Folic acid supplementation in pregnant women with hepatitis B surface antigen improves infant hepatitis B surface antibody mediated by infant IL-4.

Immunoprophylaxis has not completely eliminated hepatitis B virus (HBV) infection due to hyporesponsiveness to hepatitis B vaccine (HepB). We explored the impact of folic acid supplementation (FAS) in pregnant women with positive hepatitis B surface antigen (HBsAg) on their infant hepatitis B surface antibody (anti-HBs) and the mediation effect of infant interleukin-4 (IL-4). We recruited HBsAg-positive mothers and their neonates at baseline. Maternal FAS was obtained via a questionnaire, and neonatal anti-HBs and IL-4 were detected. Follow-up was performed at 11-13 months of age of infants, when anti-HBs and IL-4 were measured. We applied univariate and multivariate analyses. A mediation effect model was performed to explore the mediating role of IL-4. A total of 399 mother-neonate pairs were enrolled and 195 mother-infant pairs were eligible for this analysis. The infant anti-HBs geometric mean concentrations in the maternal FAS group were significnatly higher than those in the no-FAS group (383·8 mIU/ml, 95 % CI: 294·2 mIU/ml to 500·7 mIU/ml v. 217·0 mIU/ml, 95 % CI: 147·0 mIU/ml to 320·4 mIU/ml, z = -3·2, P = 0·001). Infants born to women who took folic acid (FA) within the first trimester were more likely to have high anti-HBs titres (adjusted ß-value = 194·1, P = 0·003). The fold change in IL-4 from neonates to infants partially mediated the beneficial influence of maternal FAS on infant anti-HBs (24·7 % mediation effect) after adjusting for confounding factors. FAS during the first trimester to HBsAg-positive mothers could facilitate higher anti-HBs levels in infants aged 11-13 months partly by upregulating IL-4 in infants.

Dendritic cells: In vitro culture in two- and three-dimensional collagen systems and expression of collagen receptors in tumors and atherosclerotic microenvironments.

Dendritic cells (DCs) are immune cells found in the peripheral tissues where they sample the organism for infections or malignancies. There they take up antigens and migrate towards immunological organs to contact and activate T lymphocytes that specifically recognize the antigen presented by these antigen presenting cells. In the steady state there are several types of resident DCs present in various different organs. For example, in the mouse, splenic DC populations characterized by the co-expression of CD11c and CD8 surface markers are specialized in cross-presentation to CD8 T cells, while CD11c/SIRP-1α DCs seem to be dedicated to activating CD4 T cells. On the other hand, DCs have also been associated with the development of various diseases such as cancer, atherosclerosis, or inflammatory conditions. In such disease, DCs can participate by inducing angiogenesis or immunosuppression (tumors), promoting autoimmune responses, or exacerbating inflammation (atherosclerosis). This change in DC biology can be prompted by signals in the microenvironment. We have previously shown that the interaction of DCs with various extracellular matrix components modifies the immune properties and angiogenic potential of these cells. Building on those studies, herewith we analyzed the angiogenic profile of murine myeloid DCs upon interaction with 2D and 3D type-I collagen environments. As determined by PCR array technology and quantitative PCR analysis we observed that interaction with these collagen environments induced the expression of particular angiogenic molecules. In addition, DCs cultured on collagen environments specifically upregulated the expression of CXCL-1 and -2 chemokines. We were also able to establish DC cultures on type-IV collagen environments, a collagen type expressed in pathological conditions such as atherosclerosis. When we examined DC populations in atherosclerotic veins of Apolipoprotein E deficient mice we observed that they expressed adhesion molecules capable of interacting with collagen. Finally, to further investigate the interaction of DCs with collagen in other pathological conditions, we determined that both murine ovarian and breast cancer cells express several collagen molecules that can contribute to shape their particular tumor microenvironment. Consistently, tumor-associated DCs were shown to express adhesion molecules capable of interacting with collagen molecules as determined by flow cytometry analysis. Of particular relevance, tumor-associated DCs expressed high levels of CD305/LAIR-1, an immunosuppressive receptor. This suggests that signaling through this molecule upon interaction with collagen produced by tumor cells might help define the poorly immunogenic status of these cells in the tumor microenvironment. Overall, these studies demonstrate that through interaction with collagen proteins, DCs can be capable of modifying the microenvironments of inflammatory disease such as cancer or atherosclerosis.

Enhanced Modification of Fast-Growing Wood: Application and Evaluation of Castor Oil-Based Unsaturated Polyester Resin.

A type of multifunctional maleic acid ester monomer (COEGMA) was synthesized using castor oil as raw material, and green wood-plastic composites were prepared by chemically impregnating and curing the monomer into wood. The structure of the synthesized products at various stages was determined by FT-IR spectroscopy, 1H NMR, and GPC, and the curing experimental conditions were optimized. The results show that the water absorption of wood-plastic composites treated with COEGMA is reduced from the original 167.3% to less than 20%. The compressive strength has increased from 35.7 to 86.1 MPa, and the thermal stability has also increased by 40 °C. This research provides promising prospects for the development of environmentally friendly wood-plastic composites, especially as fossil resources become scarce and environmental pollution becomes more severe.

Maternal A90V mutation in the PreS1 gene of sub-genotype C2 hepatitis B virus is associated with intrauterine transmission.

PreS/S gene mutations could impact virus secretion, infection and immune evasion. However, the relationship between PreS/S mutations and intrauterine transmission has not yet been clarified. Thus, we aimed to explore the associations between PreS/S gene mutations of HBV isolated from mothers and intrauterine transmission. We analyzed the mutations of PreS/S regions of the HBV genome in mothers with HBV DNA levels ≥ 106 IU/mL whose neonates experienced HBV intrauterine transmission (transmission group, GT) and those whose neonates did not experience intrauterine transmission (control group, GC) analyzed using clone-based sequencing. In total, 206 sequences were successfully amplified, including 98 sequences (from 21 mothers) from GT and 108 sequences (from 20 mothers) from GC of genotype C for mutational analysis. Among the 1203 nucleotides of PreS/S regions, there were 219 (18.20%) base substitutions, of which 103 (47.03%) base mutations caused amino acid changes. F80S, A90V and I68T were mutation hotspots. Mothers in GT had a higher mutation rate of A90V in the PreS1 gene than mothers in GC. The A90V mutation increased the risk of HBV intrauterine transmission after adjusting the maternal age and the mode of delivery (OR = 6.23, 95% CI: 1.18-32.97). Moreover, the area under the ROC curve (AUC) for intrauterine transmission due to A90V and a combination of A90V with the mode of delivery were 0.723 (95% CI: 0.575 to 0.891, P = 0.011) and 0.848 (95% CI: 0.723 to 0.972, P < 0.001), respectively. Mothers with the A90V mutation in the PreS1 gene may be a potential risk factor for HBV intrauterine transmission.

The top 100 most cited articles on COVID-19 vaccine: a bibliometric analysis.

This study aimed to uncover the current major topics regarding COVID-19 vaccine, and systematically evaluate the development trends for future research. The top 100 most cited original articles on COVID-19 vaccine from January 2020 to October 2022 were identified from Web of Science Core Collection database. CiteSpace (v6.1.R3) was adopted for bibliometric analysis with statistical and visual analysis. The number of citations ranged from 206 to 5881, with a median of 349.5. The USA (n = 56), England (n = 33), and China (n = 16) ranked the top three countries/regions in terms of the number of publications. Harvard Medical School (centrality = 0.71), Boston Children's Hospital (centrality = 0.67), and Public Health England (centrality = 0.57) were the top three institutions leading the way on COVID-19 vaccine research. The New England of medicine journal dominated with 22 articles in the 32 high-quality journals. The three most frequent keywords were immunization (centrality = 0.25), influenza vaccination (centrality = 0.21), and coronavirus (centrality = 0.18). Cluster analysis of keywords showed that the top four categories were protection efficacy, vaccine hesitancy, spike protein, and second vaccine dose (Q value = 0.535, S value = 0.879). Cluster analysis of cited references showed that top eight largest categories were Cov-2 variant, clinical trial, large integrated health system, COV-2 rhesus macaque, mRNA vaccine, vaccination intent, phase II study, and Cov-2 omicron variant (Q value = 0.672, S value = 0.794). The research on COVID-19 vaccine is currently the hottest topic in academic community. At present, COVID-19 vaccines researches have focused on vaccine efficacy, vaccine hesitancy, and the efficacy of current vaccines on omicron variants. However, how to increase vaccine uptake, focus on mutations in the spike protein, evaluate of the efficacy of booster vaccine, and how effective new vaccines under pre- and clinical development against omicron will be spotlight in the future.

Infant immune response to hepatitis B vaccine after fetal exposure to telbivudine.

Whether telbivudine (LdT) treatment to pregnant women with hepatitis B surface antigen (HBsAg) affects infant immune response to hepatitis B vaccine (HepB) has not been investigated. A total of 127 HBsAg positive mothers and their neonates were enrolled and followed up at 11-13 months. Mothers took LdT (LdT group) or did not receive antiviral therapy (control group). Infant anti-HBs, immune cells and cytokines were measured after HepB was administered according to 0-1-6 procedure. We performed a 1:3 propensity score matching (PSM). Immune indexes in the two groups were compared. Baseline characteristics of mother-baby pairs were comparable in LdT group and control group. Infant anti-HBs geometric mean concentration (GMC) did not differ significantly between the two groups [767.70 (745.35) vs. 711.90 (819.60), P = .599]. There was no difference between the two groups in infant positive rate of anti-HBs [97.8% (91/93) vs. 97.1% (33/34), P = .999] and strong positive rate of anti-HBs [40.9% (38/93) vs. 44.1% (15/34), P = .742]. Infants with negative, low, medium, and high anti-HBs levels were similarly distributed between the two groups (P = .511). No differences in proportion of helper T cells, cytotoxic T cells, B cells, myeloid dendritic cells, and plasmacytoid dendritic cells of infants (P > .05) were detected between the two groups. Children in the LdT and control group had comparable levels of interleukin-2, interleukin-4, interleukin-6, interleukin-10, interleukin-12, interferon-α, interferon-γ and tumor necrosis factor-α (P > .05). Intrauterine exposure to LdT was safe to infant immune response to HepB after birth.

Immunotoxicity induced by Ivermectin is associated with NF-κB signaling pathway on macrophages.

Ivermectin (IVM) has been widely used as a highly effective and broad-spectrum biopesticide in animal husbandry and agriculture. Considering the frequent environmental and occupational exposure, the various toxic effects caused by IVM should be paid more attention. The immune system is a common target of toxins due to its complexity and sensitivity. The toxicity effect of the immune system may lead to increased susceptibility to infections, with potentially fatal consequences. The immunotoxicity of IVM has received little attention, which poses a challenge to the systematic assessment of safety risks. The purpose of this study was to assess the immunotoxicity of the IVM using in vitro cellular assays. We proved that IVM could inhibit the cell viability, induce DNA damage and enhance apoptosis. In addition to the induction of cytotoxicity, IVM has also been shown to reduce the phagocytic capacity and significantly increase the mRNA expression levels of proinflammatory cytokines IL-6, IL-1 ß and TNF-α. Intracellular biochemical assay indicated that activation of the NF-κB signaling pathway, overproduction of reactive oxygen species (ROS), release of cytochrome C, DNA double strand damage. These results indicate that IVM can induce immunotoxicity through induction of immune dysfunction and cytotoxicity. In conclusion, this study supports that IVM can be immunotoxic to macrophages in different ways, and draw attention to the potential immunotoxicity of IVM.

NaCl markedly improved the reproductive capacity of the euhalophyte Suaeda salsa.

The effect of NaCl on reproductive development was investigated in euhalophyte Suaeda salsa L. under controlled conditions. Results showed that NaCl promoted the reproductive growth of S. salsa and 200mM NaCl was optimal. This was reflected in the increases of seed yield, seed number, flower number per plant and leaf axil, 1000 seed weight, as well as a decrease in flower abortion percentage with supply of NaCl. NaCl reduced the flower abortion percentage by increasing stigma receptivity instead of pollen viability. The Na+ and Cl- concentration in petals, stems and leaves were increased significantly but slightly in stamen and pistil. In contrast, the K+ concentration decreased markedly in leaves, stems and petals but a little in stamen and pistil. The Na+ and Cl- concentrations also increased significantly in seed from mother plants exposed to NaCl, whereas K+ decreased. However, seed quality was not influenced. Our results showed that high concentration of NaCl markedly increases the seed number and quality of S. salsa primarily via increasing flower number and fertility and S. salsa develops strategy to maintain ion homeostasis in reproductive organs for the generation. These factors play a pivotal role in setting up plant populations in saline environment.

Maternal A90V mutation in the PreS1 gene of sub-genotype C2 hepatitis B virus is associated with intrauterine transmission

ABSTRACT PreS/S gene mutations could impact virus secretion, infection and immune evasion. However, the relationship between PreS/S mutations and intrauterine transmission has not yet been clarified. Thus, we aimed to explore the associations between PreS/S gene mutations of HBV isolated from mothers and intrauterine transmission. We analyzed the mutations of PreS/S regions of the HBV genome in mothers with HBV DNA levels ≥ 106 IU/mL whose neonates experienced HBV intrauterine transmission (transmission group, GT) and those whose neonates did not experience intrauterine transmission (control group, GC) analyzed using clone-based sequencing. In total, 206 sequences were successfully amplified, including 98 sequences (from 21 mothers) from GT and 108 sequences (from 20 mothers) from GC of genotype C for mutational analysis. Among the 1203 nucleotides of PreS/S regions, there were 219 (18.20%) base substitutions, of which 103 (47.03%) base mutations caused amino acid changes. F80S, A90V and I68T were mutation hotspots. Mothers in GT had a higher mutation rate of A90V in the PreS1 gene than mothers in GC. The A90V mutation increased the risk of HBV intrauterine transmission after adjusting the maternal age and the mode of delivery (OR = 6.23, 95% CI: 1.18-32.97). Moreover, the area under the ROC curve (AUC) for intrauterine transmission due to A90V and a combination of A90V with the mode of delivery were 0.723 (95% CI: 0.575 to 0.891, P = 0.011) and 0.848 (95% CI: 0.723 to 0.972, P < 0.001), respectively. Mothers with the A90V mutation in the PreS1 gene may be a potential risk factor for HBV intrauterine transmission.

Adhesion to substrates induces dendritic cell endothelization and decreases immunological response.

Dendritic cells (DCs) are antigen presenting cells capable of inducing specific immune responses against microbial infections, transplant antigens, or tumors. DCs have been shown to possess a high plasticity showing different phenotypes in response to their microenvironment. For example, tumor-associated DCs can acquire an angiogenic phenotype thus promoting tumor growth. Further, DCs cultured in vitro under different conditions are able to upregulate the expression of endothelial markers and to express angiogenic factors. Indeed, it has been shown that soluble factors such as VEGF of PGE-2, that are present in the microenvironment of several tumors, affect the biology of these cells. We hypothesize that in addition to soluble factors the adhesion to different substrates will also define the phenotype and function of DCs. Herewith we demonstrate that murine myeloid(m) DCs upregulate endothelial markers such as VE-Cadherin, and to a lesser extent TIE-2, and decrease their immune capabilities when cultured on solid surfaces as compared with the same cells cultured on ultra-low binding (ULB) surfaces. On the other hand, the expression of angiogenic molecules at the level of RNA was not different among these cultures. In order to further investigate this phenomenon we used the murine ID8 model of ovarian cancer which can generate solid tumors when cancer cells are injected subcutaneously or a malignant ascites when they are injected intraperitoneally. This model gave us the unique opportunity to investigate DCs in suspension or attached to solid surfaces under the influence of the same tumor cells. We were able to determine that DCs present in solid tumors showed higher levels of expression of endothelial markers and angiogenic molecules but were not able to respond to inflammatory stimuli at the same extent as DCs recovered from ascites. Moreover, mDCs cultured on ULB surfaces in the presence of tumor factors do not expressed endothelial markers. Taking into account all these data we consider that tumor factors might be responsible for inducing angiogenic properties in DCs, but that in some settings the expression of endothelial markers such as VE-Cadherin and TIE-2 might be a function of attachment to solid surfaces and independent of the angiogenic properties of these cells.