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QL1706 (anti-PD-1 IgG4/CTLA-4 antibody) plus chemotherapy with or without bevacizumab in advanced non-small cell lung cancer: a multi-cohort, phase II study

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Signal Transduction and Targeted Therapy 2024年第2期9卷 797-806页

作者： yan Huang Yunpeng yang Yuanyuan zhao Hongyun zhao Ningning Zhou yaxiong Zhang Likun Chen ting Zhou Gang Chen ting Wu Lu Lu Shilin Xue Xiaoyan Kang Li Zhang Wenfeng Fang Department of Medical Oncology Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineNo.651 Dongfeng East RoadGuangzhouGuangdong 510060China Department of Medicine Qilu Pharmaceutical Co.Ltd.JinanChina

First-line chemoimmunotherapy(with or without bevacizumab)has improved outcomes in advanced non-small cell lung cancer(NSCLC).Here,this open-label,multi-cohort phase II study(NCT05329025)was done to investigate the safety and efficacy of QL1706(a single bifunctional MabPair product against PD-1 and CTLA-4)and chemotherapy with or without bevacizumab in this *** were enrolled into five different cohorts based on genotype(cohorts 1-4,epidermal growth factor receptor[EGFR]wild-type;cohort 5,EGFR-mutant and progressed on EGFR-tyrosine kinase inhibitors[TKIs]).Between June 11,2021 and December 29,2021,91 patients were *** frequent treatment-related adverse events(TRAEs)included decreased appetite(60[65.9%]),anemia(60[65.9%]),infusion-related reactions(48[52.7%]),and pruritus(44[48.4%]).Grade≥3 TRAEs occurred in 30(33.0%)***-seven(45%)patients with wild-type EGFR achieved partial response(PR)(objective response rate[ORR]=45%)and had a median progression-free survival(mPFS)of 6.8 months(95%CI:5.2-9.7).For 31 patients harboring mutated EGFR,17(54.8%)achieved PR(ORR=54.8%),with an mPFS of 8.5 months(95%CI:5.72-not evaluable).Overall,QL1706 plus chemotherapy,regardless of having bevacizumab,was generally tolerable and had promising antitumor activity for EGFR wild-type advanced NSCLC in first-line ***,QL1706 plus chemotherapy and bevacizumab showed favorable antitumor activity for patients who had EGFR mutated NSCLC but failed in TKI therapy,demonstrating a potential for treating this population.

关键词： bevacizumab chemotherapy phase

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Advances in memristor based artificial neuron fabrication-materials,models,and applications

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International Journal of Extreme Manufacturing 2024年第1期6卷 27-50页

作者： Jingyao Bian Zhiyong Liu Ye Tao Zhongqiang Wang Xiaoning zhao ya Lin Haiyang Xu Yichun Liu Key Laboratory for UV Light-Emitting Materials and Technology(Northeast Normal University) Ministry of Education5268 Renmin StreetChangchunPeople’s Republic of China

Spiking neural network(SNN),widely known as the third-generation neural network,has been frequently investigated due to its excellent spatiotemporal information processing capability,high biological plausibility,and low energy consumption *** to the working mechanism of human brain,the SNN system transmits information through the spiking action of ***,artificial neurons are critical building blocks for constructing SNN in *** are drawing growing attention due to low consumption,high speed,and nonlinearity characteristics,which are recently introduced to mimic the functions of biological *** have proposed multifarious memristive materials including organic materials,inorganic materials,or even two-dimensional *** advantage of the unique electrical behavior of these materials,several neuron models are successfully implemented,such as Hodgkin–Huxley model,leaky integrate-and-fire model and integrate-and-fire *** this review,the recent reports of artificial neurons based on memristive devices are *** addition,we highlight the models and applications through combining artificial neuronal devices with sensors or other electronic ***,the future challenges and outlooks of memristor-based artificial neurons are discussed,and the development of hardware implementation of brain-like intelligence system based on SNN is also prospected.

关键词： artificial neuron memristor memristive materials neuron model micro-nano manufacturing spiking neural network

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Text Difficulty Study:Do Machines Behave the Same as Humans Regarding Text Difficulty?

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Machine Intelligence Research 2024年第2期21卷 283-293页

作者： Bowen Chen Xiao Ding Yi zhao Bo Fu tingmao Lin Bing Qin ting Liu Research Center for Social Computing and Information Retrieval Harbin Institute of TechnologyHarbin 150001China Fundamental Technology Center China Construction Bank Financial Technology Co.Ltd.Beijing 100033China

With the emergence of pre-trained models,current neural networks are able to give task performance that is comparable to ***,we know little about the fundamental working mechanism of pre-trained models in which we do not know how they approach such performance and how the task is solved by the *** example,given a task,human learns from easy to hard,whereas the model learns ***,difficulty-insensitive learning leads to great success in natural language processing(NLP),but little attention has been paid to the effect of text difficulty in *** propose a human learning matching index(HLM Index)to investigate the effect of text *** results show:1)LSTM gives more human-like learning behavior than ***,UID-SuperLinear gives the best evaluation of text difficulty among four text difficulty *** nine tasks,some tasks’performance is related to text difficulty,whereas others are not.2)Model trained on easy data performs best in both easy and medium test data,whereas trained on hard data only performs well on hard test data.3)Train the model from easy to hard,leading to quicker convergence.

关键词： Cognition inspired natural language processing psycholinguistics explainability text difficulty curriculum learning

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Study on a probabilistic algorithm for the forming and 3D characterization of special-shaped surfaces under profile grinding

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Advances in Manufacturing 2024年第2期12卷 288-299页

作者： zhao-Qing Zhang Kai-Ning Shi yao-yao Shi Yi-Hui Song Zhe He ya-Song Pu School of Mechanical Engineering Northwestern Polytechnical UniversityXi’an710072People’s Republic of China Key Laboratory of High Performance Manufacturing for Aero Engine(Northwestern Polytechnical University) Ministry of Industry and Information TechnologyXi’an710072People’s Republic of China Engineering Research Center of Advanced Manufacturing Technology for Aero Engine(Northwestern Polytechnical University) Ministry of EducationXi’an710072People’s Republic of China

Profile grinding is the most crucial method for the ultra-precision machining of special-shaped ***,profile grinding produces a unique machining profile,and many random factors in the machining process lead to complex surface *** this study,the structural and probabilistic characteristics of the profile grinding of a special-shaped surface were analyzed,and a probabilistic algorithm for the forming and 3D characterization of special-shaped surfaces under profile grinding was *** forming process of a GH738 blade tenon tooth surface was considered as an example to demonstrate the *** comparison results showed that the simulation results had similar surface characteristics to the measurement results,and the relative error range of the 3D roughness parameter was 0.21%–19.76%,indicating an accurate prediction and characterization of the complex special-shaped surface under the action of multiple factors.

关键词： Special-shaped surface Profile grinding Surface morphology 3D characterization

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Research on feed-pulse collaborative control method in micro-electrical discharge machining

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Advances in Manufacturing 2024年第2期12卷 270-287页

作者： Qiang Gao ya-Ou Zhang Xue-Cheng Xi Yuan-Ding Wang Xiao-Fei Chen Wan-Sheng zhao School of Mechanical Engineering Shanghai Jiao Tong UniversityShanghai200240People’s Republic of China State Key Laboratory of Mechanical System and Vibration Shanghai200240People’s Republic of China Shanghai Institute of Space Propulsion Shanghai201112People’s Republic of China

Reducing the short-circuit rate and increasing the effective discharge rate are important targets for improving the servo control effect of micro-electrical discharge machining(micro-EDM),as these two indicators are closely related to the machining efficiency and *** this study,a feed-pulse collaborative control(FPCC)method is proposed for micro-EDM based on two dimensions(space and time).In the spatial dimension,a feed control strategy with a discharge holding process is ***,in the time dimension,a forward-looking pulse control strategy is adopted,in which the pulse interval is adjusted based on a sequence analysis of feed commands and discharge *** experiments are carried out to determine the key parameters used in this method,including the discharge holding threshold and pulse interval adjustment value(T_(off_(adj))).The feed smoothness and discharge sufficiency analyses of the experimental results show that compared to the traditional double threshold average voltage method,the FPCC method reduces the number of long-distance retreats by 64%and improves the effective discharge time by 40%.

关键词： Micro-electrical discharge machining(micro-EDM) Electrode feed control Discharge pulse control Machining surface quality

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Enhancing dielectric properties and energy storage performance of polyvinylidene fluoride composite by surface-modified AgNbO_(3) nanoparticles

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High Voltage 2024年第4期9卷 939-947页

作者： Zhuo Wang ting zhao Dan Wu Ying Xue Zhihui Yi Jinteng Kang Ronghui Ye Ning Guo Shaanxi Key Laboratory of Green Preparation and Functionalization for Inorganic Materials School of Materials Science and EngineeringShaanxi University of Science and TechnologyXi'anChina Key Laboratory of Engineering Dielectrics and Its Application Ministry of EducationHarbin University of Science and TechnologyHarbinChina

The introduction of antiferroelectric filler AgNbO_(3) into the polyvinylidene fluoride(PVDF)polymer matrix enhances its energy storage properties of ***,AgNbO_(3) and PVDF matrix are incompatible due to their distinct physical and chemical properties,resulting in poor compatibility between the two *** modification enhances the large difference in physical and chemical properties between the filler and the polymer matrix,and improves the compatibility between the two *** coupling agents(KH550,KH560),dopamine(DA),and grafted poly(methyl methacrylate)(PMMA)were used to modify the surface of AgNbO_(3) particles,and the effects of different surface modification methods on the energy storage performance of the composites were *** PVDF matrix was introduced with 0.3 wt%AgNbO_(3) particle *** results showed that the amino group in KH550 had the strongest binding with *** ester group in PMMA has a strong binding with *** epoxy group in KH560 has a weak binding with PVDF,while the amino group in DA has the worst binding with *** compatibility of the two phases in AgNbO_(3)@KH550/PVDF composites is the best,and the charge distribution on the surface of the filler is *** an electric field of 350 kV/mm,the energy storage density is 8.48 J/cm^(3).

关键词： composites composite filler

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A chromatographic method for pursuing potential GPCR ligands with the capacity to characterize their intrinsic activities of regulating downstream signaling pathway

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Chinese Chemical Letters 2024年第10期35卷 425-429页

作者： ting Li Xinxin Zheng Lejing Qu Yuanyuan Ou Sai Qiao Xue zhao yajun Zhang Xinfeng zhao Qian Li Key Laboratory of Resource Biology and Biotechnology in Western China Ministry of EducationCollege of Life SciencesNorthwest UniversityXi'an 710069China

GPCRs are dominant targets for approved drugs and the discovery of lead compound targeting them is still ***-based screening technique is a promising platform to uncover GPCR ***,the intrinsic activities of them are seldom simultaneously determined during the *** beta2-adrenoceptor(β2AR)as a probe,this work created a strategy for screening GPCR ligands with simultaneous characterization of their downstream G protein binding responses associated with *** strategy included(i)the design and expression of a protein miniature formed byβ2AR and G proteinα-subunit(Gαs)using circularly permuted HaloTag(cpHalo)as a flexible linker;(ii)immobilization of the miniature onto silica gel by a click dehalogenation reaction;(iii)systematic characterization of the immobilized miniature by fluorescent and chromatographic studies,and(iv)simulating of ligand-inducedβ2AR-Gαs signaling cascade by chromatographic assays using GTP as an *** immobilized miniature exhibited specificity toβ2AR and Gαs antibodies and *** specificity is stable at least within fifteen days with the variation less than 1%.The intrinsic activities ofβ2AR ligands were distinguished by the changes of GTP chromatographic behaviors on Gαs-cpHalo-β2AR *** strengthened the binding affinity and kinetics of GTP with Gαs,while antagonist did not give any effect on *** the intrinsic activity evaluation,we believe,it will improve the attributes of chromatographic methods for drug discovery efforts with minimizing false-positive results.

关键词： Intrinsic efficacy GPCR-G protein miniature Circularly permuted HaloTag High-performance receptor chromatography GTP binding Agonist/antagonist

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Application of CRISPR/Cas12i.3 for targeted mutagenesis in broomcorn millet(Panicum miliaceum L.)

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Journal of Integrative Plant Biology 2024年第8期66卷 1544-1547页

作者： Yuhe Bai Shengnan Liu yan Bai Zhisong Xu Hainan zhao Haiming zhao Jinsheng Lai ya Liu Weibin Song State Key Laboratory of Maize Bio-breeding Key Laboratory of Genome Editing Research and ApplicationMinistry of Agriculture and Rural AffairsDepartment of Plant Genetics and BreedingNational Maize Improvement CenterCollege of Agronomy and BiotechnologyChina Agricultural UniversityBeijing 100193China National Agricultural Technology Extension&Service Center Beijing 100125China Beijing Key Laboratory of Maize DNA Fingerprinting and Molecular Breeding Beijing Academy of Agriculture and Forestry SciencesBeijing 100097China

As the global human population continues to grow and is predicted to reach 10 billion by 2050,the demand for food volume and quality raises a tremendous challenge(OECD/FAO,2017).The worldwide arable land area is decre... 详细信息

关键词： arable continue raise

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Overview of ferroptosis and pyroptosis in acute liver failure

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World Journal of Gastroenterology 2024年第34期30卷 3856-3861页

作者： ya-Wen Sun Bo-Wen zhao Hai-Fang Li Guang-Xiao Zhang College of Life Sciences Shandong Agricultural UniversityTai’an 271018Shandong ProvinceChina

In this editorial,we comment on the article by Zhou et al published in a recent *** specifically focus on the crucial roles of ferroptosis and pyroptosis in acute liver failure(ALF),a disease with high mortality *** is the result of increased intracellular reactive oxygen species due to iron accumulation,glutathione(GSH)depletion,and decreased GSH peroxidase 4 activity,while pyroptosis is a procedural cell death mediated by gasdermin D which initiates a sustained inflammatory *** this review,we describe the characteristics of ferroptosis and pyroptosis,and discuss the involvement of the two cell death modes in the onset and development of ***,we summarize several interfering methods from the perspective of ferroptosis and pyroptosis for the alleviation of *** observations might provide new targets and a theoretical basis for the treatment of ALF,which are also crucial for improving the prognosis of patients with ALF.

关键词： Acute liver failure Ferroptosis Pyroptosis Glutathione peroxidase 4 Gasdermin D

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Programming Supramolecular Hydrogels by Constructing a Multibranch Selection Structure

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CCS Chemistry 2024年第8期6卷 1951-1964页

作者： Zhongrui Wang ting zhao Shenghao yang Yuwen Meng Xu Wang National Engineering Research Center for Colloidal Materials School of Chemistry and Chemical EngineeringShandong UniversityJinanShandong 250100 Key Laboratory of Colloid and Interface Chemistry of the Ministry of Education School of Chemistry and Chemical EngineeringShandong UniversityJinanShandong 250100

Developing chemical systems capable of executing multipath nonequilibrium processes provides valuable insights into the study of multistage dissipative structures in living ***,we report a nonequilibrium multipath evolution in a three-state supramolecular system,which is clarified by associating it with a multibranch selection *** system is constructed by synergistically combining an assembly-induced sol-gel transition with the color change of an acid-base *** on the initial condition and chemical fuel composition,this system can execute five distinct nonequilibrium *** addition,the set of structured programming can be replayed by repeatedly introducing the chemical *** is further utilized to explore the applications of information encryption and establish its *** findings offer novel avenues for future transient material design and may make significant contributions to systems chemistry.

关键词： supramolecular hydrogels nonequilibrium processes programmable self-assembly chemical fuels multibranch selection structure

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