Loosely Sandwich-Structured Membranes Decorated with UiO-66-NH2 for Efficient Antibiotic Separation and Organic Solvent Resistance.

Thin-film nanocomposite (TFN) membranes with efficient molecular separation and organic solvent resistance are active in demand in wastewater treatment and resource reclamation, meeting the goal of emission peaks and carbon neutrality. In this work, a simple and rational design strategy has been employed to construct a sandwich-structured membrane for removing fluoroquinolone antibiotics and recycling organic solvents. The sandwich-structured membrane is composed of a porous substrate, a hydrophilic tannic acid-polyethyleneimine (TA-PEI) interlayer, and a polyamide (PA) selective layer decorated with metal-organic framework (PA-MOF). Results manifest that the hydrophilic TA-PEI interlayer played a bridging and gutter effect to achieve effective control in amide storage, amine diffusion, and nanomaterial downward leakage at the immiscible interface. The PA-MOF selective layer has been changed to a loosely crumpled surface, endowing functionalities on the sandwich-structured membrane that included limited pores, strengthened electronegativity, and stronger hydrophilicity. Thus, an enhanced water flux of 87.23 ± 7.43 LMH was achieved by the TFN-2 membrane (0.04 mg·mL-1 UiO-66-NH2), which is more than five times that of the thin-film composite membrane (17.46 ± 3.88 LMH). The rejection against norfloxacin, ciprofloxacin, and levofloxacin is 92.94 ± 1.60%, 94.62 ± 1.29%, and 96.92 ± 1.05%, respectively, effectively breaking through the "trade-off" effect between membrane permeability and rejection efficiency. Further antifouling results showed that the sandwich-structured membrane had lower flux decay ratios (3.36∼7.07%) and higher flux recovery ratios (93.40∼98.40%), as well as superior long-term stability after 30 days of filtration. Moreover, organic solvent resistance testing confirms that the sandwich-structured membrane maintained stable solvent flux and better recovery rates in ethanol, acetone, isopropanol, and N,N-dimethylformamide. Detailed nanofiltration mechanism studies revealed that these outstanding performances are based on the joint effect of the TA-PEI interlayer and PA-MOF selective layer, proposing a new perspective to break through the bottleneck of nanofiltration application in a complex environment.

MERTK activation drives osimertinib resistance in EGFR-mutant non-small cell lung cancer.

Acquired resistance is inevitable in non-small cell lung cancers (NSCLCs) treated with osimertinib (OSI), and the mechanisms are not well defined. The MERTK ligand GAS6 promoted downstream oncogenic signaling in EGFR-mutated (EGFRMT) NSCLC cells treated with OSI, suggesting a role for MERTK activation in OSI resistance. Indeed, treatment with MRX-2843, a first-in-class MERTK kinase inhibitor, resensitized GAS6-treated NSCLC cells to OSI. Both GAS6 and EGF stimulated downstream PI3K/AKT and MAPK/ERK signaling in parental cells, but only GAS6 activated these pathways in OSI-resistant (OSIR) derivative cell lines. Functionally, OSIR cells were more sensitive to MRX-2843 than parental cells, suggesting acquired dependence on MERTK signaling. Furthermore, MERTK and/or its ligands were dramatically upregulated in EGFRMT tumors after treatment with OSI in both xenograft models and patient samples, consistent with induction of autocrine/paracrine MERTK activation. Moreover, treatment with MRX-2843 in combination with OSI, but not OSI alone, provided durable suppression of tumor growth in vivo, even after treatment was stopped. These data identify MERTK as a driver of bypass signaling in treatment-naive and EGFRMT-OSIR NSCLC cells and predict that MRX-2843 and OSI combination therapy will provide clinical benefit in patients with EGFRMT NSCLC.

Study on antibiotics, antibiotic resistance genes, bacterial community characteristics and their correlation in the landfill leachates.

AIM: This study aimed to investigate the contamination levels of antibiotics and antibiotic resistance genes (ARGs) in the landfill leachates and their correlations with the bacteria. METHODS AND RESULTS: Using HPLC-MS, quantitative PCR and high-throughput sequencing, we measured the pollution levels of 14 antibiotics and 10 ARGs in the leachates of the landfill in Taiyuan, China, and analysed changes in the bacterial community and the correlations of bacteria with antibiotics and ARGs. The main results showed high levels of antibiotics (like enrofloxacin, pefloxacin and oxytetracycline) and ARGs (like sulfonamides, tetracycline, macrolides, quinolones and ß-lactam-resistance genes) in the landfill leachates, along with higher diversity and richness of the bacteria. Some types of antibiotics had positive correlations with their corresponding ARGs. The dominant bacteria in the landfill leachates were Pseudomonas, Defluviitoga and Sulfurimonas, which correlated with the antibiotics and ARGs and might have potential effects on degrading them. CONCLUSIONS: Antibiotics and ARG pollution existed in the landfill leachates, while bacteria were closely associated with them. SIGNIFICANCE AND IMPACT OF THE STUDY: It will provide helpful information for the potential application of the bacteria in antibiotics and ARGs pollution control and landfill leachate management.