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作者：Kamp, Leon M.; Zanaty, Mohamed; Zareei, Ahmad; Gorissen, Benjamin; Wood, Robert J.; Bertoldi, Katia
作者单位：Harvard University; KU Leuven
摘要：Programming physical intelligence into mechanisms holds great promise for machines that can accomplish tasks such as navigation of unstructured environments while utilizing a minimal amount of computational resources and electronic components. In this study, we introduce a design approach for physically intelligent underactuated mechanisms capable of autonomously adjusting their motion in response to environmental interactions. Specifically, multistability is harnessed to sequence the motion o...
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作者：Li, Jinxi; Xiang, Ting; Zhang, Fengping; Feng, Li; Wu, Yiting; Guo, Fan; Li, Lingzhi; Fu, Ping; Ma, Liang
作者单位：Sichuan University
摘要：Kidney fibrosis is driven by multiple factors, among which impaired fatty acid oxidation has emerged as a critical determinant. Acyl-Coenzyme A (CoA) synthetase medium-chain family member 3 (ACSM3), a key enzyme of medium-chain fatty acid (MCFA) metabolism, has been implicated in metabolic syndrome, but its function in fibrotic kidney remains unexplored. Here, we found that tubular epithelial ACSM3 expression was downregulated in kidney fibrotic mice and patients and inversely correlated with ...
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作者：Samim, Saini; Dalton, Hayden; Phillips, David; Hergt, Janet
作者单位：University of Melbourne
摘要：The Turkana Basin is a renowned paleoanthropological region in Kenya and Ethiopia and is famous for discoveries of numerous hominin fossils and their associated cultural technologies. The Plio-Pleistocene sedimentary sequences hosting these important remains are interbedded with volcanic ash (tuff) beds that provide crucial bracketing age constraints. The Nariokotome Tuff Complex, comprising the Upper, Middle, and Lower Nariokotome Tuffs, preserves deposits that cover an important time interva...
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作者：Wang, Yu; Li, Tang; Zheng, Yangjie; Guo, Chenxin; Li, Kuikui; Jia, Xiaochen; Zhu, Liping; Chen, Kecai; Yin, Heng
作者单位：Chinese Academy of Sciences; Dalian Institute of Chemical Physics, CAS; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS
摘要：Steviol glycosides (SGs) from Stevia rebaudiana are prized as noncaloric sweeteners, with rebaudioside M (Reb M)-a next-generation SG known for its sucrose-like sweetness and lack of off-tastes-standing out for its superior sensory profile. However, Reb M's limited natural abundance impedes its commercial production. Here, we report the identification of a glucosyltransferase, UGT76G4 that efficiently catalyzes the conversion of Reb D to Reb M with a strong preference for C19 glycosylation. St...
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作者：Bragado, Laureano; Pozzi, Berta; Beckerman, Ines; Magalnik, Melina; Srebrow, Anabella
作者单位：University of Buenos Aires; University of Buenos Aires; Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET)
摘要：The noncoding small nuclear RNAs (snRNAs) associate with a large set of proteins to form small nuclear ribonucleoprotein particles (snRNPs). While the function of snRNAs is well characterized, the regulation of their transcription remains poorly understood. Recently, we demonstrated that SUMO conjugation regulates snRNA3 ' end processing. To further study the connection between SUMOylation and snRNA biogenesis, we generated a CRISPR/dCas9 tool comprising a catalytically inactive Cas9 (dCas9) f...
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作者：Chuang, Po-Kai; Chung, Cinya; Liao, Kuo-Shiang; Wong, Chi-Huey
作者单位：Scripps Research Institute; National Sun Yat Sen University; Kaohsiung Medical University; Kaohsiung Medical University Hospital; Academia Sinica - Taiwan
摘要：Pancreatic cancer remains one of the most lethal malignancies with limited therapeutic options. Among the alternative targets explored for pancreatic cancer, the glycolipid stage-specific embryonic antigen-4 (SSEA4) has been extensively studied. We have previously demonstrated that the chimeric anti-SSEA4 antibody with alpha-2,6-sialylated complex type biantennary glycan (SCT) or its 3-fluorosialyl derivative (FSCT) attached to the Fc-Asn297 residue exhibited enhanced binding to the Fc-recepto...
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作者：Chen, Zhengyun; Lian, Justin Z.; Huang, Haozhou; Zhu, Hengyi; Kanye, Lynda Thubelihle; Chen, Mateng; Zhang, Zhihao; Liu, Boxin; Zhang, Jiawei; Ahmed, Ajaz; Barbarossa, Valerio; Cucurachi, Stefano; Dong, Bin
作者单位：China Pharmaceutical University; Leiden University; Leiden University - Excl LUMC; New York University; China Pharmaceutical University; China Pharmaceutical University; Imperial College London; University of California System; University of California Los Angeles; China Pharmaceutical University
摘要：This study presents a comparative cradle-to-gate environmental and economic evaluation of nine synthetic routes for Molnupiravir (EIDD-2801), a broad-spectrum antiviral drug. Integrating Life Cycle Assessment (LCA) with Life Cycle Costing (LCC), we quantified the environmental impacts alongside capital and operational costs, net present costs, and break-even prices of each route. The results reveal significant variation across the schemes, with Schemes #1 and #2 exhibiting the highest impacts ...
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作者：McKay, Conor E.; Deans, Miles; Connor, Jack; Saunders, Janet C.; Lloyd, Christopher; Radford, Sheena E.; Brockwell, David J.
作者单位：University of Leeds; University of Leeds; AstraZeneca
摘要：Deep mutational scanning (DMS) assays provide a powerful method to generate large-scale datasets essential for advancing AI-driven predictions in biology. The tripartite beta- lactamase assay (TPBLA), in which a protein of interest is inserted between two domains of beta- lactamase, has previously been reported as capable of detecting and quantitating the aggregation of proteins and biologics in the oxidizing periplasm of Escherichia coli and used as a platform for identifying small molecule i...
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作者：Sefik, Esen; Philbrick, William; Zhang, Fengrui; Agrawal, Kriti; Van Lee, Brian; Sam, Johannes; Karatepe, Kutay; Zheng, Yunjiang; Liang, Kaixin; Peng, Sophia; Mirza, Haris; Rangavajhula, Athreya; Simon, Perrine; Arun, Neha; Babu, Priyanka; Eynon, Elizabeth; Chiorazzi, Michael; Shan, Liang; Halene, Stephanie; Luo, Hongbo R.; Rongvaux, Anthony; Kluger, Yuval; Flavell, Richard A.
作者单位：Yale University; Yale University; Yale University; Roche Holding; Yale University; Yale University; Yale University; Washington University (WUSTL); Saint Louis University; Yale University; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Fred Hutchinson Cancer Center; Yale University; Yale University; Howard Hughes Medical Institute
摘要：Murine and human immune systems differ significantly, particularly within the myeloid lineage. Humanized mice, generated by transplanting human hematopoietic stem, progenitor cells into genetically modified mice, are invaluable to study human immune development and function in vivo. However, a major limitation of current models is suboptimal myelopoiesis, particularly lack of functional human neutrophils, hampering the modeling of human immune responses and chronic diseases. Here, we describe ...
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作者：Vu, Han N.; Lee, Minhyeong; Situ, Alan J.; An, Woojin; Ley, Klaus; Kim, Chungho; Ulmer, Tobias S.
作者单位：University of Southern California; Korea University; University of Southern California; University System of Georgia; Augusta University
摘要：In biological membranes, proteins face a fundamentally different environment than in water. To avoid untenable lipid contacts with polar backbone atoms, they use the continuous hydrogen bonding achieved by alpha- helices or beta- barrels to traverse membranes. Here, we show that integrin alpha X, and by homology alpha M, undermine this paradigm by partially unfolding the N-terminal third of their transmembrane (TM) helix. Unfolding results in a dynamic, frayed helix that weakens the associatio...
