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Large-Scale CRISPR Screen of LDLR Pathogenic Variants

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

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Activatable photoacoustic bioprobe for visual detection of aging in vivo

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Chinese Chemical Letters 2024年第4期35卷 324-329页

作者： Zihong Li Jie Cheng Ping Huang Guoliang Wu Weiying Lin institute of Optical Materials and Chemical Biology Guangxi Key Laboratory of Electrochemical Energy MaterialsSchool of Chemistry and Chemical EngineeringGuangxi UniversityNanning 530004China

Aging is a natural physiological process with various challenges, related to the loss of homeostasis within the organism, which is not a disease, but a significantly strong risk factor for multiple diseases, including myocardial infarction, stroke, some age-related cancers, macular degeneration, osteoarthritis, neurodegeneration, and many others. In the body, the main manifestation of aging is cellular aging, which exists within tissues and has a local or global impact on tissue function. However, the lack of effective aging detection tools has always been an issue that cannot be ignored in the field of aging research. Therefore,it is necessary to construct a non-invasive tool for in vivo detection of aging. Here, we show that the photoacoustic probe(LGAL), which has peak excitation and emission wavelengths in the near-infrared optical window, binds in vivo and at high contrast to the hallmark of aging, and allows for the microscopic imaging of aging through the intact mice. Firstly, this tool LGAL has been successfully applied to detect senescence in cells, displaying stronger photoacoustic signals than normal cells. Then, by using the photoacoustic probe, the blood vessels and tissues inside the mice can be visualized. Young and elderly mice exhibit varying intensities of photoacoustic signals, marking the first time a probe has been used to explore the aging of blood vessels and tissues inside the mice. Finally, we monitored the changes in the degree of aging during tumor treatment under photoacoustic(PA) imaging for the first time. As the treatment time increased, the degree of aging of the tumor gradually deepened. We expect the powerful tool could be a noninvasive and powerful tool for the study of aging biology.

关键词： Near-infrared Photoacoustic Aging Senescence Tumor Sa-β-gal

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Atorvastatin, etanercept and the nephrogenic cardiac sympathetic remodeling in chronic renal failure rats

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Journal of Geriatric Cardiology 2024年第4期21卷 443-457页

作者： Jing-Yue XU Zheng-Kai XUE Ya-Ru ZHANG Xing LIU Xue ZHANG Xi YANG Tong LIU Kang-Yin CHEN Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease Department of CardiologyTianjin Institute of Cardiologythe Second Hospital of Tianjin Medical UniversityTianjinChina

BACKGROUND Chronic renal failure(CRF) patients are predisposed to arrhythmias, while the detailed mechanisms are unclear. We hypothesized the chronic inflammatory state of CRF patients may lead to cardiac sympathetic remodeling, increasing the incidence of ventricular arrhythmia(VA) and sudden cardiac death. And explored the role of atorvastatin and etanercept in this *** A total of 48 rats were randomly divided into sham operation group(Sham group), CRF group, CRF + atorvastatin group(CRF + statin group), and CRF + etanercept group(CRF + rhTNFR-Fcgroup). Sympathetic nerve remodeling was assessed by immunofluorescence of growth-associated protein 43(GAP-43) and tyrosine hydroxylase positive area fraction. Electrophysiological testing was performed to assess the incidence of VA by assessing the ventricular effective refractory period and ventricular fibrillation threshold. The levels of tumor necrosis factor-alpha(TNF-α) and interleukin-1beta were determined by Western blotting and enzyme-linked immunosorbent *** Echocardiogram showed that compared with the Sham group, left ventricular end-systolic diameter and ventricular weight/body weight ratio were significantly higher in the CRF group. Hematoxylin-eosin and Masson staining indicated that myocardial fibers were broken, disordered, and fibrotic in the CRF group. Western blotting, enzyme-linked immunosorbent assay,immunofluorescence and electrophysiological examination suggested that compared with the Sham group, GAP-43 and TNF-α proteins were significantly upregulated, GAP-43 and tyrosine hydroxylase positive nerve fiber area was increased, and ventricular fibrillation threshold was significantly decreased in the CRF group. The above effects were inhibited in the CRF + statin group and the CRF + *** In CRF rats, TNF-α was upregulated, cardiac sympathetic remodeling was more severe, and the nephrogenic cardiac sympathetic remodeling existed. Atorvastatin and etanercept c

关键词： remodeling cardiac inhibited

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Dynamic simulation of GEH-IES with distributed parameter characteristics for hydrogen-blending transportation

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Frontiers in Energy 2024年第4期18卷 506-524页

作者： Dengji ZHOU Jiarui HAO Wang XIAO Chen WANG Chongyuan SHUI Xingyun JIA Siyun YAN Key Laboratory of Power Machinery and Engineering of the Ministry of Education Shanghai Jiao Tong UniversityShanghai 200240China Sichuan Research institute Shanghai Jiao Tong UniversityChengdu 610042China West Pipeline Company National Petroleum and Natural Gas Pipe Network Group Co.Ltd.Urumqi 830012China institute of Intelligent Manufacturing Modern Industry Xinjiang UniversityUrumqi 830046China

For the purpose of environment protecting and energy saving,renewable energy has been distributed into the power grid in a considerable ***,the consuming capacity of the power grid for renewable energy is relatively *** an effective way to absorb the excessive renewable energy,the power to gas(P2G)technology is able to convert excessive renewable energy into ***-blending natural gas pipeline is an efficient approach for hydrogen ***,hydrogen-blending natural gas complicates the whole integrated energy system(IES),making it more problematic to cope with the equipment failure,demand response and dynamic ***,dynamic simulation of distribution parameters of gas-electricity-hydrogen(GEH)energy system,especially for hydrogen concentration,still remains a *** dynamics of hydrogen-blending IES is *** tackle the issue,an iterative solving framework of the GEH-IES and a cell segment-based method for hydrogen mixing ratio distribution are proposed in this *** typical numerical cases studying the conditions under which renewables fluctuate and generators fail are conducted on a real-word *** results show that hydrogen blending timely and spatially influences the flow parameters,of which the hydrogen mixing ratio and gas pressure loss along the gas pipeline are negatively correlated and the response to hydrogen mixing ratio is ***,the hydrogen-blending amount and position also have a significant impact on the performance of the compressor.

关键词： gas-electricity IES dynamic simulation hydrogen blending power to gas(P2G) renewable energy

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Naked-eye visualization of lymph nodes using fluorescence nanoprobes in non-human primate-animal models

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Nano Research 2024年第8期17卷 7404-7414页

作者： Xiaoyuan Ji Binbin Chu Xiaofeng Wu Zhiming Xia Airui Jiang Chenyu Wang Zhiming Chen Danni Zhong Qiaolin Wei Bin Song Wanlin Li Yiling Zhong Houyu Wang Fenglin Dong Min Zhou Yao He Suzhou Key Laboratory of Nanotechnology and Biomedicine Jiangsu Key Laboratory for Carbon-Based Functional Materials&DevicesInstitute of Functional Nano and Soft Materials(FUNSOM)Soochow UniversitySuzhou 215123China School of Public Health Shanghai Jiao Tong University School of MedicineShanghai 200025China Zhejiang University-University of Edinburgh institute(ZJU-UoE institute) Zhejiang UniversityHaining 314400China Department of Ultrasound the First Affiliated Hospital of Soochow UniversitySuzhou 215006China State Key Laboratory(SKL)of Biobased Transportation Fuel Technology Zhejiang UniversityHangzhou 310027China School of Pharmacy Hangzhou Normal UniversityHangzhou 311121China Macao Translational Medicine Center Macao University of Science and TechnologyTaipa 999078MacaoChina Macao institute of Materials Science and Engineering Macao University of Science and TechnologyTaipa 999078MacaoChina

Despite sufficient studies performed in non-primate animal models,there exists scanty information obtained from pilot trials in non-human primate animal models,severely hindering nanomaterials moving from basic research into clinical *** herein present a pioneering demonstration of nanomaterials based optical imaging-guided surgical operation by using macaques as a typical kind of non-human primate-animal ***,taking advantages of strong and stable fluorescence of the small-sized(diameter:~5 nm)silicon-based nanoparticles(SiNPs),lymphatic drainage patterns can be vividly visualized in a real-time manner,and lymph nodes(LN)are able to be sensitively detected and precisely excised from small animal models(e.g.,rats and rabbits)to non-human primate animal models(e.g.,cynomolgus macaque(Macaca fascicularis)and rhesus macaque(Macaca mulatta)).Compared to clinically used invisible near-infrared(NIR)lymphatic tracers(i.e.,indocyanine green(ICG);etc.),we fully indicate that the SiNPs feature unique advantages for naked-eye visible fluorescence-guided surgical operation in long-term *** toxicological analysis in macaque models further provides confirming evidence of favorable biocompatibility of the SiNPs *** expect that our findings would facilitate the translation of nanomaterials from the laboratory to the clinic,especially in the field of cancer treatment.

关键词： fluorescent silicon nanoparticles lymph node real-time naked-eye visualization macaque models

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Thermal and Magnetic Dual-Responsive Catheter-Assisted Shape Memory Microrobots for Multistage Vascular Embolization

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Research 2024年第3期2024卷 529-543页

作者： Qianbi Peng Shu Wang Jianguo Han Chenyang Huang Hengyuan Yu Dong Li Ming Qiu Si Cheng Chong Wu Mingxue Cai Shixiong Fu Binghan Chen Xinyu Wu Shiwei Du Tiantian Xu Guangdong Provincial Key Lab of Robotics and Intelligent Systems Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenChina University of Chinese Academy of Sciences BeijingChina Department of Neurosurgery South China HospitalMedical SchoolShenzhen University.ShenzhenChina The Key Laboratory of Biomedical Imaging Science and System Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenChina.

Catheters navigating through complex vessels,such as sharp turns or multiple U-turns,remain challenging for vascular ***,we propose a novel multistage vascular embolization strategy for hard-to-reach vessels that releases untethered swimming shape-memory magnetic microrobots(SMMs)from the prior catheter to the vessel ***,made of organo-gel with magnetic particles,ensure biocompatibility,radiopacity,thrombosis,and fast thermal and magnetic *** SMM is initially a linear shape with a 0.5-mm diameter at 20°C inserted in a *** transforms into a predetermined helix within 2 s at 38°C blood temperature after being pushed out of the catheter into the *** enable agile swimming in confined and tortuous vessels and can swim upstream using helical propulsion with rotating magnetic ***,we validated this multistage vascular embolization in living rabbits,completing 100-cm travel and renal artery embolization in 2 *** 4 weeks,the SMMs maintained the embolic position,and the kidney volume decreased by 36%.

关键词： turns maintained travel

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Learning Sequential and Structural Dependencies Between Nucleotides for RNA N6-Methyladenosine Site Identification

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IEEE/CAA Journal of Automatica Sinica 2024年第10期11卷 2123-2134页

作者： Guodong Li Bowei Zhao Xiaorui Su Dongxu Li Yue Yang Zhi Zeng Lun Hu Xinjiang Technical institute of Physics and Chemistry Chinese Academy of ScienceUrumqi 830011China College of Computer Xi’an Jiaotong UniversityXi’an 710049China IEEE

N6-methyladenosine(m6A)is an important RNA methylation modification involved in regulating diverse biological processes across multiple ***,the identification of m6A modification sites provides valuable insight into the biological mechanisms of complex diseases at the post-transcriptional *** a variety of identification algorithms have been proposed recently,most of them capture the features of m6A modification sites by focusing on the sequential dependencies of nucleotides at different positions in RNA sequences,while ignoring the structural dependencies of nucleotides in their threedimensional *** overcome this issue,we propose a cross-species end-to-end deep learning model,namely CR-NSSD,which conduct a cross-domain representation learning process integrating nucleotide structural and sequential dependencies for RNA m6A site ***,CR-NSSD first obtains the pre-coded representations of RNA sequences by incorporating the position information into single-nucleotide states with chaos game representation *** then constructs a crossdomain reconstruction encoder to learn the sequential and structural dependencies between *** minimizing the reconstruction and binary cross-entropy losses,CR-NSSD is trained to complete the task of m6A site *** experiments have demonstrated the promising performance of CR-NSSD by comparing it with several state-of-the-art m6A identification ***,the results of cross-species prediction indicate that the integration of sequential and structural dependencies allows CR-NSSD to capture general features of m6A modification sites among different species,thus improving the accuracy of cross-species identification.

关键词： Cross-domain reconstruction cross-species prediction N6-methyladenosine(m6A)modification site RNA sequence sequential and structural dependencies

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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

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Continuous-Time Channel Prediction Based on Tensor Neural Ordinary Differential Equation

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China Communications 2024年第1期21卷 163-174页

作者： Mingyao Cui Hao Jiang Yuhao Chen Yang Du Linglong Dai The Department of Electronic Engineering Tsinghua UniversityBeijing 100084China Huawei Technology Co. Ltd.Chengdu Research InstituteChengdu 611730China

Channel prediction is critical to address the channel aging issue in mobile *** channel prediction techniques are mainly designed for discrete channel prediction,which can only predict the future channel in a fixed time slot per frame,while the other intra-frame channels are usually recovered by ***,these approaches suffer from a serious interpolation loss,especially for mobile millimeter-wave *** solve this challenging problem,we propose a tensor neural ordinary differential equation(TN-ODE)based continuous-time channel prediction scheme to realize the direct prediction of intra-frame ***,inspired by the recently developed continuous mapping model named neural ODE in the field of machine learning,we first utilize the neural ODE model to predict future continuous-time *** improve the channel prediction accuracy and reduce computational complexity,we then propose the TN-ODE scheme to learn the structural characteristics of the high-dimensional channel by low-dimensional learnable *** results show that the proposed scheme is able to achieve higher intra-frame channel prediction accuracy than existing schemes.

关键词： channel prediction massive multipleinput-multiple-output millimeter-wave communications ordinary differential equation

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New measurement of the neutron-induced total cross-sections of^(nat)Cr in a wide energy range on the Back-n at CSNS

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Chinese Physics C 2024年第10期48卷 168-175页

作者： Baoqian Li Min Xiao Yonghao Chen Jieming Xue Xinxiang Li Han Yi Pinjing Cheng Rong Liu Yiwei Yang Zijie Han Dajun Zhao Haoqiang Wang Jirong Zhao Peng Luan Jing Liu Zijun Liu Chaomin Chen Wen Luo Bo Zheng Song Feng School of Nuclear Science and Technology University of South ChinaHengyang 421001China institute of High Energy Physics Chinese Academy of SciencesBeijing 100049China Spallation Neutron Source Science Center Dongguan 523803China institute of Nuclear Physics and Chemistry China Academy of Engineering PhysicsMianyang 621900China

The neutron total cross-section of ^(nat)Cr plays a crucial role in new nuclear engineering design and fundamental science.A new measurement of the neutron-induced total cross-sections of ^(nat)Cr was performed using the transmission method on the back-streaming white neutron beamline(Back-n)at the China Spallation Neutron Source(CSNS).The neutron energy was determined using the time-of-flight *** neutron total cross-sections of ^(nat)Cr were obtained across a broad energy range(0.3 eV−20 MeV)in one experiment for the first *** resulting effective total cross-sections were compared with the existing experimental data in different energy ranges,which revealed good agreement with the evaluated *** calculation of the total cross-section in the energy range of 1.5 to 20 MeV was then conducted using TALYS-1.96 and compared with the present *** measurement provides a high-quality total cross-section of ^(nat)Cr,including detailed uncertainty data across a wide energy range,offering a valuable reference for nuclear data re-evaluation and nuclear engineering design.

关键词： neutron total cross-section natural chromium Back-n white neutron beamline NTOX

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