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A Defective CXCL16/CXCR6 Axis Increases the Risk of Pregnancy Loss via the Abnormal Crosstalk between Decidual γδ T Cells and Trophoblasts

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Reproductive and Developmental Medicine 2021年第3期5卷 129-139页

作者： Deng-Xuan Fan Ming-Qing Li Wen-Jie Zhou hong-lan huang Hui-Li Yang Cong-Jian Xu Department of Gynecology Obstetrics and Gynecology HospitalFudan UniversityShanghai 200011China Department of Obstetrics and Gynecology of Shanghai Medical School Fudan UniversityShanghai200011China Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases Fudan UniversityShanghai200011China NHC Key Lab of Reproduction Regulation(Shanghai Institute of Planned Parenthood Research) Hospital of Obstetrics and GynecologyFudan UniversityShanghai200080China Department of Obstetrics and Gynecology Reproductive Medical CenterRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai200025China

Objective::The maternal-fetal interface undergoes dynamic changes to allow the fetus to grow and develop in the *** interaction between decidualγδT cells and trophoblasts plays a pivotal role during successful pregnancy;however,their physiological functions in early-term human pregnancy are still not completely *** study was undertaken to illustrate the functional roles of CXCL16/CXCR6 to prevent pregnancy loss via the crosstalk between decidualγδT cells and HTR8/SVneo trophoblast ***::The percentile of CXCR6+γδT cells in the peripheral blood from normal female and recurrent spontaneous abortion(RSA)patients was analyzed by flow *** expression of CXCR6 was detected in decidual immune cells via flow cytometry,and the expression of CXCL16 was analyzed in HTR8/SVneo trophoblast cells and lentivirus(LV)-HTR8/SVneo trophoblast cells via enzyme-linked immunosorbent *** transcriptase-polymerase chain reaction was used to verify the expression of the CXCL16 gene in LV-HTR8/SVneo trophoblast *** of granzyme B and cytokines and proliferation of decidualγδT cocultured with HTR8/SVneo trophoblast cells were analyzed by flow *** of HTR8/SVneo trophoblast cells was assessed via Matrigel transwell *** transfer was induced in vivo further to illustrate that the normal expression of CXCL16/CXCR6 could prevent pregnancy ***::The percentile of CXCR6+γδT cells in the peripheral blood from RSA patients was lower than normal *** expression of CXCR6 was highest in the decidualγδT cells among decidual immune cells,and the expression of CXCL16 increased as the amount of HTR8/SVneo trophoblast cells *** of granzyme B in the decidualγδT cells was downregulated by cocultured with HTR8/SVneo cells dependent of CXCL16,and HTR8/SVneo trophoblast cells induced the Th2 cytokines production in the decidualγδT *** the expression of CXCR6 in the decidualγδT cells and pr

关键词： CXCL16 CXCR6 DecidualγδT Cells Maternal-fetal Interface Recurrent Spontaneous Abortion Trophoblasts

Cobalamin-dependent radical S-adenosyl-L-methionine protein functions with a partner to successively methylate tricyclic indole alkaloid for chuangxinmycin maturation and derivatization

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Science China Chemistry 2025年第1期68卷 308-316页

作者： Sili Wang Jiancheng huang Yanan Du Wei huang Yufeng Xue Xiaokun Xu Guannan Zhong Yuanyuan Shi Bin hong Xiaoying Bian Wen Liu State Key Laboratory of Chemical Biology Shanghai Institute of Organic Chemistry University of Chinese Academy of SciencesChinese Academy of Sciences State Key Laboratory of Microbial Technology Shandong University National Health Commission (NHC) Key Laboratory of Biotechnology for Microbial Drugs Institute of Medicinal BiotechnologyChinese Academy of Medical Science & Peking Union Medical College

Cobalamin(Cbl)-dependent radical S-adenosyl-L-methionine(SAM) proteins constitute the largest collection of the radical SAM superfamily that has hundreds of thousands of individual members. Many of these proteins are involved in the biosynthesis of pharmaceutically important natural products to catalyze chemically demanding reactions. In the biosynthetic pathway of chuangxinmycin(CXM), a unique indole alkaloid antibiotic with potent anti-infective activity, functionalization of the characteristic thiopyrano[4,3,2-cd]indole scaffold by regio-and stereoselective C3-methylation is believed to rely on a Cbl-dependent radical process, which, however, remained to be reconstituted biochemically. We here report the dissection of this enzymatic process, which requires the incorporation of Cxm8, a Cbl-dependent radical SAM protein, with Cxm9, a DUF5825family protein that shares no homology to any proteins of known functions. Cxm8 and Cxm9 function together by forming an unexpected heterodimeric complex that selectively catalyzes C3-methylation of the tricyclic indole-S-hetero ring system in a successive manner, achieving CXM and a recently identified, C3-dimethylated congener. Detailed biochemical characterization,isotope labeling, structural simulation and bioinformatics analysis rationalized the catalysis of the Cxm8/Cxm9 complex and particularly the necessity of the DUF5825 protein for C3-methylase activity. This is the first example that a Cbl-dependent protein acts with a partner to exhibit radical SAM activity.

关键词： cbl-dependent radical SAM protein biosynthesis chuangxinmycin stereoselective methylation

PD-YOLO:Colon Polyp Detection Model Based on Enhanced Small-Target Feature Extraction

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Computers, Materials & Continua 2025年第1期82卷 913-928页

作者： Yicong Yu Kaixin Lin Jiajun hong Rong-Guei Tsai Yuanzhi huang New Engineering Industry College Putian UniversityPutian351100China Engineering Research Center of Big Data Application in Private Health Medicine(Putian University) Fujian Province UniversityPutian351100China Computer College Guangdong University of Science&TechnologyDongguan523668China

In recent years,the number of patientswith colon disease has increased *** polyps are the precursor lesions of colon *** not diagnosed in time,they can easily develop into colon cancer,posing a serious threat to patients’lives and health.A colonoscopy is an important means of detecting colon ***,in polyp imaging,due to the large differences and diverse types of polyps in size,shape,color,etc.,traditional detection methods face the problem of high false positive rates,which creates problems for doctors during the diagnosis *** order to improve the accuracy and efficiency of colon polyp detection,this question proposes a network model suitable for colon polyp detection(PD-YOLO).This method introduces the self-attention mechanism CBAM(Convolutional Block Attention Module)in the backbone layer based on YOLOv7,allowing themodel to adaptively focus on key information and ignore the unimportant *** help themodel do a better job of polyp localization and bounding box regression,add the SPD-Conv(Symmetric Positive Definite Convolution)module to the neck layer and use deconvolution instead of *** results indicate that the PD-YOLO algorithm demonstrates strong robustness in colon polyp *** to the original YOLOv7,on the Kvasir-SEG dataset,PD-YOLO has shown an increase of 5.44 percentage points in AP@0.5,showcasing significant advantages over other mainstream methods.

关键词： Polyp detection YOLOv7 SPD-Conv CBAM deconvolution

AZD1775 synergizes with SLC7A11 inhibition to promote ferroptosis

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Science China Life Sciences 2025年第1期68卷 204-218页

作者： Chen Xiong hong Ling Yingdan huang Hanzhi Dong Bangxiang Xie Qian Hao Xiang Zhou Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences Fudan University Department of Oncology Shanghai Medical CollegeFudan University Department of Breast Surgery Fudan University Shanghai Cancer CenterFudan University Department of Oncology First Affiliated Hospital of Nanchang University Beijing Institute of Hepatology Beijing Youan HospitalCapital Medical University Beijing Engineering Research Center for Precision Medicine and Transformation of Hepatitis and Liver Cancer Key Laboratory of Breast Cancer in Shanghai Fudan University Shanghai Cancer CenterFudan University Shanghai Key Laboratory of Medical Epigenetics International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology)Institutes of Biomedical SciencesFudan University

Tumor suppressor p53-mediated cell cycle arrest and DNA damage repair may exert cytoprotective effects against cancer therapies, including WEE1 inhibition. Considering that p53 activation can also lead to multiple types of cell death, the role of this tumor suppressor in WEE1 inhibitor-based therapies remains disputed. In this study, we reported that nucleolar stress-mediated p53 activation enhanced the WEE1 inhibitor AZD1775-induced ferroptosis to suppress lung cancer growth. Our findings showed that AZD1775 promoted ferroptosis by blocking cystine uptake, an action similar to that of Erastin. Meanwhile, inhibition of WEE1 by the WEE1 inhibitors or si RNAs induced compensatory upregulation of SLC7A11, which conferred resistance to ferroptosis. Mechanistically, AZD1775 prevented the enrichment of H3K9me3, a histone marker of transcriptional repression, on the SLC7A11 promoter by repressing the expression of the histone methyltransferase SETDB1, thereby enhancing NRF2-mediated SLC7A11 transcription. This finding was also validated using the H3K9me3 inhibitor BRD4770. Remarkably, we found that the nucleolar stress-inducing agent Actinomycin D(Act. D) inhibited SLC7A11 expression by activating p53, thus augmenting AZD1775-induced ferroptosis. Moreover, the combination of AZD1775 and Act. D synergistically suppressed wild-type p53-harboring lung cancer cell growth both in vitro and in vivo. Altogether, our study demonstrates that AZD1775 promotes ferroptosis by targeting cystine uptake but also mediates the adaptive activation of SLC7A11 through the WEE1-SETDB1 cascade and NRF2-induced transcription, and inhibition of SLC7A11 by Act. D boosts the anti-tumor efficacy of AZD1775 by enhancing ferroptosis in cancers with wild-type p53.

关键词： p53 NRF2 SLC7A11 WEE1 AZD1775 ferroptosis nucleolar stress

Overexpression of low-density lipoprotein receptor prevents neurotoxic polarization of astrocytes via inhibiting NLRP3 inflammasome activation in experimental ischemic stroke

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Neural Regeneration Research 2025年第2期20卷 491-502页

作者： Shuai Feng Juanji Li Tingting Liu Shiqi huang Xiangliang Chen Shen Liu Junshan Zhou hongdong Zhao Ye hong Department of Neurology Nanjing First HospitalNanjing Medical UniversityNanjingJiangsu ProvinceChina Department of Neurology Nanjing Jinling HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjingJiangsu ProvinceChina

Neurotoxic astrocytes are a promising therapeutic target for the attenuation of cerebral ischemia/reperfusion ***-density lipoprotein receptor,a classic cholesterol regulatory receptor,has been found to inhibit NLR family pyrin domain containing protein 3(NLRP3)inflammasome activation in neurons following ischemic stroke and to suppress the activation of microglia and astrocytes in individuals with Alzheimer’s ***,little is known about the effects of low-density lipoprotein receptor on astrocytic activation in ischemic *** address this issue in the present study,we examined the mechanisms by which low-density lipoprotein receptor regulates astrocytic polarization in ischemic stroke ***,we examined low-density lipoprotein receptor expression in astrocytes via immunofluorescence staining and western blotting *** observed significant downregulation of low-density lipoprotein receptor following middle cerebral artery occlusion reperfusion and oxygen-glucose deprivation/***,we induced the astrocyte-specific overexpression of low-density lipoprotein receptor using astrocyte-specific adeno-associated ***-density lipoprotein receptor overexpression in astrocytes improved neurological outcomes in middle cerebral artery occlusion mice and reversed neurotoxic astrocytes to create a neuroprotective ***,we found that the overexpression of low-density lipoprotein receptor inhibited NLRP3 inflammasome activation in oxygen-glucose deprivation/reoxygenation injured astrocytes and that the addition of nigericin,an NLRP3 agonist,restored the neurotoxic astrocyte *** findings suggest that low-density lipoprotein receptor could inhibit the NLRP3-meidiated neurotoxic polarization of astrocytes and that increasing low-density lipoprotein receptor in astrocytes might represent a novel strategy for treating cerebral ischemic stroke.

关键词： inflammation ischemia/reperfusion injury ischemic stroke low-density lipoprotein receptor neuroprotective astrocytes neurotoxic astrocytes NLRP3 inflammasome polarization

氯氟乙酯(21例)和地西泮(22例)治疗焦虑障碍的疗效和安全性比较

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中国新药与临床杂志 2004年第11期23卷 778-780页

作者：舒良张鸿燕黄兰北京大学精神卫生研究所北京100083

目的 :评价氯氟乙酯与地西泮治疗焦虑障碍的疗效和安全性。方法 :采用双盲、双模拟、随机、平行对照研究。完成 4wk治疗的病人共 4 3例。其中试验组 (氯氟乙酯组 ) 2 1例于早、午餐后服氯氟乙酯安慰剂及地西泮安慰剂各 1片 ,晚餐... 详细信息

目的 :评价氯氟乙酯与地西泮治疗焦虑障碍的疗效和安全性。方法 :采用双盲、双模拟、随机、平行对照研究。完成 4wk治疗的病人共 4 3例。其中试验组 (氯氟乙酯组 ) 2 1例于早、午餐后服氯氟乙酯安慰剂及地西泮安慰剂各 1片 ,晚餐后服氯氟乙酯 2mg及地西泮安慰剂各 1片 ,对照组(地西泮组 ) 2 2例于早、午、晚餐后服氯氟乙酯安慰剂及地西泮 2 .5mg各 1片 ,疗程均为 4wk。结果 :治疗 4wk后 ,试验组的HAMA总分显著降低 ,HAMA减分率达 (6 6± 10 ) % ,临床总有效率达95 % ,与对照组相比无显著意义 (P >0 .0 5 )。试验组的不良反应的发生率为 14 % ,与对照组相比无显著意义 (P >0 .0 5 )。结论 :氯氟乙酯治疗焦虑障碍有明显疗效 ,无明显不良反应。

关键词：地西泮药物评价焦虑障碍随机对照试验双盲法氯氟(zhuo)乙酯

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三阴交主治演变考

上海针灸杂志 2002年第4期21卷 45-46页

作者：艾红兰中国中医研究院针灸研究所文献室北京100700

目的与方法　考察三阴交穴主治的形成及演变。结果与结论　通过文献考证发现 ,三阴交穴主治在演变过程中出现了一些失误 ,并简要分析了导致失误的原因。

关键词：三阴交穴文献研究经穴主治《针灸聚英》《外台秘要方·明堂》《太平圣惠方》

Quickly obtaining densely dispersed coherent particles in steel matrix and its related mechanical property

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International Journal of Minerals,Metallurgy and Materials 2025年第1期32卷 111-118页

作者： Xiaoxiao Wang Qingsong huang School of Chemical Engineering Sichuan UniversityChengdu 610065China

Densely distributed coherent nanoparticles(DCN)in steel matrix can enhance the work-hardening ability and ductility of steel *** the routes to this end can be generally classified into the liquid-solid route and the solid-solid ***,the formation of DCN structures in steel requires long processes and complex *** far,obtaining steel with coherent particle enhancement in a short time remains a bottleneck,and some necessary steps remain ***,we show a high-efficiency liquid-phase refining process reinforced by a dynamic magnetic ***-Y-Mn-O particles had an average size of around(3.53±1.21)nm and can be obtained in just around 180 *** small nanoparticles were coherent with the matrix,implying no accumulated dislocations between the particles and the steel *** findings have a potential application for improving material machining capacity,creep resistance,and radiation resistance.

关键词： ferritic steels coherent particles microstructure compression test work hardening

Kruppel-like factor 4 promotes differentiation of endothelial progenitor cells into endothelial cells by up-regulating endothelial nitric oxide synthase

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Kruppel-like factor 4 promotes differentiation of endothelia...