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Performance of membranes for water purification is highly influenced by the interactions of solvated species with membrane surfaces, including surface adsorption of solutes upon fouling. Current efforts toward fouling-resistant membranes often pursue surface hydrophilization, frequently motivated by macroscopic measures of hydrophilicity, because hydrophobicity is thought to increase solute-surface affinity. While this heuristic has driven diverse membrane functionalization strategies, here we build on advances in the theory of hydrophobicity to critically examine the relevance of macroscopic characterizations of solute-surface affinity. Specifically, we use molecular simulations to quantify the affinities to model hydroxyl- and methyl-functionalized surfaces of small, chemically diverse, charge-neutral solutes represented in produced water. We show that surface affinities correlate poorly with two conventional measures of solute hydrophobicity, gas-phase water solubility and oil-water partitioning. Moreover, we find that all solutes show attraction to the hydrophobic surface and most to the hydrophilic one, in contrast to macroscopically based hydrophobicity heuristics. We explain these results by decomposing affinities into direct solute interaction energies (which dominate on hydroxyl surfaces) and water restructuring penalties (which dominate on methyl surfaces). Finally, we use an inverse design algorithm to show how heterogeneous surfaces, with multiple functional groups, can be patterned to manipulate solute affinity and selectivity. These findings, importantly based on a range of solute and surface chemistries, illustrate that conventional macroscopic hydrophobicity metrics can fail to predict solute-surface affinity, and that molecular-scale surface chemical patterning significantly influences affinity-suggesting design opportunities for water purification membranes and other engineered interfaces involving aqueous solute-surface interactions.

Organ-specific functions of tissue-resident macrophages in the steady-state heart are unknown. Here, we show that cardiac macrophages facilitate electrical conduction through the distal atrioventricular node, where conducting cells densely intersperse with elongated macrophages expressing connexin 43. When coupled to spontaneously beating cardiomyocytes via connexin-43-containing gap junctions, cardiac macrophages have a negative resting membrane potential and depolarize in synchrony with cardiomyocytes. Conversely, macrophages render the resting membrane potential of cardiomyocytes more positive and, according to computational modeling, accelerate their repolarization. Photostimulation of channelrhodopsin-2-expressing macrophages improves atrioventricular conduction, whereas conditional deletion of connexin 43 in macrophages and congenital lack of macrophages delay atrioventricular conduction. In the Cd11bDTR mouse, macrophage ablation induces progressive atrioventricular block. These observations implicate macrophages in normal and aberrant cardiac conduction.

Several borehole cores intersecting faults related to coseismic slip display high‐temperature features, including thermal decomposition of fault gouge. We present evidence that these features may be related to fluid drainage of the slip zone during seismic slip. We sheared water‐saturated kaolinite powders under both fluid drained and undrained conditions, expected for seismic slip at shallow crustal depths. Our results show typical dynamic weakening behavior regardless of conditions. Under fluid drained condition, restrengthening accompanied by the thermal decomposition of kaolinite occurs. In addition, thermal decomposition of kaolinite tends to be initiated at high normal stresses (>5 MPa) with short displacement (<5 m). We propose that thermal pressurization acts as a weakening mechanism but ceases because of fluid drainage, triggering kaolinite thermal decomposition. This finding explains seismic‐slip‐related clay anomalies at depth rather than at the surface, as observed in the borehole after the 1999 Mw 7.6 Chi‐Chi earthquake, Taiwan. Plain Language Summary: Seismic faulting at depth can drive thermochemical reactions within the slip zone, given the high slip velocity and large displacement. Several slip‐zone samples from deep drilling projects following catastrophic earthquakes have exhibited high‐temperature geological characteristics, which were not present in fault zone outcrops hosting surface ruptures. We sheared kaolinite (as an analogue of fault zone materials) under both fluid drained and undrained conditions, simulating conditions expected during seismic slip at borehole depths. Our results show that, regardless of the applied conditions, the materials tend to weaken dramatically during shearing. However, when fluids are allowed to drain from the slip zone, there is a subsequent strengthening accompanied by the thermal decomposition of kaolinite. We suggest that thermal pressurization operates as the weakening mechanism but is ceased due to fluid drainage, resulting in the thermal decomposition of kaolinite gouges. In addition, the thermal decomposition of kaolinite tends to be triggered at large normal stresses. Because kaolinite is a common component in both fault zones and subduction zones at shallow depths, our findings have potential implications for reported thermally driven reactions within slip zones as a potential seismic indicator at shallow crustal depths. Key Points: Thermal pressurization operates as the dynamic weakening mechanism during experimental seismic slip regardless of the ambient conditionsThermal pressurization ceases because of fluid drainage and is followed by kaolinite thermal decompositionThermal decomposition of kaolinite tends to be initiated at large normal stresses in the seismic slip range [ABSTRACT FROM AUTHOR]

Introduction Acute kidney injury (AKI) is a frequent medical complication seen in hospitalized patients. It is associated with an increased length of hospital stay, the development of chronic kidney disease, [...], Ischemic acute kidney injury (AKI), a complication that frequently occurs in hospital settings, is often associated with hemodynamic compromise, sepsis, cardiac surgery, or exposure to nephrotoxins. Here, using a murine renal ischemia/ reperfusion injury (IRI) model, we show that intercalated cells (ICs) rapidly adopted a proinflammatory phenotype after IRI. Wwe demonstrate that during the early phase of AKI either blockade of the proinflammatory P2Y14 receptor located on the apical membrane of ICs or ablation of the gene encoding the P2Y14 receptor in ICs (a) inhibited IRI-induced increase of chemokine expression in ICs, (b) reduced neutrophil and monocyte renal infiltration, (c) reduced the extent of kidney dysfunction, and (d) attenuated proximal tubule damage. These observations indicate that the P2Y14 receptor participates in the very first inflammatory steps associated with ischemic AKI. In addition, we show that the concentration of the P2Y14 receptor ligand UDP-glucose (UDP-Glc) was higher in urine samples from intensive care unit patients who developed AKI compared with patients without AKI. In particular, we observed a strong correlation between UDP-Glc concentration and the development of AKI in cardiac surgery patients. Our study identifies the UDP-Glc/P2Y14 receptor axis as a potential target for the prevention and/or attenuation of ischemic AKI.

This report describes results from our analysis of the activity and biodistribution of a novel pan-ERBB inhibitor, NT113, when used in treating mice with intracranial glioblastoma (GBM) xenografts. Approaches used in this investigation include: bioluminescence imaging (BLI) for monitoring intracranial tumor growth and response to therapy; determination of survival benefit from treatment; analysis of tumor IHC reactivity for indication of treatment effect on proliferation and apoptotic response; Western blot analysis for determination of effects of treatment on ERBB and ERBB signaling mediator activation; and high-performance liquid chromatography for determination of NT113 concentration in tissue extracts from animals receiving oral administration of inhibitor. Our results show that NT113 is active against GBM xenografts in which wild-type EGFR or EGFRvIII is highly expressed. In experiments including lapatinib and/or erlotinib, NT113 treatment was associated with the most substantial improvement in survival, as well as the most substantial tumor growth inhibition, as indicated by BLI and IHC results. Western blot analysis results indicated that NT113 has inhibitory activity, both in vivo and in vitro, on ERBB family member phosphorylation, as well as on the phosphorylation of downstream signaling mediator Akt. Results from the analysis of animal tissues revealed significantly higher NT113 normal brain-to-plasma and intracranial tumor-to-plasma ratios for NT113, relative to erlotinib, indicating superior NT113 partitioning to intracranial tissue compartments. These data provide a strong rationale for the clinical investigation of NT113, a novel ERBB inhibitor, in treating patients with GBM.