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Selective type II TRK inhibitors overcome xDFG mutation mediated acquired resistance to the second-generation inhibitors selitrectinib and repotrectinib

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Acta Pharmaceutica Sinica B 2024年第2期14卷 517-532页

作者： Shuang xiang Xiaoyun lu International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Discovery of Chinese Ministry of Education(MOE) Guangdong Provincial Key Laboratory of New Drug Design and EvaluationGuangzhou City Key Laboratory of Precision Chemical Drug DevelopmentSchool of PharmacyJinan UniversityGuangzhou 510632China

Neurotrophic receptor kinase(NTRK) fusions are actionable oncogenic drivers of multiple pediatric and adult solid tumors,and tropomyosin receptor kinase(TRK) has been considered as an attractive therapeutic target for "pan-cancer" harboring these ***,two generations TRK inhibitors have been *** representative second-generation inhibitors selitrectinib and repotrectinib were designed to overcome clinic acquired resistance of the first-generation inhibitors larotrectinib or entrectinib resulted from solvent-front and gatekeeper on-target ***,xDFG(TRKAG667C/A/S,homologous TRKCG696C/A/S) and some double mutations still confer resistance to selitrectinib and repotrectinib,and overcoming these resistances represents a major unmet clinical *** this review,we summarize the acquired resistance mechanism of the first-and second-generation TRK inhibitors,and firstly put forward the emerging selective type Ⅱ TRK inhibitors to overcome xDFG mutations mediated ***,we concluded our perspectives on new challenges and future directions in this field.

关键词： NTRK fusions TRK kinase Clinical resistance xDFG mutations Selective type II inhibitors

Biomimetic Gland Models with Engineered Stratagems

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Research 2024年第2期2023卷 583-612页

作者： xiang Lin Lingyu Sun Minhui lu Yuanjin Zhao Department of Rheumatology and Immunology Nanjng Drum Tower HospitalSchool of Biological Science and Medical EngineeringSoutheast UniversityNanjing 210096China Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)Wenzhou InstituteUniversity of Chinese Academy of SciencesWenzhouZhejiang 325001China Southeast University Shenzhen Research Institute Shenzhen 518071China

As extensively distributed tissues throughout the human body,glands play a critical role in various physiological ***,the construction of biomimetic gland models in vitro has aroused great interest in multiple *** the biological field,the researchers focus on optimizing the cell sources and culture techniques to reconstruct the specific structures and functions of glands,such as the emergence of organoid *** the perspective of biomedical engineering,the generation of biomimetic gland models depends on the combination of engineered scaffolds and microfluidics,to mimic the in vivo environment of glandular *** engineered stratagems endowed gland models with more biomimetic features,as well as a wide range of application *** this review,we first describe the biomimetic strategies for constructing different in vitro gland models,focusing on the role of microfluidics in promoting the structure and function development of biomimetic *** summarizing several common in vitro models of endocrine and exocrine glands,the applications of gland models in disease modelling,drug screening,regenerative medicine,and personalized medicine are ***,we conclude the current challenges and our perspective of these biomimetic gland models.

关键词： endowed constructing strata

Renewable biosynthesis of isoprene from wastewater through a synthetic biology approach:the role of individual organic compounds

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Frontiers of Environmental Science & Engineering 2024年第3期18卷 13-24页

作者： Min Yang xianghui Li Weixiang Chao xiang Gao Huan Wang lu lu State Key Laboratory of Urban Water Resource and Environment School of Civil and Environmental EngineeringHarbin Institute of TechnologyShenzhen 518055China Center for Materials Synthetic Biology CAS Key Laboratory of Quantitative Engineering Biology of CASShenzhen Institute of Synthetic BiologyShenzhen Institutes of Advanced TechnologyChinese Academic of ScienceShenzhen 518000China Institute of Urban Ecology and Environmental Technology School of Materials and Environmental EngineeringShenzhen Polytechnic UniversityShenzhen 518055China

The biosynthesis of isoprene offers a more sustainable alternative to fossil fuel-based approaches,yet its success has been largely limited to pure organic compounds and the cost remains a *** study proposes a waste-to-wealth strategy for isoprene biosynthesis utilizing genetically engineered *** bacteria to convert organic waste from real food *** impact of organic compounds present in wastewater on *** growth and isoprene production was systematically *** results demonstrated that with filtration pretreatment of wastewater,isoprene yield,and production achieved 115 mg/g COD and 7.1 mg/(L·h),***,even without pretreatment,isoprene yield only decreased by~24%,indicating promising ***,maltose,glycerol,and lactate are effective substrates for isoprene biosynthesis,whereas starch,protein,and acetate do not support *** *** optimum C/N ratio for isoprene production was found to be 8:***,augmenting essential nutrients in wastewater elevated the isoprene yield increased to 159 mg/g *** wastewater biosynthesis significantly reduced the cost(44%–53%decrease,p-valuelue<0.01)compared with both sugar fermentation and fossil fuel–based *** study introduced a more sustainable and economically viable approach to isoprene synthesis,offering an avenue for resource recovery from wastewater.

关键词： Wastewater Resource recovery Genetic engineering Biosynthesis Isoprene

Fabrication of corrosion inhibiting microcapsules functional coating and their high-efficiency corrosion resistance

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Rare Metals 2024年第2期43卷 842-848页

作者： Hao-Ran Yun lu lu Xue-Long Hao Xing-xiang Zhang School of Material Science and Engineering Tiangong UniversityTianjin300387China National Center of Analysis and Testing for Nonferrous Metals and Electronic Materials General Research Institute for Nonferrous MetalsBeijing100088China Guobiao(Beijing)Testing&Certification Co. Ltd.Beijing101407China

Benzotriazole(BTA)was loaded into calcium carbonate microsphere shell by self-assembly method and a new type of high-efficiency corrosion inhibiting microcapsules(CIMs)were fabricated,which were added and dispersed into epoxy resin coating to obtain a new corrosion resistance functional *** corrosion inhibition effect of benzotriazole on aluminum alloy matrix was verified by polarization curve *** effectiveness of the CIMs and their loading capacity on inhibitor were evaluated by scanning electron microscope,laser confocal Raman spectroscopy together with thermogravimetric analysis.

关键词： corrosion coating resistance

Weighted Composition Operators That Preserve Frames On Weighted Hardy Spaces

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Acta Mathematica Sinica,English Series 2024年第7期40卷 1645-1654页

作者： Ya Li Dong Rui Liu Guo xiang lu School of Mathematical Sciences and LPMC Nankai UniversityTianjin300071P.R.China School of Statistics and Mathematics Zhongnan University of Economics and LawWuhan430073P.R.China

In this paper, we characterize weighted composition operators that preserve frames on the weighted Hardy spaces in the unit disk. In particular, we obtain the symbol properties of the bounded invertible weighted composition operators. Moreover, we establish the equivalence between bounded invertible operators and frame-preserving operators. Furthermore, we show that weighted composition operator preserves frames if and only if it preserves the Riesz bases property. Additionally,we investigate the weighted composition operators that preserve tight or normalized tight frames on the Dirichlet space.

关键词： Weighted composition operators Weighted Hardy spaces frames invertible

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A projected Newton algorithm based on chemically allowed interval for chemical equilibrium computations

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Frontiers of Chemical Science and Engineering 2024年第3期18卷 25-37页

作者： Hongbin lu Shaohui Tao Xiaoyan Sun Li Xia Shuguang xiang Institute of Process Systems Engineering College of Chemical EngineeringQingdao University of Science and TechnologyQingdao266042China

The chemical equilibrium equations utilized in reactive transport modeling are complex and nonlinear,and are typically solved using the Newton-Raphson *** this algorithm is known for its quadratic convergence near the solution,it is less effective far from the solution,especially for ill-conditioned *** such cases,the algorithm may fail to converge or require excessive *** address these limitations,a projected Newton method is introduced to incorporate the concept of *** method constrains the Newton step by utilizing a chemically allowed interval that generates feasible descending ***,we utilize the positive continuous fraction method as a preconditioning technique,providing reliable initial values for solving the *** numerical results are compared with those derived using the regular Newton-Raphson method,the Newton-Raphson method based on chemically allowed interval updating rules,and the bounded variable least squares method in six different test *** numerical results highlight the robustness and efficacy of the proposed algorithm.

关键词： chemical equilibrium reactive transport modeling numerical methods projected Newton method

Enhancement of ionic conductivity and fracture toughness by infiltrating porous Li_(0.33)La_(0.56)TiO_(3) pellets

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Journal of Rare Earths 2024年第2期42卷 392-398,I0006页

作者： Xiaojuan lu Mingyang Duan Jingyu xiang Yuning Liang Songtao Liu Hebei Key Lab of Power Plant Flue Gas Multi-Pollutants Control Department of Environmental Science and EngineeringNorth China Electric Power UniversityBaoding071003China

Although solid-state lithium electrolytes have the potential to reduce the safety issues associated with organic liquid electrolytes,disadvantages such as low total conductivity,large interface impedance,and delamination of the interface due to cyclic stress still need to be *** solid-state lithium-ion conductor Li_(0.33)La_(0.56)TiO_(3)(LLTO) was prepared via a hydrothermal route by using CTAB as templates in this *** LLTO with micro-porous channels was obtained and the total conductivity is comparable to the non-porous *** LLTO pellets are infiltrated with the non-porous LLTO precursor solution,and the total conductivities of the infiltrated porous LLTO are all higher than those without *** infiltration,the porous LLTO calcined at 600℃ achieves the highest total conductivity,7.88×10^(-5) S/*** fracture toughness of the infiltrated LLTO is higher than that of the non-porous *** results demonstrate a new way to prepare solid-state lithium-ion conductors with high ionic conductivity and great tolerance to cyclic stress.

关键词： Perovskite Porous material Infiltration Ionic conductors Fracture toughness Rare earths

Block dual Toeplitz Operators on the Orthogonal Complements of Fock Spaces

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Acta Mathematica Sinica,English Series 2024年第8期40卷 1967-1988页

作者： Jian xiang DONG Chun Xu XU Yu Feng lu School of Mathematical Sciences Dalian University of TechnologyDalian 116024P.R.China School of Mathematics and Information Science Guangzhou UniversityGuangzhou 510006P.R.China

In this paper,we characterize the boundedness and compactness of the block dual Toeplitz operators acting on the orthogonal complement of the Fock spaces,and the compactness of the finite sum of two dual Toeplitz oper... 详细信息

关键词： Block dual Toeplitz operators boundedness compactness Fock space (semi)-commutator

Six million Q factor micro fused silica shell resonator with teeth-like tines released by femtosecond laser-assisted chemical etching

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Science China(Technological Sciences) 2024年第6期67卷 1923-1932页

作者： ZHAO Tao SHI Yan lu Kun XI xiang WU XueZhong XIAO DingBang College of Intelligence Science and Engineering National University of Defense TechnologyChangsha410073China

The quality factor(Q factor)is a crucial performance parameter for *** this paper,a novel release method for highquality micro fused silica shell resonators with teeth-like tines with good surface morphology is *** method is based on femtosecond laser-assisted chemical ***,the optimal energy range of femtosecond laser modification is obtained through mechanism ***,the optimal parameters for a straight line and arc pattern are determined by optimizing the average output power,processing speed,and processing *** results demonstrate why edge breakage in rounded corners is easy under different ***,according to these conclusions,the processing is performed on a micro fused silica shell resonator with a Q factor exceeding 6 *** addition,subsurface damage is rare throughout the fabrication process,and the surface roughness of the released cross section reaches the nanometer *** improved Q factor helps suppress mechanical thermal noise and reduce zero bias and zero bias drift,constituting the primary method for enhancing the performance of the resonant gyroscope.

关键词： micro hemispherical resonator fused silica laser-assisted chemical etching quality factor