{"title":"Ultrafast dynamics of electronic friction energy dissipation in defective semiconductor monolayer","authors":"Rui Han, Shihong Chen, Chong Wang, Shuchun Huang, Haowen Xu, Zejun Sun, Huixian Liu, Jianbin Luo, Dameng Liu, Huan Liu","doi":"10.1038/s41467-025-59978-7","DOIUrl":"https://doi.org/10.1038/s41467-025-59978-7","url":null,"abstract":"<p>Friction is the central cause for about 1/3 of the primary energy dissipation, severely impacting the performance limits of micro and nanoscale mechanical devices. Especially in two-dimensional semiconductor devices, electronic friction energy dissipation becomes particularly pronounced. However, the dynamic mechanisms underlying electronic friction energy dissipation remain unclear due to the ultrafast timescales of electronic behavior. Here, the ultrafast dynamics of electronic friction energy dissipation in monolayer WS<sub>2</sub> is observed using femtosecond transient absorption spectroscopy. We find that friction exhibits a significant enhancement as the rate of electron energy dissipation increases. It is experimentally found to be closely related to the generation of atomic defects at the sliding interfaces. These defects capture electrons in picoseconds and provide a new energy dissipation channel, resulting in increased friction. This study reveals the dynamics of electronic friction energy dissipation, which is vital to understand the origin of friction and improve the performance of micro and nanoscale devices.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"15 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144083335","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}
Jieqiong Ding, Yao Peng, Wei Xiong, Dongdong Wang, Ziran Xu, Qinxue Nie, Zheng Jiang, Zhi-Pan Liu, Cheng Shang, Weixin Huang
{"title":"Distinctly different active sites of ZnO-ZrO2 catalysts in CO2 and CO hydrogenation to methanol reactions","authors":"Jieqiong Ding, Yao Peng, Wei Xiong, Dongdong Wang, Ziran Xu, Qinxue Nie, Zheng Jiang, Zhi-Pan Liu, Cheng Shang, Weixin Huang","doi":"10.1038/s41467-025-59996-5","DOIUrl":"https://doi.org/10.1038/s41467-025-59996-5","url":null,"abstract":"<p>The active site of a solid catalyst varies sensitively with the catalyzed reaction. Herein, using experimentally measured elementary surface reaction kinetics of CO<sub>2</sub> or CO hydrogenation reactions over a ZnO-ZrO<sub>2</sub> catalyst under working conditions in combinations with comprehensive structural characterizations and theoretical simulations, we unveil the distinctly different active sites in catalyzing the CO<sub>2</sub> or CO hydrogenation to methanol reaction. Zn<sup>2+</sup> cations with different local environments are present on the ZnO-ZrO<sub>2</sub> surface, including Zn<sub>1</sub> single atoms exclusively with a Zn-O-Zr local structure and Zn<sub>n</sub> clusters with both Zn-O-Zr and Zn-O-Zn local structures. The -Zr-O-Zr- structure bonded to the Zn<sub>n</sub> clusters is more easily to be reduced than that bonded to the Zn<sub>1</sub> single atoms. The Zn<sub>1</sub>-single atom (-Zr-O-Zn-O-Zr-) is the active site for catalyzing the CO<sub>2</sub> hydrogenation to methanol reaction, whereas the Zn<sub>n</sub> cluster bonded to an in situ formed -Zr-V<sub>o</sub>-Zr- structure (-Zn-O-Zn(-O-Zr-V<sub>o</sub>-Zr-)-O-Zr-) is the active site for catalyzing the CO hydrogenation to methanol reaction. These results provide a reliable and effective methodology of elementary surface reaction kinetics for identifications of active sites of working catalysts in complex reactions and unveil how sensitively the active site structure varies with the catalyzed reaction.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"30 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144083254","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}
Soohyun Kim, Caelan E. Radford, Duo Xu, Jianing Zhong, Jonathan Do, Dominic M. Pham, Katie A. Travisano, Maria V. Filsinger Interrante, Theodora U. J. Bruun, Valerie Rezek, Bailey Wilder, Martina Palomares, Michael S. Seaman, Scott G. Kitchen, Jesse D. Bloom, Peter S. Kim
{"title":"A broad antibody with enhanced HIV-1 neutralization via bispecific antibody-mediated prepositioning","authors":"Soohyun Kim, Caelan E. Radford, Duo Xu, Jianing Zhong, Jonathan Do, Dominic M. Pham, Katie A. Travisano, Maria V. Filsinger Interrante, Theodora U. J. Bruun, Valerie Rezek, Bailey Wilder, Martina Palomares, Michael S. Seaman, Scott G. Kitchen, Jesse D. Bloom, Peter S. Kim","doi":"10.1038/s41467-025-60035-6","DOIUrl":"https://doi.org/10.1038/s41467-025-60035-6","url":null,"abstract":"<p>Antibodies targeting the highly conserved prehairpin intermediate (PHI) of class I viral membrane-fusion proteins are generally weakly neutralizing and are not considered viable therapeutic agents. We previously demonstrated that antibodies targeting the gp41 N-heptad repeat (NHR), which is transiently exposed in the HIV-1 PHI, exhibit enhanced broad neutralization in cells expressing the Fc receptor, FcγRI. To enhance neutralization in cells lacking FcγRI, we here develop a bispecific antibody (bsAb) by fusing an NHR-targeting antibody to an antibody against CD4, the HIV-1 receptor on T cells. The bsAb provides a 5000-fold neutralization enhancement and shows unprecedented neutralization breadth compared to existing broadly neutralizing antibodies. Importantly, the bsAb reduces viral load in HIV-1-infected humanized male mice, and viral envelope sequencing under bsAb pressure revealed an NHR mutation that potentially impairs viral fitness. These findings validate the NHR as a potential HIV-1 therapeutic target, setting the stage for a new class of broadly neutralizing antibodies.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"1 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144083334","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}
Zachary P. Rosenthal, Joseph B. Majeski, Ala Somarowthu, Davin K. Quinn, Britta E. Lindquist, Mary E. Putt, Antoneta Karaj, Chris G. Favilla, Wesley B. Baker, Golkoo Hosseini, Jenny P. Rodriguez, Mario A. Cristancho, Yvette I. Sheline, C. William Shuttleworth, Christopher C. Abbott, Arjun G. Yodh, Ethan M. Goldberg
{"title":"Electroconvulsive therapy generates a postictal wave of spreading depolarization in mice and humans","authors":"Zachary P. Rosenthal, Joseph B. Majeski, Ala Somarowthu, Davin K. Quinn, Britta E. Lindquist, Mary E. Putt, Antoneta Karaj, Chris G. Favilla, Wesley B. Baker, Golkoo Hosseini, Jenny P. Rodriguez, Mario A. Cristancho, Yvette I. Sheline, C. William Shuttleworth, Christopher C. Abbott, Arjun G. Yodh, Ethan M. Goldberg","doi":"10.1038/s41467-025-59900-1","DOIUrl":"https://doi.org/10.1038/s41467-025-59900-1","url":null,"abstract":"<p>Electroconvulsive therapy (ECT) is a fast-acting, highly effective, and safe treatment for medication-resistant depression. Historically, the clinical benefits of ECT have been attributed to generating a controlled seizure; however, the underlying neurobiology is understudied and unresolved. Using optical neuroimaging of neural activity and hemodynamics in a mouse model of ECT, we demonstrated that a second brain event follows seizure: cortical spreading depolarization (CSD). We found that ECT pulse parameters and electrode configuration directly shaped the wave dynamics of seizure and subsequent CSD. To translate these findings to human patients, we used non-invasive diffuse optical monitoring of cerebral blood flow and oxygenation during routine ECT treatments. We observed that human brains reliably generate hyperemic waves after ECT seizure which are highly consistent with CSD. These results challenge a long-held assumption that seizure is the primary outcome of ECT and point to new opportunities for optimizing ECT stimulation parameters and treatment outcomes.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"88 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144083255","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}
Nirel Bernstein, Hang Li, Benjamin Assouline, Yong-Chang Lau, Igor Rozhansky, Wenhong Wang, Amir Capua
{"title":"Spin-torque skyrmion resonance in a frustrated magnet","authors":"Nirel Bernstein, Hang Li, Benjamin Assouline, Yong-Chang Lau, Igor Rozhansky, Wenhong Wang, Amir Capua","doi":"10.1038/s41467-025-59899-5","DOIUrl":"https://doi.org/10.1038/s41467-025-59899-5","url":null,"abstract":"<p>The frustrated Fe<sub>3</sub>Sn<sub>2</sub> magnet is technologically attractive due to its extreme-temperature skyrmion stability, large topological Hall effect, and current-induced helicity switching attributed to a self-induced spin-torque. Here, we present a current-driven skyrmion resonance technique excited by self-induced spin-torque in Fe<sub>3</sub>Sn<sub>2</sub>. The dynamics are probed optically in a time-resolved measurement enabling us to distinguish between the excited modes. We find that only the breathing and rotational counterclockwise modes are excited, rather than the three modes typically observed in Dzyaloshinskii-Moriya interaction-dominated magnetic textures. When a DC current is passed through the crystal, the skyrmion resonance linewidth is modulated. Our micromagnetic simulations indicate that the linewidth broadening arises from an effective damping-like spin-orbit torque. Accordingly, we extract an effective spin Hall conductivity of <span>(sim {{bf{793}}},pm {{bf{176}}},left({{hslash }}/{{boldsymbol{e}}}right),{left({{bf{Omega}}} ; {{bf{cm}}}right)}^{-{{bf{1}}}})</span>. Complementary planar Hall measurements suggest a small yet finite contribution of the real-space spin texture in the electronic transport in addition to a primary <span>({{boldsymbol{k}}})</span>-space contribution. Our results bring new insights into the anisotropic nature of spin-torques in frustrated magnets and to the possibility of using the skyrmion resonance as a sensor for spin currents.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"33 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144083338","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}
Rafal S. Sobota, Emily M. Stucke, Drissa Coulibaly, Jonathan G. Lawton, Bryan E. Cummings, Savy Sebastian, Antoine Dara, James B. Munro, Amed Ouattara, Abdoulaye K. Kone, Bourama Kane, Karim Traoré, Bouréima Guindo, Bourama M. Tangara, Amadou Niangaly, Noah T. Ventimiglia, Modibo Daou, Issa Diarra, Youssouf Tolo, Mody Sissoko, Fayçal Maiga, Aichatou Diawara, Amidou Traore, Ali Thera, Matthew B. Laurens, Kirsten E. Lyke, Bourema Kouriba, Ogobara K. Doumbo, Christopher V. Plowe, David R. Goodlett, Joana C. Silva, Mahamadou A. Thera, Mark A. Travassos
{"title":"A shared inflammatory signature across severe malaria syndromes manifested by transcriptomic, proteomic and metabolomic analyses","authors":"Rafal S. Sobota, Emily M. Stucke, Drissa Coulibaly, Jonathan G. Lawton, Bryan E. Cummings, Savy Sebastian, Antoine Dara, James B. Munro, Amed Ouattara, Abdoulaye K. Kone, Bourama Kane, Karim Traoré, Bouréima Guindo, Bourama M. Tangara, Amadou Niangaly, Noah T. Ventimiglia, Modibo Daou, Issa Diarra, Youssouf Tolo, Mody Sissoko, Fayçal Maiga, Aichatou Diawara, Amidou Traore, Ali Thera, Matthew B. Laurens, Kirsten E. Lyke, Bourema Kouriba, Ogobara K. Doumbo, Christopher V. Plowe, David R. Goodlett, Joana C. Silva, Mahamadou A. Thera, Mark A. Travassos","doi":"10.1038/s41467-025-59281-5","DOIUrl":"https://doi.org/10.1038/s41467-025-59281-5","url":null,"abstract":"<p>Factors governing the clinical trajectory of <i>Plasmodium falciparum</i> infection remain an important area of investigation. Here we present transcriptomic, proteomic and metabolomic analyses comparing clinical subtypes of severe <i>Plasmodium falciparum</i> malaria to matched controls with uncomplicated disease in 79 children from Mali. <i>MMP8</i>, <i>IL1R2</i>, and <i>ARG1</i> transcription is higher across cerebral malaria, severe malarial anemia, and concurrent cerebral malaria and severe malarial anemia, indicating a shared inflammatory signature. Tissue inhibitor of metalloproteinases 1 is the most upregulated protein in cerebral malaria, which along with elevated <i>MMP8</i> and <i>MMP9</i> transcription, underscores the importance of the metalloproteinase pathway in central nervous system pathophysiology. L-arginine metabolites are decreased in cerebral malaria, which coupled with increased <i>ARG1</i> transcription suggests a putative mechanism impairing cerebral vasodilation. Using multi-omics approaches, we thus describe the inflammatory cascade in severe malaria syndromes, and identify potential therapeutic targets and biological markers.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"22 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144083337","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}
Gregory J. Golden, Vincent H. Wu, Jacob T. Hamilton, Kevin R. Amses, Melanie R. Shapiro, Alberto Sada Japp, Chengyang Liu, M. Betina Pampena, Leticia Kuri-Cervantes, James J. Knox, Jay S. Gardner, Mark A. Atkinson, Todd M. Brusko, Eline T. Luning Prak, Klaus H. Kaestner, Ali Naji, Michael R. Betts
{"title":"Immune perturbations in human pancreas lymphatic tissues prior to and after type 1 diabetes onset","authors":"Gregory J. Golden, Vincent H. Wu, Jacob T. Hamilton, Kevin R. Amses, Melanie R. Shapiro, Alberto Sada Japp, Chengyang Liu, M. Betina Pampena, Leticia Kuri-Cervantes, James J. Knox, Jay S. Gardner, Mark A. Atkinson, Todd M. Brusko, Eline T. Luning Prak, Klaus H. Kaestner, Ali Naji, Michael R. Betts","doi":"10.1038/s41467-025-59626-0","DOIUrl":"https://doi.org/10.1038/s41467-025-59626-0","url":null,"abstract":"<p>Autoimmune destruction of pancreatic β cells results in type 1 diabetes (T1D), with pancreatic immune infiltrate representing a key feature in this process. However, characterization of the immunological processes occurring in human pancreatic lymphatic tissues is lacking. Here, we conduct a comprehensive study of immune cells from pancreatic, mesenteric, and splenic lymphatic tissues of non-diabetic control (ND), β cell autoantibody-positive non-diabetic (AAb+), and T1D donors using flow cytometry and CITEseq. Compared to ND pancreas-draining lymph nodes (pLN), AAb+ and T1D donor pLNs display decreased CD4+ Treg and increased stem-like CD8+ T cell signatures, while only T1D donor pLNs exhibit naive T cell and NK cell differentiation. Mesenteric LNs have modulations only in CD4+ Tregs and naive cells, while splenocytes lack these perturbations. Further, T cell expression of activation markers and IL7 receptor correlate with T1D genetic risk. These results demonstrate tissue-restricted immune changes occur before and after T1D onset.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"79 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144083253","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}
Stefan Halvorsen, Molly Thomas, Mari Mino-Kenudson, Yuko Kinowaki, Kristin E. Burke, David Morgan, Kaia C. Miller, Katherine M. Williams, Jenny Gurung, Jessica McGoldrick, Megan Hopton, Brooke Hoppe, Nandini Samanta, Sidney Martin, Alice Tirard, Benjamin Y. Arnold, Jessica Tantivit, Joseph Yarze, Kyle Staller, Daniel C. Chung, Alexandra-Chloé Villani, Slim Sassi, Hamed Khalili
{"title":"Single-cell transcriptomic characterization of microscopic colitis","authors":"Stefan Halvorsen, Molly Thomas, Mari Mino-Kenudson, Yuko Kinowaki, Kristin E. Burke, David Morgan, Kaia C. Miller, Katherine M. Williams, Jenny Gurung, Jessica McGoldrick, Megan Hopton, Brooke Hoppe, Nandini Samanta, Sidney Martin, Alice Tirard, Benjamin Y. Arnold, Jessica Tantivit, Joseph Yarze, Kyle Staller, Daniel C. Chung, Alexandra-Chloé Villani, Slim Sassi, Hamed Khalili","doi":"10.1038/s41467-025-59648-8","DOIUrl":"https://doi.org/10.1038/s41467-025-59648-8","url":null,"abstract":"<p>Microscopic colitis (MC) is a chronic inflammatory disease of the large intestine and a common cause of chronic diarrhea in older adults. Here, we use single-cell RNA sequencing analysis of colonic mucosal tissue to build a cellular and molecular model for MC. Our results show that in MC, there is a substantial expansion of tissue CD8<sup>+</sup> T cells, likely arising from local expansion following T cell receptor engagement. Within the T cell compartment, MC is characterized by a shift in CD8 tissue-resident memory T cells towards a highly cytotoxic and inflammatory phenotype and expansion of CD4<sup>+</sup> T regulatory cells. These results provide insight into inflammatory cytokines shaping MC pathogenesis and highlight notable similarities and differences with other immune-mediated intestinal diseases, including a common upregulation of <i>IL26</i> and an MC-specific upregulation of <i>IL10</i>. These data help identify targets against enteric T cell subsets as an effective strategy for treatment of MC.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"79 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144083332","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":"Carbon fibre production using an ecofriendly water-soluble precursor","authors":"Takuya Morishita, Mamiko Narita, Mitsumasa Matsushita, Kenichi Hayashida, Kazuhiro Nomura, Shota Taniguchi, Yoshihiro Kikuzawa, Natsu Sakakura, Hiromitsu Tanaka, Yoshihide Katagiri, Atsuto Okamoto, Makoto Mouri, Hiroyuki Mori, Akira Kunitomo, Hideyasu Kawai, Nozomu Shigemitsu","doi":"10.1038/s41467-025-59841-9","DOIUrl":"https://doi.org/10.1038/s41467-025-59841-9","url":null,"abstract":"<p>Carbon fibre (CF) is a lightweight next-generation material with numerous applications. CF production is predominantly based on the polyacrylonitrile (PAN) precursor because of the high tensile strength of PAN-based CFs (PAN-CFs). However, expensive and toxic organic solvents are required for PAN-CF production. Moreover, the corresponding thermal stabilisation process is highly energy-intensive, leading to high CO<sub>2</sub> emissions. Herein, aqueous polyacrylamide (aqPAM) fibre—prepared via polymerisation and dry spinning using water—is proposed as a water-soluble CF precursor that can be converted into high-performance CF at high carbon yields. The incorporation of small amounts of phosphoric acid into aqPAM considerably reduces the thermal stabilisation time and increases the carbon yield compared with that obtainable using PAN-CF. Moreover, the carbonised aqPAM-based CFs exhibit a high tensile strength and tensile modulus comparable with those of PAN-CFs. The developed process generates less CO<sub>2</sub> emissions than PAN-CF production.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"127 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144083207","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 generalizable approach for programming protease-responsive conformationally inhibited artificial transcriptional factors","authors":"Yinxia Liu, Lingyun Zhao, Jinshan Long, Zhenye Huang, Ying Long, Jianjun He, Jian-Hui Jiang","doi":"10.1038/s41467-025-59828-6","DOIUrl":"https://doi.org/10.1038/s41467-025-59828-6","url":null,"abstract":"<p>Synthetic genetic circuits that harness programmable protein modules and artificial transcription factors (ATF) to devise event-triggerable cascaded pathways represent an essential class of tools for studying cell biology. Fine-tuning the general structural functionality of ATFs is important for constructing orthogonal and composable transcriptional regulators. Here, we report the design of a protease-responsive conformationally inhibited system (PRCIS). By intramolecularly linking the free DNA-binding domains of ATF to confined dimerized regions, the transcriptional binding is conformationally inactivated. The function of DNA binding is reinstated upon proteolytic cleavage of linkages, activating the downstream gene expressions. The versatility of PRCIS design is demonstrated through its adaptability to various ATFs and proteases, showcasing high activation ratios and specificity. Furthermore, the development of PRCIS-based triple-orthogonal protease-responsive and dual-orthogonal chemical-inducible platforms and Boolean logic operations are elaborated in this paper, providing a generalizable design for synthetic biology.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"141 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144066993","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}