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
Metabolic dysfunction-associated steatotic liver disease(MASLD),formerly known as nonalcoholic fatty liver disease,is a chronic liver disease characterized by hepatic lipid deposition and hepatocellular steatosis,resu...Metabolic dysfunction-associated steatotic liver disease(MASLD),formerly known as nonalcoholic fatty liver disease,is a chronic liver disease characterized by hepatic lipid deposition and hepatocellular steatosis,resulting from nonalcoholic causes and closely linked to metabolic dysfunction[1].It is strongly associated with metabolic abnormalities,including type 2 diabetes,overweight,and obesity.The global prevalence of MASLD is estimated to be approximately 25%−33%,and its incidence is rising rapidly,particularly among younger populations,due to increasingly prevalent unhealthy lifestyle behaviors such as sleep deprivation,sedentary habits,and diets rich in calories.展开更多
Lung cancer remains the leading cause of cancer-related mortality worldwide,primarily driven by metabolic reprogramming and immune evasion mechanisms within tumor cells.To adapt to the nutrient-deprived tumor microenv...Lung cancer remains the leading cause of cancer-related mortality worldwide,primarily driven by metabolic reprogramming and immune evasion mechanisms within tumor cells.To adapt to the nutrient-deprived tumor microenvironment(TME),lung cancer cells undergo profound metabolic reprogramming,characterized by enhanced glycolysis(the Warburg effect),increased glutamine dependency(mediated by GLS1),and accelerated lipid synthesis(involving enzymes such as FASN).These metabolic alterations not only remodel the TME but also dampen antitumor immune responses by promoting immunosuppressive cell populations(e.g.,Tregs and M2 macrophages)and inhibiting effector functions of CD8^(+)T cells and natural killer(NK)cells.Critically,a bidirectional crosstalk operates between tumor cell metabolism and the immunosuppressive TME:metabolic reprogramming drives immune suppression through metabolite accumulation,whereas the immunosuppressive TME,in turn,promotes tumor cell adaptability—thus forming a positive feedback loop that reinforces immune evasion and therapy resistance.This review elucidates key molecular pathways governing metabolic reprogramming in lung cancer—spanning glucose,amino acid,and lipid metabolism—and their dynamic crosstalk with immune regulation,including epigenetic modifications and non-coding RNA-mediated mechanisms.Additionally,it evaluates emerging therapeutic strategies targeting the metabolic-immune axis,such as inhibitors of HK2 or GLS1 combined with anti-PD-1/PD-L1 agents,which aim to reverse immunosuppression and improve clinical outcomes.By synthesizing recent advances,this work provides a theoretical framework for precision oncology interventions,highlighting the potential of metabolic immunotherapies and future directions integrating AI and multi-omics data to overcome resistance in lung cancer.展开更多
In light of the pressing global challenges of climate change,declining crop resilience,and hidden hunger,it is imperative to overcome the limitations of conventional crop breeding to enhance both the nutritional quali...In light of the pressing global challenges of climate change,declining crop resilience,and hidden hunger,it is imperative to overcome the limitations of conventional crop breeding to enhance both the nutritional quality and stress tolerance of crops.Synthetic metabolic engineering presents innovative strategies for the precision modification and de novo design of metabolic pathways.This approach generally encompasses three essential steps:identifying key metabolites through metabolomics,integrating multi-omics technologies to investigate the synthesis and regulation of these metabolites,and utilizing gene editing or de novo design to modify crop metabolic pathways associated with desirable agronomic traits.This review underscores the vital role of plant metabolite diversity in enhancing crop nutritional quality and stress resilience.Integrated multi-omics analyses facilitate the metabolic engineering by identifying key genes,transporters,and transcription factors that regulate metabolite biosynthesis.Precision modification strategies employ genome editing tools to reprogram endogenous metabolic networks,while de novo design reconstructs metabolic pathways through the introduction of exogenous biological elements—thereby both approaches enable the targeted enhancement of desired traits.These strategies have been effectively implemented in major food crops.However,simultaneously enhancing nutritional quality and stress resilience remains challenging due to inherent trade-offs and resource competition in distinct metabolic pathways within plants.Future research should integrate AI-driven predictive models with multi-omics datasets to decipher dynamic metabolic homeostasis and engineer climate-smart crops that maximize yield while preserving quality and environmental adaptability.展开更多
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
Tumor metabolic reprogramming is a core hallmark of cancer,characterized by pathways such as aerobic glycolysis,aberrant lipid metabolism,and glutaminolysis that support rapid proliferation and immunosuppressive micro...Tumor metabolic reprogramming is a core hallmark of cancer,characterized by pathways such as aerobic glycolysis,aberrant lipid metabolism,and glutaminolysis that support rapid proliferation and immunosuppressive microenvironments.Circular RNAs(circRNAs)are highly stable,evolutionarily conserved non-coding RNAs that have emerged as critical modulators of these metabolic shifts.This review aims to systematically elucidate the roles and mechanisms of circRNAs in reprogramming tumor metabolism,and to discuss their clinical potential as biomarkers and therapeutic targets.Through mechanisms including miRNA sponging,protein interactions,regulation of mitochondrial dynamics,and modulation of metabolic enzymes,circRNAs influence key metabolic pathways by targeting glycolytic enzymes,lipid synthesis regulators,and glutaminolysis-related molecules to either facilitate or inhibit their expression.This review systematically summarizes the unique contributions of circRNAs to tumor metabolic reprogramming,highlighting key mechanisms such as regulation of peptide-encoding protein translation,mitochondrial localization function,gene promoter-targeted transcriptional regulation,and cross-pathway metabolic mediation,which underscore their distinct biological advantages and regulatory roles in tumor metabolism.The stability and tissue specificity of circRNAs make them promising diagnostic biomarkers,while their role in drug resistance mediated by metabolic reprogramming highlights their potential as therapeutic targets.Strategies such as circRNA inhibitors,mimics,and nanoparticle-based delivery systems are being explored to modulate tumor metabolism.Despite challenges including complex regulatory networks and limited manipulation tools,advances in high-throughput technologies and clinical trials hold promise for translating circRNA research into novel cancer therapies.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
As we welcome the spring of 2026,we extend our sincere greetings and best wishes to colleagues worldwide in the field of crop science,our partners,and all those committed to sustainable agricultural development!The Ye...As we welcome the spring of 2026,we extend our sincere greetings and best wishes to colleagues worldwide in the field of crop science,our partners,and all those committed to sustainable agricultural development!The Year of the Horse symbolizes endeavor and far-reaching journeys,reflecting our own spirit of continuous exploration and breakthrough innovation on the path of crop science.Here,I extendmysincere appreciation to all our authors and reviewers for their invaluable time,expertise,and dedication,which are instrumental in the success of The Crop Journal,establishing it as a premier platform for the global crop science research community.The Crop Journal publishes its 2026 first issue as a special issue themed“Synthetic Biology for Crop Improvement”,ably vip-edited by four young scientists.The issue provides a comprehensive overview of major advances in the field.In the past few years,crop science has made long strides in metabolic engineering of important pathways in secondary metabolism.The achievements expedite the emergence of synthetic biology as a potent methodology for crop breeding and represent a fundamental paradigm shift from“deciphering crops”to“designing crops”,which is further empowered by artificial intelligence(AI).At this turning point of the New Year,I would like to take this opportunity to provide a brief retrospective and future perspective.展开更多
Objective:This study was aimed at investigating metabolic dysregulation in tumor-associated macrophages(TAMs)in breast cancer and developing a metabolically enhanced chimeric antigen receptor macrophage(CAR-M)strategy...Objective:This study was aimed at investigating metabolic dysregulation in tumor-associated macrophages(TAMs)in breast cancer and developing a metabolically enhanced chimeric antigen receptor macrophage(CAR-M)strategy to boost antitumor potency in solid tumors.Methods:Integrated scRNA-seq and metabolomic analyses were performed to characterize metabolic alterations in macrophages within the breast cancer tumor microenvironment(TME).According to the identified metabolic vulnerabilities,SLC38A2-overexpressing anti-HER2 CAR-Ms were engineered.Glutamine uptake and phagocytic activity were assessed to evaluate functional enhancement.Results:TAMs in breast cancer exhibited substantial metabolic dysregulation,particularly impaired glutamine metabolism accompanied by decreased expression of the glutamine transporter SLC38A2.Overexpression of SLC38A2 in anti-HER2 CAR-Ms,compared with conventional anti-HER2 CAR-Ms,enhanced glutamine uptake and markedly augmented phagocytosis of HER2+breast cancer cells.Conclusions:Metabolic engineering via SLC38A2 restored glutamine fitness and enhanced the antitumor activity of HER2-targeted CAR-Ms,thus providing a promising strategy to boost CAR-M–mediated tumor suppression in solid tumors.展开更多
Metabolic dysfunction-associated fatty liver disease(MAFLD)and chronic kidney disease(CKD)have shown a marked global increase in prevalence,placing a substantial burden on public health and healthcare systems worldwid...Metabolic dysfunction-associated fatty liver disease(MAFLD)and chronic kidney disease(CKD)have shown a marked global increase in prevalence,placing a substantial burden on public health and healthcare systems worldwide.Epidemiological data demonstrate a significant overlap between these two conditions,with further evidence from research identifying common pathophysiological features,such as lipid metabolism dysregulation,disrupted energy balance,and chronic systemic inflammation.Mitochondria are central to the pathophysiology of both diseases.In addition to their role in energy production,mitochondria are involved in numerous critical cellular processes,including biosynthesis,lipid metabolism,oxidative phosphorylation,signal transduction,and apoptosis regulation.Mitochondrial dysfunction,characterized by increased reactive oxygen species,impaired adenosine triphosphate synthesis,disrupted mitophagy,and changes in mitochondrial morphology,is implicated in the progression of both MAFLDandCKD.Given the pivotal role of mitochondria in maintaining cellularmetabolism homeostasis,dysfunction of this organelle is increasingly recognized as a key mechanistic link that connects the pathophysiological processes underlying both MAFLD and CKD.This review underscores mitochondrial dysfunction as a pathogenic nexus between MAFLD and CKD and examines the mechanisms that drive their pathogenesis.展开更多
Metabolic dysfunction-associated steatotic liver disease(MASLD)is now considered to be among the most prevalent chronic liver diseases worldwide.Its comprehensive management encompasses multiple stages,including risk ...Metabolic dysfunction-associated steatotic liver disease(MASLD)is now considered to be among the most prevalent chronic liver diseases worldwide.Its comprehensive management encompasses multiple stages,including risk assessment,early detection,stratified intervention,and long-term follow-up.Among these,improving diagnostic accuracy and optimizing individualized therapeutic strategies remain key challenges in both research and clinical practice.In recent years,artificial intelligence and smart devices have developed rapidly and have gradually been applied in the medical field,offering novel tools and pathways for MASLD risk stratification,non-invasive diagnosis,therapeutic evaluation,and patient self-management.This review summarizes the current applications of artificial intelligence and smart devices in MASLD care,highlights their benefits and limitations,and discusses future directions to support precision diagnosis and treatment strategies.展开更多
1.Introduction The field of exercise science is experiencing a renaissance,with recent research illuminating the molecular,cellular,and systemic effects of physical activity.This is largely due to the now unequivocal ...1.Introduction The field of exercise science is experiencing a renaissance,with recent research illuminating the molecular,cellular,and systemic effects of physical activity.This is largely due to the now unequivocal evidence that a lack of physical activity,not only has direct effects on the prevalence of non-contagious diseases(NCDs)but has profound additive effects of other risk factors for NCD such as obesity and hypertension.1 The articles in this special topic of Journal of Sport and Health Science(JSHS)are dedicated to research on Exercise biochemistry&metabolism.展开更多
Neurodegenerative diseases are chronic,age-related disorders characterized by a relentless,irreversible,and selective loss of neurons in motor,sensory,or cognitive systems(Gao et al.,2019).Despite their heterogeneity,...Neurodegenerative diseases are chronic,age-related disorders characterized by a relentless,irreversible,and selective loss of neurons in motor,sensory,or cognitive systems(Gao et al.,2019).Despite their heterogeneity,a common pathological feature across many of these diseases is the accumulation of aggregate-prone proteins.Particularly,the cytoplasmic aggregation in neurons of the Transactive response DNA-binding protein 43(TDP-43).展开更多
Aerobic glycolysis,also known as the Warburg effect,and the accumulation of lactate that it causes,are increasingly recognized outside the field of oncology as triggers of chronic non-neoplastic disorders.This review ...Aerobic glycolysis,also known as the Warburg effect,and the accumulation of lactate that it causes,are increasingly recognized outside the field of oncology as triggers of chronic non-neoplastic disorders.This review integrates preclinical and clinical evidence to evaluate the ability of melatonin to reverseWarburg-effect-like metabolic reprogramming.Literature on neurodegeneration,age-related sarcopenia,type 2 diabetes,chronic kidney disease,heart failure and pulmonary arterial hypertension(PAH)has been reviewed and synthesised.In all of these conditions,hypoxia-inducible factor 1α(HIF-1α)and pyruvate dehydrogenase kinase 4(PDK4)inhibit the pyruvate dehydrogenase complex.This diverts pyruvate away fromthe tricarboxylic acid(TCA)cycle and promotes glycolysis.In cell and animal models,melatonin consistently inhibits PDK4,destabilizes HIF-1αunder normoxic conditions,activates SIRT1/3-dependentmitochondrial biogenesis andmitophagy,and eliminates reactive oxygen and nitrogen species.These actions reduce lactate production,restore oxidative phosphorylation and attenuate tissue damage.This appears to induce cognitive and synaptic improvements in Alzheimer’s and Parkinson’s disease models,increased muscle mass and function in ageing rodents,improved insulin sensitivity alongside suppression of hepatic gluconeogenesis in diabetic models,reduced fibrosis in nephropathy,and normalization of vascular remodeling in hypoxia-induced pulmonary arterial hypertension(PAH).Early-stage clinical trials corroborate a decrease in oxidative and inflammatorymarkers,improved sleep quality and modest cognitive benefits.However,they report conflicting effects on insulin sensitivity,which are largely related to the dose and timing of administration in relation to food intake.Overall,the current data suggest that melatonin is a pleiotropic metabolic modulator capable of counteracting the Warburg phenotype in multiple organs.However,human studies remain scarce,and well-designed randomised trials incorporating chronotherapy are needed before clinical adoption.展开更多
Introduction:Advances in HIV management have transformed HIV into a chronic condition,resulting in improved prognosis and increased survival among people living with HIV(PLWH).Traditional risk factors for metabolic dy...Introduction:Advances in HIV management have transformed HIV into a chronic condition,resulting in improved prognosis and increased survival among people living with HIV(PLWH).Traditional risk factors for metabolic dysfunction-associated steatotic liver disease(MASLD)—including dyslipidemia—are prevalent in PLWH.This systematic review and meta-analysis aim to synthesize current evidence on lipid profile disturbances as contributors to MASLD in PLWH.Methods:This systematic review and meta-analysis were conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)guidelines and registered in PROSPERO with registration number CRD420251054477.We searched seven databases to identify studies reporting the prevalence and characteristics of MASLD in PLWH.Meta-analysis was conducted using Review Manager 5.4.1.Mean differences(MDs)were calculated using a random-effects model.Risk of bias was assessed using the ROBINS-E tool.Results:A total of 17 studies comprising 3933 HIV-positive participants were included,among whom 1226(37%)had MASLD.Male sex was significantly associated with MASLD(OR=1.57;95%CI:1.13-2.17;p=0.007).MASLD was significantly associated with higher body mass index(BMI)(MD=3.23 kg/m^(2);p<0.00001).Lipid profile analysis revealed that MASLD patients had higher total cholesterol(MD=6.62 mg/dL;p=0.01),low density lipoprotein(LDL)(MD=3.83 mg/dL;p=0.01),triglycerides(MD=63.02 mg/dL;p<0.00001),and lower high density lipoprotein(HDL)(MD=-3.73 mg/dL;p<0.0001).Conclusion:This study demonstrates a significant difference in lipid profiles(higher total cholesterol,LDL,triglycerides,and lower HDL)among PLWH who develop MASLD,suggesting a potential metabolic signature associated with this comorbidity.展开更多
Alzheimer’s disease(AD)is the most common form of dementia,affecting over 50 million people worldwide.This figure is projected to nearly double every 20 years,reaching 82 million by 2030 and 152 million by 2050(Alzhe...Alzheimer’s disease(AD)is the most common form of dementia,affecting over 50 million people worldwide.This figure is projected to nearly double every 20 years,reaching 82 million by 2030 and 152 million by 2050(Alzheimer’s Disease International).The apolipoproteinε4(APOE4)allele is the strongest genetic risk factor for late-onset AD(after age 65 years).Apolipoprotein E,a lipid transporter,exists in three variants:ε2,ε3,andε4.APOEε2(APOE2)is protective against AD,APOEε3(APOE3)is neutral,while APOE4 significantly increases the risk.Individuals with one copy of APOE4 have a 4-fold greater risk of developing AD,and those with two copies face an 8-fold risk compared to non-carriers.Even in cognitively normal individuals,APOE4 carriers exhibit brain metabolic and vascular deficits decades before amyloid-beta(Aβ)plaques and neurofibrillary tau tangles emerge-the hallmark pathologies of AD(Reiman et al.,2001,2005;Thambisetty et al.,2010).Notably,studies have demonstrated reduced glucose uptake,or hypometabolism,in brain regions vulnerable to AD in asymptomatic middle-aged APOE4 carriers,long before clinical symptoms arise(Reiman et al.,2001,2005).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
Metabolic dysfunction-associated steatotic liver disease(MASLD)is an increasingly prevalent condition associated with hepatic complications and cardiovascular and renal events.Given its significant clinical impact,the...Metabolic dysfunction-associated steatotic liver disease(MASLD)is an increasingly prevalent condition associated with hepatic complications and cardiovascular and renal events.Given its significant clinical impact,the development of new strategies for early diagnosis and treatment is essential to improve patient outcomes.Over the past decade,the integration of artificial intelligence(AI)into gastroenterology has led to transformative advancements in medical practice.AI represents a major step towards personalized medicine,offering the potential to enhance diagnostic accuracy,refine prognostic assessments,and optimize treatment strategies.Its applications are rapidly expanding.This article explores the emerging role of AI in the management of MASLD,emphasizing its ability to improve clinical prediction,enhance the diagnostic performance of imaging modalities,and support histopathological confirmation.Additionally,it examines the development of AI-guided personalized treatments,where lifestyle modifications and close monitoring play a pivotal role in achieving therapeutic success.展开更多
Background:The aim of the study was to develop a non-human primate model of metabolic dysfunction in Macaca fascicularis using chronic high-fat diet(HFD)to mimic clinical disease progression.Methods:Thirty-five male m...Background:The aim of the study was to develop a non-human primate model of metabolic dysfunction in Macaca fascicularis using chronic high-fat diet(HFD)to mimic clinical disease progression.Methods:Thirty-five male macaques aged 10-15 years underwent an 18-month HFD intervention.Physiological parameters(BMI,BP,hematology),liver fat fraction(evaluated by ultrasound/MRI),cardiac function(assessed by echocardiography),and histopathology(using liver biopsy)were measured before and after the intervention.Serum proteomics with KEGG/STRING analyses identified molecular mechanisms.Results:Within 6 months,HFD induced dyslipidemia(elevated TG,TCHO,HDL-C,LDL-C).After 18 months,metabolic dysfunction-associated steatohepatitis(MASH)was confirmed by histopathology in 57.14%(16/28)of macaques,diabetes(elevated FPG/HbA1c)in 17.86%(5/28),and myocardial hypertrophy(elevated LVMass/LAD)in 46.43%(13/28).Proteomics identified Bile acid-CoA:amino acid N-acyltransferase(BAAT)as a MASH hallmark protein,the level of which was inversely correlated with the degree of fibrosis.For diabetes,citrate synthase(CS)and malate dehydrogenase 1(MDH1)impaired glucose oxidation via the TCA cycle,while hexose-6-phosphate de-hydrogenase(H6PD)disrupted gluconeogenesis.Myocardial hypertrophy was associ-ated with the downregulation of SRC proto-oncogene,non-receptor tyrosine kinase(SRC),mitogen-activated protein kinase 14(MAPK14),emerin(EMD),and integrin subunit beta 1(ITGB1).Conclusions:An 18-month HFD successfully established a translational M.fascicula-ris model replicating key metabolic disorders(MASH,diabetes,cardiac hypertrophy).BAAT,CS/MDH1/H6PD,and SRC/MAPK14/EMD/ITGB1 were identified as mecha-nistic biomarkers for these conditions.展开更多
Background and AimsHepatic iron deposition(HID)in the reticuloendothelial system(RES)is associated with histological severity in metabolic dysfunction-associated steatotic liver disease(MASLD).This study aimed to asse...Background and AimsHepatic iron deposition(HID)in the reticuloendothelial system(RES)is associated with histological severity in metabolic dysfunction-associated steatotic liver disease(MASLD).This study aimed to assess the interaction between the transferrin(TF)-rs1049296 C>T variant and HID patterns on the risk of significant liver fibrosis in MASLD.MethodsWe analyzed 406 adults with liver biopsy-confirmed MASLD.HID was categorized as hepatocellular,RES,or mixed,based on Perl's iron staining.The association between iron-related genetic variants and significant liver fibrosis(fibrosis stage≥F2)was analyzed,focusing on the interactions between single-nucleotide polymorphism genotypes and iron deposition patterns.Multivariable logistic regression analysis was used to adjust for potential confounders.ResultsHID was detected in 271(66.7%)patients,with hepatocellular,RES,and mixed patterns accounting for 11.1%,18.0%,and 37.7%,respectively.A significant interaction was observed between HID and the TF-rs1049296 genotype(P=0.035 for interaction).In multivariable analysis,male sex,hypertension,severe lobular inflammation,and mixed hepatocellular/RES iron deposition were independent predictors of significant liver fibrosis.RES deposition markedly increased the risk of significant liver fibrosis(adjusted odds ratio:6.65;95%confidence interval:1.84-23.97,p<0.05),particularly in men with isolated RES iron deposition(adjusted odds ratio:5.26;95%confidence interval:1.21-22.81,p<0.05).ConclusionsThe TF-rs1049296 T allele interacts with RES iron deposition to identify a MASLD subpopulation at elevated risk of progressive liver disease,providing opportunities for refined risk stratification and personalized management.展开更多
基金support held by JPA,Collaborative Network Award BRAVEinMS,Grant/Award Number:PA-1604-08492(MG)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.
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD),formerly known as nonalcoholic fatty liver disease,is a chronic liver disease characterized by hepatic lipid deposition and hepatocellular steatosis,resulting from nonalcoholic causes and closely linked to metabolic dysfunction[1].It is strongly associated with metabolic abnormalities,including type 2 diabetes,overweight,and obesity.The global prevalence of MASLD is estimated to be approximately 25%−33%,and its incidence is rising rapidly,particularly among younger populations,due to increasingly prevalent unhealthy lifestyle behaviors such as sleep deprivation,sedentary habits,and diets rich in calories.
基金supported by the Henan Provincial Science and Technology Research and Development Plan Joint Fund(Grant No.242103810035).
文摘Lung cancer remains the leading cause of cancer-related mortality worldwide,primarily driven by metabolic reprogramming and immune evasion mechanisms within tumor cells.To adapt to the nutrient-deprived tumor microenvironment(TME),lung cancer cells undergo profound metabolic reprogramming,characterized by enhanced glycolysis(the Warburg effect),increased glutamine dependency(mediated by GLS1),and accelerated lipid synthesis(involving enzymes such as FASN).These metabolic alterations not only remodel the TME but also dampen antitumor immune responses by promoting immunosuppressive cell populations(e.g.,Tregs and M2 macrophages)and inhibiting effector functions of CD8^(+)T cells and natural killer(NK)cells.Critically,a bidirectional crosstalk operates between tumor cell metabolism and the immunosuppressive TME:metabolic reprogramming drives immune suppression through metabolite accumulation,whereas the immunosuppressive TME,in turn,promotes tumor cell adaptability—thus forming a positive feedback loop that reinforces immune evasion and therapy resistance.This review elucidates key molecular pathways governing metabolic reprogramming in lung cancer—spanning glucose,amino acid,and lipid metabolism—and their dynamic crosstalk with immune regulation,including epigenetic modifications and non-coding RNA-mediated mechanisms.Additionally,it evaluates emerging therapeutic strategies targeting the metabolic-immune axis,such as inhibitors of HK2 or GLS1 combined with anti-PD-1/PD-L1 agents,which aim to reverse immunosuppression and improve clinical outcomes.By synthesizing recent advances,this work provides a theoretical framework for precision oncology interventions,highlighting the potential of metabolic immunotherapies and future directions integrating AI and multi-omics data to overcome resistance in lung cancer.
基金supported by the Project of Sanya Yazhou Bay Science and Technology City (SKJC-JYRC-2024-26)the National Natural Science Foundation of China (32460072)+4 种基金Hainan Provincial Natural Science Foundation of China (323RC421)the Hainan Province Science and Technology Special Fund (ZDYF2022XDNY144)the Hainan Provincial Academician Innovation Platform Project (HDYSZX-202004)the Collaborative Innovation Center of Nanfan and High-Efficiency Tropical Agriculture, Hainan University (XTCX2022NYB06)Hainan Postdoctoral Research Grant Project
文摘In light of the pressing global challenges of climate change,declining crop resilience,and hidden hunger,it is imperative to overcome the limitations of conventional crop breeding to enhance both the nutritional quality and stress tolerance of crops.Synthetic metabolic engineering presents innovative strategies for the precision modification and de novo design of metabolic pathways.This approach generally encompasses three essential steps:identifying key metabolites through metabolomics,integrating multi-omics technologies to investigate the synthesis and regulation of these metabolites,and utilizing gene editing or de novo design to modify crop metabolic pathways associated with desirable agronomic traits.This review underscores the vital role of plant metabolite diversity in enhancing crop nutritional quality and stress resilience.Integrated multi-omics analyses facilitate the metabolic engineering by identifying key genes,transporters,and transcription factors that regulate metabolite biosynthesis.Precision modification strategies employ genome editing tools to reprogram endogenous metabolic networks,while de novo design reconstructs metabolic pathways through the introduction of exogenous biological elements—thereby both approaches enable the targeted enhancement of desired traits.These strategies have been effectively implemented in major food crops.However,simultaneously enhancing nutritional quality and stress resilience remains challenging due to inherent trade-offs and resource competition in distinct metabolic pathways within plants.Future research should integrate AI-driven predictive models with multi-omics datasets to decipher dynamic metabolic homeostasis and engineer climate-smart crops that maximize yield while preserving quality and environmental adaptability.
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funded by National Natural Science Foundation of China(82360801).
文摘Tumor metabolic reprogramming is a core hallmark of cancer,characterized by pathways such as aerobic glycolysis,aberrant lipid metabolism,and glutaminolysis that support rapid proliferation and immunosuppressive microenvironments.Circular RNAs(circRNAs)are highly stable,evolutionarily conserved non-coding RNAs that have emerged as critical modulators of these metabolic shifts.This review aims to systematically elucidate the roles and mechanisms of circRNAs in reprogramming tumor metabolism,and to discuss their clinical potential as biomarkers and therapeutic targets.Through mechanisms including miRNA sponging,protein interactions,regulation of mitochondrial dynamics,and modulation of metabolic enzymes,circRNAs influence key metabolic pathways by targeting glycolytic enzymes,lipid synthesis regulators,and glutaminolysis-related molecules to either facilitate or inhibit their expression.This review systematically summarizes the unique contributions of circRNAs to tumor metabolic reprogramming,highlighting key mechanisms such as regulation of peptide-encoding protein translation,mitochondrial localization function,gene promoter-targeted transcriptional regulation,and cross-pathway metabolic mediation,which underscore their distinct biological advantages and regulatory roles in tumor metabolism.The stability and tissue specificity of circRNAs make them promising diagnostic biomarkers,while their role in drug resistance mediated by metabolic reprogramming highlights their potential as therapeutic targets.Strategies such as circRNA inhibitors,mimics,and nanoparticle-based delivery systems are being explored to modulate tumor metabolism.Despite challenges including complex regulatory networks and limited manipulation tools,advances in high-throughput technologies and clinical trials hold promise for translating circRNA research into novel cancer therapies.
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).
文摘As we welcome the spring of 2026,we extend our sincere greetings and best wishes to colleagues worldwide in the field of crop science,our partners,and all those committed to sustainable agricultural development!The Year of the Horse symbolizes endeavor and far-reaching journeys,reflecting our own spirit of continuous exploration and breakthrough innovation on the path of crop science.Here,I extendmysincere appreciation to all our authors and reviewers for their invaluable time,expertise,and dedication,which are instrumental in the success of The Crop Journal,establishing it as a premier platform for the global crop science research community.The Crop Journal publishes its 2026 first issue as a special issue themed“Synthetic Biology for Crop Improvement”,ably vip-edited by four young scientists.The issue provides a comprehensive overview of major advances in the field.In the past few years,crop science has made long strides in metabolic engineering of important pathways in secondary metabolism.The achievements expedite the emergence of synthetic biology as a potent methodology for crop breeding and represent a fundamental paradigm shift from“deciphering crops”to“designing crops”,which is further empowered by artificial intelligence(AI).At this turning point of the New Year,I would like to take this opportunity to provide a brief retrospective and future perspective.
基金supported by grants from the National Key R&D Program of China(Grant Nos.2021YFA1103000 and 2021YFA1302000)National Natural Science Foundation of China(Grant Nos.82572106,82125017,and 92359302)+7 种基金Guangdong Province Youth Top Talent Special Pillar Program 2024,Natural Science Foundation of Guangdong Province(Grant No.2314050001076)Guangdong Basic and Applied Basic Research Foundation(Grant Nos.2023A1515011033,2024B1515040006,and 2025A1515012431)Guangdong Major Project of Basic Research(Grant No.2023B0303000018)Guangzhou Science and Technology Plan Project(Grant No.2025B03J0063)Noncommunicable Chronic Diseases-National Science and Technology Major Project(Grant No.2025ZD0544000)Guangdong Provincial Clinical Research Center for Breast Diseases(Grant No.2023B110005)the Science and Technology Program of Guangzhou(Grant No.2024A04J6568)New Cornerstone Science Foundation through the New Cornerstone Investigator Program,and XPLORER PRIZE.
文摘Objective:This study was aimed at investigating metabolic dysregulation in tumor-associated macrophages(TAMs)in breast cancer and developing a metabolically enhanced chimeric antigen receptor macrophage(CAR-M)strategy to boost antitumor potency in solid tumors.Methods:Integrated scRNA-seq and metabolomic analyses were performed to characterize metabolic alterations in macrophages within the breast cancer tumor microenvironment(TME).According to the identified metabolic vulnerabilities,SLC38A2-overexpressing anti-HER2 CAR-Ms were engineered.Glutamine uptake and phagocytic activity were assessed to evaluate functional enhancement.Results:TAMs in breast cancer exhibited substantial metabolic dysregulation,particularly impaired glutamine metabolism accompanied by decreased expression of the glutamine transporter SLC38A2.Overexpression of SLC38A2 in anti-HER2 CAR-Ms,compared with conventional anti-HER2 CAR-Ms,enhanced glutamine uptake and markedly augmented phagocytosis of HER2+breast cancer cells.Conclusions:Metabolic engineering via SLC38A2 restored glutamine fitness and enhanced the antitumor activity of HER2-targeted CAR-Ms,thus providing a promising strategy to boost CAR-M–mediated tumor suppression in solid tumors.
基金supported by Top Talent Support Program for young and middle-aged people of Wuxi Health Committee(Grant No.HB2023008)Top Medical Expert Team of Wuxi Taihu Talent Plan(Grant Nos.DJTD202106,GDTD202105 and YXTD202101)+2 种基金Medical Key Discipline Program ofWuxi Health.Commission(Grant Nos.ZDXK2021007 and CXTD2021005)Top Talent Support Program for Young and Middle-Aged People of Wuxi Health Committee(Grant No.BJ2023090)Scientific Research Program of Wuxi Health Commission(Grant Nos.Z20210 and M202208).
文摘Metabolic dysfunction-associated fatty liver disease(MAFLD)and chronic kidney disease(CKD)have shown a marked global increase in prevalence,placing a substantial burden on public health and healthcare systems worldwide.Epidemiological data demonstrate a significant overlap between these two conditions,with further evidence from research identifying common pathophysiological features,such as lipid metabolism dysregulation,disrupted energy balance,and chronic systemic inflammation.Mitochondria are central to the pathophysiology of both diseases.In addition to their role in energy production,mitochondria are involved in numerous critical cellular processes,including biosynthesis,lipid metabolism,oxidative phosphorylation,signal transduction,and apoptosis regulation.Mitochondrial dysfunction,characterized by increased reactive oxygen species,impaired adenosine triphosphate synthesis,disrupted mitophagy,and changes in mitochondrial morphology,is implicated in the progression of both MAFLDandCKD.Given the pivotal role of mitochondria in maintaining cellularmetabolism homeostasis,dysfunction of this organelle is increasingly recognized as a key mechanistic link that connects the pathophysiological processes underlying both MAFLD and CKD.This review underscores mitochondrial dysfunction as a pathogenic nexus between MAFLD and CKD and examines the mechanisms that drive their pathogenesis.
基金supported by the National Key Research and Development Program(2024YFA1307101).
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD)is now considered to be among the most prevalent chronic liver diseases worldwide.Its comprehensive management encompasses multiple stages,including risk assessment,early detection,stratified intervention,and long-term follow-up.Among these,improving diagnostic accuracy and optimizing individualized therapeutic strategies remain key challenges in both research and clinical practice.In recent years,artificial intelligence and smart devices have developed rapidly and have gradually been applied in the medical field,offering novel tools and pathways for MASLD risk stratification,non-invasive diagnosis,therapeutic evaluation,and patient self-management.This review summarizes the current applications of artificial intelligence and smart devices in MASLD care,highlights their benefits and limitations,and discusses future directions to support precision diagnosis and treatment strategies.
文摘1.Introduction The field of exercise science is experiencing a renaissance,with recent research illuminating the molecular,cellular,and systemic effects of physical activity.This is largely due to the now unequivocal evidence that a lack of physical activity,not only has direct effects on the prevalence of non-contagious diseases(NCDs)but has profound additive effects of other risk factors for NCD such as obesity and hypertension.1 The articles in this special topic of Journal of Sport and Health Science(JSHS)are dedicated to research on Exercise biochemistry&metabolism.
基金funded by the“Instituto de Salud Carlos III”(PI 17-000134,PI 20-0155,PI23/00176)the“Diputaciode Lleida”(PP10601-PIRS2021)to MPO+2 种基金Also from the“Diputaciode Lleida”(PP10605-PIRS2021)the“Generalitat de Catalunya”:Agency for Management of University and Research Grants(2021SGR00990)to RPSupport was also received in the form of a FUNDELA Grant,“RedELA-Plataforma Investigacion”and the“Fundacio Miquel Valls”(Jack Van den Hoek donation)(to MPO)。
文摘Neurodegenerative diseases are chronic,age-related disorders characterized by a relentless,irreversible,and selective loss of neurons in motor,sensory,or cognitive systems(Gao et al.,2019).Despite their heterogeneity,a common pathological feature across many of these diseases is the accumulation of aggregate-prone proteins.Particularly,the cytoplasmic aggregation in neurons of the Transactive response DNA-binding protein 43(TDP-43).
基金supported by Government of the Principado de Asturias through the Fundacion para el Fomento en Asturias de la Investigacion Cientifica Aplicada y a la Tecnologia(FICYT)and also co-founded by the European Union,GRUPIN(IDI/2024/000719).
文摘Aerobic glycolysis,also known as the Warburg effect,and the accumulation of lactate that it causes,are increasingly recognized outside the field of oncology as triggers of chronic non-neoplastic disorders.This review integrates preclinical and clinical evidence to evaluate the ability of melatonin to reverseWarburg-effect-like metabolic reprogramming.Literature on neurodegeneration,age-related sarcopenia,type 2 diabetes,chronic kidney disease,heart failure and pulmonary arterial hypertension(PAH)has been reviewed and synthesised.In all of these conditions,hypoxia-inducible factor 1α(HIF-1α)and pyruvate dehydrogenase kinase 4(PDK4)inhibit the pyruvate dehydrogenase complex.This diverts pyruvate away fromthe tricarboxylic acid(TCA)cycle and promotes glycolysis.In cell and animal models,melatonin consistently inhibits PDK4,destabilizes HIF-1αunder normoxic conditions,activates SIRT1/3-dependentmitochondrial biogenesis andmitophagy,and eliminates reactive oxygen and nitrogen species.These actions reduce lactate production,restore oxidative phosphorylation and attenuate tissue damage.This appears to induce cognitive and synaptic improvements in Alzheimer’s and Parkinson’s disease models,increased muscle mass and function in ageing rodents,improved insulin sensitivity alongside suppression of hepatic gluconeogenesis in diabetic models,reduced fibrosis in nephropathy,and normalization of vascular remodeling in hypoxia-induced pulmonary arterial hypertension(PAH).Early-stage clinical trials corroborate a decrease in oxidative and inflammatorymarkers,improved sleep quality and modest cognitive benefits.However,they report conflicting effects on insulin sensitivity,which are largely related to the dose and timing of administration in relation to food intake.Overall,the current data suggest that melatonin is a pleiotropic metabolic modulator capable of counteracting the Warburg phenotype in multiple organs.However,human studies remain scarce,and well-designed randomised trials incorporating chronotherapy are needed before clinical adoption.
文摘Introduction:Advances in HIV management have transformed HIV into a chronic condition,resulting in improved prognosis and increased survival among people living with HIV(PLWH).Traditional risk factors for metabolic dysfunction-associated steatotic liver disease(MASLD)—including dyslipidemia—are prevalent in PLWH.This systematic review and meta-analysis aim to synthesize current evidence on lipid profile disturbances as contributors to MASLD in PLWH.Methods:This systematic review and meta-analysis were conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)guidelines and registered in PROSPERO with registration number CRD420251054477.We searched seven databases to identify studies reporting the prevalence and characteristics of MASLD in PLWH.Meta-analysis was conducted using Review Manager 5.4.1.Mean differences(MDs)were calculated using a random-effects model.Risk of bias was assessed using the ROBINS-E tool.Results:A total of 17 studies comprising 3933 HIV-positive participants were included,among whom 1226(37%)had MASLD.Male sex was significantly associated with MASLD(OR=1.57;95%CI:1.13-2.17;p=0.007).MASLD was significantly associated with higher body mass index(BMI)(MD=3.23 kg/m^(2);p<0.00001).Lipid profile analysis revealed that MASLD patients had higher total cholesterol(MD=6.62 mg/dL;p=0.01),low density lipoprotein(LDL)(MD=3.83 mg/dL;p=0.01),triglycerides(MD=63.02 mg/dL;p<0.00001),and lower high density lipoprotein(HDL)(MD=-3.73 mg/dL;p<0.0001).Conclusion:This study demonstrates a significant difference in lipid profiles(higher total cholesterol,LDL,triglycerides,and lower HDL)among PLWH who develop MASLD,suggesting a potential metabolic signature associated with this comorbidity.
基金supported by National Institute on Aging(NIH-NIA)R01AG054459(to ALL).
文摘Alzheimer’s disease(AD)is the most common form of dementia,affecting over 50 million people worldwide.This figure is projected to nearly double every 20 years,reaching 82 million by 2030 and 152 million by 2050(Alzheimer’s Disease International).The apolipoproteinε4(APOE4)allele is the strongest genetic risk factor for late-onset AD(after age 65 years).Apolipoprotein E,a lipid transporter,exists in three variants:ε2,ε3,andε4.APOEε2(APOE2)is protective against AD,APOEε3(APOE3)is neutral,while APOE4 significantly increases the risk.Individuals with one copy of APOE4 have a 4-fold greater risk of developing AD,and those with two copies face an 8-fold risk compared to non-carriers.Even in cognitively normal individuals,APOE4 carriers exhibit brain metabolic and vascular deficits decades before amyloid-beta(Aβ)plaques and neurofibrillary tau tangles emerge-the hallmark pathologies of AD(Reiman et al.,2001,2005;Thambisetty et al.,2010).Notably,studies have demonstrated reduced glucose uptake,or hypometabolism,in brain regions vulnerable to AD in asymptomatic middle-aged APOE4 carriers,long before clinical symptoms arise(Reiman et al.,2001,2005).
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.
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD)is an increasingly prevalent condition associated with hepatic complications and cardiovascular and renal events.Given its significant clinical impact,the development of new strategies for early diagnosis and treatment is essential to improve patient outcomes.Over the past decade,the integration of artificial intelligence(AI)into gastroenterology has led to transformative advancements in medical practice.AI represents a major step towards personalized medicine,offering the potential to enhance diagnostic accuracy,refine prognostic assessments,and optimize treatment strategies.Its applications are rapidly expanding.This article explores the emerging role of AI in the management of MASLD,emphasizing its ability to improve clinical prediction,enhance the diagnostic performance of imaging modalities,and support histopathological confirmation.Additionally,it examines the development of AI-guided personalized treatments,where lifestyle modifications and close monitoring play a pivotal role in achieving therapeutic success.
基金National Key Research and Development Program of China,Grant/Award Number:2021YFF0702200Science and Technology Projects in Guangzhou,Grant/Award Number:202206010084,202206010197 and 202206060002+1 种基金Guangdong S&T programme,Grant/Award Number:2009A081000002 and 2023B0303040004Technology Planning Project of Linzhi,Grant/Award Number:2023-YZ-01。
文摘Background:The aim of the study was to develop a non-human primate model of metabolic dysfunction in Macaca fascicularis using chronic high-fat diet(HFD)to mimic clinical disease progression.Methods:Thirty-five male macaques aged 10-15 years underwent an 18-month HFD intervention.Physiological parameters(BMI,BP,hematology),liver fat fraction(evaluated by ultrasound/MRI),cardiac function(assessed by echocardiography),and histopathology(using liver biopsy)were measured before and after the intervention.Serum proteomics with KEGG/STRING analyses identified molecular mechanisms.Results:Within 6 months,HFD induced dyslipidemia(elevated TG,TCHO,HDL-C,LDL-C).After 18 months,metabolic dysfunction-associated steatohepatitis(MASH)was confirmed by histopathology in 57.14%(16/28)of macaques,diabetes(elevated FPG/HbA1c)in 17.86%(5/28),and myocardial hypertrophy(elevated LVMass/LAD)in 46.43%(13/28).Proteomics identified Bile acid-CoA:amino acid N-acyltransferase(BAAT)as a MASH hallmark protein,the level of which was inversely correlated with the degree of fibrosis.For diabetes,citrate synthase(CS)and malate dehydrogenase 1(MDH1)impaired glucose oxidation via the TCA cycle,while hexose-6-phosphate de-hydrogenase(H6PD)disrupted gluconeogenesis.Myocardial hypertrophy was associ-ated with the downregulation of SRC proto-oncogene,non-receptor tyrosine kinase(SRC),mitogen-activated protein kinase 14(MAPK14),emerin(EMD),and integrin subunit beta 1(ITGB1).Conclusions:An 18-month HFD successfully established a translational M.fascicula-ris model replicating key metabolic disorders(MASH,diabetes,cardiac hypertrophy).BAAT,CS/MDH1/H6PD,and SRC/MAPK14/EMD/ITGB1 were identified as mecha-nistic biomarkers for these conditions.
基金funded by grants from the National Natural Science Foundation of China(82070588)High-Level Creative Talents from the Department of Public Health in Zhejiang Province(S2032102600032)+2 种基金the Project of New Century 551 Talent Nurturing in WenzhouGT is supported in part by grants from the School of Medicine,University of Verona,Verona,Italy.CDB is supported in part by the Southampton NIHR Biomedical Research Centre(NIHR203319),UKCDB has received research grant support from Echosens,the manufacturer of the Fibroscan device used to assess liver fat and fibrosis in chronic liver diseases.
文摘Background and AimsHepatic iron deposition(HID)in the reticuloendothelial system(RES)is associated with histological severity in metabolic dysfunction-associated steatotic liver disease(MASLD).This study aimed to assess the interaction between the transferrin(TF)-rs1049296 C>T variant and HID patterns on the risk of significant liver fibrosis in MASLD.MethodsWe analyzed 406 adults with liver biopsy-confirmed MASLD.HID was categorized as hepatocellular,RES,or mixed,based on Perl's iron staining.The association between iron-related genetic variants and significant liver fibrosis(fibrosis stage≥F2)was analyzed,focusing on the interactions between single-nucleotide polymorphism genotypes and iron deposition patterns.Multivariable logistic regression analysis was used to adjust for potential confounders.ResultsHID was detected in 271(66.7%)patients,with hepatocellular,RES,and mixed patterns accounting for 11.1%,18.0%,and 37.7%,respectively.A significant interaction was observed between HID and the TF-rs1049296 genotype(P=0.035 for interaction).In multivariable analysis,male sex,hypertension,severe lobular inflammation,and mixed hepatocellular/RES iron deposition were independent predictors of significant liver fibrosis.RES deposition markedly increased the risk of significant liver fibrosis(adjusted odds ratio:6.65;95%confidence interval:1.84-23.97,p<0.05),particularly in men with isolated RES iron deposition(adjusted odds ratio:5.26;95%confidence interval:1.21-22.81,p<0.05).ConclusionsThe TF-rs1049296 T allele interacts with RES iron deposition to identify a MASLD subpopulation at elevated risk of progressive liver disease,providing opportunities for refined risk stratification and personalized management.
