Excessive aggressive migration and invasion are important factors that increase the mortality of cancer patients. Matrix metalloproteinase 13 (MMP13) expression is positively correlated with lung cancer malignancy. However, the mechanism underlying an elevated MMP13 expression is not clearly defined. In this study, we demonstrated that hypoxia induced by CoCl 2 enhanced the expression of HIF1α, JAK2, STAT3 and MMP13 in A549 cells. A positive correlation between HIF1α and MMP13 expression was observed in lung adenocarcinoma patients. Mechanically, hypoxia upregulated HIF1α/JAK2/STAT3 signal axis, promoted transcription factor STAT3 to bind to MMP13 promoter region, and activated MMP13 transcription, finally promoted cell invasion and migration. However, stattic (STAT3 inhibitor) could reverse this effect caused by STAT3 in A549 cells. Together our data indicated that hypoxia might promote lung cancer cell migration and invasion through the HIF1α/JAK2/STAT3 axis by activating MMP13 transcription. MMP13 could be a promising therapeutic target for lung adenocarcinoma metastasis.

PURPOSE:To investigate the effect of reducing Lysyl oxidase (LOX) overexpression on retinal ganglion cells (RGCs) apoptosis in an acute ocular hypertension (AOH) rat model. METHODS:AOH rat model was performed by anterior chamber perfusion and either received an intravitreal injection with β-aminopropionitrile (BAPN) or normal saline. After 2wk, Quantification of survival RGCs in the retina was performed using Retrograde FluoroGold labeling. The mRNA expression levels of LOX, LOXL1-4, collagen 1a1 (Col1a1), collagen 3a1 (Col3a1), collagen4a1 (Col4a1), elastin (Eln), fibronectin1 (Fbn1), fibronectin4 (Fbn4) were determined by RT-qPCR. LOX expression was determined by Western blot (WB) analysis and immunohistochemistry. The RNA expression of LOX, Eln and Col1a1 in RGCs retrograde-labeled with 1,1'-dioctadecyl-3,3,3',3' tetra-methylindocarbocyanine perchlorate(DiI)that selected through FACS sorting were determined by RT-qPCR analysis. Changes of the retinal function were detected by Electroretinogram (ERG) analysis. RESULTS:Results showed that significant LOX overexpression and loss of RGCs related to IOP exposure in AOH retinas. PCR analysis indicated significant increased mRNA level of Col1a1, Col3al and Eln in AOH retinas. Significant increase mRNA expression of LOX, Col1a1 and Eln in the RGCs were observed in AOH group compared with CON group. AOH rats injected with BAPN showed a significant decrease in LOX expression, reduced the loss of RGCs and retinal function damage. CONCLUSIONS:The results demonstrated that changes of LOX and specific ECM components in retina were correlated with AOH. Findings from this study indicated that preventing LOX over-expression may be protective against RGCs loss and retinal function damage in AOH animal model.

Pre-existing of pulmonary tuberculosis (PTB) poses increased lung cancer risk, yet the molecular mechanisms remain inadequately understood. This study sought to elucidate the potential mechanisms by performing comprehensive analyses of differentially expressed genes (DEGs) in peripheral blood mononuclear cells (PBMCs) from patients with PTB, lung adenocarcinoma (LUAD), and lung squamous cell carcinoma (LUSC). Microarray assays were employed to analyze the DEGs in PBMCs of these patients. The analyses revealed that, compared to healthy controls, the number of differentially expressed LncRNA in PBMCs from patients with PTB, LUAD, and LUSC were 801, 8,541, and 7,796, respectively. Similarly, the differentially expressed mRNA in PBMCs from patients with PTB, LUAD, and LUSC were 629, 4,865, and 4,438, respectively. These differentially expressed transcripts represent significant resources for the identifying diagnostic and differential diagnostic biomarkers for lung cancer and PTB. Pathways enriched by dysregulated mRNAs in patients with PTB, LUAD, and LUSC were identified through GO and KEGG pathway analyses. The results indicated that 9 pathways including the NOD-like receptor signaling pathway, pathways in cancer, and the MAPK signaling pathway were co-enriched across the PTB, LUAD, and LUSC groups, providing insights into the mechanisms by which PTB may increase the risk of cancer development and progression.

BackgroundCarbapenem-resistant Acinetobacter baumannii (CRAB) has emerged as a predominant strain of healthcare-associated infections worldwide, particularly in intensive care units (ICUs). Therefore, it is imperative to study the molecular epidemiology of CRAB in the ICUs using multiple molecular typing methods to lay the foundation for the development of infection prevention and control strategies. This study aimed to determine the antimicrobial susceptibility profile, the molecular epidemiology and conduct homology analysis on CRAB strains isolated from ICUs.MethodsThe sensitivity to various antimicrobials was determined using the minimum inhibitory concentration (MIC) method, Kirby-Bauer disk diffusion (KBDD), and E-test assays. Resistance genes were identified by polymerase chain reaction (PCR). Molecular typing was performed using multilocus sequence typing (MLST) and multiple-locus variable-number tandem repeat analysis (MLVA).ResultsAmong the 79 isolates collected, they exhibited high resistance to various antimicrobials but showed low resistance to levofloxacin, trimethoprim-sulfamethoxazole, and tetracyclines. Notably, all isolates of A. baumannii were identified as multidrug-resistant A. baumannii (MDR-AB). The blaOXA-51-like, adeJ, and adeG genes were all detected, while the detection rates of blaOXA-23-like (97.5%), adeB (93.67%), blaADC (93.67%), qacEΔ1-sul1 (84.81%) were higher; most of the Ambler class A and class B genes were not detected. MLST analysis on the 79 isolates identified five sequence types (STs), which belonged to group 3 clonal complexes 369. ST1145Ox was the most frequently observed ST with a count of 56 out of 79 isolates (70.89%). MLST analysis for non-sensitive tigecycline isolates, which were revealed ST1145Ox and ST1417Ox as well. By using the MLVA assay, the 79 isolates could be grouped into a total of 64 distinct MTs with eleven clusters identified in them. Minimum spanning tree analysis defined seven different MLVA complexes (MCs) labeled MC1 to MC6 along with twenty singletons. The locus MLVA-AB_2396 demonstrated the highest Simpson’s diversity index value at 0.829 among all loci tested in this study while also having one of the highest variety of tandem repeat species.ConclusionThe molecular diversity and clonal affinities within the genomes of the CRAB strains were clearly evident, with the identification of ST1144Ox, ST1658Ox, and ST1646Oxqaq representing novel findings.

BACKGROUND:Metformin is the most frequently prescribed medication for the treatment of type II diabetes mellitus and has played an anti-tumor potential in a variety of cancer types. Metformin can inhibit the growth of many cancer cells through various mechanisms, including ferroptosis. However, it is still unclear whether metformin can induce ferroptosis in lung cancer.METHODS:This study evaluated the anti-tumor effect of metformin by detecting the levels of oxidative stress factors, the levels of ferrous ions, and the expression of ferroptosis-related genes in A549 and H1299 lung cancer cell lines treated with or without metformin.RESULTS:The results showed that metformin treatment increased the levels of MDA, ROS and iron ions, while decreased the levels of GSH, T-SOD and CAT. Meanwhile, metformin treatment reduced the protein expression levels of Gpx4 and SLC7A11, Nrf2 and HO-1, while the addition of ferroptosis inhibitor ferrostatin-1 reversed the reduction.CONCLUSIONS:These results demonstrated that metformin exerts anti-tumor effects by inducing ferroptosis through the Nrf2/HO-1 signaling pathway in lung cancer cells, providing a theoretical basis for drug therapy of lung cancer patients.

目的 利用生物信息学分析技术筛选和鉴定参与肝细胞癌(HCC)进展的核心基因,并评价其在HCC发展及预后中的潜在价值.方法 从GEO数据库筛选出HCC基因数据集GSE101685、GSE84402和GSE46408,利用GEO2R对差异表达基因(DEGs)进行分析.采用DAVID数据库构建基因功能注释和通路富集分析.利用STRING数据库构建蛋白质互作网络(PPI)图,并用Cytoscape进行可视化分析,筛选出关键模块并获得核心基因.使用cBioPortal数据库进行生存分析.通过ONCOMINE数据库分析核心基因与HCC进展的关系.结果 在3个基因数据集中共筛选到261个DEGs,其中上调基因124个,下调基因137个.KEGG分析结果表明,DEGs主要参与细胞周期、DNA复制、视黄醇代谢等通路.PPI分析鉴定出10个核心基因,其中OIP5、HGFAC、FLVCR1与HCC分级、卫星结节和血管浸润有关,FLVCR1与患者生存情况有关.结论 该研究成功筛选出与HCC相关的DEGs和核心基因,其中OIP5、HGFAC、FLVCR1有望成为HCC诊疗和预后的生物标志物.

Background: Hand, foot and mouth disease (HFMD) and herpangina (HA), two of the most common childhood infectious diseases, are associated with enteroviruses (EVs) infection. The aim of this study was to identify the molecular epidemiology of enterovirus causing HFMD/HA in Zunyi, China, during 2019, and to describe the clinical features of the cases. Methods: We collected the information on demographic and clinical characteristics, laboratory data of laboratory-confirmed EVs associated HFMD/HA cases in Zunyi Medical University Third Affiliated Hospital between March 1 and July 31, 2019. EV types were determined by either one-step real time RT-PCR or partial VP1 gene sequencing and sequence alignment. Phylogenetic analysis of CVA6, CVA2, and CVA5 were established based on the partial VP1 gene sequences by neighbor-joining method. Differences in clinical characteristics and laboratory results of the cases were compared among patients infected with the most prevalent EV types. Results: From 1 March to 31 July 2019, 1,377 EVs associated HFMD/HA inpatients were confirmed. Of them, 4 (0.3%, 4/1,377) were EV-A71-associated cases, 84 (6.1%, 84/1,377) were CVA16-associated cases, and 1,289 (93.6%, 1,289/1,377) were non-EV-A71/CVA16-associated cases. Of the randomly selected 372 non-EV-A71/CVA16 cases, EV types have been successfully determined in 273 cases including 166 HFMD and 107 HA cases. For HFMD cases, the three most common types were CVA6 (80.7%, 134/166), CVA2 (5.4%, 9/166) and CVA5 (3.0%, 5/166); similarly, for HA cases, the three most prevalent serotypes were CVA6 (36.5%, 39/107), CVA2 (21.5%, 23/107) and CVA5 (18.7%, 20/107). Phylogenetic analysis showed that subclade D of CVA5, and subclade E of CVA6 and CVA2 were predominant in Zunyi during the outbreak in 2019. Compared with the cases caused by CVA16, the incidence of high fever and severe infection associated with CVA2, CVA5, and CVA6 was higher. Conclusions: The recent HFMD/HA outbreak in Zunyi is due to a larger incidence of CVA6, CVA2, and CVA5. Novel diagnostic reagents and vaccines against these types would be important to monitor and control EV infections.

林麝Moschus berezovskii是国家一级重点保护野生动物.本研究从林麝基因组和已发表的微卫星位点中筛选到7个适合林麝粪便DNA扩增的四碱基微卫星位点,建立了林麝的个体识别体系.在四川白水河国家级自然保护区20条监测样线中共收集到林麝粪便46份,基于微卫星个体识别鉴定到30只个体,使用微卫星和线粒体D-Loop进行多样性评估,结果显示,7个微卫星位点的平均期望杂合度和观察杂合度分别为0.602和0.563,4个位点显著偏离哈迪-温伯格平衡,且均表现为杂合不足.线粒体D-Loop遗传多样性检测结果显示,保护区林麝单倍型多样性和核苷酸多样性分别为0.7213和0.02344,表明保护区林麝遗传多样性处于中等水平.基于个体识别、样线调查和保护区适宜栖息地计算出保护区样线内林麝的平均密度为4.39头·km-2,保护区内约有1090头林麝.本研究为保护区林麝的遗传资源保护提供了重要的基础资料.

Effective therapeutic drugs for prevent or reverse the pathobiology of Alzheimer’s disease (AD) have not been developed. Icariin (ICA), a prenylated flavonol glycoside derived from the traditional Chinese herb Epimedium sagittatum, exerts a variety of pharmacological activities and shows promise in the treatment and prevention of AD. This study investigated the neuroprotective effects of ICA in SAMP8 mice model of aspects of early AD and explored potential underlying mechanisms. Our results showed that intragastric administration of ICA could reverse the learning and memory impairment of SAMP8 mice in the Morris water maze. Western blot of hippocampal specimens revealed that ICA down-regulated the expression of BACE1 to reduce the expression of cytotoxic Aβ1-42. Furthermore, ICA siginificantly increase the Bcl-2/Bax ratio by increasing the expression of anti-apoptotic protein Bcl-2, and decreasing the expression of pro-apoptotic protein Bax, and thus inhibit neurons apoptosis. These findings indicate that ICA could improve cognitive deficits by reducing the deposition of β1-42 and inhibition of neurons apoptosis and provide further evidence for the clinical efficacy of ICA in the treatment of AD.

该研究对卤化Ⅱ型聚酮类抗生素zunyimycins产生菌链霉菌(Streptomyces sp.) FJS31-2的次级代谢产物进行挖掘.次级代谢产物经乙酸乙酯萃取浓缩后,依次采用硅胶柱层析法、薄层层析(TLC)法、高效液相色谱(HPLC)法等方法进行分离和纯化,通过质谱(MS)法和核磁共振(NMR)等分析单体化合物的结构,并采用滤纸片法对其抗菌活性进行测试.结果 表明,初次从该菌发酵物中分离得到多环内酯类化合物UK-78623,其对小肠结肠炎耶尔森氏菌(Yersinia enterocolitica)具有明显抑制作用,其抑菌圈直径为25.2 mm.

This study performed an optimization of the fermentation conditions to activate the expression of the zunyimycin family biosynthesis genes of the zunyimycin-producing streptomycetes strain Streptomyces sp. FJS31-2. Bioassay-guided isolation and purification by varied chromatographic methods yielded two new compounds of the zunyimycin derivatives, namely, 31-2-7 and 31-2-8, accompanied with three known anthrabenzoxocinones family members of zunyimycin A, BE24566B, and chloroanthrabenzoxocinone. Their structures were elucidated by NMR, HRESIMS, IR, UV, and CD. Results showed that these two compounds were structurally similar to the previously reported compound zunyimycin A but differed in positions and number of chlorine atom substitution. The two novel compounds were called zunyimycins B and C. Antibacterial activity assay indicated that zunyimycin C showed a good inhibitory effect on the methicillin-resistant Staphylococcus aureus and Enterococci.