Zhaoning Song, Hanlin Wang, Zhenyuan Zhao, Zimu Zhou, Siting Yu, Jie Zhu, Xiao Chen, Limin Ren, Toru Wakihara, Zhendong Liu
Single-walled zeolitic nanotube features a one-dimensional, hollow tubular structure with double-layered zeolitic walls, which represents a unique type of open framework materials. The formation mechanism underlying this characteristic structure, however, remains largely unexplored. We herein demonstrate that the hydrothermal synthesis of single-walled zeolitic nanotubes involves a cascade of phase transformations driven by intricate inorganic-organic interactions. As a critical step, the rearrangement of short-range ordered aluminosilicate networks enriched with five-membered rings, coupled with geometric matching to the cylindrical micelles of the bolaform organic structure-directing agent, synergistically drives the development and closure of curvature-induced interfaces, ultimately leading to the formation of single-walled zeolitic nanotubes. The proposed mechanism provides a distinctive understanding into structure-directing behaviors for ordered porous materials. This study offers valuable insights for guiding the rational synthesis and precise property tuning of the single-walled zeolitic nanotube, which hold vast potential for applications in diverse fields.
{"title":"Consecutive phase transformations of inorganic-organic assembly in the synthesis of single-walled zeolitic nanotube","authors":"Zhaoning Song, Hanlin Wang, Zhenyuan Zhao, Zimu Zhou, Siting Yu, Jie Zhu, Xiao Chen, Limin Ren, Toru Wakihara, Zhendong Liu","doi":"10.1126/sciadv.adx1619","DOIUrl":"10.1126/sciadv.adx1619","url":null,"abstract":"<div >Single-walled zeolitic nanotube features a one-dimensional, hollow tubular structure with double-layered zeolitic walls, which represents a unique type of open framework materials. The formation mechanism underlying this characteristic structure, however, remains largely unexplored. We herein demonstrate that the hydrothermal synthesis of single-walled zeolitic nanotubes involves a cascade of phase transformations driven by intricate inorganic-organic interactions. As a critical step, the rearrangement of short-range ordered aluminosilicate networks enriched with five-membered rings, coupled with geometric matching to the cylindrical micelles of the bolaform organic structure-directing agent, synergistically drives the development and closure of curvature-induced interfaces, ultimately leading to the formation of single-walled zeolitic nanotubes. The proposed mechanism provides a distinctive understanding into structure-directing behaviors for ordered porous materials. This study offers valuable insights for guiding the rational synthesis and precise property tuning of the single-walled zeolitic nanotube, which hold vast potential for applications in diverse fields.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 3","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145964496","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}
Junhoe Kim, Farzad Jalali-Yazdi, Brian E. Jones, Gary L. Westbrook, Eric Gouaux
Autoantibodies targeting synaptic membrane proteins are associated with autoimmune encephalitis manifested by seizures, psychosis, and memory dysfunction. Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis, a prototype of these autoimmune synaptic disorders, is unexpectedly common. Unfortunately, how the native repertoire of anti-NMDAR autoantibodies recognizes NMDARs and the precise locations of antigenic epitopes remain poorly understood. Here, we used an active immunization model that closely mimics the human disease to immunize adult mice with intact GluN1/GluN2A receptors, resulting in fulminant autoimmune encephalitis. Serum was collected at 6 weeks postimmunization for single-particle cryo–electron microscopy of GluN1/GluN2A receptors complexed with purified polyclonal anti-NMDAR autoantibody fragments. Native autoantibodies recognized two distinct binding sites on the GluN1 amino-terminal domain, which we confirmed using monoclonal antibodies bound to native NMDARs purified from mouse brain. Structural analysis of autoantibody-bound NMDAR complexes identified antigenic hotspots within the GluN1 amino-terminal domain. These hotspots provide potential targets for therapeutic intervention.
{"title":"Cryo-EM of autoantibody-bound NMDA receptors reveals antigenic hotspots in an active immunization model of anti-NMDAR encephalitis","authors":"Junhoe Kim, Farzad Jalali-Yazdi, Brian E. Jones, Gary L. Westbrook, Eric Gouaux","doi":"10.1126/sciadv.aeb4249","DOIUrl":"10.1126/sciadv.aeb4249","url":null,"abstract":"<div >Autoantibodies targeting synaptic membrane proteins are associated with autoimmune encephalitis manifested by seizures, psychosis, and memory dysfunction. Anti-<i>N</i>-methyl-<span>d</span>-aspartate receptor (NMDAR) encephalitis, a prototype of these autoimmune synaptic disorders, is unexpectedly common. Unfortunately, how the native repertoire of anti-NMDAR autoantibodies recognizes NMDARs and the precise locations of antigenic epitopes remain poorly understood. Here, we used an active immunization model that closely mimics the human disease to immunize adult mice with intact GluN1/GluN2A receptors, resulting in fulminant autoimmune encephalitis. Serum was collected at 6 weeks postimmunization for single-particle cryo–electron microscopy of GluN1/GluN2A receptors complexed with purified polyclonal anti-NMDAR autoantibody fragments. Native autoantibodies recognized two distinct binding sites on the GluN1 amino-terminal domain, which we confirmed using monoclonal antibodies bound to native NMDARs purified from mouse brain. Structural analysis of autoantibody-bound NMDAR complexes identified antigenic hotspots within the GluN1 amino-terminal domain. These hotspots provide potential targets for therapeutic intervention.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 3","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145964509","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}
Membrane fusion is essential for viral entry. Unlike class I-III fusion proteins, vaccinia virus (VACV) uses a multicomponent entry fusion complex (EFC). Using cryo–electron microscopy, we determined the full-length structure of the VACV EFC at near-atomic resolution, revealing a 15-protein asymmetric assembly organized into three layers. The central A16/G9/J5 heterotrimer forms the fusion core, stabilized by conserved PXXCW and Delta motifs, and anchors two A28/H2 adaptor dimers linked to peripheral G3/L5/A21/O3 scaffolds. Structural and evolutionary analyses identify a conserved N-terminal domain in A16 containing a myristoyl-binding pocket and a phenylalanine-rich region that stabilizes the trimer and may regulate lipid engagement. An additional component, F9, binds peripherally to J5, A21, and H2 through Delta-like motifs, reinforcing the prefusion architecture. Together, these results define the VACV EFC as a unique multiprotein fusion machinery and provide a structural framework for understanding the mechanism of poxvirus entry and membrane fusion.
{"title":"Cryo-EM structure of the vaccinia virus entry fusion complex reveals a multicomponent fusion machinery","authors":"Chang Sheng-Huei Lin, Ching-An Li, Chun-Hsiung Wang, Chi-Fei Kao, Hsiao-Jung Chiu, Min-Chi Yeh, Hua-De Gao, Meng-Chiao Ho, Hsien-Ming Lee, Wen Chang","doi":"10.1126/sciadv.aec0254","DOIUrl":"10.1126/sciadv.aec0254","url":null,"abstract":"<div >Membrane fusion is essential for viral entry. Unlike class I-III fusion proteins, vaccinia virus (VACV) uses a multicomponent entry fusion complex (EFC). Using cryo–electron microscopy, we determined the full-length structure of the VACV EFC at near-atomic resolution, revealing a 15-protein asymmetric assembly organized into three layers. The central A16/G9/J5 heterotrimer forms the fusion core, stabilized by conserved PXXCW and Delta motifs, and anchors two A28/H2 adaptor dimers linked to peripheral G3/L5/A21/O3 scaffolds. Structural and evolutionary analyses identify a conserved N-terminal domain in A16 containing a myristoyl-binding pocket and a phenylalanine-rich region that stabilizes the trimer and may regulate lipid engagement. An additional component, F9, binds peripherally to J5, A21, and H2 through Delta-like motifs, reinforcing the prefusion architecture. Together, these results define the VACV EFC as a unique multiprotein fusion machinery and provide a structural framework for understanding the mechanism of poxvirus entry and membrane fusion.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 3","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145964486","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}
Cen Wang, Hui Su, Jianqiu Zheng, Yana Li, Yanjia Wang, Kuilin Zhu, Linwei Jiang
Sea ice variability in the Laptev and East Siberian Seas (LESS) notably affects Arctic climate and maritime safety. While El Niño–Southern Oscillation (ENSO) winter sea surface temperature anomalies influence global climate, their effect on subsequent autumn LESS ice remains unclear. This study reveals a post-2000 intensification of winter ENSO’s impact on subsequent autumn LESS ice, driven by accelerated ENSO phase transitions compared to the pre-2000 era. Rapid phase transitions of El Niño after 2000 generate persistent cold anomalies in the tropical central–eastern Pacific during the subsequent autumn, strengthening and displacing the Western North Pacific anticyclone (WNPAC) northward. This WNPAC triggers Rossby waves establishing an Arctic anticyclone, warming, and moistening the LESS atmosphere, thereby driving substantial ice loss. In contrast, pre-2000 slower El Niño decay exhibited weaker tropical-Arctic connectivity. These results identify ENSO phase transitions rate as a critical regulator of Arctic sea ice variability, with important implications for seasonal forecasting.
{"title":"Post-2000 faster ENSO phase transitions amplify autumn sea ice loss in the Laptev–East Siberian Sea","authors":"Cen Wang, Hui Su, Jianqiu Zheng, Yana Li, Yanjia Wang, Kuilin Zhu, Linwei Jiang","doi":"10.1126/sciadv.aea3753","DOIUrl":"10.1126/sciadv.aea3753","url":null,"abstract":"<div >Sea ice variability in the Laptev and East Siberian Seas (LESS) notably affects Arctic climate and maritime safety. While El Niño–Southern Oscillation (ENSO) winter sea surface temperature anomalies influence global climate, their effect on subsequent autumn LESS ice remains unclear. This study reveals a post-2000 intensification of winter ENSO’s impact on subsequent autumn LESS ice, driven by accelerated ENSO phase transitions compared to the pre-2000 era. Rapid phase transitions of El Niño after 2000 generate persistent cold anomalies in the tropical central–eastern Pacific during the subsequent autumn, strengthening and displacing the Western North Pacific anticyclone (WNPAC) northward. This WNPAC triggers Rossby waves establishing an Arctic anticyclone, warming, and moistening the LESS atmosphere, thereby driving substantial ice loss. In contrast, pre-2000 slower El Niño decay exhibited weaker tropical-Arctic connectivity. These results identify ENSO phase transitions rate as a critical regulator of Arctic sea ice variability, with important implications for seasonal forecasting.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 3","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145964498","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}
Yongxing Cui, Shushi Peng, Manuel Delgado-Baquerizo, Daryl L. Moorhead, Robert L. Sinsabaugh, César Terrer, Thomas P. Smith, Yakov Kuzyakov, Josep Peñuelas, Biao Zhu, Feng Tao, Songbai Hong, Ji Chen, Matthias C. Rillig
Despite extensive research on soil microbial carbon (C) use efficiency (CUE), its linkage to actual soil C storage remains ambiguous. A key uncertainty is that CUE estimates from short-term labeling incubations assume a linear negative relationship with respiration rates, overlooking nonlinear interactions and long-term microbial acclimation. Here, we use a stoichiometry-based approach to estimate CUE (CUEST), which links soil resource availability to microbial demand and captures microbial adaptability under resource constraints. We synthesized 1094 paired observations of CUEST and heterotrophic respiration rate (Rh) across natural ecosystems and found a nonlinear relationship between them governed by ecosystem productivity. In low-productivity arid and cold regions, CUEST declined with increasing Rh, whereas in productive tropical and temperate regions, CUEST stabilized at a low level (0.27 ± 0.11) as Rh exceeded 340 ± 10.8 grams of C per square meter per year. This shift reflects microbial trade-offs between C assimilation and stoichiometric homeostasis, revealing a decoupling of microbial growth from respiration that limits the capacity of productive ecosystems to store additional soil C.
尽管对土壤微生物碳(C)利用效率（CUE）进行了广泛的研究，但其与实际土壤碳储量的联系尚不明确。一个关键的不确定性是，短期标记培养的CUE估计与呼吸速率呈线性负相关，忽略了非线性相互作用和长期微生物适应。在这里，我们使用基于化学计量学的方法来估计CUE (CUEST)，该方法将土壤资源可用性与微生物需求联系起来，并捕获资源约束下微生物的适应性。我们综合了1094个自然生态系统中CUEST和异养呼吸速率（Rh）的成对观测结果，发现它们之间的非线性关系受生态系统生产力的支配。在低生产力的干旱和寒冷地区，CUEST随Rh的增加而下降，而在高产的热带和温带地区，当Rh超过340±10.8 g / m2时，CUEST稳定在较低水平（0.27±0.11）。这一转变反映了微生物在碳同化和化学计量稳态之间的权衡，揭示了微生物生长与呼吸的脱钩，这限制了生产性生态系统储存额外土壤碳的能力。
{"title":"Productivity-driven decoupling of microbial carbon use efficiency and respiration across global soils","authors":"Yongxing Cui, Shushi Peng, Manuel Delgado-Baquerizo, Daryl L. Moorhead, Robert L. Sinsabaugh, César Terrer, Thomas P. Smith, Yakov Kuzyakov, Josep Peñuelas, Biao Zhu, Feng Tao, Songbai Hong, Ji Chen, Matthias C. Rillig","doi":"10.1126/sciadv.adz5319","DOIUrl":"10.1126/sciadv.adz5319","url":null,"abstract":"<div >Despite extensive research on soil microbial carbon (C) use efficiency (CUE), its linkage to actual soil C storage remains ambiguous. A key uncertainty is that CUE estimates from short-term labeling incubations assume a linear negative relationship with respiration rates, overlooking nonlinear interactions and long-term microbial acclimation. Here, we use a stoichiometry-based approach to estimate CUE (CUE<sub>ST</sub>), which links soil resource availability to microbial demand and captures microbial adaptability under resource constraints. We synthesized 1094 paired observations of CUE<sub>ST</sub> and heterotrophic respiration rate (<i>R</i><sub>h</sub>) across natural ecosystems and found a nonlinear relationship between them governed by ecosystem productivity. In low-productivity arid and cold regions, CUE<sub>ST</sub> declined with increasing <i>R</i><sub>h</sub>, whereas in productive tropical and temperate regions, CUE<sub>ST</sub> stabilized at a low level (0.27 ± 0.11) as <i>R</i><sub>h</sub> exceeded 340 ± 10.8 grams of C per square meter per year. This shift reflects microbial trade-offs between C assimilation and stoichiometric homeostasis, revealing a decoupling of microbial growth from respiration that limits the capacity of productive ecosystems to store additional soil C.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 3","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145964488","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}
Despite the therapeutic potential of engineered immune cell therapy against metastases, it faces challenges including cytokine-driven systemic toxicity, off-target biodistribution, and host rejection. Here, we develop red/far-red light-regulated individually encapsulated (RL/FRL-EnE) cells, integrating optogenetics with biomaterial encapsulation for precise immunomodulation. This system uses a phytochrome A–based photoswitch (ΔPhyA-PCB) that enables bidirectional control. RL (660 nanometers) triggers interferon-γ, interleukin-6, and anti-CD47 expression via ΔPhyA-PCB–far-red elongated hypocotyl 1 heterodimerization, while FRL (740 nanometers) rapidly reverses production, minimizing toxicity. Single-cell nanoencapsulation prevents intercellular cross-talk and immune clearance, enabling strict light-dependent regulation and extended tumor residence. In vivo, RL/FRL-EnE cells remodeled the tumor microenvironment, reducing immunosuppressive myeloid cells (1.3- to 1.7-fold), while enhancing dendritic cell (1.4-fold) and CD8+ T cell (2.8-fold) infiltration. Collectively, this work establishes a paradigm for closed-loop cellular immunotherapy, where light-regulated living therapeutics achieve on-demand immune reprogramming.
{"title":"On-demand cancer immunotherapy via single-cell encapsulation of synthetic circuit–engineered cells","authors":"Yue Zhao, Rui Li, Yirui Han, Chaochen Shi, Kyubae Lee, Guangjun Nie, Yazhou Chen","doi":"10.1126/sciadv.aea3573","DOIUrl":"10.1126/sciadv.aea3573","url":null,"abstract":"<div >Despite the therapeutic potential of engineered immune cell therapy against metastases, it faces challenges including cytokine-driven systemic toxicity, off-target biodistribution, and host rejection. Here, we develop red/far-red light-regulated individually encapsulated (RL/FRL-EnE) cells, integrating optogenetics with biomaterial encapsulation for precise immunomodulation. This system uses a phytochrome A–based photoswitch (ΔPhyA-PCB) that enables bidirectional control. RL (660 nanometers) triggers interferon-γ, interleukin-6, and anti-CD47 expression via ΔPhyA-PCB–far-red elongated hypocotyl 1 heterodimerization, while FRL (740 nanometers) rapidly reverses production, minimizing toxicity. Single-cell nanoencapsulation prevents intercellular cross-talk and immune clearance, enabling strict light-dependent regulation and extended tumor residence. In vivo, RL/FRL-EnE cells remodeled the tumor microenvironment, reducing immunosuppressive myeloid cells (1.3- to 1.7-fold), while enhancing dendritic cell (1.4-fold) and CD8<sup>+</sup> T cell (2.8-fold) infiltration. Collectively, this work establishes a paradigm for closed-loop cellular immunotherapy, where light-regulated living therapeutics achieve on-demand immune reprogramming.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 3","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145964499","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}
Taejun Seol, Ju-Gyeong Kang, Kwangmin Ryu, Woojae Kim, Daehee Hwang, Suhyeon Cho, Daeun Song, Bomin Ku, Yen T. H. Tran, Sun-Hye Jeong, Won-Ki Cho, Dae-Sik Lim
Adipocyte differentiation from mesenchymal stem cells is governed by tightly regulated transcriptional and epigenetic programs. The Hippo pathway effectors YAP and TAZ impede this process, yet the underlying molecular mechanisms remain unclear. Here, we demonstrate how YAP/TAZ regulate transcription of the adipocyte lineage specification factor PPARγ and its target genes at the chromatin level. TAZ represses PPARγ-bound target enhancers as evidenced by a markedly reduced histone H3 acetylated at lysine-27 occupancy, resulting in the transcriptional repression of adipogenic genes, including Pparg2. Single-nucleus genomic analyses of mouse adipose tissue further revealed that YAP/TAZ activation drives extensive epigenetic modulation. Notably, the repressive effect of TAZ on adipogenic enhancers requires TEAD-dependent transcriptional activity, but not a direct interaction with PPARγ through the WW domain as previously reported. Last, we identified Vestigial-like 3 (Vgll3) as a transcriptional target of TAZ critical for repressing adipogenic enhancers. These findings reveal that the YAP/TAZ-VGLL3 axis regulates adipocyte fate by repressing the PPARγ program at its target enhancers.
{"title":"YAP/TAZ-VGLL3 governs adipocyte fate via epigenetic reprogramming of PPARγ and its target enhancers","authors":"Taejun Seol, Ju-Gyeong Kang, Kwangmin Ryu, Woojae Kim, Daehee Hwang, Suhyeon Cho, Daeun Song, Bomin Ku, Yen T. H. Tran, Sun-Hye Jeong, Won-Ki Cho, Dae-Sik Lim","doi":"10.1126/sciadv.aea7235","DOIUrl":"10.1126/sciadv.aea7235","url":null,"abstract":"<div >Adipocyte differentiation from mesenchymal stem cells is governed by tightly regulated transcriptional and epigenetic programs. The Hippo pathway effectors YAP and TAZ impede this process, yet the underlying molecular mechanisms remain unclear. Here, we demonstrate how YAP/TAZ regulate transcription of the adipocyte lineage specification factor PPARγ and its target genes at the chromatin level. TAZ represses PPARγ-bound target enhancers as evidenced by a markedly reduced histone H3 acetylated at lysine-27 occupancy, resulting in the transcriptional repression of adipogenic genes, including <i>Pparg2</i>. Single-nucleus genomic analyses of mouse adipose tissue further revealed that YAP/TAZ activation drives extensive epigenetic modulation. Notably, the repressive effect of TAZ on adipogenic enhancers requires TEAD-dependent transcriptional activity, but not a direct interaction with PPARγ through the WW domain as previously reported. Last, we identified Vestigial-like 3 (<i>Vgll3</i>) as a transcriptional target of TAZ critical for repressing adipogenic enhancers. These findings reveal that the YAP/TAZ-VGLL3 axis regulates adipocyte fate by repressing the PPARγ program at its target enhancers.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 3","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145964491","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}
Yuqi Wang, Su Yan, Xinyu Tan, Ethan Gerhard, Hui Xu, Haiyue Jiang, Jian Yang
Ideal orthopedic biomaterials should replicate both the hierarchical structure and exceptional mechanical strength of natural bone. Traditional polymer-hydroxyapatite composites, typically limited up to 40 wt % hydroxyapatite, offer only modest mechanical improvements. Efforts to enhance strength by using stiffer polymers have largely failed, as increased polymer stiffness does not translate to improved composite mechanics. In contrast, natural bone’s load-bearing capability arises from the synergy between citrate, soft collagen, and ultrathin hydroxyapatite nanocrystals (~3 nanometers). Here, we show that elastic poly(octamethylene citrate) enables up to 60 wt % hydroxyapatite incorporation, mimicking the bone’s mineral content. Through a top-down “citrification” process and hot pressing, hydroxyapatite microparticles are partially dissolved and recrystallized into superthin (~5 nanometers) nanorods, enhancing organic-inorganic integration and replicating bone’s Ca/P ratios and architecture. The resulting composites exhibit compressive strengths exceeding 250 megapascals, unprecedented in polymer-mineral systems, offering a molecular design strategy for next-generation load-bearing orthopedic implants.
{"title":"The genesis of citrated ultrathin hydroxyapatite nanorods","authors":"Yuqi Wang, Su Yan, Xinyu Tan, Ethan Gerhard, Hui Xu, Haiyue Jiang, Jian Yang","doi":"10.1126/sciadv.aeb6538","DOIUrl":"10.1126/sciadv.aeb6538","url":null,"abstract":"<div >Ideal orthopedic biomaterials should replicate both the hierarchical structure and exceptional mechanical strength of natural bone. Traditional polymer-hydroxyapatite composites, typically limited up to 40 wt % hydroxyapatite, offer only modest mechanical improvements. Efforts to enhance strength by using stiffer polymers have largely failed, as increased polymer stiffness does not translate to improved composite mechanics. In contrast, natural bone’s load-bearing capability arises from the synergy between citrate, soft collagen, and ultrathin hydroxyapatite nanocrystals (~3 nanometers). Here, we show that elastic poly(octamethylene citrate) enables up to 60 wt % hydroxyapatite incorporation, mimicking the bone’s mineral content. Through a top-down “citrification” process and hot pressing, hydroxyapatite microparticles are partially dissolved and recrystallized into superthin (~5 nanometers) nanorods, enhancing organic-inorganic integration and replicating bone’s Ca/P ratios and architecture. The resulting composites exhibit compressive strengths exceeding 250 megapascals, unprecedented in polymer-mineral systems, offering a molecular design strategy for next-generation load-bearing orthopedic implants.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 3","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145964505","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}
Oral delivery of peptide therapeutics remains challenging due to gastrointestinal (GI) degradation and poor intestinal absorption. Here, we propose a self-immolative peptide prodrug conjugate (SIPPC) platform for inflammation-targeted oral delivery, integrating a hydrophilic polyethylene glycol segment, a reactive oxygen species (ROS)–responsive hydrophobic self-immolative module, and a hydrolyzable scaffold, which collectively enable spontaneous assembly into micelle-like nanoparticles. Using three anti-inflammatory peptides (KPV, Ac-QAW, and IRW), we demonstrated that the engineered conjugates exhibit remarkable GI stability, efficient mucus penetration, and ROS-responsive release at inflamed sites. In colitis mice, the KPV-based conjugate (proKPV) achieved a 3.8-fold greater colonic accumulation than free KPV, with enhanced efficacy even at a 20-fold lower dose. Beyond therapeutic effects in the colitis model, oral proKPV substantially accumulated in inflamed lungs and exhibited potent anti-inflammatory efficacy in mice with acute lung injury. Ac-QAW and IRW-based conjugates exhibited comparable benefits, underscoring SIPPC as a transformative paradigm for oral peptide therapeutics, offering substantial promise for clinical translation in inflammatory disorders.
{"title":"Inflammation-triggered self-immolative conjugates enable oral peptide delivery by overcoming gastrointestinal barriers","authors":"Juan Cheng, Peng Wu, Chenwen Li, Ying Han, Menglong Sun, Yin Dou, Sheng Chen, Jianxiang Zhang","doi":"10.1126/sciadv.aea2989","DOIUrl":"10.1126/sciadv.aea2989","url":null,"abstract":"<div >Oral delivery of peptide therapeutics remains challenging due to gastrointestinal (GI) degradation and poor intestinal absorption. Here, we propose a self-immolative peptide prodrug conjugate (SIPPC) platform for inflammation-targeted oral delivery, integrating a hydrophilic polyethylene glycol segment, a reactive oxygen species (ROS)–responsive hydrophobic self-immolative module, and a hydrolyzable scaffold, which collectively enable spontaneous assembly into micelle-like nanoparticles. Using three anti-inflammatory peptides (KPV, Ac-QAW, and IRW), we demonstrated that the engineered conjugates exhibit remarkable GI stability, efficient mucus penetration, and ROS-responsive release at inflamed sites. In colitis mice, the KPV-based conjugate (proKPV) achieved a 3.8-fold greater colonic accumulation than free KPV, with enhanced efficacy even at a 20-fold lower dose. Beyond therapeutic effects in the colitis model, oral proKPV substantially accumulated in inflamed lungs and exhibited potent anti-inflammatory efficacy in mice with acute lung injury. Ac-QAW and IRW-based conjugates exhibited comparable benefits, underscoring SIPPC as a transformative paradigm for oral peptide therapeutics, offering substantial promise for clinical translation in inflammatory disorders.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 3","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145964487","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}
Weishun Zeng, Zhaoqing Yang, Yan Lu, Chang Lei, Yang Gao, Yuhan Yang, Xu Wang, Jiayou Chu, Shuhua Xu
The Qiang people are widely recognized as a basal layer of the Chinese gene pool, yet their genetic origins and evolutionary history remain unclear. We analyzed 20 deep-sequenced Qiang genomes together with genomic data from Tibetan highlanders and neighboring lowlanders. The Qiang genetic structure has been profoundly shaped by historical admixture with Han and Tibetans, giving rise to distinct subpopulations. Using ~450 ancient Asian genomes, we traced the most recent common ancestor of the Qiang to ancient Yellow River farmers ~5300 years ago, indicating shared ancestry with other Chinese populations. We identified several highly differentiated variants related to ethanol metabolism and pigmentation between Qiang subpopulations, which likely arose from joint effects of admixture and selection. Notably, a highly prevalent missense variant in a blood pressure regulation gene was detected, suggesting a potential role in altitude adaptation. Collectively, our findings illuminate the genetic history of the Qiang and highlight how admixture and selection shaped the diversity of Tibetan-Plateau fringe populations.
{"title":"Ancient Yellow River ancestry and divergent admixture histories in the Qiang people","authors":"Weishun Zeng, Zhaoqing Yang, Yan Lu, Chang Lei, Yang Gao, Yuhan Yang, Xu Wang, Jiayou Chu, Shuhua Xu","doi":"10.1126/sciadv.ady6667","DOIUrl":"10.1126/sciadv.ady6667","url":null,"abstract":"<div >The Qiang people are widely recognized as a basal layer of the Chinese gene pool, yet their genetic origins and evolutionary history remain unclear. We analyzed 20 deep-sequenced Qiang genomes together with genomic data from Tibetan highlanders and neighboring lowlanders. The Qiang genetic structure has been profoundly shaped by historical admixture with Han and Tibetans, giving rise to distinct subpopulations. Using ~450 ancient Asian genomes, we traced the most recent common ancestor of the Qiang to ancient Yellow River farmers ~5300 years ago, indicating shared ancestry with other Chinese populations. We identified several highly differentiated variants related to ethanol metabolism and pigmentation between Qiang subpopulations, which likely arose from joint effects of admixture and selection. Notably, a highly prevalent missense variant in a blood pressure regulation gene was detected, suggesting a potential role in altitude adaptation. Collectively, our findings illuminate the genetic history of the Qiang and highlight how admixture and selection shaped the diversity of Tibetan-Plateau fringe populations.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 3","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145964489","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}
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