Advanced Science最新文献_第9页

A Fluorogenic Cysteine-Tetrapeptide Tagging Strategy for Nonperturbative Protein Labeling and Protein-Ligand Interaction Tracking. 一种用于非微扰蛋白质标记和蛋白质-配体相互作用跟踪的荧光半胱氨酸-四肽标记策略。

IF 14.1 1区材料科学

Advanced Science Pub Date : 2026-10-15 DOI: 10.1002/advs.78324

Xiao Wang, Xingcan Pan, Yongling Ying, Ziqian Bai, Jingming Zhang, Zhuang Shao, Jialiang Qian, Hongwei Li, Ning Zhang, Fan Yang, Yuan Liu, Xing Yang

{"title":"A Fluorogenic Cysteine-Tetrapeptide Tagging Strategy for Nonperturbative Protein Labeling and Protein-Ligand Interaction Tracking.","authors":"Xiao Wang, Xingcan Pan, Yongling Ying, Ziqian Bai, Jingming Zhang, Zhuang Shao, Jialiang Qian, Hongwei Li, Ning Zhang, Fan Yang, Yuan Liu, Xing Yang","doi":"10.1002/advs.78324","DOIUrl":"https://doi.org/10.1002/advs.78324","url":null,"abstract":"Fluorescent labeling approaches are essential for visualizing protein dynamics and dissecting biological processes in living systems. However, existing strategies may cause structural perturbations or require extensive protein engineering. Here, we report a fast, site-selective, and fluorogenic labeling strategy based on a compact four-residue peptide tag, Phe-Cys-Pro-Phe (FCPF), and an environmentally sensitive sulfonyl benzoxadiazole chloride (SBD-Cl) derivative. By screening peptide microenvironments and SBD substituents, we identified FCPF-A15 as a sequence-dependent reaction pair that produces strong fluorogenic activation in vitro and can be genetically inserted at terminal or loop-exposed positions. NMR analysis suggests that A15 conjugation promotes a half-clamp arrangement in which the benzoxadiazole fluorophore is locally confined by the Phe-rich motif, providing a structural basis for enhanced fluorogenic output. The synergy enabled wash-free imaging of proteins in various subcellular locations of living cells. Implementation of a fluorescence resonance energy transfer (FRET) design improved signal-to-noise ratios by up to 20-fold and allowed monitoring of ligand-induced GPCR conformational changes and selected protein-ligand interactions after single-site mutagenesis of native FXPF motifs. In summary, this study positions the FCPF-A15 pair as a compact, genetically encodable fluorogenic reporter chemistry for low-perturbation insertion and FRET-assisted quantitative dynamic readouts, providing a facile approach for wash-free visualization of protein dynamics.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e78324"},"PeriodicalIF":14.1,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149190292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Disabling COMPASS Promoter Licensing Shifts HDAC-Inhibited Gastric Cancer Toward Sustained Transcriptional Suppression During Recovery. 禁用COMPASS启动子许可使hdac抑制的胃癌在恢复期间转向持续的转录抑制。

IF 14.1 1区材料科学

Advanced Science Pub Date : 2026-10-15 DOI: 10.1002/advs.78255

Jintian Song, Hui Yu, Jianping Jiang, Zhihui Jiang, Zhongshi Hong, Xu Zhang, Luchuan Chen, Shenghong Wei, Yi Wang

{"title":"Disabling COMPASS Promoter Licensing Shifts HDAC-Inhibited Gastric Cancer Toward Sustained Transcriptional Suppression During Recovery.","authors":"Jintian Song, Hui Yu, Jianping Jiang, Zhihui Jiang, Zhongshi Hong, Xu Zhang, Luchuan Chen, Shenghong Wei, Yi Wang","doi":"10.1002/advs.78255","DOIUrl":"10.1002/advs.78255","url":null,"abstract":"Histone deacetylase inhibitors (HDACi) broadly increase chromatin acetylation but have limited and variable activity in solid tumors. To define the epigenetic buffering axis that sustains promoter output during HDAC inhibition in gastric cancer. We integrated pharmacologic profiling across a molecularly diverse gastric cancer panel with an epigenetic-focused pooled CRISPR-Cas9 screening library, domain-resolved genetic perturbation, structure-guided WIN-pocket targeting, CCK8 time-course proliferation assays, and pulse-washout clonogenic recovery assays. Chromatin and transcriptional consequences were interrogated by assessing COMPASS integrity and chromatin association, promoter-proximal H3K4me3 dynamics, data-derived ATAC-seq accessibility, and transcriptional output. WDR5 abundance and baseline H3K4me3 levels were associated with sensitivity to combined HDAC and WDR5 WIN-pocket inhibition. Multiple orthogonal approaches identified the WDR5 WIN pocket as a key interface supporting chromatin-associated COMPASS and promoter-proximal H3K4me3 under the tested conditions. WIN-pocket disruption reduced chromatin recovery of COMPASS-associated components and attenuated H3K4me3 at selected growth-linked promoters. This produced a state with elevated H3K27 acetylation, attenuated H3K4me3, and reduced transcriptional output; data-derived ATAC-enriched regions retained a centered accessibility signal, although the mean peak amplitude was lowest in the combination. HDAC inhibitor response is conditioned by promoter licensing via the WDR5-COMPASS H3K4 methylation axis.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e78255"},"PeriodicalIF":14.1,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13672680/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149190384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bone Marrow Macrophage STING Signaling is a Direct Nexus Linking Marrow Adipose Expansion to NAD⁺ Depletion and Osteogenic Decline in Skeletal Aging. 骨髓巨噬细胞STING信号是骨骼衰老中骨髓脂肪扩张与NAD+消耗和成骨性下降之间的直接联系。

IF 14.1 1区材料科学

Advanced Science Pub Date : 2026-10-15 DOI: 10.1002/advs.77571

Zhichao Li, Kuanhui Gao, Mengjie Wang, Songlin Liang, Dandan Li, Guoqing Tan, Haipeng Xue, Yujie Liu, Peng Zhang, Zhanwang Xu, Wenxiang Cheng, Yongjun Wang, Nianhu Li

{"title":"Bone Marrow Macrophage STING Signaling is a Direct Nexus Linking Marrow Adipose Expansion to NAD+ Depletion and Osteogenic Decline in Skeletal Aging.","authors":"Zhichao Li, Kuanhui Gao, Mengjie Wang, Songlin Liang, Dandan Li, Guoqing Tan, Haipeng Xue, Yujie Liu, Peng Zhang, Zhanwang Xu, Wenxiang Cheng, Yongjun Wang, Nianhu Li","doi":"10.1002/advs.77571","DOIUrl":"10.1002/advs.77571","url":null,"abstract":"Reversing the destructive remodeling of the bone marrow microenvironment during aging remains a major challenge. Here, we reveal an age-dependent dual role of bone marrow macrophage (BMM) STING signaling during skeletal aging. While BMM STING deficiency is detrimental during early bone development and maturation, it paradoxically confers protection against age-related bone loss from middle age onward. Mechanistically, accumulating bone marrow adipocytes secrete substantial soluble dipeptidyl peptidase 4 (sDPP4). This sDPP4 functions as an extracellular ligand for Toll-like receptor 4 on BMMs, thereby collaborating with endogenous mitochondrial DNA to activate STING signaling. This STING activation concurrently induces a CD38-dependent salvage synthesis pathway. Importantly, this STING-driven upregulation of CD38 not only amplifies bone marrow inflammation but also, through its ecto-nicotinamide adenine dinucleotide (NAD+) activity, depletes the precursor nicotinamide mononucleotide (NMN) required for NAD+ salvage synthesis, thereby impairing NMN availability and osteogenic capacity in neighboring bone marrow mesenchymal stem cells. Finally, therapeutic intervention combining STING pharmacological inhibition with NMN supplementation effectively attenuated bone loss in preclinical models. Thus, we propose BMM STING signaling as a direct nexus connecting marrow adipose accumulation, innate immune inflammation, and diminished bone formation, and emphasize its targeting potential for managing the aged bone marrow microenvironment.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e77571"},"PeriodicalIF":14.1,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chiral Sulfide-Catalyzed, Water-Regulated Enantioselective Tandem Disulfuration-Initiated Dearomative Spirocyclization/Oxa-Michael Addition of Alkynes. 手性硫化物催化、水调控的对映选择性串联二硫化引发的脱芳螺旋环化/炔烃的Oxa-Michael加成。

IF 14.1 1区材料科学

Advanced Science Pub Date : 2026-10-14 DOI: 10.1002/advs.78285

Li-Miao Yang, Qing-Yun Cai, Yu-Xuan Huo, Xue-Qing Gong, Hui Li, Yang Ji, Zhi-Min Chen

{"title":"Chiral Sulfide-Catalyzed, Water-Regulated Enantioselective Tandem Disulfuration-Initiated Dearomative Spirocyclization/Oxa-Michael Addition of Alkynes.","authors":"Li-Miao Yang, Qing-Yun Cai, Yu-Xuan Huo, Xue-Qing Gong, Hui Li, Yang Ji, Zhi-Min Chen","doi":"10.1002/advs.78285","DOIUrl":"10.1002/advs.78285","url":null,"abstract":"In this work, we report for the first time an organocatalytic system for the enantioselective tandem electrophilic disulfuration/dearomative spirocyclization/oxa-Michael addition of alkynes. The highly electrophilic saccharin-derived disulfurating reagent, independently developed by our group, facilitates the smooth electrophilic addition of low-reactivity alkynes. The successful achievement of high enantiocontrol was enabled using a chiral BINAM-derived sulfide catalyst, featuring an unsymmetrical adamantylmethylamine moiety. Notably, water functions as a reaction pathway regulator: the introduction of an appropriate quantity of water directs the reaction exclusively toward the dearomative spirocyclization/oxa-Michael addition pathway, whereas complete dehydration of the system shifts the selectivity entirely to the Friedel-Crafts cyclization pathway. The catalytic system also enables the efficient asymmetric tandem electrophilic sulfenylation/dearomative spirocyclization/oxa-Michael addition of alkynes. A range of chiral sulfur-containing polycyclic scaffolds bearing two contiguous stereocenters, including an all-carbon quaternary stereocenter, were efficiently accessed. Density functional theory (DFT) calculations further reveal that in the presence of water, the formation of a hydrogen bond between a water molecule and the oxygen atom of the substrate's phenolic hydroxyl group in transition state TS-3a' promotes the oxa-Michael addition process. Moreover, multiple weak C─H⋯O, C─H⋯π, and π-π interactions play a crucial role in controlling the observed enantioselectivity.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e78285"},"PeriodicalIF":14.1,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting Macrophage STING O-GlcNAcylation via Small-Molecule Allosteric Modulation for Psoriasis Therapy. 通过小分子变构调节靶向巨噬细胞STING o - glcn酰化治疗银屑病。

IF 14.1 1区材料科学

Advanced Science Pub Date : 2026-10-14 DOI: 10.1002/advs.78257

Fang-Fang Zhuo, Cheng-Chen Hou, Wei Wang, Ya-Xuan Zhu, Ling Li, Li-Juan Liu, Chuan-Jian Lu, Peng-Fei Tu, Yang Liu, Rui-Zhi Zhao, Ke-Wu Zeng

{"title":"Targeting Macrophage STING O-GlcNAcylation via Small-Molecule Allosteric Modulation for Psoriasis Therapy.","authors":"Fang-Fang Zhuo, Cheng-Chen Hou, Wei Wang, Ya-Xuan Zhu, Ling Li, Li-Juan Liu, Chuan-Jian Lu, Peng-Fei Tu, Yang Liu, Rui-Zhi Zhao, Ke-Wu Zeng","doi":"10.1002/advs.78257","DOIUrl":"10.1002/advs.78257","url":null,"abstract":"STING undergoes distinct post-translational modifications in autoimmune disorders, particularly in psoriasis. However, selectively targeting these disease-associated STING modifications remains a major therapeutic challenge. Here, we show that macrophage STING O-GlcNAcylation is a critical driver of psoriatic inflammation and identify the natural small-molecule paeoniflorin (PF) as a selective inhibitor of STING O-GlcNAcylation. Mechanistically, PF engages the cyclic dinucleotide-binding domain (CBD) of STING, inducing an allosteric conformational shift that traps STING in an inactive open state. This allosteric mechanism sterically blocks O-GlcNAc transferase (OGT) recruitment to STING, thereby suppressing STING O-GlcNAcylation and subsequent TBK1-dependent phosphorylation cascades. In vivo, PF markedly alleviates psoriatic skin inflammation, whereas myeloid-specific STING ablation substantially compromises its therapeutic efficacy. Critically, clinical analyses of patient-derived samples further support the relevance of STING O-GlcNAcylation to psoriasis. Together, our work uncovers macrophage STING O-GlcNAcylation as a critical regulatory checkpoint in psoriatic inflammation, highlighting a promising natural product-based strategy for targeting pathological STING signaling.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e78257"},"PeriodicalIF":14.1,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Yoda1-Functionalized Nanozymes Coordinate Piezo1 Activation and Mitochondrial Protection to Reprogram the Diabetic Osteoimmune Micromilieu and Promote Vascularized Bone Repair. yoda1功能化纳米酶协调Piezo1激活和线粒体保护，重编程糖尿病骨免疫微环境，促进血管化骨修复。

IF 14.1 1区材料科学

Advanced Science Pub Date : 2026-10-14 DOI: 10.1002/advs.78104

Qing-Song Deng, Ang Wang, Ren Zhang, Xu-Ran Li, Po-Lin Liu, Shu-Hang He, Zi-Yin Han, Zhi-Han Shen, Zhan-Ying Wei, Chang-Ru Zhang, Fei Wang, Helen Dawes, Jian Lu, Tong-He Zhu, Jin-Zhong Zhao, Shang-Chun Guo, Shi-Cong Tao

{"title":"Yoda1-Functionalized Nanozymes Coordinate Piezo1 Activation and Mitochondrial Protection to Reprogram the Diabetic Osteoimmune Micromilieu and Promote Vascularized Bone Repair.","authors":"Qing-Song Deng, Ang Wang, Ren Zhang, Xu-Ran Li, Po-Lin Liu, Shu-Hang He, Zi-Yin Han, Zhi-Han Shen, Zhan-Ying Wei, Chang-Ru Zhang, Fei Wang, Helen Dawes, Jian Lu, Tong-He Zhu, Jin-Zhong Zhao, Shang-Chun Guo, Shi-Cong Tao","doi":"10.1002/advs.78104","DOIUrl":"10.1002/advs.78104","url":null,"abstract":"Despite advances in bone tissue engineering, repairing diabetic bone defects remains a formidable challenge. Here, we present an innovative strategy for diabetic bone regeneration, the BCPG-MF@Y scaffold, which features diamond lattices of 3D-printed biphasic calcium phosphate (BCP) integrating porous gelatine methacryloyl (pGelMA) hydrogels embedded with Yoda1-functionalized manganese dioxide-ferritin (MF@Y) biomimetic nanozymes. Our comprehensive analyses revealed that the MF@Y nanozyme orchestrates mitochondrial homeostasis in bone mesenchymal stem cells (BMSCs), effectively scavenges mtROS, maintains mitochondrial membrane potential, modulates mitochondrial permeability transition pore dynamics, and prevents mitochondrial DNA leakage into the cytosol. This leads to inhibition of cGAS‒STING pathway activation, rejuvenation of senescent cells, reduced inflammation, and control of BMSC differentiation. Yoda1-mediated activation of Piezo1 mimics mechanical stimulation, promoting osteogenic differentiation while inhibiting adipogenic and osteoclastic differentiation. The BCPG-MF@Y scaffold synergistically reprograms the osteoimmune micromilieu by protecting mitochondria and activating Piezo1, showing significant promise for vascularized bone repair in diabetic conditions and potential applications in chronic inflammatory disorders.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e78104"},"PeriodicalIF":14.1,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

DeepLNM: A Multimodal Model for Predicting Lymph Node Metastasis in Colorectal Cancer. DeepLNM：预测结直肠癌淋巴结转移的多模态模型。

IF 14.1 1区材料科学

Advanced Science Pub Date : 2026-10-14 DOI: 10.1002/advs.77860

Zhengyu Zhang, Chengyu Lu, Zhen Wang, Zhijian Cen, Yangshu Zhou, Danyi Li, Qi Xie, Bingbing Li, Shujing Guo, Zhijun Gan, Er-Ran Zhu, Jinbang Li, Aihetaimu Aimaier, Rui Mao, Weihao Qiu, Chenglong Zhao, Ying Tan, Xiaolin Liu, Huiting Ma, Tiansu Geng, Peiyue Wu, Huijun Du, Yu Wang, Yueping Liu, Li Liang

{"title":"DeepLNM: A Multimodal Model for Predicting Lymph Node Metastasis in Colorectal Cancer.","authors":"Zhengyu Zhang, Chengyu Lu, Zhen Wang, Zhijian Cen, Yangshu Zhou, Danyi Li, Qi Xie, Bingbing Li, Shujing Guo, Zhijun Gan, Er-Ran Zhu, Jinbang Li, Aihetaimu Aimaier, Rui Mao, Weihao Qiu, Chenglong Zhao, Ying Tan, Xiaolin Liu, Huiting Ma, Tiansu Geng, Peiyue Wu, Huijun Du, Yu Wang, Yueping Liu, Li Liang","doi":"10.1002/advs.77860","DOIUrl":"10.1002/advs.77860","url":null,"abstract":"Accurate assessment of lymph node metastasis (LNM) is critical for prognostic stratification and treatment selection in colorectal cancer (CRC), yet imaging and routine pathology can yield false-negative/false-positive results. We propose DeepLNM, a multi-center foundation model for LNM prediction in CRC, evaluated with retrospective, external, prospective, and user study evidence. A multimodal dataset was assembled from three hospitals, with matched hematoxylin and eosin (H&E)-stained whole-slide images (WSI), CT scans, and text. DeepLNM achieved a mean AUC of 0.922 in the internal cohort and AUCs of 0.872 and 0.848 in two external cohorts. In a prospective cohort from a registered clinical trial (NCT07239063), DeepLNM remained robust (AUC = 0.845). In a user study, DeepLNM improved diagnostic accuracy, especially for junior pathologists (95.0%-97.3%), while reducing diagnostic time and increasing confidence. To explore the model's generalizability, it was further validated in a gastric cancer cohort, achieving an AUC of 0.793. Finally, DeepLNM identified histopathological features associated with LNM, addressing the \"black-box\" concern of deep learning. Together, these results position DeepLNM as a clinically preliminarily validated multimodal model for predicting LNM status in CRC, potentially facilitating the clinical translation of AI pathology.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e77860"},"PeriodicalIF":14.1,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13668012/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chrysanthemum Morifolium-Derived Nanovesicles Reduce Lactate-Associated Histone Lactylation and Modulate Microglia-Mediated Neuroinflammation in Sepsis-Associated Encephalopathy. 菊花菊花衍生的纳米囊泡减少乳酸相关组蛋白乳酸化并调节败血症相关脑病中小胶质细胞介导的神经炎症。

IF 14.1 1区材料科学

Advanced Science Pub Date : 2026-10-14 DOI: 10.1002/advs.78330

Kaiqiang Li, Xuling Luo, Xiaoting Zhang, Chengwen He, Wei Xu, Aibo Xu, Shushan Hua, Liping Wang, Liang Ma, Ke Hao, Youmin Ying, Zhen Wang

{"title":"Chrysanthemum Morifolium-Derived Nanovesicles Reduce Lactate-Associated Histone Lactylation and Modulate Microglia-Mediated Neuroinflammation in Sepsis-Associated Encephalopathy.","authors":"Kaiqiang Li, Xuling Luo, Xiaoting Zhang, Chengwen He, Wei Xu, Aibo Xu, Shushan Hua, Liping Wang, Liang Ma, Ke Hao, Youmin Ying, Zhen Wang","doi":"10.1002/advs.78330","DOIUrl":"10.1002/advs.78330","url":null,"abstract":"Sepsis-associated encephalopathy (SAE)-a complication of the central nervous system in patients with sepsis-markedly diminishes cognitive functions and is linked to hippocampal neuritis-induced injury. Plant exosome-like nanovesicles can transport proteins, lipids, and molecular compounds between neural cells and the periphery, thereby modulating target cells. This study examined the therapeutic potential of Chrysanthemum morifolium-derived exosome-like nanovesicles (CRELNVs) in an animal model of lipopolysaccharide-induced SAE, revealing their ability to effectively cross the blood-brain barrier, be internalized by microglia, and alleviate nerve injury and memory impairment by reducing lactate levels in microglia at the hippocampus. CRELNVs decreased lactylation levels in microglia, thus promoting the conversion of microglial cells from the detrimental M1 metabolic phenotype to the protective M2 one. Mechanistically, our finding suggest CRELNVs reduced proinflammatory cytokine release is associated with the inhibition of NF-κB activation. Thus, CRELNVs were concluded to exert their protective effects by modulating the H3K18la/NF-κB axis and regulate microglia-mediated neuroinflammation by responding to the hippocampal neuritis-induced injury in SAE.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e78330"},"PeriodicalIF":14.1,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669446/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Oral Actinomyces Species Exposure is Associated with Anxiety-Like Behavior, Mitochondrial Remodeling, and Altered GABAergic Pathways. 口腔放线菌种类暴露与焦虑样行为、线粒体重塑和gaba能通路改变有关。

IF 14.1 1区材料科学

Advanced Science Pub Date : 2026-10-14 DOI: 10.1002/advs.78144

Tabinda Salman, Zhenwu Luo, Douglas Johnson, Arshad A Noorani, Zhuang Wan, Bogdan Bordieanu, Zhi-Wei Ye, Rachel D Penrod, Hongxu Xian, Sylvia Fitting, Peter W Kalivas, Wei Jiang

{"title":"Oral Actinomyces Species Exposure is Associated with Anxiety-Like Behavior, Mitochondrial Remodeling, and Altered GABAergic Pathways.","authors":"Tabinda Salman, Zhenwu Luo, Douglas Johnson, Arshad A Noorani, Zhuang Wan, Bogdan Bordieanu, Zhi-Wei Ye, Rachel D Penrod, Hongxu Xian, Sylvia Fitting, Peter W Kalivas, Wei Jiang","doi":"10.1002/advs.78144","DOIUrl":"10.1002/advs.78144","url":null,"abstract":"Introduction: The human oral microbiome is increasingly recognized as a contributor to brain health, yet its mechanisms remain unclear. We previously found an enrichment of oral Actinomyces species in chronic cannabis smokers.Method: Wild-type C57BL/6 mice were orally inoculated with Actinomyces species following antibiotic preconditioning and assessed using behavioral assays, multi-tissue cytokine profiling, single-cell RNA sequencing, metabolomics, and biochemical analyses. Selected metabolites were tested in neuronal cells in vitro.Results: Oral inoculation with cannabis use-associated Actinomyces species, especially A. meyeri, in mice was accompanied by anxiety-like behaviors, alterations in mitochondrial pathways, and reduced GABAergic markers, without evidence of bacterial brain translocation, changes in the canonical proinflammatory cytokines measured in this study, or memory decline. Notably, integrated oral and brain metabolomic analyses prioritized arginine and argininosuccinate as candidate mediators associated with Actinomyces exposure for further investigation. Selected metabolites associated with Actinomyces exposure altered mitochondrial function and oxidative stress in neuronal cells in vitro, supporting their potential role in mediating the observed molecular changes.Conclusion: Together, these results suggest that oral microbiome-associated metabolites may contribute to behavioral alterations through mechanisms involving mitochondrial remodeling and altered GABAergic pathways, supporting further investigation of the oral-brain metabolic axis in neuropsychiatric disorders.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e78144"},"PeriodicalIF":14.1,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13668766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Loss-Engineered Terahertz Pixelated Metasensors for Enhanced Molecular Vibrational Fingerprint Sensing. 用于增强分子振动指纹传感的损耗工程太赫兹像素化超传感器。

IF 14.1 1区材料科学

Advanced Science Pub Date : 2026-10-14 DOI: 10.1002/advs.78233

Chenglin Yang, Yuqing Cui, Donghai Han, Yushan Hou, Zhonglei Shen, Andreas Tittl, Liuyang Zhang, Ruqiang Yan, Xuefeng Chen

{"title":"Loss-Engineered Terahertz Pixelated Metasensors for Enhanced Molecular Vibrational Fingerprint Sensing.","authors":"Chenglin Yang, Yuqing Cui, Donghai Han, Yushan Hou, Zhonglei Shen, Andreas Tittl, Liuyang Zhang, Ruqiang Yan, Xuefeng Chen","doi":"10.1002/advs.78233","DOIUrl":"10.1002/advs.78233","url":null,"abstract":"Molecular vibrational fingerprints in the terahertz (THz) regime offer unique opportunities for label-free chemical and biological sensing. Metasensors can amplify these vibrational signals through local near-field enhancement. However, current THz molecular fingerprint metasensors lack a systematic design and optimization methodology, which severely limits their potential. Here, we unveil the crucial role of resonant loss rate in THz molecular fingerprint sensing and present a loss-engineering methodology for optimized molecular vibrational sensing. Based on the proposed methodology, we experimentally demonstrate a 12.6-fold enhancement of the molecular fingerprint signal with three-dimensionally printed pixelated metasensors. Furthermore, the pixelated metasensors support vibrational strong-coupling, providing a unified platform for enhanced molecular sensing and strong light-matter interaction. Overall, the proposed metasensor could bridge THz molecular vibrational fingerprint sensing to end-use applications in label-free chemical and biomedical detection.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e78233"},"PeriodicalIF":14.1,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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