In addition, K22R or K326R mutation almost completely restored ATP-binding cassette subfamily G member 1 (ABCG1)-mediated cholesterol efflux in IFN-γ-treated macrophages. Taken together, these findings indicate that IFN-γ promotes LXR-α degradation through a SUMO-ubiquitin-dependent pathway, which may inhibit cholesterol efflux mediated by ABCG1 from macrophages and promote the development of atherosclerosis. Repurposing strategies to address the COVID-19 pandemic have been accelerated. As both pregnant and paediatric patients are likely to be excluded from most planned investigations, the list of repurposed options and the available data on these drugs and vaccines provide a baseline risk assessment and identify gaps for targeted investigation. Clinical trials have been searched and reviewed; 23 repurposed drugs and drug combinations and nine candidate vaccines have been assessed regarding the availability of relevant data in paediatrics and pregnant women and to evaluate expected or unanticipated risk. Thirteen of the repurposed drugs or drug combinations are indicated for use in paediatrics in some age category albeit for indications other than COVID-19; 10 of these are indicated for use in pregnant women. Even in cases where these drugs are indicated in the populations, source data from which safety and or dosing could be extrapolated for use in COVID-19 is sparse. Vaccine trials are ongoing and generally exclude pregnant women; only in a few instances have paediatric subgroups been planned for enrolment. Data from individual case studies and RWD may suggest that subpopulations of both paediatric patients and pregnant women may be more at risk, particularly those in an increased inflammatory state. In conjunction with more prospective collaboration, plans are evolving to ensure that we will be better prepared to address similar situations especially in paediatrics and pregnant women where experience is limited and actual practice relies heavily on leveraging data from other populations and indications.In conjunction with more prospective collaboration, plans are evolving to ensure that we will be better prepared to address similar situations especially in paediatrics and pregnant women where experience is limited and actual practice relies heavily on leveraging data from other populations and indications.Isoindolinone structure is an important privileged scaffold found in a large variety of naturally occurring as well as synthetic, biologically and pharmaceutically active compounds. Owing to its crucial role in a number of applications, the synthetic methodologies for accessing this heterocyclic skeleton have received significant attention during the past decade. In general, the synthetic strategies can be divided into two categories First, direct utilization of phthalimides or phthalimidines as starting materials for the synthesis of isoindolinones; and second, construction of the lactam and/or aromatic rings by different catalytic methods, including C-H activation, cross-coupling, carbonylation, condensation, addition and formal cycloaddition reactions. Especially in the last mentioned, utilization of transition metal catalysts provides access to a broad range of substituted isoindolinones. Herein, the recent advances (2010-2020) in transition metal catalyzed synthetic methodologies via formation of new C-C bonds for isoindolinones are reviewed.Blood glucose dysregulation and hyperglycaemia caused by diabetes mellitus are intimately associated with male infertility. Two-month-old Sprague-Dawley rats were given a single dose of streptozotocin (55 mg/kg) by intraperitoneal injection to induce type I diabetes mellitus (DM group). The treatment group was given 1 unit/day of insulin for 16 weeks (INS group). The normal control group (NC group) was given food ad libitum. In the DM group, the histological analysis of caput and cauda epididymal ducts showed broken stereocilia and more lipid vacuolisations in the principal cells. The interstitial hyperplasia and inflammatory cell infiltration were observed in epididymal tissues. Transmission electron microscopy observation showed that the principal cells in the DM group contained more vacuoles, partly lost stereocilia, and swollen mitochondria. The autophagosomes were observed as well. Western blotting results of LC3II/I and P62 protein expression indicated that autophagy was downregulated in the DM group. The total antioxidant activity and GPx5 expression of epididymal tissues were also decreased. P5091 In the INS group, significant improvements were observed in epididymal tissues. Our study suggests that diabetic hyperglycaemia causes autophagy dysregulation in epididymal tissues, which may play a role in diabetes-induced rat epididymal injury. Insulin treatment is beneficial for diabetic-associated epididymal dysfunction.Acute rejection after heart transplantation increases the risk of chronic dysfunction. Disturbances in mitochondrial function may play a contributory role, however, the relationship between histological signs of rejection in the human transplanted heart and expression levels of circulating mitochondrial genes, such as the mitochondrial Ca2+ uniporter (MCU) complex, remains unexplored. We conducted an RNA-sequencing analysis to identify altered mitochondrial genes in serum and to evaluate their diagnostic accuracy for rejection episodes. We included 40 consecutive samples from transplant recipients undergoing routine endomyocardial biopsies. In total, 112 mitochondrial genes were identified in the serum of posttransplant patients, of which 28 were differentially expressed in patients with acute rejection (p 0.900 to discriminate patients with moderate or severe degrees of rejection, we found that the MCU system showed a strong capability for detection MCU (AUC = 0.944, p less then .0001), MCU/MCUR1 ratio (AUC = 0.972, p less then .0001), MCU/MCUB ratio (AUC = 0.970, p less then .0001), and MCU/MICU1 ratio (AUC = 0.970, p less then .0001). Mitochondrial alterations are reflected in peripheral blood and are capable of discriminating between patients with allograft rejection and those not experiencing rejection with excellent accuracy. The dysregulation of the MCU complex was found to be the most relevant finding.