Study on design optimization of GFRP tubular column composite structure based on machine learning method.

Circular reinforced concrete wound glass fiber reinforced polymer (GFRP) columns and reinforced concrete filled GFRP columns are extensively utilized in civil engineering practice. Various factors influence the performance of these two types of GFRP columns, thereby impacting the whole project. Therefore, it is highly significant to establish the prediction models for ultimate displacement and ultimate bearing capacity to optimize the design of the two types of GFRP columns. In this study, based on the experiments conducted under different conditions on the two kinds of GFRP columns, automatic machine learning along with four other commonly used machine learning methods were employed for modeling to analyze how the column parameters (cross section shape, concrete strength, height of GFRP column, wound GFRP wall thickness, inner diameter of wound GFRP column) affect their performance. The differences in performance among these five machine learning methods were analyzed after modeling. Subsequently, we obtained the variation patterns in ultimate displacement and ultimate bearing capacity of the columns influenced by each parameter by testing the data using the optimal model. Based on these findings, the optimal design schemes for the two types of GFRP columns are proposed. The contribution of this paper is three-fold. First, AutoML sheds light on the automatic prediction of ultimate displacement and ultimate bearing capacity of GFRP column. Second, in this paper, two optimal design schemes of GFRP columns are proposed. Third, for AEC industrial practitioners, the whole process is automatic, accurate and less reliant on data expertise and the optimization design scheme proposed in the article is relatively scientific.

Oncolytic herpes simplex virus delivery of dual CAR targets of CD19 and BCMA as well as immunomodulators to enhance therapeutic efficacy in solid tumors combined with CAR T cell therapy.

Background: The CAR T-cell therapy is a promising approach to treating hematologic malignancies. However, the application in solid tumors still has many tough challenges, including heterogenicity in antigen expressions and immunosuppressive tumor microenvironment (TME). As a new cancer treatment modality, oncolytic virotherapy can be engineered to circumvent these obstacles for CAR T cell therapy in solid tumors. Methods: In this study, an oHSV T7011 is engineered to drive ectopic expression of dual-antigens, extracellular domains of CD19 and BCMA, on the solid tumor cell surface to be targeted by approved CAR T cells. In addition, multiple immunomodulators, CCL5, IL-12, and anti-PD-1 antibody are also included to modulate the TME. The antitumor activities of T7011 in combination with CD19 or BCMA CAR T-cell were evaluated in vitro and in vivo. Results: The expression of CD19 or BMCA on the tumor cell surface could be detected after T7011 infection. The level of CCL5 in TME was also increased. Efficacy studies demonstrated that combination with T7011 and CAR-TCD19 or CAR-TBCMA cells showed significant synergistic anti-tumor responses in several solid tumor models. Conclusion: These studies indicated that the new generation of oHSV T7011 can be a promising combinational therapy with CD19 or BCMA-specific CAR T cells for the treatment of a broad range of solid tumors.

Encapsulation of catechin into nano-cyclodextrin-metal-organic frameworks: Preparation, characterization, and evaluation of storage stability and bioavailability.

This study, nanoscale α-, ß-, γ-cyclodextrin (CD)-metal-organic frameworks (MOFs) were successfully prepared using solvothermal assisted ultrasound method. CD-MOFs were used as nanocarriers to encapsulate catechin (CA), and their encapsulation capacities were evaluated. Encapsulation capacities of CD-MOFs to incorporate CA followed the order: ß-CD-MOFs > Î³-CD-MOFs > α-CD-MOFs. CA/CD-MOFs were characterized using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD) and differential scanning calorimetry (DSC). DSC and SEM results provided evidence for the formation of CA/CD-MOFs. XRD results indicated the new solid crystalline phases formed in CA/CD-MOFs complex. Results of FT-IR showed that CA was combined with CD-MOFs through hydrogen bonding and van der Waals forces. Current research demonstrated that encapsulation of CA within CD-MOFs provided it against light, oxygen and temperature. Moreover, encapsulation by CD-MOFs improved storage stability and bioavailability of CA. Thus, these CA/CD-MOFs have potential to be used as nutritional supplements and functional foods.

Power Distance Belief and Workplace Communication: The Mediating Role of Fear of Authority.

Power distance is the degree of acceptance of unequal distribution of power in societies. In a high power distance context, the acceptance of inequality conflicts with the operation of modern organizations, which causes obstacles to workplace communication or even triggers workplace accidents due to ineffective communication. We conducted four studies (N = 1063) to explore the relations between and mechanisms of power distance belief and workplace communication. In Study 1, the participants with high power distance belief had ineffective workplace communication-specifically ineffective communication with superiors-but no difference in communication with subordinates and colleagues. We further focused on the mechanism underlying the relationship between power distance belief and communication with superiors. A questionnaire study (Study 2) was conducted in three stages over a three-month period, and an experimental study (Study 3) indicated that fear of authority mediated the negative effect of high power distance on communication with superiors. A cross-culture study (Study 4) re-tested the hypotheses among Chinese and U.S. participants. This research provides insight into the mechanisms that explain the relationship between power distance belief and workplace communication, indicating that fear of authority is significant. Organizations should pay attention to power distance belief and fear of authority, as they may lead to workplace accidents due to communication disasters.

The Second-Generation XPO1 Inhibitor Eltanexor Inhibits Human Cytomegalovirus (HCMV) Replication and Promotes Type I Interferon Response.

Human cytomegalovirus (HCMV) is a ubiquitous opportunistic pathogen and can be life-threatening for immunocompromised individuals. There is currently no available vaccine for the prevention of HCMV- associated diseases and most of the available antiviral drugs that target viral DNA synthesis become ineffective in treating HCMV mutants that arise after long-term use in immunocompromised patients. Here, we examined the effects of Eltanexor, a second-generation selective inhibitor of nuclear export (SINE), on HCMV replication. Eltanexor effectively inhibits HCMV replication in human foreskin fibroblasts in a dose-dependent manner. Eltanexor does not significantly inhibit viral entry and nuclear import of viral genomic DNA, but rather suppress the transcript and protein levels of viral immediate-early (IE), early (E) and late (L) genes, and abolishes the production of infectious virions. We further found Eltanexor treatment promotes proteasome-mediated degradation of XPO1, which contributes to the nuclear retention of interferon regulatory factor 3 (IRF-3), resulting in increased expression of type I interferon as well as interferon stimulating genes ISG15 and ISG54. This study reveals a novel antiviral mechanism of Eltanexor which suggests it has potential to inhibit a broad spectrum of viral pathogens.

Heterogeneous Responses of Gastric Cancer Cell Lines to Tenovin-6 and Synergistic Effect with Chloroquine.

Gastric cancer (GC) is the fifth most frequently diagnosed cancer and the third leading cause of cancer death. Approximately 15% of GC is associated with Epstein-Barr virus (EBV). GC is largely incurable with a dismal five-year survival rate. There is an urgent need to identify new therapeutic agents for the treatment of GC. Tenovin-6 was initially identified as a p53 activator, but it was later found to inhibit autophagy flux, and the protein deacetylase activity of sirtuins. Tenovin-6 shows promising therapeutic effect in various malignancies. However, it remains unknown whether Tenovin-6 is effective for GC. In this study, we found that EBV-positive and -negative GC cell lines were sensitive to Tenovin-6 but with different response times and doses. Tenovin-6 suppressed anchorage-independent growth of GC cells. Tenovin-6 induced different levels of apoptosis and phases of cell-cycle arrest depending on the cell lines with some manifesting gap 1 (G1) and others showing synthesis (S) phase cell-cycle arrest. Mechanistically, Tenovin-6 induced autophagy or p53 activation in GC cells depending on the status of TP53 gene. However, initiation of autophagy following treatment with Tenovin-6 conferred some protective effect on numerous cells. Combined treatment with Tenovin-6 and autophagy inhibitor chloroquine increased the cytotoxic effect by inducing microtubule-associated protein 1 light chain 3B (LC3B)-II accumulation, and by enhancing apoptosis and cell-cycle arrest. These results indicated that Tenovin-6 can be used as a potential therapeutic agent for GC, but the genetic background of the cancer cells might determine the response and mechanism of action. Treatment with Tenovin-6 alone or in combination with chloroquine could be a promising therapeutic approach for GC.