An Antenna-Enriched Chemosensory Protein Plays Important Roles in the Perception of Host Plant Volatiles in Bactrocera dorsalis (Diptera: Tephritidae).

Olfaction plays indispensable roles in insect behavior such as host location, foraging, oviposition, and avoiding predators. Chemosensory proteins (CSPs) can discriminate the hydrophobic odorants and transfer them to the odorant receptors. Presently, CSPs have been identified in many insect species. However, their presence and functions remain unknown in Bactrocera dorsalis, a destructive and invasive insect pest in the fruit and vegetable industry. Here, we annotated eight CSP genes in the genome of B. dorsalis. The results of quantitative real-time polymerase chain reaction (RT-qPCR) showed that BdorCSP3 was highly expressed in the antennae. Molecular docking and in vitro binding assays showed that BdorCSP3 had a good binding ability to host volatiles methyl eugenol (ME, male-specific attractant) and ß-caryophyllene (potential female attractant). Subsequently, CRISPR/Cas9 was used to generate BdorCSP3-/- mutants. Electroantennograms (EAGs) and behavioral assays revealed that male mutants significantly reduced the preference for ME, while female mutants lost their oviposition preference to ß-caryophyllene. Our data indicated that BdorCSP3 played important roles in the perception of ME and ß-caryophyllene. The results not only expanded our knowledge of the olfaction perception mechanism of insect CSPs but also provided a potential molecular target for the control of B. dorsalis.

The E3 ligase Trim63 promotes podocyte injury and proteinuria by targeting PPARα to inhibit fatty acid oxidation.

Podocyte injury is a hallmark of glomerular disease and one of the leading causes of chronic kidney disease (CKD). Peroxisome proliferator-activated receptor α (PPARα) plays a key role in podocyte fatty acid oxidation (FAO). However, the underlying regulatory mechanisms remain unresolved. Trim63 is an E3 ubiquitin ligase that has been shown to inhibit PPARα activity; however, its role in fatty acid metabolism in the kidney has not been elucidated to date. In this study, we investigated the effects of overexpression and knockdown of Trim63 in Adriamycin (ADR)-induced nephropathy and diabetic nephropathy models and a podocyte cell line. In both rodents and human patients with proteinuric CKD, Trim63 was upregulated, particularly in the podocytes of injured glomeruli. In the ADR-induced nephropathy model, ectopic Trim63 application aggravated FAO deficiency and mitochondrial dysfunction and triggered intense lipid deposition, podocyte injury, and proteinuria. Notably, Trim63 inhibition alleviated FAO deficiency and mitochondrial dysfunction, and markedly restored podocyte injury and renal fibrosis in ADR-induced and diabetic nephropathy (DN) models. Additionally, Trim63 was observed to mediate PPARα ubiquitination and degradation, leading to podocyte injury. We demonstrate the pathological role of Trim63, which was previously unrecognized in kidney tissue, in FAO deficiency and podocyte injury. Targeting Trim63 may represent a viable therapeutic strategy for podocyte injury and proteinuria.

Protopanaxadiol ameliorates NAFLD by regulating hepatocyte lipid metabolism through AMPK/SIRT1 signaling pathway.

Non-alcoholic fatty liver disease (NAFLD) has become one of the main chronic liver diseases worldwide. Protopanaxadiol (PPD), an active compound derived from Gynostemma pentaphyllum, has been found able to improve free fatty acid-induced lipid accumulation in hepatocytes. However, the efficacy of PPD on NAFLD and the underlying mechanism remains unknown. In this study, the mice were fed with a high-fat diet for 22 weeks to induce the NAFLD model, and then were treated with PPD by gavage for 8 weeks. Moreover, AML12 and HepG2 cells induced by free fatty acids for 24 h, were treated with different doses of PPD and/or AMPK or SIRT1 inhibitor to explore the pharmacological mechanism of PPD. The results showed that mice with PPD treatment had significantly reduced liver weight and serum aminotransferase levels, less severe hepatosteatosis, and inflammatory cell infiltration in liver tissues when compared with the model mice. PPD also reversed the down-regulated activation of AMPK and SIRT1 expression as well as the change of lipid metabolism-related molecules in the mice liver tissues. Consistently, the in vitro experiments showed the effect of PPD in ameliorating lipid accumulation in hepatocytes. The inhibitor of AMPK or SIRT1 suppressed the AMPK and SIRT1 signaling and markedly diminished the anti-steatosis effect of PPD. In conclusion, our results prove the ameliorating impact of PPD on NAFLD and also reveal the involvement of regulation of AMPK/SIRT1 signaling pathway-mediated lipid metabolism in the underlying mechanism, suggesting PPD as a potential natural compound for the treatment of NAFLD.

Meta-analysis of the occurrence of hepatocellular carcinoma after the treatment of entecavir and tenofovir for chronic hepatitis B.

BACKGROUND: Tenofovir and Entecavir are recommended as the first-line medicine of treatment for chronic hepatitis B. The occurrence of hepatocellular carcinoma after the treatment of chronic hepatitis B is a major problem. For the time being it is still unclear whether there remains a difference in risk correlation of hepatocellular carcinoma after the treatment of Tenofovir and Entecavir for chronic hepatitis B. Since previous studies have raised different ideas, this article aims to come to a conclusion targeting such a topic through analyzing the latest data. METHODS: We searched some databases, such as PubMed, Web of Science, and Cochrane Library, for related studies on patients with chronic hepatitis B receiving the treatment of Tenofovir and Entecavir and then developing hepatocellular carcinoma. The search time was set to begin from the establishment time of the above-mentioned databases to May 2022. Two researchers were designated to screen the literature independently according to the inclusion and exclusion criteria set in this study; they then evaluated the quality of the literature included and extracted the data. Revman 5.3 software was used for meta-analysis. RESULTS: After screening the literature, a total of 20 pieces of cohort study literature conformed to the inclusion criteria. Among which were 62,860 cases of patients receiving Entecavir, and 27,544 cases of patients receiving Tenofovir; there were 3669 cases with the occurrence of hepatocellular carcinoma in the Entecavir group and 1089 cases with the occurrence of hepatocellular carcinoma in Tenofovir group. The result of Meta analysis of these 20 pieces of literature shows that compared with the Tenofovir group, the Entecavir group has a lower occurrence rate of hepatocellular carcinoma, and the difference is statistically significant. The results are expressed as odd ratio (OR) and 95% confident interval (95%CI), (OR = 1.66, 95%CI: 1.35-2.05, P < .05). The result of Meta analysis of 10 studies related to Korea shows that the occurrence rate of hepatocellular carcinoma in the Tenofovir group is lower than that of the Entecavir group, and the difference is statistically significant (OR = 1.59, 95%CI: 1.29-1.95, P < .05). The result of meta-analysis of 5 studies related to China shows that the occurrence rate of hepatocellular carcinoma of Tenofovir group is lower than that of Entecavir group, and the difference is statistically significant (OR = 2.35, 95%CI: 1.15-4.81, P < .05). CONCLUSION: The occurrence rate of hepatocellular carcinoma after the treatment of tenofovir for chronic hepatitis B is lower than that of the treatment of entecavir.

Health-related quality of life of young academics: A cross-sectional survey of universities in Wuhan, China.

Objective: This study aimed to assess the health-related quality of life (HRQoL) of young academics in Wuhan, China, and its determinants. Methods: A multistage stratified cluster sampling strategy was employed to recruit study participants (young academics <40 years old) from 12 universities in Wuhan. A total of 301 respondents returned a self-complete questionnaire that contained the EQ-5D-5L. Multivariate linear and Tobit regression models were established to determine the sociodemographic and job predictors of the visual analogue scale (VAS) score and the EQ-5D utility index, respectively. Results: The study participants reported a mean VAS value of 79.42 (SD = 10.51) and a mean EQ-5D utility index of 0.915 (SD = 0.090). Anxiety/depression was the most frequently reported problem (65.12%), followed by pain/discomfort (43.52%). Transitioning towards a full professorship in national key universities (p < 0.001), lower income (p < 0.05) and too much pressure for academic promotion (p < 0.001) were significant predictors of lower HRQoL; whereas, maintaining routines in physical activities (p < 0.001), sleep (p < 0.001) and meals (p < 0.001), a good relationship with colleagues and family members (p < 0.001), and social activities (p < 0.01) were significant predictors of higher HRQoL. Conclusion: Low HRQoL of young academics in China is evident, as indicated by the 7.08 and 0.049 gap in VAS and utility index, respectively, compared to the general population at the same age. Work and career pressures are associated with the low HRQoL of young academics. The findings of this study highlight the importance of work-life balance in promoting HRQoL of young academics in universities in China.

CRISPR-mediated mutagenesis of the odorant receptor co-receptor (Orco) gene disrupts olfaction-mediated behaviors in Bactrocera dorsalis.

Olfaction plays an essential role in insect behavior such as host location, foraging, mating, and oviposition. The odorant receptor co-receptor (Orco) is an obligatory odorant receptor and indispensable in odor perception. Here, we characterized the Orco gene from the oriental fruit fly, Bactrocera dorsalis (Hendel), a notorious agriculture pest. The olfactory deficiency mutants were generated by editing the BdorOrco gene using the CRISPR/Cas9 system. Electroantennograms (EAG) and olfactory preference assays confirmed that BdorOrco-/- mutant flies had reduced perception of methyl eugenol, ß-caryophyllene, and ethyl acetate. Oviposition bioassays showed that the eggs laid by BdorOrco-/- females mediated by benzothiazole and 1-octen-3-ol were significantly decreased. In addition, BdorOrco-/- mutant flies took a significantly longer time to locate the food source compared with wild type (WT) flies. Altogether, our data indicated that Orco is essential for multiple physiological processes in B. dorsalis, and it expands our understanding of the function of insect Orco.

Comparative transcriptomic analysis reveals female-biased olfactory genes potentially involved in plant volatile-mediated oviposition behavior of Bactrocera dorsalis.

BACKGROUND: Olfactory systems take on important tasks to distinguish salient information from a complex olfactory environment, such as locating hosts, mating, aggression, selecting oviposition sites, and avoiding predators. The olfactory system of an adult insect consists of two pairs of main olfactory appendages on the head, the antennae, and the palps, which are covered with sensilla. Benzothiazole and 1-octen-3-ol could elicit oviposition behavior in gravid B. dorsalis are regarded as oviposition stimulants. However, the mechanism for how B. dorsalis percepts benzothiazole and 1-octen-3-ol still remains unknown. RESULTS: We conducted a comparative analysis of the antennal transcriptomes in different genders of B. dorsalis using Illumina RNA sequencing (RNA-seq). We identified a total of 1571 differentially expressed genes (DEGs) among the two sexes, including 450 female-biased genes and 1121 male-biased genes. Among these DEGs, we screened out 24 olfaction-related genes and validated them by qRT-PCR. The expression patterns of these genes in different body parts were further determined. In addition, we detected the expression profiles of the screened female-biased chemosensory genes in virgin and mated female flies. Furthermore, the oviposition stimulants-induced expression profilings were used to identify chemosensory genes potentially responsible for benzothiazole and 1-octen-3-ol perception in this fly. CONCLUSIONS: The results from this study provided fundamental data of chemosensory DEGs in the B. dorsalis antenna. The odorant exposure assays we employed lay a solid foundation for the further research regarding the molecular mechanism of benzothiazole and 1-octen-3-ol mediated oviposition behavior in B. dorsalis.

Traditional Chinese medicine targeting cancer stem cells as an alternative treatment for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a prevalent and highly malignant cancer throughout the world. Effective treatment of this disease is impeded by the high rate of metastasis, recurrence, and chemoresistance. Recent studies have revealed the close relationship between the malignant phenotype of HCC and cancer stem cells (CSCs). Therefore, CSC-targeted therapy is considered a promising strategy to eradicate HCC. Traditional Chinese medicine (TCM) can be effective in preventing recurrence and metastasis of some advanced HCC. A growing amount of literature has discovered that extracts or compounds derived from TCM exert an anti-CSC effect. This review introduces some formulas and chemical compounds derived from TCMs that have been reported to inhibit CSCs of HCC; these TCM-related drugs may help to provide an alternative approach to help manage cancers, especially for HCC which has a great potential of metastasis, recurrence, and chemoresistance.