Abstract Background Astrocytes, far beyond passive support cells, are critical regulators in brain homeostasis, intricately regulating synaptic plasticity, neurovascular integrity, metabolic support, and neuroimmune communication. Their dysregulation is increasingly implicated in the pathophysiology of a wide range of neuropsychiatric and neurodegenerative diseases. Methods This review synthesizes fundamental research exploring how astrocytic reactivity disrupts homeostatic functions. It evaluates current mechanisms of astrocyte‐mediated circuit dysfunction, specifically focusing on tripartite synapse and the secretion of immunomodulatory factors. The analysis further explores the utility of emerging technologies, including single‐cell transcriptomics and in vivo astrocyte‐specific manipulation tools. Results The synthesis identifies that astrocytic reactivity leads to a profound disruption of the glutamate/GABA balance, contributing to impaired synaptic signaling. A central finding is that altered astrocyte–neuron–microglia crosstalk contributes to circuit dysfunction. Furthermore, A significant challenge remains in the characterization of heterogeneous, context‐dependent astrocyte states and their specific contributions to pathogenesis. Conclusion A deeper mechanistic understanding of astrocyte biology is paramount for unveiling novel disease aetiologies and unlocking the potential for innovative astrocyte‐targeted therapeutic strategies.

Abstract Background Irritable bowel syndrome (IBS) is a prevalent condition in which disrupted communication between the gut and the brain plays a central role in disease manifestation. A dynamic, bidirectional regulatory network links the gut microbiota with the central nervous system (CNS), commonly referred to as the gut–brain axis, and this network exerts broad influence over both gastrointestinal physiology and psychological states. Aims This review specifically concentrates on direct microbiota–CNS communication pathways in the context of IBS. Materials and Methods This narrative review synthesizes existing experimental and clinical evidence related to gut microbiota–brain interactions, with a particular focus on neural and neuroendocrine signaling mechanisms. Results Gut microorganisms affect CNS function via microbial metabolites and neural signalling routes, whereas the CNS modulates gastrointestinal activity through integrated neural and endocrine pathways, involving the autonomic nervous system and the enteric nervous system. Given the complexity of these reciprocal interactions, this review specifically concentrates on direct microbiota–CNS communication pathways, with particular attention to neural circuits and the hypothalamic–pituitary–adrenal axis in the context of IBS. Conclusion Furthermore, we discuss how advances in precision stratification and multi‐omics approaches may facilitate the development of personalized therapeutic strategies, ultimately improving symptom control and restoring balance between gut microbial ecosystems and neural regulation.

Abstract Background Chimeric Antigen Receptor T‐cell (CAR‐T) therapy has evolved from its initial application in hematological cancers to treating solid tumors and autoimmune diseases. Despite iterative advancements in CAR design improving efficacy and safety, challenges including limited persistence, immune‐related toxicities, tumor resistance mechanisms, and barriers posed by the tumor microenvironment (TME) remain critical obstacles. Methods This review synthesizes current evidence on CAR‐T resistance mechanisms and therapeutic strategies. Key approaches analyzed include CAR design optimization (e.g., dual‐targeting), pre‐infusion tumor burden reduction, combination therapies to mitigate immune suppression, and cytokine support (e.g., IL‐2/IL‐15) to enhance persistence. The role of the TME (hypoxia, metabolic competition, immunosuppressive factors) and tumor‐intrinsic resistance drivers (antigen loss, anti‐apoptotic signaling) are systematically evaluated. Results Major resistance mechanisms include antigen escape (masking/loss), high tumor burden, and TME‐mediated suppression (hypoxia, immune checkpoints). Clinical challenges involve manufacturing delays, insufficient CAR‐T cytotoxicity, and poor persistence. Strategies such as dual‐target CARs, preconditioning regimens, and cytokine‐augmented persistence demonstrate preclinical/clinical promise in overcoming these limitations. Conclusions CAR‐T therapy holds transformative potential but requires addressing resistance and toxicity barriers. Future directions include allogeneic CAR‐T platforms, in vivo CAR‐T delivery, and novel combinatorial approaches. While these innovations offer exciting prospects, scalability, safety, and long‐term efficacy necessitate further translational and clinical research.

Abstract Background As one of commonly used immune checkpoint inhibition therapies, PD1 monoclonal antibodies exhibit a promising cancer immunotherapy approach. However, their efficacy on tumour immunity needs to be augment, as large numbers of patients poorly respond to the treatment or suffer from recurrence in clinical. Although pan‐PI3K is involved in the performance of PD1 on T cell immunity, the study for mechanisms of PI3K subunits involved in could be helpful for proposing a potential treatment strategy for lung cancer that combines anti‐PD1 treatment with PI3Kγ inhibitor. Materials & answers Alterations of CD4 + and CD8 + T cell subpopulations in 11 types of peripheral blood mononuclear cells with healthy subjects and cancer patients were examined. The efficacy of different treatment strategies for lung cancer was then investigated, and the factors affecting the efficacy of anti‐PD1 therapy in lung cancer were discussed. Results Lung cancer is characterized by widespread variation in T cell subsets, and anti‐PD1 treatment is effective against CD4 + Tcm, CD4 + Tem and CD4 + Tn cell subsets. The involvement of PI3K in the effect of anti‐PD1 was demonstrated using single‐cell RNA sequencing. The PI3Kγ inhibitor CAY10505 was effective against CD4 + Tcm and CD4 + Tn subsets in lung cancer in vitro but not in pan‐cancer therapy, indicating that the therapeutic effect of PI3Kγ on CD4 + T cells was lung cancer‐specific. G‐protein coupled receptor 183 ( GPR183 ) was involved in migration and positioning of immune cells and associated with various immune‐related diseases. Discussion We explored the regulatory role of GPR183 in the PI3K pathway and T cell subsets and identified potential lipids involved using lipidomics. We found that inhibition of PI3Kγ upregulated CD4 + Tcm and CD4 + Tn, potentially enhancing the therapeutic efficacy of anti‐PD1 antibodies. Combining anti‐PD1 treatment with PI3Kγ inhibitor could be a potential treatment strategy for lung cancer.

Abstract Background Diabetes, metabolic disorders and feeding behaviours continue to pose significant public health challenges. Calcium/calmodulin‐dependent protein kinase ID (CAMK1D) has recently emerged as a pivotal molecule potentially bridging peripheral metabolic control with central appetite regulation. Therefore, a comprehensive review was performed to critically evaluate and synthesize current evidence regarding the role of CAMK1D in diabetes, metabolic processes and feeding behaviours. Main text The review assessed both published results (263 non‐duplicate studies; across Pubmed, WebOfScience and EMBASE) and the grey literature (including 14 patents, 3 clinical trials). Results from 43 unique studies, 2 patents and 5 genome‐wide association studies were finally summarized. CAMK1D modulates both metabolic processes and feeding behaviours, exhibiting tissue‐specific dynamics and diverging regulatory control either in the central nervous system (i.e., hypothalamic nuclei regulating appetite and satiety) or in the periphery (i.e., pancreatic beta cells). Genetic studies highlighted significant associations between CAMK1D polymorphisms and increased susceptibility to diabetes, obesity and altered feeding behaviours. Conclusions CAMK1D represents an emerging molecular target with promising implications for the treatment of a wide range of clinical conditions. However, further large‐scale, mechanistic and longitudinal studies are warranted to validate its role across physiological and pathophysiological conditions, as well as to explore its future therapeutic potential.

Abstract Tumour heterogeneity, encompassing genetic, epigenetic, and microenvironmental diversity, remains a fundamental obstacle in precision oncology. Traditional bulk sequencing captures only averaged molecular profiles, thereby masking rare yet functionally critical subpopulations that drive malignant progression and therapeutic resistance. Recently, the emergence of single‐cell sequencing technologies has overcome the limitations of bulk approaches, enabling high‐resolution analyses of the genome, transcriptome, epigenome and proteome at the single‐cell level. These advances have enabled detailed mapping of tumour ecosystems, identification of key cellular subtypes, reconstruction of evolutionary trajectories and elucidation of intercellular communication networks within the tumour microenvironment. Accumulating evidence demonstrates that single‐cell technologies elucidate fundamental aspects of tumour biology and reveal potential diagnostic and therapeutic targets. This review systematically summarises the recent advances and applications of single‐cell sequencing in the field of precision oncology, with particular emphasis on its applications in mechanistic discovery, diagnosis, therapy, and prognosis. Furthermore, we discuss current challenges related to technology, data analysis, and clinical translation, and outline future research directions. In summary, single‐cell sequencing has profoundly reshaped our understanding of tumour biology and is propelling oncology into a new era of precision, prediction, and personalisation.