As one of the most widely consumed beverages globally, coffee's relationship with digestive health has drawn significant attention. Recent studies indicate that coffee exerts bidirectional regulatory effects on the occurrence and progression of gastric ulcers. On one hand, polyphenolic compounds such as chlorogenic acid in coffee exert protective effects on the gastric mucosa by inhibiting inflammatory responses and promoting the growth of beneficial gastrointestinal bacteria. On the other hand, caffeine stimulates gastric acid secretion through multiple signaling pathways, potentially increasing the risk of ulcer development. This article systematically elucidates the regulatory mechanisms of coffee's bioactive constituents in the pathological progression of gastric ulcers, based on evidence from in vivo, in vitro, and clinical studies. It further analyzes the association between coffee consumption and gastric ulcer risk across different populations. The aim is to provide scientific recommendations for coffee consumption to the public and to offer a theoretical basis for further research and applications of coffee in digestive 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.

With the accelerating aging of the global population, osteoporosis has emerged as a major public health challenge. As one of the most widely consumed beverages, the relationship between coffee intake and osteoporosis remains controversial. Previous research has often treated coffee as a single entity, neglecting the complexity of its chemical composition. Based on the principle of bone metabolic homeostasis, this review systematically elaborates on the dual regulatory effects of its key constituents—coffee polyphenols and caffeine—on osteoporosis from a compositional perspective. Polyphenols exert protective effects on bone through mechanisms such as antioxidation, anti-inflammation, and modulation of the gut-bone axis, whereas caffeine promotes bone resorption by disrupting calcium homeostasis and potentially activating osteoclasts. By synthesizing the latest evidence and analyzing sources of heterogeneity across studies, this review concludes that the net impact of coffee on bone health is determined by the balance between these components, total daily intake, and individual physiological conditions. This work aims to provide a scientific basis for personalized dietary recommendations regarding coffee consumption for different populations and to inform the development of precise dietary guidance systems.

Caffeine is a well-established ergogenic aid in the field of sports science, with a robust body of research confirming its positive effects on exercise performance. Current evidence indicates that caffeine intake improves performance across various exercise modalities, including reaction time tasks, short-term high-intensity strength training, and endurance aerobic exercise. Empirical data suggest that an intake of 2-4 cups of coffee (equivalent to 3-6 mg/kg of caffeine) approximately 60 minutes before exercise can optimize these ergogenic benefits. However, individual metabolic sensitivity and physiological characteristics must be considered for personalized recommendations. This review systematically summarizes the effects of caffeine intake on various types of exercise performance and elucidates the underlying biological mechanisms. It aims to provide a theoretical basis for future research on the synergistic mechanisms of coffee and exercise, adaptive changes resulting from long-term consumption, and individual differences caused by genetic polymorphisms, thereby facilitating the precise application of caffeine in both competitive sports and public health.

Atherosclerosis, characterized by excess lipid deposition and chronic inflammation, is the common pathological basis of cardiovascular diseases. Macrophages, as important immune cells, are involved in the entire process of atherosclerosis. Recent studies have shown that macrophage efferocytosis is a homeostatic mechanism responsible for the clearance of dead/apoptotic cells and the resolution of inflammation. In atherosclerosis, the capacity of macrophages to participate in efferocytosis is hampered, resulting in the abnormal accumulation of apoptotic cells and necrotic tissue within the plaques, which leads to the enlargement of necrotic core, increased luminal stenosis, plaque inflammation, and ultimate plaque destabilization or rupture. In this review, we summarized the efferocytic machinery that is normally implicated in cardiovascular physiology and then highlighted the mechanisms by which efferocytosis fails in atherosclerosis, aiming to provide therapeutic approaches for this pathological process.

Inflammation is a protective mechanism of the body in response to harmful stimuli. However, persistent inflammation and excessive secretion of inflammatory mediators may lead to chronic inflammation, resulting in dysfunction of cells, tissues, or organs. The vagus nerve isone of the core components in neuro-immune regulation. In recent years, studies have shown that the vagus nerve regulates inflammatory responses, especially anti-inflammatory effects, through multiple pathways, including the cholinergic anti-inflammatory pathway, non-cholinergic anti-inflammatory pathway, and the inflammatory reflex. This review focuses on the core mechanisms underlying the anti-inflammatory effects of the vagus nerve and its clinical applications in autoimmune diseases, infectious diseases, metabolic diseases, and neurological disorders, aiming to provide new insights into clinical anti-inflammatory therapy.

Coffee, as a globally prevalent beverage, has garnered considerable research attention regarding its association with liver health. Drawing upon recent domestic and international research, this article systematically reviews the preventive and protective effects of coffee consumption on chronic liver diseases. Specifically, it focuses on the protective roles of coffee in diseases such as metabolic dysfunction-associated fatty liver disease (MAFLD), liver cancer, and other chronic liver diseases, as well as the underlying molecular mechanisms. Evidence indicates that moderate coffee intake enhances liver function and health primarily via anti-inflammatory, antioxidant, and metabolic regulatory pathways. Notably, these effects exhibit variations across genders and populations. By integrating clinical evidence with mechanistic research, this review provides a theoretical basis and reference for understanding the role of coffee in chronic liver diseases, and offers scientific recommendations for coffee consumption.

Tumor-associated macrophages (TAMs) are highly plastic innate immune cells in the tumor microenvironment of lung cancer and other solid tumors, playing key roles in tumor development, immune resistance, and therapeutic response. With the advent of single-cell sequencing and spatial transcriptomics, the heterogeneity, lineage origins, and dynamic functions of TAMs have been increasingly elucidated, challenging the traditional M1/M2 polarization model. This review summarizes the origins, distribution, polarization states, and metabolic regulation of TAMs in lung cancer, highlighting the impact of lactate-hypoxia axis, lipid metabolism, and cholesterol metabolism on their immunosuppressive functions. We also discuss the roles of TAMs in immune surveillance, tumor proliferation, angiogenesis, metastasis, and immune resistance, with a focus on TREM2+ lipid-associated TAMs in the formation of immune-cold regions and resistance to immune checkpoint inhibitors. Finally, we summarize strategies targeting TAM recruitment, phenotypic reprogramming, metabolic intervention, and combination immunotherapy, and propose personalized interventions based on TAM heterogeneity, providing a theoretical basis for optimizing lung cancer immunotherapy.

Alzheimer's disease(AD)is a neurodegenerative disease characterized by progressive cognitive dysfunction, with its pathogenesis closely associated with mitochondrial dysfunction. The PINK1/Parkin signaling pathway, as a core regulator of mitophagy, plays a key role in clearing damaged mitochondria and maintaining neuronal homeostasis. While dysfunction of this pathway in Parkinson's disease is mainly attributable to genetic mutations,in AD,it is not a primary cause but rather a secondary consequence of core pathological processes such as abnormal amyloid β-protein (Aβ)deposition and tau protein hyperphosphorylation. These pathological changes can lead to impaired function of the PINK1/Parkin pathway, which in turn triggers mitophagy deficits, creating a vicious cycle of neurodegeneration. PINK1 can activate the mitophagy program by phosphorylating Parkin proteins and ubiquitin molecules, a process that is significantly inhibited in AD. Crucially, the abnormal deposition of Aβ and pathological changes of tau in AD not only inhibit the PINK1/Parkin pathway, but also their own production and toxic effects are regulated by this pathway, forming a complex AD-specific bidirectional interactive network, which is significantly different from the pathophysiological mechanism of Parkinson's disease. Notably, pharmacological interventions aimed at activating the PINK1/Parkin pathway have shown potential in improving AD pathology and cognitive function in animal models. In this review, we systematically elucidate the molecular mechanisms and therapeutic implications of PINK1/Parkin-mediated mitophagy in AD, providing a crucial theoretical basis for the development of novel neuroprotective strategies.

The circadian rhythm is an endogenous biological oscillation with a 24-hour period. Under normal physiological conditions, the circadian rhythm of blood pressure exhibits a diurnal variation characterized by a two-peak-one-trough pattern, with higher levels during the day and lower levels at night. Extensive studies have demonstrated that the circadian regulation of blood pressure depends on the precise integrative functions of the cardiovascular centers. The brainstem and hypothalamus modulate the dynamic balance between the sympathetic and parasympathetic activities via neurotransmitters, endocrine signals, and other pathways, thereby maintaining physiological fluctuations of blood pressure. Under pathological conditions, dysregulation of cardiovascular centers can lead to abnormal circadian rhythm of blood pressure, which is closely associated with cardiovascular diseases such as hypertension. Therefore, this review systematically examines the role and molecular mechanisms of cardiovascular center in regulating blood pressure circadian rhythms, providing a theoretical basis for revealing the pathogenesis of abnormal blood pressure rhythms and developing targeted therapies.

初级感觉运动皮层(primary sensorimotor cortex, SM1)包括初级躯体感觉皮层(S1)和初级运动皮层(M1), 传统观点认为二者分别参与躯体感觉加工和运动调控。近年来越来越多的证据表明, S1和M1脑区通过下行投射共同参与感觉和运动调控, 并且刺激SM1脑区可有效缓解慢性神经病理性疼痛, 但其相关的具体细胞和环路机制尚不清楚。近日,复旦大学脑科学研究院、医学神经生物学国家重点实验室的张玉秋教授团队在《Nature Communications》上发表论文,揭示SM1中存在分别投射至中脑导水管周围灰质(periaqueductal gray,PAG)和延髓头端腹内侧区(rostroventral medulla,RVM)且解剖位置分离的两群投射神经元,协同调控神经病理性疼痛和运动功能。作者首先利用逆行病毒示踪技术,在小鼠SM1皮层的第5/6层中,鉴定出两群互不重叠的谷氨酸能神经元, 其中一群投射至PAG,称其为SM1PAG 神经元; 另一群投射至RVM,称其为SM1RVM 神经元。之后,作者利用化学遗传学手段发现, 在神经病理性疼痛模型小鼠中, 单独激活SM1PAG 或SM1RVM 神经元,均能显著缓解小鼠的疼痛症状, 并且同时激活两群神经元可产生更强的镇痛效果。（全文请点击PDF链接至知网阅读）

Snakebites are among the deadliest yet most neglected tropical diseases worldwide. Following a venomous bite, the circulatory system serves as both the medium for venom dissemination and the most direct target of the venom. Victims experience impaired hemostasis and coagulation, leading to a series of blood-associated toxic reactions, such as abnormal blood cells, platelet irregularities, microvascular issues, and blood pressure changes. These hematotoxicities also trigger secondary cardiovascular complications, which are major contributors to the high mortality and morbidity rates associated with venomous bites. This article reviews the research progress on venom-induced changes in hematotoxicity parameters, venom components and their mechanisms of action, clinical manifestations, and treatment strategies, aiming to provide a reference for the clinical treatment of snakebite victims.

Tumor development is closely related to the aberrant post-transcriptional regulation mediated by RNA-binding proteins (RBPs), which play a key role in tumor progression by regulating mRNA splicing, stability, and translation. This review systematically investigates the molecular mechanisms underlying the abnormal expression or dysfunction of RBPs during tumor development, the molecular basis of RBPs in promoting tumor progression through regulating tumor-associated signalling pathways, and the roles of RBPs in malignant transformation and therapeutic resistance, aiming to provide an important theoretical basis for developing anti-tumor therapies targeting RBPs.

神经系统正逐渐成为肿瘤微环境中的关键组成部分并参与调控肿瘤发生过程。新近一项研究深入揭示了神经系统在小细胞肺癌(small cell lung cancer, SCLC)发病机制中的核心作用, 通过多维度实验证明了神经活动依赖的机制在原发肺肿瘤和脑转移瘤中的关键调控作用。该研究发表在2025年9月Nature杂志上。 研究首次发现迷走神经支配对原发性SCLC发展的必要性:在遗传小鼠RPR2-luc模型中,单侧颈迷走神经切断术(vagotomy)显著抑制肿瘤的发生和演变,实验数据显示vagotomy组肿瘤负荷减少,肝转移发病延迟,并带来生存效益(Kaplan-Meier分析P=0.014),表明神经支配在早期肿瘤发生中的驱动作用。在脑转移环境中,研究取得了突破性发现:SCLC细胞能够形成功能性神经元-癌症突触,直接整合到神经回路中。电生理记录显示约22%的SCLC细胞表现出自发的谷氨酸能兴奋性突触后电流(sEPSCs)。同时,GABA能输入引起去极化,反转电位达-27.3 mV,细胞内氯化物浓度高,约46.8 mM,此状态驱动肿瘤增殖。钙成像实验显示,神经元活动诱发SCLC细胞钙瞬变,光遗传学刺激皮质神经元(Thy1-ChR2模型)使Ki67+细胞增殖指数从40%显著增加至60%,并促进肿瘤侵袭。分子机制上,SCLC细胞在神经元共培养后上调突触相关基因标签,包括编码神经递质受体和突触蛋白的基因,具体涉及谷氨酸和GABA受体通路。这种活动依赖性可塑性在人类脑转移样本中得到验证:单细胞RNA测序显示SCLC脑转移细胞富集神经样转录程序,与突触相关基因(如HOMER1、synapsin)表达上调相关,而颅外病变中无此现象。该研究首次系统阐明了SCLC通过突触机制利用神经活动,包括谷氨酸能和GABA能信号,并揭示了癌细胞膜去极化本身足以促进肿瘤生长(表达ChR2的SCLC细胞的光遗传学去极化使肿瘤面积翻倍)。本研究也具备转化应用的价值: 使用临床抗癫痫药物左乙拉西坦(levetiracetam)干扰突触传递,显著抑制SCLC增殖,为靶向神经元-肿瘤互作提供了可行的治疗策略,对改善SCLC患者预后具有重要临床意义。

Breast cancer, the most prevalent malignant tumor in women, exhibits high mortality rates primarily due to its metastatic potential and drug resistance. In recent years, metabolic reprogramming has been proven to play a critical role in the occurrence and development of breast cancer. Previous research has mainly focused on aberrant glucose metabolism, with limited investigation of fatty acid metabolism. Recent studies have shown that breast cancer cells provide energy and biosynthetic precursors for rapid proliferation, metastasis, and drug resistance by abnormally activating fatty acid metabolic pathways including uptake, synthesis, storage, and oxidative decomposition. This article systematically reviews the latest research progress on fatty acid metabolic reprogramming in breast cancer, and provides an in-depth exploration of potential therapeutic targets and targeted intervention strategies.

Rosacea is a chronic inflammatory skin disease primarily characterized by persistent facial erythema, telangiectasia, papules, and pustules. Its pathogenesis is closely associated with dysfunction of the gut-skin axis. Based on the gut-skin axis theory, this review systematically summarizes the relationship between gut dysbiosis and rosacea. Current evidence indicates that patients with rosacea exhibit characteristic alterations in gut microbiota composition, which contribute to the onset and progression of rosacea through multiple mechanisms, including the disruption of intestinal barrier integrity, induction of systemic immune dysregulation, and reduction of anti-inflammatory short-chain fatty acids (SCFAs).Furthermore,various therapeutic strategies targeting the gut-skin axis,such as probiotics/postbiotics,specific dietary interventions,and botanical extracts,have demonstrated potential efficacy in the management of rosacea.Future largescale prospective studies and multi-omics integrative analyses are warranted to establish causal relationships, thereby providing a theoretical foundation for the development of gut microbiometargeted personalized therapies for rosacea.

Coffee, a globally consumed beverage, contains multiple bioactive compounds, including caffeine, trigonelline, polyphenols, and diterpenes. These bioactive constituents exhibit potential anti-colorectal cancer effects through multi-target mechanisms, including suppression of the Wnt/β-catenin pathway, modulation of oxidative stress, activation of immune responses, and promotion of cancer cell apoptosis, while inhibiting growth and migration of colorectal cancer cells. Research indicates that coffee consumption significantly reduces mortality and improves prognosis for patients with advanced colorectal cancer. This article systematically reviews the biological effects and clinical relevance of coffee' s primary constituents, aiming to provide a theoretical basis for dietary interventions in the prevention and treatment of colorectal cancer.

Ubiquitination is one of the major types of protein post-translational modifications. Proteins can be labeled with polyubiquitin chains through ubiquitination, which enables their recognition and subsequent degradation by the proteasome. Ubiquitination and deubiquitination are essential mechanisms for regulating the cell cycle process. Cell cycle-associated proteins, including various cyclins (CCNs), cyclin-dependent kinases (CDKs), and cyclin-dependent kinase inhibitors (CKIs), can all undergo ubiquitination. Recent studies have found that ubiquitin-specific proteases (USPs), members of the deubiquitinating enzyme (DUB) family, can inhibit the progression of liver cancer. USPs can reverse the ubiquitin-mediated degradation of proteins, thereby affecting apoptosis, autophagy, tumor signaling pathways, cell cycle regulation, DNA damage, and chemoresistance in liver cells, ultimately influencing the initiation and development of liver cancer. This article reviews recent research progress on the role of the DUB family member USPs in regulating the cell cycle of liver cancer cells, and their effects on tumor progression and chemoresistance, aiming to provide a reference for identifying new therapeutic targets for liver cancer treatment.

Coffee, a globally consumed beverage, has gained increasing attention for its effects on metabolic health. In this review, we explore the potential mechanisms by which coffee influences metabolism through the gut microbiota. Specifically, we review the mechanisms by which coffee polyphenols and caffeine are metabolized by gut microbes into short-chain fatty acids (SCFAs) and other metabolites, which subsequently regulate glucose metabolism, lipid metabolism, inflammatory responses, and bile acid metabolism.

Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome characterized by considerable heterogeneity. Its global incidence continues to rise due to the accelerating aging population and the increasing prevalence of risk factors such as diabetes and hypertension. Although there has been gradual progress in understanding the pathophysiological mechanisms of HFpEF, its full disease progression network remains incompletely understood, and effective targeted therapeutic strategies are still lacking. Currently, clinical diagnosis of HFpEF often relies on the diagnostic framework established for heart failure with reduced ejection fraction (HFrEF). Yet, this approach may not adequately capture the distinct pathophysiological features of HFpEF. Notably, recent studies have increasingly highlighted the promising role of biomarkers in enabling more precise diagnosis and improved risk stratification of HFpEF. Therefore, this review systematically summarizes the incremental value of biomarkers in the diagnosis and prognostic evaluation of HFpEF, providing evidence-based support for the development of multi-biomarker integrated models.