PMS2 amplification contributes brain metastasis from lung cancer.

BACKGROUND: Lung adenocarcinoma metastasizing to the brain results in a notable increase in patient mortality. The high incidence and its impact on survival presents a critical unmet need to develop an improved understanding of its mechanisms. METHODS: To identify genes that drive brain metastasis of tumor cells, we collected cerebrospinal fluid samples and paired plasma samples from 114 lung adenocarcinoma patients with brain metastasis and performed 168 panel-targeted gene sequencing. We examined the biological behavior of PMS2 (PMS1 Homolog 2)-amplified lung cancer cell lines through wound healing assays and migration assays. In vivo imaging techniques are used to detect fluorescent signals that colonize the mouse brain. RNA sequencing was used to compare differentially expressed genes between PMS2 amplification and wild-type lung cancer cell lines. RESULTS: We discovered that PMS2 amplification was a plausible candidate driver of brain metastasis. Via in vivo and in vitro assays, we validated that PMS2 amplified PC-9 and LLC lung cancer cells had strong migration and invasion capabilities. The functional pathway of PMS2 amplification of lung cancer cells is mainly enriched in thiamine, butanoate, glutathione metabolism. CONCLUSION: Tumor cells elevated expression of PMS2 possess the capacity to augment the metastatic potential of lung cancer and establish colonies within the brain through metabolism pathways.

A near-infrared fluorescent probe with two-photon excitation for in situ imaging of NQO1 in human colorectum cancer tissue.

Colorectum cancer has become one of the most fatal cancer diseases, in which NAD(P)H: quinone oxidoreductase 1 (NQO1) plays a role in intracellular free radical reduction and detoxification and has been linked to colorectum cancer and chemotherapy resistance. Therefore, rational design of optical probe for NQO1 detection is urgent for the early diagnosis of colorectum cancer. Herein, we have developed a novel two-photon fluorescent probe, WHFD, which is capable of selectively detecting of intracellular NQO1 with two-photon (TP) absorption (800 nm) and near-infrared emission (620 nm). Combination with a substantial Stokes shift (175 nm) and biocompatibility, we have assessed its suitability for in vivo imaging of endogenous NQO1 activities from HepG2 tumor-bearing live animals with high tissue penetration up to 300 µm. Particularly, we for the first time used the probe to image NQO1 activities from human colorectum cancer samples by using TP microscopy, and proving our probe possesses reliable diagnostic performance to directly in situ imaging of cancer biomarker and can clearly distinguish the boundary between human colorectum cancer tissue and their surrounding normal tissue, which shows great potential for the intraoperative navigation.

High selective electrocatalytic reduction of carbon dioxide to ethylene enabled by regulating the microenvironment over Cu-Ag nanowires.

Copper-based tandem catalysts are effective candidates for yielding multi-carbon (C2+) products in electrochemical reduction of carbon dioxide (CO2RR). However, these catalysts still face a significant challenge regarding in the low selectivity for the production of a specific product. In this study, we report a high selectivity of 77.8 %±2 % at -1.0 V (vs RHE) for the production of C2H4 by using a Cu88Ag12NW catalyst which is primarily prepared through a combined Cu-Ag co-deposition and wet chemical method, employing an attractive strategy focused on regulating the microenvironment over Cu-Ag nanowires. The experimental and computational studies show that the higher *CO coverage and lower intermediate adsorption energy are important reasons for achieving the high C2H4 selectivity of Cu88Ag12NW catalyst. Comsol simulation results indicate that dense nanowires exhibit a nano-limiting effect on OH- ions, thereby leading to an increase in local pH and promoting coupling reactions. The catalyst demonstrates no noticeable decrease in current density or selectivity even after 12 h of continuous operation. The Cu-Ag nanowire composite exhibits remarkable catalytic activity, superior faradaic efficiency, excellent stability, and easy synthesis, which highlights its significant potential for electro-reducing carbon dioxide into valuable products.