The components of coffee exert multifaceted effects on skin health. Studies have shown that caffeine promotes autophagy and scavenges reactive oxygen species, significantly reducing oxidative stress, thereby delaying skin aging and enhancing skin elasticity. Chlorogenic acid, through its antioxidant and anti-inflammatory properties, inhibits the production of inflammatory factors and mitigates skin inflammation, consequently slowing skin aging and reducing the risk of skin cancer. Ferulic acid, derived from the partial degradation of chlorogenic acid during coffee bean roasting, not only exhibits anti-inflammatory and antioxidant functions but also absorbs and reflects ultraviolet (UV) radiation, helping to reduce UV-induced DNA damage and enhance the skin barrier function. Furthermore, caffeine stimulates the proliferation and migration of skin cells, thereby accelerating wound healing. This article elaborates on the roles and potential mechanisms of coffee consumption in delaying skin aging, preventing skin cancer, providing photoprotection, and promoting skin repair and regeneration, highlighting the significance and potential applications of coffee and its bioactive constituents in promoting skin health.

Depression is a prevalent mental disorder characterized by a multifaceted pathogenesis involving theories such as neurotransmitter dysregulation, microglial activation, hypothalamicpituitary-adrenal (HPA) axis dysregulation, inflammasome activation, microbiome alterations, and impaired neuroplasticity. Current first-line antidepressants, including selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), exhibit limitations such as delayed onset, low efficacy rates, and significant interindividual variability. In recent years, driven by advances in molecular biology and immunopsychiatry research, growing evidence has indicated an interplay between immune-inflammatory pathways and depression. The kynurenine pathway, a predominant route for tryptophan metabolism, generates metabolites that play significant roles in neural, immune, and inflammatory regulation, particularly exhibiting complex dual effects in immune modulation. It is essential to construct a comprehensive view of the peripheral-central immune network and delve into the mechanistic role of the tryptophankynurenine metabolic pathway within this network in the pathogenesis of depression, thus further advancing our knowledge of the pathophysiological mechanisms of depression and facilitating drug development.

2025年10月6日,诺贝尔生理学或医学奖授予两位美国科学家Mary E. Brunkow 和Frederick J. Ramsdell,以及日本科学家Shimon Sakaguchi, 以表彰他们在阐明外周免疫耐受关键机制方面所作的开创性贡献:他们成功鉴定出调节性T 细胞, 并揭示了免疫系统如何通过该类细胞维持自身稳态, 防止过度的免疫应答及自身免疫性疾病发生, 这也是一项“迟到了 30 年”的诺奖发现(https://www.nobelprize. org/prizes/medicine/ 2025/summary/) 全文请点击PDF链接至知网下载浏览。 。

Cardiovascular diseases significantly affect human health and represent an urgent public health issue that needs to be addressed.Reactive oxygen species (ROS) generated by mitochondrial metabolism are risk factors for the occurrence and progression of cardiovascular diseases. When mitochondrial function is impaired,excess ROS are generated.If the endogenous antioxidant system fails to eliminate the excess ROS,oxidative stress damage occurs,thereby compromising cardiovascular health.Therefore,improving mitochondrial function and reducing ROS through nutritional interventions has become a crucial approach to prevent and treat cardiovascular diseases.Mitoquinol mesylate (MitoQ),a mitochondria-targeted antioxidant,accumulates in the inner mitochondrial membrane,quenching mitochondrial ROS.This article reviews the molecular properties and mechanisms of action of MitoQ,as well as its benefits in improving cardiovascular diseases.Additionally,it compares the similarities and differences between MitoQ and coenzyme Q10 (CoQ10),providing a scientific basis for the future application of MitoQ in the treatment of cardiovascular diseases.

黑质致密部(substantia nigra pars compacta, SNc)为中脑重要神经核团,其含有多巴胺能神经元、胆碱能神经元等。解剖学研究表明,SNc与小脑之间存在投射;但其功能却尚不清楚。最近,美国阿尔伯特· 爱因斯坦医学院Kamran Khodakhah 团队发现:小脑投射到SNc的谷氨酸能神经纤维,可与SNc多巴胺能神经元、非多巴胺能神经元形成单突触连接,其参与基底神经节多巴胺传递、运动启动、运动活力及奖赏行为等多方面功能调控。 SNc神经元响应小脑神经纤维信号,并由此增加多巴胺合成与分泌。利用光遗传学技术,研究人员发现,小脑投射到SNc的神经纤维轴突,可激活SNc神经元,并提高SNc投射到纹状体的多巴胺量。小脑投射到SNc的神经纤维为谷氨酸能型。利用全细胞电压钳技术,研究人员发现,SNc多巴胺神经元及非多巴胺神经元均可响应小脑释放的神经递质。利用谷氨酸受体阻滞剂(AMPAR阻滞剂及NMDAR阻滞剂)可有效阻断SNc神经元激活;这表明:小脑投射到SNc的神经纤维为谷氨酸能。小脑与SNc之间投射为单突触型。利用电压门控钠通道阻滞剂(河豚毒素)及电压门控钾通道阻滞剂(4-氨基吡啶)阻断小脑切片动作电位,再利用光遗传学技术,研究人员确证:小脑投射到SNc的神经投射为单突触型。小脑发出的神经纤维广泛分布于 SNc 神经元。利用病毒介导顺行示踪技术,研究人员发现,小脑深部核团 (deep cerebellum nuclei, DCN) 发出的投射分布于 SNc 多巴胺能和非多巴胺能神经元。利用病毒介导逆行示踪技术,研究人员发现:小脑到 SNc 投射源于小脑顶核 (fastigial nucleus)、球状核 (globose nucleus)、栓状核 (emboliform nucleus) 和齿状核 (dentate nucleus)。小脑-SNc投射参与调节SNc至纹状体多巴胺释放,并由此激活运动行为。利用光遗传学技术,研究人员发现,该通路的激活程度与步行速度、步行总距离、及步行时间正相关。这些运动指标亦与小鼠纹状体多巴胺水平呈正相关。继而,神经元钙传感器技术揭示:该突触激活状态与高运动活动量之间存在偶联。小脑-SNc投射参与奖赏机制调节。应用神经元钙传感器技术,研究人员发现:小鼠获得奖赏时,小脑至SNc投射被激活,且其激活信号强度与奖赏程度相关。综上所述,该研究揭示:小脑齿状核、球状核、栓状核和顶核,向中脑 SNc 发出单突触谷氨酸能神经纤维;该神经纤维可投射至全部 SNc 神经元,其功能为参与运动启动及奖赏调控。该研究为脑神经通路研究、运动机制、及奖赏机制研究提供了新参考。(全文请点击PDF链接至知网阅读)

MG53(mitsugumin 53) is a member of the tripartite motif (TRIM) protein family of E3 ubiquitin ligases,also known as TRIM72.MG53 is a cell membrane repair protein widely expressed in cardiac and skeletal muscles,capable of rapidly accumulating at the site of membrane injury, playing a crucial role in the repair of cardiac and skeletal muscle cell membranes. In recent years, numerous studies have found that MG53 participates in the myocardial protective effect of ischemic preconditioning and postconditioning, and mitigates myocardial ischemia-reperfusion injury. Moreover, it is expressed in various organs, promoting cell membrane repair under physiological or pathological conditions. However, MG53 overexpression leads to decreased expression of the ubiquitin-dependent insulin receptor, contributing to metabolic syndrome and diabetic heart disease. This article reviews the recent advances in the physiological functions and associated mechanisms of MG53 protein, aiming to provide a reference for the clinical application of recombinant human mitsugumin53 (rhMG53).

Proteins serve as the fundamental building blocks of life processes. Their functions are highly determined by the spatial structure, making analyzing these spatial structures essential for fully comprehending their roles. The application of artificial intelligence (AI) models has significantly advanced the development of algorithms for predicting protein spatial structure. AlphaFold2 represents a groundbreaking advancement in this field, enabling rapid, accurate, and large-scale predictions of protein spatial structures. In the AlphaFold era, substantial progress has been made in fields such as protein language model development, protein-protein interaction prediction, and protein design, with notable models including ESM2, ScanNet, RFdiffusion, and RoseTTAFold-All Atom, among others. These novel AI-based algorithms have profoundly facilitated research into protein function, disease mechanisms, and drug design.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most prevalent chronic liver disease worldwide, garnering significant attention due to its close association with metabolic disorders. The pathogenesis of MAFLD involves lipid metabolism dysfunction, lipid oxidation, and gene dysregulation. This article focuses on analyzing metabolic pathways in the liver, including hepatic fatty acid uptake, de novo triglyceride synthesis, and lipid oxidation, as well as the functions of associated lipid metabolism genes, such as FATP2, FATP5, CD36, PPARα, CPT1, CPT2, FGF21, SREBP1, ChREBP, ACLY, ACC, FASN, SCD, DGAT2, GPR75, RBP4, adiponectin, and osteocalcin. Through in-depth analysis of these genes and signaling pathways, this article provides new insights and a theoretical basis for the diagnosis and treatment of MAFLD, highlighting the pivotal role of lipid metabolism regulation in the progression of MAFLD, and identifying relevant genes and molecules as potential therapeutic targets.

Single-cell RNA sequencing (scRNA-seq) is a high-throughput sequencing technology that profiles genome-wide gene expression at the single-cell level,and can efficiently resolve cellular heterogeneity.It is widely applied in fields such as developmental biology and disease research. However,scRNA-seq data often exhibit characteristics such as high noise,high dimensionality, and high sparsity,which pose significant challenges to traditional data analysis methods.In recent years,deep learning models,represented by autoencoders and generative adversarial networks, have been extensively applied to scRNA-seq data analysis tasks,including expression imputation, batch effect correction,dimensionality reduction,cell clustering,and cell type annotation. These applications demonstrate the power of deep learning. Notably, Transformer-based deep learning models, leveraging self-attention mechanisms to capture implicit dependencies among genes and associations between gene expression and cells, offer a novel strategy and direction for scRNA-seq data analysis, and provide innovative solutions with promising applications for the integration of multimodal omics data.

Periodontitis is a common oral disease and the leading cause of tooth loss in adults. The gingival epithelium is the first line of defense against external invasions. The occurrence and development of periodontitis are closely related to the invasion and destruction of the gingival epithelium by various pathogenic bacteria. Research has demonstrated that periodontitis-associated pathogens destroy the gingival epithelium,invade deep tissues,and trigger inflammatory responses through a series of virulence factors. Among them, Porphyromonas gingivalis is the main cause of periodontitis. This article reviews the regulatory effects of Porphyromonas gingivalis on the gingival epithelium, with the aim of providing a reference for the treatment of periodontitis.

Treatment-resistant depression (TRD) is a severe mental illness that poses a significant threat to the health and well-being of patients. In recent years, TRD has garnered increased attention from scholars both domestically and internationally. Currently, there is ongoing debate regarding the definition of TRD. Clinical treatment strategies for TRD primarily include optimizing drug dosage and duration, switching medications, combining drugs, and employing synergistic therapies. Additionally, various animal models of TRD, based on different pathological changes, have been successfully established and utilized in research to reveal the potential pathogenesis of TRD, such as excessive inflammatory responses, hyperactivity of the hypothalamic-pituitary-adrenal axis, dysregulation of the glutamatergic system, and disturbances in tryptophan metabolism. These findings have generated new insights for the development of novel medications for TRD, with some candidates currently in the pipeline having achieved significant breakthroughs. This review comprehensively discusses these issues, aiming to provide a reference for future research and drug development in TRD.

Despite remarkable advances in drug therapy for chronic heart failure (CHF), the related morbidity, mortality and hospitalizations remain substantial. Novel device-based interventions have emerged as potential therapies for CHF. Recently, interatrial shunt device (IASD), baroreflex activation therapy (BAT), and phrenic nerve stimulation (PNS) have shown promise in treating patients with CHF. This article summarizes the working principles and clinical research outcomes of these innovative therapeutic devices, and analyzes their advantages and disadvantages, potential risks, and future application prospects, aiming to provide new insights and references for clinical treatment.

Lysosomal storage disorders (LSD) are a rare class of diseases caused by mutations in genes encoding lysosomal hydrolases, leading to metabolic disorders. These disorders arise from either the absence of functional lysosomal hydrolases or damage to the lysosomes. Impaired degradation of complex macromolecules leads to the accumulation of substrates in tissues and subsequent dysfunction of cells and organs. Current treatment options for LSDs primarily include enzyme replacement therapy, substrate reduction therapy, and chaperone therapy. However, most of these treatments do not cure the disease, but merely delay its progression. They necessitate continuous administration of medications, which can be financially burdensome, and often fail to effectively reach target sites due to various challenges, resulting in diminished therapeutic effects. Therefore, there is an urgent need for more effective and thorough treatment options. Extracellular vesicles (EVs) are naturally secreted components with potential applications in various diseases. However, their role and therapeutic potential in the context of LSDs remain unclear. This article summarizes current research progress on EVs in two common LSDs, Fabry disease and Gaucher disease, by reviewing literature from PubMed. It discusses biomarkers associated with EVs in the diagnosis and treatment of LSDs, as well as advancements in engineered EVs for therapeutic applications.

Hyperuricemia(HUA) is a pathological condition characterized by elevated levels of uric acid in the blood,which can adversely affect female reproductive health by altering the functions of the uterus and ovaries.Epigenetic modifications, primarily influenced by environmental factors,regulate gene expression without changing the gene sequence,thereby affecting individual metabolism,and being transmitted to the offspring through epigenetic imprinting. The occurrence of HUA results from the interaction between genetic and environmental factors. Understanding the underlying epigenetic mechanisms is of great significance for effective prevention and treatment of HUA and its complications. This article discusses in detail the effects of maternal HUA on pregnancy complications,gestational metabolic syndrome,and offspring health. It summarizes the epigenetic regulatory mechanisms of HUA, aiming to elucidate the pathogenesis of HUA at the molecular level and provide new research insights for reducing maternal pregnancy risks.

Exosomes are extracellular vesicles secreted by cells into the extracellular space, carrying abundant biomolecules such as proteins, nucleic acids and metabolites. MicroRNAs(miRNAs) are non-coding RNA molecules that play important roles in cell differentiation, proliferation, and survival.Exercise can induce the secretion of exosomes,and promote the biological effects of the contained miRNAs.Recent studies have indicated a close relationship between exosomal miRNAs and chronic heart failure,exercise can alter the expression of exosomal miRNAs in body fluids and tissues.Exosomal miRNAs serve as biomarkers for the diagnosis and prognosis of heart failure,potentially ameliorating heart failure by inhibiting myocardial fibrosis,promoting myocardial mitochondrial function,and enhancing myocardial cell survival. Therefore,this article reviews the role of exosomal miRNAs in chronic heart failure and the mitochondrial mechanisms through which exercise improves chronic heart failure via exosomal miRNAs, offering a valuable basis for future diagnosis and treatment of heart failure.

High-temperature requirement factor A3 (HtrA3) is a serine protease, which has been identified as an important target molecule in diseases such as cancer and pregnancy complications. The regulatory role of this molecule is attributed to its extensive biological functions. However, there is still a lack of effective integration regarding this aspect. Therefore, in this article, we discuss the biological functions of HtrA3,including its involvement in protein quality control, immune regulation,maintenance of mitochondrial homeostasis,apoptosis,extracellular matrix degradation, and epithelial-mesenchymal transformation, as well as its role in regulating cell proliferation and migration. In addition, studies have confirmed that HtrA3 is predominantly expressed in the heart, with significant research progress made regarding this molecule in the contexts of myocardial fibrosis, heart failure, and ischemia-reperfusion injury. Given its extensive functions, HtrA3 may serve as a significant regulator of cardiovascular diseases, highlighting its important research value in the development of cardiovascular diseases.

Multilineage differentiating stress enduring (Muse) cells are a newly discovered type of stem cells that have attracted increasing attention due to their superior abilities compared to mesenchymal stem cells, such as enhanced tri-germ layer differentiation potential, stress tolerance, homing ability, in situ differentiation capacity, and non-tumorigenicity. Muse cells have shown promising effects in various animal disease models and clinical trials, highlighting their immense potential for applications in the field of regenerative medicine. However, the extremely low baseline levels of Muse cells in vivo pose a challenge for conventional culture methods, which often fail to obtain large quantities of high-purity Muse cells within a short time frame, limiting their translational applications. This article aims to discuss the characteristics and culture methods of Muse cells, as well as research progress in disease models and specific clinical trials, providing a theoretical basis for further studies on Muse cells.

The significance of redox homeostasis in the functional adaptation, injury repair, and health maintenance of skeletal muscle has been increasingly recognized. Redox homeostasis in skeletal muscle is a dynamic equilibrium process that precisely regulates the generation and clearance of reactive oxygen species (ROS). This regulation enables skeletal muscle to effectively cope with oxidative stress induced by exercise, thereby promoting cellular health and functional recovery. Moderate ROS generation helps activate the antioxidant system and facilitates adaptive responses in muscle. As crucial signaling molecules, ROS play significant roles in skeletal muscle metabolism, antioxidant responses, mitochondrial function, and protein synthesis during exercise. However, excessive ROS can trigger oxidative stress, damaging the structure and function of muscle cells, leading to muscle degeneration. This review comprehensively explores the regulatory mechanisms of redox homeostasis in skeletal muscle, particularly the processes of ROS generation and clearance. It also examines the impact of exercise on the redox status of skeletal muscle, with a focus on analyzing signaling pathways related to oxidative stress, especially the roles of the Nrf2/KEAP1 and HSP72/HSF1 pathways during exercise. In-depth research into redox signaling pathways and their regulatory mechanisms under different exercise modalities is crucial for optimizing exercise training programs, improving skeletal muscle health, and preventing and treating associated diseases.

The rapid accumulation of biological big data, primarily comprising genomics, transcriptomics, proteomics, and more, coupled with the swift advancement of artificial intelligence technologies, notably deep learning, has given rise to a variety of biological large models. Characterized by complex deep-learning architectures, massive parameter counts, high computational power requirements, and vast amounts of pre-training data, these large models' capabilities are largely dictated by the types and volumes of pre-training data, while different model architectures support various downstream tasks. Over the past two years, a variety of general-purpose and specialized large models have emerged in multiple application scenarios, including the analysis and mining of DNA, RNA, and protein sequences, single-cell expression atlases, structure prediction of biomacromolecules, de novo drug design, and interpretation of biological mechanisms. These models have demonstrated significant potential in the domains of biomedical research and translational applications. This paper aims to provide an overview of the characteristics of biological data and the technical methods used for training biological large models, considering the unique features and research application needs of different types of biological data. Furthermore, it reviews the application progress of existing models in biomedical research and disease diagnosis and treatment, offering new insights for enhancing model capabilities and expanding their application scope.

Acne vulgaris is a common chronic inflammatory skin disease that affects a wide range of adolescents and some adults. As a globally consumed beverage, coffee's effects on skin health, particularly on acne vulgaris, have attracted increasing attention. Research suggests that coffee constituents, such as caffeine and chlorogenic acid, may exert beneficial effects on acne suppression through their antioxidant, anti-inflammatory, and lipid-regulatory properties. Additionally, coffee may indirectly influence skin health by modulating the gut microbiota through the gut-skin axis. However, the effects of coffee consumption are significantly influenced by individual variability, and additives such as sugar and dairy products in coffee may exacerbate inflammation, potentially counteracting its benefits. This review summarizes current evidence regarding the effects and potential mechanisms of coffee and its major components on acne vulgaris, aiming to provide a theoretical basis and scientific guidance for understanding the potential link between coffee consumption and skin health.