Immunoprotection against influenza H5N1 virus by oral administration of enteric-coated recombinant Lactococcus lactis mini-capsules

AbstractEdible vaccines that can be made widely available and easily administered could bring great benefit to the worldwide battle against pandemic viral infections. They can be used not only for the vaccination of humans and domesticated animals, but also for wild herds and live stock which are otherwise difficult to vaccinate. In this study, we report the development of an edible mini-capsule form of live, non-persisting, recombinant Lactococcus lactis (L. lactis) vaccine against the highly virulent influenza H5N1 strain. Recombinant L. lactis-based H5N1 HA antigen expression constructs were made and shown to be able to induce higher levels of HA-specific serum IgG and fecal IgA antibody production after oral administration. The vectors were then formulated into a mini-capsule dosage form and fed to mouse. Four doses of oral administration rendered complete protection of the mouse against lethal challenges of H5N1 virus

Nitrous oxide research progress in polar and sub-polar oceans

N2O gas depletes ozone and has a powerful greenhouse effect. Oceans are among the most important N2O sources and have been the subject of extensive studies. Polar oceans are important regions for deep water formation and global-scale thermohaline circulation. Therefore, these water bodies play an important role in the N2O budget, however, these regions were not well studied. This review of previously published studies and data on polar oceans, including both the Arctic Ocean and Southern Ocean, describes the distribution pattern of N2O and possible regulating mechanism of these distribution patterns and shows that the Arctic Ocean and Southern Ocean both represent source and sink regions, suggesting that the source/sink characteristics of the Arctic and Southern oceans and their strengths need further study. Questions related to N2O circulation in polar oceans were proposed, and future work is suggested

Lycium species and variety recognition technology based on electrochemical sensing of leaf signals

Identification of plant species and variety has important application value in the process of agricultural production. In this work, we try to use electrochemical fingerprinting technology to collect the electrochemical behavior of electrochemically active substances in plant leaf tissues. Twenty Lycium species and varieties were specifically selected to investigate the recognition ability of electrochemical fingerprinting. Two different extraction solvents and electrolytes were used to create different collection environments. The results show that different Lycium spp. can exhibit different electrochemical fingerprints. Different species of the same species exhibit relatively similar electrochemical fingerprints. After the second derivative processing, the electrochemical fingerprint of plants can be used for classification and recognition by different machine learning models. Partial least squares discriminant analysis (PLS-DA), k-nearest neighbor, (KNN), support vector machine (SVM), random forest (RF) and stochastic gradient boosting (SGB) were used to establish recognition model of Lycium spp. The results show that SGB has the best identification accuracy for electrochemical fingerprint after second derivative treatment

Immune-boosting effects of nutritional formulations containing acerola cherries extractive and lactoferrin

Reduced immunity can harm the health of the organism, and nowadays, improving immunity is getting more and more attention, so the nutrients with immune boosting function (acerola cherry, taurine, zinc gluconate, and lactoferrin) are compounded in the best ratio to develop a nutritional formula food, and evaluated by cellular immunity, humoral immunity, non-specific immunity. In this study, an immunocompromised mice model was established using cyclophosphamide (CTX), the ability and difference of different components to enhance the immunity of mice were determined by the gavage of different components. The results showed that the nutritional formula food could recover the body weight of immunocompromised mice, promote the development of immune organs in immunocompromised mice, enhance the delayed-type hypersensitivity (DTH) response, the ability to produce serum hemolysin and the phagocytosis of monocytes in immunocompromised mice, and increase the levels of immunoglobulin A (IgA), IgG and IgM in the serum of immunocompromised mice. It has proved that this nutritional formula food (containing acerola cherry, taurine, zinc gluconate, and lactoferrin) has synergistic effect and can work together on humoral immunity, cellular immunity and non-specific immunity to improve the immune resistance of mice, and has promising application

FGFR2 Promotes Gastric Cancer Progression by Inhibiting the Expression of Thrombospondin4 via PI3K-Akt-Mtor Pathway

Background/Aims: Fibroblast growth factor receptor 2 (FGFR2) has attracted considerable interest as a therapeutic target in gastric cancer (GC). There is growing evidence to suggest that the bioavailability of the potent pro-tumor function of FGFR2 is associated with thrombospondins (TSPs). As a follow-on from our previous study, here we evaluated the potential clinical significance and mechanism of the relationship between FGFR2 and TSP4 in GC. Methods: Expression levels of FGFR2 and TSP4 were detected by immunohistochemistry in GC tissue microarray slides. SGC7901 and MKN28 cell lines were used to confirm the relationship between FGFR2 and TSP4. In vitro cell viability, colony formation, and invasion and migration assays were performed to evaluate the effect of FGFR2-TSP4 axis on tumor cell activities. The mechanism of TSP4 regulated by FGFG2 was explored via small molecular inhibitors in vitro and a xenograft model. Results: FGFR2 was shown to be markedly overexpressed in GC tissues and was correlated with a high risk of lymph node metastasis, late clinical stage, and poor prognosis. Low TSP4 expression was associated with shorter overall survival (OS) and advanced stage in GC patients. Interestingly, correlation analysis indicated that FGFR2 was negatively associated with TSP4. Indeed, in vitro and in vivo experiments suggested FGFR2 activation could downregulate TSP4 expression, which played an important role in the proliferation, invasion and migration of GC cells. We also found involvement of the PI3K-AKT-mTOR pathway in the FGFR2-TSP4 axis. Conclusion: The FGFR2 signal promotes human GC progression through the downregulation of TSP4 via PI3K-AKT-mTOR pathway. Our findings provide a foundation for further investigating promising therapeutic strategies for GC overexpressing FGFR2

Exploiting tertiary lymphoid structures gene signature to evaluate tumor microenvironment infiltration and immunotherapy response in colorectal cancer

BackgroundTertiary lymphoid structures (TLS) is a particular component of tumor microenvironment (TME). However, its biological mechanisms in colorectal cancer (CRC) have not yet been understood. We desired to reveal the TLS gene signature in CRC and evaluate its role in prognosis and immunotherapy response.MethodsThe data was sourced from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Based on TLS-related genes (TRGs), the TLS related subclusters were identified through unsupervised clustering. The TME between subclusters were evaluated by CIBERSORT and xCell. Subsequently, developing a risk model and conducting external validation. Integrating risk score and clinical characteristics to create a comprehensive nomogram. Further analyses were conducted to screen TLS-related hub genes and explore the relationship between hub genes, TME, and biological processes, using random forest analysis, enrichment and variation analysis, and competing endogenous RNA (ceRNA) network analysis. Multiple immunofluorescence (mIF) and immunohistochemistry (IHC) were employed to characterize the existence of TLS and the expression of hub gene.ResultsTwo subclusters that enriched or depleted in TLS were identified. The two subclusters had distinct prognoses, clinical characteristics, and tumor immune infiltration. We established a TLS-related prognostic risk model including 14 genes and validated its predictive power in two external datasets. The model’s AUC values for 1-, 3-, and 5-year overall survival (OS) were 0.704, 0.737, and 0.746. The low-risk group had a superior survival rate, more abundant infiltration of immune cells, lower tumor immune dysfunction and exclusion (TIDE) score, and exhibited better immunotherapy efficacy. In addition, we selected the top important features within the model: VSIG4, SELL and PRRX1. Enrichment analysis showed that the hub genes significantly affected signaling pathways related to TLS and tumor progression. The ceRNA network: PRRX1-miRNA (hsa-miR-20a-5p, hsa-miR-485–5p) -lncRNA has been discovered. Finally, IHC and mIF results confirmed that the expression level of PRRX1 was markedly elevated in the TLS- CRC group.ConclusionWe conducted a study to thoroughly describe TLS gene signature in CRC. The TLS-related risk model was applicable for prognostic prediction and assessment of immunotherapy efficacy. The TLS-hub gene PRRX1, which had the potential to function as an immunomodulatory factor of TLS, could be a therapeutic target for CRC

High-quality interferenceless coded aperture correlation holography with optimized high SNR holograms

Motivated by the key role of point spread function in an imaging system, we propose an interferenceless coded aperture correlation holographic (I-COACH) technology with low speckle and high energy efficiency annular sparse coded phase mask (CPM) as system pupil to improve imaging performance. In the proposed method, a modified Gerchberg–Saxton (GS) algorithm is proposed to obtain a low speckle and high energy efficiency annular sparse CPM and to suppress speckle and increase the intensity of the holograms. Therefore, the randomly distributed amplitude in the bandwidth of the GS algorithm is replaced by the annular amplitude to determine the spatial position, and the band-limited random phase and quadratic phase are used as the initial phase to approximately meet band-limited conditions; meanwhile, in the iterative process of the algorithm, appropriate constraints are imposed on the information within and outside the band limit. All are used for obtaining the CPM with low speckle and high energy efficiency. Therefore, the proposed technique here is coined as low speckle I-COACH owing to the characteristics of CPM and imaging performances. The experimental results show that, under the same experimental conditions, the proposed method can obtain holograms with low speckle and intensity enhancement of about 8%, and further improve the quality of reconstructed images due to the improvement signal-to-noise ratio (SNR) of the holograms. The proposed method provides a powerful reference method for further expanding the I-COACH system to the field of low-intensity optical signals detection and imaging