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Spodoptera exigua (Hübner) is a polyphagous pest on agricultural crops, whose control is based mainly on the application of chemical insecticides. Bacillus thuringiensis (Bt) is one of the most important biological agents that have been successfully applied as a biological control, and Cry1Ca protein is considered to be active against S. exigua. Therefore, to understand the response of S. exigua to Cry1Ca protein, high-throughput sequencing was used to analyse the S. exigua larval midgut after treatment with sublethal concentrations of Cry1Ca protein. Avotaciclib mouse Transcriptome data showed that a total of 98,571 unigenes with an N50 value of 1135 bp and a mean length of 653 bp were obtained. Furthermore, 2962 differentially expressed genes (DEGs) were identified after Cry1Ca challenge, including 1508 up-regulated and 1454 down-regulated unigenes. Among these DEGs, detoxification (CYP, CarE, and GST) and Bt resistance (ALP, APN, and ABC transporter)-related genes were differentially expressed in the midgut of S. exigua after Cry1Ca treatment. However, most DEGs of protective enzymes were down-regulated, while most DEGs related with serine protease and REPAT were up-regulated. Furthermore, almost all DEGs related to the immune signaling pathway, antimicrobial protein, and lysozyme were up-regulated by Cry1Ca treatment. These results indicated that the detoxification enzyme, protective enzymes, Bt resistance-related genes, serine protease, REPAT, and the immune response might have been involved in the response of S. exigua to Cry1Ca protein. In summary, analysis of the transcriptomal expression of genes involved in Cry1Ca protein against S. exigua provided potential clues for elucidating the host response processes and defensive mechanisms underlying Cry1Ca toxicity. © King Abdulaziz City for Science and Technology 2020.The aim of the study was to establish a reliable system of transgenic hairy roots in Codonopsis pilosula through Agrobacterium-mediated genetic transformation. For this, we optimized several steps in the process of A. rhizogenes strain C58C1 mediated hairy root induction, including the most appropriate medium, explant type, time for infection and co-cultivation. We achieved an induction rate of up to 100% when the roots of C. pilosula seedlings were used as explants, infected with A. rhizogenes C58C1 harboring pCAMBIA1305 for 5 min, followed by induction on 1/2MS supplemented with 0.2 mg/L naphthylacetic acid and 200 mg/L cefotaxime sodium. The co-transformed hairy roots were confirmed by PCR amplification of hygromycin phosphotransferase II gene and histochemical GUS assay, and the efficiency of transformation was 70% and 68.3%, respectively, when no hygromycin selection pressure was exerted. To increase biomass production, we excised and self-propagated the transformed hairy roots, which produce saponins. Our successful establishment of an in vitro culture system of transgenic hairy root for this species lays the foundation not only for assessing gene expression and function but also for obtaining high levels of secondary metabolites through genetic engineering technology. © King Abdulaziz City for Science and Technology 2020.This study aimed to formulate and characterize the folate receptor-targeted PEGylated liposome encapsulating bioactive compounds from Kappaphycus alvarezii to enhance the anticancer activity. Twenty valued bioactive compounds (3-hydroxy benzoicacid, gallicacid, chlorogenicacid, cinnamicacid, artemiseole, hydrazine carbothioamide, etc.,) are confirmed from methanol extract of K. alvarezii using analytical techniques like HPLC and GC-MS. The delivery of bioactive compounds of K. alvarezii via naturally overexpressed folate receptor (FR) to FR-positive breast cancer cells was studied. FR targeted PEGylated liposome was constructed by modified thin-film hydration technique using FA-PEG-DSPE/cholesterol/DSPC (54055) and bioactive compounds of K. alvarezii was encapsulated. Their morphology, size, shape, physiological stability and drug release kinetics were studied. The study reports of K. alvarezii extract-encapsulated PEGylated liposome showed spherical shaped particles with amorphous in nature. The mean diameteract into FR-positive breast cancer cells (MCF-7) and exhibit great potential in anticancer therapy. © King Abdulaziz City for Science and Technology 2020.This study investigated the bioprocessing of shrimp wastes to obtain chitin and its deacetylated product chitosan by a fermentation process mediated by Lactobacillus plantarum. The concentrations of glucose, bacterial inoculum, and shrimp wastes in the Man, Rogosa and Sharpe medium were optimized for the fermentation process performed in shake flasks to achieve the maximum titratable acidity to obtain chitin. The experiments were scaled up in a 700-mL working volume bioreactor, and the resulting chitin was deacetylated by the autoclave method. The bioextracted chitosan was characterized (Fourier transform infrared spectroscopy [FTIR], deacetylation degree, and molecular weight) and evaluated for its antimicrobial effects by comparing it with a commercial chitosan sample in the context of the ethanolic fermentation process for fuel alcohol production. The effect of chitosan on such a fermentation process has not been determined yet. The bacterial contaminant Lactobacillus fermentum and the main agent of ethanol approach to combat unwanted bacterial contamination. © King Abdulaziz City for Science and Technology 2020.The Kendrick analysis is used for the processing and visualization of mass spectra obtained from polymers containing C, H, O and/or Si with simple isotopic patterns (monoisotope=lightest isotope=most intense isotope for short chains). In the case of heteroatoms with complex isotopic patterns, the impact of the chosen isotope on point alignments in Kendrick plots has not been examined extensively. Rich isotopic patterns also make the evaluation of the mass and nature of the repeating unit and end-groups more difficult from the mass spectrum in the case of unknown samples due to the number of peaks and the absence of a monoisotopic peak. Using a polybrominated polycarbonate as running example, we report that horizontal point alignments can be obtained in a Kendrick plot using the mass of the most abundant isotope instead of the monoisotopic mass as is usually done. Rotating the plot ("reverse Kendrick analysis") helps to accurately evaluate the mass of the most abundant isotope of the repeating unit, as well as the nature of the brominated neutral expelled upon gentle heating (debromination or dehydrobromination). The whole procedure is then applied to the characterization of an unknown polybrominated flame retardant in an industrial formulation before and after heating. Copyright © 2020 Sayaka Nakamura, Hiroaki Sato, and Thierry N. J. Fouquet.Myeloid-derived suppressor cells (MDSCs) are immunosuppressive cells that promote tumor progression by inhibiting anti-tumor immunity and may be the cause of patient resistance to immune checkpoint inhibitors (ICIs). Therefore, MDSCs are a promising target for cancer immunotherapy, especially in combination with ICIs. Previous studies have shown that the anticonvulsant drug valproic acid (VPA) has additional anti-cancer and immunoregulatory activities due to its inhibition of histone deacetylases. We have previously shown that VPA can attenuate the immunosuppressive function of differentiated MDSCs in vitro. In the present study, we utilized anti-PD-1-sensitive EL4 and anti-PD-1-resistant B16-F10 tumor-bearing mouse models and investigated the effects of VPA on MDSCs with the aim of enhancing the anti-cancer activity of an anti-PD-1 antibody. We showed that VPA could inhibit EL4 and B16-F10 tumor progression, which was dependent on the immune system. We further demonstrated that VPA down-regulated the expression of CCR2 on monocytic (M)-MDSCs, leading to the reduced infiltration of M-MDSCs into tumors. Importantly, we demonstrated that VPA could relieve the immunosuppressive action of MDSCs on CD8+ T-cell and NK cell proliferation and enhance their activation in tumors. We also observed that the combination of VPA plus an anti-PD-1 antibody was more effective than either agent alone in both the EL4 and B16-F10 tumor models. These results suggest that VPA can effectively relieve the immunosuppressive tumor microenvironment by reducing tumor infiltration of M-MDSCs, resulting in tumor regression. Our findings also show that VPA in combination with an immunotherapeutic agent could be a potential new anti-cancer therapy. © 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.Although several biomarkers have been proposed to predict the response of patients with lung adenocarcinoma (LUAD) to immune checkpoint blockade (ICB) therapy, existing challenges such as test platform uniformity, cutoff value definition, and low frequencies restrict their effective clinical application. Here, we attempted to use deep neural networks (DNNs) based on somatic mutations to predict the clinical benefit of ICB to LUAD patients undergoing immunotherapy. We used DNNs to train and validate the predictive model in three cohorts. Kaplan-Meier estimates determined the overall survival (OS) and progression-free survival (PFS) between specific subgroups. Then, we performed a relevant analysis on the multiple-dimension data types including immune cell infiltration, programmed death receptor 1 ligand (PD-L1) expression, and tumor mutational burden (TMB) from cohorts of LUAD public database and immunotherapeutic patients. Two classification groups (C1 and C2) in the training and two validation sets were identified for the efficacy of ICB via the DNN algorithm. Patients in C1 showed remarkably long OS and PFS to programmed death 1 (PD-1) inhibitors. The C1 group was significantly associated with increased expression of immune cell infiltration, immune checkpoints, activated T-effectors, and interferon gamma signature. C1 group also exhibited significantly higher TMB, neoantigens, transversion, or transition than the C2 group. This work provides novel insights that classification of DNNs using somatic mutations in LUAD could serve as a potentially predictive approach in developing a strategy for anti-PD-1/PD-L1 immunotherapy. © 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.The tumor-suppressor gene tumor protein p53 (TP53) is one of the most commonly mutated genes in human lung cancer, and TP53 mutations are associated with a worsened prognosis and causes resistance to cancer therapy. RNA sequencing and TP53 mutation data were downloaded to determine specific TP53-associated signature based on differentially expressed genes between patients with lung squamous cell carcinoma (LUSC) with wild type (TP53 WT) and mutated (TP53 MUT) TP53. We investigated the predictive value of this signature on the immune microenvironment, tumor mutational burden (TMB), and likelihood of response to immunotherapy and chemotherapy. In total, 1,556 differentially expressed genes were identified based on TP53 mutation status. Three genes (KLK6, MUC22 and CSN1S1) identified by univariate and multivariate Cox regression analyses, comprised the prognostic signature which was an independent and specific prognostic marker of overall survival in patients with LUSC. A nomogram was also established to validate this signature for clinical use.
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