Lactate serves as a key energy metabolite in the central nervous system,facilitating essential brain functions,including energy supply,signaling,and epigenetic modulation.Moreover,it links epigenetic modifications wit...Lactate serves as a key energy metabolite in the central nervous system,facilitating essential brain functions,including energy supply,signaling,and epigenetic modulation.Moreover,it links epigenetic modifications with metabolic reprogramming.Nonetheless,the specific mechanisms and roles of this connection in astrocytes remain unclear.Therefore,this review aims to explore the role and specific mechanisms of lactate in the metabolic reprogramming of astrocytes in the central nervous system.The close relationship between epigenetic modifications and metabolic reprogramming was discussed.Therapeutic strategies for targeting metabolic reprogramming in astrocytes in the central nervous system were also outlined to guide future research in central nervous system diseases.In the nervous system,lactate plays an essential role.However,its mechanism of action as a bridge between metabolic reprogramming and epigenetic modifications in the nervous system requires future investigation.The involvement of lactate in epigenetic modifications is currently a hot research topic,especially in lactylation modification,a key determinant in this process.Lactate also indirectly regulates various epigenetic modifications,such as N6-methyladenosine,acetylation,ubiquitination,and phosphorylation modifications,which are closely linked to several neurological disorders.In addition,exploring the clinical applications and potential therapeutic strategies of lactic acid provides new insights for future neurological disease treatments.展开更多
As oncologic therapies continue to advance,the overall survival of cancer patients has markedly increased.Nevertheless,virtually every anticancer treatment modality is accompanied by some degree of cardiotoxicity.Epid...As oncologic therapies continue to advance,the overall survival of cancer patients has markedly increased.Nevertheless,virtually every anticancer treatment modality is accompanied by some degree of cardiotoxicity.Epidemiological data indicate that approximately 30%of cancer survivors ultimately die from cardiovascular disease.Among the cardiotoxic agents,the anthracycline doxorubicin(DOX)is the most widely used.It effectively suppresses a variety of malignant tumors——including breast cancer,lymphoma,and acute leukemia——but its cardiac toxicity limits further escalation of clinical dosing.Literature reports identify a cumulative dose of≥250 mg/m²as the threshold of high risk,with roughly 25%of patients receiving DOX developing varying degrees of myocardial injury;severe cases progress to heart failure.Even at cumulative doses below the traditional safety limit,some patients exhibit cardiac dysfunction after the first administration,suggesting that cardiotoxicity is not solely a linear function of dose.DOX related cardiotoxicity can be classified as acute(hours to days after administration),sub acute(weeks to months),and chronic/late onset(years later).Most patients initially exhibit only mild reductions in left ventricular ejection fraction(LVEF)or subtle abnormalities in global longitudinal strain(GLS),often without symptoms.Recently,cardiac biomarkers(cTn,NT proBNP)combined with high sensitivity echocardiography(speckle tracking)have been recommended for monitoring high risk individuals,enabling detection of subclinical injury before overt LVEF decline.Currently,several preventive and therapeutic approaches are used in clinical practice,which can be summarized into the following four points.(1)Dose limitation and administration strategies:fractionated low dose regimens,liposomal encapsulation,or continuous infusion lower peak plasma concentrations,thereby reducing cardiac exposure.(2)Pharmacologic prophylaxis:βblockers(e.g.,carvedilol)and ACE inhibitors/ARBs have shown protective effects on LVEF in some randomized trials,though results remain inconsistent and require larger confirmatory studies.(3)Metabolic targeted interventions:animal experiments indicate that activation of PPARαor supplementation with L carnitine restores fatty acid oxidation and improves ATP generation,suggesting metabolic modulators as promising cardioprotective candidates.(4)Lifestyle modifications:regular aerobic exercise up regulates mitochondrial biogenesis genes(PGC-1α)and reduces reactive oxygen species(ROS)production;small clinical studies have demonstrated a potential benefit in attenuating cTnT elevation.However,DOX-induced cardiotoxicity has not been effectively controlled,indicating that the core mechanism underlying DOX‑related cardiac toxicity remains unidentified.Cardiomyocytes are high energy demand cells,and metabolic dysregulation is considered a central component of DOX induced cardiotoxicity.DOX disrupts myocardial metabolic balance through several interrelated pathways.(1)Oxidative stress and mitochondrial damage:DOX generates abundant ROS within cells,leading to mitochondrial membrane potential loss,lipid peroxidation,and iron accumulation,which suppress electron transport chain activity and markedly reduce ATP synthesis efficiency.(2)Autophagy dysregulation:DOX interferes with autophagic flux,preventing the clearance of damaged mitochondria and further aggravating apoptosis and inflammatory responses.(3)Inflammation and cytokine release:oxidative stress activates NF‑κB,up-regulating pro inflammatory cytokines such as TNF‑αand IL-6,creating a chronic inflammatory microenvironment that weakens myocardial contractility.(4)Epigenetic modifications:studies have shown that DOX alters DNA methylation and histone acetylation patterns in cardiomyocytes,affecting the expression of key metabolic genes(e.g.,PGC-1α,CPT-1)and further inhibiting fatty acidβoxidation.These mechanisms collectively lead to suppressed fatty acid oxidation and compensatory up regulation of glycolysis,manifested by an elevated lactate/pyruvate ratio,accumulation of medium chain acyl carnitines,and a pronounced decline in ATP production.The resulting energy deficit precipitates left ventricular contractile dysfunction and,ultimately,heart failure.Despite extensive basic and clinical research on DOX cardiotoxicity,a unified risk assessment model and precise interventions targeting metabolic disturbances remain lacking.This review systematically summarizes recent progress on DOX induced cardiotoxicity and highlights that impairment of myocardial energy metabolism is a central mechanism of injury,thereby deepened our understanding of how impaired myocardial energy metabolism drives DOX induced injury,we can move toward safer chemotherapy protocols that achieve“cure cancer without harming the heart”.展开更多
Obesity is widely recognized as a global epidemic,primarily driven by an imbalance between energy expenditure and caloric intake associated with a sedentary lifestyle.Diets high in carbohydrates and saturated fats,par...Obesity is widely recognized as a global epidemic,primarily driven by an imbalance between energy expenditure and caloric intake associated with a sedentary lifestyle.Diets high in carbohydrates and saturated fats,particularly palmitic acid,are potent inducers of chronic low-grade inflammation,largely due to disruptions in glucose metabolism and the onset of insulin resistance(Qiu et al.,2022).While many organs are affected,the brain,specifically the hypothalamus,is among the first to exhibit inflammation in response to an unhealthy diet,suggesting that obesity may,in fact,be a brain-centered disease with neuroinflammation as a central factor(Thaler et al., 2012).展开更多
Understanding the molecular responses of tea leaves to mechanical stress is crucial for elucidating the mechanisms of post-harvest quality formation during oolong tea processing.This study employed an integrated multi...Understanding the molecular responses of tea leaves to mechanical stress is crucial for elucidating the mechanisms of post-harvest quality formation during oolong tea processing.This study employed an integrated multi-omics strategy to characterize the changes and interactions among metabolomic(MB),transcriptomic(TX),and proteomic(PT)profiles in mechanically stressed tea leaves.Mechanical stress initially activated damage-associated molecular patterns(DAMPs),including Ca^(2+)signaling,jasmonic acid signaling,and glutathione metabolism pathways.These processes subsequently induced quality-related metabolic pathways(QRMPs),particularly α-linolenic acid and phenylalanine metabolism.Upregulated expression of LOX,ADH1,and PAR genes,together with the increased abundance of their encoded proteins,respectively promoted the accumulation of jasmine lactone,benzyl alcohol,and 2-phenylethanol.These findings indicate that mechanical stress influences the metabolite biosynthesis in tea leaves through coordinated molecular responses.This study provides new insights into the molecular mechanisms underlying tea leaf responses to mechanical stress and a foundation for future investigations into how early molecular events may contribute to post-harvest metabolic changes during oolong tea processing.展开更多
Myelin,made by oligodendrocytes(OLs)in the central nervous system(CNS),is essential for neural transmission.In particular,myelin facilitates communication across the long connections between different brain regions th...Myelin,made by oligodendrocytes(OLs)in the central nervous system(CNS),is essential for neural transmission.In particular,myelin facilitates communication across the long connections between different brain regions that form the white matter.Myelinated segments also provide metabolic intermediates to axons,supporting their demanding energetic needs.Genetic disorders that disrupt myelin formation result in progressive neurologic degeneration.展开更多
Background:Disorders of metabolism can affect the food intake,weight changes,and behavioral alterations of the body.Metabolic disorders are usually accompanied by the occurrence of diseases.We aimed to study the effec...Background:Disorders of metabolism can affect the food intake,weight changes,and behavioral alterations of the body.Metabolic disorders are usually accompanied by the occurrence of diseases.We aimed to study the effects of the compatibility of Paeoniae Radix Rubra(PRR)and Angelicae Sinensis Radix(ASR)on the metabolic level of rats,and observe the changes in body weight and behavior.Discover the mechanism of preventing the occurrence of diseases by using PRR and ASR.Methods:Two animal models were induced by levothyroxine and low-temperature stimulation,followed by 21 days of edible traditional Chinese medicine administration.The changes in the rats’water intake,food intake,body temperature,and thermotactic behavior were recorded.Results:The results showed that PRR could cause an increase in the body weight of rats,a decrease in body temperature,and a stronger preference for warm environments.PRR inhibited thyroid function,the excitability of the nervous system,and energy metabolism.PRR upregulated the expressions of mTOR and TRPM8 while downregulating the expressions of AMPK and TRPV1.Conclusion:Our research findings suggest that the cold-natured PRR can inhibit the material and energy metabolism of the body and lower the body temperature,increasing the thermophilic behavior of rats.In contrast,ASR exhibited an antagonistic effect against PRR.展开更多
Inborn errors of metabolism(IEM)are rare disorders,most are liver-based with liver transplantation(LT)emerging as an effective cure in the pediatric population.LT has been shown to offer a cure or deter disease progre...Inborn errors of metabolism(IEM)are rare disorders,most are liver-based with liver transplantation(LT)emerging as an effective cure in the pediatric population.LT has been shown to offer a cure or deter disease progression and provide symptomatic improvement in patients with IEM.Each metabolic disorder is unique,with the missing enzyme or transporter protein causing substrate deficiency or toxic byproduct production.Knowledge about the distribution of deficient enzymes,the percentage of enzymes replaced by LT,and the extent of extrahepatic involvement helps anticipate and manage complications in the perioperative period.Most patients have multisystem involvement and can be on complex dietary regimens.Metabolic decompensation can be triggered due to the stress response to surgery,fasting and other unanticipated complications perioperatively.Thus,a multidisciplinary team’s input including those from metabolic specialists is essential to develop disease and patient-specific strategies for the perioperative management of these patients during LT.In this review,we outline the classification of IEM,indications for LT along with potential benefits,basic metabolic defects and their implications,details of extrahepatic involvement and perioperative management strategies for LT in children with some of the commonly presenting IEM,to assist anesthesiologists handling this cohort of patients.展开更多
Recent studies have shown that lipid metabolism is a key factor affecting anther development and male fertility.However,how plants regulating the metabolic balance of multiple lipids to ensure proper anther developmen...Recent studies have shown that lipid metabolism is a key factor affecting anther development and male fertility.However,how plants regulating the metabolic balance of multiple lipids to ensure proper anther development and male fertility remains unclear.Analyzing lipid molecules related to anther fertility and genes responsible for their biosynthesis is crucial for understanding the physiological significance of lipid metabolism in crop fertility.In this study,we compared the transcriptome and the composition and content of lipids in anthers of two upland cotton(Gossypium hirsutum) materials,Shida 98(WT) and its nearly-isogenic male sterile line Shida 98A(MS).Transcriptomics analysis identified many differentially expressed genes(DEGs) between the two materials,with the genes of the alpha-linolenic acid metabolism pathway being the most significantly associated with the male sterility phenotype.Investigations on lipids revealed that the MS anthers over-accumulated free fatty acids(FFAs),phosphatidic acid(PA),mono-and di-galactosyldiacylglycerol(MGDG and DGDG),and had a decreased content of triacylglycerol(TAG),which was closely related to the abnormal metabolism of alpha-linolenic acid(C18:3);therefore,the major lipids containing C18:3-acyl chains,such as PA,MGDG,DGDG,and TAG,are proposed to play a major role in cotton anther development.We also showed that an excessive level of MGDG and DGDG caused jasmonic acid(JA) overaccumulation in MS anthers,which in turn inhibited the expression of GhFAD3 and consequently reduced the C18:3 content,presumably via a feedback regulation mechanism,ultimately affecting plant fertility.Together,our results revealed the importance of a balanced lipid metabolism in regulating the development of cotton anther and pollen and consequently male fertility.展开更多
Mastitis is one of the most significant diseases affecting the development of the dairy industry and has traditionally been associated with pathogenic infections.However,emerging evidence highlights that ruminal micro...Mastitis is one of the most significant diseases affecting the development of the dairy industry and has traditionally been associated with pathogenic infections.However,emerging evidence highlights that ruminal microbial homeostasis also plays a crucial role in the pathogenesis of mastitis.Specifically,cows with mastitis exhibit reduced alpha diversity and altered microbial composition in the rumen.Inducing ruminal dysbiosis through a high-concentrate diet has been shown to trigger mastitis in cows,and transplantation of ruminal microbiota from mastitis-affected cows to recipient mice can induce mastitis in mice.Mechanistically,ruminal dysbiosis increases gastrointestinal inflammation and compromises the integrity of the gastrointestinal barrier,thereby facilitating the translocation of harmful bacterial components,metabolites,and pathobionts into the bloodstream.This disruption impairs blood-milk barrier function,leading to systemic inflammation and the development of mastitis.In this review,we summarize recent advances in understanding how ruminal dysbiosis induces mastitis and explore potential prevention and control strategies targeting the modulation of ruminal microbiota.展开更多
Epilepsy is a leading cause of disability and mortality worldwide. However, despite the availability of more than 20 antiseizure medications, more than one-third of patients continue to experience seizures. Given the ...Epilepsy is a leading cause of disability and mortality worldwide. However, despite the availability of more than 20 antiseizure medications, more than one-third of patients continue to experience seizures. Given the urgent need to explore new treatment strategies for epilepsy, recent research has highlighted the potential of targeting gliosis, metabolic disturbances, and neural circuit abnormalities as therapeutic strategies. Astrocytes, the largest group of nonneuronal cells in the central nervous system, play several crucial roles in maintaining ionic and energy metabolic homeostasis in neurons, regulating neurotransmitter levels, and modulating synaptic plasticity. This article briefly reviews the critical role of astrocytes in maintaining balance within the central nervous system. Building on previous research, we discuss how astrocyte dysfunction contributes to the onset and progression of epilepsy through four key aspects: the imbalance between excitatory and inhibitory neuronal signaling, dysregulation of metabolic homeostasis in the neuronal microenvironment, neuroinflammation, and the formation of abnormal neural circuits. We summarize relevant basic research conducted over the past 5 years that has focused on modulating astrocytes as a therapeutic approach for epilepsy. We categorize the therapeutic targets proposed by these studies into four areas: restoration of the excitation–inhibition balance, reestablishment of metabolic homeostasis, modulation of immune and inflammatory responses, and reconstruction of abnormal neural circuits. These targets correspond to the pathophysiological mechanisms by which astrocytes contribute to epilepsy. Additionally, we need to consider the potential challenges and limitations of translating these identified therapeutic targets into clinical treatments. These limitations arise from interspecies differences between humans and animal models, as well as the complex comorbidities associated with epilepsy in humans. We also highlight valuable future research directions worth exploring in the treatment of epilepsy and the regulation of astrocytes, such as gene therapy and imaging strategies. The findings presented in this review may help open new therapeutic avenues for patients with drugresistant epilepsy and for those suffering from other central nervous system disorders associated with astrocytic dysfunction.展开更多
Ecological floating bed is an important biological remediation method for water pollution control.During the removal of excess nutrients and pollutants,changes in environmental factors affect the characteristics of mi...Ecological floating bed is an important biological remediation method for water pollution control.During the removal of excess nutrients and pollutants,changes in environmental factors affect the characteristics of microorganisms in aquatic ecosystems.To understand the influences of ecological floating beds on size-fractionated microorganisms,we investigated the community assembly and nitrogen metabolic characteristics of three size-fractionated microorganism groups in the ecological floating bed area,using 18S rDNA,16S rDNA metabarcoding,and metagenomic sequencing techniques.Firstly,we discovered substantial differences between size-fractionated groups in the diversity and compositions of both microeukaryotic and bacterial communities,as well as the influences of floating beds on specific groups.The floating beds appeared to provide more habitats for heterotrophs and symbiotes while potentially inhibiting the growth of certain phytoplankton(cyanobacteria).Secondly,we observed that microeukaryotic and bacterial communities were predominantly influenced by stochastic and deterministic processes,respectively,and they both exhibited distinct patterns across different size-fractionated groups.Notably,microeukaryotic community assembly demonstrated a greater sensitivity to ecological floating beds,as indicated by an increase in dispersal limitation processes.Finally,the nitrogen metabolism functional genes revealed that microbes associated with large-sized particles played a crucial role in dissimilatory nitrate reduction to ammonium(DNRA)and denitrification processes within the floating bed area,thereby facilitating the removal of excess nitrogen nutrients from the water.In contrast,freeliving microorganisms from small-sized groups were linked mainly to the genes involved in nitrogen assimilation and assimilatory nitrate reduction to ammonium(ANRA)processes.These findings help understand the impact of ecological floating beds on the diversity and functional characteristics of microorganism communities in different size-fractionated groups.展开更多
Background Fatty liver syndrome is a prevalent metabolic disorder in transition dairy cows,characterized by excessive hepatic lipid accumulation that impairs liver function and leads to systemic metabolic disturbances...Background Fatty liver syndrome is a prevalent metabolic disorder in transition dairy cows,characterized by excessive hepatic lipid accumulation that impairs liver function and leads to systemic metabolic disturbances.Docosahexaenoic acid(DHA),a prominent n-3 polyunsaturated fatty acid(PUFA),not only exhibits anti-inflammatory and anti-oxidative properties,but also holds potential in ameliorating lipid metabolism.This study integrated in vitro bovine primary hepatocyte models and in vivo dairy cow trials to investigate the regulatory effects of DHA on hepatic lipid deposition.Results In vitro,40μmol/L DHA significantly reduced triglyceride(TAG)accumulation in steatotic hepatocytes by downregulating genes involved in fatty acid transport(FABP-1,CD36)and lipogenesis(DGAT2,FAS,SREBP-1C),while upregulating markers of lipolysis(CGI-58,ATGL)and fatty acid oxidation(ACADL,CPT1A,CPT2).Transmission electron microscopy(TEM)confirmed DHA-mediated restoration of mitochondrial ultrastructure and enhanced lipid droplet(LD)-mitochondria interactions.In vivo,dietary rumen-protected DHA(180 g/d)supplementation reduced hepatic lipid deposition,improved liver function(evidenced by decreased total bilirubin and alanine aminotransferase),reduced oxidative stress and inflammation(suppressed malondialdehyde,glutathione peroxidase,and lipopolysaccharide),coincided with relieving insulin resistance(reduced insulin and glucose,as well increased adiponectin)in dairy cows with fatty liver.These improvements may be attributed to increased expression of TOMM20 and MtCo-1,promoting mitochondrial biogenesis andβ-oxidation,along with an elevated plasma n-3/n-6 ratio.Conclusions Collectively,these findings suggest that DHA supplementation represents a promising nutritional strategy for preventing spontaneous fatty liver in transition dairy cows by enhancing hepatic lipid clearance and restoring metabolic homeostasis.展开更多
Microorganisms constitute an essential component in the indoor environment,which is closely related to hu-man health.However,there is limited evidence regarding the associations between indoor airborne microbiome and ...Microorganisms constitute an essential component in the indoor environment,which is closely related to hu-man health.However,there is limited evidence regarding the associations between indoor airborne microbiome and systemic inflammation,as well as whether this association is modified by indoor particulate matter and the underlying mechanisms.In this prospective repeated-measure study among 66 participants,indoor airborne mi-crobiome was characterized using amplicon sequencing and qPCR.Indoor fine particulate matter(PM_(2.5))and inhalable particulate matter(PM10)were measured.Systemic inflammatory biomarkers were assessed,including white blood cell(WBC),neutrophil(NEUT),monocyte,eosinophil counts,and their proportions.Targeted serum amino acid metabolomics were conducted to explore the underlying mechanisms.Linear mixed-effect models re-vealed that bacterial and fungal Simpson diversity were significantly associated with decreased WBC and NEUT.For example,for each interquartile range increase in the bacterial Simpson diversity,WBC and NEUT changed by-4.53%(95%CI:-8.25%,-0.66%)and-5.95%(95%CI:-11.3%,-0.27%),respectively.Notably,increased inflammatory risks of airborne microbial exposure were observed when indoor PM_(2.5) and PM10 levels were below the WHO air quality guidelines.Mediation analyses indicated that dopamine metabolism partially mediated the anti-inflammatory effects of fungal diversity exposure.Overall,our study indicated protection from a diverse indoor microbial environment on cardiovascular health and proposed an underlying mechanism through amino acid metabolism.Additionally,health risks associated with microbial exposure deserve more attention in con-texts of low indoor particulate matter pollution.Further research is necessary to fully disentangle the complex relationships between indoor microbiome,air pollutants,and human health.展开更多
The cerebellum is receiving increasing attention for its cognitive,emotional,and social functions,as well as its unique metabolic profiles.Cerebellar microglia exhibit specialized and highly immunogenic phenotypes und...The cerebellum is receiving increasing attention for its cognitive,emotional,and social functions,as well as its unique metabolic profiles.Cerebellar microglia exhibit specialized and highly immunogenic phenotypes under both physiological and pathological conditions.These immune cells communicate with intrinsic and systemic factors and contribute to the structural and functional compartmentalization of the cerebellum.In this review,we discuss the roles of microglia in the cerebellar microenvironment,neuroinflammation,cerebellar adaptation,and neuronal activity,the associated molecular and cellular mechanisms,and potential therapeutic strategies targeting cerebellar microglia in the context of neuroinflammation.Future directions and unresolved questions in this field are further highlighted,particularly regarding therapeutic interventions targeting cerebellar microglia,functional mechanisms and activities of microglia in the cerebellar circuitry,neuronal connectivity,and neurofunctional outcomes of their activity.Cerebellar morphology and neuronal performance are influenced by both intrinsic and systemic factors that are actively monitored by microglia in both healthy and diseased states.Under pathological conditions,local subsets of microglia exhibit diverse responses to the altered microenvironment that contribute to the structural and functional compartmentalization of the cerebellum.Microglia in the cerebellum undergo early maturation during the embryonic stage and display specialized,highly immunogenic phenotypes.In summary,cerebellar microglia have the capacity to serve as regulatory tools that influence outcomes across a wide range of neurological and systemic conditions,including neurodevelopmental,neurodegenerative,metabolic,and stress-related disorders.展开更多
Background The decline in reproductive performance of aged hens is mainly attributed to oxidative damage in reproductive organs,hepatic lipid metabolism disorders,and intestinal microbiota dysbiosis.Glycyrrhizin(GL)ha...Background The decline in reproductive performance of aged hens is mainly attributed to oxidative damage in reproductive organs,hepatic lipid metabolism disorders,and intestinal microbiota dysbiosis.Glycyrrhizin(GL)has been proven to enhance antioxidant capacity,regulate lipid metabolism and gut microbiota in mammals,but its efficacy in hens remains unclear.Hence,this study aimed to investigate whether dietary GL supplementation improves reproductive performance in hens during the late laying stage by modulating intestinal microbiota composition,hepatic lipid metabolism and ovarian antioxidant status.Results Dietary supplementation with 100 mg/kg GL significantly improved the egg production rate,egg quality,and hatching rate in aged breeder hens(P<0.05).GL supplementation also increased the serum levels of HDLC,TP and ALB,and enhanced the antioxidant capacity in both serum and ovary(P<0.05).In addition,dietary GL elevated the serum progesterone(P4)levels by enhancing the transcription level of steroid synthesis key enzymes(CYP11A1 and 3β-HSD)in the ovary(P<0.05).Dietary GL also promoted the synthesis and transport of vitellogenin(VTG)by upregulating the VTG-II(P<0.05)and APOV1(P=0.077)expression levels in the liver,thereby increasing the number of grade follicles and small yellow follicles.Moreover,dietary GL enhanced hepatic fatty acidβ-oxidation by upregulating PPARαand CPT-I(P<0.05),and downregulating ACC expression levels(P<0.05).In agreement,liver metabolomics analysis revealed that dietary GL supplementation significantly altered hepatic metabolism,with 389 differentially identified metabolites(P<0.05).The key metabolites(e.g.,taurocholic acid,tauroursodeoxycholic acid,nicotinuric acid,glycodeoxycholic acid(hydrate))were identified,and they were mainly functionally enriched in betaalanine metabolism nicotinate,taurine and hypotaurine metabolism(P<0.05).Finally,16S rRNA gene sequencing revealed that dietary GL reversed age-induced changes in gut microbiota composition,characterized by a significant increase in Lactobacillus abundance and a decrease in Bacteroides(P<0.05).Conclusions These results collectively demonstrate that dietary supplementation with 100 mg/kg GL improved reproductive performance by reversing age-induced changes in gut microbiota,enhancing hepatic vitellogenin synthesis,and ameliorating ovarian function in aged breeder hens.This study suggests that dietary GL is a potential strategy to improve reproductive performance in broiler breeder hens during the late laying period.展开更多
BACKGROUND Organ transplantation has emerged as a globally prevalent therapeutic modality for end-stage organ failure,yet the post-transplantation trajectory is increasingly complicated by a spectrum of metabolic sequ...BACKGROUND Organ transplantation has emerged as a globally prevalent therapeutic modality for end-stage organ failure,yet the post-transplantation trajectory is increasingly complicated by a spectrum of metabolic sequelae,with obesity emerging as a critical clinical challenge.AIM To systematically review the multifactorial mechanisms underlying obesity following organ transplantation and to integrate evidence from pharmacological,behavioral,and molecular perspectives,thereby providing a foundation for targeted interventions.METHODS We conducted a systematic search in PubMed and Web of Science for literature published from 2020 to 15 July 2025.The search strategy incorporated terms including“obesity”,“overweight”and“post organ transplantation”.Only randomized controlled trials,meta-analyses,and systematic reviews were included.Non-empirical publications and irrelevant studies were excluded.Data extraction and quality assessment were performed by two independent reviewers,with disagreements resolved by a third researcher.RESULTS A total of 1457 articles were initially identified,of which 146 met the inclusion criteria.These studies encompassed liver,kidney,heart,and lung transplant recipients.Key findings indicate that immunosuppressive drugs-especially corticosteroids and calcineurin inhibitors-promote hyperphagia,insulin resistance,and dyslipidemia.Post-transplant sedentary behavior and hypercaloric diets further contribute to positive energy balance.At the molecular level,immunosuppressants disrupt adipokine signaling(e.g.,leptin and adiponectin),induce inflammatory and oxidative stress responses,and activate adipogenic pathways leading to lipid accumulation.CONCLUSION Post-transplant obesity arises from a complex interplay of pharmacological,behavioral,and molecular factors.A multidisciplinary approach-incorporating pharmacological modification,nutritional management,physical activity,and molecular-targeted therapies-is essential to mitigate obesity and improve transplant outcomes.Further large-scale and mechanistic studies are warranted to establish evidence-based preventive and treatment strategies.展开更多
The global prevalence of metabolic-associated fatty liver disease(MAFLD)is on the rise,seriously threatening human health.Currently,no specific approved drugs are available for its treatment.This paper reviews the pat...The global prevalence of metabolic-associated fatty liver disease(MAFLD)is on the rise,seriously threatening human health.Currently,no specific approved drugs are available for its treatment.This paper reviews the pathogenesis of MAFLD,covering aspects like lipid accumulation and insulin resistance,oxidative stress,endoplasmic reticulum stress(ERS),lipotoxicity-induced hepatocyte damage,and fibrosis.It also elaborates on multiple treatment approaches for MAFLD,including metabolic regulation,improvement of the gut-liver axis interaction,modulation of immune and inflammatory pathways,enhancement of the adipose tissue-liver interaction,alleviation of fibrosis,prevention of hepatocyte injury,and traditional Chinese medicine(TCM)external therapies.Additionally,natural product research advancements,individual Chinese medicine components,and mixed herbal formulas for MAFLD treatment is provided.Many natural products and traditional Chinese medicines exhibit favorable effects in regulating lipid metabolism,anti-inflammation,and anti-oxidation,offering new directions and potential drug options for MAFLD treatment.This is expected to provide a reference for future clinical treatment and drug development.展开更多
The rapidly aging population directly contributes to the increasing cases of neurological disorders.Due to the chronic progressive nature of neurodegeneration,numerous neurological conditions are considered“multifact...The rapidly aging population directly contributes to the increasing cases of neurological disorders.Due to the chronic progressive nature of neurodegeneration,numerous neurological conditions are considered“multifactorial”with systemic metabolic alterations.Even so,treatments for neurological disorders have remained unchanged for the past decades.Recently,metabolic drugs such as metformin and glucagon-like peptide 1 agonists have demonstrated promising health outcomes for neurodegeneration.展开更多
Recently,Prevotella spp.,a major genus of gram-negative commensal bacteria in humans,have emerged as a key microbial contributor to host metabolism due to its ability to ferment dietary fibers,produce beneficial short...Recently,Prevotella spp.,a major genus of gram-negative commensal bacteria in humans,have emerged as a key microbial contributor to host metabolism due to its ability to ferment dietary fibers,produce beneficial short-chain fatty acids,and influence immune responses.However,their diversity and functional differences have created challenges for their development and therapeutic use.Recent studies have shown that specific Prevotella species,such as P.copri,P.intestinalis,and P.histicola,can strengthen gut barrier integrity and reduce metabolic imbalances.Notably,Prevotella populations can be increased through high-fiber or herbal-based treatments.Traditional herbal medicines,including fiber-rich decoctions,also demonstrate the potential to boost endogenous Prevotella communities,enhance microbial fermentation,and improve glucose and lipid balance.This perspective examines the context-dependent roles of Prevotella spp.,with emphasis on the functional heterogeneity of key species such as P.copri,suggests a framework for combining herbal modulation with species-level microbiota profiling,and outlines a research plan to explore microbe-herb synergy in treating obesity,type 2 diabetes,and related metabolic disorders.This strategy offers a new,ecology-based approach to complement standard metabolic interventions.展开更多
Head-splitting is a prevalent physiological disorder in cabbage that causes substantial economic losses.However,the genetic factors and molecular mechanisms underlying head-splitting resistance remain largely unexplor...Head-splitting is a prevalent physiological disorder in cabbage that causes substantial economic losses.However,the genetic factors and molecular mechanisms underlying head-splitting resistance remain largely unexplored.This study identified a genomic region(q NLQ3.1) for head-splitting resistance on chromosome C03 through the combination of QTLseq and GPS analysis in an F_(2) population derived from hybridizing two cabbage inbred lines,‘Dazhengfu'(ZF,susceptible) and ‘103'(resistant).Traditional genetic linkage analysis narrowed q NLQ3.1 to a 74.6 kb region.Furthermore,comparative analysis of the two parental lines using transcriptomic and metabolic profiling demonstrated the crucial role of hormones in regulating head-splitting resistance.Bol028000,encoding a homologue of Arabidopsis Cytokinin Response Factor 3(CRF3),emerged as a promising candidate for head-splitting resistance and was subsequently validated through Sanger sequencing and quantitative RT-PCR(qRT-PCR).Subcellular localisation analysis revealed that Bol028000 was mainly expressed in the nucleus.Additionally,one kompetitive allele-specific PCR(KASP) marker from Bol028000 was developed and utilized to screen 42 inbred lines.These findings enhance the theoretical understanding of head-splitting resistance and provide valuable insights for the molecular breeding of head-splitting resistant cabbages.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82071383,82371392(to BN)the Natural Science Foundation of Shandong Province of China(Key Project),No.ZR2020KH007(to BN)+1 种基金“Taishan Scholar Distinguished Expert Program”of Shandong Province,No.tstp20231257(to BN)Health Commission Science and Technology Plan Project of Jinan,No.2023-1-8(to YZ).
文摘Lactate serves as a key energy metabolite in the central nervous system,facilitating essential brain functions,including energy supply,signaling,and epigenetic modulation.Moreover,it links epigenetic modifications with metabolic reprogramming.Nonetheless,the specific mechanisms and roles of this connection in astrocytes remain unclear.Therefore,this review aims to explore the role and specific mechanisms of lactate in the metabolic reprogramming of astrocytes in the central nervous system.The close relationship between epigenetic modifications and metabolic reprogramming was discussed.Therapeutic strategies for targeting metabolic reprogramming in astrocytes in the central nervous system were also outlined to guide future research in central nervous system diseases.In the nervous system,lactate plays an essential role.However,its mechanism of action as a bridge between metabolic reprogramming and epigenetic modifications in the nervous system requires future investigation.The involvement of lactate in epigenetic modifications is currently a hot research topic,especially in lactylation modification,a key determinant in this process.Lactate also indirectly regulates various epigenetic modifications,such as N6-methyladenosine,acetylation,ubiquitination,and phosphorylation modifications,which are closely linked to several neurological disorders.In addition,exploring the clinical applications and potential therapeutic strategies of lactic acid provides new insights for future neurological disease treatments.
基金supported by grants from the Applied Basic Research Foundation of Yunnan Province(202301AT070095)the Candidate Talents Training Fund of Yunnan Province(H-2024069)。
文摘As oncologic therapies continue to advance,the overall survival of cancer patients has markedly increased.Nevertheless,virtually every anticancer treatment modality is accompanied by some degree of cardiotoxicity.Epidemiological data indicate that approximately 30%of cancer survivors ultimately die from cardiovascular disease.Among the cardiotoxic agents,the anthracycline doxorubicin(DOX)is the most widely used.It effectively suppresses a variety of malignant tumors——including breast cancer,lymphoma,and acute leukemia——but its cardiac toxicity limits further escalation of clinical dosing.Literature reports identify a cumulative dose of≥250 mg/m²as the threshold of high risk,with roughly 25%of patients receiving DOX developing varying degrees of myocardial injury;severe cases progress to heart failure.Even at cumulative doses below the traditional safety limit,some patients exhibit cardiac dysfunction after the first administration,suggesting that cardiotoxicity is not solely a linear function of dose.DOX related cardiotoxicity can be classified as acute(hours to days after administration),sub acute(weeks to months),and chronic/late onset(years later).Most patients initially exhibit only mild reductions in left ventricular ejection fraction(LVEF)or subtle abnormalities in global longitudinal strain(GLS),often without symptoms.Recently,cardiac biomarkers(cTn,NT proBNP)combined with high sensitivity echocardiography(speckle tracking)have been recommended for monitoring high risk individuals,enabling detection of subclinical injury before overt LVEF decline.Currently,several preventive and therapeutic approaches are used in clinical practice,which can be summarized into the following four points.(1)Dose limitation and administration strategies:fractionated low dose regimens,liposomal encapsulation,or continuous infusion lower peak plasma concentrations,thereby reducing cardiac exposure.(2)Pharmacologic prophylaxis:βblockers(e.g.,carvedilol)and ACE inhibitors/ARBs have shown protective effects on LVEF in some randomized trials,though results remain inconsistent and require larger confirmatory studies.(3)Metabolic targeted interventions:animal experiments indicate that activation of PPARαor supplementation with L carnitine restores fatty acid oxidation and improves ATP generation,suggesting metabolic modulators as promising cardioprotective candidates.(4)Lifestyle modifications:regular aerobic exercise up regulates mitochondrial biogenesis genes(PGC-1α)and reduces reactive oxygen species(ROS)production;small clinical studies have demonstrated a potential benefit in attenuating cTnT elevation.However,DOX-induced cardiotoxicity has not been effectively controlled,indicating that the core mechanism underlying DOX‑related cardiac toxicity remains unidentified.Cardiomyocytes are high energy demand cells,and metabolic dysregulation is considered a central component of DOX induced cardiotoxicity.DOX disrupts myocardial metabolic balance through several interrelated pathways.(1)Oxidative stress and mitochondrial damage:DOX generates abundant ROS within cells,leading to mitochondrial membrane potential loss,lipid peroxidation,and iron accumulation,which suppress electron transport chain activity and markedly reduce ATP synthesis efficiency.(2)Autophagy dysregulation:DOX interferes with autophagic flux,preventing the clearance of damaged mitochondria and further aggravating apoptosis and inflammatory responses.(3)Inflammation and cytokine release:oxidative stress activates NF‑κB,up-regulating pro inflammatory cytokines such as TNF‑αand IL-6,creating a chronic inflammatory microenvironment that weakens myocardial contractility.(4)Epigenetic modifications:studies have shown that DOX alters DNA methylation and histone acetylation patterns in cardiomyocytes,affecting the expression of key metabolic genes(e.g.,PGC-1α,CPT-1)and further inhibiting fatty acidβoxidation.These mechanisms collectively lead to suppressed fatty acid oxidation and compensatory up regulation of glycolysis,manifested by an elevated lactate/pyruvate ratio,accumulation of medium chain acyl carnitines,and a pronounced decline in ATP production.The resulting energy deficit precipitates left ventricular contractile dysfunction and,ultimately,heart failure.Despite extensive basic and clinical research on DOX cardiotoxicity,a unified risk assessment model and precise interventions targeting metabolic disturbances remain lacking.This review systematically summarizes recent progress on DOX induced cardiotoxicity and highlights that impairment of myocardial energy metabolism is a central mechanism of injury,thereby deepened our understanding of how impaired myocardial energy metabolism drives DOX induced injury,we can move toward safer chemotherapy protocols that achieve“cure cancer without harming the heart”.
文摘Obesity is widely recognized as a global epidemic,primarily driven by an imbalance between energy expenditure and caloric intake associated with a sedentary lifestyle.Diets high in carbohydrates and saturated fats,particularly palmitic acid,are potent inducers of chronic low-grade inflammation,largely due to disruptions in glucose metabolism and the onset of insulin resistance(Qiu et al.,2022).While many organs are affected,the brain,specifically the hypothalamus,is among the first to exhibit inflammation in response to an unhealthy diet,suggesting that obesity may,in fact,be a brain-centered disease with neuroinflammation as a central factor(Thaler et al., 2012).
基金supported by the National Key Research and Development Program of China(2022YFD2101101)the Earmarked Fund for CARS-19+2 种基金the National Natural Science Foundation of China(32402634)the Modern Agricultural(Tea)Industry Technology System of Fujian Province,China(2025 No.593)the Special Fund for Science and Technology Innovation of Fujian Zhang Tianfu Tea Development Foundation,China(FJZTF01)。
文摘Understanding the molecular responses of tea leaves to mechanical stress is crucial for elucidating the mechanisms of post-harvest quality formation during oolong tea processing.This study employed an integrated multi-omics strategy to characterize the changes and interactions among metabolomic(MB),transcriptomic(TX),and proteomic(PT)profiles in mechanically stressed tea leaves.Mechanical stress initially activated damage-associated molecular patterns(DAMPs),including Ca^(2+)signaling,jasmonic acid signaling,and glutathione metabolism pathways.These processes subsequently induced quality-related metabolic pathways(QRMPs),particularly α-linolenic acid and phenylalanine metabolism.Upregulated expression of LOX,ADH1,and PAR genes,together with the increased abundance of their encoded proteins,respectively promoted the accumulation of jasmine lactone,benzyl alcohol,and 2-phenylethanol.These findings indicate that mechanical stress influences the metabolite biosynthesis in tea leaves through coordinated molecular responses.This study provides new insights into the molecular mechanisms underlying tea leaf responses to mechanical stress and a foundation for future investigations into how early molecular events may contribute to post-harvest metabolic changes during oolong tea processing.
基金support held by JPA,Collaborative Network Award BRAVEinMS,Grant/Award Number:PA-1604-08492(MG),and from the Multiple Sclerosis Society of Canada,Grant/Award Number:1038154(to TEK).
文摘Myelin,made by oligodendrocytes(OLs)in the central nervous system(CNS),is essential for neural transmission.In particular,myelin facilitates communication across the long connections between different brain regions that form the white matter.Myelinated segments also provide metabolic intermediates to axons,supporting their demanding energetic needs.Genetic disorders that disrupt myelin formation result in progressive neurologic degeneration.
基金the preparation of this manuscript.This study was supported by the General Projects-Youth project(2022JQ-817)the Shaanxi University of Traditional Chinese Medicine Shaanxi Provincial Key Laboratory of Basic and New Drug Research Open Project(KF202303)+1 种基金the Research on process optimization and quality standard enhancement of five large varieties,including Four Seasons Antiviral Combination(2024CY-JJQ-36)the Shaanxi provincial science and technology department project(2025JC-YBMS-1033).
文摘Background:Disorders of metabolism can affect the food intake,weight changes,and behavioral alterations of the body.Metabolic disorders are usually accompanied by the occurrence of diseases.We aimed to study the effects of the compatibility of Paeoniae Radix Rubra(PRR)and Angelicae Sinensis Radix(ASR)on the metabolic level of rats,and observe the changes in body weight and behavior.Discover the mechanism of preventing the occurrence of diseases by using PRR and ASR.Methods:Two animal models were induced by levothyroxine and low-temperature stimulation,followed by 21 days of edible traditional Chinese medicine administration.The changes in the rats’water intake,food intake,body temperature,and thermotactic behavior were recorded.Results:The results showed that PRR could cause an increase in the body weight of rats,a decrease in body temperature,and a stronger preference for warm environments.PRR inhibited thyroid function,the excitability of the nervous system,and energy metabolism.PRR upregulated the expressions of mTOR and TRPM8 while downregulating the expressions of AMPK and TRPV1.Conclusion:Our research findings suggest that the cold-natured PRR can inhibit the material and energy metabolism of the body and lower the body temperature,increasing the thermophilic behavior of rats.In contrast,ASR exhibited an antagonistic effect against PRR.
文摘Inborn errors of metabolism(IEM)are rare disorders,most are liver-based with liver transplantation(LT)emerging as an effective cure in the pediatric population.LT has been shown to offer a cure or deter disease progression and provide symptomatic improvement in patients with IEM.Each metabolic disorder is unique,with the missing enzyme or transporter protein causing substrate deficiency or toxic byproduct production.Knowledge about the distribution of deficient enzymes,the percentage of enzymes replaced by LT,and the extent of extrahepatic involvement helps anticipate and manage complications in the perioperative period.Most patients have multisystem involvement and can be on complex dietary regimens.Metabolic decompensation can be triggered due to the stress response to surgery,fasting and other unanticipated complications perioperatively.Thus,a multidisciplinary team’s input including those from metabolic specialists is essential to develop disease and patient-specific strategies for the perioperative management of these patients during LT.In this review,we outline the classification of IEM,indications for LT along with potential benefits,basic metabolic defects and their implications,details of extrahepatic involvement and perioperative management strategies for LT in children with some of the commonly presenting IEM,to assist anesthesiologists handling this cohort of patients.
基金supported by the Science and Technology Major Program of Bingtuan,China (2023AA008)the National Natural Science Foundation of China (31960369)+1 种基金the Bingtuan Science and Technology Program,China (2025DA001)the Henan Provincial Science and Technology Research Project,China (222102110200)。
文摘Recent studies have shown that lipid metabolism is a key factor affecting anther development and male fertility.However,how plants regulating the metabolic balance of multiple lipids to ensure proper anther development and male fertility remains unclear.Analyzing lipid molecules related to anther fertility and genes responsible for their biosynthesis is crucial for understanding the physiological significance of lipid metabolism in crop fertility.In this study,we compared the transcriptome and the composition and content of lipids in anthers of two upland cotton(Gossypium hirsutum) materials,Shida 98(WT) and its nearly-isogenic male sterile line Shida 98A(MS).Transcriptomics analysis identified many differentially expressed genes(DEGs) between the two materials,with the genes of the alpha-linolenic acid metabolism pathway being the most significantly associated with the male sterility phenotype.Investigations on lipids revealed that the MS anthers over-accumulated free fatty acids(FFAs),phosphatidic acid(PA),mono-and di-galactosyldiacylglycerol(MGDG and DGDG),and had a decreased content of triacylglycerol(TAG),which was closely related to the abnormal metabolism of alpha-linolenic acid(C18:3);therefore,the major lipids containing C18:3-acyl chains,such as PA,MGDG,DGDG,and TAG,are proposed to play a major role in cotton anther development.We also showed that an excessive level of MGDG and DGDG caused jasmonic acid(JA) overaccumulation in MS anthers,which in turn inhibited the expression of GhFAD3 and consequently reduced the C18:3 content,presumably via a feedback regulation mechanism,ultimately affecting plant fertility.Together,our results revealed the importance of a balanced lipid metabolism in regulating the development of cotton anther and pollen and consequently male fertility.
基金supported by the National Key R&D Program of China(2023YFD1801100)China National Postdoctoral Program for Innovative Talents(BX20230140)China Postdoctoral Science Foundation(2023M741348)。
文摘Mastitis is one of the most significant diseases affecting the development of the dairy industry and has traditionally been associated with pathogenic infections.However,emerging evidence highlights that ruminal microbial homeostasis also plays a crucial role in the pathogenesis of mastitis.Specifically,cows with mastitis exhibit reduced alpha diversity and altered microbial composition in the rumen.Inducing ruminal dysbiosis through a high-concentrate diet has been shown to trigger mastitis in cows,and transplantation of ruminal microbiota from mastitis-affected cows to recipient mice can induce mastitis in mice.Mechanistically,ruminal dysbiosis increases gastrointestinal inflammation and compromises the integrity of the gastrointestinal barrier,thereby facilitating the translocation of harmful bacterial components,metabolites,and pathobionts into the bloodstream.This disruption impairs blood-milk barrier function,leading to systemic inflammation and the development of mastitis.In this review,we summarize recent advances in understanding how ruminal dysbiosis induces mastitis and explore potential prevention and control strategies targeting the modulation of ruminal microbiota.
基金supported by the National Key Research and Development Program of China,No. 2023YFF0714200 (to CW)the National Natural Science Foundation of China,Nos. 82472038 and 82202224 (both to CW)+3 种基金the Shanghai Rising-Star Program,No. 23QA1407700 (to CW)the Construction Project of Shanghai Key Laboratory of Molecular Imaging,No. 18DZ2260400 (to CW)the National Science Foundation for Distinguished Young Scholars,No. 82025019 (to CL)the Greater Bay Area Institute of Precision Medicine (Guangzhou)(to CW)。
文摘Epilepsy is a leading cause of disability and mortality worldwide. However, despite the availability of more than 20 antiseizure medications, more than one-third of patients continue to experience seizures. Given the urgent need to explore new treatment strategies for epilepsy, recent research has highlighted the potential of targeting gliosis, metabolic disturbances, and neural circuit abnormalities as therapeutic strategies. Astrocytes, the largest group of nonneuronal cells in the central nervous system, play several crucial roles in maintaining ionic and energy metabolic homeostasis in neurons, regulating neurotransmitter levels, and modulating synaptic plasticity. This article briefly reviews the critical role of astrocytes in maintaining balance within the central nervous system. Building on previous research, we discuss how astrocyte dysfunction contributes to the onset and progression of epilepsy through four key aspects: the imbalance between excitatory and inhibitory neuronal signaling, dysregulation of metabolic homeostasis in the neuronal microenvironment, neuroinflammation, and the formation of abnormal neural circuits. We summarize relevant basic research conducted over the past 5 years that has focused on modulating astrocytes as a therapeutic approach for epilepsy. We categorize the therapeutic targets proposed by these studies into four areas: restoration of the excitation–inhibition balance, reestablishment of metabolic homeostasis, modulation of immune and inflammatory responses, and reconstruction of abnormal neural circuits. These targets correspond to the pathophysiological mechanisms by which astrocytes contribute to epilepsy. Additionally, we need to consider the potential challenges and limitations of translating these identified therapeutic targets into clinical treatments. These limitations arise from interspecies differences between humans and animal models, as well as the complex comorbidities associated with epilepsy in humans. We also highlight valuable future research directions worth exploring in the treatment of epilepsy and the regulation of astrocytes, such as gene therapy and imaging strategies. The findings presented in this review may help open new therapeutic avenues for patients with drugresistant epilepsy and for those suffering from other central nervous system disorders associated with astrocytic dysfunction.
基金Supported by the National Natural Science Foundation of China(Nos.42141003,42176147)the National Key Research and Development Program of China(No.2022YFF0802204)the Xiamen Key Laboratory of Urban Sea Ecological Conservation and Restoration(USER)(Nos.USER2021-1,USER2021-5)。
文摘Ecological floating bed is an important biological remediation method for water pollution control.During the removal of excess nutrients and pollutants,changes in environmental factors affect the characteristics of microorganisms in aquatic ecosystems.To understand the influences of ecological floating beds on size-fractionated microorganisms,we investigated the community assembly and nitrogen metabolic characteristics of three size-fractionated microorganism groups in the ecological floating bed area,using 18S rDNA,16S rDNA metabarcoding,and metagenomic sequencing techniques.Firstly,we discovered substantial differences between size-fractionated groups in the diversity and compositions of both microeukaryotic and bacterial communities,as well as the influences of floating beds on specific groups.The floating beds appeared to provide more habitats for heterotrophs and symbiotes while potentially inhibiting the growth of certain phytoplankton(cyanobacteria).Secondly,we observed that microeukaryotic and bacterial communities were predominantly influenced by stochastic and deterministic processes,respectively,and they both exhibited distinct patterns across different size-fractionated groups.Notably,microeukaryotic community assembly demonstrated a greater sensitivity to ecological floating beds,as indicated by an increase in dispersal limitation processes.Finally,the nitrogen metabolism functional genes revealed that microbes associated with large-sized particles played a crucial role in dissimilatory nitrate reduction to ammonium(DNRA)and denitrification processes within the floating bed area,thereby facilitating the removal of excess nitrogen nutrients from the water.In contrast,freeliving microorganisms from small-sized groups were linked mainly to the genes involved in nitrogen assimilation and assimilatory nitrate reduction to ammonium(ANRA)processes.These findings help understand the impact of ecological floating beds on the diversity and functional characteristics of microorganism communities in different size-fractionated groups.
基金supported by the National Key R&D Program of China(No.2022YFD1301001)。
文摘Background Fatty liver syndrome is a prevalent metabolic disorder in transition dairy cows,characterized by excessive hepatic lipid accumulation that impairs liver function and leads to systemic metabolic disturbances.Docosahexaenoic acid(DHA),a prominent n-3 polyunsaturated fatty acid(PUFA),not only exhibits anti-inflammatory and anti-oxidative properties,but also holds potential in ameliorating lipid metabolism.This study integrated in vitro bovine primary hepatocyte models and in vivo dairy cow trials to investigate the regulatory effects of DHA on hepatic lipid deposition.Results In vitro,40μmol/L DHA significantly reduced triglyceride(TAG)accumulation in steatotic hepatocytes by downregulating genes involved in fatty acid transport(FABP-1,CD36)and lipogenesis(DGAT2,FAS,SREBP-1C),while upregulating markers of lipolysis(CGI-58,ATGL)and fatty acid oxidation(ACADL,CPT1A,CPT2).Transmission electron microscopy(TEM)confirmed DHA-mediated restoration of mitochondrial ultrastructure and enhanced lipid droplet(LD)-mitochondria interactions.In vivo,dietary rumen-protected DHA(180 g/d)supplementation reduced hepatic lipid deposition,improved liver function(evidenced by decreased total bilirubin and alanine aminotransferase),reduced oxidative stress and inflammation(suppressed malondialdehyde,glutathione peroxidase,and lipopolysaccharide),coincided with relieving insulin resistance(reduced insulin and glucose,as well increased adiponectin)in dairy cows with fatty liver.These improvements may be attributed to increased expression of TOMM20 and MtCo-1,promoting mitochondrial biogenesis andβ-oxidation,along with an elevated plasma n-3/n-6 ratio.Conclusions Collectively,these findings suggest that DHA supplementation represents a promising nutritional strategy for preventing spontaneous fatty liver in transition dairy cows by enhancing hepatic lipid clearance and restoring metabolic homeostasis.
基金supported by the National Key Research and Development Program of China(No.2022YFC3702704)the National Natural Science Foundation of China(Nos.22376005,22076006 and 82073506).
文摘Microorganisms constitute an essential component in the indoor environment,which is closely related to hu-man health.However,there is limited evidence regarding the associations between indoor airborne microbiome and systemic inflammation,as well as whether this association is modified by indoor particulate matter and the underlying mechanisms.In this prospective repeated-measure study among 66 participants,indoor airborne mi-crobiome was characterized using amplicon sequencing and qPCR.Indoor fine particulate matter(PM_(2.5))and inhalable particulate matter(PM10)were measured.Systemic inflammatory biomarkers were assessed,including white blood cell(WBC),neutrophil(NEUT),monocyte,eosinophil counts,and their proportions.Targeted serum amino acid metabolomics were conducted to explore the underlying mechanisms.Linear mixed-effect models re-vealed that bacterial and fungal Simpson diversity were significantly associated with decreased WBC and NEUT.For example,for each interquartile range increase in the bacterial Simpson diversity,WBC and NEUT changed by-4.53%(95%CI:-8.25%,-0.66%)and-5.95%(95%CI:-11.3%,-0.27%),respectively.Notably,increased inflammatory risks of airborne microbial exposure were observed when indoor PM_(2.5) and PM10 levels were below the WHO air quality guidelines.Mediation analyses indicated that dopamine metabolism partially mediated the anti-inflammatory effects of fungal diversity exposure.Overall,our study indicated protection from a diverse indoor microbial environment on cardiovascular health and proposed an underlying mechanism through amino acid metabolism.Additionally,health risks associated with microbial exposure deserve more attention in con-texts of low indoor particulate matter pollution.Further research is necessary to fully disentangle the complex relationships between indoor microbiome,air pollutants,and human health.
基金supported by grants from STI2030-Major Projects,No.2021ZD0204000(to YS)Key Strategic Science and Technology Cooperation Project of the Ministry of Science and Technology of China,No.SQ2023YFE0201430(to YS)+1 种基金the National Natural Science Foundation of China,Nos.31820103005(to YS),32200620(to LW)the Natural Science Foundation of Zhejiang Province of China,No.LZ24C090003(to YS)。
文摘The cerebellum is receiving increasing attention for its cognitive,emotional,and social functions,as well as its unique metabolic profiles.Cerebellar microglia exhibit specialized and highly immunogenic phenotypes under both physiological and pathological conditions.These immune cells communicate with intrinsic and systemic factors and contribute to the structural and functional compartmentalization of the cerebellum.In this review,we discuss the roles of microglia in the cerebellar microenvironment,neuroinflammation,cerebellar adaptation,and neuronal activity,the associated molecular and cellular mechanisms,and potential therapeutic strategies targeting cerebellar microglia in the context of neuroinflammation.Future directions and unresolved questions in this field are further highlighted,particularly regarding therapeutic interventions targeting cerebellar microglia,functional mechanisms and activities of microglia in the cerebellar circuitry,neuronal connectivity,and neurofunctional outcomes of their activity.Cerebellar morphology and neuronal performance are influenced by both intrinsic and systemic factors that are actively monitored by microglia in both healthy and diseased states.Under pathological conditions,local subsets of microglia exhibit diverse responses to the altered microenvironment that contribute to the structural and functional compartmentalization of the cerebellum.Microglia in the cerebellum undergo early maturation during the embryonic stage and display specialized,highly immunogenic phenotypes.In summary,cerebellar microglia have the capacity to serve as regulatory tools that influence outcomes across a wide range of neurological and systemic conditions,including neurodevelopmental,neurodegenerative,metabolic,and stress-related disorders.
基金supported and funded by the National Key Research and Development Program of China(2023YFD1300801)the Agricultural Science and Technology Innovation Program in Chinese Academy of Agricultural Sciences(ASTIP-IAS-08)。
文摘Background The decline in reproductive performance of aged hens is mainly attributed to oxidative damage in reproductive organs,hepatic lipid metabolism disorders,and intestinal microbiota dysbiosis.Glycyrrhizin(GL)has been proven to enhance antioxidant capacity,regulate lipid metabolism and gut microbiota in mammals,but its efficacy in hens remains unclear.Hence,this study aimed to investigate whether dietary GL supplementation improves reproductive performance in hens during the late laying stage by modulating intestinal microbiota composition,hepatic lipid metabolism and ovarian antioxidant status.Results Dietary supplementation with 100 mg/kg GL significantly improved the egg production rate,egg quality,and hatching rate in aged breeder hens(P<0.05).GL supplementation also increased the serum levels of HDLC,TP and ALB,and enhanced the antioxidant capacity in both serum and ovary(P<0.05).In addition,dietary GL elevated the serum progesterone(P4)levels by enhancing the transcription level of steroid synthesis key enzymes(CYP11A1 and 3β-HSD)in the ovary(P<0.05).Dietary GL also promoted the synthesis and transport of vitellogenin(VTG)by upregulating the VTG-II(P<0.05)and APOV1(P=0.077)expression levels in the liver,thereby increasing the number of grade follicles and small yellow follicles.Moreover,dietary GL enhanced hepatic fatty acidβ-oxidation by upregulating PPARαand CPT-I(P<0.05),and downregulating ACC expression levels(P<0.05).In agreement,liver metabolomics analysis revealed that dietary GL supplementation significantly altered hepatic metabolism,with 389 differentially identified metabolites(P<0.05).The key metabolites(e.g.,taurocholic acid,tauroursodeoxycholic acid,nicotinuric acid,glycodeoxycholic acid(hydrate))were identified,and they were mainly functionally enriched in betaalanine metabolism nicotinate,taurine and hypotaurine metabolism(P<0.05).Finally,16S rRNA gene sequencing revealed that dietary GL reversed age-induced changes in gut microbiota composition,characterized by a significant increase in Lactobacillus abundance and a decrease in Bacteroides(P<0.05).Conclusions These results collectively demonstrate that dietary supplementation with 100 mg/kg GL improved reproductive performance by reversing age-induced changes in gut microbiota,enhancing hepatic vitellogenin synthesis,and ameliorating ovarian function in aged breeder hens.This study suggests that dietary GL is a potential strategy to improve reproductive performance in broiler breeder hens during the late laying period.
基金Supported by the National Natural Science Foundation of China,No.82305376the Youth Talent Support Project of the China Acupuncture and Moxibustion Association,No.2024-2026ZGZJXH-QNRC005+2 种基金the 2024 Jiangsu Province Youth Science and Technology Talent Support Project,No.JSTJ-2024-3802025 Jiangsu Provincial Science and Technology Think Tank Program Project,No.JSKX0125035and 2025 College Student Innovation Training Program Project,No.X202510315373。
文摘BACKGROUND Organ transplantation has emerged as a globally prevalent therapeutic modality for end-stage organ failure,yet the post-transplantation trajectory is increasingly complicated by a spectrum of metabolic sequelae,with obesity emerging as a critical clinical challenge.AIM To systematically review the multifactorial mechanisms underlying obesity following organ transplantation and to integrate evidence from pharmacological,behavioral,and molecular perspectives,thereby providing a foundation for targeted interventions.METHODS We conducted a systematic search in PubMed and Web of Science for literature published from 2020 to 15 July 2025.The search strategy incorporated terms including“obesity”,“overweight”and“post organ transplantation”.Only randomized controlled trials,meta-analyses,and systematic reviews were included.Non-empirical publications and irrelevant studies were excluded.Data extraction and quality assessment were performed by two independent reviewers,with disagreements resolved by a third researcher.RESULTS A total of 1457 articles were initially identified,of which 146 met the inclusion criteria.These studies encompassed liver,kidney,heart,and lung transplant recipients.Key findings indicate that immunosuppressive drugs-especially corticosteroids and calcineurin inhibitors-promote hyperphagia,insulin resistance,and dyslipidemia.Post-transplant sedentary behavior and hypercaloric diets further contribute to positive energy balance.At the molecular level,immunosuppressants disrupt adipokine signaling(e.g.,leptin and adiponectin),induce inflammatory and oxidative stress responses,and activate adipogenic pathways leading to lipid accumulation.CONCLUSION Post-transplant obesity arises from a complex interplay of pharmacological,behavioral,and molecular factors.A multidisciplinary approach-incorporating pharmacological modification,nutritional management,physical activity,and molecular-targeted therapies-is essential to mitigate obesity and improve transplant outcomes.Further large-scale and mechanistic studies are warranted to establish evidence-based preventive and treatment strategies.
基金supported by the National Natural Science Foundation of China(82574477)the Jiangsu Provincial Traditional Chinese Medicine Science and Technology Development Plan(QN202426)+5 种基金Jiangsu Province“333 High-level Talents Training Project”((2024)3-0189)Youth Talent Support Project of the Jiangsu Association for Science and Technology(TJ-2023-053)Shanxi Provincial Department-Municipal Key Laboratory Cultivation Base for Quality Enhancement and Utilization of Shangdang Chinese Medicinal Materials(KF202401)Fundamental Research Program of Shanxi Province(202403021221211)the research project supported by the Shanxi Scholarship Council of China(No.2023-158)Open Project of Key Laboratory of Tibetan Medicine Basic Research,Ministry of Education.
文摘The global prevalence of metabolic-associated fatty liver disease(MAFLD)is on the rise,seriously threatening human health.Currently,no specific approved drugs are available for its treatment.This paper reviews the pathogenesis of MAFLD,covering aspects like lipid accumulation and insulin resistance,oxidative stress,endoplasmic reticulum stress(ERS),lipotoxicity-induced hepatocyte damage,and fibrosis.It also elaborates on multiple treatment approaches for MAFLD,including metabolic regulation,improvement of the gut-liver axis interaction,modulation of immune and inflammatory pathways,enhancement of the adipose tissue-liver interaction,alleviation of fibrosis,prevention of hepatocyte injury,and traditional Chinese medicine(TCM)external therapies.Additionally,natural product research advancements,individual Chinese medicine components,and mixed herbal formulas for MAFLD treatment is provided.Many natural products and traditional Chinese medicines exhibit favorable effects in regulating lipid metabolism,anti-inflammation,and anti-oxidation,offering new directions and potential drug options for MAFLD treatment.This is expected to provide a reference for future clinical treatment and drug development.
文摘The rapidly aging population directly contributes to the increasing cases of neurological disorders.Due to the chronic progressive nature of neurodegeneration,numerous neurological conditions are considered“multifactorial”with systemic metabolic alterations.Even so,treatments for neurological disorders have remained unchanged for the past decades.Recently,metabolic drugs such as metformin and glucagon-like peptide 1 agonists have demonstrated promising health outcomes for neurodegeneration.
基金supported by the National Research Foundation of Korea(2020R1F1A1074155).
文摘Recently,Prevotella spp.,a major genus of gram-negative commensal bacteria in humans,have emerged as a key microbial contributor to host metabolism due to its ability to ferment dietary fibers,produce beneficial short-chain fatty acids,and influence immune responses.However,their diversity and functional differences have created challenges for their development and therapeutic use.Recent studies have shown that specific Prevotella species,such as P.copri,P.intestinalis,and P.histicola,can strengthen gut barrier integrity and reduce metabolic imbalances.Notably,Prevotella populations can be increased through high-fiber or herbal-based treatments.Traditional herbal medicines,including fiber-rich decoctions,also demonstrate the potential to boost endogenous Prevotella communities,enhance microbial fermentation,and improve glucose and lipid balance.This perspective examines the context-dependent roles of Prevotella spp.,with emphasis on the functional heterogeneity of key species such as P.copri,suggests a framework for combining herbal modulation with species-level microbiota profiling,and outlines a research plan to explore microbe-herb synergy in treating obesity,type 2 diabetes,and related metabolic disorders.This strategy offers a new,ecology-based approach to complement standard metabolic interventions.
基金funded by the Agricultural Development Program through Science and Technology of Shanghai,China (2022-02-08-00-12-F01099)the National Key R&D Program of China (2023YFD1201501)+1 种基金the Science and Technology Commission of Shanghai Municipality,China (22DX1900100)the Excellent Team Project of Shanghai Academy of Agricultural Sciences,China (2022(007))。
文摘Head-splitting is a prevalent physiological disorder in cabbage that causes substantial economic losses.However,the genetic factors and molecular mechanisms underlying head-splitting resistance remain largely unexplored.This study identified a genomic region(q NLQ3.1) for head-splitting resistance on chromosome C03 through the combination of QTLseq and GPS analysis in an F_(2) population derived from hybridizing two cabbage inbred lines,‘Dazhengfu'(ZF,susceptible) and ‘103'(resistant).Traditional genetic linkage analysis narrowed q NLQ3.1 to a 74.6 kb region.Furthermore,comparative analysis of the two parental lines using transcriptomic and metabolic profiling demonstrated the crucial role of hormones in regulating head-splitting resistance.Bol028000,encoding a homologue of Arabidopsis Cytokinin Response Factor 3(CRF3),emerged as a promising candidate for head-splitting resistance and was subsequently validated through Sanger sequencing and quantitative RT-PCR(qRT-PCR).Subcellular localisation analysis revealed that Bol028000 was mainly expressed in the nucleus.Additionally,one kompetitive allele-specific PCR(KASP) marker from Bol028000 was developed and utilized to screen 42 inbred lines.These findings enhance the theoretical understanding of head-splitting resistance and provide valuable insights for the molecular breeding of head-splitting resistant cabbages.
