Metasurface-Controlled Holographic Microcavities.

Optical microcavities confine light to wavelength-scale volumes and are a key component for manipulating and enhancing the interaction of light, vacuum states, and matter. Current microcavities are constrained to a small number of spatial mode profiles. Imaging cavities can accommodate complicated modes but require an externally preshaped input. Here, we experimentally demonstrate a visible-wavelength, metasurface-based holographic microcavity that overcomes these limitations. The micrometer-scale metasurface cavity fulfills the round-trip condition for a designed mode with a complex-shaped intensity profile and thus selectively enhances light that couples to this mode, achieving a spectral bandwidth of 0.8 nm. By imaging the intracavity mode, we show that the holographic mode changes quickly with the cavity length and that the cavity displays the desired spatial mode profile only close to the design cavity length. When a metasurface is placed on a distributed Bragg reflector and steep phase gradients are realized, the correct choice of the reflector's top layer material can boost metasurface performance considerably. The applied forward-design method can be readily transferred to other spectral regimes and mode profiles.

Hybrid silicon-organic Huygens' metasurface for phase modulation.

Spatial light modulators have desirable applications in sensing and free space communication because they create an interface between the optical and electronic realms. Electro-optic modulators allow for high-speed intensity manipulation of an electromagnetic wavefront. However, most surfaces of this sort pose limitations due to their ability to modulate intensity rather than phase. Here we investigate an electro-optic modulator formed from a silicon-organic Huygens' metasurface. In a simulation-based study, we discover a metasurface design immersed in high-performance electro-optic molecules that can achieve near-full resonant transmission with phase coverage over the full 2π range. Through the electro-optic effect, we show 140 ∘ (0.79π) modulation over a range of -100 to 100 V at 1330 nm while maintaining near-constant transmitted field intensity (between 0.66 and 0.8). These results potentiate the fabrication of a high-speed spatial light modulator with the resolved parameters.

Serotonin reduction in post-acute sequelae of viral infection.

Post-acute sequelae of COVID-19 (PASC, "Long COVID") pose a significant global health challenge. The pathophysiology is unknown, and no effective treatments have been found to date. Several hypotheses have been formulated to explain the etiology of PASC, including viral persistence, chronic inflammation, hypercoagulability, and autonomic dysfunction. Here, we propose a mechanism that links all four hypotheses in a single pathway and provides actionable insights for therapeutic interventions. We find that PASC are associated with serotonin reduction. Viral infection and type I interferon-driven inflammation reduce serotonin through three mechanisms: diminished intestinal absorption of the serotonin precursor tryptophan; platelet hyperactivation and thrombocytopenia, which impacts serotonin storage; and enhanced MAO-mediated serotonin turnover. Peripheral serotonin reduction, in turn, impedes the activity of the vagus nerve and thereby impairs hippocampal responses and memory. These findings provide a possible explanation for neurocognitive symptoms associated with viral persistence in Long COVID, which may extend to other post-viral syndromes.

Gigahertz free-space electro-optic modulators based on Mie resonances.

Electro-optic modulators are essential for sensing, metrology and telecommunications. Most target fiber applications. Instead, metasurface-based architectures that modulate free-space light at gigahertz (GHz) speeds can boost flat optics technology by microwave electronics for active optics, diffractive computing or optoelectronic control. Current realizations are bulky or have low modulation efficiencies. Here, we demonstrate a hybrid silicon-organic metasurface platform that leverages Mie resonances for efficient electro-optic modulation at GHz speeds. We exploit quasi bound states in the continuum (BIC) that provide narrow linewidth (Q = 550 at [Formula: see text] nm), light confinement to the non-linear material, tunability by design and voltage and GHz-speed electrodes. Key to the achieved modulation of [Formula: see text] are molecules with r33 = 100 pm/V and optical field optimization for low-loss. We demonstrate DC tuning of the resonant frequency of quasi-BIC by [Formula: see text] 11 nm, surpassing its linewidth, and modulation up to 5 GHz (fEO,-3dB = 3 GHz). Guided mode resonances tune by [Formula: see text] 20 nm. Our hybrid platform may incorporate free-space nanostructures of any geometry or material, by application of the active layer post-fabrication.

Local externalization of phosphatidylserine mediates developmental synaptic pruning by microglia.

Neuronal circuit assembly requires the fine balance between synapse formation and elimination. Microglia, through the elimination of supernumerary synapses, have an established role in this process. While the microglial receptor TREM2 and the soluble complement proteins C1q and C3 are recognized as key players, the neuronal molecular components that specify synapses to be eliminated are still undefined. Here, we show that exposed phosphatidylserine (PS) represents a neuronal "eat-me" signal involved in microglial-mediated pruning. In hippocampal neuron and microglia co-cultures, synapse elimination can be partially prevented by blocking accessibility of exposed PS using Annexin V or through microglial loss of TREM2. In vivo, PS exposure at both hippocampal and retinogeniculate synapses and engulfment of PS-labeled material by microglia occurs during established developmental periods of microglial-mediated synapse elimination. Mice deficient in C1q, which fail to properly refine retinogeniculate connections, have elevated presynaptic PS exposure and reduced PS engulfment by microglia. These data provide mechanistic insight into microglial-mediated synapse pruning and identify a novel role of developmentally regulated neuronal PS exposure that is common among developing brain structures.

Gastrointestinal symptom improvement from fiber, STW 5, peppermint oil, and probiotics use-Results from an online survey.

OBJECTIVES: Several common supplements are used by a significant number of patients affected by gastrointestinal (GI) disorders to improve symptoms and quality of life. We investigated the impact of GI symptom improvement with the use of fiber, STW 5, probiotics, and peppermint oil in relation to overall GI pain and quality of life via an online survey. DESIGN: We used a cross-sectional, descriptive, correlation design. A Qualtrics online survey was utilized to collect data from January to June 2013 through various websites. Areas evaluated included participant demographics, use of supplements, and gastrointestinal symptom severity. RESULTS: The rate of supplement use among patients with GI disorders was high (90% in past year) and consultation with healthcare providers was reported by 80%. Participants who completed the survey (n = 68) reported a strong correlation between GI symptom severity and overall quality of life (r2 = 0.8682, p < 0.001). The use of fiber improved GI symptom severity while both STW 5 and probiotics were linked to specific improvements. CONCLUSIONS: Persons with chronic GI disorders often choose the complementary use of common supplements to mitigate GI symptoms and consult with their healthcare providers frequently. The use of STW 5 and probiotics specifically is linked to overall reduction in GI symptoms and improvement of quality of life.

In vitro and ex vivo screening of candidate therapeutics to restore neurotransmission in nerve terminals intoxicated by botulinum neurotoxin serotype A1.

Botulinum neurotoxins (BoNTs) are exceedingly potent neurological poisons that block cholinergic release in the peripheral nervous system and cause death by asphyxiation. While post-exposure prophylaxis can effectively eliminate toxin in the bloodstream, there are no clinically effective treatments to prevent or reverse disease once BoNT has entered the neuron. To address the need for post-symptomatic countermeasures, we designed and developed an in vitro assay based on whole-cell, patch-clamp electrophysiological monitoring of miniature excitatory post-synaptic currents in synaptically active murine embryonic stem cell-derived neurons. This synaptic function-based assay was used to assess the efficacy of rationally selected drugs to restore neurotransmission in neurons comprehensively intoxicated by BoNT/A. Based on clinical reports suggesting that elevated Ca2+ signaling promotes symptomatic relief from botulism, we identified seven candidate drugs that modulate presynaptic Ca2+ signaling and assessed their ability to reverse BoNT/A-induced synaptic blockade. The most effective drugs from the screen were found to phasically agonize voltage-gated calcium channel (VGCC) activity. Lead candidates were then applied to ex vivo studies in BoNT/A-paralyzing mouse phrenic nerve-hemidiaphragm (PND) preparations. Treatment of PNDs with VGCC agonists after paralytic onset transiently potentiated nerve-elicited muscle contraction and delayed progression to neuromuscular failure. Collectively, this study suggests that Ca2+-modulating drugs represent a novel symptomatic treatment for neuromuscular paralysis following BoNT/A poisoning.