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Journal of Pharmaceutical Analysis 2024年第2期14卷 211-224页

作者： Jingjing Wang Qi Su Kun Chen qing Wu Jiayan Ren Wenjuan Tang Yu Hu Zeren zhu Cheng Cheng Kaihui Tu Huaizhen He Yanmin Zhang School of Pharmacy Health Science CenterXi'an Jiaotong UniversityXi'an710061China

Hepatocellular carcinoma (HCC) is one of the most common tumor types and remains a major clinical challenge. Increasing evidence has revealed that mitophagy inhibitors can enhance the effect of chemotherapy on HCC. However, few mitophagy inhibitors have been approved for clinical use in humans. Pyrimethamine (Pyr) is used to treat infections caused by protozoan parasites. Recent studies have reported that Pyr may be beneficial in the treatment of various tumors. However, its mechanism of action is still not clearly defined. Here, we found that blocking mitophagy sensitized cells to Pyr-induced apoptosis. Mechanistically, Pyr potently induced the accumulation of autophagosomes by inhibiting autophagosome-lysosome fusion in human HCC cells. In vitro and in vivo studies revealed that Pyr blocked autophagosome-lysosome fusion by upregulating BNIP3 to inhibit synaptosomal-associated protein 29 (SNAP29)-vesicle-associated membrane protein 8 (VAMP8) interaction. Moreover, Pyr acted synergistically with sorafenib (Sora) to induce apoptosis and inhibit HCC proliferation in vitro and in vivo. Pyr enhances the sensitivity of HCC cells to Sora, a common chemotherapeutic, by inhibiting mitophagy. Thus, these results provide new insights into the mechanism of action of Pyr and imply that Pyr could potentially be further developed as a novel mitophagy inhibitor. Notably, Pyr and Sora combination therapy could be a promising treatment for malignant HCC.

关键词： Pyrimethamine BNIP3 SNARE Autophagosome-lysosome fusion Hepatocellular carcinoma Sorafenib

Electroacupuncture Promotes Functional Recovery after Facial Nerve Injury in Rats by Regulating Autophagy via GDNF and PI3K/m TOR Signaling Pathway

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Chinese Journal of Integrative Medicine 2024年第3期30卷 251-259页

作者： YAO Jun-peng FENG Xiu-mei WANG Lu LI Yan-qiu zhu Zi-yue YAN Xiang-yun YANG Yu-qing LI Ying ZHANG Wei Acupuncture and Tuina School Chengdu University of Traditional Chinese MedicineChengdu611137China Department of Rehabilitation Medicine Guanghan People’s HospitalGuanghanSichuan Province618399China Academic Affairs Office Chengdu University of Traditional Chinese MedicineChengdu611137China

Objective:To explore the mechanism of electroacupuncture(EA) in promoting recovery of the facial function with the involvement of autophagy,glial cell line-derived neurotrophic factor(GDNF),and phosphatidylinositol-3-kinase(PI3K)/mammalian target of rapamycin(mTOR) signaling ***:Seventy-two male Sprague-Dawley rats were randomly allocated into the control,sham-operated,facial nerve injury(FNI),EA,EA+3-methyladenine(3-MA),and EA+GDNF antagonist groups using a random number table,with 12 rats in each *** FNI rat model was established with facial nerve crushing *** intervention was conducted at Dicang(ST 4),Jiache(ST 6),Yifeng(SJ 17),and Hegu(LI 4) acupoints for 2 *** Simone’s 10-Point Scale was utilized to monitor the recovery of facial *** histopathological evaluation of facial nerves was performed using hematoxylin-eosin(HE) *** levels of Beclin-1,light chain 3(LC3),and P62 were detected by immunohistochemistry(IHC),immunofluorescence,and reverse transcriptionpolymerase chain reaction,***,IHC was also used to detect the levels of GDNF,Rai,PI3K,and ***:The facial functional scores were significantly increased in the EA group than the FNI group(P0.05 or P0.01).HE staining showed nerve axons and myelin sheaths,which were destroyed immediately after the injury,were recovered with EA *** expressions of Beclin-1 and LC3 were significantly elevated and the expression of P62 was markedly reduced in FNI rats(P0.01);however,EA treatment reversed these abnormal changes(P0.01).Meanwhile,EA stimulation significantly increased the levels of GDNF,Rai,PI3K,and mTOR(P0.01).After exogenous administration with autophagy inhibitor 3-MA or GDNF antagonist,the repair effect of EA on facial function was attenuated(P0.05 or P0.01).Conclusions:EA could promote the recovery of facial function and repair the facial nerve damages in a rat model of *** may exert this neuroreparative effect through

关键词： electroacupuncture facial nerve injury autophagy glial cell line-derived neurotrophic factor phosphatidylinositol-3-kinase/mammalian target of rapamycin Chinese medicine

Prevention and control strategies for antibiotic resistance:from species to community level

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Soil Ecology Letters 2024年第3期6卷 17-34页

作者： Yan-Zi Wang Hu Li qing-Lin Chen Ting Pan Yong-Guan zhu Dirk Springael Jian-Qiang Su Key Laboratory of Urban Environment and Health Ningbo Observation and Research StationInstitute of Urban EnvironmentChinese Academy of SciencesXiamen 361021China University of Chinese Academy of Sciences Beijing 100049China State Key Laboratory of Urban and Regional Ecology Research Center for Eco-Environmental SciencesChinese Academy of SciencesBeijing 100085China Division of Soil and Water Management KU LeuvenKasteelpark Arenberg 20 Box 24593001 HeverleeBelgium

Antibiotic resistance genes(ARGs)and antibiotic resistant bacteria(ARB)in the environment pose serious threats to environmental security and public *** is an urgent need for methods to specifically and effectively control environmental pollution or pathogen infection associated with ARGs and *** review aims to provide an overview of methods abating the prevalence and spread of ARGs and ARB from species to community *** the species level,species-specific technologies,such as nanoparticle-,photosensitizer-,CRISPR-Cas-,and phage-related technology can be utilized to clear a particular class of ARGs or ARB,and in combination with low-dose antibiotics,a higher removal efficiency can be ***,the combination of antibiotics can be used to reverse microbial resistance and treat recurrent antibiotic resistant pathogen *** the community level,community-specific strategies,such as biochar,hyperthermophilic compost,and fecal microbiota transplantation can eradicate most types of ARGs or ARB in one shot,reducing the probability of resistance *** some progress has been made to eliminate ARGs and ARB in disease treatment or decontamination scenarios,further research is still needed to elucidate their mechanisms of action and scopes of application,and efforts should be made to explore novel strategies to counter the prevalence of antibiotic resistance.

关键词： antibiotic resistance genes antibiotic resistant bacteria treatment strategy disinfection

High patatin like phospholipase domain containing 8 expression as a biomarker for poor prognosis of colorectal cancer

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 787-797页

作者： Peng-Yang Zhou De-Xiang zhu Yi-Jiao Chen qing-Yang Feng Yi-Hao Mao Ao-Bo zhuang Jian-Min Xu Department of General Surgery Zhongshan Hospital Fudan UniversityShanghai 200032China

BACKGROUND Patatin like phospholipase domain containing 8(PNPLA8)has been shown to play a significant role in various cancer *** studies have focused on its roles as an antioxidant and in lipid ***,the role of PNPLA8 in colorectal cancer(CRC)progression is *** To explore the prognostic effects of PNPLA8 expression in *** A retrospective cohort containing 751 consecutive CRC patients was ***8 expression in tumor samples was evaluated by immunohistochemistry staining and semi-quantitated with immunoreactive *** patients were divided into high and low PNPLA8 expression groups based on the cut-off va-lues,which were calculated by X-tile *** prognostic value of PNPLA8 was identified using univariate and multivariate Cox regression *** over-all survival(OS)rates of CRC patients in the study cohort were compared with Kaplan-Meier analysis and Log-rank *** PNPLA8 expression was significantly associated with distant metastases in our cohort(P=0.048).CRC patients with high PNPLA8 expression indicated poor OS(median OS=35.3,P=0.005).CRC patients with a higher PNPLA8 expression at either stage I and II or stage III and IV had statistically significant shorter *** patients with left-sided colon and rectal cancer,the survival curves of two PN-PLA8-expression groups showed statistically significant *** analysis also confirmed that high PNPLA8 expression was an independent prog-nostic factor for overall survival(hazard ratio HR=1.328,95%CI:1.016-1.734,P=0.038).

关键词： Biomarker Colorectal cancer Expression level Overall survival Patatin like phospholipase domain containing 8 Prognosis

NLRP3-mediated autophagy dysfunction links gut microbiota dysbiosis to tau pathology in chronic sleep deprivation

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Zoological Research 2024年第4期45卷 857-874页

作者： Na Zhao Xiu Chen Qiu-Gu Chen Xue-Ting Liu Fan Geng Meng-Meng zhu Fu-Ling Yan Zhi-Jun Zhang qing-Guo Ren Department of Neurology School of MedicineSoutheast UniversityNanjingJiangsu 210009China Department of Neurology Affiliated Zhongda HospitalSoutheast UniversityNanjingJiangsu 210009China

Emerging evidence indicates that sleep deprivation(SD)can lead to Alzheimer’s disease(AD)-related pathological changes and cognitive ***,the underlying mechanisms remain *** the present study,we identified the existence of a microbiota-gut-brain axis in cognitive deficits resulting from chronic SD and revealed a potential pathway by which gut microbiota affects cognitive functioning in chronic *** findings demonstrated that chronic SD in mice not only led to cognitive decline but also induced gut microbiota dysbiosis,elevated NLRP3 inflammasome expression,GSK-3βactivation,autophagy dysfunction,and tau hyperphosphorylation in the *** with the“SD microbiota”replicated the pathological and behavioral abnormalities observed in chronic sleep-deprived ***,both the deletion of NLRP3 in NLRP3-/-mice and specific knockdown of NLRP3 in the hippocampus restored autophagic flux,suppressed tau hyperphosphorylation,and ameliorated cognitive deficits induced by chronic SD,while GSK-3βactivity was not regulated by the NLRP3 inflammasome in chronic ***,deletion of NLRP3 reversed NLRP3 inflammasome activation,autophagy deficits,and tau hyperphosphorylation induced by GSK-3βactivation in primary hippocampal neurons,suggesting that GSK-3β,as a regulator of NLRP3-mediated autophagy dysfunction,plays a significant role in promoting tau ***,gut microbiota dysbiosis was identified as a contributor to chronic SD-induced tau pathology via NLRP3-mediated autophagy dysfunction,ultimately leading to cognitive ***,these findings highlight GSK-3βas a regulator of NLRP3-mediated autophagy dysfunction,playing a critical role in promoting tau hyperphosphorylation.

关键词： Chronic sleep deprivation Tau pathology NLRP3 inflammasome Autophagy GSK-3β Microbiota-gut-brain axis

Discovery and characterization of naturally occurring covalent inhibitors of SARS-CoV-2 M^(pro)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 qing ZHANG Yiwen CHEN Pengcheng ZHANG Yani zhu Guanghao LIU Wei WANG Chaoran ZHENG Shuilian SHEN Nonger WANG Haonan HUANG Ping GE Guangbo Center for Clinical Pharmacy Cancer CenterDepartment of PharmacyZhejiang Provincial People’s Hospital(Affiliated People’s Hospital)Hangzhou Medical CollegeHangzhou 310014China Shanghai Frontiers Science Center of TCM Chemical Biology Institute of Interdisciplinary Integrative Medicine ResearchShanghai University of Traditional Chinese MedicineShanghai 201203China Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine Shanghai 200021China Dalian Institute of Chemical Physics Chinese Academy of SciencesDalian 116023China

The Chinese herb Ephedra(also known as Mahuang)has been extensively utilized for the prevention and treatment of coronavirus-induced diseases,including coronavirus disease 2019(COVID-19).However,the specific anti-SARS-CoV-2 compounds and mechanisms have not been fully *** main protease(M^(pro))of SARS-CoV-2 is a highly conserved enzyme responsible for proteolytic processing during the viral life cycle,making it a critical target for the development of antiviral *** study aimed to identify naturally occurring covalent inhibitors of SARS-CoV-2 M^(pro)from Ephedra and to investigate their covalent binding *** results demonstrated that the non-alkaloid fraction of Ephedra(ENA)exhibited a potent inhibitory effect against the SARS-CoV-2 M^(pro)effect,whereas the alkaloid fraction did ***,the chemical constituents in ENA were identified,and the major constituents'anti-SARS-CoV-2 M^(pro)effects were *** the tested constituents,herbacetin(HE)and gallic acid(GA)were found to inhibit SARS-CoV-2 M^(pro)in a time-and dose-dependent *** combination displayed a significant synergistic effect on this key ***,various techniques,including inhibition kinetic assays,chemoproteomic methods,and molecular dynamics simulations,were employed to further elucidate the synergistic anti-M^(pro)mechanisms of the combination of HE and ***,this study deciphers the naturally occurring covalent inhibitors of SARS-CoV-2 M^(pro)from Ephedra and characterizes their synergistic anti-M^(pro)synergistic effect,providing robust evidence to support the anti-coronavirus efficacy of Ephedra.

关键词： Main protease Ephedra Ephedra non-alkaloid fraction Covalent inhibitors Synergistic effect

生态风险与生态系统健康对生态系统服务的影响

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地理学报 2024年第5期79卷 1303-1317页

作者：朱青蔡永立上海交通大学设计学院风景园林系上海200240 自然资源部国土空间生态治理数字工程技术创新中心上海200240 云南洱海湖泊生态系统国家野外科学观测研究站大理671000

生态风险、生态系统健康和生态系统服务是描述区域生态安全的关键特征。生态风险和生态系统健康分别代表生态系统的压力侧和状态侧,二者相互作用共同影响着生态系统服务。鲜有研究将生态风险、生态系统健康和生态系统服务联系起来分析...

生态风险、生态系统健康和生态系统服务是描述区域生态安全的关键特征。生态风险和生态系统健康分别代表生态系统的压力侧和状态侧,二者相互作用共同影响着生态系统服务。鲜有研究将生态风险、生态系统健康和生态系统服务联系起来分析三者之间的影响机制。本文选择淮河流域为研究区,通过InVEST模型和最大熵模型从空间上量化生态系统的供给服务、调节服务和文化服务;采用增强回归树算法和结构方程模型探究生态风险要素(自然灾害风险、人类活动风险和景观格局风险)和生态系统健康要素(活力、组织力和恢复力)对不同生态系统服务类型的影响程度和路径。结果表明,2020年淮河流域的生态系统供给服务、调节服务和文化服务的空间异质性明显,三者整体处于较低等级水平。区域生态安全特征之间的作用路径包括生态风险→生态系统服务和生态风险→生态系统健康→生态系统服务,其中活力对供给服务的直接正向影响较大,但恢复力的直接抑制作用更为明显,相对重要性为32.79%;恢复力对调节服务的直接促进作用最强,相对重要性为70.52%,其次是人类活动风险的间接抑制作用;人类活动风险对文化服务具有最高的直接正向影响和较弱的间接负向影响,相对重要性为55.40%。研究结果有助于深化人们对生态风险、生态系统健康与生态系统服务之间内在关系的认识,为区域生态系统管理和决策提供科学依据。

关键词：生态安全特征内在关系影响机制淮河流域

Optical colorimetric LiTaO_(3)wafers for highprecision lithography on frequency control of SAW devices

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Photonics Research 2024年第2期12卷 341-349页

作者： MING HUI FANG YINONG XIE FANGQI XUE ZHILIN WU JUN SHI SHENG YU YANG YILIN LIU ZHIHUANG LIU HSIN CHI WANG FAJUN LI qing HUO LIU JINFENG zhu School of Electronic Science and Engineering Xiamen UniversityXiamen 361005China Quanzhou San’an Integrated Circuit Co. Ltd.Quanzhou 362300China Eastern Institute of Technology Ningbo 315200China

Surface acoustic wave(SAW)resonators based on lithium tantalate(LT,LiTaO_(3))wafers are crucial elements of mobile communication *** use of intrinsic LT wafers typically brings about low fabrication accuracy of SAW resonators due to strong UV reflection in the lithography *** hinders their resonance frequency control seriously in industrial *** doping and chemical reduction could be applied to decrease the UV reflection of LT wafers for high lithographic ***,conventional methods fail to provide a fast and nondestructive approach to identify the UV performance of standard single-side polished LT wafers for highprecision frequency ***,we propose a convenient on-line sensing scheme based on the colorimetry of reduced Fe-doped LT wafers and build up an automatic testing system for industrial *** levels of Fe doping and chemical reduction are evaluated by the lightness and color difference of LT-based *** correlation between the wafer visible colorimetry and UV reflection is established to refine the lithography process and specifically manipulate the frequency performance of SAW *** study provides a powerful tool for the fabrication control of SAW resonators and will inspire more applications on sophisticated devices of mobile communication.

关键词： lithography doping wafer

Corneal nerve changes by anti-glaucoma medications examined by in vivo confocal microscopy

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International Journal of Ophthalmology(English edition) 2024年第9期17卷 1645-1653页

作者： Xin-Yuan zhu qing-Shu Ge Zong-Yi Li Long-Fang Zhou Qian-Wen Bu Ying Su Xin-Jie Wang qing-Jun Zhou Xiao-Jing Pan Die Hu School of Clinical Medicine Shandong Second Medical UniversityWeifang 261053Shandong ProvinceChina Eye Institute of Shandong First Medical University Qingdao Eye Hospital of Shandong First Medical UniversityQingdao 266071Shandong ProvinceChina State Key Laboratory Cultivation Base Shandong Provincial Key Laboratory of OphthalmologyQingdao 266071Shandong ProvinceChina School of Ophthalmology Shandong First Medical UniversityQingdao 266071Shandong ProvinceChina

AIM:To evaluate the effects of antiglaucoma eye drops on corneal nerves by in vivo confocal microscopy(IVCM).METHODS:This study comprised 79 patients diagnosed with glaucoma and 16 healthy control *** the glaucoma patients,54 were treated with medication,while 25 remained *** corneal images were evaluated by IVCM,and then ACCMetrics was used to calculate the following parameters:corneal nerve fiber density(CNFD),branch density(CNBD),fiber length(CNFL),total branch density(CTBD),fiber area(CNFA),fiber width(CNFW),and fractal dimension(CNFrD).The correlation between IVCM parameters and drugs was evaluated using non-parametric measurements of Spearman’s rank correlation ***:The CNFD was reduced in glaucoma groups compared to healthy subjects(P0.01).Patients using anti-glaucoma medications exhibited poorer confocal parameters compared to untreated *** the number of medications and usage count increased,CNFD,CNBD,CNFL,CTBD,CNFA,and CNFrD experienced a decline,while CNFW increased(all P0.01).For the brinzolamide-therapy group,there was a significant decrease in CNFD and CNFL compared to the other monotherapy groups(P0.001).In the absence of medication,CNFD in males was lower than that in females(P0.05).Among patients under medication therapy,CNFD remained consistent between males and ***:Antiglaucoma eye drops affect the microstructure of corneal *** and ACCMetrics are useful tools that could be used to evaluate the corneal nerve changes.

关键词： glaucoma therapy corneal nerve fibers in vivo confocal microscopy ACCMetrics

Reinforcing oxygen electrocatalytic activity via selective dualphase heterointerface engineering for rechargeable Zn-air batteries

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Rare Metals 2024年第4期43卷 1524-1536页

作者： Chao Cheng Chuang Zhi Zhong-Ti Sun Yong-Qiang Ming Ting-Ting Xiang qing-Chao zhu Zi-Rui Wu Bing Li Yi Li Cheng Jin Yong Cao Juan Yang School of Materials Science and Engineering Jiangsu UniversityZhenjiang212013China Faculty of Material Science and Engineering Kunming University of Science and TechnologyKunming650093China

Dual-phase heterointerface electrocatalysts(DPHE)constructed by oxygen reduction reaction(ORR)-and oxygen evolution reaction(OER)-active elements exhibit excellent bifunctional activity and long-term durability due to the abundant interface exposure and synergistic catalytic ***,low-dimensional N-doped graphene nanoribbons(N-GNRs)coupling with ultrathin CoO nanocomposites(N-GNRs/CoO)were controllably fabricated through a facile two-step approach using synthesized Co(OH)_2 nanosheet as CoO *** functional theory(DFT)calculations and experimental characterizations prove that the formation of interface between N-GNRs and CoO can induce local charge redistribution,contributing to the improvement of catalytic activity and *** optimal N-GNRs/CoO DPHE possesses hierarchically porous architectures and presents outstanding bifunctional activities with a small potential gap of 0.729 V between the potential at 10 mA·cm^(-2)for OER and the halfwave potential for ORR,which outperforms Pt/C+IrO_(2)and the majority of noble-metal-free bifunctional ***-and solid-state rechargeable Zn-air batteries assembled with N-GNRs/CoO as the cathode also display high peak power density and fantastic cycle stability,superior to that of benchmark Pt/C+IrO_(2)*** is anticipated to offer significant benefits toward high activity,stability and mechanical flexibility bifunctional oxygen electrocatalysts for rechargeable Zn-air batteries.

关键词： Interface engineering Graphene nanoribbons CoO Bifunctional electrocatalyst Zn-air batteries