Interdisciplinary Medicine最新文献

{"title":"Unveiling the roles of extracellular vesicles in hematologic malignancies: Pathogenesis, diagnostic tools, and clinical translation (4/2026)","authors":"Fengyu Chen,&nbsp;Zhiyuan Wu,&nbsp;Feng Zhang,&nbsp;Yuan Meng,&nbsp;Hongyan Liao,&nbsp;Tony Y. Hu","doi":"10.1002/inmd.70169","DOIUrl":"https://doi.org/10.1002/inmd.70169","url":null,"abstract":"<p>The cover depicts extracellular vesicles (EVs) within the malignant bone marrow microenvironment of hematological malignancies. Cold blue, disorganized fibrous structures represent eroded trabecular bone and increased reticular fibers, while warm-toned malignant hematopoietic cells dominate the pathological marrow niche. At the center, EVs are shown being released from tumor cells and traveling through the marrow space, highlighting their role as nanoscale mediators of intercellular communication. Transparent and cross-sectional vesicles reveal their bioactive cargo, including nucleic acids, proteins, and metabolites, symbolizing how EVs transfer molecular signals between malignant cells, stromal cells, immune cells, and residual hematopoietic cells. Scattered erythrocytes, leukocytes, adipocytes, and macrophages further emphasize the disrupted cellular composition of the tumor-associated marrow environment. By integrating pathological features such as marrow fibrosis, vascular distortion, and cellular imbalance with the dynamic movement of EVs, the image visualizes how vesicle-mediated communication contributes to microenvironmental remodeling, tumor cell survival, immune suppression, angiogenic alteration, metabolic adaptation, and drug resistance in hematological malignancies. This visual concept reflects the biological basis for understanding the diverse functions of EVs in hematologic disease progression and their emerging translational significance. Designed by Guo Jialin, Guangzhou Academy of Fine Arts.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":100686,"journal":{"name":"Interdisciplinary Medicine","volume":"4 4","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/inmd.70169","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148533642","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":"Tiny carriers, big impact: How Fusobacterium nucleatum extracellular vesicles drive oral diseases and beyond (4/2026)","authors":"Rongyang Ma,&nbsp;Jiahui Huang,&nbsp;Yitong Chen,&nbsp;Haoxuan Wang,&nbsp;Hang Zou,&nbsp;Wanghong Zhao,&nbsp;Zilong Deng","doi":"10.1002/inmd.70168","DOIUrl":"https://doi.org/10.1002/inmd.70168","url":null,"abstract":"<p>The cover visualizes <i>Fusobacterium nucleatum</i> deploying extracellular vesicles (<i>F. nucleatum</i> EVs) as rocket-like “long-range weapons,” mirroring our review on how these nano-carriers mediate host-pathogen interactions to target distal organs, driving oral and systemic diseases.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":100686,"journal":{"name":"Interdisciplinary Medicine","volume":"4 4","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/inmd.70168","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148534143","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":"Potent monoclonal antibodies against multidrug-resistant hypervirulent Klebsiella pneumoniae","authors":"Yushan Jiang,&nbsp;Zhuolin Li,&nbsp;Yang Yang,&nbsp;Zihan He,&nbsp;Tyuji Hoshino,&nbsp;Vladislav Victorovich Khrustalev,&nbsp;Qing Zhu,&nbsp;Weiling Wu,&nbsp;Wei Zhao,&nbsp;Chenguang Shen,&nbsp;Shi Ouyang","doi":"10.1002/inmd.70115","DOIUrl":"https://doi.org/10.1002/inmd.70115","url":null,"abstract":"<p>Multidrug-resistant hypervirulent <i>Klebsiella pneumoniae</i> (MDR-hvKP) infections present a therapeutic challenge owing to profound antibiotic resistance and the paucity of cross-serotype protective strategies against distinct serovars (e.g., K1/K2). Mice were subcutaneously immunized with the viable, hypovirulent, multidrug-resistant (MDR) strain Kp00198874 (serotype K64). Cross-reactive monoclonal antibodies (mAbs) were derived using hybridoma technology. Immunization elicited cross-serotype protective antibodies, ensuring 100% survival rates against lethal challenges posed by the K1/K2 serotype strains. In contrast to single neutralizing antibodies, mAbs 2D4 and 2E10 modulate phagocytic bacteria and immune responses. Prophylactic administration of mAbs conferred 100% survival rates against Kp-GZ8 and significantly prolonged the median survival time against ATCC43816 cells. Therapeutic intervention with mAbs mitigated post-infection pulmonary hemorrhage and inflammatory responses. mAbs 2D4 and 2E10 synergistically targeted capsular polysaccharide/protein epitopes to achieve cross-serotype-protective efficacy. This study established live Kp00198874 immunization as a novel platform for generating cross-protective mAbs against lethal MDR-hvKP, with 2D4 and 2E10 providing complementary mechanisms (rapid pathogen clearance and immunomodulation) through conserved epitope targeting, offering an antibody-based alternative for resistant infections.</p>","PeriodicalId":100686,"journal":{"name":"Interdisciplinary Medicine","volume":"4 4","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/inmd.70115","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148533841","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":"Freeze-resistant, conductive semi-interpenetrating network hydrogels enable oxidative stress regulation and enhanced wound healing","authors":"Xiaomin Sun,&nbsp;Yanqin Yu,&nbsp;Xinyuan He,&nbsp;Kaiyi Tang,&nbsp;Lijing Teng,&nbsp;Tianbao Qian,&nbsp;Zhu Zeng,&nbsp;Zuquan Hu","doi":"10.1002/inmd.70097","DOIUrl":"https://doi.org/10.1002/inmd.70097","url":null,"abstract":"<p>Accumulation of reactive oxygen species (ROS) following skin injury impairs tissue regeneration by inducing inflammation, oxidative damage, and cellular apoptosis. To address this challenge, we developed a multifunctional semi-interpenetrating polymer network hydrogel composed of silk fibroin methacrylate (SFMA) and Pluronic F127 (PF). The optimized SFMA9/PF1 hydrogel exhibits excellent mechanical compliance, electrical conductivity, antioxidant activity, and anti-freezing capacity. Incorporation of PF enhanced porosity, water retention, and ionic conductivity (∼0.42 S·cm⁻¹), while preserving optical transparency and tunable viscoelasticity. Rheological and degradation analyses demonstrated outstanding elasticity, thermal stability, strain resistance, and sustained biodegradability under physiological conditions. Notably, the hydrogel maintains flexibility and structural integrity at subzero temperatures (−20°C and −80°C), indicating strong freeze resistance. In vitro assays confirmed superior cytocompatibility, with significant promotion of fibroblast adhesion, migration, and proliferation. The hydrogel also exhibited potent antioxidant capacity, effectively scavenging 1,1-diphenyl-2-picrylhydrazyl and H₂O₂ radicals and reducing intracellular ROS levels. In a full-thickness skin wound model in SD rats, SFMA9/PF1 hydrogel accelerated wound closure, enhanced re-epithelialization, and promoted organized collagen remodeling. Histological and immunofluorescence analyses revealed increased angiogenesis (CD31), reduced myofibroblast activation (α-SMA), and suppressed pro-inflammatory cytokine expression (IL-6), indicating the establishment of a regenerative and anti-inflammatory microenvironment. Overall, the SFMA9/PF1 hydrogel integrates mechanical adaptability, bioactivity, and oxidative stress modulation, representing a promising platform for advanced wound healing and skin tissue engineering.</p>","PeriodicalId":100686,"journal":{"name":"Interdisciplinary Medicine","volume":"4 4","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/inmd.70097","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148534230","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":"Unveiling the roles of extracellular vesicles in hematologic malignancies: Pathogenesis, diagnostic tools, and clinical translation","authors":"Fengyu Chen,&nbsp;Zhiyuan Wu,&nbsp;Feng Zhang,&nbsp;Yuan Meng,&nbsp;Hongyan Liao,&nbsp;Tony Y. Hu","doi":"10.1002/inmd.70147","DOIUrl":"https://doi.org/10.1002/inmd.70147","url":null,"abstract":"<p>Hematologic malignancies (HMs) are aggressive neoplasms originating from lymphoid or myeloid lineages. They are characterized by heterogeneous clinical manifestations, high refractoriness, and frequent relapse. Recent advances in extracellular vesicle (EV) research have revealed their translational potential in improving the diagnosis, prognosis, and treatment of HMs. EVs are nanoscale membrane-bound particles secreted by cells. They carry bioactive cargo, including nucleic acids, proteins, and metabolites, and mediate intercellular communication. In HMs, EVs play essential roles in tumor initiation, progression, metastasis, angiogenesis, metabolic reprogramming, and drug resistance, positioning them as pivotal contributors to disease pathogenesis. Leveraging their functional versatility and disease-specific molecular signatures, EVs show promise as non-invasive biomarkers for early detection and disease monitoring. They also represent potential therapeutic targets to disrupt tumor-microenvironment crosstalk, and as engineered drug delivery systems for precision medicine. This review systematically examines the pathobiological functions of EVs in HMs and highlights emerging clinical applications, offering valuable insights to guide future research.</p>","PeriodicalId":100686,"journal":{"name":"Interdisciplinary Medicine","volume":"4 4","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/inmd.70147","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148534312","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":"Hydrogel-based drug delivery systems for intracerebral hemorrhage with therapeutic advances and emerging roles of the bone–brain axis","authors":"Haojun Shi,&nbsp;Min Chen,&nbsp;Yisheng Chen,&nbsp;MengYao Li,&nbsp;Jiale Ma,&nbsp;Zuozhen Yin,&nbsp;Li Wu,&nbsp;YangBao Miao,&nbsp;Zemin Ou,&nbsp;Ke Wu,&nbsp;Zhijie Xu,&nbsp;Lizhi Li,&nbsp;Shaocong Zhao,&nbsp;Shiwei He,&nbsp;Bin Huang,&nbsp;Guanwen He,&nbsp;Guanghui Wu,&nbsp;John H. Zhang,&nbsp;Liang Shi","doi":"10.1002/inmd.70138","DOIUrl":"https://doi.org/10.1002/inmd.70138","url":null,"abstract":"<p>Intracerebral hemorrhage (ICH) is a severe neurological condition characterized by high mortality and long-term disability. The pathophysiology of ICH involves not only primary hematoma formation but also secondary injury mechanisms such as blood–brain barrier disruption, oxidative stress, excitotoxicity, and neuroinflammation. Hematoma-derived factors like hemoglobin, iron, and thrombin, together with pro-inflammatory cytokines from activated glial and immune cells, exacerbate neurovascular dysfunction. Emerging research highlights the role of the bone-brain axis, where bone marrow-derived cells and osteokines influence systemic inflammation, angiogenesis, and tissue repair. Hydrogel-based drug delivery systems (HDDS) have gained attention for their potential to address these challenges, offering controlled release, biocompatibility, and targeted delivery. This review summarizes recent advancements in hydrogel-based therapeutic strategies for ICH treatment, focusing on structure-activity relationships and the integration of bone-brain axis modulation for enhanced neuroregeneration. We discuss key translational barriers, including biosafety, manufacturing scalability, and inter-patient heterogeneity. Future advances are expected to rely on the development of dynamic, microenvironment-responsive hydrogels that can synchronize drug release with stage-specific pathological cues, improving therapeutic precision. Moreover, combining HDDS with multimodal therapies and minimally invasive neurosurgical techniques may further enhance clinical outcomes. The potential for HDDS to target both local brain injury and systemic inter-organ crosstalk represents a promising direction for advancing clinical applications in ICH.</p>","PeriodicalId":100686,"journal":{"name":"Interdisciplinary Medicine","volume":"4 4","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/inmd.70138","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148522864","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":"Sleep deprivation aggravates hepatocytes steatosis and insulin resistance by regulating exosomal microRNAs","authors":"Xinxin Xu,&nbsp;Lulu Li,&nbsp;Ying Cao,&nbsp;Ying Wang,&nbsp;Chao Yang,&nbsp;Alexander Nikolaevich Orekhov,&nbsp;Yuanfeng Lu,&nbsp;Houbin Chu,&nbsp;Chuanrong Zhao,&nbsp;Guixue Wang,&nbsp;Guohua Song","doi":"10.1002/inmd.70129","DOIUrl":"https://doi.org/10.1002/inmd.70129","url":null,"abstract":"<p>Sleep deprivation (SD) threatens human health and increases the prevalence of disease with abnormal glycolipid metabolism, including metabolic dysfunction-associated steatotic liver disease (MASLD) and insulin resistance (IR). However, the mechanism underlying SD induced MASLD and IR remains incompletely understood. Plasma samples were collected, and circulating exosomes were isolated. Differentially expressed miRNAs in exosomes were identified using an miRNA array and quantitative real-time PCR (qPCR). MiRNA mimics or inhibitors were transfected into the cells to mimic the change in miRNA expression, and the biological effects of differentially expressed miRNAs were detected. Western blot and dual-luciferase reporter assay were used to detect the specific target gene and molecular mechanism of miRNAs. Sleep deprived rats derived circulating exosomes strongly induced hepatic steatosis and IR. miRNA array combined with qPCR identified miR-3572-5p and miR-183-5p in exosomes that impacted abnormal glycolipid metabolism. Subsequently, miR-3572-5p inhibited fatty acid β-oxidation by targeting PGC-1α aggravated hepatic lipid accumulation. Meanwhile, both miR-3572-5p and miR-183-5p exerted an inhibitory effect on the PI3K/Protein Kinase B/GLUT4 insulin signaling pathway through distinct targeting of IRS1 and IGFBP7, which in turn contributed to the aggravation of IR. Notably, circulating exosomes enriched in miR-3572-5p were traced to peripheral blood monocytes, whereas those carrying miR-183-5p were pinpointed to adipose tissue. SD accelerates the progression of MASLD and IR by up-regulating the expression of miR-3572-5p and down-regulating the expression of miR-183-5p in circulating exosomes, thereby inhibiting fatty acid β-oxidation and disrupting insulin signaling pathways.</p>","PeriodicalId":100686,"journal":{"name":"Interdisciplinary Medicine","volume":"4 4","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/inmd.70129","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148533013","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":"A dendrimer enhanced CRISPR/Cas12a performance for the evaluation of acidogenic capacity in cariogenic bacteria","authors":"Yuan Zhang,&nbsp;Yining Zhao,&nbsp;Murtaza Sayed,&nbsp;Feng Chen,&nbsp;Juan Zhang","doi":"10.1002/inmd.70110","DOIUrl":"10.1002/inmd.70110","url":null,"abstract":"<p>Dental caries, a highly prevalent global health issue, is fundamentally driven by the acidogenic metabolism of cariogenic bacteria such as <i>Streptococcus mutans</i>. Conventional approaches for assessing acidogenic capacity remain limited by complex operational requirements and insufficient sensitivity for point-of-care use. Herein, we engineer a CRISPR/Cas12a-powered dendritic DNA nanostructure via hybridization chain reaction to construct a highly efficient signal amplification system. The designed activator strands self-assemble into dendritic nano-assemblies that enable multivalent immobilization of Cas12a-crRNA complexes through programmable base pairing, resulting in a confined microdomain with dramatically enhanced local enzyme density and accelerated trans-cleavage kinetics. The CRISPR/Cas dendritic aggregate enables high-density immobilization of Cas12a, resulting in increased local enzyme concentration and enhanced catalytic cleavage efficiency. By integrating this system with a smart pH-responsive molecular release mechanism, we further develop a paper-based origami biosensor (CDEOB) for the on-site and equipment-free quantification of acidogenic pathogens. The biosensor achieves an ultra-low detection limit of 98.1 CFU/mL in saliva and demonstrates excellent reliability across 101 clinical samples without pre-amplification. This work provides a novel functional nucleic acid material design strategy and a versatile biosensing platform, highlighting substantial potential for early diagnosis of dental caries and other infectious diseases at the point of care.</p>","PeriodicalId":100686,"journal":{"name":"Interdisciplinary Medicine","volume":"4 4","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/inmd.70110","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147381901","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":"Multi-omics biomarkers for intestinal infection and inflammation in inflammatory bowel disease: Current evidence, translational challenges, and diagnostic opportunities","authors":"Ziyu Yang,&nbsp;Jiayi Yao,&nbsp;Xinxian Zhao,&nbsp;Yan Xu,&nbsp;Yifan Chen,&nbsp;Tianchi Chen,&nbsp;Ying Jian,&nbsp;Min Li","doi":"10.1002/inmd.70143","DOIUrl":"https://doi.org/10.1002/inmd.70143","url":null,"abstract":"<p>Inflammatory bowel disease (IBD) is characterized by gut microbial dysbiosis, dysregulated host immune responses and increased susceptibility to certain intestinal infections. These factors complicate the distinction between active infection, inflammatory flare, and mixed inflammatory infectious states. Conventional diagnostics remain essential in clinical practice, but a single test is often insufficient to separate colonization, true infection, and inflammation-related symptoms. This review summarizes current evidence on multi-omics biomarkers relevant to intestinal infection and inflammation in IBD, including metagenomics, metabolomics, proteomics, single-cell RNA sequencing, spatial transcriptomics and radiomics features. Biomarkers linked more closely to infection are considered alongside those that mainly reflect inflammatory activity, with attention to areas of overlap. The review also examines the degree of validation across studies, major sources of heterogeneity and confounding, and the strengths and limitations of emerging diagnostic platforms and artificial intelligence (AI) assisted integrative approaches. Overall, multi-omics strategies may improve diagnostic stratification and deepen understanding of disease mechanisms in IBD. However, most candidate biomarkers and related platforms remain insufficiently validated for routine clinical use.</p>","PeriodicalId":100686,"journal":{"name":"Interdisciplinary Medicine","volume":"4 4","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/inmd.70143","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148522756","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":"Complement C3 mediates adolescent social isolation-induced hippocampal synaptic deficits and sex-specific emotional dysfunction","authors":"Yuwan Qi,&nbsp;Siying Weng,&nbsp;Qiao Yin,&nbsp;Mengqi Li,&nbsp;Liang Shen,&nbsp;Enyou Qiao,&nbsp;Lu Gao,&nbsp;Yihan Wang,&nbsp;Yuxuan Li,&nbsp;Weifeng Luo,&nbsp;Qilin Zhang,&nbsp;Jing Wang,&nbsp;Jianfeng Feng,&nbsp;Qifei Cong","doi":"10.1002/inmd.70118","DOIUrl":"https://doi.org/10.1002/inmd.70118","url":null,"abstract":"<p>Social isolation during adolescence is a critical risk factor for negative emotional symptoms, yet its neurobiological mechanisms remain incompletely understood. Here, we integrate human and mouse data to investigate the behavioral, functional, and molecular consequences of social isolation across development. In humans from the Human Connectome Project in Development, reduced social connectedness was robustly associated with greater depressive and anxiety symptoms across adolescence, with sex-specific patterns in effect distribution. At the neural level, social experience was preferentially associated with alterations in hippocampal functional connectivity (FC) rather than gross structure, and exhibited sex- and hemisphere-dependent coupling with large-scale cortical networks. In parallel, adolescent mice exposed to chronic social isolation exhibited marked reductions in hippocampal synaptic density and calcium signaling, accompanied by astrocyte-associated upregulation of complement components C3 and complement factor properdin and enhanced complement-mediated microglial synaptic pruning. Genetic deletion of C3 rescued synaptic deficits and alleviated depressive-like behaviors. Together, these findings identify a conserved neuroimmune pathway through which adolescent social isolation disrupts hippocampal FC, with sex- and species-specific phenotypic expression across behavioral and neural levels, highlighting a sex-specific mechanism linking social experience to neuropsychiatric risk.</p>","PeriodicalId":100686,"journal":{"name":"Interdisciplinary Medicine","volume":"4 4","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/inmd.70118","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148533842","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}