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Chinese Journal of Chemistry 2024年第6期42卷 605-610页

作者： Xiuhe Zhao Mengxue Lv Xiaonan Xi Yaxin Lu Liang Wang yue chen The State Key Laboratory of Medicinal Chemical Biology College of PharmacyNankai UniversityTianjin300350 China College of Chemistry Nankai UniversityTianjin300071 China

The total synthesis of majusculamide D(1)was achieved from commercially available materials.In addition,we synthesized eight analogues including three stereoisomers of majusculamide D that differ in the fatty acid chain.Six analogues including a simplified analogue 29 exhibited significant nanomolar-level IC50 values against Panc-1 cells in MTT assays.A preliminary SAR analysis indicated that the hydroxyl group at C10 and C2−C3 unsaturated double bond of majusculamide D were essential in maintaining the high activity against Panc-1 cells and the orientation of C40-Me and C42-Me groups was tolerable.

关键词： Majusculamide D Natural products SAR Anti-pancreatic cancer Lipopentapeptide

5S-Heudelotinone alleviates experimental colitis by shaping the immune system and enhancing the intestinal barrier in a gut microbiota-dependent manner

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2153-2176页

作者： Qing Meng Jianshuang Guo Ke Lv Yang Liu Jin Zhang Mingyue Li Xirui cheng Shenghua chen Xiaoguang Huo Quan Zhang yue chen Jing Li State Key Laboratory of Medicinal Chemical Biology College of PharmacyNankai UniversityTianjin 300353China College of Chemistry and Frontiers Science Center for New Organic Matter Haihe Laboratory of Sustainable Chemical TransformationsNankai UniversityTianjin 300071China Accendatech Company Ltd.Tianjin 300193China

Aberrant changes in the gut microbiota are implicated in many diseases,including inflammatory bowel disease(IBD).Gut microbes produce diverse metabolites that can shape the immune system and impact the intestinal barrier integrity,indicating that microbe-mediated modulation may be a promising strategy for preventing and treating IBD.Although fecal microbiota transplantation and probiotic supplementation are well-established IBD therapies,novel chemical agents that are safe and exert strong effects on the gut microbiota are urgently needed.Herein,we report the total synthesis of heudelotinone and the discovery of 5S-heudelotinone(an enantiomer)as a potent agent against experimental colitis that acts by modulating the gut microbiota.5S-Heudelotinone alters the diversity and composition of the gut microbiota and increases the concentration of short-chain fatty acids(SCFAs);thus,it regulates the intestinal immune system by reducing proinflammatory immune cell numbers,and maintains intestinal mucosal integrity by modulating tight junctions(TJs).Moreover,5S-heudelotinone(2)ameliorates colitis-associated colorectal cancer(CAC)in an azoxymethane(AOM)/dextran sulfate sodium(DSS)-induced in situ carcinoma model.Together,these findings reveal the potential of a novel natural product,namely,5S-heudelotinone,to control intestinal inflammation and highlight that this product is a safe and effective candidate for the treatment of IBD and CAC.

关键词： 5S-heudelotinone Total synthesis Inflammatory bowel disease Gut microbiota Short-chain fatty acids Immune system Intestinal barrier Drug discovery

Amitriptyline inhibits NLRP3 inflammasome activation via the ASM/CE pathway in a cell model of NAFLD

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BIOCELL 2024年第5期48卷 759-769页

作者： QIN LIU CHUNYAN NIU QIANG ZHANG SHIQIN SUN yue chen YONGQIANG SHI Shengli Clinical Medical College Fujian Medical UniversityFuzhou350001China Department of Gastroenterology Nanjing Lishui People’s HospitalZhongda Hospital Lishui BranchSoutheast UniversityNanjing211200China Department of Gastroenterology Yancheng Third People’s Hospital(The Yancheng School of Clinical Medicine of Nanjing Medical University)Yancheng224000China Administrative Department of Teaching and Scientific Research Nanjing Lishui People’s HospitalZhongda Hospital Lishui BranchSoutheast UniversityNanjing211200China

Background:Nonalcoholic fatty liver disease(NAFLD)is a global health concern with the acid sphingomyelinase(ASM)/ceramide(CE)pathway and the NOD-like receptor family,pyrin domain-containing protein 3(NLRP3)inflammasome identified as pivotal players in lipid disorders and inflammation.This study explores the interaction mechanism between the ASM/CE pathway and NLRP3 in NAFLD cell models,aiming to understand the impact of amitriptyline(Ami),an ASM inhibitor,on lipid deposition and hepatocyte injury by regulating the ASM/CE-NLRP3 pathway.Methods:HepG2 and HL-7702 cells were exposed to free fatty acids(FFAs)to establish the NAFLD model.The cells were divided into 5 groups:control group,model group,Ami group,tumor necrosis factoralpha(TNF-α)group,and Ami+TNF-αgroup.Intracellular lipid droplets were visualized using Oil Red O staining,and Western blot analysis quantified ASM,NLRP3,and caspase 1 protein expression.Enzyme linked immunosorbent assay(ELISA)was measured CE and ASM levels,while qRT-PCR assessed mRNA expression.The apoptotic rate was evaluated by flow cytometry(FCM).Results:Following FFAs incubation,significant increases in ASM and CE levels were observed in HepG2 and HL-7702 cells,accompanied by elevated expression of NLRP3,and caspase 1,and IL-1β.TNF-αtreatment further amplified these indicators.Ami demonstrated a reduction in lipid deposition,suppressed ASM/CE pathway activation,downregulated NLRP3 and caspase 1 expression,and improved apoptosis.Additionally,MCC950,a selective inhibitor of the NLRP3,mitigated NLRP3,caspase 1,and IL-1βexpression,alleviating lipid deposition and apoptosis in the NAFLD cell model.Conclusion:The ASM/CE-NLRP3 pathway in NAFLD cells promotes hepatocyte steatosis,inflammation,and cell damage.Ami emerges as a promising therapeutic agent by inhibiting the ASM/CE-NLRP3 pathway,underscoring its potential as a key target for NAFLD treatment.

关键词： Nonalcoholic fatty liver disease Hepatocyte Amitriptyline ASM/CE pathway NLRP3 Nonalcoholic steatohepatitis

Thermoelectric transport properties of p-type Bi2Se3-Sb2Se3-In2Se3 high entropy compounds

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Rare Metals 2024年第7期43卷 3415-3421页

作者： Feng Jiang cheng-Liang Xia Yong-Bin Zhu Jun Li yue chen Wei-Shu Liu Department of Materials Science and Engineering Southern University of Science and Technology Department of Mechanical Engineering The University of Hong Kong Guangdong Provincial Key Laboratory of Functional Oxide Materials and Devices Southern University of Science and Technology

The introduction of entropy concept into thermoelectric materials recently has attracted broad interest.Herein,we showed the phase diagram of the ternary systems of Bi2Se3-Sb2Se3-In2Se3.Among the high entropy compounds （HECs）,we have identified an intrinsic p-type region near our previously reported Bi0.8Sb0.8In0.4Se3in the phase diagram.

关键词： Selenium compounds

Solidification behaviour and hot cracking susceptibility of a novel Ni-based superalloy

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Journal of Iron and Steel Research(International) 2024年第4期31卷 956-966页

作者： yue chen Shao-min Lv Xing-fei Xie Xiao-can Wen Jng-long Qu Jin-hui Du High-Temperature Materials Institute China Iron and Steel Research Institute Group Co.Ltd.Beijing 100081China Beijing GAONA Materials and Technology Co. Ltd.Beijing 100081China Sichuan CISRI-GAONA Forging Co. Ltd.Deyang 610000SichuanChina

A novel Ni-based superalloy GH4151,with a γ′ volume fraction of about 55%and a service temperature capability up to 8oo oC,was investigated.Due to the different cooling conditions of various regions during the solidification of ingots,significant cooling rate variations may lead to the occurrence of hot cracking.Conventional scanning laser microscope was utilised to investigate the solidification process and phase precipitation behaviour of the GH4151 under wide range cooling rates.The characteristics of L→γ transformation were analysed,and the growth rates of at each stage were calculated.The segregation behaviour was predicted using the Scheil equation,and the predicted results match well with the experimental results.The sensitivity coefficient for hot cracking was modified,and cracking sensitivity coefficient values for the alloy under different cooling rates were computed,revealing that the alloy is most susceptible to hot cracking at 10℃/min cooling rate.Therefore,controlling the cooling rate can reduce the possibility of hot cracking in ingot.

关键词： Ni-based superalloy Solidification behaviour In-situ observation Clyne and Davies's criterion:Hot cracking susceptibility

Degradation of FAK-targeting by proteolytic targeting chimera technology to inhibit the metastasis of hepatocellular carcinoma

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Oncology Research 2024年第4期32卷 679-690页

作者： XINFENG ZHANG SHUANG LI MEIRU SONG yue chen LIANGZHENG CHANG ZHERUI LIU HONGYUAN DAI YUTAO WANG GANGQI YANG YUN JIANG YINYING LU The PLA 307 Clinical College of Anhui Medical University The Fifth Clinical Medical College of Anhui Medical UniversityHefei230032China Liver Tumor Diagnosis and Research Center 5th Medical Center of the PLA General HospitalBeijing100039China Department of Infection Diseases Guizhou Medical UniversityGuiyang550025China 4302 Clinical Medical School Peking UniversityBeijingChina Cell and Gene Therapy Innovation Center Beijing Lotuslake BiomedicalScience and Technology ParkBeijing102206China State Key Laboratory of Chemical Oncogenomics and the Institute of Biopharmaceutical and Health Engineering(iBHE) Shenzhen International Graduate SchoolTsinghua UniversityShenzhen518055China

Liver cancer is a prevalent malignant cancer,ranking third in terms of mortality rate.Metastasis and recurrence primarily contribute to the high mortality rate of liver cancer.Hepatocellular carcinoma(HCC)has low expression of focal adhesion kinase(FAK),which increases the risk of metastasis and recurrence.Nevertheless,the efficacy of FAK phosphorylation inhibitors is currently limited.Thus,investigating the mechanisms by which FAK affects HCC metastasis to develop targeted therapies for FAK may present a novel strategy to inhibit HCC metastasis.This study examined the correlation between FAK expression and the prognosis of HCC.Additionally,we explored the impact of FAK degradation on HCC metastasis through wound healing experiments,transwell invasion experiments,and a xenograft tumor model.The expression of proteins related to epithelial-mesenchymal transition(EMT)was measured to elucidate the underlying mechanisms.The results showed that FAK PROTAC can degrade FAK,inhibit the migration and invasion of HCC cells in vitro,and notably decrease the lung metastasis of HCC in vivo.Increased expression of E-cadherin and decreased expression of vimentin indicated that EMT was inhibited.Consequently,degradation of FAK through FAK PROTAC effectively suppressed liver cancer metastasis,holding significant clinical implications for treating liver cancer and developing innovative anti-neoplastic drugs.

关键词： Hepatocellular carcinoma(HCC) Focal adhesion kinase(FAK) Proteolytic targeting chimera technology(PROTAC) Epithelial-mesenchymal transformation(EMT) Metastasis

Role of land-atmosphere coupling in persistent extreme climate events in eastern China in summer 2022

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Atmospheric and Oceanic Science Letters 2024年第2期17卷 19-26页

作者： yue chen Aihui Wang Nansen-Zhu International Research Centre Institute of Atmospheric PhysicsChinese Academy of SciencesBeijingChina Collaborative Innovation Center on Forecast and Evaluation of Meteorological Disasters(CIC-FEMD) Nanjing University of Information Science&TechnologyNanjingChina

2022年暖季,中国东部地区遭受持续性高温,少雨和土壤干旱的复合极端事件.特征分析指出,在研究时段内,中国东部地区的气温,降水和土壤湿度呈现明显的季节内变化和南北差异。由1940-2022年的气候态可知,长江流域和东南地区的土壤含水充足... 详细信息

2022年暖季,中国东部地区遭受持续性高温,少雨和土壤干旱的复合极端事件.特征分析指出,在研究时段内,中国东部地区的气温,降水和土壤湿度呈现明显的季节内变化和南北差异。由1940-2022年的气候态可知,长江流域和东南地区的土壤含水充足,蒸散主要受限于陆面有效能量.然而,潜在机制研究指出,2022年土壤湿度对蒸散的限制作用在上述区域异常偏强,土壤湿度与气候要素之间的强反馈可能在2022年复合极端事件的演变和持续中发挥了关键作用。

关键词：复合极端事件陆气耦合土壤湿度干旱中国东部

Study on improving hematopoietic function of rats with blood deficiency syndrome by Shengxuebao mixture

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Traditional Medicine Research 2024年第8期9卷 35-46页

作者： Yan Shu Hong-Na Liu Yang Zhao Jin-Yi Cao yue chen Yi Qiao Hui Guo Zhi-Fu Yang College of Pharmacy Shaanxi University of Chinese MedicineXianyang 712046China Tsing Hua De Ren Xi’an Happiness Pharmaceutical Co. Ltd.Xi’an 710400China Department of Pharmacy Xijing HospitalFourth Military Medical UniversityXi’an 710000China State Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral DiseasesShaanxi Engineering Research Center for Dental Materials and Advanced ManufactureDepartment of PharmacySchool of Stomatologythe Fourth Military Medical UniversityXi’an 710000China

Background:Shengxuebao mixture(SXBM)is a novel herbal drug approved by China State Food and Drug Administration for the treatment of Leukopenia and iron deficiency anemia caused by radiotherapy and chemotherapy.Methods:To explore the mechanism of SXBM in treating blood deficiency syndrome(BDS).Firstly,network pharmacology and in vivo experiments were used to screen candidate targets and important signaling pathways of SXBM,GO functional enrichment and KEGG pathway analysis were performed.Secondly,a BDS rat model was established to verify the results of the analysis of network pharmacological enrichment.Histopathology and routine peripheral blood examination were observed.The expressions of tumor necrosis factor-α,interleukin(IL)-6,HIF-1αand NF-κB were detected by Western blot,and the expressions of IL-6,IL-1βwere detected by ELISA.Results:62 bioactive components,66 potential targets and 131 signaling pathways of BDS were successfully identified by network pharmacology.Molecular docking simulation techniques showed that key targets tumor necrosis factor-α,IL-6,IL-1βcan dock well with crucial components,and the BDS-related signaling pathways HIF-1 and JAK-STAT play a vital role.The combined model experiment of acetylphenylhydrazine and cyclophosphamide showed that the model group had obvious blood deficiency,and the histopathology and blood routine were effectively restored after administration.Our findings indicate that SXBM’s therapeutic effect on BDS primarily involves the mediation of the HIF-1α/NF-κB signaling pathway and the regulation of hematopoietic factor expression.Conclusion:This study not only affirmed the protective properties of SXBM against BDS but also provided insights into a potential mechanism for blood replenishment in the treatment of BDS using SXBM.

关键词： network pharmacology molecular docking technology blood deficiency syndrome hematopoietic factors HIF-1α/NF-κB

Composition,function,and timing:exploring the early‑life gut microbiota in piglets for probiotic interventions

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Journal of Animal Science and Biotechnology 2024年第2期15卷 659-678页

作者： Jianping Quan Cineng Xu Donglin Ruan Yong Ye Yibin Qiu Jie Wu Shenping Zhou Menghao Luan Xiang Zhao yue chen Danyang Lin Ying Sun Jifei Yang Enqin Zheng Gengyuan Cai Zhenfang Wu Jie Yang College of Animal Science and National Engineering Research Center for Breeding Swine Industry South China Agricultural UniversityGuangzhouGuangdongPeople’s Republic of China Guangdong Provincial Key Laboratory of Agro‑Animal Genomics and Molecular Breeding South China Agricultural UniversityGuangzhouGuangdongChina Yunfu Subcenter of Guangdong Laboratory for Lingnan Modern Agriculture YunfuGuangdongChina National Engineering Research Center for Breeding Swine Industry Wens Foodstuff Group Co.Ltd.YunfuGuangdongPeople’s Republic of China

Background The establishment of a robust gut microbiota in piglets during their early developmental stage holds the potential for long-term advantageous effects.However,the optimal timeframe for introducing probiotics to achieve this outcome remains uncertain.Results In the context of this investigation,we conducted a longitudinal assessment of the fecal microbiota of 63 piglets at three distinct pre-weaning time points.Simultaneously,we gathered vaginal and fecal samples from 23 sows.Employing 16S rRNA gene and metagenomic sequencing methodologies,we conducted a comprehensive analysis of the fluctuation patterns in microbial composition,functional capacity,interaction networks,and colonization resistance within the gut microbiota of piglets.As the piglets progressed in age,discernible modifications in intestinal microbial diversity,composition,and function were observed.A source-tracking analysis unveiled the pivotal role of fecal and vaginal microbiota derived from sows in populating the gut microbiota of neonatal piglets.By D21,the microbial interaction network displayed a more concise and efficient configuration,accompanied by enhanced colonization resistance relative to the other two time points.Moreover,we identified three strains of Ruminococcus sp.at D10 as potential candidates for improving piglets’weight gain during the weaning phase.Conclusions The findings of this study propose that D10 represents the most opportune juncture for the introduction of external probiotic interventions during the early stages of piglet development.This investigation augments our comprehension of the microbiota dynamics in early-life of piglets and offers valuable insights for guiding forthcoming probiotic interventions.

关键词： Colonization resistance Intestinal microbiota Piglet Weaning Weight gain

Midpoint transverse process to pleura block for postoperative analgesia following laparoscopic renal cyst decortication:Two case reports

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World Journal of Clinical Cases 2024年第18期12卷 3629-3635页

作者： Wei-Jie He Wen-Xing Xu Xu-Dong Zhang yue chen Shu-Ying He Xian-Qin Wei Xiao-Lan Huang Department of Anesthesiology Liuzhou People's Hospital affiliated to Guangxi Medical UniversityLiuzhou 545000Guangxi Zhuang Autonomous RegionChina Department of Ultrasound Medicine Liuzhou People's Hospital affiliated to Guangxi Medical UniversityLiuzhou 545000Guangxi Zhuang Autonomous RegionChina

BACKGROUND The midpoint transverse process to pleura(MTP)block,a novel technique for thoracic paravertebral block(TPVB),was first employed in laparoscopic renal cyst decortication.CASE SUMMARY Thoracic paravertebral nerve block is frequently employed for perioperative analgesia during laparoscopic cyst decortication.To address safety concerns associated with TPVBs,we administered MTP blocks in two patients prior to administering general anesthesia for laparoscopic cyst decortication.The MTP block was performed at the T9 level under ultrasound guidance,with 20 mL of 0.5%ropivacaine injected.Reduced sensation to cold and pinprick was observed from the T8 to T11 dermatome levels.Immediately postoperative Numeric Pain Rating Scale scores were 0/10 at rest and on movement,with none exceeding a mean 24 h numeric rating scale>3.CONCLUSION MTP block was effective technique for providing postoperative analgesia for patients undergoing laparoscopic renal cyst decortication.

关键词： Midpoint transverse process to pleura block Laparoscopic renal cyst decortication Pain Analgesia Case report