Cross-Continental Dispersal of Major HIV-1 CRF01_AE Clusters in China.

Since the 1990s, several distinct clusters of human immunodeficiency virus-type 1 (HIV-1) CRF01_AE related to a large epidemic in China have been identified, but it is yet poorly understood whether its transmission has dispersed globally. We aimed to characterize and quantify the genetic relationship of HIV-1 CRF01_AEs circulating in China and other countries. Using representative sequences of Chinese clusters as queries, all relevant CRF01_AE pol sequences in two large databases (the Los Alamos HIV sequence database and the UK HIV Drug Resistance Database) were selected with the online basic local alignment search (BLAST) tool. Phylogenetic and phylogeographic analyses were then carried out to characterize possible linkage of CRF01_AE strains between China and the rest of the world. We identified that 269 strains isolated in other parts of the world were associated with five major Chinese CRF01_AE clusters. 80.7% were located within CN.01AE.HST/IDU-2, most of which were born in Southeast Asia. 17.8% were clustered with CN.01AE.MSM-4 and -5. Two distinct sub-clusters associated with Chinese men who have sex with men (MSM) emerged in HK-United Kingdom and Japan after 2000. Our analysis suggests that HIV-1 CRF01_AE strains related to viral transmission in China were initially brought to the United Kingdom or other countries during the 1990s by Asian immigrants or returning international tourists from Southeast Asia, and then after having circulated among MSM in China for several years, these Chinese strains dispersed outside again, possibly through MSM network. This study provided evidence of regional and global dispersal of Chinese CRF01_AE strains. It would also help understand the global landscape of HIV epidemic associated with CRF01_AE transmission and highlight the need for further international collaborative study in this field

Ice and Supercooled Liquid Water Distributions Over the Southern Ocean Based on In Situ Observations and Climate Model Simulations

Three climate models are evaluated using in situ airborne observations from the Southern Ocean Clouds, Radiation, Aerosol Transport Experimental Study (SOCRATES) campaign. The evaluation targets cloud phases, microphysical properties, thermodynamic conditions, and aerosol indirect effects from −40°C to 0°C. Compared with 580-s averaged observations (i.e., 100 km horizontal scale), the Community Atmosphere Model version 6 (CAM6) shows the most similar result for cloud phase frequency distribution and allows more liquid-containing clouds below −10°C compared with its predecessor—CAM5. The Energy Exascale Earth System Model (E3SM) underestimates (overestimates) ice phase frequencies below (above) −20°C. CAM6 and E3SM show liquid and ice water contents (i.e., LWC and IWC) similar to observations from −25°C to 0°C, but higher LWC and lower IWC than observations at lower temperatures. Simulated in-cloud RH shows higher minimum values than observations, possibly restricting ice growth during sedimentation. As number concentrations of aerosols larger than 500 nm (Na500) increase, observations show increases of LWC, IWC, liquid, and ice number concentrations (Nliq, Nice). Number concentrations of aerosols larger than 100 nm (Na100) only show positive correlations with LWC and Nliq. From −20°C to 0°C, higher aerosol number concentrations are correlated with lower glaciation ratio and higher cloud fraction. From −40°C to −20°C, large aerosols show positive correlations with glaciation ratio. CAM6 shows small increases of LWC and Nliq with Na500 and Na100. E3SM shows small increases of Nice with Na500. Overall, CAM6 and E3SM underestimate aerosol indirect effects on ice crystals and supercooled liquid droplets over the Southern Ocean

Reconstructed covalent organic frameworks

Covalent organic frameworks (COFs) are distinguished from other organic polymers by their crystallinity1–3, but it remains challenging to obtain robust, highly crystalline COFs because the framework-forming reactions are poorly reversible4,5. More reversible chemistry can improve crystallinity6–9, but this typically yields COFs with poor physicochemical stability and limited application scope5. Here we report a general and scalable protocol to prepare robust, highly crystalline imine COFs, based on an unexpected framework reconstruction. In contrast to standard approaches in which monomers are initially randomly aligned, our method involves the pre-organization of monomers using a reversible and removable covalent tether, followed by confined polymerization. This reconstruction route produces reconstructed COFs with greatly enhanced crystallinity and much higher porosity by means of a simple vacuum-free synthetic procedure. The increased crystallinity in the reconstructed COFs improves charge carrier transport, leading to sacrificial photocatalytic hydrogen evolution rates of up to 27.98 mmol h−1 g−1. This nanoconfinement-assisted reconstruction strategy is a step towards programming function in organic materials through atomistic structural control

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie