Nanoscale Spatiotemporal Dynamics of Microbial Adhesion: Unveiling Stepwise Transitions with Plasmonic Imaging.

Understanding bacterial adhesion at the nanoscale is crucial for elucidating biofilm formation, enhancing biosensor performance, and designing advanced biomaterials. However, the dynamics of the critical transition from reversible to irreversible adhesion has remained elusive due to analytical constraints. Here, we probed this adhesion transition, unveiling nanoscale, step-like bacterial approaches to substrates using a plasmonic imaging technique. This method reveals the discontinuous nature of adhesion, emphasizing the complex interplay between bacterial extracellular polymeric substances (EPS) and substrates. Our findings not only deepen our understanding of bacterial adhesion but also have significant implications for the development of theoretical models for biofilm management. By elucidating these nanoscale step-like adhesion processes, our work provides avenues for the application of nanotechnology in biosensing, biofilm control, and the creation of biomimetic materials.

Lansoprazole (LPZ) reverses multidrug resistance (MDR) in cancer through impeding ATP-binding cassette (ABC) transporter-mediated chemotherapeutic drug efflux and lysosomal sequestration.

AIMS: Lansoprazole is one of the many proton pump inhibitors (PPIs) that acts more strongly with ABCB1 and ABCG2. The present study is to investigate the potential of lansoprazole on reversal of ABCB1/G2-mediated MDR in cancer, in vitro and in vivo. METHODS: Reversal studies and combination evaluation were conducted to determine the synergistic anti-MDR effects on lansoprazole. Lysosomal staining was used to determination of lansoprazole on ABCB1-mediated lysosomal sequestration. Substrate accumulation and efflux assays, ATPase activity, and molecular docking were conducted to evaluate lansoprazole on ABCB1/G2 functions. Western blot and immunofluorescence were used to detect lansoprazole on ABCB1/G2 expression and subcellular localization. MDR nude mice models were established to evaluate the effects of lansoprazole on MDR in vivo. RESULTS: Lansoprazole attenuated ABCB1/G2-mediated MDR and exhibited synergistic effects with substrate drugs in MDR cells. In vivo experiments demonstrated that lansoprazole attenuated ABCB1/G2-mediated MDR and exhibited synergistic effects that augmented the sensitivity of substrate anticancer drugs in ABCB1/G2-mediated settings without obvious toxicity. Lansoprazole impeded lysosomal sequestration mediated by ABCB1, leading to a substantial increase in intracellular accumulation of substrate drugs. The effects of lansoprazole were not attributable to downregulation or alterations in subcellular localization of ABCB1/G2. Lansoprazole promoted the ATPase activity of ABCB1/G2 and competitively bound to the substrate-binding region of ABCB1/G2. CONCLUSIONS: These findings present novel therapeutic avenues whereby the combination of lansoprazole and chemotherapeutic agents mitigates MDR mediated by ABCB1/G2 overexpression.

Early changes in cardiac troponin T and NT-proBNP levels in neonates receiving ECMO support: a single-center experience.

OBJECTIVE: This study aimed to examine the changes in absolute value and decline rate of early serum cardiac troponin T (cTnT) and N-terminal pro b-type natriuretic peptide (NT-proBNP) in neonates who received veno-arterial (V-A) extracorporeal membrane oxygenation (ECMO) support therapy within the first week of life. METHODS: We retrospectively collected clinical data and laboratory test results of 18 neonates who underwent V-A ECMO support within one week of birth, from July 2021 to June 2023, using the electronic medical record system. These patients were categorized into survival and death groups. Comparative analyses of the absolute values and decline rates of cTnT and NT-proBNP were made between the groups at baseline, and at 24, 48, and 72 h post-ECMO initiation. RESULTS: Out of the 18 neonates, 12 survived (survival rate: 66.7%), while 6 succumbed. The survival group exhibited significantly lower absolute values of cTnT and NT-proBNP than the death group, and their decline rates were significantly higher. Notably, all neonates without an early decline in cTnT and NT-proBNP levels were in the death group. CONCLUSION: The early changes in the absolute value and decline rate of serum cTnT and NT-proBNP in neonates undergoing V-A ECMO may serve as predictors of their prognosis.

Formyl phloroglucinol meroterpenoids from the leaves of Eucalyptus globulus subsp. maidenii and their ATP-citrate lyase inhibitory activities.

Three new formyl phloroglucinol meroterpenoids, eumaidials A-C (1-3), were isolated from the leaves of Eucalyptus globulus subsp. maidenii, along with ten known analogues (4-13). Their chemical structures were determined by various spectral data and electronic circular dichroism calculations. Eumaidial A (1) is the first ß-caryophyllene-based formyl phloroglucinol meroterpenoids from the genus Eucalyptus. Compounds 1-4 and 10 exhibited ATP-citrate lyase inhibitory activities, and compounds 2 and 3 suppressed the hepatocyte lipogenesis.

miR-204 suppresses cancer stemness and enhances osimertinib sensitivity in non-small cell lung cancer by targeting CD44.

Osimertinib is an effective treatment option for patients with advanced non-small cell lung cancer (NSCLC) with EGFR activation or T790M resistance mutations; however, acquired resistance to osimertinib can still develop. This study explored novel miRNA-mRNA regulatory mechanisms that contribute to osimertinib resistance in lung cancer. We found that miR-204 expression in osimertinib-resistant lung cancer cells was markedly reduced compared to that in osimertinib-sensitive parental cells. miR-204 expression levels in cancer cells isolated from treatment-naive pleural effusions were significantly higher than those in cells with acquired resistance to osimertinib. miR-204 enhanced the sensitivity of lung cancer cells to osimertinib and suppressed spheroid formation, migration, and invasion of lung cancer cells. Increased miR-204 expression in osimertinib-resistant cells reversed resistance to osimertinib and enhanced osimertinib-induced apoptosis by upregulating BIM expression levels and activating caspases. Restoration of CD44 (the direct downstream target gene of miR-204) expression reversed the effects of miR-204 on osimertinib sensitivity, recovered cancer stem cell and mesenchymal markers, and suppressed E-cadherin expression. The study demonstrates that miR-204 reduced cancer stemness and epithelial-to-mesenchymal transition, thus overcoming osimertinib resistance in lung cancer by inhibiting the CD44 signaling pathway.