Improving immunogenicity and safety of flagellin as vaccine carrier by high-density display on virus-like particle surface

Flagellin is a protein-based adjuvant that activates toll-like receptor (TLR) 5. Flagellin has been actively explored as vaccine adjuvants and carriers. Preclinical and clinical studies find flagellin-based vaccines have a risk to induce systemic adverse reactions potentially due to its overt activation of TLR5. To improve safety and immunogenicity of flagellin as vaccine carriers, FljB was displayed at high densities on hepatitis b core (HBc) virus-like particle (VLP) surface upon c/e1 loop insertion. FljB-HBc (FH) VLPs showed significantly reduced ability to activate TLR5 or induce systemic interleukin-6 release as compared to FljB. FH VLPs also failed to significantly increase rectal temperature of mice, while FljB could significantly increase rectal temperature of mice. These data indicated systemic safety of FljB could be significantly improved by high-density display on HBc VLP surface. Besides improved safety, FH VLPs and FljB similarly boosted co-administered ovalbumin immunization and FH VLPs were found to induce two-fold higher anti-FljB antibody titer than FljB. These data indicated preserved adjuvant potency and improved immunogenicity after high-density display of FljB on HBc VLP surface. Consistent with the high immunogenicity, FH VLPs were found to be more efficiently taken up by bone marrow-derived dendritic cells and stimulate more potent dendritic cell maturation than FljB. Lastly, FH VLPs were found to be a more immunogenic carrier than FljB, HBc VLPs, or the widely used keyhole limpet hemocyanin for nicotine vaccine development with a good local and systemic safety. Our data support FH VLPs to be a potentially safer and more immunogenic carrier than FljB for vaccine development

PO-024 Associations between the Sedentary Behavior and Cardiovascular Risk Factors in Adults of 40-49year

Objective Large amounts of pieces of evidence suggest sedentary behavior(SB) might have a negative impact on all-cause mortality, cardiovascular disease, and metabolic system. Our aim is to explore the associations between sedentary behavior and cardiovascular risk factors in adults of 40-49year. Methods Participants(N=372) were adults 40-49 years old who had a survey by using adult sit-Q-7d. The indexes of body mass index(BMI) and Waist circumference(WC) were measured as per standard protocols and blood pressure measured using an automated sphygmomanometer (Carescape V100; GE Healthcare, UK) following five minutes seated rest. HDL cholesterol (HDL-C), LDL cholesterol (LDL-C), triglycerides(TG) and fasting plasma glucose(FPG) were assessed for blood sampling of venous blood following an overnight fast (Cholestech LDX; Alere Inc, USA). We analyzed data in 2 h/day and 1 h/day as segmentation criteria of sitting time were classified as 8 groups(0<2, 2-4, 4-6, 6-8, 8-10, >10 h/day) and 10 groups(<1, 1-2, 2-3, 3-4, 4-5, 5-6, 6-7, 7-8, 8-9，>9 h/day). Statistical analyses were performed using STATA software 15.0(STATA Corp, College Station, TX). We performed multiple linear regression models adjusting for health-related confounders to assess the associations between SB of difference range and risk factors of cardiovascular disease. Results (1)When the sitting time as category criteria in 2 h/day, the relationship of LDL-C(β=0.651，95%CI=0.069 to 1.232, P=0.028)  and HDL-C(β=0.129，95%CI=0.013 to 0.245, P=0.028)  to sitting time in segment of 6-8h/day were statistically significant after adjustment for relative factor of risk; and the same in TC(β=0.932，95%CI=0.244 to 1.620, P=0.008) to sitting time in segment of 8-10h/day; (2) When the sitting time as category criteria in 1 h/day, in 3-4h/day segment, the index of BMI(β=1.550，95%CI=0.025 to 3.074, P=0.046) had a significant rise; in 7-8h/day segment, the index of LDL-C(β=0.919，95%CI=0.155 to 1.683, P=0.019) also had a significant rise; as well as, in 8-9h/day segment, the index of TC(β=1.531，95%CI=0.497 to 2.565, P=0.004) had a highly significant. (3) As has mentioned above, the threshold for each segment of sitting time for the index of LDL-C in 7-8h/day segment and the index of TC in 8-9h/day. Conclusions This study suggests that (1) the different category criteria of sitting time, for categories criteria in 1h/d or 2h/d, will help reduce the risk of Cardiovascular risk in some degree and determining to their dose-response relationships. (2) For the 40-49year adult of health, the sitting time threshold is less than 7 h/d, in order to decrease the detrimental effects on metabolic markers associated with cardiovascular disease and metabolic system. (3) As well as the sitting time threshold is less than 3 h/d for adding to the negative aging effect on risk of cardiovascular markers

Rapid Preparation of Spherical Granules via the Melt Centrifugal Atomization Technique

Granules with superior fluidity and low moisture absorption are ideal for tableting and capsule filling. Melt granulation as a solvent-free technology has attracted increasing interest for the granulation of moisture-sensitive drugs. The objective of the present study was to develop a solvent-less and high throughput melt granulation method via the melt centrifugal atomization (MCA) technique. The granule formability of various drugs and excipients via MCA and their dissolution properties were studied. It was found that the yield, fluidity, and moisture resistance of the granules were affected by the drug and excipient types, operation temperature, and collector diameter. The drugs were in an amorphous state in pure drug granules, or were highly dispersed in excipients as solid dispersions. The granules produced via MCA showed an improved drug dissolution. The present study demonstrated that the solvent-free, one-step, and high-throughput MCA approach can be used to produce spherical granules with superior fluidity and immediate drug release characteristics for poorly water-soluble and moisture-sensitive therapeutics

JMJD3 promotes survival of diffuse large B-cell lymphoma subtypes via distinct mechanisms.

JMJD3 (Jumonji domain containing-3), a histone H3 Lys27 (H3K27) demethylase, has been reported to be involved in the antigen-driven differentiation of germinal center B-cells. However, insight into the mechanism of JMJD3 in DLBCL (Diffuse large B-cell lymphoma) progression remains poorly understood. In this study, we investigated the subtype-specific JMJD3-dependent survival effects in DLBCL. Our data showed that in the ABC subtype, silencing-down of JMJD3 inhibited interferon regulatory factor 4 (IRF4) expression in a demethylase activity-dependent fashion. IRF4 reciprocally stimulated expression of JMJD3, forming a positive feedback loop that promoted survival in these cells. Accordingly, IRF4 expression was sufficient to rescue the pro-apoptotic effect of JMJD3 suppression in the ABC, but not in the GCB subtype. In contrast, ectopic overexpression of BCL-2 completely offset JMJD3-mediated survival in the GCB DLBCL cells. In vivo, treatment with siRNA to JMJD3 reduced tumor volume concordant with increased apoptosis in either subtype. This suggests it is a common target, though the distinctive signaling axes regulating DCBCL survival offer different strategic options for treating DLBCL subtypes

The Current Status and Development of Insect-Resistant Genetically Engineered Poplar in China

Poplar is one of the main afforestation tree species in China, and the use of a single, or only a few, clones with low genetic diversity in poplar plantations has led to increasing problems with insect pests. The use of genetic engineering to cultivate insect-resistant poplar varieties has become a hot topic. Over the past 20 years, there have been remarkable achievements in this area. To date, nearly 22 insect-resistant poplar varieties have been created and approved for small-scale field testing, environmental release, or pilot-scale production. Here, we comprehensively review the development of insect-resistant genetically modified (GM) poplars in China. This review mostly addresses issues surrounding the regulation and commercialization of Bt poplar in China, the various insecticidal genes used, the effects of transgenic poplars on insects, toxic protein expression, multigene transformation, the stability of insect resistance, and biosafety. The efficacy of GM poplars for pest control differed among different transgenic poplar clones, larval instars, and insect species. The Bt protein analysis revealed that the expression level of Cry3A was significantly higher than that of Cry1Ac. Temporal and spatial studies of Bt protein showed that its expression varied with the developmental stage and tissue. The inheritance and expression of the exogenous gene were reviewed in transgenic hybrid poplar progeny lines and grafted sections. Biosafety issues, in terms of transgene stability and the effects on soil microorganisms, natural enemies of insects, and arthropod communities are also discussed

Dietary Patterns and Changes in Weight Status Among Chinese Men and Women During the COVID-19 Pandemic.

To identify dietary patterns during the coronavirus disease-2019 (COVID-19) pandemic and to examine their association with changes in weight status in the Chinese population. The 2020 China COVID-19 cross-sectional survey is an anonymous 74-item survey administered social media across 31 provinces in mainland China between April and May 2020. Dietary data were assessed by a Food Frequency Questionnaire and the changes in weight status were self-reported. Exploratory factor analysis using the principal component analysis method was applied to identify dietary patterns. The multinomial regression models were conducted, and forest plots were used to present the associations between dietary patterns and changes in weight status. Of a total of 10,545 adults (aged ≥18 years), more than half of participants reported to have weight gain, with 18.6% of men and 16.3% of women having weight gain >2.5 kg. Approximately 8% of participants reported to have weight loss, with 2.1% of men and 2.5% women having weight loss >2.5 kg. Two dietary patterns, namely, the modern and prudent dietary patterns, were identified during the COVID-19 pandemic. The modern dietary pattern was loaded heavily with soft drinks, fried foods, pickles, and inversely with fresh vegetables. The prudent dietary pattern was characterized by high intake of fresh fruits, vegetables, and inversely with soft drinks and fried food. The modern dietary pattern was positively associated with weight gain in men and women, while the prudent dietary pattern was negatively associated with both weight gain and loss in men and women during the COVID-19 pandemic. Dietary patterns during COVID-19 are significantly associated with the changes in weight status, which may subsequently increase the risk of diet-related non-communicable disease among the Chinese population

Laparoscopic Radical Hysterectomy Results in Higher Recurrence Rate Versus Open Abdominal Surgery for Stage IB1 Cervical Cancer Patients With Tumor Size Less Than 2 Centimeter: A Retrospective Propensity Score-Matched Study

ObjectiveTo compare the oncologic outcomes between laparoscopic and open radical hysterectomy in patients with stage IB1 cervical cancer lesion less than 2 cm.MethodsPatients diagnosed FIGO (2009) stage IB1 (tumor diameter <2 cm) and underwent radical hysterectomy in our hospital between March 2008 and November 2018 were studied. A propensity-matched comparison (1:2) was conducted to minimize selection biases. Demographic and baseline oncologic characteristics were balanced between groups. Overall survival (OS) and disease-free survival (DFS) were assessed using the Kaplan–Meier model, along with univariable and multivariable regression analysis.ResultsA total of 261 patients were enrolled in this study after propensity-matching, with 174 in the open group and 87 in the laparoscopic group. Disease relapsed in seven patients in laparoscopy group, and the recurrence rate was 8.0% (7/87). There were eight patients underwent abdominal radical hysterectomy experienced recurrence, and the recurrence rate was 4.6% (8/174). The multivariate analysis model revealed that laparoscopic operation was associated with higher risk of recurrence than abdominal radical hysterectomy (HR, 3.789; 95% CI, 1.143–12.559; p = 0.029). There were five patients or 2.9% (5/174) died in open surgery group and the corresponding percentage in laparoscopy group was 2.3% (2/87). No difference was found in OS between the two groups (HR, 1.823; 95% CI, 0.2673–12.44; log-rank p = 0.5398). All the recurrence occurred within two years after operation in the laparoscopy group, among which pelvic recurrence (85.7%) was dominant.ConclusionTraditional laparotomy radical hysterectomy has a lower recurrence rate when compared with laparoscopic operation in those cervical cancer patients with a foci diameter less than 2 cm. However, no detrimental effect on survival was found in minimal invasive operation group. Further multi-center prospective trials are needed to confirm our results on a large scale