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In vivo evaluation of guide-free Cas9-induced safety risks in a pig model

Signal Transduction and Targeted Therapy 2024年第8期9卷 3493-3506页

作者： Weikai Ge Shixue Gou Xiaozhu zhao Qin Jin Zhenpeng Zhuang Yu zhao Yanhui liang Zhen Ouyang Xiaoyi Liul Fangbing Chen Hui Shi Haizhao Yan Han Wu liangxue Lai Kepin Wang china-New Zealand Joint Laboratory on Biomedicine and Health CAS Key Laboratory of Regenerative BiologyGuangdong Provincial Key Laboratory of Stem Cell and Regenerative MedicineJoint School of Life SciencesGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou Medical UniversityGuangzhou 510530China Sanya institute of Swine resource Hainan Provincial Research Center of Laboratory AnimalsSanya 572000China Guangdong Provincial Key Laboratory of Large Animal models for Biomedicine Wuyi UniversityJiangmen 529020China Guangzhou National Laboratory Guangzhou 510005China Suniversity of Chinese Academy of sciences 100049 BeijingChina Research Unit of Generation of Large Animal Disease Models Chinese Academy of Medical Sciences(2019RU015)Guangzhou 510530China

The CRISPR/Cas9 system has shown great potential for treating human genetic diseases through gene ***,there are concerns about the safety of this system,specifically related to the use of guide-free *** studies have shown that guidefree Cas9 can induce genomic instability in ***,the in vivo safety risks associated with guide-free Cas9 have not been evaluated,which is necessary for the development of gene therapy in clinical *** this study,we used doxycycline-inducible Cas9-expressing pigs to evaluate the safety risks of guide-free Cas9 in *** findings demonstrated that expression of guide-free Cas9 could induce genomic damages and transcriptome changes in *** severity of the genomic damages and transcriptome changes were correlate with the expression levels of Cas9 ***,prolonged expression of Cas9 in pigs led to abnormal phenotypes,including a significant decrease in body weight,which may be attributable to genomic damage-induced nutritional absorption and metabolic ***,we observed an increase in whole-genome and tumor driver gene mutations in pigs with long-term Cas9 expression,raising the risk of tumor *** in vivo evaluation of guide-free Cas9 in pigs highlights the necessity of considering and monitoring the detrimental effects of Cas9 alone as genome editing via the CRISPR/Cas9 system is implemented in clinical gene *** research emphasizes the importance of further study and implementation of safety measures to ensure the successful and safe application of the CRiSPR/Cas9 system in clinical practice.

关键词： CRISPR/Cas9 vivo alone

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Deep learning-based inpainting of saturation artifacts in optical coherence tomography images

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Journal of Innovative Optical Health sciences 2024年第3期17卷 1-10页

作者： Muyun Hu Zhuoqun Yuan Di Yang Jingzhu zhao Yanmei liang Institute of Modern Optics Nankai UniversityTianjin Key Laboratory of Micro-scale Optical Information Science and TechnologyTianjin 300350China Department of Thyroid and Neck Tumor Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjin 300060China

Limited by the dynamic range of the detector,saturation artifacts usually occur in optical coherence tomography(OCT)imaging for high scattering *** available methods are difficult to remove saturation artifacts and restore texture completely in OCT *** proposed a deep learning-based inpainting method of saturation artifacts in this *** generation mechanism of saturation artifacts was analyzed,and experimental and simulated datasets were built based on the *** super-resolution generative adversarial networks were trained by the clear–saturated phantom image *** perfect reconstructed results of experimental zebrafish and thyroid OCT images proved its feasibility,strong generalization,and robustness.

关键词： Optical coherence tomography saturation artifacts deep learning image inpainting.

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Double-ended passivator enables dark-current-suppressed colloidal quantum dot photodiodes for CMOS-integrated infrared imagers

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InfoMat 2024年第1期6卷 108-122页

作者： Peilin Liu Shuaicheng Lu Jing Liu Bing Xia Gaoyuan Yang Mo Ke Xuezhi zhao Junrui Yang Yuxuan Liu Ciyu Ge Guijie liang Wei Chen Xinzheng Lan Jianbing Zhang liang Gao Jiang Tang Wuhan National Laboratory for Optoelectronics(WNLO)and School of Optical and Electronic Information Huazhong University of Science and TechnologyWuhanthe People's Republic of China Wenzhou Advanced Manufacturing Technology Institute Huazhong University of Science and TechnologyWenzhouthe People's Republic of China School of Physics and Electronic Engineering Hubei University of Arts and ScienceXiangyangthe People's Republic of China School of Integrated Circuits Huazhong University of Science and TechnologyWuhanthe People's Republic of China School of Engineering Physics Shenzhen Technology UniversityShenzhenthe People's Republic of China Optics Valley Laboratory Wuhanthe People's Republic of China Shenzhen Huazhong university of Science and Technology Research Institute Shenzhenthe People's Republic of China

Lead sulfide(PbS)colloidal quantum dot(CQD)photodiodes integrated with silicon-based readout integrated circuits(ROICs)offer a promising solution for the next-generation short-wave infrared(SWIR)imaging *** their potential,large-size CQD photodiodes pose a challenge due to high dark currents resulting from surface states on nonpassivated(100)facets and trap states generated by CQD *** this work,we present a novel approach to address this issue by introducing double-ended ligands that supplementally passivate(100)facets of halidecapped large-size CQDs,leading to suppressed bandtail states and reduced defect *** results demonstrate that the dark current density is highly suppressed by about an order of magnitude to 9.6 nA cm^(2) at -10 mV,which is among the lowest reported for PbS CQD ***,the performance of the photodiodes is exemplary,yielding an external quantum efficiency of 50.8%(which corresponds to a responsivity of 0.532 A W^(-1))and a specific detectivity of 2.5×10^(12) Jones at 1300 *** integrating CQD photodiodes with CMOS ROICs,the CQD imager provides high-resolution(640×512)SWIR imaging for infrared penetration and material discrimination.

关键词： CMOS integration colloidal quantum dots dark current suppression double-ended passivation infrared imager

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Recent advances in core-shell organic framework-based photocatalysts for energy conversion and environmental remediation

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Journal of Energy Chemistry 2024年第8期95卷 168-199,I0004页

作者： Qibing Dong Ximing Li Yanyan Duan Qingyun Tian Xinxin liang Yiyin Zhu Lin Tian Junjun Wang Atif Sial Yongqian Cui Ke zhao Chuanyi Wang School of Environmental Science and Engineering Shaanxi University of Science and TechnologyXi’an 710021ShaanxiChina Guangdong Engineering Technology Research center for Environmental Purification and Functional Materials Guangzhou Institute of Industrial IntelligenceGuangzhou 511400GuangdongChina Jiangxi Key Lab of Flexible Electronics Flexible Electronics Innovation InstituteJiangxi Science and Technology Normal UniversityNanchang 330013JiangxiChina Helmholtz-Zentrum Berlin für Materialien und Energie Kekuléstraße 512489 BerlinGermany

Direct conversion of solar energy into chemical energy in an environmentally friendly manner is one of the most promising strategies to deal with the environmental pollution and energy *** a variety of materials developed as photocatalysts,the core-shell metal/covalent-organic framework(MOF or COF)photocatalysts have garnered significant attention due to their highly porous structure and the adjustability in both structure and *** existing reviews on core-shell organic framework photocatalytic materials have mainly focused on core-shell MOF ***,there is still a lack of indepth reviews specifically addressing the photocatalytic performance of core-shell COFs and MOFs@***,there is an urgent need for a comprehensive review encompassing these three types of core-shell *** on this,this review aims to provide a comprehensive understanding and useful guidelines for the exploration of suitable core-shell organic framework photocatalysts towards appropriate photocatalytic energy conversion and environmental ***,the classification,synthesis,formation mechanisms,and reasonable regulation of core-shell organic framework were ***,the photocatalytic applications of these three kinds of core-shell structures in different areas,such as H_(2)evolution,CO_(2)reduction,and pollutants degradation are ***,the main challenges and development prospects of core-shell organic framework photocatalysts were *** review aims to provide insights into the development of a novel generation of efficient and stable core-shell organic framework materials for energy conversion and environmental remediation.

关键词： Organic framework Core-shell structure Photocatalysis Energy conversion Environmental remediation

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Atomic-Scale Insights into Damage Mechanisms of GGr15 Bearing Steel Under Cyclic Shear Fatigue

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Acta Metallurgica Sinica(English Letters) 2024年第7期37卷 1265-1278页

作者： Qiao-Sheng Xia Dong-Peng Hua Qing Zhou Ye-Ran Shi Xiang-Tao Deng Kai-Ju Lu Hai-Feng Wang Xiu-Bing liang zhao-Dong Wang State Key Laboratory of Solidification Processing Center of Advanced Lubrication and Seal MaterialsNorthwestern Polytechnical UniversityXi’an710072China State Key Laboratory of Rolling and Automation Northeastern UniversityShenyang110819China Defense Innovation Institute Academy of Military ScienceBeijing100071China

Alternating shear stress is a critical factor in the accumulation of damage during rolling contact fatigue,severely limiting the service life of ***,the specific mechanisms responsible for the cyclic shear fatigue damage in bearing steel have not been fully *** the mechanical response and microstructural evolution of a model GGr15 bearing steel under cyclic shear loading are investigated through the implementation of molecular dynamics *** samples undergo 30 cycles under three different loading conditions with strains of 6.2%,9.2%,and 12.2%,*** findings indicate that severe cyclic shear deformation results in early cyclic softening and significant accumulation of plastic damage in the bearing ***,samples subjected to higher strain-controlled loading exhibit higher plastic strain energy and shorter fatigue ***,strain localization is identified as the predominant damage mechanism in cyclic shear fatigue of the bearing steel,which accumulates and ultimately results in fatigue ***,simulation results also revealed the microstructural reasons for the strain localization(e.g.,BCC phase transformation into FCC and HCP phase),which well explained the formation of white etching *** study provides fresh atomic-scale insights into the mechanisms of cyclic shear fatigue damage in bearing steels.

关键词： Cyclic shear fatigue Molecular dynamic simulation Bearing steels Plastic damage accumulation

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A Pt/CeO_(2)Hybrid Nanozyme with Stable Peroxidase Activity for the Detection of Acetylcholine

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Chemical Research in Chinese Universities 2024年第2期40卷 268-271页

作者： CUI Xulian MA Baofu PAN Hui XIA Yu LIU Li zhao Baofeng liang Zhen ZHANG Lihua ZHANG Yukui State Key Laboratory of Medical Proteomics Dalian Institute of Chemical PhysicsChinese Academy of ScienceDalian116023P.R.China The Research center for Medical Genomics Key Laboratory of Medical Cell BiologyMinistry of EducationSchool of Life ScienceChina Medical UniversityShenyang110001P.R.China River Fisheries Research Institute Chinese Academy of Fishery SciencesGuangzhou510000P.R.China

Acetylcholine(ACh)is a common neurotransmitterl)that is secreted by cholinergic neurons[2]and is found mainly in the peripheral and central nervous systems.[3]ACh transmits nerve signals from presynaptic to postsynapt... 详细信息

关键词： Acetylcholine/choline Nanozyme Hydrogen peroxide Alzheimer’s disease

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Cisplatin-based miRNA delivery strategy inspired by the circCPNE1/miR-330-3p pathway for oral squamous cell carcinoma

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2748-2760页

作者： Hua-yang Fan Ming-da zhao Hong-jie Jiang Zhen-wei Yu Yu-jiang Fan Xin-hua liang Ya-ling Tang Yong Sun State Key Laboratory of Oral Diseases&National center for Stomatology&National Clinical Research center for Oral Diseases&Department of Oral and Maxillofacial Surgery West China Hospital of StomatologySichuan UniversityChengdu 610041China National Engineering Research center for Biomaterials Sichuan UniversityChengdu 610065China State Key Laboratory of Oral Diseases&National center for Stomatology&National Clinical Research center for Oral Diseases&Department of Oral Pathology West China Hospital of StomatologySichuan UniversityChengdu 610041China

Circular RNAs(circRNAs)are ideal biomarkers of oral squamous cell carcinoma(OSCC)because of their highly stable closed-loop structure,and they can act as microRNA(miRNA)sponges to regulate OSCC *** analyzing clinical samples,we identified circCPNE1,a dysregulated circRNA in OSCC,and its expression level was negatively correlated with the clinical stage of OSCC ***-of-function assays revealed the tumor-suppressive effect of circCPNE1,which was then identified as a miR-330-3p ***-330-3p was recognized as a tumor promoter in multiple studies,consistent with our finding that it could promote the proliferation,migration,and invasion of OSCC *** results indicated that selective inhibition of miR-330-3p could be an effective strategy to inhibit OSCC ***,we designed cationic polylysine-cisplatin prodrugs to deliver antagomiR-330-3p(a miRNA inhibitory analog)via electrostatic interactions to form PP@miR nanoparticles(NPs).Paratumoral administration results revealed that PP@miR NPs effectively inhibited subcutaneous tumor progression and achieved partial tumor elimination(2/5),which confirmed the critical role of miR-330-3p in OSCC *** findings provide a new perspective for the development of OSCC treatments.

关键词： Oral squamous cell carcinoma CircRNA MiRNA sponge Antagomir MiRNA delivery Cisplatin-based nanoparticles Drug delivery systems Tumor elimination

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Identification of LRRC46 as a novel candidate gene for high myopia

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Science china(Life sciences) 2024年第9期67卷 1941-1956页

作者： Lingxi Jiang Chao Dai Yao Wei Bo zhao Qi Li Zhengzheng Wu liang Zou Zimeng Ye Zhenglin Yang Lulin Huang Yi Shi Sichuan Provincial Key Laboratory for Human Disease Gene Study and the center for Medical Genetics Department of Laboratory MedicineSichuan Academy of Medical Sciences&Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengdu 610072China Department of Ophthalmology Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengdu 610072China Research Unit for Blindness Prevention of Chinese Academy of Medical sciences(2019RU026) Sichuan Academy of Medical Sciences&Sichuan Provincial People’s HospitalChengdu 610072China School of Food and Bioengineering Chengdu UniversityChengdu 610106China School of Medicine University of SydneySydney 2050Australia Jinfeng Laboratory Chongging 400000China

High myopia(HM)is the primary cause of blindness,with the microstructural organization and composition of collagenous fibers in the cornea and sclera playing a crucial role in the biomechanical behavior of these *** a previously reported myopic linkage region,MYP5(17q21-22),a potential candidate gene,LRRC46(c.C235T,p.Q79X),was identified in a large Han Chinese ***46 is expressed in various eye tissues in humans and mice,including the retina,cornea,and *** subsequent cell experiments,the mutation(c.C235T)decreased the expression of LRRC46 protein in human corneal epithelial cells(HCE-T).Further investigation revealed that Lrrc46^(-/-)mice(KO)exhibited a classical myopia *** thickness of the cornea and sclera in KO mice became thinner and more pronounced with age,the activity of limbal stem cells decreased,and microstructural changes were observed in the fibroblasts of the sclera and *** performed RNA-seq on scleral and corneal tissues of KO and normal control wild-type(WT)mice,which indicated a significant downregulation of the collagen synthesis-related pathway(extracellular matrix,ECM)in KO *** in vitro studies further indicated that LRRC46,a member of the important LRR protein family,primarily affected the formation of *** study suggested that LRRC46 is a novel candidate gene for HM,influencing collagen protein VⅢ(Col8a1)formation in the eye and gradually altering the biomechanical structure of the cornea and sclera,thereby promoting the occurrence and development of HM.

关键词： high myopia LRRC46 biomechanics collagen protein VⅢ

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Establishing a new testing protocol of the electrochemical stability window for electric double-layer capacitors

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Science china Chemistry 2024年

作者： Ruilin Hou Xiaoxi zhao Tingting liang Qingyun Dou Shan Xu Xingbin Yan School of Materials Science and Engineering Sun Yat-sen University Laboratory of Clean Energy Chemistry and Materials Lanzhou Institute of Chemical PhysicsChinese Academy of Sciences College of Engineering and Applied sciences Nanjing University center of Industrial Analysis and Testing Guangdong Academy of Science

The electrochemical stability window (ESW) is crucial for determining the energy density of electric double-layer capacitors(EDLCs).However,current ESW testing protocols of EDLCs are strongly affected by artificial factors,thereby leading to unreliable *** solve this problem,we first identify the key shortcomings of the traditional protocols by analyzing their test ***,taking an aqueous carbon-based EDLC as an example,we design a side reaction descriptor to represent the response difference in the charging capacitance to side reactions between the cyclic voltammetry and galvanostatic chargedischarge *** the aid of this descriptor,we propose a new ESW testing protocol,which is not only able to completely avoid the adverse influence of subjective factors but also fully consider the operating condition *** protocol can be extended from the single electrode to the full *** work proposes a more rigorous definition of ESW and provides a reliable protocol for evaluating the ESW of EDLCs.

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Key Physical Factors Affecting Spatial-temporal Variation of Labile Organic Carbon Fractions by Biochar Driven in Mollisols Region of Northeast china

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Journal of Northeast Agricultural university(English Edition) 2024年第1期31卷 28-41页

作者： zhao Wei liang Fangyuan liang Ying zhao Hongrui Hao Shuai Wang Hongyan Wang Daqing College of Resources and Environment Northeast Agricultural UniversityHarbin 150030China Ulanqab Science and Technology Development center Ulanqab 012000XinjiangChina Heilongjiang Agricultural Reclamation Economic Research Institute Harbin 150090China

Biochar is widely used to improve soil physical properties and carbon sequestration. However, few studies focuse on the impact of maize stalk biochar on labile organic carbon(LOC) pool and the relationship between physical properties and LOC fractions. A field positioning experiment was performed in Mollisols region of Northeast china to evaluate the influence of maize stalk biochar on the spatial distribution and temporal changes of physical properties and LOC fractions. Maize stalk biochar treatments included C1(1.5 kg·hm^(-2)), C2(3 kg·hm^(-2)), C3(15 kg·hm^(-2)), C4(30 kg·hm^(-2)), and CK(0). The results showed that maize stalk biochar increased soil water contents(SWC) and soil porosity(SP), but reduced bulk density(BD). Maize stalk biochar reduced dissolved organic carbon(DOC) contents in the 0-20 cm soil layer, ranging from 0.25 g·kg^(-1) to 0.31 g·kg^(-1) in harvest period, while increased in the 20-40 cm soil layer. In addition, the application of biochar had a significant impact on the spatial distribution and temporal change of SWC, BD, SP, DOC, hot-water extractable carbon(HWC), acid hydrolyzed organic carbon(AHC Ⅰ, Ⅱ), and readily oxidized organic carbon(ROC). High amounts of maize stalk biochar up-regulated the contents of soil organic carbon SOC, HWC, AHC Ⅰ, AHC Ⅱ, and ROC. In addition, SWC and SP were the key physical factors to affect LOC fractions. In conclusions, maize stalk biochar could improve physical properties, and then influence LOC fractions, and maize stalk biochar could be used as an organic amendment for restoring degraded soils governed by their rates of addition.

关键词： maize stalk biochar labile organic carbon fraction Mollisols region soil physical property dissolved organic carbon

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