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Inhibition mechanisms of CRISPR-Cas9 by AcrⅡA25.1 and AcrⅡA32

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Science China(Life Sciences) 2024年第9期67卷 1781-1791页

作者： Jianlin Zheng yuwei Zhu Tengjin huang Wenbo Gao Jiale He Zhiwei huang HIT Center for Life Sciences School of Life Science and TechnologyHarbin Institute of TechnologyHarbin 150080China Westlake Center for Genome Editing Westlake Laboratory of Life Sciences and BiomedicineSchool of Life SciencesWestlake UniversityHangzhou 310024China

In the ongoing arms race between bacteria and bacteriophages,bacteriophages have evolved anti-CRISPR proteins to counteract bacterial CRISPR-Cas ***,AcrⅡA25.1 and AcrⅡA32 have been found to effectively inhibit the activity of Spy Cas9 both in bacterial and human ***,their molecular mechanisms remain ***,we report the cryo-electron microscopy structures of ternary complexes formed by AcrⅡA25.1 and AcrⅡA32 bound to Spy Cas9-sg *** structural analysis and biochemical experiments,we revealed that AcrⅡA25.1 and AcrⅡA32 recognize a novel,previously-unidentified anti-CRISPR binding site on Spy *** found that both AcrⅡA25.1 and AcrⅡA32 directly interact with the WED domain,where they spatially obstruct conformational changes of the WED and PI domains,thereby inhibiting Spy Cas9 from recognizing protospacer adjacent motif(PAM)and unwinding double-stranded *** addition,they may inhibit nuclease activity by blocking the dynamic conformational changes of the Spy Cas9 surveillance *** summary,our data elucidate the inhibition mechanisms of two new anti-CRISPR proteins,provide new strategies for the modulation of Spy Cas9 activity,and expand our understanding of the diversity of anti-CRISPR protein inhibition mechanisms.

关键词： anti-CRISPR cryo-EM Spy Cas9 AcrⅡA25.1 AcrⅡA32 inhibiton

Increasing polymer scission rate by tying an overhand knot

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Science China Chemistry 2024年

作者： yuheng Hu Jennifer T.Ou Jim y.huang yuanning Feng Department of Chemistry and Biochemistry The University of Oklahoma

Similar to the phenomenon of knotted ropes in life, knotted climbing ropes will reduce their strength due to knots. Although computer simulations [1], theoretical speculation[2,3], and intuition [3] suggest that similar processes may occur at the nanoscale, this hypothesis has not been experimentally proven before. With the increasing maturity of molecular recognition and self-assembly, a research communication by Leigh et al. [4]

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Understanding the Low Predictability of the 2015/16 El Niño Event Based on a Deep Learning Model

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Advances in Atmospheric Sciences 2024年第7期41卷 1313-1325页

作者： Tingyu WANG Ping huang Xianke yANG Center for Monsoon System Research Institute of Atmospheric PhysicsChinese Academy of SciencesBeijing 100029China National Space Science Center Chinese Academy of SciencesBeijing 100190China State Key Laboratory of Space Weather National Space Science CenterChinese Academy of SciencesBeijing 100190China College of Plant Science and Technology Huazhong Agricultural UniversityWuhan 430070China

The 2015/16 El Niño event ranks among the top three of the last 100 years in terms of intensity,but most dynamical models had a relatively low prediction skill for this event before the summer ***,the attribution of this particular event can help us to understand the cause of super El Niño–Southern Oscillation events and how to forecast them *** present study applies attribute methods based on a deep learning model to study the key factors related to the formation of this event.A deep learning model is trained using historical simulations from 21 CMIP6 models to predict the Niño-3.4 *** integrated gradient method is then used to identify the key signals in the North Pacific that determine the evolution of the Niño-3.4 *** crucial signals are then masked in the initial conditions to verify their roles in the *** addition to confirming the key signals inducing the super El Niño event revealed in previous attribution studies,we identify the combined contribution of the tropical North Atlantic and the South Pacific oceans to the evolution and intensity of this event,emphasizing the crucial role of the interactions among them and the North *** approach is also applied to other El Niño events,revealing several new precursor *** study suggests that the deep learning method is useful in attributing the key factors inducing extreme tropical climate events.

关键词： ENSO attribution deep learning ENSO prediction extreme El Niño

Caudal hematopoietic tissue supports definitive erythrocytes via epoa and is dispensable for definitive neutrophils

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Journal of Genetics and Genomics 2024年第6期51卷 669-672页

作者： Zhujuan huang yongtai Xu Zhongkai Qiu yunyun Jiang Jiaye Wu Qing Lin Sicong He Jianan y.Qu Jiahao Chen Jin Xu Innovation Centre of Ministry of Education for Development and Diseases School of MedicineSouth China University of TechnologyGuangzhouGuangdong 510006China Department of Biology School of Life SciencesSouthern University of Science and TechnologyShenzhenGuangdong 518055China Department of Electronic and Computer Engineering The Hong Kong University of Science and TechnologyKowloonHongkong 999077China

The blood system originates from hematopoietic stem cells(HSCs),capable of self-renewal and differentiation,generating diverse blood cell types(Eaves,2015;Lucas,2021).The concept of the hematopoietic niche was first proposed in 1978(Schofield,1978),which is crucial for maintaining hematopoietic *** following studies,particularly in mammals,have utilized targeted genetic manipulation to identify and define these niches.

关键词： hematopoietic manipulation utilized

Review on synergistic damage effect of irradiation and corrosion on reactor structural alloys

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Nuclear Science and Techniques 2024年第3期35卷 109-141页

作者： Hui Liu Guan-Hong Lei He-Fei huang Shanghai Institute of Applied Physics Chinese Academy of SciencesShanghai 201800China School of Nuclear Science and Technology University of Chinese Academy of SciencesBeijing 100049China

The synergistic damage effect of irradiation and corrosion of reactor structural materials has been a prominent research *** paper provides a comprehensive review of the synergistic effects on the third-and fourth-generation fission nuclear energy structural materials used in pressurized water reactors and molten salt *** competitive mechanisms of multiple influencing factors,such as the irradiation dose,corrosion type,and environmental temperature,are summarized in this *** approaches are proposed to alleviate the synergistic damage caused by irradiation and corrosion,thereby promoting in-depth research in the future and solving this key challenge for the structural materials used in reactors.

关键词： Irradiation and corrosion Synergistic effect Austenitic stainless steels Nickel-based alloys Reactors

Electrochemical protein biosensors for disease marker detection:progress and opportunities

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Microsystems & Nanoengineering 2024年第3期10卷 1-20页

作者： Lanpeng Guo yunong Zhao Qing huang Jing huang yanbing Tao Jianjun Chen Hua-yao Li Huan Liu School of Integrated Circuits Wuhan National Laboratory for OptoelectronicsOptics Valley LaboratoryHuazhong University of Science and TechnologyWuhan 430074China Key Laboratory of Intelligent Computing and Signal Processing of Ministry of Education School of Integrated CircuitsAnhui UniversityHefei 230601China School of Optoelectronic Materials and Technology Jianghan UniversityWuhan 430056China Department of Otorhinolaryngology Union HospitalTongji Medical CollegeHuazhong University of Science and Technology1277 Jiefang AvenueWuhan 430022China Wenzhou Institute of Advanced Manufacturing Technology Huazhong University of Science and TechnologyWenzhou 325000China

The development of artificial intelligence-enabled medical health care has created both opportunities and challenges for next-generation biosensor *** are extensively used as biological macromolecular markers in disease diagnosis and the analysis of therapeutic *** protein biosensors have achieved desirable specificity by using the specific antibody–antigen binding principle in ***,the active centers of protein biomarkers are surrounded by a peptide matrix,which hinders charge transfer and results in insufficient sensor ***,electrode-modified materials and transducer devices have been designed to increase the sensitivity and improve the practical application prospects of electrochemical protein *** this review,we summarize recent reports of electrochemical biosensors for protein biomarker *** highlight the latest research on electrochemical protein biosensors for the detection of cancer,viral infectious diseases,inflammation,and other *** corresponding sensitive materials,transducer structures,and detection principles associated with such biosensors are also addressed ***,we present an outlook on the use of electrochemical protein biosensors for disease marker detection for the next few years.

关键词： diagnosis specificity Electrochemical

Catalytic enantioselective N-silylation of sulfoximine

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Chinese Chemical Letters 2024年第4期35卷 352-356页

作者： Xingfen huang Jiefeng Zhu Chuan He Shenzhen Grubbs Institute and Department of Chemistry Guangdong Provincial Key Laboratory of CatalysisSouthern University of Science and TechnologyShenzhen 518055China Key Laboratory of Organosilicon Chemistry and Material Technology of Ministry of Education Hangzhou Normal UniversityHangzhou 311121China

A rhodium/diphosphine-catalyzed asymmetric cross-dehydrogenative coupling between sulfoximines and dihydrosilanes has been achieved. This is the first report on the enantioselective N-silylation of sulfoximines. The protocol gives access to a variety of Si-stereogenic N-silylated sulfoximines in decent yield(up to 99%) with excellent stereoselectivity(up to 99%), featuring high atom economy, and a cleaner manner with H2as the sole byproduct. The obtained bis-Si-stereogenic monohydrosilane product can be further converted into the corresponding chiral polymer with pendant sulfoximine groups.

关键词： N-Silylation of sulfoximine Chiral silylamine Si-stereogenic silanes Si-CADC Asymmetric catalysis

Fli1 acts in parallel with Pu.1 to control macrophage and neutrophil fate in zebrafish

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Journal of Genetics and Genomics 2024年第3期51卷 359-362页

作者： Ao Zhang Jingao Lu Shachuan Feng Huapeng yu Tao yu Shizheng Zhao Kemin Chen Zhibin huang Jin Xu Jianan y.Qu Zilong Wen Division of Life Science Hong Kong University of Science and TechnologyClear Water BayKowloonHong KongChina Division of Cell Developmental and Integrative BiologySchool of MedicineSouth China University of TechnologyGuangzhouGuangdong 510006China Department of Immunology and Microbiology School of Life ScienceSouthern University of Science and TechnologyShenzhenGuangdong 518055China Biomedical Research Institute Shenzhen Peking University-Hong Kong University of Science and Technology Medical CenterShenzhenGuangdong 518036China Department of Electronic and Computer Engineering Hong Kong University of Science and TechnologyClear Water BayKowloonHong KongChina Greater Bay Biomedical Innocenter Shenzhen Bay LaboratoryShenzhenGuangdong 518067China

Macrophages and neutrophils are key components of myeloid cells and play critical roles in innate immune responses,organ formation,and tissue *** integrity of their functions heavily relies on the generation of a proper number of mature macrophages and neutrophils through embryonic and adult *** mammalian adult myelopoiesis,oligopotent common myeloid progenitors(CMPs)are known to be the earliest myeloid progenitors,which give rise to granulocyte-macrophage progenitors(GMPs),subsequently differentiate into unipotent neutrophil and macrophage precursors,and finally,mature macrophages and neutrophils(Orkin and Zon,2008).In contrast,the ontogeny of embryonic myelopoiesis and the mechanism underlying the formation of macrophages and neutrophils remainless understood.

关键词： fish macrophage homeostasis

Geochronology and Geochemistry of the Xingxingxia Triassic A-type Granites in Central Tianshan,NW China:Petrogenesis and Tectonic Implications

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Acta Geologica Sinica(English Edition) 2024年第2期98卷 337-351页

作者： huang Zengbao LI Xiyao ZHAO Hao LU Qing Geological Survey of Gansu Province Lanzhou 735000China Key Laboratory of Submarine Geosciences and Prospecting Techniques MOE and College of Marine GeosciencesOcean University of ChinaQingdaoShandong 266100China Research Institute of Petroleum Exploration and Development Shengli OilfieldSINOPECDongyingShandong 257000China

The Triassic granitoids in Central Tianshan play a key role in determining the petrogenesis and tectonic evolution on the southern margin of the Central Asian orogenic *** this study,we present SHRIMP zircon U-Pb ages,Hf isotopic and geochemical data on the Xingxingxia biotite granite,amazonite granite and granitic pegmatite in Central Tianshan,NW *** U-Pb dating yielded formation ages of 242 Ma for the biotite granite and 240 Ma for the amazonite *** granitoid rocks have high K_(2)O with low MgO and CaO *** are enriched in Nb,Ta,Hf and y,while being depleted in Ba and Sr,showing flat HREE patterns and negative Eu *** have typical A-type granite geochemical signatures with high Ga/A_(1)(8–13)and TFeO/(TFeO+MgO)ratios,showing an A_(2) affinity for biotite granite and an A_(1) affinity for amazonite granite and granitic *** ε_(Hf)(t)values of the granitoids are 0.45–2.66,with Hf model ages of 0.99–1.17 *** suggests that these A-type granites originated from partial melting of the lower *** propose that Xingxingxia Triassic A-type granites formed under lithospheric extension from post-orogenic to anorogenic intraplate settings and NE-trending regional strike-slip fault-controlled magma emplacement in the upper crust.

关键词： Triassic A-type granite Xingxingxia Central Tianshan Central Asian orogenic belt