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Compton Knox posted an update 6 months, 2 weeks ago
Research on direct targets of traditional Chinese medicine (TCM) is the key to study the mechanism and material basis of it, but there is still no effective methods at present. We took Compound Danshen dropping pills (CDDP) as a study case to establish a strategy to identify significant direct targets of TCM. As a result, thirty potential active kinase targets of CDDP were identified. Nine of them had potential dose-dependent effects. In addition, the direct inhibitory effect of CDDP on three kinases, AURKB, MET and PIM1 were observed both on biochemical level and cellular level, which could not only shed light on the mechanisms of action involved in CDDP, but also suggesting the potency of drug repositioning of CDDP. Our results indicated that the research strategy including both in silico models and experimental validation that we built, were relatively efficient and reliable for direct targets identification for TCM prescription, which will help elucidating the mechanisms of TCM and promoting the modernization of TCM.Multi-component active plasmas are modeled in the presence of a constant oblique magnetic field by using the hydrodynamics equations. Assuming the electrons and negative ions have Boltzmann distribution and the positive ions have finite temperature, the sheath formation criterion is derived by analyzing the Sagdeev potential. It is found that the Bohm velocity of positive ions depends sensitively on the plasma parameters such as ion-neutral collision frequency, electron impact ionization frequency, positive and negative ion temperatures, initial densities of the charged particles and direction of the applied magnetic field. Also, using our obtained Bohm criterion, the sheath properties of an active magnetized plasma consisting of electrons and positive and negative ion species are investigated numerically and the results are compared with the results of a similar quiescent plasma.Early classification and risk assessment for COVID-19 patients are critical for improving their terminal prognosis, and preventing the patients deteriorate into severe or critical situation. We performed a retrospective study on 222 COVID-19 patients in Wuhan treated between January 23rd and February 28th, 2020. A decision tree algorithm has been established including multiple factor logistic for cluster analyses that were performed to assess the predictive value of presumptive clinical diagnosis and features including characteristic signs and symptoms of COVID-19 patients. Selleckchem DC661 Therapeutic efficacy was evaluated by adopting Kaplan-Meier survival curve analysis and cox risk regression. The 222 patients were then clustered into two groups cluster I (common type) and cluster II (high-risk type). High-risk cases can be judged from their clinical characteristics, including age > 50 years, chest CT images with multiple ground glass or wetting shadows, etc. Based on the classification analysis and risk factor analysis, a decision tree algorithm and management flow chart were established, which can help well recognize individuals who needs hospitalization and improve the clinical prognosis of the COVID-19 patients. Our risk factor analysis and management process suggestions are useful for improving the overall clinical prognosis and optimize the utilization of public health resources during treatment of COVID-19 patients.The recycled Al alloys have a Fe level above the recommended limits, leading to the precipitation of β-Fe intermetallic particles in their microstructure. The brittle β-Fe particles show a rough morphology in the form of highly-faceted platelets, which is detrimental to the alloy’s mechanical performance containing these precipitates. This work analyses the possible interactions of the addition of 0-1 wt% of the grain refiner Nb + B to the morphology and size of β-Fe precipitates in alloys melted with Al-(7, 9, 12) wt% Si and 1 wt% Fe. The results indicate that the addition of the Nb + B inoculant revealed a significant change in the precipitates’ size and morphology, which have become remarkably refined and spheroidized. Moreover, deepening the study through qualitative and quantitative analyses, it was found that the behaviour of the β-Fe precipitates follows an exponential decay with the increasing addition of Nb + B, a curve analogous to the primary α-Al grain refinement one, revealing a direct correlation between the events. Finally, it was possible to suggest a mechanism that shows how the phenomenon of morphological transformation of the β-Fe precipitates occurs in the material with the addition of the Nb + B inoculant.Tobacco smoking is the largest risk factor for developing chronic obstructive pulmonary disease (COPD), and is associated with hyperresponsiveness of airway smooth muscle (ASM). Chronic exposure to cigarette smoke (CS) leads to airway inflammation and remodelling. However, the direct effect of gaseous CS or CS extract (CSE) on human airway smooth muscle cell (hASMC) function remains poorly understood. This study investigated the acute effect of CS/CSE on calcium homeostasis, a key regulator of ASM physiology and pathophysiology. Primary hASMC were isolated from non-smoking donor lungs, and subjected to Ca2+ imaging studies. We found that both CS, and CSE, rapidly elevated cytosolic Ca2+ in hASMC through stimulation of plasmalemmal Ca2+ influx, but excluded store-operated and L-type Ca2+ channels as mediators of this effect. Using a specific pharmacological inhibitor, or shRNA-driven knockdown, we established that both CS and CSE stimulated Ca2+ influx in hASMC through the neurogenic pain receptor channel, transient receptor potential ankyrin 1 (TRPA1). CS/CSE-dependent, TRPA1-mediated Ca2+ influx led to myosin light-chain phosphorylation, a key process regulating ASM contractility. We conclude that TRPA1 is likely an important link between CS/CSE exposure and airway hyperresponsiveness, and speculate that acute CS/CSE-induced Ca2+ influx could lead to exacerbated ASM contraction and potentially initiate further chronic pathological effects of tobacco smoke.A disintegrin and metalloprotease 17 (ADAM17) is the major sheddase that processes more than 80 substrates, including tumour necrosis factor-α (TNFα). The homozygous genetic deficiency of ADAM17 causing a complete loss of ADAM17 expression was reported to be linked to neonatal inflammatory skin and bowel disease 1 (NISBD1). Here we report for the first time, a family with NISBD1 caused by functionally confirmed compound heterozygous missense variants of ADAM17, namely c.1699T>C (p.Cys567Arg) and c.1799G>A (p.Cys600Tyr). Both variants were detected in two siblings with clinical features of NISBD1, such as erythroderma with exudate in whole body, recurrent skin infection and sepsis and prolonged diarrhoea. In a cell-based assay using Adam10/17 double-knockout mouse embryonic fibroblasts (Adam10/17-/- mEFs) exogenously expressing each of these mutants, phorbol 12-myristate 13-acetate-stimulated shedding was strongly reduced compared with wild-type ADAM17. Thus, in vitro functional assays demonstrated that both missense variants cause the loss-of-function of ADAM17, resulting in the development of NISBD1.