Over 300 billion of cells die every day in the human body,producing a large number of endogenous apoptotic extracellular vesicles(apoEVs).Also,allogenic stem cell transplantation,a commonly used therapeutic approach i...Over 300 billion of cells die every day in the human body,producing a large number of endogenous apoptotic extracellular vesicles(apoEVs).Also,allogenic stem cell transplantation,a commonly used therapeutic approach in current clinical practice,generates exogenous apoEVs.It is well known that phagocytic cells engulf and digest apoEVs to maintain the body’s homeostasis.In this study,we show that a fraction of exogenous apoEVs is metabolized in the integumentary skin and hair follicles.Mechanistically,apoEVs activate the Wnt/β-catenin pathway to facilitate their metabolism in a wave-like pattern.The migration of apoEVs is enhanced by treadmill exercise and inhibited by tail suspension,which is associated with the mechanical force-regulated expression of DKK1 in circulation.Furthermore,we show that exogenous apoEVs promote wound healing and hair growth via activation of Wnt/β-catenin pathway in skin and hair follicle mesenchymal stem cells.This study reveals a previously unrecognized metabolic pathway of apoEVs and opens a new avenue for exploring apoEV-based therapy for skin and hair disorders.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
A growing global population and the increasing prevalence of diet-related health issues such as“hidden hunger”,obesity,hypertension,and diabetes necessitate a fundamental rethinking of crop design and breeding.Synth...A growing global population and the increasing prevalence of diet-related health issues such as“hidden hunger”,obesity,hypertension,and diabetes necessitate a fundamental rethinking of crop design and breeding.Synthetic metabolic engineering offers a method to modify and redesign metabolic pathways to increase the nutritional value of crops.We summarize recent advances in the biofortification of key nutrients including provitamin A,vitamin C,vitamin B9,iron,zinc,anthocyanins,flavonoids,and unsaturated fatty acids.We discuss the potential of multi-gene stacking,gene editing,enzyme engineering,and artificial intelligence in synthetic metabolic engineering.We propose future research directions and potential solutions centered on leveraging AI-driven systems biology,precision gene editing,enzyme engineering,agrobacterium-mediated genotype-independent transformation,and modular metabolic engineering strategies to develop next-generation nutritionally enhanced super crops and transform global food systems.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
Metabolic dysfunction-associated steatotic liver disease(MASLD)has become the most prevalent chronic liver disease worldwide,affecting approximately 32%-38%of the adult population and posing a growing public health bu...Metabolic dysfunction-associated steatotic liver disease(MASLD)has become the most prevalent chronic liver disease worldwide,affecting approximately 32%-38%of the adult population and posing a growing public health burden.MASLD represents a continuous disease spectrum ranging from simple steatosis to metabolic dysfunction-associated steatohepatitis(MASH),progressive hepatic fibrosis,cirrhosis,and ultimately hepatocellular carcinoma(HCC).The pathological core of MASLD lies in disruption of hepatic lipid metabolic homeostasis,characterized by an imbalance among de novo lipogenesis,fatty acidβ-oxidation,and very-low-density lipoprotein(VLDL)-mediated lipid export.This metabolic disequilibrium subsequently drives inflammatory injury and fibrotic progression.Among the multiple regulatory pathways involved,thyroid hormone(TH)signaling has emerged as a central regulator of hepatic metabolic homeostasis.The liver is a major peripheral target organ of TH action,where TH predominantly exerts its metabolic effects through thyroid hormone receptorβ(TRβ).Large-scale epidemiological studies and metaanalyses have demonstrated that hypothyroidism is significantly associated with increased MASLD prevalence,more severe histological injury,and advanced hepatic fibrosis,suggesting that dysregulation of TH signaling may participate throughout the entire MASLD disease spectrum.At the molecular level,TH regulates hepatic lipid metabolism by coordinating suppression of lipogenesis,enhancement of mitochondrial fatty acid oxidation,and promotion of VLDL assembly and secretion through integrated genomic actions of the T3-TRβaxis and non-genomic signaling pathways.Across different stages of MASLD,TH signaling exerts stagedependent protective effects.In the steatosis stage,TH improves metabolic flexibility by modulating insulin sensitivity,glucose metabolism,and lipid droplet clearance,thereby alleviating early lipotoxic stress.During progression to MASH,TH attenuates inflammatory amplification by improving mitochondrial homeostasis,suppressing activation of the NOD-like receptor family pyrin domain containing 3(NLRP3)inflammasome,and modulating the gut-liver axis microenvironment.In advanced stages,TH signaling influences hepatic stellate cell activation and extracellular matrix deposition,partly through interaction with the transforming growth factor-β(TGF-β)/SMAD pathway,while alterations in intrahepatic TH availability,mediated by dynamic changes in iodothyronine deiodinase 1(DIO1),contribute to fibrosis progression and hepatocellular dedifferentiation.In hepatocellular carcinoma,coordinated downregulation of TRβand DIO1 establishes a tumor-associated hypothyroid state that promotes metabolic reprogramming and tumor progression.The clinical relevance of TH signaling in MASLD has been underscored by the recent approval of Resmetirom,a liver-targeted TRβ-selective agonist,for the treatment of non-cirrhotic MASH with moderate-to-severe fibrosis(F2-F3).This approval represents a landmark transition from mechanistic understanding to metabolismcentered precision therapy in MASLD.Clinical trials have demonstrated that Resmetirom not only improves key histological endpoints,including MASH resolution and fibrosis regression,but also favorably modulates atherogenic lipid profiles,highlighting the therapeutic potential of selectively targeting hepatic TH pathways.This review systematically summarizes the multidimensional regulatory roles of TH across the MASLD disease spectrum and discusses emerging diagnostic and therapeutic implications of THbased interventions,aiming to inform future mechanistic research and optimize clinical management strategies.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
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
Inborn errors of metabolism(IEMs)are a large group of disorders resulting from deficient activities in several metabolic pathways due to the dysfunction of a distinct enzyme associated with a biochemical pathway[1,2]....Inborn errors of metabolism(IEMs)are a large group of disorders resulting from deficient activities in several metabolic pathways due to the dysfunction of a distinct enzyme associated with a biochemical pathway[1,2].Toxic intermediates will be produced due to the dysfunction of biochemical pathways.The liver is responsible for many essential metabolic processes,therefore it becomes one of the most severely affected organ by metabolic diseases[3].Early onset of liver disorders in IEMs includes jaundice,hepatomegaly,splenomegaly,ascites,hepatic encephalopathy,and liver failure[4].In infants and young children under 3 years old with acute liver failure(ALF),IEMs account for 18.9%-43%[5].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
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
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
Curcuma is a traditional Chinese medicine that has been utilized for centuries in the treatment of various diseases. Terpenoids, particularly monoterpenes and sesquiterpenes, constitute the primary bioactive component...Curcuma is a traditional Chinese medicine that has been utilized for centuries in the treatment of various diseases. Terpenoids, particularly monoterpenes and sesquiterpenes, constitute the primary bioactive components of the essential oil derived from Curcuma species.Among these, curdione—one of the key active constituents—has been identified in 25 Curcuma species, with the highest concentration reported in the rhizome essential oil of Curcuma trichosantha Gagnep. Curdione can also be synthesized through chemical methods,and its regio-and stereo-selectivity can be further optimized via chemo-bio transformations.This compound demonstrates significant therapeutic potential, including anticancer, antithrombotic, anti-inflammatory, anti-viral, anti-fungal, anti-diabetic, and multi-organ protective properties. Despite these promising biological activities, its clinical application is hindered by poor water solubility and potential toxicity. This review summarizes current knowledge on the natural sources, chemical synthesis, chemo-bio transformations, metabolism, pharmacokinetics, pharmacological effects, potential toxicities, and molecular mechanisms of curdione. Furthermore, perspectives on future drug development are discussed with the aim of promoting the clinical translation of this promising natural compound.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
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
Background: We monitored changes in salivary creatine pre-and post-high-intensity exercise in young adults while also investigating the potential correlation between salivary and serum creatine levels.Method: Saliva a...Background: We monitored changes in salivary creatine pre-and post-high-intensity exercise in young adults while also investigating the potential correlation between salivary and serum creatine levels.Method: Saliva and serum samples were collected before and immediately after an incremental running-toexhaustion treadmill test in fifteen young adults(mean age [23.9 ± 2.9] years, eight females), with samples analyzed for guanidinoacetic acid, creatine, and creatinine using a liquid chromatography–tandem mass spectrometry method.Results: Following exercise, there was a substantial elevation in salivary creatine levels from(17.5 ± 14.2)μmol·L^(-1) to(43.6 ± 30.4) μmol·L^(-1)(p < 0.001), coupled with a significant increase in salivary creatinine from(11.3 ± 5.8) μmol·L^(-1) to(17.0 ± 9.3) μmol·L^(-1)(p = 0.04). In contrast, serum creatine levels were unaffected by exercise(p = 0.80), while creatinine levels exhibited a strong tendency to decrease post-exercise(from [81.8 ±17.5] μmol·L^(-1) to [73.1 ± 11.6] μmol·L^(-1);p = 0.06). A comparison of the slopes of the two regression lines(saliva vs. serum) revealed significant differences for both creatine(p = 0.01) and creatinine(p = 0.03).Conclusions: The above findings suggest a potential difference in the dynamics of creatine metabolites in these two bodily fluids, both pre and post-exercise.展开更多
Breast cancer is one of the most prevalent malignancies among women and comprises a heterogeneous spectrum of molecular subtypes with distinct biological behaviors.Among various regulatory molecules,sphingolipids play...Breast cancer is one of the most prevalent malignancies among women and comprises a heterogeneous spectrum of molecular subtypes with distinct biological behaviors.Among various regulatory molecules,sphingolipids play pivotal roles in dynamically modulating fundamental cellular processes such as proliferation,apoptosis,and metastasis through metabolic interconversions,including phosphorylation,glycosylation,and the generation of sphingosine-1-phosphate.This review aims to elucidate the mechanisms through which sphingolipid metabolism orchestrates cancer cell fate and drives breast cancer progression.Particular emphasis is placed on the balance between proapoptotic ceramides and pro-survival metabolites,such as sphingosine-1-phosphate,which collectively influence tumor growth and the therapeutic response.Additional sphingolipid species,including glucosylceramide and gangliosides(GD2,GD3,GM1,and GM3),have also been implicated in promoting breast cancer development.Furthermore,sphingolipid-based therapeutic strategies,including immunotherapy and antibody therapy,are discussed.By providing a comprehensive overview of sphingolipid metabolism,this review aims to identify novel therapeutic targets that may help overcome treatment resistance and improve clinical outcomes in breast cancer.展开更多
Ascorbate(Asc),commonly known as vitamin C,is a vital molecule for plant growth,development,and stress resilience.It is also known to play a crucial role in various physiological processes,including photosynthesis,cel...Ascorbate(Asc),commonly known as vitamin C,is a vital molecule for plant growth,development,and stress resilience.It is also known to play a crucial role in various physiological processes,including photosynthesis,cell division,and differentiation.This article thoroughly explores the processes governing the metabolism of Asc in plants and its roles in physiological functions.It lays down a robust theoretical groundwork for delving into Asc production,transportation,functions,and its potential applications in stress alleviation and horticulture.Furthermore,recent studies indicate that Asc plays a role in regulating fruit development and affecting postharvest storage characteristics,thereby influencing fruit ripening and resilience to stress.Hence,there is a growing importance in studying the synthesis and utilization of Asc in plants.Although the critical role of Asc in controlling plant redox signals has been extensively studied,the precise mechanisms by which it manages cellular redox homeostasis to maintain the equilibrium between reactive oxygen scavenging and cell redox signaling remain elusive.This gap in knowledge presents fresh opportunities to explore how the production of Asc in plants is regulated and how plants react to environmental stressors.Furthermore,this article delves into the potential for a comprehensive investigation into the essential function of Asc in fruits,the development of Asc-rich fruits,and the enhancement of postharvest storage properties.展开更多
Copper ions are essential for cellular function but can induce cytotoxic effects when dysregulated.This review explores the multifaceted role of copper in cancer metabolism with a focus on the novel concept of cupropt...Copper ions are essential for cellular function but can induce cytotoxic effects when dysregulated.This review explores the multifaceted role of copper in cancer metabolism with a focus on the novel concept of cuproptosis,a regulated form of cell death triggered by copper accumulation.The mechanisms underlying copper homeostasis are detailed,including dietary absorption,systemic distribution,and intracellular utilization.Key transporters,such as copper transporter 1(CTR1)and ATPase copper transporting alpha/b(ATP7A/B),are highlighted.Cancer cells often exhibit elevated copper levels,supporting proliferation and metastasis through pro-tumorigenic pathways.Recent studies have shown that disrupting copper homeostasis can induce cuproptosis,which is characterized by the aggregation of lipoylated mitochondrial proteins and disruption of iron-sulfur cluster biogenesis.Advances in copper-based nanotechnology have enabled targeted delivery of copper to tumors,enhancing therapeutic efficacy through synergistic effects with reactive oxygen species(ROS)generation and immunomodulation.However,the hypoxic tumor microenvironment poses significant challenges by upregulating copper-sequestering proteins and downregulating key cuproptosis mediators.Future directions include integrating multi-omics approaches to identify novel therapeutic targets and developing combination therapies to overcome hypoxia-induced resistance.This review provides a comprehensive overview of copper metabolism in cancer,emphasizing the potential of cuproptosis induction as a powerful strategy for oncologic intervention.展开更多
基金supported by grants from the National Key R&D Program of China(2021YFA1100600 to S.S.)the Guangdong Financial Fund for High-Caliber Hospital Construction(174-2018-XMZC-0001-03-0125,D-07 to S.S.,D-11 to X.K.)+5 种基金the Pearl River Talent Recruitment Program(2019ZT08Y485)the National Science and Technology Major Project of the Ministry of Science and Technology of China(2018ZX10302207-001-002)the Sun Yat-sen University Young Teacher Key Cultivation Project(18ykzd05 to X.K.)the Natural Science Foundation of Guangdong(2016A030313262 to X.M.)the National Natural Science Foundation of China(82170924 to X.K.,81700928 to L.M.)the Youth Teacher Training Project of Sun Yat-sen University(17ykpy71 to L.M.).
文摘Over 300 billion of cells die every day in the human body,producing a large number of endogenous apoptotic extracellular vesicles(apoEVs).Also,allogenic stem cell transplantation,a commonly used therapeutic approach in current clinical practice,generates exogenous apoEVs.It is well known that phagocytic cells engulf and digest apoEVs to maintain the body’s homeostasis.In this study,we show that a fraction of exogenous apoEVs is metabolized in the integumentary skin and hair follicles.Mechanistically,apoEVs activate the Wnt/β-catenin pathway to facilitate their metabolism in a wave-like pattern.The migration of apoEVs is enhanced by treadmill exercise and inhibited by tail suspension,which is associated with the mechanical force-regulated expression of DKK1 in circulation.Furthermore,we show that exogenous apoEVs promote wound healing and hair growth via activation of Wnt/β-catenin pathway in skin and hair follicle mesenchymal stem cells.This study reveals a previously unrecognized metabolic pathway of apoEVs and opens a new avenue for exploring apoEV-based therapy for skin and hair disorders.
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 grants from the Guangxi Science and Technology Major Project(GKAA24206023)the Biological Breeding-National Science and Technology Major Project(2024ZD04077)+2 种基金the National Natural Science Foundation of China(32272120)the National Key Research and Development Program of China(2024YFF1000800)the Guangdong Basic Research Center of Excellence for Precise Breeding of Future Crops Major Project(FCBRCE-202502,FCBRCE-202504).
文摘A growing global population and the increasing prevalence of diet-related health issues such as“hidden hunger”,obesity,hypertension,and diabetes necessitate a fundamental rethinking of crop design and breeding.Synthetic metabolic engineering offers a method to modify and redesign metabolic pathways to increase the nutritional value of crops.We summarize recent advances in the biofortification of key nutrients including provitamin A,vitamin C,vitamin B9,iron,zinc,anthocyanins,flavonoids,and unsaturated fatty acids.We discuss the potential of multi-gene stacking,gene editing,enzyme engineering,and artificial intelligence in synthetic metabolic engineering.We propose future research directions and potential solutions centered on leveraging AI-driven systems biology,precision gene editing,enzyme engineering,agrobacterium-mediated genotype-independent transformation,and modular metabolic engineering strategies to develop next-generation nutritionally enhanced super crops and transform global food systems.
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.
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD)has become the most prevalent chronic liver disease worldwide,affecting approximately 32%-38%of the adult population and posing a growing public health burden.MASLD represents a continuous disease spectrum ranging from simple steatosis to metabolic dysfunction-associated steatohepatitis(MASH),progressive hepatic fibrosis,cirrhosis,and ultimately hepatocellular carcinoma(HCC).The pathological core of MASLD lies in disruption of hepatic lipid metabolic homeostasis,characterized by an imbalance among de novo lipogenesis,fatty acidβ-oxidation,and very-low-density lipoprotein(VLDL)-mediated lipid export.This metabolic disequilibrium subsequently drives inflammatory injury and fibrotic progression.Among the multiple regulatory pathways involved,thyroid hormone(TH)signaling has emerged as a central regulator of hepatic metabolic homeostasis.The liver is a major peripheral target organ of TH action,where TH predominantly exerts its metabolic effects through thyroid hormone receptorβ(TRβ).Large-scale epidemiological studies and metaanalyses have demonstrated that hypothyroidism is significantly associated with increased MASLD prevalence,more severe histological injury,and advanced hepatic fibrosis,suggesting that dysregulation of TH signaling may participate throughout the entire MASLD disease spectrum.At the molecular level,TH regulates hepatic lipid metabolism by coordinating suppression of lipogenesis,enhancement of mitochondrial fatty acid oxidation,and promotion of VLDL assembly and secretion through integrated genomic actions of the T3-TRβaxis and non-genomic signaling pathways.Across different stages of MASLD,TH signaling exerts stagedependent protective effects.In the steatosis stage,TH improves metabolic flexibility by modulating insulin sensitivity,glucose metabolism,and lipid droplet clearance,thereby alleviating early lipotoxic stress.During progression to MASH,TH attenuates inflammatory amplification by improving mitochondrial homeostasis,suppressing activation of the NOD-like receptor family pyrin domain containing 3(NLRP3)inflammasome,and modulating the gut-liver axis microenvironment.In advanced stages,TH signaling influences hepatic stellate cell activation and extracellular matrix deposition,partly through interaction with the transforming growth factor-β(TGF-β)/SMAD pathway,while alterations in intrahepatic TH availability,mediated by dynamic changes in iodothyronine deiodinase 1(DIO1),contribute to fibrosis progression and hepatocellular dedifferentiation.In hepatocellular carcinoma,coordinated downregulation of TRβand DIO1 establishes a tumor-associated hypothyroid state that promotes metabolic reprogramming and tumor progression.The clinical relevance of TH signaling in MASLD has been underscored by the recent approval of Resmetirom,a liver-targeted TRβ-selective agonist,for the treatment of non-cirrhotic MASH with moderate-to-severe fibrosis(F2-F3).This approval represents a landmark transition from mechanistic understanding to metabolismcentered precision therapy in MASLD.Clinical trials have demonstrated that Resmetirom not only improves key histological endpoints,including MASH resolution and fibrosis regression,but also favorably modulates atherogenic lipid profiles,highlighting the therapeutic potential of selectively targeting hepatic TH pathways.This review systematically summarizes the multidimensional regulatory roles of TH across the MASLD disease spectrum and discusses emerging diagnostic and therapeutic implications of THbased interventions,aiming to inform future mechanistic research and optimize clinical management strategies.
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”.
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Inborn errors of metabolism(IEMs)are a large group of disorders resulting from deficient activities in several metabolic pathways due to the dysfunction of a distinct enzyme associated with a biochemical pathway[1,2].Toxic intermediates will be produced due to the dysfunction of biochemical pathways.The liver is responsible for many essential metabolic processes,therefore it becomes one of the most severely affected organ by metabolic diseases[3].Early onset of liver disorders in IEMs includes jaundice,hepatomegaly,splenomegaly,ascites,hepatic encephalopathy,and liver failure[4].In infants and young children under 3 years old with acute liver failure(ALF),IEMs account for 18.9%-43%[5].
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)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.
基金supported by the National Natural Science Foundation of China (Nos. 82192913 and 82304851)the Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences (Nos. CI2023E002, CI2021B016, and CI2021A04801)the Fundamental Research Funds for the Central Public Welfare Research Institutes (Nos. ZZ13-YQ-055 and ZXKT22044)。
文摘Curcuma is a traditional Chinese medicine that has been utilized for centuries in the treatment of various diseases. Terpenoids, particularly monoterpenes and sesquiterpenes, constitute the primary bioactive components of the essential oil derived from Curcuma species.Among these, curdione—one of the key active constituents—has been identified in 25 Curcuma species, with the highest concentration reported in the rhizome essential oil of Curcuma trichosantha Gagnep. Curdione can also be synthesized through chemical methods,and its regio-and stereo-selectivity can be further optimized via chemo-bio transformations.This compound demonstrates significant therapeutic potential, including anticancer, antithrombotic, anti-inflammatory, anti-viral, anti-fungal, anti-diabetic, and multi-organ protective properties. Despite these promising biological activities, its clinical application is hindered by poor water solubility and potential toxicity. This review summarizes current knowledge on the natural sources, chemical synthesis, chemo-bio transformations, metabolism, pharmacokinetics, pharmacological effects, potential toxicities, and molecular mechanisms of curdione. Furthermore, perspectives on future drug development are discussed with the aim of promoting the clinical translation of this promising natural compound.
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.
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.
文摘Background: We monitored changes in salivary creatine pre-and post-high-intensity exercise in young adults while also investigating the potential correlation between salivary and serum creatine levels.Method: Saliva and serum samples were collected before and immediately after an incremental running-toexhaustion treadmill test in fifteen young adults(mean age [23.9 ± 2.9] years, eight females), with samples analyzed for guanidinoacetic acid, creatine, and creatinine using a liquid chromatography–tandem mass spectrometry method.Results: Following exercise, there was a substantial elevation in salivary creatine levels from(17.5 ± 14.2)μmol·L^(-1) to(43.6 ± 30.4) μmol·L^(-1)(p < 0.001), coupled with a significant increase in salivary creatinine from(11.3 ± 5.8) μmol·L^(-1) to(17.0 ± 9.3) μmol·L^(-1)(p = 0.04). In contrast, serum creatine levels were unaffected by exercise(p = 0.80), while creatinine levels exhibited a strong tendency to decrease post-exercise(from [81.8 ±17.5] μmol·L^(-1) to [73.1 ± 11.6] μmol·L^(-1);p = 0.06). A comparison of the slopes of the two regression lines(saliva vs. serum) revealed significant differences for both creatine(p = 0.01) and creatinine(p = 0.03).Conclusions: The above findings suggest a potential difference in the dynamics of creatine metabolites in these two bodily fluids, both pre and post-exercise.
基金supported by National Research Foundation(NRF)of Korea grants funded by the Korean government,the Ministry of Science and ICT[NRF-2022R1A2C1006737 to Joo-Won Park,NRF-2022R1I1A1A0106408112 to Min Hee Kim].
文摘Breast cancer is one of the most prevalent malignancies among women and comprises a heterogeneous spectrum of molecular subtypes with distinct biological behaviors.Among various regulatory molecules,sphingolipids play pivotal roles in dynamically modulating fundamental cellular processes such as proliferation,apoptosis,and metastasis through metabolic interconversions,including phosphorylation,glycosylation,and the generation of sphingosine-1-phosphate.This review aims to elucidate the mechanisms through which sphingolipid metabolism orchestrates cancer cell fate and drives breast cancer progression.Particular emphasis is placed on the balance between proapoptotic ceramides and pro-survival metabolites,such as sphingosine-1-phosphate,which collectively influence tumor growth and the therapeutic response.Additional sphingolipid species,including glucosylceramide and gangliosides(GD2,GD3,GM1,and GM3),have also been implicated in promoting breast cancer development.Furthermore,sphingolipid-based therapeutic strategies,including immunotherapy and antibody therapy,are discussed.By providing a comprehensive overview of sphingolipid metabolism,this review aims to identify novel therapeutic targets that may help overcome treatment resistance and improve clinical outcomes in breast cancer.
基金supported by the Lendület/Momentum Programme of the Hungarian Academy of Sciencesthe National Research, Development, and Innovation Office, Hungary (Grant Nos. LP2024/21 and K146791)+2 种基金Bayers fellowship program MEDHA and Department of Botany, University of Calicutthe financial assistance provided in the form of Junior Research Fellowship from the University Grants Commission (UGC), Indiathe financial assistance provided by the Council for Scientific and Industrial Research(CSIR), India
文摘Ascorbate(Asc),commonly known as vitamin C,is a vital molecule for plant growth,development,and stress resilience.It is also known to play a crucial role in various physiological processes,including photosynthesis,cell division,and differentiation.This article thoroughly explores the processes governing the metabolism of Asc in plants and its roles in physiological functions.It lays down a robust theoretical groundwork for delving into Asc production,transportation,functions,and its potential applications in stress alleviation and horticulture.Furthermore,recent studies indicate that Asc plays a role in regulating fruit development and affecting postharvest storage characteristics,thereby influencing fruit ripening and resilience to stress.Hence,there is a growing importance in studying the synthesis and utilization of Asc in plants.Although the critical role of Asc in controlling plant redox signals has been extensively studied,the precise mechanisms by which it manages cellular redox homeostasis to maintain the equilibrium between reactive oxygen scavenging and cell redox signaling remain elusive.This gap in knowledge presents fresh opportunities to explore how the production of Asc in plants is regulated and how plants react to environmental stressors.Furthermore,this article delves into the potential for a comprehensive investigation into the essential function of Asc in fruits,the development of Asc-rich fruits,and the enhancement of postharvest storage properties.
基金supported by the National Natural Science Foundation of China(Grant Nos.82303206,82372749,and 82072951)Science and Technology Commission of Shanghai Municipality(Grant Nos.20Y11914300 and 22Y21900100)+2 种基金Shanghai Anticancer Association(Grant No.SACAAX202213)Major Research Projects of Taizhou Clinical Medical College(Grant No.TZKY20230308)Natural Science Foundation in University of Jiangsu Province(Grant No.BK20231261).
文摘Copper ions are essential for cellular function but can induce cytotoxic effects when dysregulated.This review explores the multifaceted role of copper in cancer metabolism with a focus on the novel concept of cuproptosis,a regulated form of cell death triggered by copper accumulation.The mechanisms underlying copper homeostasis are detailed,including dietary absorption,systemic distribution,and intracellular utilization.Key transporters,such as copper transporter 1(CTR1)and ATPase copper transporting alpha/b(ATP7A/B),are highlighted.Cancer cells often exhibit elevated copper levels,supporting proliferation and metastasis through pro-tumorigenic pathways.Recent studies have shown that disrupting copper homeostasis can induce cuproptosis,which is characterized by the aggregation of lipoylated mitochondrial proteins and disruption of iron-sulfur cluster biogenesis.Advances in copper-based nanotechnology have enabled targeted delivery of copper to tumors,enhancing therapeutic efficacy through synergistic effects with reactive oxygen species(ROS)generation and immunomodulation.However,the hypoxic tumor microenvironment poses significant challenges by upregulating copper-sequestering proteins and downregulating key cuproptosis mediators.Future directions include integrating multi-omics approaches to identify novel therapeutic targets and developing combination therapies to overcome hypoxia-induced resistance.This review provides a comprehensive overview of copper metabolism in cancer,emphasizing the potential of cuproptosis induction as a powerful strategy for oncologic intervention.
