PF-06651600, a newly discovered potent JAK3-selective inhibitor, is highly efficacious at inhibiting γc cytokine signaling, which is dependent on both JAK1 and JAK3. PF-06651600 allowed the comparison of JAK3-selective inhibition to pan-JAK or JAK1-selective inhibition, in relevant immune cells to a level that could not be achieved previously without such potency and selectivity. In vitro, PF-06651600 inhibits Th1 and Th17 cell differentiation and function, and in vivo it reduces disease pathology in rat adjuvant-induced arthritis as well as in mouse experimental autoimmune encephalomyelitis models. Importantly, by sparing JAK1 function, PF-06651600 selectively targets γc cytokine pathways while preserving JAK1-dependent anti-inflammatory signaling such as the IL-10 suppressive functions following LPS treatment in macrophages and the suppression of TNFα and IL-1β production in IL-27-primed macrophages. Thus, JAK3-selective inhibition differentiates from pan-JAK or JAK1 inhibition in various immune cellular responses, which could potentially translate to advantageous clinical outcomes in inflammatory and autoimmune diseases.
Interface engineering is an effective approach to achieve abundant surface catalytic active sites and strong electronic interactions among active materials of heterostructured catalysts.
Ion beam sputtering deposition (IBSD) is used to synthesize high quality few-layer hexagonal boron nitride (h-BN) on copper foils. Compared to the conventional chemical vapor deposition, the IBSD technique avoids the use of unconventional precursors and is much easier to control, which should be very useful for the large-scale production of h-BN in the future.
ObjectiveRecently, there have been several studies on the clinical characteristics of patients with coronavirus disease 2019 (COVID-19); however, these studies have mainly been concentrated in Wuhan, China; the sample sizes of each article were different; and the reported clinical characteristics, especially blood biochemical indices, were quite different. This study aimed to summarize the blood biochemistry characteristics of COVID-19 patients by performing a systemic review and meta-analysis of published studies.MethodsComprehensive studies were screened from PubMed, Embase, and Cochrane Library through March 11, 2020. The inclusion criteria included studies investigating the biochemical indexes of patients with COVID-19. The statistical software R3.6.3 was used for meta-analysis.ResultsTen studies including 1745 COVID-19 patients met the inclusion criteria for our meta-analysis. Meta-analysis showed that 16% and 20% of patients with COVID-19 had alanine transaminase (ALT) and aspartate aminotransferase (AST) levels higher than the normal range, respectively. Thirty-four percent of patients showed albumin (ALB) levels lower than the normal range, and 6% of patients showed abnormal total bilirubin (TBil) levels. The levels of creatinine (CRE) were increased in 8% of patients. The creatine kinase (CK) level of 13% of patients exceeded the normal range, and 52% of patients had elevated lactate dehydrogenase (LDH) levels. In addition, six studies met the inclusion criteria for the systemic review evaluating the relevance between LDH levels and the severity of COVID-19, and all six studies showed a positive association between these two factors.ConclusionsSome patients with COVID-19 had different degrees of blood biochemical abnormalities, which might indicate multiple organ dysfunction. Some biochemical indexes, such as abnormal ALB and LDH, could reflect the severity of the disease to a certain extent. These blood biochemical indicators should be considered in the clinical management of the disease.
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