Revealing Differential Expression of Phytohormones in Sorghum in Response to Aphid Attack Using the Metabolomics Approach

Sorghum (Sorghum bicolor) is an important multipurpose crop grown worldwide, but like many other crops, it is often threatened by insect pests. Sugarcane aphid (SCA, Melanaphis sacchari Zehntner), for example, is one of the most severe pests in sorghum, which causes plant damage and yield loss. The main objective of this study was to assess the effect of phytohormones on host plant resistance to aphid attack. Two sorghum genotypes, BTx623 (susceptible) and Tx2783 (resistant), were selected for a comparative analysis of differential expression of a group of phytohormones in response to aphid infestation. The quantification of phytohormones through LC-MS demonstrated higher levels of jasmonic acid (JA), salicylic acid (SA), abscisic acid (ABA), and auxins in the resistant genotype infested with SCA. The PCA plot supports the strong differential responses between resistant and susceptible genotypes, indicating a positive correlation between JA and ABA and a negative correlation between SA and auxins. Similarly, RT-PCR results of the phytohormones-related marker genes showed higher expression in the resistant genotype compared to the susceptible one. Furthermore, to corroborate the role of phytohormones in plant defense, the susceptible genotype was treated with SA, JA, and ABA. The exogenous application of SA and JA + ABA significantly reduced plant mortality, aphid number, and damage in the susceptible genotype, suggesting a strong correlation between phytohormones and plant survival. Our findings indicate that phytohormones play positive roles in plant defense against aphids and provide new insights into the molecular mechanisms operating in plants for self-protection. These findings could also stimulate further research into the mystery about the regulation of phytohormone production during plant interaction with aphids.     

N-Linked Glycosylation in Chinese Hamster Ovary Cells Is Critical for Insulin-like Growth Factor 1 Signaling

Cell surface proteins carrying N-glycans play important roles in inter- and intracellular processes including cell adhesion, development, and cellular recognition. Dysregulation of the glycosylation machinery has been implicated in various diseases, and investigation of global differential cell surface proteome effects due to the loss of N-glycosylation will provide comprehensive insights into their pathogenesis. Cell surface proteins isolated from Parent Pro^–5 CHO cells (W5 cells), two CHO mutants with loss of N-glycosylation function derived from Pro^–5 CHO (Lec1 and Lec4 cells), were subjected to proteome analysis via high-resolution LCMS. We identified 44 and 43 differentially expressed membrane proteins in Lec1 and Lec4 cells, respectively, as compared to W5 cells. The defective N-glycosylation mutants showed increased abundance of integrin subunits in Lec1 and Lec4 cells at the cell surface. We also found significantly reduced levels of IGF-1R (Insulin like growth factor-1 receptor); a receptor tyrosine kinase; and the GTPase activating protein IQGAP1 (IQ motif-containing GTPase activating protein), a highly conserved cytoplasmic scaffold protein) in Lec1 and Lec4 cells. In silico docking studies showed that the IQ domain of IQGAP1 interacts with the kinase domain of IGF-1R. The integrin signaling and insulin growth factor receptor signaling were also enriched according to GSEA analysis and pathway analysis of differentially expressed proteins. Significant reductions of phosphorylation of ERK1 and ERK2 in Lec1 and Lec4 cells were observed upon IGF-1R ligand (IGF-1 LR3) stimulation. IGF-1 LR3, known as Long arginine3-IGF-1, is a synthetic protein and lengthened analog of insulin-like growth factor 1. The work suggests a novel mechanism for the activation of IGF-1 dependent ERK signaling in CHO cells, wherein IQGAP1 plausibly functions as an IGF-1R-associated scaffold protein. Appropriate glycosylation by the enzymes MGAT1 and MGAT5 is thus essential for processing of cell surface receptor IGF-1R, a potential binding partner in IQGAP1 and ERK signaling, the integral components of the IGF pathway.     

Antioxidant and Antibacterial Effects of Potential Probiotics Isolated from Korean Fermented Foods

A total of sixteen bacterial strains were isolated and identified from the fourteen types of Korean fermented foods that were evaluated for their in vitro probiotic potentials. The results showed the highest survivability for Bacillus sp. compared to Lactobacillus sp. in simulated gastric pH, and it was found to be maximum for B. inaquosorum KNUAS016 (8.25 ± 0.08 log10 CFU/mL) and minimum for L. sakei KNUAS019 (0.8 ± 0.02 log10 CFU/mL) at 3 h of incubation. Furthermore, B. inaquosorum KNUAS016 and L. brevis KNUAS017 also had the highest survival rates of 6.86 ± 0.02 and 5.37 ± 0.01 log10 CFU/mL, respectively, in a simulated intestinal fluid condition at 4 h of incubation. The percentage of autoaggregation at 6 h for L. sakei KNUAS019 (66.55 ± 0.33%), B. tequilensis KNUAS015 (64.56 ± 0.14%), and B. inaquosorum KNUAS016 (61.63 ± 0.19%) was >60%, whereas it was lower for L. brevis KNUAS017 (29.98 ± 0.09%). Additionally, B. subtilis KNUAS003 showed higher coaggregation at 63.84 ± 0.19% while B. proteolyticus KNUAS001 found at 30.02 ± 0.33%. Among them, Lactobacillus sp. showed the best non-hemolytic activity. The highest DPPH and ABTS radical scavenging activity was observed in L. sakei KNUAS019 (58.25% and 71.88%). The cell-free supernatant of Lactobacillus sp. considerably inhibited pathogenic growth, while the cell-free supernatant of Bacillus sp. was moderately inhibited when incubated for 24 h. However, the overall results found that B. subtilis KNUAS003, B. proteolyticus KNUAS012, L. brevis KNUAS017, L. graminis KNUAS018, and L. sakei KNUAS019 were recognized as potential probiotics through different functional and toxicity assessments.     

In-Silico Drug Toxicity and Interaction Prediction for Plant Complexes Based on Virtual Screening and Text Mining

Potential drug toxicities and drug interactions of redundant compounds of plant complexes may cause unexpected clinical responses or even severe adverse events. On the other hand, super-additivity of drug interactions between natural products and synthetic drugs may be utilized to gain better performance in disease management. Although without enough datasets for prediction model training, based on the SwissSimilarity and PubChem platforms, for the first time, a feasible workflow of prediction of both toxicity and drug interaction of plant complexes was built in this study. The optimal similarity score threshold for toxicity prediction of this system is 0.6171, based on an analysis of 20 different herbal medicines. From the PubChem database, 31 different sections of toxicity information such as “Acute Effects”, “NIOSH Toxicity Data”, “Interactions”, “Hepatotoxicity”, “Carcinogenicity”, “Symptoms”, and “Human Toxicity Values” sections have been retrieved, with dozens of active compounds predicted to exert potential toxicities. In Spatholobus suberectus Dunn (SSD), there are 9 out of 24 active compounds predicted to play synergistic effects on cancer management with various drugs or factors. The synergism between SSD, luteolin and docetaxel in the management of triple-negative breast cancer was proved by the combination index assay, synergy score detection assay, and xenograft model.     

Open Questions in Cold Atmospheric Plasma Treatment in Head and Neck Cancer: A Systematic Review

Over the past decade, we witnessed a promising application of cold atmospheric plasma (CAP) in cancer therapy. The aim of this systematic review was to provide an exhaustive state of the art of CAP employed for the treatment of head and neck cancer (HNC), a tumor whose late diagnosis, local recurrence, distant metastases, and treatment failure are the main causes of patients’ death. Specifically, the characteristics and settings of the CAP devices and the in vitro and in vivo treatment protocols were summarized to meet the urgent need for standardization. Its molecular mechanisms of action, as well as the successes and pitfalls of current CAP applications in HNC, were discussed. Finally, the interesting emerging preclinical hypotheses that warrant further clinical investigation have risen. A total of 24 studies were included. Most studies used a plasma jet device (54.2%). Argon resulted as the mostly employed working gas (33.32%). Direct and indirect plasma application was reported in 87.5% and 20.8% of studies, respectively. In vitro investigations were 79.17%, most of them concerned with direct treatment (78.94%). Only eight (33.32%) in vivo studies were found; three were conducted in mice, and five on human beings. CAP showed pro-apoptotic effects more efficiently in tumor cells than in normal cells by altering redox balance in a way that oxidative distress leads to cell death. In preclinical studies, it exhibited efficacy and tolerability. Results from this systematic review pointed out the current limitations of translational application of CAP in the urge of standardization of the current protocols while highlighting promising effects as supporting treatment in HNC.     

The Multifaceted Role of Signal Peptide-CUB-EGF Domain-Containing Protein (SCUBE) in Cancer

Signal peptide, CUB, and EGF-like domain-containing proteins (SCUBE) are secretory cell surface glycoproteins that play key roles in the developmental process. SCUBE proteins participate in the progression of several diseases, including cancer, and are recognized for their oncogenic and tumor suppressor functions depending on the cellular context. SCUBE proteins promote cancer cell proliferation, angiogenesis, invasion, or metastasis, stemness or self-renewal, and drug resistance. The association of SCUBE with other proteins alters the expression of signaling pathways, including Hedgehog, Notch, TGF-β/Smad2/3, and β-catenin. Further, SCUBE proteins function as potential prognostic and diagnostic biomarkers for breast cancer, renal cell carcinoma, endometrial carcinoma, and nasopharyngeal carcinoma. This review presents key features of SCUBE family members, and their structure and functions, and highlights their contribution in the development and progression of cancer. A comprehensive understanding of the role of SCUBE family members offers novel strategies for cancer therapy.     

TMAO Suppresses Megalin Expression and Albumin Uptake in Human Proximal Tubular Cells Via PI3K and ERK Signaling

Trimethylamine-N-oxide (TMAO) is a uremic toxin, which has been associated with chronic kidney disease (CKD). Renal tubular epithelial cells play a central role in the pathophysiology of CKD. Megalin is an albumin-binding surface receptor on tubular epithelial cells, which is indispensable for urine protein reabsorption. To date, no studies have investigated the effect of TMAO on megalin expression and the functional properties of human tubular epithelial cells. The aim of this study was first to identify the functional effect of TMAO on human renal proximal tubular cells and second, to unravel the effects of TMAO on megalin-cubilin receptor expression. We found through global gene expression analysis that TMAO was associated with kidney disease. The microarray analysis also showed that megalin expression was suppressed by TMAO, which was also validated at the gene and protein level. High glucose and TMAO was shown to downregulate megalin expression and albumin uptake similarly. We also found that TMAO suppressed megalin expression via PI3K and ERK signaling. Furthermore, we showed that candesartan, dapagliflozin and enalaprilat counteracted the suppressive effect of TMAO on megalin expression. Our results may further help us unravel the role of TMAO in CKD development and to identify new therapeutic targets to counteract TMAOs effects.     

Physical modeling and numerical investigation of fluid flow and solidification behavior in a slab caster mold using hexa-furcated nozzle

Slag entrapment from metal–slag interface during continuous casting operations has been a major area of concern for steelmakers globally. The presence of inactive regions in the upper region of the mold poses another challenge. Proper flow behavior of the molten metal coming out of the nozzle in the mold is required to overcome these challenges. Nozzle design greatly affects the flow pattern of the molten steel inside the mold. The present investigation is an attempt to study the flow and solidification behavior in a slab caster mold with the use of a novel-designed hexa-furcated nozzle using numerical investigation results. The casting speed and submerged entry nozzle (SEN) depth are varied to study the effect of these parameters on minimizing the inactive zones in the mold and the steel/slag interface fluctuations. The results show that the interface fluctuation increases at higher casting speed and lower SEN depth. The residence time distribution (RTD) analysis was also performed for different cases to investigate the flow behavior. The validation of the fluid flow and RTD curve inside the computational domain is carried out with the use of physical modeling.     

Organic bulk heterojunction enabled with nanocapsules of hydrate vanadium pentaoxide layer for high responsivity self-powered photodetector

This article demonstrates the fabrication of organic-based devices using a low-cost solution-processable technique. A blended heterojunction of chlorine substituted 2D-conjugated polymer PBDB-T-2Cl, and PC₇₁BM supported nanocapsules hydrate vanadium penta oxides (HVO) as hole transport layer (HTL) based photodetector fabricated on an ITO coated glass substrate under ambient condition. The device forms an excellent organic junction diode with a good rectification ratio of ~200. The device has also shown excellent photodetection properties under photoconductive mode (at reverse bias) and zero bias for green light wavelength. A very high responsivity of ~6500 mA/W and high external quantum efficiency (EQE) of 1400% have been reported in the article. The proposed organic photodetector exhibits an excellent response and recovery time of ~30 and ~40 ms, respectively.