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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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Application of Dorzagliatin in peritoneal dialysis patients with type 2 diabetes mellitus:A case report

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World Journal of Diabetes 2025年第1期16卷 204-210页

作者： Fang Chen Bo An wen-Cheng An Gang fu Wei Huang Hui-Xian yan Department of Endocrinology Beijing Haidian HospitalBeijing 100080China Department of Nephrology Beijing Haidian HospitalBeijing Haidian Section of Peking University Third HospitalBeijing 100080China

BACKGROUND Treating diabetes in dialysis patients remains a challenge,with many hypoglycemic drugs requiring dose adjustments or avoidance in these *** SUMMARY This report describes an 83-year-old female patient with a 30-year history of type 2 diabetes(T2DM)who had struggled to control her blood sugar for more than a *** had a history of high blood pressure for 30 years,had undergone continuous ambulatory peritoneal dialysis for more than two years,was 163 cm tall,weighed 77 kg,and had a body mass index of 28.98 kg/*** intensive insulin therapy at a daily dose of 150 units,adding Dorzagliatin at a dosage of 75 mg orally twice daily led to immediate blood sugar improvement and a gradual reduction in insulin *** one month of follow-up,the fasting plasma glucose was 6-8 mmol/L,and the 2-hour postprandial glucose was 8-12 mmol/*** To our knowledge,this report is the first to use Dorzagliatin to treat type 2 diabetes peritoneal dialysis patients with challenging glucose ***,a novel glucokinase activator primarily metabolized by the liver,exhibits no pharmacokinetic differences among patients with varying degrees of chronic kidney *** has a high plasma protein binding rate and may not be cleared by peritoneal dialysis,potentially offering a new glycemic control option for Type 2 diabetic patients on peritoneal dialysis.

关键词： Dorzagliatin Type 2 diabetes mellitus Peritoneal dialysis Glucokinase activator Glucose control Case report

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Prediction and stratification for the surgical adverse events after minimally invasive esophagectomy:A two-center retrospective study

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World Journal of Gastroenterology 2025年第3期31卷 50-61页

作者： Qi-Hong Zhong Jiang-Shan Huang Fei-Long Guo Jing-Yu Wu Mao-Xiu Yuan Jia-fu Zhu wen-Wei Lin Sui Chen Zhen-yang Zhang Jiang-Bo Lin Department of Thoracic Surgery Fujian Medical University Union HospitalFuzhou 350001Fujian ProvinceChina The Graduate School Fujian Medical UniversityFuzhou 350001Fujian ProvinceChina Department of Thoracic Surgery Affiliated Hospital of Jinggangshan UniversityJi’an 343000Jiangxi ProvinceChina

BACKGROUND Minimally invasive esophagectomy(MIE)is a widely accepted treatment for esophageal cancer,yet it is associated with a significant risk of surgical adverse events(SAEs),which can compromise patient recovery and long-term *** preoperative identification of high-risk patients is critical for improving *** To establish and validate a risk prediction and stratification model for the risk of SAEs in patients with *** This retrospective study included 747 patients who underwent MIE at two centers from January 2019 to February *** were separated into a train set(n=549)and a validation set(n=198).After screening by least absolute shrinkage and selection operator regression,multivariate logistic regression analyzed clinical and intraoperative variables to identify independent risk factors for SAEs.A risk stratification model was constructed and validated to predict the probability of *** SAEs occurred in 10.2%of patients in train set and 13.6%in the validation *** with SAE had significantly higher complication rate and a longer hospital stay after *** key independent risk factors identified included chronic obstructive pulmonary disease,a history of alcohol consumption,low forced expiratory volume in the first second,and low albumin *** stratification model has excellent prediction accuracy,with an area under the curve of 0.889 for the training set and an area under the curve of 0.793 for the validation *** The developed risk stratification model effectively predicts the risk of SAEs in patients undergoing MIE,facilitating targeted preoperative interventions and improving perioperative management.

关键词： Surgical adverse events Minimally invasive esophagectomy Esophageal cancer Stratification model Perioperative management

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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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Hot Deformation and Dynamic Recrystallization Behavior of Austenite-Based Low-Density Fe–Mn–Al–C Steel

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Acta Metallurgica Sinica(English Letters) 2016年第5期29卷 441-449页

作者： ya-Ping Li Ren-Bo Song Er-Ding wen fu-Qiang yang School of Materials Science and Engineering University of Science and Technology BeijingBeijing 100083China R&D Center BAIC Motor Corporation LTDBeijing 101300China

The hot deformation and dynamic recrystallization （DRX） behavior of austenite-based Fe-27Mn-ll.5A1- 0.95C steel with a density of 6.55 g cm-3 were investigated by compressive deformation at the temperature range of 900-1150 ℃ and strain rate of 0.01-10 s-1. Typical DRX behavior was observed under chosen deformation conditions and yield-point-elongation-like effect caused by DRX of 6-ferrite. The flow stress characteristics were determined by DRX of the 6-ferrite at early stage and the austenite at later stage, respectively. On the basis of hyperbolic sine function and linear fitting, the calculated thermal activation energy for the experimental steel was 294.204 kJ mo1-1. The occurrence of DRX for both the austenite and the 6-ferrite was estimated and plotted by related Zener-Hollomon equations. A DRX kinetic model of the steel was established by flow stress and peak strain without considering dynamic recovery and 6-ferrite DRX. The effects of deformation temperature and strain rate on DRX volume fraction were discussed in detail. Increasing deformation temperature or strain rate contributes to DRX of both the austenite and the 6-ferrite, whereas a lower strain rate leads to the austenite grains growth and the 6-ferrite evolution, from banded to island-like structure.

关键词： Fe-Mn-AI-C steel Hot deformation Dynamic recrystallization Yield-point-elongation-likeeffect

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Landslide distribution and sliding mode control along the Anninghe fault zone at the eastern edge of the Tibetan Plateau

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Journal of Mountain Science 2021年第8期18卷 2094-2107页

作者： ZHOU Hong-fu LIU Bin YE Fei fu wen-xi TANG wen-qing QIN ya-dong FANG Tian Chengdu Center China Geological SurveyChengdu610081China Sichuan Geological Survey Chengdu610081China State Key Laboratory of Hydraulics and Mountain Rivers Protection Sichuan UniversityChengdu610065China College of Earth Science and Engineering Shandong University of Science and TechnologyQingdao266590China

Tibetan Plateau is known as the roof of the *** to the continuous uplift of the Tibetan Plateau,many active fault zones are *** active fault zones such as the Anninghe fault zone have a significant influence on the formation of special geomorphology and the distribution of geological hazards at the eastern edge of the Tibetan *** Anninghe fault zone is a key part of the Y-shaped fault pattern in the Sichuan-Yunnan block of *** this paper,high-resolution topographic data,multitemporal remote sensing images,numerical calculations,seismic records,and comprehensive field investigations were employed to study the landslide distribution along the active part of the *** influence of active faults on the lithology,rock mass structures and slope stress fields were also *** results show that the faults within the Anninghe fault zone have damaged the structure and integrity of the slope rock mass,reduced the mechanical strength of the rock mass and controlled the slope failure *** faults have also controlled the stress field,the distribution of the plastic strain zone and the maximum shear strain zone of the slope,thus have promoted the formation and evolution of *** find that the studied landslides are linearly distributed along the Anninghe fault zone,and more than 80%of these landslides are within 2–3 km of the fault rupture ***,the Anninghe fault zone provides abundant substance for landslides or debris *** paper presents four types of sliding mode control of the Anninghe fault zone,e.g.,constituting the whole landslide body,controlling the lateral boundary of the landslide,controlling the crown of the landslide,and constituting the toe of the *** results presented merit close attention as a valuable reference source for local infrastructure planning and engineering projects.

关键词： Tibetan Plateau Anninghe fault zone Landslide distribution Sliding mode control

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Dielectric analysis on phase transition and micelle shape of polyoxyethylene trisiloxane surfactant in dilute aqueous solution

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Chinese Chemical Letters 2011年第6期22卷 745-748页

作者： ya wen Zhou Wei Zhou fu Han Bao Cai Xu School of Chemistry and Environmental Engineering Beijing Technology and Business University Beijing 100048 China

The cloudy Silwet L-77 aqueous solution on the concentration range from 0.5%to 50%was investigated by dielectric relaxation *** concentration dependence of phase microstructure was confirmed by means of analyzing the dielectric parameters of bulk *** relaxation behavior was assigned to the interfacial polarization between the micelle and the medium,and the relaxation distribution parameter was used to figure the shape transition from sphere to ellipsoid with the concentration *** synchronous reduction of permittivity and conductivity indicated the formation of the lamellar phase. As compensation,the quantity of the surfactant liquid phase gradually decreased,whose shape constantly kept ellipsoidal.

关键词： Dielectric relaxation Siloxane surfactant Cloudy state Phase microstructure

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