Search

Regulating the upstream of the cytokines production could be a promising strategy to the treatment of COVID-19. We suggest to pay more attention to the dysregulated IFN-I production in COVID-19 and to considerate cGAS, ALK and STING as potential therapeutic targets preventing cytokine storm. Approved drugs like suramin and ALK inhibitors are worthy of clinical trials., Comment: 9 pages, 3 figure

I kappa B kinase β (IKKβ) is one of the primary targets to regulate canonical NF-κB activity. The misregulation of NF-κB is associated with various diseases, including chronic inflammation and cancers. Most of the known IKKβ inhibitors target its active form and suffer from poor selectivity. In the present study, we aim to design inhibitors that can bind to the IKKβ inactive form and block its activation. We identified a potential allosteric site between the kinase domain (KD) and ubiquitin-like domain (ULD) of human IKKβ and used it to virtually screen a chemical library for allosteric inhibitors. Among the 133 compounds tested, 16 inhibited NF-κB activity by over 50% at 50 μM in a reporter gene assay. Further quantitative measurements and cytotoxicity study gave one compound

Ovarian neoplasms are group of aggressive and lethal diseases. Surgical and radiochemical therapies on ovarian neoplasm are conventional approaches but with limited progress in years. Targeted therapy with drugs targeting specific genetic alterations and/or protein molecules have brought new hope fighting against ovarian neoplasms. Targeted therapy on genetic alterations of BRAF, ROS-1 and HER2 have been carried out in melanoma, lung cancer and breast cancer with promising results. However, knowledge of these genetic alterations in ovarian neoplasms is limited and deserves further exploration. In this study, we screened genetic alterations of BRAF, ROS-1 and HER2 by immunohistochemistry (IHC) on a variety of ovarian neoplasm, including 13 mucinous carcinomas, 12 clear cell carcinomas, 9 endometrioid carcinomas, 9 serous borderline tumors and 10 high grade serous tumor of fallopian tube. Although ROS-1 and HER2 abnormalities were not identified, BRAF V600E mutations were identified in 2 of 9 (22%) in borderline serous tumors. This finding has provided a knowledge base to further study the possibility of targeted therapy using BRAF inhibitor, such as vemurafeni, on borderline serous tumor of the ovary.

Large scale fire tests of building external wall insulation system were conducted. In the experiment, thermal-couples were mounted to measure the insulation system surface temperature and the gas temperature inside rooms at the second and third floors. Photos were also taken during the fire tests. The measurement provides information of the ignition and fire spread of the external insulation system which consists of surface protection layer, glass fibre net, bonding thin layer, anchor and the load bearing wall. Comprehensive simulations of the fire tests were carried out using an advanced CFD fire simulation software Simtec (Simulation of Thermal Engineering Complex) (1, 2), which is now released by Simtec Soft Sweden, with the turbulent flow, turbulent combustion, thermal radiation, soot formation, convective heat transfer, the fully coupled three dimensional heat transfer inside solid materials, the 'burn-out' of the surface protection layer and the pyrolysis of the insulation layer, etc, all computed. The simulation is compared with experimental measurement for validation. The simulation well captured the burning and fire spread of the external insulation wall. With strategic implementation of building energy conservation, external wall insulation system has been widely used in China. Thin plaster external thermal insulation systems (TPETIS), with advantages such as light weight, low thermal conductivity, wall structure protective, simplicity in construction and etc., have become the most widely used type of wall insulation system. Typical insulating materials used in TPETIS are EPS (Expanded Polystyrene), XPS, (Extruded Polystyrene) PUR (Polyurethane) and PIR (Polyisocyanurate). In recent years, however, a number of serious fire accidents of high-rise building are related to TPETIS. This has drawn people's high attention to the fire safety of TPETIS. The fire performance of TPETIS is mainly affected by factors such as ignition source, system structure and combustion property of the insulation materials. For ignition source factor, Lee (3-5) has analyzed of the spreading mechanism of window fires (the external wall insulation system fire is usually started by window fires) and proposed a new length scale for correlating window fire's flame height, plume temperature and heat flux. Himoto (6) considered pressure gradient effect of window fire plume, and proposed a model for predicting the trajectory of window flame ejected from a fire compartment. For system structure factor, Oleszkiewicz (7) pointed out that laterally projecting structure of building facade can reduce radiant heat flow by 90%, and the vertical extending structure can increase radiation heat flux by 50%. For TPETIS, he also proposed fire-barrier belts to be used between every one or two floors. In recent years, a number of scientists (8-10) have carried out a number of window and corner fire experimental studies and indicated that the systems with improved structure (such as additional This is an Open Access article distributed under the terms of the Creative Commons Attribution License 2.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

The kinase Mirk/dyrk1B mediated the clonogenic growth of pancreatic cancer cells in earlier studies. It is now shown that Mirk levels increased 7-fold in SU86.86 pancreatic cancer cells when over a third of the cells were accumulated in a quiescent G0 state, defined by Hoechst/Pyronin Y staining. Depletion of Mirk by a doxycycline-inducible short hairpin RNA increased the G0 fraction to about 50%, suggesting that Mirk provided some function in G0. Mirk reduced the levels of reactive oxygen species (ROS) in quiescent cultures of SU86.86 cells and of Panc1 cells by increasing transcription of the antioxidant genes ferroxidase, superoxide dismutase 2 (SOD2), and superoxide dismutase 3 (SOD3). These genes were functional antioxidant genes in pancreatic cancer cells because ectopic expression of SOD2 and ferroxidase in Mirk-depleted cells lowered ROS levels. Quiescent pancreatic cancer cells quickly lost viability when depleted of Mirk because of elevated ROS levels, exhibiting up to 4-fold less colony forming activity and 4-fold less capability for dye exclusion. As a result, reduction of ROS by N-acetyl cysteine led to more viable cells. Mirk also destabilizated cyclin D1 and D3 in quiescent cells. Thus quiescent pancreatic cancer cells depleted of Mirk became less viable because they were damaged by ROS, and had increased levels of G1 cyclins to prime cells to escape quiescence.