Inflammation Causes Exacerbation of COVID-19: How about Skin Inflammation?

COVID-19 is a recently emerged viral infection worldwide. SARS-CoV-2, the causative virus, is believed to have emerged from bat coronaviruses, probably through host conversion. The bat coronavirus which has the highest gene homology to SARS-CoV-2 specifically infects deep forest bats in China whose habitat extends through the Middle East to Southern Europe. Host conversion might have occurred due to the deforestation by humans exposing wild bats to the environment they had never encountered before. SARS-CoV-2 infects cells through two mechanisms: through its receptor ACE2 with the help of enzyme TMPRSS and through membrane fusion with the help of elastases in the inflammatory condition. Obesity, hypertension, diabetes mellitus, and pulmonary diseases cause poor prognosis of COVID-19. Aging is another factor promoting poor prognosis. These diseases and aging cause low-level and persistent inflammation in humans, which can promote poor prognosis of COVID-19. Psoriasis and atopic dermatitis are the major inflammatory skin diseases. These inflammatory skin conditions, however, do not seem to cause poor prognosis for COVID-19 based on the epidemiological data accumulated so far. These mechanisms need to be elucidated.     

Dimethyl Fumarate Induces Apoptosis via Inhibition of NF-κB and Enhances the Effect of Paclitaxel and Adriamycin in Human TNBC Cells

Triple-negative breast cancer (TNBC) has the poorest prognosis of all breast cancer subtypes. Recently, the activation of NF-κB, which is involved in the growth and survival of malignant tumors, has been demonstrated in TNBC, suggesting that NF-κB may serve as a new therapeutic target. In the present study, we examined whether dimethyl fumarate (DMF), an NF-κB inhibitor, induces apoptosis in TNBC cells and enhances the apoptosis-inducing effect of paclitaxel and adriamycin. Cell survival was analyzed by the trypan blue assay and apoptosis assay. Protein detection was examined by immunoblotting. The activation of NF-κB p65 was correlated with poor prognosis in patients with TNBC. DMF induced apoptosis in MDA-MB-231 and BT-549 cells at concentrations that were non-cytotoxic to the normal mammary cell line MCF-10A. Furthermore, DMF inhibited NF-κB nuclear translocation and Survivin, XIAP, Bcl-xL, and Bcl-2 expression in MDA-MB-231 and BT-549 cells. Moreover, DMF enhanced the apoptosis-inducing effect of paclitaxel and adriamycin in MDA-MB-231 cells. These findings suggest that DMF may be an effective therapeutic agent for the treatment of TNBC, in which NF-κB is constitutively active. DMF may also be useful as an adjuvant therapy to conventional anticancer drugs.     

Mechanism of Selective Phytotoxicity of l-3,4-Dihydroxyphenylalanine (l-Dopa) in Barnyardglass and Lettuce

l-3,4-Dihydroxyphenylalanine (l-dopa) is one of the few allelochemicals in which the phytotoxic action mechanism has been studied. Excess exogenous l-dopa suppresses root elongation in some plant species, and the inhibitory action is species-selective. The main factor of phytotoxicity of l-dopa is considered to be oxidative damage by reactive oxygen species (ROS) and/or free radical species (FRS). This study was performed to elucidate the mechanism of species-selective phytotoxicity. The involvement of ROS/FRS and polyphenol oxidase (PPO) in species-selective phytotoxicity was examined with barnyardgrass (Echinochloa crus-galli L.) and lettuce (Lactuca sativa L.), tolerant and susceptible species, respectively. Lipid peroxidation and melanin accumulation correlated with growth inhibition by L-dopa. Antioxidants, ascorbic acid and α-tocopherol, decreased lipid peroxidation and melanin accumulation and rescued lettuce root from growth inhibition. The oxidation of L-dopa by PPO was much greater in lettuce than in barnyardgrass. From these results, the phytotoxicity of L-dopa is considered due to the oxidative damage caused by ROS/FRS generated from the melanin synthesis pathway. PPO activity might be involved in the mechanism of species-selective phytotoxicity between barnyardgrass and lettuce.     

Effect of polymer precursors on carbon molecular sieve structure and separation performance properties

Polymer precursor and processing method have a significant effect on the separation performance of carbon molecular sieve (CMS) membranes. The authors previously developed a polymer processing method involving oxygen exposure during pyrolysis using synthesized polyimide, 6FDA/BPDA-DAM. The objectives of this work were (i) to demonstrate the generality of the oxygen doping method with a commercially available polymer Matrimid®, (ii) to investigate resultant CMS membrane structures, and (iii) to engineer the CMS performance observed with Matrimid® precursor by tuning the pyrolysis temperature. The investigation of the pore structures is challenging due to their amorphous structures. Various researchers investigated using traditional characterization methods, such as XRD and adsorption, yet molecular sieving structure in ultramicropore region is still not known. Here, the authors investigated using gas molecules as a probe. By interpolating the characterization results, hypothetical ultramicropore size distributions for each CMS membranes are suggested. The results are used to explain dramatically different separation performance trends observed between 6FDA/BPDA-DAM and Matrimid® CMS membranes and to adapt the doping method on Matrimid® CMS membrane for better performance.     

Review of the main developments in the analytic hierarchy process

In this paper the authors review the developments of the analytic hierarchy process (AHP) since its inception. The focus of this paper is a neutral review on the methodological developments rather than reporting its applications that have appeared since its introduction. In particular, we discuss problem modelling, pair-wise comparisons, judgement scales, derivation methods, consistency indices, incomplete matrix, synthesis of the weights, sensitivity analysis and group decisions. All have been important areas of research in AHP.     

A pilot survey of 39 Victorian WWTP effluents using a high speed luminescent umu test in conjunction with a novel GC-MS-database technique for automatic identification of micropollutants

In 2007, samples of treated effluent were collected at point of discharge to the environment from 39 wastewater treatment plants (WWTPs) located across Victoria, Australia grouped by treatment type. Sample genotoxicity was assessed with a high-throughput luminescent umu test method using Salmonella typhimurium TL210 strain, with and without addition of a commercially available metabolic activation system. Samples were also screened using a gas chromatographic-mass spectrometric mass-structure database recognition method. A genotoxic response was observed in half of the samples tested without metabolic activation system (相似文献   

Loading sequence plays an important role in enhanced load sensitivity of left ventricular relaxation in conscious dogs with tachycardia-induced cardiomyopathy

BACKGROUND: Left ventricular relaxation rate in the failing heart depends more on the systolic load than in the normal heart. To elucidate the mechanisms for the enhanced load sensitivity of left ventricular relaxation in heart failure, we examined the relative contributions of changes in end-systolic volume and loading sequence to the left ventricular relaxation rate. METHODS AND RESULTS: In seven conscious dogs, the time constant (Td) of left ventricular pressure decay, end-systolic volume, systolic circumferential force, and time to peak force during caval occlusion were compared before and after development of tachycardia-induced heart failure. Rapid ventricular pacing decreased the slope of the end-systolic pressure-volume relation from 4.5 to 2.8 mm Hg/mL (P < .01) and prolonged Td from 33 to 49 ms (P < .01). In normal conditions, caval occlusion reduced end-systolic force (-580 g, P < .01) and end-systolic volume (-7 mL, P < .01) but did not change Td or time to peak force. In heart failure, however, caval occlusion shortened Td (-11 ms, P < .01), with a concomitant decrease in the time to peak force (-30 ms, P < .01), while end-systolic volume and force declined slightly. Consequently, for a comparable reduction in end-systolic force, Td decreased more in heart failure than in normal hearts, suggesting enhanced load sensitivity. Moreover, changes in Td correlated well with those in the time to peak force (r = .79, P < .01) but not with those in end-systolic volume. CONCLUSIONS: Loading sequence rather than elastic recoil seems to play the predominant role in the enhanced load sensitivity of left ventricular relaxation in heart failure.     

Static Coarse Grain Task Scheduling with Cache Optimization Using OpenMP

Effective use of cache memory is getting more important with increasing gap between the processor speed and memory access speed. Also, use of multigrain parallelism is getting more important to improve effective performance beyond the limitation of loop iteration level parallelism. Considering these factors, this paper proposes a coarse grain task static scheduling scheme considering cache optimization. The proposed scheme schedules coarse grain tasks to threads so that shared data among coarse grain tasks can be passed via cache after task and data decomposition considering cache size at compile time. It is implemented on OSCAR Fortran multigrain parallelizing compiler and evaluated on Sun Ultra80 four-processor SMP workstation using Swim and Tomcatv from the SPEC fp 95. As the results, the proposed scheme gives us 4.56 times speedup for Swim and 2.37 times on 4 processors for Tomcatv respectively against the Sun Forte HPC Ver. 6 update 1 loop parallelizing compiler.     

Amorphous nanosilicas induce consumptive coagulopathy after systemic exposure

We previously reported that well-dispersed amorphous nanosilicas with particle size 70 nm (nSP70) penetrate skin and produce systemic exposure after topical application. These findings underscore the need to examine biological effects after systemic exposure to nanosilicas. The present study was designed to examine the biological effects. BALB/c mice were intravenously injected with amorphous nanosilicas of sizes 70, 100, 300, 1000 nm and then assessed for survival, blood biochemistry, and coagulation. As a result, injection of nSP70 caused fatal toxicity, liver damage, and platelet depletion, suggesting that nSP70 caused consumptive coagulopathy. Additionally, nSP70 exerts procoagulant activity in vitro associated with an increase in specific surface area, which increases as diameter reduces. In contrast, nSP70-mediated procoagulant activity was absent in factor XII-deficient plasma. Collectively, we revealed that interaction between nSP70 and intrinsic coagulation factors such as factor XII, were deeply related to nSP70-induced harmful effects. In other words, it is suggested that if interaction between nSP70 and coagulation factors can be suppressed, nSP70-induced harmful effects may be avoided. These results would provide useful information for ensuring the safety of nanomaterials (NMs) and open new frontiers in biological fields by the use of NMs.