Pyrroloquinoline quinone is a quinone described as a cofactor for many bacterial dehydrogenases and is reported to exert an effect on metabolism in mammalian cells/tissues.Pyrroloquinoline quinone is present in the di...Pyrroloquinoline quinone is a quinone described as a cofactor for many bacterial dehydrogenases and is reported to exert an effect on metabolism in mammalian cells/tissues.Pyrroloquinoline quinone is present in the diet being available in foodstuffs,conferring the potential of this compound to be supplemented by dietary administration.Pyrroloquinoline quinone’s nutritional role in mammalian health is supported by the extensive deficits in reproduction,growth,and immunity resulting from the dietary absence of pyrroloquinoline quinone,and as such,pyrroloquinoline quinone has been considered as a“new vitamin.”Although the classification of pyrroloquinoline quinone as a vitamin needs to be properly established,the wide range of benefits for health provided has been reported in many studies.In this respect,pyrroloquinoline quinone seems to be particularly involved in regulating cell signaling pathways that promote metabolic and mitochondrial processes in many experimental contexts,thus dictating the rationale to consider pyrroloquinoline quinone as a vital compound for mammalian life.Through the regulation of different metabolic mechanisms,pyrroloquinoline quinone may improve clinical deficits where dysfunctional metabolism and mitochondrial activity contribute to induce cell damage and death.Pyrroloquinoline quinone has been demonstrated to have neuroprotective properties in different experimental models of neurodegeneration,although the link between pyrroloquinoline quinone-promoted metabolism and improved neuronal viability in some of such contexts is still to be fully elucidated.Here,we review the general properties of pyrroloquinoline quinone and its capacity to modulate metabolic and mitochondrial mechanisms in physiological contexts.In addition,we analyze the neuroprotective properties of pyrroloquinoline quinone in different neurodegenerative conditions and consider future perspectives for pyrroloquinoline quinone’s potential in health and disease.展开更多
Cholesterol is an important component of plasma membranes and participates in many basic life functions,such as the maintenance of cell membrane stability,the synthesis of steroid hormones,and myelination.Cholesterol ...Cholesterol is an important component of plasma membranes and participates in many basic life functions,such as the maintenance of cell membrane stability,the synthesis of steroid hormones,and myelination.Cholesterol plays a key role in the establishment and maintenance of the central nervous system.The brain contains 20%of the whole body’s cholesterol,80%of which is located within myelin.A huge number of processes(e.g.,the sterol regulatory element-binding protein pathway and liver X receptor pathway)participate in the regulation of cholesterol metabolism in the brain via mechanisms that include cholesterol biosynthesis,intracellular transport,and efflux.Certain brain injuries or diseases involving crosstalk among the processes above can affect normal cholesterol metabolism to induce detrimental consequences.Therefore,we hypothesized that cholesterol-related molecules and pathways can serve as therapeutic targets for central nervous system diseases.Intracerebral hemorrhage is the most severe hemorrhagic stroke subtype,with high mortality and morbidity.Historical cholesterol levels are associated with the risk of intracerebral hemorrhage.Moreover,secondary pathological changes after intracerebral hemorrhage are associated with cholesterol metabolism dysregulation,such as neuroinflammation,demyelination,and multiple types of programmed cell death.Intracellular cholesterol accumulation in the brain has been found after intracerebral hemorrhage.In this paper,we review normal cholesterol metabolism in the central nervous system,the mechanisms known to participate in the disturbance of cholesterol metabolism after intracerebral hemorrhage,and the links between cholesterol metabolism and cell death.We also review several possible and constructive therapeutic targets identified based on cholesterol metabolism to provide cholesterol-based perspectives and a reference for those interested in the treatment of intracerebral hemorrhage.展开更多
Alzheimer's disease,the primary cause of dementia,is characterized by neuropathologies,such as amyloid plaques,synaptic and neuronal degeneration,and neurofibrillary tangles.Although amyloid plaques are the primar...Alzheimer's disease,the primary cause of dementia,is characterized by neuropathologies,such as amyloid plaques,synaptic and neuronal degeneration,and neurofibrillary tangles.Although amyloid plaques are the primary characteristic of Alzheimer's disease in the central nervous system and peripheral organs,targeting amyloid-beta clearance in the central nervous system has shown limited clinical efficacy in Alzheimer's disease treatment.Metabolic abnormalities are commonly observed in patients with Alzheimer's disease.The liver is the primary peripheral organ involved in amyloid-beta metabolism,playing a crucial role in the pathophysiology of Alzheimer's disease.Notably,impaired cholesterol metabolism in the liver may exacerbate the development of Alzheimer's disease.In this review,we explore the underlying causes of Alzheimer's disease and elucidate the role of the liver in amyloid-beta clearance and cholesterol metabolism.Furthermore,we propose that restoring normal cholesterol metabolism in the liver could represent a promising therapeutic strategy for addressing Alzheimer's disease.展开更多
Alzheimer’s disease not only affects the brain,but also induces metabolic dysfunction in peripheral organs and alters the gut microbiota.The aim of this study was to investigate systemic changes that occur in Alzhei...Alzheimer’s disease not only affects the brain,but also induces metabolic dysfunction in peripheral organs and alters the gut microbiota.The aim of this study was to investigate systemic changes that occur in Alzheimer’s disease,in particular the association between changes in peripheral organ metabolism,changes in gut microbial composition,and Alzheimer’s disease development.To do this,we analyzed peripheral organ metabolism and the gut microbiota in amyloid precursor protein-presenilin 1(APP/PS1)transgenic and control mice at 3,6,9,and 12 months of age.Twelve-month-old APP/PS1 mice exhibited cognitive impairment,Alzheimer’s disease-related brain changes,distinctive metabolic disturbances in peripheral organs and fecal samples(as detected by untargeted metabolomics sequencing),and substantial changes in gut microbial composition compared with younger APP/PS1 mice.Notably,a strong correlation emerged between the gut microbiota and kidney metabolism in APP/PS1 mice.These findings suggest that alterations in peripheral organ metabolism and the gut microbiota are closely related to Alzheimer’s disease development,indicating potential new directions for therapeutic strategies.展开更多
Surgical intervention is currently the primary treatment for hepatolithiasis;how-ever,some patients still experience residual stones and high recurrence rates after surgery.Cholesterol metabolism seems to play an impo...Surgical intervention is currently the primary treatment for hepatolithiasis;how-ever,some patients still experience residual stones and high recurrence rates after surgery.Cholesterol metabolism seems to play an important role in hepatoli-thiasis pathogenesis.A high cholesterol diet is one of the significant reasons for the increasing incidence of hepatolithiasis.Therefore,regular diet and appropriate medical intervention are crucial measures to prevent hepatolithiasis and reduce recurrence rate after surgery.Reducing dietary cholesterol and drugs that increase cholesterol stone solubility are key therapeutic approaches in treating hepato-lithiasis.This article discusses the cholesterol metabolic pathways related to the pathogenesis of hepatolithiasis,as well as food intake and targeted therapeutic drugs.展开更多
BACKGROUND The progression of diabetic kidney disease(DKD)affects the patient’s kidney glomeruli and tubules,whose normal functioning is essential for maintaining normal calcium(Ca)and phosphorus(P)metabolism in the ...BACKGROUND The progression of diabetic kidney disease(DKD)affects the patient’s kidney glomeruli and tubules,whose normal functioning is essential for maintaining normal calcium(Ca)and phosphorus(P)metabolism in the body.The risk of developing osteoporosis(OP)in patients with DKD increases with the aggravation of the disease,including a higher risk of fractures,which not only affects the quality of life of patients but also increases the risk of death.AIM To analyze the risk factors for the development of OP in patients with DKD and their correlation with Ca-P metabolic indices,fibroblast growth factor 23(FGF23),and Klotho.METHODS One hundred and fifty-eight patients with DKD who were admitted into the Wuhu Second People’s Hospital from September 2019 to May 2021 were selected and divided into an OP group(n=103)and a normal bone mass group(n=55)according to their X-ray bone densitometry results.Baseline data and differences in Ca-P biochemical indices,FGF23,and Klotho were compared.The correlation of Ca-P metabolic indices with FGF23 and Klotho was discussed,and the related factors affecting OP in patients with DKD were examined by multivariate logistic regression analysis.RESULTS The OP group had a higher proportion of females,an older age,and a longer diabetes mellitus duration than the normal group(all P<0.05).Patients in the OP group exhibited significantly higher levels of intact parathyroid hormone(iPTH),blood P,Ca-P product(Ca×P),fractional excretion of phosphate(FeP),and FGF23,as well as lower estimated glomerular filtration rate,blood Ca,24-hour urinary phosphate excretion(24-hour UPE),and Klotho levels(all P<0.05).In the OP group,25-(OH)-D3,blood Ca,and 24-hour UPE were negatively correlated with FGF23 and positively correlated with Klotho.In contrast,iPTH,blood Ca,Ca×P,and FeP exhibited a positive correlation with FGF23 and an inverse association with Klotho(all P<0.05).Moreover,25-(OH)-D3,iPTH,blood Ca,FePO4,FGF23,Klotho,age,and female gender were key factors that affected the lumbar and left femoral neck bone mineral density.CONCLUSION The Ca-P metabolism metabolic indexes,FGF23,and Klotho in patients with DKD are closely related to the occurrence and development of OP.展开更多
In the article titled“Astrocytic endothelin-1 overexpression impairs learning and memory ability in ischemic stroke via altered hippocampal neurogenesis and lipid metabolism,”published on pages 650-656,Issue 3,Volum...In the article titled“Astrocytic endothelin-1 overexpression impairs learning and memory ability in ischemic stroke via altered hippocampal neurogenesis and lipid metabolism,”published on pages 650-656,Issue 3,Volume 19 of Neural Regeneration Research(Li et al.,2024),there were two errors that needed to be corrected.展开更多
Infection is a public health problem and represents a spectrum of disease that can result in sepsis and septic shock.Sepsis is characterized by a dysregulated immune response to infection.Septic shock is the most seve...Infection is a public health problem and represents a spectrum of disease that can result in sepsis and septic shock.Sepsis is characterized by a dysregulated immune response to infection.Septic shock is the most severe form of sepsis which leads to distributive shock and high mortality rates.There have been significant advances in sepsis management mainly focusing on early identification and therapy.However,complicating matters is the lack of reliable diagnostic tools and the poor specificity and sensitivity of existing scoring tools i.e.,systemic inflammatory response syndrome criteria,sequential organ failure assessment(SOFA),or quick SOFA.These limitations have underscored the modest progress in reducing sepsis-related mortality.This review will focus on novel therapeutics such as oxidative stress targets,cytokine modulation,endothelial cell modulation,etc.,that are being conceptualized for the management of sepsis and septic shock.展开更多
Background:The emerging incidence of pathogenic liver conditions is turning into a major concern for global health.Induction of pyroptosis in hepatocytes instigates cel-lular disintegration,which in turn liberates sub...Background:The emerging incidence of pathogenic liver conditions is turning into a major concern for global health.Induction of pyroptosis in hepatocytes instigates cel-lular disintegration,which in turn liberates substantial quantities of pro-inflammatory intracellular substances,thereby accelerating the advancement of liver fibrosis.Consequently,directing therapeutic efforts towards inhibiting pyroptosis could po-tentially serve as an innovative approach in managing inflammation related chronic hepatic disorders.Methods:GSDMD-NT^(ki/wt)mice and Alb-cre^(ki/wt)mice were generated using CRISPR/Cas9 technology.After crossing the two strains together,we induced conditional cell death by doxycycline to construct a mouse model of liver fibrosis.We analyzed differ-entially expressed genes by RNA sequencing and explored their biological functions.The efficacy of obeticholic acid(OCA)in the treatment of liver fibrosis was assessed.Results:Doxycycline-treated GSDMD-NT^(ki/wt)×Alb-cre^(ki/wt)mice showed severe liver damage,vacuolation of hepatocytes,increased collagen fibers,and accumulation of lipid droplets.The expression of liver fibrosis related genes was greatly increased in the doxycycline-treated mouse liver compared with untreated mouse liver.RNA-sequencing showed that upregulated differentially expressed genes were involved in inflammatory responses,cell activation,and metabolic processes.Treatment with OCA alleviated the liver fibrosis,with reduced ALT and AST levels seen in the GSDMD-NT^(ki/wt)×Alb-cre^(ki/wt)mice.Conclusions:We successfully constructed a novel mouse model for liver fibrosis.This GSDMD-NT-induced fibrosis may be mediated by abnormal lipid metabolism.Our re-sults demonstrated that we successfully constructed a mouse model of liver fibrosis,and GSDMD-NT induced fibrosis by mediating lipid metabolism.展开更多
Neuron-derived clone 77 (Nur77) is a member of the NR4A subfamily that plays critical roles in apoptosis, survival, proliferation, autophagy, angiogenesis, inflammatory responses, DNA repair, glycolipid metabolism and...Neuron-derived clone 77 (Nur77) is a member of the NR4A subfamily that plays critical roles in apoptosis, survival, proliferation, autophagy, angiogenesis, inflammatory responses, DNA repair, glycolipid metabolism and energy consumption. The deregulation of Nur77 signalling often relates to various serious diseases, including cancer and non-cancer diseases. A systematic review is necessary for the better understanding of Nur77 in clinical treatment. In this article, we comprehensively conclude the lipid regulation function and expression of Nur77, and its role in COPD. Finally, we prospect that development of drugs and clinical biochemical investigations targeting of Nur77 has considerable potential within healthcare.展开更多
Background Dysregulation of lipid metabolism and its consequences on growth performance in young ruminants have attracted attention,especially in the context of alternative feeding strategies.This study aims to elucid...Background Dysregulation of lipid metabolism and its consequences on growth performance in young ruminants have attracted attention,especially in the context of alternative feeding strategies.This study aims to elucidate the effects of milk replacer(MR)feeding on growth,lipid metabolism,colonic epithelial gene expression,colonic microbiota composition and systemic metabolism in goat kids compared to breast milk(BM)feeding,addressing a critical knowledge gap in early life nutrition.Methods Ten female goat kids were divided into 2 groups:those fed breast milk(BM group)and those fed a milk replacer(MR group).Over a period of 28 d,body weight was monitored and blood and tissue samples were collected for biochemical,transcriptomic and metabolomic analyses.Profiling of the colonial microbiota was performed using 16S rRNA gene sequencing.Intestinal microbiota transplantation(IMT)experiments in gnotobiotic mice were per-formed to validate causality.Results MR-fed pups exhibited reduced daily body-weight gain due to impaired lipid metabolism as evidenced by lower serum and liver total cholesterol(TC)and non-esterified fatty acid(NEFA)concentrations.Transcriptomic analysis of the colonic epithelium revealed upregulated genes involved in negative regulation of lipid metabolism,concomitant with microbiota shifts characterized by a decrease in Firmicutes and an increase in Actinobacteria.Specifically,genera such as Bifidobacterium and Prevotella were enriched in the MR group,while Clostridium and Fae-calibacterium were depleted.Metabolomics analyses confirmed alterations in bile acid and fatty acid metabolic path-ways.IMT experiments in mice recapitulated the metabolic phenotype observed in MR-fed goats,confirming the role of the microbiota in modulating host lipid metabolism.Conclusions Milk replacer feeding in goat kids disrupts lipid metabolism and gut microbiota dynamics,result-ing in reduced growth rates and metabolic alterations.These findings highlight the importance of early nutritional intervention on metabolic programming and suggest that modulation of the gut microbiota may be a target for improving growth and metabolic health in ruminants.This study contributes to the understanding of nutritional management strategies in livestock and their impact on animal health and productivity.展开更多
Background During the transition period,excessive negative energy balance(NEB)lead to metabolic disorders and reduced milk yield.Rumen microbes are responsible for resolving plant material and producing volatile fatty...Background During the transition period,excessive negative energy balance(NEB)lead to metabolic disorders and reduced milk yield.Rumen microbes are responsible for resolving plant material and producing volatile fatty acids(VFA),which are the primary energy source for cows.In this study,we aimed to investigate the effect of citrus peel extract(CPE)supplementation on rumen microbiota composition,energy metabolism and milk performance of peri-partum dairy cows.Methods Dairy cows were fed either a basal diet(CON group)or the same basal diet supplemented with CPE via intragastric administration(4 g/d,CPE group)for 6 weeks(3 weeks before and 3 weeks after calving;n=15 per group).Samples of serum,milk,rumen fluid,adipose tissue,and liver were collected to assess the effects of CPE on rumen microbiota composition,rumen fermentation parameters,milk performance,and energy metabolic status of dairy cows.Results CPE supplementation led to an increase in milk yield,milk protein and lactose contents,and serum glucose levels,while reduced serum concentrations of non-esterified fatty acid,β-hydroxybutyric acid,insulin,aspartate aminotransferase,alanine aminotransferase,and haptoglobin during the first month of lactation.CPE supplemen-tation also increased the content of ruminal VFA.Compared to the CON group,the abundance of Prevotellaceae,Methanobacteriaceae,Bacteroidales_RF16_group,and Selenomonadaceae was found increased,while the abun-dance of Oscillospiraceae,F082,Ruminococcaceae,Christensenellaceae,Muribaculaceae UCG-011,Saccharimona-daceae,Hungateiclostridiaceae,and Spirochaetaceae in the CPE group was found decreased.In adipose tissue,CPE supplementation decreased lipolysis,and inflammatory response,while increased insulin sensitivity.In the liver,CPE supplementation decreased lipid accumulation,increased insulin sensitivity,and upregulated expression of genes involved in gluconeogenesis.Conclusions Our findings suggest that CPE supplementation during the peripartum period altered rumen micro-biota composition and increased ruminal VFA contents,which further improved NEB and lactation performance,alleviated lipolysis and inflammatory response in adipose tissue,reduced lipid accumulation and promoted gluconeo-genesis in liver.Thus,CPE might contribute to improve energy metabolism and consequently lactation performance of dairy cows during the transition period.展开更多
Background Energy deficiency is a leading cause of the high pre-weaning mortality of neonatal piglets in the swine industry.Thus,optimal energy metabolism is of crucial importance for improving the survivability of ne...Background Energy deficiency is a leading cause of the high pre-weaning mortality of neonatal piglets in the swine industry.Thus,optimal energy metabolism is of crucial importance for improving the survivability of neonatal piglets.The effective utilization of milk fat as primary energy is indispensably required.Methods Pregnant sows(n=27)were randomly assigned into 3 treatments.Each treatment received a standard diet(3,265 kcal ME/kg)supplemented with either 0,0.25%or 0.5%clofibrate(w/w)from d 107 of gestation to d 7 of lacta-tion.The effects of maternal clofibrate on their milk fatty acid(FA)and performance of the piglets were evaluated.The evaluations were performed via measuring sow productive performance,milk FA composition,and hepatic FA oxida-tion of the piglets at birth and d 1,7,14 and 19 after birth.Results Maternal supplementation of clofibrate had no effect on reproductive performance of the sows at farrowing and weaning(P>0.05).However,the mortality at weaning was reduced for piglets from sows with 0.25%of clofi-brate,and the average weekly(and daily)gain was higher in piglets from sows that received clofibrate than sows without clofibrate in the first week(P<0.0001).Maternal clofibrate increased percentage of milk C12:0 and C14:0 FAs but decreased C18:2 and n-6 polyunsaturated FAs.Maternal clofibrate also increased plasma ketone body levels and hepatic FA oxidation measured at the first day of birth,but the increase was not detected in piglets on d 7,14 or 19.Clofibrate was not detected in milk collected from the clofibrate-treated sows.The percentage of FA oxidation decreased,and the percentage of FA esterification increased with increasing in postnatal age.Supplemental carni-tine increased FA oxidation regardless of succinate dehydrogenase inhibition,and the increase had no effect on FA esterification.Conclusions Maternal supplementation of clofibrate during late gestation and early lactation increases hepatic FA oxidative metabolism at birth and improves growth performance of newborn piglets.Maternal clofibrate transfer to suckling piglets via milk was not detected.Carnitine availability is critical for piglets to maintain a high FA oxidation rate during the suckling period.展开更多
BACKGROUND Body composition analysis(BCA)is primarily used in the management of conditions such as obesity and endocrine disorders.However,its potential in providing nutritional guidance for patients with Alzheimer’s...BACKGROUND Body composition analysis(BCA)is primarily used in the management of conditions such as obesity and endocrine disorders.However,its potential in providing nutritional guidance for patients with Alzheimer’s disease(AD)remains relatively unexplored.AIM To explore the clinical efficacy of BCA-based dietary nutrition scheme on bone metabolism in AD patients.METHODS This retrospective study included 96 patients with AD complicated by osteoporosis who were admitted to The Third Hospital of Quzhou between January 2023 and December 2024.Based on data from previous similar studies,the patients were randomly assigned to either a routine diet(RD)group(n=48)or a personalized nutrition(PN)group(n=48).The RD group received conventional dietary guidance,while the PN group received individualized diet intervention measures based on human BCA.The intervention period lasted for 12 weeks.Bone mineral density(BMD),body mass index(BMI),muscle mass,mineral content,osteocalcin,25-hydroxyvitamin D,procollagen type I N-terminal propeptide(PINP),beta C-terminal telopeptide of type I collagen(β-CTX),and serum calcium were measured and compared between the two groups before and 12 weeks after the intervention.RESULTS No significant differences were observed between groups in terms of age,sex,height,BMI,or other baseline data(P>0.05).In both groups,BMI did not show significant changes after the intervention(P>0.05),whereas muscle mass and mineral content were significantly increased(P<0.05).After the intervention,BMI in the PN group did not differ significantly from that of the RD group,but muscle mass and mineral content were significantly higher in the PN group(P<0.05).After the intervention,a higher proportion of patients in the PN group had a T score>-1 compared to the RD group(P<0.05).The mini-mental state examination(MMSE)score was similar in both groups before the intervention.However,12 weeks after the intervention,the MMSE score in the PN group was significantly higher than that in the RD group(P<0.05).In both groups,the MMSE score significantly increased 12 weeks post-intervention compared to pre-intervention levels(P<0.05).Before the intervention,the levels of osteocalcin,serum calcium,PINP,β-CTX,and 25-hydroxyvitamin D were not significantly different between the two groups(P>0.05).After 12 weeks of intervention,the PN group exhibited higher levels of osteocalcin,serum calcium,and 25-hydroxyvitamin D,as well as lower levels of PINP andβ-CTX,compared to the RD group(P<0.05).In both groups,osteocalcin,serum calcium,and 25-hydroxyvitamin D levels were significantly higher,while PINP andβ-CTX levels were significantly lower after 12 weeks of intervention compared to baseline(P<0.05).CONCLUSION The human BCA-based dietary nutrition regimen plays a crucial role in improving BMD and bone metabolism,with effects that surpass those of conventional nutrition strategies.The findings of this study provide strong evidence for the nutritional management of AD patients.展开更多
This study focuses on urgent research on restoring and enhancing carbon storage capacity in the Beibu Gulf Urban Agglomer-ation of China,a key area in the‘Belt and Road’Initiative,which aligns with carbon peaking an...This study focuses on urgent research on restoring and enhancing carbon storage capacity in the Beibu Gulf Urban Agglomer-ation of China,a key area in the‘Belt and Road’Initiative,which aligns with carbon peaking and neutrality goals.This research ana-lyzes the spatial characteristics of carbon metabolism from 2000 to 2020 and uses models to identify stable carbon sink areas,positive carbon flow corridors,and carbon sequestration nodes.The goal is to construct a carbon metabolism spatial security pattern(CMSSP)and propose territorial ecological restoration strategies under different development demand scenarios.The results show the following:1)in 2020,the study area’s carbon sink decreased by 8.29×10^(4) t C/yr compared with that in 2010 and by 10.83×10^(4) t C/yr compared with that in 2000.High-carbon sinks were found mainly in mountainous areas,whereas low-carbon sinks are concentrated in urban con-struction land,rural residential areas,and land margins.2)From 2000 to 2020,the spatial security pattern of carbon metabolism tended to be‘high in the middle of the east and west and low in the gulf.’In 2000,2010,and 2020,16 stable carbon sinks were identified.The carbon energy flow density in Guangxi was greater than that in Guangdong and Hainan,with positive carbon flow corridors located primarily in Guangxi and Guangdong.The number of carbon sequestration nodes remained stable at approximately 15,mainly in Guangxi and Hainan.3)Scenario simulations revealed that under the Nature-based mild restoration scenario,the carbon sink rate will reach 611.85×10^(4) t C/yr by 2030 and increase to 612.45×10^(4) t C/yr by 2060,with stable carbon sinks increasing to 18.In the restora-tion scenario based on Anti-globalization,the carbon sink will decrease from 610.24×10^(4) t C/yr in 2030 to 605.19×10^(4) t C/yr in 2060,with the disappearance of some positive carbon flow corridors and stable carbon sinks.Under the Human-based sustainable restoration scenario,the carbon sink area will decrease from 607.00×10^(4) t C/yr in 2030 to 596.39×10^(4) t C/yr in 2060,with carbon sink areas frag-menting and positive carbon flow corridors becoming less dense.4)On the basis of the current and predicted CMSSPs,this study ex-plores spatial ecological restoration strategies for high-carbon storage areas in bay urban agglomerations at four levels:the land control region,urban agglomeration structure system,carbon sink structure and bay structure control region.展开更多
Background AflatoxinB1(AFB_(1))is a prevalent contaminant in agricultural products,presenting significant risks to animal health.CotA laccase from Bacillus licheniformis has shown significant efficacy in degrading myc...Background AflatoxinB1(AFB_(1))is a prevalent contaminant in agricultural products,presenting significant risks to animal health.CotA laccase from Bacillus licheniformis has shown significant efficacy in degrading mycotoxins in vitro test.The efficacy of Bacillus CotA laccase in animals,however,remains to be confirmed.A 2×2 factorial design was used to investigate the effects of Bacillus CotA laccase level(0 or 1 U/kg),AFB_(1) challenge(challenged or unchal-lenged)and their interactions on ducks.The purpose of this study was to evaluate the efficacy of Bacillus CotA laccase in alleviatingAFB_(1) toxicosis of ducks.Results Bacillus CotA laccase alleviatedAFB_(1)-induced declines in growth performance of ducks accompanied by improved average daily gain(ADG)and lower feed/gain ratio(F/G).Bacillus CotA laccase amelioratedAFB_(1)-induced gut barrier dysfunctions and inflammation testified by increasing the jejunal villi height/crypt depth ratio(VH/CD)and the mRNA expression of tight junction protein 1(TJP1)and zonula occluden-1(ZO-1)as well as decreasing the expression of inflammation-related genes in the jejunum of ducks.Amino acid metabolome showed that Bacillus CotA laccase amelioratedAFB_(1)-induced amino acid metabolism disorders evidenced by increasing the level of glu-tamic acid in serum and upregulating the expression of amino acid transport related genes in jejunum of ducks.Bacil-lus CotA laccase amelioratedAFB_(1)-induced liver injury testified by suppressing oxidative stress,inhibiting apoptosis,and downregulating the expression of hepatic metabolic enzyme related genes of ducks.Moreover,Bacillus CotA laccase degradedAFB_(1) in digestive tract of ducks,resulting in the reduced absorption level ofAFB_(1) across intestinal epithelium testified by the decreased level ofAFB_(1)-DNA adduct in the liver,and the reduced content ofAFB_(1) residues in liver and feces of ducks.Conclusions Bacillus CotA laccase effectively improved the growth performance,intestinal health,amino acid metabolism and hepatic aflatoxin metabolism of ducks fedAFB_(1) diets,highlighting its potential as an efficient and safe feed enzyme forAFB_(1) degradation in animal production.展开更多
Lactate,a byproduct of glycolysis,was thought to be a metabolic waste until the discovery of the Warburg effect.Lactate not only functions as a metabolic substrate to provide energy but can also function as a signalin...Lactate,a byproduct of glycolysis,was thought to be a metabolic waste until the discovery of the Warburg effect.Lactate not only functions as a metabolic substrate to provide energy but can also function as a signaling molecule to modulate cellular functions under pathophysiological conditions.The Astrocyte-Neuron Lactate Shuttle has cla rified that lactate plays a pivotal role in the central nervous system.Moreover,protein lactylation highlights the novel role of lactate in regulating transcription,cellular functions,and disease development.This review summarizes the recent advances in lactate metabolism and its role in neurodegenerative diseases,thus providing optimal pers pectives for future research.展开更多
Vascular etiology is the second most prevalent cause of cognitive impairment globally.Endothelin-1,which is produced and secreted by endothelial cells and astrocytes,is implicated in the pathogenesis of stroke.However...Vascular etiology is the second most prevalent cause of cognitive impairment globally.Endothelin-1,which is produced and secreted by endothelial cells and astrocytes,is implicated in the pathogenesis of stroke.However,the way in which changes in astrocytic endothelin-1 lead to poststroke cognitive deficits following transient middle cerebral artery occlusion is not well understood.Here,using mice in which astrocytic endothelin-1 was overexpressed,we found that the selective overexpression of endothelin-1 by astrocytic cells led to ischemic stroke-related dementia(1 hour of ischemia;7 days,28 days,or 3 months of reperfusion).We also revealed that astrocytic endothelin-1 overexpression contributed to the role of neural stem cell proliferation but impaired neurogenesis in the dentate gyrus of the hippocampus after middle cerebral artery occlusion.Comprehensive proteome profiles and western blot analysis confirmed that levels of glial fibrillary acidic protein and peroxiredoxin 6,which were differentially expressed in the brain,were significantly increased in mice with astrocytic endothelin-1 overexpression in comparison with wild-type mice 28 days after ischemic stroke.Moreover,the levels of the enriched differentially expressed proteins were closely related to lipid metabolism,as indicated by Kyoto Encyclopedia of Genes and Genomes pathway analysis.Liquid chromatography-mass spectrometry nontargeted metabolite profiling of brain tissues showed that astrocytic endothelin-1 overexpression altered lipid metabolism products such as glycerol phosphatidylcholine,sphingomyelin,and phosphatidic acid.Overall,this study demonstrates that astrocytic endothelin-1 overexpression can impair hippocampal neurogenesis and that it is correlated with lipid metabolism in poststroke cognitive dysfunction.展开更多
Diabetic peripheral neuropathy is a common complication of diabetes mellitus.Elucidating the pathophysiological metabolic mechanism impels the generation of ideal therapies.However,existing limited treatments for diab...Diabetic peripheral neuropathy is a common complication of diabetes mellitus.Elucidating the pathophysiological metabolic mechanism impels the generation of ideal therapies.However,existing limited treatments for diabetic peripheral neuropathy expose the urgent need for cell metabolism research.Given the lack of comprehensive understanding of energy metabolism changes and related signaling pathways in diabetic peripheral neuropathy,it is essential to explore energy changes and metabolic changes in diabetic peripheral neuropathy to develop suitable treatment methods.This review summarizes the pathophysiological mechanism of diabetic peripheral neuropathy from the perspective of cellular metabolism and the specific interventions for different metabolic pathways to develop effective treatment methods.Various metabolic mechanisms(e.g.,polyol,hexosamine,protein kinase C pathway)are associated with diabetic peripheral neuropathy,and researchers are looking for more effective treatments through these pathways.展开更多
Leaf senescence is an orderly and highly coordinated process,and finely regulated by ethylene and nitrogen(N),ultimately affecting grain yield and nitrogen-use efficiency(NUE).However,the underlying regulatory mechani...Leaf senescence is an orderly and highly coordinated process,and finely regulated by ethylene and nitrogen(N),ultimately affecting grain yield and nitrogen-use efficiency(NUE).However,the underlying regulatory mechanisms on the crosstalk between ethylene-and N-regulated leaf senescence remain a mystery in maize.In this study,ethylene biosynthesis gene ZmACS7 overexpressing(OE-ZmACS7)plants were used to study the role of ethylene regulating leaf senescence in response to N deficiency,and they exhibited the premature leaf senescence accompanied by increased ethylene release,decreased chlorophyll content and F_v/F_m ratio,and accelerated chloroplast degradation.Then,we investigated the dynamics changes of transcriptome reprogramming underlying ethylene-accelerated leaf senescence in response to N deficiency.The differentially expressed genes(DEGs)involved in chlorophyll biosynthesis were significantly down-regulated,while DEGs involved in chlorophyll degradation and autophagy processes were significantly up-regulated,especially in OE-ZmACS7 plants in response to N deficiency.A gene regulatory network(GRN)was predicted during ethylene-accelerated leaf senescence in response to N deficiency.Three transcription factors(TFs)ZmHSF4,Zmb HLH106,and ZmEREB147 were identified as the key regulatory genes,which targeted chlorophyll biosynthesis gene ZmLES22,chlorophyll degradation gene ZmNYC1,and autophagy-related gene ZmATG5,respectively.Furthermore,ethylene signaling key genes might be located upstream of these TFs,generating the signaling cascade networks during ethylene-accelerated leaf senescence in response to N deficiency.Collectively,these findings improve our molecular knowledge of ethylene-accelerated maize leaf senescence in response to N deficiency,which is promising to improve NUE by manipulating the progress of leaf senescence in maize.展开更多
基金supported by Karolinska Institutet in the form of a Board of Research Faculty Funded Career Positionby St.Erik Eye Hospital philanthropic donationsVetenskapsrådet 2022-00799.
文摘Pyrroloquinoline quinone is a quinone described as a cofactor for many bacterial dehydrogenases and is reported to exert an effect on metabolism in mammalian cells/tissues.Pyrroloquinoline quinone is present in the diet being available in foodstuffs,conferring the potential of this compound to be supplemented by dietary administration.Pyrroloquinoline quinone’s nutritional role in mammalian health is supported by the extensive deficits in reproduction,growth,and immunity resulting from the dietary absence of pyrroloquinoline quinone,and as such,pyrroloquinoline quinone has been considered as a“new vitamin.”Although the classification of pyrroloquinoline quinone as a vitamin needs to be properly established,the wide range of benefits for health provided has been reported in many studies.In this respect,pyrroloquinoline quinone seems to be particularly involved in regulating cell signaling pathways that promote metabolic and mitochondrial processes in many experimental contexts,thus dictating the rationale to consider pyrroloquinoline quinone as a vital compound for mammalian life.Through the regulation of different metabolic mechanisms,pyrroloquinoline quinone may improve clinical deficits where dysfunctional metabolism and mitochondrial activity contribute to induce cell damage and death.Pyrroloquinoline quinone has been demonstrated to have neuroprotective properties in different experimental models of neurodegeneration,although the link between pyrroloquinoline quinone-promoted metabolism and improved neuronal viability in some of such contexts is still to be fully elucidated.Here,we review the general properties of pyrroloquinoline quinone and its capacity to modulate metabolic and mitochondrial mechanisms in physiological contexts.In addition,we analyze the neuroprotective properties of pyrroloquinoline quinone in different neurodegenerative conditions and consider future perspectives for pyrroloquinoline quinone’s potential in health and disease.
基金supported by the National Natural Science Foundation of China,No.82072110Suzhou Municipal Science and Technology Bureau,No.SKJY2021046+1 种基金Shanghai Key Lab of Forensic Medicine&Key Lab of Forensic Science,Ministry of Justice,China(Academy of Forensic Science),No.KF202201a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)(all to TW).
文摘Cholesterol is an important component of plasma membranes and participates in many basic life functions,such as the maintenance of cell membrane stability,the synthesis of steroid hormones,and myelination.Cholesterol plays a key role in the establishment and maintenance of the central nervous system.The brain contains 20%of the whole body’s cholesterol,80%of which is located within myelin.A huge number of processes(e.g.,the sterol regulatory element-binding protein pathway and liver X receptor pathway)participate in the regulation of cholesterol metabolism in the brain via mechanisms that include cholesterol biosynthesis,intracellular transport,and efflux.Certain brain injuries or diseases involving crosstalk among the processes above can affect normal cholesterol metabolism to induce detrimental consequences.Therefore,we hypothesized that cholesterol-related molecules and pathways can serve as therapeutic targets for central nervous system diseases.Intracerebral hemorrhage is the most severe hemorrhagic stroke subtype,with high mortality and morbidity.Historical cholesterol levels are associated with the risk of intracerebral hemorrhage.Moreover,secondary pathological changes after intracerebral hemorrhage are associated with cholesterol metabolism dysregulation,such as neuroinflammation,demyelination,and multiple types of programmed cell death.Intracellular cholesterol accumulation in the brain has been found after intracerebral hemorrhage.In this paper,we review normal cholesterol metabolism in the central nervous system,the mechanisms known to participate in the disturbance of cholesterol metabolism after intracerebral hemorrhage,and the links between cholesterol metabolism and cell death.We also review several possible and constructive therapeutic targets identified based on cholesterol metabolism to provide cholesterol-based perspectives and a reference for those interested in the treatment of intracerebral hemorrhage.
基金financially supported by the Science and Technology Innovation Program of Hunan Province,No.2022RC1220(to WP)China Postdoctoral Science Foundation,No.2022M711733(to ZZ)+2 种基金the National Natural Science Foundation of China,No.82160920(to ZZ)Hebei Postdoctoral Scientific Research Project,No.B2022003040(to ZZ)Hunan Flagship Department of Integrated Traditional Chinese and Western Medicine(to WP)。
文摘Alzheimer's disease,the primary cause of dementia,is characterized by neuropathologies,such as amyloid plaques,synaptic and neuronal degeneration,and neurofibrillary tangles.Although amyloid plaques are the primary characteristic of Alzheimer's disease in the central nervous system and peripheral organs,targeting amyloid-beta clearance in the central nervous system has shown limited clinical efficacy in Alzheimer's disease treatment.Metabolic abnormalities are commonly observed in patients with Alzheimer's disease.The liver is the primary peripheral organ involved in amyloid-beta metabolism,playing a crucial role in the pathophysiology of Alzheimer's disease.Notably,impaired cholesterol metabolism in the liver may exacerbate the development of Alzheimer's disease.In this review,we explore the underlying causes of Alzheimer's disease and elucidate the role of the liver in amyloid-beta clearance and cholesterol metabolism.Furthermore,we propose that restoring normal cholesterol metabolism in the liver could represent a promising therapeutic strategy for addressing Alzheimer's disease.
基金financially supported by the National Natural Science Foundation of China,No.823 74552 (to WP)the Science and Technology Innovation Program of Hunan Province,No.2022RC1220 (to WP)+1 种基金the Natural Science Foundation of Hunan Province of China,Nos.2020JJ4803 (to WP),2022JJ40723 (to MY)the Scientific Research Launch Project for New Employees of the Second Xiangya Hospital of Central South University (to MY)
文摘Alzheimer’s disease not only affects the brain,but also induces metabolic dysfunction in peripheral organs and alters the gut microbiota.The aim of this study was to investigate systemic changes that occur in Alzheimer’s disease,in particular the association between changes in peripheral organ metabolism,changes in gut microbial composition,and Alzheimer’s disease development.To do this,we analyzed peripheral organ metabolism and the gut microbiota in amyloid precursor protein-presenilin 1(APP/PS1)transgenic and control mice at 3,6,9,and 12 months of age.Twelve-month-old APP/PS1 mice exhibited cognitive impairment,Alzheimer’s disease-related brain changes,distinctive metabolic disturbances in peripheral organs and fecal samples(as detected by untargeted metabolomics sequencing),and substantial changes in gut microbial composition compared with younger APP/PS1 mice.Notably,a strong correlation emerged between the gut microbiota and kidney metabolism in APP/PS1 mice.These findings suggest that alterations in peripheral organ metabolism and the gut microbiota are closely related to Alzheimer’s disease development,indicating potential new directions for therapeutic strategies.
基金Supported by Hebei Natural Science Foundation,No.H2022206539Hebei Provincial Government Funded Clinical Talents Training Project,No.ZF2023143.
文摘Surgical intervention is currently the primary treatment for hepatolithiasis;how-ever,some patients still experience residual stones and high recurrence rates after surgery.Cholesterol metabolism seems to play an important role in hepatoli-thiasis pathogenesis.A high cholesterol diet is one of the significant reasons for the increasing incidence of hepatolithiasis.Therefore,regular diet and appropriate medical intervention are crucial measures to prevent hepatolithiasis and reduce recurrence rate after surgery.Reducing dietary cholesterol and drugs that increase cholesterol stone solubility are key therapeutic approaches in treating hepato-lithiasis.This article discusses the cholesterol metabolic pathways related to the pathogenesis of hepatolithiasis,as well as food intake and targeted therapeutic drugs.
文摘BACKGROUND The progression of diabetic kidney disease(DKD)affects the patient’s kidney glomeruli and tubules,whose normal functioning is essential for maintaining normal calcium(Ca)and phosphorus(P)metabolism in the body.The risk of developing osteoporosis(OP)in patients with DKD increases with the aggravation of the disease,including a higher risk of fractures,which not only affects the quality of life of patients but also increases the risk of death.AIM To analyze the risk factors for the development of OP in patients with DKD and their correlation with Ca-P metabolic indices,fibroblast growth factor 23(FGF23),and Klotho.METHODS One hundred and fifty-eight patients with DKD who were admitted into the Wuhu Second People’s Hospital from September 2019 to May 2021 were selected and divided into an OP group(n=103)and a normal bone mass group(n=55)according to their X-ray bone densitometry results.Baseline data and differences in Ca-P biochemical indices,FGF23,and Klotho were compared.The correlation of Ca-P metabolic indices with FGF23 and Klotho was discussed,and the related factors affecting OP in patients with DKD were examined by multivariate logistic regression analysis.RESULTS The OP group had a higher proportion of females,an older age,and a longer diabetes mellitus duration than the normal group(all P<0.05).Patients in the OP group exhibited significantly higher levels of intact parathyroid hormone(iPTH),blood P,Ca-P product(Ca×P),fractional excretion of phosphate(FeP),and FGF23,as well as lower estimated glomerular filtration rate,blood Ca,24-hour urinary phosphate excretion(24-hour UPE),and Klotho levels(all P<0.05).In the OP group,25-(OH)-D3,blood Ca,and 24-hour UPE were negatively correlated with FGF23 and positively correlated with Klotho.In contrast,iPTH,blood Ca,Ca×P,and FeP exhibited a positive correlation with FGF23 and an inverse association with Klotho(all P<0.05).Moreover,25-(OH)-D3,iPTH,blood Ca,FePO4,FGF23,Klotho,age,and female gender were key factors that affected the lumbar and left femoral neck bone mineral density.CONCLUSION The Ca-P metabolism metabolic indexes,FGF23,and Klotho in patients with DKD are closely related to the occurrence and development of OP.
文摘In the article titled“Astrocytic endothelin-1 overexpression impairs learning and memory ability in ischemic stroke via altered hippocampal neurogenesis and lipid metabolism,”published on pages 650-656,Issue 3,Volume 19 of Neural Regeneration Research(Li et al.,2024),there were two errors that needed to be corrected.
文摘Infection is a public health problem and represents a spectrum of disease that can result in sepsis and septic shock.Sepsis is characterized by a dysregulated immune response to infection.Septic shock is the most severe form of sepsis which leads to distributive shock and high mortality rates.There have been significant advances in sepsis management mainly focusing on early identification and therapy.However,complicating matters is the lack of reliable diagnostic tools and the poor specificity and sensitivity of existing scoring tools i.e.,systemic inflammatory response syndrome criteria,sequential organ failure assessment(SOFA),or quick SOFA.These limitations have underscored the modest progress in reducing sepsis-related mortality.This review will focus on novel therapeutics such as oxidative stress targets,cytokine modulation,endothelial cell modulation,etc.,that are being conceptualized for the management of sepsis and septic shock.
基金National Natural Science Foundation of China,Grant/Award Number:82174292Key Project of Jiangsu Provincial Administration of Traditional Chinese Medicine,Grant/Award Number:ZD202312+2 种基金Natural Science Foundation of Laboratory Medicine School in Chengdu Medical College,Grant/Award Number:JYZK202203Sichuan Province Science and Technology Program,Grant/Award Number:2024NSFSC0577 and 2021YFG0316Technology innovation group project of Foshan 2019,Grant/Award Number:FS0AA-KJ919-4402-0027。
文摘Background:The emerging incidence of pathogenic liver conditions is turning into a major concern for global health.Induction of pyroptosis in hepatocytes instigates cel-lular disintegration,which in turn liberates substantial quantities of pro-inflammatory intracellular substances,thereby accelerating the advancement of liver fibrosis.Consequently,directing therapeutic efforts towards inhibiting pyroptosis could po-tentially serve as an innovative approach in managing inflammation related chronic hepatic disorders.Methods:GSDMD-NT^(ki/wt)mice and Alb-cre^(ki/wt)mice were generated using CRISPR/Cas9 technology.After crossing the two strains together,we induced conditional cell death by doxycycline to construct a mouse model of liver fibrosis.We analyzed differ-entially expressed genes by RNA sequencing and explored their biological functions.The efficacy of obeticholic acid(OCA)in the treatment of liver fibrosis was assessed.Results:Doxycycline-treated GSDMD-NT^(ki/wt)×Alb-cre^(ki/wt)mice showed severe liver damage,vacuolation of hepatocytes,increased collagen fibers,and accumulation of lipid droplets.The expression of liver fibrosis related genes was greatly increased in the doxycycline-treated mouse liver compared with untreated mouse liver.RNA-sequencing showed that upregulated differentially expressed genes were involved in inflammatory responses,cell activation,and metabolic processes.Treatment with OCA alleviated the liver fibrosis,with reduced ALT and AST levels seen in the GSDMD-NT^(ki/wt)×Alb-cre^(ki/wt)mice.Conclusions:We successfully constructed a novel mouse model for liver fibrosis.This GSDMD-NT-induced fibrosis may be mediated by abnormal lipid metabolism.Our re-sults demonstrated that we successfully constructed a mouse model of liver fibrosis,and GSDMD-NT induced fibrosis by mediating lipid metabolism.
文摘Neuron-derived clone 77 (Nur77) is a member of the NR4A subfamily that plays critical roles in apoptosis, survival, proliferation, autophagy, angiogenesis, inflammatory responses, DNA repair, glycolipid metabolism and energy consumption. The deregulation of Nur77 signalling often relates to various serious diseases, including cancer and non-cancer diseases. A systematic review is necessary for the better understanding of Nur77 in clinical treatment. In this article, we comprehensively conclude the lipid regulation function and expression of Nur77, and its role in COPD. Finally, we prospect that development of drugs and clinical biochemical investigations targeting of Nur77 has considerable potential within healthcare.
基金financially supported by National Natural Science Foundation of China (32160801)China Agriculture Research System (CARS-39-12)+1 种基金Young Talent Fund of Association for Science and Technology in Shaanxi, China (2023-6-2-1)“Double-chain” project on livestock breeding (2022GDTSLD-46)
文摘Background Dysregulation of lipid metabolism and its consequences on growth performance in young ruminants have attracted attention,especially in the context of alternative feeding strategies.This study aims to elucidate the effects of milk replacer(MR)feeding on growth,lipid metabolism,colonic epithelial gene expression,colonic microbiota composition and systemic metabolism in goat kids compared to breast milk(BM)feeding,addressing a critical knowledge gap in early life nutrition.Methods Ten female goat kids were divided into 2 groups:those fed breast milk(BM group)and those fed a milk replacer(MR group).Over a period of 28 d,body weight was monitored and blood and tissue samples were collected for biochemical,transcriptomic and metabolomic analyses.Profiling of the colonial microbiota was performed using 16S rRNA gene sequencing.Intestinal microbiota transplantation(IMT)experiments in gnotobiotic mice were per-formed to validate causality.Results MR-fed pups exhibited reduced daily body-weight gain due to impaired lipid metabolism as evidenced by lower serum and liver total cholesterol(TC)and non-esterified fatty acid(NEFA)concentrations.Transcriptomic analysis of the colonic epithelium revealed upregulated genes involved in negative regulation of lipid metabolism,concomitant with microbiota shifts characterized by a decrease in Firmicutes and an increase in Actinobacteria.Specifically,genera such as Bifidobacterium and Prevotella were enriched in the MR group,while Clostridium and Fae-calibacterium were depleted.Metabolomics analyses confirmed alterations in bile acid and fatty acid metabolic path-ways.IMT experiments in mice recapitulated the metabolic phenotype observed in MR-fed goats,confirming the role of the microbiota in modulating host lipid metabolism.Conclusions Milk replacer feeding in goat kids disrupts lipid metabolism and gut microbiota dynamics,result-ing in reduced growth rates and metabolic alterations.These findings highlight the importance of early nutritional intervention on metabolic programming and suggest that modulation of the gut microbiota may be a target for improving growth and metabolic health in ruminants.This study contributes to the understanding of nutritional management strategies in livestock and their impact on animal health and productivity.
基金National Key R&D Program of China(Beijing,China,grant no.2023YFE0116900 and 2023YFD1801400)National Natural Science Foundation of China(Beijing,China,grant no.32473105,32302943,and 32302941)Postdoctoral Fellowship Program of CPSF(GZC20230951).
文摘Background During the transition period,excessive negative energy balance(NEB)lead to metabolic disorders and reduced milk yield.Rumen microbes are responsible for resolving plant material and producing volatile fatty acids(VFA),which are the primary energy source for cows.In this study,we aimed to investigate the effect of citrus peel extract(CPE)supplementation on rumen microbiota composition,energy metabolism and milk performance of peri-partum dairy cows.Methods Dairy cows were fed either a basal diet(CON group)or the same basal diet supplemented with CPE via intragastric administration(4 g/d,CPE group)for 6 weeks(3 weeks before and 3 weeks after calving;n=15 per group).Samples of serum,milk,rumen fluid,adipose tissue,and liver were collected to assess the effects of CPE on rumen microbiota composition,rumen fermentation parameters,milk performance,and energy metabolic status of dairy cows.Results CPE supplementation led to an increase in milk yield,milk protein and lactose contents,and serum glucose levels,while reduced serum concentrations of non-esterified fatty acid,β-hydroxybutyric acid,insulin,aspartate aminotransferase,alanine aminotransferase,and haptoglobin during the first month of lactation.CPE supplemen-tation also increased the content of ruminal VFA.Compared to the CON group,the abundance of Prevotellaceae,Methanobacteriaceae,Bacteroidales_RF16_group,and Selenomonadaceae was found increased,while the abun-dance of Oscillospiraceae,F082,Ruminococcaceae,Christensenellaceae,Muribaculaceae UCG-011,Saccharimona-daceae,Hungateiclostridiaceae,and Spirochaetaceae in the CPE group was found decreased.In adipose tissue,CPE supplementation decreased lipolysis,and inflammatory response,while increased insulin sensitivity.In the liver,CPE supplementation decreased lipid accumulation,increased insulin sensitivity,and upregulated expression of genes involved in gluconeogenesis.Conclusions Our findings suggest that CPE supplementation during the peripartum period altered rumen micro-biota composition and increased ruminal VFA contents,which further improved NEB and lactation performance,alleviated lipolysis and inflammatory response in adipose tissue,reduced lipid accumulation and promoted gluconeo-genesis in liver.Thus,CPE might contribute to improve energy metabolism and consequently lactation performance of dairy cows during the transition period.
基金Animal Nutrition,Growth and Lactation(grant no.2015–67015-23245/project accession no.1005855)Animal Health and Production and Animal Products(grant no.2023–67015-39663/1030033)from the USDA National Institute of Food and AgricultureNorth Carolina Agricultural Research Hatch projects 1016618 and 02780.
文摘Background Energy deficiency is a leading cause of the high pre-weaning mortality of neonatal piglets in the swine industry.Thus,optimal energy metabolism is of crucial importance for improving the survivability of neonatal piglets.The effective utilization of milk fat as primary energy is indispensably required.Methods Pregnant sows(n=27)were randomly assigned into 3 treatments.Each treatment received a standard diet(3,265 kcal ME/kg)supplemented with either 0,0.25%or 0.5%clofibrate(w/w)from d 107 of gestation to d 7 of lacta-tion.The effects of maternal clofibrate on their milk fatty acid(FA)and performance of the piglets were evaluated.The evaluations were performed via measuring sow productive performance,milk FA composition,and hepatic FA oxida-tion of the piglets at birth and d 1,7,14 and 19 after birth.Results Maternal supplementation of clofibrate had no effect on reproductive performance of the sows at farrowing and weaning(P>0.05).However,the mortality at weaning was reduced for piglets from sows with 0.25%of clofi-brate,and the average weekly(and daily)gain was higher in piglets from sows that received clofibrate than sows without clofibrate in the first week(P<0.0001).Maternal clofibrate increased percentage of milk C12:0 and C14:0 FAs but decreased C18:2 and n-6 polyunsaturated FAs.Maternal clofibrate also increased plasma ketone body levels and hepatic FA oxidation measured at the first day of birth,but the increase was not detected in piglets on d 7,14 or 19.Clofibrate was not detected in milk collected from the clofibrate-treated sows.The percentage of FA oxidation decreased,and the percentage of FA esterification increased with increasing in postnatal age.Supplemental carni-tine increased FA oxidation regardless of succinate dehydrogenase inhibition,and the increase had no effect on FA esterification.Conclusions Maternal supplementation of clofibrate during late gestation and early lactation increases hepatic FA oxidative metabolism at birth and improves growth performance of newborn piglets.Maternal clofibrate transfer to suckling piglets via milk was not detected.Carnitine availability is critical for piglets to maintain a high FA oxidation rate during the suckling period.
基金Supported by Science and Technology Bureau of Quzhou,No.2022079.
文摘BACKGROUND Body composition analysis(BCA)is primarily used in the management of conditions such as obesity and endocrine disorders.However,its potential in providing nutritional guidance for patients with Alzheimer’s disease(AD)remains relatively unexplored.AIM To explore the clinical efficacy of BCA-based dietary nutrition scheme on bone metabolism in AD patients.METHODS This retrospective study included 96 patients with AD complicated by osteoporosis who were admitted to The Third Hospital of Quzhou between January 2023 and December 2024.Based on data from previous similar studies,the patients were randomly assigned to either a routine diet(RD)group(n=48)or a personalized nutrition(PN)group(n=48).The RD group received conventional dietary guidance,while the PN group received individualized diet intervention measures based on human BCA.The intervention period lasted for 12 weeks.Bone mineral density(BMD),body mass index(BMI),muscle mass,mineral content,osteocalcin,25-hydroxyvitamin D,procollagen type I N-terminal propeptide(PINP),beta C-terminal telopeptide of type I collagen(β-CTX),and serum calcium were measured and compared between the two groups before and 12 weeks after the intervention.RESULTS No significant differences were observed between groups in terms of age,sex,height,BMI,or other baseline data(P>0.05).In both groups,BMI did not show significant changes after the intervention(P>0.05),whereas muscle mass and mineral content were significantly increased(P<0.05).After the intervention,BMI in the PN group did not differ significantly from that of the RD group,but muscle mass and mineral content were significantly higher in the PN group(P<0.05).After the intervention,a higher proportion of patients in the PN group had a T score>-1 compared to the RD group(P<0.05).The mini-mental state examination(MMSE)score was similar in both groups before the intervention.However,12 weeks after the intervention,the MMSE score in the PN group was significantly higher than that in the RD group(P<0.05).In both groups,the MMSE score significantly increased 12 weeks post-intervention compared to pre-intervention levels(P<0.05).Before the intervention,the levels of osteocalcin,serum calcium,PINP,β-CTX,and 25-hydroxyvitamin D were not significantly different between the two groups(P>0.05).After 12 weeks of intervention,the PN group exhibited higher levels of osteocalcin,serum calcium,and 25-hydroxyvitamin D,as well as lower levels of PINP andβ-CTX,compared to the RD group(P<0.05).In both groups,osteocalcin,serum calcium,and 25-hydroxyvitamin D levels were significantly higher,while PINP andβ-CTX levels were significantly lower after 12 weeks of intervention compared to baseline(P<0.05).CONCLUSION The human BCA-based dietary nutrition regimen plays a crucial role in improving BMD and bone metabolism,with effects that surpass those of conventional nutrition strategies.The findings of this study provide strong evidence for the nutritional management of AD patients.
基金Under the auspices of the National Natural Science Foundation of China(No.52268008)。
文摘This study focuses on urgent research on restoring and enhancing carbon storage capacity in the Beibu Gulf Urban Agglomer-ation of China,a key area in the‘Belt and Road’Initiative,which aligns with carbon peaking and neutrality goals.This research ana-lyzes the spatial characteristics of carbon metabolism from 2000 to 2020 and uses models to identify stable carbon sink areas,positive carbon flow corridors,and carbon sequestration nodes.The goal is to construct a carbon metabolism spatial security pattern(CMSSP)and propose territorial ecological restoration strategies under different development demand scenarios.The results show the following:1)in 2020,the study area’s carbon sink decreased by 8.29×10^(4) t C/yr compared with that in 2010 and by 10.83×10^(4) t C/yr compared with that in 2000.High-carbon sinks were found mainly in mountainous areas,whereas low-carbon sinks are concentrated in urban con-struction land,rural residential areas,and land margins.2)From 2000 to 2020,the spatial security pattern of carbon metabolism tended to be‘high in the middle of the east and west and low in the gulf.’In 2000,2010,and 2020,16 stable carbon sinks were identified.The carbon energy flow density in Guangxi was greater than that in Guangdong and Hainan,with positive carbon flow corridors located primarily in Guangxi and Guangdong.The number of carbon sequestration nodes remained stable at approximately 15,mainly in Guangxi and Hainan.3)Scenario simulations revealed that under the Nature-based mild restoration scenario,the carbon sink rate will reach 611.85×10^(4) t C/yr by 2030 and increase to 612.45×10^(4) t C/yr by 2060,with stable carbon sinks increasing to 18.In the restora-tion scenario based on Anti-globalization,the carbon sink will decrease from 610.24×10^(4) t C/yr in 2030 to 605.19×10^(4) t C/yr in 2060,with the disappearance of some positive carbon flow corridors and stable carbon sinks.Under the Human-based sustainable restoration scenario,the carbon sink area will decrease from 607.00×10^(4) t C/yr in 2030 to 596.39×10^(4) t C/yr in 2060,with carbon sink areas frag-menting and positive carbon flow corridors becoming less dense.4)On the basis of the current and predicted CMSSPs,this study ex-plores spatial ecological restoration strategies for high-carbon storage areas in bay urban agglomerations at four levels:the land control region,urban agglomeration structure system,carbon sink structure and bay structure control region.
基金National Key Research and Development Program of China(2021YFC2103003)National Natural Science Foundation of China(31972604)+1 种基金Jinan Introductory Innovation Team Project(No.202228037)China Postdoctoral Science Foundation(2023M730998).
文摘Background AflatoxinB1(AFB_(1))is a prevalent contaminant in agricultural products,presenting significant risks to animal health.CotA laccase from Bacillus licheniformis has shown significant efficacy in degrading mycotoxins in vitro test.The efficacy of Bacillus CotA laccase in animals,however,remains to be confirmed.A 2×2 factorial design was used to investigate the effects of Bacillus CotA laccase level(0 or 1 U/kg),AFB_(1) challenge(challenged or unchal-lenged)and their interactions on ducks.The purpose of this study was to evaluate the efficacy of Bacillus CotA laccase in alleviatingAFB_(1) toxicosis of ducks.Results Bacillus CotA laccase alleviatedAFB_(1)-induced declines in growth performance of ducks accompanied by improved average daily gain(ADG)and lower feed/gain ratio(F/G).Bacillus CotA laccase amelioratedAFB_(1)-induced gut barrier dysfunctions and inflammation testified by increasing the jejunal villi height/crypt depth ratio(VH/CD)and the mRNA expression of tight junction protein 1(TJP1)and zonula occluden-1(ZO-1)as well as decreasing the expression of inflammation-related genes in the jejunum of ducks.Amino acid metabolome showed that Bacillus CotA laccase amelioratedAFB_(1)-induced amino acid metabolism disorders evidenced by increasing the level of glu-tamic acid in serum and upregulating the expression of amino acid transport related genes in jejunum of ducks.Bacil-lus CotA laccase amelioratedAFB_(1)-induced liver injury testified by suppressing oxidative stress,inhibiting apoptosis,and downregulating the expression of hepatic metabolic enzyme related genes of ducks.Moreover,Bacillus CotA laccase degradedAFB_(1) in digestive tract of ducks,resulting in the reduced absorption level ofAFB_(1) across intestinal epithelium testified by the decreased level ofAFB_(1)-DNA adduct in the liver,and the reduced content ofAFB_(1) residues in liver and feces of ducks.Conclusions Bacillus CotA laccase effectively improved the growth performance,intestinal health,amino acid metabolism and hepatic aflatoxin metabolism of ducks fedAFB_(1) diets,highlighting its potential as an efficient and safe feed enzyme forAFB_(1) degradation in animal production.
基金supported by the National Natural Science Foundation of China,Nos.82230042 and 81930029(to ZY),U2004201(to FG and RYP)the China Postdoctoral Science Foundation,No.2020M683748(to RYP)。
文摘Lactate,a byproduct of glycolysis,was thought to be a metabolic waste until the discovery of the Warburg effect.Lactate not only functions as a metabolic substrate to provide energy but can also function as a signaling molecule to modulate cellular functions under pathophysiological conditions.The Astrocyte-Neuron Lactate Shuttle has cla rified that lactate plays a pivotal role in the central nervous system.Moreover,protein lactylation highlights the novel role of lactate in regulating transcription,cellular functions,and disease development.This review summarizes the recent advances in lactate metabolism and its role in neurodegenerative diseases,thus providing optimal pers pectives for future research.
基金financially supported by the National Natural Science Foundation of China,No.81303115,81774042 (both to XC)the Pearl River S&T Nova Program of Guangzhou,No.201806010025 (to XC)+3 种基金the Specialty Program of Guangdong Province Hospital of Chinese Medicine of China,No.YN2018ZD07 (to XC)the Natural Science Foundatior of Guangdong Province of China,No.2023A1515012174 (to JL)the Science and Technology Program of Guangzhou of China,No.20210201 0268 (to XC),20210201 0339 (to JS)Guangdong Provincial Key Laboratory of Research on Emergency in TCM,Nos.2018-75,2019-140 (to JS)
文摘Vascular etiology is the second most prevalent cause of cognitive impairment globally.Endothelin-1,which is produced and secreted by endothelial cells and astrocytes,is implicated in the pathogenesis of stroke.However,the way in which changes in astrocytic endothelin-1 lead to poststroke cognitive deficits following transient middle cerebral artery occlusion is not well understood.Here,using mice in which astrocytic endothelin-1 was overexpressed,we found that the selective overexpression of endothelin-1 by astrocytic cells led to ischemic stroke-related dementia(1 hour of ischemia;7 days,28 days,or 3 months of reperfusion).We also revealed that astrocytic endothelin-1 overexpression contributed to the role of neural stem cell proliferation but impaired neurogenesis in the dentate gyrus of the hippocampus after middle cerebral artery occlusion.Comprehensive proteome profiles and western blot analysis confirmed that levels of glial fibrillary acidic protein and peroxiredoxin 6,which were differentially expressed in the brain,were significantly increased in mice with astrocytic endothelin-1 overexpression in comparison with wild-type mice 28 days after ischemic stroke.Moreover,the levels of the enriched differentially expressed proteins were closely related to lipid metabolism,as indicated by Kyoto Encyclopedia of Genes and Genomes pathway analysis.Liquid chromatography-mass spectrometry nontargeted metabolite profiling of brain tissues showed that astrocytic endothelin-1 overexpression altered lipid metabolism products such as glycerol phosphatidylcholine,sphingomyelin,and phosphatidic acid.Overall,this study demonstrates that astrocytic endothelin-1 overexpression can impair hippocampal neurogenesis and that it is correlated with lipid metabolism in poststroke cognitive dysfunction.
基金supported by the Projects of the National Key R&D Program of China,Nos.2021YFC2400803(to YO),2021YFC2400801(to YQ)the National Natural Science Foundation of China,Nos.82002290(to YQ),82072452(to YO),82272475(to YO)+5 种基金the Young Elite Scientist Sponsorship Program by Cast,No.YESS20200153(to YQ)the Sino-German Mobility Programme,No.M-0699(to YQ)the Excellent Youth Cultivation Program of Shanghai Sixth People’s Hospital,No.ynyq202201(to YQ)the Shanghai Sailing Program,No.20YF1436000(to YQ)the Medical Engineering Co-Project of University of Shanghai for Science and Technology,10-22-310-520(to YO)a grant from Shanghai Municipal Health Commission,No.202040399(to YO).
文摘Diabetic peripheral neuropathy is a common complication of diabetes mellitus.Elucidating the pathophysiological metabolic mechanism impels the generation of ideal therapies.However,existing limited treatments for diabetic peripheral neuropathy expose the urgent need for cell metabolism research.Given the lack of comprehensive understanding of energy metabolism changes and related signaling pathways in diabetic peripheral neuropathy,it is essential to explore energy changes and metabolic changes in diabetic peripheral neuropathy to develop suitable treatment methods.This review summarizes the pathophysiological mechanism of diabetic peripheral neuropathy from the perspective of cellular metabolism and the specific interventions for different metabolic pathways to develop effective treatment methods.Various metabolic mechanisms(e.g.,polyol,hexosamine,protein kinase C pathway)are associated with diabetic peripheral neuropathy,and researchers are looking for more effective treatments through these pathways.
基金funded by the National Natural Science Foundation of China (31871546)China Postdoctoral Science Foundation (2022M720418)。
文摘Leaf senescence is an orderly and highly coordinated process,and finely regulated by ethylene and nitrogen(N),ultimately affecting grain yield and nitrogen-use efficiency(NUE).However,the underlying regulatory mechanisms on the crosstalk between ethylene-and N-regulated leaf senescence remain a mystery in maize.In this study,ethylene biosynthesis gene ZmACS7 overexpressing(OE-ZmACS7)plants were used to study the role of ethylene regulating leaf senescence in response to N deficiency,and they exhibited the premature leaf senescence accompanied by increased ethylene release,decreased chlorophyll content and F_v/F_m ratio,and accelerated chloroplast degradation.Then,we investigated the dynamics changes of transcriptome reprogramming underlying ethylene-accelerated leaf senescence in response to N deficiency.The differentially expressed genes(DEGs)involved in chlorophyll biosynthesis were significantly down-regulated,while DEGs involved in chlorophyll degradation and autophagy processes were significantly up-regulated,especially in OE-ZmACS7 plants in response to N deficiency.A gene regulatory network(GRN)was predicted during ethylene-accelerated leaf senescence in response to N deficiency.Three transcription factors(TFs)ZmHSF4,Zmb HLH106,and ZmEREB147 were identified as the key regulatory genes,which targeted chlorophyll biosynthesis gene ZmLES22,chlorophyll degradation gene ZmNYC1,and autophagy-related gene ZmATG5,respectively.Furthermore,ethylene signaling key genes might be located upstream of these TFs,generating the signaling cascade networks during ethylene-accelerated leaf senescence in response to N deficiency.Collectively,these findings improve our molecular knowledge of ethylene-accelerated maize leaf senescence in response to N deficiency,which is promising to improve NUE by manipulating the progress of leaf senescence in maize.
