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

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

Optimized reconstruction with noise suppression for interferenceless coded aperture correlation holography

A modified nonlinear reconstruction technique with a noise modulation parameter is proposed for interferenceless coded aperture correlation holography (I-COACH), and thus the signal-to-noise ratio of a reconstructed image is improved without sacrifice of the field of view and temporal resolution of the system. In order to obtain the optimal reconstructed image, no-reference structural sharpness (NRSS) is introduced as the evaluation metric of reconstructed image quality during nonlinear reconstruction. On the other hand, the noise modulation function is built in order to analyze the effect of phase on noise when the amplitude of the point spread hologram and object hologram is unity of 1. Both the NRSS and noise modulation functions are combined with nonlinear reconstruction in I-COACH for improving imaging performance. The validities of the proposed method under different experimental conditions have been demonstrated by experiments

Potential Drug Prediction of Glioblastoma Based on Drug Perturbation-Induced Gene Expression Signatures

Objectives. Glioblastoma (GBM) is a malignant brain tumor which is the most common and aggressive type of central nervous system cancer, with high morbidity and mortality. Despite lots of systematic studies on the molecular mechanism of glioblastoma, the pathogenesis is still unclear, and effective therapies are relatively rare with surgical resection as the frequently therapeutic intervention. Identification of fundamental molecules and gene networks associated with initiation is critical in glioblastoma drug discovery. In this study, an approach for the prediction of potential drug was developed based on perturbation-induced gene expression signatures. Methods. We first collected RNA-seq data of 12 pairs of glioblastoma samples and adjacent normal samples from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified by DESeq2, and coexpression networks were analyzed with weighted gene correlation network analysis (WGCNA). Furthermore, key driver genes were detected based on the differentially expressed genes and potential chemotherapeutic drugs and targeted drugs were found by correlating the gene expression profiles with drug perturbation database. Finally, RNA-seq data of glioblastoma from The Cancer Genome Atlas (TCGA) dataset was collected as an independent validation dataset to verify our findings. Results. We identified 1771 significantly DEGs with 446 upregulated genes and 1325 downregulated genes. A total of 24 key drivers were found in the upregulated gene set, and 81 key drivers were found in the downregulated gene set. We screened the Crowd Extracted Expression of Differential Signatures (CREEDS) database to identify drug perturbations that could reverse the key factors of glioblastoma, and a total of 354 drugs were obtained with p value < 10-10. Finally, 7 drugs that could turn down the expression of upregulated factors and 3 drugs that could reverse the expression of downregulated key factors were selected as potential glioblastoma drugs. In addition, similar results were obtained through the analysis of TCGA as independent dataset. Conclusions. In this study, we provided a framework of workflow for potential therapeutic drug discovery and predicted 10 potential drugs for glioblastoma therapy