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Single-cell omics: experimental workflow, data analyses and applications

Science China Life Sciences 2025年第1期68卷 5-102页

作者： Fengying Sun Haoyan Li Dongqing Sun Shaliu Fu Lei Gu Xin Shao Qinqin Wang Xin Dong Bin Duan Feiyang Xing Jun Wu Minmin Xiao Fangqing Zhao Jing-Dong J.Han Qi Liu Xiaohui Fan Chen Li Chenfei Wang Tieliu Shi Department of Clinical laboratory the Affiliated Wuhu Hospital of East China Normal University (The Second People's Hospital of Wuhu City) Pharmaceutical Informatics Institute College of Pharmaceutical SciencesZhejiang University Key laboratory of Spine and Spinal Cord Injury Repair and Regeneration (Tongji University) Ministry of EducationOrthopaedic DepartmentTongji HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji University Frontier Science Center for Stem Cells School of Life Sciences and TechnologyTongji University Translational Medical Center for Stem Cell Therapy and Institute for Regenerative medicine Shanghai East HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji University Research Institute of Intelligent Computing Zhejiang Lab Shanghai Research Institute for Intelligent Autonomous systems Center for Single-cell Omics School of Public HealthShanghai Jiao Tong University School of Medicine National Key laboratory of Chinese medicine Modernization Innovation Center of Yangtze River DeltaZhejiang University Center for Bioinformatics and Computational Biology Shanghai Key Laboratory of Regulatory Biologythe Institute of Biomedical Sciences and School of Life SciencesEast China Normal University Beijing Institutes of Life Science Chinese Academy of Sciences Peking-Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary StudiesCenter for Quantitative Biology (CQB)Peking University zhejiang Key laboratory of precision Diagnosis and Therapy for Major Gynecological Diseases Women's HospitalZhejiang University School of Medicine Key laboratory of Advanced Theory and Application in Statistics and Data Science-MOE School of StatisticsEast China Normal University

Cells are the fundamental units of biological systems and exhibit unique development trajectories and molecular features. Our exploration of how the genomes orchestrate the formation and maintenance of each cell, and control the cellular phenotypes of various organismsis, is both captivating and intricate. Since the inception of the first single-cell RNA technology, technologies related to single-cell sequencing have experienced rapid advancements in recent years. These technologies have expanded horizontally to include single-cell genome, epigenome,proteome, and metabolome, while vertically, they have progressed to integrate multiple omics data and incorporate additional information such as spatial sc RNA-seq and CRISPR screening. Single-cell omics represent a groundbreaking advancement in the biomedical field,offering profound insights into the understanding of complex diseases, including cancers. Here, we comprehensively summarize recent advances in single-cell omics technologies, with a specific focus on the methodology section. This overview aims to guide researchers in selecting appropriate methods for single-cell sequencing and related data analysis.

关键词： single-cell sequencing genome epigenome proteomics metabolomics multimodal spatial transcriptomics CRISPR screening

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Double [5]carbohelicene: facile synthesis, chiroptical properties,isomerization study, and lasing application

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Science China Chemistry 2025年第1期68卷 233-240页

作者： Peipei Liu Yantong Li Meng-Xiang Wu Hao Kang Xiao-Li Zhao Lin Xu Linlin Liu Xiaodong Li Junfeng Fang Zhiwei Fang Ya Cheng Hai-Bo Yang Huakang Yu Xueliang Shi State Key laboratory of Petroleum Molecular & Process Engineering Shanghai Key Laboratory of Green Chemistry and Chemical ProcessesSchool of Chemistry and Molecular Engineering East China Normal University School of Physics and Optoelectronics South China University of Technology Institute of Polymer Optoelectronic Materials & Devices State Key Laboratory of Luminescent Materials & Devices South China University of Technology School of Physics and Electronic Science Engineering Research Center of Nanophotonics & Advanced Instrument Ministry of EducationEast China Normal University State Key laboratory of precision Spectroscopy School of Physics and Electronic Science East China Normal University

Double carbohelicenes have attracted considerable attention due to their aesthetic structures, distinct π-conjugation extension, inherent chirality, and intriguing optical and electronic properties. Herein, the concise de novo synthesis of a new double[5]carbohelicene 1 together with its chiroptical properties, isomerization process and lasing application is presented. 1 was synthesized by a simple protocol involving the formation of a 6,6′-bipentacene as the key intermediate. It is worth noting that1 existed as two diastereomers 1-PP/MM and 1-PM, which were successfully isolated and unambiguously confirmed by Xray crystallography. The optical resolution of the racemic 1-PP/MM was successfully achieved by chiral-phase highperformance liquid chromatography（HPLC）, and 1-PP and 1-MM were characterized by circular dichroism. Interestingly, it was found that 1-PP/MM could be completely isomerized to 1-PM upon heating, and the detailed thermodynamics and kinetics of the isomerization process were systematically investigated. 1-PM exhibited deep-red luminescence with emission maximum at 723 nm and fluorescence quantum yield as high as 32.95%. Consequently, we can showcase the lasing application of 1-PM by doping with epoxy resin to assemble a bottle microlaser spontaneously, which the lasing wavelength is 796.6 nm at a threshold of 0.8 m J cm-2. We believe that our studies, including the facile synthesis methodology, detailed isomerization studies, and lasing application, will shed some light on the design and synthesis of novel carbohelical systems with more functions.

关键词： double carbohelicene optical resolution organic laser isomerization X-ray diffraction

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Pharmacogenomics of Drug Metabolizing Enzymes and Transporters:Relevance to precision medicine

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Genomics, Proteomics & Bioinformatics 2016年第5期14卷 298-313页

作者： Shabbir Ahmed Zhan Zhou Jie Zhou Shu-Qing Chen Department of precision medicine and Biopharmaceutics College of Pharmaceutical SciencesZhejiang University International Center for precision medicine Zhejiang California International Nano Systems Institute

The interindividual genetic variations in drug metabolizing enzymes and transporters influence the efficacy and toxicity of numerous drugs. As a fundamental element in precision med- icine, pharmacogenomics, the study of responses of individuals to medication based on their genomic information, enables the evaluation of some specific genetic variants responsible for an individual＇s particular drug response. In this article, we review the contributions of genetic polymorphisms to major individual variations in drug pharmacotherapy, focusing specifically on the pbarmacogenomics of phase-I drug metabolizing enzymes and transporters. Substantial frequency differences in key variants of drug metabolizing enzymes and transporters, as well as their possible functional consequences, have also been discussed across geographic regions. The current effort illustrates the common presence of variability in drug responses among individuals and across all geographic regions. This information will aid health-care professionals in prescribing the most appropriate treatment aimed at achieving the best possible beneficial outcomes while avoiding unwanted effects for a particular patient.

关键词： Pharmacogenomics precision medicine Genetic polymorphism Phase-I drug-metabolizingenzymes Drug transporters

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Real-Time Iterative Compensation Framework for precision Mechatronic Motion Control systems

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IEEE/CAA Journal of Automatica Sinica 2022年第7期9卷 1218-1232页

作者： Chuxiong Hu Ran Zhou Ze Wang Yu Zhu Masayoshi Tomizuka State Key laboratory of Tribology Department of Mechanical EngineeringTsinghua UniversityBeijing 100084 Beijing Key laboratory of precision/Ultra-precision Manufacture Equipments and Control Tsinghua UniversityBeijing 100084China Department of Mechanical Engineering University of CaliforniaBerkeleyCA 94720-1740 USA IEEE

With regard to precision/ultra-precision motion systems,it is important to achieve excellent tracking performance for various trajectory tracking tasks even under uncertain external *** this paper,to overcome the limitation of robustness to trajectory variations and external disturbances in offline feedforward compensation strategies such as iterative learning control(ILC),a novel real-time iterative compensation(RIC)control framework is proposed for precision motion systems without changing the inner closed-loop ***,the RIC method can be divided into two parts,i.e.,accurate model prediction and real-time iterative *** accurate prediction model considering lumped disturbances is firstly established to predict tracking errors at future sampling *** light of predicted errors,a feedforward compensation term is developed to modify the following reference trajectory by real-time iterative *** the prediction and compen-sation processes are finished in a real-time motion control sampling *** stability and convergence of the entire control system after real-time iterative compensation is analyzed for different *** simulation results consistently demonstrate that the proposed RIC framework possesses satisfactory dynamic regulation capability,which contributes to high tracking accuracy comparable to ILC or even better and strong robustness.

关键词： precision motion control prediction model real-time iterative compensation trajectory tracking

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High-precision tip positioning composite feedforward control of linear colocated motion systems with Bi-Loop iterative feedforward tuning

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Science China Technological Sciences 2025年

作者： Junyu HU Yourui TAO Shanhu LI Xu HAN College of Mechanical and Vehicle Engineering Hunan University State Key laboratory of Reliability and Intelligence of Electrical Equipment Hebei University of Technology

To enhance the tip positioning accuracy and robustness against disturbances of linear colocated motion systems, a novel composite feedforward (COMFF) control with Bi-Loop iterative feedforward tuning (IFFT) is proposed. The tip positioning error consists of the coupled tip residual vibration and linear motor tracking error. Given the influence of nonlinear friction and load flexibility, the topology of COMFF is designed as decoupled structures so that COMFF can suppress the tip residual vibration and compensate for the linear motor tracking error compatibly. Furthermore, Bi-Loop IFFT is built to improve the robustness of COMFF in high-precision motor tracking performance. In the state space of the linear motor tracking error based on the projection theorem, two loops are performed in parallel along the iteration direction. One is the P-type iteration loop that drives linear motor tracking errors to converge to the zero state. The other is the observation loop constructed by the recursive least square with forgetting factors to accelerate the P-type iteration loop. Driven by the P-type iteration loop with the aid of the observation loop, the proposed COMFF is integrated with fast convergence and high robustness when confronted with model disturbances. The effectiveness of the proposed COMFF combined with Bi-Loop IFFT is validated by experiments.

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Beyond Performance of Learning Control Subject to Uncertainties and Noise: A Frequency-Domain Approach Applied to Wafer Stages

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IEEE/CAA Journal of Automatica Sinica 2025年第1期 198-214页

作者： Fazhi Song Ning Cui Shuaiqi Chen Kai Zhang Yang Liu Xinkai Chen Jiubin Tan IEEE the Center of Ultra-precision Optoelectronic Instrument Engineering Harbin Institute of Technology the Key laboratory of Ultra-precision Intelligent Instrumentation Ministry of Industry and Information Technology the State Key laboratory of precision Electronic Manufacturing Technology and Equipment Guangdong University of Technology the Center of Ultraprecision Optoelectronic Instrument Engineering Harbin Institute of Technology the Key laboratory of Ultraprecision Intelligent Instrumentation Ministry of Industry and Information Technology the Department of Electronic and Information systems Shibaura Institute of Technology

The increasingly stringent performance requirement in integrated circuit manufacturing, characterized by smaller feature sizes and higher productivity, necessitates the wafer stage executing a extreme motion with the accuracy in terms of nanometers. This demanding requirement witnesses a widespread application of iterative learning control(ILC), given the repetitive nature of wafer scanning. ILC enables substantial performance improvement by using past measurement data in combination with the system model knowledge. However, challenges arise in cases where the data is contaminated by the stochastic noise, or when the system model exhibits significant uncertainties, constraining the achievable performance. In response to this issue, an extended state observer(ESO) based adaptive ILC approach is proposed in the frequency *** being model-based, it utilizes only a rough system model and then compensates for the resulting model uncertainties using an ESO, thereby achieving high robustness against uncertainties with minimal modeling effort. Additionally, an adaptive learning law is developed to mitigate the limited performance in the presence of stochastic noise, yielding high convergence accuracy yet without compromising convergence speed. Simulation and experimental comparisons with existing model-based and data-driven inversion-based ILC validate the effectiveness as well as the superiority of the proposed method.

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Targeting“undruggable”c-Myc protein by synthetic lethality

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Frontiers of medicine 2021年第4期15卷 541-550页

作者： Chen Wang Hui Fang Jiawei Zhang Ying Gu Division of Genome medicine and Cancer Institute(Key laboratory of Cancer Prevention and Intervention China National Ministry of Education)the Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China Institute of Genetics Zhejiang University and Department of GeneticsZhejiang University School of MedicineHangzhou 310058China zhejiang laboratory for systems&precision medicine Zhejiang University Medical CenterHangzhou 311121China

Synthetic lethal screening,which exploits the combination of mutations that result in cell death,is a promising method for identifying novel drug *** method provides a new avenue for targeting Uundruggable,9 proteins,such as ***,we revisit current methods used to target c-Myc and discuss the important functional nodes related to c-Myc in non-oncogene addicted network,whose inhibition may cause a catastrophe for tumor cell destiny but not for normal *** further discuss strategies to identify these functional nodes in the context of synthetic *** review the progress and shortcomings of this research field and look forward to opportunities offered by synthetic lethal screening to treat tumors potently.

关键词： synthetic lethality undruggable transcription factor c-Myc

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High-precision magnetic field measurement system based on a coherent population trapping magnetometer onboard the SATech-01 satellite

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Science China Technological Sciences 2025年

作者： Hongbo XUE Wei SONG Haoran ZHAO Yiteng ZHANG Shanzhi YE Jindong WANG Ran TAO Peng SANG Keli CHEN Xingzi BI Bingjun CHENG Bin ZHOU Yongliang XUE Yingying TANG Liu LIU Jinsong LI Xiaocheng ZHU Baoquan LI Jinguo LIU Wen CHEN Xiaofeng ZHANG Yonghe ZHANG Lei LI State Key laboratory of Space Weather National Space Science Center Chinese Academy of Sciences Key laboratory of Solar Activity and Space Weather National Space Science Center Chinese Academy of Sciences Key laboratory of Electronics and Information Technology for Space systems National Space Science Center Chinese Academy of Sciences State Key laboratory of Robotics Shenyang Institute of Automation Chinese Academy of Sciences Innovation Academy for Microsatellites Chinese Academy of Sciences

On July 27, 2022, a high-precision system for measuring the magnetic field based on a coherent population trapping magnetometer（referred to as the CPT system） was launched onboard the Space Advanced Technology demonstration satellite（SATech-01） by a ZK-1A rocket. The payload comprises a scalar coherent population trapping magnetometer（CPTM）, triaxial anisotropic magnetoresistance magnetometer（AMRM）, and nano star tracker mounted on a non-magnetic telescopic tubular mast. This configuration enables synchronized measurement of scalar and vector geomagnetic fields, as well as the attitude,making the payload with its compact sensors suitable for applications on miniature satellite platforms. On November 7, 2022,the novel telescopic tubular mast was deployed in orbit, extending to a length of 5.28 m. The CPTM, an absolute scalar magnetometer with an omnidirectional sensor, is the first China-developed quantum/atomic magnetometer successfully operating in space. In orbit, the CPTM has sensitivity of ～10 pT/Hz1/2and can automatically operate under complex magnetic field variations. The difference between the scalar fields obtained using the CPTM and CHAOS model has a mean deviation of–3.73 n T and a standard deviation of 26.11 nT（1σ）, without on-orbit calibration or correction. The miniaturized AMRM has a sensitivity of ～0.3 n T/Hz1/2and maintains stable and reliable operation in orbit. The low-power and miniaturized nano star tracker has a measurement uncertainty of 14.23″（1σ） in orbit. The mission has realized the on-orbit technical verification of the integrated and synchronized detection of the vector magnetic field and attitude and fully validated the system's performance,automation level, and reliability.

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Anomalous quality factor evolution of induced transparency in a virtualized coupled-oscillator system

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Science China(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 148-155页

作者： Yunhan Yang Han Jia Tuo Liu Yuzhen Yang Jun Yang Key laboratory of Noise and Vibration Research Institute of Acoustics Chinese Academy of Sciences University of Chinese Academy of Sciences State Key laboratory of Acoustics Institute of Acoustics Chinese Academy of Sciences

The phenomenon of induced transparency, characterized by a high quality(Q) factor, holds significant importance in the fields of high-precision sensing, energy storage and wave manipulation. Conventional transparency systems are often constrained by the limited experimentally accessible parameter space and the lack of independent control over intrinsic parameters, thereby hindering advanced research on high-Q effects. Here we propose a virtualized coupled-oscillator system that enables reconfigurable induced transparency in the reflection spectrum. By virtually incorporating a pair of coupled oscillators into an individual acoustic meta-atom, we achieve the manipulation of induced transparency in a decoupled, wide-ranging, and elaborate manner. Exploiting the diverse evolutions across the intrinsic parameter space, we show experimentally a counter-intuitive increase in the Q-factor of the transparency window, which is attributed to the enhanced dissipation of the bright ***, a constant group delay at the center frequency is observed accompanying this evolution. Our work demonstrates an intriguing platform as well as a novel strategy to engineer high-Q induced transparency phenomenon, and paves the way towards applications in programmable acoustic sensors, filters and slow-wave devices.

关键词： induced transparency acoustic meta-atom high quality-factor scattering programmable intrinsic parameter

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Combination of CRISPR/Cas9 System and CAR-T Cell Therapy:A New Era for Refractory and Relapsed Hematological Malignancies

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Current Medical Science 2021年第3期41卷 420-430页

作者： Ke-jia HU Elaine Tan Su YIN Yong-xian HU He HUANG Bone Marrow Transplantation Center the First Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310003China zhejiang Province Engineering laboratory for Stem Cell and Immunity Therapy Hangzhou 310003China Institute of Hematology Zhejiang UniversityHangzhou 310003China zhejiang laboratory for systems&precision medicine Zhejiang University Medical CenterHangzhou 310003China Liangzhu laboratory Zhejiang University Medical CenterHangzhou 311121China

Chimeric antigen receptor T(CAR-T)cell therapy is the novel treatment strategy for hematological malignancies such as acute lymphoblastic leukemia(ALL),lymphoma and multiple ***,treatment-related toxicities such as cytokine release syndrome(CRS)and immune effector cell-associated neurotoxicity syndrome(ICANS)have become significant hurdles to CAR-T *** strategies were established to alter the CAR structure on the genomic level to improve efficacy and reduce ***,the innovative gene-editing technology-clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated nuclease9(Cas9)system,which particularly exhibits preponderance in knock-in and knockout at specific sites,is widely utilized to manufacture CAR-T *** application of CRISPR/Cas9 to CAR-T cell therapy has shown promising clinical results with minimal *** this review,we summarized the past achievements of CRISPR/Cas9 in CAR-T therapy and focused on the potential CAR-T targets.

关键词： chimeric antigen receptor T cell treatment clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated nuclease9 gene editing immunotherapy hematologic malignancy

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