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Microglia are the main effector cells of immune response in central nervous system and are important targets for disease prevention and treatment. Κ-carrageenan Oligosaccharide (KOS), obtained by enzymatic hydrolysis from carrageenan of marine red algae, can inhibit the release of inflammatory factors from the over-activated microglia. The mechanism of microglia autophagy induced by KOS and its relationship with inflammation were studied to explore the development prospect of KOS in the research and treatment of inflammatory related diseases. The effect of KOS on inducing autophagy was detected by the secretion of cytokines by lipopolysaccharide (LPS)-activated microglia, respectively. The protein expression of autophagy-related signaling pathways were detected by Western Blot. The results showed that KOS could significantly protect the microglia from over-activated inflammatory by inducing the autophagy and inhibiting the release of inflammatory cytokines. And KOS could reduce the expression of the protein that related to the AMPK/ULK1 pathways in microglia, so as to regulate the autophagy pathway, and inhibit the inflammatory response of over-activated microglia. The study on the effect of KOS on microglia autophagy and excessive inflammatory response will provide a theoretical basis for further studies on the inhibition of nerve injury by regulating microglia autophagy and inflammatory response., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Organic azides have been increasingly employed as nitrogen sources for catalytic olefine aziridination due to their ease of preparation and generation of benign N 2 as the only byproduct. Among common organic azides, carbonyl azides have not been previously demonstrated as effective nitrogen sources for intermolecular olefin aziridination despite the synthetic utilities of N-carbonyl aziridines. As a new application of metalloradical catalysis, we have developed a catalytic system that can effectively employ the carbonyl azide TrocN 3 for highly asymmetric aziridination of alkenes at room temperature. The resulting enantioenriched N -Trocaziridines have been shown as valuable chiral synthons for stereoselective synthesis of other chiral aziridines and various chiral amines. The Co(II)-based metalloradical system, which proceeds with distinctive stepwise radical mechanism, may provide a general method for asymmetric synthesis of chiral aziridines from alkenes with organic azides.

Background: We hypothesized that a high ticagrelor loading dose (LD) may improve platelet inhibition in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) undergoing percutaneous coronary intervention (PCI)., Methods: This interventional multicentre open-label trial randomized 278 patients with NSTE-ACS to a high (360 mg) or conventional (180 mg) ticagrelor LD. The primary outcome was the platelet reactivity index (PRI) 1 hour after administration of the LD. Secondary outcomes included PRI at 0.5 hour, 1 hour, 8 hours, and 24 hours; periprocedural myocardial infarction (PMI); major cardiac adverse events; and bleeding events., Results: Two hundred sixty-two patients completed the major end points. PRI was lower in the high-LD group than in the conventional-LD group at any time point (all, P < 0.05), including at 1 hour (12.2% vs 16.7%; P = 0.023). At 0.5 hour, the high-LD group showed a lower high-platelet reactivity rate (49.6% vs 60.2%; P = 0.013) and a higher low-platelet reactivity rate (24.8% vs 12.8%; P = 0.017) than did the conventional LD group. No significant differences in the bleeding rates were found between the 2 groups (14% vs 14.3%). Four cases of PMI and 1 death in each group, as well as 1 acute myocardial infarction in the conventional LD group, occurred. There was no stroke, target lesion revascularization, or target vessel revascularization., Conclusions: Doubling the ticagrelor LD achieved faster onset and greater platelet inhibition without an increase in adverse events in patients with NSTE-ACS undergoing PCI., (Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Pancreatic cancer is one of the most aggressive malignancies and chemotherapy is an effective strategy for advanced pancreatic cancer. Gemcitabine (GEM) is one of first-line agents. However, GEM-based combination therapy has shown promising efficacy in patients with advanced pancreatic cancer. This meta-analysis aimed to compare the efficacy and safety of GEM-based combination therapy versus GEM alone in the treatment of advanced pancreatic cancer., Data Sources: A comprehensive search of literature was performed using PubMed, EMBASE, Web of Science and Cochrane Central Register of Controlled Trials. A quantitative meta-analysis was performed based on the inclusion criteria from all eligible randomized controlled trials. The outcome indicators included overall survival (OS), 6-month survival, 1-year survival, progression-free survival/time-to-progression (PFS/TTP), and toxicities., Results: A total of nine randomized controlled trials involving 1661 patients were included in this meta-analysis. There was significant improvement in the GEM-based combination therapy with regard to the OS (HR=0.85, 95% CI: 0.76-0.95, P=0.003), PFS (HR=0.76, 95% CI: 0.65-0.90, P=0.002), 6-month survival (RR=1.09, 95% CI: 1.01-1.17, P=0.03), and the overall toxicity (RR=1.68, 95% CI: 1.52-1.86, P<0.01). However, there was no significant difference in the 1-year survival., Conclusions: GEM-based combination chemotherapy might improve the OS, 6-month survival, and PFS in advanced pancreatic cancer. However, combined therapy also added toxicity.

Aryloxysulfonyl azides can be effectively activated by commercially available cobalt(II) complex of meso -tetraphenylporphyrin ([Co(TPP)]) at room temperature under neutral and nonoxidative conditions for selective radical aziridination of alkenes via metalloradical catalysis. The [Co(TPP)]-catalyzed radical aziridination system is suitable for different combinations of olefin substrates and aryloxysulfonyl azides, producing various N -aryloxysulfonyl aziridine derivatives in good to excellent yields. In addition to generating the environmentally benign N 2 as the only byproduct, this Co(II)-based metalloradical aziridination process features mild reaction conditions and operational simplicity.

Background: Ischemia/reperfusion (I/R) injury is an important barrier to liver surgery and transplantation because it impairs remnant liver/reduced-size-graft regeneration. Ischemic preconditioning (IPC), as an effective measure to overcome I/R injury, has been shown to enhance the regenerative capacity of hepatocytes. However, investigations have always focused on regeneration in the late phase after reperfusion. This study aimed to investigate whether IPC enhances hepatocyte proliferation in the early phase after reperfusion and possible underlying mechanisms., Methods: A total of 90 rats were divided into three groups: hemi-hepatectomy alone (PHx group), 60 minutes of ischemia plus hemi-hepatectomy (I/R group), and a cycle of 10 minutes of alternating I/R prior to 60 minutes of ischemia plus hemi-hepatectomy (IPC group). Each group was divided into five subgroups sacrificed after 0.5, 2, 6, 12 or 24 hours (n=6/subgroup). Subsequently, serum concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) were measured; caspase-3 and proliferating cell nuclear antigen (PCNA) proteins were also determined by Western blotting. Furthermore, PCNA was detected by immunohistochemistry to identify the expression site., Results: Serum ALT and AST levels after 2-24 hours of reperfusion in the PHx and IPC groups were remarkably decreased compared to the I/R group, and the serum TNF-alpha was relatively lower. A significant increase of serum IL-6 levels was found in the PHx and IPC groups compared with the I/R group at each time point. Furthermore, PCNA expression was remarkably increased in the IPC group after 6-12 hours of reperfusion, and in the earlier 0.5 and 6 hours time points after reperfusion have shown the massive PCNA-positive hepatocytes. At the same time, the expression of liver p-JNK was higher in the IPC group in the early phase after reperfusion than that of the I/R group and its expression was consistent with the PCNA., Conclusion: IPC can initiate hepatocyte proliferation in the early phase after ischemia under hemi-hepatectomy, and may be associated with p-JNK expression and triggered by TNF-alpha/IL-6 signals.

This paper studies the cumulative effect of various parameters, namely anionic polyacrylamide (APAM) concentration, oil concentration, pH, trans-membrane pressure (TMP), and total dissolved solid (TDS), and obtains optimal parameters for the minimum relative flux (J/J(0)) declining in aqueous solutions with response surface methodology (RSM). In order to analyze the mutual interaction and optimal values of parameters affecting ultrafiltration, a central composite rotatable design (CCRD), one method of RSM, was employed. The analysis of variance (ANOVA) of the cubic polynomial model demonstrated that this model was highly significant and reliable. The results show that the effect of APAM and oil on J/J(0) has an inverse trend with pH value increasing. Moreover, the mutual interaction of initial APAM (oil) concentration (C(APAM(oil))) and pH (TMP) were negligible, while the mutual interaction of C(APAM) and C(oil) has an obvious effect, i.e. the effect of initial feed C(APAM) became more important at higher values of initial feed C(oil), and the J/J(0) was only about 4%. The favorable operate conditions in this ultrafiltration process were at low C(APAM), C(oil), pH, and TMP, which agreed with the conclusions of many authors, while considering water production, C(APAM) and C(oil) < 50 mg/L, pH < 4, and TMP < 0.075 MPa could be accepted., (Copyright © 2011 Elsevier B.V. All rights reserved.)

To determine the isotherm parameters and kinetic parameters of adsorption of anion polyacrylamide (APAM) from aqueous solution on PVDF ultrafiltration membrane (PM) and modified PVDF ultrafiltration membrane (MPM) is important in understanding the adsorption mechanism of ultrafiltration processes. Effect of variables including adsorption time, initial solution concentration, and temperature were investigated. The Redlich-Peterson equation of the five different isotherm models we chose was the most fitted model, and the R(2) was 0.9487, 0.9765 for PM and MPM, respectively; while, the pseudo-first-order model was the best choice among all the four kinetic models to describe the adsorption behavior of APAM onto membranes, suggesting that the adsorption mechanism was a chemical and physical combined adsorption on heterogeneous surface. The thermodynamic parameters were also calculated from the temperature dependence (Δ(r)G(m)(θ), Δ(r)H(m)(θ), Δ(r)S(m)(θ)), which showed that the process of adsorption is not spontaneous but endothermic process and high temperature favors the adsorption., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: Liver transplantation is so far the most effective therapeutic modality for end-stage liver diseases, but ischemia/reperfusion (I/R) injury represents a critical barrier to liver transplantation. Primary graft dysfunction and small-for-size syndrome are closely associated with I/R injury. Ischemic preconditioning (IPC) is defined as a brief period of liver ischemia followed by reperfusion, and has demonstrated protections against a prolonged I/R injury and improved the capacity of regeneration. The article aimed to review IPC literatures for the understanding of the effects of IPC on I/R injury involving in the procurement of donor liver and protective mechanisms., Data Sources: A literature search of MEDLINE and Web of Science databases using "liver transplantation", "liver regeneration", "hepatectomy", "ischemia/reperfusion" and "ischemic preconditioning" was performed, and then a large amount of related data was collected., Results: The literature search provided a huge amount of evidence for the protective effects of IPC on I/R injury in liver transplantation, including reduction of blood loss in hepatectomy, intraoperative hemodynamic stability and its significant role in liver regeneration. The mechanism involves in balancing inflammatory cytokines, enhancing energy status and mitigating microcirculatory disturbance., Conclusion: IPC plays an essential role in hepatectomy before and after harvest of living donor liver and implantation of liver graft.