Crystalline-Amorphous Interfaces Engineering of CoO-InOx for Highly Efficient CO2 Electroreduction to CO.

As a fundamental product of CO2 conversion through two-electron transfer, CO is used to produce numerous chemicals and fuels with high efficiency, which has broad application prospects. In this work, it has successfully optimized catalytic activity by fabricating an electrocatalyst featuring crystalline-amorphous CoO-InOx interfaces, thereby significantly expediting CO production. The 1.21%CoO-InOx consists of randomly dispersed CoO crystalline particles among amorphous InOx nanoribbons. In contrast to the same-phase structure, the unique CoO-InOx heterostructure provides plentiful reactive crystalline-amorphous interfacial sites. The Faradaic efficiency of CO (FECO) can reach up to 95.67% with a current density of 61.72 mA cm-2 in a typical H-cell using MeCN containing 0.5 M 1-Butyl-3-methylimidazolium hexafluorophosphate ([Bmim]PF6) as the electrolyte. Comprehensive experiments indicate that CoO-InOx interfaces with optimization of charge transfer enhance the double-layer capacitance and CO2 adsorption capacity. Theoretical calculations further reveal that the regulating of the electronic structure at interfacial sites not only optimizes the Gibbs free energy of *COOH intermediate formation but also inhibits HER, resulting in high selectivity toward CO.

Exosomal miR-211-5p regulates glucose metabolism, pyroptosis, and immune microenvironment of melanoma through GNA15.

Despite the unprecedented advancement of cancer treatment, the prognosis for patients with metastatic stage of cancer remains poor. The challenge that underlines this clinical dilemma is the complexity of metastasis. The conventional experiment-driven discovery approaches (the "wet lab") yield overly simplified one-to-one mechanistic relationships that are inept of elucidating the complexity of metastasis. Metastasis research also suffers from the knowledge and skill deficiency of the individual investigators. The importance of the present study is the demonstration that the "dry-lab-driven discovery and wet-lab validation" approach can improve the efficiency of studying complex biological behaviors, and can yield more reliable, objective and comprehensive mechanistic findings that are have clinical significance. Specifically, we applied this approach to study the mechanisms that underline the involvement of exosomal miRNAs in transferring the metastatic capability between heterogenous melanoma cancer cells. We show that the highly metastatic melanoma tumor cells (POL) can transfer their metastatic competency to the low-metastatic melanoma tumor cells (OL) by exosomal miR-211-5p. The oncogenic activity of miR-211-5p is mediated by the target gene guanine nucleotide-binding protein subunit alpha-15 (GNA15) through modifying the immune function of the tumor microenvironment extrinsically; as well as through inhibiting pyroptosis and augmenting glycolysis within OL cells intrinsically. In addition, we show that exosomal sorting of miR-211-5p is like selective and is subjected to regulation by a transcriptional feedback loop between miR-211-5p and zinc finger FYVE-type containing 26 (ZFYVE26). Furthermore, the "8-genes pyroptosis Risk model" derived from LASSO regression analysis was verified as an independent prognostic factor for melanoma.

Sec23a inhibits the self-renewal of melanoma cancer stem cells via inactivation of ER-phagy.

BACKGROUND: The genesis and developments of solid tumors, analogous to the renewal of healthy tissues, are driven by a subpopulation of dedicated stem cells, known as cancer stem cells (CSCs), that exhibit long-term clonal repopulation and self-renewal capacity. CSCs may regulate tumor initiation, growth, dormancy, metastasis, recurrence and chemoresistance. While autophagy has been proposed as a regulator of the stemness of CSCs, the underlying mechanisms requires further elucidation. METHODS: The CSC component in human melanoma cell lines M14 and A375 was isolated and purified by repetitive enrichments for cells that consistently display anchorage-independent spheroid growth. The stemness properties of the CSCs were confirmed in vitro by the expressions of stemness marker genes, the single-cell cloning assay and the serial spheroid formation assay. Subcutaneous tumor transplantation assay in BALB/c nude mice was performed to test the stemness properties of the CSCs in vivo. The autophagic activity was confirmed by the protein level of LC3 and P62, mRFP-LC3B punta and cytoplasmic accumulation of autolysosomes. The morphology of ER was detected with transmission electron microscopy. RESULTS: In the present study, by employing stable CSC cell lines derived from human melanoma cell lines M14 and A375, we show for the first time that Sec23a inhibits the self-renewal of melanoma CSCs via inactivation of ER-phagy. Mechanistically, inhibition of Sec23a reduces ER stress and consequently FAM134B-induced ER-phagy. Furthermore, TCGA data mining and analysis show that Sec23a is a favorable diagnostic and prognostic marker for human skin cutaneous melanoma. CONCLUSION: This study has elucidated a new mechanism underlying the regulation of autophagy on stemness, i.e. CSCs can exploit the SEC23A/ER-stress/FAM134B/ER-phagy axis for the self-renewal. These observations provide new ideas for exploration of the regulatory network of CSC self-renewal to develop CSCs-based therapy strategies for malignant tumors. Video Abstract.

Melanoma stem cells promote metastasis via exosomal miR-1268a inactivation of autophagy.

BACKGROUND: Metastatic melanoma has a high mortality rate and poor survival. This is associated with efficient metastatic colonization, but the underlying mechanisms remain elusive. Communication between cancer stem cells (CSCs) and cancer cells plays an important role in metastatic dissemination. Whether cancer stem cells can alter the metastatic properties of non-CSC cells; and whether exosomal crosstalk can mediate such interaction, have not been demonstrated in melanoma prior to this report. RESULTS: The results revealed that exosomes secreted by highly metastatic melanoma CSCs (OL-SCs) promoted the invasiveness of the low metastatic melanoma cells (OL) and accelerated metastatic progression. miR-1268a was up-regulated in cells and exosomes of OL-SCs. Moreover, OL-SCs-derived exosomal miR-1268a, upon taking up by OL cells, promoted the metastatic colonization ability of OL cells in vitro and in vivo. In addition, the pro-metastatic activity of exosomal miR-1268a is achieved through inhibition of autophagy. CONCLUSION: Our study demonstrates that OL cells can acquire the "metastatic ability" from OL-SCs cells. OL-SCs cells achieves this goal by utilizing its exosomes to deliver functional miRNAs, such as miR-1268a, to the targeted OL cells which in turn augments metastatic colonization by inactivating the autophagy pathway in OL cells.

Liquid-liquid phase equilibrium and the effect of a water-soluble polymer on the interaction between droplets in water-in-oil microemulsions.

The liquid-liquid phase equilibria of {water/PEG200/sodium bis(2-ethylhexyl)sulfosuccinate (AOT)/n-decane} with the molar ratio of water to AOT being 37.9 and various concentrations cPEG of PEG in water were measured in this study. The critical exponent ß corresponding to the width of the coexistence curve was determined, which showed good agreement with the 3D-Ising value and supported the proposal of the pseudo binary droplet solution for these multiple microemulsions. A previously developed thermodynamic approach based on the Carnahan-Starling-van der Waals type equation was improved and used to analyze the coexistence curve data of {water/PEG200/AOT/n-decane} microemulsions to deduce the interaction properties between droplets and further to investigate the effect of the additive PEG200 on these interactions. It was found that the addition of PEG200 into the {water/AOT/n-decane} microemulsion resulted in the decrease in the critical temperature and the interaction enthalpy and entropy. Both the interaction enthalpy and entropy decreased first, then increased with an increase of cPEG and had minimum values at cPEG = 25 g L-1, which showed the same tendency as the isothermal titration microcalorimetric results for the {water/PEG200/AOT/isooctane} microemulsion we reported very recently. The effects of the interaction enthalpy and the entropy on the phase separation and their dependences on cPEG were discussed and related to the effects of the additive on the rigidity of the interface layer of the microemulion droplet.

How public commuting stress promotes employee turnover intention: an examination through the lens of the transactional theory of stress.

BACKGROUND AND OBJECTIVES: The potential detrimental effects of commuting stress have gradually attracted scholars' interest in recent years. Going beyond the perspectives of prior studies (e.g., conservation of resources theory), this study offers a new explanatory framework for the relationship between employees' commuting stress and turnover intention based on the transactional theory of stress. Specifically, this study aims to investigate the mediating effect of hindrance appraisal and the moderating effect of trait mindfulness. DESIGN AND METHOD: To test the hypotheses, we collected two-wave data from 243 employees working in various Chinese firms. Path analysis was used for the analysis. RESULTS: The findings demonstrated that hindrance appraisal mediated the positive relationship between commuting stress and turnover intention. In addition, trait mindfulness buffered the relationship between commuting stress and turnover intention as well as the indirect effect of hindrance appraisal on this relationship. CONCLUSIONS: The findings highlight the stressor appraisal mechanism in the association between commuting stress and turnover intention and identify trait mindfulness as a key coping mechanism for reducing commuting stress.

Informational Analysis and Prediction of Obsessive-Compulsive Disorder Pathogenesis.

OBJECTIVE: We aimed to predict the possible mechanism of obsessive-compulsive disorder (OCD) by integrating and analyzing mRNA sequencing results from two datasets and to provide direction for future studies into the pathogenesis of OCD. METHODS: Two OCD datasets, GSE78104 and GSE60190, were obtained, and the intersection of the two gene sets with differential expression in OCD samples was selected. Kyoto Encyclopedia of Genes and Genomes (KEGG) signal pathway enrichment and Gene Ontology (GO) analyses were performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) online analysis website for the genes at the intersection, and the data were mapped using http://www.bioinformatics.com.cn. After genes with p≤0.05 had been screened out, protein-protein interaction (PPI) interaction analysis was conducted using Metascape to screen the key Molecular Complex Detection (MCODE) genes. MCODE genes were then enriched using the KEGG signaling pathway and GO classification. RESULTS: A total of 3,449 differentially expressed genes (DEGs) were obtained from the GSE78104 and GSE60190 datasets. KEGG, GO, and Gene Set Enrichment Analysis analyses of DEGs showed that the onset of OCD was related to oxidative phosphorylation and other metabolic processes, which may have a similar pathogenesis to other neurodegenerative diseases. Single-gene PPI analysis of SAPAP3 revealed that the mechanism by which SAPAP3 knockout induces OCD may also be caused by affecting oxidative phosphorylation. CONCLUSION: The mechanism of SAPAP3 knockout-induced OCD in mice may be due to the oxidative phosphorylation process in the body. Future studies on the neural circuit mechanism of OCD should be conducted.

Impact of indigenous Oenococcus oeni and Lactiplantibacillus plantarum species co-culture on Cabernet Sauvignon wine malolactic fermentation: Kinetic parameters, color and aroma.

Malolactic fermentation (MLF) is a crucial process to enhance wine quality, and the utilization of indigenous microorganisms has the potential to enhance wine characteristics distinct to a region. Here, the MLF performance of five indigenous Oenococcus oeni strains and six synthetic microbial communities (SynComs), were comparatively evaluated in Cabernet Sauvignon wine. In terms of malate metabolism rate and wine aroma diversity, the strain of O. oeni Oe114-46 demonstrated comparable MLF performance to the commercial strain of O. oeni Oe450 PreAc. Furthermore, the corresponding SynComs (Oe144-46/LpXJ25) exhibited improved fermentation properties, leading to increased viable cell counts of both species, more rapid and thorough MLF, and increased concentrations of important aroma compounds, such as linalool, 4-terpinenol, α-terpineol, diethyl succinate, and ethyl lactate. These findings highlight the remarkable MLF performance of indigenous O. oeni and O. oeni-L. plantarum microbial communities, emphasizing their immense potential in improving MLF efficiency and wine quality.

Improving Soluble Phenolic Profile and Antioxidant Activity of Grape Pomace Seeds through Fungal Solid-State Fermentation.

Grape pomace seeds contain abundant phenolic compounds, which are also present in both soluble and insoluble forms, similar to many other plant matrices. To further increase the extractable soluble phenolics and their antioxidant activities, grape pomace seeds were fermented with different fungi. Results showed that solid-state fermentation (SSF) with Aspergillus niger, Monascus anka, and Eurotium cristatum at 28 °C and 65% humidity had a significantly positive impact on the release of soluble phenolics in grape pomace seeds. Specifically, SSF with M. anka increased the soluble phenolic contents by 6.42 times (calculated as total phenolic content) and 6.68 times (calculated as total flavonoid content), leading to an overall improvement of antioxidant activities, including DPPH (increased by 2.14 times) and ABTS (increased by 3.64 times) radical scavenging activity. Furthermore, substantial changes were observed in the composition and content of individual phenolic compounds in the soluble fraction, with significantly heightened levels of specific phenolics such as chlorogenic acid, syringic acid, ferulic acid, epicatechin gallate, and resveratrol. Notably, during M. anka SSF, positive correlations were identified between the soluble phenolic content and hydrolase activities. In particular, there is a strong positive correlation between glycosidase and soluble phenols (r = 0.900). The findings present an effective strategy for improving the soluble phenolic profiles and bioactivities of grape pomace seeds through fungal SSF, thereby facilitating the valorization of winemaking by-products.

Association between duration of progesterone supplementation and clinical outcomes in artificial frozen-thawed embryo transfer cycles.

Objective: The administration of progesterone before transfer in hormone replacement treatment (HRT) is crucial for the clinical outcomes of frozen-thawed embryo transfer (FET), but the optimal duration of progesterone remains controversial. This study aimed to investigate the effect of the duration of progesterone administration on the clinical outcomes of FET cycles. Methods: This prospective cohort study included 353 artificial FET cycles conducted at a reproductive medicine center between April and October 2021. The FET cycles were stratified into four groups based on the duration of progesterone supplementation before the procedure and the embryonic development stage: group P3 (73 patients) received intramuscular progesterone for 3 days and group P4 (87 patients) for 4 days before Day 3 frozen embryo transfer, group P5 (70 patients) for 5 days and group P6 (123 patients) for 6 days before frozen blastocyst transfer. This trial was performed using one or two vitrified embryo(s) when the endometrial thickness reached 7 mm after estrogen supplementation in an artificial cycle. The primary outcome was clinical pregnancy, and secondary outcomes included biochemical pregnancy, implantation, early pregnancy loss, and live births. Results: There were no significant differences in the demographic and clinical characteristics between the groups. No significant difference was observed in the clinical pregnancy rates between groups: 23/73 (31.5%) in group P3 vs 28/87 (32.2%) in group P4 (P = 0.927). Compared to group P5 (41/70, 58.6%), the clinical pregnancy rate was not significantly different in group P6 (77/123, 62.6%, P = 0.753). There was no significant difference in the implantation rates between groups: 33/136 (24.3%) in group P3 vs 34/166 (20.5%) in group P4 (P = 0.431), and 62/133 (46.6%) in group P5 vs 107/231 (46.3%) in group P6 (P = 0.956). The duration of progesterone supplementation (mean: 3.5 ± 0.5 days; range:3-4 days) before Day 3 frozen embryo transfer did not impact clinical pregnancy (odds ratio [OR] 1.048; 95% confidence interval [CI], 0.518-2.119). The duration of progesterone administration (mean: 5.6 ± 0.5 days; range:5-6 days) before frozen blastocyst transfer may not affect clinical pregnancy (OR 1.339; 95% CI, 0.717-2.497). Conclusion: There may be no significant correlation between the duration of progesterone supplementation and pregnancy outcomes in artificial FET cycles, although the clinical pregnancy rate was higher when progesterone supplementation was extended for one day before FET.

Exosomal microRNA-4535 of Melanoma Stem Cells Promotes Metastasis by Inhibiting Autophagy Pathway.

High mortality rate and poor survival in melanoma are associated with efficient metastatic colonization. The underlying mechanisms remain elusive. Elucidating the role of exosomes in mediating the interactions between cancer cells and the metastatic microenvironment has been focused on cancer cell derived exosomes in modulating the functions of stromal cells. Whether cancer stem cells (CSCs) can modify the metastatic properties of non-CSC cells, and whether exosomal crosstalk plays a role have not been demonstrated prior to this report. In this study, a paired M14 melanoma derivative cell line, i.e., melanoma parental cell (MPC) and its CSC derivative cell line melanoma stem cell (MSC) were employed. We demonstrated that exosomal crosstalk betwen MSCs and non-CSC MPCs is a new mechanism that underlies melanoma metastasis. Low metastatic melanoma cells (MPCs) can acquire the "metastatic power" from highly metastatic melanoma CSCs (MSCs). We illustrated an uncharacterized microRNA, miR-4535 in mediating such exosomal crosstalk. MSCs deliver its exosomal miR-4535 to the targeted MPCs. Upon entering MPCs, miR-4535 augments metastatic colonization of MPCs by inactivating the autophagy pathway.

Synergistic inhibition of NUDT21 by secretory S100A11 and exosomal miR-487a-5p promotes melanoma oligo- to poly-metastatic progression.

Although early diagnosis and therapeutic advances have transformed the living quality and outcome of cancer patients, the poor prognosis for metastatic patients has not been significantly improved. Mechanisms underlying the complexity of metastasis cannot be simply determined by the straightforward 'cause-and-effect relationships'. We have developed a 'dry-lab-driven knowledge discovery and wet-lab validation' approach to embrace the complexity of cancer and metastasis. We have revealed for the first time that polymetastatic (POL) melanoma cells can utilize both the secretory protein pathway (S100A11-Sec23a) and the exosomal crosstalk (miR-487a-5p) to transfer their 'polymetastatic competency' to the oligometastatic (OL) melanoma cells, via synergistic co-targeting of the tumor-suppressor Nudt21. The downstream deregulated glycolysis was verified to regulate metastatic colonization efficiency. Further, two gene sets conferring independent prognosis in melanoma were identified, which have the potential for clinical translation and merit future clinical validation.

GRSF1 antagonizes age-associated hypercoagulability via modulation of fibrinogen mRNA stability.

Age-associated hypercoagulability is accompanied by the increase of plasma levels of some coagulation factors including fibrinogen which may contribute to the increased risk of cardiovascular, cerebrovascular, and thrombotic diseases in elderly people. However, the underlying mechanism of increased plasma fibrinogen concentration during aging is still elusive. GRSF1 belongs to the heterogeneous nuclear ribonucleoproteins F/H (hnRNP F/H) subfamily. Here, we report that GRSF1 attenuates hypercoagulability via negative modulation of fibrinogen expression. We demonstrated that GRSF1 negatively regulated fibrinogen expression at both mRNA and protein levels. GRSF1 directly interacted with the coding region (CDS) of FGA, FGB, and FGG mRNAs, and decreased their stability thus mitigating fibrinogen expression. We further identified that only a few G-tracts within the Fib C domain of FGA, FGB, and FGG CDS and the qRRM2 domain of GRSF1 were required for their interaction. Moreover, we confirmed hypercoagulability and the decrease of GRSF1 expression level during mice aging. Functionally, GRSF1 overexpression in old mice liver decreased fibrinogen plasma level, reduced hypercoagulability, and mitigated blood coagulation activity, whereas GRSF1 knockdown in young mice liver increased fibrinogen plasma level and promoted blood coagulation activity. Collectively, our findings unveil a novel posttranscriptional regulation of fibrinogen by GRSF1 and uncover a critical role of GRSF1 in regulating blood coagulation activity.

High-Metastatic Melanoma Cells Promote the Metastatic Capability of Low-Metastatic Melanoma Cells via Exosomal Transfer of miR-411-5p.

Melanoma is characterized by high rate of metastasis and mortality. Effective management of metastatic melanoma depends on renewed mechanistic understanding underlying melanoma progression and metastasis. The role of exosomes in mediating the interactions between cancer cells and the metastatic microenvironment is at the forefront of cancer research. Previous researches on the function of exosomes in metastasis have been primarily focused on tumor cell-derived exosomes in modifying the biological functions of stromal cells. Whether the cancer cells at the involved organ can modify the metastatic capability of each other has not been demonstrated. In this study, a paired M14 melanoma derivative cell line, i.e., M14-OL and POL, that we established and characterized were employed. Oligo-metastatic (M14-OL) and poly-metastatic (M14-POL) cell line were generated from three consecutive rounds of in vivo selection and passage. They exhibit high (POL cells) and low (OL cells) metastatic colonization efficiency in vivo, respectively. We show that exosomal crosstalk between metastatic cancer cells is a new mechanism of cancer metastasis. High-metastatic melanoma cells (POL) can augment the metastatic colonization capability of the low-metastatic melanoma cells (OL). POL achieves this goal by utilizing its exosomes to deliver functional miRNAs, in this case, miR-411-5p, to the OL cell. Upon entering OL cells, exosomal miR-411-5p enhance metastatic colonization efficiency by activation of the ERK signaling pathway. Moreover, miR-411-5p expression is higher in cancer tissues of other cancer types (colon, lung, rectum) compared with that of respective normal tissues. The clinical relevance of the present finding merits future investigations.

Low-metastatic melanoma cells acquire enhanced metastatic capability via exosomal transfer of miR-199a-1-5p from highly metastatic melanoma cells.

The mean survival of metastatic melanoma is less than 1 year. While the high mortality rate is associated with the efficient metastatic colonization of the involved organs, the underlying mechanisms remain elusive. The role of exosomes in facilitating the interactions between cancer cells and the metastatic microenvironment has received increasing attention. Previous studies on the role of exosomes in metastasis have been heavily focused on cancer cell-derived exosomes in modulating the functions of stromal cells. Whether the extravasated neighboring cancer cells at the distant organ can alter the metastatic properties of one another, a new mechanism of metastatic colonization, has not been demonstrated prior to this report. In this study, a paired M4 melanoma derivative cell lines, i.e., M14-OL and POL, that we established and characterized were employed. They exhibit high (POL cells) and low (OL cells) metastatic colonization efficiency in vivo, respectively. We show that exosomal crosstalk between metastatic cancer cells is a new mechanism that underlies cancer metastasis and heterogeneity. Low metastatic melanoma cells (OL) can acquire the "metastatic power" from highly metastatic melanoma cells (POL). POL achieves this goal by utilizing its exosomes to deliver functional miRNAs, such as miR-199a-1-5p, to the targeted OL cell which in turn inactivates cell cycle inhibitor CDKN1B and augments metastatic colonization.

Extracellular vesicles microRNA-592 of melanoma stem cells promotes metastasis through activation of MAPK/ERK signaling pathway by targeting PTPN7 in non-stemness melanoma cells.

Melanoma, one of the most aggressive malignancies, its high mortality and low survival rates are associated with effective metastatic colonization. Melanoma metastasis hinges on the bidirectional cell-cell communication within the complex metastatic microenvironments (MME). Extracellular vesicles (EVs) are recognized as a new class of molecular mediator in MME programing. Published studies show that melanoma EVs can educate MME stromal cells to acquire the pro-metastatic phenotype to enhance metastatic colonization. Whether EVs can mediate the interactions between heterogenous cancer cells within the MME that alter the course of metastasis has not been investigated at the mechanistic level. In this study, melanoma parental cells (MPCs) and paired derivative cancer stem cell line melanoma stem cells (MSCs) that were derived from melanoma cell line M14 were used. We demonstrate that the EVs-mediated crosstalk between the MSCs and the MPCs is a novel mechanism for melanoma metastasis. We characterized miR-592, a relatively novel microRNA of prognostic potential, in mediation of such intercellular crosstalk. EVs can encapsulate and deliver miR-592 to target MPCs. Upon entering, miR-592 inhibits the expression of its gene target protein tyrosine phosphatase non-receptor type7 (PTPN7), a phosphatase targeting MAPKs. This leads to the relief of the inhibitory effect of PTPN7 on MAPK/ERK signaling and consequently the augmentation of metastatic colonization of MPCs. Thus, via the extracellular vesicle miR-592/PTPN7/MAPK axis, melanoma-CSCs can transfer their metastatic ability to the low-metastatic non-CSC melanoma cells.

Validation of the Chinese Version of the Procrastination at Work Scale.

The purpose of this study was to validate the Chinese version of the Procrastination at Work Scale (PAWS), a recently developed scale aimed at assessing procrastination in the work context. We translated the PAWS into Chinese and conducted exploratory factor analysis on participants in sample A (N = 236), resulting in a two-factor solution consistent with the original PAWS. In sample B (N = 227), confirmatory factor analysis showed that a two-factor, bifactor model fit the data best. Configural, metric, and scalar invariance models were tested, which demonstrated that the Chinese version of the PAWS did not differ across groups by gender, age, education, or job position. Validity testing demonstrated that the scale relates to work engagement, counterproductive work behavior, task performance, workplace well-being, and organizational commitment. This study indicated that the Chinese version of the PAWS could be used in future research to measure procrastination at work in China.

Autophagy augments the self-renewal of lung cancer stem cells by the degradation of ubiquitinated p53.

It has been postulated that cancer stem cells (CSCs) are involved in all aspects of human cancer, although the mechanisms governing the regulation of CSC self-renewal in the cancer state remain poorly defined. In the literature, both the pro- and anti-oncogenic activities of autophagy have been demonstrated and are context-dependent. Mounting evidence has shown augmentation of CSC stemness by autophagy, yet mechanistic characterization and understanding are lacking. In the present study, by generating stable human lung CSC cell lines with the wild-type TP53 (A549), as well as cell lines in which TP53 was deleted (H1229), we show, for the first time, that autophagy augments the stemness of lung CSCs by degrading ubiquitinated p53. Furthermore, Zeb1 is required for TP53 regulation of CSC self-renewal. Moreover, TCGA data mining and analysis show that Atg5 and Zeb1 are poor prognostic markers of lung cancer. In summary, this study has elucidated a new CSC-based mechanism underlying the oncogenic activity of autophagy and the tumor suppressor activity of p53 in cancer, i.e., CSCs can exploit the autophagy-p53-Zeb1 axis for self-renewal, oncogenesis, and progression.

SEC23A Is an Independent Prognostic Biomarker in Bladder Cancer Correlated With MAPK Signaling.

Clinical data mining and bioinformatics analysis can be employed effectively to elucidate the function and underlying mechanisms of the gene of interest. Here, we have proposed a framework for the identification and validation of independent biomarkers in human cancer and for mechanistic profiling using gene sets enrichment analysis and pathway analysis. This is followed by validation with in vitro experiments. Using this framework to analyze the clinical relevance of SEC23A, we have discovered the prognostic potential of SEC23A in different cancers and identified SEC23A as an independent prognostic factor for poor prognosis in bladder cancer, which implicates SEC23A, for the first time, as an oncogene. Bioinformatic analyses have elucidated an association between SEC23A expression and the upregulation of the MAPK signaling pathway. Using the T24 human bladder cell line, we confirmed that knockdown of SEC23A expression could effectively impact the MAPK signaling pathway. Further, through PCR verification, we showed that MEF2A, one of the key genes of the MAPK signaling pathway, might be a downstream factor of the SEC23A gene.

The mitochondrial fission factor FIS1 promotes stemness of human lung cancer stem cells via mitophagy.

Mitophagy, a form of autophagy, plays a role in cancer development, progression and recurrence. Cancer stem cells (CSCs) also play a key role in these processes, although it not known whether mitophagy can regulate the stemness of CSCs. Here, we employed the A549-SD human non-small cell lung adenocarcinoma CSC model that we have developed and characterized to investigate the effect of mitophagy on the stemness of CSCs. We observed a positive relationship between mitophagic activity and the stemness of lung CSCs. At the mechanistic level, our results suggest that augmentation of mitophagy in lung CSCs can be induced by FIS1 through mitochondrial fission. In addition, we assessed the clinical relevance of FIS1 in lung adenocarcinoma using The Cancer Genome Atlas database. An elevation in FIS1, when observed together with other prognostic markers for lung cancer progression, was found to correlate with shorter overall survival.