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.

2024年10月7日,瑞典卡罗琳医学院宣布,授予美国科学家Victor Ambros 和Gary Ruvkun 2024年诺贝尔生理学或医学奖,以表彰他们在基因表达调控研究中的杰出贡献:发现微小RNA(microRNA, miRNA)及其在转录后基因调控中的作用(http://www.nobelprizemedicine.org)。Victor Ambros在1953年出生于美国新罕布 什尔州汉诺威。他于1979年在马萨诸塞州剑桥的麻省理工学院(MIT)获得博士学位,并于1979年至1985年在那里从事博士后研究。1985年,他成为哈佛大学的主要研究员。1992年至2007年期间,他担任达特茅斯医学院的教授。如今,他是马萨诸塞大学医学院伍斯特分校的自然科学教授。Gary Ruvkun在1952年出生于美国加利福尼亚州伯克利。他于1982年在哈佛大学获得博士学位,并于1982年至1985年在MIT 从事博士后研究。1985年,他成为马萨诸塞总医院和哈佛医学院的主要研究员,现任遗传学教授。Victor Ambros和Gary Ruvkun发现的miRNA调控机制描述了一种全新的基因表达调控机制,这一机制促进了越来越复杂的生物体的进化和多样性。（全文请点击PDF链接知网下载阅读）

Titin (TTN), the largest protein by molecular weight in humans, extends beyond its roles in providing structural stability to the sarcomere and storing elastic potential energy. It also plays a crucial regulatory role in muscle hypertrophy and protein quality control. The protein complex encompassing the Z-disk, I-band, and M-line regions of TTN acts as a mechanosensor, dynamically modulating the transduction of myocellular hypertrophic signaling in response to mechanical tension. TTN induces skeletal muscle remodeling after exercise, mediating the repair and degradation of damaged TTN through protein protection and quality control mechanisms. Under appropriate mechanical stimulation, the TTN mechanosensory complex is activated, thereby triggering a series of hypertrophic responses. Conversely, following overload exercise, severely damaged TTN promotes its degradation through interactions of T-cap with MDM2, the proximal Ig region with calpain 1, and the N2A and M-line regions with calpain 3, as well as engagement of the MuRF1 binding site within the M-line domain. In this article, we delve into the role of the cytoskeletal protein TTN as a central signaling hub for skeletal muscle remodeling. Initially, the basic structure of TTN is elucidated, followed by an in-depth analysis of the mechanisms by which different regions contribute to muscle hypertrophy and protein quality control.

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 aorta is one of the most important arteries in the human body. Although its basic vascular functions have been extensively studied, its multiple physiological roles as an independent organ have often been overlooked. Recent studies have shown that the aorta not only plays a central role in blood pressure maintenance, but also participates in key physiological processes such as metabolism, endocrinology, nervous system regulation, and immune stress. The unique structure and function of the aorta endow it with significant roles in a variety of physiological and pathological states. This article reviews the importance of the aorta as an independent organ and discusses its structural and functional uniqueness. Emphasis is placed on the metabolic and endocrine regulatory functions of aortic endothelial cells and smooth muscle cells, as well as the role of the aorta in neuroregulation and immune stress. The discussion of these research advances provides new perspectives for an in-depth understanding of the physiological and pathological functions of the aorta and offers potential research directions for future studies.

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.

Ferroptosis is a form of programmed cell death associated with abnormal iron metabolism and excessive accumulation of lipid peroxides, characterized by unique biological processes and pathophysiological features. Lipid peroxidation represents the most fundamental mechanism underlying ferroptosis. Increasing evidence indicates that ferroptosis plays significant regulatory roles in the onset, development, and treatment of tumors.Induction of ferroptosis in tumor cells can effectively inhibit tumor growth and metastasis, and improve the therapeutic sensitivity of anti-tumor drugs. This article reviews the mechanisms by which lipid metabolic processes, such as the synthesis and remodeling of phospholipids,the storage and release of phospholipids,as well as the uptake and oxidation of fatty acids,regulate ferroptosis.It summarizes the effects of lipid metabolism-associated signaling pathways on ferroptosis and targeted therapeutic strategies, aiming to provide new insights for ferroptosis-associated basic research and clinical tumor therapy.

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.

Copper plays a crucial role in a variety of cellular processes, such as energy metabolism, mitochondrial respiration, and antioxidation. Intracellular copper homeostasis relies on the dynamic balance among copper intake, storage, and efflux. Disruptions in copper metabolism can impact cellular function and viability. Elevated copper levels have been observed in various neurodegenerative diseases and tumors, with the underlying pathological mechanisms closely associated with cuproptosis induced by copper overload. This article provides in-depth insights into intracellular copper homeostasis and its maintenance, as well as the roles and molecular mechanisms of copper metabolic disorders and cuproptosis in neurodegenerative diseases and tumorigenesis.

Hypoxic cell damage is implicated in the etiology of various diseases, posing a significant threat to human health. Therefore, a comprehensive exploration of the underlying mechanisms of hypoxic cell damage is of crucial importance. Recent research has elucidated a compelling correlation between hypoxic cell damage and key cellular processes, including apoptosis, autophagy, pyroptosis, ferroptosis, cuproptosis, and parthanatos. The aim of this article is to integrate current knowledge on the mechanisms underlying hypoxic cell injury. It seeks to clarify the critical determinants and regulatory pathways involved in these processes, and to offer innovative perspectives on preventive and therapeutic approaches for hypoxia-induced diseases.

Autophagy is a dynamic protective mechanism that degrades macromolecules and organelles within cells to maintain organismal balance. Most eukaryotic cells rely on autophagy to regulate intracellular homeostasis. Under certain stress conditions, such as ischemia and hypoxia, autophagy exerts protective effects to counteract cellular damage. However, selective overactivation of autophagy can lead to a unique form of programmed cell death, distinct from apoptosis and necrosis, termed autosis. This review summarizes the distinctions between autosis and other cell death modalities, the morphological characteristics of autosis, the conditions that induce autosis, and current research progress on autosis, aiming to provide a theoretical basis for further research on autosis and to offer a scientific reference for subsequent studies and future clinical disease treatment.

Suplatast Tosilate is a specific Th2 cell inhibitor that has been widely used in the treatment of various allergic and inflammatory diseases such as asthma and atopic dermatitis, with good efficacy and high safety. Research has shown that Suplatast Tosilate can inhibit the production and function of Th2 cells and Th2-type cytokines such as IL-4 by regulating GATA3 and chloride channels, thereby exerting a therapeutic effect on allergic diseases. Additionally, Suplatast Tosilate also has regulatory effects on dendritic cells, monocytes, eosinophils, and neurons. Therefore, Suplatast Tosilate has become a focus of attention in the research field of treating Th2 cell-mediated allergic inflammatory diseases.

Neuropsychiatric disorders impact the lives of tens of millions of people globally and have become an increasingly severe social problem. Genetics is one of the critical factors contributing to the etiology of neuropsychiatric disorders. However, disease-associated risk loci, identified by genome-wide association studies (GWAS), are primarily located in non-coding regions of the human genome, presenting one of the most significant challenges in identifying disease-associated risk genes and elucidating the pathogenesis. Three-dimensional (3D) genomics focuses on spatial chromatin architecture and long-distance chromatin interactions. The development and application of 3D genomic technologies contribute to the identification of disease-associated risk genes, providing direct evidence of the chromatin interactions between disease-associated risk loci and their target genes. Meanwhile, cell-type-specific interactions bring new insights into the comprehension of pathogenesis. Lastly, the reorganization of spatial chromatin architectures regulates the transcription of multiple genes collectively, which may explain the complexity and heterogeneity of neuropsychiatric disorders. Based on a brief introduction to the basic concepts and applications of 3D genomics, this review primarily discusses the research progress of 3D genomics in the field of neuropsychiatric disorders, including schizophrenia (SCZ), Alzheimer's disease (AD), autism spectrum disorder (ASD), and others, aiming to offer new perspectives on associated diseases pathogenesis.

Cardiac arrhythmias are among cardiovascular diseases with high morbidity and mortality rates worldwide, associated with impaired cardiac ion channel function and abnormal conduction of electrophysiological signals in cardiomyocytes. The cardiac sodium channel NaV1.5 plays a crucial role in the initiation and propagation of action potentials in cardiomyocytes. Abnormal expression and regulation of NaV1.5 due to gene mutations constitute a significant biological basis for the occurrence of arrhythmias. This article summarizes the structure and function of NaV1.5, as well as its relationship with cardiac arrhythmias, with the aim of providing a theoretical basis for future research and development of cardiovascular drugs, their clinical applications, and drug-induced cardiotoxicity.

Sphingosine-1-phosphate (S1P), a metabolite of cell membrane sphingolipids, exerts its physiological functions by binding to G protein-coupled sphingosine-1-phosphate receptors (S1PRs) in various tissues of the human body. The S1P-S1PR signaling pathway plays a crucial role in mediating inflammatory responses, cardiac development, angiogenesis, as well as the migration, proliferation, and differentiation of immune cells. S1PRs have emerged as promising therapeutic targets for a variety of diseases, including autoimmune diseases, inflammation, cardiovascular diseases, and even cancer. However, the lack of in-depth understanding of S1PRs has hindered the development of clinical drugs. Therefore, this article reviews the current research status of S1PRs, focusing on S1PR-associated physiological functions, disease progression, and the development of representative drugs, with the aim of providing new insights for the clinical treatment of associated diseases.

Protein lactylation is a recently discovered post-translational modification, and its neuroprotective effect in cerebral ischemia-reperfusion injury has garnered increasing attention. Cerebral ischemia-reperfusion injury is a complex pathological process that occurs following reperfusion therapy after ischemic stroke, involving oxidative stress and inflammatory responses. This article reviews the neuroprotective mechanisms of protein lactylation in cerebral ischemia-reperfusion injury and highlights recent research progress. Lactate molecules can covalently bind to lysine residues and affect the function and activity of proteins, thus playing significant roles in cell metabolism, gene expression regulation, and cell signaling. Research has indicated that protein lactylation exerts neuroprotective effects by regulating inflammatory and oxidative stress responses, helping to reduce neuronal damage and apoptosis. In-depth studies of the biological functions of protein lactylation and its mechanism of action in cerebral ischemia-reperfusion injury not only aid in elucidating the pathophysiological mechanisms underlying cerebral ischemia-reperfusion injury, but also provide potential targets and theoretical basis for the development of new therapeutic drugs for cerebral ischemia-reperfusion injury.

Pregnancy is a complex physiological process. In recent years, it has been discovered that exosomes play a crucial regulatory role in both physiological and pathological pregnancies by facilitating communication between the mother and fetus. Exosomes regulate various biological functions, such as embryo implantation, angiogenesis, endothelial cell migration, and resistance to viral infections. Additionally, they mediate maternal-fetal immune tolerance by modulating immune cells such as natural killer (NK) cells, T cells, and monocytes. Furthermore, exosomes are involved in the regulation of multiple pregnancy complications, including preeclampsia, gestational diabetes mellitus, preterm delivery, and fetal growth restriction.This article elaborates on the regulatory role of exosomes in physiological and pathological pregnancies,offering valuable insights for the future diagnosis and treatment of these pregnancy complications.

The sodium iodine symporter (NIS) is widely distributed in various organs of the human body and serves as the structural and functional basis for the transport of iodide (I- ) in these organs. NIS is primarily expressed on the basolateral membrane of cells, providing the required I- for various life activities. It is known that the regulatory mechanism of NIS involves the actions of hormones, cytokines, transcription factors, and signaling molecules. In addition, NIS is gaining attention as an important therapeutic target for thyroid cancer, although complications arising from the absorption of radioactive iodine by other organs, such as salivary glands, during the treatment process also deserve attention. In this article, we focus on the research progress on the expression, role, and regulatory mechanism of NIS, aiming to provide new insights for clinical intervention targeting disease processes associated with NIS abnormalities.

Post-stroke cognitive impairment (PSCI) is a common complication following stroke, posing a significant threat to patients' quality of life and survival time. Microglia, the major immune cells in the central nervous system, play a crucial role in the pathogenesis of PSCI by mediating immune responses and exerting neuroprotective effects. Research has indicated that triggering receptor expressed on myeloid cells 2 (TREM2), an immune response receptor predominantly expressed on microglia, is involved in the regulation of microglial number, phagocytosis, cytokine release, and metabolic functions. In this article, we elucidate the effect of TREM2-mediated regulation of microglial activity on PSCI, and explore the potential of TREM2 as a therapeutic target for the prevention and treatment of PSCI.

Exosomes play an important role in intercellular communication by transferring substances such as proteins, lipids and nucleic acids between cells. The types and quantities of substances carried by exosomes vary depending on their cellular origin, resulting in heterogeneity in both the characteristics and functions of exosomes derived from different cell types. This heterogeneity underpins the basis of exosome function. Focusing on the heterogeneity of exosomes in terms of cellular origin and content, this article systematically elucidates the biological characteristics and functions of exosomes, providing a basis for future exosome screening and applications.