Intramolecular Palladium(II)-Catalyzed Regioselective 6-endo or 6-exo C-H Benzannulation: An Approach for the Diversity-Oriented Synthesis of Quinolinone Derivatives from Pyridones.

Herein, a new intramolecular palladium(II)-catalyzed regioselective 6-endo-trig or 6-exo-trig annulation through direct C-H activation is presented as a method for the diversity-oriented synthesis of highly substituted quinolinones from pyridones. The reaction occurs under mild conditions and exhibits excellent regioselectivity, good functional group tolerance, and broad applications. This innovative approach has been successfully utilized in the synthesis of Glycopentanolone A and an intermediate of (R)-(+)-Tipifarnib.

Effects of dietary dihydromyricetin on growth performance, antioxidant capacity, immune response and intestinal microbiota of shrimp (Litopenaeus vannamei).

A 56-day culture trial was conducted to evaluate the effects of dietary dihydromyricetin (DMY) on growth performance, antioxidant capacity, immune response and intestinal microbiota of shrimp (Litopenaeus vannamei). 840 healthy shrimp (1.60 ± 0.21 g) in total were fed with four different levels of DMY diets at 0 (Control), 100 (D1), 200 (D2), and 300 (D3) mg/kg, respectively. Samples were collected after the culture trial, and then, a 7-day challenge experiment against Vibrio parahaemolyticus was conducted. The results demonstrated that DMY significantly enhanced the activity of protease, amylase and lipase as well as the expression of lipid and protein transport-related genes (P < 0.05). The results of plasma lipid parameters indicated that DMY reduced lipid deposition, manifested by significantly (P < 0.05) decreased plasma total cholesterol (T-CHO), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C). The expression of genes involved in fatty acid ß-oxidation and triglyceride catabolism was significantly up-regulated (P < 0.05), and genes involved in triglyceride synthesis were significantly down-regulated in DMY groups when compared to control group (P < 0.05). Moreover, dietary DMY also significantly (P < 0.05) increased the total antioxidant capacity (T-AOC), antioxidant enzymes activity and glutathione (GSH) content of shrimp, and a significant increase of total hemocytes count (THC), phagocytic rate (PR), antibacterial activity (AA) and bacteriolytic activity (BA) was observed in DMY groups (P < 0.05). The addition of DMY to the diet significantly augmented immune response by up-regulating the expression of genes related to toll-like receptors (Toll) signaling pathway, immune deficiency (IMD) signaling pathway and intestinal mucin. Furthermore, dietary DMY could modulate the composition and abundance of intestinal microbiota. In conclusion, DMY showed promising potential as a functional feed additive for shrimp to improve the growth performance and physiological health.

Immunotoxicity and the mechanisms of aflatoxin B1-induced growth retardation in shrimp and alleviating effects of bile acids.

Aflatoxin B1 (AFB1) is one of the most toxic mycotoxins prevalent in the environment and food chain, posing severe health risks to humans and animals. Bile acids are natural detergents synthesized from cholesterol and play a key role in the excretion of toxins in vertebrates. Here, pacific white shrimp (Litopenaeus vannamei) served as an animal model to examine the toxicity mechanisms of AFB1 and assess the potential alleviating effects of bile acids against AFB1. Our results revealed that AFB1 exposure significantly inhibited the growth performance and immune response of shrimp, accompanied by AFB1 accumulation and histological damage. Mechanistically, AFB1-induced DNA damage activated DNA repair mechanisms and induced the arrest of cell cycle via the ATR-cyclin B/cdc2 pathway. Additionally, AFB1 directly suppressed the immune response and growth performance of shrimp by inhibiting Toll and IMD pathways and the secretion of digestive enzymes. Notably, dietary bile acids significantly reduced AFB1 accumulation and alleviated AFB1-induced growth retardation and immunotoxicity in shrimp, and CCKAR, ATR, and Relish may be key mediators of the alleviating effects of bile acids. Our study provided new insights into the toxicity mechanisms of AFB1 in invertebrates and highlighted the potential of bile acids to alleviate AFB1 toxicity.

Effects of dietary trans-cinnamaldehyde on growth performance, lipid metabolism, immune response and intestinal microbiota of Litopenaeus vannamei.

The purpose of this study was to evaluate the effects of dietary trans-cinnamaldehyde (TC) on growth performance, lipid metabolism, immune response and intestinal microbiota of Litopenaeus vannamei. Shrimp were randomly divided into 4 groups, with 3 replicants in each group and 70 shrimp in each replicant. The contents of TC in the four groups were 0, 0.4, 0.8 and 1.2 g kg-1, respectively. Samples were taken after 56 days, followed by a 7-day vibrio harveyi challenge experiment. The results showed that TC significantly improved the growth performance by enhancing the activity of digestive enzymes in shrimp (P < 0.05). TC also reduced the content of crude fat (P < 0.05). The addition of TC to the diet attenuated lipid deposition, as evidenced by a reduction in the content of crude fat and a decrease in plasma levels of cholesterol and triglycerides (P < 0.05). The expression of key genes for fatty acid and triglycerides synthesis were significantly down-regulated and key genes for fatty acid ß-oxidation were significantly up-regulated (P < 0.05). In addition, the immune response and antioxidant capability of shrimp were significantly enhanced by the addition of TC to the diet (P < 0.05). Meanwhile, TC could improve intestinal health by increasing the abundance of beneficial bacteria and decreasing the abundance of pathogenic bacteria, but had no significant effect on alpha diversity and beta diversity (P > 0.05). In addition, the results of histopathological sections and plasma transaminase studies showed that TC could improve the health status of hepatopancreas and was a safe nutritional supplement. After the 7-day Vibrio harveyi challenge, the cumulative mortality of shrimp decreased with increasing levels of dietary TC compared with control group (P < 0.05). These results suggested that TC could be used as a nutritional supplement for shrimp to enhance disease resistance and reduce lipid accumulation.

Investigation of Dropwise Condensation Heat Transfer on Laser-Ablated Superhydrophobic/Hydrophilic Hybrid Copper Surfaces.

Heterogeneous surfaces with wetting contrast have gained extensive attention in recent years because of their potential application in condensation heat transfer enhancement. In this work, we engineered superhydrophobic/hydrophilic hybrid (SHH) surfaces on copper substrates via a laser-ablation process. We demonstrated that the as-fabricated SHH surfaces present dropwise condensation behavior; the condensate droplet growth, departure, and heat transfer performance depend strongly on the spacing of the hydrophilic spot. The surface with the hydrophilic spot spacing of 100 µm (SHH100) exhibits the most efficient dropwise condensation in terms of fast droplet growth rate, efficient coalescence-induced droplet departure, as well as enhanced heat transfer coefficient (HTC) compared to the homogeneous superhydrophobic (SHPo) surface. The mechanism underlying the enhanced condensation heat transfer performance is analyzed. A 12% enhancement on condensation HTC was found was found on SHH100 surface compared with the SHPo surface. Our results provide important insights for the design of hybrid surfaces with wetting contrast for enhancing condensation heat transfer performance in many industrial applications.

HTNV-induced upregulation of miR-146a in HUVECs promotes viral infection by modulating pro-inflammatory cytokine release.

Increasing research has shown a link between viruses and miRNAs, such as miRNA-146a, in regulating virus infection and replication. In the current study, the association between miR-146a and hantaan virus (HTNV) infection in human umbilical vein endothelial cells (HUVECs) was investigated, with a focus on examining the expression of pro-inflammatory cytokines. The results showed that HTNV infection promoted the production of miR-146a in HUVECs and activated nuclear factor-κB (NF-κB) signaling, along with the upregulation of pro-inflammatory cytokines, including interleukin 8 (IL-8), C-C Motif Chemokine Ligand 5 (CCL5, also RANTES), interferon-inducible protein-10 (IP-10) and interferon beta (IFN-ß). Moreover, miR-146a exhibited a negative regulatory effect on the NF-κB pathway. Accordingly, a miR-146a inhibitor increased the expression of IL-8, CCL5, IP-10 and IFN-ß, whereas a miR-146a mimic reduced the levels of these cytokines. Consequently, exogenous transduction of miR-146a significantly enhanced HTNV replication in HUVEC cells. We also discovered that viral proteins (NP/GP) contributed to miR-146a expression via enhancement the activity of miR-146a promoter. In conclusion, these results imply the negative regulation of miR-146a on the production of HTNV-induced pro-inflammatory cytokines contributes to virus replication, which suggest that miR-146a may be regarded as a novel therapeutic target for HTNV infection.

[Influence of electroacupuncture stimulation of "tianshu" (ST 25), "quchi" (LI 11) and "shangjuxu" (ST 37) and their pairs on gastric motility in the rat].

OBJECTIVE: To observe the effect of electroacupuncture (EA) stimulation of different acupoints or acupoint pairs on gastric motility so as to explore their modulation regularities under different conditions. METHODS: SD rats were randomly divided into normal control, starvation (food-deprivation for 24 h), atropine (antagonist for M-receptor), acetylcholine (Ach, agonist for M-receptor), propranolol (antagonist for beta-receptor) and clenbuterol (agonist for beta 2-receptor) and paired-acupoint groups (30 rats/group). The intragastric pressure was measured via a pressure transducer connected to a balloon inserted in the stomach cavity. EA (2 Hz /15 Hz, 2 mA) was applied to the left "Tianshu" (ST 25),"Quchi" (LI 11) and "Shangjuxu" (ST 37) which were formed in pairs: ST 25-LI 11, ST 25-ST 37 and LI 11-ST 37 for 2 min following intravenous injection of atropine (0.1%, 0.8 mL/kg, 40 microL x min(-1) x kg(-1)), 0.1% acetylcholine (20 microL x min(-1) x kg(-1)), 0. 2% clenbuterol (80 microL x min(-1) x kg(-1)) and 0.4% propranolol (1 mL/kg,40 microL x min(-1) x kg(-1)) under food-deprivation conditions. RESULTS: After intravenous injection of atropine and clenbuterol, the intragastric pressure were decreased significantly (P < 0.05), while after administration of Ach and propranolol, the intragastric pressure increased markedly (P < 0.05). Under normal and starvation conditions, and after intravenous administration of M-receptor antagonist (atropine) and agonist (Ach), beta-receptor antagonist (propranolol) and agonist (clenbuterol), EA stimulation of ST 25 produced an apparently inhibitory effects on gastric motility (80.00%, 86.67%, 76.67%, 86.67%, 73.33% and 86.67%, respectively) and intragatric pressure (P < 0.05) with the tendency being starvation > normal, acetylcholine > atropine and clenbuterol > propranolol. Whereas EA stimulation of LI 11 and ST 37 mainly produced an excitatory effect on gastric motility (60.00%, 56.67%, 93.33%, 40.00%, 53.33% and 50.00%, respectively for LI 11; 66.67%, 60.00%, 80.00%, 53.33%, 46.67% and 73.33%, respectively for ST 37). Following EA stimulation of the paired-acupoint groups, ST 25-ST 37 induced a predominately inhibitory effect on gastric motility (50.00%) and intragastric pressure, while LI 11-ST 37 stimulation had a principally excitatory effect on gastric motility (53.33%), and ST 25-LI 11 showed no apparent effect (50.00%). CONCLUSION: EA stimulation of ST 25 area at the abdomen produces a predominant inhibitory effect on gastric motility, while EA of LI 11 and ST 37 on the upper and lower limbs induces an excitatory effect on gastric movement, when applied in pairs, EA of ST 25-ST 37 suppresses the gastric activity, and LI 11-ST 37 promotes the gastric activity, suggesting a specificity of the effect of different acupoint stimulation.