We present an unprecedented set of high-resolution climate simulations, consisting of a 500-year pre-industrial control simulation and a 250-year historical and future climate simulation from 1850 to 2100. A high-resolution configuration of the Community Earth System Model version 1.3 (CESM1.3) is used for the simulations with a nominal horizontal resolution of 0.25°for the atmosphere and land models and 0.1°for the ocean and sea-ice models. At these resolutions, the model permits tropical cyclones and ocean mesoscale eddies, allowing interactions between these synoptic and mesoscale phenomena with large-scale circulations. An overview of the results from these simulations is provided with a focus on model drift, mean climate, internal modes of variability, representation of the historical and future climates, and extreme events. Comparisons are made to solutions from an identical set of simulations using the standard resolution (nominal 1°) CESM1.3 and to available observations for the historical period to address some key scientific questions concerning the impact and benefit of increasing model horizontal resolution in climate simulations. An emerging prominent feature of the high-resolution pre-industrial simulation is the intermittent occurrence of polynyas in the Weddell Sea and its interaction with an Interdecadal Pacific Oscillation. Overall, high-resolution simulations show significant improvements in representing global mean temperature changes, seasonal cycle of sea-surface temperature and mixed layer depth, extreme events and in relationships between extreme events and climate modes. Plain Language Summary Although the current generation of climate models has demonstrated high fidelity in simulating and projecting global temperature change, these models show large uncertainties when it comes to questions concerning how rising global temperatures will impact local weather conditions. This is because the resolution (~100 km) at which the majority of climate models simulate the climate is not fine enough to resolve these small-scale regional features. Conducting long-term (multi-centuries) high-resolution (~10 km) climate simulations has been a great challenge for the research community due to the extremely high computational demands. Through international

Future changes in tropical cyclone properties are an important component of climate change impacts and risk for many tropical and midlatitude countries. In this study we assess the performance of a multimodel ensemble of climate models, at resolutions ranging from 250 to 25 km. We use a common experimental design including both atmosphere‐only and coupled simulations run over the period 1950–2050, with two tracking algorithms applied uniformly across the models. There are overall improvements in tropical cyclone frequency, spatial distribution, and intensity in models at 25 km resolution, with several of them able to represent very intense storms. Projected tropical cyclone activity by 2050 generally declines in the South Indian Ocean, while changes in other ocean basins are more uncertain and sensitive to both tracking algorithm and imposed forcings. Coupled models with smaller biases suggest a slight increase in average TC 10 m wind speeds by 2050.

A novel end-on azide-bridged homospin 1D chain, Co(bt)(N3)2 (1) (bt = 2,2'-bithiazoline), is constructed by sharing edges of Co(II) distorted octahedrons to form a helix, which shows magnetic hysteresis with steps and slow relaxation below 5-6 K, typical of single-chain magnet behavior.

COVID-19 pandemic caused by SARS-CoV-2 constitutes a global public health crisis with enormous economic consequences. Monoclonal antibodies against SARS-CoV-2 can provide an important treatment option to fight COVID-19, especially for the most vulnerable populations. In this work, potent antibodies binding to SARS-CoV-2 Spike protein were identified from COVID-19 convalescent patients. Among them, P4A1 interacts directly with and covers majority of the Receptor Binding Motif of the Spike Receptor-Binding Domain, shown by high-resolution complex structure analysis. We further demonstrate the binding and neutralizing activities of P4A1 against wild type and mutant Spike proteins or pseudoviruses. P4A1 was subsequently engineered to reduce the potential risk for Antibody-Dependent Enhancement of infection and to extend its half-life. The engineered antibody exhibits an optimized pharmacokinetic and safety profile, and it results in complete viral clearance in a rhesus monkey model of COVID-19 following a single injection. These data suggest its potential against SARS-CoV-2 related diseases.

Background: Apoptosis is recognized as an important mechanism in contrast-induced nephropathy (CIN). As tetramethylpyrazine (TMP) has been recently found to be renoprotective and anti-apoptotic in multiple kidney injuries, we hypothesized that TMP would prevent CIN. Methods: An experimental model of CIN was established in rats. Serum creatinine, blood urea nitrogen, plasma cystatin C, urinary N-acetyl-β-glucosaminidase, and urinary γ-glutamyl transpeptidase were measured to evaluate kidney function. Apoptosis was assessed by transmission electron microscopy, transferase-mediated deoxyuridine triphosphate nick end-labeling staining, and poly-ADP-ribose polymerase cleavage. Fork-head box O1 transcriptional factor (FoxO1) mRNA expression was evaluated by quantitative real-time PCR. Phospho-p38 mitogen-activated protein kinase (MAPK) protein expression was assessed by immunohistochemistry and Western blotting. Results: TMP significantly attenuated the resulting renal dysfunction and renal tubular cell apo-ptosis. Mechanistically, TMP decreased the expression of phospho-p38 MAPK protein and attenuated the increased FoxO1 mRNA and nuclear protein expression. In addition, TMP inhibited inducible nitric oxide synthase and Bax protein expression while it upregulated Bcl-2. Conclusion: In summary, this study demonstrated the protective role of TMP against CIN and indicated the effects of TMP may be mediated by the inhibition of p38 MAPK and FoxO1 pathways. Thus, TMP may be a new potential therapeutic agent to prevent CIN.