Recombinant Newcastle disease virus (NDV/Anh-IL-2) expressing human IL-2 as a potential candidate for suppresses growth of hepatoma therapy

AbstractNewcastle disease virus (NDV) have shown oncolytic therapeutic efficacy in preclinical study and are currently approved for clinical trials. NDV Anhinga strain which is a mesogenic strain should be classified as lytic strain and has a therapeutic efficacy in hepatocellular cancer. In this study, we evaluated the capacity of NDV Anhinga strain to elicit immune reaction in vivo and the possibility for using as a vaccine vector for expressing tumor therapeutic factors. Interleukin-2 (IL-2) could boost the immune response against the tumor cells. Therefore, we use NDV Anhinga strain as backbone to construct a recombinant virus (NDV/Anh-IL-2) expressing IL-2. The virus growth curve showed that the production of recombinant NDV/Anh-IL-2 was slightly delayed compared to the wild type. The NDV/Anh-IL-2 strain could express soluble IL-2 and effectively inhibit the growth of hepatocellular carcinoma in vivo. 60 days post-treatment, mice which were completely cured by previous treatment were well protected when rechallenged with the same tumor cell. From the H&E-stained sections, intense infiltration of lymphocyte was observed in the NDV Anhinga strain treated group, especially in NDV/Anh-IL-2 group. The NDV Anhinga strain could not only kill the tumor directly, but could also elicit immune reaction and a potent immunological memory when killing tumor in vivo. In conclusion, the Anhinga strain could be an effective vector for tumor therapy; the recombinant NDV/Anh-IL-2 strain expressing soluble IL-2 is a promising candidate for hepatoma therapy

Process of Extraction Protein from Selenium-enriched Lyophyllum decastes Mycelia and Analysis of Its Amino Acid

The process of extracting seleno-protein from the selenium enriched Lyophyllum decastes mycelia cultured in a 20 L fermentor was optimized, and the effects of selenium enrichment on both types and contents of amino acids in Lyophyllum decastes mycelia were analyzed. Single factor tests and Box-Benhnken central combined response surface test were used to optimize process of extracting seleno-protein from Lyophyllum decastes mycelia. The content of protein was determined by 3,3'-diaminobenzidine spectrophotometry. The types and contents of amino acids in mycelia protein before and after selenium enrichment were compared by means of amino acid analyzer. The results showed that the optimal conditions of extracting seleno-protein from mycelia of Lyophyllum decastes were extraction temperature of 64 ℃, extraction time of 60 min, liquid-solid ratio of 200:1 g/mL, and extraction times of 2. The protein extraction rate was 75.13%, and the content of selenium in mycelia was 63.87 μg/g. The amino acid composition were analyzed by means amino acid score (AAS) and chemical score (CS), and the nutritional value of the protein in the selenium-enriched Lyophyllum decastes mycelia was evaluated. The varieties of amino acids in the selenium-enriched Lyophyllum decastes mycelia were abundant and the content of essential amino acids for human body was 17.20 g/100 g, 19.75% higher than that in the non-selenium-ecriched Lyophyllum decastes mycelia. The ratio of EAA/NEAA was 0.51, close to the recommended value proposed by WHO, and the values of both AAS and CS were close to the those in the model protein. In summary, the protein extraction rate could be improved by optimizing the extraction process, and there was selenium in the protein from selenium-enriched mycelia, which promoted the increase of amino acid content. The nutritional value of protein in selenium-enriched mycelia was higher than that in non-selenium-riched mycelia, and selenium-enrichec mycelia had potential edible and application value

Algorithms for Assembly Consolidation and Prediction of Large-Scale Genome Structures

Genome structure is the order and orientation of pieces of DNA comprising a genome, which contains the information of life. With advances in DNA sequencing technology and now massive availability of sequence data, the study of genome structure cannot be easily carried out without efficient and expressly designed algorithms. In this dissertation, we study three genome structure-related problems: structural error correction of draft genome assemblies, inversion prediction, and predicting operons. Our work with draft genome assemblies explores a novel Maximum Alternating Path Cover (MAPC) model to improve genome correctness and downstream analysis. Our work on inversion prediction aims to predict and catalog inversions by exploring the well-known Range Maximum Query model and Max-Cut model for what we call “global” inversions, and the novel Rectangle Clustering model and Representative Rectangle Prediction model for more localized inversions. For operon prediction, we again apply the MAPC model (with improved algorithms and theoretical analysis), coupled with a novel Intro-Column Exclusive Clustering model, to predict and catalog operons in closely related species. Evaluated using both simulated and real genome data, our algorithms and implementations have shown substantial promise for accurate computational analysis of genome structure in significantly shorter time

Ferroptosis, Necroptosis, and Pyroptosis in Gastrointestinal Cancers: The Chief Culprits of Tumor Progression and Drug Resistance

Abstract In recent years, the incidence of gastrointestinal cancers is increasing, particularly in the younger population. Effective treatment is crucial for improving patients’ survival outcomes. Programmed cell death, regulated by various genes, plays a fundamental role in the growth and development of organisms. It is also critical for maintaining tissue and organ homeostasis and takes part in multiple pathological processes. In addition to apoptosis, there are other types of programmed cell death, such as ferroptosis, necroptosis, and pyroptosis, which can induce severe inflammatory responses. Notably, besides apoptosis, ferroptosis, necroptosis, and pyroptosis also contribute to the occurrence and development of gastrointestinal cancers. This review aims to provide a comprehensive summary on the biological roles and molecular mechanisms of ferroptosis, necroptosis, and pyroptosis, as well as their regulators in gastrointestinal cancers and hope to open up new paths for tumor targeted therapy in the near future

Single molecule sequencing-guided scaffolding and correction of draft assemblies

Abstract Background Although single molecule sequencing is still improving, the lengths of the generated sequences are inevitably an advantage in genome assembly. Prior work that utilizes long reads to conduct genome assembly has mostly focused on correcting sequencing errors and improving contiguity of de novo assemblies. Results We propose a disassembling-reassembling approach for both correcting structural errors in the draft assembly and scaffolding a target assembly based on error-corrected single molecule sequences. To achieve this goal, we formulate a maximum alternating path cover problem. We prove that this problem is NP-hard, and solve it by a 2-approximation algorithm. Conclusions Our experimental results show that our approach can improve the structural correctness of target assemblies in the cost of some contiguity, even with smaller amounts of long reads. In addition, our reassembling process can also serve as a competitive scaffolder relative to well-established assembly benchmarks

Increased SERPINA3 Level Is Associated with Ulcerative Colitis

Ulcerative colitis (UC) is a recurrent, chronic intestinal disease that is currently incurable. Its pathogenesis remains to be further understood. Therefore, seeking new biomarkers and potential drug targets is urgent for the effective treatment of UC. In this study, the gene expression profile GSE38713 was obtained from the GEO (Gene Expression Omnibus) database. Data normalisation and screening of the differentially expressed genes (DEGs) were conducted using R software, and gene ontology (GO) enrichment was performed using Metascape online tools. The PubMed database was used to screen new genes that have not been reported, and SERPINA3 was selected. The correlation between SERPINA3 and other inflammatory factors was analysed by Spearman correlation analysis. Finally, colitis model mice and an in-vitro model were established to validate the function of the SERPINA3 gene. SERPINA3 gene expression was markedly increased in UC patient samples, colitis models and in-vitro models and showed an association with other inflammatory factors. ROC analysis indicated that SERPINA3 could represent a potential biomarker of active UC. Additionally, silencing SERPINA3 in an in-vitro intestinal epithelial inflammatory model significantly decreased the mRNA level of inflammatory factors. This study provides supportive evidence that SERPINA3 may act as a key biomarker and potential drug target in UC treatment

The effect of reactively-sputtered alumina films on the oxidation resistance of CoCrAlY coatings

Thin alumina films have found applications in electronic circuits and cutting tools and have been recently explored as protective coatings against high temperature oxidation, but these studies have been relatively rare. In this study, amorphous alumina films 3.5 µm thick were produced by reactive sputtering on Co-30Cr-6Al-0.5Y coatings, using a pure aluminum target in Ar + O2 atmosphere. Isothermal oxidation tests were carried out at 1000-1100 °C in static air. The results showed that the alumina films improved the oxidation resistance at all testing temperatures. At 1000°C, the Co-30Cr-6Al-0.5Y coating could form pure alumina scale on its surface, but the reactively-sputtered alumina films reduced the oxidation rate. At 1100 °C, the Co-30Cr-6Al-0.5Y coating could not form pure alumina scale, as a result of a severe internal oxidation of aluminum along the columnar defects. The scales were composed of Al2O3, Cr2O3 and TiO2, which were not so protective as pure alumina scales. On the contrary, the Co-30Cr- 6Al-0.5Y coatings with 3.5 µm preformed alumina films exhibited excellent oxidation resistance at 1100 °C. Only minor amounts of TiO2 were detected on the surface. Moreover, the reactively-sputtered alumina films were very adherent to the CoCrAlY coatings. At 1000 °C no spallation was found, while at 1100 °C only a little spallation produced during cooling was observed