ABSTRACTBone metastasis (BoMet) is a common complication in various cancers. Approximately 20–30% of patients with cancer develop BoMet, which is most frequently associated with solid tumors, such as breast, prostate, and lung cancers. BoMet can lead to skeletal‐related events such as fractures, bone pain, and hypercalcemia, negatively affecting the patient's quality of life and markedly shortening overall survival. The development of BoMet is a complex, multistep process driven by dynamic interactions between tumor cells and the bone microenvironment. The bone microenvironment provides a supportive niche for disseminated tumor cells, where intricate signaling networks and stromal interactions regulate the initiation, dormancy, reactivation, and progression of BoMet. Although current bone‐targeted therapies can reduce the incidence of these complications, the clinical outcomes for patients with BoMet remain poor. Therefore, elucidating the molecular mechanisms governing these interactions is essential for identifying new therapeutic strategies. This review systematically explores the molecular drivers of BoMet progression, dynamic interactions within the metastatic niche, available preclinical models, established treatment modalities, and emerging therapeutic approaches. As fundamental research continues to advance toward clinical translation, the outlook for patients with BoMet is expected to improve significantly.

ABSTRACTThe advent of neuroimmunology has dismantled the traditional doctrine of the brain's immune privilege, uncovering a sophisticated and dynamic bidirectional regulatory interplay between the nervous and immune systems. This review synthesizes pivotal advances in neuroimmunology, integrating recent anatomical and molecular discoveries to refine the understanding of neuro‐immune communication. It highlights the pathological roles of neurotransmitters, cytokines, and their signaling networks in neurodegenerative, psychiatric, and neoplastic diseases, while critically examining contested regulatory mechanisms. The review further evaluates the clinical translational potential and challenges of innovative strategies such as vagus nerve stimulation, optogenetics, multiomics sequencing, and cytokine‐targeted therapies. By integrating multidisciplinary perspectives, this review consolidates a theoretical framework for neuro‐immune research and provides insights into precision medicine for related diseases. On the basis of synthesizing existing knowledge, it proposes promising research directions, identifies priorities and potential challenges for future investigations, and emphasizes the value of neuro‐immune mechanisms in guiding therapeutic development—including target identification, design of individualized treatment strategies, and cross‐disciplinary collaborative innovation to advance clinical interventions for neuro‐immune diseases. Finally, the review delves into the recent advances and challenges in combined neuromodulation‐immunotherapy strategies.

ABSTRACTReproductive toxicity testing is essential for evaluating whether xenobiotics, including pharmaceuticals, environmental chemicals, or ionizing radiation, adversely affect reproductive function. However, conventional assessments rely on mating outcomes or histopathology, which are labor‐intensive, variable, and require large numbers of animals. Acrosin, a serine protease encoded by the Acr gene and localized in the acrosome of spermatozoa, plays a critical role in sperm penetration of the zona pellucida. To exploit this germ cell‐specific expression, we generated a genetically engineered mouse model in which the Luciferase (Luc) reporter gene is driven by the Acr promoter. This Acr‐Luc knock‐in (KI) model enables longitudinal and quantitative imaging of spermatogenesis using bioluminescence. We demonstrate that this platform captures radiation‐induced impairments in male fertility in real time, eliminating the need for terminal analyses. By allowing repeated evaluation within the same individuals, our approach reduces interindividual variability and enables a substantial reduction in animal use, aligning with the “Reduction” principle of the 3Rs. Moreover, it reveals both the onset and recovery phases of spermatogenic disruption with high temporal resolution. The Acr‐Luc KI model provides a reliable preclinical platform for reproductive toxicity testing and offers broad utility for studies in reproductive biology, toxicology, and oncofertility research.

ABSTRACTThe clinical utility of mesenchymal stem cells (MSCs) is often limited by pulmonary entrapment and poor systemic distribution, particularly in diseases constrained by physiological barriers such as rheumatoid arthritis (RA), where joint accessibility restricts therapeutic efficacy. This study systematically compares the immunomodulatory capacity and inflammation‐targeting potential of human gingiva‐derived MSCs (GMSCs) and their extracellular vesicles (GMSC‐EVs) in vivo. Using an experimental RA model, we demonstrate that GMSC‐EVs exhibit superior tropism to inflamed joints compared to GMSCs, resulting in significantly greater amelioration of disease severity, including reduced joint swelling, bone destruction, and balanced pathogenic T‐cell responses. Mechanistically, we identify C‐C chemokine receptor type 2 (CCR2) as the critical molecular driver of this targeted homing. Genetic ablation of CCR2 via CRISPR‐Cas9/sgRNA knockdown abolishes both the joint‐specific accumulation of GMSC‐EVs and their therapeutic efficacy. These findings elucidate the molecular basis for GMSC‐EVs tropism to arthritic lesions and establish CCR2 as a pivotal target for developing precision‐engineered EVs therapies with enhanced specificity for RA treatment.

ABSTRACTSepsis, a life‐threatening dysregulated host response to infection, is frequently exacerbated by pyroptosis—a programmed, proinflammatory cell death process mediated by Gasdermin D (GSDMD) activation. Using high‐throughput screening, we identified emestrin‐type epidithiodiketopiperazines (ETPs) as potent inhibitors of GSDMD cleavage during pyroptosis in Tohoku Hospital Pediatrics‐1 (THP‐1, a human acute monocytic Leukemia cell line)‐derived macrophages. Combined surface plasmon resonance and western blotting analyses demonstrated that these ETPs activate caspase‐3/7, which in turn cleaves GSDMD at aspartic acid residue 87 to generate a p10 fragment. This process prevents the formation of the pore‐forming p30 fragment, thereby mitigating its associated inflammatory effects. Building on these results, in vivo studies showed that a low dose of the lead emestrin‐type ETP (compound 2) protected against lethal lipopolysaccharide (LPS)‐induced septic shock and attenuated lung inflammation. This protective effect was further validated in the clinically relevant cecal ligation and puncture (CLP) model, where compound 2 significantly enhanced survival by suppressing the infiltration of GSDMD‐positive neutrophils and monocytes. scRNA‐seq of murine lung tissue showed that compound 2 suppressed LPS‐induced systemic inflammation by inhibiting moDC maturation. Collectively, these findings establish the therapeutic potential of targeting GSDMD‐driven pyroptosis with ETPs in sepsis and suggest their promise for clinical translation.

ABSTRACTOrgan transplantation has progressed from a life‐saving surgical intervention to a multidisciplinary field integrating immunology, bioengineering, and data science. Despite major advances in donor management, perioperative care, and immunosuppression, long‐term graft survival remains limited due to chronic rejection, infection, and organ scarcity. Recent breakthroughs in organ preservation, particularly in hypothermic and normothermic machine perfusion, have enabled real‐time graft assessment, metabolic reconditioning, and localized therapeutic delivery. Emerging precision immunomodulation strategies, including regulatory T‐cell therapy, gene‐edited cellular platforms, tolerogenic dendritic cells, and biomarker‐guided minimization, are reshaping alloimmune control toward durable tolerance. Innovations in xenotransplantation, multigene‐edited donor animals, and tissue biofabrication offer potential solutions to structural organ shortages, although they are accompanied by regulatory and ethical challenges. Artificial intelligence further enhances donor–recipient matching, risk prediction, and personalized immunosuppressive management. This review synthesizes advances in preservation technologies, immune engineering, cellular tolerance induction, artificial intelligence‐driven decision support, and xenotransplantation and provides a comprehensive overview of the evolving transplant landscape. By integrating mechanistic insights into translational progress, we outline future pathways for regenerative, immune‐educational, and precision organ medicine.

ABSTRACTMelanoma is the most aggressive skin malignant tumor, typically exhibiting a high mutation burden and potentially harboring mutations in NRAS, BRAF, or NF1. To enhance survival rates, these driver alterations can achieve significant antitumor activity through targeted therapy. In the past decade, BRAF inhibitors combined with MEK inhibitors significantly improved the prognosis of BRAF mutation melanoma. Nevertheless, researchers have attempted various strategies to block the NRAS signaling pathway, NRAS mutation in melanoma is still considered to be untargetable. In recent years, MEK inhibitors like binimetinib and tunlametinib have displayed the efficacy for NRASmut melanoma, with tunlametinib being the first and only approved MEK inhibitor for advanced NRASmut melanoma. On the other hand, immune checkpoint inhibitors including PD‐1/PD‐L1 inhibitors and cytotoxic T‐lymphocyte antigen 4 （CTLA‐4） inhibitors changed the treatment landscape of advanced melanoma. In this review, we have summarized the current knowledge of molecular pathogenesis and classification of melanoma. Subsequently, we explored current and potential treatment approaches for melanoma, primarily encompassing BRAF inhibitors, MEK inhibitors, and immunotherapy, with a particular focus on their clinical relevance of development. Finally, the challenges in the treatment of melanoma, particularly in immunotherapy and targeted therapy, are summarized and discussed.

ABSTRACTCancer and tissue regeneration pose great challenges to global health, as cancer treatment is impeded by tumor heterogeneity and therapy resistance, while regenerative medicine is constrained by donor shortages and difficulties in replicating native tissue structures. Organoids, as advanced three‐dimensional multicellular structures derived from stem cells, have emerged as transformative tools in biomedical research. They recapitulate key aspects of native human tissue composition and functions, offering enhanced physiological relevance over traditional models. Therefore, this review aims to highlight the latest advancements in organoid technology within the fields of cancer research and regenerative medicine. We begin by discussing the fundamental aspects of organoid generation, characterization, and application. Furthermore, recent progress in both cancer‐oriented and regeneration‐focused organoids is summarized, with an emphasis on their applications in disease modeling, drug screening, mechanistic analysis, and precision medicine. Based on an extensive review of the literature, the current challenges and future directions in the development and application of organoid models are discussed. As organoid technology continues to evolve, it is anticipated that more high‐quality studies will further advance medical science and foster innovation in personalized therapeutics.

ABSTRACTEvidence for the use of prophylactic anti‐seizure medication (ASM) in traumatic brain injury (TBI) in reducing the occurrence of early post‐traumatic seizure (EPTS) remains equivocal. This study aimed to analyze the prevalence of EPTS in children with TBI, compare clinical characteristics of those with and without EPTS, and explore the association between prophylactic ASM and EPTS. We performed an observational study among 28 pediatric intensive care units in 15 countries from January 2014 to October 2022. The rate of EPTS was compared between individuals prescribed prophylactic ASM and those who were not. Logistic regression was used to examine the association between ASM and EPTS. Among 697 children with TBI, 161 (23.1%) developed EPTS and 280 (40.2%) received prophylactic ASM treatment. Use of prophylactic ASM was associated with a lower likelihood of developing EPTS (27/280 (9.6%) vs. 134/417 (32.1%), p < 0.001). The most frequently used prophylactic ASMs were phenytoin, levetiracetam, and phenobarbital. Age ≤ 4 years and GCS ≤ 8 were associated with increased odds of developing EPTS (aOR 2.29, 95% CI 1.54–3.40, p < 0.001 and aOR 1.80, 95% CI 1.18–2.74, p = 0.01). Our data provide evidence supporting the potential protective role of prophylactic ASM against EPTS.

ABSTRACTThe metabolic signature of anti‐leucine‐rich glioma‐inactivated 1 (anti‐LGI1) autoimmune encephalitis remains poorly defined. We sought to delineate disease‐specific 18F‐FDG PET patterns and assess their relationships with clinical severity and cognition. Forty‐seven patients with anti‐LGI1 encephalitis and 25 healthy controls underwent 18F‐FDG PET/CT, and voxel‐wise comprised to identify regional metabolic alterations. A disease‐specific metabolic pattern was derived with fivefold cross‐validation, and a metabolic covariance network was mapped using the Brainnetome atlas. Pattern expression scores were correlated with clinical assessments. Compared to controls, patients demonstrated hypermetabolism in the hippocampal rostal, nucleus accumbens (NAc), and hypothalamus, alongside hypometabolism in the dorsolateral prefrontal cortex and posterior cingulate cortex (PCC). We identified a robust metabolic pattern centered on the NAc with extensions to the hippocampus, prefrontal cortex, and PCC; expression of this pattern correlated positively with both clinical severity and cognitive impairment. Subgroup analyses showed no significant differences in basal ganglia metabolism between patients with and without faciobrachial dystonic seizures (FBDS), or in hypothalamic metabolism between those with and without hyponatremia. Overall, 18F‐FDG PET uncovers a NAc‐centered metabolic network that parallels disease severity in anti‐LGI1 encephalitis. Our study offers potential biomarker for clinical evaluation and provides valuable insights into the underlying pathogenesis of clinical manifestations.