Our work leverages the advantages of the gain switching and the pulse pumping techniques, and establishes the merits of combining distinct compact comb platforms that enhance the potential of energy-efficient chipscale microcombs.In several species, Piwi/piRNA genome silencing defects cause immediate sterility that correlates with transposon expression and transposon-induced genomic instability. In C. elegans, mutations in the Piwi-related gene (prg-1) and other piRNA deficient mutants cause a transgenerational decline in fertility over a period of several generations. Here we show that the sterility of late generation piRNA mutants correlates poorly with increases in DNA damage signaling. Instead, sterile individuals consistently exhibit altered perinuclear germ granules. We show that disruption of germ granules does not activate transposon expression but induces multiple phenotypes found in sterile prg-1 pathway mutants.  https://www.selleckchem.com/products/abc294640.html  Furthermore, loss of the germ granule component pgl-1 enhances prg-1 mutant infertility. Environmental restoration of germ granule function for sterile pgl-1 mutants restores their fertility. We propose that Piwi mutant sterility is a reproductive arrest phenotype that is characterized by perturbed germ granule structure and is phenocopied by germ granule dysfunction, independent of genomic instability.The well-developed preform-to-fiber thermal drawing technique owns the benefit to maintain the cross-section architecture and obtain an individual micro-scale strand of fiber with the extended length up to thousand meters. In this work, we propose and demonstrate a two-step soluble-core fabrication method by combining such an inherently scalable manufacturing method with simple post-draw processing to explore the low viscosity polymer fibers and the potential of soft fiber electronics. As a result, an ultra-stretchable conductive fiber is achieved, which maintains excellent conductivity even under 1900% strain or 1.5 kg load/impact freefalling from 0.8-m height. Moreover, by combining with triboelectric nanogenerator technique, this fiber acts as a self-powered self-adapting multi-dimensional sensor attached on sports gears to monitor sports performance while bearing sudden impacts. Next, owing to its remarkable waterproof and easy packaging properties, this fiber detector can sense different ion movements in various solutions, revealing the promising applications for large-area undersea detection.Post-translational changes in the redox state of cysteine residues can rapidly and reversibly alter protein functions, thereby modulating biological processes. The nematode C. elegans is an ideal model organism for studying cysteine-mediated redox signaling at a network level. Here we present a comprehensive, quantitative, and site-specific profile of the intrinsic reactivity of the cysteinome in wild-type C. elegans. We also describe a global characterization of the C. elegans redoxome in which we measured changes in three major cysteine redox forms after H2O2 treatment. Our data revealed redox-sensitive events in translation, growth signaling, and stress response pathways, and identified redox-regulated cysteines that are important for signaling through the p38 MAP kinase (MAPK) pathway. Our in-depth proteomic dataset provides a molecular basis for understanding redox signaling in vivo, and will serve as a valuable and rich resource for the field of redox biology.In the mammalian hippocampus, adult-born granule cells (abGCs) contribute to the function of the dentate gyrus (DG). Disruption of the DG circuitry causes spontaneous recurrent seizures (SRS), which can lead to epilepsy. Although abGCs contribute to local inhibitory feedback circuitry, whether they are involved in epileptogenesis remains elusive. Here, we identify a critical window of activity associated with the aberrant maturation of abGCs characterized by abnormal dendrite morphology, ectopic migration, and SRS. Importantly, in a mouse model of temporal lobe epilepsy, silencing aberrant abGCs during this critical period reduces abnormal dendrite morphology, cell migration, and SRS. Using mono-synaptic tracers, we show silencing aberrant abGCs decreases recurrent CA3 back-projections and restores proper cortical connections to the hippocampus. Furthermore, we show that GABA-mediated amplification of intracellular calcium regulates the early critical period of activity. Our results demonstrate that aberrant neurogenesis rewires hippocampal circuitry aggravating epilepsy in mice.Sarcopenia is a degenerative condition that consists in age-induced atrophy and functional decline of skeletal muscle cells (myofibers). A common hypothesis is that inducing myofiber hypertrophy should also reinstate myofiber contractile function but such model has not been extensively tested. Here, we find that the levels of the ubiquitin ligase UBR4 increase in skeletal muscle with aging, and that UBR4 increases the proteolytic activity of the proteasome. Importantly, muscle-specific UBR4 loss rescues age-associated myofiber atrophy in mice. However, UBR4 loss reduces the muscle specific force and accelerates the decline in muscle protein quality that occurs with aging in mice. Similarly, hypertrophic signaling induced via muscle-specific loss of UBR4/poe and of ESCRT members (HGS/Hrs, STAM, USP8) that degrade ubiquitinated membrane proteins compromises muscle function and shortens lifespan in Drosophila by reducing protein quality control. Altogether, these findings indicate that these ubiquitin ligases antithetically regulate myofiber size and muscle protein quality control.Millimeter wave (mmWave) generation using photonic techniques has so far been limited to the use of near-infrared lasers that are down-converted to the mmWave region. However, such methodologies do not currently benefit from a monolithic architecture and suffer from the quantum defect i.e. the difference in photon energies between the near-infrared and mmWave region, which can ultimately limit the conversion efficiency. Miniaturized terahertz (THz) quantum cascade lasers (QCLs) have inherent advantages in this respect their low energy photons, ultrafast gain relaxation and high nonlinearities open up the possibility of innovatively integrating both laser action and mmWave generation in a single device. Here, we demonstrate intracavity mmWave generation within THz QCLs over the unprecedented range of 25 GHz to 500 GHz. Through ultrafast time resolved techniques, we highlight the importance of modal phases and that the process is a result of a giant second-order nonlinearity combined with a phase matched process between the THz and mmWave emission.