Selective CH4 oxidation to CH3OH or HCHO with O2 in H2O under mild conditions provides a desired sustainable pathway for synthesis of commodity chemicals. However, manipulating reaction selectivity while maintaining high productivity remains a huge challenge due to the difficulty in the kinetic control of the formation of a desired oxygenate against its overoxidation. Here, we propose a highly efficient strategy, based on the precise control of the type of as-formed radicals by rational design on photocatalysts, to achieve both high selectivity and high productivity of CH3OH and HCHO in CH4 photooxidation for the first time. Through tuning the band structure and the size of active sites (i.e., single atoms or nanoparticles) in our Au/In2O3 catalyst, we show alternative formation of two important radicals, •OOH and •OH, which leads to distinctly different reaction paths to the formation of CH3OH and HCHO, respectively. This approach gives rise to a remarkable HCHO selectivity and yield of 97.62% and 6.09 mmol g–1 on In2O3-supported Au single atoms (Au1/In2O3) and an exceptional CH3OH selectivity and yield of 89.42% and 5.95 mmol g–1 on In2O3-supported Au nanoparticles (AuNPs/In2O3), respectively, upon photocatalytic CH4 oxidation for 3 h at room temperature. This work opens a new avenue toward efficient and selective CH4 oxidation by delicate design of composite photocatalysts.

Purpose: To investigate the expression of myeloid differentiation factor 88 (MyD88) in hepatocellular carcinoma (HCC) and its prognostic value in patients with HCC.Experimental Design: Expression of MyD88 was detected by immunohistochemistry in surgical HCC specimens (n ¼ 110). The correlation of MyD88 expression to clinicopathologic characteristics was analyzed. The involvement of MyD88 in tumor growth and invasion was investigated.Results: The expression of MyD88 was significantly higher in HCC tumors than that in adjacent nontumor tissues. Particularly, high expression of MyD88 was found in HCCs with late tumor stage (P ¼ 0.029). Patients with high MyD88 staining revealed a higher recurrence rate (65% vs. 40%; P ¼ 0.008). Kaplan-Meier analysis showed that recurrence-free survival (RFS; P ¼ 0.011) and overall survival (OS; P ¼ 0.022) were significantly worse among patients with high MyD88 staining. Univariate and multivariate analyses revealed that MyD88 was an independent predictor for OS and RFS. Ectopic expression of MyD88 promoted HCC cell proliferation and invasion in vitro. Suppression of MyD88 expression with lentivirus encoding short hairpin RNA reduced tumor growth and invasion, as well as lung metastasis. Finally, silencing of MyD88 inhibited the activation of NF-kB and AKT in HCC cells, whereas forced expression of MyD88 was able to enhance the activation of NF-kB and p38/extracellular signal-regulated kinase without Toll-like receptor/interleukin-1 receptor (TLR/IL-1R) signaling.Conclusion: Elevated expression of MyD88 may promote tumor growth and metastasis via both TLR/IL-1R-dependent and -independent signaling and may serve as a biomarker for prognosis of patients with HCC.

There is increasing evidence to suggest that hepatocellular carcinomas (HCCs) are sustained by a distinct subpopulation of self-renewing cells known as cancer stem cells. However, the precise signals required for maintenance of stemness-like properties of these cells are yet to be elucidated. Here, we demonstrated that the level of oncoprotein osteopontin (OPN) in tumor cells of the edge of bulk tumors was significantly correlated with the clinical prognosis of patients with HCC. OPN was highly expressed in side population fractions of HCC cell lines, as well as in dormant cells, spheroids and chemo-resistant cancer cells, all of which are considered as having stemness-like cellular features. Depletion of OPN in HCC cell lines resulted in a reduction in the proportion of side population fractions, formation of hepato-spheroids, expression of stem-cell-associated genes and decreased tumorigenecity in immunodeficient mice. Mechanistically, OPN was demonstrated to bind to integrin αvβ3 and activate the transcription factor NF-κB, which resulted in upregulation of HIF-1α transcription and its downstream gene, BMI1, to mediate maintenance of the stemness-like phenotype. Suppression of the αvβ3–NF-κB–HIF-1α pathway decreased OPN-mediated self-renewal capabilities. Levels of OPN protein expression were significantly correlated with HIF-1α protein levels in HCC tumor tissue samples. OPN might promote a cancer stem cell-like phenotype via the αvβ3–NF-κB–HIF-1α pathway. Our findings offer strong support for OPN requirement in maintaining stem-like properties in HCC cells.

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