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Superior Fidelity and Distinct Editing Outcomes of SaCas9 Compared with SpCas9 in Genome Editing

Genomics, Proteomics & Bioinformatics 2023年第6期21卷 1206-1220页

作者： Zhi-Xue yang ya-wen fu Juan-Juan Zhao Feng Zhang Si-Ang Li Mei Zhao Wei wen Lei Zhang Tao Cheng Jian-Ping Zhang Xiao-Bing Zhang State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood DiseasesHaihe Laboratory of Cell EcosystemInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300020China Center for Stem Cell Medicine Chinese Academy of Medical SciencesTianjin 300020China Department of Stem Cell&Regenerative Medicine Peking Union Medical CollegeTianjin 300020China

A series of clustered regularly interspaced short palindromic repeats(CRISPR)-CRISPR associated protein 9(Cas9)systems have been engineered for genome *** most widely used Cas9 is SpCas9 from Streptococcus pyogenes and SaCas9 from Staphylococcus ***,a comparison of their detailed gene editing outcomes is still *** characterizing the editing outcomes of 11 sites in human induced pluripotent stem cells(iPSCs)and K562 cells,we found that SaCas9 could edit the genome with greater efficiencies than *** also compared the effects of spacer lengths of single-guide RNAs(sgRNAs;18–21 nt for SpCas9 and 19–23 nt for SaCas9)and found that the optimal spacer lengths were 20 nt and 21 nt for SpCas9 and SaCas9,***,the optimal spacer length for a particular sgRNA was 18–21 nt for SpCas9 and 21–22 nt for ***,SpCas9 exhibited a more substantial bias than SaCas9 for nonhomologous end-joining(NHEJ)+1 insertion at the fourth nucleotide upstream of the protospacer adjacent motif(PAM),indicating a characteristic of a staggered ***,editing with SaCas9 led to higher efficiencies of NHEJ-mediated double-stranded oligodeoxynucleotide(dsODN)insertion or homology-directed repair(HDR)-mediated adeno-associated virus serotype 6(AAV6)donor ***,GUIDE-seq analysis revealed that SaCas9 exhibited significantly reduced off-target effects compared with *** work indicates the superior performance of SaCas9 to SpCas9 in transgene integration-based therapeutic gene editing and the necessity to identify the optimal spacer length to achieve desired editing results.

关键词： SpCas9 SaCas9 Spacer length Indel pattern Knock-in efficiency Off-target

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HDAC inhibitors improve CRISPR-mediated HDR editing efficiency in iPSCs

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Science China(Life Sciences) 2021年第9期64卷 1449-1462页

作者： Jian-Ping Zhang Zhi-Xue yang Feng Zhang ya-wen fu Xin-Yue Dai Wei wen Beldon Zhang Hannah Choi Wanqiu Chen Meredith Brown David Baylink Lei Zhang Hongyu Qiu Charles Wang Tao Cheng Xiao-Bing Zhang State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood DiseasesInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300020China School of Medicine Loma Linda UniversityLoma LindaCA 92354USA Center for Genomics School of MedicineLoma Linda UniversityLoma LindaCA 92350USA CAMS Key Laboratory of Gene Therapy for Blood Diseases Tianjin 300020China Center for Stem Cell Medicine Chinese Academy of Medical SciencesTianjin 300020China Department of Stem Cell&Regenerative Medicine Peking Union Medical CollegeTianjin 300020China Tianjin Key Laboratory of Gene Therapy for Blood Diseases Tianjin 300020China Center of Molecular and Translational Medicine Institution of Biomedical ScienceGeorgia State UniversityAtlantaGA 30303USA

Genome-edited human induced pluripotent stem cells(iPSCs)hold great promise for therapeutic ***,low editing efficiency has hampered the applications of CRISPR-Cas9 technology in creating knockout and homology-directed repair(HDR)-edited iPSC lines,particularly for silent *** is partially due to chromatin compaction,inevitably limiting Cas9 access to the target *** the six HDAC inhibitors we examined,vorinostat,or suberoylanilide hydroxamic acid(SAHA),led to the highest HDR efficiency at both open and closed loci,with acceptable *** inhibitors equally increased non-homologous end joining(NHEJ)editing efficiencies(~50%)at both open and closed loci,due to the considerable HDAC inhibitor-mediated increase in Cas9 and sgRNA ***,we observed more substantial HDR efficiency improvement at closed loci relative to open chromatin(2.8 vs.1.7-fold change).These studies provide a new strategy for HDRediting of silent genes in iPSCs.

关键词： HDAC inhibitors CRISPR-Cas9 genome editing iPSC

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Goal-directed Fluid Therapy May Improve Hemodynamic Stability of Parturient with Hypertensive Disorders of Pregnancy Under Combined Spinal Epidural Anesthesia for Cesarean Delivery and the Well-being of Newborns

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Chinese Medical Journal 2015年第14期128卷 1922-1931页

作者： Wei Xiao Qing-Fang Duan wen-ya fu Xin-Zuo Chi Feng-Ying Wang Da-Qing Ma Tian-Long Wang Lei Zhao Department of Anesthesiology Xuan Wu Hospital Capital Medical University Beijing 100053 China Department of Obstetrics and Gynecology Xuan Wu Hospital Capital Medical University Beijing 100053 China Department of Surgery and Cancer Pain Medicine and Intensive Care Faculty of Medicine Chelsea and Westminster Hospital Imperial College London United Kingdom

Background： Hypotension induced by combined spinal epidural anesthesia in parturient with hypertensive disorders of pregnancy （HDP） can easily compromise blood supply to vital organs including uteroplacental perfusion and result in fetal distress. The aim of this study was to investigate whether the goal-directed fluid therapy （GDFT） with LiDCOrapid system can improve well-being of both HDP parturient and their babies. Methods： Fifty-two stable HDP parturient scheduled for elective cesarean delivery were recruited. After loading with 10 ml/kg lactated Ringer＇s solution （LR）, parturient were randomized to the GDFT and control group. In the GDFT group, individualized fluid therapy was guided by increase in stroke volume （ASV） provided via LiDCO rapid system. The control group received the routine fluid therapy. The primary endpoints included maternal hypotension and the doses of vasopressors administered prior to fetal delivery. The secondary endpoints included umbilical blood gas abnormalities and neonatal adverse events. Results： The severity of HDP was similar between two groups. The total LR infusion （P 〈 0.01） and urine output （P 〈 0.05） were higher in the GDFT group than in the control group. Following twice fluid challenge tests, the systolic blood pressure, mean blood pressure, cardiac output and SV in the GDFT group were significantly higher, and the heart rate was lower than in the control group. The incidence of maternal hypotension and doses of phenylephrine used prior to fetal delivery were significantly higher in the control group than in the GDFT group （P 〈 0.01）. There were no differences in the Apgar scores between two groups. In the control group, the mean values of pH in umbilical artery/vein were remarkably decreased （P 〈 0.05）, and the incidences of neonatal hypercapnia and hypoxemia were statistically increased （P 〈 0.05） than in the GDFT group. Conclusions： Dynamic responsiveness guided fluid therapy with the LiDCOrapid system may provide po

关键词： Cesarean Delivery Fluid Therapy Hypertensive Disorders of Pregnancy LiDCOrapid System Parturient

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岛礁建筑物耐久性综合治理初探

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施工技术 2006年第S1期35卷 177-178,180页

作者：许亚文符超南方工程建设局广东湛江524002

通过采取在混凝土中掺加钢筋阻锈剂、改性聚酯纤维、高效减水剂及絮凝剂,在混凝土结构表面涂刷防水涂层等措施,对混凝土耐久性进行综合治理,显著改善了海洋环境条件下建筑物的抗腐蚀性能。

关键词：混凝土耐久性海洋环境,阻锈剂减水剂

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Reducing the measurement errors in nonadiabatic holonomic quantum computers

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Science China(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 64-70页

作者： Guo-fu Xu Department of Physics Shandong University

Nonadiabatic holonomic quantum computers serve as the physical platform for nonadiabatic holonomic quantum *** quantum computation has entered the noisy intermediate-scale era, building accurate intermediate-scale nonadiabatic holonomic quantum computers is clearly necessary. Given that measurements are the sole means of extracting information, they play an indispensable role in nonadiabatic holonomic quantum computers. Accordingly, developing methods to reduce measurement errors in nonadiabatic holonomic quantum computers is of great importance. However, while much attention has been given to the research on nonadiabatic holonomic gates, the research on reducing measurement errors in nonadiabatic holonomic quantum computers is severely lacking. In this study, we propose a measurement error reduction method tailored for intermediate-scale nonadiabatic holonomic quantum computers. The reason we say this is because our method can not only reduce the measurement errors in the computer but also be useful in mitigating errors originating from nonadiabatic holonomic gates. Given these features,our method significantly advances the construction of accurate intermediate-scale nonadiabatic holonomic quantum computers.

关键词： quantum holonomy quantum computation measurement errors

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Loss Aware Feature Attention Mechanism for Class and Feature Imbalance Issue

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Computers, Materials & Continua 2025年第1期82卷 751-775页

作者： Yuewei Wu Ruiling fu Tongtong Xing fulian Yin College of Information and Communication Engineering Communication University of ChinaBeijing100024China State Key Laboratory of Media Convergence and Communication Communication University of ChinaBeijing100024China

In the Internet era,recommendation systems play a crucial role in helping users find relevant information from large *** imbalance is known to severely affect data quality,and therefore reduce the performance of recommendation *** to the imbalance,machine learning algorithms tend to classify inputs into the positive(majority)class every time to achieve high prediction *** can be categorized such as by features and classes,but most studies consider only class *** this paper,we propose a recommendation system that can integrate multiple networks to adapt to a large number of imbalanced features and can deal with highly skewed and imbalanced datasets through a loss *** propose a loss aware feature attention mechanism(LAFAM)to solve the issue of feature *** network incorporates an attention mechanism and uses multiple sub-networks to classify and learn *** better results,the network can learn the weights of sub-networks and assign higher weights to important *** propose suppression loss to address class imbalance,which favors negative loss by penalizing positive loss,and pays more attention to sample points near the decision *** on two large-scale datasets verify that the performance of the proposed system is greatly improved compared to baseline methods.

关键词： Imbalanced data deep learning e-commerce recommendation loss function big data analysis

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Advancements and Challenges in Organic–Inorganic Composite Solid Electrolytes for All‑Solid‑State Lithium Batteries

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Nano-Micro Letters 2025年第1期17卷 46-97页

作者： Xueyan Zhang Shichao Cheng Chuankai fu Geping Yin Liguang Wang Yongmin Wu Hua Huo State Key Laboratory of Space Power‑Sources School of Chemistry and Chemical EngineeringHarbin Institute of TechnologyHarbin 150001People’s Republic of China College of Chemical and Biological Engineering Zhejiang UniversityHangzhou 310058People’s Republic of China State Key Laboratory of Space Power-Sources 2965 Dongchuan RoadMinhang DistrictShanghai 200240People’s Republic of China

To address the limitations of contemporary lithium-ion batteries,particularly their low energy density and safety concerns,all-solid-state lithium batteries equipped with solid-state electrolytes have been identified as an up-and-coming *** the various SEs,organic–inorganic composite solid electrolytes(OICSEs)that combine the advantages of both polymer and inorganic materials demonstrate promising potential for large-scale ***,OICSEs still face many challenges in practical applications,such as low ionic conductivity and poor interfacial stability,which severely limit their *** review provides a comprehensive overview of recent research advancements in ***,the influence of inorganic fillers on the main functional parameters of OICSEs,including ionic conductivity,Li+transfer number,mechanical strength,electrochemical stability,electronic conductivity,and thermal stability are systematically *** lithium-ion conduction mechanism of OICSE is thoroughly analyzed and concluded from the microscopic ***,the classic inorganic filler types,including both inert and active fillers,are categorized with special emphasis on the relationship between inorganic filler structure design and the electrochemical performance of ***,the advanced characterization techniques relevant to OICSEs are summarized,and the challenges and perspectives on the future development of OICSEs are also highlighted for constructing superior ASSLBs.

关键词： Composite solid electrolytes Inorganic filler Interfacial stability Li-ion conduction mechanism Characterization techniques

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Quantum public-key crypto via EPR pairs

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Science China(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 58-63页

作者： Xiang-Qun fu Hong-Wei Li Jian-Hong Shi Tan Li Wan-Su Bao Henan Key Laboratory of Quantum Information and Cryptography Information Engineering University Synergetic Innovation Center of Quantum Information and Quantum Physics University of Science and Technology of China

With the development of quantum computing technology, quantum public-key cryptography is gradually becoming an alternative to the existing classical public-key cryptography. This paper designs a quantum trapdoor one-way function via EPR pairs and quantum measurements. Based on this, a new quantum public-key cryptosystem is presented, which offers forward security,and can resist the chosen-plaintext attack and chosen-ciphertext attack. Compared with the existing quantum public-key cryptos,eavesdropping can be automatically detected in this new quantum public-key cryptosystem under a necessary condition, which is also detailed in the paper.

关键词： quantum public-key crypto trapdoor one-way function EPR pairs

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Bidirectional regulation of the brain-gut-microbiota axis following traumatic brain injury

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Neural Regeneration Research 2025年第8期20卷 2153-2168页

作者： Xinyu You Lin Niu Jiafeng fu Shining Ge Jiangwei Shi yanjun Zhang Pengwei Zhuang National Key Laboratory of Chinese Medicine Modernization Tianjin University of Traditional Chinese MedicineTianjinChina Haihe Laboratory of Modern Chinese Medicine Tianjin University of Traditional Chinese MedicineTianjinChina First Teaching Hospital of Tianjin University of Traditional Chinese Medicine TianjinChina National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion TianjinChina

Traumatic brain injury is a prevalent disorder of the central nervous *** addition to primary brain parenchymal damage,the enduring biological consequences of traumatic brain injury pose long-term risks for patients with traumatic brain injury;however,the underlying pathogenesis remains unclear,and effective intervention methods are *** dysfunction is a significant consequence of traumatic brain *** the most densely innervated peripheral tissue in the body,the gut possesses multiple pathways for the establishment of a bidirectional“brain-gut axis”with the central nervous *** gut harbors a vast microbial community,and alterations of the gut niche contribute to the progression of traumatic brain injury and its unfavorable prognosis through neuronal,hormonal,and immune pathways.A comprehensive understanding of microbiota-mediated peripheral neuroimmunomodulation mechanisms is needed to enhance treatment strategies for traumatic brain injury and its associated *** comprehensively reviewed alterations in the gut microecological environment following traumatic brain injury,with a specific focus on the complex biological processes of peripheral nerves,immunity,and microbes triggered by traumatic brain injury,encompassing autonomic dysfunction,neuroendocrine disturbances,peripheral immunosuppression,increased intestinal barrier permeability,compromised responses of sensory nerves to microorganisms,and potential effector nuclei in the central nervous system influenced by gut ***,we reviewed the mechanisms underlying secondary biological injury and the dynamic pathological responses that occur following injury to enhance our current understanding of how peripheral pathways impact the outcome of patients with traumatic brain *** review aimed to propose a conceptual model for future risk assessment of central nervous system-related diseases while elucidating novel insights into the bidirectional effec

关键词： traumatic brain injury brain-gut-microbiome axis gut microbiota neuroimmune immunosuppression host defense vagal afferents bacterial infection dorsal root ganglia nociception neural circuitry

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Dynamical Algebras in the 1+1 Dirac Oscillator and the Jaynes–Cummings Model

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Chinese Physics Letters 2020年第5期37卷 1-4页

作者： wen-ya Song fu-Lin Zhang Department of Physics School of ScienceTianjin UniversityTianjin 300072

We study the algebraic structure of the one-dimensional Dirac oscillator by extending the concept of spin symmetry to a noncommutative *** SO(4)algebra is found connecting the eigenstates of the Dirac oscillator,in wh... 详细信息

关键词： Dirac oscillator Cummings

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