Effects of Nitrogen Gas Packaging on Freshness, Microbial Flora and Volatile Flavor Compounds of Pelteobagrus fulvidraco during Cold Storage

Air-packaged and nitrogen-packaged Pelteobagrus fulvidraco were evaluated for changes in freshness indices, microbial flora and volatile flavor substances during cold storage at 4 ℃. The results showed that nitrogen gas packaging slowed down the growth rate of total bacterial count (TBC), total volatile basic nitrogen (TVB-N) value and pH, effectively maintained the color, hardness and sensory quality, and prolonged the shelf-life of P. fulvidraco by two days. Nitrogen gas packaging affected the changes in the microfloral structure of P. fulvidraco during cold storage, and prevented Pseudomonas from becoming the dominant spoilage bacteria. Notably, it had a significant inhibitory effect on Acinetobacter on the 3rd day of cold storage (P < 0.01). Compared with the non-nitrogen group, nitrogen gas packaging reduced the types and contents of alcohols, aldehydes, ketones and esters in P. fulvidraco during the refrigeration process. The results of redundancy analysis (RDA) performed on microbial communities and volatile flavor substances showed that Pseudomonas aeruginosa and Bacillus immobilis played an important role in the flavor changes, and were positively correlated with the production of spoilage markers such as n-octanal, 3-hydroxy-2-butanone, 3-methylbutanol and 1-octanol. Therefore, nitrogen gas packaging could slow down the growth of dominant spoilage bacteria for a short period, thus delaying the deterioration of the freshness and flavor of P. fulvidraco, which could be a simple and effective method to prolong the shelf-life of P. fulvidraco

Hyperprogressive disease in non-small cell lung cancer after PD-1/PD-L1 inhibitors immunotherapy: underlying killer

Immune checkpoint inhibitors (ICIs) target the negative regulatory pathway of T cells and effectively reactive the anti-tumor immune function of T cells by blocking the key pathway of the immune escape mechanism of the tumor—PD-1/PD-L1, and fundamentally changing the prospect of immunotherapy for non-small cell lung cancer patients. However, such promising immunotherapy is overshadowed by Hyperprogressive Disease, a response pattern associated with unwanted accelerated tumor growth and characterized by poor prognosis in a fraction of treated patients. This review comprehensively provides an overview of Hyperprogressive Disease in immune checkpoint inhibitor-based immunotherapy for non-small cell lung cancer including its definition, biomarkers, mechanisms, and treatment. A better understanding of the black side of immune checkpoint inhibitors therapy will provide a more profound insight into the pros and cons of immunotherapy

High Expressions of CUL4A and TP53 in Colorectal Cancer Predict Poor Survival

Background/Aims: Cullin 4A (CUL4A) is vital in cell survival, development, growth and cell cycle, it plays an important role in chaperone-mediated ubiquitination and interacts with TP53 in carcinogenesis. However, the clinicopathologic significance of CUL4A expression in colorectal cancer is unknown; in particular, the prognostic value of CUL4A combined with TP53 expression has not been explored. Methods: We analyzed the expression of CUL4A in both public database (Oncomine) and 180 cases of colorectal cancer and paired normal tissues by real-time polymerase chain reaction and western blotting. Colony formation, wound healing, migration and invasion assays and tumorigenesis in nude mice were used to explore the function of CUL4A in CRC proliferation and metastasis in vitro and in vivo. Markers of epithelial to mesenchymal transition (EMT) were evaluated by western blotting. Immunohistochemistry (IHC) was used to analyse the relationship between CUL4A expression and E-cadherin expression. Results: CUL4A and TP53 protein expression was significantly higher in cancerous tissues compared to normal tissues. Significant correlation between CUL4A and TP53 expression was observed. CUL4A expression was an independent prognostic factor for overall survival (OS) and disease-free survival (DFS). Interestingly, patients with tumors that had both CUL4A overexpression and mutant TP53 protein accumulation relapsed and died within a significantly short period after surgery (P &#x3c; 0.001). Multivariate analysis showed that patients with both CUL4A+ and TP53+ positive tumors had extremely poor OS and DFS. Knockdown of CUL4A by a short interfering RNA (siRNA) significantly suppressed the progression of EMT, proliferation, migration, and invasion of colon cancer cells in vitro and tumor growth in vivo. ZEB1 silencing blocked CUL4A-driven these processes. Conclusion: CUL4A expression correlated positively with the prognosis of colorectal cancer. Mechanistically, ZEB1 was confirmed to mediate the function of CUL4A in regulating the EMT. The assessment of both CUL4A and mutant TP53 expression will be helpful in predicting colon cancer prognosis