Numerical study on local scour characteristics around submarine pipelines in the Yellow River Delta silty sandy soil under waves and currents

Due to their high reliability and cost-efficiency,submarine pipelines are widely used in offshore oil and gas resource engineering.Due to the interaction of waves,currents,seabed,and pipeline structures,the soil around submarine pipelines is prone to local scour,severely affecting their operational safety.With the Yellow River Delta as the research area and based on the renormalized group(RNG)k-εturbulence model and Stokes fifth-order wave theory,this study solves the Navier-Stokes(N-S)equation using the finite difference method.The volume of fluid(VOF)method is used to describe the fluid-free surface,and a threedimensional numerical model of currents and waves-submarine pipeline-silty sandy seabed is established.The rationality of the numerical model is verified using a self-built waveflow flume.On this basis,in this study,the local scour development and characteristics of submarine pipelines in the Yellow River Delta silty sandy seabed in the prototype environment are explored and the influence of the presence of pipelines on hydrodynamic features such as surrounding flow field,shear stress,and turbulence intensity is analyzed.The results indicate that(1)local scour around submarine pipelines can be divided into three stages:rapid scour,slow scour,and stable scour.The maximum scour depth occurs directly below the pipeline,and the shape of the scour pits is asymmetric.(2)As the water depth decreases and the pipeline suspension height increases,the scour becomes more intense.(3)When currents go through a pipeline,a clear stagnation point is formed in front of the pipeline,and the flow velocity is positively correlated with the depth of scour.This study can provide a valuable reference for the protection of submarine pipelines in this area.

High-throughput screening identifies established drugs as SARS-CoV-2 PLpro inhibitors

A new coronavirus(SARS-CoV-2)has been identified as the etiologic agent for the COVID-19 outbreak.Currently,effective treatment options remain very limited for this disease;therefore,there is an urgent need to identify new anti-COVID-19 agents.In this study,we screened over 6,000 compounds that included approved drugs,drug candidates in clinical trials,and pharmacologically active compounds to identify leads that target the SARS-CoV-2 papain-like protease(PLpro).Together with main protease(Mpro),PLpro is responsible for processing the viral replicase polyprotein into functional units.There-fore,it is an attractive target for antiviral drug develop-ment.Here we discovered four compounds,YM155,cryptotanshinone,tanshinone I and GRL0617 that inhibit SARS-CoV-2 PLpro with IC50 values ranging from 1.39 to 5.63 pmol/L.These compounds also exhibit strong antiviral activities in cell-based assays.YM155,an anti-cancer drug candidate in clinical trials,has the most potent antiviral activity with an EC50 value of 170 nmol/L.In addition,we have determined the crystal structures of this enzyme and its complex with YM155,revealing a unique binding mode.YM155 simultaneously targets three"hot"spots on PLpro,including the substrate-binding pocket,the interferon stimulating gene product 15(ISG15)binding site and zinc finger motif.Our results demonstrate the efficacy of this screening and repur-posing strategy,which has led to the discovery of new drug leads with clinical potential for COVID-19 treatments.

钯催化有机卤化物与烷基炔的Heck型反应

烯烃的Heck反应经过几十年的发展已日趋成熟,但相应的钯催化有机卤化物与烷基炔的Heck反应生成联烯虽然有着原料简单易得的优点,但发展严重滞后。这一方面是由于活性中间体烯基钯自身难以发生β-H消除,导致其更容易发生质子化反应、碳卤化反应以及串联反应等竞争性反应,另一方面,联烯异构化以及非对称烷基炔的区域选择性问题同样限制了烷基炔Heck反应的研究进展。目前能高效促进烯基钯中间体β-H消除的方法主要有提高反应温度、芳基卤化合物引入取代基和改变配体等。本文主要叙述烷基炔的Heck反应过程中涉及到的烯基钯β-H消除生成联烯以及质子化反应、碳卤化反应和串联反应等竞争性反应,最后总结该反应存在的问题,并对其研究方向进行展望。