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Therapeutic growth factor delivery typically requires supraphysiological dosages, which can cause undesirable off-target effects. The aim of this study was to 3D bioprint implants containing spatiotemporally defined patterns of growth factors optimized for coupled angiogenesis and osteogenesis. Using nanoparticle functionalized bioinks, it was possible to print implants with distinct growth factor patterns and release profiles spanning from days to weeks. The extent of angiogenesis in vivo depended on the spatial presentation of vascular endothelial growth factor (VEGF). Higher levels of vessel invasion were observed in implants containing a spatial gradient of VEGF compared to those homogenously loaded with the same total amount of protein. Printed implants containing a gradient of VEGF, coupled with spatially defined BMP-2 localization and release kinetics, accelerated large bone defect healing with little heterotopic bone formation. This demonstrates the potential of growth factor printing, a putative point of care therapy, for tightly controlled tissue regeneration.Hair cells detect sound and motion through a mechano-electric transduction (MET) process mediated by tip links connecting shorter stereocilia to adjacent taller stereocilia. Adaptation is a key feature of MET that regulates a cell's dynamic range and frequency selectivity. A decades-old hypothesis proposes that slow adaptation requires myosin motors to modulate the tip-link position on taller stereocilia. This "motor model" depended on data suggesting that the receptor current decay had a time course similar to that of hair-bundle creep (a continued movement in the direction of a step-like force stimulus). Using cochlear and vestibular hair cells of mice, rats, and gerbils, we assessed how modulating adaptation affected hair-bundle creep. Our results are consistent with slow adaptation requiring myosin motors. However, the hair-bundle creep and slow adaptation were uncorrelated, challenging a critical piece of evidence upholding the motor model. Considering these data, we propose a revised model of hair cell adaptation.CLC family proteins translocate chloride ions across cell membranes to maintain the membrane potential, regulate the transepithelial Cl- transport, and control the intravesicular pH among different organelles. CLC-7/Ostm1 is an electrogenic Cl-/H+ antiporter that mainly resides in lysosomes and osteoclast ruffled membranes. Mutations in human CLC-7/Ostm1 lead to lysosomal storage disorders and severe osteopetrosis. Here, we present the cryo-electron microscopy (cryo-EM) structure of the human CLC-7/Ostm1 complex and reveal that the highly glycosylated Ostm1 functions like a lid positioned above CLC-7 and interacts extensively with CLC-7 within the membrane. Our complex structure reveals a functionally crucial domain interface between the amino terminus, TMD, and CBS domains of CLC-7. Structural analyses and electrophysiology studies suggest that the domain interaction interfaces affect the slow gating kinetics of CLC-7/Ostm1. Thus, our study deepens understanding of CLC-7/Ostm1 transporter and provides insights into the molecular basis of the disease-related mutations.Anisotropic mesoporous inorganic materials have attracted great interest due to their unique and intriguing properties, yet their controllable synthesis still remains a great challenge. Here, we develop a simple synthesis approach toward mesoporous inorganic bowls and two-dimensional (2D) nanosheets by combining block copolymer (BCP)-directed self-assembly with asymmetric phase migration in ternary-phase blends. The homogeneous blend solution spontaneously self-assembles to anisotropically stacked hybrids as the solvent evaporates. Two minor phases-BCP/inorganic precursor and homopolystyrene (hPS)-form closely stacked, Janus domains that are dispersed/confined in the major homopoly(methyl methacrylate) (hPMMA) matrix. hPS phases are partially covered by BCP-rich phases, where ordered mesostructures develop. With increasing the relative amount of hPS, the anisotropic shape evolves from bowls to 2D nanosheets. Benefiting from the unique bowl-like morphology, the resulting transition metal oxides show promise as high-performance anodes in potassium-ion batteries.Switches between global sleep and wakefulness states are believed to be dictated by top-down influences arising from subcortical nuclei. Using forward genetics and in vivo electrophysiology, we identified a recessive mouse mutant line characterized by a substantially reduced propensity to transition between wake and sleep states with an especially pronounced deficit in initiating rapid eye movement (REM) sleep episodes. [https://www.selleckchem.com/products/pembrolizumab.html find more] The causative mutation, an Ile102Asn substitution in the synaptic vesicular protein, VAMP2, was associated with morphological synaptic changes and specific behavioral deficits, while in vitro electrophysiological investigations with fluorescence imaging revealed a markedly diminished probability of vesicular release in mutants. Our data show that global shifts in the synaptic efficiency across brain-wide networks leads to an altered probability of vigilance state transitions, possibly as a result of an altered excitability balance within local circuits controlling sleep-wake architecture.Strain accumulated on the deep extension of some faults is episodically released during transient slow-slip events, which can subsequently load the shallow seismogenic region. At the San Andreas fault, the characteristics of slow-slip events are difficult to constrain geodetically due to their small deformation signal. Slow-slip events (SSEs) are often accompanied by coincident tremor bursts composed of many low-frequency earthquakes. Here, we probabilistically estimate the spatiotemporal clustering properties of low-frequency earthquakes detected along the central San Andreas fault. We find that tremor bursts follow a power-law spatial and temporal decay similar to earthquake aftershock sequences. The low-frequency earthquake clusters reveal that the underlying slow-slip events have two modes of rupture velocity. Compared to regular earthquakes, these slow-slip events have smaller stress drop and rupture velocity but follow similar magnitude-frequency, moment-area, and moment-duration scaling. Our results connect a broad spectrum of transient fault slip that spans several orders of magnitude in rupture velocity.