Hydroxychloroquine (HCQ) is an antimalarial drug also used in treating autoimmune diseases. Its antiviral activity was demonstrated in restricting HIV infection in vitro; however, the clinical implications remain controversial. Infection with dengue virus (DENV) is a global public health problem, and we lack an antiviral drug for DENV. Here, we evaluated the anti-DENV potential of treatment with HCQ. Immunofluorescence assays demonstrated that HCQ could inhibit DENV serotype 1-4 infection in vitro. RT-qPCR analysis of HCQtreated cells showed induced expression of interferon (IFN)-related antiviral proteins and certain inflammatory cytokines. Mechanistic study suggested that HCQ activated the innate immune signaling pathways of IFN-b, AP-1, and NFkB. Knocking down mitochondrial antiviral signaling protein (MAVS), inhibiting TANK binding kinase 1 (TBK1)/inhibitor-kB kinase e (IKKe), and blocking type I IFN receptor reduced the efficiency of HCQ against DENV-2 infection. Furthermore, HCQ significantly induced cellular production of reactive oxygen species (ROS), which was involved in the host defense system. Suppression of ROS production attenuated the innate immune activation and anti-DENV-2 effect of HCQ. In summary, HCQ triggers the host defense machinery by inducing ROS-and MAVS-mediated innate immune activation against DENV infection and may be a candidate drug for DENV infection.

Ubiquitin-conjugating enzyme 2C (UBE2C) contributes to ubiquitin-mediated proteasome degradation of cell cycle progression in breast cancer. Microcalcification (MC) is the most common mammographic feature of early breast cancer. In this study, we evaluated whether UBE2C could be a tumor marker of early breast cancer with MC found on screening mammography. UBE2C protein and mRNA expression were measured in breast core biopsy pairs of MC and adjacent non-MC breast tissue from each subject. Immunohistochemistry revealed UBE2C positivity in 69.4% of MC samples and 77.6% negativity in non-MC samples (p<0.0001). On RT-qPCR, 56.1% of malignant MC lesion samples showed high mRNA level of UBE2C and 80% of benign MC lesion samples showed a low level of UBE2C (p = 0.1766). We investigated the carcinogenic role of UBE2C in MCF-7 breast cancer cells with UBE2C knockdown; UBE2C knockdown downregulated cell proliferation and activated the cellular apoptosis pathway to inhibit cell colony formation. Furthermore, UBE2C expression was associated with that of carcinogenic genes human epidermal growth factor receptor type 2 (HER2), cellular c-Ki-ras2 proto-oncogene (KRAS), vascular endothelial growth factor (VEGF), CXC chemokine receptor 4 (CXCR4), C-C motif chemokine 5 (CCL5), neural precursor cell expressed, developmentally downregulated 9 (NEDD9) and Ras homolog family member C (RhoC). UBE2C may be a marker for diagnosis of nonpalpable breast lesions but not benign or malignant tumors in mammography core biopsies. Suppression of UBE2C may be a potential therapy target in breast cancer.

Epidemiological studies based on the “hygiene hypothesis” declare that the level of childhood exposure to environmental microbial products is inversely related to the incidence of allergic diseases in later life. Multiple types of immune cell-mediated immune regulation networks support the hygiene hypothesis. Epithelial cells are the first line of response to microbial products in the environment and bridge the innate and adaptive immune systems; however, their role in the hygiene hypothesis is unknown. To demonstrate the hygiene hypothesis in airway epithelial cells, we examined the effect of lipopolysaccharide (LPS; toll-like receptor 4 ligand) on the expression of the proallergic cytokines thymic stromal lymphopoietin (TSLP) and interleukin 33 (IL33) in H292 cells (pulmonary mucoepidermoid carcinoma cells). Stimulation with the TLR ligand polyI:C and human parechovirus type 1 (HPeV1) but not LPS-induced TSLP and IL33 through interferon regulatory factor 3 (IRF3) and NF-κB activity, which was further validated by using inhibitors (dexamethasone and Bay 11-7082) and short hairpin RNA-mediated gene knockdown. Importantly, polyI:C and HPeV1-stimulated TSLP and IL33 induction was reduced by LPS treatment by attenuating TANK-binding kinase 1, IRF3, and NF-κB activation. Interestingly, the basal mRNA levels of TLR signaling proteins were downregulated with long-term LPS treatment of H292 cells, which suggests that such long-term exposure modulates the expression of innate immunity signaling molecules in airway epithelial cells to mitigate the allergic response. In contrast to the effects of LPS treatment, the alarmin high-mobility group protein B1 acts in synergy with polyI:C to promote TSLP and IL33 expression. Our data support part of the hygiene hypothesis in airway epithelia cells in vitro. In addition to therapeutic targeting of TSLP and IL33, local application of non-pathogenic LPS may be a rational strategy to prevent allergies.

Dengue virus types 1-4 (DENV-1-4) are positive-strand RNA viruses with an envelope that belongs to the Flaviviridae. DENV infection threatens human health worldwide. However, other than supportive treatments, no specific therapy is available for the infection. In order to discover novel medicine against DENV, we tested 59 crude extracts, without cytotoxicity, from 23 plants in vitro; immunofluorescence assay revealed that the methanol extracts of fruit, heartwood, leaves and stem from Ficus septica Burm. f. had a promising anti-DENV-1 and DENV-2 effect. However, infection with the non-envelope picornavirus, Aichi virus, was not inhibited by treatment with F. septica extracts. F. septica may be a candidate antiviral drug against an enveloped virus such as DENV.

The iNOS/NO system may be important in the pathophysiology of nasal polyposis. The increased peroxynitrite may result from increased iNOS expression but is not related to decreased SODs.

Purpose Glass fibers were introduced to increase the fracture resistance of resin‐based composites restorations; however, the poor polymerization between fibers and resin‐based composite were sometimes noted and can cause debonding and failure. The purpose of this study was to investigate the effects of different polymerization methods as well as fiber types on the mechanical behavior of fiber‐reinforced resin‐based composites. Materials and Methods Seventy‐five specimens were fabricated and divided into one control group and four experimental groups (n = 15), according to the type of glass fiber (strip or mesh) and polymerization methods (one‐ or two‐step). A 0.2‐mm‐thick fiber layer was fabricated with different polymerization methods, on top of which a 1.8 mm resin‐based composite layer was added to make a bar‐shape specimen, followed by a final polymerization. Specimens were tested for flexural strength and flexural modulus. The failure modes of specimens were observed by scanning electron microscopy. Results The fiber types showed significant effect on the flexural strength of test specimens (F = 469.48, p < 0.05), but the polymerization methods had no significant effect (F = 0.05, p = 0.82). The interaction between these two variables was not significant (F = 1.73, p = 0.19). In addition, both fiber type (F = 9.71, p < 0.05) and polymerization method (F = 12.17, p < 0.05) affected the flexural modulus of test specimens; however, the interaction between these two variables was not significant (F = 0.40, p = 0.53). Conclusions The strip fibers showed better mechanical behavior than mesh fibers and were suggested for resin‐based composites restorations reinforcement; however, different polymerization methods did not have a significant effect on the strength and failure mode of fiber‐reinforced resin‐based composites.

The flexural behavior of reinforced concrete beams strengthened by CFRP is analyzed by using the way which connected tests with finite element simulation.First,through the test to get the load data of one unstrengthened and one strengthened reinforced concrete beam.Then,the finite element model is carried out based on Ansys finite element analysis software.The reinforced beam carrying capacity is improved based on the test data and finite element calculation results.Steel bars stress change curve, CFRP stress curve and the load displacement curves are in good agreement with experimental results.