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Large-Scale CRISPR Screen of LDLR Pathogenic Variants

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research 2024年第2期2023卷 213-225页

作者： Mengjing Li Lerong Ma Yiwu Chen Jianing Li Yanbing Wang Wenni You Hongming Yuan Xiaochun Tang Hongsheng Ouyang Daxin Pang Key lab for Zoonoses research Ministry of EducationAnimal Genome Editing Technology Innovation CenterCollege of Animal SciencesJilin UniversityChangchunJilin Province 130062China The Institute of Translational Medicine Tianjin Union Medical Center of Nankai UniversityTianjin 300071China Chongqing researchInstitute Jilin UniversityChongqing 401123China Chongqing Jitang Biotechnology research Institute Co.Ltd. ChongqingChina

Familial hypercholesterolemia(FH)is a frequently occurring genetic disorder that is linked to early-onset cardiovascular *** left untreated,patients with this condition can develop severe cardiovascular ***,many patients remain undiagnosed,and even when diagnosed,the treatment is often not *** mutations in the LDLR gene are the primary cause of FH,predicting whether novel variants are pathogenic is not a straightforward *** the functionality of LDLR variants is crucial in uncovering the genetic basis of *** study utilized CRISPR/Cas9 cytosine base editors in pooled screens to establish a novel approach for functionally assessing tens of thousands of LDLR variants on a large scale.A total of more than 100 single guide RNAs(sgRNAs)targeting LDLR pathogenic mutations were successfully screened with relatively high *** of these,5 sgRNAs were further subjected to functional verification studies,including 1 in the promoter,1 in the antisense RNA,1 in the exon,and 2 in the *** for the variant caused by the sgRNA located at intron 16,the functionalities of the other LDLR variants were all *** high similarity of LDLR intron sequences may lead to some false ***,these results confirm the reliability of the large-scale screening strategy for functional analysis of LDLR variants,and the screened candidate pathogenic mutations could be used as an auxiliary means of clinical gene detection to prevent FH-induced heart disease.

关键词： LDLR Screen straight

Steric hindrance modulation of hexaazatribenzanthraquinone isomers for high-capacity and wide-temperature-range aqueous proton battery

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National Science Review 2024年第4期11卷 271-282页

作者： Mingsheng Yang Yuxin Hao Bei Wang Yan Wang Liping Zheng Rui Li Huige Ma Xinyu Wang Xiaoming Jing Hongwei Li Mengxiao Li Zhihui Wang Yujie Dai Guangcun Shan Mingjun Hu Jun Luo Jun Yang School of Materials Science and Engineering Beihang University Beijing Institute of Nanoenergy &Nanosystems Chinese Academy of Sciences Center on Nanoenergy research School of Physical Science & TechnologyGuangxi University School of Chemistry and Chemical Engineering Center on Nanoenergy Research Guangxi University School of Instrumentation Science and Opto-electronics Engineering Beihang University ShenSi lab Shenzhen Institute for Advanced StudyUniversity of Electronic Science and Technology of China

Organic materials with rich active sites are good candidates of high-capacity anodes in aqueous batteries,but commonly low utilization of active sites limits their ***,two isomers,symmetric and asymmetric hexaazatribenzanthraquinone（s-HATBAQ and a-HATBAQ）,with rich active sites have been synthesized in a controllable *** has been revealed for the first time that a sulfuric acid catalyst can facilitate the stereoselective formation of *** to the reduced steric hindrance in favor of proton insertion as well as the amorphous structure conducive to electrochemical dynamics,s-HATBAQ exhibits 1.5 times larger specific capacity than ***,the electrode of s-HATBAQ with50% reduced graphene oxide（s-HATBAQ-50%rGO） delivers a record high specific capacity of405 mAh g-1in ***,the assembled MnO2//s-HATBAQ-50%rGO aqueous proton full batteries show an exceptional cycling stability at 25℃ and can maintain ～92% capacity after1000 cycles at 0.5 A g-1at-80℃.This work demonstrates the controllable synthesis of isomers,showcases a wide-temperature-range prototype proton battery and highlights the significance of precise mole cular structure modulation in organic energy storage.

关键词： stereoisomers steric effect aqueous battery super cycling stability ultra-low temperature proton battery

Adaptive PI Control Based Stability Margin Configuration of Aircraft Control Systems with Unknown System Parameters and Time Delay

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Journal of Systems Science & Complexity 2024年第4期37卷 1507-1525页

作者： ZHANG Zhibing ZHOU Dapeng WANG Yeguang GAO Wanxin ZHANG Yanjun AVIC Shenyang Aircraft Design and research Institute Shenyang 110035China School of Automation Beijing Institute of TechnologyBeijing 100081China State Key lab of Autonomous Intelligent Unmanned Systems Beijing Institute of TechnologyBeijing 100081China

The stability margin is a vital indicator for assessing the safety level of aircraft control *** should maintain sufficient stability margin to ensure safety during flight,especially in the process of large maneuver *** stability margin is generally quantified by the Bode diagram,which strictly depends on the system parameters and the open-loop transfer ***,due to the uncertain flight environments,transmission delays of sensors and mode switchings,etc.,there exist large parameter and structure uncertainties in the aircraft control systems,which make it difficult to precisely configure the stability margin to the desired value by the usual control *** address this problem,an indirect adaptive control strategy is proposed in this paper,where an adaptive PI control law with the capability of self-configuration of stability margin is *** developed control law not only achieves stable time-varying command tracking in the time domain,but also is able to automatically configure the phase margin and gain margin in the frequency ***,the simulation of the one-degree-of-freedom roll rate control model of the air vehicle verifies the validity of the proposed control method.

关键词： Adaptive control aircraft control parameter uncertainty stability margin configuration

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Foeniculum vulgare *** lipopolysaccharide-induced microglia activation and ameliorates neuroinflammation-mediated behavioral deficits in mice

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Asian Pacific Journal of Tropical Biomedicine 2024年第1期14卷 28-39页

作者： Sushruta Koppula Ramesh Alluri Spandana Rajendra Kopalli College of Biomedical and Health Sciences Konkuk UniversityChungju-SiChungcheongbuk Do27478Republic of Korea Cognitive Science research Initiative lab Department of PharmacologyVishnu Institute of Pharmaceutical Education and ResearchNarsapurTelangana502313India Department of Bioscience and Biotechnology Sejong UniversityGwangjin-guSeoul 05006Republic of Korea

Objective:To investigate the effect of Foeniculum vulgare extract against lipopolysaccharide(LPS)-induced microglial activation in vitro as well as cognitive behavioral deficits in ***:LPS-activated BV-2 cell viability was measured using MTT assay and reactive oxygen species(ROS)was studied using DCF-DA *** antioxidative enzymes and pro-inflammatory mediators were analyzed using respective ELISA kits and Western *** in vivo testing,LPS(1 mg/kg,i.p.)was given daily for five days in male Swiss albino mice to produce chronic *** and behavioral tests were performed using open-field,passive avoidance,and rotarod experiments in LPS-induced ***:Foeniculum vulgare extract(25,50 and 100μg/mL)significantly attenuated the LPS-activated increase in nitric oxide(NO),ROS,cyclooxygenase-2,inducible NO synthase,IL-6,and TNF-alpha(P<0.05).Moreover,LPS-induced oxidative stress and reduced antioxidative enzyme levels were significantly improved by Foeniculum vulgare extract(P<0.05).The extract also regulated the NF-κB/MAPK signaling in BV-2 *** an in vivo study,Foeniculum vulgare extract(50,100,and 200 mg/kg)markedly mitigated the LPS-induced cognitive and locomotor impairments in *** fingerprinting analysis showed distinctive peaks with rutin,kaempferol-3-O-glucoside,and anethole as identifiable ***:Foeniculum vulgare extract can ameliorate LPS-stimulated neuroinflammatory responses in BV-2 microglial cells and improve cognitive and locomotor performance in LPS-administered mice.

关键词： Foeniculum vulgare Microglia Lipopolysaccharide Antioxidant Neuroinflammation MAPK signaling Cognition

Highly sensitive flexible strain sensor based on the two-dimensional semiconductor tellurium with a negative gauge factor

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Science China(Information Sciences) 2024年第7期67卷 295-304页

作者： Jiarui HE Yusong QU Shengyao CHEN Cong WANG Lena DU Xiaoshan DU Yuanyuan ZHENG Guozhong ZHAO He TIAN College of Mathematics and Physics Beijing University of Chemical Technology School of Integrated Circuits Tsinghua University Beijing China & The Beijing National Research Center for Information Science and Technology (BNRist)Tsinghua University CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology &University of Chinese Academy of Sciences Beijing Key lab of Terahertz Spectroscopy and Imaging Key Lab of Terahertz OptoelectronicsMinistry of Education Department of Physics Capital Normal University

research on flexible strain sensors has advanced rapidly in recent years, with particular attention being devoted to two-dimensional(2D) semiconductor materials owing to their exceptional mechanical and electrical properties that are conducive to sophisticated sensing performance. However, resistive strain sensors based on 2D semiconductor materials typically exhibit positive gauge factors(GF), while materials for strain sensors with a negative GF remain elusive. We have identified a trend of reduction in the band gap of the emerging 2D semiconductor material tellurium(Te) under strain in simulations reported in past research,and have observed a negative GF in the Te-based strain sensor. In this study, we combined Te with a flexible polyethylene terephthalate(PET) substrate to manufacture a flexible strain sensor with a significantly negative GF. The results of tests revealed that the Te-based strain sensor achieved an impressive maximum sensitivity of-139.7 within a small range of bending-induced strain(< 1%). Furthermore, it exhibited excellent linearity and good cyclic stability, and was successfully applied to monitor limb movements. The work here verifies the significant potential for the use of Te-based strain sensors in next-generation flexible electronics.

关键词： 2D semiconductor materials 2D tellurium flexibleelectronics strain sensors negative gauge factor high sensitivity

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980 nm Near-Infrared Light-Emitting Diode Using All-Inorganic Perovskite Nanocrystals Doped with Ytterbium Ions

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Tsinghua Science and Technology 2024年第1期29卷 207-215页

作者： Zhenglan Ye Taoran Liu Dan Chen Yazhou Yang Jiayi Li Yaqing Pang Xiangquan Liu Yuhua Zuo Jun Zheng Zhi Liu Buwen Cheng State Key laboratory on Integrated Optoelectronics Institute of SemiconductorsChinese Academy of SciencesBeijing 100083China Center of Materials Science and Optoelectronics Engineering University of Chinese Academy of SciencesBeijing 100049China Intelligent Network research Institute Zhejiang LabHangzhou 311100China

All-inorganic perovskite(CsPbX3)nanocrystals(NCs)have recently been widely investigated as versatile solution-processable light-emitting *** to its wide-bandgap nature,the all-inorganic perovskite NC Light-Emitting Diode(LED)is limited to the visible region(400-700 nm).A particularly difficult challenge lies in the practical application of perovskite NCs in the infrared-spectrum *** this work,a 980 nm NIR all-inorganic perovskite NC LED is demonstrated,which is based on an efficient energy transfer from wide-bandgap materials(CsPbCl3 NCs)to ytterbium ions(Yb3+)as an NIR emitter doped in perovskite *** optimized CsPbCl3 NC with 15 mol%Yb3+doping concentration has the strongest 980 nm photoluminescence(PL)peak,with a PL quantum yield of 63%.An inverted perovskite NC LED is fabricated with the structure of ITO/PEDOT:PSS/poly-TPD/CsPbCl3:15 mol%Yb3+NCs/TPBi/LiF/*** LED has an External Quantum Efficiency(EQE)of 0.2%,a Full Width at Half Maximum(FWHM)of 47 nm,and a maximum luminescence of 182 cd/m?.The introduction of Yb3+doping in perovskite NCs makes it possible to expand its working wavelength to near-infrared band for next-generation light sources and shows potential applications for optoelectronic integration.

关键词： perovskite nanocrystals rare-earth doping Light-Emitting Diode(LED) near-infrared optical interconnection

EVEscape: Revealing potential escape sites based on the viral variation landscape

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Biophysics Reports 2024年第2期10卷 133-134页

作者： Yaling Li Aiping Wu Hang-Yu Zhou Zhejiang lab State Key laboratory of Common Mechanism research for Major Diseases Suzhou Institute of Systems MedicineChinese Academy of Medical Sciences & Peking Union Medical College

The continuous mutation and evolution of viruses to evade the host immune response present a formidable challenge to combating infectious diseases. Accurate prediction of viral immune escape sites is crucial for disease diagnosis, therapy development, vaccine design, and other strategies aimed at combating emerging infectious diseases. During the COVID-19 pandemic,

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Model architecture level privacy leakage in neural networks

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Science China(Information Sciences) 2024年第3期67卷 20-32页

作者： Yan LI Hongyang YAN Teng HUANG Zijie PAN Jiewei LAI Xiaoxue ZHANG Kongyang CHEN Jin LI Institute of Artificial Intelligent and Blockchain Guangzhou University Pazhou lab

Privacy leakage is one of the most critical issues in machine learning and has attracted growing interest for tasks such as demonstrating potential threats in model attacks and creating model *** recent years, numerous studies have revealed various privacy leakage risks(e.g., data reconstruction attack, membership inference attack, backdoor attack, and adversarial attack) and several targeted defense approaches(e.g., data denoising, differential privacy, and data encryption). However, existing solutions generally focus on model parameter levels to disclose(or repair) privacy threats during the model training and/or model interference process, which are rarely applied at the model architecture level. Thus, in this paper, we aim to exploit the potential privacy leakage at the model architecture level through a pioneer study on neural architecture search(NAS) paradigms which serves as a powerful tool to automate a neural network *** investigating the NAS procedure, we discover two attack threats in the model architecture level called the architectural dataset reconstruction attack and the architectural membership inference attack. Our theoretical analysis and experimental evaluation reveal that an attacker may leverage the output architecture of an ongoing NAS paradigm to reconstruct its original training set, or accurately infer the memberships of its training set simply from the model architecture. In this work, we also propose several defense approaches related to these model architecture attacks. We hope our work can highlight the need for greater attention to privacy protection in model architecture levels(e.g., NAS paradigms).

关键词： neural architecture search data reconstruction attack membership inference attack

Enhancing thermoelectric performance of p-type SnTe through manipulating energy band structures and decreasing electronic thermal conductivity

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Rare Metals 2024年第7期43卷 3232-3241页

作者： Xin Qian Hao-Ran Guo Jia-Xin Lyu Bang-Fu Ding Xing-Yuan San Xiao Zhang Jiang-Long Wang Shu-Fang Wang Hebei Key lab of Optic-Electronic Information and Materials College of Physics Science and TechnologyHebei UniversityBaoding 071002China College of Electron and Information Engineering Hebei UniversityBaoding 071002China research Institute for Frontier Science Beihang UniversityBeijing100191China

SnTe has received considerable attention as an environmentally friendly alternative to the representative thermoelectric material of ***,excessive hole carrier concentration in SnTe results in an extremely low Seebeck coefficient and high thermal conductivity,which makes it exhibit relatively inferior thermoelectric *** this work,the thermoelectric performance of p-type SnTe is enhanced through regulating its energy band structures and reducing its electronic thermal conductivity by combining Bi doping with CdSe ***,the carrier concentration of SnTe is successfully suppressed via Bi doping,which significantly decreases the electronic thermal ***,the convergence and flattening of the valence bands by alloying CdSe effectively improves the effective mass of SnTe while restraining its carrier ***,a maximum figure of merit(ZT) of~ 0.87 at 823 K and an average ZT of~ 0.51 at 300-823 K have been achieved in Sn_(0.96)Bi_(0.04)Te-5%*** results indicate that decreasing the electronic thermal conductivity is an effective means of improving the performance of thermoelectric materials with a high carrier concentration.

关键词： Thermoelectric materials SnTe Energy band structure Electronic thermal conductivity ZT value

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