Research最新文献

{"title":"Decoding Sepsis: Unraveling Key Signaling Pathways for Targeted Therapies.","authors":"Lingxuan Tang, Wangzheqi Zhang, Yan Liao, Weijie Wang, Yuxian Wu, Zui Zou, Changli Wang","doi":"10.34133/research.0811","DOIUrl":"https://doi.org/10.34133/research.0811","url":null,"abstract":"<p><p>Sepsis is a complex clinical syndrome marked by dysregulated immune responses, systemic inflammation, and subsequent organ dysfunction. Sepsis involves the interplay of multiple signaling pathways. Traditional sepsis treatment mainly depends on antibiotics and early directed therapy, with limited effectiveness. This article reviews major signaling pathways in sepsis, such as those related to nuclear factor κB (NF-κB), Janus kinase/signal transducer and activator of transcription (JAK/STAT), Toll-like receptors (TLRs), mitogen-activated protein kinase (MAPK), hypoxia-inducible factor 1α (HIF-1α), and nuclear factor-erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/Keap1). These molecules are pivotal in regulating immune activation, inflammation, and immune cell metabolism. Moreover, mitochondrial dysfunction and metabolic reprogramming substantially contribute to sepsis development, as they greatly affect energy production and immune cell function. Selectively inhibiting these pathways shows potential for effectively reducing hyperinflammation and preventing organ failure. We discussed how future research on these signaling pathways can translate into clinical applications and how personalized treatment strategies can handle the complexity and variability of sepsis. Given the dynamic nature of sepsis, treatment strategies should not solely rely on traditional single-target interventions. Instead, a dynamic and personalized multi-target modulatory approach is needed. While reducing side effects of single-target inhibition, inflammatory responses, immune balance, and metabolic disorders can be more precisely regulated. By precisely monitoring multiple sepsis-related signaling pathways and adjusting treatment regimens in real time, we aim to identify more effective intervention points in the complex dynamics of diseases, thus providing new hope for improving prognosis of septic patients.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0811"},"PeriodicalIF":10.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12484860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intercellular Nanotube Mitochondrial Transplantation Strategy Mediating T Cell \"Supercharging\".","authors":"Baikun Liu, Jie Chen, Wenguo Cui","doi":"10.34133/research.0927","DOIUrl":"https://doi.org/10.34133/research.0927","url":null,"abstract":"<p><p>The functional exhaustion of T cells in the tumor immune microenvironment is closely related to mitochondrial dysfunction. Current mitochondrial-targeted strategies have failed to restore the mitochondrial impaired function effectively. Mitochondrial transplantation technology has brought a revolution to the treatment of organelle-related diseases. Here, we first summarize the therapeutic potential and available platforms for mitochondrial transplantation, and focus on a type of mitochondrial transplantation technology mediated by tunneling nanotubes. This technology transfers functional mitochondria from bone marrow mesenchymal stem cells to CD8⁺ T cells, obtaining \"supercharged T cells\", which markedly enhance the metabolic adaptability and antitumor efficacy of T cells. It provides new ideas and technical platforms for the application of organelle medicine in tumor immunotherapy.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0927"},"PeriodicalIF":10.7,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12480746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145207464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"General Intelligence Framework to Predict Virus Adaptation Based on a Genome Language Model.","authors":"Shu-Yang Jiang, Shi-Shun Zhao, Jun-Qing Wei, Sen Zhang, Zhongpeng Zhao, Yigang Tong, Wei Liu, Jianwei Wang, Tao Jiang, Jing Li","doi":"10.34133/research.0871","DOIUrl":"https://doi.org/10.34133/research.0871","url":null,"abstract":"<p><p>Most human viral pandemics are caused by animal-originated viruses with human adaptation. It is challenging to infer adaptation from viral genes or their coded protein sequences, particularly when the data labels for modeling are inadequate or the input sequence to be predicted is incomplete. Here, we developed a semi-supervised General Intelligence framework to predict Virus Adaptation based on Language-model-embedded protein sequences (GIVAL) for blind input of virus sequences. The language model in GIVAL, named virus Bidirectional Encoder Representations from Transformers (vBERT), was pretrained for embedding using hidden Markov model-contextualized tokens of viral protein sequences. vBERT outperformed prevalent pretrained models like DNABERT-2, proteinBERT, ESM-2, Transformer, and Word2Vec on distinguishing viral proteins with various-grained labels, such as serotypes and single phenotype-altering mutation. The semi-supervised GIVAL obtained higher accuracy in virus adaptation prediction and better fault tolerance on raw labels in the training dataset, overcoming the obstacle of modeling with insufficient labels and predicting blind input. GIVAL was applicable to the adaptation prediction of diverse viruses. For influenza A viruses (IAVs), higher human adaptation was predicted for equine-origin H3N8 IAVs and bovine H5N1 IAVs with simulated mutations. For coronaviruses, GIVAL predicted an adaptation shift of receptor binding from Middle East respiratory syndrome-related coronavirus (MERS-CoV) receptor to severe acute respiratory syndrome coronavirus receptor of 2 recently reported MERS-CoV-like virus variants. For monkeypox viruses, GIVAL quantified an incremental adaptation shift of viral variants, matching the rise in human monkeypox cases. Summarily, GIVAL provides a generally intelligent framework for predicting virus adaptation based on its genotype, with the potential to extend to more genotype-to-phenotype prediction scenarios.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0871"},"PeriodicalIF":10.7,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12480747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145207434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer-Associated Fibroblast-Derived GDF15 Induces Oxidative Stress and Neutrophil Infiltration in Head and Neck Squamous Cell Carcinoma through the PI3K/AKT/STAT3 Axis Cascade.","authors":"Zhijie Zhao, Huabao Cai, Zhenzhen Zhao, Xiaojing Wang, Wenyang Nie, Fu Zhao, Yisheng Chen, Yanyu Ding, Zhiwen Luo, Zhiheng Lin, Yantao Ding","doi":"10.34133/research.0901","DOIUrl":"https://doi.org/10.34133/research.0901","url":null,"abstract":"<p><p><b>Background:</b> Head and neck squamous cell carcinoma (HNSCC) is a malignant tumor of the oral mucosal epithelium. The high incidence of recurrence and metastasis presents substantial challenges for treatment, underscoring the complex molecular landscape underlying the disease. The purpose of this work is to clarify how HNSCC tumor cells and cancer-associated fibroblasts (CAFs) interact. <b>Methods:</b> Spatial transcriptome sequencing and single-cell RNA sequencing had been employed to describe the biological characteristics of CAFs in HNSCC. The biological connection between CAFs and tumor cells was verified by molecular interaction experiments. In addition, the regulatory effect of CAFs on oxidative stress in tumor cells and the phenotypic conversion of neutrophils were explored through a coculture system, a knockdown/overexpression method, flow cytometry, and animal experiments. Finally, potential small-molecule inhibitors were screened by molecular dynamics simulation and validated through in vitro and in vivo assays. <b>Results:</b> Growth differentiation factor 15 (GDF15) promoted tumor cell growth and invasion by enhancing PCNA clamp associated factor (PCLAF) transcription through interferon regulatory factor 5 modulation. Its interaction with the receptor GDNF family receptor alpha like (GFRAL) triggered chronic inflammatory signaling via the phosphatidylinositol-3 kinase/protein kinase b/signal transducer and activator of transcription 3 pathway, which led to oxidative stress imbalance and contributed to tumor progression and the development of drug resistance. Moreover, GDF15 activated the extracellular signal-regulated kinase 1/2 pathway through tumor necrosis factor-α, thereby facilitating neutrophil infiltration and promoting lung metastasis in HNSCC. Notably, risperidone (SM-2) emerged as a potential inhibitory regulator capable of disrupting the cascade effects mediated by the GDF15-GFRAL axis, underscoring its therapeutic relevance. <b>Conclusion:</b> This study identifies the GDF15-GFRAL signaling axis as a critical regulator of oxidative stress and immune evasion in HNSCC and demonstrates that the novel small-molecule SM-2 effectively targets this pathway, highlighting its potential as a promising therapeutic strategy.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0901"},"PeriodicalIF":10.7,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12480759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145207440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Membrane Electrode Assembly Design for High-Efficiency Anion Exchange Membrane Water Electrolysis.","authors":"Liming Yang, Shengbing Dong, Tao Yang, Jianhe Liu, Shuang Liu, Kang Wang, Enhui Wang, Hongyang Wang, Kuo-Chih Chou, Xinmei Hou","doi":"10.34133/research.0907","DOIUrl":"https://doi.org/10.34133/research.0907","url":null,"abstract":"<p><p>Growing interest in low-cost clean hydrogen production has positioned anion exchange membrane water electrolysis (AEMWE) as a leading sustainable technology. Its appeal lies in compatibility with platinum-group metal-free catalysts, inexpensive anode flow fields, and cost-effective bipolar plates. Recent advances in AEMWE focus critically on optimizing membrane electrode assembly (MEA) design to achieve industrially viable efficiency and durability. Key progress includes component-level innovations, such as developing nonprecious metal catalysts, fabricating anion exchange membranes (AEMs) with high ionic conductivity and alkaline stability, and engineering gas diffusion layers (GDLs) with hierarchical porosity for effective mass transport. Central to improving performance is interfacial engineering within the MEA, which combines catalyst layers (CLs), AEM, and GDLs to reduce ionic/charge transfer resistance and prevent mechanical delamination. A transformative breakthrough involves ordered, gap-free electrode assembly. This approach utilizes strategies such as ionomer-bonded architectures to establish continuous ion-conducting pathways or in situ catalyst deposition directly onto AEM surfaces, creating vertically aligned triple-phase boundaries. These ordered structures maximize catalyst utilization, markedly reduce voltage losses at industrially relevant current densities, and mitigate interfacial degradation during differential-pressure operation. Future advancements require scalable manufacturing of these ordered architectures to bridge material innovations with industrial deployment.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0907"},"PeriodicalIF":10.7,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12480755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145207517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interleukin-4-Mediated NLRP3 Inflammasome Activation in Microglia Contributes to Allergic Rhinitis via Central Sensitization.","authors":"Hao Lv, Yunfei Wang, Lu Tan, Yulie Xie, Peiqiang Liu, Mengting Guan, Jianchao Cong, Yu Xu","doi":"10.34133/research.0897","DOIUrl":"10.34133/research.0897","url":null,"abstract":"<p><p><b>Background:</b> The hypersensitive state of the central nervous system, commonly known as central sensitization, presumably drives allergic rhinitis (AR) pathogenesis. However, the involvement of central sensitization in AR and its related mechanisms have rarely been studied. <b>Methods:</b> An AR mouse model was induced via ovalbumin treatment. Activation of trigeminal nucleus caudalis (TNC) neurons was assessed by electrophysiological recordings and immunofluorescence staining. The role of TNC neurons in AR was investigated by selectively manipulating them through chemogenetics. The contribution of microglial neuroinflammation to central sensitization and AR was assessed by pharmacologically inhibiting microglial activation. The mechanism of central sensitization in AR was further determined using a microglia-neuron co-culture system. The role of interleukin (IL)-4 in neuroinflammation in AR was explored using in vivo and in vitro methods. <b>Results:</b> The intrinsic neuronal excitability and molecular markers of central sensitization were increased within the TNC of AR mice. Chemogenetic inhibition of TNC neurons ameliorated nasal symptoms, histological changes, autonomic dysfunction, and immune imbalance in AR mice. Moreover, AR mice exhibited an increased number of pro-inflammatory microglia, activation of the NOD-like receptor protein 3 (NLRP3) inflammasome, and enhanced IL-1β production in the TNC. Pharmacological inhibition of microglial activation reduced central sensitization in AR mice and was accompanied by remission of AR. Transcriptomics analysis revealed the inflammatory-prone characteristics of IL-4-treated microglia. IL-4 exposure enhanced lipopolysaccharide-stimulated NLRP3 inflammasome activation in microglia. Intracerebral injection of IL-4 neutralizing antibodies ameliorates neuroinflammation and central sensitization in AR mice and was accompanied by remission of AR. <b>Conclusions:</b> This research uncovers a previously unidentified mechanism wherein microglial neuroinflammation-induced central sensitization in the TNC contributes to AR, providing a new promising approach for the treatment of AR. IL-4 induces noncanonical pro-inflammatory-prone microglia and participates in microglial NLRP3 inflammasome activation in AR.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"2025 ","pages":"0897"},"PeriodicalIF":10.7,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12463543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145186706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ultra-efficient, Anisotropic Cellulose Aerogel with Polydopamine Interfacial Bridged Structure and Photothermal Modification for Seawater Desalination.","authors":"Miao Sun, Xin Wang, Yuan Yu, Meichen Li, Meng Wang, Wenbo Zhang, Zhaolin Yang, Jiazuo Zhou, Haiyue Yang, Chengyu Wang","doi":"10.34133/research.0888","DOIUrl":"10.34133/research.0888","url":null,"abstract":"<p><p>Solar-driven interfacial evaporators represent a promising technique to address the energy crisis and freshwater scarcity issues. However, simultaneously achieving both high evaporation efficiency and long-term stability in a single evaporator system under multifactorial environmental conditions remains challenging. Herein, inspired by the anisotropic channel structure of wood, a novel evaporator featuring a vertical channel structure and excellent photothermal conversion performance for evaporation is developed through the covalent-bond bridging of MXene-polydopamine-cellulose nanocrystals. Polydopamine-modified MXene acts as a photothermal material, exhibiting excellent photothermal conversion efficiency. The vertical channels endow the evaporator with efficient thermal management and rapid mass transfer capabilities to dynamically balance the feedwater supply and photothermic energy input. Thereby, the evaporator exhibits an enhanced evaporation rate of 2.29 kg m^-2 h^-1, accompanied by a remarkable 97.34% evaporation efficiency under 1-sun illumination. Additionally, the evaporator possesses a mechanical strength as high as 0.454 MPa, which ensures its long-term stability. Over 14 d of testing, stable evaporation rates of 2.27 kg m^-2 h^-1 were maintained over 8-h cycles with no salt crystallization. This work introduces a novel evaporator design with a strong evaporation capability, which has potential applications in addressing the energy crisis and water scarcity challenges.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0888"},"PeriodicalIF":10.7,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12463581/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145186622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Boosting Output Performance of Triboelectric Nanogenerator via Interface Self-Regulation Strategy.","authors":"Yanrui Zhao, Yuming Feng, Qi Gao, Hengyu Li, Xin Guo, Jianlong Wang, Xinxian Wang, Lu Dong, Yang Yu, Zhong Lin Wang, Tinghai Cheng","doi":"10.34133/research.0906","DOIUrl":"10.34133/research.0906","url":null,"abstract":"<p><p>The long-term durability of triboelectric nanogenerators (TENGs) remains a critical challenge for their practical deployment. Although approaches like reducing interfacial friction or contact duration can enhance durability, they often compromise electrical performance. The charge self-excitation method can improve the output performance. However, when it is introduced into the sliding mode with small capacitance change, it increases the complexity of the circuit and cannot solve the problem of charge attenuation caused by material wear. Herein, we propose a self-regulation strategy that concurrently controls the interface contact state and contact force. This approach synergistically combines the advantages of both sliding and contact-separation configurations, enabling the triboelectric materials to micro-slide and deform adaptively, ensuring stable dynamic interfacial contact under minimal normal pressure. Such a mechanism promotes strong electron cloud overlap at the microscale, thereby enhancing charge transfer efficiency. Compared to conventional TENGs, the self-regulating TENG achieves a 72.5-fold reduction in frictional force and a 13-fold increase in energy output. Furthermore, a wireless self-powered sensing system is integrated, achieving a power density of 242.4 mW/m² under real water flow conditions. The system maintains 97.6% of the initial output after 10 h of continuous operation, confirming the practical feasibility of the proposed approach. This work presents a universal method to enhance the electrical performance and durability of TENGs, paving the way for their broader application.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0906"},"PeriodicalIF":10.7,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12463547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145186681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic Polarization Control of Nonlinear Terahertz Photoresponse via Topological Phase Transitions.","authors":"Libo Zhang, Xuyang Lv, Zhuo Dong, Debasis Dutta, Liu Yang, Raihan Ahammed, Atasi Chakraborty, Dong Wang, Zhen Hu, Mengjie Jiang, Kaixuan Zhang, Li Han, Kai Zhang, Amit Agarwal, Xiaoshuang Chen, Lin Wang","doi":"10.34133/research.0899","DOIUrl":"10.34133/research.0899","url":null,"abstract":"<p><p>Precise modulation of topologically protected states via external stimuli, such as electric, optical, and magnetic fields, is a cornerstone for advancing robust topological photonics and quantum technologies. However, the realization of dynamic and noninvasive control remains constrained by the high-energy thresholds of conventional stimuli, which can disrupt delicate topological states. Here, we employ low-energy terahertz excitation to directly probe the photoresponse across a temperature-induced topological phase transition in ultrathin ZrTe₅, a material at the intersection of topological physics and low-dimensional systems, leveraging its unique ability to interact with low-energy quasiparticle states without compromising coherence in the system. We observe a giant and robust nonlinear terahertz photoresponse characterized by in situ tunable geometric properties of Bloch quasiparticles. The response exhibits colossal behavior and a sign reversal across a temperature-driven topological phase transition, linked to a nonvanishing Berry curvature dipole that serves as a direct marker of symmetry-breaking evolution between weak (<i>m</i> < 0) and strong (<i>m</i> > 0) topological insulator phases. The observed device exhibits a response time of ~1 μs with a noise equivalent power of 5.6 pW/Hz^0.5 across the 0.5-THz range, demonstrating the potential of topological phase transitions for terahertz detection. These findings underscore the potential of low-energy terahertz excitation for dynamically polarizing and controlling topological states in ultrathin materials, offering a versatile framework for exploring symmetry-breaking phenomena and advancing next-generation optoelectronic devices.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0899"},"PeriodicalIF":10.7,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12460995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145186691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Joint Aging Patterns in Brain Function and Structure Revealed Using 27,793 Samples.","authors":"Yuhui Du, Ruotong Li, Ying Xing, Vince D Calhoun","doi":"10.34133/research.0887","DOIUrl":"10.34133/research.0887","url":null,"abstract":"<p><p>Aging has important impacts on both the function and structure of the brain, yet the interplay between these changes remains unclear. Here, we present a unified framework including both single-modal and multimodal age predictions using a large UK Biobank dataset (27,793 healthy subjects, 49 to 76 years) to identify and validate brain functional network connectivity (FNC) and gray matter volume (GMV) changes associated with aging, then propose a novel analysis method to reveal various joint aging patterns, and finally investigate the association between joint function-structure changes and cognitive declines. Multimodality outperforms single modality in the age prediction, underscoring the significance of multimodal aging-related changes. Aging primarily induces synergistic changes, with both FNC and GMV decreased in the cerebellum, frontal pole, paracingulate gyrus, and precuneus cortex, indicating consistent degeneration in motor control, sensory processing, and emotional regulation, and contradictory changes with increased FNC magnitude but decreased GMV in the occipital pole, lateral occipital cortex, and frontal pole, acting as a compensatory mechanism as one ages to preserve visual acuity, cognitive ability, and behavioral modulation. Particularly, joint changes, with both FNC and GMV decreased in the crus I cerebellum and the paracingulate gyrus, show a strong Pearson correlation with the reaction time. In summary, our study unveils diverse joint function-structure changes, providing strong evidence for understanding distinct cognitive deteriorations during aging.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0887"},"PeriodicalIF":10.7,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12460996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145186651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}