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Exploring noncoding variants in genetic diseases:from detection to functional insights

Journal of Genetics and Genomics 2024年第2期51卷 111-132页

作者： Ke wu Fengxiao Bu Yang wu Gen Zhang xin Wang Shunmin He Mo-Fang Liu Runsheng Chen Huijun Yuan Institute of Rare Diseases West China Hospital of Sichuan UniversityChengduSichuan 610041China Key Laboratory of Systems Health Science of Zhejiang Province School of Life ScienceHangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhouZhejiang 310024China Key Laboratory of RNA Biology Center for Big Data Research in HealthInstitute of BiophysicsChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China State Key Laboratory of Molecular Biology State Key Laboratory of Cell BiologyShanghai Key Laboratory of Molecular AndrologyShanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesShanghai 200031China

Previous studies on genetic diseases predominantly focused on protein-coding variations, overlooking the vast noncoding regions in the human genome. The development of high-throughput sequencing technologies and functional genomics tools has enabled the systematic identification of functional noncoding variants. These variants can impact gene expression, regulation, and chromatin conformation, thereby contributing to disease pathogenesis. Understanding the mechanisms that underlie the impact of noncoding variants on genetic diseases is indispensable for the development of precisely targeted therapies and the implementation of personalized medicine strategies. The intricacies of noncoding regions introduce a multitude of challenges and research opportunities. In this review, we introduce a spectrum of noncoding variants involved in genetic diseases, along with research strategies and advanced technologies for their precise identification and in-depth understanding of the complexity of the noncoding genome. We will delve into the research challenges and propose potential solutions for unraveling the genetic basis of rare and complex diseases.

关键词： Noncoding variation Genetic disease Research approach Challenge

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Embedded Scenario Clustering for Wind and Photovoltaic Power,and Load Based on Multi-head Self-attention

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Protection and Control of Modern Power Systems 2024年第1期9卷 122-132页

作者： Lijun Liu xin Hu Junsheng Chen Ruixing wu Feixiong Chen School of Electrical Engineering and Automation Fuzhou UniversityFuzhou 350108China State Grid Fuzhou Power Supply Company Fujian Smart Electrical Engineering Technology Research Center

The source and load uncertainties arising from increased applications of renewable energy sources such as wind and photovoltaic energy in the power system have had adverse effects on optimal planning and *** for generating typical renewable energy and load scenarios are constructed to reduce such effects and improve the applicability of a planning and optimal dispatching model of power systems with a high proportion of renewable *** traditional clustering-based model for representing such scenarios cannot handle high-dimensional time-series data and consequently the feature-related information obtained cannot fully reflect the characteristics of the ***,a deep convolutional embedded clustering model based on multi-head self-attention is ***,a variational mode decomposition model is optimized to reduce the influence of noise-related signals on the feature *** deep features are then extracted from the data using an improved convolutional autoencoder,and the appropriate number of clusters is determined using the elbow *** this,the network parameters are optimized based on the sum of losses during reconstruction and ***,typical scenarios are then generated based on the optimized network ***,the proposed method is evaluated based on data visualization and evaluation *** is shown that the quality of features and the accuracy of clustering can be effectively improved by the proposed scenario generation method.

关键词： handle Embedded network

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MOF-mediated synthesis of novel PtFeCoNiMn high-entropy nanoalloy as bifunctional oxygen electrocatalysts for zinc-air battery

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Nano Research 2024年第6期17卷 5288-5297页

作者： Mingkuan Xie xin Xiao Duojie wu Cheng Zhen Chunsheng wu Wenjuan Wang Hao Nian Fayan Li Meng Danny Gu Qiang Xu Shenzhen Key Laboratory of Micro/Nano-Porous Functional Materials(SKLPM) Shenzhen 518055China Department of Chemistry Southern University of Science and TechnologyShenzhen 518055China Department of Materials Science and Engineering Southern University of Science and TechnologyShenzhen 518055China SUSTech-Kyoto University Advanced Energy Materials Joint Innovation Laboratory(SKAEM-JIL) Shenzhen 518055China Key University Laboratory of Highly Efficient Utilization of Solar Energy and Sustainable Development of Guangdong Southern University of Science and TechnologyShenzhen 518055China Eastern Institute for Advanced Study Eastern Institute of TechnologyNingbo 315200China

High-entropy alloy(HEA)-based materials are expected to be promising oxygen electrocatalysts due to their exceptional *** electronic structure regulation of HEAs plays a pivotal role in enhancing their elctrocatalytic ***,PtFeCoNiMn nanoparticles(NPs)with subtle lattice distortions are constructed on metal-organic framework-derived nitrogen-doped carbon by an ultra-rapid Joule heating *** to the modulated electronic structure and the inherent cocktail effect of HEAs,the as-synthesized PtFeCoNiMn/NC exhibits superior bifunctional electrocatalytic performance with a positive half-wave potential of 0.863 V *** hydrogen electrode(RHE)for oxygen reduction reaction and a low overpotential of 357 mV at 10 mA·cm^(-2)for oxygen evolution *** assembled quasi-solid-state zinc-air battery using PtFeCoNiMn/NC as air electrode shows a high peak power density of 192.16 mW·cm^(-2),low charge−discharge voltage gap,and excellent durability over 500 cycles at 5 mA·cm^(-2).This work demonstrates an effective route for rational design of bifunctional nanostructured HEA electrocatalysts with favorable electronic structures,and opens up a fascinating directions for energy storage and conversion,and beyond.

关键词： oxygen reduction reaction oxygen evolution reaction high-entropy nano-alloy zinc-air battery

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I_(2)-DMSO-Mediated Multicomponent [2+1+1+1] Annulation Reaction via Ethyl Nitroacetate C-NO_(2), Bond Cleavage as a C1 Synthon: A Route to Multisubstituted 6-Pyrrolidinones Derivatives with a Quaternary Center

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Chinese Journal of Chemistry 2024年第17期42卷 2029-2034页

作者： Zhi-Cheng Yu Xi Shen You Zhou Xiang-Long Chen Li-Sheng Wang Yan-Dong wu An-xin wu National Key Laboratory of Green Pesticide International Joint Research Centerfor Intelligent BiosensorTechnologyand HealthCollegeof ChemistryCentral ChinaNormal UniversityWuhanHubei 430079China

A[2+1+1+1]cyclization reaction has been developed for the synthesis of multisubstituted 6-pyrrolidinones from commercially available aryl methyl ketones,primary amines,and ethyl *** this I_(2)-DMSO-meditated process,the C-NO_(2) bond of ethyl nitroacetate is cleaved,affording a C1 synthon,and the formation of two C-C and two C-N bonds and a quaternary carbon center are constructed in one *** method has good substrate compatibility and permits the late-stage modification of pharmaceutical compounds.

关键词： Cyclization Multisubstituted 6-pyrrolidinones I_(2)-DMSO C1 building blocks Quaternary carbon center Late-stage modification Cracking

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Evolved differential model for sporadic graph time-series prediction

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Intelligent and Converged Networks 2024年第3期5卷 237-247页

作者： Yucheng xing Jacqueline wu Yingru Liu Xuewen Yang xin Wang Department of Electrical and Computer Engineering Stony Brook UniversityStony BrookNY 11794USA New York University New YorkNY 10012USA

Sensing signals of many real-world network systems,such as traffic network or microgrid,could be sparse and irregular in both spatial and temporal domains due to reasons such as cost reduction,noise corruption,or device *** is a fundamental but challenging problem to model the continuous dynamics of a system from the sporadic observations on the network of nodes,which is generally represented as a *** this paper,we propose a deep learning model called Evolved Differential Model(EDM)to model the continuous-time stochastic process from partial observations on *** model incorporates diffusion convolutional network to parameterize continuous-time system dynamics by graph Ordinary Differential Equation(ODE)and graph Stochastic Differential Equation(SDE).The graph ODE is applied to accurately capture the spatial-temporal relation and extract hidden features from the *** graph SDE can efficiently capture the underlying uncertainty of the network *** the recurrent ODE-SDE scheme,EDM can serve as an accurate online predictive model that is effective for either monitoring or analyzing the real-world networked *** extensive experiments on several datasets,we demonstrate that EDM outperforms existing methods in online prediction tasks.

关键词： graph sequence prediction sporadic time series continuous model stochastic model differential equation

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Midkine ameliorates LPS-induced apoptosis of airway smooth muscle cells via the Notch2 pathway

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Asian Pacific Journal of Tropical Biomedicine 2022年第12期12卷 512-519页

作者： Qi-Feng Huang Bo Wang Yu-Qing Weng Tang Deng Li-Hua Li Jin Qian Qi Li Kai-Wen Lin Dong-Mei Sun Shuang-Qin Xu Hang-Fei Wang xin-xin wu Yuan-Tian Sun Xiao-Ran Liu Emergency Department The First Affiliated Hospital of Hainan Medical UniversityHaikou 570102China Jiangdong Health Center Haikou 571126China Department of Pulmonary and Critical Care Medicines Zhuhai People’s Hospital(Zhuhai Hospital Affiliated with Jinan University)Zhuhai 519050China College of Pharmacy Hainan Medical UniversityHaikou 570100China Shandong Heze Mudan People’s Hospital Heze 274007China Emergency and Trauma College Hainan Medical UniversityHaikou 570100China College of Basic Medicine and Life Sciences Hainan Medical UniversityHaikou 570100China Key Laboratory of Emergency and Trauma of Ministry of Education Haikou 570100China

Objective:To evaluate the effect of midkine on lipopolysaccharide(LPS)-induced airway smooth muscle cells(ASMCs).Methods:LPS-stimulated acute lung injury model was used to analyze the effect of midkine on ASMCs in *** midkine and midkine siRNA were used to investigate the role of Notch2 signaling *** proliferation was assessed using Cell Counting Kit-8 ***,apoptosis was measured by flow cytometry and protein and mRNA expression of midkine and Notch2 was assessed by Western blotting and qPCR,*** analysis was also ***:LPS increased the mRNA and protein expression of midkine and *** silencing reduced LPS-induced midkine and Notch2 *** addition,midkine silencing further reduced the viability and increased apoptosis of ASMCs induced by LPS,which was attenuated by recombinant ***:The midkine/Notch2 signaling pathway plays a regulatory role in ASMC proliferation and apoptosis in airway inflammation.

关键词： Acute lung injury Airway smooth muscle cells Midkine Notch2 Lipopolysaccharide

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Potential effects of aerosol generation and transmission during bedside endoscope cleaning

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第7期25卷 628-632页

作者： Tingting SHENG xin wu Li CEN Ye LU Chenying ZHOU Qing GU Nursing Department the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Department of Gastroenterology the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Zhejiang Provincial Center for Disease Control and Prevention Hangzhou 310051China

Airborne transmission is among the most frequent types of nosocomial *** years have witnessed frequent outbreaks of airborne diseases,such as severe acute respiratory syndrome(SARS)in 2002,Middle East respiratory syndrome(MERS)in 2012,and coronavirus disease 2019(COVID-19),with the latter being on the rampage since the end of 2019 and bringing the effect of aerosols on health back to the fore(Gralton et al.,2011;Wang et al.,2021).An increasing number of studies have shown that certain highly transmissible pathogens can maintain long-term stability and efficiently spread through aerosols(Leung,2021;Lv et al.,2021).As reported previously,influenza viruses that can spread efficiently through aerosols remain stable for a longer period compared to those that *** World Health Organization(WHO)has stated that aerosol-generating procedures(AGPs)play an important role in aerosol transmission in hospitals(Calderwood et al.,2021).AGPs,referring to medical procedures that produce aerosols,including dental procedures,endotracheal intubation,sputum aspiration,and laparoscopic surgeries,have been reported to be significantly associated with an increased risk of nosocomial infection among medical personnel(Hamilton,2021).

关键词： Endoscopy Endoscopic surgery Aerosol transmission Bedside endoscope precleaning

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Lignin-reinforced PVDF electrolyte for dendrite-free quasi-solid-state Li metal battery

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Rare Metals 2024年第3期43卷 1006-1016页

作者： xin-Yang Chen Xue-Jie Gao Han-Yan wu Yu-Long Liu Xiao-Fei Yang Run-Cang Sun Center for Lignocellulosic Chemistry and Biomaterials College of Light Industry and Chemical EngineeringDalian Polytechnic UniversityDalian116034China Division of Energy Storage Dalian National Laboratory for Clean EnergyDalian Institute of Chemical PhysicsChinese Academy of SciencesDalian116023China School of Chemistry Northeast Normal UniversityChangchun130024China

Quasi-solid-state lithium metal batteries(QSSLMBs)assembled with polyvinylidene fluoride(PVDF)are a promising class of next-generation rechargeable batteries due to their safety,high energy density,and superior interfacial ***,PVDF has a series of inherent drawbacks such as low ionic conductivity,ease of crystallization,and hydrophobic character that leading to poor cell *** tackle these issues,a lignin-reinforced PVDF electrolyte is proposed in this work to solve these drawbacks of PVDF and enhance the comprehensive performance of *** lithophilic polar groups of lignin can promote uniform deposition of Li on the *** with the improved mechanical properties can efficiently prevent Li dendrites penetration through the *** addition,more active sites provided by lignin can also enhance Li^(+)transport and lead to a faster electrochemical reaction *** from the ingenious design,Li symmetric cells with 5%lignin-PVDF quasi-solid-state electrolyte can operate for 900 h at a high current density/capacity of 5 mA·cm^(-2)/5 mAh·cm^(-2),while shortcircuiting occurs after 56 h for the counterpart(pure PVDF).Moreover,a full cell of Li/5%lignin-PVDF/LFP cell demonstrates a high capacity of 96.2 mAh·g^(-1)after 2000 cycles at 10 *** work is expected to open up promising opportunities to develop other high-energy/power-density QSSLMBs.

关键词： Quasi-solid-state electrolyte Lignin PVDF Dendrite-free Li metal battery

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Fusobacterium nucleatum-induced imbalance in microbiome-derived butyric acid levels promotes the occurrence and development of colorectal cancer

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World Journal of Gastroenterology 2024年第14期30卷 2018-2037页

作者： Qi-Long wu Xiao-Ting Fang xin-xin Wan Qing-Yong Ding Yan-Jun Zhang Ling Ji Yong-Liang Lou Xiang Li School of Laboratory Medicine and Life Sciences Wenzhou Medical UniversityKey Laboratory of Laboratory MedicineMinistry of EducationWenzhou 325035Zhejiang ProvinceChina Department of Health Inspection and Quarantine School of Laboratory Medicine and Life SciencesWenzhou 325035Zhejiang ProvinceChina School of Laboratory Medicine and Life Sciences Wenzhou Medical UniversityZhejiang Provincial Key Laboratory of Medical GeneticsMinistry of EducationWenzhou 325035Zhejiang ProvinceChina Department of General Surgery The First Affiliated Hospital of Wenzhou Medical UniversityWenzhou 325035Zhejiang ProvinceChina School of Laboratory Medicine and Life Sciences Institute of One HealthWenzhou Medical UniversityZhejiang Provincial Key Laboratory of Medical GeneticsMinistry of EducationWenzhou 325035Zhejiang ProvinceChina Department of Health Inspection and Quarantine School of Laboratory Medicine and Life SciencesInstitute of One HealthWenzhou Medical UniversityZhejiang Provincial Key Laboratory of Medical GeneticsMinistry of EducationWenzhou 325035Zhejiang ProvinceChina

BACKGROUND Colorectal cancer(CRC)ranks among the most prevalent malignant tumors *** reports suggest that Fusobacterium nucleatum(***)contributes to the initiation,progression,and prognosis of ***,a short-chain fatty acid derived from the bacterial fermentation of soluble dietary fiber,is known to inhibit various *** study is designed to explore whether *** influences the onset and progression of CRC by impacting the intestinal metabolite butyric *** To investigate the mechanism by which *** affects CRC occurrence and *** Alterations in the gut microbiota of BALB/c mice were observed following the oral administration of ***,DLD-1 and HCT116 cell lines were exposed to sodium butyrate(NaB)and *** in vitro to examine the effects on proliferative proteins and mitochondrial *** Our research indicates that the prevalence of *** in fecal samples from CRC patients is significantly greater than in healthy counterparts,while the prevalence of butyrate-producing bacteria is notably *** mice colonized with ***,the population of butyrate-producing bacteria decreased,resulting in altered levels of butyric acid,a key intestinal metabolite of *** to NaB can impair mitochondrial morphology and diminish mitochondrial membrane potential in DLD-1 and HCT116 CRC ***,this leads to modulated production of adenosine triphosphate and reactive oxygen species,thereby inhibiting cancer cell ***,NaB triggers the adenosine monophosphate-activated protein kinase(AMPK)signaling pathway,blocks the cell cycle in HCT116 and DLD-1 cells,and curtails the proliferation of CRC *** combined presence of *** and NaB attenuated the effects of the *** employing small interfering RNA to suppress AMPK,it was demonstrated that AMPK is essential for NaB’s inhibition of CRC cell *** F.n

关键词： Colorectal cancer Fusobacterium nucleatum Butyric acid Gut microbiota Adenosine monophosphate-activated protein kinase signal pathway

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Hierarchical Voronoi Structure Inspired by Cat Paw Pads Substantially Enhances Landing Impact Energy Dissipation

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Journal of Bionic Engineering 2024年第4期21卷 1847-1861页

作者： Da Lu Baoqing Pei Yangyang Xu Mengyuan Hu Shijia Zhang Le Zhang xin Huang Yangwei Wang Xueqing wu Beijing Key Laboratory for Design and Evaluation Technology of Advanced Implantable&Interventional Medical Devices Beijing Advanced Innovation Center for Biomedical EngineeringSchool of Biological Science and Medical EngineeringBeihang University100083BeijingChina National Key Laboratory of Science and Technology on Materials under Shock and Impact Beijing Institute of Technology100081BeijingChina Shenzhen Institute of Beihang University 518000ShenzhenChina

When a human lands from a high drop,there is a high risk of serious injury to the lower *** the other hand,cats can withstand jumps and falls from heights without being fatally wounded,largely due to their impact-resistant paw *** aim of the present study was to investigate the biomechanism of impact resistance in cat paw pads,propose an optimal hierarchical Voronoi structure inspired by the paw pads,and apply the structure to bionic cushioning shoes to reduce the impact force of landing for *** microstructure of cat paw pads was observed via tissue section staining,and a simulation model was reconstructed based on CT to verify and optimize the structural cushioning *** distribution pattern,wall thickness of compartments,thickness ratio of epidermis and dermis,and number of compartments in the model were changed and simulated to achieve an optimal composed structure.A bionic sole was 3D-printed,and its performance was evaluated via compression test and a jumping-landing *** results show that cat paw pads are a spherical cap structure,divided from the outside to the inside into the epidermis,dermis,and compartments,each with different cushioning capacities.A finite element simulation of different cushioning structures was conducted in a cylinder with a diameter of 20 mm and a height of 10 mm,featuring a three-layer *** optimal configuration of the three layers should have a uniform distribution with 0.3–0.5 mm wall thickness,a 1:1–2 thickness ratio of epidermis and dermis,and 100–150 compartments.A bionic sole with an optimized structure can reduce the peak impact force and delay the peak arrival *** energy absorption rate is about 4 times that of standard *** jumping 80,100,and 120 cm,the normalized ground reaction force is also reduced by 8.7%,12.6%and 15.1%compared with standard *** study provides theoretical and technical support for effective protection against human lower limb landing injuries.

关键词： Cat paw pads Hierarchical Voronoi structure Landing impact Energy dissipation Bionic sole

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