Guangdong Institute of Biological Products and Drugs

ABSTRACTThis work is meant to study the effect of galacto‐oligosaccharide (GOS) intervention in the fecal microbiota of obese mice on lipid metabolism and anti‐obesity in mice. A pseudo‐germ‐free mice model was established by administration of a mixture of antibiotics. The fecal microbiota of GOS‐fed obese mice are transplanted into pseudo‐germ‐free mice. To investigate the effects of GOS intervention on lipid metabolism, lipid quadruple, bile acid metabolism, and intestinal microbiota in obese mice. At the same time, the expression of BAS synthase and the effects of FXR‐SHP and FXR‐FGF15‐FGFR4 signaling pathways on BAS homeostasis were also explored. The fecal microbiota of obese mice intervened by GOS could reshape the structure of intestinal microbiota, regulate the synthesis of bile acids in the enterohepatic circulation and the expression of transport‐related factors, and promote metabolic ability to exert anti‐obesity effects.

ABSTRACTBackgroundAs pregnant women are excluded from clinical trials of inactivated SARS-CoV-2 vaccines, it is important to assess the immune response in women receiving the vaccination while unknowingly pregnant.MethodsIn a multicenter cross-sectional study, we enrolled 873 pregnant women aged 18–45 years. Serum antibody levels induced by inactivated vaccines were determined. Adverse events were collected by self-reported survey after vaccination. Logistic regression model and restricted cubic spline model were used to investigate the association of factors with antibody positivity.ResultsAs the doses of the vaccine increase, neutralizing antibody (NAb) positivity was 98.3%, 39.5%, and 9.5% in pregnant women, respectively. The dose of vaccine and duration since vaccination were associated with NAb positivity. The OR of two and three doses of vaccines were 7.20 and 458.33 (P < 0.05). NAb levels and duration since vaccination showed a linear relationship in pregnant women vaccinated two doses, with a decrease to a near seropositivity threshold at 22 weeks. Adverse events were mainly mild or moderate after vaccinated during pregnancy, with no increase in incidence compared with whom vaccinated during pre-pregnancy.ConclusionsThe use of inactivated vaccines during pregnancy induced favorable immune persistence, and the incidence of adverse events did not increase.

Microplastics (MPs) and chemical pollutants usually coexist in aquatic environments. The bioaccumulation and metabolism of pollutants in aquatic organisms can be influenced by MPs. In this study, the bioaccumulation of triclosan (TCS) in tilapia tissues was determined, and metabolomics in the liver, gills, and gut were investigated after 10-day exposure to micro-sized polystyrene (PS) and TCS in water. The results showed that TCS bioaccumulated in various tissues, with the highest average concentration of 2728 ± 577 ng g-1 in the gut. The log bioaccumulation factors (BAFs) for TCS in these tissues were in the range of 0.99-3.56. Compared to the TCS treatment alone, MPs showed enhancement on the bioaccumulation of TCS in tilapia skin, liver, gut, gills, and stomach tissues in the TCS plus MP exposure. Especially in the skin and liver, the TCS concentrations were up to 2.06 and 1.38 times higher in the co-exposure of TCS and MPs, respectively. Based on the metabolomic analysis, MPs mainly disturbed the lipid and energy metabolism in tilapia fish. The altered metabolites between treatment with TCS alone and TCS + MPs were consistent, indicating that TCS has stronger disturbance in lipid and energy metabolism than MPs. This implies that the metabolism influence by the mixture of MPs and compounds is complicated in fish tissues.

BackgroundCritical questions remain regarding the need for intensity to continue NPIs as the public was vaccinated. We evaluated the association of intensity and duration of non-pharmaceutical interventions (NPIs) and vaccines with COVID-19 infection, death, and excess mortality in Europe. MethodsData comes from Our Word in Data. We included 22 European countries from January 20, 2020, to May 30, 2021. The time-varying constrained distribution lag model was used in each country to estimate the impact of different intensities and duration of NPIs on COVID-19 control, considering vaccination coverage. Country-specific effects were pooled through meta-analysis. ResultsThis study found that high-intensity and long-duration of NPIs showed a positive main effect on reducing infection in the absence of vaccines, especially in the intensity above the 80th percentile and lasted for 7 days (RR = 0.93, 95% CI: 0.89–0.98). However, the adverse effect on excess mortality also increased with the duration and intensity. Specifically, it was associated with an increase of 44.16% (RR = 1.44, 95% CI: 1.27–1.64) in the excess mortality under the strict intervention (the intensity above the 80th percentile and lasted for 21 days). As the vaccine rollouts, the inhibition of the strict intervention on cases growth rate was increased (RR dropped from 0.95 to 0.87). Simultaneously, vaccination also alleviated the negative impact of the strict intervention on excess mortality (RR decreased from 1.44 to 1.25).Besides, maintaining the strict intervention appeared to more reduce the cases, as well as avoids more overall burden of death compared with weak intervention. ConclusionsOur study highlights the importance of continued high-intensity NPIs in low vaccine coverage. Lifting of NPIs in insufficient vaccination coverage may cause increased infections and death burden. Policymakers should coordinate the intensity and duration of NPIs and allocate medical resources reasonably with widespread vaccination.

Tyrosyl-DNA phosphodiesterase 2 (TDP2) is a recently discovered DNA repair enzyme that can repair topoisomerase 2-mediated DNA damage, resulting in cancer cell resistance. In this study, two compounds, robustadial A and B, were isolated from a fraction of the ethyl acetate extract of Eucalyptus globulus Labill. fruits based on TDP2 inhibition screening. The biological experiments indicated that robustadial A and B have TDP2 inhibitory activity with EC50 values of 17 and 42 μM, respectively, but no tyrosyl-DNA phosphodiesterase 1 inhibition at 100 μM. Robustadial A showed significant synergistic effects with the anticancer drug etoposide in four human cancer cell lines, non-small cell lung cancer cell line (A549), prostate cancer cell line (DU145), breast cancer cell line (MCF-7), colorectal adenocarcinoma cell line (HCT-116), and chicken lymphoma cell line (DT40), and chicken lymphoma cell line complementation with human TDP2 (DT40 hTDP2) with combination index values ranging from 0.21 to 0.74. This work will facilitate future efforts for the development of robustadial A-based TDP2 selective inhibitors.

Chitosan oligosaccharides (COSs) are widely used biopolymers that have been studied in relation to a variety of abnormal biological activities in the food and biomedical fields. Since different COS preparation technologies produce COS compounds with different structural characteristics, it has not yet been possible to determine whether one or more chito-oligomers are primarily responsible for the bioactivity of COSs. The inherent biocompatibility, mucosal adhesion and nontoxic nature of COSs are well documented, as is the fact that they are readily absorbed from the intestinal tract, but their structure-activity relationship requires further investigation. This review summarizes the methods used for COS preparation, and the research findings with regard to the antioxidant, anti-inflammatory, anti-obesity, bacteriostatic and antitumour activity of COSs with different structural characteristics. The correlation between the molecular structure and bioactivities of COSs is described, and new insights into their structure-activity relationship are provided.

Insights into the potential candidate hub genes may facilitate the generation of safe and effective immunity against seasonal influenza as well as the development of personalized influenza vaccines for the elderly at high risk of influenza virus infection. This study aimed to identify the potential hub genes related to the immune induction process of the 2018/19 seasonal quadrivalent inactivated influenza vaccines (QIVs) in the elderly ≥60 years by using weighted gene co-expression network analysis (WGCNA). From 63 whole blood samples from16 elderly individuals, a total of 13,345 genes were obtained and divided into eight co-expression modules, with two modules being significantly correlated with vaccine-induced immune responses. After functional enrichment analysis, genes under GO terms of vaccine-associated immunity were used to construct the sub-network for identification and functional validation of hub genes. MCEMP1 and SPARC were confirmed as the hub genes with an obvious effect on QIVs-induced immunity. The MCEMP1 expression was shown to be negatively correlated with the QIVs-associated reactogenicity within 7 days after vaccination, which could be suppressed by the CXCL 8/IL-8 and exacerbated by the Granzyme-B cytotoxic mediator. Meanwhile, the SPARC expression was found to increase the immune responses to the QIVs and contribute to the persistence of protective humoral antibody titers. These two genes can be used to predict QIVs-induced adverse reaction, the intensity of immune responses, and the persistence of humoral antibody against influenza. This work has shed light on further research on the development of personalized QIVs with appropriate immune responses and long-lasting immunity against the forthcoming seasonal influenza.