Tyrosine kinase inhibitor is an effective chemo-therapeutic drug against tumors with deregulated EGFR pathway. Recently, a genetic variant rs10251977 (G>A) in exon 20 of EGFR reported to act as a ...prognostic marker for HNSCC. Genotyping of this polymorphism in oral cancer patients showed a similar frequency in cases and controls. EGFR-AS1 expressed significantly high level in tumors and EGFR-A isoform expression showed significant positive correlation (r = 0.6464, p < 0.0001) with reference to EGFR-AS1 expression levels, consistent with larger TCGA HNSCC tumor dataset. Our bioinformatic analysis showed enrichment of alternative splicing marks H3K36me3 and presence of intronic polyA sites spanning around exon 15a and 15b of EGFR facilitates skipping of exon 15b, thereby promoting the splicing of EGFR-A isoform. In addition, high level expression of PTBP1 and its binding site in EGFR and EGFR-AS1 enhances the expression of EGFR-A isoform (r = 0.7404, p < 0.0001) suggesting that EGFR-AS1 expression modulates the EGFR-A and D isoforms through alternative splicing. In addition, this polymorphism creates a binding site for miR-891b in EGFR-AS1 and may negatively regulate the EGFR-A. Collectively, our results suggested the presence of genetic variant in EGFR-AS1 modulates the expression of EGFR-D and A isoforms.
•Secondary protein conformations are unaffected by RF processing.•RF processing does affect egg white protein-gel GI digestibility.•GI epithelial cell viability and integrity is not compromised by RF ...processing.•RF processing does not compromise peptide absorption.
Radiofrequency (RF) assisted thermal processing can significantly enhance the gel firmness of egg white powder compared to the traditional hot room (HR) processing. Thus, the present study aims to delineate the impact of RF processing on the proteins' structure and bio-functional properties of egg white protein gels. The secondary protein conformations of egg white proteins exhibited no significant alteration upon RF-assisted thermal processing over traditional HR processing. In-vitro gastrointestinal (GI) digestion of egg white gels demonstrated that the RF processing did not compromise the accessibility of digestive proteases despite a more robust gel network. Peptides from the GI digest of egg white gel showed that Ovalbumin and Ovotransferrin were the parent proteins of most of the unique peptides generated, and minor structural differences accounted for these peptides. The bioavailability of the egg protein-derived peptides remains unaffected after RF processing without compromising the viability and integrity of the GI epithelial cells.
The current microbial reduction techniques have low consumer acceptance or may have an adverse effect on the quality of spices and herbs. This requires a need for an alternative decontamination ...method that can effectively reduce the microbial load and minimize the food quality losses. Radio frequency (RF) heating is a dielectric heating method that has been proven effective to pasteurize various low-moisture foods. The present research was designed to evaluate the efficacy of RF heating for the reduction of Salmonella in dried basil leaves, evaluate the suitability of Enterococcus faecium NRRL B-2354 as a surrogate for Salmonella, and assess the quality of dried basil leaves post RF treatment. Dried basil leaves inoculated with a Salmonella cocktail or E. faecium were conditioned to a higher moisture content such that the moisture content of the treated sample post RF treatment fall within the typical range. The inoculated samples were packaged in the teabag and placed in the identified cold spot (top center) of a laminated paper tray filled with uninoculated sample. Samples were subjected to RF heating for 45, 55, and 65 s during which the cold-spot temperature reached 65, 80, and 100 °C, respectively. The results showed that at 55 s, Salmonella and E. faecium population decreased by 4.8 and 2.7 log CFU/g, respectively. Both microorganisms reached below the detection limit (>6.5 log CFU/g reduction) at 65 s of RF heating. Therefore, the quality analysis of the dried basil leaves was performed with the samples treated with RF for 65 s. The results showed that the RF heating had no significant effect on the quality parameters (color, total volatiles, total phenolics, and antioxidant activity) of the dried basil leaves. Therefore, RF processing results in rapid heating of the dried basil leaves enhancing food safety with insignificant impact on quality. Furthermore, the food processing facility may use E. faecium as an appropriate surrogate for Salmonella when conducting an in-plant validation study.
•Salmonella population was below the detection limit during 65 s of RF heating.•E.faecium is a valid surrogate for Salmonella for RF heating of dried basil leaves.•Color, total phenolics, and antioxidant activity were not significantly affected.•1 out of 25 volatile compounds had a significant drop (5–10%) post RF treatment.•RF process can be effectively used for pasteurizing and drying of basil leaves.
•The advent of molecular targeted therapies and the more recent introduction of immune checkpoint inhibitors (ICIs) have altered and improved the therapeutic landscape of non-small cell lung cancer ...(NSCLC).•ICIs confer a durable response in a subset of patients; however, their therapeutic role in oncogene-driven NSCLC remains unclear, as the vast majority of trials was conducted without patients harbouring established oncogenic mutations.•The only randomised data available on the efficacy of ICIs on oncogene addicted NSCLC come from the IMpower 150 trial and concern only EGFR mutated NSCLC patients.•At present, no biomarker is clearly predictive for response or benefit to ICIs in oncogene addicted NSCLC. These are often characterised by low tumour mutation burden (TMB) and a less inflammatory tumour microenvironment, poor in tumour-infiltrating CD8+ lymphocytes. PD-L1 can be constitutionally overexpressed without having any clinical significance.
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•Visible light driven AgCl@g-C3N4 composite was fabricated and well characterized.•AgCl@g-C3N4 composite exhibits enhanced photocatalytic activity for CO2 reduction reaction.•Effects ...of various rate determining parameters are studied.•Artificial Z-scheme charge separation mechanism for AgCl@g-C3N4 composite was proposed.
A direct Z-scheme AgCl@g-C3N4 composite with different ratios of AgCl loaded on g-C3N4 was constructed through modified deposition-precipitation method and as prepared composite was well characterized. The photocatalytic performance efficiency of AgCl@g-C3N4 composite was evaluated for the reduction of CO2 in an aqueous medium under visible light irradiation. The gas chromatographic analysis confirms the formation of methane, acetic acid and formic acid as products. The experimental results indicated that the AgCl@g-C3N4 composite displays better photocatalytic activity than pure AgCl and g-C3N4. Effects of metal loading concentration (0.5–1.5 wt%), catalyst dosage (1–4 g L−1), reaction medium (triethanolamine (TEA)), water and sodium hydroxide (NaOH)), irradiation time and catalyst stability on the CO2 reduction reaction were investigated. The maximum yield and selectivity of methane, acetic acid and formic acid from CO2 in TEA medium over was about 53.03 μmol g−1, 6.01 μmol g−1, 2.51 μmol g−1 and 88.87%, 10.08% and 1.05% respectively for 8 h, 3 g L−1 of 1%AgCl@g-C3N4. However, no formation of acetic acid and formic acid were observed in the water mediated system. The enhanced photocatalytic activity towards CO2 reduction reaction was attributed to the combination effect of Z-scheme g-C3N4 and AgCl heterojunction, an absence of electron mediator, which efficiently inhibits the recombination rate and improved photocatalytic activity of g‐C3N4. This study will provide a new insight for fabrication of Z-scheme g-C3N4 based photocatalytic system for environmental remediation.
Manganese (Mn) is an essential trace element for humans, but long‐term environmental or occupational exposures can lead to numerous health problems. Although many studies have identified an ...association between Mn exposures and neurological abnormalities, emerging data suggest that occupationally and environmentally relevant levels of Mn may also be linked to multiple organ dysfunction in the general population. In this regard, many experimental and clinical studies provide support for a causal link between Mn exposure and structural and functional changes that are responsible for organ dysfunction in major organs like lung, liver, and kidney. The underlying mechanisms suggested to Mn toxicity include altered activities of the components of intracellular signaling cascades, oxidative stress, apoptosis, affected cell cycle regulation, autophagy, angiogenesis, and an inflammatory response. We further discussed the sources and possible mechanisms of Mn absorption and distribution in different organs. Finally, treatment strategies available for treating Mn toxicity as well as directions for future studies were discussed.
A comprehensive review was executed to find out the effect of high levels of manganese exposure on major organs, including lung, liver, and kidney. Many experimental and clinical studies reveal a causal link between manganese exposure and organ dysfunction. The underlying mechanisms are oxidative stress, apoptosis, affected cell cycle regulation, autophagy, angiogenesis, and an inflammatory response. Hence, manganese toxicity occurs to organs other than brain as a result of industrial and/or environmental exposures.
Here we develop general analytical results on the linear instability problem of inviscid compressible axial flows in the annular region between two coaxial cylinders to axisymmetric disturbances. For ...shear-free basic flows the non-existence of propagating subsonic modes is shown. An instability region for subsonic modes within which the complex wave velocity should lie is shown to be a semi-ellipse-type region that depends on the compressibility. For near-neutral subsonic modes some estimates for growth rates are derived and it is shown further that the growth rate tends to zero as the axial wave number tends to infinity.
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► Lead-dithiocarbamate complexes based on benzyl and furfuryl groups were prepared. ► En capped PbS nanoparticles were prepared within 2min from lead dithiocarbamate. ► PbS particles ...were characterized by XRD, SEM, EDAX, UV–vis, fluorescence and FTIR. ► PbS nanoparticles are single phase with face centered cubic structure.
Nine lead bis(dithiocarbamate) complexes based on benzyl and furfuryl groups have been prepared. The complexes were characterized using IR and NMR spectroscopy. All the complexes showed the expected signals in 1H and 13C NMR spectra associated with the dithiocarbamate ligands. IR and 13C NMR spectral studies indicate that the S2CN double bond character increases with increase in length of alkyl chain bonded to nitrogen atom. Bis(N-benzyl-N-(2-phenylethyl)dithiocarbamato-S,S′)lead(II) (3) and bis(N-furfuryl-N-(2-phenylethyl)dithiocarbamato-S,S′)lead(II) (4) have been used as single source precursors for the synthesis of ethylenediamine capped PbS nanoparticles. Powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), FTIR, UV–vis and fluorescence spectroscopy have been used to characterize the as-prepared lead sulfide nanoparticles. The PXRD measurements suggest that PbS nanoparticles are single phase with face-centered-cubic structure.
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