(-)-Epicatechin gallate ameliorates cyprodinil-induced cardiac developmental defects through inhibiting aryl hydrocarbon receptor in zebrafish.

BACKGROUND: Cyprodinil is a widely used fungicide with broad-spectrum activity, but it has been associated with cardiac abnormalities. (-)-Epicatechin gallate (ECG), a natural polyphenolic compound, has been shown to possess protective properties in cardiac development. METHODS: In this study, we investigated whether ECG could mitigate cyprodinil-induced heart defects using zebrafish embryos as a model. Zebrafish embryos were exposed to cyprodinil with or without ECG. RESULTS: Our results demonstrated that ECG significantly improved the survival rate, embryo movement, and hatching delay induced by cyprodinil. Furthermore, ECG effectively ameliorated cyprodinil-induced cardiac developmental toxicity, including pericardial anomaly and impairment of cardiac function. Mechanistically, ECG attenuated the cyprodinil-induced alterations in mRNA expression related to cardiac development, such as amhc, vmhc, tbx5, and gata4, as well as calcium ion channels, such as ncx1h, atp2a2a, and cdh2. Additionally, ECG was found to inhibit the activity of the aryl hydrocarbon receptor (AhR) signaling pathways induced by cyprodinil. CONCLUSIONS: In conclusion, our findings provide evidence for the protective effects of ECG against cyprodinil-induced cardiac developmental toxicity, mediated through the inhibition of AhR activity. These findings contribute to a better understanding of the regulatory mechanisms and safe utilization of pesticide, such as cyprodinil.

Association between monocyte to high-density lipoprotein-cholesterol ratio and osteoporosis: An analysis of the National Health and Nutrition Examination Survey 2013-2014.

The monocyte to high-density lipoprotein-cholesterol (HDL-C) ratio (monocyte-to-HDL-C ratio) was proposed as a marker of atherosclerosis. Osteoporosis and atherosclerosis share common risk factors and pathophysiological mechanisms. This study aimed to assess the relationship between monocyte-to-HDL-C ratio and osteoporosis. Participants aged ≥50 years with complete bone mineral density (BMD), monocyte, and HDL-C examination data from the National Health and Nutrition Examination Survey (NHANES) 2013-2014 were included. Descriptive analysis was performed separately according to males and females. Weight linear regression and weight logistic regression analyses were used to analyze the association between the monocyte-to-HDL-C ratio and BMD and osteopenia and osteoporosis and vertebral fracture. A total of 1804 participants were included. Among the participants with osteopenia, 398 (48.31%) were males and 466 (51.91%) were females. Among those with osteoporosis, 38 (2.77%) were males and 95 (9.50%) were females. In females, monocyte-to-HDL-C ratio was negatively associated with femoral neck BMD (regression coefficient (ß) = -0.18; 95% confidence interval (CI): (-0.29, -0.07)) and high monocyte-to-HDL-C ratio was associated with higher odds of osteopenia (odds ratio (OR) = 1.22; 95% CI: (1.01, 1.47)) and osteoporosis (OR = 1.68; 95% CI: (1.13, 2.49)) after adjusting for confounders. In males, only monocyte-to-HDL-C ratio >0.35 was observed to be associated with higher odds of osteoporosis (OR = 1.96; 95% CI: (1.02, 3.79)). Stratified analyses showed that similar results were also found in different populations. This study showed that the monocyte-to-HDL-C ratio was negatively associated with BMD and the risk of osteopenia and osteoporosis in females. The monocyte-to-HDL-C ratio may be a new marker of osteoporosis or osteopenia.

Antibacterial and Antiviral Activities of 1,3,4-Oxadiazole Thioether 4H-Chromen-4-one Derivatives.

Various 1,3,4-oxadiazole thioether 4H-chromen-4-one derivatives were conceived. The title compounds demonstrated striking inhibitory effects against Xac, Psa, and Xoo. EC50 data exhibited that A8 (19.7 µg/mL) had better antibacterial activity against Xoo than myricetin, BT, and TC. Simultaneously, the mechanism of action of A8 had been verified by SEM. The results of anti-tobacco mosaic virus indicated that A9 had the best in vivo antiviral effect compared with ningnanmycin. From the data of MST, it could be seen that A9 (0.003 ± 0.001 µmol/L) exhibited a strong binding capacity, which was far superior to ningnanmycin (2.726 ± 1.301 µmol/L). This study shows that the 1,3,4-oxadiazole thioether 4H-chromen-4-one derivatives may become agricultural drugs with great potential.

Design, Synthesis and Antibacterial Activity of Novel Pyrimidine-Containing 4H-Chromen-4-One Derivatives*.

A series of pyrimidine-containing 4H-chromen-4-one derivatives were designed and synthesized by combining bioactive substructures. Preliminary biological activity results showed that most of the compounds displayed significant inhibitory activities in vitro against Xanthomonas axonopodis pv. Citri (X. axonopodis), Xanthomonas oryzae pv. oryzae (X. oryzae) and Ralstonia solanacearum (R. solanacearum). In particular, compound 2-[(3-{[5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-1-benzopyran-3-yl]oxy}propyl)sulfanyl]-4-(4-methylphenyl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile (4c) demonstrated a good inhibitory effect against X. axonopodis and X. oryzae, with the half-maximal effective concentration (EC50 ) values of 15.5 and 14.9 µg/mL, respectively, and compound 2-[(3-{[5,7-Dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-1-benzopyran-3-yl]oxy}propyl)sulfanyl]-4-(3-fluorophenyl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile (4h) showed the best antibacterial activity against R. solanacearum with an EC50 value of 14.7 µg/mL. These results were better than commercial reagents bismerthiazol (BT, 51.7, 70.1 and 52.7 µg/mL, respectively) and thiodiazole copper (TC, 77.9, 95.8 and 72.1 µg/mL, respectively). In vivo antibacterial activity results indicated that compound 4c displayed better curative (42.4 %) and protective (49.2 %) activities for rice bacterial leaf blight than BT (35.2, 39.1 %) and TC (30.8, 27.3 %). The mechanism of compound 4c against X. oryzae was analyzed through scanning electron microscopy (SEM). These results indicated that pyrimidine-containing 4H-chromen-4-one derivatives have important value in the research of new agrochemicals.

Novel penta-1,4-diene-3-one derivatives containing quinazoline and oxime ether fragments: Design, synthesis and bioactivity.

A series of novel penta-1,4-diene-3-one derivatives containing quinazoline and oxime ether moieties were designed and synthesized. Their anticancer activities were evaluated by MTT assay, the results showed that most compounds exhibited extremely inhibitory effects against hepatoma SMMC-7721 cells. In particular, compounds Q2 and Q8 displayed the more potent inhibitory activity with IC50 values of 0.64 and 0.63 µM, which were better than that of gemcitabine (1.40 µM). Further mechanism studies indicated that compounds Q2, Q8, Q13 and Q19 could control the migration of SMMC-7721 cells effectively, and inhibit the proliferation of cancer cells by inhibiting the DNA replication. Western-blot results showed that compounds Q2 and Q8 induced irreversible apoptosis of SMMC-7721 cells by regulating the expression level of apoptose-related proteins. Those studies demonstrated that the penta-1,4-diene-3-one derivatives containing quinazoline and oxime ether fragments merited further research as potential anticancer agents.

Effect of Transcriptional Regulatory Factor FoxO3a on Central Nervous System Oxygen Toxicity.

Central nervous system (CNS) oxygen toxicity (CNS-OT) is a toxic reaction that appears after the inhalation of gas at an excessive oxygen partial pressure during underwater operation or hyperbaric oxygen (HBO) treatment. The mechanism of CNS-OT has not been clearly characterized. Though it has been attributed to the excessive oxidative stress induced by HBO, evidences against this hypothesis have been reported. Here we find that Forkhead box protein O3 (FoxO3a) is important for CNS-OT protection. FoxO3a knock-out (KO) mice had a shorter latency to develop convulsions and greater number of seizures within a certain period of time. The acute lung injury (ALI) induced by CNS-OT was also more severe in FoxO3a KO mice. Further analysis reveals a significant decrease in the activity of catalase (CAT), an antioxidant enzyme and a significant increase in the content of malondialdehyde (MDA), an oxidative product, in brain tissues of FoxO3a KO mice. Short-time HBO exposure could increase FoxO3a expression level and trigger its nuclear translocation. The level of nuclear localized FoxO3a peaked at 8 h after exposure. Our results demonstrate that the activity of FoxO3a is highly sensitive to HBO exposure and FoxO3a plays important roles in protecting CNS-OT. Further mechanic analysis reveals that FoxO3a protects CNS-OT via activating antioxidative signaling pathway.

Effect of Interaction between Adenosine and Nitric Oxide on Central Nervous System Oxygen Toxicity.

The metabolism of adenosine (ADO) and nitric oxide (NO) in brain tissues is closely associated with the change of oxygen content. They have contrary effects in the onset of hyperbaric oxygen (HBO)-induced central nervous system oxygen toxicity (CNS OT): ADO can suppress the onset, while NO promotes it. We adopted the ADO-augmenting measure and NO-inhibiting measure in this study and found the combined use had a far superior preventive and therapeutic effect in protecting against CNS OT compared with the use of either measure alone. So we hypothesized that there is an interaction between ADO and NO which has an important impact on the onset of CNS OT. On this basis, we administered ADO-augmenting or ADO-inhibiting drugs to rats. After exposure to HBO, the onset of CNS OT was evaluated, followed by the measurement of NO content in brain tissues. In another experiment, rats were administered NO-augmenting or NO-inhibiting drugs. After exposure to HBO, the onset of CNS OT was evaluated, followed by measurement of the activities of ADO metabolism-related enzymes in brain tissues. The results showed that, following ADO augmentation, the content of NO and its metabolite was significantly reduced, and the onset of CNS OT significantly improved. After ADO inhibition, just the opposite was observed. NO promotion resulted in a decrease in the activity of ADO-producing enzyme, an increase in the activity of ADO-decomposing enzyme, and an aggravation in CNS OT. The above results were all reversed after an inhibition in NO content. Studies have shown that exposure to HBO has a significant impact on the content of ADO and NO in brain tissues as well as their biological effects, and ADO and NO might have an intense interaction, which might generate an important effect on the onset of CNS OT. The prophylaxis and treatment effects of CNS OT can be greatly enhanced by augmenting ADO and inhibiting NO.

[Analysis and estimate of corn CNCPS component by near infrared reflectance (NIR) spectroscopy].

The objective of the present study was to investigate the feasibility of predicting the CNCPS (cornell net carbohydrate and protein system) composition of corn by near infrared reflectance spectroscopy (NIRS). Sixty-five corn samples from Heilongjiang province were used. The partial least square (PLS) regression method, second derivative and Norris derivative filter were applied in the NIRS prediction of CNCPS. For dry matter, crude protein, ash, fat, starch, neutral-detergent fiber and acid-detergent fiber, the determination coefficients were 0.974 3, 0.968 3, 0.947 8, 0.909 8, 0.977 7, 0.935 4 and 0.926 9, and the SD/RMSEP values for them were 3.96, 4.78, 3.75, 4.25, 4.13, 3.88 and 3.12, respectively. The determination coefficient and SD/RMSEP value were 0.857 5 and 3.06 for soluble protein, but low determination coefficients of 0.531 9 and 0.683 3 with SD/RMSEP values of 5.50 and 2.85 were observed for acid-detergent insoluble protein and neutral-detergent insoluble protein. If the SD/RMSEP value < 5 and > 3, then the effect of model is ideal, and if the SD/RMSEP value > 5 or < 3, the effect of model is not ideal, and at this time, the degree of accuracy of model needs further to be improved. The results of this study indicated that corn nutritive values could be fast and accurately predicted by NIRS. This model was significant in practice for enriching the rapid quantitative methods of determining animal feed materials.