1.Alamandine inhibits pathological retinal neovascularization by targeting the MrgD-mediated HIF-1α/VEGF pathway.
Kun ZHAO ; Yaping JIANG ; Wen HUANG ; Yukang MAO ; Yihui CHEN ; Peng LI ; Chuanxi YANG
Journal of Zhejiang University. Science. B 2025;26(10):1015-1036
Retinopathy of prematurity (ROP) is a vision-threatening disorder that leads to pathological growth of the retinal vasculature due to hypoxia. Here, we investigated the potential effects of alamandine, a novel heptapeptide in the renin-angiotensin system (RAS), on hypoxia-induced retinal neovascularization and its underlying mechanisms. In vivo, the C57BL/6J mice with oxygen-induced retinopathy (OIR) were injected intravitreally with alamandine (1.0 μmol/kg per eye). In vitro, human retinal microvascular endothelial cells (HRMECs) were utilized to investigate the effects of alamandine (10 μg/mL) on proliferation, apoptosis, migration, and tubular formation under vascular endothelial growth factor (VEGF) stimulation. Single-cell RNA sequencing (scRNA-seq) matrix data from the Gene Expression Omnibus (GEO) database and RAS-related genes from the Molecular Signatures Database (MSigDB) were sourced for subsequent analyses. By integrating scRNA-seq data across multiple species, we identified that RAS-associated endothelial cell populations were highly related to retinal neovascularization. The liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis revealed a significant decrease in alamandine levels in both the serum and retina of OIR mice compared to those in the control group. Next, alamandine ameliorated hypoxia-induced retinal pathological neovascularization and physiologic revascularization in OIR mice. In vitro, alamandine effectively mitigated VEGF-induced proliferation, scratch wound healing, and tube formation of HRMECs primarily by inhibiting the hypoxia-inducible factor-1α (HIF-1α)/VEGF pathway. Further, coincubation with D-Pro7 (Mas-related G protein-coupled receptor D (MrgD) antagonist) hindered the beneficial impacts of alamandine on hypoxia-induced pathological angiogenesis both in vivo and in vitro. Our findings suggested that alamandine could mitigate retinal neovascularization by targeting the MrgD-mediated HIF-1α/VEGF pathway, providing a potential therapeutic agent for OIR prevention and treatment.
Animals
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Retinal Neovascularization/prevention & control*
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Mice, Inbred C57BL
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Vascular Endothelial Growth Factor A/metabolism*
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Humans
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Mice
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Hypoxia-Inducible Factor 1, alpha Subunit/metabolism*
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Oligopeptides/therapeutic use*
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Signal Transduction/drug effects*
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Cell Proliferation/drug effects*
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Endothelial Cells/drug effects*
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Retinopathy of Prematurity/drug therapy*
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Apoptosis/drug effects*
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Cell Movement/drug effects*
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Renin-Angiotensin System/drug effects*
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Cells, Cultured
2.Trihalomethanes and haloacetamides as disinfection by-products in different types of drinking water of Wuxi
Run ZHOU ; Li YANG ; Yukang WU ; Zhifei XU ; Yuanhua MENG ; Xinliang DING ; Xiaofeng CHEN
Journal of Environmental and Occupational Medicine 2023;40(4):456-461
Background The concentrations of disinfection by-products (DBPs) are varied by different water sources, disinfectants, or treatment processes in Wuxi, and the associated health risks are also different. Objective To understand the levels of trihalomethanes (THMs) and haloacetamides (HAcAms) in drinking water in Wuxi, and their variations by water sources, seasons, disinfectants or treatment processes, aiming to provide technical support for ensuring the safety of drinking water. Methods In dry period (December 2019) and wet period (July 2020), the finished water and tap water (from the beginning, middle, and end of the drinking water distribution network) from 12 centralized water treatment plants in Wuxi were collected to detect the concentrations of THMs and HAcAms in water samples. A purge and trap-gas chromatography-mass spectrometry method was applied to detect trichloromethane (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and tribromomethane (TBM), and a solid-phase extraction-gas chromatography-mass spectrometry method to detect dichloroacetamide (DCAcAm), trichloroacetamide (TCAcAm), bromochloroacetamide (BCAcAm), dibromoacetamide (DBAcAm), bromodichloroacetamide (BDCAcAm), dibromochloroacetamide (DBCAcAm), and tribromoacetamide (TBAcAm). Analyses and comparisons were made on the concentrations of THMs and HAcAms in drinking water by water sources (the Yangtze River/the Taihu Lake/reservoir), wet/dry seasons, disinfection methods (liquid chlorine/sodium hypochlorite), and treatment processes (conventional treatment/conventional+advanced treatment). Results A total of 96 drinking water samples were collected in Wuxi. THMs were positive in all the water samples (100%), with concentration ranging from 1.027 to 40.225 μg·L−1 and the M (P25, P75) concentration being 24.782 (17.784, 30.932) μg·L−1. None of the 4 THMs exceeded the standard limit of the Standards for drinking water quality (GB 5749-2022 ), and the order of the 4 THMs concentrations from high to low was TCM > BDCM > DBCM > TBM. Five of the 7 HAcAms were detected, the total concentration ranged from 0.137 to 3.288 μg·L−1, and the M (P25, P75) was 0.808 (0.482, 1.704) μg·L−1. The DCAcAm concentration was the highest (2.448 μg·L−1), followed by BCAcAm, while TCAcAm and DBCAcAm were not detected. The M (P25, P75) of the total concentration of THMs in the drinking water from the Taihu Lake was 33.353 (26.649, 36.217) μg·L−1, that of the Yangtze River was 27.448 (24.312, 31.393) μg·L−1, and both were higher than the level of the reservoir [16.359 (2.305, 21.553) μg·L−1] (P<0.05), while the M (P25, P75) of the total concentration of HAcAms in the drinking water from the Taihu Lake was 0.616 (0.363, 0.718) μg·L−1, which was lower than those of the Yangtze River [0.967 (0.355, 2.283) μg·L−1] and the reservoir [1.071 (0.686, 1.828) μg·L−1] (P<0.05). There were no statistically significant differences in the total concentrations of THMs and HAcAms between wet season and dry season, or between different disinfection methods (P>0.05). The M (P25, P75) concentrations of THMs and HAcAms in drinking water after advanced treatment process involving ozone, activated carbon, and membrane were 20.565 (3.316, 27.185) μg·L−1 and 0.623 (0.452, 1.286) μg·L−1 respectively, and were lower than the corresponding values after conventional treatment process, 28.740 (23.431, 35.085) μg·L−1 and 0.934 (0.490, 2.116) μg·L−1 respectively (P<0.05). Conclusion The concentrations of THMs and HAcAms in drinking water in Wuxi are generally at a low level. The levels of controlled THMs meet the requirements of national standards, and the levels of uncontrolled HAcAms as new DBPs are up to μg·L−1. The concentrations of the two kinds of DBPs in drinking water vary by water sources. The concentrations of THMs and HAcAms produced by the advanced treatment process are lower than that by the conventional treatment process.
3.Development of the iGEM high school track.
Yue TANG ; Yukang LI ; Xudong ZHU ; Dong YANG ; Xiaoran HAO
Chinese Journal of Biotechnology 2022;38(12):4816-4826
The international genetically engineered machine (iGEM) competition is a global top college academic competition in synthetic biology. The iGEM competition has exhibited extensive international influence and attracted teams from more than 40 countries and regions around the world to participate in. The annual iGEM outputs have attracted the attention of top academic journals or international media such as Science, Nature, Scientific American, The Economist, British Broadcasting Corporation (BBC), etc. High school teams participated in iGEM since 2011, and the number of high school teams has increased year by year. High school participants are increasingly becoming one of the most important forces to promote the development of iGEM and synthetic biology. IGEM competition has also become an important platform to foster the core literacy of high school students. This paper summarized the track rules, topic selection tendency and awards of high school teams based on data of 2017 to 2021 iGEM competition. In addition, we analyzed the significance of iGEM competition on fostering of high school students' core literacy and discussed the development trend of global high school teams, with the aim to provide a reference for high school team building in the future.
Humans
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Genetic Engineering
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Students
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Universities
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Synthetic Biology
4.Prognostic evaluation of cardiac markers in early diagnosis of cardiac dysfunction in sepsis
Yukang SONG ; Yewuzi LI ; Miaoshu WANG
The Journal of Practical Medicine 2017;33(10):1631-1633
Objective To study the application value of myocardial markers combined with BNP in the early diagnosis of cardiac dysfunction in patients with sepsis. Methods diagnosed patients 66 cases as the research object of this paper,on the basis of 3~5 days in 66 patients with left ventricular ejection fraction after admission of LVEF > 50% and LVEF < 50% were divided into two groups ,two groups were monitored for 0 days ,3 days , 5 days,12 days LVEF,BNP and TNI. Results the left ventricular ejection fraction LVEF>50%and LVEF<50%two groups:3,5 days when the BNP value was significantly higher than that of non cardiac injury heart injury;cardiac injury group EF was negatively correlated with TNI value ,value and blood 3~5 days EF troponin levels in patients admitted to hospital after the show was negatively correlated;the concentration of EF and patients admitted to the hospital after twelfth days of blood troponin value is displayed as a negative correlation. TNI can directly reflect the cardiac function of patients. Research shows that the BNP value had a significant positive correlation in fifth days and APACHE Ⅱ score. Conclusion the data show that TNI and BNP can directly reflect the sepsis patients with heart dysfunction ,that BNP combined with TNI can effectively evaluate the clinical treatment of severe sepsis and septic shock patients ,prognosis has high significance.
5.Non-medical students first aid awareness and training needs survey of Shiyan city
Cui LIU ; Tao LI ; Yan WAN ; Wei ZHOU ; Junjie LIANG ; Yukang CHEN ; Sifei GAN ; Ningtao SUN
Chongqing Medicine 2017;46(23):3248-3250
Objective In order to know first aid awareness and training needs of non-medical college students in Shiyan city,and to provide the basis for an efficient first-aid training.Methods A total of 1063 non-medical colleges in Shiyan city were surveyed by random sampling method.Results 64.61% of students awared of their own lack of knowledge of first aid,only 3.8 % feel rich;based on the first aid knowledge they obtained at present,46.92 % did not hesitate to rescue the stranger.After receiving systematic training,the rate rise to 78.9 %,68.09 % of students worried about their lack of first aid skills were the biggest obstacle for them to implement of rescue;98.3% of the students asked to undergo first aid training,92.27% of students like approach first aid skills was hands-on model.33.03% of students believe that medical schools were the best institutions to undertake emergency training,23.46% of students chose the hospital.Conclusion Non-medical college students in Shiyan city have a bad awareness for firstaid knowledge and a strong desire for training.It is necessary that relevant departments will formulate targeted training programs to improve college students' first-aid response and improve regional emergency level.
6.Advances in research on ultrasound-guided percutaneous ethanol injection for treatment of benign cystic thyroid nodules
Yukang ZHANG ; Lijuan NIU ; Junying LIU ; Zhengjiang LI
China Oncology 2016;(1):112-116
Because of development and popularization of the ultrasound techniques, the detection rate of nodal thyroid has increased. Surgery is the long-established therapeutic option. However, due to the surgical trauma, compli-cations and the effect on quality of life, various minimally invasive treatments have been proposed and widely used. A large number of foreign studies have shown that ultrasound-guided percutaneous ethanol injection is a more commonly used minimally invasive way to treat benign pure cystic and predominantly cystic thyroid nodules. This article provides an up-to-date review of the overseas studies and summarized on percutaneous ethanol injection for the treatment of benign cystic thyroid nodules.
7.Application of Fuzzy Comprehensive Evaluation in Formulation Screening
Longlong LI ; Pengbin HAO ; Wenpeng WANG ; Yukang FENG ; Yunping QU ; Guozhi JIANG ; Zhenjiang LI
China Pharmacy 2015;(28):3957-3959,3960
OBJECTIVE:To investigate the application of fuzzy comprehensive evaluation in formulation screening. METH-ODS:Taking Compound paracetamol and chlorphenamine maleate granules as model drug,based on single factor experiment,L9(34) orthogonal test was used to screen the formulation with the amount of aspartame,hawthorn powder essence,milk powder essence and saccharose as factors,using dissolution rate of caffeine as index. The granules prepared by 9 kinds of formulation in orthogonal test were evaluated with fuzzy comprehensive evaluation in terms of taste,aroma,color and dissolubility. The optimized formula-tion was validated and compared with original formulation. RESULTS:The formulation 5 was the optimal choice in both orthogo-nal test and fuzzy comprehensive evaluation,and obtained same results. Compared with sensory comprehensive score (63.12) and dissolution rate of caffeine (91.3%) in original formulation,two indicators of optimized formulation in 3 tests were 84.00 and 99.07% in average (RSD<2.0%,n=3). CONCLUSIONS:Fuzzy comprehensive evaluation can be used for the formulation screening of sensory evaluation index. It is scientific and accurate.
8.The expression and identification of NS3-NS4 gene of hepatitis Cvirus
Xiaoge KOU ; Yong LI ; Yukang YUAN ; Guangxiao YANG ; Quanying WANG
Journal of Xi'an Jiaotong University(Medical Sciences) 2004;0(05):-
Objective To construct and expr es s a recombinant plasmid of nonstructural protein NS3-NS4 of hepatitis C virus ( HCV), and to identify the antigenicity of the expressed protein. Methods A gene region encompassing the nonstructural protei n NS3-NS4 of HCV was amplified by polymerase chain reaction (PCR) from the pUC1 9/HCV template. The recombinant expression plasmid containing the pBV220/NS3-NS 4 sequence was constructed, and the nonfused NS3-NS4 recombinant protein was ex pressed in E.coli DH5? efficiently. The recombinant protein was det ected by SDS-PAGE and ELISA. Results We successfully constructed and expressed the recom binant plasmid in prokaryote. Its antigenicity was detected with 50 standard ser a. Compared with the second-generation diagnostic Kit, the total detection rate was 96%. Conclusion The whole NS3-NS4 protein, a region of dominant immunogenicity, should be the effective component of the HCV diagnostic Kit and provide the clue for developing HCV DNA vaccine.
9.The metastatic pattern of thoracic lymph nodes in 306 patients with lung cancer.
Yukang KUANG ; Laiduo ZENG ; Jiufa WU ; Qun LI ; Dongsheng WANG ; Binglin YIN ; Zhaoge WANG ; Jian HUANG ; Zhisheng HE
Chinese Journal of Lung Cancer 2003;6(1):59-62
BACKGROUNDTo study the metastatic pattern of thoracic lymph nodes in patients with resectable lung cancer.
METHODSFrom January 1992 to December 2000, radical lobectomy or pneumonectomy and systemic lymphadenectomy were performed in 306 patients with lung cancer. Number, size, colour and hardness of lymph nodes in each region were recorded and neoplastic metastasis was examined by pathology.
RESULTSOut of 4 614 resected lymph nodes from 2 456 regions, 954 lymph nodes from 521 regions were confirmed to have metastasis. The metastatic rates of thoracic lymph nodes and mediastinal lymph nodes were 61.8% and 43.5% , respectively. The metastatic frequencies in regions around the hilar or root of lung (11,10,7,5,4) were higher than those of regions far from the root of lung (9,6,3,2,1). There was a remarkably higher metastatic rate of lymph nodes in small cell lung cancer than that in non small cell lung cancer (P < 0.01 ). The metastatic rate was closely related to size, colour and hardness of lymph nodes (P < 0.001, P < 0.001 , P < 0.001 ).
CONCLUSIONSMost of neoplastic metastasis of lymph nodes spreads from proximal to distal areas, lower to upper regions, and from the hilar to the mediastinal. A few mediastinal lymph nodes show a skipping pattern. It is necessary to perform systemic lymphadenectomy during pulmonary resection.
10.Genetic polymorphism of D16S539, D7S820 and D13S317 loci in the Kazak ethnic population.
Xueling CHEN ; Chen HUANG ; Yukang YUAN ; Riming LIU ; Jian XU ; Tusheng SONG ; Shengbin LI
Chinese Journal of Medical Genetics 2002;19(1):55-57
OBJECTIVETo analyze the genetic polymorphism of D16S539, D7S820 and D13S317 in Chinese Kazak ethnic population from Xinjiang.
METHODSOne hundred and two unrelated individuals and a sample of families (n=42) were investigated by multiplex amplification, 6% denaturing PAGE and silver staining. And, the obtained allele frequencies were compared with those of other populations.
RESULTSEight, seven, eight alleles were observed at the 3 STR loci respectively and the genotypes distributions were in accordance with Hardy-Weinberg equilibrium. The expected heterozygosities for these loci were 0.9439, 0.9356 and 0.9304; the calculated polymorphism formation content (PIC) was 0.9905; the discrimination power (DP), 0.9998; the paternity exclusion (PE), 0.9572. In addition, significant difference was found in comparison with other populations, and in the sample of families (n=42) no new mutations could be found.
CONCLUSIONThe multiplex examination of 3 STR loci can be used in forensic identification and population genetics research.
China ; ethnology ; European Continental Ancestry Group ; genetics ; Female ; Gene Frequency ; Genetics, Population ; Genotype ; Humans ; Male ; Polymorphism, Genetic ; Tandem Repeat Sequences ; genetics

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