Distribution and significance of interstitial fibrosis and stroma-infiltrating B cells in tongue squamous cell carcinoma

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CHD1L protein is overexpressed in human ovarian carcinomas and is a novel predictive biomarker for patients survival

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Small-Molecule Synthetic Compound Norcantharidin Reverses Multi-Drug Resistance by Regulating Sonic Hedgehog Signaling in Human Breast Cancer Cells

Multi-drug resistance (MDR), an unfavorable factor compromising treatment efficacy of anticancer drugs, involves upregulated ATP binding cassette (ABC) transporters and activated Sonic hedgehog (Shh) signaling. By preparing human breast cancer MCF-7 cells resistant to doxorubicin (DOX), we examined the effect and mechanism of norcantharidin (NCTD), a small-molecule synthetic compound, on reversing multidrug resistance. The DOX-prepared MCF-7R cells also possessed resistance to vinorelbine, characteristic of MDR. At suboptimal concentration, NCTD significantly inhibited the viability of DOX-sensitive (MCF-7S) and DOX-resistant (MCF-7R) cells and reversed the resistance to DOX and vinorelbine. NCTD increased the intracellular accumulation of DOX in MCF-7R cells and suppressed the upregulated the mdr-1 mRNA, P-gp and BCRP protein expression, but not the MRP-1. The role of P-gp was strengthened by partial reversal of the DOX and vinorelbine resistance by cyclosporine A. NCTD treatment suppressed the upregulation of Shh expression and nuclear translocation of Gli-1, a hallmark of Shh signaling activation in the resistant clone. Furthermore, the Shh ligand upregulated the expression of P-gp and attenuated the growth inhibitory effect of NCTD. The knockdown of mdr-1 mRNA had not altered the expression of Shh and Smoothened in both MCF-7S and MCF-7R cells. This indicates that the role of Shh signaling in MDR might be upstream to mdr-1/P-gp, and similar effect was shown in breast cancer MDA-MB-231 and BT-474 cells. This study demonstrated that NCTD may overcome multidrug resistance through inhibiting Shh signaling and expression of its downstream mdr-1/P-gp expression in human breast cancer cells

Assessing impacts of climate change and human activities on streamflow and sediment discharge in the Ganjiang River basin (1964-2013)

© 2019 by the authors. National large-scale soil and water conservation controls on the Gangjiang River basin have been documented, but the effect of governance on regional watershed hydrology and how the main driving factors act have not been systematically studied yet. To do this, this study evaluated changing trends and detected transition years for both streamflow and sediment discharge using long-term historical records at seven hydrological stations in the Ganjiang River basin over the past 50 years. The double mass curve (DMC) method was used to quantify the effects of both climate change and human activities on hydrological regime shifts. The results showed that the distributions of precipitation, streamflow, and sediment discharge within a year are extremely uneven and mainly concentrated in the flood season of Jiangxi Province. None of the stations showed significant trends over time for either annual precipitation or streamflow, while the annual sediment discharge at most stations decreased significantly over time. The estimation of sediment discharge via DMC indicated that after the transition years, there were rapid reductions in sediment discharge at all hydrological stations, and the average decline degree of midstream and downstream were much larger than that of upstream. Human activities, especially the increase of vegetation cover and construction of large and medium-sized reservoirs, provided a significantly greater contribution to the reduction of sediment discharge than did precipitation changes. As a case study of river evolution under global change environment, this study could provide scientific basis for the control of soil erosion and the management of water resources in Ganjiang River, as well as for the related research of Poyang Lake and the Yangtze River basin of China

Ablation of EIF5A2 induces tumor vasculature remodeling and improves tumor response to chemotherapy via regulation of matrix metalloproteinase 2 expression

Hepatocellular carcinoma (HCC) is a highly vascularized tumor with poor clinical outcome. Our previous work has shown that eukaryotic initiation factor 5A2 (EIF5A2) over-expression enhances HCC cell metastasis. In this study, EIF5A2 was identified to be an independent risk factor for poor disease-specific survival among HCC patients. Both in vitro and in vivo assays indicated that ablation of endogenous EIF5A2 inhibited tumor angiogenesis by reducing matrix metalloproteinase 2 (MMP-2) expression. Given that MMP-2 degrades collagen IV, a main component of the vascular basement membrane (BM), we subsequently investigated the effect of EIF5A2 on tumor vasculature remodeling using complementary approaches, including fluorescent immunostaining, transmission electron microscopy, tumor perfusion assays and tumor hypoxia assays. Taken together, our results indicate that EIF5A2 silencing increases tumor vessel wall continuity, increases blood perfusion and improves tumor oxygenation. Additionally, we found that ablation of EIF5A2 enhanced the chemosensitivity of HCC cells to 5-Fluorouracil (5-FU). Finally, we demonstrated that EIF5A2 might exert these functions by enhancing MMP-2 activity via activation of p38 MAPK and JNK/c-Jun pathways. Conclusion: This study highlights an important role of EIF5A2 in HCC tumor vessel remodeling and indicates that EIF5A2 represents a potential therapeutic target in the treatment of HCC.published_or_final_versio

Systemic delivery of microRNA-101 potently inhibits hepatocellular carcinoma in vivo by repressing multiple targets

Targeted therapy based on adjustment of microRNA (miRNA)s activity takes great promise due to the ability of these small RNAs to modulate cellular behavior. However, the efficacy of miR-101 replacement therapy to hepatocellular carcinoma (HCC) remains unclear. In the current study, we first observed that plasma levels of miR-101 were significantly lower in distant metastatic HCC patients than in HCCs without distant metastasis, and down-regulation of plasma miR-101 predicted a worse disease-free survival (DFS, P<0.05). In an animal model of HCC, we demonstrated that systemic delivery of lentivirus-mediated miR-101 abrogated HCC growth in the liver, intrahepatic metastasis and distant metastasis to the lung and to the mediastinum, resulting in a dramatic suppression of HCC development and metastasis in mice without toxicity and extending life expectancy. Furthermore, enforced overexpression of miR-101 in HCC cells not only decreased EZH2, COX2 and STMN1, but also directly down-regulated a novel target ROCK2, inhibited Rho/Rac GTPase activation, and blocked HCC cells epithelial-mesenchymal transition (EMT) and angiogenesis, inducing a strong abrogation of HCC tumorigenesis and aggressiveness both in vitro and in vivo. These results provide proof-of-concept support for systemic delivery of lentivirus-mediated miR-101 as a powerful anti-HCC therapeutic modality by repressing multiple molecular targets. © 2015 Zheng et al.published_or_final_versio

Community Engagement in Vaccination Promotion: Systematic Review and Meta-Analysis

Background: Community engagement plays a vital role in global immunization strategies, offering the potential to overcome vaccination hesitancy and enhance vaccination confidence. Although there is significant backing for community engagement in health promotion, the evidence supporting its effectiveness in vaccination promotion is fragmented and of uncertain quality. Objective: This review aims to systematically examine the effectiveness of different contents and extent of community engagement for promoting vaccination rates. Methods: This study was performed in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A comprehensive and exhaustive literature search was performed in 4 English databases (PubMed, Embase, Web of Science, and Cochrane Library) and 2 Chinese databases (CNKI and Wan Fang) to identify all possible articles. Original research articles applying an experimental study design that investigated the effectiveness of community engagement in vaccination promotion were eligible for inclusion. Two reviewers independently performed the literature search, study selection, quality assessment, and data extraction. Discrepancies were resolved through discussion, with the arbitration of a third reviewer where necessary. Results: A total of 20 articles out of 11,404 records from 2006 to 2021 were retrieved. The studies used various designs: 12 applied single-group pre-post study designs, 5 were cluster randomized controlled trials (RCTs), and 3 were non-RCTs. These studies targeted multiple vaccines, with 8 focusing on children’s immunization, 8 on human papillomavirus vaccine, 3 on hepatitis B virus vaccine, and 1 on COVID-19 vaccine. The meta-analysis revealed significant increases in vaccination rates both in pre-post comparison (rate difference [RD] 0.34, 95% CI 0.21-0.47, I2=99.9%, P<.001) and between-group comparison (RD 0.18, 95% CI 0.07-0.29, I2=98.4%, P<.001). The meta-analysis revealed that participant recruitment had the largest effect size (RD 0.51, 95% CI 0.36-0.67, I2=99.9%, P<.001), followed by intervention development (RD 0.36, 95% CI 0.23-0.50, I2=100.0%, P<.001), intervention implementation (RD 0.35, 95% CI 0.22-0.47, I2=99.8%, P<.001), and data collection (RD 0.34, 95% CI 0.19-0.50, I2=99.8%, P<.001). The meta-analysis indicated that high community engagement extent yielded the largest effect size (RD 0.49, 95% CI 0.17-0.82, I2=100.0%, P<.001), followed by moderate community engagement extent (RD 0.45, 95% CI 0.33-0.58, I2=99.6%, P<.001) and low community engagement extent (RD 0.15, 95% CI 0.05-0.25, I2=99.2%, P<.001). The meta-analysis revealed that “health service support” demonstrated the largest effect sizes (RD 0.45, 95% CI 0.25-0.65, I2=99.9%, P<.001), followed by “health education and discussion” (RD 0.39, 95% CI 0.20-0.58, I2=99.7%, P<.001), “follow-up and reminder” (RD 0.33, 95% CI 0.23-0.42, I2=99.3%, P<.001), and “social marketing campaigns and community mobilization” (RD 0.24, 95% CI 0.06-0.41, I2=99.9%, P<.001). Conclusions: The results of this meta-analysis supported the effectiveness of community engagement in vaccination promotion with variations in terms of engagement contents and extent. Community engagement required a “fit-for-purpose” approach rather than a “one-size-fits-all” approach to maximize the effectiveness of vaccine promotion. Trial Registration: PROSPERO CRD42022339081; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=33908

EZH2 protein: A promising immunomarker for the detection of hepatocellular carcinomas in liver needle biopsies

Background and aims: A previous study of ours indicated that enhancer of zeste homologue 2 (EZH2) plays an important role in hepatocellular carcinoma (HCC) tumorigenesis. The aim of the present study was to investigate the potential diagnostic utility of EZH2 in HCC. Methods: Immunohistochemistry was performed to examine the expression dynamics of EZH2 in two independent surgical cohorts of HCC and non-malignant liver tissues to develop a diagnostic yield of EZH2, HSP70 and GPC3 for HCC detection. The diagnostic performances of EZH2 and a three-marker panel in HCC were re-evaluated by using an additional biopsy cohort. Results: Immunohistochemistry analysis demonstrated that the sensitivity and specificity of EZH2 for HCC detection was 95.8% and 97.8% in the testing cohort. Similar results were confirmed in the validation cohort. For diagnosis of well-differentiated HCCs, the sensitivity and specificity were 68.9% and 91.5% for EZH2, 62.5% and 98.5% for HSP70, 50.0% and 92.1% for GPC3, and 75.0% and 100% for a three-marker panel. In biopsies, positive cases for at least one marker increased from large regenerative nodule and hepatocellular adenoma (0/12) to focal nodular hyperplasia (2/20), dysplastic nodule (7/25), well-differentiated HCC (16/18) and moderately and poorly differentiated HCC (54/54). When at least two positive markers were considered, regardless of their identity, the positive cases were detected in 0/12 large regenerative nodules and hepatocellular adenomas, 0/20 focal nodular hyperplasias, 0/25 dysplastic nodules, 11/18 well-differentiated HCCs, 32/37 moderately differentiated HCCs and 15/17 poorly differentiated HCCs. Conclusion: Our findings suggest that EZH2 protein, as examined by immunohistochemistry, may serve as a promising diagnostic biomarker of HCCs, and the use of a three-marker panel (EZH2, HSP70 and GPC3) can improve the rate of detection of HCCs in liver biopsy tissues.published_or_final_versio

Effect of laser remelting on microstructure and properties of WC reinforced Fe-based amorphous composite coatings by laser cladding

The WC reinforced Fe-based amorphous composite coatings were prepared by laser cladding with rectangular spot. The effect of laser remelting on the microstructure and properties of composite coatings was investigated. The results showed that laser remelting can reduce the cracks and porosities of the cladding coating and improve its surface quality. Large amounts of crystalline phases were precipitated at the top of the cladding and remelting coatings. However, the microstructure at the top of the remelting coating was finer compared to that at the top of the cladding coating. With increasing distance from the surface of substrate, the amorphous phase appeared within the remelting coating and large amounts of carbides rich in Fe and Mo, Fe23B6, gamma-Fe and Cr-9.1.Si-0.9 Slag phases were also precipitated in the remelting coating. As a result, the corrosion resistance of the remelting coating was higher than that of the cladding coating. The microhardness of the remelting coating was approximately 1.13 times higher than that of the cladding coating. (C) 2018 Elsevier Ltd. All rights reserved

Spatio-Temporal Characteristics of Global Warming in the Tibetan Plateau during the Last 50 Years Based on a Generalised Temperature Zone - Elevation Model

Temperature is one of the primary factors influencing the climate and ecosystem, and examining its change and fluctuation could elucidate the formation of novel climate patterns and trends. In this study, we constructed a generalised temperature zone elevation model (GTEM) to assess the trends of climate change and temporal-spatial differences in the Tibetan Plateau (TP) using the annual and monthly mean temperatures from 1961-2010 at 144 meteorological stations in and near the TP. The results showed the following: (1) The TP has undergone robust warming over the study period, and the warming rate was 0.318°C/decade. The warming has accelerated during recent decades, especially in the last 20 years, and the warming has been most significant in the winter months, followed by the spring, autumn and summer seasons. (2) Spatially, the zones that became significantly smaller were the temperature zones of -6°C and -4°C, and these have decreased 499.44 and 454.26 thousand sq km from 1961 to 2010 at average rates of 25.1% and 11.7%, respectively, over every 5-year interval. These quickly shrinking zones were located in the northwestern and central TP. (3) The elevation dependency of climate warming existed in the TP during 1961-2010, but this tendency has gradually been weakening due to more rapid warming at lower elevations than in the middle and upper elevations of the TP during 1991-2010. The higher regions and some low altitude valleys of the TP were the most significantly warming regions under the same categorizing criteria. Experimental evidence shows that the GTEM is an effective method to analyse climate changes in high altitude mountainous regions