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DNA-delivered monoclonal antibodies targeting the p53 R175H mutant epitope inhibit tumor development in mice

Genes & Diseases 2024年第4期11卷 368-380页

作者： Dafei Chai Xu Wang Praveen Neeli shan Zhou Xingfang yu Kanaga Sabapathy Yong Li Department of Medicine Section of Epidemiology and Population SciencesDan L Duncan Comprehensive Cancer CenterBaylor College of MedicineHoustonTX 77030USA Division of Cellular&Molecular Research Humphrey Oei Institute of Cancer ResearchNational Cancer Centre SingaporeSingapore 168583Singapore

tThe tumor suppressor p53 is the most common mutated gene in cancer,with the R175H as the most frequent p53 missense ***,there are currently no approved targeted therapies or immunotherapies against mutant ***,we characterized and inves-tigated a monoclonal antibody(mAb)that recognizes the mutant p53-R175H for its affinity,specificity,and activity against tumor cells in *** then delivered DNA plasmids expres-sing the anti-R175H mAb or a bispecific antibody(BsAb)into mice to evaluate their therapeutic *** results showed that the anti-R175H mAb specifically bound to the p53-R175H an-tigen with a high affinity and recognized the human mutant p53-R175H antigen expressed on HEK293T or MC38 cells,with no cross-reactivity with wild-type *** cultured cells,the anti-R175H mAb showed higher cytotoxicity than the control but did not induce antibody-dependent cellular *** made a recombinant MC38 mouse cell line(MC38-p53-R175H)that overexpressed the human p53-R175H after knocking out the endogenous mutant p53 *** vivo,administration of the anti-R175H mAb plasmid elicited a robust anti-tumor effect against MC38-p53-R175H in *** administration of the anti-R175H BsAb plasmid showed no therapeutic effects,yet potent anti-tumor activity was observed in combination with the anti-PD-1 *** results indicate that targeting specific mutant epitopes using DNA-delivered mAbs or BsAbs presents a form of improved natural immunity derived from tumor-infiltrating B cells and plasma cells against intracellular tumor antigens.

关键词： BsAb Cytotoxicity mAb Mutant p53 PD-1 R175H

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Computational and dark-field ghost imaging with ultraviolet light

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Photonics Research 2024年第2期12卷 226-234页

作者： JIAQI SONG BAOLEI liu YAO WANG CHAOHAO CHEN XUCHEN shan XIAOLAN ZHONG LING-AN WU FAN WANG School of Physics Beihang UniversityBeijing 102206China Australian Research Council Centre of Excellence for Transformative Meta-Optical Systems Department of Electronic Materials EngineeringResearch School of PhysicsThe Australian National UniversityCanberraACT 2600Australia Institute of Physics Chinese Academy of SciencesBeijing 100190China

Ultraviolet(UV)imaging enables a diverse array of applications,such as material composition analysis,biological fluorescence imaging,and detecting defects in semiconductor ***,scientific-grade UV cameras with high quantum efficiency are expensive and include complex thermoelectric cooling ***,we demonstrate a UV computational ghost imaging(UV-CGI)method to provide a cost-effective UV imaging and detection *** applying spatial–temporal illumination patterns and using a 325 nm laser source,a singlepixel detector is enough to reconstruct the images of *** use UV-CGI to distinguish four UV-sensitive sunscreen areas with different densities on a ***,we demonstrate dark-field UV-CGI in both transmission and reflection *** only collecting the scattered light from objects,we can detect the edges of pure phase objects and small scratches on a compact *** results showcase a feasible low-cost solution for nondestructive UV imaging and *** combining it with other imaging techniques,such as hyperspectral imaging or time-resolved imaging,a compact and versatile UV computational imaging platform may be realized for future applications.

关键词： ghost illumination versatile

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Tanshinone IIA ameliorates energy metabolism dysfunction of pulmonary fibrosis using 13C metabolic flux analysis

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Journal of Pharmaceutical Analysis 2024年第2期14卷 244-258页

作者： Baixi shan Haoyan Zhou Congying Guo Xiaolu liu Mingyu Wu Rao Zhai Jun Chen State Key Laboratory of Natural Medicines China Pharmaceutical UniversityNanjing210009China Department of Pharmacognosy School of Traditional Chinese PharmacyChina Pharmaceutical UniversityNanjing210009China

Evidence indicates that metabolic reprogramming characterized by the changes in cellular metabolic patterns contributes to the pathogenesis of pulmonary fibrosis (PF). It is considered as a promising therapeutic target anti-PF. The well-documented against PF properties of Tanshinone IIA (Tan IIA) have been primarily attributed to its antioxidant and anti-inflammatory potency. Emerging evidence suggests that Tan IIA may target energy metabolism pathways, including glycolysis and tricarboxylic acid (TCA) cycle. However, the detailed and advanced mechanisms underlying the anti-PF activities remain obscure. In this study, we applied [U-13C]-glucose metabolic flux analysis (MFA) to examine metabolism flux disruption and modulation nodes of Tan IIA in PF. We identified that Tan IIA inhibited the glycolysis and TCA flux, thereby suppressing the production of transforming growth factor-β1 (TGF-β1)-dependent extracellular matrix and the differentiation and proliferation of myofibroblasts in vitro. We further revealed that Tan IIA inhibited the expression of key metabolic enzyme hexokinase 2 (HK2) by inhibiting phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/hypoxia-inducible factor 1α (HIF-1α) pathway activities, which decreased the accumulation of abnormal metabolites. Notably, we demonstrated that Tan IIA inhibited ATP citrate lyase (ACLY) activity, which reduced the collagen synthesis pathway caused by cytosol citrate consumption. Further, these results were validated in a mouse model of bleomycin-induced PF. This study was novel in exploring the mechanism of the occurrence and development of Tan IIA in treating PF using 13C-MFA technology. It provided a novel understanding of the mechanism of Tan IIA against PF from the perspective of metabolic reprogramming.

关键词： Pulmonary fibrosis Tanshinone IIA 13C-metabolic flux analysis Metabolic reprogramming

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Neural stem cells promote neuroplasticity: a promising therapeutic strategy for the treatment of Alzheimer’s disease

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Neural Regeneration Research 2024年第3期19卷 619-628页

作者： Jun Chang yujiao Li Xiaoqian shan Xi Chen Xuhe Yan Jianwei liu Lan Zhao First Teaching Hospital of Tianjin University of Traditional Chinese Medicine TianjinChina National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion TianjinChina Tianjin University of Traditional Chinese Medicine TianjinChina

Recent studies have demonstrated that neuroplasticity,such as synaptic plasticity and neurogenesis,exists throughout the normal lifespan but declines with age and is significantly impaired in individuals with Alzheimer’s ***,promoting neuroplasticity may represent an effective strategy with which Alzheimer’s disease can be *** to their significant ability to self-renew,differentiate,and migrate,neural stem cells play an essential role in reversing synaptic and neuronal damage,reducing the pathology of Alzheimer’s disease,including amyloid-β,tau protein,and neuroinflammation,and secreting neurotrophic factors and growth factors that are related to *** events can promote synaptic plasticity and neurogenesis to repair the microenvironment of the mammalian ***,neural stem cells are considered to represent a potential regenerative therapy with which to improve Alzheimer’s disease and other neurodegenerative *** this review,we discuss how neural stem cells regulate neuroplasticity and optimize their effects to enhance their potential for treating Alzheimer’s disease in the clinic.

关键词： Alzheimer’s disease amyloid-β cell therapy extracellular vesicle neural stem cell synaptic plasticity tau

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Hybrid ionic thermoelectric and photocatalytic materials(i-TEPC):a new choice for energy harvesting

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Science China Chemistry 2024年第7期67卷 2127-2129页

作者： Qikai Li Mao yu Weishu liu Department of Materials Science and Engineering Southern University of Science and TechnologyShenzhen 518055China

Ionic thermoelectric(i-TE)material is a kind of new functional material that can convert heat energy into electric energy,which is of great significance for renewable energy technologies and sustainable development[1].The fundamental constitution of i-TE material mainly comprises an electrolyte matrix,ion providers and redox pairs.

关键词： energy harvesting convert

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Simulating the GRF of Humanoid Robot Vertical Jumping Using a Simplified Model with a Foot Structure for Foot Design

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Journal of Bionic Engineering 2024年第1期21卷 112-125页

作者： Chuanku Yi Xuechao Chen yu Zhang Zhangguo yu Haoxiang Qi Yaliang liu Qiang Huang School of Mechatronical Engineering Beijing Institute of TechnologyZizhuyaunHaidianBeijing 100081China Beijing Advanced Innovation Center for Intelligent Robots and Systems Beijing Institute of Tec

There are many theories and tools for human or robot motion simulation,but most of them require complex *** LNZN model(a simplified model named by the proposers)simplifies the human model and facilitates simulation of the Ground Reaction Force(GRF)of body landing by spring damping model and ignoring joint rotation movements,which can reduce the amount of computation *** this paper,the LNZN model of human running is selected as the basis and is modified to obtain the LNZN model of a robot,which expands the application of the LNZN *** to the structure of the human foot,a foot structure is then added to the simplified model to reduce the *** also applied driving forces to the new model to simulate the whole high jump motion of the robot to expand the functions of the LNZN *** obtained GRF data were anastomotic to the actual experimental *** addition,the effects of variables,such as the mass,hardness,and damping,of the foot on the GRF at the moment of landing were also ***,based on the guidelines obtained for the design of the robot’s foot structure,we fabricated new robot’s feet and installed them on the actual robot and achieved a better cushioning effect than the original foot in experiments.

关键词： LNZN model-GRF simulation Humanoid foot structure Foot parameters

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Oncogenic MORC2 in cancer development and beyond

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Genes & Diseases 2024年第2期11卷 861-873页

作者： shan Zhang Ayao Guo Huan Wang Jia liu Chenshuang Dong Junyi Ren Guiling Wang Key Laboratory of Cell Biology Department of Cell BiologyMinistry of Public Health and Key Laboratory of Medical Cell BiologyMinistry of EducationChina Medical UniversityShenyangLiaoning 110122China Department of Breast Surgery The First Affiliated Hospital of China Medical UniversityShenyangLiaoning 110001China

Microrchidia CW-type zinc finger 2(MORC2)is a member of the MORC superfamily of nuclear *** evidence has shown that MORC2 not only participates in gene transcription and chromatin remodeling but also plays a key in human disease and tumor development by regulating the expression of downstream oncogenes or tumor *** present review provides an updated overview of MORC2 in the aspect of cancer hallmark and therapeutic resistance and summarizes its upstream regulators and downstream target *** systematic review may provide a favorable theoretical basis for emerging players of MORC2 in tumor development and new insight into the potential clinical application of basic science discoveries in the future.

关键词： Cancer development Hallmarks of cancer MORC2 Therapeutic target Treatment resistance

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Constructing energetic covalent organic frameworks with high stability and low sensitivity

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Chinese Chemical Letters 2024年第3期35卷 544-548页

作者： Hui-Min Guo Xiao-yu Dong shan Wang Qian-You Wang Shuang-Quan Zang Henan Key Laboratory of Crystalline Molecular Functional Materials Green Catalysis Centerand College of ChemistryZhengzhou UniversityZhengzhou 450001China

Developing new functional explosives that display high stability,good energy performance,and low sensitivity are one of the key directions of energetic materials *** this work,two-dimensional(2D)Schiff-based energetic covalent organic frameworks(COFs)are prepared based on triaminoguanidine salts with different anions as building *** from the robust covalent bond in 2D extended polygons and strongπ-πinteractions in the eclipsed interlayers,the synthesized energetic COFs showed higher thermal stability and lower mechanical sensitivity than their precursor *** importantly,incorporating triaminoguanidine salts into COFs effectively increase the corrosion resistance to metal under high humidity conditions,which is due to the imine moieties in COFs functioning asπacceptors and offering strong bonding with metallic *** work provides a new pathway for the development of high-performance energetic materials.

关键词： Covalent organic frameworks Energetic materials High thermal stability Low sensitivity Corrosion resistance

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Homological dimensions of gentle algebras via geometric models

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Science China Mathematics 2024年第4期67卷 733-766页

作者： yu-Zhe liu Hanpeng Gao Zhaoyong Huang Department of Mathematics Nanjing UniversityNanjing 210093China School of Mathematical Sciences Anhui UniversityHefei 230601China

Let A=kQ/I be a finite-dimensional basic algebra over an algebraically closed field k,which is a gentle algebra with the marked ribbon surface(SA,MA,ΓA).It is known that SAcan be divided into some elementary polygons{Δi|1≤i≤d}byΓA,which has exactly one side in the boundary of ***■(Δi)be the number of sides ofΔibelonging toΓAif the unmarked boundary component of SAis not a side ofΔi;otherwise,■(Δi)=∞,and let f-Δbe the set of all the non-co-elementary polygons and FA(resp.f-FA)be the set of all the forbidden threads(*** finite length).Then we have(1)the global dimension of A is max1≤i≤d■(Δi)-1=maxΠ∈FAl(Π),where l(Π)is the length ofΠ;(2)the left and right self-injective dimensions of A are 0,if Q is either a point or an oriented cycle with full ***Δi∈f-Δ{1,■(Δi)-1}=max n∈f-F_(A)l(П),otherwise,As a consequence,we get that the finiteness of the global dimension of gentle algebras is invariant under AvellaGeiss(AG)-*** addition,we get that the number of indecomposable non-projective Gorenstein projective modules over gentle algebras is also invariant under AG-equivalence.

关键词： global dimension self-injective dimension gentle algebras marked ribbon surfaces geometric models AG-equivalence

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Multi-scale Modeling and Finite Element Analyses of Thermal Conductivity of 3D C/SiC Composites Fabricating by Flexible-Oriented Woven Process

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Chinese Journal of Mechanical Engineering 2024年第3期37卷 275-288页

作者： Zheng Sun Zhongde shan Hao Huang Dong Wang Wang Wang Jiale liu Chenchen Tan Chaozhong Chen Nanjing University of Aeronautics and Astronautics Nanjing 210016China School of Mechanical Engineering Beijing Institute of TechnologyBeijing 100081China CRRC Institute Corporation Limited Beijing 100070China

Thermal conductivity is one of the most significant criterion of three-dimensional carbon fiber-reinforced SiC matrix composites(3D C/SiC).Represent volume element(RVE)models of microscale,void/matrix and mesoscale proposed in this work are used to simulate the thermal conductivity behaviors of the 3D C/SiC *** entirely new process is introduced to weave the preform with three-dimensional orthogonal *** 3D steady-state analysis step is created for assessing the thermal conductivity behaviors of the composites by applying periodic temperature boundary *** RVE models of cuboid,hexagonal and fiber random distribution are respectively developed to comparatively study the influence of fiber package pattern on the thermal conductivities at the ***,the effect of void morphology on the thermal conductivity of the matrix is analyzed by the void/matrix *** prediction results at the mesoscale correspond closely to the experimental *** effect of the porosities and fiber volume fractions on the thermal conductivities is also taken into *** multi-scale models mentioned in this paper can be used to predict the thermal conductivity behaviors of other composites with complex structures.

关键词： 3D C/SiC composites Finite element analyses Multi-scale modeling Thermal conductivity

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