanol B inhibits glioblastoma progression by inducing senescence and apoptosis via the RNF6/p27 signaling axis.Phytomedicine.DOI:10.1016/j.phymed.2025.157056.(2025)[题目]Albanol B通过RNF6/p27信号轴诱导细胞衰老与凋亡,从而抑制胶质母细胞瘤进展。
基金supported by grants from the National Natural Science Foundation of China(81930025,82201013,82371020,82370949,82100992)the Young Science and Technology Rising Star Project of Shaanxi Province(2023KJXX-027)the China Postdoctoral Science Foundation(BX20230485).
文摘Healthy aging is a common goal for humanity and society,and one key to achieving it is the rejuvenation of senescent resident stem cells and empowerment of aging organ regeneration.However,the mechanistic understandings of stem cell senescence and the potential strategies to counteract it remain elusive.Here,we reveal that the aging bone microenvironment impairs the Golgi apparatus thus diminishing mesenchymal stem cell(MSC)function and regeneration.Interestingly,replenishment of cell aggregates-derived extracellular vesicles(CA-EVs)rescues Golgi dysfunction and empowers senescent MSCs through the Golgi regulatory protein Syntaxin 5.Importantly,in vivo administration of CA-EVs significantly enhanced the bone defect repair rate and improved bone mass in aging mice,suggesting their therapeutic value for treating age-related osteoporosis and promoting bone regeneration.Collectively,our findings provide insights into Golgi regulation in stem cell senescence and bone aging,which further highlight CA-EVs as a potential rejuvenative approach for aging bone regeneration.
基金supported by grants from the Postdoctoral Science Foundation of China (Grant No. 2020M672072)。
文摘Senescent macrophages have emerged as dynamic cells within the tumor microenvironment that significantly promote tumor progression through complex cellular and molecular functional alterations. This review explores the multifaceted roles of macrophage senescence in cancer, and establishes links between senescent macrophages and tumor progression from multiple perspectives, on the basis of the first comprehensive analysis of the molecular mechanisms and pathways involved. By systematically examining the diverse changes in senescent macrophages, this review integrates and analyzes their effects on tumors, thus offering a comprehensive and novel theoretical foundation, and practical insights for cancer treatment. Notably, by integrating current molecular research and therapeutic advancements, we summarize novel therapeutic strategies targeting senescent macrophages, including senolytics, senescence modulators, and cutting-edge immunotherapies, thereby highlighting the potential of senescent macrophages as a therapeutic target and introducing new opportunities for cancer treatment.
基金Supported by The Department of Veterans Affairs Biomedical Laboratory Research&Development Service Award,No.BX003486(to McMillin M)National Institutes of Health Awards,No.R01DK112803 and No.R01DK135995(to DeMorrow S).
文摘BACKGROUND Acute liver failure(ALF)is a loss of liver function due to a severe hepatic insult.Studies utilizing the azoxymethane(AOM)mouse model of ALF,which also generates hepatic encephalopathy,have primarily focused on development of neurological deficits.However,the molecular processes that generate liver damage have not been fully characterized.Therefore,a more comprehensive characterization of the hepatic consequences of AOM toxicity is needed to better understand this disease model.AIM To identify molecular pathology contributing to hepatic injury during the progression of AOM-induced ALF.METHODS C57BL/6 mice were injected with AOM to produce ALF and hepatic encephalopathy.Tissue was collected at defined stages of neurological decline up to coma.Liver injury,CYP2E1 expression,oxidative stress,inflammation,apoptosis,necroptosis,and hepatocellular senescence were assessed.RESULTS Increased hepatic necrosis and exacerbated liver injury were observed after AOM injection as mice progressed towards coma.CYP2E1 expression decreased in AOM-treated mice as liver injury progressed.Malondialdehyde,myeloperoxidase and other measures of oxidative stress were significantly increased during AOM-induced ALF.Hepatic CCL2 and tumor necrosis factorαexpression increased as AOM-induced liver injury progressed.Mixed lineage kinase domain-like protein phosphorylation was increased early during the progression of AOM-induced liver injury.Measures of apoptosis and cellular senescence all increased as the time course of AOM progressed.CONCLUSION These data support that necrosis,oxidative stress,inflammation,apoptosis,and senescence were elevated in AOMtreated mice,with inflammation being the earliest significant change.
文摘There is still no effective treatment for pancreatic cancer,one of the deadliest malignancies among the gastrointestinal diseases.Jiang et al demonstrated the presence of senescent cancer-associated fibroblasts(CAFs)in pancreatic cancer tissues,supporting the use of CAFs as potential anti-cancer targets.The study indicated that a natural plant-derived compound resveratrol can reverse senescent CAF phenotype and decrease the growth,migration,and invasiveness of pancreatic cancer cells.Notably,the study indicated that resveratrol might be involved in regulating epithelial-to-mesenchymal transition in the tumor microenvironment.This editorial shares insights on the future investigation of resveratrol signaling in cancer cells and the tumor microenvironment,and discusses resveratrol-based treatment perspectives.
基金Supported by the Ministry of Science and Technology of China,No.2021YFA1101502。
文摘BACKGROUND Extracellular vesicles derived from mesenchymal stromal cells(MSC-EVs)can be used for anti-aging therapy and treating various aging-related diseases.However,the clinical application of MSC-EVs is still limited,mainly due to insufficient in-formation on the preparation process,quality,and mechanism of action of MSC-EVs.To study the biological effects of MSC-EVs in regulating cellular senescence.METHODS In this study,we developed a clinical-grade production process for MSC-EVs and defined the release criteria for products suitable for human use.To support the clinical use of our product as a therapeutic agent,we performed efficacy assays to evaluate the anti-aging capacity of MSC-EVs in vitro and in vivo.RESULTS The functional analysis results revealed that MSC-EVs significantly reduced the levels of senescence-associatedβ-galactosidase,matrix metallopeptidase 1,P21,and interleukin-1βand increased the level of collagen I in a naturally aged cell model of human dermal fibroblasts.Similarly,treatment with MSC-EVs effectively improved D-gal-induced subacute aging in mice,aging-related histopathological changes,oxidative stress,and aging-related gene expression.CONCLUSION These findings indicate that MSC-EVs can partially alleviate D-gal-induced senescence by reducing oxidative stress and regulating metabolism.Overall,these findings strongly suggest that MSC-EVs hold promise for aging therapy.
基金made possible by the National Natural Science Foundation of China (32060422)。
文摘Drought is one of the important stress factors affecting the growth and development processes of wheat in China's arid zones, which severely limits the yield. This study examined the impact of deficit irrigation on the flag leaf protection system and yield of drip-irrigated spring wheat during the growth stages in arid zones. In addition, this study aimed to determine the optimal water supply mode for efficient production under drip irrigation conditions and to provide technical support for water-saving and high-yield cultivation of drip-irrigated wheat. The experiment was conducted with a split plot design using the water-sensitive variety Xinchun 22(XC22) and the drought-tolerant variety Xinchun 6(XC6) as the main plots, while a fully irrigated control(CK, 75–80% FC, where FC is field water holding capacity), mild deficit(T1, 60–65% FC) and moderate deficit(T2, 45–50% FC) at the tillering stage, and mild deficit(J1, 60–65% FC) and moderate deficit(J2, 45–50% FC) at the jointing stage were used as the subplots. Systematic studies were conducted on the regulatory effects of deficit irrigation during the tillering and jointing stages on protective substances, membrane lipid metabolism, endogenous hormones in the flag leaf, and yield of spring wheat. Compared with treatments T2 and J2, treatments T1 and J1 were beneficial for increasing the activities of superoxide dismutase(SOD), peroxidase(POD), and catalase(CAT), the levels of proline(Pro), indole-3-acetic acid(IAA), and zeatin riboside(ZR), and the ratios IAA/abscisic acid(ABA), ZR/ABA, IAA/ZR, and(IAA+ZR)/ABA, while reducing the levels of hydrogen peroxide(H2O2), superoxide anion radicals(O2–·), malondialdehyde(MDA), phosphatidic acid(PA), free fatty acids(FFA), ABA, phospholipase D(PLD), and lipoxygenase(LOX), alleviating flag leaf senescence, and increasing yield. Under treatment T1, the SOD, POD, CAT, and Pro levels of flag leaves in XC6 were 11.14, 8.08, 12.98, and 3.66% higher than those of treatment CK, and under treatment J1, they were 6.43, 4.49, 7.36, and 2.50% higher than those of treatment CK. Under treatment T1 in XC6, the IAA, ZR level of the flag leaf, spike number, grains per spike, 1,000-grain weight and yield were 10.50, 5.79, 3.10, 8.84, 3.78, and 10.52% higher than those of treatment CK, and under treatment J1, they were 5.36, 3.94, 2.40, 3.72, 1.37, and 4.46% higher than those of treatment CK. Compared with XC22, XC6 was more conducive to the improvement of flag leaf protective substances, IAA, ZR, dry matter weight, yield components and yield. The correlation analysis showed significant positive correlations between IAA and ZR with SOD, POD, CAT, proline, and yield. IAA and ZR promoted the enhancement of protective enzyme activities, thereby clearing reactive oxygen species to cope with the oxidative stress caused by drought and achieve the effect of delaying senescence. Principal component analysis showed that yield components and dry matter weight, had direct effects on yield. Mild deficiency during the tillering stage without water stress in other stages could effectively optimize yield components, not only achieving high yield while increasing protective substances, but also reducing the reactive oxygen species content. This strategy can be recommended as a water-saving and high-yield production mode for drip irrigation of spring wheat in Xinjiang, China.
基金supported by the National Natural Science Foundation of China(No.32171492)。
文摘Decabromodiphenyl ether(BDE-209)has been recognized for its adverse effects on the male reproductive system.The specific negative effects and underlying mechanisms through which BDE-209 impacts the reproductive function of offspring are not yet fully understood.The present study classified institute of cancer research(ICR)mice into control and BDE-209 treatment groups,administering doses of 0 and 75 mg/(kg·day),respectively.After 50 days of exposure,normal female mice were co-housed with the male mice,and their male offspring were sacrificed at 2 and 12 months of age.Paternal BDE-209 exposure reduced both sperm quantity and quality in offspring.Furthermore,exposure to BDE-209 resulted in DNA damage and the upregulation of the cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)DNA-sensing and inflammatory signaling pathways.The activation resulted in Z-DNA binding protein 1(ZBP1)binding to the mitochondrial antiviral signaling protein(MAVS),subsequently activating mitochondrial apoptosis in the testes.The activation of the cGAS-STING pathway inhibited mitophagy,leading to senescence in the testes of male offspring.In vitro studies indicated that the cGAS inhibitor RU320521(RU.521)effectively reversed the cGAS-STING pathway activation,alleviated the mitophagy inhibition,and decreased apoptosis and senescence in mouse spermatocyte line GC-2spd cells treated with BDE-209.The results showed that paternal BDE-209 exposure might disrupt spermatogenesis in mouse offspring by activating the cGAS-STING pathway and inhibiting mitophagy.This study provides essential data on the toxicity of BDE-209 to male reproduction and have important scientific and practical implications for maintaining biodiversity and population health in general.
基金funded by National Research Foundation(NRF)of the Ministry of Science and ICT(MSIT),Republic of Korea(Grant Nos.2022R1C1C1002941,2020R1A2C1004273,2020R1A2C1101915)。
文摘Senescence,a crucial developmental process in the life cycle of plants,involves programmed destruction of cellular components of leaves.The onset of senescence is synchronized with other developmental processes for successful reproduction since senescence eventually leads to cell death.Arabinosyltransferase FASCIATED AND BRANCHED 2(FAB2)is known to control meristem proliferation.Here,we show that FAB2 could inhibit premature leaf senescence in tomato plants.Both chemically mutagenized and CRISPR-generated fab2 mutants exhibited excessively accelerated senescence,which resulted in sterility.Transcriptome analysis revealed that FAB2 extended leaf longevity by suppressing transcription of genes highly expressed in mature leaves.Transcription of FAB2 was increased in younger leaves,potentially inhibiting premature leaf senescence.The precocious senescence of fab2 mutants was in contrast to fasciated inflorescence(fin)mutants,which carried mutations in a hydroxyproline O-arabinosyltransferase gene,leading to meristem overproliferation.Our observations indicate that complex genetic hierarchy in the cascade of tomato arabinosyltransferases could control different aspects of developmental processes such as stem cell proliferation and senescence.
基金funded by the National Key Research and Development Program of China(2022ZD0115703)the National Natural Science Foundation of China(32372196)+1 种基金the Beijing Joint Research Program for Germplasm Innovation and New Variety Breeding(G20220628002)National Natural Science Foundation of China(32250410307)。
文摘Non-destructive time-series assessment of chlorophyll content in flag-leaf(FLC)accurately mimics the senescence rate and the identification of genetic loci associated with senescence provides valuable knowledge to improve yield stability under stressed environments.In this study,we employed both unmanned aerial vehicles(UAVs)equipped with red–green–blue(RGB)camera and ground-based SPAD-502 instrument to conduct temporal phenotyping of senescence.A total of 262 recombinant inbred lines derived from the cross of Zhongmai 578/Jimai 22 were evaluated for senescence-related traits across three environments,spanning from heading to 35 d post-anthesis.The manual senescence rate(MSR)was quantified using the FLC and the active accumulated temperature,and UAV derived vegetation index were utilized to assess the stay-green rate(USG)facilitating the identification of senescent and stay-green lines.Results indicated that higher senescence rates significantly impacted grain yield,primarily by influencing thousand-kernel weight,and plant height.Quantitative trait loci(QTL)mapping for FLC,USG,and MSR using the 50K SNP array identified 38 stable loci associated with RGB-based vegetation indices and senescence-related traits:among which 19 loci related to senescence traits from UAV and FLC were consistently detected across at least two growth stages,with nine loci likely representing novel QTL.This study highlights the potential of UAV-based high-throughput phenotyping and phenology in identifying critical loci associated with senescence rates in wheat,validating the relationship between senescence rates and yield-related traits in wheat,offering valuable opportunities for gene discovery and significant applications in breeding programs.
基金supported by the National Natural Science Foundation of China(Nos.82474164,82374124,82073914,82173874,82274185,82305046 and 82304902)the Natural Science Foundation of Jiangsu Province(Nos.BK20230458 and BK20220467)+1 种基金the General Project of the Natural Science Research of Jiangsu Higher Education Institutions(No.23KJB310017)Young Elite Scientists Sponsorship Program by CACM(No.2022-QNRC2-B15).
文摘Developing and identifying effective medications and targets for treating hepatic fibrosis is an urgent priority.Our previous research demonstrated the efficacy of artesunate(ART)in alleviating liver fibrosis by eliminating activated hepatic stellate cells(HSCs).However,the underlying mechanism remains unclear despite these findings.Notably,endocytic adaptor protein(NUMB)has significant implications for treating hepatic diseases,but current research primarily focuses on liver regeneration and hepatocellular carcinoma.The precise function of NUMB in liver fibrosis,particularly its ability to regulate HSCs,requires further investigation.This study aims to elucidate the role of NUMB in the anti-hepatic fibrosis action of ART in HSCs.We observed that the expression level of NUMB significantly decreased in activated HSCs compared to quiescent HSCs,exhibiting a negative correlation with the progression of liver fibrosis.Additionally,ART induced senescence in activated HSCs through the NUMB/P53 tumor suppressor(P53)axis.We identified NUMB as a crucial regulator of senescence in activated HSCs and as a mediator of ART in determining cell fate.This research examines the specific target of ART in eliminating activated HSCs,providing both theoretical and experimental evidence for the treatment of liver fibrosis.
