Teapolyphenols are the generic term of polyphenols in tea.Tea polyphenols are non-toxic and odorless with high oxidation resistance.Heat stress causes oxidative stress,which impairs the capacity of antioxidant defense...Teapolyphenols are the generic term of polyphenols in tea.Tea polyphenols are non-toxic and odorless with high oxidation resistance.Heat stress causes oxidative stress,which impairs the capacity of antioxidant defense system and immunity,thereby seriously affecting the production performance of animals.Teapolyphenols could reduce heatstress response in animals by scavenging harmful free radicals and increasing the activities of antioxidant enzymes.展开更多
Irisin is a polypeptide hormone derived from the proteolytic cleavage of fibronectin-type III domain- containing 5 （FNDC5） protein. Once released to circulation upon exercise or cold exposure, irisin stimulates brow...Irisin is a polypeptide hormone derived from the proteolytic cleavage of fibronectin-type III domain- containing 5 （FNDC5） protein. Once released to circulation upon exercise or cold exposure, irisin stimulates browning of white adipose tissue （WAT） and uncoupling protein I （UCP1） expression, leading to an increase in total body energy expenditure by augmented UCPl-mediated thermogenesis. It is currently unknown whether irisin is secreted by bone upon exercise or whether it regulates bone metabolism in vivo. In this study, we found that 2 weeks of voluntary wheel-running exercise induced high levels of FNDC5 messenger RNA as well as FNDC5/irisin protein expression in murine bone tissues. Increased immunoreactivity due to exercise-induced FNDC5/irisin expression was detected in different regions of exercised femoral bones, including growth plate, trabecular bone, cortical bone, articular cartilage, and bone-tendon interface. Exercise also increased expression of osteogenic markers in bone and that of UCP1 in WAT, and led to bodyweight loss. Irisin intraperitoneal （IP） administration resulted in increased trabecular and cortical bone thickness and osteoblasts numbers, and concurrently induced UCP1 expression in subcutaneous WAT. Lentiviral FNDC5 IP administration increased cortical bone thickness. In vitro studies in bone cells revealed irisin increases osteoblastogenesis and mineralization, and inhibits receptor activator of nuclear factor-kB ligand （RANKL）- induced osteoclastogenesis. Taken together, our findings show that voluntary exercise increases irisin production in bone, and that an increase in circulating irisin levels enhances osteogenesis in mice.展开更多
Okadaic acid： Okadaic acid （OKA）, a polyether （C38 fatty acid） toxin, is a potent and selective inhibitor of protein phosphatase, PP1 and protein phosphatase 2A （PP2A）. It is mainly extracted from a black spong...Okadaic acid： Okadaic acid （OKA）, a polyether （C38 fatty acid） toxin, is a potent and selective inhibitor of protein phosphatase, PP1 and protein phosphatase 2A （PP2A）. It is mainly extracted from a black sponge Hallichondria okadaii and has been suggested to play a potent probe for studying the various molecular, cellular, biochemical and mechanism of neurotoxicity. It is known as a selective and potent in- hibitor of serine/threonine phosphatases 1 and 2A induces hyperphosphorylation of tau in vitro and in vivo. It has been reported that Alzheimer＇s disease （AD） is a complex multi- factorial neurodegenerative disorder and hyperphosphor- ylated tau protein is a major pathological hallmark of AD. The reduced activity of phosphatases like, PP2A has been implicated in the brain of AD patients. OKA also induced inhibition of protein phosphatases cause neurofibrillary tangles （NFTs） like pathological changes and tau hyperphos- phorylation seen in AD pathology. Our and others reports inferred that OKA induces neurodegeneration along with tau hyperphosphorylation, GSK3β activation, oxidative stress, neuroinflammation and neurotoxicity which are char- acteristic of AD pathology （Figure 1）.展开更多
MicroRNA(miRNA)plays a key role in the molecular regulation of neurological diseases,and the molecular mechanism of miRNA is closely related to the occurrence and development of hypoxic-ischemic encephalopathy.Recentl...MicroRNA(miRNA)plays a key role in the molecular regulation of neurological diseases,and the molecular mechanism of miRNA is closely related to the occurrence and development of hypoxic-ischemic encephalopathy.Recently,it has been reported that various miRNA molecules can inhibit target mRNA and even degrade target mRNA by changing the complete complementary or incomplete complementary binding to the target mRNA.Therefore,miRNA is of great significance for the study of mRNA related to hypoxic ischemic encephalopathy.This article briefly reviews the molecular mechanisms,functions and regulation of miRNAs on hypoxic-ischemic encephalopathy.展开更多
Global climate change-caused drought stress,high temperatures and other extreme weather profoundly impact plant growth and development,restricting sustainable crop production.To cope with various environmental stimuli...Global climate change-caused drought stress,high temperatures and other extreme weather profoundly impact plant growth and development,restricting sustainable crop production.To cope with various environmental stimuli,plants can optimize the opening and closing of stomata to balance CO_(2)uptake for photosynthesis and water loss from leaves.Guard cells perceive and integrate various signals to adjust stomatal pores through turgor pressure regulation.Molecular mechanisms and signaling networks underlying the stomatal movements in response to environmental stresses have been extensively studied and elucidated.This review focuses on the molecular mechanisms of stomatal movements mediated by abscisic acid,light,CO_(2),reactive oxygen species,pathogens,temperature,and other phytohormones.We discussed the significance of elucidating the integrative mechanisms that regulate stomatal movements in helping design smart crops with enhanced water use efficiency and resilience in a climate-changing world.展开更多
Reprogramming of energy metabolism is one of the basic characteristics of cancer and has been proved to be an important cancer treatment strategy.Isocitrate dehydrogenases(IDHs)are a class of key proteins in energy me...Reprogramming of energy metabolism is one of the basic characteristics of cancer and has been proved to be an important cancer treatment strategy.Isocitrate dehydrogenases(IDHs)are a class of key proteins in energy metabolism,including IDH1,IDH2,and IDH3,which are involved in the oxidative decarboxylation of isocitrate to yield a-ketoglutarate(a-KG).Mutants of IDH1 or IDH2 can produce D-2-hydroxyglutarate(D-2HG)with a-KG as the substrate,and then mediate the occurrence and development of cancer.At present,no IDH3 mutation has been reported.The results of pan-cancer research showed that IDH1 has a higher mutation frequency and involves more cancer types than IDH2,implying IDH1 as a promising anti-cancer target.Therefore,in this review,we summarized the regulatory mechanisms of IDH1 on cancer from four aspects:metabolic reprogramming,epigenetics,immune microenvironment,and phenotypic changes,which will provide guidance for the understanding of IDH1 and exploring leading-edge targeted treatment strategies.In addition,we also reviewed available IDH1 inhibitors so far.The detailed clinical trial results and diverse structures of preclinical candidates illustrated here will provide a deep insight into the research for the treatment of IDH1-related cancers.展开更多
Background In poultry, the smooth transition of follicles from the preovulatory-to-postovulatory phase impacts egg production in hens and can benefit the poultry industry. However, the regulatory mechanism underlying ...Background In poultry, the smooth transition of follicles from the preovulatory-to-postovulatory phase impacts egg production in hens and can benefit the poultry industry. However, the regulatory mechanism underlying follicular ovulation in avians is a complex biological process that remains unclear.Results Critical biochemical events involved in ovulation in domestic chickens(Gallus gallus) were evaluated by transcriptomics, proteomics, and in vitro assays. Comparative transcriptome analyses of the largest preovulatory follicle(F1) and postovulatory follicle(POF1) in continuous laying(CL) and intermittent laying(IL) chickens indicated the greatest difference between CL_F1 and IL_F1, with 950 differentially expressed genes(DEGs), and the smallest difference between CL_POF1 and IL_POF1, with 14 DEGs. Additionally, data-independent acquisition proteomics revealed 252 differentially abundant proteins between CL_F1 and IL_F1. Perivitelline membrane synthesis, steroid biosynthesis, lysosomes, and oxidative phosphorylation were identified as pivotal pathways contributing to ovulation regulation. In particular, the regulation of zona pellucida sperm-binding protein 3, plasminogen activator, cathepsin A, and lactate dehydrogenase A(LDHA) was shown to be essential for ovulation. Furthermore, the inhibition of LDHA decreased cell viability and promoted apoptosis of ovarian follicles in vitro.Conclusions This study reveals several important biochemical events involved in the process of ovulation, as well as crucial role of LDHA. These findings improve our understanding of ovulation and its regulatory mechanisms in avian species.展开更多
Flower and fruit abscission is a highly programmed physiological process,which is closely related to the yield of horticultural plants.The coordination of many regulatory factors associated with metabolic and signalin...Flower and fruit abscission is a highly programmed physiological process,which is closely related to the yield of horticultural plants.The coordination of many regulatory factors associated with metabolic and signaling pathways plays a key role in the flower and fruit shedding.Hormones,peptides,carbohydrates,polyamines or cell wall modifying proteins regulate flower and fruit shedding.This article reviewed the recent studies of flower and fruit abscission,including the molecular regulation mechanism of abscission zone formation,typical structure and location of abscission zones,and other factors affecting flower and fruit abscission,such as stresses,hormones,peptides,carbohydrates,polyamines and cell wall modifying proteins.Overall,the review summarizes the developmental mechanism and the diversity of abscission zones,and the key factors affecting flower and fruit abscission of horticultural plants,aiming to provide guidance for studying the molecular regulatory mechanism of flower and fruit abscission.展开更多
Objective To explore the expression of S100A14 in breast cancer tissue,and the EGF and S100A14 feedback regulatory mechanism.Methods S100A14 mRNA level in 52 cases of breast cancer and adjacent normal tissue was detec...Objective To explore the expression of S100A14 in breast cancer tissue,and the EGF and S100A14 feedback regulatory mechanism.Methods S100A14 mRNA level in 52 cases of breast cancer and adjacent normal tissue was detected by quantitative real-time PCR.S100A14 protein in 21 cases of breast cancer and adjacent normal tissue was detected by Western blot.展开更多
Eukaryotic genomes are hierarchically packaged into cell nucleus,affecting gene regulation.The genome is organized into multiscale structural units,including chromosome territories,compartments,topologically associati...Eukaryotic genomes are hierarchically packaged into cell nucleus,affecting gene regulation.The genome is organized into multiscale structural units,including chromosome territories,compartments,topologically associating domains(TADs),and DNA loops.The identification of these hierarchical structures has benefited from the development of experimental approaches,such as 3C-based methods(Hi-C,ChIA-PET,etc.),imaging tools(2D-FISH,3D-FISH,Cryo-FISH,etc.)and ligation-free methods(GAM,SPRITE,etc.).In recent two decades,numerous studies have shown that the 3D organization of genome plays essential roles in multiple cellular processes via various mechanisms,such as regulating enhancer activity and promoter-enhancer interactions.However,there are relatively few studies about the 3D genome in livestock species.Therefore,studies for exploring the function of 3D genomes in livestock are urgently needed to provide a more comprehensive understanding of potential relationships between the genome and production traits.In this review,we summarize the recent advances of 3D genomics and its biological functions in human and mouse studies,drawing inspiration to explore the 3D genomics of livestock species.We then mainly focus on the biological functions of 3D genome organization in muscle development and its implications in animal breeding.展开更多
3,3′,5-Triiodo-L-thyronine(T3)is a key endocrine hormone in the human body that plays crucial roles in growth,development,metabolism,and immune function.Macrophages,the key regulatory cells within the immune system,e...3,3′,5-Triiodo-L-thyronine(T3)is a key endocrine hormone in the human body that plays crucial roles in growth,development,metabolism,and immune function.Macrophages,the key regulatory cells within the immune system,exhibit marked“heterogeneity”and“plasticity”,with their phenotype and function subject to modulation by local environmental signals.The interplay between the endocrine and immune systems is well documented.Numerous studies have shown that T3 significantly target macrophages,highlighting them as key cellular components in this interaction.Through the regulation of macrophage function and phenotype,T3 influences immune function and tissue repair in the body.This review comprehensively summarizes the regulatory actions and mechanisms of T3 on macrophages,offering valuable insights into further research of the immunoregulatory effects of T3.展开更多
Ferroptosis is a pattern of iron-mediated regulatory cell death characterized by oxidative damage.The molecular regulatory mechanisms are related to iron metabolism,lipid peroxidation,and glutathione metabolism.Additi...Ferroptosis is a pattern of iron-mediated regulatory cell death characterized by oxidative damage.The molecular regulatory mechanisms are related to iron metabolism,lipid peroxidation,and glutathione metabolism.Additionally,some immunological signaling pathways,such as the cyclic GMP-AMP synthase-stimulator of the interferon gene axis,the Janus kinase-signal transducer and activator of transcription 1 axis,and the transforming growth factor beta 1-Smad3 axis,may also participate in the regulation of ferroptosis.Studies have shown that ferroptosis is significantly associated with many diseases such as cancer,neurodegenerative diseases,inflammatory diseases,and autoimmune diseases.Considering the pivotal role of ferroptosis-regulating signaling in the pathogenesis of diverse diseases,the development of ferroptosis inducers or inhibitors may have significant clinical potential for the treatment of aforementioned conditions.展开更多
In order to scientifically deal with the problems of less water and more sediment in the Yellow River and the uncoordinated relationship between water and sediment,it is necessary to establish a perfect water and sedi...In order to scientifically deal with the problems of less water and more sediment in the Yellow River and the uncoordinated relationship between water and sediment,it is necessary to establish a perfect water and sediment regulation system.Through the calculation of the sediment transport capacity of the Yellow River and the application of the water and sediment regulation system,it is found that the sediment transport efficiency of the Yellow River will increase with the increase of water flow,and there will be an obvious inflection point near the flat discharge.The joint regulation of the backbone reservoir group can discharge the large discharge close to the minimum flat discharge of the downstream river,which improves the sediment transport capacity of the river and alleviates the problem of sediment deposition.In this paper,through the introduction of the Yellow River water and sediment regulation project system,regulation indicators and mechanisms,the author discusses in detail the Yellow River water and sediment regulation scheme and its operation effect,hoping to provide help promote the improvement of the Yellow River governance effect.展开更多
Increasing tiller number is a target of high-yield rice breeding. Identification of tiller-defect mutants and their corresponding genes is helpful for clarifying the molecular mechanism of rice tillering. Summarizing ...Increasing tiller number is a target of high-yield rice breeding. Identification of tiller-defect mutants and their corresponding genes is helpful for clarifying the molecular mechanism of rice tillering. Summarizing research progress on the two processes of rice tiller formation, namely the formation and growth of axillary meristem, this paper reviews the effects of genetic factors, endogenous hormones, and exogenous environment on rice tillering, finding that multiple molecular mechanisms and signal pathways regulating rice tillering cooperate rice tillering, and discusses future research objectives and application of its regulatory mechanism. Elucidation of theis mechanism will be helpful for breeding high-yielding rice cultivars with ideal plant type via molecular design breeding.展开更多
Drug transporters are essential players in the transmembrane transport of a wide variety of clinical drugs.The broad substrate spectra and versatile distribution pattern of these membrane proteins infer their pharmaco...Drug transporters are essential players in the transmembrane transport of a wide variety of clinical drugs.The broad substrate spectra and versatile distribution pattern of these membrane proteins infer their pharmacological and clinical significance.With our accumulating knowledge on the three-dimensional structure of drug transporters,their oligomerization status has become a topic of intense study due to the possible functional roles carried out by such kind of post-translational modification(PTM).In-depth studies of oligomeric complexes formed among drug transporters as well as their interactions with other regulatory proteins can help us better understand the regulatory mechanisms of these membrane proteins,provide clues for the development of novel drugs,and improve the therapeutic efficacy.In this review,we describe different oligomerization forms as well as their structural basis of major drug transporters in the ATP-binding cassette and solute carrier superfamilies,summarize our current knowledge on the influence of oligomerization for protein expression level and transport function of these membrane proteins,and discuss the regulatory mechanisms of oligomerization.Finally,we highlight the challenges associated with the current oligomerization studies and propose some thoughts on the pharmaceutical application of this important drug transporter PTM.展开更多
To avoid credit fraud,social credit within an economic system has become an increasingly important criterion for the evaluation of economic agent activity and guaranteeing the development of a market economy with mini...To avoid credit fraud,social credit within an economic system has become an increasingly important criterion for the evaluation of economic agent activity and guaranteeing the development of a market economy with minimal supervision costs.This paper provides a comprehensive review of the social credit literature from the perspectives of theoretical foundation,scoring methods,and regulatory mechanisms.The study considers the credit of various economic agents within the social credit system such as countries(or governments),corporations,and individuals and their credit variations in online markets(i.e.,network credit).A historical review of the theoretical(or model)development of economic agents is presented together with significant works and future research directions.Some interesting conclusions are summarized from the literature review.(1)Credit theory studies can be categorized into traditional and emerging schools both focusing on the economic explanation of social credit in conjunction with creation and evolution mechanisms.(2)The most popular credit scoring methods include expert systems,econometric models,artificial intelligence(AI)techniques,and their hybrid forms.Evaluation indexes should vary across different target agents.(3)The most pressing task for regulatory mechanisms that supervise social credit to avoid credit fraud is the establishment of shared credit databases with consistent data standards.展开更多
Plasmacytoma variant translocation 1 (PVT1) is a long non-coding RNA (lncRNA) gene identified as a recurrent breakpoint of Burkitt’s lymphomas. Human PVT1 gene is located on region 8q24.21, a well-known cancer risk r...Plasmacytoma variant translocation 1 (PVT1) is a long non-coding RNA (lncRNA) gene identified as a recurrent breakpoint of Burkitt’s lymphomas. Human PVT1 gene is located on region 8q24.21, a well-known cancer risk region, and encodes at least 26 linear ncRNA isoforms and 26 circular RNA isoforms, as well as 6 microRNAs. Several PVT1 functioning models have been reported recently such as competing endogenous RNA (ceRNA) activity and regulating protein stability of oncogenes, especially MYC oncogene. The promoter of PVT1 gene is a boundary element of tumor-suppressor DNA. CircPVT1 derived from PVT1 gene is also a critical non-coding oncogenic RNA. Although substantial advancements have been made in understanding the roles of PVT1 in cancer recently, the detailed mechanisms underlying its functions remain unclear. Herein, we summarize the recent progressions on the mechanisms underlying PVT1 regulated gene expression at different levels. We also discuss the interaction between lncRNA and protein, RNA and DNA, as well as the potential cancer therapy strategy by targeting these networks.展开更多
State transition is a fundamental light acclimation mechanism of photosynthetic organisms in response to the environmental light conditions.This process rebalances the excitation energy between photosystemI(PSl)and ph...State transition is a fundamental light acclimation mechanism of photosynthetic organisms in response to the environmental light conditions.This process rebalances the excitation energy between photosystemI(PSl)and photosystem Il through regulated reversible binding of the light-harvesting complex Il(LHCll)to PSl.However,the structural reorganization of PSI-LHCI,the dynamic binding of LHCll,and the regulatory mechanisms underlying state transitions are less understood in higher plants.In this study,using cryoelectron microscopy we resolved the structures of PSI-LHCI in both state 1(PSI-LHCI-ST1)and state 2(PSILHCI-LHCll-ST2)from Arabidopsis thaliana.Combined genetic and functional analyses revealed novel contacts between Lhcb1 and PsaK that further enhanced the binding of the LHCll trimer to the PSI core with the known interactions between phosphorylated Lhcb2 and the PsaL/PsaH/PsaO subunits.Specifically,PsaO was absent in the PSI-LHCI-ST1 supercomplex but present in the PSI-LHCI-LHCIl-ST2 supercomplex,in which the PsaL/PsaK/PsaA subunits undergo several conformational changes to strengthen the binding of PsaO in ST2.Furthermore,the PSI-LHCI module adopts a more compact configuration with shorter Mg-to-Mg distances between the chlorophylls,which may enhance the energy transfer efficiency from the peripheral antenna to the PSl core in ST2.Collectively,our work provides novel structural and functional insights into the mechanisms of light acclimation during state transitions in higher plants.展开更多
Cell death is a central process for organismal health.Pyroptosis,namely pyroptotic cell death,is recognized as a critical type that disrupts membrane and triggers pro-inflammatory cytokine secretion via gasdermins,pro...Cell death is a central process for organismal health.Pyroptosis,namely pyroptotic cell death,is recognized as a critical type that disrupts membrane and triggers pro-inflammatory cytokine secretion via gasdermins,providing a robust form of cytolysis.Meanwhile,along with the thorough research,a great deal of evidence has demonstrated the dual effects of pyroptosis in host defense and inflammatory diseases.More importantly,the recent identification of abundant gasdermin-like proteins in bacteria and fungi suggests an ancient origin of pyroptosis-based regulated cell death in the life evolution.In this review,we bring a general overview of pyroptosis pathways focusing on gasdermin structural biology,regulatory mechanisms,and recent progress in induction and inhibition strategies for disease treatment.We look forward to providing an insightful perspective for readers to comprehend the frame and challenges of the pyroptosis field,and to accelerating its clinical application.展开更多
Regulated cell death(RCD)is a controlled form of cell death orchestrated by one or more cascading signaling pathways,making it amenable to pharmacological intervention.RCD subroutines can be categorized as apoptotic o...Regulated cell death(RCD)is a controlled form of cell death orchestrated by one or more cascading signaling pathways,making it amenable to pharmacological intervention.RCD subroutines can be categorized as apoptotic or non-apoptotic and play essential roles in maintaining homeostasis,facilitating development,and modulating immunity.Accumulating evidence has recently revealed that RCD evasion is frequently the primary cause of tumor survival.Several non-apoptotic RCD subroutines have garnered attention as promising cancer therapies due to their ability to induce tumor regression and prevent relapse,comparable to apoptosis.Moreover,they offer potential solutions for overcoming the acquired resistance of tumors toward apoptotic drugs.With an increasing understanding of the underlying mechanisms governing these non-apoptotic RCD subroutines,a growing number of small-molecule compounds targeting single or multiple pathways have been discovered,providing novel strategies for current cancer therapy.In this review,we comprehensively summarized the current regulatory mechanisms of the emerging non-apoptotic RCD subroutines,mainly including autophagy-dependent cell death,ferroptosis,cuproptosis,disulfidptosis,necroptosis,pyroptosis,alkaliptosis,oxeiptosis,parthanatos,mitochondrial permeability transition(MPT)-driven necrosis,entotic cell death,NETotic cell death,lysosome-dependent cell death,and immunogenic cell death(ICD).Furthermore,we focused on discussing the pharmacological regulatory mechanisms of related small-molecule compounds.In brief,these insightful findings may provide valuable guidance for investigating individual or collaborative targeting approaches towards different RCD subroutines,ultimately driving the discovery of novel small-molecule compounds that target RCD and significantly enhance future cancer therapeutics.展开更多
文摘Teapolyphenols are the generic term of polyphenols in tea.Tea polyphenols are non-toxic and odorless with high oxidation resistance.Heat stress causes oxidative stress,which impairs the capacity of antioxidant defense system and immunity,thereby seriously affecting the production performance of animals.Teapolyphenols could reduce heatstress response in animals by scavenging harmful free radicals and increasing the activities of antioxidant enzymes.
基金supported by a R01DE21464 through the National Institutes of Healthan Innovation in Oral Care Award through International Association for Dental Research and Glaxo Smith Kline Consumer Healthcare+2 种基金an Award through International Team of Implantology to JCby GZUCM Science Fund for Creative Research Groups(2016KYTD10)GZUCM Torch Program(A1-AFD015142Z08)to JZ
文摘Irisin is a polypeptide hormone derived from the proteolytic cleavage of fibronectin-type III domain- containing 5 （FNDC5） protein. Once released to circulation upon exercise or cold exposure, irisin stimulates browning of white adipose tissue （WAT） and uncoupling protein I （UCP1） expression, leading to an increase in total body energy expenditure by augmented UCPl-mediated thermogenesis. It is currently unknown whether irisin is secreted by bone upon exercise or whether it regulates bone metabolism in vivo. In this study, we found that 2 weeks of voluntary wheel-running exercise induced high levels of FNDC5 messenger RNA as well as FNDC5/irisin protein expression in murine bone tissues. Increased immunoreactivity due to exercise-induced FNDC5/irisin expression was detected in different regions of exercised femoral bones, including growth plate, trabecular bone, cortical bone, articular cartilage, and bone-tendon interface. Exercise also increased expression of osteogenic markers in bone and that of UCP1 in WAT, and led to bodyweight loss. Irisin intraperitoneal （IP） administration resulted in increased trabecular and cortical bone thickness and osteoblasts numbers, and concurrently induced UCP1 expression in subcutaneous WAT. Lentiviral FNDC5 IP administration increased cortical bone thickness. In vitro studies in bone cells revealed irisin increases osteoblastogenesis and mineralization, and inhibits receptor activator of nuclear factor-kB ligand （RANKL）- induced osteoclastogenesis. Taken together, our findings show that voluntary exercise increases irisin production in bone, and that an increase in circulating irisin levels enhances osteogenesis in mice.
基金supported in part by Council of Scientific and Industrial Research(CSIR),IndiaNational Institute of Health,USA
文摘Okadaic acid： Okadaic acid （OKA）, a polyether （C38 fatty acid） toxin, is a potent and selective inhibitor of protein phosphatase, PP1 and protein phosphatase 2A （PP2A）. It is mainly extracted from a black sponge Hallichondria okadaii and has been suggested to play a potent probe for studying the various molecular, cellular, biochemical and mechanism of neurotoxicity. It is known as a selective and potent in- hibitor of serine/threonine phosphatases 1 and 2A induces hyperphosphorylation of tau in vitro and in vivo. It has been reported that Alzheimer＇s disease （AD） is a complex multi- factorial neurodegenerative disorder and hyperphosphor- ylated tau protein is a major pathological hallmark of AD. The reduced activity of phosphatases like, PP2A has been implicated in the brain of AD patients. OKA also induced inhibition of protein phosphatases cause neurofibrillary tangles （NFTs） like pathological changes and tau hyperphos- phorylation seen in AD pathology. Our and others reports inferred that OKA induces neurodegeneration along with tau hyperphosphorylation, GSK3β activation, oxidative stress, neuroinflammation and neurotoxicity which are char- acteristic of AD pathology （Figure 1）.
基金National Natural Science Foundation of China(No.30671803,81273174)National University Student Innovation and Entrepreneurship Project(No.201810222013)
文摘MicroRNA(miRNA)plays a key role in the molecular regulation of neurological diseases,and the molecular mechanism of miRNA is closely related to the occurrence and development of hypoxic-ischemic encephalopathy.Recently,it has been reported that various miRNA molecules can inhibit target mRNA and even degrade target mRNA by changing the complete complementary or incomplete complementary binding to the target mRNA.Therefore,miRNA is of great significance for the study of mRNA related to hypoxic ischemic encephalopathy.This article briefly reviews the molecular mechanisms,functions and regulation of miRNAs on hypoxic-ischemic encephalopathy.
基金supported by grants from the National Natural Science Foundation of China(32070306,31921001,and 32202458)the National Key R&D Program of China(2022YFF1001600,2021YFF1000500 and 2022YFD1900704)+1 种基金the Chinese Universities Scientific Fund(2023RC015)the 2115 Talent Development Program of China Agricultural University。
文摘Global climate change-caused drought stress,high temperatures and other extreme weather profoundly impact plant growth and development,restricting sustainable crop production.To cope with various environmental stimuli,plants can optimize the opening and closing of stomata to balance CO_(2)uptake for photosynthesis and water loss from leaves.Guard cells perceive and integrate various signals to adjust stomatal pores through turgor pressure regulation.Molecular mechanisms and signaling networks underlying the stomatal movements in response to environmental stresses have been extensively studied and elucidated.This review focuses on the molecular mechanisms of stomatal movements mediated by abscisic acid,light,CO_(2),reactive oxygen species,pathogens,temperature,and other phytohormones.We discussed the significance of elucidating the integrative mechanisms that regulate stomatal movements in helping design smart crops with enhanced water use efficiency and resilience in a climate-changing world.
基金supported by National Natural Science Foundation of China(NSFC)(No.81773637,82141216,U1803122)Chunhui Program-Cooperative Research Project of the Ministry of Education+2 种基金Shenyang Young and Middle-aged Innovative Talents Support Program(RC210446,China)Liaoning Province Natural Science Foundation(Nos.2022-MS-241,2020-MZLH-31,China)support from National-Local Joint Engineering Research Center for Molecular Biotechnology of Fujian&Taiwan TCM,Fujian Key Laboratory of Chinese Materia Medica,Fujian University Key Laboratory for Research and Development of TCM Resources,at Fujian University of Traditional Chinese Medicine。
文摘Reprogramming of energy metabolism is one of the basic characteristics of cancer and has been proved to be an important cancer treatment strategy.Isocitrate dehydrogenases(IDHs)are a class of key proteins in energy metabolism,including IDH1,IDH2,and IDH3,which are involved in the oxidative decarboxylation of isocitrate to yield a-ketoglutarate(a-KG).Mutants of IDH1 or IDH2 can produce D-2-hydroxyglutarate(D-2HG)with a-KG as the substrate,and then mediate the occurrence and development of cancer.At present,no IDH3 mutation has been reported.The results of pan-cancer research showed that IDH1 has a higher mutation frequency and involves more cancer types than IDH2,implying IDH1 as a promising anti-cancer target.Therefore,in this review,we summarized the regulatory mechanisms of IDH1 on cancer from four aspects:metabolic reprogramming,epigenetics,immune microenvironment,and phenotypic changes,which will provide guidance for the understanding of IDH1 and exploring leading-edge targeted treatment strategies.In addition,we also reviewed available IDH1 inhibitors so far.The detailed clinical trial results and diverse structures of preclinical candidates illustrated here will provide a deep insight into the research for the treatment of IDH1-related cancers.
基金supported by the National Key Research and Development Program of China (2022YFD1600902)Key Research and Development Program of Shandong (2022LZGC013)China Agriculture Research System (CARS-40)。
文摘Background In poultry, the smooth transition of follicles from the preovulatory-to-postovulatory phase impacts egg production in hens and can benefit the poultry industry. However, the regulatory mechanism underlying follicular ovulation in avians is a complex biological process that remains unclear.Results Critical biochemical events involved in ovulation in domestic chickens(Gallus gallus) were evaluated by transcriptomics, proteomics, and in vitro assays. Comparative transcriptome analyses of the largest preovulatory follicle(F1) and postovulatory follicle(POF1) in continuous laying(CL) and intermittent laying(IL) chickens indicated the greatest difference between CL_F1 and IL_F1, with 950 differentially expressed genes(DEGs), and the smallest difference between CL_POF1 and IL_POF1, with 14 DEGs. Additionally, data-independent acquisition proteomics revealed 252 differentially abundant proteins between CL_F1 and IL_F1. Perivitelline membrane synthesis, steroid biosynthesis, lysosomes, and oxidative phosphorylation were identified as pivotal pathways contributing to ovulation regulation. In particular, the regulation of zona pellucida sperm-binding protein 3, plasminogen activator, cathepsin A, and lactate dehydrogenase A(LDHA) was shown to be essential for ovulation. Furthermore, the inhibition of LDHA decreased cell viability and promoted apoptosis of ovarian follicles in vitro.Conclusions This study reveals several important biochemical events involved in the process of ovulation, as well as crucial role of LDHA. These findings improve our understanding of ovulation and its regulatory mechanisms in avian species.
基金funded by the National Natural Science Foundation of China(Grant Nos.31972470,32002100,31772370)Key research and development project of Sichuan Provincial Science and Technology Department(Grant No.2021YFQ0071)。
文摘Flower and fruit abscission is a highly programmed physiological process,which is closely related to the yield of horticultural plants.The coordination of many regulatory factors associated with metabolic and signaling pathways plays a key role in the flower and fruit shedding.Hormones,peptides,carbohydrates,polyamines or cell wall modifying proteins regulate flower and fruit shedding.This article reviewed the recent studies of flower and fruit abscission,including the molecular regulation mechanism of abscission zone formation,typical structure and location of abscission zones,and other factors affecting flower and fruit abscission,such as stresses,hormones,peptides,carbohydrates,polyamines and cell wall modifying proteins.Overall,the review summarizes the developmental mechanism and the diversity of abscission zones,and the key factors affecting flower and fruit abscission of horticultural plants,aiming to provide guidance for studying the molecular regulatory mechanism of flower and fruit abscission.
文摘Objective To explore the expression of S100A14 in breast cancer tissue,and the EGF and S100A14 feedback regulatory mechanism.Methods S100A14 mRNA level in 52 cases of breast cancer and adjacent normal tissue was detected by quantitative real-time PCR.S100A14 protein in 21 cases of breast cancer and adjacent normal tissue was detected by Western blot.
基金supported by the National Natural Science Foundation of China(31972558)the Agricultural Improved Seed Project of Shandong Province,China(2020LZGC014)。
文摘Eukaryotic genomes are hierarchically packaged into cell nucleus,affecting gene regulation.The genome is organized into multiscale structural units,including chromosome territories,compartments,topologically associating domains(TADs),and DNA loops.The identification of these hierarchical structures has benefited from the development of experimental approaches,such as 3C-based methods(Hi-C,ChIA-PET,etc.),imaging tools(2D-FISH,3D-FISH,Cryo-FISH,etc.)and ligation-free methods(GAM,SPRITE,etc.).In recent two decades,numerous studies have shown that the 3D organization of genome plays essential roles in multiple cellular processes via various mechanisms,such as regulating enhancer activity and promoter-enhancer interactions.However,there are relatively few studies about the 3D genome in livestock species.Therefore,studies for exploring the function of 3D genomes in livestock are urgently needed to provide a more comprehensive understanding of potential relationships between the genome and production traits.In this review,we summarize the recent advances of 3D genomics and its biological functions in human and mouse studies,drawing inspiration to explore the 3D genomics of livestock species.We then mainly focus on the biological functions of 3D genome organization in muscle development and its implications in animal breeding.
文摘3,3′,5-Triiodo-L-thyronine(T3)is a key endocrine hormone in the human body that plays crucial roles in growth,development,metabolism,and immune function.Macrophages,the key regulatory cells within the immune system,exhibit marked“heterogeneity”and“plasticity”,with their phenotype and function subject to modulation by local environmental signals.The interplay between the endocrine and immune systems is well documented.Numerous studies have shown that T3 significantly target macrophages,highlighting them as key cellular components in this interaction.Through the regulation of macrophage function and phenotype,T3 influences immune function and tissue repair in the body.This review comprehensively summarizes the regulatory actions and mechanisms of T3 on macrophages,offering valuable insights into further research of the immunoregulatory effects of T3.
基金supported by the National Key Research and Development Program of China(Grant No.2022YFA1303900 to S.Y.)the National Natural Science Foundation of China(Grant Nos.32270921 and 82070567 to S.Y.,and 82204354 to Y.H.)+4 种基金the Open Project of State Key Laboratory of Reproductive Medicine of Nanjing Medical University(Grant No.SKLRM-2021B3 to S.Y.)'the Talent Cultivation Project of"Organized Scientific Research"of Nanjing Medical University(Grant No.NJMURC20220014 to S.Y.)the Natural Science Foundation of Jiangsu Province(Grant No.BK20221352 to B.W.)the Jiangsu Provincial Outstanding Postdoctoral Program(Grant No.2022ZB419 to Y.H.)the Postdoctoral Research Funding Project of Gusu School(Grant No.GSBSHKY202104 to Y.H.)the China Postdoctoral Science Foundation(Grant No.2023T160329 to Y.H.).
文摘Ferroptosis is a pattern of iron-mediated regulatory cell death characterized by oxidative damage.The molecular regulatory mechanisms are related to iron metabolism,lipid peroxidation,and glutathione metabolism.Additionally,some immunological signaling pathways,such as the cyclic GMP-AMP synthase-stimulator of the interferon gene axis,the Janus kinase-signal transducer and activator of transcription 1 axis,and the transforming growth factor beta 1-Smad3 axis,may also participate in the regulation of ferroptosis.Studies have shown that ferroptosis is significantly associated with many diseases such as cancer,neurodegenerative diseases,inflammatory diseases,and autoimmune diseases.Considering the pivotal role of ferroptosis-regulating signaling in the pathogenesis of diverse diseases,the development of ferroptosis inducers or inhibitors may have significant clinical potential for the treatment of aforementioned conditions.
文摘In order to scientifically deal with the problems of less water and more sediment in the Yellow River and the uncoordinated relationship between water and sediment,it is necessary to establish a perfect water and sediment regulation system.Through the calculation of the sediment transport capacity of the Yellow River and the application of the water and sediment regulation system,it is found that the sediment transport efficiency of the Yellow River will increase with the increase of water flow,and there will be an obvious inflection point near the flat discharge.The joint regulation of the backbone reservoir group can discharge the large discharge close to the minimum flat discharge of the downstream river,which improves the sediment transport capacity of the river and alleviates the problem of sediment deposition.In this paper,through the introduction of the Yellow River water and sediment regulation project system,regulation indicators and mechanisms,the author discusses in detail the Yellow River water and sediment regulation scheme and its operation effect,hoping to provide help promote the improvement of the Yellow River governance effect.
基金supported by the National Natural Science Foundation of China (32071993, 32188102, 31971872, 31861143006,U2004204)Key Agricultural Technology Project(NK2022010302)。
文摘Increasing tiller number is a target of high-yield rice breeding. Identification of tiller-defect mutants and their corresponding genes is helpful for clarifying the molecular mechanism of rice tillering. Summarizing research progress on the two processes of rice tiller formation, namely the formation and growth of axillary meristem, this paper reviews the effects of genetic factors, endogenous hormones, and exogenous environment on rice tillering, finding that multiple molecular mechanisms and signal pathways regulating rice tillering cooperate rice tillering, and discusses future research objectives and application of its regulatory mechanism. Elucidation of theis mechanism will be helpful for breeding high-yielding rice cultivars with ideal plant type via molecular design breeding.
基金This work was supported by Natural Science Foundation of Guangdong Province(grant number 2022A1515010552,China)National Natural Science Foundation of China(grant number U1832101 and 81373473).
文摘Drug transporters are essential players in the transmembrane transport of a wide variety of clinical drugs.The broad substrate spectra and versatile distribution pattern of these membrane proteins infer their pharmacological and clinical significance.With our accumulating knowledge on the three-dimensional structure of drug transporters,their oligomerization status has become a topic of intense study due to the possible functional roles carried out by such kind of post-translational modification(PTM).In-depth studies of oligomeric complexes formed among drug transporters as well as their interactions with other regulatory proteins can help us better understand the regulatory mechanisms of these membrane proteins,provide clues for the development of novel drugs,and improve the therapeutic efficacy.In this review,we describe different oligomerization forms as well as their structural basis of major drug transporters in the ATP-binding cassette and solute carrier superfamilies,summarize our current knowledge on the influence of oligomerization for protein expression level and transport function of these membrane proteins,and discuss the regulatory mechanisms of oligomerization.Finally,we highlight the challenges associated with the current oligomerization studies and propose some thoughts on the pharmaceutical application of this important drug transporter PTM.
基金supported by grants from the National Science Fund for Distinguished Young Scholars(NSFC No.71025005)the National Natural Science Foundation of China(NSFC No.71433001 and NSFC No.71301006)the National Program for Support of Top-Notch Young Professionals and the Fundamental Research Funds for the Central Universities in BUCT.
文摘To avoid credit fraud,social credit within an economic system has become an increasingly important criterion for the evaluation of economic agent activity and guaranteeing the development of a market economy with minimal supervision costs.This paper provides a comprehensive review of the social credit literature from the perspectives of theoretical foundation,scoring methods,and regulatory mechanisms.The study considers the credit of various economic agents within the social credit system such as countries(or governments),corporations,and individuals and their credit variations in online markets(i.e.,network credit).A historical review of the theoretical(or model)development of economic agents is presented together with significant works and future research directions.Some interesting conclusions are summarized from the literature review.(1)Credit theory studies can be categorized into traditional and emerging schools both focusing on the economic explanation of social credit in conjunction with creation and evolution mechanisms.(2)The most popular credit scoring methods include expert systems,econometric models,artificial intelligence(AI)techniques,and their hybrid forms.Evaluation indexes should vary across different target agents.(3)The most pressing task for regulatory mechanisms that supervise social credit to avoid credit fraud is the establishment of shared credit databases with consistent data standards.
文摘Plasmacytoma variant translocation 1 (PVT1) is a long non-coding RNA (lncRNA) gene identified as a recurrent breakpoint of Burkitt’s lymphomas. Human PVT1 gene is located on region 8q24.21, a well-known cancer risk region, and encodes at least 26 linear ncRNA isoforms and 26 circular RNA isoforms, as well as 6 microRNAs. Several PVT1 functioning models have been reported recently such as competing endogenous RNA (ceRNA) activity and regulating protein stability of oncogenes, especially MYC oncogene. The promoter of PVT1 gene is a boundary element of tumor-suppressor DNA. CircPVT1 derived from PVT1 gene is also a critical non-coding oncogenic RNA. Although substantial advancements have been made in understanding the roles of PVT1 in cancer recently, the detailed mechanisms underlying its functions remain unclear. Herein, we summarize the recent progressions on the mechanisms underlying PVT1 regulated gene expression at different levels. We also discuss the interaction between lncRNA and protein, RNA and DNA, as well as the potential cancer therapy strategy by targeting these networks.
基金the National Key Research and Development Program of China(2020YFA0907600 to L.Z.)the National Natural Science Foundation of China(National Science Foundation of China)(32241030 to S.S.).
文摘State transition is a fundamental light acclimation mechanism of photosynthetic organisms in response to the environmental light conditions.This process rebalances the excitation energy between photosystemI(PSl)and photosystem Il through regulated reversible binding of the light-harvesting complex Il(LHCll)to PSl.However,the structural reorganization of PSI-LHCI,the dynamic binding of LHCll,and the regulatory mechanisms underlying state transitions are less understood in higher plants.In this study,using cryoelectron microscopy we resolved the structures of PSI-LHCI in both state 1(PSI-LHCI-ST1)and state 2(PSILHCI-LHCll-ST2)from Arabidopsis thaliana.Combined genetic and functional analyses revealed novel contacts between Lhcb1 and PsaK that further enhanced the binding of the LHCll trimer to the PSI core with the known interactions between phosphorylated Lhcb2 and the PsaL/PsaH/PsaO subunits.Specifically,PsaO was absent in the PSI-LHCI-ST1 supercomplex but present in the PSI-LHCI-LHCIl-ST2 supercomplex,in which the PsaL/PsaK/PsaA subunits undergo several conformational changes to strengthen the binding of PsaO in ST2.Furthermore,the PSI-LHCI module adopts a more compact configuration with shorter Mg-to-Mg distances between the chlorophylls,which may enhance the energy transfer efficiency from the peripheral antenna to the PSl core in ST2.Collectively,our work provides novel structural and functional insights into the mechanisms of light acclimation during state transitions in higher plants.
基金supported by National Key R&D Program of China(2021YFC2301403)National Natural Science Foundation of China(22237003,82225028,82172287 and 22307019)+4 种基金Fujian Provincial Natural Science Foundation(2023J01506,China)Fujian Provincial Foundation for Education and Scientific Research Projects of Young and Middle-aged Teachers(JAT220044,China)Xiang An Biomedicine Laboratory(2023XAKJ0101011,China)Scientific Research Start-up Fund for High-Level Talents in Fujian Normal University(China)the Cultivation Plan for Science and Technology Innovation Team from the College of Life Sciences,Fujian Normal University(China).
文摘Cell death is a central process for organismal health.Pyroptosis,namely pyroptotic cell death,is recognized as a critical type that disrupts membrane and triggers pro-inflammatory cytokine secretion via gasdermins,providing a robust form of cytolysis.Meanwhile,along with the thorough research,a great deal of evidence has demonstrated the dual effects of pyroptosis in host defense and inflammatory diseases.More importantly,the recent identification of abundant gasdermin-like proteins in bacteria and fungi suggests an ancient origin of pyroptosis-based regulated cell death in the life evolution.In this review,we bring a general overview of pyroptosis pathways focusing on gasdermin structural biology,regulatory mechanisms,and recent progress in induction and inhibition strategies for disease treatment.We look forward to providing an insightful perspective for readers to comprehend the frame and challenges of the pyroptosis field,and to accelerating its clinical application.
基金supported by the National Natural Science Foundation of China(Grant No.22277102).
文摘Regulated cell death(RCD)is a controlled form of cell death orchestrated by one or more cascading signaling pathways,making it amenable to pharmacological intervention.RCD subroutines can be categorized as apoptotic or non-apoptotic and play essential roles in maintaining homeostasis,facilitating development,and modulating immunity.Accumulating evidence has recently revealed that RCD evasion is frequently the primary cause of tumor survival.Several non-apoptotic RCD subroutines have garnered attention as promising cancer therapies due to their ability to induce tumor regression and prevent relapse,comparable to apoptosis.Moreover,they offer potential solutions for overcoming the acquired resistance of tumors toward apoptotic drugs.With an increasing understanding of the underlying mechanisms governing these non-apoptotic RCD subroutines,a growing number of small-molecule compounds targeting single or multiple pathways have been discovered,providing novel strategies for current cancer therapy.In this review,we comprehensively summarized the current regulatory mechanisms of the emerging non-apoptotic RCD subroutines,mainly including autophagy-dependent cell death,ferroptosis,cuproptosis,disulfidptosis,necroptosis,pyroptosis,alkaliptosis,oxeiptosis,parthanatos,mitochondrial permeability transition(MPT)-driven necrosis,entotic cell death,NETotic cell death,lysosome-dependent cell death,and immunogenic cell death(ICD).Furthermore,we focused on discussing the pharmacological regulatory mechanisms of related small-molecule compounds.In brief,these insightful findings may provide valuable guidance for investigating individual or collaborative targeting approaches towards different RCD subroutines,ultimately driving the discovery of novel small-molecule compounds that target RCD and significantly enhance future cancer therapeutics.
