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N-acetylcysteine ameliorates erectile dysfunction in rats with hyperlipidemia by inhibiting oxidative stress and corpus cavernosum smooth muscle cells phenotypic modulation

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Asian Journal of Andrology 2024年第1期26卷 99-106页

作者： Wei Ding Jun-Hong Fan Li-Ren Zhong Nan-Xiong Wang lu-Hao Liu Hai-Bo Zhang Li Wang ming-Qiang Wang Bing-Lin He An-Yang Wei Department of Urology The First Affiliated Hospital of Guizhou University of Traditional Chinese MedicineGuiyang 550002China Department of Urology Guangdong Provincial People's HospitalGuangdong Academy of Medical SciencesGuangzhou 510000China Department of Urology Nanfang HospitalSouthern Medical UniversityGuangzhou 510000China Department of Urology Shenzhen Immigration Inspection General Station HospitalShenzhen 518000China Department of Organ Transplantation The Second Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510000China Department of Endocrinology The First Affiliated Hospital of Guizhou University of Traditional Chinese MedicineGuiyang 550002China

Hyperlipidemia is a major risk factor for erectile dysfunction(ED).Oxidative stress and phenotypic modulation of corpus cavernosum smooth muscle cells(CcSMCs)are the key pathological factors of ED.N-acetylcysteine(NAC)can inhibit oxidative stress;however,whether NAc can alleviate pathological variations in the corpus cavernosum and promote erectile function recovery in hyperlipidemic rats remains unclear.A hyperlipidemia model was established using 27 eight-week-old male Sprague-Dawley(SD)rats fed a high-fat and high-cholesterol diet(hyperlipidemic rats,HR).In addition,9 male SD rats were fed a normal diet to serve as controls(NC).HR rats were divided into three groups:HR,HR+normal saline(NS),and HR+NAC(n=9 for each group;NS or NAc intraperitoneal injections were administered daily for 16 weeks).Subsequently,the lipid profiles,erectile function,oxidative stress,phenotypic modulation markers of ccsMCs,and tissue histology were analyzed.The experimental results revealed that erectile function was significantly impaired in the HR and HR+NS groups,but enhanced in the HR+NAC group.Abnormal lipid levels,over-activated oxidative stress,and multi-organ lesions observed in the HR and HR+NS groups were improved in the HR+NAC group.Moreover,the HR group showed significant phenotypic modulation of CCSMCs,which was also inhibited by NAC treatment.This report focuses on the therapeutic effect of NAc in restoring erectile function using a hyperlipidemic rat model by preventing CcSMC phenotypic modulationand attenuating oxidativestress.

关键词： erectile dysfunction hyperlipidemia N-acetylcysteine oxidative stress henotypic modulation

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Molecular features of gastroenteropancreatic neuroendocrine carcinoma: A comparative analysis with lung neuroendocrine carcinoma and digestive adenocarcinomas

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Chinese Journal of Cancer Research 2024年第1期36卷 90-102页

作者： Jianwei Zhang Hanxiao Chen Junli Zhang Sha Wang Yanfang Guan Wenguang Gu Jie Li Xiaotian Zhang Jian Li Xicheng Wang Zhihao lu Jun Zhou Zhi Peng Yu Sun Yang Shao Lin Shen minglei Zhuo ming lu Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of Gastrointestinal OncologyPeking University Cancer Hospital&InstituteBeijing 100142China Department of Radiation Therapy National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital&Shenzhen HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeShenzhen 518172China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department I of Thoracic OncologyPeking University Cancer Hospital&InstituteBeijing 100142China Medical Department Nanjing Geneseeq Technology Inc.Nanjing 210061China Geneplus-Beijing Beijing 102200China State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchDepartment of Gastrointestinal OncologyPeking University Cancer Hospital&InstituteBeijing 100142China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of PathologyPeking University Cancer Hospital&InstituteBeijing 100142China

Objective: There is an ongoing debate about whether the management of gastroenteropancreatic(GEP)neuroendocrine carcinoma(NEC) should follow the guidelines of small-cell lung cancer(SCLC). We aim to identify the genetic differences of GEPNEC and its counterpart.Methods: We recruited GEPNEC patients as the main cohort, with lung NEC and digestive adenocarcinomas as comparative cohorts. All patients undergone next-generation sequencing(NGS). Different gene alterations were compared and analyzed between GEPNEC and lung NEC(LNEC), GEPNEC and adenocarcinoma to yield the remarkable genes.Results: We recruited 257 patients, including 99 GEPNEC, 57 LNEC, and 101 digestive adenocarcinomas.Among the mutations, KRAS, RB1, TERT, IL7R, and CTNNB1 were found to have different gene alterations between GEPNEC and LNEC samples. Specific genes for each site were revealed: gastric NEC(TERT amplification),colorectal NEC(KRAS mutation), and bile tract NEC(ARID1A mutation). The gene disparities between small-cell NEC(SCNEC) and large-cell NEC(LCNEC) were KEAP1 and CDH1. Digestive adenocarcinoma was also compared with GEPNEC and suggested RB1, APC, and KRAS as significant genes. The TP53/RB1 mutation pattern was associated with first-line effectiveness. Putative targetable genes and biomarkers in GEPNEC were identified in22.2% of the patients, and they had longer progression-free survival(PFS) upon targetable treatment [12.5 months vs. 3.0 months, HR=0.40(0.21-0.75), P=0.006].Conclusions: This work demonstrated striking gene distinctions in GEPNEC compared with LNEC and adenocarcinoma and their clinical utility.

关键词： Neuroendocrine carcinoma gastroenteropancreatic lung genetic alterations molecular markers

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Prioritization of risk genes in colorectal cancer by integrative analysis of multi-omics data and gene networks

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Science China(Life Sciences) 2024年第1期67卷 132-148页

作者： ming Zhang Xiaoyang Wang Nan Yang Xu Zhu Zequn lu Yimin Cai Bin Li Ying Zhu Xiangpan Li Yongchang Wei Shaokai Zhang Jianbo Tian Xiaoping Miao Department of Epidemiology and Biostatistics School of Public HealthDepartment of Gastrointestinal OncologyZhongnan Hospital of Wuhan UniversityDepartment of Radiation OncologyRenmin Hospital of Wuhan UniversityTaiKang Center for Life and Medical SciencesWuhan UniversityWuhan 430071China Research Center of Public Health Renmin hospital of Wuhan UniversityWuhan UniversityWuhan 430060China Department of Cancer Epidemiology The Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer HospitalHenan Engineering Research Center of Cancer Prevention and ControlHenan International Joint Laboratory of Cancer PreventionZhengzhou 450008China Department of Gastrointestinal Surgery Renmin Hospital of Wuhan UniversityWuhan 430060China Department of Radiation Oncology Renmin Hospital of Wuhan UniversityWuhan 430060China Department of Gastrointestinal Oncology Hubei Cancer Clinical Study CenterZhongnan Hospital of Wuhan UniversityWuhan 430062China Department of Epidemiology and Biostatistics School of Public HealthTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430073China Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine Nanjing Medical UniversityNanjing 211166China

Genome-wide association studies(GWASs)have identified over 140 colorectal cancer(CRC)-associated loci;however,target genes at the majority of loci and underlying molecular mechanisms are poorly understood.Here,we utilized a Bayesian approach,integrative risk gene selector(iRIGS),to prioritize risk genes at CRC GWAS loci by integrating multi-omics data.As a result,a total of 105 high-confidence risk genes(HRGs)were identified,which exhibited strong gene dependencies for CRC and enrichment in the biological processes implicated in CRC.Among the 105 HRGs,CEBPB,located at the 20q13.13 locus,acted as a transcription factor playing critical roles in cancer.Our subsequent assays indicated the tumor promoter function of CEBPB that facilitated CRC cell proliferation by regulating multiple oncogenic pathways such as MAPK,PI3K-Akt,and Ras signaling.Next,by integrating a fine-mapping analysis and three independent case-control studies in Chinese populations consisting of 8,039 cases and 12,775 controls,we elucidated that rs1810503,a putative functional variant regulating CEBPB,was associated with CRC risk(OR=0.90,95%CI=0.86–0.93,P=1.07×10^(−7)).The association between rs1810503 and CRC risk was further validated in three additional multi-ancestry populations consisting of 24,254 cases and 58,741 controls.Mechanistically,the rs1810503 A to T allele change weakened the enhancer activity in an allele-specific manner to decrease CEBPB expression via longrange promoter-enhancer interactions,mediated by the transcription factor,REST,and thus decreased CRC risk.In summary,our study provides a genetic resource and a generalizable strategy for CRC etiology investigation,and highlights the biological implications of CEBPB in CRC tumorigenesis,shedding new light on the etiology of CRC.

关键词： susceptibility genes gene screening models multi-omics GWAS CEBPB long-range promoter-enhancer interactions

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An improved initial rotor position estimation method using high-frequency pulsating voltage injection for PMSM

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Defence Technology（防务技术） 2024年第3期33卷 19-29页

作者： Yang Jiang ming Cheng School of Electrical Engineering Southeast UniversityNanjing 210096China

High frequency pulsating voltage injection method is a good candidate for detecting the initial rotor position of permanent magnet synchronous motor.However,traditional methods require a large number of filters,which leads to the deterioration of system stability and dynamic performance.In order to solve these problems,a new signal demodulation method is proposed in this paper.The proposed new method can directly obtain the amplitude of high-frequency current,thus eliminating the use of filters,improving system stability and dynamic performance and saving the work of adjusting filter parameters.In addition,a new magnetic polarity detection method is proposed,which is robust to current measurement noise.Finally,experiments verify the effectiveness of the method.

关键词： Initial position detection Signal demodulation algorithm Magnetic polarity detection Filter elimination

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A Deep Learning Method for Computing Eigenvalues of the Fractional Schrödinger Operator

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Journal of Systems Science & Complexity 2024年第2期37卷 391-412页

作者： GUO Yixiao ming Pingbing LSEC Institute of Computational Mathematics and Scientific/Engineering ComputingAcademy of Mathematics and Systems ScienceChinese Academy of SciencesBeijing 100190China School of Mathematical Sciences University of Chinese Academy of SciencesBeijing 100049China

The authors present a novel deep learning method for computing eigenvalues of the fractional Schrödinger operator.The proposed approach combines a newly developed loss function with an innovative neural network architecture that incorporates prior knowledge of the problem.These improvements enable the proposed method to handle both high-dimensional problems and problems posed on irregular bounded domains.The authors successfully compute up to the first 30 eigenvalues for various fractional Schrödinger operators.As an application,the authors share a conjecture to the fractional order isospectral problem that has not yet been studied.

关键词： Eigenvalue problem deep learning fractional Schrödinger operator isospectral problem

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Endophthalmitis in silicone oil-filled eye: A case report

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World Journal of Clinical Cases 2024年第1期12卷 163-168页

作者： Hui-Chao Yan Ze-lu Wang Wen-Zhen Yu ming-Wei Zhao Jian-Hong Liang Hong Yin Xuan Shi Heng Miao Department of Ophthalmology Peking University People’s HospitalBeijing 100044China

BACKGROUND Endophthalmitis occurring in silicone oil-filled eyes is a very rare occurrence,with reported incidence rates ranging between 0.07%and 0.039%.Traditional methods of management of infectious endophthalmitis include the removal of silicone oil,washout of the vitreous cavity,administration of intravitreal antibiotics,and reinjection of silicone oil.CASE SUMMARY Herein,we report the case of a 39-year-old man with unilateral endophthalmitis after pars plana vitrectomy and silicone oil tamponade.Intravitreal injections of full-dose antibiotics and anterior chamber washout were used to treat the patient.No signs of retinal toxicity were observed during the follow-up period.CONCluSION Intravitreal full-dose antibiotic injections and anterior chamber washout are promising alternatives to traditional therapies for endophthalmitis in silicone oilfilled eyes.

关键词： Endophthalmitis Intravitreal injection Silicone oil-filled eye Pars plana vitrectomy Washout Case report

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Relationship between Phenotypic Changes of Dendritic Cell Subsets and the Onset of Plateau Phase during Intermittent Interferon Therapy in Patients with CHB

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Biomedical and Environmental Sciences 2024年第3期37卷 303-314页

作者： YANG Liu WANG Shi Yu JIANG Ting Ting DENG Wen CHANG Min WU Shu Ling CAO Wei Hua lu Yao SHEN Ge LIU Ru Yu GAO Yuan Jiao XU Meng Jiao HU Lei Ping ZHANG lu XIE Yao LI ming Hui Department of Hepatology Division 2 Beijing Ditan HospitalCapital Medical UniversityBeijing 100015China Center for Infectious Diseases Second Affiliated Hospital of Air Force Medical UniversityXi'an 710038ShaanxiChina Department of Hepatology Division 2 Peking University Ditan Teaching HospitalBeijing 100015China

Objective This study aimed to evaluate whether the onset of the plateau phase of slow hepatitis B surface antigen decline in patients with chronic hepatitis B treated with intermittent interferon therapy is related to the frequency of dendritic cell subsets and expression of the costimulatory molecules CD40,CD80,CD83,and CD86.Method This was a cross-sectional study in which patients were divided into a natural history group(namely NH group),a long-term oral nucleoside analogs treatment group(namely NA group),and a plateau-arriving group(namely P group).The percentage of plasmacytoid dendritic cell and myeloid dendritic cell subsets in peripheral blood lymphocytes and monocytes and the mean fluorescence intensity of their surface costimulatory molecules were detected using a flow cytometer.Results In total,143 patients were enrolled(NH group,n=49;NA group,n=47;P group,n=47).The results demonstrated that CD141/CD1c double negative myeloid dendritic cell(DNmDC)/lymphocytes and monocytes(%)in P group(0.041[0.024,0.069])was significantly lower than that in NH group(0.270[0.135,0.407])and NA group(0.273[0.150,0.443]),and CD86 mean fluorescence intensity of DNmDCs in P group(1832.0[1484.0,2793.0])was significantly lower than that in NH group(4316.0[2958.0,5169.0])and NA group(3299.0[2534.0,4371.0]),Adjusted P alllusion Reduced DNmDCs and impaired maturation may be associated with the onset of the plateau phase during intermittent interferon therapy in patients with chronic hepatitis B.

关键词： CHB Dendritic Cells Intermittent Interferon Therapy Plateau Phase

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Flexible MXene/sodium alginate composite fabric with high structural stability and oxidation resistance for electromagnetic interference shielding

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Nano Research 2024年第6期17卷 5326-5335页

作者： Hao-Wen Zhang lu-Yao Yang Meng-Lin huang ming-Hua Cheng Zhe-Sheng Feng Fanbin Meng Zifeng Lin Yan Wang School of Materials and Energy University of Electronic Science and Technology of ChinaChengdu 610054China Laboratory of Advanced Technologies of Materials(Ministry of Education) School of Materials Science and EngineeringSouthwest Jiaotong UniversityChengdu 610031China College of Materials Science and Engineering Sichuan UniversityChengdu 610065China

Wearable electromagnetic interference(EMI)shielding fabrics with excellent electromagnetic shielding performance,oxidation resistance,and structural stability are highly demanded for the rapid development of electronic devices and wireless communication.MXenes are metallic conductive materials with exceptional EMI shielding properties,but they are prone to oxidation in air and have poor structural stability and durability on fabric substrates.Herein,we present a one-step assembly method to fabricate fabrics coated with MXenes and polymeric sodium alginate(SA)composite(MXene-SA).SA protects MXenes from oxidation and forms a stable interlayer structure by bonding to MXenes.The MXene-SA coated fabrics are breathable and flexible,and have a low sheet resistance of 2.12±0.08Ω/sq and a high EMI shielding performance of 37.05 dB at X-band,which is comparable to the best 42.31 dB.Moreover,the MXene-SA coated fabrics exhibit high structural stability and oxidation resistance under various conditions of sonication disintegration,mechanical abuse,chemical corrosion,and humidity,compared to pure MXenes coated fabrics.We believe that the wearable and high-performance MXene-SA fabrics have great potential for the next generation of ultra-portable and wearable EMI shielding products.

关键词： MXenes electromagnetic interference shielding fabric one-step assembly

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Protective effects and microarray-based mechanism of sea cucumber hydrolysates against high-glucose induced nephrotoxicity in mouse glomerulus mesangial cells

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未来食品学报(英文) 2024年第3期4卷 233-240页

作者： Lingxin Geng Jiaojiao Han Jun Zhou Ye Li Tinghong ming Zhen Zhang Chenyang lu Xiurong Su State Key Laboratory for Quality and Safety of Argo-products School of Marine ScienceNingbo UniversityNingbo 315211China

Diabetic nephropathy(DN)is a common type of end-stage renal disease and glomerular mesangial cells(GMCs)are widely used as a cell model for DN.This study firstly investigated the inhibitory effects of the Apostichopus japonicus and Acaudina leucoprocta hydrolysates on cellular growth under high-glucose treatment,better inhibitory effect of A.japonicus hydrolysate was observed compared to that of A.leucoprocta hydrolysate.Subsequently,the global transcription profiles obtained via microarray analysis showed that 6070 and 7015 genes were identified in the A.japonicus and A.leucoprocta groups compared with the model group,respectively.Among them,transcriptions of the slc30a4,slc35dl,tppp3,tp53inpl,bcl-2,apafl,alox12b and adrala genes were restored from the levels of the model group to those of the control group,contributed to cell mitosis and proliferation in both treatment groups.In addition,other apoptosis-related genes,such as bcl-6,clu,foxo3 and akt,showed opposite trends between two groups,which might cause the difference in inhibitory effect.We preliminarily proposed that the regulation effects of A.japonicus and A.leucoprocta on the genes involved in cellular mitosis,proliferation and apoptosis,might contribute to their inhibitory activity on GMCs under high-glucose environment.

关键词： Diabetic nephropathy Apostichopus japonicus Acaudina leucoprocta Hydrolysate Rat mesangial cell Microarray

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富营养化湖泊藻华腐解产生的溶解性有机质动态变化及其环境效应

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环境科学 2024年第3期45卷 1539-1552页

作者：张瑾陈明滢郝智能钟寰何欢雷沛南京大学环境学院污染控制与资源化研究国家重点实验室南京210023 南京师范大学环境学院南京210023 中国科学院生态环境研究中心环境化学与生态毒理学国家重点实验室北京100085 中国科学院大学北京100049 中国科学院生态环境研究中心环境水质学国家重点实验室北京100085

富营养化和有害藻华是湖泊面临的主要环境问题,富营养化湖泊藻华在后期会发生衰亡和腐解并产生大量藻源溶解性有机质(DOM),影响水体DOM的质量和活性,并对关键元素的生物地球化学循环产生重要调控作用.为探究不同富营养化程度湖泊水体藻... 详细信息

富营养化和有害藻华是湖泊面临的主要环境问题,富营养化湖泊藻华在后期会发生衰亡和腐解并产生大量藻源溶解性有机质(DOM),影响水体DOM的质量和活性,并对关键元素的生物地球化学循环产生重要调控作用.为探究不同富营养化程度湖泊水体藻华腐解过程,对藻华腐解过程中水体DOM总量、生物有效性、相对分子质量和组分的动态变化进行分析,并探讨了藻华腐解引发的环境效应.结果表明,藻华腐解显著提高DOM浓度、生物有效性和各荧光组分强度.随着腐解的进行,DOM浓度逐渐降低,而相对分子质量逐渐增大.在分子水平上,超高分辨率质谱结果显示腐解过程中不饱和烃和脂肪族化合物优先被微生物利用,并生成木质素、缩合烃和高O/C值的单宁酸等惰性分子.藻华腐解过程中细菌群落主要优势种从变形菌门(46%)逐渐变为拟杆菌门(42%).此外,藻华腐解还导致水体CO_(2)和CH_(4)排放显著升高1.2~5倍,且排放量可以由DOM光学指标a254预测.该结果为全面揭示藻华腐解过程中DOM特征的动态变化,以及湖泊富营养化治理和环境效应预测提供理论依据和科学支撑.

关键词：溶解性有机质生物有效性相对分子质量藻华腐解温室气体

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