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Site-specific genome editing in treatment of inherited diseases:possibility,progress,and perspectives

Medical Review 2022年第5期2卷 471-500页

作者： Chao Huang Qing Li Jinsong Li Key Laboratory of Systems Health Science of Zhejiang Province School of Life ScienceHangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesNo.1 Sub-Lane XiangshanHangzhou 310024ZhejiangChina State Key Laboratory of Cell Biology Shanghai Key Laboratory of Molecular AndrologyCAS Center for Excellence in Molecular Cell ScienceShanghai Institute of Biochemistry and Cell BiologyChinese Academy of SciencesUniversity of Chinese Academy of SciencesNo.320 Yueyang RoadShanghai 200031China Key Laboratory of Systems Health Science of Zhejiang Province School of Life ScienceHangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhouZhejiangChina State Key Laboratory of Cell Biology Shanghai Key Laboratory of Molecular AndrologyCAS Center for Excellence in Molecular Cell ScienceShanghai Institute of Biochemistry and Cell BiologyChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghaiChina

Advancements in genome editing enable permanent changes of DNA sequences in a site-specific manner,providing promising approaches for treating human genetic disorders caused by gene ***,genome editing has been applied and achieved significant progress in treating inherited genetic disorders that remain incurable by conventional ***,we present a review of various programmable genome editing systems with their principles,advantages,and *** introduce their recent applications for treating inherited diseases in the clinic,including sickle cell disease(SCD),β-thalassemia,Leber congenital amaurosis(LCA),heterozygous familial hypercholesterolemia(HeFH),*** also discuss the paradigm of ex vivo and in vivo editing and highlight the promise of somatic editing and the challenge of germline ***,we propose future directions in delivery,cutting,and repairing to improve the scope of clinical applications.

关键词： clinical applications genome editing inherited diseases mutations principles.

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One-step synthesis of site-specific antibody-drug conjugates by reprograming IgG glycoengineering with LacNAc-based substrates

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Acta Pharmaceutica Sinica B 2022年第5期12卷 2417-2428页

作者： Wei Shi Wanzhen Li Jianxin Zhang Tiehai Li Yakai Song Yue Zeng Qian Dong Zeng Lin Likun Gong Shuquan Fan Feng Tang Wei Huang cas Key Laboratory of Receptor research CAS Center for Excellence in Molecular Cell ScienceCenter for Biotherapeutics Discovery ResearchShanghai Institute of Materia Medica Chinese Academy of SciencesShanghai 201203China School of Pharmaceutical Science and Technology Hangzhou Institute of Advanced StudyHangzhou 310024China University of Chinese Academy of Sciences Beijing 100049China School of Chinese Materia Medica Nanjing University of Chinese MedicineNanjing 210023China School of Life Science Liaocheng UniversityLiaocheng 252059China

Glycosite-specific antibody-drug conjugatess(gsADCs), harnessing Asn297 N-glycan of IgG Fc as the conjugation site for drug payloads, usually require multi-step glycoengineering with two or more enzymes, which limits the substrate diversification and complicates the preparation ***, we report a series of novel disaccharide-based substrates, which reprogram the IgG glycoengineering to one-step synthesis of gsADCs, catalyzed by an endo-N-acetylglucosaminidase(ENGase) of Endo-S2. IgG glycoengineering via ENGases usually has two steps: deglycosylation by wild-type(WT) ENGases and transglycosylation by mutated ENGases. But in the current method, we have found that disaccharide LacNAc oxazoline can be efficiently assembled onto IgG by WT Endo-S2 without hydrolysis of the product, which enables the one-step glycoengineering directly from native *** studies on substrate specificity revealed that this approach has excellent tolerance on various modification of 6-Gal motif of LacNAc. Within 1 h, one-step synthesis of gsADC was achieved using the LacNAc-toxin substrates including structures free of bioorthogonal groups. These gsADCs demonstrated good homogeneity, buffer stability, in vitro and in vivo anti-tumor activity. This work presents a novel strategy using LacNAc-based substrates to reprogram the multi-step IgG glycoengineering to a one-step manner for highly efficient synthesis of gsADCs.

关键词： Site-specific ADCs ENGase LacNAc One-step assembly Potent in vivo efficacy

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Wave propagation across fluid-solid interfaces with LBM-LSM coupling schemes

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Petroleum Science 2024年第5期21卷 3125-3141页

作者： Mu-Ming Xia Hui Zhou Chun-Tao Jiang Han-Ming Chen Jin-Ming Cui Can-Yun Wang Chang-Chun Yang cas Engineering Laboratory for Deep Resources Equipment and Technology Institute of Geology and Geophysicsand Innovation Academy for Earth ScienceChinese Academy of SciencesChaoyangBeijing100029China State Key Laboratory of Petroleum Resources and Engineering CNPC Key Lab of Geophysical ExplorationChina University of Petroleum(Beijing)ChangpingBeijing102249China Qingdao Institute of Marine Geology China Geological SurveyQingdao266237ShandongChina AI Sonic Technology research Center Research Institute of Tsinghua University in ShenzhenShenzhen518057GuangdongChina

Seismic wave propagation in fluid-solid coupled media is currently a popular topic. However, traditional wave equation-based simulation methods have to consider complex boundary conditions at the fluid-solid interface. To address this challenge, we propose a novel numerical scheme that integrates the lattice Boltzmann method(LBM) and lattice spring model(LSM). In this scheme, LBM simulates viscoacoustic wave propagation in the fluid area and LSM simulates elastic wave propagation in the solid area. We also introduce three different LBM-LSM coupling strategies, a standard bounce back scheme, a specular reflection scheme, and a hybrid scheme, to describe wave propagation across fluid-solid boundaries. To demonstrate the accuracy of these LBM-LSM coupling schemes, we simulate wave propagation in a two-layer model containing a fluid-solid interface. We place excitation sources in the fluid layer and the solid layer respectively, to observe the wave phenomena when seismic waves propagate to interface from different sides. The simulated results by LBM-LSM are compared with the reference wavefields obtained by the finite difference method(FDM) and the analytical solution(ANA).Our LBM-LSM coupling scheme was verified effective, as the relative errors between the LBM-LSM solutions and reference solutions were within an acceptable range, sometimes around 1.00%. The coupled LBM-LSM scheme is further used to model seismic wavefields across a more realistic rugged seabed,which reveals the potential applications of the coupled LBM-LSM scheme in marine seismic imaging techniques, such as reverse-time migration and full-waveform inversion. The method also has potential applications in simulating wave propagation in complex two-and multi-phase media.

关键词： Lattice Boltzmann method(LBM) Lattice spring model(LSM) LBM-LSM coupling Finite difference method(FDM) Fluid-solid configuration Seismic wave simulation

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Big Disaster from Small Watershed:Insights into the Failure and Disaster‑Causing Mechanism of a Debris Flow on 25 September 2021 in Tianquan,China

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International Journal of Disaster Risk Science 2024年第4期15卷 622-639页

作者： Runing Hou Mingyang Wu Zhi Li Ningsheng Chen Xiaohu Chen Taixin Peng Na Huang Key Laboratory of Mountain Hazards and Surface Processes Institute of Mountain Hazards and EnvironmentChinese Academy of SciencesChengdu 610041China School of Geosciences Yangtze UniversityWuhan 430100China Academy of Plateau Science and Sustainability Xining 810016China University of Chinese Academy of Sciences Beijing 100049China

The occurrence of debris flow events in small-scale watersheds with dense vegetation in mountainous areas that result in significant loss of life and missing individuals challenges our understanding and expertise in investigating and preventing these disasters. This has raised concerns about the occurrence of large debris flow disasters from small watersheds. This study focused on a catastrophic debris flow that took place in Longtou Gully(0.45 km^(2)) in Tianquan County, Ya'an City on 25 September 2021, which resulted in 14 deaths and missing individuals. Through comprehensive field investigations, highprecision remote sensing data analyses, and numerical simulations, we analyzed the triggering mechanisms and dynamic processes of this event. Our results indicate that the convergence hollow at the channel head exhibited higher hydraulic conditions during rainfall compared to gentle slopes and convex terrains, leading to the instability of colluvial soil due to the expansion of the saturated zone near the soil–bedrock interface. The entrainment of material eroded from the channel resulted in an approximately 4.7 times increase in volume, and the channel scarp with a height of about 200 m amplified the destructive power of the debris flow. We emphasize the need to take seriously the possibility of catastrophic debris flows in small-scale watersheds, with colluvial deposits in hollows at the channel head under vegetation cover that serve as precursor material sources, and the presence of channel scarps formed by changes in the incision rate of the main river, which is common in the small watershed on both sides. This study provides insights for risk assessment of debris flows in small-scale catchments with dense vegetation cover in mountainous areas, highlighting the importance of vigilance in addressing disasters in small-scale catchments, particularly in regions with increasing human–environment conflicts.

关键词： China Colluvial soil Low-frequency debris fows Risk reduction Topographic hollows

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Parallel evolution of twoAIM24 protein subfamilies and their conserved functions in ER stress tolerance in land plants

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Plant Communications 2023年第3期4卷 183-196页

作者： Yanlong Guan Guanxiao Chang Jinjie Zhao Qia Wang Jiali Qin Mengmeng Tang Shuanghua Wang Lan Ma Jianchao Ma Guiling Sun Yun Zhou Jinling Huang Key Laboratory for Plant Diversity and Biogeography of East Asia Yunnan Key Laboratory for Fungal Diversity and Green DevelopmentKunming Institute of BotanyChinese Academy of SciencesKunming 650201China State Key Laboratory of Crop Stress Adaptation and Improvement School of Life SciencesHenan UniversityKaifeng 475004China Yunnan Key Laboratory for Wild Plant Resources Kunming Institute of BotanyChinese Academy of SciencesKunming 650201China Department of Biology East Carolina UniversityGreenvilleNC 27858USA

Despite decades of efforts in genome sequencing and functional characterization,some important protein families remain poorly *** this study,we report the classification,evolution,and functions of the largely uncharacterized AIM24 protein family in plants,including the identification of a novel *** show that two AIM24 subfamilies(AIM24-A and AIM24-B)are commonly distributed in major plant *** two subfamilies not only have modest sequence similarities and different gene structures but also are of independent bacterial *** performed comparative functional investigations on the two AIM24 subfamilies using three model plants:the moss Physcomitrium patens,the liverwort Marchantia polymorpha,and the flowering plant Arabidopsis ***,despite their significant differences in sequence and gene structure,both AIM24 subfamilies are involved in ER stress tolerance and the unfolded protein response(UPR).In addition,transformation of the AIM24-A gene from *** into the AIM24-B null mutant of *** could at least partially rescue ER stress tolerance and the *** also discuss the role of AIM24 genes in plant development and other cellular *** study provides a unique example of parallel evolution in molecular functions and can serve as a foundation for further investigation of the AIM24 family in plants.

关键词： Physcomitrium Marchantia unfolded protein response lncRNA

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Origin of a giant fuzzy reflection zone and its implication for natural gas exploration in the southwestern Qiongdongnan Basin of the South China Sea

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Journal of Oceanology and Limnology 2023年第2期41卷 710-728页

作者： Junhui YU Pin YAN Yanlin WANG Yan QIU Guanghong TU Changliang CHEN Key Laboratory of Ocean and Marginal Sea Geology South China Sea Institute of OceanologyInnovation Academy of South China Sea Ecology and Environmental EngineeringChinese Academy of SciencesGuangzhou 510301China Southern Marine Science and Engineering Guangdong Laboratory(Guangzhou) Guangzhou 511458China Key Laboratory of Marine Geology and Environment Institute of OceanologyChinese Academy of SciencesQingdao 266071China Key Laboratory of Marine Mineral Resources Guangzhou Marine Geological SurveyChina Geological SurveyMinistry of Natural ResourcesGuangzhou 511458China University of Chinese Academy of Sciences Beijing 100049China

The southwestern depression of the Qiongdongnan Basin(QDNB)hosts thick Cenozoic sediments and awaits major hydrocarbon *** seismic(MCS)profile CFT2011 across the southwestern QDNB reveals a~60-km-wide fuzzy reflection zone(FRZ)within the sediments,but its origin and distribution remain *** ocean bottom seismometer(OBS)data of Line CFT2011 are processed with focus on the velocity structures by traveltime tomography inversion and analyzed together with the coincident and adjacent MCS *** OBS velocity results show that the giant FRZ features lower velocity with difference up to 1.5 km/s and smaller vertical velocity gradient than the surrounding sedimentary sequences at the same depth,likely resulting from enhanced fluid *** MCS profile exhibits that the giant FRZ is about 3-9-km thick and extends from the Paleogene strata rich in organic matters upward to the lower Pleistocene *** the shallow overlying sediments,multiple bright spots with reverse polarity are imaged and their reflection amplitudes increase with offset,consistent with the features of gas-charged *** are probably shallow gas reservoirs with gases sourced from the deep ***,the FRZ is proposed to be a giant gas-charged zone,which probably contains lots of hydrocarbon gases migrated vertically from the deep Paleogene source rocks through the boundary faults of the depressions and the minor fractures generated under *** FRZ is also imaged on the adjacent MCS profiles MCS-L1 and MCS-L2 with the width of about 40 km and 68 km,*** is roughly estimated to cover an area of~1900 km2 and host a volume of~11400 km3 assuming an average thickness of 6 km,implying huge natural gas potential in the sedimentary depression of the southwestern QDNB of the South China Sea.

关键词： southwestern Qiongdongnan Basin fuzzy reflection zone low velocity gas charging natural gas potential

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Reaction^(55)Mn+^(159)Tb:preparation for the synthesis of new elements

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Chinese Physics C 2023年第5期47卷 147-151页

作者：陈立欣徐苏扬张志远王建国黄明辉张明明马龙杨华彬杨春莉吴晓蕾周厚兵赵圳黄鑫源周浩张旭孙路冲李宗池甘再国 Department of Physics Guangxi Normal UniversityGuilin 541004China cas Key Laboratory of High Precision Nuclear Spectroscopy Institute of Modern PhysicsChinese Academy of SciencesLanzhou 730000China School of Nuclear Science and Technology University of Chinese Academy of SciencesBeijing 100049China Guangxi Key Laboratory of Nuclear Physics and Technology Guangxi Normal UniversityGuilin 541004China

The complete fusion reaction of^(55)Mn+^(159)Tb was studied on the gafilled recoil separator *** ER-α1-α2 decay chains from^(210)Th produced from the 4n evaporation channel were *** a-particle energy and half-life of 210Th were determined as 7922(14)keV and 14(4)ms,*** addition,the decay properties of Eα=7788(14)keV and T_(1/2)=36+15-8 ms were obtained for *** measured a decay prop-erties of^(210)Th and^(211)Th were consistent with literature *** cross sections were measured to be 0.59+035 nb and 0.19-012 nb for^(210)Th and^(211)Th,*** equilibrium charge state of the recoiled nucleus^(210)Th was determined *** new data were helpful for estimating the equilibrium charge states of elements 119 and 120,which could be produced via the^(240)Pu(^(55)Mn,3n)^(292)119 and^(243)Am(^(55)Mn,3m)^(295)120 reactions,respect-ively.

关键词： fusion reaction αdecay heavy nuclei gas-filled recoil separator

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LAMOST medium-resolution spectroscopic survey of binarity and exotic star(LAMOST-MRS-B):Observation strategy and target selection

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Chinese Physics B 2023年第1期32卷 56-67页

作者：李蛟李江丹郭彦君韩占文陈雪飞刘超葛宏伟姜登凯李立芳章博刘佳明田浩张昊彤袁海龙崔文元任娟娟蔡靖豪施建荣 Key Laboratory of Space Astronomy and Technology National Astronomical ObservatoriesChinese Academy of SciencesBeijing 100101China Yunnan Observatories Chinese Academy of SciencesKunming 650011China School of Astronomy and Space Science University of Chinese Academy of SciencesBeijing 100049China Key Laboratory of Optical Astronomy National Astronomical ObservatoriesChinese Academy of SciencesBeijing 100101China Department of Physics Hebei Normal UniversityShijiazhuang 050024China

LAMOST-MRS-B is one of the sub-surveys of LAMOST medium-resolution(R~7500)spectroscopic *** aims at studying the statistical properties(e.g.,binary fraction,orbital period distribution,mass ratio distribution)of binary stars and exotic *** intend to observe about 30000 stars(10 mag≤Gproject,we set the identified exotic and low-metallicity stars with the highest observation *** the rest of the selected stars,we gave the higher priority to the relatively brighter stars in order to obtain high quality spectra as many as *** of49129 stars have been obtained in LAMOST-MRS-B field and released in DR8,of which 28828 and 3375 stars have been visited more than twice and ten times with SNR≥10,*** of the sources are B-,A-,and F-type stars with-0.6<[Fe/H]<0.4 *** also obtain 347 identified variable and exotic stars and about 250 stars with[Fe/H]<-1 *** measure radial velocities(RVs)by using 892233 spectra of the *** uncertainties of RV achieve about 1 km·s^(-1)and 10 km·s^(-1)for 95%of late-and early-type stars,*** datasets presented in this paper are available at http://***/10.57760/sciencedb.j00113.00035.

关键词： surveys spectroscopy catalogs binary

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Syntropic spin alignment at the interface between ferromagnetic and superconducting nitrides

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National Science Review 2024年第8期11卷 167-179页

作者： Qiao Jin Qinghua Zhang He Bai Meng Yang Yonglong Ga Shengru Chen Haitao Hong Ting Cui Dongke Rong Ting Lin Jia-Ou Wang Chen Ge Can Wang Yanwei Cao Lin Gu Guozhu Song Shanmin Wang Kun Jiang Zhi-Gang Cheng Tao Zhu Hongxin Yang Kui-juan Jin Er-Jia Guo Beijing National Laboratory for Condensed Matter Physics and Institute of Physics Chinese Academy of Sciences Spallation Neutron Source Science Center Department of Physics & Center of Materials Science and Optoelectronics Engineering University of Chinese Academy of Sciences Ningbo Institute of Materials Technology &Engineering Chinese Academy of Sciences Institute of High Energy Physics Chinese Academy of Sciences Songshan Lake Materials Laboratory National Center for Electron Microscopy in Beijing and School of Materials Science and Engineering Tsinghua University Department of Physics Southern University of Science and Technology School of Physics Zhejiang University

The magnetic correlations at the superconductor/ferromagnet（S/F） interfaces play a crucial role in realizing dissipation-less spin-based logic and memory technologies,such as triplet-sup ercurrent spin-valves and 'π'Josephson *** we report the observation of an induced large magnetic moment at high-quality nitride S/F *** polarized neutron reflectometry and DC S QUID measurements,we quantitatively determined the magnetization profile of the S/F bilayer and confirmed that the induced magnetic moment in the adjacent superconductor only exists below ***,the direction of the induced moment in the superconductors was unexpectedly parallel to that in the ferromagnet,which contrasts with earlier findings in S/F heterostructures based on metals or ***-principles calculations verified that the unusual interfacial spin texture observed in our study was caused by the Heisenberg direct exchange coupling with constant J～4.28 meV through d-orbital overlapping and severe charge transfer across the *** work establishes an incisive experimental probe for understanding the magnetic proximity behavior at S/F interfaces and provides a prototype epitaxial 'building block' for superconducting spintronics.

关键词： magnetic proximity effects nitride interfaces polarized neutron reflectometry superconductor/ferromagnetic interfaces superconducting spintronics

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Large-Area Gravure-Printed AgNWs Electrode on Water/Oxygen Barrier Substrate for Long-Term Stable Large-Area Flexible Organic Solar Cells

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Chinese Journal of Chemistry 2024年第5期42卷 478-484页

作者： Hao Wang Yaqin Pan Yunfei Han Zhuo Chen Tianyu Liu Lianping Zhang Qun Luo Chang-Qi Ma Printable Electronics research Center & i-Lab Suzhou Institute of Nano-Tech and Nano-BionicsChinese Academy of Sciences (CAS)SuzhouJiangsu215123 China Nano Science and Technology Institute University of Science and Technology of China166 Ren Ai RoadSEID SIPSuzhouJiangsu215123 China

Large-area AgNWs electrodes(25 cm×10 cm)were fabricated through roll-to-roll printing on the polyvinyl alcohol(PVA)modified water and oxygen barrier *** modification of the barrier film with PVA improved the wettability of silver nanowires on the barrier films and led to the formation of homogenous large-area AgNWs *** mechanical flexibility,especially the adhesion force between the silver electrode and the barrier film substrate was dramatically improved through PVA *** efficiency of 13.51%for the flexible OSCs with an area of 0.64 cm2 was achieved based on the PET/barrier film/PVA/AgNWs *** long-term stability showed the flexible OSCs based on the PET/barrier film/PVA/AgNWs electrode have a significantly improved stability relative to the device on PET/AgNWs electrode,and comparable air stability as the rigid device with glass/ITO *** unencapsulated devices maintained nearly 50%of the original efficiency after storage for 600 h in *** a simple top encapsulation,the flexible devices remained at 60%of the initial efficiency after 2000 h in the ***,the flexible AgNWs electrode based on the barrier film would have the potential to improve the air storage stability of organic flexible solar cells.

关键词： Flexible organic solar cell AgNWs electrode Air storage stability Barrier films substrate Energy conversion Flexible electronics Interface

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