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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

Enhanced preparation of dendritic metallic vanadium in recyclable NaCl-KCl-VCl_(2) molten salt by V_(2)CO electrolysis

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Rare Metals 2024年第8期43卷 3961-3973页

作者： Jia-Liang An Ming-yong wang yong-zheng Jia Jin-Tao zhang Bao-yan feng Shu-Qiang Jiao State Key Laboratory of Advanced Metallurgy University of Science and Technology BeijingBeijing 100083China College of Material Science and Engineering Hebei Province Laboratory of Inorganic Nonmetallic MaterialsNorth China University of Science and TechnologyTangshan 063210China

A promising method for the preparation of pure metallic vanadium via V_(2)CO anode electrolysis was proposed and *** simple and controllable synthesis of a molten chloride salt containing VCl_(2) by an insitu reaction between VCl_(3) and metallic vanadium was verified through thermodynamic analysis and ***-KCl-VCl_(2) molten salt exhibited excellent recycling performance and could be repetitively used to prepare metallic vanadium by V_(2)CO *** V^(2+) ions remained in the molten salt after *** electrolysis conditions,such as the cathode diameter,current density,V^(2+) ion concentration,and temperature,were optimised to maximise the current *** was also simulated to reveal the regulatory *** highest current efficiency was 85%.The purity of metallic vanadium was up to 99.8%.In this study,an easy and efficient preparation of pure metallic vanadium was achieved.

关键词： V_(2)CO Metallic vanadium Current efficiency Molten salt electrolysis

Multi-omics analyses provide insights into the evolutionary history and the synthesis of medicinal components of the Chinese wingnut

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Plant Diversity 2024年第3期46卷 309-320页

作者： Zi-yan zhang He-Xiao Xia Meng-Jie Yuan feng Gao Wen-hua Bao lan Jin Min Li yong Li College of Life Science and Technology Inner Mongolia Normal UniversityHohhot 010020China Key Laboratory of Biodiversity Conservation and Sustainable Utilization in Mongolian Plateau for College and University of Inner Mongolia Autonomous Region Hohhot 010022China College of landscape and Art Henan Agricultural UniversityZhengzhou 450002China State Key Laboratory of Tree Genetics and Breeding Chinese Academy of ForestryBeijing 100091China

Chinese wingnut(Pterocarya stenoptera)is a medicinally and economically important tree species within the family ***,the lack of high-quality reference genome has hindered its in-depth *** this study,we successfully assembled its chromosome-level genome and performed multiomics analyses to address its evolutionary history and synthesis of medicinal components.A thorough examination of genomes has uncovered a significant expansion in the Lateral Organ Boundaries Domain gene family among the winged group in *** notable increase may be attributed to their frequent exposure to flood-prone *** further differentiation between Chinese wingnut and Cyclocarya paliurus,significant positive selection occurred on the genes of NADH dehydrogenase related to mitochondrial aerobic respiration in Chinese wingnut,enhancing its ability to cope with waterlogging *** genomic analysis revealed Chinese wingnut evolved more unique genes related to arginine synthesis,potentially endowing it with a higher capacity to purify nutrient-rich water *** of terpene synthase families enables the production of increased quantities of terpenoid volatiles,potentially serving as an evolved defense mechanism against herbivorous *** combined transcriptomic and metabolomic analysis,we identified the candidate genes involved in the synthesis of terpenoid *** study offers essential genetic resources for Chinese wingnut,unveiling its evolutionary history and identifying key genes linked to the production of terpenoid volatiles.

关键词： Genome Medicinal components Metabolome Pterocarya stenoptera Transcriptome

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

Analysis of debris flow control effect and hazard assessment in xinqiao Gully,Wenchuan M_(s)8.0 earthquake area based on numerical simulation

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China Geology 2024年第2期7卷 248-263页

作者： Chang yang yong-bo Tie Xian-zheng zhang yan-feng zhang Zhi-jie Ning Zong-liang Li Chinese Academy of Geological Sciences Beijing 100037China Chengdu Center of China Geological Survey China Geological SurveyChengdu 610081China Technology innovation center for risk prevention and mitigation of geohazard Ministry of Natural ResourcesChengdu 611734China Observation and Research Station of Chengdu Geological Hazards Ministry of Natural ResourcesChengdu 610000China

xinqiao Gully is located in the area of the 2008 Wenchuan M_(s)8.0 earthquake in Sichuan province,*** on the investigation of the 2023"6-26"xinqiao Gully debris flow event,this study assessed the effectiveness of the debris flow control project and evaluated the debris flow *** field investigation and numerical simulation methods,the indicators of flow intensity reduction rate and storage capacity fullness were proposed to quantify the effectiveness of the engineering measures in the debris flow *** simulation results show that the debris flow control project reduced the flow intensity by41.05%to 64.61%.The storage capacity of the dam decreases gradually from upstream to the mouth of the gully,thus effectively intercepting and controlling the debris *** evaluating the debris flow of different recurrence intervals,further measures are recommended for managing debris flow events.

关键词： landslide Debris flow Hazard assessment Numerical simulation OpenLISEM Prevention and control project Wenchuan M_(s)8.0 earthquake xinqiao Gully Sichuan province Geological hazards survey engineering

PRSS50-mediated inhibition of MKP3/ERK signaling is crucial for meiotic progression and sperm quality

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Zoological Research 2024年第5期45卷 1037-1047页

作者： Chun-Xue Niu Jia-Wei Li Xiao-Li Li Lin-Lin zhang yan lang Zhen-Bo Song Chun-lei Yu Xiao-Guang yang Hai-feng zhao Jia-Ling Sun Li-hua zheng Xue wang Ying Sun Xiao-Hong Han Guan-Nan wang yong-Li Bao National Engineering Laboratory for Druggable Gene and Protein Screening Northeast Normal UniversityChangchunJilin 130117China China International Joint Research Center for Human Stem Cell Bank Northeast Normal UniversityChangchunJilin 130117China Jilin Institute for Drug Control ChangchunJilin 130022China

Serine protease 50(PRSS50/TSP50)is highly expressed in *** study investigated its role in testicular development and ***,PRSS50 knockdown was observed to impair DNA synthesis in *** further explore this,we generated PRSS50 knockout(Prss50^(−/−))mice(Mus musculus),which exhibited abnormal spermatid nuclear compression and reduced male ***,dysplastic seminiferous tubules and decreased sex hormones were observed in 4-week-old Prss50^(−/−)mice,accompanied by meiotic progression defects and increased apoptosis of spermatogenic *** analysis indicated that PRSS50 deletion resulted in increased phosphorylation of extracellular signal-regulated protein kinases 1 and 2(ERK1/2)and elevated levels of MAP kinase phosphatase 3(MKP3),a specific ERK antagonist,potentially accounting for testicular dysplasia in adolescent Prss50−/−*** together,these findings suggest that PRSS50 plays an important role in testicular development and spermatogenesis,with the MKP3/ERK signaling pathway playing a significant role in this process.

关键词： PRSS50(TSP50) Meiotic progression Sperm quality MKP3 ERK

Research on the development methodology for clinical practice guidelines for organic integration of traditional Chinese medicine and Western medicine

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Military Medical Research 2024年第3期11卷 313-322页

作者： Ying-Hui Jin yan-Ping wang Ying-lan Xie Gui-hua Tian Xiao-Yu zhang Nan-Nan Shi Ke-Hu yang xin Sun Yao-Long Chen Da-Rong Wu xin-feng Guo Long Ge Chen zhao Cheng lu Yin Jiang Jing Guo Si-Yu yan yong-Bo wang Qiao huang Xiang-Ying Ren Ying-Yue Rao Yun-Yun wang Meng-Qian Yuan Xian-Tao Zeng Hong-Cai Shang Center for Evidence-Based and Translational Medicine Zhongnan Hospital of Wuhan UniversityWuhan 430071China Institute of Basic Research in Clinical Medicine China Academy of Chinese Medical SciencesBeijing 100700China China Center for Evidence Based Traditional Chinese Medicine Beijing 100029China Hubei Provincial Hospital of Traditional Chinese Medicine Wuhan 430074China Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing Dongzhimen HospitalBeijing University of Chinese MedicineBeijing 100700China Evidence-Based Medicine Center School of Basic Medical SciencesLanzhou UniversityLanzhou 730000China China Center for Evidence-Based Medicine West China Hospital of Sichuan UniversityChengdu 610041China State Key Laboratory of Dampness Syndrome of Chinese Medicine the Second Affliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510120China Evidence-based Medicine Team Guangdong Provincial Hospital of Traditional Chinese MedicineGuangzhou 510120China Nanjing University of Chinese Medicine Nanjing 210023China Jiangsu Province Hospital of Chinese Medicine Nanjing 210029China

Integrated traditional Chinese medicine(TCM)and Western medicine(WM)is a new medical science grounded in the knowledge bases of both TCM and WM,which then forms a unique modern medical system in *** TCM and WM has a long history in China,and has made important achievements in the process of clinical diagnosis and ***,the methodological defects in currently published clinical practice guidelines(CPGs)limit its *** organic integration of TCM and WM is a deeper integration of TCM and *** realize the progression of"integration"to"organic integration",a targeted and standardized guideline development methodology is ***,the purpose of this study is to establish a standardized development procedure for clinical practice guidelines for the organic integration of TCM and WM to promote the systematic integration of TCM and WM research results into clinical practice guidelines in order to achieve optimal results as the whole is greater than the sum of the parts.

关键词： Methodology Traditional Chinese medicine Western medicine Organic integration Clinical practice guidelines(CPGs)

Five-blade scratcher for treating severe rhinophyma:A retrospective study

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World Journal of Clinical Cases 2024年第20期12卷 4180-4190页

作者： Yu-Ping zheng Xu-feng He yan-feng zhang lan-xin Geng Hui-Min zhang hua Wan Xiang He Department of Dermatology Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai 201203China Department of Galactophore Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai 201203China

BACKGROUND Rhinophyma,a late-stage subtype of rosacea,is characterized by excessive sebaceous glands and connective tissue *** may experience respiratory disturbances and psychological distress that significantly affect their quality of life when excessive nasal hyperplasia obstructs the external nasal *** is the treatment of choice for ***,excessive bleeding,scarring,pigmentation,and high recurrence rates frequently characterize current surgical *** To evaluate the clinical effectiveness and recurrence rates after treating severe rhinophyma with the five-blade *** This study retrospectively analyzed the clinical records of 28 patients with severe rhinophyma *** Global Flushing Severity Score(GFSS),Clinician Erythema Assessment(CEA),Rhinophyma Severity Index(RHISI),Glasgow Benefit Inventory(GBI),and satisfaction scores were used to assess the recovery of patients at 6 months and 5 years,with the recurrence rate calculated at 5 years *** addition,the levels of pro-inflammatory factors(TNF-α,IL-1β,and IL-6)in the serum of patients before and after surgery were detected by *** The GFSS,CEA,and RHISI scores at 6 months and 5 years postoperatively were significantly lower than those preoperatively(Pluding simplicity,safety,efficacy,and cost-effectiveness,coupled with reduced bleeding,minimized scarring,lower recurrence rates,reduced the level of pro-infla

关键词： Rhinophyma Five-blade scratcher Retrospective study Efficacy Recurrence rate

Risk factors for renal outcomes in children with antineutrophil cytoplasmic antibody-associated vasculitis:a nationwide retrospective study in China

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World Journal of Pediatrics 2024年第5期20卷 506-516页

作者： Li-Wen Tan Jun-Li Wan Chun-hua Zhu Hong Xu zheng-Kun Xia Li-Zhi Chen Xiao-Chuan Wu Fang wang Xiao-Rong Liu Cheng-Guang zhao Xiao-Zhong Li Jian-hua Mao Xiao-Wen wang Wen-yan huang Yu-Hong Li Jian-Jiang zhang Shi-Pin feng Jun yang Jiao-Jiao Liu Chun-Lin Gao Li-Ping Rong lan-Jun Shuai Ke Xu He-Jia zhang Qiu Li Ai-hua zhang Mo wang Department of Nephrology Children’s Hospital of Chongqing Medical UniversityZhongshan 2nd Rd.136Chongqing400014China Ministry of Education Key Laboratory of Child Development and Disorders National Clinical Research Center for Child Health and DisordersChina International Science and Technology Cooperation Base of Child Development and Critical DisordersChildren’s Hospital of Chongqing Medical UniversityChongqingChina Chongqing Key Laboratory of Pediatrics Children’s Hospital of Chongqing Medical UniversityChongqingChina Department of Nephrology Children’s Hospital of Nanjing Medical University72 Guangzhou RoadNanjing210008China Department of Nephrology Children’s Hospital of Fudan UniversityNational Paediatric Medical Center of ChinaShanghaiChina Department of Pediatrics Jinling HospitalNanjing Medical UniversityNanjingChina Department of Pediatrics Jinling HospitalThe First School of Clinical MedicineSouthern Medical UniversityNanjingChina Department of Pediatrics Jinling HospitalMedical School of Nanjing UniversityNanjingChina Department of Pediatric Nephrology and Rheumatology The First Affiliated Hospital of Sun Yat-Sen UniversityGuangzhouChina Department of Pediatrics The Second Xiangya Hospital of Central South UniversityChangshaChina Department of Pediatrics Peking University First HospitalBeijingChina Department of Nephrology Beijing Children’s HospitalCapital Medical UniversityBeijing100045China National Center for Children’s Health BeijingChina Department of Pediatrics Shengjing Hospital of China Medical UniversityShenyangChina Department of Nephrology and Immunology Children’s Hospital of Soochow UniversitySuzhouChina Department of Nephrology Children HospitalZhejiang University School of MedicineHangzhouChina Department of Nephrology Wuhan Children’s Hospital(Wuhan Maternal and Child Healthcare Hospital)Tongji Medical CollegeHuazhong University of Science&TechnologyWuhanChina Department of Nephrology and Rheumatology Shanghai Children’s HospitalSchool

Background Pediatric antineutrophil cytoplasmic antibody-associated vasculitis(AAV)is a life-threatening systemic vasculitis featured by liability to renal ***,there are few studies on the risk factors and predictive models for renal outcomes of AAV in *** Data from 179 AAV children in multiple centers between January 2012 and March 2020 were collected *** risk factors and predictive model of end-stage renal disease(ESRD)in AAV were *** Renal involvement was the most typical manifestation(95.5%),and the crescent was the predominant pathological lesion(84.9%).The estimated glomerular filtration rate(eGFR)was evaluated in 114 patients,of whom 59.6%developed ESRD,and the median time to ESRD was 3.20 *** eGFR[P=0.006,odds ratio(OR)=0.955,95%confidence interval(CI)=0.924–0.987]and the percentages of global glomerulosclerosis(pGGS;P=0.018,OR=1.060,95%CI=1.010–1.112)were independent risk factors for ESRD of renal *** on the pGGS and eGFR at renal biopsy,we developed three risk grades of ESRD and one predictive *** Kaplan‒Meier curve indicated that renal outcomes were significantly different in different risk grades(P<0.001).Compared with serum creatinine at baseline,the predictive model had higher accuracy(0.86 versus 0.58,P<0.001)and a lower coefficient of variation(0.07 versus 0.92)in external *** Renal involvement is the most common manifestation of pediatric AAV in China,of which more than half deteriorates into *** predictive model based on eGFR at renal biopsy and the pGGS may be stable and accurate in speculating the risk of ESRD in AAV children.

关键词： Antineutrophil cytoplasmic antibody End-stage renal disease Glomerulonephritis Pediatric nephrology Vasculitis