COQ10B Knockdown Modulates Cell Proliferation, Invasion, Migration, and Apoptosis in Esophageal Squamous Cell Carcinoma.

Objective: Esophageal squamous-cell carcinoma (ESCC) is an aggressive malignant tumor, accounting for more than 90% of esophageal cancers. However, treatments such as surgical resection, radiotherapy, and chemotherapy are unable to achieve ideal clinical outcomes. The purpose of this study was to explore the effects of COQ10B on proliferation, apoptosis, migration, and invasion of esophageal squamous-cell carcinoma (ESCC) cells. Methods: Quantitative real-time PCR (qRT-PCR) was used to detect the expression of COQ10B in ESCC and normal tissues and in ESCC cell lines (KYSE-15 and TE-1). MTT assay and flow cytometry were applied to investigate the effects of COQ10B shRNA lentivirus (LV-shCOQ10B) on ESCC cell proliferation and apoptosis, respectively. The effect of COQ10B silencing on ESCC cell migration and invasion was determined by wound healing assay and transwell invasion assay, respectively. Results: The expression of COQ10B mRNA in ESCC tissues was higher than that in surrounding tissues. The decreased COQ10B level in KYSE-15 and TE-1 cells by LV-shCOQ10B could inhibit cell proliferation, promote cell apoptosis, and reduce the ability of invasion and migration (all P < 0.05). Conclusion: COQ10B was highly expressed in human ESCC tissues. COQ10B silencing contributed to the inhibition of proliferation, invasion, and migration of ESCC cells and the promotion of cell apoptosis, suggesting COQ10B may be a potential molecular target for the diagnosis and treatment of ESCC.

Computational Drug Repurposing Approach to Identify Novel Inhibitors of ILK Protein for Treatment of Esophageal Squamous Cell Carcinoma.

Purpose: Esophageal squamous cell cancer (ESCC) is a deadly malignant tumor characterized by an overall 5-year survival rate below 20%, with China accounting for approximately 50% of all cases worldwide. Our previous studies have demonstrated that high integrin-linked kinase (ILK) expression plays a key role in development and progression of ESCC both in vitro and in vivo. Here, we employed the drug repurposing approach to identify a novel FDA-approved anticancer inhibitor against ILK-induced tumorigenesis and progression. Methods: We screened the ZINC15 database and predicted the molecular docking ability among FDA-approved and publicly available drugs to ILK and then performed computational docking and visual inspection analyses of the top 10 ranked drugs. Two computer-based virtual screened drugs were evaluated in vitro for their ability to directly bind purified ILK by surface plasmon resonance. Cytotoxicity of the two candidate drugs was validated in vitro using CCK-8 and LDH assays. Results: We initially selected the top 10 compounds, based on their minimum binding energy to the ILK crystal, after molecular docking and subjected them to further screening. Taking the binding energy of -10 kcal/mol as the threshold, we selected two drugs, namely, nilotinib and teniposide, for the wet-lab experiment. Surface plasmon resonance (SPR) revealed that nilotinib and teniposide had equilibrium dissociation constant (KD) values of 6.410E - 6 and 1.793E - 6, respectively, which were lower than 2.643E - 6 observed in ILK-IN-3 used as the positive control. The IC50 values for nilotinib and teniposide in ESCC cell lines were 40 µM and 200-400 nM, respectively. Results of the CCK-8 assay demonstrated that both nilotinib and teniposide significantly inhibited proliferation of cells (P < 0.01). LDH results revealed that both drugs significantly suppressed the rate of cell death (P < 0.01). Conclusion: The drug repositioning procedure can effectively identify new therapeutic tools for ESCC. Our findings suggest that nilotinib and teniposide are efficacious inhibitors of ILK and thus have potential to target ILK-mediated signaling pathways for management of ESCC.

Correction: Functionality of Top-Rated Mobile Apps for Depression: Systematic Search and Evaluation.

[This corrects the article DOI: 10.2196/15321.].

Functionality of Top-Rated Mobile Apps for Depression: Systematic Search and Evaluation.

BACKGROUND: In the last decade, there has been a proliferation of mobile apps claiming to support the needs of people living with depression. However, it is unclear what functionality is actually provided by apps for depression, or for whom they are intended. OBJECTIVE: This paper aimed to explore the key features of top-rated apps for depression, including descriptive characteristics, functionality, and ethical concerns, to better inform the design of apps for depression. METHODS: We reviewed top-rated iPhone OS (iOS) and Android mobile apps for depression retrieved from app marketplaces in spring 2019. We applied a systematic analysis to review the selected apps, for which data were gathered from the 2 marketplaces and through direct use of the apps. We report an in-depth analysis of app functionality, namely, screening, tracking, and provision of interventions. Of the initially identified 482 apps, 29 apps met the criteria for inclusion in this review. Apps were included if they remained accessible at the moment of evaluation, were offered in mental health-relevant categories, received a review score greater than 4.0 out of 5.0 by more than 100 reviewers, and had depression as a primary target. RESULTS: The analysis revealed that a majority of apps specify the evidence base for their intervention (18/29, 62%), whereas a smaller proportion describes receiving clinical input into their design (12/29, 41%). All the selected apps are rated as suitable for children and adolescents on the marketplace, but 83% (24/29) do not provide a privacy policy consistent with their rating. The findings also show that most apps provide multiple functions. The most commonly implemented functions include provision of interventions (24/29, 83%) either as a digitalized therapeutic intervention or as support for mood expression; tracking (19/29, 66%) of moods, thoughts, or behaviors for supporting the intervention; and screening (9/29, 31%) to inform the decision to use the app and its intervention. Some apps include overtly negative content. CONCLUSIONS: Currently available top-ranked apps for depression on the major marketplaces provide diverse functionality to benefit users across a range of age groups; however, guidelines and frameworks are still needed to ensure users' privacy and safety while using them. Suggestions include clearly defining the age of the target population and explicit disclosure of the sharing of users' sensitive data with third parties. In addition, we found an opportunity for apps to better leverage digital affordances for mitigating harm, for personalizing interventions, and for tracking multimodal content. The study further demonstrated the need to consider potential risks while using depression apps, including the use of nonvalidated screening tools, tracking negative moods or thinking patterns, and exposing users to negative emotional expression content.

Surface complexation modeling of Cu(II) sorption to montmorillonite-bacteria composites.

Surface complexation modeling, isothermal titration calorimetry, and batch adsorption were employed to characterize the adsorption of Cu onto montmorillonite, Pseudomonas putida X4, and their composites at mass ratios of 2:1, 6:1, and 12:1, respectively. Different enthalpy values were found for Cu adsorption to permanent (-6.43kJ/mol) and variable charge sites (8.51kJ/mol) on montmorillonite. The component additivity (CA) method was used to predict the adsorption of Cu on the composites by combining end member models for montmorillonite and P. putida. A reduced adsorption was observed at pH<5.5 due to physical blocking between montmorillonite and P. putida. By contrast, the enhanced binding at high pH levels was ascribed to the formation of bridging structures among the clay mineral-Cu-bacteria complexes. These deviations in the CA method were corrected by adding reactions of >RCOOH…XNa and >RCOOCuOHXNa. The increased adsorption of the composites confirmed the decrease of permanent negative charge sites and the formation of ternary complexes. The results help elucidate the effect of Cu adsorption onto clay minerals-bacteria composites. The newly developed "CA-site masking-bridging" model can be used to predict Cu speciation in systems in which the active interaction of bacteria and clay minerals occurs.

OsCESA9 conserved-site mutation leads to largely enhanced plant lodging resistance and biomass enzymatic saccharification by reducing cellulose DP and crystallinity in rice.

Genetic modification of plant cell walls has been posed to reduce lignocellulose recalcitrance for enhancing biomass saccharification. Since cellulose synthase (CESA) gene was first identified, several dozen CESA mutants have been reported, but almost all mutants exhibit the defective phenotypes in plant growth and development. In this study, the rice (Oryza sativa) Osfc16 mutant with substitutions (W481C, P482S) at P-CR conserved site in CESA9 shows a slightly affected plant growth and higher biomass yield by 25%-41% compared with wild type (Nipponbare, a japonica variety). Chemical and ultrastructural analyses indicate that Osfc16 has a significantly reduced cellulose crystallinity (CrI) and thinner secondary cell walls compared with wild type. CESA co-IP detection, together with implementations of a proteasome inhibitor (MG132) and two distinct cellulose inhibitors (Calcofluor, CGA), shows that CESA9 mutation could affect integrity of CESA4/7/9 complexes, which may lead to rapid CESA proteasome degradation for low-DP cellulose biosynthesis. These may reduce cellulose CrI, which improves plant lodging resistance, a major and integrated agronomic trait on plant growth and grain production, and enhances biomass enzymatic saccharification by up to 2.3-fold and ethanol productivity by 34%-42%. This study has for the first time reported a direct modification for the low-DP cellulose production that has broad applications in biomass industries.