Early childhood, spanning from the prenatal period to three years of age, represents a critical window for the coordinated development of the gut microbiota and the immune system. These two systems form a bidirectional regulatory network via the gut-immune axis, which plays a significant role in lifelong health. The gut microbiota matures progressively through four stages: prenatal preparation, initial colonization, stable diversification, and dynamic equilibrium. Concurrently, the immune system establishes immune tolerance and refines its functional capabilities. The microbiota regulates immune cell differentiation through metabolites and molecular interactions, while the immune system reciprocally shapes the structure of the microbiota. Exogenous factors such as mode of delivery, feeding practices, and antibiotic use can influence this synergistic process. Disruption of this balance may increase the risk of allergic, digestive, and metabolic disorders. Targeted strategies, including probiotic supplementation and dietary interventions, can provide a scientific foundation for promoting early childhood health. Research on the underlying mechanisms and interventions also lays the groundwork for clinical translation.

Non-suicidal self-injury (NSSI) refers to the deliberate, self-inflicted destruction of body tissue without suicidal intent and for purposes not socially or culturally sanctioned. This behavior is particularly prevalent among adolescents. NSSI is characterized by its urgency, compulsivity, and the sense of relief following the act, leading to its conceptualization as a behavior with addictive features. Through a systematic review of the literature, this article synthesizes current advances in the biology of adolescent NSSI from several perspectives: genetic and environmental factors, neurobiological development, pain perception, stress response and inflammation regulation, as well as the reward system and reward response. The overarching aim is to provide a scientific basis for the early identification of high-risk individuals, the prevention of adolescent NSSI, and the formulation of targeted intervention strategies and clinical research.

Neonatal sepsis is a severe systemic infection for which timely and accurate diagnosis is crucial to reduce mortality and improve patient outcomes. While traditional inflammatory markers such as C-reactive protein and white blood cell count are widely used in clinical diagnosis, their limitations in specificity and sensitivity can lead to diagnostic delays or errors. With advancements in molecular biology and immunology, a range of novel molecular markers—including cytokines, microRNAs, and metabolomic biomarkers—have been identified, offering new possibilities for the early diagnosis of neonatal sepsis. This review summarizes the current research on both traditional inflammatory markers and novel molecular markers for the diagnosis of neonatal sepsis, analyzes their advantages and limitations, and explores their clinical application potential and future directions. The aim is to provide a theoretical basis and practical guidance for optimizing clinical diagnostic strategies and enabling personalized treatment.

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.

Heart failure (HF) represents the terminal stage of various cardiovascular diseases, and one of its core characteristics is the structural and functional disorders of cardiomyocytes. In recent years, with the advancement of molecular biology and genetic technologies, the research focus has shifted from the macroscopic organ failure to the microscopic molecular networks, including gene expression regulation, metabolic remodeling, immune-inflammatory responses, and dynamic changes in the extracellular matrix and cytoskeletal proteins. As the "internal scaffold" of cardiomyocytes, cytoskeletal proteins have increasingly demonstrated their critical role in the occurrence and progression of HF. This review aims to systematically summarize the current research status of pathological remodeling, molecular mechanisms, and potential therapeutic targets of the cardiomyocyte cytoskeleton (including microfilaments, microtubules, and intermediate filaments) as well as the extracellular matrix in HF. It also outlooks future research directions, providing references for the basic research and clinical treatment of HF, with the expectation of offering new theoretical foundations and directions for the precise prevention and treatment of HF.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder, and its prevalence is rising in tandem with the aging of the population. The primary pathological characteristics of AD encompass the aggregation of amyloid β-protein and the formation of neurofibrillary tangles resulting from the hyperphosphorylation of tau protein. The dynamic equilibrium between mitochondrial fission and fusion is fundamental for maintaining neuronal energy metabolism and cellular homeostasis, and the disruption of this equilibrium represents a key pathological event in the early stages of AD. Aberrant mitochondrial dynamics play a critical role in the pathogenesis of AD, predominantly characterized by enhanced mitochondrial fission and impaired fusion, which subsequently induce cell death and neuronal injury. This review delves into the pathological mechanisms of mitochondrial fission and fusion regulated by amyloid β-protein, tau protein, APOE4, and ferroptosis, with the aim of providing novel intervention targets for the prevention and treatment of AD.

The Piezo (Piezoelectric) ion channels are an important class of mechanosensitive cation channels that are widely distributed across various tissues and serve as crucial mediators in the conversion of mechanical stimuli into electrical signals. The major subtypes include Piezo1 and Piezo2: Piezo1 is primarily expressed in endothelial cells and certain sensory neurons, playing a role in the modulation of mechanical pain, whereas Piezo2 is predominantly localized in the dorsal root ganglia where it is essential for the transmission of touch and pain sensations. Emerging studies have demonstrated that Piezo channels are critically involved in the onset and maintenance of cancer pain, inflammatory pain, and neuropathic pain. This review summarizes recent advances in the research on mechanosensitive Piezo ion channels and their signaling pathways in various pain types, providing potential therapeutic targets and theoretical foundations for the development of novel analgesic strategies.

Osteoarthritis is a chronic and highly prevalent joint degenerative disease with an increasing prevalence year by year, which imposes a heavy economic burden on society and seriously threatens public health. Cuproptosis is a copper-dependent non-apoptotic regulated form of cell death, and its regulatory process involves the participation of various signaling molecules. Recent studies have confirmed a close link between cuproptosis and the progression of osteoarthritis. It influences the onset and development of osteoarthritis by regulating key pathophysiological processes such as inflammatory responses and oxidative stress. This article combs and summarizes the regulatory effect of cuproptosis on osteoarthritis and its related mechanisms, aiming to provide new ideas and strategies for the clinical treatment of osteoarthritis.

Venetoclax, the first selective inhibitor of B-cell lymphoma 2 (BCL-2), has demonstrated remarkable therapeutic efficacy in the treatment of various hematologic malignancies.However, the emergence of drug resistance during clinical application has limited the durability of its efficacy and adversely affected patient prognosis. In recent years, accumulating evidence has revealed that exosomes, as critical mediators of intercellular communication, play a pivotal role in the development of venetoclax resistance. Exosomes can transport bioactive molecules, including proteins,microRNAs (miRNAs), and long non-coding RNAs (lncRNAs), thereby regulating apoptotic signaling pathways, mediating metabolic reprogramming, promoting drug efflux, and inducing remodeling of the tumor microenvironment. Through these mechanisms, exosomes enhance tumor cell survival and allow evasion of venetoclax-induced apoptosis. This review systematically summarizes the latest advances in exosome-mediated mechanisms of venetoclax resistance, aiming to elucidate the network-based regulatory mechanisms underlying resistance development, help reverse drug resistance and restore drug sensitivity, and provide theoretical foundations and research directions for the development of exosome-targeted therapeutic strategies.

Although significant progress has been made in pharmacological and device-based treatments for heart failure (HF), it remains an escalating public health challenge, closely associated with high disability rates, frequent hospital readmissions, and substantial economic burden. Alleviating pulmonary edema is one of the core goals in HF treatment. However, clinical practice currently lacks an assessment method capable of rapidly, non-invasively, and precisely quantifying pulmonary fluid content. The emergence of remote dielectric sensing (ReDSTM ) technology provides a novel solution, enabling non-invasive quantitative measurement of pulmonary fluid percentage within minutes, offering an innovative tool for volume management in HF patients. This article aims to systematically review the working principles of this technology, as well as its clinical applications and research advances in the volume management of HF patients.

The dark proteome refers to proteins or sequence regions whose three-dimensional structures cannot be resolved experimentally or reliably predicted by homology modeling. These elements often originate from noncanonical open reading frames, including those embedded in lncRNAs, the untranslated regions of mRNAs, circular RNAs, and cryptic coding sequences generated by alternative splicing. With advances in proteomics, the critical roles of dark proteins in the immune system have increasingly come to light. Typically short, lacking known structural domains yet potentially possessing stable folding characteristics, dark proteins participate in signaling regulation, protein processing, and tissue-specific biological functions. Within immune processes, they are involved in antigen presentation, tumor immunity,inflammatory regulation, and viral immune evasion, making them an emerging focus in immune-related disease research. For example, microproteins derived from ncORFs can serve as important sources of MHC-I-presented antigens; viral dark proteins exploit intrinsically disordered regions to disrupt host antiviral pathways; and some microproteins modulate autoimmune and inflammatory responses. As their essential roles in cancer, neurodegenerative disorders, and infectious diseases continue to be uncovered, the dark proteome is increasingly recognized as a promising reservoir of novel biomarkers and therapeutic targets, offering new opportunities for precision medicine and drug development.

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.