Lactic acid is a decomposed product of anaerobic oxidation of glucose. Recent studies have shown that lactic acid is an important energy substance, signaling molecule, and immunomodulatory molecule, playing a significant role in cellular physiological and pathological processes. In vivo, both histone and non-histone proteins can undergo lactylation modification, thereby participating in the regulation of gene transcription, induction of macrophage polarization, and other processes. The discovery of protein lactylation modification has provided new directions for research on tumors and inflammation. Given the increasing attention paid to lactylation in the study of disease pathogenesis, this article summarizes the research progress of histone and nonhistone lactylation modification, and expound the key roles of lactylation modification in inflammation, cancer, cardiovascular and cerebrovascular diseases, as well as neurodegenerative diseases.

Mechanotransduction occurs when tissues or cells are stimulated by external mechanical forces, initiating a series of signaling processes, with mechanosensitive ion channels playing a pivotal role in this signaling cascade. Among these channels, Piezo1 has been widely studied. Piezo1 has been found in a variety of mammalian tissues and can affect multiple signaling pathways after mechanical stimulation, involving processes such as vasodilation, cell migration, and inflammatory response. To explore the potential therapeutic value of Piezo1 and improve the understanding of its function, this article reviews literature on Piezo1 and summarizes the latest research progress on Piezo1 in the cardiovascular system, locomotor system, nervous system, respiratory system, digestive system, and reproductive system.

IL-15 is a key molecule in immune regulation and is secreted by myeloid cells. IL-15 plays an important role in the homeostasis and function of T cells, natural killer (NK) cells, and memory CD8+ T cells. Due to its characteristics of wide expression and strict secretion, IL-15 holds significant therapeutic potential in various immune-related diseases. After IL-15 specifically binds to IL-15 receptor, it activates a variety of signaling pathways such as JAK/STAT, Ras/Raf/MAPK and PI3K/AKT, inducing cell proliferation, differentiation and apoptosis, thus exerting biological effects such as anti-tumor and anti-infection effects. This article reviews the role and associated mechanisms of IL-15 in diseases such as tumors, autoimmune diseases, cardiovascular diseases, and neuropsychiatric diseases, and summarizes the small molecule agonists and antagonists with IL-15 as potential therapeutic targets, aiming to provide a scientific basis for further investigation of the pathogenesis and drug research of IL-15 in immune system diseases and neuropsychiatric diseases.

Short-chain fatty acids (SCFAs) are produced by the gut microbiota through the fermentation of dietary fibers, which include acetic acid, propionic acid, and butyric acid. These SCFAs regulate various physiological functions in the body, such as immune, metabolic, and neurological functions, and are considered key factors affecting host health. SCFAs contribute to promoting lactate metabolism, increasing glycogen storage, and improving intestinal barrier function, thereby enhancing exercise performance. However, different types of SCFAs exhibit variations in their mechanisms of action and effects. This review discusses how SCFAs synthesized by the gut microbiota influence exercise performance and the underlying mechanisms, providing new insights and directions for the use of SCFAs derived from the gut microbiota to improve exercise performance.

Chronic pain and depression are two common diseases that endanger human health. They often co-occur and mutually influence each other, greatly increasing the difficulty of treatment. The occurrence of chronic pain and depression involves common or interacting neural circuits and neurotransmitter systems. Neuroinflammation also plays an important role in the pathogenesis of chronic pain and depression. Dysfunction in related neural circuitry and neuroinflammation are important mechanisms underlying the comorbidity between chronic pain and depression. Chronic stress is a critical cause of inducing depression and chronic pain. Previous studies have shown that dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis is the pathological basis for chronic stress-induced depression and comorbid pain. Chronic stress may promote neuroinflammatory response and dysfunction of neural circuits through HPA axis dysfunction, leading to the comorbidity of chronic pain and depression. This review discusses the pathogenesis of chronic stress-induced pain comorbid with depression, and elaborates on the pathogenesis of chronic stress-induced comorbidity of chronic pain and depression from the aspects of the HPA axis function, neuroinflammation, brain structure and neural circuits involved.

With the rapid development of tumor chemotherapy, the overall survival of tumor patients has been continuously prolonged. However, the cardiovascular toxic side effects caused by chemotherapy seriously limit the effectiveness of tumor treatment, and have become a high-risk factor affecting the quality of life and survival rate of patients. Among them, chemotherapy-related vascular endothelial injury can disrupt vascular homeostasis, which serves as the pathological basis of cardiovascular toxic side effects such as acute vascular events (vasospasm, acute myocardial infarction, stroke, etc.), atherosclerosis, hypertension, and aneurysms. Exploring the mechanisms and protective strategies of chemotherapy-related vascular endothelial injury is of great clinical significance. This review aims to summarize the latest progress in the mechanisms of chemotherapy-associated vascular endothelial injury and related protective strategies.

Ischemic stroke is a leading cause of death and disability worldwide, with a complex pathogenesis and limited therapeutic options. In recent years, nano-drug delivery systems (NDDS) have shown great potential in the treatment of brain diseases. Nanocarriers can transport drugs across the blood-brain barrier and target diseased cells through the modification of targeting ligands. This article reviews the pathogenesis of ischemic stroke and the limitations of current therapeutic approaches, focusing on the progress of nano-drug delivery systems in the treatment of ischemic stroke. The challenges and future directions in this field are proposed, aiming to advance the development of nanomedicine delivery systems for the treatment of ischemic stroke.

Alzheimer's disease (AD) is a progressive neurodegenerative disease, the pathogenesis of which remains unclear. Recent studies have shown that the gut microbiota can affect the host’ s cognition and behavior by affecting central nervous system function, making it a potential therapeutic target for neurodegenerative diseases. Dysbiosis of the gut microbiota and disruption of the intestinal physiological barrier can induce peripheral inflammatory responses, which, through mediating the release of physiologically active substances such as neurotransmitters and microbiota secretions, can affect neurogenesis and neuronal signaling, resulting in inflammatory reactions in the central nervous system, synergistically promoting the neurodegenerative progression of AD pathology. Therefore, investigations into the possible mechanisms by which dysbiosis of the gut microbiota affects the pathology of AD may provide new perspectives for the prevention and alleviation of AD, offering new strategies for promoting healthy aging.

Macrophages are important components of the immune system and play a core role in immune regulation and tissue repair. Macrophages are plastic cells that can polarize into many subtypes with different functions under different stimuli. Macrophages in different polarization states play crucial roles in disease development and prognosis. In-depth studies of macrophage polarization contribute to exploring new strategies for disease prevention and treatment. In this article, we summarize the different polarization phenotypes and main functions of macrophages under different microenvironmental signal stimuli, focusing on the role of macrophage polarization in the tumor, atherosclerosis, and type 2 diabetes, as well as the therapeutic strategies targeting macrophage polarization.

The maximal strength and power output, fastest contraction speed and strength generation rate of muscles, as well as muscle endurance, are key factors affecting athletic performance. The generation of muscle strength involves a series of biological cascade reactions, starting from excitations in the cerebral cortex to the activation of motor units and excitation-contraction coupling, ultimately leading to muscle activation. The generation and maintenance of muscle strength can be affected by multiple factors, including the imbalance of the internal environment, disruption of neuromodulation, oxidative stress, and inflammatory reactions, as well as the functional disorders during the process of neuroendocrine remodeling induced by disruption of energy metabolic homeostasis and muscle-organ crosstalk mediated by exerkines, eventually leading to exercise-induced fatigue. Appropriate modalities of exercise training and the activation of key targets responsible for the regulation and transcriptional control in exercise metabolism play a crucial protective role in promoting adaptive changes and preventing exercise-induced fatigue. Taking neuroendocrine remodeling, key targets of exercise epigenetics, and specific biomarkers associated with exercise-induced fatigue as entry points, this article systematically reviews the research progress on the molecular mechanisms and intervention approaches involving exercise-induced fatigue, aiming to provide novel insights and theoretical references for early monitoring and reasonable intervention of exercise-induced fatigue.

Exosomes are a subtype of extracellular vesicles derived from endosomes and released by membrane fusion and exocytosis. Exosome-mediated intercellular communication plays a critical role in multiple physiological and pathological processes. Due to their low immunogenicity and ability to mediate long-distance transport of bioactive substances, exosomes are considered ideal biological carriers for drugs. Engineered exosomes can improve the targeting of drug delivery, making research on exosome-based drug delivery exceedingly promising. However, some studies have indicated that exosomes can facilitate pathological processes in diseased organisms. For instance, exosomes secreted by tumor cells can "mislead" immune cells or establish a favorable microenvironment, thus promoting tumor proliferation and migration. In neurodegenerative diseases, exosomes exacerbate the disease by promoting inflammatory responses and the spread of pathogenic proteins. This article reviews the development and pathological propagation of neurodegenerative diseases mediated by exosomes carrying toxic pathogenic proteins , offering new insights into the occurrence and development of neurodegenerative diseases, as well as cautions and recommendations for exosome engineering and clinical applications.

With the deepening of social aging, age-related cognitive dysfunction has attracted widespread attention. Aerobic exercise, as an effective means of promoting human health, has been confirmed to improve cognitive function, as well as delay the occurrence and development of neurodegenerative diseases. This review summarizes the latest research on the effects of aerobic exercise on alleviating neuroinflammation, enhancing neuroplasticity, and reducing Aβ deposits, a major pathological feature of Alzheimer’s disease, and analyzes the molecular mechanisms underlying exercise-induced improvements in cognitive function, with the aim of providing a theoretical basis for the application of exercise interventions in the prevention and treatment of age-related cognitive dysfunction.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for approximately 80%~85% of all lung cancer cases. The early diagnosis of NSCLC presents challenges due to limited diagnostic methods and lack of effective biomarkers. Furthermore, surgical intervention in the advanced stages of NSCLC is difficult, and the recurrence rate is high. MicroRNA (miRNA) and long non-coding RNA (lncRNA) are two crucial types of gene expression regulatory molecules that are widely involved in various biological activities and closely associated with multiple diseases. Quantities of miRNAs and lncRNAs exhibit significant differential expression in NSCLC and play crucial regulatory roles in the occurrence and development of tumors, thereby holding potential as biomarkers for NSCLC. This article reviews the research progress on the regulatory roles of miRNAs and lncRNAs in the occurrence and development of NSCLC.

Over the past decade, since the initial elucidation of self-assembling brain organoid construction protocols, significant progress has been made in this field. These brain organoids exhibit cell types and structures highly similar to those of the developing human brain, making them ideal models for studying the pathogenesis and etiology of both acquired and inherited brain diseases. In addition, the development of region-specific brain organoids has provided targeted platforms for drug discovery and toxicity testing. As a research tool, brain organoids offer new perspectives for unraveling the molecular mechanisms underlying human neurological diseases. In this article, we review the techniques for constructing brain organoids, and their applications in modeling neurological diseases, to provide valuable insights and references for applied research in this field.

Aquaporins (AQPs) are a family of water channels predominantly expressed on cell membranes. They are widely distributed throughout the human body and play crucial roles in multiple biological processes, such as homeostasis maintenance. Additionally, AQPs are actively involved in the pathophysiological processes of neurological disorders. They are closely associated with fluid movement, cerebrospinal fluid circulation, energy metabolism, signal transduction, neurogenesis, neural regeneration, and the development and stabilization of the blood-brain barrier within the central nervous system (CNS), contributing to the onset and progression of various CNS diseases, including cerebral edema, Alzheimer's disease, neuromyelitis optica, intracranial hypertension, and Parkinson's disease. So far, multiple types of AQPs have been identified in the CNS, with research attention mainly devoted to AQP1, AQP4, and AQP9. The study of AQPs is instrumental in deepening our understanding of CNS and providing potential therapeutic targets for associated diseases. This article demonstrates the physiological distribution of AQPs in the CNS, their regulatory mechanisms, physiological functions, and their associations with CNS diseases, offering novel insights for relevant neuroscientific research.

N6-methyladenosine (m6A), which belongs to the field of the epigenetic modifications, is a common and reversible mRNA modification in eukaryotic RNA. Regulated by methyltransferases, demethyltransferases, and reader proteins, m6A modification affects the expression of relevant proteins by mediating RNA transcription, splicing, translation, and other processes, thereby regulating the physiological and biochemical processes of the organism. Major depressive disorder (MDD), characterized by a high incidence, low cure rate, and a high recurrence rate, is a psychiatric disorder with multiple etiological factors, including genetic factors, environmental factors and epigenetic factors. However, the specific mechanisms underlying MDD remain unclear. Recent studies have found a close relationship between m6A modification and the pathogenesis of MDD, making it a hot topic in MDD research. This article reviews the m6A methylation, as well as the expression and roles of related enzymes in the central nervous system of MDD patients, aiming to provide new insights and potential drug targets for the research and treatment of MDD.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that primarily affects the lungs and causes coronavirus disease 2019 (COVID-19). Recent clinical cases have reported the cardiovascular complications of COVID-19, including myocarditis, arrhythmia, myocardial infarction, and so on. Among them, COVID-19-related myocarditis exhibits diverse symptoms, which can occur at different ages and has a delayed onset. Moreover, COVID-19-related myocarditis is positively correlated with the poor prognosis and mortality of COVID-19 patients. The exploration of its clinical characteristics, potential pathogenesis and treatment may provide new ideas and strategies for the prevention and drug development of COVID-19-related myocarditis in the future. This article provides an overview of both domestic and foreign researches on COVID-19-related myocarditis.

肥胖(obesity)是指由于食物摄入过多导致的机体脂肪蓄积过度或分布异常;其常伴有运动缺乏及相关精神症状等。肥胖具有高发病率及全球流行趋势。目前,常用体重指数(body mass index, BMI)作为判断肥胖的标准;在我国,成人BMI≥24为超重,BMI≥28为肥胖。促进脂肪水解利用,是治疗肥胖的重要策略。因此,脂肪水解(lipolysis)机制研究成为世界医学界研究热点。脂肪水解的典型途径是由支配脂肪组织的交感神经释放去甲肾上腺素(norepinephrine, NE),激活脂 肪细胞表面β-肾上腺素能受体,由此活化环腺苷酸(cAMP)-蛋白激酶A(PKA)-激素敏感性脂肪酶(HSL)和脂滴蛋白1(PLIN1)信号轴以启动脂肪水解。然而,美国哈佛医学院的Erwei Li团队的发现,对上述经典机制进行了补充。2023年12月13日,该团队在Nature杂志发表论文揭示:催产素(oxytocin, OXT)/催产素受体-细胞外信号调节激酶(extracellular signal-regulated kinase, ERK)信号,对NE能交感神经启动脂肪水解过程发挥重要调节作用。催产素是由9个氨基酸组成的肽类激素,由下丘脑室旁核和视上核合成,经垂体后叶分泌,对分娩哺乳等生理过程发挥重要调节作用。研究人员发现,催产素受体(oxytocin receptor, OXTR)在小鼠白色脂肪组织高表达,且在内脏白色脂肪组织表达水平最高。体外研究发现,用催产素处理人类或小鼠脂肪细胞,均可引起脂肪细胞甘油释放。值得注意的是,将OXTR-flox小鼠和AdipoqCRE小鼠杂交,以特异性敲除小鼠白色脂肪细胞催产素受体,可导致该小鼠在禁食、冷暴露情况下,血清游离脂肪酸和甘油水平显著低于野生型小鼠,证实催产素对脂肪水解过程有上调作用。催产素对NE启动的β-肾上腺素受体活化有显著协同作用。该研究显示,催产素可增加NE敏感性,从 而提升异丙肾上腺素驱动的脂肪水解水平;而催产素受体拮抗剂阿托西班(Atosiban)或特异性敲除小鼠白色脂肪细胞催产素受体,均可有效抵消上述现象。这些发现表明,催产素是脂肪水解的内源性调节因子,催产素-催产素受体信号传导NE启动的白色脂肪细胞中的脂肪水解。禁食及冷暴露条件下,催产素在脂肪组织的表达水平显著高于血清水平,提示脂肪组织的催产素可能并非源于下丘脑。研究人员将OXT-Cre小鼠与Ai9小鼠杂交杂交,以用红色荧光蛋白tdTomato标记产生催产素的细胞;又将OXT-Cre小鼠与表达绿色荧光GFP或红色荧光mCherry的Nuclear Tagging and Translating Ribosome Affinity Purification(NuTRAP)小鼠杂交以标记产生催产素的细胞;并使用脂肪组织特异三维成像技术(Adipo-Clear Three-Dimensional Imaging)来可视化荧光蛋白;同时,用交感神经标记物酪氨 酸羟化酶(tyrosine hydroxylase, TH)抗体标记交感神经神经元。研究者发现,在支配附睾白色脂肪组织(eWAT)和腹股沟白色脂肪组织(iWAT)的交感神经节神经元,催产素与TH 共定位。进一步地,将表达Cre诱导型mCherry的逆向腺相关病毒(AAV)注射到OXT-Cre小鼠eWAT 和iWAT,亦证实上述催产素与TH 共定位。支配白色脂肪组织的交感神经元可释放催产素。研究人员采用化学遗传技术(DREADD),将AAV8-hSyn-DIO-hM3Dq-mCherry注射到Vglut3-IRES-Cre小鼠脑中缝苍白球核团,从而在该核团的谷氨酸能神经元表达hM3Dq,以用皮下植入微型泵递送氯氮平N-氧化物(CNO)特异激活这些神经元;该激活显著导致小鼠血清血脂水平升高,表明激活中缝苍白球可经交感神经启动脂肪水解。进一步,研究人员将OXT-Cre小鼠与Ai32小鼠杂交,使Ai32小鼠以Cre依赖的方式表达视紫红质,并用蓝光照射离体白色脂肪组织,导致培养基甘油水平显著增加。以上结果证实了脑中缝苍白球谷氨酸能神经元对脂肪水解的调控作用、以及脂肪组织内部交感神经末梢可释放催产素激活脂肪细胞启动脂肪水解。综上所述,该研究发现:支配白色脂肪组织的交感神经元表达分泌催产素,该催产素具有促进脂肪水解、 或提升去甲肾上腺素敏感性从而间接促进脂肪水解脂解的功能。该研究完善了脂肪分解的调节机制,为肥胖等相关疾病治疗提供了新思路。

RNAs are subject to a variety of chemical modifications that confer structural diversity to the nucleotides and are involved in the regulation of RNA metabolism, protein synthesis and a variety of cellular functions.N4-acetylcytidine (ac4C) is the only known form of RNA acetylation in eukaryotes.Ac4C has long been identified in ribosomal RNA (rRNA) and transfer RNA (tRNA). Recent studies have shown that ac4C also occurs in messenger RNA (mRNA), promoting mRNA stability and translation efficiency. Compared with the widely studied mRNA methylation modifications (e.g.m6A), the functions and regulatory mechanisms of ac4C modifications of mR-NA are far less well-known. This review aims to summarize the function of ac4C modifications of mRNA in physiological and pathological processes in the nervous system, such as learning and memory, pain, and Alzheimer’s disease. Moreover, this review will discuss the critical questions that should be addressed in the ac4C field to promote the research of RNA modification in the nervous system.

Atherosclerosis (AS) is a chronic inflammatory vascular disease and the main pathological basis for numerous cardiovascular and cerebrovascular diseases. The pathogenesis of AS is complex and not yet fully elucidated. Vascular smooth muscle cells (VSMCs) are one of the main cell types that constitute the vascular wall. They are involved in regulating the systolic and diastolic functions of the vascular wall and maintaining the vascular tone. However, under the stimulation of AS promoting factors, the phenotypic switch occurs in systolic VSMCs, exhibiting characteristics such as proliferation, migration, adhesion, and calcification, which may directly lead to the formation or rupture of AS plaques. Integrins play a critical role in coordinating the transmembrane connections between the extracellular matrix and cytoskeleton, contributing to pathological processes of various diseases. They also play key roles in regulating the transdifferentiation of VSMCs into mesenchymal stem cells, myofibroblasts, macrophages, osteoblasts, and other cell types. To conclude, integrins can indirectly affect the formation and progression of AS by regulating the phenotypic transformation of VSMC, thereby presenting the potential as a new therapeutic target for AS. In this article, we review the classification of VSMC phenotypic transformation and the regulatory role of integrins in VSMC phenotypic transformation, aiming to provide new targets and strategies for the early treatment and intervention of AS.