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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

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CircZFR promotes colorectal cancer progression via stabilizing BCLAF1 and regulating the miR-3127-5p/RTKN2 axis

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Science China Life Sciences 2024年

作者： Jiaxin Chen Huijuan Wang Jianbin Xu Engeng Chen qing meng Jiawei Wang Haoyi Xiang Wei Zhou Ge Shan Zhenyu Ju Zhangfa Song Department of Colorectal Surgery Sir Run Run Shaw Hospital Zhejiang University School of Medicine Key Laboratory of Biological Treatment of Zhejiang Province Department of Breast Surgery the Second Affiliated Hospital Zhejiang University School of Medicine Department of Orthopedic Surgery the Second Affiliated Hospital Zhejiang University School of Medicine Department of Pulmonary and Critical Care Medicine Regional medical center for National Institute of Respiratory Disease Sir Run Run Shaw Hospital Zhejiang University School of Medicine Key Laboratory of Regenerative Medicine of Ministry of Education Institute of Aging and Regenerative Medicine Jinan University

Aberrant expression of circular RNAs (circRNAs) is frequently linked to colorectal cancer (CRC). Here, we identified circZFR as a promising biomarker for CRC diagnosis and prognosis. CircZFR was upregulated in CRC tissues and serum exosomes and its level was linked to cancer incidence, advanced-stages, and metastasis. In both in vitro and in vivo settings, circZFR promoted the growth and spread while suppressing apoptosis of CRC. Exosomes with circZFR overexpression promoted the proliferation and migration of cocultured CRC cells. Mechanistically,epithelial splicing regulatory protein 1 (ESRP1) in CRC cells may enhance the production of circZFR. BCL2-associated transcription factor 1(BCLAF1) bound to circZFR, which prevented its ubiquitinated degradation. Additionally, circZFR sponged miR-3127-5p to boost rhotekin 2(RTKN2) expression. Our TCP1-CD-QDs nanocarrier was able to carry and deliver circZFR siRNA (si-circZFR) to the vasculature of CRC tissues and cells, which inhibited the growth of tumors in patient-derived xenograft (PDX) models. Taken together, our results show that circZFR is an oncogenic circRNA, which promotes the development and spread of CRC in a BCLAF1 and miR-3127-5p-dependent manner.CircZFR is a possible serum biopsy marker for the diagnosis and a desirable target for further treatment of CRC.

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Bioinspired design of integral molded Janus silk fibroin-MXene evaporator for efficient solar vapor generation

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Nano Research 2024年第4期17卷 2824-2835页

作者： Ling-qing Kong Zhi-Cheng Zeng Guang-Zong Min Zhao-Hui meng Guo-qing meng Xiao-Xiao Guo Nai-Bo Lin Xiang-Yang Liu The Higher Educational Key Laboratory for Biomedical Engineering of Fujian Province Research Center of Biomedical Engineering of XiamenDepartment of BiomaterialsCollege of MaterialsXiamen UniversityXiamen 361005China The State Key Laboratory of Marine Environmental Science(MEL) College of Ocean and Earth SciencesXiamen UniversityXiamen 361005China

Solar vapor generation is a promising sustainable technology that uses solar distillation to produce fresh water from seawater and wastewater,helping relieve global water resource shortage.Here,inspired by naturally grown integrally molded mulberry leaves with a Janus hydrophilic and hydrophobic structure,a novel,simple,and efficient integrated molding method is proposed to break through the limitations of the traditional split manufacturing strategy and realizes the integrated formation of Janus evaporator.Based on the spontaneous sedimentation characteristics of MXene in silk fibroin solution and its regulation of mesoscopic structure and hydrophilicity of silk fibroin,layered structures with different compositions and hydrophilicities were obtained in one step.Meanwhile,ethanol and glutaraldehyde were added to construct a physical crystallization-chemical crosslinking dual stabilization structure in silk fibroin.Our evaporator has the evaporation rate of 3.07 kg·m^(-2)·h^(-1) and the efficiency of 86.8%under 1 sun and maintains high evaporation performance under various extreme test conditions including vigorous washing,repeated compression,and high-intensity ultraviolet(UV)irradiation.Additionally,the evaporator performs well in practical application scenarios,its evaporation rate in the simulated Dead Sea seawater exceeds 2.13 kg·m^(-2)·h^(-1),and more than 99.9%of the salt,heavy metal ions,oil pollution,and dyes are purified.

关键词： silk fibroin MXene bioinspired integrated molding Janus structure solar vapor generation

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Dielectric and energy storage properties of PbO–SrO–Nb_(2)O_(5)–Na_(2)O–Si thin films by annealing

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Rare Metals 2024年第1期43卷 351-355页

作者： Fei-Hu Tan qing-meng Zhang Feng Wei Hong-Bin Zhao Xiao Zhang Jun Du State Key Laboratory of Advanced Materials for Smart Sensing General Research Institute for Nonferrous MetalsBeijing 100088China Advanced Electronic Materials Institute General Research Institute for Nonferrous MetalsBeijing 100088China

Dielectric and energy storage properties of PbOSrO-Na_(2)O-Nb_(2)O_(5)-SiO_(2)(PSNNS) thin films with annealing temperature from 700 to 850 ℃ were investigated by measuring their capacitance-electric filed curve and hysteresis loops.The results show that the highest dielectric constant and energy density are 81.2 and 17.0 J·cm^(-3),respectively,which is obtained in the sample with annealing temperature of 800 ℃.Annealed from 700 to800 ℃,the dielectric constant and energy storage performance of PSNNS films are continuously improved.However,with annealing temperature up to 850 ℃,their dielectric constant decreases,which might be related with the removal of interfacial defects as a function of annealing temperature.Defect is one of the causes of space charge phenomenon,resulting in the increase in dielectric constant.Moreover,the micro structure analysis by X-ray diffraction(XRD) and transmission electron microscope(TEM) indicates that the change of crystallization phase and interfacial polarization takes responsibility to the results.

关键词： Thin film Pulse laser deposition Annealing temperature Energy storage density

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Prevalence and clinical impact of sarcopenia in liver transplant recipients:A meta-analysis

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World Journal of Gastroenterology 2024年第8期30卷 956-968页

作者： Min-Jie Jiang Mu-Chen Wu Zhong-Hui Duan Jing Wu Xiao-Tong Xu Juan Li qing-Hua meng Department of Hepatology Beijing You-An HospitalCapital Medical UniversityBeijing 100069China Department of Emergency Beijing You-An HospitalCapital Medical UniversityBeijing 100069China

BACKGROUND The prevalence of sarcopenia in patients undergoing liver transplantation(LT)remains to be determined partly because of different diagnostic criteria.Sarcopenia has recently been recognized as a new prognostic factor for predicting outcomes in LT candidates.AIM To estimate the prevalence of sarcopenia and evaluate its clinical effect on LT candidates.METHODS This systematic search was conducted in PubMed,Web of Science,Embase,and Cochrane Library for original English-language articles that investigated the prevalence and influence of sarcopenia in patients undergoing LT from database inception to November 30,2022.Cohort studies of the definition of sarcopenia that estimate sarcopenia prevalence and evaluate its effect on clinical outcomes and the risk of mortality were included.RESULTS Twenty-five studies involving 7760 patients undergoing LT were included.The pooled prevalence of sarcopenia in patients undergoing LT was 40.7%[95%confidence intervals(95%CI):32.1-49.6].The 1-,3-,and 5-year cumulative probab-ilities of post-LT survival in patients with preoperative sarcopenia were all lower than those without sarcopenia(P<0.05).Sarcopenia was associated with an increased risk of post-LT mortality in patients undergoing LT(adjusted hazard ratio:1.58;95%CI:1.21-2.07).Patients with preoperative sarcopenia had a longer intensive care unit stay,a high risk ratio of sepsis,and serious post-LT complications than those without sarcopenia.CONCLUSION Sarcopenia is prevalent in a substantial proportion of patients undergoing LT and is strongly and independently associated with higher a risk of mortality risk.

关键词： Sarcopenia Liver transplantation Mortality Clinical outcomes

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Dynamically switchable porphyrin-based molecular tweezer for on-off fullerene recognition

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Chinese Chemical Letters 2024年第6期35卷 283-287页

作者： Zhimin Sun Xin-Hui Guo Yue Zhao qing-Yu meng Li-Juan Xing He-Lue Sun College of Chemistry and Materials Science Hebei Key Laboratory of Organic Functional MoleculesHebei Normal UniversityShijiazhuang 050024China

Herein,a novel molecular tweezer based on 2,2'-bipyridine-bridged porphyrin subunits was constructed for efficient fullerenes recognition.The syn conformation of the molecule,which was obtained by Zn(Ⅱ)coordination,gives rise to a proper cavity to interact with fullerene guests to form a stable 1:1 complex in toluene solution.It exhibits distinct binding selectivity towards C_(60)over C_(70).Moreover,the fullerene recognition capacity can be adequately suppressed by importing H_(2)PO_(4)^(-)to competitively capture Zn(Ⅱ)along with syn-anti conformational conversion.Subsequently,the molecular tweezer regenerated to bind the fullerene by introducing the Ca^(2+)into the system.Significantly,the association-disassociation process can be switched reversibly and repeatedly.

关键词： Molecular tweezer Fullerene recognition Supramolecular chemistry Conformation conversion Coordination

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A deep learning model based on contrast-enhanced computed tomography for differential diagnosis of gallbladder carcinoma

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 376-384页

作者： Fei Xiang qing-Tao meng Jing-Jing Deng Jie Wang Xiao-Yuan Liang Xing-Yu Liu Sheng Yan Department of Hepatobiliary Pancreatic Surgery Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Department of Radiology Affiliated Chuzhou First People’s HospitalAnhui Medical UniversityChuzhou 239000China

Background:Gallbladder carcinoma(GBC)is highly malignant,and its early diagnosis remains difficult.This study aimed to develop a deep learning model based on contrast-enhanced computed tomography(CT)images to assist radiologists in identifying GBC.Methods:We retrospectively enrolled 278 patients with gallbladder lesions(>10 mm)who underwent contrast-enhanced CT and cholecystectomy and divided them into the training(n=194)and validation(n=84)datasets.The deep learning model was developed based on ResNet50 network.Radiomics and clinical models were built based on support vector machine(SVM)method.We comprehensively compared the performance of deep learning,radiomics,clinical models,and three radiologists.Results:Three radiomics features including LoG_3.0 gray-level size zone matrix zone variance,HHL firstorder kurtosis,and LHL gray-level co-occurrence matrix dependence variance were significantly different between benign gallbladder lesions and GBC,and were selected for developing radiomics model.Multivariate regression analysis revealed that age≥65 years[odds ratios(OR)=4.4,95%confidence interval(CI):2.1-9.1,P37 U/mL(OR=4.0,95%CI:1.6-10.0,P=0.003)were significant clinical risk factors of GBC.The deep learning model achieved the area under the receiver operating characteristic curve(AUC)values of 0.864(95%CI:0.814-0.915)and 0.857(95%CI:0.773-0.942)in the training and validation datasets,which were comparable with radiomics,clinical models and three radiologists.The sensitivity of deep learning model was the highest both in the training[90%(95%CI:82%-96%)]and validation[85%(95%CI:68%-95%)]datasets.Conclusions:The deep learning model may be a useful tool for radiologists to distinguish between GBC and benign gallbladder lesions.

关键词： Gallbladder carcinoma Computed tomography Deep learning Radiomics

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COVID-19 pandemic amplified mortality rates among adolescents with bipolar disorder through family-related factors

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World Journal of Clinical Cases 2024年第11期12卷 1929-1935页

作者： Zhuo-Fan Ye Yi-Han Hong Jian-Lin Yang meng-qing Tan Ju-Min Xie Zu-Cai Xu Department of Neurology The Affiliated Hospital of Zunyi Medical UniversityZunyi 563000Guizhou ProvinceChina Hubei Key Laboratory of Renal Disease Occurrence and Intervention Medical SchoolHubei Polytechnic UniversityHuangshi 435003Hubei ProvinceChina Psychological Children's Ward Mental Health Center of HuangshiHuangshi 435111Hubei ProvinceChina The Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine Zunyi Medical UniversityZunyi 563000Guizhou ProvinceChina

BACKGROUND Recently,a growing number of adolescents have been afflicted with mental disorders,with annual morbidity rates on the rise.This trend has been exacerbated by the global coronavirus disease 2019(COVID-19)pandemic,leading to a surge in suicide and self-harm rates among this demographic.AIM To investigate the impact of the COVID-19 pandemic on adolescent bipolar disorder(BD),along with the underlying factors contributing to heightened rates of suicide and self-harm among adolescents.METHODS A comprehensive statistical analysis was conducted utilizing clinical interviews and self-reports obtained from patients or their guardians.Diagnostic criteria for BDs were based on the Diagnostic and statistical manual of mental disorders,international classification of diseases-11,and the National institute of mental health research domain criteria.Statistical analyses were performed using SPSS 26.0 software,with significance set at P<0.05.RESULTS A cohort of 171 adolescents diagnosed with BD between January 1,2018,and December 31,2022,was included in the analysis.The gender distribution was 2.8:1(female to male),with ages ranging from 11 to 18 years old.Major factors contributing to adolescent BDs included familial influences,academic stress,genetic predisposition and exposure to school-related violence.Notably,a significant increase in suicide attempts and self-harm incidents was observed among adolescents with BD during the COVID-19 pandemic.Statistical analysis indicated that the pandemic exacerbated familial discord and heightened academic stress,thereby amplifying the prevalence of suicidal behavior and self-harm among adolescents.CONCLUSION The COVID-19 pandemic has exacerbated familial tensions and intensified the incidence of suicide and self-harm among adolescents diagnosed with BD.This study underscores the urgent need for societal,familial and educational support systems to prioritize the well-being of adolescents and offers valuable insights and guidelines for the prevention,diagnosis and treatment of ad

关键词： Adolescents Bipolar disorder COVID-19 Suicide Self-harm

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Absorbed Bioactive Compounds Replicate GuanxinⅡ-Induced Endothelium-Associated in/ex vivo Vasodilation

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Chinese Journal of Integrative Medicine 2024年第5期30卷 387-397页

作者： XU Min LIU Hao SU meng-qing LI Lan YU Ai-ling CHEN Ken HUANG Yun-ke ZHAO Qiu-long HUANG Wen-ya HUANG Xi Institute of Traditional Chinese Medicine Related Comorbid Depression Nanjing University of Chinese MedicineNanjing 210029China Department of Gynecology Women's HospitalZhejiang University School of MedicineHangzhou 310053China

Objective:To develop an interference-free and rapid method to elucidate GuanxinⅡ(GXⅡ)'s representative vasodilator absorbed bioactive compounds(ABCs)among enormous phytochemicals.Methods:The contents of ferulic acid,tanshinol,and hydroxysafflor yellow A(FTA)in GXⅡ/rat serum after the oral administration of GXⅡ(30 g/kg)were detected using ultra-performance liquid chromatography-mass spectrometry.Totally 18 rats were randomly assigned to the control group(0.9%normal saline),GXⅡ(30 g/kg)and FTA(5,28 and 77 mg/kg)by random number table method.Diastolic coronary flow velocity-time integral(VTI),i.e.,coronary flow or coronary flow-mediated dilation(CFMD),and endothelium-intact vascular tension of isolated aortic rings were measured.After 12 h of exposure to blank medium or 0.5 mmol/L H_(2)O_(2),endothelial cells(ECs)were treated with post-dose GXⅡof supernatant from deproteinized serum(PGSDS,300μL PGSDS per 1 m L of culture medium)or FTA(237,1539,and 1510 mg/m L)for 10 min as control,H_(2)O_(2),PGSDS and FTA groups.Nitric oxide(NO),vascular endothelial growth factor(VEGF),endothelin-1(ET-1),superoxide dismutase(SOD),malondialdehyde(MDA)and phosphorylated phosphoinositide 3 kinase(p-PI3K),phosphorylated protein kinase B(p-AKT),phosphorylated endothelial nitric oxide synthase(p-e NOS)were analyzed.PGSDS was developed as a GXⅡproxy of ex vivo herbal crude extracts.Results:PGSDS effectively eliminates false responses caused by crude GXⅡpreparations.When doses equaled the contents in GXⅡ/its post-dose serum,FTA accounted for 98.17%of GXⅡ-added CFMD and 92.99%of PGSDS-reduced vascular tension.In ECs,FTA/PGSDS was found to have significant antioxidant(lower MDA and higher SOD,P<0.01)and endothelial function-protective(lower VEGF,ET-1,P<0.01)effects.The increases in aortic relaxation,endothelial NO levels and phosphorylated PI3K/Akt/e NOS protein induced by FTA/PGSDS were markedly abolished by NG-nitro-L-arginine methyl ester(L-NA,e NOS inhibitor)and wortmannin(PI3K/AKT inhibitor),respectively,indicating an endothelium-depende

关键词： ultra-performance liquid chromatography-mass spectrometry endothelium-dependent vasodilation herbal extract GuanxinⅡ absorbed bioactive compound

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Identifying the risk factors for pancreatic fistula after laparoscopic pancreaticoduodenectomy in patients with pancreatic cancer

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World Journal of Gastrointestinal Surgery 2024年第6期16卷 1609-1617页

作者： Hang Xu qing-Cai meng Jie Hua Wei Wang Department of Pancreatic Surgery Fudan University Shanghai Cancer CenterShanghai 200032China Department of Oncology Shanghai Medical CollegeFudan UniversityShanghai 200032China

BACKGROUND Laparoscopic pancreaticoduodenectomy(LPD)is a surgical procedure for treating pancreatic cancer;however,the risk of complications remains high owing to the wide range of organs involved during the surgery and the difficulty of anastomosis.Pancreatic fistula(PF)is a major complication that not only increases the risk of postoperative infection and abdominal hemorrhage but may also cause multi-organ failure,which is a serious threat to the patient’s life.This study hypothesized the risk factors for PF after LPD.AIM To identify the risk factors for PF after laparoscopic pancreatoduodenectomy in patients with pancreatic cancer.METHODS We retrospectively analyzed the data of 201 patients admitted to the Fudan University Shanghai Cancer Center between August 2022 and August 2023 who underwent LPD for pancreatic cancer.On the basis of the PF’s incidence(grades B and C),patients were categorized into the PF(n=15)and non-PF groups(n=186).Differences in general data,preoperative laboratory indicators,and surgery-related factors between the two groups were compared and analyzed using multifactorial logistic regression and receiver-operating characteristic(ROC)curve analyses.RESULTS The proportions of males,combined hypertension,soft pancreatic texture,and pancreatic duct diameter≤3 mm;surgery time;body mass index(BMI);and amylase(Am)level in the drainage fluid on the first postoperative day(Am>1069 U/L)were greater in the PF group than in the non-PF group(P24.91 kg/m²[odds ratio(OR)=13.978,95%confidence interval(CI):1.886-103.581],hypertension(OR=8.484,95%CI:1.22-58.994),soft pancreatic texture(OR=42.015,95%CI:5.698-309.782),and operation time>414 min(OR=15.41,95%CI:1.63-145.674)were risk factors for the development of PF after LPD for pancreatic cancer(all P<0.05).The areas under the ROC curve for BMI,hypertension,soft pancreatic texture,and time pr

关键词： Pancreatic cancer Laparoscopy Pancreaticoduodenectomy Pancreatic fistula Risk factors Receiver-operating characteristic curve

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