Wiley最新文献

{"title":"Circulating Neurodegenerative Brain Injury Markers and Hip Fracture and Fall Hospitalizations: The Cardiovascular Health Study (CHS).","authors":"Jane A Cauley, Petra Buzkova, Howard A Fink, Joshua I Barzilay, Rachel E Elam, Oscar L Lopez, Lauren Carlson, John A Robbins, Luc Djousse, Kenneth J Mukamal","doi":"10.1093/jbmr/zjaf155","DOIUrl":"https://doi.org/10.1093/jbmr/zjaf155","url":null,"abstract":"<p><p>Individuals with dementia have a heightened hip fracture and fall risk but whether markers of brain injury are associated with hip fracture and falls is unknown. We tested the hypothesis that higher circulating brain injury markers were associated with increased risk of hip fracture and fall hospitalizations. Brain injury markers were measured in 2141 participants (mean age 77.9 years 60% women). Brain Injury markers included neurofilament light chain (NfL), a marker of axonal injury; glial fibrillary acidic protein (GFAP), a marker of astrocytic injury; total Tau, whose many functions include neuron microtubule stabilization; and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), a major protein of neurons. Incident hip fractures and hospitalizations for falls were identified through participant report and confirmed with medical records or Medicare claims. Hazard ratios were computed for a doubling exposure (log2 transformed brain injury marker) using multivariable-adjusted Cox models. After a median follow-up of 11 years, 304 incident hip fractures and 284 incident fall hospitalizations occurred. Doubling of GFAP and NfL were associated with a 22% (p=0.048) and 42% (p<0.001) higher risk of hip fracture, respectively. Additional adjustment for cognitive function, gait speed, grip strength, inflammatory markers, and depressive symptoms had no effect on results. Models that adjusted for all 4 brain markers showed that only NfL was independent of the other markers. NfL was also associated with a 47% increase risk of hospitalization for falls. There was no association of total Tau or UCH-L1 with hip fracture or falls. GFAP was also unrelated to fall hospitalizations. NfL, was independently associated with an incident risk of hip fracture and fall hospitalizations. These results suggest that subclinical degrees of brain injury may contribute to falls and hip fracture. Future research is needed to test whether the association between NfL and hip fracture is independent of falls.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Linking Comparative Genomics, Morphology and In Vitro Assays to Understand Deep Diving in Cetaceans.","authors":"Matt J Thorstensen","doi":"10.1111/mec.70161","DOIUrl":"https://doi.org/10.1111/mec.70161","url":null,"abstract":"","PeriodicalId":210,"journal":{"name":"Molecular Ecology","volume":" ","pages":"e70161"},"PeriodicalIF":3.9,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Easy Proteomics Sample Preparation: Technical Repeatability and Workflow Optimization Across 8 Biological Matrices in a New Core Facility Setting.","authors":"Paraskevi Karousi, Maria Voumvouraki, Panagiota Efstathia Nikolaou, Ioannis Kollias, Foteini Paradeisi, Elena Sampanai, Vasiliki Gkalea, Ioannis Morianos, Jerome Zoidakis, Efstathios Kastritis, Nikolaos Thomaidis, Guillaume Médard, Julie Courraud","doi":"10.1002/pmic.70064","DOIUrl":"https://doi.org/10.1002/pmic.70064","url":null,"abstract":"<p><p>Bottom-up proteomics relies on efficient and repeatable sample preparation for accurate protein identification and precise quantification. This study evaluates the performance of adapted SPEED (Sample Preparation by Easy Extraction and Digestion) protocol, a simplified, detergent-free approach tailored for various biological matrices, including lysis-resistant samples. Protein extraction and denaturation steps were refined for 8 biological matrices enabling standardized, cheap, and scalable proteomics analysis on 96-well plates. For tissue samples requiring downstream applications like Western blotting, we used a low-detergent RIPA buffer. Notably, the protocols demonstrate remarkable down-scalability, enabling robust proteomics measurements from as few as 3000 cells per sample for preparation and even down to 300 cells per LC-MS/MS analysis. Key advancements include a 30-min nanoLC-MS/MS run, achieving a 15-20 samples-per-day throughput, and leveraging the power of diaPASEF using thoroughly optimized DIA-windows to enhance proteome coverage. These adaptations streamline workflows, enabling proteomics analyses in matrices with challenging physical and biochemical properties. This study underscores the importance of early-stage optimization and feasibility testing in proteomics pipelines to inform study design and sample selection. By showcasing robust, scalable adaptations of the SPEED protocol, we provide a foundation for reproducible, high-throughput proteomic studies across diverse biological contexts.</p>","PeriodicalId":224,"journal":{"name":"Proteomics","volume":" ","pages":"e70064"},"PeriodicalIF":3.9,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Highly-Efficient Recycling of Poly(ethylene terephthalate)/Polyethylene Film through Low-Temperature Methanolysis Catalyzed by Nonmetallic Deep Eutectic Solvent.","authors":"Xiashi Wang, Xin Wei, Jingwen Qiu, Weizhong Zheng, Weizhen Sun, Ling Zhao","doi":"10.1002/cssc.202501863","DOIUrl":"https://doi.org/10.1002/cssc.202501863","url":null,"abstract":"<p><p>While the poly(ethylene terephthalate) (PET)/polyethylene (PE) multilayer films find extensive applications, particularly in packaging, the recovery of single PE layer or high-purity monomers from these films is seriously hindered by their complex compositions. Herein, a novel low-temperature methanolysis strategy for the highly efficient recycling PET/PE multilayer films with nonmetallic deep eutectic solvent (DES) is developed, where PET can be depolymerized to dimethyl terephthalate (DMT) and ethylene glycol (EG) monomers at 115 °C and 0.45 MPa for 60 min with 100% PET conversion and up to 97.1% DMT yield while PE maintains its stability. The process flow for the high-efficient recycling of PET/PE multilayer films is proposed, consisting of the methanolysis step and two solid-liquid separation ones to obtain the PE, DMT, and EG products. The process optimization, catalyzed mechanism, and swelling behaviors of DES for the PET methanolysis are studied. Finally, the kilogram-scale experiments under best conditions also can obtain 100% PET conversion and 87.8% DMT yield with complete recovery of PE, which efficiently confirms scalability of the proposed recycling pathway. This work establishes a sustainable pathway for closed-loop recycling of multilayer plastics by integrating PE material recovery with PET chemical upcycling.</p>","PeriodicalId":149,"journal":{"name":"ChemSusChem","volume":" ","pages":"e202501863"},"PeriodicalIF":6.6,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-PD-1 Nanobody-Armored MSLN CAR-T Therapy for Malignant Mesothelioma: Preclinical and Clinical Studies.","authors":"Yan Sun, Haochen Yang, Qing Xu, Xingya Li, Jinxing Lou, Jianchun Duan, Jiachen Xu, Zhuqing Liu, Yong Xia, Zhicai Lin, Linlin Li, Dan Sun, Jiaguo Li, Tao Liu, Jun Guo, Wenfeng Xu, Weimin Zhu, Yi Liu, Boyang Sun, Jia Zhong, Lijie Rong, Qijun Qian, Chenqi Xu, Jie Wang","doi":"10.1002/advs.202508754","DOIUrl":"https://doi.org/10.1002/advs.202508754","url":null,"abstract":"<p><p>Malignant mesothelioma (MM) is an aggressive and currently incurable cancer with limited therapeutic options. Due to the high expression of mesothelin in this cancer, anti-PD-1 nanobody-armored mesothelin-targeting CAR-T (NAC-T) cells are developed. Based on the enhanced anti-tumor activity observed in preclinical in vitro and in vivo studies, a first-in-human clinical trial is initiated. Eleven patients with malignant mesothelioma who have progressed after standard therapies receive intravenous infusions of 5-20 × 10⁶ per kg NAC-T cells following lymphodepletion. The treatment is well tolerated, with no dose-limiting toxicity observed. The overall response rate is 63.6%, including one complete response, and the disease control rate is 100%. The median progression-free survival is 5.0 months, and the median overall survival is 25.6 months. Moreover, T cell receptor and single-cell sequencing analyses in patients with varying responses revealed specific clonal expansion of T cell subtypes and enhanced reactivity to tumor-associated antigens. These findings suggest that NAC-T cell therapy represents a promising therapeutic strategy for patients with malignant mesothelioma.</p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e08754"},"PeriodicalIF":14.1,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353068","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}

{"title":"Interactions of Antibody Drug Conjugate Anti-Tubulin and Topoisomerase I Inhibitor Payloads with Radiotherapy to Potentiate Immunotherapy.","authors":"Jacqueline Lesperance, Bryan S Yung, Michael M Allevato, Marcus M Cheng, Maria F Camargo, Robert Saddawi-Konefka, Kanika Dhawan, Ashwyn K Sharma, Mahsa Mortaja, Sophie Bice, Daniel J Scanderbeg, Diego Alvarado, Jyoti Mayadev, Ramez N Eskander, Stephen R Adams, Pippa F Cosper, J Silvio Gutkind, Sunil J Advani","doi":"10.1002/advs.202506552","DOIUrl":"https://doi.org/10.1002/advs.202506552","url":null,"abstract":"<p><p>The most effective treatments for locally advanced cancers rely on non-targeted chemotherapies given with radiotherapy. Advances in cancer biology have identified vulnerabilities amenable to precision oncology approaches including antibody drug conjugates (ADCs). In theory, ADCs combine specificity of cancer cell receptor antibody targeting with potent cytotoxins. However, toxicities and resistance limit ADC clinical efficacy. Delivering ADCs with radiotherapy can improve their therapeutic index. Here, the combination of ADC payloads (anti-tubulin monomethyl auristatin E (MMAE) or topoisomerase I inhibitors DXd and SN-38) with radiotherapy is reported in immune-competent murine models. To directly compare ADC payload effects and remove targeting bias, the payloads are tested as free drugs and as tumor-targeted ADC or peptide-drug conjugates in combination with ionizing radiation. Both DXd and MMAE induce anti-tumor immune response that block re-challenge tumor growth. As monotherapy, DXd is more potent than MMAE at inhibiting tumor formation. In contrast when combined with ionizing radiation at subtherapeutic doses, MMAE but not DXd radiosensitizes resulting in improved tumor control and greater immune activation with MMAE. The differential effects of anti-tubulin versus topoisomerase I inhibitors when combined with ionizing radiation and immunotherapies can inform and optimize clinical development of ADC based chemo-radio-immunotherapy combinations for cancer patients.</p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e06552"},"PeriodicalIF":14.1,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353078","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}

{"title":"An Efficient CO₂-Upcycling Platform Based on Engineered Halomonas TD with Enhanced Acetate-Utilizing Capacity via Adaptive Laboratory Evolution.","authors":"Chi Wang, Ting-Ting Chen, Yu-Jiao Yang, Yu-Xi Li, Yi-Xin Chang, Yan-Chun Xiao, Wen-Tai Guo, Ye Zheng, Rui-Zhe Deng, Yu-Xiang Tian, Wei Situ, Hong-Wei Shen, Yu Chen, Ya-Bin Wang, Jie Xing, Hui Wang, Lin Xia, Yi-Na Lin, Jian-Wen Ye","doi":"10.1002/advs.202513060","DOIUrl":"https://doi.org/10.1002/advs.202513060","url":null,"abstract":"<p><p>Biohybrid conversion of carbon dioxide (CO₂) into value-added bioproducts via engineered microbes using CO₂-derived electrolytes (CDE) addresses global CO₂ emissions, but most recombinants have poor saline CDE tolerance and low carbon conversion rate (CCR). Herein, Halomonas TD (salt-resistant) was adaptively evolved into TD80, which efficiently uses acetate; its aceE gene mutation (encoding pyruvate dehydrogenase) drives acetate utilization. Subsequently, different biosynthesis pathways in TD80 enabled high yields of poly-3-hydroxybutyrate (PHB), poly-3-hydroxybutyrate-co-4-hydroxybutyrate (P34HB), 3-hydroxybutyrate (3HB), violacein, ectoine, 1,3-diaminopropane (1,3-DAP) and superoxide dismutase (SOD), respectively. Moreover, 26.0 g L^-1 ectoine and 29.6 g L^-1 PHB can be achieved by recombinant TD80 strains during fed-batch studies. Finally, a non-canonical pathway was designed to recycle the excess malonyl-CoA into PHB. The resultant PHB content in fed-batch study was increased from 60 wt% to 80 wt%. Moreover, co-producing ectoine and PHB could further boost the CCR of CDE-to-product up to 53.7 mol%, which exemplified promising potential for biohybrid CO₂ upcycling involved in carbon capture and utilization system. Furthermore, TD80 was engineered to grow on formate only aiming to achieve the full use of CDE. The establishment of technology and economy assessment (TEA) confirmed the Halomonas-based platform's efficiency and economic viability for carbon footprint reduction.</p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e13060"},"PeriodicalIF":14.1,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353099","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}

{"title":"Combination of Serum Neurofilament Light Chain and Serum Cardiac Troponin T as Biomarkers Improves Diagnostic Accuracy in Amyotrophic Lateral Sclerosis.","authors":"Paula Lindenborn, Rachel Fabian, Torsten Grehl, Huelya Nazlican, Thomas Meyer, Sarah Bernsen, Patrick Weydt","doi":"10.1002/ana.78066","DOIUrl":"https://doi.org/10.1002/ana.78066","url":null,"abstract":"<p><strong>Objective: </strong>We aimed to evaluate the clinical utility of serum neurofilament light chain (sNfL) and cardiac troponin T (cTnT) in amyotrophic lateral sclerosis (ALS) and assess whether their combination improves diagnostic accuracy.</p><p><strong>Methods: </strong>We retrospectively analyzed 293 ALS patients, 85 neurodegenerative disease controls, and 29 healthy controls. A validation cohort of 501 ALS patients was analyzed to confirm reproducibility of the results. Receiver operating characteristic (ROC) curve analysis was performed for sNfL, cTnT, and their combination, and the area under the curve (AUC) was compared across groups. An ALS-specific cTnT cut-off of 8.35ng/L was determined using the Youden index and applied in subgroup analyses, in which \"biomarker-negative\" ALS patients were compared to \"biomarker-positive\" patients regarding disease duration and progression.</p><p><strong>Results: </strong>sNfL showed excellent performance in discriminating ALS patients from healthy controls (AUC = 0.94), but only moderate performance in discriminating neurodegenerative disease controls (AUC = 0.82). Combining sNfL and cTnT improved diagnostic accuracy for ALS over neurodegenerative controls, with an AUC of 0.90, whereas cTnT alone showed an AUC of 0.77. The validation cohort showed similar AUCs. \"Biomarker-negative\" ALS patients had a longer disease duration (73.0 vs 18.0 months, p = 0.0003) and a lower progression rate (0.19 vs 0.70 points per months, p < 0.0001) than \"biomarker-positive\" patients.</p><p><strong>Interpretation: </strong>Although sNfL alone performs well in distinguishing ALS from healthy controls, repurposing cTnT for ALS provides additional value in discriminating ALS from disease controls. The combination of sNfL and cTnT improves diagnostic accuracy and may help identify prognostically distinct ALS subgroups. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electrically and Geometrically Tunable Photon Pair Entanglement from Ferroelectric Nematic Liquid Crystal.","authors":"Sara Klopčič, Aljaž Kavčič, Nerea Sebastián, Matjaž Humar","doi":"10.1002/advs.202515206","DOIUrl":"https://doi.org/10.1002/advs.202515206","url":null,"abstract":"<p><p>Entangled photons are a cornerstone of quantum technologies, enabling applications from secure communication to quantum computing. A longstanding challenge is to develop a compact source that would generate polarization-entangled photons with tunable quantum state on demand. The promising materials for such sources are ferroelectric nematic liquid crystals (FNLCs), due to their nonlinear optical properties and easily controllable configuration. In this work, it is demonstrated that the polarization state and the degree of entanglement of photon pairs generated within FNLCs can be changed in a controllable and reversible manner. First, tuning of the entanglement is demonstrated via sample geometry with twisted FNLC configurations in a sample of varying thickness. Secondly, by applying an electric field, the degree of entanglement can be tuned in real time. In both scenarios, the degree of entanglement can be adjusted from nearly entirely separate photons to fully entangled. These findings represent a significant step toward tunable quantum sources that can produce any desired polarization state on demand. In the future, by adding more electrodes, different parts of the sample could be controlled individually, allowing for the creation of pixelated quantum light sources.</p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e15206"},"PeriodicalIF":14.1,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353038","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}

{"title":"Controlled Photocatalytic Reduction of CO₂ by Precise Atomic-Level Interface Modification and Engineering of Silver Nanoclusters.","authors":"Hangmin Xu, Xiang Liu, Ganghua Zhou, Chuanzhou Bi, Qing Liu, Weiyi Jiang, Bin Wang, Xingwang Zhu, Paul K Chu, Xiaozhi Wang","doi":"10.1002/advs.202516096","DOIUrl":"https://doi.org/10.1002/advs.202516096","url":null,"abstract":"<p><p>The emission of carbon dioxide (CO₂) and other greenhouse gases has raised serious environmental concerns, and artificial photosynthesis is a promising approach to reducing the carbon footprint. The primary challenge for photocatalytic systems is how to optimally separate interfacial charges, while the hydrogen evolution reaction limits the selectivity of products in the photocatalytic reduction of CO₂. Herein, highly stable Ag₄₄ nanoclusters (Ag₄₄ NCs) protected by thiol salt ligands are prepared with atomic-level precision. The ultra-small Ag₄₄ NCs shorten the distance for electrons to migrate from the bulk phase to the surface and accelerate interfacial charge transfer. Furthermore, the molecule-like properties of Ag₄₄ NCs broaden the light absorption range of the semiconducting substrate, and quantum confinement rendered by Ag₄₄ NCs produces a potential well, which promotes electron aggregation and generates a long-range ordered electric field to transfer electrons directionally. Since the electrostatic repulsion of positively charged Ag₄₄ NCs hinders electron transfer and proton coupling, the hydrogen evolution reaction is inhibited.</p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e16096"},"PeriodicalIF":14.1,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353120","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}