Clusterin confers gmcitabine resistance in pancreatic cancer

<p>Abstract</p> <p>Objective</p> <p>To measure clusterin expression in pancreatic cancer tissues and cell lines and to evaluate whether clusterin confers resistance to gmcitabine in pancreatic cancer cells.</p> <p>Methods</p> <p>Immunohistochemistry for clusterin was performed on 50 primary pancreatic cancer tissues and 25 matched backgrounds, and clusterin expression in 5 pancreatic cancer cell lines was quantified by Western blot and PT-PCR. The correlation between clusterin expression level and gmcitabine IC50 in pancreatic cancer cell lines was evaluated. The effect of an antisense oligonucleotide (ASO) against clusterin(OGX-011) on gmcitabine resistance was evaluated by MTT assays. Xenograft model was used to demonstrate tumor growth.</p> <p>Results</p> <p>Pancreatic cancer tissues expressed significantly higher levels of clusterin than did normal pancreatic tissues (<it>P </it>< 0.01). Clusterin expression levels were correlated with gmcitabine resistance in pancreatic cancer cell lines, and OGX-011 significantly decreased BxPc-3 cells resistance to gmcitabine (<it>P </it>< 0.01). <it>In vivo </it>systemic administration of AS clusterin and gmcitabine significantly decreased the s.c. BxPC-3 tumor volume compared with mismatch control ODN plus gmcitabine.</p> <p>Conclusion</p> <p>Our finding that clusterin expression was significantly higher in pancreatic cancer than in normal pancreatic tissues suggests that clusterin may confer gmcitabine resistance in pancreatic cancer cells.</p

Direction finding and mutual coupling estimation for uniform rectangular arrays

A novel two-dimensional (2-D) direct-of-arrival (DOA) and mutual coupling coefficients estimation algorithm for uniform rectangular arrays (URAs) is proposed. A general mutual coupling model is first built based on banded symmetric Toeplitz matrices, and then it is proved that the steering vector of a URA in the presence of mutual coupling has a similar form to that of a uniform linear array (ULA). The 2-D DOA estimation problem can be solved using the rank-reduction method. With the obtained DOA information, we can further estimate the mutual coupling coefficients. A better performance is achieved by our proposed algorithm than those auxiliary sensor-based ones, as verified by simulation results

A third (booster) dose of the inactivated SARS-CoV-2 vaccine elicits immunogenicity and T follicular helper cell responses in people living with HIV

IntroductionThis study sought to explore the immunogenicity of a booster dose of an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in people living with human immunodeficiency virus (HIV) and identify the factors affecting the magnitude of anti-SARS-CoV-2 antibody levels.Materials and methodsA total of 34 people living with HIV (PLWH) and 34 healthy donors (HD) were administered a booster dose of the same SARS-CoV-2 vaccine. Anti-SARS-CoV-2 antibody and immunoglobulin G (IgG) levels were measured using the SARS-CoV-2 S protein neutralizing antibody Enzyme-Linked Immunosorbent Assay (ELISA) and 2019-nCov IgG Chemiluminescent Immunoassay Microparticles, respectively. Spearman correlation analysis was used to measure the correlation between laboratory markers and neutralizing antibody and IgG levels. Peripheral blood mononuclear cells (PBMCs) were extracted from each subject using density gradient centrifugation and the numbers of memory T and T follicular helper (Tfh) cells were determined using flow cytometry.ResultsPLWH had a marked reduction in CD4 and B cell levels that was accompanied by a lower CD4/CD8 T cell ratio. However, those who received a supplementary dose of inactivated SARS-CoV-2 vaccines exhibited antibody positivity rates that were analogous to levels previously observed. The booster vaccine led to a reduction in IgG and neutralizing antibody levels and the amplitude of this decline was substantially higher in the PLWH than HD group. Correlation analyses revealed a strong correlation between neutralizing antibody levels and the count and proportion of CD4 cells. Anti-SARS-CoV-2 IgG antibody levels followed a similar trend. The expression of memory T and Tfh cells was considerably lower in the PLWH than in the HD group.DiscussionPLWH had an attenuated immune response to a third (booster) administration of an inactivated SARS-CoV-2 vaccine, as shown by lower neutralizing antibody and IgG levels. This could be attributed to the reduced responsiveness of CD4 cells, particularly memory T and cTfh subsets. CD4 and cTfh cells may serve as pivotal markers of enduring and protective antibody levels. Vaccination dose recalibration may be critical for HIV-positive individuals, particularly those with a lower proportion of CD4 and Tfh cells

ESPRIT-like two-dimensional direction finding for mixed circular and strictly noncircular sources based on joint diagonalization

In this paper, a two-dimensional (2-D) direction-of-arrival (DOA) estimation method for a mixture of circular and strictly noncircular signals is presented based on a uniform rectangular array (URA). We first formulate a new 2-D array model for such a mixture of signals, and then utilize the observed data coupled with its conjugate counterparts to construct a new data vector and its associated covariance matrix for DOA estimation. By exploiting the second-order non-circularity of incoming signals, a computationally effective ESPRIT-like method is adopted to estimate the 2-D DOAs of mixed sources which are automatically paired by joint diagonalization of two direction matrices. One particular advantage of the proposed method is that it can solve the angle ambiguity problem when multiple incoming signals have the same angle θ or β. Furthermore, the theoretical error performance of the proposed method is analyzed and a closed-form expression for the deterministic Cramer-Rao bound (CRB) for the considered signal scenario is derived. Simulation results are provided to verify the effectiveness of the proposed method

ZEB2 Mediates Multiple Pathways Regulating Cell Proliferation, Migration, Invasion, and Apoptosis in Glioma

BACKGROUND: The aim of the present study was to analyze the expression of Zinc finger E-box Binding homeobox 2 (ZEB2) in glioma and to explore the molecular mechanisms of ZEB2 that regulate cell proliferation, migration, invasion, and apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: Expression of ZEB2 in 90 clinicopathologically characterized glioma patients was analyzed by immunohistochemistry. Furthermore, siRNA targeting ZEB2 was transfected into U251 and U87 glioma cell lines in vitro and proliferation, migration, invasion, and apoptosis were examined separately by MTT assay, Transwell chamber assay, flow cytometry, and western blot. RESULTS: The expression level of ZEB2 protein was significantly increased in glioma tissues compared to normal brain tissues (P<0.001). In addition, high levels of ZEB2 protein were positively correlated with pathology grade classification (P = 0.024) of glioma patients. Knockdown of ZEB2 by siRNA suppressed cell proliferation, migration and invasion, as well as induced cell apoptosis in glioma cells. Furthermore, ZEB2 downregulation was accompanied by decreased expression of CDK4/6, Cyclin D1, Cyclin E, E2F1, and c-myc, while p15 and p21 were upregulated. Lowered expression of ZEB2 enhanced E-cadherin levels but also inhibited β-Catenin, Vimentin, N-cadherin, and Snail expression. Several apoptosis-related regulators such as Caspase-3, Caspase-6, Caspase-9, and Cleaved-PARP were activated while PARP was inhibited after ZEB2 siRNA treatment. CONCLUSION: Overexpression of ZEB2 is an unfavorable factor that may facilitate glioma progression. Knockdown ZEB2 expression by siRNA suppressed cell proliferation, migration, invasion and promoted cell apoptosis in glioma cells

Interpretive Structural Analysis of Interrelationships among the Elements of Characteristic Agriculture Development in Chinese Rural Poverty Alleviation

Eradicating poverty is a strategic priority in the pursuit of Sustainable Development Goals. This study intends to identify and quantify the elements affecting the Characteristic Agriculture Development (CAD) project implemented in area of Chinese poverty and reveals the interrelationships between those elements. First-hand data for the structural modeling were collected through semi-structured interviews with a group of selected experts. As a result, this study has identified seventeen representative elements, and the interrelationships between them have been examined based on the Interpretive Structural Modeling (ISM) method. Furthermore, these elements were further categorized into four categories depending on their driving power and dependence power by using the cross-impact matrix multiplication applied to classification (MICMAC) analysis. The combination result of the elements identification, ISM modeling and MICMAC analysis provide a conceptual framework for designing, implementing, and managing CAD projects conducted in rural China. Finally, we suggest that an appropriate approach should be applied to empower the poor, promote target group participation, optimize the regional agriculture structure, and increase the agro value chain competiveness in CAD project implementation

Interpretive Structural Analysis of Interrelationships among the Elements of Characteristic Agriculture Development in Chinese Rural Poverty Alleviation

Eradicating poverty is a strategic priority in the pursuit of Sustainable Development Goals. This study intends to identify and quantify the elements affecting the Characteristic Agriculture Development (CAD) project implemented in area of Chinese poverty and reveals the interrelationships between those elements. First-hand data for the structural modeling were collected through semi-structured interviews with a group of selected experts. As a result, this study has identified seventeen representative elements, and the interrelationships between them have been examined based on the Interpretive Structural Modeling (ISM) method. Furthermore, these elements were further categorized into four categories depending on their driving power and dependence power by using the cross-impact matrix multiplication applied to classification (MICMAC) analysis. The combination result of the elements identification, ISM modeling and MICMAC analysis provide a conceptual framework for designing, implementing, and managing CAD projects conducted in rural China. Finally, we suggest that an appropriate approach should be applied to empower the poor, promote target group participation, optimize the regional agriculture structure, and increase the agro value chain competiveness in CAD project implementation