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The emergence of multidrug resistance in Gram-negative pathogens is critically determined by the interplay between efflux pumps activity and low permeation outer membrane. Although phenotypic heterogeneity in isogenic cells is recognized as a key factor of treatment failure, a mathematical framework able to integrate growth dynamics and single-cell heterogeneity in antimicrobial resistance, remains absent. Here we provide such framework that bridges single-cell and colony scales in the context of bacterial survival and efficacy against drugs. Using experimental inputs, our approach produces testable outputs and reveals nontrivial collective effects with key implications for fitness and survival of the colony. This framework provides a mathematical tool to test stress response strategies in organisms that can potentially guide experiments in natural and synthetic cellular systems.Two-dimensional (2D) ferroelectric (FE) hybrid organic-inorganic perovskites (HOIPs) are promising for potential applications as miniaturized flexible ferroelectric/piezoelectric devices. Recently, several 2D HOIPs [e.g., Ruddlensden-Popper type HOIP BA2PbCl4 (BA = C6H5CH2NH3+)] were reported to possess room-temperature ferroelectricity. However, the underlying microscopic mechanisms for ferroelectricity in 2D HOIPs remain elusive. Here, by performing first-principles calculations and symmetry mode analysis, we demonstrate that there exists a cooperative coupling between A-site organic molecules and B-site inorganic Pb2+ ions that is essential to the ferroelectricity in 2D BA2PbCl4. The nonpolar ground state of the closely related compounds BA2PbBr4 and BA2PbI4 can also be explained in terms of the weakened cooperative coupling. We further predict that 2D BA2PbF4 displays in-plane ferroelectricity with a higher Curie temperature and larger electric polarization. selleck inhibitor Our work not only reveals the unusual FE mechanism in 2D HOIPs but also provides a solid theoretical basis for the rational design of 2D multifunctional materials.Bacterial pili are proteinaceous motorized nanomachines that play various functional roles including surface adherence, bacterial motion, and virulence. The surface-contact sensor type IVc (or Tad) pilus is widely distributed in both Gram-positive and Gram-negative bacteria. In Caulobacter crescentus, this nanofilament, though crucial for surface colonization, has never been thoroughly investigated at the molecular level. As Caulobacter assembles several surface appendages at specific stages of the cell cycle, we designed a fluorescence-based screen to selectively study single piliated cells and combined it with atomic force microscopy and genetic manipulation to quantify the nanoscale adhesion of the type IVc pilus to hydrophobic substrates. We demonstrate that this nanofilament exhibits high stickiness compared to the canonical type IVa/b pili, resulting mostly from multiple hydrophobic interactions along the fiber length, and that it features nanospring mechanical properties. Our findings may be helpful to better understand the structure-function relationship of bacterial pilus nanomachines.The design of solid polymer electrolytes (SPE) with high ionic conductivity and excellent mechanical properties is challenging because these two properties are often conflicting. To achieve both, a reaction-controlled strategy is proposed based on the nanophase separation of an ionic transport pathway and a supporting matrix to balance ionic mobility and mechanical properties. Specifically, an elastic epoxy polymer electrolyte (eEPE), synthesized via two-step polymerization, combines outstanding mechanical strength (toughness of 3.4 MJ m-3) and high ionic conductivity (3.5 × 10-4 S cm-1 at 25 °C). The nanostructured eEPE is both tough and flexible, therefore promotes uniform deposition of Li even under a high current density (2 mA cm-2 and 2 mAh cm-2). Importantly, eEPE composite films greatly improve the safety performance of the LiFePO4/Li pouch cells safe operations are achieved under several abusive conditions. This work highlights an alternative route for high-safety solid-state lithium metal batteries of the next generation.Except for routine scaling and root planing, there are few effective nonsurgical therapeutic interventions for periodontitis and associated alveolar bone loss. Simvastatin (SIM), one of the 3-hydroxy-3-methylglutaryl-cosenzyme A reductase inhibitors, which is known for its capacity as a lipid-lowering medication, has been proven to be an effective anti-inflammatory and bone anabolic agent that has shown promising benefits in mitigating periodontal bone loss. The local delivery of SIM into the periodontal pocket, however, has been challenging due to SIM's poor water solubility and its lack of osteotropicity. To overcome these issues, we report a novel SIM formulation of a thermoresponsive, osteotropic, injectable hydrogel (PF127) based on pyrophosphorolated pluronic F127 (F127-PPi). After mixing F127-PPi with F127 at a 11 ratio, the resulting PF127 was used to dissolve free SIM to generate the SIM-loaded formulation. The thermoresponsive hydrogel's rheologic behavior, erosion and SIM release kinetics, osteotropic property, and biocompatibility were evaluated in vitro. The therapeutic efficacy of SIM-loaded PF127 hydrogel on periodontal bone preservation and inflammation resolution was validated in a ligature-induced periodontitis rat model. Given that SIM is already an approved medication for hyperlipidemia, the data presented here support the translational potential of the SIM-loaded PF127 hydrogel for better clinical management of periodontitis and associated pathologies.Understanding the influence of fine atmospheric particles (PM2.5) on cellular biophysical properties is an integral part for comprehending the mechanisms underlying PM2.5-induced diseases because they are closely related to the behaviors and functions of cells. However, hitherto little work has been done in this area. In the present work, we aimed to interrogate the influence of the PM2.5 water-soluble compound (PM2.5-WSC) on the biophysical performance of a human lung carcinoma epithelial cell line (A549) by exploring the cellular morphological and mechanical changes using atomic force microscopy (AFM)-based imaging and nanomechanics. AFM imaging showed that PM2.5-WSC treated cells exhibited evidently reduced lamellipodia and an increased height when compared to the control group. AFM nanomechanical measurements indicated that the treated cells had higher elastic energy and lower adhesion work than the control group. Our western blot assay and transmission electron microscopy (TEM) results revealed that after PM2.
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