Genome Wide Association Identifies PPFIA1 as a Candidate Gene for Acute Lung Injury Risk Following Major Trauma

Acute Lung Injury (ALI) is a syndrome with high associated mortality characterized by severe hypoxemia and pulmonary infiltrates in patients with critical illness. We conducted the first investigation to use the genome wide association (GWA) approach to identify putative risk variants for ALI. Genome wide genotyping was performed using the Illumina Human Quad 610 BeadChip. We performed a two-stage GWA study followed by a third stage of functional characterization. In the discovery phase (Phase 1), we compared 600 European American trauma-associated ALI cases with 2266 European American population-based controls. We carried forward the top 1% of single nucleotide polymorphisms (SNPs) at p<0.01 to a replication phase (Phase 2) comprised of a nested case-control design sample of 212 trauma-associated ALI cases and 283 at-risk trauma non-ALI controls from ongoing cohort studies. SNPs that replicated at the 0.05 level in Phase 2 were subject to functional validation (Phase 3) using expression quantitative trait loci (eQTL) analyses in stimulated B-lymphoblastoid cell lines (B-LCL) in family trios. 159 SNPs from the discovery phase replicated in Phase 2, including loci with prior evidence for a role in ALI pathogenesis. Functional evaluation of these replicated SNPs revealed rs471931 on 11q13.3 to exert a cis-regulatory effect on mRNA expression in the PPFIA1 gene (p = 0.0021). PPFIA1 encodes liprin alpha, a protein involved in cell adhesion, integrin expression, and cell-matrix interactions. This study supports the feasibility of future multi-center GWA investigations of ALI risk, and identifies PPFIA1 as a potential functional candidate ALI risk gene for future research

Multi-temperature indentation creep tests on nanotwinned copper

202402 bcchAccepted ManuscriptOthersThe Hong Kong Polytechnic University; National Natural Science Foundation of China; Science and Technology Commission of Shanghai Municipality; 111 project from the Ministry of Education and the State Administration of Foreign Experts Affairs, PRC.PublishedGreen (AAM

Sample Grating Distributed Feedback Quantum Cascade Laser Array

A sample grating distributed feedback quantum cascade laser array aim at broad tunability and enhanced side mode suppression ratios is presented. Utilizing a sample grating dependence on emission wavelength and epitaxial side down bonding technique, the array of laser ridges exhibited three separated single mode emissions centered at 4.760, 4.721, and 4.711 μm respectively, in continuous wave at room temperature. Side mode suppression ratios of >35 dB and continuous wave output powers of >10 mW per laser ridge were obtained

The relationship between the expression of USP22, BMI1, and EZH2 in hepatocellular carcinoma and their impacts on prognosis

Run Zhai,1,2,* Fang Tang,3,* Jianhua Gong,1,2,* Jing Zhang,1,2 Biao Lei,1,2 Bo Li,2 Yangchao Wei,1,2 Xingsi Liang,1 Bo Tang,1,2 Songqing He1,2 1Laboratory of Liver Injury and Repair Molecular Medicine, Guilin Medical University, Guilin, Guangxi, People&rsquo;s Republic of China; 2Department of Hepatobiliary Surgery, Affiliated Hospital, Guilin Medical University, Guilin, Guangxi, People&rsquo;s Republic of China; 3Pathology Department, Affiliated Hospital, Guilin Medical University, Guilin, Guangxi, People&rsquo;s Republic of China *These authors contributed equally to this work Abstract: Recent studies have shown that deubiquitination plays a key role in tumor progression, metastasis, resistance to chemotherapy drugs, and prognosis. In this study, we investigated the effects of the deubiquitinating enzyme USP22 on the expression of the drug-resistance genes BMI1 and EZH2 in hepatocellular carcinoma (HCC) and on prognosis. Downregulation of USP22 expression with interference ribonucleic acid in resistant HCC cell lines with high USP22 expression resulted in decreased BMI1 expression, but had no effect on EZH2 expression. USP22, BMI1, and EZH2 were highly expressed in HCC tissue, and the expression levels were positively correlated with tumor grade and clinical stage. Correlation analysis showed that USP22 expression was positively correlated with that of BMI1. Kaplan&ndash;Meier analysis showed that high levels of USP22 and BMI1 expression were associated with poor overall survival and relapse-free survival in all of the cases and in patients treated with transcatheter arterial chemoembolization. These results suggested that high levels of USP22 expression played an important role in drug resistance to chemotherapeutic drugs in HCC patients by upregulating the expression of BMI1; therefore, coexpression of USP22 and BMI1 may become a new predictor for HCC prognosis and may help guide clinical treatment. Keywords: hepatocellular carcinoma, USP22, BMI1, EZH

The mechanism underlying alpinetin-mediated alleviation of pancreatitis-associated lung injury through upregulating aquaporin-1

Xingsi Liang,1,2,* Bin Zhang,3,* Quan Chen,4,* Jing Zhang,1,5 Biao Lei,1,5 Bo Li,5 Yangchao Wei,1,5 Run Zhai,1,5 Zhiqing Liang,2 Songqing He,1,5 Bo Tang1,5 1Laboratory of Liver Injury and Repair Molecular Medicine, Guilin Medical University, 2Department of Infectious Diseases, Guilin Medical University, Affiliated Hospital, Guilin, Guangxi, 3Department of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 4Department of Anesthesiology, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning, 5Department of Hepatobiliary Surgery, Guilin Medical University, Affiliated Hospital, Guilin, Guangxi, People&rsquo;s Republic of China *These authors contributed equally to this work Abstract: Characterized by its acute onset, critical condition, poor prognosis, and high mortality rate, severe acute pancreatitis (SAP) can cause multiple organ failure at its early stage, particularly acute lung injury (ALI). The pathogenesis of ALI is diffuse alveolar damage, including an increase in pulmonary microvascular permeability, a decrease in compliance, and invasion of many inflammatory cells. Corticosteroids are the main treatment method for ALI; however, the associated high toxicity and side effects induce pain in patients. Recent studies show that the effective components in many traditional Chinese medicines can effectively inhibit inflammation with few side effects, which can decrease the complications caused by steroid consumption. Based on these observations, the main objective of the current study is to investigate the effect of alpinetin, which is a flavonoid extracted from Alpinia katsumadai Hayata, on treating lung injury induced by SAP and to explore the mechanism underlying the alpinetin-mediated decrease in the extent of ALI. In this study, we have shown through in vitro experiments that a therapeutic dose of alpinetin can promote human pulmonary microvascular endothelial cell proliferation. We have also shown via in vitro and in vivo experiments that alpinetin upregulates aquaporin-1 and, thereby, inhibits tumor necrosis factor-&alpha; expression as well as reduces the degree of lung injury. Overall, our study shows that alpinetin alleviates SAP-induced ALI. The likely molecular mechanism includes upregulated aquaporin expression, which inhibits tumor necrosis factor-&alpha; and, thus, alleviates SAP-induced ALI. Keywords: alpinetin, aquaporin-1, severe acute pancreatitis, acute lung injury, HPMVEC, tumor necrosis factor-&alpha