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Since the main canal of the Middle Route of South-to-North Water Diversion Project was put into operation, the species, quantity and biomass of algae and shellfish have responded quickly to the environment, and a single dominant species has appeared in the community, demonstrating the remarkably abnormal proliferation property of algae and shellfish. In order to evaluate the safety risk of abnormal proliferation of algae and shellfish in the Middle Route and realize dynamic analysis of all kinds of influencing factors, a comprehensive risk evaluation system of algae and shellfish in the Middle Route of South-to-North Water Diversion Project based on comprehensive weighting and Four-Element Connection Number (MCEN) was constructed by integrating the Analytic Hierarchy Process (AHP) and the weight assignment theory of CRITIC. The system consists of 21 evaluation indexes selected from risk factors and carriers. Taking Henan section in the Middle Route as an example, comprehensive risk evaluation system of algae and shellfish in the Middle Route of South-to-North Water Diversion Project was applied to calculate the partial connection number of each order and obtain the risk development trend of each indicator. The results showed that algae and shellfish in the Middle Route were in a very safe state at the safety risk level of level Ⅰ. Finally, reasonable measures to reduce the risks facing algae and shellfish in the Middle Route of South-to-North Water Diversion Project are given, which effectively make up the deficiency of existing evaluation methods.

The present study was to investigate the therapeutical effects and mechanisms of Asiatic acid from Potentilla Chinensis against alcoholic hepatitis. Rats were intragastrically fed with alcohol for 12 weeks to induce alcoholic hepatitis and then treated with various drugs for further 12 weeks. The results showed that Asiatic acid significantly alleviated liver injury caused by alcohol in rats, as evidenced by the improved histological changes and the lower levels of AST, ALT, and TBIL. Besides, Asiatic acid significantly enhanced the activity of ADH and ALDH, promoting alcohol metabolism. Asiatic acid suppressed CYP2E1 activity and NADP+/NADPH ratio, resulting in low ROS production. Further study revealed that Asiatic acid markedly reduced hepatocyte apoptosis by regulating the expression levels of the caspase and Bcl-2 families. Moreover, Asiatic acid could regulate the Keap1/Nrf2 and NF-κB signaling pathway, attenuating oxidative stress and inflammation as a result. Interestingly, the comprehensive analysis of transcriptomics and metabolomics indicated that Asiatic acid regulated the gene expression of Gpat4 and thereby affected the biosynthesis of the metabolites (1-acyl-Sn-glycerol-3-phosphocholine, phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine), regulating the glycerophospholipid metabolism pathway and ultimately ameliorating hepatocyte damage. In conclusion, this study demonstrates that Asiatic acid can ameliorate alcoholic hepatitis by modulating the NF-κB and Keap1/Nrf2 signaling pathways and the glycerophospholipid metabolism pathway, which may be developed as a potential medicine for the treatment of alcoholic hepatitis.

Background Hepatocellular carcinoma (HCC) generally arises from a background of liver cirrhosis (LC). Patients with cirrhosis and suspected HCC are recommended to undergo serum biomarker tests and imaging diagnostic evaluation. However, the performance of routine diagnostic methods in detecting early HCC remains unpromising. Methods Here, we conducted a large-scale, multicenter study of 1675 participants including 490 healthy controls, 577 LC patients, and 608 HCC patients from nine clinical centers across nine provinces of China, profiled gene mutation signatures of cell-free DNA (cfDNA) using Circulating Single-Molecule Amplification and Resequencing Technology (cSMART) through detecting 931 mutation sites across 21 genes. Results An integrated diagnostic model called “Combined method” was developed by combining three mutation sites and three serum biomarkers. Combined method outperformed AFP in the diagnosis of HCC, especially early HCC, with sensitivities of 81.25% for all stages and 66.67% for early HCC, respectively. Importantly, the integrated model exhibited high accuracy in differentiating AFP-negative, AFP-L3-negative, and PIVKA-II-negative HCCs from LCs.

Background The left-sided and right-sided colon cancer (LCCs and RCCs, respectively) have unique molecular features and clinical heterogeneity. This study aimed to identify the characteristics of immune cell infiltration (ICI) subtypes for evaluating prognosis and therapeutic benefits. Methods The independent gene datasets, corresponding somatic mutation and clinical information were collected from The Cancer Genome Atlas and Gene Expression Omnibus. The ICI contents were evaluated by “ESTIMATE” and “CIBERSORT.” We performed two computational algorithms to identify the ICI landscape related to prognosis and found the unique infiltration characteristics. Next, principal component analysis was conducted to construct ICI score based on three ICI patterns. We analyzed the correlation between ICI score and tumor mutation burden (TMB), and stratified patients into prognostic-related high- and low- ICI score groups (HSG and LSG, respectively). The role of ICI scores in the prediction of therapeutic benefits was investigated by "pRRophetic" and verified by Immunophenoscores (IPS) (TCIA database) and an independent immunotherapy cohort (IMvigor210). The key genes were preliminary screened by weighted gene co-expression network analysis based on ICI scores. And they were further identified at various levels, including single cell, protein and immunotherapy response. The predictive ability of ICI score for prognosis was also verified in IMvigor210 cohort. Results The ICI features with a better prognosis were marked by high plasma cells, dendritic cells and mast cells, low memory CD4+ T cells, M0 macrophages, M1 macrophages, as well as M2 macrophages. A high ICI score was characterized by an increased TMB and genomic instability related signaling pathways. The prognosis, sensitivities of targeted inhibitors and immunotherapy, IPS and expression of immune checkpoints were significantly different in HSG and LSG. The genes identified by ICI scores and various levels included CA2 and TSPAN1. Conclusion The identification of ICI subtypes and ICI scores will help gain insights into the heterogeneity in LCC and RCC, and identify patients probably benefiting from treatments. ICI scores and the key genes could serve as an effective biomarker to predict prognosis and the sensitivity of immunotherapy.

In recent decades, path planning for unmanned surface vehicles (USVs) in complex environments, such as harbours and coastlines, has become an important concern. The existing algorithms for real-time path planning for USVs are either too slow at replanning or unreliable in changing environments with multiple dynamic obstacles. In this study, we developed a novel path planning method based on the D* lite algorithm for real-time path planning of USVs in complex environments. The proposed method has the following advantages: (1) the computational time for replanning is reduced significantly owing to the use of an incremental algorithm and a new method for modelling dynamic obstacles; (2) a constrained artificial potential field method is employed to enhance the safety of the planned paths; and (3) the method is practical in terms of vehicle performance. The performance of the proposed method was evaluated through simulations and compared with those of existing algorithms. The simulation results confirmed the efficiency of the method for real-time path planning of USVs in complex environments.

The deprotonative functionalization of toluenes, for their weak acidity, generally needs strong bases, thus leading to the requirement of harsh conditions and the generation of by-products. Direct nucleophilic acyl substitution reaction of amides with organometallic reagents could provide an ideal solution for ketone synthesis. However, the inert amides and highly reactive organometallic reagents bring great challenges for an efficient and selective synthetic approach. Herein, we reported an lithium diisopropylamide (LDA)-promoted benzylic aroylation of toluenes with unactivated tertiary benzamides, providing a direct and efficient synthesis of various aryl benzyl ketones. This process features a kinetic deprotonative functionalization of toluenes with a readily available base LDA. Mechanism studies revealed that the directed ortho-lithiation of the tertiary benzamide with LDA promoted the benzylic kinetic deprotonation of toluene and triggered the nucleophilic acyl substitution reaction with the amide.

“Using active chemicals as excipients” refers to a preparation strategy. It makes use of the drugs owning the special physical and chemical properties as the roles of excipients to assist the preparation forming or achieve some specific drug delivery function, especially in the compound preparation. This paper proposed the concept of “using active chemicals as excipients”, expounded the advantages and potentials of “medicine as excipient’s use”, and analyzed the research status of “using active chemicals as excipients” from the aspects of chemical compound preparations and traditional Chinese medicine preparations. We classified the excipient function of drugs in formulations, and expounded the functional principles and characteristics of drugs as excipients from drug physical properties and drug dispersing forms in preparation. This preparation strategy has the advantages of reducing the amount of excipients, improving drugs compliance and reducing production costs. It is an important development direction of modern pharmaceutical preparation research and production. In a word, “using active chemicals as excipients” is a potential preparation strategy, which should be paid attention to and be implemented in the process of preparation research and development.

Currently, the dynamic behavior of high-speed long-runout landslides triggered by earthquakes remains unclear due to the complexity of such phenomena. Degradation in the shear strength of rock masses is considered a primary factor contributing to the high velocities and long runout distances of these landslides. In this study, the strength degradation induced by changes in rock joint morphology is analyzed considering a numerical model of the Donghekou landslide, by using discontinuous deformation analysis (DDA). First, an exponential joint roughness degradation function (i.e., JRCm) that depends on displacement is incorporated with the nonlinear Barton–Bandis (B–B) shear strength criterion, and this modified B–B criterion is combined with the DDA. Moreover, a virtual joint is introduced in the DDA to model the propagation of cracks in intact rock masses, in order to simulate the dynamic phenomenon of earthquake-induced landslides. Subsequently, this improved DDA (IDDA) is validated via simulations of a shear test and a sliding block over an inclined plane. Finally, the IDDA is employed to simulate the Donghekou landslide, which was induced by the 2008 Wenchuan earthquake in China. Furthermore, the entire dynamic process of the landslide, including crack propagation, instability, initiation, and motion, is depicted. The simulated deposit patterns obtained via the IDDA are in good agreement with the results of field investigations. The simulation results also prove that the IDDA can reflect key movement behaviors of Donghekou landslide and that the degradation of rock joints significantly influences the long runout distance and high velocity of sliding mass.

Climate is a critical factor considered in predicting the potential distributions of species. However, the distribution of susceptible host plants is another important constraint in retrospective and predictive analyses of invasive insect pests, particularly for wood-boring insects. In the present study, we first modeled the geographic distribution of the invasive emerald ash borer (EAB), Agrilus planipennis Fairmaire (Coleoptera: Buprestidae), and its susceptible host trees using MaxEnt. We then compared the differences between the predicted and actual distribution of EAB in its native (China) and invaded (the United States and Canada) ranges by incorporating the distribution of its susceptible host plants. Results from our models indicate that: (1) in addition to climatic factors, the presence of susceptible host tree species plays a major role in delineating the pest’s distribution; (2) it is more accurate to project EAB’s potential range distribution by considering the suitability of potential areas for its susceptible host plants; and (3) there is a high risk of EAB expanding its current distribution areas in both its native and invasive ranges. The inclusion of susceptible host plant presence as a factor enables more effective predictive modeling and risk assessment for biological invasions, especially for oligophagous insects.