Coupling of N7-methyltransferase and 3′-5′ exoribonuclease with SARS-CoV-2 polymerase reveals mechanisms for capping and proofreading

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Design,synthesis and biological evaluation of nitric oxide releasing derivatives of dapagliflozin as potential anti-diabetic and anti-thrombotic agents

The cardiovascular complications were highly prevalent in type 2 diabetes mellitus (T2DM), even at the early stage of T2DM or the state of intensive glycemic control. Therefore, there is an urgent need for the intervention of cardiovascular complications in T2DM. Herein, the new hybrids of NO donor and SGLT2 inhibitor were design to achieve dual effects of anti-hyperglycemic and anti-thrombosis. As expected, the preferred hybrid 2 exhibited moderate SGLT2 inhibitory effects and anti-platelet aggregation activities, and its anti-platelet effect mediated by NO was also confirmed in the presence of NO scavenger. Moreover, compound 2 revealed significantly hypoglycemic effects and excretion of urinary glucose during an oral glucose tolerance test in mice. Potent and multifunctional hybrid, such as compound 2, is expected as a potential candidate for the intervention of cardiovascular complications in T2DM.     

β‐catenin regulates IRF3‐mediated innate immune signalling in colorectal cancer

Objective

β‐catenin is one of the most critical oncogenes associated with many kinds of human cancers, especially in the human CRC. Innate immunity recognizes tumour derived damage‐associated molecular patterns (DAMPs) and primes the anti‐tumour adaptive responses. While the function of β‐catenin in CRC tumourigenesis is well established, its impact on innate immune evasion is largely unknown. The aim of this study is to characterize the role of β‐catenin in inhibiting RIG‐I‐like receptor (RLR)‐mediated IFN‐β signalling in colorectal cancer.

Materials and Methods

Immunohistochemical staining and western blotting were conducted to study the expression of β‐catenin, IRF3 and phospho‐IRF3 (p‐IRF3) in CRC samples and cell lines. Plaque assay determining virus replication was performed to assess the regulation of β‐catenin on IFN‐β signalling. The inhibition of β‐catenin on RLR‐mediated IFN‐β signalling was further studied by real‐time analyses and reporter assays in the context of lentiviral‐mediated β‐catenin stably knocking down. Lastly, co‐immunoprecipitation and nuclear fractionation assay were conducted to monitor the interaction between β‐catenin and IRF3.

Results

We found that high expression of β‐catenin positively correlated with the expression of IRF3 in CRC cells. Overexpression of β‐catenin increased the viral replication. Conversely knocking down of β‐catenin inhibited viral replication. Furthermore, our data demonstrated that β‐catenin could inhibit the expression of IFN‐β and interferon‐stimulated gene 56 (ISG56). Mechanistically, we found that β‐catenin interacted with IRF3 and blocked its nuclear translocation.

Conclusion

Our study reveals an unprecedented role of β‐catenin in enabling innate immune evasion in CRC.

     

CuS Microspheres with Tunable Interlayer Space and Micropore as a High‐Rate and Long‐Life Anode for Sodium‐Ion Batteries

Layered transition metal sulfides (LTMSs) have tremendous commercial potential in anode materials for sodium‐ion batteries (SIBs) in large‐scale energy storage application. However, it is a great challenge for most LTMS electrodes to have long cycling life and high‐rate capability due to their larger volume expansion and the formation of soluble polysulfide intermediates caused by the conversion reaction. Herein, layered CuS microspheres with tunable interlayer space and pore volumes are reported through a cost‐effective interaction method using a cationic surfactant of cetyltrimethyl ammonium bromide (CTAB). The CuS–CTAB microsphere as an anode for SIBs reveals a high reversible capacity of 684.6 mAh g^?1 at 0.1 A g^?1, and 312.5 mAh g^?1 at 10 A g^?1 after 1000 cycles with high capacity retention of 90.6%. The excellent electrochemical performance is attributed to the unique structure of this material, and a high pseudocapacitive contribution ensures its high‐rate performance. Moreover, in situ X‐ray diffraction is applied to investigate their sodium storage mechanism. It is found that the long chain CTAB in the CuS provides buffer space, traps polysulfides, and restrains the further growth of Cu particles during the conversion reaction process that ensure the long cycling stability and high reversibility of the electrode material.     

Predicting soils and environmental impacts associated with switchgrass for bioenergy production: a DAYCENT modeling approach

Switchgrass (Panicum virgatum L.) production has the potential to improve soils and the environment. However, little is known about the long‐term future assessment of soil and environmental impacts associated with switchgrass production. In this study, soil organic carbon (SOC), soil nitrate (), water‐filled pore space (WFPS), carbon dioxide (CO₂) and nitrous oxide (N₂O) fluxes, and biomass yield from switchgrass field were predicted using DAYCENT models for 2016 through 2050. Measured data for model calibration and validation at this study site managed with nitrogen fertilization rates (N rates) (low, 0 kg N ha^?1; medium, 56 kg N ha^?1; and high, 112 kg N ha^?1) and landscape positions (shoulder and footslope) for switchgrass production were collected from the previously published studies. Modeling results showed that the N fertilization can enhance SOC and soil NO₃^?, but increase soil N₂O and CO₂ fluxes. In this study, medium N fertilization was the optimum rate for enhancing switchgrass yield and reducing negative impact on the environment. Footslope position can be beneficial for improving SOC, , and yield, but contribute higher greenhouse gas (GHG) emissions compared to those of the shoulder. An increase in temperature and decrease in precipitation (climate scenarios) may reduce soil , WFPS, and N₂O flux. Switchgrass production can improve and maintain SOC and , and reduce N₂O and CO₂ fluxes over the predicted years. These findings indicate that switchgrass could be a sustainable bioenergy crop on marginally yielding lands for improving soils without significant negative impacts on the environment in the long run.     

Vegetation succession of abandoned croplands in Ruanliang and Yingliang in the Ordos Plateau

Shrub encroachment has been a key phenomenon in arid and semi-arid grasslands over the last century. However, little research has been dedicated to vegetation dynamics in the abandoned croplands, which are surrounded by shrub-encroached grasslands. In this study, several abandoned croplands in Ruanliang and Yingliang in the Ordos Plateau were selected, and the biomass, coverage, density, root pattern, and plant litter dynamics were studied. The results showed that: (1) The abandoned croplands in Ruanliang experienced three community types, including weeds community, the subshrub Artemisia ordosica community, and the perennial grass community, while the abandoned croplands in Yingliang experienced three community types, including weeds community, perennial Stipa bungeana with Artemisia frigida community, and S. bungeana community. (2) The important value for the annual or biennial grass in abandoned croplands in Ruanliang declined during the restoration process, for the perennial grass it increased, and for the subshrub it first increased and then went down to zero. In Yingliang abandoned croplands, however, the perennial grass remained dominant during the succession process. (3) The root of A. ordosica in Ruanliang abandoned croplands was mainly distributed in soil depths of 0–30?cm; the root of the perennial grass was mainly in the 0–20?cm range, and S. bungeana was found at soil depths of 0–5?cm. To restore to a natural vegetation state, about 20?years would be needed to recover the total biomass, and 10?years would be needed to restore the vegetation coverage in Ruanliang abandoned croplands. For Yingliang abandoned croplands, about 15 and 20?years would be needed to restore the total biomass and vegetation coverage, respectively, to a state of natural vegetation.