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Celastrol activates caspase-3/GSDME-dependent pyroptosis in tumor cells by inducing endoplasmic reticulum stress

j.urnal of Traditional Chinese Medical Sciences 2024年第3期11卷 330-339页

作者： guo j. Cui D. Tang Y. Wang S. Ma C. Ma W. School of Life Sciences Beijing University of Chinese Medicine Beijing 102488 China These authors have contributed equally to this work. Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility Shaanxi University of Chinese Medicine Xi'an 712046 China School of Literature and History Mianyang Teachers' College Mianyang 621000 China

Obj.ctive: To investigate the pyroptosis-inducing effects of celastrol on tumor cells and to explore the potential mechanisms involved, specifically focusing on the role of the caspase-3/gasdermin E (GSDME) signaling pathway and the impact of endoplasmic reticulum (ER) stress and autophagy. Methods: Necrostatin-1 (Nec-1), lactate dehydrogenase release (LDH) assay, and Hoechst/propidium iodide (PI) double staining were employed to validate the mode of cell death. Western blot was used to detect the cleavage of GSDME and the expression of light chain 3 (LC3) and BIP. Results: Celastrol induced cell swelling with large bubbles, which is consistent with the pyroptotic phenotype. Moreover, treatment with celastrol induced GSDME cleavage, indicating the activation of GSDME-mediated pyroptosis. GSDME knockout via CRISPR/Cas9 blocked the pyroptotic morphology of celastrol in HeLa cells. In addition, cleavage of GSDME was attenuated by a specific caspase-3 inhibitor in celastrol-treated cells, suggesting that GSDME activation was induced by caspase-3. Mechanistically, celastrol induced endoplasmic reticulum (ER) stress and autophagy in HeLa cells, and other ER stress inducers produced effects consistent with those of celastrol. Conclusion: These findings suggest that celastrol triggers caspase-3/GSDME-dependent pyroptosis via activation of ER stress, which may shed light on the potential antitumor clinical applications of celastrol. © 2024 Beij.ng University of Chinese Medicine

关键词： Caspase-3 Celastrol Cell death Endoplasmic reticulum stress stress GSDME Pyroptosis Traditional Chinese medicine Tumor cells

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Identification of residues in Lassa virus glycoprotein 1 involved in receptor switch

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Virologica Sinica 2024年第4期39卷 600-608页

作者： guo j. Wan Y. Liu Y. j.a X. Dong S. Xiao G. Wang W. State Key Laboratory of Virology Wuhan Institute of Virology Center for Biosafety Mega-Science Chinese Academy of Sciences Wuhan 430071 China The Xi'an Key Laboratory of Pathogenic Microorganism and Tumor Immunity School of Basic Medicine Xi'an Medical University Xi'an 710021 China University of the Chinese Academy of Sciences Beijing 100049 China

Lassa virus (LASV) is an enveloped, negative-sense RNA virus that causes Lassa hemorrhagic fever. Successful entry of LASV requires the viral glycoprotein 1 (GP1) to undergo a receptor switch from its primary receptor alpha-dystroglycan (α-DG) to its endosomal receptor lysosome-associated membrane protein 1 (LAMP1). A conserved histidine triad in LASV GP1 has been reported to be responsible for receptor switch. To test the hypothesis that other non-conserved residues also contribute to receptor switch, we constructed a series of mutant LASV GP1 proteins and tested them for binding to LAMP1. Four residues, L84, K88, L107, and H170, were identified as critical for receptor switch. Substituting any of the four residues with the corresponding lymphocytic choriomeningitis virus (LCMV) residue (L84 N, K88E, L10F, and H170S) reduced the binding affinity of LASV GP1 for LAMP1. Moreover, all mutations caused decreases in glycoprotein precursor (GPC)-mediated membrane fusion at both pH 4.5 and 5.2. The infectivity of pseudotyped viruses bearing either GPCL84N or GPCK88E decreased sharply in multiple cell types, while L107F and H170S had only mild effects on infectivity. Using biolayer light interferometry assay, we found that all four mutants had decreased binding affinity to LAMP1, in the order of binding affinity being L84 N > L107F > K88E > H170S. The four amino acid loci identified for the first time in this study have important reference significance for the in-depth investigation of the mechanism of receptor switching and immune escape of LASV occurrence and the development of reserve anti-LASV infection drugs. © 2024 The Authors

关键词： Glycoprotein Lassa virus (LASV) Lysosome-associated membrane protein 1 (LAMP1) Membrane fusion Receptor switch

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Applications of genetic code expansion technology in eukaryotes

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Protein & Cell 2024年第5期15卷 331-363页

作者： Qiao-ru guo Yu j.Cao State Key Laboratory of Chemical Oncogenomic Guangdong Provincial Key Laboratory of Chemical GenomicsPeking University Shenzhen Graduate SchoolShenzhen 518055China Institute of Chemical Biology Shenzhen Bay LaboratoryShenzhen 518132China

Unnatural amino acids(UAAs)have gained significant attention in protein engineering and drug development owing to their ability to introduce new chemical functionalities to *** eukaryotes,genetic code expansion(GCE)enables the incorporation of UAAs and facilitates posttranscriptional modification(PTM),which is not feasible in prokaryotic *** is also a powerful tool for cell or animal imaging,the monitoring of protein interactions in target cells,drug development,and switch ***,there is keen interest in utilizing GCE in eukaryotic *** review provides an overview of the application of GCE in eukaryotic systems and discusses current challenges that need to be addressed.

关键词： genetic code expansion unnatural amino acid eukaryotes basic research therapeutic applications

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Liquid metal compartmented by polyphenol-mediated nanointerfaces enables high-performance thermal management on electronic devices

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InfoMat 2024年第1期6卷 83-95页

作者： Chaoj.n Zhang Yang Tang Tianyu guo Yizhou Sang Ding Li Xiaoling Wang Orlando j.Roj.s j.nling guo BMI Center for Biomass Materials and Nanointerfaces College of Biomass Science and EngineeringSichuan UniversityChengduSichuanthe People's Republic of China Bioproducts Institute Departments of Chemical and Biological EngineeringThe University of British ColumbiaVancouverBritish ColumbiaCanada Institute of Development Studies Southwestern University of Finance and EconomicsChengduSichuanthe People's Republic of China National Engineering Laboratory for Clean Technology of Leather Manufacture Sichuan UniversityChengduSichuanthe People's Republic of China State Key Laboratory of Polymer Materials Engineering Sichuan UniversityChengduSichuanthe People's Republic of China

The exponentially increasing heat generation in electronic devices,induced by high power density and miniaturization,has become a dominant issue that affects carbon footprint,cost,performance,reliability,and *** metals(LMs)with high thermal conductivity are promising candidates for effective thermal management yet are facing pump-out and surface-spreading *** in the form of metallic particles can address these problems,but apparent alloying processes elevate the LM melting point,leading to severely deteriorated ***,we propose a facile and sustainable approach to address these challenges by using a biogenic supramolecular network as an effective diffusion barrier at copper particle-LM(EGaIn/Cu@TA)interfaces to achieve superior thermal *** supramolecular network promotes LM stability by reducing unfavorable alloying and fluidity *** EGaIn/Cu@TA exhibits a record-high metallic-mediated thermal conductivity(66.1 W m^(-1) K^(-1))and fluidic ***,mechanistic studies suggest the enhanced heat flow path after the incorporation of copper particles,generating heat dissipation suitable for computer central processing units,exceeding that of commercial *** results highlight the prospects of renewable macromolecules isolated from biomass for the rational design of nanointerfaces based on metallic particles and LM,paving a new and sustainable avenue for high-performance thermal management.

关键词： Electronic devices High thermal conductivity Liquid metals Natural polyphenols Thermal management

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Vertically aligned montmorillonite aerogel-encapsulated polyethylene glycol with directional heat transfer paths for efficient solar thermal energy harvesting and storage

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International j.urnal of Minerals,Metallurgy and Materials 2024年第5期31卷 907-916页

作者： Qij.ng guo Cong guo Hao Yi Feifei j.a Shaoxian Song Key Laboratory of Green Utilization of Critical Non-metallic Mineral Resources Ministry of EducationWuhan University of TechnologyWuhan 430070China School of Resources and Environmental Engineering Wuhan University of TechnologyWuhan 430070China Hubei Key Laboratory of Mineral Resources Processing and Environment Wuhan University of TechnologyWuhan 430070China

The conversion and storage of photothermal energy using phase change materials(PCMs)represent an optimal approach for harnessing clean and sustainable solar ***,we encapsulated polyethylene glycol(PEG)in montmorillonite aerogels(3D-Mt)through vacuum impregnation to prepare 3D-Mt/PEG composite *** used as a support matrix,3D-Mt can effectively prevent PEG leakage and act as a flame-retardant barrier to reduce the flammability of ***,3D-Mt/PEG demonstrates outstanding shape retention,increased thermal energy storage density,and commendable thermal and chemical *** phase transition enthalpy of 3D-Mt/PEG can reach 167.53 j.g and remains stable even after 50 heating-cooling ***,the vertical sheet-like structure of 3D-Mt establishes directional heat transport channels,facilitating efficient phonon *** configuration results in highly anisotropic thermal conductivities that ensure swift thermal responses and efficient heat *** study addresses the shortcomings of PCMs,including the issues of leakage and inadequate flame *** achieves the development and design of 3D-Mt/PEG with ultrahigh strength,superior flame retardancy,and directional heat ***,this work offers a design strategy for the preparation of high-performance composite *** 3D-Mt/PEG with vertically aligned and well-ordered array structure developed in this research shows great potential for thermal management and photothermal conversion applications.

关键词： montmorillonite aerogel polyethylene glycol phase change materials solar thermal energy storage flame retardant

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Light People:*** May Lau,newly elected US NAE member in Hong Kong,talks about future of photonics and women in science

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Light(Science & Applications) 2024年第4期13卷 602-608页

作者： Yating Wan Chenzi guo Electrical and Computer Engineering the ComputerElectrical and Mathematical Sciences and Engineering DivisionKing Abdullah University of Science and Technology23955-6900 ThuwalSaudi Arabia Changchun Institute of Optics Fine Mechanics and PhysicsChinese Academy of SciencesChangchunChina

Editorial Photonics technology remains a driving force in today’s scientific landscape,marked by continuous innovation and crossdisciplinary *** an enlighting conversation with Light:Science&Applications,*** May Lau,a pioneer in photonics research,shares her deep insights on the evolution of technologies of LEDs,lasers,challenges of hetero-epitaxy,and the future of micro-LEDs and quantum dot *** honored as a member of the US National Academy of Engineering(NAE)for her significant contributions to photonics and electronics using III-V semiconductors on silicon,*** stands out as the sole Hong Kong scholar inducted into the NAE this year,j.ining 114 new and 21 international *** this exclusive Light People interview,*** shares her j.urney as a pioneering woman in engineering,her commitment to mentorship and academia,and her perspective on advancing female representation in *** summary provided is distilled from ***’s thoughtful responses during the *** a deeper exploration of ***’s experiences and advice,the full interview is available in the Supplementary material.

关键词： interview lighting driving

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Corrosion behavior of Gd_(2)Zr_(2)O_(7)thermal barrier coatings under Fe-containing environmental sediment attack

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j.urnal of Advanced Ceramics 2024年第4期13卷 447-462页

作者： Lei guo Yanyan Li Kai Yan School of Materials Science and Engineering Tianjin UniversityTianjin 300072China Tianj.n Key Laboratory of Advanced j.ining Technology Key Lab of Advanced Ceramics and Machining Technology of Ministry of EducationTianjin 300072China Key Laboratory of Special Equipment Safety and Energy-saving for State Market Regulation China Special Equipment Inspection&Research InstituteBeijing 100029China

Environmental sediments mainly consisting of CaO–MgO–Al_(2)O_(3)–SiO_(2)(CMAS)corrosion are a serious threat to thermal barrier coatings(TBCs),in which Fe element is usually ***_(2)Zr_(2)O_(7)TBCs are famous for their excellent CMAS *** this study,the characteristics of Fe-containing environmental sediments(CMAS-Fe)and their corrosiveness to Gd_(2)Zr_(2)O_(7)coatings were *** types of CMAS-Fe glass with different Fe contents were *** melting points were measured to be 1322–1344℃,and the high-temperature viscosity showed a decreasing trend with increasing Fe *** corrosion behavior of four types of CMAS-Fe to Gd_(2)Zr_(2)O_(7)coatings at 1350℃was *** the initial corrosion stage(0.1 h),anorthite was precipitated in CMAS-Fe with a high Ca:Si ratio,while Fe-garnet was formed in the melt with the highest Fe *** the corrosion time resulted in the formation of a reaction layer,which exhibited an interpenetrating network composed of Gd-oxyapatite,ZrO_(2),and residual *** spinel was precipitated within the reaction *** 1 h or even longer time,the reaction layers tended to be stable and compact,which had comparable hardness and fracture toughness to those of Gd_(2)Zr_(2)O_(7)*** the cyclic CMAS-Fe attack,the residual CMAS-Fe in the interpenetrating network provided a pathway for the redeposited CMAS-Fe infiltration,resulting in the continuous growth of the reaction *** a result,the Gd_(2)Zr_(2)O_(7)coatings had a large consumption in the thickness,degrading the coating ***,the Gd_(2)Zr_(2)O_(7)coatings exhibit unsatisfactory corrosion resistance to CMAS-Fe attack.

关键词： thermal barrier coatings(TBCs) Gd_(2)Zr_(2)O_(7) Fe-containing CaO-MgO-Al2O3-SiO_(2)(CMAS) corrosion resistance reaction layer

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Chlorogenic acid ameliorates heart failure by attenuating cardiomyocyte ferroptosis

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j.urnal of Traditional Chinese Medical Sciences 2024年第2期11卷 191-198页

作者： Huang K. Li F. Tang j. Pu H. Sukhorukov V. Orekhov A.N. guo S. School of Traditional Chinese Medicine Beijing University of Chinese Medicine Beijing 102488 China Laboratory of Angiopathology Institute of General Pathology and Pathophysiology Russian Academy of Medical Sciences Moscow 125315 Russian Federation

Obj.ctive: To elucidate the effects of chlorogenic acid (CGA), a bioactive polyphenol compound prevalent in traditional Chinese medicine and various foods, including Lonicera j.ponica Thunb. (j.n Yin Hua), Eucommia ulmoides Oliv. (Du Zhong Ye), tea, and coffee, on cardiomyocyte ferroptosis and heart failure. Methods: We assessed the effect of CGA on cardiac function using a mouse model of heart failure induced by transverse aortic constriction (TAC). These indicators included the left ventricular ej.ction fraction (LVEF), fractional shortening (LVFS), end-systolic volume (LVESV), end-diastolic volume (LVEDV), end-systolic diameter (LVESD), and end-diastolic diameter (LVEDD). An isoprenaline hydrochloride (ISO)-induced H9c2 cardiomyocyte cell model was also established, and the cells were treated with various concentrations of CGA. To assess the effect of CGA on ferroptosis in cardiomyocytes, we measured cell viability and evaluated the levels of intracellular reactive oxygen species (ROS), ferrous ions (Fe2+), and lipid peroxidation using fluorescent staining. To clarify the ferroptosis signaling pathway regulated by CGA, western blotting was used to examine the expression of ferroptosis biomarkers, specifically solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), in H9c2 cardiomyocytes and mouse myocardial tissues. Results: CGA significantly enhanced cardiac performance indices such as LVEF, LVFS, LVESV, LVEDV, LVESD, and LVEDD. H9c2 cardiomyocytes exposed to ISO showed decreased cell viability and increased ROS levels, Fe2+ content, and lipid peroxidation levels. However, CGA treatment significantly ameliorated these changes. Additionally, in both H9c2 cardiomyocytes and myocardial tissue obtained from mice with TAC, CGA increased the expression of ferroptosis-related proteins, including SLC7A11 and GPX4. Conclusion: CGA has the potential to enhance cardiac function and diminish lipid peroxidation and ROS levels in cardiomyocytes via th

关键词： Chlorogenic acid Ferroptosis H9c2 cardiomyocyte Heart failure Traditional Chinese medicine

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Novel data-driven sparse polynomial chaos and analysis of covariance for aerodynamics of compressor cascades with dependent geometric uncertainties

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Chinese j.urnal of Aeronautics 2024年第6期37卷 89-108页

作者： Zhengtao guo Wuli CHU Haoguang ZHANG Tianyuan j. School of Power and Energy Northwestern Polytechnical UniversityXi’an 710072China

Polynomial Chaos Expansion(PCE)has gained significant popularity among engineers across various engineering disciplines for uncertainty ***,traditional PCE suffers from two maj.r ***,the orthogonality of polynomial basis functions holds only for independent input variables,limiting the model’s ability to propagate uncertainty in dependent ***,PCE encounters the"curse of dimensionality"due to the high computational cost of training the model with numerous polynomial *** practical manufacturing,compressor blades are subj.ct to machining precision limitations,leading to deviations from their ideal geometric *** deviations require a large number of geometric parameters to describe,and exhibit significant *** efficiently quantify the impact of high-dimensional dependent geometric deviations on the aerodynamic performance of compressor blades,this paper firstly introduces a novel approach called Data-driven Sparse PCE(DSPCE).The proposed method addresses the aforementioned challenges by employing a decorrelation algorithm to directly create multivariate basis functions,accommodating both independent and dependent random ***,the method utilizes an iterative Diffeomorphic Modulation under Observable Response Preserving Homotopy regression algorithm to solve the unknown coefficients,achieving model sparsity while maintaining fitting ***,the study investigates the simultaneous effects of seven dependent geometric deviations on the aerodynamics of a high subsonic compressor cascade by using the DSPCE method proposed and sensitivity analysis of *** j.int distribution of the dependent geometric deviations is determined using Quantile-Quantile plots and normal copula functions based on finite measurement *** results demonstrate that the correlations between geometric deviations significantly impact the variance of aerodynamic performance and the flow ***,

关键词： Data-driven sparse polyno-mial chaos Analysis of covariance Dependent uncertainty Aerodynamic performance Compressor cascade

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Study on thermal decomposition kinetics of azobenzene-4,4′-dicarboxylic acid by using compensation parameter method and nonlinear fitting evaluation

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Chinese j.urnal of Chemical Engineering 2024年第6期70卷 269-279页

作者： Shuyi Shen Song guo Sining Chen j.nhua Zhao Nanj.ng University of Science&Technology Nanjing 210094China China Academy of Safety Science and Technology Beijing 100012China

Recently,azobenzene-4,4'-dicarboxylic acid(ADCA)has been produced gradually for use as an organic synthesis or pharmaceutical intermediate due to its eminent *** large quantities put into application in the future,the thermal stability of this substance during storage,transportation,and use will become quite ***,in this work,the thermal decomposition behavior,thermal decomposition kinetics,and thermal hazard of ADCA were *** were conducted by using a SENSYS evo DSC device.A combination of differential iso-conversion method,compensation parameter method,and nonlinear fitting evaluation were also used to analyze thermal kinetics and mechanism of ADCA *** results show that when conversion rate α increases,the activation energies of ADCA's first and main decomposition peaks *** amount of heat released during decomposition varies between 182.46 and 231.16 j.g^(-1).The proposed kinetic equation is based on the Avrami-Erofeev model,which is consistent with the decomposition *** the Frank-Kamenetskii model,a calculated self-accelerating decomposition temperature of 287.0℃is obtained.

关键词： Azobenzene-4,4′-dicarboxylic acid Thermal decomposition behavior Kinetic mechanism Thermal hazard evaluation Compensation parameter effect

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