Necroptosis is a programmed necrosis that is mediated by receptor-interacting protein kinases RIPK1, RIPK3 and the mixed lineage kinase domain-like protein, MLKL. Necroptosis must be strictly regulated to maintain normal tissue homeostasis, and dysregulation of necroptosis leads to the development of various inflammatory, infectious, and degenerative diseases. Ubiquitylation is a widespread post-translational modification that is essential for balancing numerous physiological processes. Over the past decade, considerable progress has been made in the understanding of the role of ubiquitylation in regulating necroptosis. Here, we will discuss the regulatory functions of ubiquitylation in necroptosis signaling pathway. An enhanced understanding of the ubiquitylation enzymes and regulatory proteins in necroptotic signaling pathway will be exploited for the development of new therapeutic strategies for necroptosis-related diseases.
Spirulina platensis was cultivated in a bench-scale airlift photobioreactor using synthetic wastewater (total nitrogen 412 mg L(-1), total phosphorous 90 mg L(-1), pH 9-10) with varying ammonia/total nitrogen ratios (50-100% ammonia with balance nitrate) and hydraulic residence times (15-25 d). High average biomass density (3500-3800 mg L(-1)) and productivity (5.1 g m(-2) d(-1)) were achieved when ammonia was maintained at 50% of the total nitrogen. Both high ammonia concentrations and mutual self-shading, which resulted from the high biomass density in the airlift reactor, were found to partially inhibit the growth of S. platensis. The performance of the airlift bioreactor used in this study compared favorably with other published studies. The system has good potential for treatment of high strength wastewater combined with production of algae for biofuels or other products, such as human and animal food, food supplements or pharmaceuticals. 相似文献
Flaviviral NS2B is a required cofactor for NS3 serine protease activity and plays an important role in promoting functional NS2B-NS3 protease configuration and maintaining critical interactions with protease catalysis substrates. The residues D80DDG in West Nile virus (WNV) NS2B are important for protease activity. To investigate the effects of D80DDG in NS2B on protease activity and viral replication, the negatively charged region D80DD and the conserved residue G83 of NS2B were mutated (D80DD/E80EE, D80DD/K80KK, D80DD/A80AA, G83F, G83S, G83D, G83K, and G83A), and NS3 D75A was designated as the negative control. The effects of the mutations on NS2B-NS3 activity, viral translation, and viral RNA replication were analyzed using kinetic analysis of site-directed enzymes and a transient replicon assay. All substitutions resulted in significantly decreased enzyme activity and blocked RNA replication. The negative charge of D80DD is not important for maintaining NS2B function, but side chain changes in G83 have dramatic effects on protease activity and RNA replication. These results demonstrate that NS2B is important for viral replication and that D80DD and G83 substitutions prevent replication; they will be useful for understanding the relationship between NS2B and NS3. 相似文献
The administration of ACEI/ARB (angiotensin-converting enzyme inhibitors/Angiotension II receptor blockers) in COVID-19 (coronavirus disease 2019) patients with hypertension exhibits a lower risk of mortality compared with ACEI/ARB non-users. In this context, an important question arises: is ACEI or ARB more suitable for the treatment of hypertensive COVID-19 patients? Taken into consideration the following four rationales, ARB may offer a more significant benefit than ACEI for the short-term treatment of hypertensive COVID-19 patients: 1. ACEI has no inhibition on non-ACE-mediated Ang II production under infection conditions, whereas ARB can function properly regardless of how Ang II is produced; 2. ACEI-induced bradykinin accumulation may instigate severe ARDS while ARB has no effects on kinin metabolism; 3. ARB alleviates viscous sputa production and inflammatory reaction significantly in contrast to ACEI; 4. ARB may attenuate the lung fibrosis induced by mechanical ventilation in severe patients and improve their prognosis significantly compared with ACEI. To examine the advantages of ARB over ACEI on hypertensive COVID-19 patients, retrospective case-control studies comparing the clinical outcomes for COVID-19 patients receiving ARB or ACEI treatment is strikingly needed in order to provide guidance for the clinical application. 相似文献