为了解决海量数据的高速传输问题,本文以AXIe(Advanced TCA Extensions for Instrumentation)总线为传输架构,重点设计数据的高速缓存和传输接口,并设计时间交织数据采集模块完成AXIe数据采集传输接口验证.通过两片ADC实现时间交织数据...为了解决海量数据的高速传输问题,本文以AXIe(Advanced TCA Extensions for Instrumentation)总线为传输架构,重点设计数据的高速缓存和传输接口,并设计时间交织数据采集模块完成AXIe数据采集传输接口验证.通过两片ADC实现时间交织数据采样功能,将DDR3作为数据的深存储单元,采用PCI Express实现数据高速传输.在FPGA上完成设计,使用ILA嵌入式逻辑分析仪进行功能验证.结果表明,该设计能很好地实现交织采样功能,完成基于AXIe总线的数据传输.展开更多
Intracerebral hemorrhage is the most dangerous subtype of stroke,characterized by high mortality and morbidity rates,and frequently leads to significant secondary white matter injury.In recent decades,studies have rev...Intracerebral hemorrhage is the most dangerous subtype of stroke,characterized by high mortality and morbidity rates,and frequently leads to significant secondary white matter injury.In recent decades,studies have revealed that gut microbiota can communicate bidirectionally with the brain through the gut microbiota–brain axis.This axis indicates that gut microbiota is closely related to the development and prognosis of intracerebral hemorrhage and its associated secondary white matter injury.The NACHT,LRR,and pyrin domain-containing protein 3(NLRP3)inflammasome plays a crucial role in this context.This review summarizes the dysbiosis of gut microbiota following intracerebral hemorrhage and explores the mechanisms by which this imbalance may promote the activation of the NLRP3 inflammasome.These mechanisms include metabolic pathways(involving short-chain fatty acids,lipopolysaccharides,lactic acid,bile acids,trimethylamine-N-oxide,and tryptophan),neural pathways(such as the vagus nerve and sympathetic nerve),and immune pathways(involving microglia and T cells).We then discuss the relationship between the activated NLRP3 inflammasome and secondary white matter injury after intracerebral hemorrhage.The activation of the NLRP3 inflammasome can exacerbate secondary white matter injury by disrupting the blood–brain barrier,inducing neuroinflammation,and interfering with nerve regeneration.Finally,we outline potential treatment strategies for intracerebral hemorrhage and its secondary white matter injury.Our review highlights the critical role of the gut microbiota–brain axis and the NLRP3 inflammasome in white matter injury following intracerebral hemorrhage,paving the way for exploring potential therapeutic approaches.展开更多
Short-chain fatty acids,metabolites produced by the fermentation of dietary fiber by gut microbiota,have garnered significant attention due to their correlation with neurodegenerative diseases,particularly Parkinson’...Short-chain fatty acids,metabolites produced by the fermentation of dietary fiber by gut microbiota,have garnered significant attention due to their correlation with neurodegenerative diseases,particularly Parkinson’s disease.In this review,we summarize the changes in short-chain fatty acid levels and the abundance of short-chain fatty acid-producing bacteria in various samples from patients with Parkinson’s disease,highlighting the critical role of gut homeostasis imbalance in the pathogenesis and progression of the disease.Focusing on the nervous system,we discuss the molecular mechanisms by which short-chain fatty acids influence the homeostasis of both the enteric nervous system and the central nervous system.We identify key processes,including the activation of G protein-coupled receptors and the inhibition of histone deacetylases by short-chain fatty acids.Importantly,structural or functional disruptions in the enteric nervous system mediated by these fatty acids may lead to abnormalα-synuclein expression and gastrointestinal dysmotility,which could serve as an initiating event in Parkinson’s disease.Furthermore,we propose that short-chain fatty acids help establish communication between the enteric nervous system and the central nervous system via the vagal nerve,immune circulation,and endocrine signaling.This communication may shed light on their potential role in the transmission ofα-synuclein from the gut to the brain.Finally,we elucidate novel treatment strategies for Parkinson’s disease that target short-chain fatty acids and examine the challenges associated with translating short-chain fatty acid-based therapies into clinical practice.In conclusion,this review emphasizes the pivotal role of short-chain fatty acids in regulating gut-brain axis integrity and their significance in the pathogenesis of Parkinson’s disease from the perspective of the nervous system.Moreover,it highlights the potential value of short-chain fatty acids in early intervention for Parkinson’s disease.Future research into the molecular mechanisms of short-chain fatty acids and their synergistic interactions with other gut metabolites is likely to advance the clinical translation of innovative short-chain fatty acid-based therapies for Parkinson’s disease.展开更多
The gut microbiota has emerged as a pivotal regulator of host lipid metabolism and energy homeostasis.A growing body of evidence reveals that variations in the composition and metabolic activity of intestinal microbes...The gut microbiota has emerged as a pivotal regulator of host lipid metabolism and energy homeostasis.A growing body of evidence reveals that variations in the composition and metabolic activity of intestinal microbes are closely associated with differences in adipose tissue deposition across species.Notably,increased abundance of Firmicutes and a reduced proportion of Bacteroidetes and butyrate-producing bacteria have been linked to enhanced fat accumulation.Key microbial metabolites such as short-chain fatty acids(SCFAs)influence lipid metabolism through multiple pathways,including the activation of GPR41/43 receptors,modulation of the bile acid–FXR/TGR5 axis,and regulation of hepatic lipogenesis.Additionally,the gut–brain axis plays a critical role in controlling feeding behavior via neuroendocrine signaling.This review summarizes current advances in understanding the roles of dominant bacterial phyla and beneficial genera—including Clostridium butyricum and Faecalibacterium prausnitzii—in fat metabolism.We further explore the mechanisms by which gut microbiota modulate lipid synthesis and catabolism through SCFA production,bile acid signaling,and AMPK/PPAR-related pathways.These insights highlight the potential of microbiota-targeted strategies to restore lipid metabolic balance,offering novel opportunities for applications in health management,nutritional interventions,and microbial therapeutics.展开更多
Early life stress correlates with a higher prevalence of neurological disorders,including autism,attention-deficit/hyperactivity disorder,schizophrenia,depression,and Parkinson's disease.These conditions,primarily...Early life stress correlates with a higher prevalence of neurological disorders,including autism,attention-deficit/hyperactivity disorder,schizophrenia,depression,and Parkinson's disease.These conditions,primarily involving abnormal development and damage of the dopaminergic system,pose significant public health challenges.Microglia,as the primary immune cells in the brain,are crucial in regulating neuronal circuit development and survival.From the embryonic stage to adulthood,microglia exhibit stage-specific gene expression profiles,transcriptome characteristics,and functional phenotypes,enhancing the susceptibility to early life stress.However,the role of microglia in mediating dopaminergic system disorders under early life stress conditions remains poorly understood.This review presents an up-to-date overview of preclinical studies elucidating the impact of early life stress on microglia,leading to dopaminergic system disorders,along with the underlying mechanisms and therapeutic potential for neurodegenerative and neurodevelopmental conditions.Impaired microglial activity damages dopaminergic neurons by diminishing neurotrophic support(e.g.,insulin-like growth factor-1)and hinders dopaminergic axon growth through defective phagocytosis and synaptic pruning.Furthermore,blunted microglial immunoreactivity suppresses striatal dopaminergic circuit development and reduces neuronal transmission.Furthermore,inflammation and oxidative stress induced by activated microglia can directly damage dopaminergic neurons,inhibiting dopamine synthesis,reuptake,and receptor activity.Enhanced microglial phagocytosis inhibits dopamine axon extension.These long-lasting effects of microglial perturbations may be driven by early life stress–induced epigenetic reprogramming of microglia.Indirectly,early life stress may influence microglial function through various pathways,such as astrocytic activation,the hypothalamic–pituitary–adrenal axis,the gut–brain axis,and maternal immune signaling.Finally,various therapeutic strategies and molecular mechanisms for targeting microglia to restore the dopaminergic system were summarized and discussed.These strategies include classical antidepressants and antipsychotics,antibiotics and anti-inflammatory agents,and herbal-derived medicine.Further investigations combining pharmacological interventions and genetic strategies are essential to elucidate the causal role of microglial phenotypic and functional perturbations in the dopaminergic system disrupted by early life stress.展开更多
Acute pancreatitis(AP)is sudden inflammation of the pancreas,which can lead to multiple organ dysfunction in severe cases.Hypertriglyceridemia(HTG)is the third most common cause.In recent years,HTG-induced AP(HTG-AP)h...Acute pancreatitis(AP)is sudden inflammation of the pancreas,which can lead to multiple organ dysfunction in severe cases.Hypertriglyceridemia(HTG)is the third most common cause.In recent years,HTG-induced AP(HTG-AP)has garnered increasing attention.Compared to AP caused by other causes,HTG-AP often has a more subtle onset but is more likely to progress to a severe,critical illness that poses a serious threat to a patient’s life and health.Research suggests a potential connection between the gut microbiota and AP,which could be mediated by bacterial metabolites,immune cells,and inflammatory factors.This is supported by observations of microbial imbalance and higher intestinal permeability in patients with AP.In addition,studies have shown that HTG-induced changes in gut microbiota can worsen AP by negatively impacting the host metabolism,immune response,and function of the intestinal barrier.In this review,we summarize recent clinical and animal studies on the role and mechanism of gut microbiota in the severity of AP aggravated by HTG.The application prospects of the newly proposed microbial-host-isozyme concept are summarized,focusing on its potential for the precision diagnosis and treatment of HTG-AP through gut microbiota regulation.展开更多
Background:Immunosuppression compromises the host’s ability to combat pathogens,thereby increasing susceptibility to multisystem disorders.However,safe and effective curative treatments for this condition are current...Background:Immunosuppression compromises the host’s ability to combat pathogens,thereby increasing susceptibility to multisystem disorders.However,safe and effective curative treatments for this condition are currently lacking.Modulating the gut microbiota and their metabolites represents a promising therapeutic strategy.Notably,the Chinese herbal compound Yunzhi Guben Gao(YZG)has demonstrated multi-target immunomodulatory potential.Methods:A mouse model of dexamethasone-induced immunosuppression was employed to evaluate the effects of YZG.Immune organ indices(thymus,spleen),serum cytokine levels(IL-2,TNF-α),mucosal immunity markers(pulmonary/colonic SIgA),gut microbiota structure,and short-chain fatty acids(SCFAs)abundance were evaluated.Key microbial genera and metabolites were identified via Spearman correlation analysis.Pseudo-germ-free model mice established via quadruple antibiotic treatment combined with isovaleric acid intervention were employed to evaluate whether YZG efficacy depends on the intestinal microbiota and its metabolites,and whether its intrinsic mechanisms involve the promotion of isovaleric acid production.Results:YZG intervention ameliorated systemic and mucosal immune function in immunosuppressed mice.Mechanistically,YZG remodeled gut microbiota structure and significantly increased SCFAs levels.Notably,the abundance of the genus Ligilactobacillus exhibited the strongest positive correlation with isovaleric acid levels.Ligilactobacillus abundance was also positively correlated with immune-enhancing parameters and negatively correlated with the proinflammatory cytokine TNF-α,suggesting that Ligilactobacillus plays a pivotal role in the YZG regulatory network.Experiments using pseudo-germ-free mice and isovaleric acid intervention further demonstrated that the immunoprotective effects of YZG are closely related to intestinal microbiota remodeling and increased isovaleric acid production.Conclusion:YZG alleviates immunosuppression through multiple mechanisms,primarily involving the enrichment of the probiotic genus Ligilactobacillus and the consequent increase in isovaleric acid production.This process coordinately modulates mucosal immunity,cytokine networks,and immune organ function.The elucidation of this“microbiota-metabolite-immunity”axis provides both a pharmacological basis for the clinical application of YZG and novel immune-restorative strategies targeting gut microecological regulation.展开更多
BACKGROUND Organ transplantation has emerged as a globally prevalent therapeutic modality for end-stage organ failure,yet the post-transplantation trajectory is increasingly complicated by a spectrum of metabolic sequ...BACKGROUND Organ transplantation has emerged as a globally prevalent therapeutic modality for end-stage organ failure,yet the post-transplantation trajectory is increasingly complicated by a spectrum of metabolic sequelae,with obesity emerging as a critical clinical challenge.AIM To systematically review the multifactorial mechanisms underlying obesity following organ transplantation and to integrate evidence from pharmacological,behavioral,and molecular perspectives,thereby providing a foundation for targeted interventions.METHODS We conducted a systematic search in PubMed and Web of Science for literature published from 2020 to 15 July 2025.The search strategy incorporated terms including“obesity”,“overweight”and“post organ transplantation”.Only randomized controlled trials,meta-analyses,and systematic reviews were included.Non-empirical publications and irrelevant studies were excluded.Data extraction and quality assessment were performed by two independent reviewers,with disagreements resolved by a third researcher.RESULTS A total of 1457 articles were initially identified,of which 146 met the inclusion criteria.These studies encompassed liver,kidney,heart,and lung transplant recipients.Key findings indicate that immunosuppressive drugs-especially corticosteroids and calcineurin inhibitors-promote hyperphagia,insulin resistance,and dyslipidemia.Post-transplant sedentary behavior and hypercaloric diets further contribute to positive energy balance.At the molecular level,immunosuppressants disrupt adipokine signaling(e.g.,leptin and adiponectin),induce inflammatory and oxidative stress responses,and activate adipogenic pathways leading to lipid accumulation.CONCLUSION Post-transplant obesity arises from a complex interplay of pharmacological,behavioral,and molecular factors.A multidisciplinary approach-incorporating pharmacological modification,nutritional management,physical activity,and molecular-targeted therapies-is essential to mitigate obesity and improve transplant outcomes.Further large-scale and mechanistic studies are warranted to establish evidence-based preventive and treatment strategies.展开更多
The mechanisms leading to neurological and neurodegenerative diseases are not completely known,and new,more effective,therapeutic treatments are necessary for most neurological pathologies.The treatment of neurologica...The mechanisms leading to neurological and neurodegenerative diseases are not completely known,and new,more effective,therapeutic treatments are necessary for most neurological pathologies.The treatment of neurological and neurodegenerative diseases is complicated due to the blood-brain barrier,which makes it difficult for drugs to access the brain areas in which they must act to improve the pathology.A tool that can help to overcome this difficulty is the use of extracellular vesicles,which can easily cross the blood-brain barrier.The extracellular vesicles are considered a main way of communication between the brain and the rest of the body,with important implications for the physiopathology and therapy of neurological diseases.In recent years,the involvement of microbiota in many neurological pathologies,as well as its possible therapeutic role,has also become evident.A key mediator in the pathologic and beneficial effects of microbiota seems to be the bacterial extracellular vesicles.There is an important communication between the brain and the intestinal microbiota(the gut-brain axis),by which the microbiota influences brain function,impacts on mental health,and plays a role in different neurological and neurodegenerative diseases.The identification of the mechanisms involved in this gut-brain axis is essential to understanding the mechanisms of neurological pathologies and to developing more effective treatments for these diseases.Bacterial extracellular vesicles would play a relevant role in these processes.This review compiles the recent information and evidence on the role of bacterial extracellular vesicles in brain pathologies and on the therapeutic utility of bacterial extracellular vesicles in neurological and neurodegenerative diseases.One advantage of bacterial extracellular vesicles compared to extracellular vesicles derived from other cell types,such as stem cells,is that bacterial extracellular vesicles are generally easier to produce and modify.Bacterial extracellular vesicles may be easily modified to target a specific pathology and/or to enhance its therapeutic efficacy.Although the studies are still scarce,they open a wide field of possibilities for future studies,which will lead to a deeper understanding of the role of microbiota and bacterial extracellular vesicles in neurological pathologies and the underlying mechanisms,as well as to the development of new treatments based on the use of bacterial extracellular vesicles in neurological diseases.展开更多
Acute kidney injury(AKI)is a critical condition with limited effective therapies.Akkermansia muciniphila(A.muciniphila)is a probiotic with multiple beneficial effects,including the regulation of epithelial cell tight ...Acute kidney injury(AKI)is a critical condition with limited effective therapies.Akkermansia muciniphila(A.muciniphila)is a probiotic with multiple beneficial effects,including the regulation of epithelial cell tight junctions.Since renal pathophysiology is associated with gut barrier integrity,we hypothesized that A.muciniphila may have preventive effects on AKI.We established a lipopolysaccharide(LPS)-induced AKI mouse model to evaluate the effects of A.muciniphila.Our findings showed that pretreatment with A.muciniphila significantly attenuated kidney injury,as evidenced by reduced serum creatinine and urea nitrogen levels,alongside decreased tubular necrosis and apoptosis.A.muciniphila preserved intestinal barrier integrity and induced marked shifts in gut microbial ecology and the metabolome.A.muciniphila notably induced an increase in the relative abundance of the phylum Proteobacteria while decreasing in that of the phylum Bacteroidetes.At the genus level,Prevotella,Faecalibaculum,Moraxella,and Lactobacillus were more abundant in A.muciniphilapretreated mice.Metabolomic analysis revealed that A.muciniphila altered the gut metabolome,with changes involving pathways such as tyrosine metabolism,alanine/aspartate/glutamate homeostasis,cancer-related carbon flux,and GABAergic synaptic signaling.In conclusion,our findings indicate that A.muciniphila exerts renoprotective effects by modulating the gut-kidney axis,thereby establishing a foundation for future studies to explore the connection between gut microbiota and AKI.展开更多
BACKGROUND Post-stroke depression(PSD)is associated with hypothalamic-pituitary-adrenal(HPA)axis dysfunction and neurotransmitter deficits.Selective serotonin reuptake inhibitors(SSRIs)are commonly used,but their effi...BACKGROUND Post-stroke depression(PSD)is associated with hypothalamic-pituitary-adrenal(HPA)axis dysfunction and neurotransmitter deficits.Selective serotonin reuptake inhibitors(SSRIs)are commonly used,but their efficacy is limited.This study investigated whether combining SSRIs with traditional Chinese medicine(TCM)Free San could enhance their therapeutic effects.AIM To evaluate the clinical efficacy and safety of combining SSRIs with Free San in treating PSD,and to assess its impact on HPA axis function.METHODS Ninety-two patients with PSD were enrolled and randomly divided into control groups(n=46)and study groups(n=46).The control group received the SSRI paroxetine alone,whereas the study group received paroxetine combined with Free San for 4 weeks.Hamilton Depression Scale and TCM syndrome scores were assessed before and after treatment.Serum serotonin,norepinephrine,cortisol,cor-ticotropin-releasing hormone,and adrenocorticotropic hormone were measured.The treatment responses and adverse reactions were recorded.RESULTS After treatment,the Hamilton Depression Scale and TCM syndrome scores were significantly lower in the study group than in the control group(P<0.05).Serum serotonin and norepinephrine levels were significantly higher in the study group than in the control group,whereas cortisol,corticotropin-releasing hormone,and adrenocorticotropic hormone levels were significantly lower(P<0.05).The total efficacy rates were 84.78%and 65.22%in the study and control groups,respectively(P<0.05).No significant differences in adverse reactions were observed between the two groups(P>0.05).CONCLUSION Combining SSRIs with Free San can enhance therapeutic efficacy,improve depressive symptoms,and regulate HPA axis function in patients with PSD with good safety and clinical application value.展开更多
Background Excessive abdominal fat in broilers not only reduces feed efficiency and increases processing costs but also raises environmental concerns.This pathological overaccumulation results from complex metabolic d...Background Excessive abdominal fat in broilers not only reduces feed efficiency and increases processing costs but also raises environmental concerns.This pathological overaccumulation results from complex metabolic dysregulation across multiple organs.While current research largely centers on adipogenesis within adipose tissue,a comprehensive understanding of the cross-organ regulatory factors influencing this process remains elusive.Results Here,we employed a high-fat diet(HFD)model and multi-omics approaches to investigate cross-organ regulatory mechanisms underlying abdominal fat deposition in broilers.Our results demonstrated that HFD not only promoted fat accumulation but also altered meat quality traits.Through 16S rRNA amplicon sequencing,we identified significant gut microbiota dysbiosis in HFD-fed chickens,manifested by an increased abundance of Lactobacillus and a decreased abundance of Enterococcus.However,jejunal microbiota transplantation from HFD donors did not induce abdominal fat deposition in recipient chickens.Metabolomic profiling revealed that HFD elevated the level of succinic acid,a metabolite positively correlated with Lactobacillus abundance and potentially generated by Lactobacillus.This increase in succinic acid(SA)further triggered metabolic inflammation response in both jejunal tissue and serum.In vivo validation established succinic acid as a key inflammatory mediator facilitating HFD-induced cross-organ communication between the jejunum and abdominal adipose tissue,enhancing intestinal lipid uptake and subsequent abdominal fat deposition.Bulk and single-nucleus RNA sequencing(snRNA-seq)revealed that HFD induced macrophage population expansion and intensified adipocyte-macrophage crosstalk.Adipocyte-macrophage co-culture systems further elucidated that macrophages are an indispensable factor in succinic acid-induced fat deposition.Conclusion This study delineates a succinic acid-driven"gut-fat axis"governing abdominal fat deposition in broilers,integrating gut microbiota dysbiosis and macrophage-mediated inflammatory adipogenesis.By identifying succinic acid as a cross-organ signaling molecule that enhances lipid absorption and activates macrophage-dependent adipogenesis,we establish systemic metabolic-immune crosstalk as a pivotal regulatory mechanism.These findings redefine fat deposition as a process extending beyond adipose-centric models,advancing multi-omics-guided strategies for sustainable poultry production.展开更多
基金supported by the Guangdong Basic and Applied Basic Research Foundation,No.2023A1515030045(to HS)Presidential Foundation of Zhujiang Hospital of Southern Medical University,No.yzjj2022ms4(to HS)。
文摘Intracerebral hemorrhage is the most dangerous subtype of stroke,characterized by high mortality and morbidity rates,and frequently leads to significant secondary white matter injury.In recent decades,studies have revealed that gut microbiota can communicate bidirectionally with the brain through the gut microbiota–brain axis.This axis indicates that gut microbiota is closely related to the development and prognosis of intracerebral hemorrhage and its associated secondary white matter injury.The NACHT,LRR,and pyrin domain-containing protein 3(NLRP3)inflammasome plays a crucial role in this context.This review summarizes the dysbiosis of gut microbiota following intracerebral hemorrhage and explores the mechanisms by which this imbalance may promote the activation of the NLRP3 inflammasome.These mechanisms include metabolic pathways(involving short-chain fatty acids,lipopolysaccharides,lactic acid,bile acids,trimethylamine-N-oxide,and tryptophan),neural pathways(such as the vagus nerve and sympathetic nerve),and immune pathways(involving microglia and T cells).We then discuss the relationship between the activated NLRP3 inflammasome and secondary white matter injury after intracerebral hemorrhage.The activation of the NLRP3 inflammasome can exacerbate secondary white matter injury by disrupting the blood–brain barrier,inducing neuroinflammation,and interfering with nerve regeneration.Finally,we outline potential treatment strategies for intracerebral hemorrhage and its secondary white matter injury.Our review highlights the critical role of the gut microbiota–brain axis and the NLRP3 inflammasome in white matter injury following intracerebral hemorrhage,paving the way for exploring potential therapeutic approaches.
基金supported by the National Key R&D Program of China,No.2021YFC2501200(to PC).
文摘Short-chain fatty acids,metabolites produced by the fermentation of dietary fiber by gut microbiota,have garnered significant attention due to their correlation with neurodegenerative diseases,particularly Parkinson’s disease.In this review,we summarize the changes in short-chain fatty acid levels and the abundance of short-chain fatty acid-producing bacteria in various samples from patients with Parkinson’s disease,highlighting the critical role of gut homeostasis imbalance in the pathogenesis and progression of the disease.Focusing on the nervous system,we discuss the molecular mechanisms by which short-chain fatty acids influence the homeostasis of both the enteric nervous system and the central nervous system.We identify key processes,including the activation of G protein-coupled receptors and the inhibition of histone deacetylases by short-chain fatty acids.Importantly,structural or functional disruptions in the enteric nervous system mediated by these fatty acids may lead to abnormalα-synuclein expression and gastrointestinal dysmotility,which could serve as an initiating event in Parkinson’s disease.Furthermore,we propose that short-chain fatty acids help establish communication between the enteric nervous system and the central nervous system via the vagal nerve,immune circulation,and endocrine signaling.This communication may shed light on their potential role in the transmission ofα-synuclein from the gut to the brain.Finally,we elucidate novel treatment strategies for Parkinson’s disease that target short-chain fatty acids and examine the challenges associated with translating short-chain fatty acid-based therapies into clinical practice.In conclusion,this review emphasizes the pivotal role of short-chain fatty acids in regulating gut-brain axis integrity and their significance in the pathogenesis of Parkinson’s disease from the perspective of the nervous system.Moreover,it highlights the potential value of short-chain fatty acids in early intervention for Parkinson’s disease.Future research into the molecular mechanisms of short-chain fatty acids and their synergistic interactions with other gut metabolites is likely to advance the clinical translation of innovative short-chain fatty acid-based therapies for Parkinson’s disease.
基金supported by National Key R&D Program of China(2024YFF1001500)Sichuan Science and Technology Program(2021YFYZ0007,2024NSFSC0298,SCCXTD-2025-8)+1 种基金China Agriculture Research System(CARS-35)National Natural Science Foundation of China(32421005)。
文摘The gut microbiota has emerged as a pivotal regulator of host lipid metabolism and energy homeostasis.A growing body of evidence reveals that variations in the composition and metabolic activity of intestinal microbes are closely associated with differences in adipose tissue deposition across species.Notably,increased abundance of Firmicutes and a reduced proportion of Bacteroidetes and butyrate-producing bacteria have been linked to enhanced fat accumulation.Key microbial metabolites such as short-chain fatty acids(SCFAs)influence lipid metabolism through multiple pathways,including the activation of GPR41/43 receptors,modulation of the bile acid–FXR/TGR5 axis,and regulation of hepatic lipogenesis.Additionally,the gut–brain axis plays a critical role in controlling feeding behavior via neuroendocrine signaling.This review summarizes current advances in understanding the roles of dominant bacterial phyla and beneficial genera—including Clostridium butyricum and Faecalibacterium prausnitzii—in fat metabolism.We further explore the mechanisms by which gut microbiota modulate lipid synthesis and catabolism through SCFA production,bile acid signaling,and AMPK/PPAR-related pathways.These insights highlight the potential of microbiota-targeted strategies to restore lipid metabolic balance,offering novel opportunities for applications in health management,nutritional interventions,and microbial therapeutics.
基金supported by the National Natural Science Foundation of China,Nos.82304990(to NY),81973748(to JC),82174278(to JC)the National Key R&D Program of China,No.2023YFE0209500(to JC)+4 种基金China Postdoctoral Science Foundation,No.2023M732380(to NY)Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine,No.202102010014(to JC)Huang Zhendong Research Fund for Traditional Chinese Medicine of Jinan University,No.201911(to JC)National Innovation and Entrepreneurship Training Program for Undergraduates in China,No.202310559128(to NY and QM)Innovation and Entrepreneurship Training Program for Undergraduates at Jinan University,Nos.CX24380,CX24381(both to NY and QM)。
文摘Early life stress correlates with a higher prevalence of neurological disorders,including autism,attention-deficit/hyperactivity disorder,schizophrenia,depression,and Parkinson's disease.These conditions,primarily involving abnormal development and damage of the dopaminergic system,pose significant public health challenges.Microglia,as the primary immune cells in the brain,are crucial in regulating neuronal circuit development and survival.From the embryonic stage to adulthood,microglia exhibit stage-specific gene expression profiles,transcriptome characteristics,and functional phenotypes,enhancing the susceptibility to early life stress.However,the role of microglia in mediating dopaminergic system disorders under early life stress conditions remains poorly understood.This review presents an up-to-date overview of preclinical studies elucidating the impact of early life stress on microglia,leading to dopaminergic system disorders,along with the underlying mechanisms and therapeutic potential for neurodegenerative and neurodevelopmental conditions.Impaired microglial activity damages dopaminergic neurons by diminishing neurotrophic support(e.g.,insulin-like growth factor-1)and hinders dopaminergic axon growth through defective phagocytosis and synaptic pruning.Furthermore,blunted microglial immunoreactivity suppresses striatal dopaminergic circuit development and reduces neuronal transmission.Furthermore,inflammation and oxidative stress induced by activated microglia can directly damage dopaminergic neurons,inhibiting dopamine synthesis,reuptake,and receptor activity.Enhanced microglial phagocytosis inhibits dopamine axon extension.These long-lasting effects of microglial perturbations may be driven by early life stress–induced epigenetic reprogramming of microglia.Indirectly,early life stress may influence microglial function through various pathways,such as astrocytic activation,the hypothalamic–pituitary–adrenal axis,the gut–brain axis,and maternal immune signaling.Finally,various therapeutic strategies and molecular mechanisms for targeting microglia to restore the dopaminergic system were summarized and discussed.These strategies include classical antidepressants and antipsychotics,antibiotics and anti-inflammatory agents,and herbal-derived medicine.Further investigations combining pharmacological interventions and genetic strategies are essential to elucidate the causal role of microglial phenotypic and functional perturbations in the dopaminergic system disrupted by early life stress.
基金Supported by the Innovation Foundation for Doctor Dissertation of Northwestern Polytechnical University,No.CX2023021.
文摘Acute pancreatitis(AP)is sudden inflammation of the pancreas,which can lead to multiple organ dysfunction in severe cases.Hypertriglyceridemia(HTG)is the third most common cause.In recent years,HTG-induced AP(HTG-AP)has garnered increasing attention.Compared to AP caused by other causes,HTG-AP often has a more subtle onset but is more likely to progress to a severe,critical illness that poses a serious threat to a patient’s life and health.Research suggests a potential connection between the gut microbiota and AP,which could be mediated by bacterial metabolites,immune cells,and inflammatory factors.This is supported by observations of microbial imbalance and higher intestinal permeability in patients with AP.In addition,studies have shown that HTG-induced changes in gut microbiota can worsen AP by negatively impacting the host metabolism,immune response,and function of the intestinal barrier.In this review,we summarize recent clinical and animal studies on the role and mechanism of gut microbiota in the severity of AP aggravated by HTG.The application prospects of the newly proposed microbial-host-isozyme concept are summarized,focusing on its potential for the precision diagnosis and treatment of HTG-AP through gut microbiota regulation.
基金supported by the Research Fund Project of the Education Department of Yunnan Province(No.2023Y0464)Research Project for Scientific Research Funds of Provincial Research Institutions in Heilongjiang Province(No.CZBZ2025ZR003).
文摘Background:Immunosuppression compromises the host’s ability to combat pathogens,thereby increasing susceptibility to multisystem disorders.However,safe and effective curative treatments for this condition are currently lacking.Modulating the gut microbiota and their metabolites represents a promising therapeutic strategy.Notably,the Chinese herbal compound Yunzhi Guben Gao(YZG)has demonstrated multi-target immunomodulatory potential.Methods:A mouse model of dexamethasone-induced immunosuppression was employed to evaluate the effects of YZG.Immune organ indices(thymus,spleen),serum cytokine levels(IL-2,TNF-α),mucosal immunity markers(pulmonary/colonic SIgA),gut microbiota structure,and short-chain fatty acids(SCFAs)abundance were evaluated.Key microbial genera and metabolites were identified via Spearman correlation analysis.Pseudo-germ-free model mice established via quadruple antibiotic treatment combined with isovaleric acid intervention were employed to evaluate whether YZG efficacy depends on the intestinal microbiota and its metabolites,and whether its intrinsic mechanisms involve the promotion of isovaleric acid production.Results:YZG intervention ameliorated systemic and mucosal immune function in immunosuppressed mice.Mechanistically,YZG remodeled gut microbiota structure and significantly increased SCFAs levels.Notably,the abundance of the genus Ligilactobacillus exhibited the strongest positive correlation with isovaleric acid levels.Ligilactobacillus abundance was also positively correlated with immune-enhancing parameters and negatively correlated with the proinflammatory cytokine TNF-α,suggesting that Ligilactobacillus plays a pivotal role in the YZG regulatory network.Experiments using pseudo-germ-free mice and isovaleric acid intervention further demonstrated that the immunoprotective effects of YZG are closely related to intestinal microbiota remodeling and increased isovaleric acid production.Conclusion:YZG alleviates immunosuppression through multiple mechanisms,primarily involving the enrichment of the probiotic genus Ligilactobacillus and the consequent increase in isovaleric acid production.This process coordinately modulates mucosal immunity,cytokine networks,and immune organ function.The elucidation of this“microbiota-metabolite-immunity”axis provides both a pharmacological basis for the clinical application of YZG and novel immune-restorative strategies targeting gut microecological regulation.
基金Supported by the National Natural Science Foundation of China,No.82305376the Youth Talent Support Project of the China Acupuncture and Moxibustion Association,No.2024-2026ZGZJXH-QNRC005+2 种基金the 2024 Jiangsu Province Youth Science and Technology Talent Support Project,No.JSTJ-2024-3802025 Jiangsu Provincial Science and Technology Think Tank Program Project,No.JSKX0125035and 2025 College Student Innovation Training Program Project,No.X202510315373。
文摘BACKGROUND Organ transplantation has emerged as a globally prevalent therapeutic modality for end-stage organ failure,yet the post-transplantation trajectory is increasingly complicated by a spectrum of metabolic sequelae,with obesity emerging as a critical clinical challenge.AIM To systematically review the multifactorial mechanisms underlying obesity following organ transplantation and to integrate evidence from pharmacological,behavioral,and molecular perspectives,thereby providing a foundation for targeted interventions.METHODS We conducted a systematic search in PubMed and Web of Science for literature published from 2020 to 15 July 2025.The search strategy incorporated terms including“obesity”,“overweight”and“post organ transplantation”.Only randomized controlled trials,meta-analyses,and systematic reviews were included.Non-empirical publications and irrelevant studies were excluded.Data extraction and quality assessment were performed by two independent reviewers,with disagreements resolved by a third researcher.RESULTS A total of 1457 articles were initially identified,of which 146 met the inclusion criteria.These studies encompassed liver,kidney,heart,and lung transplant recipients.Key findings indicate that immunosuppressive drugs-especially corticosteroids and calcineurin inhibitors-promote hyperphagia,insulin resistance,and dyslipidemia.Post-transplant sedentary behavior and hypercaloric diets further contribute to positive energy balance.At the molecular level,immunosuppressants disrupt adipokine signaling(e.g.,leptin and adiponectin),induce inflammatory and oxidative stress responses,and activate adipogenic pathways leading to lipid accumulation.CONCLUSION Post-transplant obesity arises from a complex interplay of pharmacological,behavioral,and molecular factors.A multidisciplinary approach-incorporating pharmacological modification,nutritional management,physical activity,and molecular-targeted therapies-is essential to mitigate obesity and improve transplant outcomes.Further large-scale and mechanistic studies are warranted to establish evidence-based preventive and treatment strategies.
基金funded by the Ministerio de Ciencia e Innovación Spain(PID2020-113388RB-I00,AEI/10.13039/501100011033)Consellería de Innovación,Universidades,Ciencia y Sociedad Digital,Generalitat Valenciana(CIPROM/2021/082)+2 种基金co-funded with European Regional Development Funds(ERDF)(PID2020-113388RB-I00,and CIPROM/2021/082)PID2022-136874OB-C33 from MCIN/AEI/10.13039/501100011033by the European Union NextGenerationEU/PRTR(to VF).
文摘The mechanisms leading to neurological and neurodegenerative diseases are not completely known,and new,more effective,therapeutic treatments are necessary for most neurological pathologies.The treatment of neurological and neurodegenerative diseases is complicated due to the blood-brain barrier,which makes it difficult for drugs to access the brain areas in which they must act to improve the pathology.A tool that can help to overcome this difficulty is the use of extracellular vesicles,which can easily cross the blood-brain barrier.The extracellular vesicles are considered a main way of communication between the brain and the rest of the body,with important implications for the physiopathology and therapy of neurological diseases.In recent years,the involvement of microbiota in many neurological pathologies,as well as its possible therapeutic role,has also become evident.A key mediator in the pathologic and beneficial effects of microbiota seems to be the bacterial extracellular vesicles.There is an important communication between the brain and the intestinal microbiota(the gut-brain axis),by which the microbiota influences brain function,impacts on mental health,and plays a role in different neurological and neurodegenerative diseases.The identification of the mechanisms involved in this gut-brain axis is essential to understanding the mechanisms of neurological pathologies and to developing more effective treatments for these diseases.Bacterial extracellular vesicles would play a relevant role in these processes.This review compiles the recent information and evidence on the role of bacterial extracellular vesicles in brain pathologies and on the therapeutic utility of bacterial extracellular vesicles in neurological and neurodegenerative diseases.One advantage of bacterial extracellular vesicles compared to extracellular vesicles derived from other cell types,such as stem cells,is that bacterial extracellular vesicles are generally easier to produce and modify.Bacterial extracellular vesicles may be easily modified to target a specific pathology and/or to enhance its therapeutic efficacy.Although the studies are still scarce,they open a wide field of possibilities for future studies,which will lead to a deeper understanding of the role of microbiota and bacterial extracellular vesicles in neurological pathologies and the underlying mechanisms,as well as to the development of new treatments based on the use of bacterial extracellular vesicles in neurological diseases.
基金funded by the National Natural Science Foundation of China(Grant No.82470766 to H.M.)the Jiangsu Provincial Medical Key Discipline(Laboratory)Cultivation Unit(Grant No.JSDW202206 to C.X.)the First Affiliated Hospital of Nanjing Medical University Clinical Capacity Enhancement Project(Grant No.JSPH-MC-2022-18 to C.X.).
文摘Acute kidney injury(AKI)is a critical condition with limited effective therapies.Akkermansia muciniphila(A.muciniphila)is a probiotic with multiple beneficial effects,including the regulation of epithelial cell tight junctions.Since renal pathophysiology is associated with gut barrier integrity,we hypothesized that A.muciniphila may have preventive effects on AKI.We established a lipopolysaccharide(LPS)-induced AKI mouse model to evaluate the effects of A.muciniphila.Our findings showed that pretreatment with A.muciniphila significantly attenuated kidney injury,as evidenced by reduced serum creatinine and urea nitrogen levels,alongside decreased tubular necrosis and apoptosis.A.muciniphila preserved intestinal barrier integrity and induced marked shifts in gut microbial ecology and the metabolome.A.muciniphila notably induced an increase in the relative abundance of the phylum Proteobacteria while decreasing in that of the phylum Bacteroidetes.At the genus level,Prevotella,Faecalibaculum,Moraxella,and Lactobacillus were more abundant in A.muciniphilapretreated mice.Metabolomic analysis revealed that A.muciniphila altered the gut metabolome,with changes involving pathways such as tyrosine metabolism,alanine/aspartate/glutamate homeostasis,cancer-related carbon flux,and GABAergic synaptic signaling.In conclusion,our findings indicate that A.muciniphila exerts renoprotective effects by modulating the gut-kidney axis,thereby establishing a foundation for future studies to explore the connection between gut microbiota and AKI.
基金Supported by Open Project of Jiangsu Province Key Laboratory of Integrated Traditional Chinese and Western Medicine for the Prevention and Treatment of Geriatric Diseases,No.202232.
文摘BACKGROUND Post-stroke depression(PSD)is associated with hypothalamic-pituitary-adrenal(HPA)axis dysfunction and neurotransmitter deficits.Selective serotonin reuptake inhibitors(SSRIs)are commonly used,but their efficacy is limited.This study investigated whether combining SSRIs with traditional Chinese medicine(TCM)Free San could enhance their therapeutic effects.AIM To evaluate the clinical efficacy and safety of combining SSRIs with Free San in treating PSD,and to assess its impact on HPA axis function.METHODS Ninety-two patients with PSD were enrolled and randomly divided into control groups(n=46)and study groups(n=46).The control group received the SSRI paroxetine alone,whereas the study group received paroxetine combined with Free San for 4 weeks.Hamilton Depression Scale and TCM syndrome scores were assessed before and after treatment.Serum serotonin,norepinephrine,cortisol,cor-ticotropin-releasing hormone,and adrenocorticotropic hormone were measured.The treatment responses and adverse reactions were recorded.RESULTS After treatment,the Hamilton Depression Scale and TCM syndrome scores were significantly lower in the study group than in the control group(P<0.05).Serum serotonin and norepinephrine levels were significantly higher in the study group than in the control group,whereas cortisol,corticotropin-releasing hormone,and adrenocorticotropic hormone levels were significantly lower(P<0.05).The total efficacy rates were 84.78%and 65.22%in the study and control groups,respectively(P<0.05).No significant differences in adverse reactions were observed between the two groups(P>0.05).CONCLUSION Combining SSRIs with Free San can enhance therapeutic efficacy,improve depressive symptoms,and regulate HPA axis function in patients with PSD with good safety and clinical application value.
基金supported by the National Key Research and Development Program of China(2022YFF1000201)National Scientific Foundation of China(32272861)the China Agriculture Research System of MOF and MARA(CARS-41)。
文摘Background Excessive abdominal fat in broilers not only reduces feed efficiency and increases processing costs but also raises environmental concerns.This pathological overaccumulation results from complex metabolic dysregulation across multiple organs.While current research largely centers on adipogenesis within adipose tissue,a comprehensive understanding of the cross-organ regulatory factors influencing this process remains elusive.Results Here,we employed a high-fat diet(HFD)model and multi-omics approaches to investigate cross-organ regulatory mechanisms underlying abdominal fat deposition in broilers.Our results demonstrated that HFD not only promoted fat accumulation but also altered meat quality traits.Through 16S rRNA amplicon sequencing,we identified significant gut microbiota dysbiosis in HFD-fed chickens,manifested by an increased abundance of Lactobacillus and a decreased abundance of Enterococcus.However,jejunal microbiota transplantation from HFD donors did not induce abdominal fat deposition in recipient chickens.Metabolomic profiling revealed that HFD elevated the level of succinic acid,a metabolite positively correlated with Lactobacillus abundance and potentially generated by Lactobacillus.This increase in succinic acid(SA)further triggered metabolic inflammation response in both jejunal tissue and serum.In vivo validation established succinic acid as a key inflammatory mediator facilitating HFD-induced cross-organ communication between the jejunum and abdominal adipose tissue,enhancing intestinal lipid uptake and subsequent abdominal fat deposition.Bulk and single-nucleus RNA sequencing(snRNA-seq)revealed that HFD induced macrophage population expansion and intensified adipocyte-macrophage crosstalk.Adipocyte-macrophage co-culture systems further elucidated that macrophages are an indispensable factor in succinic acid-induced fat deposition.Conclusion This study delineates a succinic acid-driven"gut-fat axis"governing abdominal fat deposition in broilers,integrating gut microbiota dysbiosis and macrophage-mediated inflammatory adipogenesis.By identifying succinic acid as a cross-organ signaling molecule that enhances lipid absorption and activates macrophage-dependent adipogenesis,we establish systemic metabolic-immune crosstalk as a pivotal regulatory mechanism.These findings redefine fat deposition as a process extending beyond adipose-centric models,advancing multi-omics-guided strategies for sustainable poultry production.
