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Discovery of a potent and highly selective inhibitor of SIRT6 against pancreatic cancer metastasis in vivo

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1302-1316页

作者： Xinyuan xu Qian zhang xufeng Wang Jing Jin Chengwei Wu Li Feng Xiuyan yang Mingzhu Zhao Yingyi Chen Shaoyong lu Zhen Zheng Xiaobing Lan Yi Wang yan Zheng xuefeng lu Qiufen zhang Jian zhang State Key Laboratory of Medical Genomics National Research Center for Translational Medicine at ShanghaiRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China Medicinal Chemistry and BioinformaticsCenter Shanghai Jiao Tong University School of MedicineShanghai 200025China Department of General Surgery Huashan HospitalCancer Metastasis InstituteFudan UniversityShanghai 200040China Institute of Immunology and the CAS Key Laboratory of Innate Immunity and Chronic Disease School of Basic Medicine and Medical CenterUniversity of Science and Technology of ChinaHefei 230026China Department of Assisted Reproduction Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai 200011China College of Pharmacy Ningxia Medical UniversityYinchuan 750004China Department of Pancreatic Surgery Shanghai General HospitalShanghai Key Laboratory of Pancreatic DiseaseInstitute of Pancreatic DiseaseShanghai Jiao Tong University School of MedicineShanghai 200080China

Pancreatic cancer,one of the most aggressive malignancies,has no effective treatment due to the lack of targets and drugs related to tumour ***6 can promote the migration of pancreatic cancer and could be a potential target for antimetastasis of pancreatic ***,highly selective and potency SIRT6 inhibitor that can be used in vivo is yet to be ***,we developed a noveSIRT6 allosteric inhibitor,compound 11e,with maximal inhibitory potency and an IC_(50) value of 0.98±0.13μmol/***,compound 11e exhibited significant selectivity against other histone deacetylases(HADC1-11 and SIRT1-3)at concentrations up to 100μmol/*** allosteric site and the molecular mechanism of inhibition were extensively elucidated by cocrystal complex structure and dynamic structural ***,we confirmed the antimetastatic function of such inhibitors in four pancreatic cancer cell lines as well as in two mouse models of pancreatic cancer liver *** our knowledge,this is the first study to reveal the in vivo effects of SIRT6 inhibitors on liver metastatic pancreatic *** not only provides a promising lead compound for subsequent inhibitor developmentargeting SIRT6 but also provides a potential approach to address the challenge of metastasis in pancreatic cancer.

关键词： SIRT6 Inhibitor Allosteric Selectivity Cocrystal Pancreatic cancer metastasis

Tuning interaction strength between CeO_(2) and iridium to promote CO oxidation over Ir/TiO_(2)

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Journal of Rare Earths 2024年第4期42卷 651-659页

作者： lu Dai Binghua Li Yuhan Peng Xianwei Hao Runquan xuan Hua Huang Yiming Bi Liping xu yanhui zhang yun Guo Fangqi Du Li Wang Hui Wang Technology Center China Tobacco Zhejiang Industrial Co.Ltd.Hangzhou310024China Research Institute of Industrial Catalysis East China University of Science and TechnologyShanghai200237China

The interaction between support and noble metal plays a crucial role in heterogeneous catalysis ***,how to tune metal support interactions to optimize the activity still needs further ***_(2) was introduced to promote CO oxidation ove r Ir/TiO_(2) by adjusting the interaction strength between iridium(Ir)and CeO_(2).The strong interaction between Ir and CeO_(2) blocks CO adsorption and causes low CO oxidation ***,introducing CeO_(2) on Ir/TiO_(2) produces localized interaction between Ir and CeO_(2),which can tune the surface electronic state of Ir,so a"volcano curve"relationship between CO oxidation activity and electronic state is *** amount of CeO_(2) on Ir/TiO_(2)(Ir/Ce_(0.2)Ti)leads to CO complete oxidization at 22℃,and a new pathway for CO oxidation was *** study demonstrates that the utilization of tuning interaction strength between active metal and support is a potential method to increase the catalytic activity.

关键词： CO oxidation CeO_(2) Localized interaction Interaction strength Supported Ir catalysts Rareearths

Individualized anti-thrombotic therapy for acute myocardial infarction complicated with left ventricular thrombus: A case report

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World Journal of Clinical Cases 2024年第4期12卷 835-841页

作者： yan Song Hua Li Xia zhang Lei Wang Hong-yan xu Zhi-Chao lu Xiao-Gang Wang Bo Liu Department of Clinical Pharmacy Zibo Municipal HospitalZibo 255400Shandong ProvinceChina Department of Cardiology Zibo Municipal HospitalZibo 255400Shandong ProvinceChina Department of Pharmacy Zibo Municipal HospitalZibo 255400Shandong ProvinceChina Department of Imaging Zibo Municipal HospitalZibo 255400Shandong ProvinceChina Department of Pulmonary and Critical Care Medicine Department of Clinical MicrobiologyZibo City Key Laboratory of Respiratory Infection and Clinical MicrobiologyZibo City Engineering Technology Research Center of Etiology Molecular DiagnosisZibo Municipal HospitalZibo 255400Shandong ProvinceChina

BACKGROUND Presently,there is no established standard anti-blood clot therapy for patients facing acute myocardial infarction(AMI)complicated by left ventricular thrombus(LVT).While vitamin K antagonists are the preferred choice for oral blood thinning,determining the best course of blood-thinning medication remains *** is unclear if non-vitamin K antagonist oral blood thinners have different effectiveness in treating *** study significantly contributes to the medical *** SUMMARY The blood-thinning treatment of a patient with AMI and LVT was *** blood-thinning therapy included daily enteric-coated aspirin tablets at 0.1 g,daily clopidogrel hydrogen sulfate at 75 mg,and dabigatran etexilate at 110 mg twice *** 15 d,the patient’s LVT did not decrease but instead *** pharmacists comprehensively analyzed the cases from the perspective of the patient’s disease status and drug *** drug regimen was reformulated for the patient,replacing dabigatran etexilate with warfarin,and was administered for six *** clinical pharmacist provided the patient with professional and standardized pharmaceutical *** patient’s condition was discharged after meeting the international normalized ratio value(2-3)*** patient fully complied with the follow-up,and the time in the therapeutic range was 78.57%,with no serious adverse effects during pharmaceutical *** Warfarin proves to be an effective drug for patients with AMI complicated by LVT,and its blood-thinning course lasts for six months.

关键词： Myocardial infarction Left ventricular thrombus Dabigatran etexilate Warfarin Clinical pharmacist Case report

Simultaneous determination of 6 carbamate pesticides and relevant metabolites in oilseeds and oil with the modified fast QuEChERS method by ultra-performance liquid chromatography-tandem mass spectrometry

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未来食品学报(英文) 2024年第1期4卷 97-104页

作者： Bangben Yao yun Li Ru zhang Li Yao Jianguo xu Chao yan Wei Chen Anui Province Inustinute of Prodtuct Quality Supenvision&Inspection Hefei 230051China Engineering Reseanch Center of Bio-Proess MOESchool of Food cand Biological EngineerngHefei University of TechmologyHefei 230009China School of Ijfe Science Anhui UniversityHefei 230601China

A sensitive and reliable method was developed and validated for the simu1taneous determination of 6 carbamate pesticides and relevant metabolites based on the modified fast QuEChERS(quick,easy,cheap,effective,rugged and safe)method combined with ultra-performance 1iquid chromatography-tandem mass spectrometry(UPLC-MS/MS).The method was also applied in the analysis of 23 commonly consumed oilseeds and oil *** sample was extracted with acetonitrile for three times and then the extracted solution was filtered directly though 250 mg precipitated silica adsorbent(PSA)and 250 mg Cis The mobile phase was water(containing 0.1%formic acid)and *** extemal standard protocols were adopted to validate the method in terms of recovery,1inearity,precision,sensitivity,and relative standard deviation(RSD)under the optimized *** linear calibration curves with different ranges were established with R^(2)>0.9973,limit of detections(LODs)ranged from 0.100μg/kg to 20000μg/kg and limit of quantitations(LOQs)ranged from 0.300μg/kg to 6.000μg/*** LODs meets the detection requirement for the maximum residue limits in practical ***,the recoveries ranged from 60.2%to 116.6%with associated RSDs ranged from 0.33%to 5.35%in 10 oilseeds matrices and ranged from 61.9%to 116.9%with RSDs ranged from 0.30%to 5.02%in 13 oil *** features do make the UPLC-MSMS an ideal analytical platform for accurate and high throughput analysis of carbamates residues in the complex matrix.

关键词： Carbamate pesticides Oiseeds and oil Dispersive solid-phase extraction U1tra-performance 1iquid chromatography-tandem mass spectometry Simu1taneous determination High throughput

The energy response of LaBr_(3)(Ce),LaBr_(3)(Ce,Sr),and NaI(Tl)crystals for GECAM

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Nuclear Science and Techniques 2024年第2期35卷 110-122页

作者： Pei-Yi Feng Xi-Lei Sun Zheng-Hua An Yong deng Cheng-Er Wang Huang Jiang Jun-Jie Li Da-Li zhang Xin-Qiao Li Shao-Lin Xiong Chao Zheng Ke Gong Sheng yang Xiao-Jing Liu Min Gao Xiang-yang Wen Ya-Qing liu yan-Bing xu Xiao-yun Zhao Jia-Cong Liu Fan zhang Hong lu Particle and Astrophysics Center Institute of High Energy PhysicsChinese Academy of SciencesBeijing 100049China Key Laboratory of Particle Astrophysics Institute of High Energy PhysicsChinese Academy of SciencesBeijing 100049China University of Chinese Academy of Sciences Chinese Academy of SciencesBeijing 100049China Experimental Physics Center Institute of High Energy PhysicsChinese Academy of SciencesBeijing 100049China State Key Laboratory of Particle Detection and Electronics Institute of High Energy PhysicsChinese Academy of SciencesBeijing 100049China School of Nuclear Science and Technology University of South ChinaHengyang 421001China National Engineering Research Center for Rare Earth Grirem Advanced Materials Co.Ltd.and General Research Institute for Nonferrous MetalsBeijing 100088China

The GECAM series of satellites utilizes LaBr_(3)(Ce),LaBr_(3)(Ce,Sr),and NaI(Tl)crystals as sensitive materials for gamma-ray detectors(GRDs).To investigate the nonlinearity in the detection of low-energy gamma rays and address the errors in the calibration of the E-C relationship,comprehensive tests and comparative studies of the three aforementioned crystals were conducted using Compton electrons,radioactive sources,and mono-energetic *** nonlinearity test results of the Compton electrons and X-rays demonstrated substantial differences,with all three crystals presenting a higher nonlinearity for X/-rays than for Compton *** the LaBr_(3)(Ce)and LaBr_(3)(Ce,Sr)crystals having higher absolute light yields,they exhibited a noticeable nonlinear decrease in the light yield,especially at energies below 400 *** NaI(Tl)crystal demonstrated an"excess"light output in the 6-200 keV range,reaching a maximum"excess"of 9.2%at 30 keV in the X-ray testing and up to 15.5%at 14 keV during Compton electron testing,indicating a significant advantage in the detection of low-energy gamma ***,we explored the underlying causes of the observed nonlinearity in these *** study not only elucidates the detector responses of GECAM,but also initiates a comprehensive investigation of the nonlinearity of domestically produced lanthanum bromide and sodium iodide crystals.

关键词： LaBr_(3)(Ce)detector LaBr_(3)(Ce,Sr)detector NaI(Tl)detector GECAM Energy response Light yield nonlinearity

Minimalistic approach to left atrial appendage occlusion guided by cardiac computed tomography angiography

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Journal of Geriatric Cardiology 2024年第4期21卷 431-442页

作者： Xian-Sai MENG Qing-Song WANG Xin-yan WANG xu lu yang MU Jing WANG Ting-Ting SONG yun-Dai CHEN Tao CHEN Jun GUO Graduate School of Chinese PLA Medical College BeijingChina Senior Department of Cardiology the Sixth Med-ical CenterChinese PLA General HospitalBeijingChina

OBJECTIVE To assess the feasibility and safety of the minimalistic approach to left atrial appendage occlusion(LAAO) guided by cardiac computed tomography angiography(CCTA).METHODS Ninety consecutive patients who underwent LAAO, with or without CCTA-guided, were matched(1:2). Each step of the LAAO procedure in the computed tomography(CT) guidance group(CT group) was directed by preprocedural CT planning. In the control group, LAAO was performed using the standard method. All patients were followed up for 12 months, and device surveillance was conducted using *** A total of 90 patients were included in the analysis, with 30 patients in the CT group and 60 matched patients in the control group. All patients were successfully implanted with Watchman devices. The mean ages for the CT group and the control group were 70.0 ± 9.4 years and 68.4 ± 11.9 years(P = 0.52), respectively. The procedure duration(45.6 ± 10.7 min vs. 58.8 ± 13.0 min,P < 0.001) and hospital stay(7.5 ± 2.4 day vs. 9.6 ± 2.8 day, P = 0.001) in the CT group was significantly shorter compared to the control group. However, the total radiation dose was higher in the CT group compared to the control group(904.9 ± 348.0 m Gy vs.711.9 ± 211.2 m Gy, P = 0.002). There were no significant differences in periprocedural pericardial effusion(3.3% vs. 6.3%, P = 0.8) between the two groups. The rate of postprocedural adverse events(13.3% vs. 18.3%, P = 0.55) were comparable between both groups at 12 months *** CCTA is capable of detailed LAAO procedure planning. Minimalistic LAAO with preprocedural CCTA planning was feasible and safe, with shortened procedure time and acceptable increased radiation and contras consumption. For patients with contraindications to general anesthesia and/or transesophageal echocardiography, this promising method may be an alternative to conventional LAAO.

关键词： anesthesia matched approach

1959-2021年间热带雨林区域的蒸发皿蒸发量呈下降趋势

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Journal of Plant Ecology 2024年第1期17卷 1-16页

作者： yan Jin Ying zhang Xin yang Mou zhang Xin-Bo Guo yun deng Yue-Hua Hu Hua-Zheng lu Zheng-Hong Tan School of Ecology and Environmental Science Yunnan UniversityKunming 650091China International Center for Climate and Environment Sciences Institution of Atmospheric PhysicsChinese Academy of SciencesBeijing 100029China CAS Key Laboratory of Tropical Forest Ecology Xishuangbanna Tropical Botanical GardenChinese Academy of SciencesMenglaMenglun 666303China Center for Plant Ecology Core Botanical GardensChinese Academy of SciencesMenglaMenglun 666303China

蒸发皿蒸发量(E_(pan))是衡量大气蒸发需求的重要指标。基于物理模型对西双版纳热带植物园中热带雨林综合气象观测场(XTBG气象站)的气象资料进行分析,有助于提高我们对西双版纳热带雨林区域水文循环状况的认识。本文利用1959-2021年的... 详细信息

蒸发皿蒸发量(E_(pan))是衡量大气蒸发需求的重要指标。基于物理模型对西双版纳热带植物园中热带雨林综合气象观测场(XTBG气象站)的气象资料进行分析,有助于提高我们对西双版纳热带雨林区域水文循环状况的认识。本文利用1959-2021年的观测资料,研究了E_(pan)的长期变化趋势,并进行了趋势检验、周期性评价和突变分析等相关分析。基于1979-2008年D20 E_(pan)数据和相关气象资料,利用Penman-Monteith和PenPan模型对E_(pan)进行模拟,采用偏微分归因法分析了影响E_(pan)的主导因素。研究结果表明,E_(pan)具有明显的周期变化,19 a为第一主周期。而且,西双版纳地区存在明显的‘蒸发悖论’现象。E_(pan)在1959-2008年和2009-2018年均呈下降趋势,其中1959-2008年下降幅度达到显著水平,为-3.404 mm·a^(-2)。通过对比分析,认为PenPan模型更适合用于模拟西双版纳地区的E_(pan)。为了确定影响E_(pan)的主要气象因子,选取了D20蒸发皿完整监测时期的数据(1979-2008)进行归因计算。太阳净辐射和饱和蒸汽压差的减小趋势可以有效抵消气温上升对E_(pan)的促进作用。因此,净辐射和饱和蒸汽压差的变化是西双版纳‘蒸发悖论’现象的主要触发因素。

关键词：蒸发皿蒸发量蒸发悖论 PenPan模型偏微分归因法驱动因素

Enhanced degradation of florfenicol by microscale SiC/Fe:Dechlorination via hydrogenolysis

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Chinese Chemical Letters 2024年第7期35卷 218-221页

作者： yun-Fei zhang Chun-Hui zhang Jian-Hui xu Lei Li Dan Li Jin-Hong Fan Jiale Gao Xin Quan Qi Wu Yue Zou yan-Ling Liu Dongguan University of Technology School of Environment and Civil EngineeringDongguan 523830China State Key Laboratory of Pollution Control and Resource Reuse School of Environmental Science and EngineeringTongji UniversityShanghai 200092China

Herein,the degradation of florfenicol(FLO)over zero-valent iron(ZVI)enhanced by SiC was systematically *** was found that 5 g/L of ZVI/SiC(1:3)at pH 3.0 could completely degrade 20 mg/L of FLO within 1 h,with a Kobsvalue of 0.0873 min^(-1),12.5 times greater than that of pure ZVI(0.0069 min^(-1)).Vibrating sample magnetometer(VSM)characterizations revealed that the use of SiC supporter reduces the magnetic intensity of ZVI,which mitigates iron particle agglomeration,increases Brunauer-Emmett-Teller(BET)surface area,and enhances FLO degradation ***,ZVI/SiC exhibits a much lower hydrogen evolution potential(HEP)and significantly higher corrosion currents compared to pure *** was proposed to undergo degradation via reductive dechlorination,involving a hydrogenolysis mechanism that entails the cleavage of theσ*** study provides new insights into the reduction hydrogenation mechanism of ZVI.

关键词： Zero-valent iron Silicon carbide Reductive dechlorination Hydrogenolysis Florfenicol

Contactin-associated protein-like 2(CNTNAP2)mutations impair the essentialα-secretase cleavages,leading to autism-like phenotypes

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1625-1636页

作者： Qing zhang Mengen Xing Zhengkai Bao lu xu yang Bai Wanqi Chen Wenhao Pan Fang Cai Qunxian Wang Shipeng Guo Jing zhang Zhe Wang Yili Wu yun zhang Jia-Da Li Weihong Song Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)Zhejiang Key Laboratory of Alzheimer's DiseaseZhejiang Provincial Clinical Research Center for Mental DisordersSchool of Mental Health and Wenzhou Kangning HospitalThe Second Affiliated Hospital and Yuying Children's HospitalInstitute of AgingWenzhou Medical UniversityWenzhouZhejiang 325035China Townsend Family Laboratories Department of PsychiatryBrain Research CenterThe University of British Columbia2255 Wesbrook MallVancouverBC V6T 1Z3Canada Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders Ministry of Education Key Laboratory of Child Development and DisordersChildren's Hospital of Chongqing Medical UniversityChongqing 400014China Center for Medical Genetics Hunan Key Laboratory of Animal Models for Human DiseasesHunan Key Laboratory of Medical GeneticsHunan International Scientific and Technological Cooperation Base of Animal Models for Human DiseasesSchool of Life SciencesCentral South UniversityChangsha 410078 HunanChina The National Clinical Research Center for Geriatric Disease Xuanwu HospitalCapital Medical UniversityBeijing 100053Chin

Mutations in the Contactin-associated protein-like 2(CNTNAP2)gene are associated with autism spectrum disorder(ASD),and ectodomain shedding of the CNTNAP2 protein plays a role in its ***,key enzymes involved in the C-terminal cleavage of CNTNAP2 remain largely unknown,and the effect of ASD-associated mutations on this process and its role in ASD pathogenesis remain *** this report we showed that CNTNAP2 undergoes sequential cleavages by furin,ADAM10/17-dependent a-secretase and presenilindependent *** identified that the cleavage sites of ADAM10 and ADAM17 in CNTNAP2 locate at its C-terminal residue I79 and L96,and the main a-cleavage product C79 by ADAM10 is required for the subsequent y-secretase cleavage to generate CNTNAP2 intracellular domain(CICD).ASD-associated CNTNAP2 mutations impair the a-cleavage to generate C79,and the inhibition leads to ASDIlike repetitive and social behavior abnormalties in the Cntnap2l1254T knock-in ***,exogenous expression of 79 improves autism-ike phenotypes in the Cntnap2^(11254T) knock-in and Cntnap2^(-/-)knockout *** data demonstrates that the a-secretase is essential for CNTNAP2 processing and its *** study indicates that inhibition of the cleavage by pathogenic mutations underlies ASD pathogenesis,and upregulation of its C-terminal fragments could have therapeutical potentials for ASD treatment.

关键词： NAP2 cleavage subsequent