This study investigated the impact and related mechanisms of single-nucleotide variants (SNVs) in the HBV pre-S/S region on tumor development, and evaluated the role of antiviral therapy.

In gene therapy via genome editing, it is essential to precisely repair disease-associated gene sequences without introducing random mutations. However, achieving highly accurate genome editing remains challenging owing to the low efficiency of homology-directed repair (HDR)-mediated gene repair, which relies on template DNA. Therefore, if Cas9 mutants capable of enhancing HDR can be identified, they could enable more precise gene therapies.

Ulcerative colitis (UC) is one of the two major types of inflammatory bowel disease (IBD), characterized by inflammation of the colon and rectum. The colorectal epithelium, which covers the mucosal surface, maintains homeostasis by supporting commensal microorganisms in the outer mucus layer. Most colorectal epithelial cells (CECs) are absorptive colonocytes distributed primarily in the upper portion of the crypts. These CECs constitute the front-line barrier that modulates mucosal immunity and facilitates the transfer of immune molecules into the lumen. In patients with UC, CECs undergo both apoptosis and pyroptosis. Apoptosis is a physiological, programmed, caspase-dependent, and tightly regulated form of cell death that eliminates aged and damaged cells. In contrast, pyroptosis is an inflammatory, caspase-dependent form of lytic cell death that occurs in response to harmful stressors and toxins. Pyroptosis in CECs involves a broad array of signaling and effector molecules, many of which serve as measurable biomarkers with diagnostic, prognostic, and therapeutic potential.

Dendritic cells (DCs) play a crucial role in the coordination of immune responses and have emerged as a potential target for cancer immunotherapy. However, existing DC-based immunotherapies face several clinical challenges, including suboptimal manipulation strategies, poor cross-presentation, and impaired migration. Besides, the complex tumor milieu drives DCs towards a tolerogenic state, leading to immune evasion and cancer progression. Hence, innovative engineering strategies emerging from a thorough understanding of the genetic and molecular aspects of the factors driving DCs to an immune-compromised status will benefit cancer immunotherapy. Taking advantage of the multiplexing potential of gene editing methods such as CRISPR/Cas9 and viral vectors will ensure multiple genome modifications in DCs that can result in higher migration, cross-presentation, and immune-activating cytokine production in a single manipulation step. Such precise DC modifications with high accuracy require the involvement of nanocarrier formulations with high surface functionalization and targeting potential. In this regard, our review provides a comprehensive summary of critical tumor-induced dysfunctions in DCs and promising genome engineering strategies, highlighting nanocarrier-based approaches to mitigate these challenges.

Since the COVID-19 pandemic, there has been a documented rise in the incidence of neurological manifestations among individuals complicated with encephalitis or myelitis. The spectrum of neurological symptoms associated with HCoVs infections is expanding. However, the infection characteristics and pathogenesis of seasonal HCoVs to the central nervous system remain obscure. No pharmacological agents have demonstrated the capacity to specifically and efficaciously mitigate the neurological symptoms induced by HCoVs infections to date.

The human liver and pancreas are central to metabolic regulation, with the autonomic nervous system orchestrating processes that maintain glucose homeostasis and respond to dynamic physiological demands-ranging from acute energy mobilization during stress to postprandial glucose uptake and storage. However, visualizing and examining the intricate three-dimensional (3D) neural networks within clinical liver and pancreas specimens remains challenging, as conventional two-dimensional (2D) histological methods cannot fully resolve the spatial complexity of autonomic innervation in the liver and pancreas. This review identifies and discusses key biological and technical factors-including tissue autofluorescence, autolysis, photobleaching, and steatosis-that compromise the reliability of 3D neurohistological analysis of the human liver and pancreas. We also highlight emerging optical and chemical methodologies that enable high- and super-resolution 3D tissue imaging, improving signal fidelity, preserving structural detail, and supporting consistent, reproducible analysis. Ultimately, these advances aim to facilitate precise mapping of human liver and pancreas innervation, offering deeper insight into the neural regulation of nutrient assimilation, glucose utilization, and metabolic homeostasis in both physiological and pathological contexts.

Monoclonal antibodies (mAbs) represent a major class of therapeutics with widespread clinical applications in oncology, immunology, hematology, neurology and infectious disease. Since the introduction of hybridoma technology in 1975, the field has been advanced by a succession of innovations including chimeric and humanized antibody engineering, phage display, transgenic mouse platforms and high-throughput single B cell isolation. These technological developments have enhanced the specificity, potency and safety of mAbs, resulting in 144 FDA-approved antibody drugs on the market and 1,516 worldwide candidates in clinical development as of August 2025. Engineering breakthroughs have led to new modalities of antibody-based therapeutics, such as antibody-drug conjugates (ADCs), bispecific antibodies (bsAbs), and chimeric antigen receptor T (CAR-T) cell therapies. Each of these modalities has therapeutic utility across multiple disease domains. Recent advances in delivery strategies, notably mRNA-lipid nanoparticles (LNPs) and antibody-directed in vivo CAR-T cell reprogramming, can enable precision therapies while reducing off-target effects and manufacturing complexity. The integration of artificial intelligence (AI) and machine learning (ML), next-generation sequencing (NGS), and structural modeling tools has further accelerated antibody discovery, affinity maturation and immunogenicity prediction, allowing for more efficient and rational antibody design. The advances in antibody technology are reflected in the rapid market growth of antibody-based therapeutics, which had global sales exceeding USD 267 billion in 2024. This review provides a comprehensive update on recent developments in antibody discovery platforms, therapeutic formats and market trends, highlighting emerging strategies that are reshaping the landscape of antibody-based medicine. Furthermore, we discuss clinical translation, regulatory landscapes, and the integration of engineering, biology and informatics. Together, these aspects shape a dynamic and multidisciplinary future for the therapeutic antibody field, which is poised to address unmet clinical needs and global healthcare priorities.

Physical differences between acute kidney injury and chronic kidney disease, particularly in matrix stiffness, may influence mesenchymal stem cells to promote either regeneration or fibrosis; however, the underlying mechanisms remain unclear. Here, we investigate the role of paraspeckles and the long non-coding RNA Neat1 in TGF-β1-induced stem cell fate determination.

Programmed death-ligand 1 (PD-L1) is a well-recognized predictive biomarker for immunotherapy in non-oncogene-addicted non-small cell lung cancer (NSCLC). However, its role in epidermal growth factor receptor (EGFR)-mutant NSCLC remains unclear. This study aims to investigate the impact of PD-L1 on the signaling pathways in EGFR-mutant NSCLC.

Aging has become an important public health concern with the accelerated aging of the global population. The rising impetus to extend lifespan as well as healthspan has drawn attention to the gut microbiome, an indispensable yet modifiable determinant of the aging process. This narrative review addresses the complex interaction between the gut microbiome and aging, synthesizing findings in logical order. Evidence from model organisms supports the causal influence of gut microbes on host aging and longevity. Developmental evolution of the human gut microbiome throughout life stages reflects its adaptive nature affected by diet, lifestyle, hormone levels, and immune function, regulating aging through the gut-muscle and the gut-brain axes in late life. Signature characteristics of the long-lived gut microbiome, including increased diversity, elevated beneficial taxa, and enhanced gut homeostasis, lead to strategies to extend longevity. Intake of fiber, regular exercise, and pro-/pre-/postbiotic supplements are potential interventions on the gut microbiome to foster vitality in later years. Centering on these connected topics, this review identifies questions warranting investigation, with potential to improve therapeutic strategies for healthy aging.

Dietary restriction (DR) refers to a broad set of interventions that limit the intake of specific nutrients or overall food consumption, either in quantity or timing, without causing malnutrition. DR has long been considered the most robust intervention for increasing healthspan and lifespan. This includes, not exhaustively, caloric restriction (CR), protein restriction (PR), amino acid restriction (AAR), intermittent fasting (IF), and time-restricted fasting (TRF), each with overlapping but distinct metabolic and physiological effects. This brief review examines the current scientific understanding of how some of the most commonly employed DR regimens may impact metabolism, lifespan, and healthspan. Particular attention is given to the underlying biological mechanisms and supporting evidence derived from both human clinical studies and fundamental biological research conducted with model organisms ranging from yeast to non-human primates.

Cervical cancer (CC) remains a significant global health challenge for women, especially in advanced stages where effective treatments are limited. Current immunotherapies, including PD-1/PD-L1 blockades and adoptive T cell therapies, show limited response rates and durability. Dimethyl fumarate (DMF), an FDA-approved drug for autoimmune diseases, has demonstrated direct antitumor activity in several cancers. However, its influence on anti-tumor immunity and its function in CC remain poorly understood. This study aims to investigate the therapeutic potential of DMF in CC models and elucidate its underlying mechanisms of action.

Exposure of mammals to ototoxic compounds causes hair cell (HC) loss in the vestibular sensory epithelia of the inner ear. In chronic exposure models, this loss often occurs by extrusion of the HC from the sensory epithelium towards the luminal cavity. HC extrusion is preceded by several steps that begin with detachment and synaptic uncoupling of the cells from the afferent terminals of their postsynaptic vestibular ganglion neurons. The purpose of this study was to identify gene expression mechanisms that drive these responses to chronic ototoxic stress.

Extracellular vesicles (EVs) are heterogeneous populations of membrane-bound particles released from almost all cell types in an organism and play pivotal roles in cell-cell communication. EVs carry nucleic acids, proteins, metabolites and other bioactive substances, which are taken by the recipient cells to alter cell physiology and functions. The cargo landscapes of EVs are influenced by the cell contexts and the biogenesis mechanisms of EVs, in which certain molecules govern both biogenesis and cargo sorting. In this review, we discuss the biogenesis and secretion mechanisms of various types of EVs, including several atypical EVs. In addition, given that the tumor immune microenvironment (TIME) is intricately controlled by the communication between tumor cells and various immune cells, we summarize the latest update about how tumor-derived EVs influence the phenotypes of various immune cells in tumor microenvironment for tumor immune evasion, and, conversely, how EVs secreted from immune cells in TIME control the malignancies of tumor cells. In particular, we discuss the roles of several atypical EVs in regulating TIME. Lastly, we highlight the advantages of utilizing EVs as liquid biopsies for cancer diagnosis, the application and challenge of EVs in different anti-tumor therapies, and the recent clinical trials that exploit EVs as drug carriers. As the continuous advances in our understanding of the complex biogenesis mechanisms and the pleiotropic actions of EVs in TIME as well as the technology improvements in harnessing EVs' clinical benefits, we can expect to further unlock the biomedical potential of EVs in cancer and other diseases.

Enteroviruses, including Coxsackie B (CVB) viruses, can cause severe diseases such as myocarditis, pancreatitis, and meningitis. Vaccines can prevent these complications, but conserved non-neutralizing epitopes in the viral capsid may limit their effectiveness. The immunodominant PALXAXETG motif, located in the VP1 N-terminus, is a highly conserved region in enteroviruses that elicits non-neutralizing antibody responses. Virus-like particles (VLPs) offer a safe and effective vaccine platform because of their structural similarity to native viruses but lack viral genetic material. Importantly, VLPs can be structurally modified to exclude specific epitopes.

Oncometabolites are aberrant metabolic byproducts that arise from mutations in enzymes of the tricarboxylic acid (TCA) cycle or related metabolic pathways and play central roles in tumor progression and immune evasion. Among these, 2-hydroxyglutarate (2-HG), succinate, and fumarate are the most well-characterized, acting as competitive inhibitors of α-ketoglutarate-dependent dioxygenases to alter DNA and histone methylation, cellular differentiation, and hypoxia signaling. More recently, itaconate, an immunometabolite predominantly produced by activated macrophages, has been recognized for its dual roles in modulating inflammation and tumor immunity. These metabolites influence cancer development through multiple mechanisms, including epigenetic reprogramming, redox imbalance, and post-translational protein modifications. Importantly, their effects are not limited to cancer cells but extend to various components of the tumor microenvironment, such as T cells, macrophages, dendritic cells, and endothelial cells, reshaping immune responses and contributing to immune suppression. In this review, we highlight the emerging insights into the roles of TCA cycle-associated oncometabolites in cancer biology and immune regulation. We discuss how these metabolites impact both tumor-intrinsic processes and intercellular signaling within the tumor microenvironment. Finally, we examine therapeutic strategies targeting oncometabolite pathways, including mutant IDH inhibitors, α-ketoglutarate mimetics, and immunometabolic interventions, with the goal of restoring immune surveillance and improving cancer treatment outcomes.

PPM1D (protein phosphatase Mg⁺/Mn⁺ dependent 1D) is a Ser/Thr phosphatase that negatively regulates p53 and functions as an oncogenic driver. Its gene amplification and overexpression are frequently observed in various malignancies and disruption of PPM1D degradation has also been reported as a cause of cancer progression. However, the precise mechanisms regulating PPM1D stability remain to be elucidated.

While the Warburg effect links glycolysis to de novo lipid synthesis in carcinogenesis, the roles of lipids in cancer prognosis remain elusive. Here, a multi-omics approach was conducted in a cohort of hepatocellular carcinoma (HCC) to elucidate the role of lipid metabolites as prognostic markers.