Up-regulated ORC1 promotes lung adenocarcinoma by inhibiting ferroptosis via SLC7A11 dependent pathway.

Background: Lung adenocarcinoma (LUAD) is a pulmonary malignant disease that poses a high risk of mortality and morbidity. Previous study indicated that ORC1 plays an oncogenic function. However, the precise regulatory function that ORC1 serves in the progression of LUAD is still not clearly known. Methods: Bioinformatics analyses were performed using TCGA and GEO datasets. The human LUAD cell line NCIH1355, NCIH1568 as well as BEAS-2B cell line (human normal lung epithelial cell) were utilized for in vitro study. LUAD cell proliferation were determined via CCK-8 assays and RT-qPCR for ki-67. The relation of ORC1 and SLC7A11 was detected by Western blot and qPCR with or without sh-RNA. The expression level ACSL4, the biomarker of ferroptosis, were detected using RT-qPCR. Results: ORC1 and SLC7A11 exhibit high expression levels in both LUAD patients and cell lines, and are strongly associated with poor prognosis. In vitro experiments demonstrate that ORC1 and SLC7A11 promote proliferation of LUAD cell lines while inhibiting gefitinib-induced ferroptosis. Additionally, the function of ORC1 in LUAD cells is dependent on SLC7A11. Conclusion: ORC1 promotes LUAD cell proliferation and inhibits ferroptosis in a SLC7A11-dependent manner. This implies that ORC1 could potentially serve as a useful diagnosis biomarker and treatment target.

Erbium Single Atom Composite Photocatalysts for Reduction of CO2 under Visible Light: CO2 Molecular Activation and 4f Levels as an Electron Transport Bridge.

It is still challenging to design a stable and efficient catalyst for visible-light CO2 reduction. Here, Er3+ single atom composite photocatalysts are successfully constructed based on both the special role of Er3+ and the special advantages of Zn2 GeO4 /g-C3 N4 heterojunction in the photocatalysis reduction of CO2 . Especially, Zn2 GeO4 :Er3+ /g-C3 N4 obtained by in situ synthesis is not only more conducive to the tight junction of Zn2 GeO4 and g-C3 N4 , but also more favorable for g-C3 N4 to anchor rare-earth atoms. Under visible-light irradiation, Zn2 GeO4 :Er3+ /g-C3 N4 shows more than five times enhancement in the catalytic efficiency compared to that of pure g-C3 N4 without any sacrificial agent in the photocatalytic reaction system. A series of theoretical and experimental results show that the charge density around Er, Ge, Zn, and O increases compared with Zn2 GeO4 :Er3+ , while the charge density around C decreases compared with g-C3 N4 . These results show that an efficient way of electron transfer is provided to promote charge separation, and the dual functions of CO2 molecular activation of Er3+ single atom and 4f levels as electron transport bridge are fully exploited. The pattern of combining single-atom catalysis and heterojunction opens up new methods for enhancing photocatalytic activity.

Aminoantipyrine based efficient chemosensor for Zn(II) ions and its effectiveness in live cell imaging.

A simple imine based receptor NA-1 has been synthesized for detection of Zinc ions. Probe NA-1 showed the selective colorimetric changes with Zinc (II) ions whereas other metal ions didn't showed any observable colorimetric changes. The probe showed the very selective turn-on fluorescence response with Zn(II) ions among other rival metal ions like Cd(II) and Hg(II). The mode of binding was studied by 1H-nmr titrations and fluorescence spectroscopy. Jobs plot analysis confirming that the probe NA-1 forms 1:1 complex with Zn(II). The observed fluorescence and absorption change further supported by theoretical calculations. The turn-on fluorescence of the probe NA-1 is probably attributable to the interruption of intramolecular charge transfer as well as ESIPT. The limit of detection of the probe for Zn(II) sensing is in the range of 14 nano molar. Cytotoxicity (MTT) assay of the probe in live HeLa cells is showing that the probe is least toxic to cells. The probe NA-1 is effectively applied to detect Zn(II) ions in HeLa cells and suggesting the probe is NA-l permeable to cell wall and viable for Zinc(II) ions imaging in live cells.

Depletion of SIRT7 sensitizes human non-small cell lung cancer cells to gemcitabine therapy by inhibiting autophagy.

Anti-metabolic therapy, as a major chemotherapy, is an important option in the treatment of lung cancer. However, tumor resistance to cytotoxic chemotherapy has become more common. It has been reported that autophagy is one of the processes contributing to such resistance. In our study, we find that SIRT7 protein level elevated dramatically in response to an anti-metabolic drug-gemcitabine treatment. Moreover, autophagy induced by gemcitabine in non-small cell lung cancer cells is SIRT7-dependent. Furthermore, depletion of SIRT7 promoted Gemcitabine-induced cell death. Our report also shows that SIRT7 knockdown markedly improves the anti-tumor activity of gemcitabine treatment in mice. These results suggest that SIRT7-elicits an autophagic response that plays a protective role against cell death and the SIRT7-inhibition has a potential to improve the efficacy of anti-metabolic therapy in non-small cell lung cancer cells.