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Effect of double-extrusion following by stepwise-hot-rolling on microstructures and mechanical properties of Mg-Gd-Y-Zn-Zr alloy

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Journal of Magnesium and Alloys 2025年

作者： Wang, Jinjun Khan, Muhammad Abubaker Dai, Shang Feng, Yun Wang, Han Afifi, Mohamed A. Li, Jingyuan Beijing Advanced Innovation Center for Materials Genome Engineering National Key Laboratory of Advanced Stainless Steel School of Materials Science and Engineering University of Science and Technology Beijing Beijing100083 China Mechanical Engineering Program School of Engineering and Applied Sciences Nile University Giza12677 Egypt Nile University Giza12677 Egypt

Mg alloys with a combination of high strength and excellent ductility are increasingly required for structural applications. This study investigates the influence of advanced processing techniques on the mechanical properties and microstructural evolution of Mg-Gd-Y-Zn-Zr alloys. Utilizing a combination of double extrusion and stepwise hot rolling followed by aging treatments, significant enhancements in the mechanical performance of these alloys are demonstrated. The processing techniques applied lead to notable refinement in grain-size and modifications in the microstructure, including the transformation of LPSO phases from 18R to 24R and the dispersion of β phase particles. These microstructural transformations contribute to a substantial increase in yield-strength, ultimate-tensile-strength, and ductility. Furthermore, findings reveal that these improvements are also supported by alterations in material texture, which influence dislocation dynamics as indicated by changes in Kernel Average Misorientation (KAM) values. The combined effect of grain boundary (GB) strengthening, phase distribution, and texture modification elucidates the observed mechanical enhancements. This research provides valuable insights into the design and optimization of Mg-Gd-Y-Zn-Zr alloys for critical applications in aerospace and automotive industries where high strength and ductility are paramount. © 2025

关键词： Tensile strength

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Barriers to human remains identification using forensic odontology in resource-constrained settings

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Forensic science International: Synergy 2025年 10卷 100575页

作者： Guzman, Ernest Joie T. De Ungria, Maria Corazon A. Philippine Genome Center Program on Biodiversity Ethnicity and Forensics University of the Philippines Philippines Department of Science and Technology Science Education Institute Taguig City Philippines DNA Analysis Laboratory Natural Sciences Research Institute University of the Philippines Diliman Philippines Research Ethics Board University of the Philippines Diliman Philippines

An effective strategy for human remains identification with a high success rate and low cost is vital for low to low-middle-income countries. Prompt identification of human remains is essential for the swift recovery of families and communities affected by large-scale disasters. However, the systematic integration of forensic disciplines into standard practice remains to be implemented in many areas. Even countries like the Philippines – where over 20 typhoons occur annually, leaving numerous, even thousands of persons remain missing so many years after the disaster, institutions continue to struggle in adopting standard protocols for human remains identification (HRI). This paper examines the barriers to implementing such protocols and explores the feasibility of maximizing the use of forensic odontology in the identification process in resource-constrained settings. The discussion highlights the situation in the Philippines resulting from these barriers and provides actionable plans for overcoming these challenges. In doing this, we can maximize the use of available technologies such as forensic odontology when local resources are limited, trained professionals are scarce and a sustainable and efficient operational local framework to handle mass fatality incidents (MFI) is not in place. © 2025 The Authors

关键词： Dentistry Disaster victim identification Forensic odontology Human identification Philippine forensic science Resource-constrained

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Systematic transcriptomics analysis of calorie restriction and rapamycin unveils their synergistic interaction in prolonging cellular lifespan

Communications Biology

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Communications Biology 2025年第1期8卷 1-16页

作者： Zhang, Yizhong Naaz, Arshia Cheng, Trishia Yi Ning Lin, Jovian Jing Gao, Mingtong Dorajoo, Rajkumar Alfatah, Mohammad Bioinformatics Institute (BII) Agency for Science Technology and Research (A*STAR) Singapore Singapore Genome Institute of Singapore (GIS) Agency for Science Technology and Research (A*STAR) Singapore Singapore Healthy Longevity Translational Research Program Yong Loo Lin School of Medicine National University of Singapore Singapore Singapore Centre for Healthy Longevity National University Health System Singapore Singapore Department of Paediatrics Yong Loo Lin School of Medicine National University of Singapore Singapore Singapore

Aging is a multifaceted biological process marked by the decline in both mitotic and postmitotic cellular function, often central to the development of age-related diseases. In the pursuit of slowing or even reversing the aging process, a prominent strategy of significant interest is calorie restriction (CR), also known as dietary restriction, and the potential influence of a drug called rapamycin (RM). Both CR and RM have demonstrated the capacity to extend healthspan and lifespan across a diverse array of species, including yeast, worms, flies, and mice. Nevertheless, their individual and combined effects on mitotic and postmitotic cells, as well as their comparative analysis, remain areas that demand a thorough investigation. In this study, we employ RNA-sequencing methodologies to comprehensively analyze the impact of CR, RM, and their combination (CR + RM) on gene expression in yeast cells. Our analysis uncovers distinctive, overlapping, and even contrasting patterns of gene regulation, illuminating the unique and shared effects of CR and RM. Furthermore, the transcriptional synergistic interaction of CR + RM is validated in extending the lifespan of both yeast and human cells. © The Author(s) 2025.

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BPS2025 - Elucidating the nanoscale clustering profiles of chimeric antigen receptors

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Biophysical Journal 2025年第3期124卷 105a-105a页

作者： Robert J. Pyron Sarah Binion Sarah A. Shelby Genome Science and Technology Program University of Tennessee Knoxville TN USA Department of Biochemistry and Cellular and Molecular Biology University of Tennessee Knoxville TN USA

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Artificial intelligence goes from predicting structure to predicting stability

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Magnetic Resonance Letters 2025年第1期5卷 75-76页

作者： Gary J.Pielak Conggang Li Maili Liu Department of Chemistry Department of Biochemistry&BiophysicsLineberger Cancer Centerand Integrative Program for Biological and Genome SciencesUniversity of North Carolina at Chapel HillChapel HillNC 27599United States Key Laboratory of Magnetic Resonance in Biological Systems State Key Laboratory of Magnetic Resonance and Atomic and Molecular PhysicsNational Center for Magnetic Resonance in WuhanWuhan Institute of Physics and MathematicsInnovation Academy for Precision Measurement Science and TechnologyChinese Academy of SciencesWuhan430071China

AlphaFold[1]has turned everyone into a structural *** need for knowledge of Fourier transforms or spectral density,driven by artificial intelligence(AI),all one needs to do is enter the primary structure of a folded p... 详细信息

关键词： structure. structure predicting

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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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A Germline Heterozygous Dominant Negative IKZF2 Variant Causing Syndromic Primary Immune Regulatory Disorder and ICHAD

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Journal of Clinical Immunology 2025年第1期45卷 1-18页

作者： Lu, Henry Y. Vaseghi-Shanjani, Maryam Lam, Avery J. Sharma, Mehul Mohajeri, Arezoo Silva, Leandro B. R. Gillies, Jana Yang, Gui Xiang Lin, Susan Fu, Maggie P. Salman, Areesha Rahmanian, Ronak Armstrong, Linlea Halparin, Jessica Yang, Connie L. Chilvers, Mark Henkelman, Erika Rehmus, Wingfield Morrison, Douglas Setiadi, Audi Mostafavi, Sara Kobor, Michael S. Kozak, Frederick K. Biggs, Catherine M. van Karnebeek, Clara Hildebrand, Kyla J. Levings, Megan K. Turvey, Stuart E. Department of Pediatrics BC Children’s Hospital The University of British Columbia 950 West 28 th Avenue Vancouver V5Z 4H4 BC Canada Experimental Medicine Program Faculty of Medicine The University of British Columbia Vancouver BC Canada BC Children’s Hospital Research Institute Vancouver BC Canada Department of Surgery The University of British Columbia Vancouver BC Canada Department of Medical Genetics The University of British Columbia Vancouver BC Canada Genome Science and Technology Program Faculty of Science The University of British Columbia Vancouver BC Canada Centre for Molecular Medicine and Therapeutics Vancouver BC Canada Division of Otolaryngology – Head & Neck Surgery BC Children’s Hospital The University of British Columbia Vancouver BC Canada Division of Hematology Oncology & Bone Marrow Transplant BC Children’s Hospital The University of British Columbia Vancouver BC Canada Division of Respiratory Medicine BC Children’s Hospital The University of British Columbia Vancouver BC Canada Division of Plastic Surgery BC Children’s Hospital The University of British Columbia Vancouver BC Canada Division of Dermatology BC Children’s Hospital The University of British Columbia Vancouver BC Canada Department of Pathology and Laboratory Medicine BC Children’s Hospital The University of British Columbia Vancouver BC Canada Department of Statistics The University of British Columbia Vancouver BC Canada Division of Immunology BC Children’s Hospital The University of British Columbia Vancouver BC Canada School of Biomedical Engineering The University of British Columbia Vancouver BC Canada

Monogenic defects that impair the control of inflammation and tolerance lead to profound immune dysregulation, including autoimmunity and atopy. Studying these disorders reveals important molecular and cellular factors that regulate human immune homeostasis and identifies potential precision medicine targets. Here, we provide a detailed immunological assessment of a pediatric patient with a recently discovered syndrome causing Immunodysregulation, Craniofacial anomalies, Hearing impairment, Athelia, and Developmental delay (or ICHAD syndrome). The immunodysregulation resulted in autoimmune hemolytic anemia (AIHA) and atopic dermatitis. The patient carried a de novo germline heterozygous c.406+540_574+13477dup;***136_Ser191dup variant in IKAROS family zinc finger 2 (IKZF2), which encodes HELIOS. This variant led to reduced HELIOS protein expression and dominant interference of wild-type HELIOS-mediated repression of the IL2 promoter. Multi-parameter flow cytometry analyses of patient peripheral blood mononuclear cells revealed strongly impaired natural killer cell differentiation and function, and increased CD8⁺ T cell activation and cytokine secretion. Strikingly, patient CD4⁺ T cells were hyperactive, produced elevated levels of nearly all T helper (T_H) cytokines, and readily proliferated in response to stimulation. Patient regulatory T cells (Tregs) developed normally but aberrantly produced high levels of many T_H cytokines. Single-cell RNA sequencing revealed largely normal Tregs (albeit mostly memory), but naïve CD4⁺ T cells that were more enriched in genes related to activation, proliferation, metabolism, and T_H differentiation. This work describes the immunological phenotype of one of the first reported cases of germline dominant negative HELIOS deficiency, expands our understanding of the pathogenesis of AIHA on a single cell level, and provides valuable insights into HELIOS function in a var

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Activity and structure of human (d)CTP deaminase CDADC1

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Proceedings of the National Academy of sciences of the United States of America 2025年第19期122卷 e2424245122页

作者： Slyvka, Anton Rathore, Ishan Yang, Renbin Gewartowska, Olga Kanai, Tapan Lountos, George T. Skowronek, Krzysztof Czarnocki-Cieciura, Mariusz Wlodawer, Alexander Bochtler, Matthias Laboratory of Structural Biology International Institute of Molecular and Cell Biology in Warsaw Warsaw 02-109 Poland Center for Structural Biology National Cancer Institute NIH Frederick MD 21702 United States Cancer Research Technology Program Leidos Biomedical Research Inc. Frederick United States Genome Engineering Facility International Institute of Molecular and Cell Biology in Warsaw Warsaw 02-109 Poland Basic Science Program Frederick National Laboratory for Cancer Research Frederick MD 21702 United States Biophysics Facility International Institute of Molecular and Cell Biology in Warsaw Warsaw 02-109 Poland Laboratory of Protein Structure International Institute of Molecular and Cell Biology in Warsaw Warsaw 02-109 Poland Institute of Biochemistry and Biophysics Warsaw 02-106 Poland

Vertebrates have evolved an understudied protein termed CDADC1 (NYD-SP15) that contains an inactive N-terminal and active C-terminal DCTD-like domain. Here, we show that human CDADC1 is a (d)CTP-specific deaminase, with a roughly 2-fold in vitro preference for dCTP over CTP. We determined high-resolution cryo-EM structures of CDADC1 in the absence of substrate and in complex with dCTP and 5-methyl-dCTP. The structures show that CDADC1 forms trimers and dimers of trimers in solution. The (d)CTP substrate is selected by a narrow pocket for the cytosine base and multiple lysine and arginine contacts to the triphosphate. Substrate binding promotes the association of trimers into hexamers and the transition of the hexamers from a loose to a tighter arrangement. Genetic experiments in mice show that loss of Cdadc1 is surprisingly well tolerated, even in the absence of the dCMP deaminase Dctd that is considered as the main source of dUMP, the precursor of dTTP. Copyright © 2025 the Author(s).

关键词： cryoelectron microscopy cytidine deaminase nucleotide metabolism triphosphate

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Pathogenic variants in the Alport genes are prevalent in the Singapore multiethnic population with highest frequency in the Chinese

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Scientific Reports 2025年第1期15卷 1-12页

作者： Lim, Tina Si Ting Koh, Chee Teck Savige, Judith Ng, Alvin Yu-Jin Ng, Jun Li Chin, Hui-Lin Lim, Weng Khong Chan, Gek Cher Yeo, See Cheng Leow, Esther Hui Min Yan, Benedict Junrong Ng, Kar Hui Zhang, Yaochun Department of Paediatrics Yong Loo Lin School of Medicine National University of Singapore Singapore Singapore Khoo Teck Puat-National University Children’s Medical Institute National University Health System Singapore Singapore University of Melbourne Melbourne Australia Department of Laboratory Medicine Molecular Diagnosis Centre National University Hospital Singapore Singapore Cancer & Stem Cell Biology Program Duke-NUS Medical School Singapore Singapore Laboratory of Genome Variation Analytics Genome Institute of Singapore Agency for Science Technology and Research (A*STAR) Singapore Singapore Department of Medicine Yong Loo Lin School of Medicine National University of Singapore Singapore Singapore Department of Medicine National University Health System Singapore Singapore Department of Renal Medicine Tan Tock Seng Hospital Singapore Singapore Department of Paediatrics Nephrology Service KK Women’s and Children’s Hospital Singapore Singapore

Alport syndrome is a common monogenic kidney disease resulting from pathogenic variants in COL4A3, COL4A4 or COL4A5 genes. The estimated global population prevalence is one in 106 individuals for autosomal dominant (AD) and one in 2,320 for sex-linked (XL) conditions. Here, we aimed to estimate the population prevalence of individuals carrying pathogenic variants that cause Alport syndrome in Singapore, and to stratify the prevalence by ancestry. We used population-scale genomic data of 9,051 unrelated subjects, comprising 5,443 (60.8%) Chinese, 1,922 (21.4%) Indian and 1,686 (17.8%) Malay individuals. The prevalence of individuals with pathogenic variants that cause AD and XL Alport syndrome are 1 in 165 and 1 in 2,262 respectively. Additionally, 0.8% of Chinese and 0.3% of Malay populations carry pathogenic Alport syndrome variants, with Chinese individuals being 2.7 times more affected than Malays (95% CI:1.147–6.437, P = 0.027). Interestingly, each pathogenic variant was associated with people of a single ancestry. The two most prevalent pathogenic variants, COL4A3: c.3856G > A (***1286Arg) (n = 8) and COL4A3: c.4793T > G (***1598Arg) (n = 4), were exclusively found in the Chinese population. In conclusion, AD Alport syndrome may be prevalent in Singapore, with higher frequencies among the Chinese. Furthermore, founder effects may exist within the ancestries. © The Author(s) 2025.

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Phage therapy

NATURE REVIEWS METHODS PRIMERS

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NATURE REVIEWS METHODS PRIMERS 2025年第1期5卷 1页

作者： [Anonymous] Human Microbiome Research Program Department of Bacteriology and Immunology Faculty of Medicine University of Helsinki Helsinki Finland European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Non-traditional Antibacterial Therapy (ESGNTA) Basel Switzerland Institute of Biomedical and Oral Research (IBOR) Faculty of Dental Medicine Hebrew University of Jerusaleum Jerusalem Israel The Israeli Phage Center (IPTC) of the Hebrew University and Hadassah Medical Center Jerusalem Israel Department of Clinical Microbiology and Infectious Diseases Hadassah–Hebrew University Medical Center Jerusalem Jerusalem Israel Laboratory of Gene Technology Department of Biosystems KU Leuven Leuven Belgium Leicester Centre for Phage Research Department of Genetics and Genome Biology University of Leicester Leicester UK Center for Evolutionary Hologenomics Globe Institute University of Copenhagen Copenhagen Denmark Centre of Excellence for Omics-Driven Computational Biodiscovery (COMBio) AIMST University Bedong Kedah Malaysia Laboratory of Phage Molecular Biology Institute of Immunology and Experimental Therapy Wrocław Poland Wrocław University of Science and Technology Faculty of Medicine Wrocław Poland Department of Biological Sciences University of Pittsburgh Pittsburgh PA USA Laboratory for Molecular and Cellular Technology Queen Astrid Military Hospital Brussels Belgium Department of Biological and Environmental Science Nanoscience Center University of Jyväskylä Jyväskylä Finland Chemical Engineering Department Loughborough University Loughborough UK

Bacteriophage (phages) are viruses that exclusively use bacterial cells for propagation, killing the bacterial host in the process. In phage therapy, phages are used to reduce bacterial numbers, thereby curing bacterial infections. Although this principle is conceptually straightforward, its practical application faces several hurdles. In this Primer, the practical aspects of phage therapy are outlined. We introduce the microbiological methods used to prepare and characterize phages and elucidate their interactions with bacteria. The discussion covers how the information in complete phage genome sequences is used, along with how RNA sequencing can enhance our understanding of phage biology. Selection parameters for therapeutic phages for clinical applications and key elements in industrial-scale phage production are provided. A summary of clinical trials both past and present, phage administration and dosing issues is analysed, as well as limitations associated with phage therapy and mitigation strategies. Finally, we speculate on the future of phage therapy.

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