Cytotoxic Effect of Recombinant Mycobacterium tuberculosis CFP-10/ESAT-6 Protein on the Crucial Pathways of WI-38 Cells

To unravel the cytotoxic effect of the recombinant CFP-10/ESAT-6 protein (rCFES) on WI-38 cells, an integrative analysis approach, combining time-course microarray data and annotated pathway databases, was proposed with the emphasis on identifying the potentially crucial pathways. The potentially crucial pathways were selected based on a composite criterion characterizing the average significance and topological properties of important genes. The analysis results suggested that the regulatory effect of rCFES was at least involved in cell proliferation, cell motility, cell survival, and metabolisms of WI-38 cells. The survivability of WI-38 cells, in particular, was significantly decreased to 62% with 12.5 μM rCFES. Furthermore, the focal adhesion pathway was identified as the potentially most-crucial pathway and 58 of 65 important genes in this pathway were downregulated by rCFES treatment. Using qRT-PCR, we have confirmed the changes in the expression levels of LAMA4, PIK3R3, BIRC3, and NFKBIA, suggesting that these proteins may play an essential role in the cytotoxic process in the rCFES-treated WI-38 cells

Dual Associated Encoder for Face Restoration

Restoring facial details from low-quality (LQ) images has remained a challenging problem due to its ill-posedness induced by various degradations in the wild. The existing codebook prior mitigates the ill-posedness by leveraging an autoencoder and learned codebook of high-quality (HQ) features, achieving remarkable quality. However, existing approaches in this paradigm frequently depend on a single encoder pre-trained on HQ data for restoring HQ images, disregarding the domain gap between LQ and HQ images. As a result, the encoding of LQ inputs may be insufficient, resulting in suboptimal performance. To tackle this problem, we propose a novel dual-branch framework named DAEFR. Our method introduces an auxiliary LQ branch that extracts crucial information from the LQ inputs. Additionally, we incorporate association training to promote effective synergy between the two branches, enhancing code prediction and output quality. We evaluate the effectiveness of DAEFR on both synthetic and real-world datasets, demonstrating its superior performance in restoring facial details.Comment: Technical Repor

DYNAMIC KEY BLOCK DECISION WITH SPATIO-TEMPORAL ANALYSIS FOR WYNER-ZIV VIDEO CODING

ABSTRACT Wyner-Ziv coding has been recognized as the most popular method up to now. For traditional WZC, side information is generated from intra-coded frames for use in the decoding of WZ frames. The unit for intra-coding is a frame and the distance between key-frames is kept constant. In this paper, the unit for intra-coding is a block, and the temporal distance between two consecutive key blocks can varying with time. A block is assigned a mode (WZ or intra-coded), depending on the result of spatio-temporal analysis, and encoded in an alternative manner. This strategy improves the overall coding efficiency, while maintaining a low encoder complexity. The performance gain can achieve up to 6 dB with respect to the traditional pixel-domain WZC

Estimating Probable Maximum Precipitation and Probable Maximum Flood by Considering the Combined Effect of Typhoon and Monsoon Weather System under Climate Change

Source: ICHE Conference Archive - https://mdi-de.baw.de/icheArchive

Proopiomelanocortin gene delivery induces apoptosis in melanoma through NADPH oxidase 4-mediated ROS generation

AbstractHypoxia in the tumor microenvironment triggers differential signaling pathways for tumor survival. In this study, we characterize the involvement of hypoxia and reactive oxygen species (ROS) generation in the antineoplastic mechanism of proopiomelanocortin (POMC) gene delivery in a mouse B16-F10 melanoma model in vivo and in vitro. Histological analysis revealed increased TUNEL-positive cells and enhanced hypoxic activities in melanoma treated with adenovirus encoding POMC (Ad-POMC) but not control vector. Because the apoptotic cells were detected mainly in regions distant from blood vessels, it was hypothesized that POMC therapy might render melanoma cells vulnerable to hypoxic insult. Using a hypoxic chamber or cobalt chloride (CoCl2), we showed that POMC gene delivery elicited apoptosis and caspase-3 activation in cultured B16-F10 cells only under hypoxic conditions. The apoptosis induced by POMC gene delivery was associated with elevated ROS generation in vitro and in vivo. Blocking ROS generation using the antioxidant N-acetyl-l-cysteine abolished the apoptosis and caspase-3 activities induced by POMC gene delivery and hypoxia. We further showed that POMC-derived melanocortins, including α-MSH, β-MSH, and ACTH, but not γ-MSH, contributed to POMC-induced apoptosis and ROS generation during hypoxia. To elucidate the source of ROS generation, application of the NADPH oxidase inhibitor diphenyleneiodonium attenuated α-MSH-induced apoptosis and ROS generation, implicating the proapoptotic role of NADPH oxidase in POMC action. Of the NADPH oxidase isoforms, only Nox4 was expressed in B16-F10 cells, and Nox4 was also elevated in Ad-POMC-treated melanoma tissues. Silencing Nox4 gene expression with Nox4 siRNA suppressed the stimulatory effect of α-MSH-induced ROS generation and cell apoptosis during hypoxia. In summary, we demonstrate that POMC gene delivery suppressed melanoma growth by inducing apoptosis, which was at least partly dependent on Nox4 upregulation

The relationship between gallbladder status and recurrent biliary complications in patients with choledocholithiasis following endoscopic treatment

AbstractBackgroundEndoscopic methods are currently the treatment of choice for patients with common bile duct (CBD) stones, but subsequent management of the intact gallbladder for patients following endoscopic treatment is still controversial. The primary aim of this study was to discover the association between gallbladder status and recurrent biliary complications for patients with CBD stones after endoscopic treatment. Additionally, we also sought to determine risk factors for recurrent biliary complications in these patients.MethodsThe records of 1625 patients with CBD stones following endoscopic treatment were reviewed. A total of 681 patients were enrolled and subsequently categorized into four groups: Group 1 (n = 201), calculous gallbladder; Group 2 (n = 140), acalculous gallbladder; Group 3 (n = 175), elective cholecystectomy after endoscopic treatment; and Group 4 (n = 165), prior cholecystectomy. The basic demographics and recurrent biliary complications during follow-up among these four groups were analyzed by Chi-square test, ANOVA, Kaplan-Meier analysis, and log-rank test.ResultsDuring the median follow-up period of 34 months, 133 patients (20%) with recurrent biliary complications were identified. The recurrence rates of Groups 1, 2, 3, and 4 were 29%, 11%, 15%, and 19%, respectively. Kaplan-Meier analysis showed that patients with calculous gallbladder had a significantly higher rate of recurrent biliary complication. In multivariate analysis, patients with a history of cirrhosis, juxta-papillary diverticulum, calculous gallbladder, CBD size ≥1.5 cm, and endoscopic management with endoscopic sphincterotomy were at a higher risk for developing biliary complications (p = 0.029, p = 0.039, p < 0.001, p = 0.002, p = 0.021, respectively.)ConclusionPatients with cholecystolithiasis and CBD stones had a higher incidence of recurrent biliary complications. For some of these patients, elective cholecystectomy following endoscopic treatment may be considered. However, routine elective cholecystectomy in patients with normal gallbladder is not appropriate because of the low recurrence of biliary complications. Whether gallbladder function affects the biliary clearance and biliary complications requires further research

A Novel Invadopodia-Specific Marker for Invasive and Pro-Metastatic Cancer Stem Cells

IntroductionStem-like cancer cells or cancer stem cells (CSCs) may comprise a phenotypically and functionally heterogeneous subset of cells, whereas the molecular markers reflecting this CSC hierarchy remain elusive. The glycolytic enzyme alpha-enolase (ENO1) present on the surface of malignant tumor cells has been identified as a metastasis-promoting factor through its function of activating plasminogen. The expression pattern of surface ENO1 (sENO1) concerning cell-to-cell or CSC heterogeneity and its functional roles await further investigation.MethodsThe cell-to-cell expression heterogeneity of sENO1 was profiled in malignant cells from different types of cancers using flow cytometry. The subcellular localization of sENO1 and its functional roles in the invadopodia formation and cancer cell invasiveness were investigated using a series of imaging, molecular, and in vitro and in vivo functional studies.ResultsWe showed here that ENO1 is specifically localized to the invadopodial surface of a significant subset (11.1%-63.9%) of CSCs in human gastric and prostate adenocarcinomas. sENO1+ CSCs have stronger mesenchymal properties than their sENO1- counterparts. The subsequent functional studies confirmed the remarkable pro-invasive and pro-metastatic capacities of sENO1+ CSCs. Mechanistically, inhibiting the surface localization of ENO1 by downregulating caveolin-1 expression compromised invadopodia biogenesis, proteolysis, and CSC invasiveness.ConclusionsOur study identified the specific expression of ENO1 on the invadopodial surface of a subset of highly invasive and pro-metastatic CSCs. sENO1 may provide a diagnostically and/or therapeutically exploitable target to improve the outcome of patients with aggressive and metastatic cancers