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A Transformer-Based Ensemble Framework for the Prediction of Protein-Protein Interaction Sites

Research 2024年第2期2023卷 703-718页

作者： Minjie Mou Ziqi Pan Zhimeng Zhou Lingyan Zheng Hanyu Zhang Shuiyang Shi Fengcheng Li Xiuna Sun Feng Zhu College of Pharmaceutical Sciences The Second Affliated HospitalZhejiang University School of MedicineNational Key Laboratory of Advanced Drug Delivery and Release SystemsZhejiang UniversityHangzhou 310058China Innovation Institute for Artificial Intelligence in Medicine of zhejiang University Alibaba-Zhejiang University Joint Research Center of Future Digital HealthcareHangzhou 330110China

The identification of protein-protein interaction (PPI) sites is essential in the research of protein function and the discovery of new drugs. So far, a variety of computational tools based on machine learning have been developed to accelerate the identification of PPI sites. However, existing methods suffer from the low predictive accuracy or the limited scope of application. Specifically, some methods learned only global or local sequential features, leading to low predictive accuracy, while others achieved improved performance by extracting residue interactions from structures but were limited in their application scope for the serious dependence on precise structure information. There is an urgent need to develop a method that integrates comprehensive information to realize proteome-wide accurate profiling of PPI sites. Herein, a novel ensemble framework for PPI sites prediction, EnsemPPIS, was therefore proposed based on transformer and gated convolutional networks. EnsemPPIS can effectively capture not only global and local patterns but also residue interactions. Specifically, EnsemPPIS was unique in (a) extracting residue interactions from protein sequences with transformer and (b) further integrating global and local sequential features with the ensemble learning strategy. Compared with various existing methods, EnsemPPIS exhibited either superior performance or broader applicability on multiple PPI sites prediction tasks. Moreover, pattern analysis based on the interpretability of EnsemPPIS demonstrated that EnsemPPIS was fully capable of learning residue interactions within the local structure of PPI sites using only sequence information. The web server of EnsemPPIS is freely available at http://***/ensemppis.

关键词： residue extracting ensemble

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Effectiveness of Histopathological Examination of Ultrasound-guided Puncture Biopsy Samples for Diagnosis of Extrapulmonary Tuberculosis

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Biomedical and Environmental Sciences 2024年第2期37卷 170-177页

作者： GU Wen Fei SHI Xia MA Xin YU Jun Lei XU Jin Chuan QIAN Cheng Cheng HU Zhi Dong ZHANG Hui Shanghai Public Health Clinical center Fudan UniversityShanghai 201508China School of laboratory Medicine and Life Science Wenzhou Medical UniversityWenzhou 325000ZhejiangChina Department of laboratory Medicine Zhejiang Putuo HospitalZhoushan 316100ZhejiangChina Zhongshan Hospital Fudan UniversityShanghai 200032China

Objective To evaluate the diagnostic value of histopathological examination of ultrasound-guided puncture biopsy samples in extrapulmonary tuberculosis(EPTB).Methods This study was conducted at the Shanghai Public Health Clinical center.A total of 115patients underwent ultrasound-guided puncture biopsy,followed by MGIT 960 culture(culture),smear,Gene Xpert MTB/RIF(Xpert),and histopathological *** assays were performed to evaluate their effectiveness in diagnosing EPTB in comparison to two different diagnostic criteria:liquid culture and composite reference standard(CRS).Results When CRS was used as the reference standard,the sensitivity and specificity of culture,smear,Xpert,and histopathological examination were(44.83%,89.29%),(51.72%,89.29%),(70.11%,96.43%),and(85.06%,82.14%),*** on liquid culture tests,the sensitivity and specificity of smear,Xpert,and pathological examination were(66.67%,72.60%),(83.33%,63.01%),and(92.86%,45.21%),*** examination showed the highest sensitivity but lowest ***,we found that the combination of Xpert and histopathological examination showed a sensitivity of 90.80%and a specificity of 89.29%.Conclusion Ultrasound-guided puncture sampling is safe and effective for the diagnosis of *** with culture,smear,and Xpert,histopathological examination showed higher sensitivity but lower *** combination of histopathology with Xpert showed the best performance characteristics.

关键词： Extrapulmonary tuberculosis Diagnosis Biopsy Histopathological examination Puncture samples

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Granular Ionogel Particle Inks for 3D Printed Tough and Stretchable Ionotronics

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Research 2024年第1期2023卷 429-442页

作者： Yuan Yao Yue Hui Zhenhua Wang Hehao Chen Heng Zhu Nanjia Zhou Key laboratory of 3D Micro/Nano Fabrication and Characterization of zhejiang Province School of EngineeringWestlake UniversityHangzhou 310024Zhejiang ProvinceChina Institute of Advanced Technology Westlake Institute for Advanced StudyHangzhou 310024Zhejiang ProvinceChina School of Chemical Engineering and Advanced Materials the University of AdelaideAdelaide 5005South AustraliaAustralia State Key laboratory of Fluid Power&Mechatronic System Key Laboratory of Soft Machines and Smart Devices of Zhejiang ProvinceCenter for X-MechanicsDepartment of Engineering MechanicsZhejiang UniversityHangzhou 310027China

Ionogels have garnered great attention as promising soft conducting materials for the fabrication of flexible energy storage devices,soft actuators,and ***,the leakage of the ionic liquids,weak mechanical strength,and poor manufacturability have greatly limited their reliability and ***,we propose a new ionogel synthesis strategy by utilizing granular zwitterionic microparticles to stabilize ionic *** ionic liquids swell the microparticles and physically crosslink microparticles via either electronic interaction or hydrogen *** introducing a photocurable acrylic monomer enables the fabrication of double-network(DN)ionogels with high stretchability(>600%)and ultrahigh toughness(fracture energy>10 kJ/m^(2)).The synthesized ionogels exhibit a wide working temperature of−60 to 90℃.By tuning the crosslinking density of microparticles and physical crosslinking strength of ionogels,we synthesize DN ionogel inks and print them into three-dimensional(3D)*** ionogelbased ionotronics are 3D printed as demonstrations,including strain gauges,humidity sensors,and ionic skins made of capacitive touch sensor *** covalently linking ionogels with silicone elastomers,we integrate the ionogel sensors onto pneumatic soft actuators and demonstrate their capacities in sensing large *** our last demonstration,multimaterial direct ink writing is harnessed to fabricate highly stretchable and durable alternating-current electroluminescent devices with arbitrary *** printable granular ionogel ink represents a versatile platform for the future manufacturing of ionotronics.

关键词： crosslinking utilizing gauge

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The Functional Redundancy of Neddylation E2s and E3s in Modulating the Fitness of Regulatory T Cells

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Research 2024年第2期2023卷 373-387页

作者： Di Wu Yi Sun Cancer Institute(Key laboratory of Cancer Prevention and Intervention China National Ministry of Education)of the Second Affiliated Hospital and Institute of Translational MedicineZhejiang University School of MedicineHangzhou 310029China Cancer center of zhejiang University Hangzhou 310029China Zhejang Provincial Clinical Research center for Cancer Zhejang ProvinceChina Key laboratory of Molecular Biology in Medical Sciences Zhejang ProvinceChina Research center for Life Science and Human Health Binjiang Institute of Zhejiang UniversityHangzhou 310053China

Neddylation is necessary for activation of Cullin-RING ligases(CRLs),which degrade various immune regulatory *** recent study showed that while depletion of neddylation E2-E3 pair Ube2f-Sag in regulatory T(T_(reg))cells had no obvious phenotype,the same depletion of either Ube2m or Rbx1 caused inflammation disorders with different *** these E2s or E3s compensate each other in functional regulations of T_(reg)cells is,however,previously *** this report,we generated Foxp3^(Cre);Ube2m^(fl/fl);Ube2f^(fl/fl)or Foxp3^(Cre);Rbx1^(fl/fl);Sag^(fl/fl)double-null mice by simultaneous deletion of both neddylation E2s or E3s in T_(reg)cells,***,Ube2m&Ube2f double-null mice developed much severe autoimmune phenotypes than did Ube2m-null mice,indicating that Ube2m markedly compensates Ube2f in T_(reg)*** minor worsened autoimmune phenotypes seen at the very early stage in Rbx1&Sag double-null than Rbx1-null mice is likely due to already severe phenotypes of the later,indicating a minor compensation of Rbx1 for *** RNA profiling-based analyses revealed that up-and down-regulations of few signaling pathways in T_(reg)cells are associated with the severity of autoimmune ***,severer inflammation phenotypes seen in mice with double E3-null than with double E2-null T_(reg)cells indicate a neddylation-independent mechanism of 2 E3s,also known to serve as the RING component of CRLs in regulation of T_(reg)cell fitness.

关键词： Foxp3 inflammation markedly

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CRISPR/Cas9 system and its applications in nervous system diseases

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Genes & Diseases 2024年第2期11卷 675-686页

作者： Haibin Jiang Mengyan Tang Zidi Xu Yanan Wang Mopu Li Shuyin Zheng Jianghu Zhu Zhenlang Lin Min Zhang The Second School of Medicine Wenzhou Medical UniversityWenzhouZhejiang 325035China The First School of Medicine Wenzhou Medical UniversityWenzhouZhejiang 325035China Department of Pediatrics The Second School of MedicineThe Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical UniversityWenzhouZhejiang 325027China Key laboratory of Perinatal Medicine of Wenzhou WenzhouZhejiang 325027China Key laboratory of Structural Malformations in Children of zhejiang Province WenzhouZhejiang 325000China zhejiang Provincial Clinical Research center for Pediatric Disease WenzhouZhejiang 325027China

The clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)system is an acquired immune system of many bacteria and archaea,comprising CRISPR loci,Cas genes,and its associated *** system can recognize exogenous DNA and utilize the Cas9 protein's nuclease activity to break DNA double-strand and to achieve base insertion or deletion by subsequent DNA *** recent years,multiple laboratory and clinical studies have revealed the therapeutic role of the CRISPR/Cas9 system in neurological *** article reviews the CRISPR/Cas9-mediated gene editing technology and its potential for clinical application against neurological diseases.

关键词： CRISPR/Cas9 Gene editing Mutation Neurological diseases Therapeutics

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Both gain-and loss-of-function variants of KCNA1 are associated with paroxysmal kinesigenic dyskinesia

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Journal of Genetics and Genomics 2024年第8期51卷 801-810页

作者： Wan-Bing Sun Jing-Xin Fu Yu-Lan Chen Hong-Fu Li Zhi-Ying Wu Dian-Fu Chen Department of Medical Genetics and center for Rare Diseases and Department of Neurologyand Zhejiang Key Laboratory of Rare Diseases for Precision Medicine and Clinical Translation in Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310009China Nanhu Brain-computer Interface Institute HangzhouZhejiang 314050China MOE Frontier Science center for Brain Science and Brain-machine Integration School of Brain Science and Brain MedicineZhejiang UniversityHangzhouZhejiang 310012China

KCNA1 is the coding gene for Kv1.1 voltage-gated potassium-channelα*** variants of KCNA1 have been reported to manifest as paroxysmal kinesigenic dyskinesia(PKD),but the correlation between them remains unclear due to the phenotypic complexity of KCNA1 variants as well as the rarity of PKD *** the whole exome sequencing followed by Sanger sequencing,we screen for potential pathogenic KCNA1 variants in patients clinically diagnosed with paroxysmal movement disorders and identify three previously unreported missense variants of KCNA1 in three unrelated Chinese *** proband of one family(c.496G>A,p.A166T)manifests as episodic ataxia type 1,and the other two(c.877G>A,p.V293I and c.1112C>A,p.T371A)manifest as *** pathogenicity of these variants is confirmed by functional studies,suggesting that p.A166T and p.T371A cause a loss-of-function of the channel,while p.V293I leads to a gain-of-function with the property of voltage-dependent gating and activation kinetic *** reviewing the locations of PKD-manifested KCNA1 variants in Kv1.1 protein,we find that these variants tend to cluster around the pore domain,which is similar to ***,our study strengthens the correlation between KCNA1 variants and PKD and provides more information on genotype–phenotype correlations of KCNA1 channelopathy.

关键词： Paroxysmal kinesigenic dyskinesia KCNA1 Loss-of-function Gain-of-function Channelopathy Episodicataxiatype1

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A General Authentication and Key Agreement Framework for Industrial Control System

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Chinese Journal of Electronics 2024年第4期33卷 1046-1062页

作者： Shan GAO Junjie CHEN Bingsheng ZHANG Kui REN Xiaohua YE Yongsheng SHEN School of Cyber Science and Technology Zhejiang University Hangzhou Global Scientific and Technological Innovation center Zhejiang University zhejiang Provincial Key laboratory of Blockchain and Cyberspace Governance Hangzhou City Brain Co. Ltd

In modern industrial control systems(ICSs), when user retrieving the data stored in field device like smart sensor, there exists two main problems: one is lack of the verification for identification of user and field device;the other is that user and field device need exchange a key to encrypt sensitive data transmitted over the *** propose a comprehensive authentication and key agreement framework that enables all connected devices in an ICS to mutually authenticate each other and establish a peer-to-peer session key. The framework combines two types of protocols for authentication and session key agreement: The first one is an asymmetric cryptographic key agreement protocol based on transport layer security handshake protocol used for Internet access, while the second one is a newly designed lightweight symmetric cryptographic key agreement protocol specifically for field devices. This proposed lightweight protocol imposes very light computational load and merely employs simple operations like one-way hash function and exclusive-or(XOR) operation. In comparison to other lightweight protocols, our protocol requires the field device to perform fewer computational operations during the authentication phase. The simulation results obtained using Open SSL demonstrates that each authentication and key agreement process in the lightweight protocol requires only 0.005 ms. Our lightweight key agreement protocol satisfies several essential security features, including session key secrecy, identity anonymity, untraceability, integrity, forward secrecy, and mutual authentication. It is capable of resisting impersonation, man-in-the-middle, and replay attacks. We have employed the Gong-NeedhamYahalom(GNY) logic and automated validation of Internet security protocols and application tool to verify the security of our symmetric cryptographic key agreement protocol.

关键词： Performance evaluation Protocols Costs Industrial control Internet security Authentication Time measurement

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The intrinsic developmental age signal defines an age-dependent climbing behavior in cucumber

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Horticultural Plant Journal 2024年第3期10卷 797-808页

作者： Zezhou Hong Xinrui Wang Zipei Fan Jiahao Wang Aiyi Yang Guochao Yan Yong He Huasen Wang Zhujun Zhu Yunmin Xu College of Horticulture Science Zhejiang Agriculture and Forestry UniversityHangzhouZhejiang 311300China Key laboratory of Quality and Safety Control for Subtropical Fruit and Vegetable Ministry of Agriculture and Rural AffairsHangzhouZhejiang 311300China Collaborative Innovation center for Efficient and Green Production of Agriculture in Mountainous Areas of zhejiang Province HangzhouZhejiang 311300China

The tendril is a climbing organ in cucurbits and functions in physical support and to avoid shading by neighboring ***,how cucurbits produce tendrils to obtain climbing ability is largely *** this study,tendril phenotypes were investigated during different developmental *** results revealed that tendril growth exhibited an age-dependent pattern in *** growth was inhibited,and the tendril was formed as a short tendril[nonfunctional tendril(nonF-tendril),approximately 0.1 cm]during the seedling *** contrast,enhanced cell proliferation and cell expansion led to rapid elongation of the tendril during the climbing stage,and the tendril formed as a functional tendril(F-tendril,approximately 30 cm)to obtain climbing ***-qPCR detection showed that age-dependent tendril growth correlated negatively with the abundance of the conserved age regulator *** induced CsmiR156 to inhibit CsSPLs,and F-tendril formation and climbing ability were delayed in defoliated cucumbers,which confirmed the role of CsmiR156 in regulating tendril growth in ***,exogenous gibberellin(GA)treatment showed that GA positively regulated tendril growth,and RT-qPCR detection showed that the GA bio-synthetic genes and metabolic genes were affected by age pathway,suggesting that the age pathway depended on GA bio-synthetic and metabolic pathway to regulate cell expansion to determine tendril *** summary,our work reveals that change in tendril type is an important marker of phase transition in cucumber,and tendril growth is regulated by an intrinsic developmental age signal,ensuring that the cucumber obtains climbing ability at a suitable age.

关键词： Cucumber Tendril Age CsmiR156 CsSPL Climbing ability

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Defects evolution in n-type 4H-SiC induced by electron irradiation and annealing

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Journal of Semiconductors 2024年第7期45卷 77-83页

作者： Huifan Xiong Xuesong Lu Xu Gao Yuchao Yan Shuai Liu Lihui Song Deren Yang Xiaodong Pi State Key laboratory of Silicon and Advanced Semiconductor Materials&School of Materials Science and Engineering Zhejiang UniversityHangzhou 310027China Key laboratory of Power Semiconductor Materials and Devices of zhejiang Province&Institute of Advanced Semiconductors ZJU-Hangzhou Global Scientific and Technological Innovation CenterZhejiang UniversityHangzhou 311200China

Radiation damage produced in 4H-SiC by electrons of different doses is presented by using multiple characterization techniques. Raman spectra results indicate that SiC crystal structures are essentially impervious to 10 Me V electron irradiation with doses up to 3000 kGy. However, irradiation indeed leads to the generation of various defects, which are evaluated through photoluminescence(PL) and deep level transient spectroscopy(DLTS). The PL spectra feature a prominent broad band centered at 500 nm, accompanied by several smaller peaks ranging from 660 to 808 nm. The intensity of each PL peak demonstrates a linear correlation with the irradiation dose, indicating a proportional increase in defect concentration during irradiation. The DLTS spectra reveal several thermally unstable and stable defects that exhibit similarities at low irradiation ***, after irradiating at the higher dose of 1000 kGy, a new stable defect labeled as R_(2)(Ec-0.51 eV) appeared after annealing at 800 K. Furthermore, the impact of irradiation-induced defects on SiC junction barrier Schottky diodes is discussed. It is observed that high-dose electron irradiation converts SiC n-epilayers to semi-insulating layers. However, subjecting the samples to a temperature of only 800 K results in a significant reduction in resistance due to the annealing out of unstable defects.

关键词： 4H-SiC deep level transient spectroscopy(DLTS) photoluminescence(PL) defects

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Effects of Diesel Concentration on the Thermal Conductivity,Specific Heat Capacity and Thermal Diffusivity of Diesel-Contaminated Soil

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Journal of Thermal Science 2024年第2期33卷 696-709页

作者： WU Yuhao WU Yuefei LUO Gubai ZHANG Teng WANG Qing FAN Liwu SONG Xin YU Zitao Key laboratory of Clean Energy and Carbon Neutrality of zhejiang Province Zhejiang UniversityHangzhou310027China State Key laboratory of Clean Energy Utilization Zhejiang UniversityHangzhou310027China Institute of Thermal Science and Power Systems School of Energy EngineeringZhejiang UniversityHangzhou310027China center Environmental Protection Technology Company Limited Beijing100176China Institute of Soil Science Chinese Academy of SciencesNanjing210008China

High energy consumption is a serious issue associated with in situ thermal desorption(TD)remediation of sites contaminated by petroleum hydrocarbons(PHs).The knowledge on the thermophysical properties of contaminated soil can help predict accurately the transient temperature distribution in a remediation site,for the purpose of energy ***,such data are rarely reported for PH-contaminated *** this study,by taking diesel as a representative example for PHs,soil samples with constant dry bulk density but different diesel mass concentrations ranging from 0% to 20% were prepared,and the variations of their thermal conductivity,specific heat capacity and thermal diffusivity were measured and analyzed over a wide temperature range between 0℃ and 120℃.It was found that the effect of diesel concentration on the thermal conductivity of soil is negligible when it is below 1%.When diesel concentration is below 10%,the thermal conductivity of soil increases with raising the ***,when diesel concentration becomes above 10%,the change of the thermal conductivity of soil with temperature exhibits the opposite *** is mainly due to the competition between soil minerals and diesel,because the thermal conductivity of minerals increases with temperature,whereas the thermal conductivity of diesel decreases with *** analysis results showed that,compared with temperature,the diesel concentration has more significant effects on soil thermal *** of the diesel concentration,with the increase of temperature,the specific heat capacity of soil increases,while the thermal diffusivity of soil *** addition,the results of a control experiment exhibited that the relative differences of the thermal conductivity of the soil samples containing the same concentration of both diesel and a pure alkane are all below 10%,indicating that the results obtained with diesel in this study can be extended to the family of PHs.A theo

关键词： contaminated soil diesel concentration thermal conductivity specific heat capacity thermal diffusivity thermal desorption fractal model

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