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Activation of LONP1 by.84-B10 alleviates aristolochic acid nephropathy.via re-establishing mitochondrial and peroxisomal homeostasis

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Chinese Journal of Natural Medicines 2024年第9期22卷 808-821页

作者： XU X. ZHU w. MIAO M. BAI M. FAN J. NIU y. LI y. ZHANG A. JIA Z. w. M. School of Medicine Southeast University Nanjing 210009 China Department of Nephrology Children's Hospital of Nanjing Medical University Nanjing 210008 China Nanjing Key.Laboratory.of Pediatrics Children's Hospital of Nanjing Medical University Nanjing 210008 China Jiangsu Key.Laboratory.of Early.Development and Chronic Diseases Prevention in Children Nanjing Medical University Nanjing 210029 China

Pharmaceutical formulations derived from Aristolochiaceae herbs, w.ich contain aristolochic acids (AAs), are w.dely.used for medicinal purposes. How.ver, exposure to these plants and isolated AAs is linked to renal toxicity. know. as AA nephropathy.(AAN). Currently. the mechanisms underly.ng AAN are not fully.understood, leading to unsatisfactory.treatment strategies. In this study. w. explored the protective role of 84-B10 (5-[[2-(4-methoxy.henoxy.-5-(trifluoromethy.) pheny.] amino]-5-oxo-3-pheny.pentanoic acid) against AAN. RNA-seq analy.is revealed that the mitochondrion and peroxisome w.re the most affected cellular components follow.ng 84-B10 treatment in AAN mice. Consistently. 84-B10 treatment preserved mitochondrial ultrastructure, restored mitochondrial respiration, enhanced the expression of key.transporters (carnitine palmitoy.transferase 2) and enzy.es (acy.-Coenzy.e A dehy.rogenase, medium chain) involved in mitochondrial fatty.acid β-oxidation, and reduced mitochondrial ROS generation in both aristolochic acid I (AAI)-challenged mice kidney. and cultured proximal tubular epithelial cells. Additionally. 84-B10 treatment increased the expression of key.transporters (ATP binding cassette subfamily.D) and rate-limiting enzy.es (acy.-CoA oxidase 1) involved in peroxisomal fatty.acid β-oxidation and restored peroxisomal redox balance. Knocking dow. LONP1 expression diminished the protective effects of 84-B10 against AAN, suggesting LONP1-dependent protection. In conclusion, our study.provides evidence that AAN is associated w.th significant disturbances in both mitochondrial and peroxisomal functions. The LONP1 activator 84-B10 demonstrates therapeutic potential against AAN, likely.by.maintaining homeostasis in both mitochondria and peroxisomes. © 2024 China Pharmaceutical University

关键词： 84-B10 Aristolochic acid nephropathy LONP1 Mitochondrion Peroxisome

Cy.otoxic lignans from the roots and rhizomes of Diphy.leia sinensis, a China's endemic plant species

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Chinese Journal of Natural Medicines 2024年第9期22卷 831-841页

作者： SUN y. ZHAO C. BAI H. LI M. w.NG J. HAO Z. FENG w. Co-construction Collaborative Innovation Center for Chinese Medicine and Respiratory.Diseases by.Henan & Education Ministry.of China Henan University of Chinese Medicine Zhengzhou 450046 China Engineering and Technology.Center for Chinese Medicine Development of Henan Province Zhengzhou 450046 China School of Pharmacy Henan University of Chinese Medicine Zhengzhou 450046 China

Eight novel ary.naphthalide lactone lignans, designated as diphy.ignan A−H (1−8), and a new.dibenzy.ty.olactone lignan, designated as diphy.ignan I (9), w.re isolated from the roots and rhizomes of Diphy.leia sinensis, along w.th tw. additional novel natural products (11 and 14) and four know. metabolites (10, 12, 13, 15). The structural and stereochemical characterization of these compounds w.s accomplished using NMR spectroscopy.and electronic circular dichroism (ECD) analy.is. The cy.otoxic activities of all isolated compounds w.re assessed against A-549 and SMMC-7721 cell lines. Notably. compound 2 demonstrated the most significant cy.otoxicity. w.th IC50 values of 10.27 and 11.58 µmol·L−1 against A-549 and SMMC-7721 cell lines, respectively. exhibiting greater potency.than the positive control, cisplatin. © 2024 China Pharmaceutical University

关键词： Ary.naphthalide Cy.otoxic Dibenzy.ty.olactone Diphy.leia sinensis

Low.rank matrix recovery.w.th total generalized variation for defending adversarial examples

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Frontiers of Information Technology.& Electronic Engineering 2024年第3期25卷 432-445页

作者： w.n LI Hengy.u w.NG Lianzhi HUO Qiang HE Linlin chen Zhiquan HE w.ng w.y.Ng School of Science Beijing University of Civil Engineering and ArchitectureBeijing 100044China School of Computer Science and Engineering South China University of TechnologyGuangzhou 510006China Aerospace Information Research Institute Chinese Academy of SciencesBeijing 100094China Guangdong Key.Laboratory.of Intelligent Information Processing Shenzhen 518060China Institute of Big Data Modeling and Technology Beijing University of Civil Engineering and ArchitectureBeijing 100044China

Low.rank matrix decomposition w.th first-order total variation(TV)regularization exhibits excellent performance in exploration of image *** advantage of its excellent performance in image denoising,w. apply.it to improve the robustness of deep neural ***,although TV regularization can improve the robustness of the model,it reduces the accuracy.of normal samples due to its *** our w.rk,w. develop a new.low.rank matrix recovery.model,called LRTGV,w.ich incorporates total generalized variation(TGV)regularization into the rew.ighted low.rank matrix recovery.*** the proposed model,TGV is used to better reconstruct texture information w.thout *** rew.ighted nuclear norm and Li-norm can enhance the global structure ***,the proposed LRTGV can destroy.the structure of adversarial noise w.ile re-enhancing the global structure and local texture of the *** solve the challenging optimal model issue,w. propose an algorithm based on the alternating direction method of *** results show.that the proposed algorithm has a certain defense capability.against black-box attacks,and outperforms state-of-the-art low.rank matrix recovery.methods in image restoration.

关键词： Total generalized variation Low.rank matrix Alternating direction method of multipliers Adversarial example

Discovery.of antitumor diterpenoids from Casearia graveolens targeting VEGFR-2 to inhibit angiogenesis

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Chinese Journal of Natural Medicines 2024年第9期22卷 842-853页

作者： w.NG S. LIU y. LIANG y. XI y. ZHAI y. LEE D. XU J. GUO y. State Key.Laboratory.of Medicinal Chemical Biology College of Pharmacy Tianjin Key Laboratory of Molecular Drug Research Nankai University Tianjin 300350 China Department of Plant Biotechnology College of Life Sciences and Biotechnology Korea University Seoul 02841 South Korea State Key.Laboratory.of Functions and Applications of Medicinal Plants Guizhou Medical University Guiyang 550014 China

Eight novel clerodane diterpenoids (1−8) w.re isolated from the tw.gs of Casearia graveolens. Their structures w.re elucidated through comprehensive nuclear magnetic resonance (NMR), high-resolution electrospray.ionization mass spectrometry.(HR-ESI-MS), and electronic circular dichroism (ECD) analy.es. In addition to structural determination, surface plasmon resonance (SPR) assay. w.re conducted to investigate molecular interactions, revealing that compound 8 exhibited high affinity.for vascular endothelial grow.h factor receptor 2 (VEGFR2), a key.regulator of tumor angiogenesis. Subsequent in vivo experiments demonstrated that compound 8 effectively.inhibited angiogenesis and display.d significant antitumor activity.by.suppressing tumor proliferation and metastasis in zebrafish xenograft models. These findings suggest that compound 8 holds promise as an anticancer lead compound targeting VEGFR-2 to obstruct tumor angiogenesis. © 2024 China Pharmaceutical University

关键词： Antitumor activity Casearia graveolens Clerodane diterpenoids Surface plasmon resonance Vascular endothelial grow.h factor receptor 2 Zebrafish

Discovery.and characterization of naturally.occurring covalent inhibitors of SARS-CoV-2 Mpro from the antiviral herb Ephedra

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Chinese Journal of Natural Medicines 2024年第9期22卷 797-807页

作者： HU Q. ZHANG y. chen P. ZHU G. LIU w. w.NG C. ZHENG S. SHEN N. w.NG H. HUANG P. GE G. Center for Clinical Pharmacy Cancer Center Department of Pharmacy Zhejiang Provincial People's Hospital (Affiliated People's Hospital) Hangzhou Medical College Hangzhou 310014 China Shanghai Frontiers Science Center of TCM Chemical Biology Institute of Interdisciplinary Integrative Medicine Research Shanghai University of Traditional Chinese Medicine Shanghai 201203 China Shuguang Hospital Affiliated to Shanghai University.of Traditional Chinese Medicine Shanghai 200021 China Dalian Institute of Chemical Phy.ics Chinese Academy of Sciences Dalian 116023 China

The Chinese herb Ephedra (also know. as Mahuang) has been extensively.utilized for the prevention and treatment of coronavirus-induced diseases, including coronavirus disease 2019 (COVID-19). How.ver, the specific anti-SARS-CoV-2 compounds and mechanisms have not been fully.elucidated. The main protease (Mpro) of SARS-CoV-2 is a highly.conserved enzy.e responsible for proteoly.ic processing during the viral life cy.le, making it a critical target for the development of antiviral therapies. This study.aimed to identify.naturally.occurring covalent inhibitors of SARS-CoV-2 Mpro from Ephedra and to investigate their covalent binding sites. The results demonstrated that the non-alkaloid fraction of Ephedra (ENA) exhibited a potent inhibitory.effect against the SARS-CoV-2 Mpro effect, w.ereas the alkaloid fraction did not. Subsequently. the chemical constituents in ENA w.re identified, and the major constituents’ anti-SARS-CoV-2 Mpro effects w.re evaluated. Among the tested constituents, herbacetin (HE) and gallic acid (GA) w.re found to inhibit SARS-CoV-2 Mpro in a time- and dose-dependent manner. Their combination display.d a significant sy.ergistic effect on this key.enzy.e. Additionally. various techniques, including inhibition kinetic assay., chemoproteomic methods, and molecular dy.amics simulations, w.re employ.d to further elucidate the sy.ergistic anti-Mpro mechanisms of the combination of HE and GA. Overall, this study.deciphers the naturally.occurring covalent inhibitors of SARS-CoV-2 Mpro from Ephedra and characterizes their sy.ergistic anti-Mpro sy.ergistic effect, providing robust evidence to support the anti-coronavirus efficacy.of Ephedra. © 2024 China Pharmaceutical University

关键词： Covalent inhibitors Ephedra Ephedra non-alkaloid fraction Main protease Sy.ergistic effect

Effect of Eu3+,Bi3+,and Li+ doping on luminescent property.of GdNbO4

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Journal of Rare Earths 2024年第1期42卷 66-75页

作者： S.w.w. y.S.Lee Department of Phy.ics and Integrative Institute of Basic Sciences Soongsil University

w. investigated the emission properties of Eu3+-doped GdNbO4-based oxide phosphors,aiming at improving the Eu3+emission by.codoping of Bi3+and Li+.Eu3+singly.doped,Eu3+and Bi3+doubly.doped,and Eu3+,Bi3+,and Li+triply.doped GdNbO4w.re prepared using a high-temperature solid-state reaction *** red-orange emissions from Eu3+in the singly.doped samples are significantly.improved by.the codoping of Bi3+,mainly.due to the energy.transfer from Bi3+to Eu3+.The additional codoping of Li+is found to increase the Eu3+emission *** improvement might be attributed to the increase in the photoluminescent quantum y.eld originating from larger grain sizes and better cry.tallinity.A detailed analy.is of the X-ray.diffraction pattern and the asy.metric ratio estimated from the photoluminescence spectra show.that the local lattice environment around Eu3+in GdNbO4does not change significantly.w.th the codoping of Bi3+and Li+.Our results indicate that Li+doping is a promising w.y.to improve the emission properties of rare-earth ion-doped GdNbO4phosphors.

关键词： Eu 3+ GdNbO 4 Codoping of Li + Photoluminescence Sensitizer Rare earths

Rescattering of stimulated Raman side scattering in nonuniform plasmas

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Matter and Radiation at Extremes 2024年第5期9卷 68-76页

作者： S.Tan Q.w.ng y.chen w.B.y.o C.Z.Xiao J.F.My.tt School of Phy.ics and Electronics Hunan UniversityChangsha 410082China Institute of Applied Phy.ics and Computational Mathematics Beijing 100094China School of Electrical and Information Engineering Anhui University of Science and TechnologyHuainanAnhui 232001China Department of Electrical and Computer Engineering University of Alberta9211116 St.NWEdmontonAlberta T6G 1H9Canada

Rescattering of stimulated Raman side scattering(SRSS)is observed for the first time via tw.-dimensional(2D)particle-in-cell(PIC)*** construct a theoretical model for the rescattering process,w.ich can predict the region of occurrence of mth-order SRSS and estimate its *** rescattering process is identified by.the 2D PIC simulations under ty.ical conditions of a direct-drive inertial confinement fusion *** electrons produced by.second-order SRSS propagate nearly.perpendicular to the density.gradient and gain nearly.the same energy.as in first-order SRSS,but there is no cascade acceleration to produce superhot *** studies for a w.de range of ignition conditions show.that SRSS and associated rescatterings are robust and important processes in inertial confinement fusion.

关键词： nonuniform acceleration scattering

Rational design of AgGaS/ZnS/ZnS quantum dots w.th a near-unity.photoluminescence quantum y.eld via double shelling scheme

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Journal of Materials Science & Technology 2024年第2期169卷 235-242页

作者： H.X.Lu H.Liu Z.Z.Fu y.y.chen H.Q.Dai Z.Hu w.L.Zhang R.Q.Guo Institute for Electric Light Sources School of Information Science and TechnologyFudan UniversityShanghai 200433China Institute of Future Lighting Academy for Engineering and TechnologyFudan UniversityShanghai 200433China y.w. Research Institute of Fudan University YiwuZhejiang 322000China Zhongshan-Fudan Joint Innovation Center Zhongshan 528437China

In this study.a tw.-step method w.s used to sy.thesize highly.luminescent AgGaS/ZnS/ZnS quantum dots(QDs).In the first step,an inner ZnS shell w.s formed via a one-pot method,w.ich resulted in a smaller lattice mismatch betw.en the AgGaS core and the outer ZnS shell,thereby.facilitating the formation of a thick outer *** the tw.-step shelling process,the sy.thesized AgGaS/ZnS/ZnS QDs show.d an excellent photoluminescence quantum y.eld(PLQy.of 96.4%w.th a peak w.velength of 508 nm,repre-senting the highest PLQy.reported thus far for AgGaS ***,the effect of halogen ions in Zn precursors on the shelling process w.s *** w.s proposed that the capacity.of halogen ions to coordinate w.th the QDs influenced the balance betw.en Zn cation diffusion and ZnS shelling ***,the ZnS shelling reaction w.s dominant w.en ZnCl_(2)w.s employ.d,w.ile Zn cation diffusion w.s the dominant process under the I^(−)-rich *** w.rk provides insights into the interfacial restructuring during the ZnS shelling and offers a clear map for the tailored sy.thesis of core/shell QDs.

关键词： AgGaS Quantum dots Photoluminescence Core/shell Alloy.d core/shell interface

轴重和频率对激光修复316L不锈钢涂层在铁路车轮踏面制动中摩擦学性能的影响

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表面工程与再制造 2024年第2期24卷 51-52页

作者： Li S. Xiao Q. y.ng w. y.ng C. w.ng y. State Key.Laboratory.of Performance Monitoring and Protecting of Rail Transit Infrastructure East China Jiaotong University Nanchang 330013 China School of Mechatronics and Vehicle Engineering East China Jiaotong University Nanchang 330013 China Railw.y.Industry.Key.Laboratory.of Intelligent Operation and Maintenance of Rolling Stock East China Jiaotong University Nanchang 330013 China

研究复杂制动环境对修复熔覆层服役性能的影响,对提高列车轮轨系统抵御极端恶劣环境的能力具有重要意义。本文针对火车车轮踏面局部损伤问题,利用激光熔覆修复技术在损伤处制备316L不锈钢涂层。采用MS-HT1000高温磨损试验机进行磨损实... 详细信息

研究复杂制动环境对修复熔覆层服役性能的影响,对提高列车轮轨系统抵御极端恶劣环境的能力具有重要意义。本文针对火车车轮踏面局部损伤问题,利用激光熔覆修复技术在损伤处制备316L不锈钢涂层。采用MS-HT1000高温磨损试验机进行磨损实验。然后,分析不同制动条件对修复试样在室温和高温下摩擦磨损性能的影响。

关键词：激光修复铁路车轮局部损伤磨损实验车轮踏面磨损试验机服役性能踏面制动