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Covering: 2017.01 to 2023.11 Natural products biosynthesized by myxobacteria are appealing due to their sophisticated chemical skeletons, remarkable biological activities, and intriguing biosynthetic enzymology. This review aims to systematically summarize the advances in the discovery methods, new structures, and bioactivities of myxobacterial NPs reported in the period of 2017–2023. In addition, the peculiar biosynthetic pathways of several structural families are also highlighted. [ABSTRACT FROM AUTHOR]

The article provides a summary of the background and past activities of the E6 Discussion Group established under the International Pharmaceutical Regulators Forum. Topics discusses include the establishment of the Regulators Forum to create a regulator-only environment, the development of a statement on general principles for the training and education of Good Clinical Practice (GCP) inspectors which will serve as a reference to regulatory agencies.

Abstract: Although prenatal morphine exposure experimentally induces seizures in rat offspring, underlying mechanisms remain unclear. This study addresses whether prenatal morphine exposure altered subunit compositions of γ-aminobutyric acid receptor subtype A (GABAAR) in the hippocampal CA1 area and temporal cortex and increased seizure susceptibility of young rat offspring, at a representative age (postneonatal days 14; P14). Therapeutic efficacy of dextromethorphan (a noncompetitive antagonist of N-methyl-d-aspartate receptors (NMDARs)), in such offspring was also evaluated. From P7 to 14, Sprague–Dawley rat offspring were intraperitoneally (ip) injected a representative dose of dextromethorphan (3mg/kg) twice a day. At P14, some offspring were ip injected pentylenetetrazol to estimate seizure susceptibility, while the others were studied for GABAAR subunit (α1, β2, γ2) expression. Prenatal morphine exposure caused the up-regulated α1 subunit and down-regulated β2/γ2 subunit expression of GABAAR within hippocampus and temporal cortex in rat offspring associated to increase seizure susceptibility. The magnitudes of upregulated α1 subunit and downregulated β2 subunit expression in the hippocampus were greater than which in the temporal cortex. The use of dextromethorphan markedly reversed the prenatal morphine-induced alterations, indicating the possible therapeutic actions of dextromethorphan. These results suggest that the altered subunit compositions (α1, β2, γ2) of GABAAR in the hippocampal CA1 area and temporal cortex may contribute, at least in part, to the increased seizure susceptibility of rat offspring subjected to prenatal morphine exposure. More importantly, dextromethorphan may be a promising clinical agent acting against these alterations. [ABSTRACT FROM AUTHOR]

Objective: To determine the epidemiological characteristics and associated risk factors of hepatitis B surface antigens (HBsAg) prevalence in rural areas of Hua County, Henan Province, and to provide scientific evidence for Hepatitis B prevention and control in local areas., Methods: On the basis of an ongoing esophageal cancer cohort study in rural Anyang, a total of 5 104 subjects aged 25-65 years were clustered and selected from 5 targeted villages for this study in rural areas of Hua County, Henan Province. HBsAg was detected in their blood samples and a questionnaire was completed by all the subjects in a manner of one-on-one interview. All statistical analyses were conducted using SPSS for Windows version 13.0., Results: Of the 5 104 studied subjects (overall participation rate: 92.05%), 5.17% were positive for HBsAg. The detection rate was significantly higher in males than in females (6.54% vs. 3.87%, P<0.001) and the highest detection rates were observed in the 25-29 and 55-59 years groups in both males and females. Multiple Logistic analyses showed unmarried status (OR=1.80, 95% CI: 1.00-3.25) and high frequency of sexual intercourse (Ptrend=0.049) were associated with higher the risk for hepatitis B virus (HBV) infection., Conclusion: The prevalence of HBsAg in rural Hua County, Henan Province, was slightly lower than the national average of the same time period. More attention should be attached to high risk groups of HBV infection in this population, i.e. males aged 25-29 years and 55-59 years and sexually active population. Immunization and health education projects against hepatitis B should be carried out in this population to further reduce the overall prevalence of hepatitis B.

Objective: To research on the main pattern of hepatic cells death during hepatic ischemia/ reperfusion (I/R) injury in cirrhotic rat., Methods: Cirrhotic rat model was established by carbon tetrachloride replication. These rats were randomly divided into sham operation group and I/R group. In the I/R group, 70% i/R injury model was established and then the liver samples were taken 0, 1, 6, 24, and 48 hours after reperfusion. Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) levels, Na+ - K+ ATPase, and Ca2+ ATPase were compared. the percentage of apoptotic/oncotic hepatic cells was measured with flow cytometry, and the changes in hepatic cellular structures were observed under transmission electron microscope., Results: Compared with the sham operation group, the levels of serum AST and ALT significantly increased in the I/R group (P < 0.05), reaching their peak levels at the 6th hour. The activities of Na+ - K+ ATPase and Ca2+ ATPase dramatically decreased one hour after reperfusion and then gradually recovered (P < 0.05). Hepatic cells mainly suffered oncosis at the early stage after reperfusion (within 6 hours); at the late stage (around 24 hours after reperfusion), apoptosis became the main death pattern., Conclusion: Oncosis is the main pattern of hepatic cells death during I/R injury in cirrhotic rat, and the severity of hepatic injury correlates with the oncosis.