Clinical and translational discovery最新文献

{"title":"Sex differences in genomics, immune microenvironment and immunotherapy response in adult grade 4 gliomas","authors":"Feng Tang,&nbsp;Zhen-Yuan Liu,&nbsp;Xi Chen,&nbsp;Jin-Zhou Yang,&nbsp;Zhi-Qiang Li","doi":"10.1002/ctd2.70133","DOIUrl":"https://doi.org/10.1002/ctd2.70133","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>Sex differences in the prevalence of gliomas have been reported; however, whether there are sex differences in the development and immunotherapy of gliomas remains poorly understood. This study aims to explore sex differences in genomics, immune microenvironment, and immunotherapy response in adult grade 4 gliomas.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The clinical and pathological data of 238 patients with adult grade 4 gliomas in our cohort, data of a large tumour immunotherapy cohort (a total of 1512 patients), and several glioma-related cohorts (a total of 2272 patients) were collected. To comprehensively explore sex-based differences in grade 4 gliomas, we performed a retrospective analysis, assessed immune-cell infiltration, and conducted a meta-analysis. Further characterisation was achieved through immunohistochemistry, Kaplan–Meier survival analysis, Gene Ontology enrichment and Kyoto Encyclopaedia of Genes and Genomes pathway analyses to investigate underlying biological mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that female grade 4 patients receiving immune checkpoint inhibitor treatment presented a poorer prognosis than male patients, while those receiving non-immunotherapy exhibited a better prognosis than male patients. Compared to male grade 4 gliomas, female patients had higher levels of tumour-infiltrating monocyte-macrophages but lower levels of circulating monocytes. In addition, there were also differences in genomics between female and male grade 4 gliomas.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>There were sex differences in overall survival, immune microenvironment, and genomics in patients with grade 4 gliomas.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 2","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70133","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147565351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences in genomics, immune microenvironment and immunotherapy response in adult grade 4 gliomas","authors":"Feng Tang,&nbsp;Zhen-Yuan Liu,&nbsp;Xi Chen,&nbsp;Jin-Zhou Yang,&nbsp;Zhi-Qiang Li","doi":"10.1002/ctd2.70133","DOIUrl":"https://doi.org/10.1002/ctd2.70133","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>Sex differences in the prevalence of gliomas have been reported; however, whether there are sex differences in the development and immunotherapy of gliomas remains poorly understood. This study aims to explore sex differences in genomics, immune microenvironment, and immunotherapy response in adult grade 4 gliomas.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The clinical and pathological data of 238 patients with adult grade 4 gliomas in our cohort, data of a large tumour immunotherapy cohort (a total of 1512 patients), and several glioma-related cohorts (a total of 2272 patients) were collected. To comprehensively explore sex-based differences in grade 4 gliomas, we performed a retrospective analysis, assessed immune-cell infiltration, and conducted a meta-analysis. Further characterisation was achieved through immunohistochemistry, Kaplan–Meier survival analysis, Gene Ontology enrichment and Kyoto Encyclopaedia of Genes and Genomes pathway analyses to investigate underlying biological mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that female grade 4 patients receiving immune checkpoint inhibitor treatment presented a poorer prognosis than male patients, while those receiving non-immunotherapy exhibited a better prognosis than male patients. Compared to male grade 4 gliomas, female patients had higher levels of tumour-infiltrating monocyte-macrophages but lower levels of circulating monocytes. In addition, there were also differences in genomics between female and male grade 4 gliomas.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>There were sex differences in overall survival, immune microenvironment, and genomics in patients with grade 4 gliomas.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 2","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70133","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147565465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Linking physical stimulation to molecular responses: The role and value of exosomes in mediating the systemic effects of Chinese Tuina","authors":"Lifen Zhan,&nbsp;Ji Zhang,&nbsp;Yiping Chen,&nbsp;Suyu Chen,&nbsp;Xiantao Tai","doi":"10.1002/ctd2.70122","DOIUrl":"https://doi.org/10.1002/ctd2.70122","url":null,"abstract":"<p>Chinese Tuina, a fundamental manual therapy technique in traditional Chinese medicine (TCM), treats diseases by applying precisely regulated mechanical forces to the human body. Although its clinical benefits have been extensively documented across a range of conditions—from musculoskeletal pain to neurological disorders—the molecular mechanisms underlying its systemic effects remain partially understood. Meanwhile, exosomes, ubiquitous nanoscale extracellular vesicles, have emerged as key mediators of intercellular communication. These vesicles transfer proteins, lipids and nucleic acids to coordinate bodily homeostasis and responses to stimuli. This review integrates these two fields, proposing that the mechanical forces generated by Chinese Tuina (pressure: 50–300 kPa; shear force: 10–50 dyn/cm²; tension: 5%–20% strain; typical session duration: 15–45 min) constitute an efficient, non-invasive physiological stimulus capable of systemically regulating the production and release of functional exosomes. We systematically dissect the complete pathway initiating from the perception of mechanical forces at the site of manipulation, followed by exosome release from target cells, distribution via the circulatory system, and finally, the multi-dimensional impacts on distant organs. By defining Chinese Tuina as a “mechanical stimulator of the exosome network,” this review aims to establish a novel biological paradigm for manual therapy, providing profound insights into understanding its mechanisms of action and advancing the development of precision rehabilitation medicine.</p>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 2","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70122","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147563303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Linking physical stimulation to molecular responses: The role and value of exosomes in mediating the systemic effects of Chinese Tuina","authors":"Lifen Zhan,&nbsp;Ji Zhang,&nbsp;Yiping Chen,&nbsp;Suyu Chen,&nbsp;Xiantao Tai","doi":"10.1002/ctd2.70122","DOIUrl":"https://doi.org/10.1002/ctd2.70122","url":null,"abstract":"<p>Chinese Tuina, a fundamental manual therapy technique in traditional Chinese medicine (TCM), treats diseases by applying precisely regulated mechanical forces to the human body. Although its clinical benefits have been extensively documented across a range of conditions—from musculoskeletal pain to neurological disorders—the molecular mechanisms underlying its systemic effects remain partially understood. Meanwhile, exosomes, ubiquitous nanoscale extracellular vesicles, have emerged as key mediators of intercellular communication. These vesicles transfer proteins, lipids and nucleic acids to coordinate bodily homeostasis and responses to stimuli. This review integrates these two fields, proposing that the mechanical forces generated by Chinese Tuina (pressure: 50–300 kPa; shear force: 10–50 dyn/cm²; tension: 5%–20% strain; typical session duration: 15–45 min) constitute an efficient, non-invasive physiological stimulus capable of systemically regulating the production and release of functional exosomes. We systematically dissect the complete pathway initiating from the perception of mechanical forces at the site of manipulation, followed by exosome release from target cells, distribution via the circulatory system, and finally, the multi-dimensional impacts on distant organs. By defining Chinese Tuina as a “mechanical stimulator of the exosome network,” this review aims to establish a novel biological paradigm for manual therapy, providing profound insights into understanding its mechanisms of action and advancing the development of precision rehabilitation medicine.</p>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 2","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70122","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147563471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Invited letter MUC4 mutations as an amplifier of complement-mediated thrombosis in paroxysmal nocturnal haemoglobinuria","authors":"Eng Soo Yap,&nbsp;Edwin Wei Sheng Thong,&nbsp;Cheryl Xiu Qi Lim","doi":"10.1002/ctd2.70130","DOIUrl":"10.1002/ctd2.70130","url":null,"abstract":"&lt;p&gt;Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired clonal disorder arising from somatic mutations in the X-linked PIGA gene in hematopoietic stem cells, resulting in deficiency of glycosylphosphatidylinositol (GPI)-anchored proteins.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; The absence of complement regulators CD55 (decay-accelerating factor) and CD59 renders PNH erythrocytes and platelets susceptible to uncontrolled complement activation, leading to chronic intravascular haemolysis and a 5- to 10-fold increased risk of life-threatening thrombosis&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; often at unusual sites (e.g. hepatic, cerebral or dermal veins).&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; The anti-C5 monoclonal antibody eculizumab, and its long-acting successor ravulizumab, have transformed PNH management by blocking terminal complement activation, producing marked reductions in intravascular haemolysis and substantially lowering thrombotic risk.&lt;span&gt;&lt;sup&gt;4, 5&lt;/sup&gt;&lt;/span&gt; However, thromboses persist in a small proportion of treated patients, particularly during episodes of breakthrough haemolysis or periods of suboptimal complement blockade.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; This residual risk underscores the contribution of complementary prothrombotic pathways beyond direct membrane attack complex (MAC) formation. Recent genomic studies have identified MUC4 (transmembrane mucin-4) mutations as a potential novel risk modifier. In a Chinese cohort of patients with classic PNH, Chen et al. reported a significantly higher prevalence of MUC4 exon 2 mutations among individuals with thrombotic events compared with those without thrombosis, with multivariate analysis identifying MUC4 mutation as an independent risk factor.&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt; Cumulative thrombosis incidence was markedly increased among mutation carriers. This unexpected finding implicates a transmembrane mucin in PNH thrombogenesis and challenges us to reconsider how genetic modifiers shape phenotypic severity.&lt;/p&gt;&lt;p&gt;Thrombosis in PNH is not a singular consequence of haemolysis but rather the result of a complex, self-amplifying network involving complement activation, coagulation, inflammation, and endothelial dysfunction. Loss of CD55 and CD59 permits unregulated C3b deposition and MAC formation on blood cells. On platelets, sublytic MAC triggers activation, microparticle release, and surface phosphatidylserine exposure, creating pro-thrombotic particles.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; Concurrently, C5a generation activates neutrophils and monocytes via C5aR1, promoting tissue factor (TF) expression and neutrophil extracellular trap (NET) formation.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; NETs serve as a scaffold for platelet aggregation, while thrombin generated via TF activation can further cleave C5, establishing a complement-coagulation feedback loop.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Intravascular haemolysis liberates cell-free haemoglobin and haem, which act as danger-associated molecular patterns. Haemoglobin scavenges nitric oxide, caus","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 2","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70130","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147562525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Invited letter MUC4 mutations as an amplifier of complement-mediated thrombosis in paroxysmal nocturnal haemoglobinuria","authors":"Eng Soo Yap,&nbsp;Edwin Wei Sheng Thong,&nbsp;Cheryl Xiu Qi Lim","doi":"10.1002/ctd2.70130","DOIUrl":"https://doi.org/10.1002/ctd2.70130","url":null,"abstract":"&lt;p&gt;Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired clonal disorder arising from somatic mutations in the X-linked PIGA gene in hematopoietic stem cells, resulting in deficiency of glycosylphosphatidylinositol (GPI)-anchored proteins.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; The absence of complement regulators CD55 (decay-accelerating factor) and CD59 renders PNH erythrocytes and platelets susceptible to uncontrolled complement activation, leading to chronic intravascular haemolysis and a 5- to 10-fold increased risk of life-threatening thrombosis&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; often at unusual sites (e.g. hepatic, cerebral or dermal veins).&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; The anti-C5 monoclonal antibody eculizumab, and its long-acting successor ravulizumab, have transformed PNH management by blocking terminal complement activation, producing marked reductions in intravascular haemolysis and substantially lowering thrombotic risk.&lt;span&gt;&lt;sup&gt;4, 5&lt;/sup&gt;&lt;/span&gt; However, thromboses persist in a small proportion of treated patients, particularly during episodes of breakthrough haemolysis or periods of suboptimal complement blockade.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; This residual risk underscores the contribution of complementary prothrombotic pathways beyond direct membrane attack complex (MAC) formation. Recent genomic studies have identified MUC4 (transmembrane mucin-4) mutations as a potential novel risk modifier. In a Chinese cohort of patients with classic PNH, Chen et al. reported a significantly higher prevalence of MUC4 exon 2 mutations among individuals with thrombotic events compared with those without thrombosis, with multivariate analysis identifying MUC4 mutation as an independent risk factor.&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt; Cumulative thrombosis incidence was markedly increased among mutation carriers. This unexpected finding implicates a transmembrane mucin in PNH thrombogenesis and challenges us to reconsider how genetic modifiers shape phenotypic severity.&lt;/p&gt;&lt;p&gt;Thrombosis in PNH is not a singular consequence of haemolysis but rather the result of a complex, self-amplifying network involving complement activation, coagulation, inflammation, and endothelial dysfunction. Loss of CD55 and CD59 permits unregulated C3b deposition and MAC formation on blood cells. On platelets, sublytic MAC triggers activation, microparticle release, and surface phosphatidylserine exposure, creating pro-thrombotic particles.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; Concurrently, C5a generation activates neutrophils and monocytes via C5aR1, promoting tissue factor (TF) expression and neutrophil extracellular trap (NET) formation.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; NETs serve as a scaffold for platelet aggregation, while thrombin generated via TF activation can further cleave C5, establishing a complement-coagulation feedback loop.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Intravascular haemolysis liberates cell-free haemoglobin and haem, which act as danger-associated molecular patterns. Haemoglobin scavenges nitric oxide, caus","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 2","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70130","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147562551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Astrocytes as central integrators of neural circuit function: Mechanisms and dysregulation in neuropsychiatric disorders","authors":"Xinyu Liu,&nbsp;Xinyue Zhou,&nbsp;Ruotong Meng,&nbsp;Yanxi Chen,&nbsp;You Chen,&nbsp;Blake Highet,&nbsp;Maurice Curtis,&nbsp;Bernhard Hirt,&nbsp;Shunying Yu,&nbsp;Jin Zhou,&nbsp;Linya You","doi":"10.1002/ctd2.70128","DOIUrl":"10.1002/ctd2.70128","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>A deeper mechanistic understanding of astrocyte biology is paramount for unveiling novel disease aetiologies and unlocking the potential for innovative astrocyte-targeted therapeutic strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 2","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70128","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147562201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Astrocytes as central integrators of neural circuit function: Mechanisms and dysregulation in neuropsychiatric disorders","authors":"Xinyu Liu,&nbsp;Xinyue Zhou,&nbsp;Ruotong Meng,&nbsp;Yanxi Chen,&nbsp;You Chen,&nbsp;Blake Highet,&nbsp;Maurice Curtis,&nbsp;Bernhard Hirt,&nbsp;Shunying Yu,&nbsp;Jin Zhou,&nbsp;Linya You","doi":"10.1002/ctd2.70128","DOIUrl":"https://doi.org/10.1002/ctd2.70128","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>A deeper mechanistic understanding of astrocyte biology is paramount for unveiling novel disease aetiologies and unlocking the potential for innovative astrocyte-targeted therapeutic strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 2","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70128","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147562238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From channel-spatial attention to state space models: A review of evolving mechanisms in tumour segmentation","authors":"Yanfei Sun,&nbsp;Junyu Wang,&nbsp;Rui Yin","doi":"10.1002/ctd2.70127","DOIUrl":"10.1002/ctd2.70127","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This review delineates the evolution of attention architectures in automated tumor segmentation across three pivotal paradigms: classic Pre-Transformer attention, dominant Transformer-based self-attention, and emerging Mamba-based state space models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We synthesize their functional roles—from channel enhancement to long-range dependency modelingand critically assess hybrid structures designed for multimodal clinical oncology scenarios.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Findings/Results</h3>\u0000 \u0000 <p>The review establishes attention mechanisms as a foundational pillar for the next generation of intelligent segmentation tools, highlighting their potential in feature enhancement and localization.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Interrogating current challenges and charting future trajectories, these mechanisms are poised to profoundly impact the landscape of precision medicine.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 2","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70127","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147569169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of T cells in sepsis of distinct infectious aetiologies","authors":"Xuanqi Liu,&nbsp;Bijun Zhu,&nbsp;Wanxin Duan,&nbsp;Ruixiang Kang,&nbsp;Xiangdong Wang,&nbsp;Liyang Li","doi":"10.1002/ctd2.70125","DOIUrl":"10.1002/ctd2.70125","url":null,"abstract":"<p>Sepsis is a complex and life-threatening syndrome resulting from infection and characterized by dysregulated host immune responses. T cells play a central role in orchestrating immune defence against pathogens, yet their function undergoes profound alterations during sepsis. The impact of sepsis on T cell function varies depending on the causative pathogen. T cells exhibit an initial hyperactivation phase in bacterial sepsis, followed by a state of exhaustion, characterised by reduced cytokine production, impaired proliferation, and metabolic dysfunction. Such disorders are associated with disruptions in T cell receptor signalling, upregulation of immune checkpoint molecules such as PD-1 and CTLA4, and mitochondrial damage. T cell dysfunction is often linked to immunosuppression in viral sepsis, with an inhibition of antiviral responses and induction of immune tolerance. The distinct immune evasion strategies impair T cell-mediated pathogen clearance in viral sepsis, while altered T cell subsets are observed in fungal and parasitic sepsis. Such immune dysregulations exacerbate sepsis-induced immune suppression, increase susceptibility to secondary infections, and worsen clinical outcomes. Elucidating the pathogen-specific pathways that underlie T cell dysfunction in sepsis is crucial for the development of precise immunotherapies. These insights could inform the design of therapeutic strategies aimed at restoring T cell function and improving the prognosis of septic patients.</p>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 2","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70125","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147569498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}