n, we reveal that elevated Mgll levels in cultured adult NPCs from both 3xTg-AD and CbpS436A animal models are responsible for their NPC neuronal differentiation deficits. Conclusion Our findings set the stage for development of a clinical protocol where Mgll would serve as a biomarker in early stages of AD to identify potential metformin-responsive AD patients to restore their neurogenesis and spatial memory.Fluorescence microscopy is widely used for high content screening in 2D cell cultures and 3D models. In particular, 3D tissue models are gaining major relevance in modern drug development. Enabling direct multiparametric evaluation of complex samples, fluorescence lifetime imaging (FLIM) adds a further level to intensity imaging by the sensitivity of the fluorescence lifetime to the microenvironment. However, the use of FLIM is limited amongst others by the acquisition of sufficient photon numbers without phototoxic effects in live cells. Herein, we developed a new cluster-based analysis method to enhance insight, and significantly speed up analysis and measurement time for the accurate translation of fluorescence lifetime information into pharmacological pathways. Methods We applied a fluorescently-labeled dendritic core-multishell nanocarrier and its cargo Bodipy as molecules of interest (MOI) to human cells and reconstructed human tissue. Following the sensitivity and specificity assessment of the fitting-al resolution at short exposure times and low fluorophore concentrations. Thereby, Cluster-FLIM increases the applicability of FLIM in high content analysis of target molecules in drug development and beyond.Temperate phages integrated with clustered regularly interspaced short palindromic repeat (CRISPR)/Cas systems have been gaining attention as potential strategies for combating bacteria resistant to antimicrobials. To further advance this technology, phage recombination procedure should be improved, and the bactericidal effect should be examined in detail and compared with conventional lytic phage strategy. The possibility of the emergence of mutational resistance, a phenomenon commonly observed with lytic phage therapy, should be illustrated. Methods Here, we developed a novel one-step cloning method to fulfil the recombination of CRISPR/Cas9 system within the genome of a new isolated lysogenic Escherichia coli phage. Then, we proposed and developed a phage-delivered resistance eradication with subsequent antibiotic treatment (PRESA) strategy. The removal efficiency and antimicrobial effect of the plasmids were analysed. Long-term antimicrobial effect was evaluated by continued OD600 monitoring for 240 hoursd inhibition effect against resistant bacteria. By restoring the efficacy of low-cost antibiotics, PRESA could be developed as an efficient and economical therapy for infections of antibiotic resistant bacteria.Multifunctional magnetic nanoparticles and derivative nanocomposites have aroused great concern for multimode imaging and cancer synergistic therapies in recent years. Among the rest, functional magnetic iron oxide nanoparticles (Fe3O4 NPs) have shown great potential as an advanced platform because of their inherent magnetic resonance imaging (MRI), biocatalytic activity (nanozyme), magnetic hyperthermia treatment (MHT), photo-responsive therapy and drug delivery for chemotherapy and gene therapy. Magnetic Fe3O4 NPs can be synthesized through several methods and easily surface modified with biocompatible materials or active targeting moieties. The MRI capacity could be appropriately modulated to induce response between T 1 and T 2 modes by controlling the size distribution of Fe3O4 NPs. selleck chemicals Besides, small-size nanoparticles are also desired due to the enhanced permeation and retention (EPR) effect, thus the imaging and therapeutic efficiency of Fe3O4 NP-based platforms can be further improved. Here, we firstly retrospect the typical synthesis and surface modification methods of magnetic Fe3O4 NPs. Then, the latest biomedical application including responsive MRI, multimodal imaging, nanozyme, MHT, photo-responsive therapy and drug delivery, the mechanism of corresponding treatments and cooperation therapeutics of multifunctional Fe3O4 NPs are also be explained. Finally, we also outline a brief discussion and perspective on the possibility of further clinical translations of these multifunctional nanomaterials. This review would provide a comprehensive reference for readers to understand the multifunctional Fe3O4 NPs in cancer diagnosis and treatment.Despite the recent advances in the treatment of cancers, acquired drug resistance remains a major challenge in cancer management. While earlier studies suggest Darwinian factors driving acquired drug resistance, recent studies point to a more dynamic process involving phenotypic plasticity and tumor heterogeneity in the evolution of acquired drug resistance. Chronic stress after drug treatment induces intrinsic cellular reprogramming and cancer stemness through a slow-cycling persister state, which subsequently drives cancer progression. Both epigenetic and metabolic mechanisms play an important role in this dynamic process. In this review, we discuss how epigenetic and metabolic reprogramming leads to stress-induced phenotypic plasticity and acquired drug resistance, and how the two reprogramming mechanisms crosstalk with each other.Although the enzyme catalytic nanoreactors reported so far have achieved excellent therapeutic efficacy, how to accurately exert enzyme activity in the tumor microenvironment to specifically kill tumor cells and avoid systemic oxidative damage would be an inevitable challenge for catalytic nanomedicine. At the present study, we fabricate an advanced biomimetic nanoreactor, SOD-Fe0@Lapa-ZRF for tumor multi-enzyme cascade delivery that combined specifically killing tumor cells and protect cells from oxidative stress. Methods We first synthesized the FeNP-embedded SOD (SOD-Fe0) by reduction reaction using sodium borohydride. Next, SOD-Fe0 and Lapa cargo were encapsulated in ZIF-8 by self-assembly. In order to protect the cargo enzyme from digestion by protease and prolong blood circulating time, SOD-Fe0@Lapa-Z was further cloaked with RBC membrane and functionalized with folate targeting, resulting in the final advanced biomimetic nanoreactor SOD-Fe0@Lapa-ZRF. Results Once internalized, ZIF-8 achieves pH-triggered disassembly in weakly acidic tumor microenvironment.