Interfacial Se–O Bonds Modulating Spatial Charge Distribution in FeSe₂/Nb:Fe₂O₃ with Rapid Hole Extraction for Efficient Photoelectrochemical Water Oxidation

Surface engineering is an effective strategy to improve the photoelectrochemical (PEC) catalytic activity of hematite, and the defect states with abundant coordinative unsaturation atoms can serve as anchoring sites for constructing intimate connections between semiconductors. On this basis, we anchored an ultrathin FeSe2 layer on Nb5+-doped Fe2O3 (FeSe2/Nb:Fe2O3) via interfacial Se–O chemical bonds to tune the surface potential. Density functional theory (DFT) calculations indicate that amorphous FeSe2 decoration could generate electron delocalization over the composite photoanodes so that the electron mobility was improved to a large extent. Furthermore, electrons could be transferred via the newly formed Se–O bonds at the interface and holes were collected at the surface of electrode for PEC water oxidation. The desired charge redistribution is in favor of suppressing charge recombination and extracting effective holes. Later, work function calculations and Mott–Schottky (M–S) plots demonstrate that a type-II heterojunction was formed in FeSe2/Nb:Fe2O3, which further expedited carrier separation. Except for spatial carrier modulation, the amorphous FeSe2 layer also provided abundant active sites for intermediates adsorption according to the d band center results. In consequence, the target photoanodes attained an improved photocurrent density of 2.42 mA cm–2 at 1.23 V versus the reversible hydrogen electrode (RHE), 2.5 times as that of the bare Fe2O3. This study proposed a defect-anchoring method to grow a close-connected layer via interfacial chemical bonds and revealed the spatial charge distribution effects of FeSe2 on Nb:Fe2O3, giving insights into rational designation in composite photoanodes

Co-Catalyzed Dual C5/C8–H Bond Functionalization of Imidazo[1,2<i>-a</i>]pyrazines with Disulfides and Grignard Reagents

An efficient difunctionalization at C5/C8 of imidazo[1,2-a]pyrazines has been developed using disulfides and Grignard reagents under cheap cobalt catalysis. This one-pot, two-step, three-component transformation is performed under mild conditions; various Grignard reagents (aryl and alkyl) and disulfides are tolerated. Mechanistic studies and control experiments demonstrate this reaction proceeded via an anionic intermediate

Co-Catalyzed Dual C5/C8–H Bond Functionalization of Imidazo[1,2<i>-a</i>]pyrazines with Disulfides and Grignard Reagents

An efficient difunctionalization at C5/C8 of imidazo[1,2-a]pyrazines has been developed using disulfides and Grignard reagents under cheap cobalt catalysis. This one-pot, two-step, three-component transformation is performed under mild conditions; various Grignard reagents (aryl and alkyl) and disulfides are tolerated. Mechanistic studies and control experiments demonstrate this reaction proceeded via an anionic intermediate

DataSheet_1_Lactate increases tumor malignancy by promoting tumor small extracellular vesicles production via the GPR81-cAMP-PKA-HIF-1α axis.docx

Lactate and tumor cell-derived extracellular vesicles (TEVs) both contribute to tumor progression. However, it is still unclear whether lactate can accelerate tumor development by directly promoting TEV production. Here, we show that lactate decreases intracellular cAMP levels and subsequent PKA activation via GPR81, which inhibits the PKA-induced ubiquitination of HIF-1α that causes degradation. Then, the HIF-1α-mediated transcription of Rab27a is enhanced, leading to increased TEV release. In this way, lactate promotes lung metastasis by murine melanoma. In addition, we show that serum lactate levels are positively correlated with serum EV levels and Rab27a and HIF-1α protein levels in the tumor tissues of lung cancer patients. Thus, our results reveal a novel mechanism underlying lactate-mediated tumor progression induced by TEVs and provide new strategies for tumor therapy.</p

Activation of Fas signaling upregulated Fascin expression in AGS cells through activation of STAT3.

<p>The AGS cells were stimulated with 5 μg/ml of anti-Fas in the indicated times. (A) The phosphorylated STAT3 was detected by Western blot. (B) The expression of Fascin mRNA was assayed by real-time PCR. (C) After stimulation with 5 μg/ml anti-Fas for 24 h, the protein level of phosphorylated STAT3 and Fascin in AGS cells was detected by Western blot. (D) The AGS cells were pre-treated with 10 μM of Stattic for 2 h and followed by 5 μg/ml of anti-Fas stimulation for 24 h; the protein level of phosphorylated STAT3 and Fascin was detected by Western blot. After transfection with STAT3 siRNA or NC siRNA for 36 h, (E) the STAT3 expression in the AGS cells was detected by Western blot; (F) the AGS cells were then stimulated with 5 μg/ml of anti-Fas for 2 h, and the Fascin expression in the cells was detected by Western blot. Data are representative of three independent experiments.</p

Activation of Fas signaling promotes the migration of GC cells.

<p>(A) The Fas expression in AGS and MNK-45 cells were detected by real-time PCR (upper) and Western blot (down). (B) Susceptibility of AGS and MNK-45 cells to Fas-induced apoptosis was measured by staining with Annexin V and PI after both cells were stimulated with anti-Fas or ISO at the indicated concentrations for 24 h (left) and the apoptotic cells were statistically analyzed (right) (n = 3). (C) After stimulated with 5 μg/ml anti-Fas or ISO for 2 h, the AGS cells were collected and seeded into the top chamber. Forty-eight hours later, the number of cells on the bottom of the Transwell filter was imaged (left) and quantified (right) (n = 5). Magnification: 200×. (D) The proliferation of AGS cells was measured by CCK8 assay after stimulation with 5 μg/ml of anti-Fas or ISO in the indicated timepoint. Data are representative of three independent experiments. (*p <0.05, ***p <0.001)</p

Correlation of the mRNA levels of Fas and Fascin in tumor tissues from GC patients.

<p>Fas and Fascin mRNA expression was measured by real-time PCR and normalized to β-actin mRNA (n = 23). Positive correlation was obtained by Spearman correlation analysis.</p

Fas signaling promotes AGS cell metastasis <i>in vivo</i> through STAT3/Fascin pathway.

<p>2 × 10⁶ AGS tumor cells pre-stimulated with anti-Fas or ISO for 2 h were intravenously injected nude mice. (A) The number of lung tumor foci was counted (n = 5). (B) The expression of Fascin in tumor tissues from lung was detected by immunohistochemistry. 2 × 10⁶ AGS tumor cells were intravenously injected into nude mice and 24 h later, the mice received intravenous injection of S3I-201 at 5 mg/kg every 2 days for total 3 times. (C) The number of lung tumor foci was counted (n = 5). (D) The expression of Fascin in tumor tissues from lung was detected by immunohistochemistry (magnification: ×100). Data are representative of two independent experiments. (*p <0.05, ***p <0.001)</p

Patient characteristics.

<p>NOTE: Data are mean ± standard deviation.</p><p>*According to American Joint Committee on Cancer.</p><p>Abbreviation: ECOG PS, Eastern Cooperative Oncology Group Performance Status.</p><p>Patient characteristics.</p

Fas signaling promoted AGS cell migration dependent on STAT3/Fascin pathway.

<p>(A) AGS cells were transfected with Fascin siRNA or NC siRNA for 36 h, and Fascin expression in the cells was detected by Western blot. After (B) inhibition of Fascin expression by siRNA; or (C) treated with 10 μM Stattic for 2 h; or (D) inhibition of STAT3 expression by siRNA, and stimulated with 5 μg/ml of anti-Fas for 2 h, the number of AGS cells which migrated to the bottom of the Transwell filter was quantified (n = 5). Data are representative of three independent experiments. (**p <0.01)</p