Synthesis of biheteroaryls via 2-methyl quinoline C(sp^(3))-H functionalization under metal-free conditions

An acetic acid-promoted C(sp^(3))-H functionalization of 2-methyl quinoline,enaminoesters and elemental sulfur for the synthesis of 3,4,5-trisubstituted isothiazoles under metal-free conditions has been developed.This approach provides viable access to various 5-(quinolin-2-yl)isothiazoles in moderate to good yields with good functional group tolerance.Moreover,the success of the gram-scale reaction gives this reaction a great potential application.

ABM-based emergency evacuation modelling during urban pluvial floods:A“7.20”pluvial flood event study in Zhengzhou,Henan Province

Increasing urban pluvial flood disasters due to climate change and rapid urbanisation have been a great challenge worldwide.Timely and effective emergency evacuation is important for reducing casualties and losses.This has become a bottleneck for emergency management.This study aimed to develop a commonly used Agent-Based Mode(ABM)for pluvial flood emergency evacuation at the city scale,exploring the cascading impacts of pluvial flooding on human behaviour and emergency evacuation.The July 2021 pluvial flood event in Zhengzhou,Henan Province,claiming 380 lives and 40.9 billion yuan in direct losses,was selected as this case study.A raster-based hydraulic model(ECNU Flood-Urban)was used to predict flood inundation(extent and depth)during an event in Zhengzhou’s centre.Moreover,a comparative analysis of emergency evacuations was conducted before and after the pluvial flood event.The results showed that crowd behaviour plays an important role in an emergency evacuation,and extensive flooding leads to an 11-83%reduction in the number of evacuees.This study highlights the importance of risk education and contingency plans in emergency response.The ABM model developed in this study is proven to be effective and practical and will provide support for decision-making in urban flood emergency management.

Linking a Storm Water Management Model to a Novel Two-Dimensional Model for Urban Pluvial Flood Modeling

This article describes a new method of urban pluvial flood modeling by coupling the 1D storm water management model(SWMM)and the 2D flood inundation model(ECNU Flood-Urban).The SWMM modeling results(the overflow of the manholes)are used as the input boundary condition of the ECNU Flood-Urban model to simulate the rainfall–runoff processes in an urban environment.The analysis is applied to the central business district of East Nanjing Road in downtown Shanghai,considering 5-,10-,20-,50-,and 100-year return period rainfall scenarios.The results show that node overflow,water depth,and inundation area increase proportionately with the growing return periods.Water depths are mostly predicted to be shallow and surface flows generally occur in the urban road network due to its low-lying nature.The simulation result of the coupled model proves to be reliable and suggests that urban surface water flooding could be accurately simulated by using this methodology.Adaptation measures(upgrading of the urban drainage system)can then be targeted at specific locations with significant overflow and flooding.

Identification of a novel PAK1 inhibitor to treat pancreatic cancer

Pancreatic cancer is one of the most aggressive cancers with poor prognosis and a low 5-year survival rate.The family of P21-activated kinases(PAKs)appears to modulate many signaling pathways that contribute to pancreatic carcinogenesis.In this work,we demonstrated that PAK1 is a critical regulator in pancreatic cancer cell growth.PAK1-targeted inhibition is therefore a new potential therapeutic strategy for pancreatic cancer.Our small molecule screening identified a relatively specific PAK1-targeted inhibitor,CP734.Pharmacological and biochemical studies indicated that CP734 targets residue V342 of PAK1 to inhibit its ATPase activity.Further in vitro and in vivo studies elucidated that CP734 suppresses pancreatic tumor growth through depleting PAK1 kinase activity and its downstream signaling pathways.Little toxicity of CP734 was observed in murine models.Combined with gemcitabine or 5-fluorouracil,CP734 also showed synergistic effects on the anti-proliferation of pancreatic cancer cells.All these favorable results indicated that CP734 is a new potential therapeutic candidate for pancreatic cancer.

Evaluating the Influence of Multisource Typhoon Precipitation Data on Multiscale Urban Pluvial Flood Modeling

Based on station precipitation observations,radar quantitative precipitation estimates(QPE), and radar fusion data during Typhoon Fitow(2013), the influence of multisource precipitation data on multiscale urban typhoon pluvial flood modeling is studied. Using Shanghai, China,as the study area, a simplified 2D hydrodynamic model is applied to simulations. Combined with actual flood incidents reported by the public and soil moisture data, we perform multiscale verifications and determine the applicability of three precipitation datasets in the modeling. The results are as follows:(1) At the city scale, although QPE have higher spatial resolution, these estimates are lower than station observations. Radar fusion data have both high accuracy and high spatial resolution. For flood depths above 5 cm, the radar fusion precipitation scenario can improve the matching probability by 6%.(2) At the neighborhood scale, the radar fusion precipitation scenario can effectively mitigate the problems of an uneven spatial distribution of stations and a weak QPE to accurately capture pluvial details.(3)One fixed-point assessment shows that different precipitation data have little influence on the temporal characteristics of the modeling result-all three types of data can accurately reflect flood occurrence times. This work can provide a scientific basis for constructing effective urban pluvial flood monitoring systems.

A Novel Undulatory Propulsion Strategy for Underwater Robots

Stingrays can undulate their wide pectoral fins to thrust themselves and swim freely underwater.Many researchers have used bionics to directly imitate their undulating mechanism and manufacture undulatory underwater robots.Based on the limitations of the existing undulatory underwater robots,this paper proposes a novel undulatory propulsion strategy,which aims to use the stingray undulating mechanism more thoroughly.First,the mathematical models of both traditional and novel structures are established to accurately describe their undulating mechanism.Then,based on the dynamic mesh technology,the flow field vortex structure they generated is analyzed through fluid-structure interaction simulation,and the thrust force and lateral force generated by them are calculated,which verified that this novel propulsion strategy is indeed more effective.Finally,a prototype robot based on the improved propulsion strategy is manufactured.Compared with the existing stingray robots,the prototype has obvious advantages,thus verifying the accuracy of the simulation results.