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An engineered DNA aptamer-based PROTAC for precise therapy of p53-R175H hotspot mutant-driven cancer

Science Bulletin 2024年第13期69卷 2122-2135页

作者： Lingping Kong Fanlu meng Ping Zhou Ruixin Ge Xiaoshan Geng Zhihao Yang Guo Li Linlin Zhang jing Wang Jinfeng Ma Cheng Dong Jun Zhou Sijin Wu Diansheng Zhong Songbo Xie Department of Medical Oncology Tianjin Medical University General HospitalTianjin 300052China Center for Cell Structure and Function Collaborative Innovation Center of Cell Biology in Universities of ShandongCollege of Life SciencesShandong Normal UniversityJinan 250014China The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics Key Laboratory of Immune Microenvironment and Disease(Ministry of Education)School of Basic Medical SciencesTianjin Medical UniversityTianjin 300070China Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment Lung Cancer InstituteTianjin Medical University General HospitalTianjin 300052China Haihe Laboratory of Cell Ecosystem State Key Laboratory of Medicinal Chemical BiologyCollege of Life SciencesNankai UniversityTianjin 300071China Wisdom Lake Academy of Pharmacy Xi’an Jiaotong-Liverpool UniversitySuzhou 215028China Department of Ophthalmology Tianjin Medical University General HospitalLaboratory of Molecular OphthalmologyTianjin Key Laboratory of Ocular TraumaTianjin Medical UniversityTianjin 300052China

Targeting oncogenic mutant p53 represents an attractive strategy for cancer treatment due to the high frequency of gain-of-function mutations and ectopic expression in various cancer *** extensive efforts,the absence of a druggable active site for small molecules has rendered these mutants therapeutically *** we develop a selective and effective proteolysis-targeting chimera(PROTAC)for p53-R175H,a common hotspot mutant with dominant-negative and oncogenic *** a novel iterative molecular docking-guided post-SELEX(systematic evolution of ligands by exponential enrichment)approach,we rationally engineer a high-performance DNA aptamer with improved affinity and specificity for *** this resulting aptamer as a binder for PROTACs,we successfully developed a selective p53-R175H degrader,named ***53m induces the ubiquitin–protea some-dependent degradation of p53-R175H while sparing wildtype ***,dp53m demonstrates significant antitumor efficacy in p53-R175H-driven cancer cells both in vitro and in vivo,without ***,dp53m significantly and synergistically improves the sensitivity of these cells to cisplatin,a commonly used chemotherapy *** findings provide evidence of the potential therapeutic value of dp53m in p53-R175H-driven cancers.

关键词： P53 Aptamer PROTAC Cancer Drug resistance

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Boosting Electrochemical Urea Synthesis via Constructing Ordered Pd–Zn Active Pair

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Nano-Micro Letters 2024年第11期16卷 529-540页

作者： Weiliang Zhou Chao Feng Xuan Li Xingxing Jiang Lingyan jing Shuai Qi Qihua Huo Miaoyuan Lv Xinbao Chen Tianchi Huang jingwen Zhao Na meng hengpan Yang Qi Hu Chuanxin He College of Chemistry and Environmental Engineering Shenzhen UniversityShenzhen 518060GuangdongPeople’s Republic of China School of Chemistry and Chemical Engineering/State Key Laboratory Incubation Base for Green Processing of Chemical Engineering Shihezi UniversityShihezi 832003XinjiangPeople’s Republic of China

Electrochemical co-reduction of nitrate(NO_(3)^(-))and carbon dioxide(CO_(2))has been widely regarded as a promising route to produce urea under ambient conditions,however the yield rate of urea has remained ***,we report an atomically ordered intermetallic pallium-zinc(PdZn)electrocatalyst comprising a high density of PdZn pairs for boosting urea *** is found that Pd and Zn are responsible for the adsorption and activation of NO_(3)^(-)and CO_(2),respectively,and thus the co-adsorption and co-activation NO_(3)^(-)and CO_(2) are achieved in ordered PdZn *** importantly,the ordered and well-defined PdZn pairs provide a dual-site geometric structure conducive to the key C-N coupling with a low kinetical barrier,as demonstrated on both operando measurements and theoretical ***,the PdZn electrocatalyst displays excellent performance for the co-reduction to generate urea with a maximum urea Faradaic efficiency of 62.78%and a urea yield rate of 1274.42μg mg^(-1) h^(-1),and the latter is 1.5-fold larger than disordered pairs in PdZn *** work paves new pathways to boost urea electrosynthesis via constructing ordered dual-metal pairs.

关键词： Electrochemical C-N coupling Urea electrosynthesis Intermetallic compounds Geometric structures Active pairs

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WEAK APPROXIMATIONS OF STOCHASTIC PARTIAL DIFFERENTIAL EQUATIONS WITH FRACTIONAL NOISE

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Journal of Computational Mathematics 2024年第3期42卷 735-754页

作者： meng Cai Siqing Gan Xiaojie Wang School of Mathematics and Statistics HNP-LAMACentral South UniversityChangshaChina

This paper aims to analyze the weak approximation error of a fully discrete scheme for a class of semi-linear parabolic stochastic partial differential equations(SPDEs)driven by additive fractional Brownian motions with the Hurst parameter H∈(1/2,1).The spatial approximation is performed by a spectral Galerkin method and the temporal discretization by an exponential Euler *** far as we know,the weak error analysis for approximations of fractional noise driven SPDEs is absent in the literature.A key difficulty in the analysis is caused by the lack of the associated Kolmogorov *** the present work,a novel and efficient approach is presented to carry out the weak error analysis for the approximations,which does not rely on the associated Kolmogorov equations but relies on the Malliavin *** the best of our knowledge,the rates of weak convergence,shown to be higher than the strong convergence rates,are revealed in the fractional noise driven SPDE setting for the first *** examples corroborate the claimed weak orders of convergence.

关键词： Parabolic SPDEs Fractional Brownian motion Weak convergence rates Spec-tral Galerkin method Exponential Euler method Malliavin calculus

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UNCONDITIONAL ERROR ANALYSIS OF VEMS FOR A GENERALIZED NONLINEAR SCHRODINGER EQUATION

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Journal of Computational Mathematics 2024年第2期42卷 500-543页

作者： meng Li Jikun Zhao Shaochun Chen School of Mathematics and Statistics Zhengzhou UniversityZhengzhouHenan 450001China

In this work,we focus on the conforming and nonconforming leap-frog virtual element methods for the generalized nonlinear Schrodinger equation,and establish their unconditional stability and optimal error *** constructing a time-discrete system,the error between the solutions of the continuous model and the numerical scheme is separated into the temporal error and the spatial error,which makes the spatial error τ-*** inverse inequalities in the existing conforming and new constructed nonconforming virtual element spaces are utilized to derive the L^(∞)-norm uniform boundedness of numerical solutions without any restrictions on time-space step ratio,and then unconditionally optimal error estimates of the numerical schemes are obtained *** needs to be emphasized is that if we use the pre-existing nonconforming virtual elements,there is no way to derive the L^(∞)-norm uniform boundedness of the functions in the nonconforming virtual element spaces so as to be hard to get the corresponding inverse ***,several numerical examples are reported to confirm our theoretical results.

关键词： Conforming and nonconforming Virtual element methods Leap-frog scheme Generalized nonlinear Schrodinger system Unconditionally optimal error estimates

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Attractor for the Extensible Beam Equation with Nonlocal Weak Damping on Time–Dependent Space

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Acta Mathematica Sinica,English Series 2024年第4期40卷 1115-1126页

作者： Chun Xiang ZHAO Feng Juan meng Institute of Applied System Analysis Jiangsu UniversityZhenjiang 212013P.R.China School of Mathematics and Physics Jiangsu University of TechnologyChangzhou 213001P.R.China

In this article,we consider the long-time behavior of extensible beams with nonlocal weak damping:ε(t)u_(tt)+Δ^(2)u-m(‖▽u‖^(2))Δu+‖u_(t)‖^(p_(u_(t)))+f(u)=h,whereε(t)is a decreasing function vanishing at *** the theory of process on time-dependent spaces,we investigate the existence of the time-dependent attractor by using the Condition(C_(t))method and more detailed *** results obtained essentially improve and complete some previous works.

关键词： Time-dependent attractor extensible beams equation nonlocal weak damping

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A Swin Transformer and Residualnetwork Combined Model for Breast Cancer Disease Multi-Classification Using Histopathological Images

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Instrumentation 2024年第1期11卷 112-120页

作者： Jianjun Zhuang Xiaohui Wu Dongdong meng Shenghua jing School of Electronic and Information Engineering Nanjing University of Information Science and TechnologyNanJing 210044China Institute for AI in Medicine School of Artificial IntelligenceNanjing University of Information Science and TechnologyNanjing 210044China Department of Radiation Oncology Jinling HospitalSchool of Medicine Nanjing UniversityNanjing 210002China

Breast cancer has become a killer of women's health *** order to exploit the potential representational capabilities of the models more comprehensively,we propose a multi-model fusion ***,we combine two differently structured deep learning models,ResNet101 and Swin Transformer(SwinT),with the addition of the Convolutional Block Attention Module(CBAM)attention mechanism,which makes full use of SwinT's global context information modeling ability and ResNet101's local feature extraction ability,and additionally the cross entropy loss function is replaced by the focus loss function to solve the problem of unbalanced allocation of breast cancer data *** multi-classification recognition accuracies of the proposed fusion model under 40X,100X,200X and 400X BreakHis datasets are 97.50%,96.60%,96.30 and 96.10%,*** with a single SwinT model and ResNet 101 model,the fusion model has higher accuracy and better generalization ability,which provides a more effective method for screening,diagnosis and pathological classification of female breast cancer.

关键词： breast cancer pathological image swin transformer ResNet101 focal loss

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Plasmon coupling-driven enhanced high-order multiphoton excited fluorescent performance of metal-organic frameworks

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Nano Research 2024年第7期17卷 6502-6508页

作者： Tong meng Bo Li Linlin Zeng Xianshun Sun Yupeng Tian Hongping Zhou meng Zhou Dandan Li Institutes of Physical Science and Information Technology Key Laboratory of Structure and Functional Regulation of Hybrid MaterialsMinistry of EducationAnhui UniversityHefei 230601China School of Chemistry and Chemical Engineering Anhui UniversityHefei 230601China Hefei National Research Center for Physical Sciences at the Microscale University of Science and Technology of ChinaHefei 230026China

Accessing high-order multiphoton excited fluorescence(H-MPEF)materials is challenging yet and needs complicated synthesis *** this study,we successfully assembled plasmonic Au nanorods(Au NRs)with multiphoton responsive metalorganic frameworks(MOFs),resulting in a significant several-fold enhancement of *** extent of multiphoton enhancement was found to be strongly dependent on the degree of overlap between the multiphoton excitation wavelength of MOFs and the localized surface plasmon resonance absorbance of Au NRs,indicating the importance of plasmon-induced resonance energy ***,plasmon-induced hot electron transfer played a vital role in enhanced multiphoton activity as ***,the optimum H-MPEF enhancement occurs at the second near-infrared(NIR-II)region,which provides a promising platform for fluorescent *** findings provide a feasible and practical method to fabricate optimized H-MPEF materials for biological imaging using tissue-penetrating NIR-II light.

关键词： metal-organic framework(MOF) plasmon resonance multiphoton activity fluorescence imaging

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A Tri-mode of Mock-Walker Cells

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Advances in Atmospheric Sciences 2024年第4期41卷 671-679页

作者： Han QIN Ji NIE Zhiyong meng Laboratory for Climate and Ocean-Atmosphere Studies Department of Atmospheric and Oceanic SciencesSchool of PhysicsPeking UniversityBeijing 100871China China Meteorological Administration Tornado Key Laboratory Foshan 528061China

This work uses cloud-resolving simulations to study mock-Walker cells driven by a specified sea surface temperature(SST).The associated precipitation in the mock-Walker cells exhibits three different modes,including a single peak of precipitation over the SST maximum(mode 1),symmetric double peaks of precipitation straddling the SST maximum(mode 2),and a single peak of precipitation on one side of the SST maximum(mode 3).The three modes are caused by three distinct convective activity center migration *** indicate that the virtual effect of water vapor plays an important role in differentiating the three *** the SST gradient is large,the virtual effect may be strong enough to overcome the temperature effect,generating a low-level low-pressure anomaly below the ascending branch of the Walker cell off the *** results here highlight the importance of the virtual effect of water vapor and its interaction with convection and large-scale circulation in the Walker circulation.

关键词： Walker circulation cloud-resolving simulation virtual effect

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Multimodal imaging diagnosis and analysis of prognostic factors in patients with adult-onset Coats disease

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International Journal of Ophthalmology(English edition) 2024年第8期17卷 1469-1476页

作者： Wei Zhou Hui Zhou Yuan-Yuan Liu meng-Xuan Li Xiao-Han Wu Jiao Liang jing Hao Sheng-Nan Liu Chun-Jie Jin Department of Ophthalmology Tianjin Medical University General HospitalTianjin 300052China Department of Ophthalmology Shanxi Yuncheng Tongde HospitalYuncheng 044000Shanxi ProvinceChina Department of Information Tianjin Medical University General HospitalTianjin 300052China

AIM:To describe the multimodal imaging features,treatment,and outcomes of patients diagnosed with adultonset Coats ***:This retrospective study included patients first diagnosed with Coats disease at≥18 years of age between September 2017 and September *** patients received anti-vascular endothelial growth factor(VEGF)therapy(conbercept,0.5 mg)as the initial treatment,which was combined with laser photocoagulation as *** the patients underwent best corrected visual acuity(BCVA)and intraocular pressure examinations,fundus color photography,spontaneous fluorescence tests,fundus fluorescein angiography,optical coherence tomography(OCT),OCT angiography,and other *** alterations and multimodal image findings in the affected eyes following treatment were compared and the prognostic factors were ***:The study included 15 patients who were aged 24-72(57.33±12.61)y at *** hypertension was the most common associated systemic condition,occurring in 13(86.7%)*** BCVA ranged from 2.0 to 5.0(4.0±1.1),which showed improvement following treatment(4.2±1.0).Multimodal imaging revealed retinal telangiectasis in 13 patients(86.7%),patchy hemorrhage in 5 patients(33.3%),and stage 2B disease(Shield’s staging criteria)in 11 patients(73.3%).OCT revealed that the baseline central macular thickness(CMT)ranged from 129 to 964μm(473.0±230.1μm),with 13 patients(86.7%)exhibiting a baseline CMT exceeding 250μ***,8 patients(53.3%)presented with an epiretinal membrane at baseline or during ***-reflective scars were observed on OCT in five patients(33.3%)with poor visual *** deteriorated in one patient who did not receive *** vision was stable in three patients who received laser treatment,whereas improvement was observed in one of two patients who received anti-VEGF therapy *** addition,8 of 9 patients(88.9%)who received laser treatment and conbercept exhibited sta

关键词： adult-onset Coats disease multimodal imaging anti-vascular endothelial growth factor conbercept

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In memoriam:Shizhu Wen(1932-2023)

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Friction 2024年第7期12卷 1341-1346页

作者： Jianbin LUO Yonggang meng Yu TIAN State Key Laboratory of Tribology in Advanced Equipment Tsinghua UniversityBeijing 100084China

Professor Shizhu Wen,the winner of the 2015 Tribology Gold Medal,passed away due to illness on November 3,2023,at the age of *** was a professor of Tsinghua University,an academician of the Chinese Academy of Sciences,and the Honorary President of the Chinese Tribology Institute(CTI)from 1997 to *** Wen was born in 1932 in Jiangxi Province of China and graduated from Tsinghua University in 1955,where he was awarded the Outstanding Graduate Gold Medal and then remained as an assistant professor at the *** Wen was promoted to full professor in *** had undertaken tribology research at the Imperial College London in 1979 and *** 1985,he presided over the establishment of the State Key Laboratory of Tribology(SKLT)of Tsinghua University and served as the first director of the SKLT.

关键词： sided professor zhu

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