Investigation of the mechanism of nephrotoxicity of nux-vomica by PTGS2/CYP2C9-mediated arachidonic acid pathway and Jian Pi Tong Luo compound's protective effect.

The clinical effectiveness of nux-vomica in treating rheumatism and arthralgia is noteworthy; however, its nephrotoxicity has sparked global concerns. Hence, there is value in conducting studies on detoxification methods based on traditional Chinese medicine compatibility theory. Blood biochemistry, enzyme-linked immunosorbent assay, and pathological sections were used to evaluate both the nephrotoxicity of nux-vomica and the efficacy of the Jian Pi Tong Luo (JPTL) compound in mitigating this toxicity. Kidney metabolomics, using ultra-high-performance liquid chromatography-quadrupole-time-of-flight-MS (UPLC-Q-TOF-MS), was applied to elucidate the alterations in small-molecule metabolites in vivo. In addition, network pharmacology analysis was used to verify the mechanism and pathways underlying the nephrotoxicity associated with nux-vomica. Finally, essential targets were validated through molecular docking and western blotting. The findings indicated significant nephrotoxicity associated with nux-vomica, while the JPTL compound demonstrated the ability to alleviate this toxicity. The mechanism potentially involves nux-vomica activating the "PTGS2/CYP2C9-phosphatidylcholine-arachidonic acid metabolic pathway." This study establishes a scientific foundation for the clinical use of nux-vomica and lays groundwork for further research and safety assessment of toxic Chinese herbal medicines.

Endoplasmic reticulum stress regulates apoptosis and chemotherapeutic via enhancing TNFRSF10B recycling to the cell membrane in triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) is the most common malignant tumor in China. The expression and cell surface levels of TNF receptor superfamily member 10B (TNFRSF10B) are associated with apoptosis and chemotherapy. However, the precise molecular mechanisms that govern the regulation of TNFRSF10B remain unclear. MATERIALS AND METHODS: RNA-Seq data related to TNBC chemotherapy resistance were acquired from the GEO database. The mRNA and protein levels of TNFRSF10B were detected using RT-PCR and Western blotting, respectively. Cell Counting Kit-8 (CCK-8) and colony formation assays were used to detect cell proliferation. Annexin V/7-AAD staining was used to evaluate apoptosis. The cell membrane TNFRSF10B was analyzed by Western blotting and immunofluorescence. Inducers and inhibitors of endoplasmic reticulum stress (ERS) were used to assess the effect of ERS on TNFRSF10B localization. RESULTS: TNFRSF10B expression was downregulated in TNBC and was associated with prognosis. TNFRSF10B overexpression inhibits the growth of TNBC both in vivo and in vitro and can partially counteract chemotherapy resistance. ERS activation in TNBC promotes the expression of TNFRSF10B, leading to its enrichment on the cell membrane surface, thereby activating the apoptotic pathways. CONCLUSION: ERS regulates the expression and subcellular localization of TNFRSF10B in TNBC cells. They synergistically affect anti-apoptosis and chemotherapy resistance in TNBC cells.

Impact of Environmental Food Intake on the Gut Microbiota of Endangered Père David's Deer: Primary Evidence for Population Reintroduction.

Reintroduction has been successful in re-establishing several endangered wild animals in their historical habitats, including Père David's deer (Elaphurus davidianus). Continuous monitoring of reintroduced individuals is essential for improving the sustainability of ex situ conservation efforts. Despite an increased recognition of the significance of the gut microbiome for animal health, the correlation between diet and the gut microbiome in E. davidianus is unclear. In this study, 15 fresh fecal samples of E. davidianus were collected from Tianjin Qilihai Wetland and the association between dietary and gut microbiota composition was evaluated. Microscopic observations showed that Nymphoides peltata [relative density (RD = 0.3514), Phragmites australis (RD = 0.2662), Setaria viridis (RD = 0.1211), and Typha orientalis (RD = 0.1085) were the main dietary plants in the fecal samples. High-throughput 16S rRNA sequencing showed a predominance of the phyla Firmicutes and Proteobacteria and the genus Psychrobacillus (26.53%) in the gut microbiota. The RD of N. peltata was significantly positively correlated with the abundance of Firmicutes (p = 0.005) and the genus UCG-005 (p = 0.024). This study indicates a close association between food digestion and nutrient intake, providing basic monitoring data for the full reintroduction and recovery of wild E. davidianus.

Similarities and differences: species and diet impact gut microbiota of captive pheasants.

The fecal microbiota plays an important role in maintaining animal health and is closely related to host life activities. In recent years, there have been an increasing number of studies on the fecal microbiota from birds. An exploration of the effects of species and living environments on the composition of gut microbiota will provide better protection for wildlife. In this study, non-injury sampling and 16S rDNA high-throughput sequencing were used to investigate the bacterial composition and diversity of the fecal microbiota in silver pheasants (Lophura nycthemera) and golden pheasants (Chrysolophus pictus) from Tianjin Zoo and Beijing Wildlife Park. The results showed that the abundance of Firmicutes was the highest in all fecal samples. At the genus level, Bacteroides was the common dominant bacteria, while there were some differences in other dominant bacteria genera. There were significant differences in fecal microbial composition between the golden pheasants from Tianjin Zoo and Beijing Wildlife Park. The metabolic analysis and functional prediction suggested that the gut microbiota composition and host metabolism were influenced by dietary interventions and living conditions. The results of this study provide the basis for further research of intestinal microbial of L. nycthemera and C. pictus, and valuable insights for conservation of related species.

Diet Drives Gut Bacterial Diversity of Wild and Semi-Captive Common Cranes (Grus grus).

The gut microbiota of wild animals can regulate host physical health to adapt to the environment. High-throughput sequencing from fecal samples was used to analyze the gut microbiota communities in common cranes (Grus grus) without harming them. Herein, we compared the fecal microbiome of fifteen G. grus in Tianjin Tuanbo Bird Natural Reserve (wild group) and six G. grus sampled from Beijing Wildlife Park (semi-captive group) in China, using 16S amplicon sequencing and bioinformatic analysis. The results showed that microbiota diversity and composition varied in different groups, suggesting that the gut microbiota was interactively influenced by diet and the environment. A total of 38 phyla and 776 genera were analyzed in this study. The dominant phyla of the G. grus were Firmicutes and Proteobacteria. Meanwhile, the microbiota richness of the semi-captive group was higher than the wild group. Data on beta diversity highlighted significant differences based on different dietary compositions. Zea mays, Glycine max, and Phragmites australia showed a significant correlation with intestinal bacteria of G. grus. This study provides a comprehensive analysis of diet and microbiomes in semi-captive and wild G. grus living in different environments, thus helping us to evaluate the influence on animal microbiomes and improve conservation efforts for this species.

Variation on gut microbiota diversity of endangered red pandas (Ailurus fulgens) living in captivity acrosss geographical latitudes.

The gut microbiome plays important roles in metabolic and immune system related to the health of host. This study applied non-invasive sampling and 16S rDNA high-throughput sequencing to study the gut microbiota structure of red pandas (Ailurus fulgens) for the first time under different geographical latitudes in captivity. The results showed that the two predominant phyla Firmicutes (59.30%) and Proteobacteria (38.58%) constituted 97.88% of the total microbiota in all the fecal samples from north group (red pandas from Tianjin Zoo and Jinan Zoo) and south group (red pandas from Nanjing Hongshan Forest Zoo). The relative abundance of Cyanobacteria in north group was significantly higher than that in south group. At the genus level, Escherichia-Shigella (24.82%) and Clostridium_sensu_stricto_1 (23.00%) were common dominant genera. The relative abundance of norank_f__norank_o__Chloroplast, Terrisporobacter and Anaeroplasma from south group was significantly higher than that of north group. Alpha and Beta analysis consistently showed significant differences between north group and south group, however, the main functions of intestinal microbiota were basically the same, which play an important role in metabolic pathways, biosynthesis of secondary metabolites, microbial metabolism in different environments, and amino acid biosynthesis. The variations in gut microbiota between the northern and southern populations of the same species, both kept in captivity, which are primarily driven by significant differences in climate and diet. These findings provide a deeper understanding of the gut microbiota in red pandas and have important implications for their conservation, particularly in optimizing diet and environmental conditions in captivity.

Electronic inhomogeneity and phase fluctuation in one-unit-cell FeSe films.

One-unit-cell FeSe films on SrTiO3 substrates are of great interest owing to significantly enlarged pairing gaps characterized by two coherence peaks at ±10 meV and ±20 meV. In-situ transport measurement is desired to reveal novel properties. Here, we performed in-situ microscale electrical transport and combined scanning tunneling microscopy measurements on continuous one-unit-cell FeSe films with twin boundaries. We observed two spatially coexisting superconducting phases in domains and on boundaries, characterized by distinct superconducting gaps ( Δ 1 ~15 meV vs. Δ 2 ~10 meV) and pairing temperatures (Tp1~52.0 K vs. Tp2~37.3 K), and correspondingly two-step nonlinear V ~ I α behavior but a concurrent Berezinskii-Kosterlitz-Thouless (BKT)-like transition occurring at T BKT ~28.7 K. Moreover, the onset transition temperature T c onset ~54 K and zero-resistivity temperature T c zero ~31 K are consistent with Tp1 and T BKT , respectively. Our results indicate the broadened superconducting transition in FeSe/SrTiO3 is related to intrinsic electronic inhomogeneity due to distinct two-gap features and phase fluctuations of two-dimensional superconductivity.