综合性期刊最新文献

{"title":"CryoRhodopsins: A comprehensive characterization of a group of microbial rhodopsins from cold environments","authors":"Gerrit H. U. Lamm,&nbsp;Egor Marin,&nbsp;Alexey Alekseev,&nbsp;Anna V. Schellbach,&nbsp;Artem Stetsenko,&nbsp;Jose Manuel Haro-Moreno,&nbsp;Gleb Bourenkov,&nbsp;Valentin Borshchevskiy,&nbsp;Marvin Asido,&nbsp;Michael Agthe,&nbsp;Sylvain Engilberge,&nbsp;Samuel L. Rose,&nbsp;Nicolas Caramello,&nbsp;Antoine Royant,&nbsp;Thomas R. Schneider,&nbsp;Alex Bateman,&nbsp;Thomas Mager,&nbsp;Tobias Moser,&nbsp;Francisco Rodriguez-Valera,&nbsp;Josef Wachtveitl,&nbsp;Albert Guskov,&nbsp;Kirill Kovalev","doi":"10.1126/sciadv.adv1015","DOIUrl":"10.1126/sciadv.adv1015","url":null,"abstract":"<div >Microbial rhodopsins are omnipresent on Earth; however, the vast majority of them remain uncharacterized. Here, we describe a rhodopsin group found in microorganisms from cold environments, such as glaciers, denoted as CryoRhodopsins (CryoRs). A distinguishing feature of the group is the presence of a buried arginine residue close to the cytoplasmic face. Combining single-particle cryo–electron microscopy and x-ray crystallography with rhodopsin activation by light, we demonstrate that the arginine stabilizes an ultraviolet (UV)–absorbing intermediate of an extremely slow CryoRhodopsin photocycle. Together with extensive spectroscopic characterization, our investigations on CryoR1 and CryoR2 proteins reveal mechanisms of photoswitching in the identified group. Our data suggest that CryoRs are sensors for UV irradiation and are also capable of inward proton translocation modulated by UV light.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 27","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adv1015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558347","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":"Adipocyte CLDN5 promotes thermogenesis and energy expenditure through regulation of IL10 expression.","authors":"Ke Feng, Wenqin Wang, Xianlong Gao, Hejie Yan, Mengyuan Xu, Baozhen Fan, Qianfeng Jia, Chao Wang, Jian Yu, Yi Li, Qinfeng Xu, Yanan An, Peng Jiao, Mingxia Wang, Hui Sun, Feng Kong, Yongfeng Gong, Shengtian Zhao","doi":"10.1038/s41467-025-61371-3","DOIUrl":"https://doi.org/10.1038/s41467-025-61371-3","url":null,"abstract":"<p><p>The claudin protein family plays key roles in maintaining normal structure and function of epithelial and endothelial tight junctions. While several prior studies have addressed the expression of claudin in adipocytes that do not form tight junctions, here we demonstrate that CLDN5 is selectively expressed in non-thermogenic adipocytes within adipose tissue. Ablation of CLDN5 in adipocyte impairs thermogenesis and energy expenditure. CLDN5 deficiency also significantly increases diet-induced fat mass in mice, accompanied with glucose intolerance and insulin resistance. Mechanistically, CLDN5 affects the subcellular localization of Y-box protein 3, which directly regulates IL10 expression via binding to its promoter and specific sites in 3'-untranslated region, thereby acts in a paracrine manner to signal through IL10R in neighbouring thermogenic adipocytes. These findings expand our understanding about location and function of the extra-tight junction claudin proteins and provide molecular insights into signaling mechanisms underlying adipose thermogenesis that could inform future therapy.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"16 1","pages":"6151"},"PeriodicalIF":14.7,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A universal chimeric antigen receptor (CAR)–fragment antibody binder (FAB) split system for cancer immunotherapy","authors":"Ainhoa Arina,&nbsp;Edwin Arauz,&nbsp;Elham Masoumi,&nbsp;Karolina W. Warzecha,&nbsp;Annika Sääf,&nbsp;Łukasz Widło,&nbsp;Tomasz Slezak,&nbsp;Aleksandra Zieminska,&nbsp;Karolina Dudek,&nbsp;Zachary P. Schaefer,&nbsp;Maria Lecka,&nbsp;Svitlana Usatyuk,&nbsp;Ralph R. Weichselbaum,&nbsp;Anthony A. Kossiakoff","doi":"10.1126/sciadv.adv4937","DOIUrl":"10.1126/sciadv.adv4937","url":null,"abstract":"<div >Chimeric antigen receptor (CAR) T cell therapy has shown extraordinary results in treating hematological cancer but faces challenges like antigen loss, toxicity, and complex manufacturing. Universal and modular CAR constructs offer improved flexibility, safety, and cost-effectiveness over conventional CAR constructs. We present a CAR–fragment antibody binder (Fab) platform on the basis of an engineered protein G variant (GA1) and Fab scaffolds. Expression of GA1CAR on human CD8⁺ T cells leads to antigen recognition and T cell effector function that can be modulated according to the affinity of the CAR for the Fab and of the Fab for the target. GA1CAR T cells can recognize multiple Fab-antigen pairs on breast and ovarian cancer cell lines. Adoptively transferred GA1CAR T cells control tumors in breast cancer xenograft models, and their targeting can be quickly redirected using different Fabs. This versatile “plug-and-play” CAR T platform has potential for application in personalized therapy, preventing antigen loss variant escape, decreasing toxicity, and increasing access.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 27","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adv4937","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558272","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":"Effects of incoming polygonal fault systems on subduction zone and slow slip behavior","authors":"Maomao Wang,&nbsp;Philip M. Barnes,&nbsp;Demian Saffer,&nbsp;Gregory F. Moore,&nbsp;Haoran Ma,&nbsp;Ming Wang,&nbsp;Jinbao Su","doi":"10.1126/sciadv.adu4227","DOIUrl":"10.1126/sciadv.adu4227","url":null,"abstract":"<div >The physical properties of subduction inputs profoundly influence megathrust slip behavior. Seismic data reveal extensive polygonal fault systems (PFSs) in the input sequences of the Hikurangi Margin and Nankai Trough. The mechanical and hydrological effects of these incoming PFSs on subduction zones are potentially substantial. Here, we investigate their effects following transport into the accretionary wedge by integrating discrete-element modeling with three-dimensional seismic interpretation. We find that the typical dips of the incoming PFSs overlap with modeled dips prone to reactivation and confirm that subducting PFSs can be reactivated and gradually evolve into major thrust faults. Comparisons with electromagnetic data indicate that PFSs may provide conduits for fluid leakage along the plate interface, coincide with disrupted strata and decreased shear stress, and enhance geometric and stress heterogeneity along the megathrust. These suggest that PFSs may play a previously unrecognized role in contributing to shallow slow earthquake phenomena in subduction zones.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 27","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adu4227","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558276","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":"Correlation between the dome-shaped superconducting phase diagram, charge order, and normal-state electronic properties in LaRu₃Si₂.","authors":"KeYuan Ma, Igor Plokhikh, Jennifer N Graham, Charles Mielke Iii, Vahid Sazgari, Hiroto Nakamura, Shams Sohel Islam, Soohyeon Shin, Petr Král, Orion Gerguri, Hubertus Luetkens, Fabian O von Rohr, Jiaxin Yin, Ekaterina Pomjakushina, Claudia Felser, Satoru Nakatsuji, Björn Wehinger, Dariusz J Gawryluk, Sergey Medvedev, Zurab Guguchia","doi":"10.1038/s41467-025-61383-z","DOIUrl":"https://doi.org/10.1038/s41467-025-61383-z","url":null,"abstract":"<p><p>The interplay between superconductivity and charge or spin order is a key focus in condensed matter physics, with kagome lattice systems providing unique insights. The kagome superconductor LaRu₃Si₂ (T_c ≃ 6.5 K) features a characteristic kagome band structure and a hierarchy of charge order transitions at T_co,I ≃ 400 K and T_co,II ≃ 80 K, along with an additional transition at T* ≃ 35 K associated with electronic and magnetic responses. Using magnetotransport under pressure up to 40 GPa, we find T_c peaks at 9 K (2 GPa)-the highest among kagome superconductors-remains nearly constant up to 12 GPa, and then decreases to 2 K at 40 GPa, forming a dome-shaped phase diagram. Similarly, both the resistivity anomaly at T* and the magnetoresistance exhibit a dome-shaped pressure dependence. Moreover, above 12 GPa, X-ray diffraction reveals that the charge order evolves from long-range to short-range, coinciding with the suppression of T_c. These observations indicate that superconductivity in LaRu₃Si₂ is closely linked to the charge-ordered state and the electronic responses at T_co,II and T*.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"16 1","pages":"6149"},"PeriodicalIF":14.7,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DDX1 methylation mediated MATR3 splicing regulates intervertebral disc degeneration by initiating chromatin reprogramming.","authors":"Dingchao Zhu, Huaizhen Liang, Bide Tong, Zhi Du, Gaocai Li, Weifeng Zhang, Di Wu, Xingyu Zhou, Jie Lei, Xiaoguang Zhang, Liang Ma, Bingjin Wang, Xiaobo Feng, Kun Wang, Lei Tan, Yu Song, Cao Yang","doi":"10.1038/s41467-025-61486-7","DOIUrl":"https://doi.org/10.1038/s41467-025-61486-7","url":null,"abstract":"<p><p>Low back pain (LBP), primarily driven by intervertebral disc degeneration (IVDD), has become a core challenge in public health. DDX1, an RNA-binding protein, plays key roles in RNA metabolism but its function in IVDD remains unclear. We identify DDX1 as a substrate of methyltransferase EZH2, which methylates DDX1 at lysine 234 (K234), promoting IVDD in vitro and in vivo. EZH2 inhibition restores matrix homeostasis in nucleus pulposus (NP) cells and slows IVDD progression. Methylation at DDX1 K234 disrupts its interaction with splicing factors and RNA targets, promoting exon 14 skipping in MATR3. This truncated MATR3 disrupts nuclear architecture, increases chromatin accessibility, and activates signaling pathways such as Wnt, leading to NP cell senescence and apoptosis. Notably, delivery of MATR3-L-overexpressing mRNA via cationic lipid nanoparticles reduces NP cell degeneration and significantly alleviates IVDD, offering important insights into IVDD pathogenesis and potential therapeutic strategies.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"16 1","pages":"6153"},"PeriodicalIF":14.7,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Japan requires name change after marriage - with big effects on female scientists.","authors":"Smriti Mallapaty","doi":"10.1038/d41586-025-02081-0","DOIUrl":"https://doi.org/10.1038/d41586-025-02081-0","url":null,"abstract":"","PeriodicalId":18787,"journal":{"name":"Nature","volume":" ","pages":""},"PeriodicalIF":50.5,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ez-CAZy a reference annotation database for linking glycoside hydrolase sequence to enzymatic activity.","authors":"Daniel S Erdody, Nicholas G Griffin, Renaud Berlemont","doi":"10.1038/s41598-025-08859-6","DOIUrl":"https://doi.org/10.1038/s41598-025-08859-6","url":null,"abstract":"<p><p>Glycoside Hydrolases (GH) are carbohydrate-active enzymes that play a critical role in the degradation of carbohydrates, impacting ecosystem function, human health, and biotechnological applications. The functional annotation of GHs within the CAZy database is hindered by the lack of sequence-specific definitions, annotation tools, and reliance on generalized \"majority rule\" activity assumptions. Here, we introduce ez-CAZy, a custom reference database designed to link GH sequences, as well as other CAZy, to their enzymatic activities. By reannotating over 7,000 biochemically characterized GHs using Hidden Markov Model profiles and other publicly accessible tools, we provide detailed sequence metadata, domain architectures, and functional predictions. Our analysis reveals the clustered distribution of enzymatic activities and multi-domain architectures within GH families, facilitating more precise functional predictions for newly identified sequences. The predictive accuracy of ez-CAZy was validated using over 500 recently characterized GHs, demonstrating functional annotation. ez-CAZy addresses critical gaps in GH annotation pipelines and offers a publicly accessible tool to support sequence analysis and enzymatic research. This work underscores the need for standardized enzyme characterization and expanded substrate testing to enhance annotation accuracy in future studies.</p>","PeriodicalId":21811,"journal":{"name":"Scientific Reports","volume":"15 1","pages":"23841"},"PeriodicalIF":3.8,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144561145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Droplet microfluidics–based detection of rare antibiotic-resistant subpopulations in Escherichia coli from bloodstream infections","authors":"Sagar N. Agnihotri,&nbsp;Nikos Fatsis-Kavalopoulos,&nbsp;Jonas Windhager,&nbsp;Maria Tenje,&nbsp;Dan I. Andersson","doi":"10.1126/sciadv.adv4558","DOIUrl":"10.1126/sciadv.adv4558","url":null,"abstract":"<div >Population heterogeneity in bacterial phenotypes, such as antibiotic resistance, is increasingly recognized as a medical concern. Heteroresistance occurs when a predominantly susceptible bacterial population harbors a rare resistant subpopulation. During antibiotic exposure, these resistant bacteria can be selected and lead to treatment failure. Standard antibiotic susceptibility testing methods often fail to reliably detect these subpopulations due to their low frequency, highlighting the need for improved diagnostic approaches. Here, we present a droplet microfluidics method where bacteria are encapsulated in droplets containing growth medium and antibiotics. The growth of rare resistant cells is detected by observing droplet shrinkage under microscopy. We validated this method for three clinically important antibiotics in <i>Escherichia coli</i> isolates obtained from bloodstream infections and showed that it can detect resistant subpopulations as infrequent as 10⁻⁶ using only 200 to 300 droplets. In addition, we designed a multiplex microfluidic chip to increase the throughput of the assay.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 27","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adv4558","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558295","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":"Discovery of an autoinhibited conformation in mesotrypsin reveals a strategy for selective serine protease inhibition","authors":"Matt Coban,&nbsp;Mahesh Gokara,&nbsp;Luis M. Forero Vargas,&nbsp;Sarah D. Tanzer,&nbsp;Sherry X. Zhou,&nbsp;Alexandra Hockla,&nbsp;Banumathi Sankaran,&nbsp;Thomas R. Caulfield,&nbsp;Evette S. Radisky","doi":"10.1126/sciadv.adu9129","DOIUrl":"10.1126/sciadv.adu9129","url":null,"abstract":"<div >Selective inhibition of the more than 100 S1 family serine proteases is a long-standing challenge due to their active site similarity. Mesotrypsin, implicated in cancer progression, exemplifies these difficulties; no current inhibitors achieve selectivity over other human trypsins. We found an unexpected autoinhibited conformation of mesotrypsin via x-ray crystallography, revealing a cryptic pocket adjacent to the active site. Using high-throughput virtual screening targeting this cryptic pocket, we identified a conformationally selective small-molecule inhibitor that stabilizes the inactive state of mesotrypsin. This inhibitor demonstrates selectivity for mesotrypsin over other trypsins. Our findings challenge the accepted view of digestive trypsins as constitutively active enzymes lacking potential for allosteric regulation. Furthermore, analyses of other structures suggest that dynamic sampling of closed states with analogous allosteric cryptic pockets appears widespread among S1 serine proteases. These observations point to a potentially generalizable strategy to achieve selective inhibition, offering broad implications for drug development targeting serine proteases in cancer and other diseases.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 27","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adu9129","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558296","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}