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Small molecule deoxynyboquinone triggers alkylation and ubiquitination of Keap1 at Cys489 on Kelch domain for Nrf2 activation and inflammatory therapy

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Journal of Pharmaceutical Analysis 2024年第3期14卷 401-415页

作者： Ke-Gang Linghu Tian zhang Guang-Tao zhang Peng Lv Wen-Jun zhang Guan-Ding Zhao Shi-Hang Xiong Qiu-Shuo Ma Ming-Ming Zhao Meiwan Chen Yuan-Jia Hu chang-sheng zhang Hua Yu State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao SARChina Macao Centre for Research and Development in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao SARChina Key Laboratory of Tropical Marine Bio-resources and Ecology Guangdong Key Laboratory of Marine Materia MedicaRNAM Center for Marine MicrobiologySouth China Sea Institute of OceanologyChinese Academy of SciencesGuangzhou510301China State Key Laboratory of Functions and Applications of Medicinal Plants&School of Pharmaceutical Sciences Guizhou Medical UniversityGuiyang550025China

Activation of nuclear factor erythroid 2-related factor 2(Nrf2)by Kelch-like ECH-associated protein 1(Keap1)alkylation plays a central role in anti-inflammatory ***,activators of Nrf2 through alkylation of Keap1-Kelch domain have not been ***(DNQ)is a natural small molecule discovered from marine *** current study was designed to investigate the anti-inflammatory effects and molecular mechanisms of DNQ via alkylation of *** exhibited significant anti-inflammatory properties both in vitro and in *** pharmacophore responsible for the anti-inflammatory properties of DNQ was determined to be theα,β-unsaturated amides moieties by a chemical reaction between DNQ and *** exerted anti-inflammatory effects through activation of Nrf2/ARE ***1 was demonstrated to be the direct target of DNQ and bound with DNQ through conjugate addition reaction involving *** specific alkylation site of DNQ on Keap1 for Nrf2 activation was elucidated with a synthesized probe in conjunction with liquid chromatography-tandem mass *** triggered the ubiquitination and subsequent degradation of Keap1 by alkylation of the cysteine residue 489(Cys489)on Keap1-Kelch domain,ultimately enabling the activation of *** findings revealed that DNQ exhibited potent anti-inflammatory capacity throughα,β-unsaturated amides moieties active group which specifically activated Nrf2 signal pathway via alkylation/ubiquitination of Keap1-Kelch domain,suggesting the potential values of targeting Cys489 on Keap1-Kelch domain by DNQ-like small molecules in inflammatory therapies.

关键词： Deoxynyboquinone Anti-inflammation Target Keap1/Nrf2 Alkylation Ubiquitination

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Neurotoxicity of tetramethylammonium ion on larval and juvenile zebrafish:Effects on neurobehaviors and multiple biomarkers

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Journal of Environmental Sciences 2024年第9期143卷 138-147页

作者： Ruixin zhang Rui Wang Jiajun chang GDaniel sheng Daqiang Yin Key Laboratory of Yangtze River Water Environment Ministry of EducationCollege of Environmental Science and EngineeringTongji UniversityShanghai 200092China Shanghai Institute of Pollution Control and Ecological Security Shanghai 200092China

Tetramethylammonium hydroxide(TMAH)is an important compound that utilized and released by the rapidly expanding semiconductor industry,which could hardly be removed by the conventional wastewater treatment *** a cholinergic agonist,the tetramethylammonium ion(TMA^(+))has been reported to induce toxicity to muscular and respiratory systems of mammals and human,however the toxicity on aquatic biota remains poorly *** investigated the neurotoxic effects of TMA^(+)exposure on zebrafish,based on neurobehavior tests and a series of *** inhibitions on the swimming distance of zebrafish larvae were observed when the exposure level exceeded 50 mg/L,and significant alterations on swimming path angles(straight and deflective movements)occurred even at 10 mg/*** tested neurobehavioral endpoints of zebrafish larvae were significantly positively correlated with reactive oxygen species(ROS)and malondialdehyde(MDA),significantly negatively related with the activities of antioxidant enzymes,but not significantly correlated with the level of acetylcholinesterase(AChE).Such relationship indicates that the observed neurotoxic effects on swimming behavior of zebrafish larvae is mainly driven by oxidative stress,rather than the alterations of *** the highest exposure concentration(200 mg/L),TMA^(+)evoked more severe toxicity on zebrafish juveniles,showing significantly stronger elevation on the MDA activity,and greater inhibitions on the activities of antioxidant enzymes and ACh E,suggesting juveniles were more susceptible to TMA^(+)exposure than larval zebrafish.

关键词： Tetramethylammonium Zebrafish Oxidative stress Acetylcholinesterase Neurobehavior

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Degradation behaviors of Nabumetone and its metabolite during UV/monochloramine process:Experimental and theoretical study

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Journal of Environmental Sciences 2024年第8期142卷 103-114页

作者： Xiang Tu Yunsong Bai Qing Fu sheng chang Kunfeng zhang Yang Pan Ruiyang Xiao Yifu Fu Qi zhang State Key Laboratory of Environmental Criteria and Risk Assessment State Environmental Protection Key Laboratory of Drinking Water Source ProtectionResearch Centre of Lake EnvironmentNational Engineering Laboratory for Lake Pollution Control and Ecological RestorationChinese Research Academy of Environmental SciencesBeijing 100012China School of Environmental Science and Engineering Suzhou University of Science and TechnologySuzhou 215009China Institute of Environmental Engineering School of Metallurgy and EnvironmentCentral South UniversityChangsha 410083China School of Forestry Northeast Forestry UniversityHarbin 150040China

This study investigated degradation behaviors of a nonsteroidal anti-inflammatory drug Nabumetone(NMT)and its major metabolite 6-methoxy-2-naphthylacetic acid(MNA)in the coupling process of ultraviolet and monochloramine(UV/NH2Cl).The second-order rate constants of the contaminants reacting with reactive radicals(HO·,Cl·,Cl_(2)·-,and CO_(3)·^(-))were determined by laser flash photolysis ***·and Cl·contributed predominantly with 52.3%and 21.7%for NMT degradation and 60.8%and 22.3%for MNA *** presence of chlorides retarded the degradation of NMT,while promoted the destruction of MNA,which was ascribed to the photosensitization effects of MNA under UV *** functional theory(DFT)calculations revealed that radical adduct formation(RAF)was dominant pathway for both HO·and Cl·reacting with the contaminants,and hydrogen atom transfer(HAT)preferred to occur on side chains of NMT and *** reacted with NO_(2)·through single electron transfer(SET)with the second-order rate constant calculated to be 5.35×10^(7)(mol/L)^(-1)sec^(-1),and the contribution of NO_(2)·was predicted to be 13.0%of the total rate constant of NMT in pure water,which indicated that NO_(2)·played a nonnegligible role in the degradation of *** acute toxicity and developmental toxicity of NMT were enhanced after UV/NH_(2)Cl treatment,while those of MNA were *** transformation products of both NMT and MNA exhibited higher mutagenicity than their parent *** study provides a deep understanding of the mechanism of radical degradation of NMT and MNA in the treatment of UV/NH2Cl.

关键词： UV/NH_(2)Cl Reactive species Degradation kinetics Reaction mechanism Degradation products

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Efficacy comparison between Mathieu combined urethral plate incision and onlay island flap urethroplasty for distal hypospadias in patients with urethral plate stenosis

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Asian Journal of Andrology 2024年第4期26卷 433-438页

作者： Tao zhang An-Bang Zhu chang-Kun Mao Yong-sheng Cao Department of Urology Anhui Provincial Children’s HospitalHefei 230000China The Fifth School of Clinical Medicine Anhui Medical UniversityHefei 230000China.

The aim of the study was to compare the efficacy of Mathieu combined urethral plate incision(Mathieu-IP)versus onlay island flap urethroplasty in patients with distal hypospadias complicated by urethral *** clinical data of 70 patients with distal hypospadias complicated by urethral plate stenosis treated in the Department of Urology,Anhui Provincial Children’s Hospital(Hefei,China),from May 2019 to May 2022,were retrospectively ***-eight patients underwent Mathieu-IP(Mathieu-IP group)and 32 underwent onlay island flap urethroplasty(Onlay group).Follow-ups at 1 month,6 months,and 12 months postoperatively assessed operative time,complications,urethral meatus morphology,and family *** Mathieu-IP group had significantly shorter operative time(mean±standard deviation[s.d.]:81.58±5.18 min)versus the Onlay group(mean±s.d.:110.75±6.05 min;P0.05).Complications were comparable between the *** Mathieu-IP group resulted in a vertical slit-shaped urethral meatus in 89.5%versus 13.8%in the Onlay group(P<0.05).Family satisfaction with general penile appearance and skin shape showed no significant differences,but the Mathieu-IP group had higher satisfaction with meatal position(P<0.05).Mathieu-IP offers simplicity,safety,and shorter operative time compared to *** the techniques effectively treat urethral plate stenosis in distal hypospadias,with reduced postoperative complications compared to tubularized incised plate ***-IP results in a vertical slit-shaped urethral meatus which enhances urinary stream,indicating its potential for broader adoption.

关键词： longitudinal urethral plate incision Mathieu onlay island flap urethroplasty urethral stenosis

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Influence of the Acoustic Liner in Large Eddy Simulation of Longitudinal Thermoacoustic Instability in a Model Annular Combustor

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Journal of Thermal Science 2024年第2期33卷 710-724页

作者： MENG sheng zhang Man GAO Yi AECC Commercial Aircraft Engine Co. Ltd.Shanghai200241China School of Aeronautics and Astronautics Shanghai Jiao Tong UniversityShanghai200240China

Although extensive efforts have been made to dampen the thermoacoustic instability,successfully controlling the pressure oscillations in modern gas turbines or aeroengines remains *** influence of the acoustic liner on the longitudinal thermoacoustic mode in a model annular combustor is investigated by Large Eddy Simulation(LES) in this *** result of the self-excited longitudinal thermoacoustic instability without the liner agrees well with the frequency and acoustic analysis of the pressure mode based on experimental *** different bias flow velocities of the liner located downstream of the combustor are then *** results reveal that the existence of the liner influences not only the acoustic field but also the flow *** the bias velocity is large,it leads to intense turbulence-induced fluctuations,and the pressure oscillation is modulated *** shows that the weak coupling between flow and pressure oscillations plays a significant role in the onset of the intermittency of a thermoacoustic *** on the dynamic analysis of the thermoacoustic system with the acoustic liner,this intermittency is caused by the influence of the flow field on the flame-acoustic ***,a low-order modeling method based on Van der Pol(VdP) oscillator with additive stochastic forcing is conducted to reproduce the evolving dynamics of the thermoacoustic *** the numerical cases demonstrated in this work are relatively simpler than those in a practical combustion system,the results are helpful for us to understand the effect of the acoustic liner and show the attractive potential to apply this device to suppress thermoacoustic instability.

关键词： thermoacoustic instability acoustic liner Large Eddy Simulation low-order modeling

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Streamflow abrupt change and the driving factors in glacierized basins of Tarim Basin,Northwest China

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Advances in Climate change Research 2024年第1期15卷 75-89页

作者： Cheng-De YANG Min XU Shi-chang KANG Cong-sheng FU Wei zhang Di-Di HU State Key Laboratory of Cryospheric Science Northwest Institute of Eco-Environment and ResourcesChinese Academy of SciencesLanzhou 730000China University of Chinese Academy of Sciences Beijing 100049China Key Laboratory of Watershed Geographic Sciences Nanjing Institute of Geography and LimnologyChinese Academy of SciencesNanjing 210000China

A climate transition towards warm-wet conditions in Northwest China has drawn much *** continuous climate change and universal glacier degradation,increasing water-related hazards and vulnerability have become one of the important problems facing the Tarim ***,the impacts of the climate transition on streamflow abrupt change and extreme hydrological events were less discussed,especially in glacial *** the present study,the discharge datasets in four glacial basins of Tarim Basin from 1979 to 2018 were constructed using the GRU-GSWAT+model *** differences in streamflow characteristics,the shift of hydrological extreme pattern,and potential changes of the controlling factors before and after the abrupt changes were *** results indicated that the abrupt change point(ACP)in streamflow occurred in 2000 in the Qarqan River Basin,2002 in the Weigan River Basin,and 1994 in the Aksu River Basin and the Yarkant River Basin.A general decrease in streamflow before the ACP has shifted to a notable upward trend in the Qarqan River Basin and the Aksu River Basin,while minor upward fluctuations were observed in other ***,the hydrological characteristics in extreme events vary dramatically before and after the ACPs,characterized by a pronouncing shift from drought-dominant pattern to wet events dominated *** driven climate factors have been altered after the ACPs with notable spatial heterogeneity,in which temperature remained as the dominant role in meltwater-dominated basins while the influence of precipitation has increased after the ACPs,whereas the sensitivity of temperature on streamflow change has been enhanced in basins dominated by precipitation such as the Qarqan River *** to the evident warming-wetting trend and glacier compensation effect,both the inter-annual and intra-annual streamflow fluctuations can be efficiently smoothed in basins with a high glacier area ratio(GAR).These findings provide a

关键词： Abrupt change Streamflow Hybrid model Tarim Basin Glacier

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Thermodynamic Calculations of Melt in Melt Pool During Laser Cladding High Silicon Coatings

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Journal of Iron and Steel Research(International) 2008年第3期15卷 5-10页

作者： DONG Dan-yang LIU chang-sheng zhang Bin Key Laboratory for Anisotropy and Texture of Materials Ministry of Education Northeastern UniversityShenyang 110004 Liaoning China

Based on the Miedema＇s formation heat model for binary alloys and the Toop＇s asymmetric model for ternary alloys, the formation heat, excess entropy, and activity coefficients of silicon ranging from 1 900 K to 4 100 K in the Fe-Si-C melt formed during the laser cladding high silicon coatings process were calculated. The results indicated that all values of lnγ^0Si, ε^CSi,ρ^SiSi and ρ^CSi are negative in the temperature range and these values increase as the temperature increases. And all values of ε^SiSi and ρ^Si-CSi are positive and these values decrease with increasing temperature. The iso-activity lines of silicon are distributed axisymmetrically to the incident laser beam in the melt pool vertical to the laser scanning direction. And the iso-activity lines of silicon in the front of the melt pool along the laser scanning direction are more intensive than those in the back of the melt pool. The activity of silicon on the bottom of the melt pool is lower than that in the effecting center of laser beam on the top surface of the melt pool and it may be the important reason for the formation of the silicides and excellent metallurgical bonding between the laser cladding coating and the substrate.

关键词： laser cladding silicon steel high silicon content coating thermodynamic calculation Miedema's formation heat model

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Asymmetry in circulation system and cardiovascular diseases

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Medicine in Novel Technology and Devices 2024年第1期21卷 1-9页

作者： chang Liu sheng Xie Yangchen Li Da zhang Deyu Li Chi zhang Key Laboratory of Biomechanics and Mechanobiology Beijing Advanced Innovation Center for Biomedical EngineeringSchool of Biological Science and Medical EngineeringBeihang UniversityBeijing100191China Department of Radiology China-Japan Friendship HospitalBeijing100029China Children’s Hospital Capital Institute of Pediatrics Beijing100020China Department of Physics Sichuan Cancer HospitalChengdu610041China State Key Laboratory of Virtual Reality Technology and Systems Beihang UniversityBeijing100191China

Asymmetries in the human vascular system and cardiovascular disease are *** physiological asymmetry can manifest in the morphological structure and blood flow state,whereas pathological asymmetry can reflect differences in the occurrence and cure of bilateral vascular *** causes associated with these asymmetrical differences may be demand-driven or due to vascular grading or asymmetries in other physiological *** article aims to review the asymmetry of several typical arteries,including cerebral,cervical,and limb arteries,and lists possible causes to emphasize the necessity of considering asymmetric factors in the prevention,treatment,and rehabilitation of vascular *** research on asymmetries in the vascular system may improve the risk assessment and personalized treatment of vascular diseases.

关键词： Vascular morphology Hemodynamics Cardiovasculardiseases Asymmetry

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Preface to the Special Issue:Additive Manufacturing—Expanding Production Horizon

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Acta Metallurgica Sinica(English Letters) 2024年第1期37卷 1-2页

作者： Lai-chang zhang Centre for Advanced Materials and Manufacturing School of EngineeringEdith Cowan University270 Joondalup DriveJoondalupPerthWA6027Australia

Additive manufacturing(AM),commonly known as 3D printing,has become a transformative technology that has a profound impact on various industrial *** encompasses a set of techniques for building objects layer by layer from digital *** conventional subtractive manufacturing methods that involve removing material from large blocks,AM adds material incrementally,providing unprecedented design flexibility and efficiency.

关键词： removing printing Expanding

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Restraining growth of Zn dendrites by poly dimethyl diallyl ammonium cations in aqueous electrolytes

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Rare Metals 2024年第8期43卷 3735-3747页

作者： Xiang-Xin zhang Yuan-Qiang Chen chang-Xin Lin Yuan-sheng Lin Guo-Lin Hu Yong-Chuan Liu Xi-Lai Xue Su-Jing Chen Zhan-Lin Yang Bai-sheng Sa Yi-Ning zhang Key Laboratory of Optoelectronic Materials Chemistry and Physics Fujian Institute of Research on the Structure of MatterChinese Academy of SciencesFuzhou 350002China Helmholtz Institute Ulm(HIU) 89081 UlmGermany Karlsruhe Institute of Technology(KIT) 76021 KarlsruheGermany College of Materials Science and Engineering Fuzhou UniversityFuzhou350108China

Metallic zinc is an excellent anode material for Zn-ion batteries,but the growth of Zn dendrite severely hinders its practical ***,an efficient and economical cationic additive,poly dimethyl diallyl ammonium(PDDA) was reported,used in aqueous Zn-ion batteries electrolyte for stabilizing Zn *** growth of zinc dendrites can be significantly restrained by benefiting from the pronounced electrostatic shielding effect from PDDA on the Zn metal ***,the PDDA is preferentially absorbed on Zn(002) plane,thus preventing unwanted side reactions on Zn *** to the introduction of a certain amount of PDDA additive into the common ZnSO_(4)-based electrolyte,the cycle life of assembled Zn‖Zn cells(1 mA·cm^(-2) and 1 mAh·cm^(-2)) is prolonged to more than 1100 *** response to the perforation issue of Zn electrodes caused by PDDA additives,the problem can be solved by combining foamy copper with zinc *** real application,Zn-ion hybrid supercapacitors and MnO_(2)‖Zn cells were assembled,which exhibited excellent cycling stability with PDDA *** work provides a new solution and perspective to cope with the dendrite growth problem of Zn anode.

关键词： PDDA Electrostatic shielding effect Zn anode Zn dendrites

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