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 Genomic analyses of head and neck squamous cell carcinoma (HNSCC) have highlighted alterations in the phosphatidylinositol 3-kinase (PI3K) signaling pathway, presenting a therapeutic target for multiple ongoing clinical trials with PI3K or PI3K/MTOR inhibitors. However, these inhibitors can potentially increase autophagy in HNSCC and indirectly support cancer cell survival. Here, we sought to understand the relationship between the PI3K signaling pathway and autophagy during their dual inhibition in a panel of HNSCC cell lines. We used acridine orange staining, immunoblotting, and tandem sensor Red Fluorescent Protein- Green Fluorescent Protein-, microtubule-associated protein 1 light chain 3 beta (RFP-GFP-LC3B) expression analysis to show that PI3K inhibitors increase autophagosomes in HNSCC cells, but that chloroquine treatment effectively inhibits the autophagy that is induced by PI3K inhibitors. Using the Bliss independence model, we determined that the combination of chloroquine with PI3K inhibitors works in synergy to decrease cancer cell proliferation, independent of the PIK3CA status of the cell line. Our results indicate that a strategy focusing on autophagy inhibition enhances the efficacy of therapeutics already in clinical trials. Our results suggest a broader application for this combination therapy that can be promptly translated to in vivo studies.Aberrant expression of mucins (MUCs) can promote the epithelial-mesenchymal transition (EMT), which leads to enhanced tumorigenesis. Carcinogenesis-related pathways involving c-MET and β-catenin are associated with MUCs. In this study, we characterized the expression of EMT-relevant proteins including MET, β-catenin, and E-cadherin in human gastric cancer (GC) cell lines, and further characterized the differential susceptibility of these cell lines compared with the c-MET inhibitor tepotinib. We assessed the antitumor activity of tepotinib in GC cell lines. The effects of tepotinib on cell viability, apoptotic cell death, EMT, and c-MET and β-catenin signaling were evaluated by 3-(4,5 dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl-2-(4-sulfophenyl)-2H-tetrazolium (MTS), flow cytometry, Western blotting, and qRT-PCR. The antitumor efficacy was assessed in MKN45 xenograft mice. Tepotinib treatment induced apoptosis in c-MET-amplified SNU620, MKN45, and KATO III cells, but had no effect on c-MET-reduced MKN28 or AGS cells. Tepotinib treatment also significantly reduced the protein levels of phosphorylated and total c-MET, phosphorylated and total ERK, β-catenin, and c-MYC in SNU620 and MKN45 cells. In contrast, this drug was only slightly active against KATO III cells. Notably, tepotinib significantly reduced the expression of EMT-promoting genes such as MMP7, COX-2, WNT1, MUC5B, and c-MYC in c-MET-amplified GC cells and increased the expression of EMT-suppressing genes such as MUC5AC, MUC6, GSK3β, and E-cadherin. In a mouse model, tepotinib exhibited good antitumor growth activity along with increased E-cadherin and decreased phosphorylated c-MET (phospho-c-MET) protein levels. Collectively, these results suggest that tepotinib suppresses tumor growth and migration by negatively regulating c-MET-induced EMT. These findings provide new insights into the mechanism by which MUC5AC and MUC6 contribute to GC progression.
  Although previous qualitative studies suggested the link between infertility treatment and negative emotions towards infants, few empirical population-based studies have investigated the association of infertility treatment with the perception of infant crying, bonding impairment, and abusive behavior towards one's infant.
 
  Women who participated in a four month health-checkup program in Aichi Prefecture, Japan (
  = 6590) were asked to a complete a questionnaire that included infertility treatment history, perception of infant crying, maternal-infant bonding impairment assessed by the Mother to Infant Bonding Scale Japanese version, and abusive behavior towards one's infant. Outcomes were dichotomized, and a conditional logistic regression was applied, using the propensity score match for infertility treatment exposure adjusted for known covariates.
 
  A total of 690 participants (11.1%) reported infertility treatment history, and 625 cases were matched. We found that mothers with infertility treatment history were 1.36 times more likely to perceive a higher frequency of infant crying (95% confidence interval (CI)1.05-1.78), but no association with maternal-infant bonding impairment (odds ratio (OR) 1.18; 95% CI 0.81-1.72) and abusive behavior towards the infant (OR 0.82; 95% CI 0.49-1.36).
 
  Infertility treatment may be associated with the perception of a higher frequency of infant crying, but it is not associated with bonding impairment and abusive behavior. Further longitudinal study is needed to replicate the findings.
 Infertility treatment may be associated with the perception of a higher frequency of infant crying, but it is not associated with bonding impairment and abusive behavior. Further longitudinal study is needed to replicate the findings.Powdery mildew caused by the airborne ascomycete fungus Blumeria graminis f. sp. hordei (Bgh) is one of most common diseases of barley (Hordeum vulgare). This, as with many other plant pathogens, can be efficiently controlled by inexpensive and environmentally-friendly genetic resistance.  https://www.selleckchem.com/products/liraglutide.html  General requirements for resistance to the pathogens are effectiveness and durability. Resistance of barley to Bgh has been studied intensively, and this review describes recent research and summarizes the specific resistance genes found in barley varieties since the last conspectus. Bgh is extraordinarily adaptable, and some commonly recommended strategies for using genetic resistance, including pyramiding of specific genes, may not be effective because they can only contribute to a limited extent to obtain sufficient resistance durability of widely-grown cultivars. In spring barley, breeding the nonspecific mlo gene is a valuable source of durable resistance.  https://www.selleckchem.com/products/liraglutide.html  Pyramiding of nonspecific quantitative resistance genes or using introgressions derived from bulbous barley (Hordeum bulbosum) are promising ways for breeding future winter barley cultivars.