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SSRN 2025年

作者： Wang, Lu Liu, Junjie Zhang, Hui Gao, Shengjie Mao, Yu Qu, Hao Zheng, Lei School of Food and Biological Engineering Hefei University of Technology Hefei230009 China Engineering Research Center of Bioprocess Ministry of Education Hefei University of Technology Hefei230009 China Anhui Provincial International Science and Technology Cooperation Base for Major Metabolic Diseases and Nutritional Interventions Hefei230009 China Intelligent Interconnected Systems Laboratory of Anhui Province Hefei University of Technology Hefei230009 China

Copper is a vital trace element that plays a crucial role in various physiological processes due to its ability to exist in multiple oxidation states. Inspired by natural enzymes, researchers have developed copper-based nanozymes that mimic enzyme functions, offering cost-effective and stable alternatives to traditional enzymes. Despite their promising properties, the design and synthesis of these nanozymes can be complex and challenging. To address this issue, this work explores an intuitive approach to construct "soft" nanozymes simply by binding Cu2+ with its aptamers to form Cu(II)-aptamer complexes. Using a screening strategy, we identified a specific aptamer against Cu2+, designated P8, that significantly enhanced peroxidase-like activity when complexed with Cu2+, demonstrated by a notably smaller Km value. Furthermore, we investigated the effects of various lengths of a "molecular clamp" on the conformational dynamics of the P8 aptamer, which perturbs the encapsulation of Cu2+ and modulated its peroxidase activity. Our findings indicate that optimizing the molecular clamp to a moderate length (Nd = 20) can further enhance the peroxidase activity of the Cu2+-P8 complex, highlighting a novel and straightforward approach to improve the enzymatic properties of copper-based nanozymes. The peroxidase-like soft nanozymes based on copper(II)-aptamer complexes were finally utilized for label-free detection of EDTA. The developed colorimetric sensing method exhibits outstanding detection capabilities for EDTA in Sprite and mineral water samples, achieving an extended dynamic range that accommodates higher concentrations through the incorporation of molecular clamps. This innovative approach effectively addresses the limitations of narrow detection ranges commonly observed in traditional methods. © 2025, The Authors. All rights reserved.

关键词： Diagnosis

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MorPhiC Consortium: towards functional characterization of all human genes

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Nature 2025年第8050期638卷 351-359页

作者： Adli, Mazhar Przybyla, Laralynne Burdett, Tony Burridge, Paul W. Cacheiro, Pilar Chang, Howard Y. Engreitz, Jesse M. Gilbert, Luke A. Greenleaf, William J. Hsu, Li Huangfu, Danwei Hung, Ling-Hong Kundaje, Anshul Li, Shuzhao Parkinson, Helen Qiu, Xiaojie Robson, Paul Schürer, Stephan C. Shojaie, Ali Skarnes, William C. Smedley, Damian Studer, Lorenz Sun, Wei Vidović, Dušica Vierbuchen, Thomas White, Brian S. Yeung, Ka Yee Yue, Feng Zhou, Ting Žurauskienė, Justina Zhong, Aaron Zheng, Shujian Zhao, Hengqiang Zhang, Nan Zhang, Zhehao Zhang, Stephen Zeng, Tony Yu, Bo Yordanova, Galabina N. Yang, Dapeng Xing, De Wang, Xianming Wang, Ping Torre, Denis Tang, Wenzhuo Shivalikanjli, Anu Sengupta, Kaustav Seker, Fidan Ventura, Enrique Sapena Ross, Nicolette C. Rivera-Diaz, Jamilex Rana, Arushi Pongpamorn, Praeploy Poirion, Olivier B. Pillai, Ajay Pilarczyk, Marcin Parker, Devon Ning, Gang Neyisci, Ozlem Nasam, Niharika Mittal, Varun Mitchell, Joshua M. Metzl-Raz, Eyal Meng, Chen Melo-Carrillo, Adrian McDonough, Justin A. Marengo, Gabriel Mao, Yuzhen Leite, Davi Lyra Luo, Renhe Liu, Nianping Liu, Dingyu Liu, Zukai Liu, Si Li, Zhaoheng Kraft, Katerina Koci, Orges A. Kirsammer, Gina Kendra, Angelina Hutter, Carolyn Huebner, Aaron J. Huang, Yung-Hsin Hu, Nan Gupta, Dipayan Gupta, Revant Guo, Tingfeng Griffiths, Alexandra M. Goyal, Juhee Glenn, Rachel A. Garofalo, Jessica L. Fukuda, Bryce Nobutoshi Fu, Yihao Flynn, William F. Flores, Jesse Fletcher, Colin F. Fleming, Patrick J. Felsenfeld, Adam L. Eraslan, Basak Doty, Anthony Dahlstrom, Thomas J. Chung, Caty E. Choudhary, Anshul Cho, Hyein S. Chen, Xintong Chen, Sijie Chan, Chia Baroch, Jacob J. Baker, Dylan S. Bai, Tao Avireddy, Rohan N. V. S. R. K. Amiri, Anahita Diniz, Juliana Alcoforado Abbaszadeh, Neda Robert H. Lurie Comprehensive Cancer Center Department of Obstetrics and Gynecology Northwestern University Feinberg School of Medicine Chicago IL United States Department of Biochemistry and Biophysics University of California San Francisco CA United States Omics Section European Bioinformatics Institute (EMBL-EBI) European Molecular Biology Laboratory Hinxton United Kingdom Department of Pharmacology Center for Pharmacogenomics Northwestern University Feinberg School of Medicine Evanston IL United States William Harvey Research Institute Clinical Pharmacology and Precision Medicine Queen Mary University of London London United Kingdom Department of Dermatology Stanford University Stanford CA United States Department of Genetics Stanford University Stanford CA United States Basic Science and Engineering (BASE) Initiative Stanford University Stanford CA United States Department of Urology University of California San Francisco CA United States Department of Biostatistics Public Health Sciences Fred Hutchinson Cancer Center Seattle WA United States Developmental Biology Program Sloan Kettering Institute New York NY USA School of Engineering and Technology University of Washington Tacoma Tacoma WA United States Departments of Genetics and Computer Science Stanford University Stanford CA United States Jackson Laboratory for Genomic Medicine Farmington CT United States Knowledge Management Section European Bioinformatics Institute (EMBL-EBI) European Molecular Biology Laboratory Hinxton United Kingdom Molecular and Cellular Pharmacology Sylvester Comprehensive Cancer Center University of Miami Coral Gables FL USA Department of Biostatistics University of Washington Seattle WA United States Department of Biochemistry and Molecular Genetics Robert H. Lurie Comprehensive Cancer Center Northwestern University Feinberg School of Medicine Chicago IL United States

Recent advances in functional genomics and human cellular models have substantially enhanced our understanding of the structure and regulation of the human genome. However, our grasp of the molecular functions of human genes remains incomplete and biased towards specific gene classes. The Molecular Phenotypes of Null Alleles in Cells (MorPhiC) Consortium aims to address this gap by creating a comprehensive catalogue of the molecular and cellular phenotypes associated with null alleles of all human genes using in vitro multicellular systems. In this Perspective, we present the strategic vision of the MorPhiC Consortium and discuss various strategies for generating null alleles, as well as the challenges involved. We describe the cellular models and scalable phenotypic readouts that will be used in the consortium's initial phase, focusing on 1,000 protein-coding genes. The resulting molecular and cellular data will be compiled into a catalogue of null-allele phenotypes. The methodologies developed in this phase will establish best practices for extending these approaches to all human protein-coding genes. The resources generated-including engineered cell lines, plasmids, phenotypic data, genomic information and computational tools-will be made available to the broader research community to facilitate deeper insights into human gene functions. © 2025. Springer Nature Limited.

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Fundus Image Quality Assessment and Enhancement: a Systematic Review

arXiv

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arXiv 2025年

作者： Li, Heng Li, Haojin Ou, Mingyang Yu, Xiangyang Zhang, Xiaoqing Niu, Ke Fu, Huazhu Liu, Jiang Research Institute of Trustworthy Autonomous Systems SUSTech Shenzhen China Department of Computer Science and Engineering SUSTech Shenzhen China Center for High Performance Computing and Shenzhen Key Laboratory of Intelligent Bioinformatics Shenzhen Institute of Advanced Technology Chinese Academy of Sciences Shenzhen China Computer School Beijing Information Science and Technology University Beijing China Singapore

As an affordable and convenient eye scan, fundus photography holds the potential for preventing vision impairment, especially in resource-limited regions. However, fundus image degradation is common under intricate imaging environments, impacting following diagnosis and treatment. Consequently, image quality assessment (IQA) and enhancement (IQE) are essential for ensuring the clinical value and reliability of fundus images. While existing reviews offer some overview of this field, a comprehensive analysis of the interplay between IQA and IQE, along with their clinical deployment challenges, is lacking. This paper addresses this gap by providing a thorough review of fundus IQA and IQE algorithms, research advancements, and practical applications. We outline the fundamentals of the fundus photography imaging system and the associated interferences, and then systematically summarize the paradigms in fundus IQA and IQE. Furthermore, we discuss the practical challenges and solutions in deploying IQA and IQE, as well as offer insights into potential future research directions. Copyright © 2025, The Authors. All rights reserved.

关键词： Photography

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A Mn2+-S redox electrochemistry for energetic aqueous manganese ion battery

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Joule 2025年

作者： Li, Xinran Zhang, Tengsheng Li, Gaoyang Wang, Boya Jin, Hongrun Zhang, Yanyan Liu, Xin Feng, Yutong Wang, Yifeng Zhou, Wanhai Zhao, Jingwen Li, Wei Fan, Hongjin Zhao, Dongyuan Chao, Dongliang Laboratory of Advanced Materials Aqueous Battery Center Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials Shanghai Wusong Laboratory of Materials Science Electron Microscope Center of Fudan University Faculty of Chemistry and Materials Fudan University Shanghai200433 China School of Electrical and Electronic Engineering Harbin University of Science and Technology Harbin150080 China School of Physical and Mathematical Sciences Nanyang Technological University Singapore637371 Singapore Qingdao Industrial Energy Storage Research Institute Qingdao Institute of Bioenergy and Bioprocess Technology Chinese Academy of Sciences Qingdao266101 China

Aqueous manganese ion batteries (AMIBs) have recently garnered attention due to the abundance of manganese and their intrinsic safety. However, the development of current AMIBs remains plagued by restrictive actual capacities. Herein, we propose an energetic Mn2+-S redox electrochemistry with a solid-liquid-solid redox pathway. Operando X-ray absorption fine spectroscopy and synchrotron X-ray diffraction unveil the Mn2+ storage mechanism of S8 ↔ MnS4 ↔ MnS2 ↔ MnS. A capacity of 1,242 mAh g−1 with a high sulfur utilization of 74.3 wt % can be achieved, surpassing the capacity limitations of previously reported AMIBs. As a proof of concept, a system intergrating the S/MnS and MnO2/Mn2+ redox couples delivers an energy density of 396 Wh kgS+MnO2−1 and cycles for 800 cycles stably at 4 A g−1. We have elucidated the mechanism underlying the redox of Mn2+-S and may open an avenue for the next high-energy AMIBs. © 2025 Elsevier Inc.

关键词： Crystallization kinetics

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Biomedical data and AI

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Science China Life Sciences 2025年第5期68卷 1536-1540页

作者： Hao Xu Shibo Zhou Zefeng Zhu Vincenzo Vitelli Liangyi Chen Ziwei Dai Ning Yang Luhua Lai Shengyong Yang Sergey Ovchinnikov Zhuoran Qiao Sirui Liu Chen Song Jianfeng Pei Han Wen Jianfeng Feng Yaoyao Zhang Zhengwei Xie Yang-Yu Liu Zhiyuan Li Fulai Jin Hao Li Mohammad Lotfollahi Xuegong Zhang Ge Yang Shihua Zhang Ge Gao Pulin Li Qi Liu Jing-Dong Jackie Han Peking-Tsinghua Center for Life Sciences (CLS) Academy for Advanced Interdisciplinary StudiesPeking University Center for Quantitative Biology (CQB) Academy for Advanced Interdisciplinary StudiesPeking University Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program Academy for Advanced Interdisciplinary StudiesPeking University Department of Physics University of Chicago School of Life Sciences Southern University of Science and Technology Peking University Chengdu Academy for Advanced Interdisciplinary Biotechnologies College of Chemistry and Molecular Engineering Peking University Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan University Department of Biology Massachusetts Institute of Technology Lambic Therapeutics Inc. Changping Laboratory Al for Science Institute Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence Fudan University Department of Obstetrics and Gynecology West China Second University HospitalSichuan University Peking University International Cancer Institute and Peking University-Yunnan Baiyao International Medical Institute and State Key Laboratory of Natural and Biomimetic Drugs Department of Molecular and Cellular PharmacologySchool of Pharmaceutical SciencesPeking University Health Science CenterPeking University Channing Division of Network Medicine Department of MedicineBrigham and Women's Hospital and Harvard Medical School Center for Artificial Intelligence and Modeling the Carl R.Woese Institute for Genomic BiologyUniversity of Illinois Urbana-Champaign Department of Genetics and Genome Sciences School of Medicine and Department of Computer and Data Sciences and Department of Population and Quantitative Health SciencesCase Western Reserve University Department of Biochemistry and Biophysics University of California Sanger Institute Department of Automation Tsinghua University State Key Laboratory of Multimodal Artificial Intelligence Systems I

The development of artificial intelligence(AI) and the mining of biomedical data complement each other. From the direct use of computer vision results to analyze medical images for disease screening, to now integrating biological knowledge into models and even accelerating the development of new AI based on biological discoveries, the boundaries of both are constantly expanding, and their connections are becoming closer.

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Depth-Width Tradeoffs in Algorithmic Reasoning of Graph Tasks with Transformers

arXiv

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arXiv 2025年

作者： Yehudai, Gilad Sanford, Clayton Bechler-Speicher, Maya Fischer, Orr Gilad-Bachrach, Ran Globerson, Amir Courant Institute of Mathematical Sciences New York University United States Google Research United States Blavatnik School of Computer Science Tel-Aviv University Meta United States Bar-Ilan University Computer Science Department Department of Bio-Medical Engineering Tel-Aviv University Edmond J. Safra Center for Bioinformatics Tel-Aviv University

Transformers have revolutionized the field of machine learning. In particular, they can be used to solve complex algorithmic problems, including graph-based tasks. In such algorithmic tasks a key question is what is the minimal size of a transformer that can implement a task. Recent work has begun to explore this problem for graph-based tasks, showing that for sub-linear embedding dimension (i.e., model width) logarithmic depth suffices. However, an open question, which we address here, is what happens if width is allowed to grow linearly. Here we analyze this setting, and provide the surprising result that with linear width, constant depth suffices for solving a host of graph-based problems. This suggests that a moderate increase in width can allow much shallower models, which are advantageous in terms of inference time. For other problems, we show that quadratic width is required. Our results demonstrate the complex and intriguing landscape of transformer implementations of graph-based algorithms. We support our theoretical results with empirical evaluations. Copyright © 2025, The Authors. All rights reserved.

关键词： Graph algorithms

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Biosynthesis of R-3-hydroxyalkanoic acids by metabolically engineered Escherichia coli.

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Applied biochemistry and biotechnology 2004年第1-3期113-116卷 373-379页

作者： Park, Si Jae Lee, Sang Yup Lee, Young Metabolic and Biomolecular Engineering National Research Laboratory Department of Chemical &amp Biomolecular Engineering BioProcess Engineering Research Center

An efficient system for the production of (R)-hydroxyalkanoic acids (RHAs) was developed in natural polyhydroxyalkanoate (PHA)-producing bacteria and recombinant Escherichia coli. Acidic alcoholysis of purified PHA and in vivo depolymerization of PHA accumulated in the cells allowed the production of RHAs. In recombinant E. coli, RHA production was achieved by removing CoA from (R)-3-hydroxyacyl-CoA and by in vivo depolymerization of PHA. When the recombinant E. coli harboring the Ralstonia eutropha PHA biosynthesis genes and the depolymerase gene was cultured in a complex or a chemically defined medium containing glucose, (R)-3-hydroxybutyric acid (R3HB) was produced as monomers and dimers. R3HB dimers could be efficiently converted to monomers by mild alkaline heat treatment. A stable recombinant E. coli strain in which the R. eutropha PHA biosynthesis genes were integrated into the chromosome disrupting the pta gene was constructed and examined for the production of R3HB. When the R. eutropha intracellular depolymerase gene was expressed by using a stable plasmid containing the hok/sok locus of plasmid R1, R3HB could be efficiently produced.

关键词： Index Entries (R)-Hydroxyalkanoic acids polyhydroxyalkanoate Escherichia coli poly-(R)-3-hydroxybutyrate (R)-3-hydroxybutyric acid

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Recombinant antibodies from clonally expanded cancer-associated plasma cells

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Cancer immunology, immunotherapy : CII 2025年第7期74卷 201页

作者： Wonkyung Kim Ji-Hye Oh Chae Won Park Hyori Kim Young Gwang Kang Da Eun Oh Hee Jin Lee Ji Hun Kim Chang Ohk Sung Department of Medical Science Brain Korea 21 Project Asan Medical Institute of Convergence Science and Technology University of Ulsan College of Medicine Seoul Republic of Korea. Department of Pathology Asan Medical Center University of Ulsan College of Medicine 88 Olympic-ro 43-gil Songpa-gu Seoul 05505 Republic of Korea. Bioinformatics Core Laboratory Convergence Medicine Research Center Asan Medical Center Asan Institute for Life Sciences Seoul Republic of Korea. Antibody Development Core Laboratory Convergence Medicine Research Center Asan Medical Center Asan Institute for Life Sciences Seoul Republic of Korea. Department of Pathology Asan Medical Center University of Ulsan College of Medicine 88 Olympic-ro 43-gil Songpa-gu Seoul 05505 Republic of Korea. backlila1@amc.seoul.kr. NeogenTC Corp. Seoul Republic of Korea. backlila1@amc.seoul.kr. Graduate School of Medical Science and Engineering Korea Advanced Institute of Science and Technology Daejeon 34141 Korea. jihkim@kaist.ac.kr. Department of Medical Science Brain Korea 21 Project Asan Medical Institute of Convergence Science and Technology University of Ulsan College of Medicine Seoul Republic of Korea. co.sung@amc.seoul.kr. Department of Pathology Asan Medical Center University of Ulsan College of Medicine 88 Olympic-ro 43-gil Songpa-gu Seoul 05505 Republic of Korea. co.sung@amc.seoul.kr. Bioinformatics Core Laboratory Convergence Medicine Research Center Asan Medical Center Asan Institute for Life Sciences Seoul Republic of Korea. co.sung@amc.seoul.kr.

Although the clinical significance of plasma cells within tumors has been recognized, studies on the development of plasma cells and the characteristics of the antibodies they secrete within the tumor microenvironment remain limited. We investigated the properties of plasma cells within cancer tissues using single-cell RNA and single cell B cell receptor sequencing. We characterized plasma cells exhibiting clonal expansion and synthesized the antibodies produced by these cells, confirming the clinical relevance of immunoglobulin H (IGH) isotypes. Plasma cells comprised approximately 5% of the total immune cell population within the tumor; clonal expansion was more prevalent in plasma cells than in B cells. Among plasma cells, the most frequent immunoglobulin isotype was IGHG1 and IGKC. We synthesized six recombinant antibodies, including those from the largest clonal plasma cells. Two antibodies that formed clones showed membranous staining in cancer cells. The cancer cells that metastasized to the lymph node showed a loss of expression as observed by immunohistochemistry. Analysis of bulk RNA sequencing data from 1078 patients with breast cancer revealed that tumor-infiltrating plasma cells expressing IGHG1 were associated with favorable prognoses. These tumors exhibited increased B cell receptor diversity, immunogenic mutation, and intratumoral heterogeneity. This study suggests the potential for discovering cancer-associated antibodies derived from intratumoral plasma cells.

关键词： B cell receptor Cancer Plasma cell Recombinant antibody Single-cell sequencing

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Decoupling of adsorption and conversion of CO2RR intermediates on BiOBr for boosting photocatalytic CO evolution

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Applied Catalysis B: Environmental 2025年 375卷

作者： Luo, Jinwei Xue, Xiangdong Pan, Wenyuan Chen, Tengfei Jian, Yaliu Zeng, Jianrong Dong, Wenjun Beijing Advanced Innovation Center for Materials Genome Engineering School of Materials Science and Engineering University of Science and Technology Beijing Beijing100083 China State Key Laboratory of Photoelectric Conversion and Utilization of Solar Energy Qingdao New Energy Shandong Laboratory Qingdao Institute of Bioenergy and Bioprocess Technology Chinese Academy of Sciences Qingdao266101 China Shanghai Synchrotron Radiation Facility Shanghai Advanced Research Institute Chinese Academy of Sciences Shanghai201204 China Shanghai Institute of Applied Physics Chinese Academy of Sciences Shanghai201800 China

Balancing the thermodynamic processes of intermediates adsorption and conversion is critical to optimize the photocatalytic CO2 reduction reaction (CO2RR). Nevertheless, the intrinsic coupling of the processes, featuring with trade-off between adsorption and conversion, results in the absence of efficacious implementation means for balancing the thermodynamic. Herein, based on the differences in the contribution of covalent and non-covalent interactions to the intermediate adsorption and conversion processes, the modulation strategy of oxygen vacancies and indium doping is proposed to enhance the CO2RR performance of BiOBr (BiOBr-OVs-In), wherein the dominant interaction is regulated individually at each stage. Therefore, the adsorption and conversion processes are individually regulated (that is, decoupled) to achieve the thermodynamic equilibrium and enhance the efficiency of the photocatalytic CO2RR. The experimental and theoretical analysis reveal that the covalent interaction is intensified by oxygen vacancy-induced active sites, promoting the *COOH adsorption. While the non-covalent interaction is modulated through indium doping, which attenuate the hydrogen bond between surface hydroxyls and *COOH, facilitating the *COOH hydrodehydration processes. The optimized BiOBr-OVs-In photocatalyst exhibits remarkable CO evolution rate of 13.95 μmol·g−1·h−1 under visible light irradiation without any sacrificial agent, which is 6.5-fold compared with that of pristine-BiOBr (2.13 μmol·g−1·h−1). © 2025 Elsevier B.V.

关键词： Photocatalytic activity

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Biosynthesis of poly(3-hydroxybutyrate- co-3-hydroxyalkanoates) by metabolically engineered Escherichia coli strains.

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Applied biochemistry and biotechnology 2004年第1-3期113-116卷 335-346页

作者： Park, Si Jae Lee, Sang Yup Metabolic and Biomolecular Engineering National Research Laboratory Department of Chemical &amp Biomolecular Engineering BioProcess Engineering Research Center

Biosynthesis of polyhydroxyalkanoates (PHAs) consisting of 3-hydroxy-alkanoates (3HAs) of 4 to 10 carbon atoms was examined in metabolically engineered Escherichia coli strains. When the fadA and/or fadB mutant E. coli strains harboring the plasmid containing the Pseudomonas sp. 61-3 phaC2 gene and the Ralstonia eutropha phaAB genes were cultured in Luria-Bertani (LB) medium supplemented with 2 g/L of sodium decanoate, all the recombinant E. coli strains synthesized PHAs consisting of C4, C6, C8, and C10 monomer units. The monomer composition of PHA was dependent on the E. coli strain used. When the fadA mutant E. coli was employed, PHA containing up to 63 mol% of 3-hydroyhexanoate was produced. In fadB and fadAB mutant E. coli strains, 3-hydroxybutyrate (3HB) was efficiently incorporated into PHA up to 86 mol%. Cultivation of recombinant fadA and/or fadB mutant E. coli strains in LB medium containing 10 g/L of sodium gluconate and 2 g/L of sodium decanoate resulted in the production of PHA copolymer containing a very high fraction of 3HB up to 95 mol%. Since the material properties of PHA copolymer consisting of a large fraction of 3HB and a small fraction of medium-chain-length 3HA are similar to those of low-density polyethylene, recombinant E. coli strains constructed in this study should be useful for the production of PHAs suitable for various commercial applications.

关键词： Index Entries Polyhydroxyalkanoates Escherichia coli ?-oxidation sodium decanoate copolymer

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