(-)-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.

Drugs associated with a risk of supraventricular tachycardia: analysis using the OpenVigil database.

OBJECTIVE: The OpenVigil database can be used to assess medications that may cause supraventricular tachycardia (SVT) and to produce a reference for their safe use in clinical settings. METHODS: We analyzed first-quarter data from 2004 to 2023, obtained by searching the OpenVigil database using the keyword "supraventricular tachycardia." Trade names and generic names were obtained by querying the RxNav database, and the proportions were summarized. The proportionate reporting ratio (PRR), reporting odds ratio, and chi-square values were also summarized. We created Asahi diagrams and set the screening criteria to drug events ≥30, PRR >2, and chi-square >4. Outcomes were evaluated using the Side Effect Resource database, several scientific literature databases, and the Hangzhou Yiyao Rational Medication System. RESULTS: A total of 2435 distinct medications were found to induce SVT between the first quarter of 2004 and 2023, leading to 22,375 documented adverse events related to SVT. Further investigation revealed that salbutamol, paroxetine, formoterol, paclitaxel, venlafaxine, and theophylline were most likely to cause SVT. CONCLUSION: We conducted signal mining of adverse drug events using the OpenVigil database and evaluated the six drugs most likely to cause SVT. The results of this research can serve as a drug safety reference in the clinic.

Adapting Decomposed Directions for Evolutionary Multiobjective Optimization.

Decomposition methods have been widely employed in evolutionary algorithms for tackling multiobjective optimization problems (MOPs) due to their good mathematical explanation and promising performance. However, most decomposition methods only use a single ideal or nadir point to guide the evolution, which are not so effective for solving MOPs with extremely convex/concave Pareto fronts (PFs). To solve this problem, this article proposes an effective method to adapt decomposed directions (ADDs) for solving MOPs. Instead of using one single ideal or nadir point, each weight vector has one exclusive ideal point in our method for decomposition, in which the decomposed directions are adapted during the search process. In this way, the adapted decomposed directions can evenly and entirely cover the PF of the target MOP. The effectiveness of our method is analyzed theoretically and verified experimentally when embedding it into three representative multiobjective evolutionary algorithms (MOEAs), which can significantly improve their performance. When compared to seven competitive MOEAs, the experiments also validate the advantages of our method for solving 39 artificial MOPs with various PFs and one real-world MOP.

Study of the therapy of multiple myeloma monoclonal antibody.

This paper aims to discuss the initial clinical effect of treating bone defect of long bone osteomyelitis with Masquelet technology. A retrospective analysis was made among the recruited 25 patients with long bone osteomyelitis patients from April, 2013 to February 2014 from Henan Provincial People's Hospital. Clinical effect of treating long bone osteomyelitis with Masquelet technology and the possible effects of vancomycin in different doses on knitting were also evaluated in follow-up visit lasting for 6~18 months, and 22 cases' bone was healed on imaging at the last follow up. According to Samantha X ray score criteria, Samantha score of regular dose group and high dose group in 4 months after operation was 4.16 and 3.09, respectively. There were 12 cases in regular-dose antibiotic group, among which, 1 case had delayed wound healing, and 3 cases reoccurred; there were 10 cases in high-dose antibiotic group, among which, no cases reoccurred after operation. Masquelet technology is a reliable and easy osteomyelitis treatment. Notably, it shows significant advantages for long bone reconstruction induced by infection and trauma. Bone cement with high dose of vancomycin has better effect on controlling osteomyelitis than bone cement with regular dose of vancomycin.