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A non-peptide-based chymotrypsin-targeted long-wavelength emission fluorescent probe with large Stokes shift and its application in bioimaging

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Chinese Chemical Letters 2024年第10期35卷 456-462页

作者： Chuanfeng Fan Jian Gao Yingkai Gao Xintong Yang Gaoning Li Xiaochun Wang Fei Li jin Zhou Haifeng Yu Yi Huang jin Chen Yingying Shan Li Chen Key Laboratory of Optic-electric Sensing and Analytical Chemistry for Life Science MOE Shandong Provincial Key Laboratory of Biochemical EngineeringQingdao Nucleic Acid Rapid Detection Engineering Research Center College of Marine Science and Biological Engineering Qingdao University of Science and Technology School of Chemistry and Life Science Anshan Normal University Liaoning Key Laboratory of Development and Utilization for Natural Products Active Molecules Biomedical Analysis Center Army Medical University School of Pharmacy Weifang Medical University College of Chemistry Baicheng Normal University

As a hydrolase, chymotrypsin(CHT) is involved in many physiological activities, and its abnormal activity is closely related to diabetes, pancreatic fibrosis, chronic pancreatitis and pancreatic cancer. In this work,an innovative long-wavelength emission fluorescent probe TCF-CHT was designed and synthesized for the high specificity detection of CHT, which utilized TCF-OH and a mimetic peptide substrate 4-bromobutyryl as chromogenic group and recognition group, respectively. TCF-CHT exhibited excellent selectivity and eye-catching sensitivity(8.91 ng/m L) towards CHT, “off-on” long-wavelength emission at 670 nm and large Stokes shift(140 nm). Furthermore, the successful fulfillment and perfect performance in imaging endogenous CHT in complex organisms(P815 cells, HepG2 cells, zebrafish and tumor-bearing mice) verified its potential as a powerful tool for the recognition of CHT in complicated biological environments.

关键词： Bioimaging Chymotrypsin Fluorescent probe Large Stokes shift Long-wavelength emission

Predictive value of preoperative routine examination for the prognosis of patients with pT2N0M0 or pT3N0M0 colorectal cancer

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2429-2438页

作者： Peng-Fei jing jin Chen En-Da Yu Chao-Yu Miao Department of Colorectal Surgery Changhai HospitalSecond Military Medical University/Naval Medical UniversityShanghai 200433China Department of Endocrinology and Metabolism Changhai HospitalSecond Military Medical University/Naval Medical UniversityShanghai 200433China Department of Pharmacology Second Military Medical University/Naval Medical UniversityShanghai 200433China

BACKGROUND In recent years,the incidence of colorectal cancer(CRC)has been *** the popularization of endoscopic technology,a number of early CRC has been ***,despite current treatment methods,some patients with early CRC still experience postoperative recurrence and *** To search for indicators associated with early CRC recurrence and metastasis to identify high-risk *** A total of 513 patients with pT2N0M0 or pT3N0M0 CRC were retrospectively enrolled in this *** of blood routine test,liver and kidney function tests and tumor markers were collected before *** were followed up through disease-specific database and telephone *** recurrence,metastasis or death were used as the end point of study to find the risk factors and predictive value related to early CRC recurrence and *** We comprehensively compared the predictive value of preoperative blood routine,blood biochemistry and tumor markers for disease-free survival(DFS)and overall survival(OS)of *** multivariate analysis demonstrated that low platelet count was significantly associated with poor DFS[hazard ratio(HR)=0.995,95% confidence interval(CI):0.991-0.999,P=0.015],while serum carcinoembryonic antigen(CEA)level(HR=1.008,95%CI:1.001-1.016,P=0.027)and serum total cholesterol level(HR=1.538,95%CI:1.026-2.305,P=0.037)were independent risk factors for *** cutoff value of serum CEA level for predicting OS was 2.74 ng/*** the OS of CRC patients with serum CEA higher than the cutoff value was worse than those with lower CEA level,the difference between the two groups was not statistically significant(P=0.075).CONCLUSION For patients with T2N0M0 or T3N0M0 CRC,preoperative platelet count was a protective factor for DFS,while serum CEA level was an independent risk factor for *** that these measures are easier to detect and more acceptable to patients,they may have broader applications.

关键词： Colorectal cancer Platelet count Serum carcinoembryonic antigen Total cholesterol level Overall survival Disease-free survival

Effect of Menopausal Hormone Replacement Therapy on Cytokine Patterns in a Perimenopausal Mouse Model Established by the Ovarian Castration Method

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Chinese Journal of Biomedical Engineering(English Edition) 2024年第1期33卷 40-48页

作者： HE Bin-bin ZHAng Ju-shun WAng jin-yong Longyan First Affiliated Hospital of Fujian Medical University Longyan Fujian 364000China

Objective: To investigate the effect of perimenopausal hormone replacement therapy(HRT) on cytokine patterns in a perimenopausal mouse model established by ovarian castration. Methods: The mice were divided into natural menopause group,ovariectomy group and HRT group, with 15 mice in each group, and the estrous cycle, estrous frequency and menopausal time of the mice were determined by vaginal cytology,and the estrous cycle, estrous frequency and menopausal time were compared among the three groups. The serum levels of estradiol(E2) and progesterone(P4) in each group were detected by double-antibody sandwich ELISA, and the levels of interferon gamma(IFN-γ), interleukin-2(IL-2), IL-4 and IL-10 in the spleen γ tissues of mice were detected by ELISA. Results: The time of menopause(53.07±3.99) d in the HRT group was between that of the natural menopause group(80.80±3.26) d and that of the ovariectomy group(16.27±4.35) d, with a statistically significant difference in the two-by-two comparison of the three groups(Png/L and P4(14.2 ±6.0) ng/L in the HRT therapy group are between those of the ovariectomy group and the natural menopause group, with statistically significant differences between the groups(P<0.05). The levels of IL-2(30.9±5.3) pg/ml, IL-4(9.4±1.6) pg/ml, IL-10(19.7±3.1) pg/ml, IFN-γ(22.0±3.7) pg/ml in the HRT group were all between those of natural menopause group and ovariectomy group. The Th1/Th2 ratio in the ovariectomy group was 7.55±1.57, higher than that in the natural menopause group(1.53±0.48) and HRT group(2.38 ±0.44), with statistically significant differences(P<0.05). Conclusion:Menopausal HRT can partially correct the imbalance of Th1/Th2 cytokines, which is able to provide an experimental basis for the regulation of menopause-related immune imbalance by HRT.

关键词： menopause hormone replacement therapy(HRT) ovariectomy mouse model cytokine pattern

The diagnostic value of tenascin-C in acute aortic syndrome

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Journal of Geriatric Cardiology 2024年第3期21卷 359-368页

作者： Ming MA Wei CHEN Hai-Long CAO Jun PAN Qing ZHOU Xin-Long TAng Dong-jin WAng Department of Thoracic and Cardiovascular Surgery Nanjing Drum Tower Hospital Clinical College of Nanjing Medical UniversityNanjingChina Department of Thoracic and Cardiovascular Surgery Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjingChina Department of Thoracic surgery Kunshan Hospital of Traditional Chinese MedicineJiangsuChina

OBJECTIVES Misdiagnosis of acute aortic syndrome(AAS)significantly increases ***-C(TN-C)is an extracellular matrix glycoprotein related to cardiovascular *** elevation of TN-C in AAS and whether it can discriminate suddenonset of acute chest pain in Chinese remains *** We measured the plasma concentration of TN-C by ELISA in a cohort of 376 patients with chest or back *** to discriminate AAS from acute coronary syndrome(ACS)were compared and *** From October 2016 to September 2021,376 undiagnosed patients with chest or back pain were enrolled.166 of them were finally diagnosed as AAS,100 were ACS and 110 without cardiovascular diseases(NCV).TN-C was significantly elevated in AAS at 18.18 ng/mL(IQR:13.10–27.68)compared with 7.51 ng/mL(IQR:5.67–11.38)in ACS(Png/mL(IQR:2.50–5.29)in NCV(Png the subtypes of *** the 166 AAS patients,the peaked level of TN-C was at acute stage(P=0.012),then a slight of decrease was observed at subacute *** area under receiver operating characteristic curve for AAS patients versus NCV was 0.979(95%CI:0.964-0.994)for *** a cutoff level of 11.474 ng/mL,TN-C has a sensitivity of 76.0%,specificity of 85.5%,accuracy of 82.0%,positive predictive value(PPV)of 76.0%,negative predictive value(NPV)of 85.5%.Diagnostic performance of TN-C was superior to D-dimer and *** The concentration of serum TN-C in AAS patients was significantly higher than that in ACS patients and ***-C could be a new biomarker to distinguish AAS patients in the early stage after symptoms onset from other pain diseases.

关键词： acute cardiovascular elevated

Quercetin Alleviates Lipopolysaccharide-Induced Cardiac Inflammation via Inhibiting Autophagy and Programmed Cell Death

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Biomedical and Environmental Sciences 2024年第1期37卷 54-70页

作者： YU jin Hai HU Guo Liang GUO Xiao Quan CAO Hua Bin XIA Zhao Fei AMIN Buhe Jiangxi Provincial Key Laboratory for Animal Health Institute of Animal Population HealthCollege of Animal Science and TechnologyJiangxi Agricultural UniversityNanchang 330045JiangxiChina Internal Medicine Laboratory Department of Veterinary Clinical MedicineCollege of Veterinary MedicineChina Agricultural UniversityBeijing 100091China Department of Cancer Surgery Beijing Shijitan Hospital Affiliated with Capital Medical UniversityBeijing 100038China

Objective The aim of this study is to explore the potential modulatory role of quercetin against Endotoxin or lipopolysaccharide(LPS)induced septic cardiac *** Specific pathogen-free chicken embryos(n=120)were allocated untreated control,phosphate buffer solution(PBS)vehicle,PBS with ethanol vehicle,LPS(500 ng/egg),LPS with quercetin treatment(10,20,or 40 nmol/egg,respectively),Quercetin groups(10,20,or 40 nmol/egg).Fifteenday-old embryonated eggs were inoculated with abovementioned solutions via the allantoic *** embryonic day 19,the hearts of the embryos were collected for histopathological examination,RNA extraction,real-time polymerase chain reaction,immunohistochemical investigations,and Western *** They demonstrated that the heart presented inflammatory responses after LPS *** LPS-induced higher mRNA expressions of inflammation-related factors(TLR4,TNFα,MYD88,NF-κB1,IFNγ,IL-1β,IL-8,IL-6,IL-10,p38,MMP3,and MMP9)were blocked by quercetin with three *** significantly decreased immunopositivity to TLR4 and MMP9 in the treatment group when compared with the LPS *** significantly decreased protein expressions of TLR4,IFNγ,MMP3,and MMP9 when compared with the LPS *** treatment prevented LPS-induced increase in the mRNA expression of Claudin 1 and ZO-1,and significantly decreased protein expression of claudin 1 when compared with the LPS *** significantly downregulated autophagyrelated gene expressions(PPARα,SGLT1,APOA4,AMPKα1,AMPKα2,ATG5,ATG7,Beclin-1,and LC3B)and programmed cell death(Fas,Bcl-2,CASP1,CASP12,CASP3,and RIPK1)after LPS *** significantly decreased immunopositivity to APOA4,AMPKα2,and LC3-II/LC3-I in the treatment group when compared with the LPS *** significantly decreased protein expressions of AMPKα1,LC3-I,and *** significantly decreased the protein expression to CASP1 and CASP3 by immunohistochemical investigation or

关键词： Quercetin Lipopolysaccharide Inflammation Autophagy Programmed cell death Myocardiocytes permeability

Fate of organophosphate esters from the Northwestern Pacific to the Southern Ocean:Occurrence,distribution,and fugacity model simulation

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Journal of Environmental Sciences 2024年第3期137卷 347-357页

作者： Tengda Shi Ruijing Li Jie Fu Chao Hou Hui Gao Guanjie Cheng Haibo Zhang Shuaichen jin Liang Kong Guangshui Na College of Marine Technology and Environment Dalian Ocean UniversityDalian 116023China Laboratory for coastal marine eco-environment process and carbon sink of Hainan province/Yazhou Bay Innovation Institute Hainan Tropical Ocean UniversitySanya 572022China National Marine Environmental Monitoring Center Dalian 116023China College of Marine Ecology and Environment Shanghai Ocean UniversityShanghai 201306China NCS Testing Technology Co. Ltd.Beijing 10081China

Eleven organophosphate esters(OPEs)in the air and seawater were investigated from the northwestern Pacific Ocean to the Southern Ocean during the 2018 Chinese 34th Antarctic Scientific *** concentration of total OPEs ranged from 164.82 to 3501.79 pg/m~3in air and from 4.54 to 70.09 ng/L in *** halogenated OPEs,tri(chloropropyl)phosphate(TCPP)and tri(2-chloroethyl)phosphate(TCEP),were generally more abundant than the non-halogenated OPEs.A levelⅢfugacity model was developed to simulate the transfer and fate of seven OPEs in the air and seawater regions of the central Ross *** model results indicate that OPEs are transferred from the air to the seawater in the central Ross Sea in summer,during which the Ross Sea acts as a final OPE *** and wet deposition dominated the processes involving OPE transfer to *** OPE degradation process was also found to be more pervasive in the atmosphere than in the seawater *** findings highlights the importance of long-range transport of OPEs and their air–seawater interface behavior in the Antarctic.

关键词： Organophosphate esters(OPEs) Long-range transport Fugacity model Antarctic Fate

MicroRNA-630 alleviates inflammatory reactions in rats with diabetic kidney disease by targeting toll-like receptor 4

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World Journal of Diabetes 2024年第3期15卷 488-501页

作者： Qi-Shun Wu Dan-Na Zheng Cheng Ji Hui Qian Juan jin Qiang He Graduate School Medical College of Soochow UniversitySuzhou 215006Jiangsu ProvinceChina Department of Nephrology Zhejiang Provincial People’s HospitalAffiliated People’s HospitalHangzhou 314408Zhejiang ProvinceChina Department of Nephrology Affiliated Hospital of Jiangsu UniversityZhenjiang 212001Jiangsu ProvinceChina Department of Nephrology Zhejiang Provincial People’s HospitalAffiliated People’s HospitalHangzhou Medical CollegeHangzhou 314408Zhejiang ProvinceChina Molecular Inspection Laboratory School of MedicineJiangsu UniversityZhenjiang 212000Jiangsu ProvinceChina Department of Nephrology The First Affiliated Hospital of Zhejiang Chinese Medical UniversityZhejiang Provincial Hospital of Traditional Chinese MedicineHangzhou 310060Zhejiang ProvinceChina

BACKGROUND Diabetic kidney disease(DKD)is a major complication of diabetes *** tubular epithelial cell(TEC)damage,which is strongly associated with the inflammatory response and mesenchymal trans-differentiation,plays a significant role in DKD;However,the precise molecular mechanism is *** recently identified microRNA-630(miR-630)has been hypothesized to be closely associated with cell migration,apoptosis,and ***,the association between miR-630 and DKD and the underlying mechanism remain *** To investigate how miR-630 affects TEC injury and the inflammatory response in DKD *** Streptozotocin was administered to six-week-old male rats to create a hypergly cemic diabetic *** the second week of modeling,the rats were divided into control,DKD,negative control of lentivirus,and miR-630 overexpression *** 8 wk,urine and blood samples were collected for the kidney injury assays,and renal tissues were removed for further molecular *** target gene for miR-630 was predicted using bioinformatics,and the association between miR-630 and toll-like receptor 4(TLR4)was confirmed using in vitro investigations and double luciferase reporter gene *** of miR-630 in DKD rats led to changes in body weight,renal weight index,basic blood parameters and histopathological *** The expression level of miR-630 was reduced in the kidney tissue of rats with DKD(Png quantitative reverse transcription polymerase chain *** mRNA expression level of miR-630 was significantly lower in the high-glucose(HG)and HG+mimic negative control(NC)groups than in the normal glucose(ng)group(P<0.05).In contrast,the mRNA expression level of TLR4 was significantly higher in these groups(P<0.05).However,miR-630 mRNA expression increased and TLR4 mRNA expression significantly decreased in the HG+miR-630 mimic group than in the HG

关键词： Diabetic kidney disease MicroRNA-630 Toll-like receptor 4 Mouse model Renal tubular epithelial cells damage Hyperglycemic model

Molecular Characteristics of Cephalosporin-Resistant Neisseria gonorrhoeae Strains in China:A Retrospective Study

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International Journal of Dermatology and Venereology 2024年第2期7卷 78-83页

作者： jin Zhang Xiao-Yu Zhu jing-Wei Liu Yue-Ping Yin Shao-Chun Chen Reference Laboratory for STD Control Hospital for Skin Diseases(Institute of Dermatology)Chinese Academy of Medical Sciences&Peking Union Medical CollegeNanjingJiangsu 210042China National Center for STD Control Chinese Center for Disease Control and PreventionNanjingJiangsu 210042China

Objective:An increasing level of antimicrobial resistance to extended-spectrum cephalosporins has been reported,so we conducted this study to investigate the molecular characteristics of cephalosporin resistant Neisseria gonorrhoeae(ng)strains isolated from China Gonococcal Antimicrobial Resistance Surveillance Programme(China-GRSP).Methods:In total,2,038 ng isolates were collected from the China-GRSP between 2015 and *** multiantigen sequence typing(ng-MAST),multilocus sequence typing(MLST),and ng sequence typing for antimicrobial resistance(ng-STAR)were used to determine characteristics and resistant determinants of cephalosporin-resistant *** results are described as ***:Seventy-four(3.6%)cephalosporin-resistant isolates were ***_(ST7363)was the most prevalent MLST among cefixime-resistant(CFX-R)isolates,whereas MLST_(ST7365)(n=8)in was the most prevalent sequence type among ceftriaxone-resistant(CRO-R)***-R strains were mainly associated with penA-X(n=27,44.3%),penA-XIII(n=6,9.8%),penA-XVIII(n=5,8.2%),and CRO-R strains were mainly related to penA-XVIII(n=10,25.6%),penA-43(n=9,23.1%),penA-XIII(n=7,17.9%).Conclusion:The main conclusion of this study is that the predominant cephalosporin-resistant clones in China include locally emerged and imported *** CFX-R and CRO-R strains are primarily related to penA mutations,and their predominant genotypes are *** the increase in international travel,tracking high-risk-resistant clones and identifying outbreaks and their associations with epidemiological characteristics are critical to improve public health.

关键词： gonorrhea resistance cephalosporin cefixime ceftriaxone

An Efficient Probe for Bacterial Nitroreductase Imaging and Detection Based on NanoLuc-Furimazine Bioluminescent Pair

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Chinese Journal of Chemistry 2024年第12期42卷 1373-1380页

作者： Ximeng Shi Yumeng Wang Jiaoyang Yu Yating Yang Zecheng jin Hanghang Wang Dalei Wu Wei Chen Jianming Guo Yinan Zhang Jiangsu Key LaboratoryforFunctional Substances of Chinese Medicine School of PharmacyNanjing Universityof Chinese MedicineNanjingJiangsu210023China Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization School of PharmacyNanjing University of ChineseMedicineNanjingJiangsu210023China Clinical Research Center the Second Hospital of NanjingAffiliated Hospital to Nanjing University of Chinese MedicineNanjingJiangsu210003China Key Laboratory of Resources Biology and Biotechnology in Western China Ministry of EducationCollege of Life SciencesNorthwestUniversityXi'anShaanxi710069China Helmholtz International Lab State Key Laboratoryof Microbial TechnologyShandong UniversityQingdaoShandong 266237China

Comprehensive SummaryThe detection of critical endogenous species, such as bacteria in microenvironments in the body, requires better imaging tools for visualization and monitoring of biological events. Bioluminescence imaging is the most popular strategy for obtaining real-time in living cells and organisms. Herein, we introduced a nitroaryl group on the C-3 position and a hydroxy group at the C-6 phenyl ring on furimazine to report the first bioluminescent probe (7) based on NanoLuc-furimazine bioluminescent pair for the detection of nitroreductase in bacteria. The probe, which possessed up to 560-fold intensity increase with a low detection limit of 16 ng/mL of nitroreductase, has the most efficient uncage efficiency in comparison with other bioluminescent congeners, thus enabling highly selective and sensitive visualization of NTR activity in a panel of clinical priority pathogens. Additionally, imaging of the recombinant strain as well as the NTR from mouse feces indicated the potential of this probe in the application of different mouse disease models.

关键词： Nitroreductase NanoLuc-furimazine Biosensors Analytical methods Luminescence Imaging agents