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risk of the unfavourable outcome was higher for pregnant women, WHO III/IV clinical stage and elevated creatinine. CONCLUSIONS Compared to SOC, Treat-All resulted in comparable retention, improved viral suppression and comparable composite outcomes of retention without viral failure. © 2020 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.The self-assembly of short peptides gives rise to versatile nanoassemblies capable of promoting efficient catalysis. We have semi-rationally designed a series of seven-residue peptides that form hemin-binding catalytic amyloids to facilitate enantioselective cyclopropanation with efficiencies that rival those of engineered hemin proteins. These results demonstrate that 1) Catalytic amyloids can bind complex metallocofactors to promote practically important multisubstrate transformations. 2) Even essentially flat surfaces of amyloid assemblies can impart a substantial degree of enantioselectivity without the need for extensive optimization. 3) The ease of peptide preparation allows for straightforward incorporation of unnatural amino acids and the preparation of peptides made from d-amino acids with complete reversal of enantioselectivity. © 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.Accumulating evidence suggests that p53 plays a suppressive role in cancer metastasis, yet the underlying mechanism remains largely unclear. Regulation of actin dynamics is essential for the control of cell migration, which is an important step in metastasis. The Arp2/3 complex is a major nucleation factor to initiate branched actin polymerization that drives cell migration. However, it is unknown whether p53 could suppress metastasis through modulating Arp2/3 function. Here, we report that WDR63 is transcriptionally upregulated by p53. We show with migration assays and mouse xenograft models that WDR63 negatively regulates cell migration, invasion, and metastasis downstream of p53. Mechanistically, WDR63 interacts with the Arp2/3 complex and inhibits Arp2/3-mediated actin polymerization. Furthermore, WDR63 overexpression is sufficient to dampen the increase in cell migration, invasion, and metastasis induced by p53 depletion. Together, these findings suggest that WDR63 is an important player in the regulation of Arp2/3 function and also implicate WDR63 as a critical mediator of p53 in suppressing metastasis. © 2020 The Authors.BK polyomavirus (BKPyV or BKV) is a non-enveloped, circular double-stranded DNA virus that may exceed 80% seroprevalence in adults. BKV infection typically occurs during childhood, and the majority of adults are latently infected. While BKV infection is rarely associated with clinical disease in most individuals, in immunosuppressed individuals, reactivation may cause kidney (BK-associated nephropathy) or bladder (hemorrhagic cystitis and ureteral stenosis) injury. No antiviral therapies have been approved for the treatment of BKV infection. Reducing immunosuppression is the most effective therapy, although this is not feasible in many patients. Thus, a robust understanding of viral pathogenesis and viral diversity remains important for the development of future therapeutic strategies. Studies of BKV diversity are quite sparse compared to other common viral infections; thus, much of our understanding of BVK variability and evolution relies heavily analogous studies of other viruses such as HIV or viral hepatitis. We provide a comprehensive review of BKV diversity at the population and individual level with careful consideration of how viral variability may impact viral replication, pathogenesis, tropism, and protein function. We also discuss a number of outstanding questions related to BK virus diversity that should be explored rigorously in future studies. © 2020 John Wiley & Sons, Ltd.We report a new molecular-design principle for creating double-gyroid nanostructured molecular assemblies based on atropisomerization. Ionic amphiphiles containing two imidazolium rings close to each other were designed and synthesized. NMR data revealed that the rotation of the imidazolium rings is restricted, with an activation energy as high as 63 kJ mol-1 in DMSO-d6 solution (DFT prediction for a model compound in the vacuum 90-100 kJ mol-1 ). Due to the restricted rotation, the amphiphiles feature "double" atropisomeric axes in their ionic segments and form three stable atropisomers meso, R, and S. These isomers co-organize into I a 3 ‾ d -type bicontinuous cubic liquid-crystalline mesophases through nanosegregation of the ionic and non-ionic parts. Considering the intrinsic characteristic of I a 3 ‾ d -type bicontinuous cubic structures that they are composed of intertwined right- and left-handed single gyroids, we propose that the simultaneous presence of both R- and S-atropisomers is an important contributor to the formation of double-gyroid structures. © 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.AIMS To determine the optimal dose(s) of once-monthly (QM) administration of efpeglenatide, a long-acting glucagon-like peptide-1 receptor agonist (GLP-1 RA), in patients with type 2 diabetes inadequately controlled on metformin. Piceatannol chemical structure MATERIALS AND METHODS In this phase 2, randomized, placebo-controlled, double-blind trial (NCT02081118), patients were randomized 1111 to subcutaneous efpeglenatide (8, 12 or 16 mg QM; n = 158) or placebo (n = 51). The 16-week treatment period included a 4-week titration phase with once-weekly (QW) efpeglenatide 4 mg, followed by one dose of efpeglenatide 8 mg QM and two doses of the assigned QM dose. The primary endpoint was change in HbA1c from baseline to Week 17. RESULTS All efpeglenatide doses significantly reduced HbA1c versus placebo (P  less then  0.0001 for all). Overall, the least squares mean difference in HbA1c reductions between efpeglenatide and placebo was -0.71% (-7.7 mmol/mol; baseline to Week 17). At Week 17, a significantly greater proportion of efpeglenatide patients had HbA1c less then 7% ( less then 53 mmol/mol) versus placebo (48.7% vs 30.6%; P = 0.0320). Significant body weight loss occurred across all efpeglenatide doses (placebo-corrected reduction -2.0 kg [efpeglenatide overall]; P = 0.0003). The safety profile was consistent with GLP-1 RAs, with gastrointestinal disorders being the most common treatment-emergent adverse events. Fluctuations in effects on glucose levels and rates of gastrointestinal events occurred between peak and trough efpeglenatide concentrations. CONCLUSIONS Efpeglenatide QM (following QW titration) has significant benefits on HbA1c and weight reduction versus placebo in patients with type 2 diabetes. Further studies are needed to evaluate the long-term efficacy and safety of efpeglenatide QM. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.