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Strategies that regulate LSD1 for novel therapeutics

Acta Pharmaceutica Sinica B 2024年第4期14卷 1494-1507页

作者： meng Li mengge Dai bing cheng Shaotong Li Enhui Guo Junwei Fu Ting ma Bin Yu School of Pharmaceutical Sciences&Key Laboratory of Advanced Drug Preparation Technologies Ministry of EducationZhengzhou UniversityZhengzhou 450001China College of Chemistry Zhengzhou UniversityZhengzhou 450001China Tianjian Laboratory of Advanced Biomedical Sciences Institute of Advanced Biomedical SciencesZhengzhou UniversityZhengzhou 450000China Pingyuan Laboratory State Key Laboratory of Antiviral DrugsHenan Normal UniversityXinxiang 453007China State Key Laboratory of Pharmaceutical Biotechnology Nanjing UniversityNanjing 210023China

Histone methylation plays crucial roles in regulating chromatin structure and gene transcrip-tion in epigenetic ***-specific demethylase 1(LSD1),the first identified histone de-methylase,is universally overexpressed in various ***1 dysregulation is closely associated with cancer,viral infections,and neurodegenerative diseases,etc.,making it a promising therapeutic *** LSD1 inhibitors and two small-molecule degraders(Um171 and BEA-17)have entered the clinical ***1 can remove methyl groups from histone 3 at lysine 4 or lysine 9(H3K4 or H3K9),resulting in either transcription repression or *** the roles of LSD1 in transcrip-tional regulation are well-established,studies have revealed that LSDl can also be dynamically regulated by other *** example,the expression or activity of LSD1 can be regulated by many proteins that form transcriptional corepressor complexes with ***,some post-transcriptional modifica-tions and cellular metabolites can also regulate LSD1 expression or its demethylase ***,in this review,we will systematically summarize how proteins involved in the transcriptional corepressor complex,various post-translational modifications,and metabolites act as regulatory factors for LSD1 ac-tivity.

关键词： LSD1 regulation Transcription repression Transcription activation the Corepressor complex Post-transcriptional modifications metabolites

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Dielectric nanocomposites with superb high-temperature capacitive performance based on high intrinsic dielectric constant polymer

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Nano Research 2024年第9期17卷 8504-8512页

作者： Ding Ai Yuan Chang Haoliang Liu chenglong Wu Yao Zhou Yuting Han Hao Yu bing Xiao Yonghong cheng Guanglei Wu Zirui Jia State Key Laboratory of Electrical Insulation and Power Equipment School of Electrical EngineeringXi’an Jiaotong UniversityXi’an 710049China Institute of materials for Energy and Environment State Key Laboratory of Bio-Fibers and Eco-TextilesCollege of Materials Science and EngineeringQingdao UniversityQingdao 266071China

Advancements in power electronics necessitate dielectric polymer films capable of operating at high temperatures and possessing high energy *** significant strides have been achieved by integrating inorganic fillers into high-temperature polymer matrices,the inherently low dielectric constants of these matrices have tempered the magnitude of *** this work,we report an innovative nanocomposite based on sulfonylated polyimide(SPI),distinguished by the incorporation of sulfonyl groups within the SPI backbone and the inclusion of wide bandgap hafnium dioxide(HfO_(2))*** nanocomposite has demonstrated notable enhancements in thermal stability,dielectric properties,and capacitive performance at elevated *** simulations at both molecular and mesoscopic levels have elucidated the mechanisms behind these improvements,which could be attributed to confined segmental motion,an optimized electronic band structure,and a diminished incidence of dielectric breakdown ascribed to the presence of sulfonyl ***,the SPI-HfO_(2)nanocomposite demonstrates a high charge-discharge efficiency of 95.7%at an elevated temperature of 150℃and an applied electric field of 200 mV/***,it achieves a maximum discharged energy density of 2.71 J/cm^(3),signalling its substantial potential for energy storage applications under extreme conditions.

关键词： dielectric polymer nanocomposites high-temperature high dielectric constant sulfonyl groups energy storage performance

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Data-driven mapping-relationship mining between hardness and mechanical properties of dual-phase titanium alloys via random forest and statistical analysis

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Rare metals 2024年第2期43卷 829-841页

作者： Hai-Chao Gong Qun-Bo Fan Hong-mei Zhang Xing-Wang cheng Wen-Qiang Xie Kai Chen Lin Yang Jun-Jie Zhang bing-Qiang Wei Shun Xu School of materials Science and Engineering Beijing Institute of TechnologyBeijing100081China National Key Laboratory of Science and Technology on materials Under Shock and Impact Beijing100081China Beijing Institute of Technology Chongqing Innovation Center Chongqing401135China Department of mechanical and materials Engineering University of Nebraska-LincolnLincolnNE68588USA

In order to accelerate the research on the property optimization of titanium alloy based on high-throughput methods,it is necessary to reveal the relationship between hardness and other mechanical properties which is still *** this work,taking Ti20C alloy as research object,almost all the microstructure of dual-phase titanium alloys were covered by traversing over 100 heat treatment ***,massive experiments including microstructure characterization and performance test were conducted,obtaining 51,590 pieces of microstructure data and 3591 pieces of mechanical property ***,based on large-scale data-driven technology,the quantitative mapping relationship between hardness and other mechanical properties was deeply *** results of random forest models showed that the correlation between hardness(H)and Charpy impact energy(A_(k))(or elongation,A)was hardly dependent on the microstructure types,while the relationship between H and tensile strength(R_(m))(or yield strength,R_(p0.2))was highly dependent on microstructure ***,combined with statistical analysis,it was found that the relationship between H and Ak(or A)were negatively ***,the relationship between H and strength was positively linear for equiaxed microstructure,and strength was linked to d^(−1/2)(d,equivalent circle diameter)ofα-grains in the form of classical Hall–Petch formula;but for other microstructures,the relationships were ***,the above rules were nearly the same in the rolling direction and transverse ***,a"four-quadrant partition map"between H and R_(p0.2)/R_(m) was established as a versatile material-screening tool,which can provide guidance for on-demand selection of titanium alloys.

关键词： Dual-phase titanium alloy Data-driven Hardness mapping relationship

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A vibration isolator with a controllable quasi-zero stiffness region based on nonlinear force design

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Applied mathematics and mechanics(English Edition) 2024年第8期45卷 1279-1294页

作者： Xinyu LIAN bing LIU Huaxia DENG Xinglong GONG CAS Key Laboratory of mechanical Behavior and Design of materials Department of Modern MechanicsUniversity of Science and Technology of ChinaHefei 230027China State Key Laboratory of Nonlinear mechanics Institute of MechanicsChinese Academy of SciencesBeijing 100190China State Key Laboratory of Fire Science University of Science and Technology of ChinaHefei 230026China

To achieve stability optimization in low-frequency vibration control for precision instruments,this paper presents a quasi-zero stiffness(QZS)vibration isolator with adjustable nonlinear ***,the stress-magnetism coupling model is established through meticulous theoretical *** controllable QZS interval is constructed via parameter design and magnetic control,effectively segregating the high static stiffness bearing section from the QZS vibration isolation ***,a displacement control scheme utilizing a magnetic force is proposed to regulate entry into the QZS working range for the vibration isolation *** results demonstrate that the operation within this QZS region reduces the peak-to-peak acceleration signal by approximately 66.7%compared with the operation outside this region,thereby significantly improving the low frequency performance of the QZS vibration isolator.

关键词： low frequency nonlinear vibration isolator quasi-zero stiffness(QzS)

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A Study on the Impact of Chemical Structure on the Evolution of Aggregate Structure in Fiber-shaped High Density Polyethylene Vitrimer

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Chinese Journal of Polymer Science 2024年第10期42卷 1557-1565,I0013页

作者： bing Wang Yuan-Chu Gao Hai Wang Hui Niu State Key Laboratory of Fine Chemicals School of Chemical EngineeringDalian University of TechnologyDalian116024China

Vitrimers have emerged as a prominent research area in the field of polymer *** of the studies have focused on synthesizing polymers with versatile dynamic crosslinking structures,while the impact of chemical structure on aggregate structure of vitrimers,particularly during polymer processing,remains insufficiently *** present study employed commercial maleic anhydride-grafted-high density polyethylene(m-g-HDPE)as the matrix and hexanediol as the crosslinker to facilely obtain fiber-shaped HDPE vitrimers through a reaction extrusion and post-drawing *** chemical structure characterization,morphology observation,thermal and mechanical properties investigation,as well as aggregate structure analysis,this work revealed the influence of dynamic bonds on the formation of aggregate structures during fiber-shaped vitrimers processing.A small amount of dynamic bonds in HDPE restricts the motion of PE chain during melt-extruding and post-drawing,resulting in a lower orientation of the PE ***,lamellar growth and fibril formation during post-drawing at high temperature are enhanced to some extent due to the competition between dynamic bond and chain *** uneven morphology of fibershaped HDPE vitrimers can be attributed to the stronger elastic effect brought by dynamic bonding,which plays a more dominant role in determining the mechanical properties of fiber-shaped vitrimers compared to aggregate *** Vitrimers have emerged as a prominent research area in the field of polymer *** of the studies have focused on synthesizing polymers with versatile dynamic crosslinking structures,while the impact of chemical structure on aggregate structure of vitrimers,particularly during polymer processing,remains insufficiently *** present study employed commercial maleic anhydride-grafted-high density polyethylene(m-g-HDPE)as the matrix and hexanediol as the crosslinker to facilely obtain fiber-shap

关键词： High density polyethylene vitrimer Fiber-shaped Aggregate structures Transesterification reaction

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The crosstalk between enteric nervous system and immune system in intestinal development,homeostasis and diseases

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Science China(Life Sciences) 2024年第1期67卷 41-50页

作者： Xindi Wang Chenbo Ding Hua-bing Li Shanghai Institute of Immunology State Key Laboratory of Oncogenes and Related GenesShanghai Jiao Tong University School of MedicineShanghai 200025China Shanghai Jiao Tong University School of medicine-Yale Institute for Immune metabolism Shanghai Jiao Tong University School of MedicineShanghai 200025China

The gut is the largest digestive and absorptive organ,which is essential for induction of mucosal and systemic immune responses,and maintenance of metabolic-immune *** intestinal components contain the epithelium,stromal cells,immune cells,and enteric nervous system(ENS),as well as the outers,such as gut microbiota,metabolites,and *** dyshomeostasis of intestinal microenvironment induces abnormal intestinal development and functions,even colon diseases including dysplasia,inflammation and *** recent studies have identified that ENS plays a crucial role in maintaining the immune homeostasis of gastrointestinal(GI)*** crosstalk between ENS and immune cells,mainly macrophages,T cells,and innate lymphoid cells(ILCs),has been found to exert important regulatory roles in intestinal tissue programming,homeostasis,function,and *** this review,we mainly summarize the critical roles of the interactions between ENS and immune cells in intestinal homeostasis during intestinal development and diseases progression,to provide theoretical bases and ideas for the exploration of immunotherapy for gastrointestinal diseases with the ENS as potential novel targets.

关键词： enteric nervous system macrophages T cells innate lymphoid cells neuro-immune interactions

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Effects of physical crust on soil detachment by overland flow in the Loess Plateau region of China

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International Soil and Water Conservation Research 2024年第1期12卷 107-120页

作者： Jiaxin Liu Liding Chen bing Wang Xiaoyu Peng School of Ecology and Environmental Science Yunnan UniversityKunming650091China State Key Laboratory of Soil Erosion and Dryland Farming on the Loess Plateau Institute of Soil and Water ConservationNorthwest A&F UniversityYanglingShaanxi712100China University of Chinese Academy of Sciences Beijing100049China

Physical soil crust(PSC),a key component of surface soil structure,exists extensively in loess *** is considered to have a significant effect on soil detachment ***,the long-term effects and the corresponding mechanisms of PSC on soil detachment by overland flow are still not well understood,especially in natural *** investigate temporal variation in soil erosion resistance and the underlying factors during PSC formation,an 8×8-m soil plot was exposed to natural conditions in the Loess Plateau over a 524-day period spanning two rainy seasons and a winter between them.A flume test was conducted to determine soil detachment capacity(Dc)under six designed flow shear stress levels(5.66-22.11 Pa)using crusted(SC)and non-crusted(NSC)soil samples at different PSC development ***,two soil erosion resistance parameters,rill erodibility(K_(r))and critical shear stress(τ_(c)),were *** time,in the SC and NSC treatments,K_(r)decreased from 0.516 to 0.120 s m^(-1)and 0.521 to 0.223 s m^(-1),respectively,whileτ_(c)increased from 0.49 to 4.42 Pa and 0.26-2.46 Pa,*** in soil erosion resistance was rapid in the first one to two months,and then slowed down,with slight fluctuations *** the SC treatment,K_(r)was 42%lower andτ_(c)was 67%greater than those in the NSC *** properties changed greatly for both *** increased from 0 to 7.09 mm in the SC *** increased from 2.91 to 9.04 kPa and 3.01-4.78 kPa in SC and NSC treatments,*** soil erosion resistance parameters could be well predicted by SCT and Coh in the SC treatment(R^(2)≥0.82),while their best predictor was Coh in the NSC treatment(R^(2)≥0.90).The results demonstrate that PSC formation enhances soil erosion resistance in the soil detachment process in the loess region under natural *** study revealed the important role and complexity of PSC in the process of soil erosion,and provided theor

关键词： Physical soil crust formation Soil heterogeneity Rill erodibility Critical shear stress

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Impact of mo/Ni alloying on microstructural modulation and low-temperature toughness of high-strength low-alloy steel

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Journal of Iron and Steel Research International 2024年第7期31卷 1746-1762页

作者： Wei Liu Hong-li Zhao bing-xing Wang Yong Tian State Key Laboratory of Rolling and Automation Northeastern UniversityShenyang 110819LiaoningChina

The high-strength low-alloy steel plates with varying Ni/mo contents were manufactured using the thermos-mechanical control *** investigation was conducted to explore the effect of Ni/mo microalloying on microstructure evolution and mechanical properties of the *** results revealed that the increase in Ni content from 1 to 2 wt.%reduced the transition temperature of ferrite and the growth range of ferritic grain was narrowed,which promoted grain *** optimized combination of grain size,high-angle grain boundaries(HAGBs),and martensite-austenite(m-A)islands parameter contributed to the excellent impact toughness of S1 steel at-100℃(impact absorbed energy of 218.2 J at-100℃).As the mo increases from 0 to 2 wt.%,the matrix structure changes from multiphase structure to granular bainite,which increases the average effective grain size to~4.62 pm and reduces HAGBs proportion to~36.22%.With these changes,the low-temperature impact toughness of S3 steel is *** addition,based on the analysis of the characteristics of crack propagation path,it was found that m-A islands with low content(~2.21%)and small size(~1.76 pm)significantly retarded crack propagation,and the fracture model of m-A islands with different morphologies was further ***,correlation between behaviour of delamination and toughness was further analysed by observing delamination size and impact energy parameters.

关键词： High-strength low-alloy steel microstructural regulation Ni addition mo addition Crack propagation Low-temperature toughness

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medicinal chemistry strategies towards the development of non-covalent SARS-CoV-2 mpro inhibitors

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Acta Pharmaceutica Sinica B 2024年第1期14卷 87-109页

作者： Letian Song Shenghua Gao bing Ye mianling Yang Yusen cheng Dongwei Kang Fan Yi Jin-Peng Sun Luis menéndez-Arias Johan Neyts Xinyong Liu Peng Zhan Department of medicinal Chemistry Key Laboratory of Chemical Biology(Ministry of Education)School of Pharmaceutical SciencesCheeloo College of MedicineShandong UniversityJinan 250012China Shenzhen Research Institute of Shandong University Shenzhen 518057China The Key Laboratory of Infection and Immunity of Shandong Province Department of PharmacologySchool of Basic Medical SciencesShandong UniversityJinan 250012China Key Laboratory Experimental Teratology of the ministry of Education Department of Biochemistry and Molecular BiologySchool of Basic Medical SciencesCheeloo College of MedicineShandong UniversityJinan 250012China Centro de Biologı´a molecular“Severo Ochoa”(Consejo Superior de Investigaciones Cientı´ficas&Autonomous University of madrid) Madrid 28049Spain KU Leuven Department of Microbiology and ImmunologyRega Institute for Medical ResearchLaboratory of Virology and ChemotherapyLeuven 3000Belgium

The main protease(m^(pro))of SARS-CoV-2 is an attractive target in anti-COVID-19 therapy for its high conservation and major role in the virus life *** covalent m^(pro)inhibitor nirmatrelvir(in combination with ritonavir,a pharmacokinetic enhancer)and the non-covalent inhibitor ensitrelvir have shown efficacy in clinical trials and have been approved for therapeutic *** antiviral drugs are needed to fight the pandemic,while non-covalent m^(pro)inhibitors could be promising alternatives due to their high selectivity and favorable *** non-covalent m^(pro)inhibitors with desirable properties have been developed based on available crystal structures of m^(pro).In this article,we describe medicinal chemistry strategies applied for the discovery and optimization of non-covalent m^(pro)inhibitors,followed by a general overview and critical analysis of the available *** viewpoints and insights into current strategies for the development of non-covalent m^(pro)inhibitors are also discussed.

关键词： COVID-19 SARS-CoV-2 main protease Non-covalent inhibitors medicinal chemistry strategies

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A Strong,Tough,and Self-Healing Strengthening Thioctic Acid-based Elastomer for Highly Reliable Flexible Strain Sensor

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Chinese Journal of Polymer Science 2024年第10期42卷 1610-1618,I0016页

作者： Xin-Yu Chen Yu-bing Fu Xue-Ling Yan Lan Liu School of materials Science and Engineering Key Lab of Guangdong Province for High Property and Functional Polymer MaterialsSouth China University of TechnologyGuangzhou510641China

Elastomers with high strength and toughness,excellent self-healing properties,and biocompatibility have broad application prospects in wearable electronics and other fields,but preparing it remains a *** this work,we propose a highly adaptable strategy by introducing the small molecule crosslinking agent of triethanolamine(TEA)to the poly(thioctic acid)(PTA)chains and preparing the PAx Ey elastomers using a simple synthesis *** strategy stabilizes the PTA chains by constructing multiple non-covalent cross-linked dynamic networks,endowing materials with excellent strength and toughness(tensile strength of 288 kPa,toughness of 278.2 kJ/m3),admirable self-healing properties(self-healing efficiency of 121.6%within 7 h at 70℃),and good *** PAx Ey elastomers can also be combined with mWNTs to become flexible strain sensors,which can be used to monitor human joint movements with high sensitivity,repeatable responses,and stability.

关键词： Thioctic acid Ion clusters multiple dynamic networks Self-healing strengthening Flexible strain sensor

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