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SHR-A1811(antibody-drug conjugate)in advanced HER2.mutant non-small cell lung cancer:a multicenter,open-label,phase 1/2.study

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Signal Transduction and Targeted Therapy 2024年第8期9卷 3483-3492页

作者： Ziming Li Zhengbo Song Wei Hong Nong Yang Yongsheng Wang Hong Jian Zibin Liang sheng Hu Min Peng Yan Yu Yan Wang Zicong Jiao Kaijing Zhao Ke Song {2. Li Wei Shi Shun Lu Shanghai Lung Cancer Center Shanghai Chest HospitalShanghai Jiaotong University School of MedicineShanghai 200030China Phase I Clinical Trial Ward Zhejiang Cancer HospitalHangzhou 310000China Department of Thoracic Oncology Zhejiang Cancer HospitalHangzhou 310000China Department of Lung&Gastrointestinal Oncology Hunan Cancer HospitalChangsha 410031China Thoracic Oncology Ward/Cancer Center West China Hospital of Sichuan UniversityChengdu 610041China Department of Thoracic Oncology The Fifth Affiliated Hospital of Sun Yat-Sen UniversityZhuhai 51900China Department of Medical Oncology Hubei Cancer HospitalWuhan 43000China Department of Oncology Renmin Hospital of Wuhan UniversityWuhan 430200China Department of Thoracic Medicine Harbin Medical University Cancer HospitalHarbin 150081China Department of Medical Oncology Cancer HospitalChinese Academy of Medical SciencesBeijing 100021China Geneplus-Beijing CoLtd.Beijing 102206China Jiangsu Hengrui Pharmaceuticals Co.Ltd.Shanghai 200120China

A dose-escalation and expansion,phase 1/2.study(***,NCT04818333)was conducted to assess the novel antibodydrug conjugate SHR-A1811 in pretreated HER2.altered advanced non-small cell lung cancer(NSCLC).Here,we report results from the phase 1 *** who had previously failed or were intolerant to platinum-based chemotherapy were enrolled and received SHR-A1811 intravenously at doses of 3.2.to 8.0 mg/kg every 3 *** escalation followed a Bayesian logistic regression model that included overdose control,with subsequent selection of tolerable levels for dose ***,63 patients were enrolled,including 43 receiving a recommended dose for expansion of 4.8 mg/*** patients had HER2.mutant ***-limiting toxicity occurred in one patient in the 8.0 mg/kg dose ***≥3 treatment-related adverse events occurred in 2.(46.0%)*** patient in the 6.4 mg/kg cohort died due to interstitial lung *** of April 11,2.2.,the 4.8 mg/kg cohort showed an objective response rate of 41.9%(95%Cl 2..0-57.9),and a disease control rate of 95.3%(95%Cl 84.2.99.4).The median duration of response was 13.7 months,with 13 of 18 responses *** median progression-free survival was 8.4 months(95%CI 7.1-15.0).SHR-A1811 demonstrated favourable safety and clinically meaningful efficacy in pretreated advanced HER2.mutantNSCLC.

关键词： SHR HER2 doses

New formula for predicting the plastic buckling pressure of steel torispherical heads under internal pressure

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Journal of Zhejiang University-Science A(Applied Physics & Engineering) 2024年第8期25卷 618-630页

作者： sheng YE Keming LI Jinyang ZHENG Shan SUN Institute of Process Equipment Zhejiang UniversityHangzhou 310027China Engineering Research Center for High Pressure Process Equipment and Safety of Ministry of Education Hangzhou 310027China State Key Laboratory of Fluid Power and Mechatronic Systems Hangzhou 310058China

Thin-walled torispherical heads under internal pressure can fail by plastic buckling because of compressive circumferential stresses in the head ***,existing formulas still have limitations,such as complicated expressions and low accuracy,in determining buckling *** this paper,we propose a new formula for calculating the buckling pressure of torispherical heads based on elastic-plastic analysis and experimental ***,a finite element(FE)method based on the arc-length method is established to calculate the plastic buckling pressure of torispherical heads,considering the effects of material strain hardening and geometrical *** buckling pressure results calculated by the FE method in this paper have good consistency with those of BOSOR5,which is a program for calculating the elastic-plastic bifurcation buckling pressure based on the finite difference energy ***,the effects of geometric parameters,material parameters,and restraint form of head edge on buckling pressure are ***,a new formula for calculating plastic buckling pressure is developed by fitting the curve of FE results and introducing a reduction factor determined from experimental ***,based on the experimental results,we compare the predictions of the new formula with those of existing *** is shown that the new formula has a higher accuracy than the existing ones.

关键词： Torispherical head Plastic buckling Elastic-plastic analysis Prediction formula Finite element method

A Deep Model for Partial Multi-label Image Classification with Curriculum-based Disambiguation

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Machine Intelligence Research 2024年第4期21卷 801-814页

作者： Feng Sun Ming-Kun Xie sheng-Jun Huang MIIT Key Laboratory of Pattern Analysis and Machine Intelligence College of Computer Science and TechnologyNanjing University of AeronauticsandAstronauticsNanjing211106China

In this paper,we study the partial multi-label(PML)image classification problem,where each image is annotated with a candidate label set consisting of multiple relevant labels and other noisy *** PML methods typically design a disambiguation strategy to filter out noisy labels by utilizing prior knowledge with extra assumptions,which unfortunately is unavailable in many real ***,because the objective function for disambiguation is usually elaborately designed on the whole training set,it can hardly be optimized in a deep model with stochastic gradient descent(SGD)on *** this paper,for the first time,we propose a deep model for PML to enhance the representation and discrimination *** the one hand,we propose a novel curriculum-based disambiguation strategy to progressively identify ground-truth labels by incorporating the varied difficulties of different *** the other hand,consistency regularization is introduced for model training to balance fitting identified easy labels and exploiting potential relevant *** experimental results on the commonly used benchmark datasets show that the proposed method significantlyoutperforms the SOTA methods.

关键词： Partial multi-label image classification curriculum-based disambiguation consistency regularization label difficulty candidatelabel set.

Adaptive Observer-Based Finite-Time Fault Tolerant Control for Non-Strict Feedback Systems

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Journal of Systems Science & Complexity 2024年第4期37卷 1526-1544页

作者： sheng Ning LIU Yang CHI Ronghu AI Zidong College of Automation and Electronic Engineering Qingdao University of Science and TechnologyQingdao 266042China

This paper considers the adaptive finite-time control and observer design method for a class of non-strict feedback systems with unmeasurable states,unknown nonlinear dynamics and actuator *** this paper,an observer is proposed to estimate the unmeasurable states in finite-time based on adaptive technique and neural networks,while the actuator faults are not *** filter is used to solve the computational explosion and singularity problems caused by the traditional backstepping and non-strict feedback structure,*** the fault efficiency indicators in real systems are not available,two-layer neural networks are adopted,where the first network is to estimate the unknown nonlinearities of systems and the second one is to estimate fault efficiency indicators and unknown nonlinear *** proposed scheme guarantees that states are bounded through stability ***,two experiments including a numerical example and a spring-mass-damper system are given to verify the effectiveness of the proposed method.

关键词： Command filter fault tolerant control finite-time control non-strict systems two-layer neural networks

Recent Advances in Deciphering the Mechanisms and Biological Functions of DNA Demethylation

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Chinese Journal of Chemistry 2024年第6期42卷 645-651页

作者： Yang Feng sheng-Jun Chen Bi-Feng Yuan Key Laboratory of Aquatic Product Processing Ministry of Agriculture and Rural AffairsNational R&D Center for Aquatic Product ProcessingSouth China Sea Fisheries Research InstituteChinese Academy of Fishery SciencesGuangzhouGuangdong510300 China School of Public Health Research Center of Public HealthRenmin Hospital of Wuhan UniversityWuhan UniversityWuhanHubei430071 China

5-Methylcytosine (5mC) is a dynamic and reversible epigenetic modification in genomic DNA of higher *** has been well-established that the demethylation of 5mC occurs through the ten-eleven translocation (TET)-mediated oxidation of 5mC followed by thymine DNA glycosylase (TDG)-initiated base excision repair (BER).Recent findings also have identified an alternative pathway of DNA *** this pathway,TET enzymes directly oxidize 5mC to form 5-formylcytosine (5fC) or 5-carboxylcytosine (5caC).These modified bases can undergo direct deformylation or decarboxylation,***,DNA demethylation can also occur through the deamination of 5mC and 5hmC,resulting in the production of thymine and 5-hydroxymethyluracil (5hmU),*** DNA demethylation pathways possess critical functional implications and roles in biological *** Recent Advances article will focus on the studies of mechanisms and biological functions of DNA demethylation,shedding light on the reversible nature of the epigenetic modification of 5mC.

关键词： Epigenetics DNA DNA methylation 5-Methylcytosine Demethylation Mechanisms Biological functions C—C bond cleavage Mass spectrometry

The ubiquitin codes in cellular stress responses

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Protein & Cell 2024年第3期15卷 157-190页

作者： Xiangpeng sheng Zhixiong Xia Hanting Yang Ronggui Hu Key Laboratory of Systems Health Science of Zhejiang Province School of Life ScienceHangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhou 310024China State Key Laboratory of Molecular Biology Shanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesShanghai 200031China State Key Laboratory of Animal Disease Control Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150069China Department of Neurology State Key Laboratory of Medical NeurobiologyInstitute for Translational Brain ResearchMOE Frontiers Center for Brain ScienceZhongshan HospitalFudan UniversityShanghai 200032China

Ubiquitination/ubiquitylation,one of the most fundamental post-translational modifications,regulates almost every critical cellular process in *** evidence has shown that essential components of numerous biological processes undergo ubiquitination in mammalian cells upon exposure to diverse stresses,from exogenous factors to cellular reactions,causing a dazzling variety of functional *** forms of ubiquitin sig-nals generated by ubiquitylation events in specific milieus,known as ubiquitin codes,constitute an intrinsic part of myriad cellular stress *** ubiquitination events,leading to proteolytic turnover of the substrates or just switch in functionality,initiate,regulate,or supervise multiple cellular stress-associated responses,supporting adaptation,homeostasis recovery,and survival of the stressed *** this review,we attempted to summarize the crucial roles of ubiquitination in response to different environmental and intracellular stresses,while discussing how stresses modulate the ubiquitin *** review also updates the most recent advances in understanding ubiquitination machinery as well as different stress responses and discusses some important questions that may warrant future investigation.

关键词： ubiquitin E3 ligase environmental stresses intercellular stresses stress response homeostasis

Plant RNA-binding proteins:Phase separation dynamics and functional mechanisms underlying plant development and stress responses

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Molecular Plant 2024年第4期17卷 531-551页

作者： sheng Fan Yu Zhang Shaobo Zhu Lisha Shen Temasek Life Sciences Laboratory 1 Research LinkNational University of Singapore1 Research LinkSingapore 117604Singapore Department of Biological Sciences National University of Singapore14 Science Drive 4Singapore 117543Singapore

RNA-binding proteins(RBPs)accompany RNA from synthesis to decay,mediating every aspect of RNA metabolism and impacting diverse cellular and developmental processes in *** RBPs undergo phase separation along with their bound RNA to form and function in dynamic membraneless biomolecular condensates for spatiotemporal coordination or regulation of RNA *** evidence suggests that phase-separating RBPs with RNA-binding domains and intrinsically disordered regions play important roles in plant development and stress ***,we summarize the current knowledge about how dynamic partitioning of RBPs into condensates controls plant development and enables sensing of experimental changes to confer growth plasticity under stress conditions,with a focus on the dynamics and functional mechanisms of RBP-rich nuclear condensates and cytoplasmic granules in mediating RNA *** also discuss roles of multiple factors,such as environmental signals,protein modifications,and N6-methyladenosine RNA methylation,in modulating the phase separation behaviors of RBPs,and highlight the prospects and challenges for future research on phase-separating RBPs in crops.

关键词： RNA-binding proteins phase separation biomolecular condensates RNA metabolism development stress resilience

Catalytically generated noncovalent ammonium dienolate:a versatile platform for the development of organocatalytic asymmetric cascade reactions

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Science China Chemistry 2024年第8期67卷 2524-2546页

作者： Jun-Bing Lin Dong-sheng Ji Peng-Fei Xu State Key Laboratory of Applied Organic Chemistry College of Chemistry and Chemical EngineeringLanzhou UniversityLanzhou 730000China Shaanxi Key Laboratory of Chemical Reaction Engineering College of Chemistry and Chemical EngineeringYan’an UniversityYan’an 716000China

Organocatalytic cascade reactions represent a powerful strategy for the rapid construction of complex chiral molecules with multiple stereocenters from simple substrates under mild conditions. The intriguing structural feature and diverse reactivity of catalytically generated dienolate species render them competent and versatile intermediates for the development of practical and valuable cascade reactions. Over the past years, a plethora of innovative and pioneering noncovalent ammonium dienolatemediated cascade reactions have been designed and implemented under the catalysis of chiral organocatalysts, making dienolate activation a general, robust, and complementary method for the functionalization of unsaturated carbonyl compounds and related substances. This review illustrates the recent advances in organocatalytic noncovalent ammonium dienolate-mediated cascade reactions(mainly from 2.10 to 2.2.), including the cascade transformations of ammonium dienolates directly generated from unsaturated ketone/aldehyde, ester/lactone/azlactone, amide/lactam/pyrazolone/oxindole, and alkylidene nitrile compounds. The contents are arranged based on the reaction types of the ammonium dienolates, with an emphasis on cascade 2.5-, 3,5-, and 4,5-difunctionalizations of these intermediates. Furthermore, other cascade reactions involving the 1,3-, 2.3-, and even more complex 3,4,5-reactivities of ammonium dienolates were also discussed. The reaction pathway, reaction stereoinduction, and synthetic applications of the ammonium dienolate-mediated cascade reactions were highlighted throughout the article. As a stimulating and ever-growing research area, the organocatalytic noncovalent ammonium dienolate-mediated cascade reactions are expected to continue demonstrating their magic power for constructing chiral targets in the future and further expanding the boundaries of asymmetric catalysis.

关键词： organocatalysis asymmetric catalysis ammonium dienolate cascade reaction difunctionalization

Exoskeleton active assistance strategy for human muscle activation reduction during linear and circular walking

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Advances in Manufacturing 2024年第3期12卷 484-496页

作者： Wen-Tao sheng Ke-Yao Liang Hai-Bin Tang School of Intelligent Manufacturing Nanjing University of Science and TechnologyNanjing210094People’s Republic of China School of Mechatronics Engineering Harbin Institute of TechnologyHarbin150001People’s Republic of China

The exoskeleton is employed to assist humans in various domains including military missions,rehabilitation,industrial operation,and activities of daily living(ADLs).Walking is a fundamental ADL,and exoskeletons are capable of reducing the activation and metabolism of lower extremity muscles through active assistance during *** improve the performance of active assistance strategy,this article proposes a framework using an active hip ***,it correlates to an already established Bayesian-based human gait recognition algorithm,with a particular focus on linear and circular walking within industrial and ADL *** theorizing this strategy for exoskeletons,this study further reveals,in part,the activation characteristics of human hip muscles for the instruction and regulation of active assistance duration and onset *** proposed active assistance strategy provides new insights for enhancing the performance of assistive robots and facilitating human robot interaction within the context of ADLs.

关键词： Human-robot interaction Hip exoskeleton Muscle activation Walking assistance