Harvesting energetic carriers from plasmonic resonance has been a hot topic in the field of photodetection in the last decade. By interfacing a plasmonic metal with a semiconductor, the photoelectric ...conversion mechanism, based on hot carrier emission, is capable of overcoming the band gap limitation imposed by the band-to-band transition of the semiconductor. To date, most of the existing studies focus on plasmonic structural engineering in a single metal-semiconductor (MS) junction system and their responsivities are still quite low in comparison to conventional semiconductor, material-based photodetection platforms. Herein, we propose a new architecture of metal-semiconductor-metal (MSM) junctions on a silicon platform to achieve efficient hot hole collection at infrared wavelengths with a photoconductance gain mechanism. The coplanar interdigitated MSM electrode’s configuration forms a back-to-back Schottky diode and acts simultaneously as the plasmonic absorber/emitter, relying on the hot-spots enriched on the random Au/Si nanoholes structure. The hot hole-mediated photoelectric response was extended far beyond the cut-off wavelength of the silicon. The proposed MSM device with an interdigitated electrode design yields a very high photoconductive gain, leading to a photocurrent responsivity up to several A/W, which is found to be at least 1000 times higher than that of the existing hot carrier based photodetection strategies.
Designing efficient narrow-band near-infrared photodetectors integrated on silicon for telecommunications remains a significant challenge in silicon photonics. This paper proposes a novel ...silicon-based hot-electron photodetector employing Tamm plasmons (Si-based TP-HE PD) for narrow-band near-infrared photodetection. The device combines a one-dimensional photonic crystal (1DPC) structure, an Au layer, and a silicon substrate with a back electrode. Simulation results show that the absorption of the TP device with a back electrode is 1.5 times higher than without a back electrode, due to increased absorption from multiple reflections between the back electrode and the 1DPC structure. Experimentally, the responsivity of the fabricated device reaches 0.195 mA/W at a wavelength of 1400 nm. A phenomenological model was developed to analyze the photoelectric conversion mechanism, revealing reasonable agreement between the theoretically calculated and experimentally measured internal quantum efficiencies. Additional experiments and simulations demonstrate the tunability of the resonance wavelength from 1200 nm to 1700 nm by adjusting structural parameters. The Si-based TP-HE PD shows potential for silicon-based optoelectronic applications, offering the advantages of a simple structure, low cost, and compatibility with silicon photonic integrated circuits. This work represents the first demonstration of a silicon-based hot electron NIR photodetector utilizing Tamm plasmons.
Active metasurface provides an efficient way to achieve optical response in the subwavelength range, dielectric metasurface has attracted much attention due to its low-loss mode and excitable ...electric/magnetic resonance mode, resulting in a far wider range of applications. However, the resonance spectrum is relatively broad due to the strong radiative loss of the symmetric dielectric metasurface, which limits its application in large modulation extinction ratio. Hence, an active metasurface integrated with the phase change material Ge2Sb2Te5 (GST) is proposed. The active metasurface can support the symmetry-protected quasi bound states in the continuum (QBIC) and excite resonance modes with extremely high quality-factors. As an active medium, the GST layer undergoes a transition from the amorphous state to the crystalline state when the temperature increases, leading to a change in the amplitude/phase of the reflection spectrum. It is demonstrated that dual reflection modulation and the figure-of-merit (FoM) can reach up to 92.0% at the wavelength of 1.45 μm and 92.5% at the wavelength of 1.52 μm as the GST layer is in the middle of nanodisks. An extremely high FoM of 98.5% is also realized when the surface of silicon nanodisks is coated with the GST layer. In addition, the modulation mechanism of the optical response of the active metasurface has been investigated, which is of great significance to the design of the active metasurface. The proposed active all-dielectric asymmetric metasurface has a huge potential in tunable nonlinear optical devices.
Plasmonic harvesting of hot carriers (HCs) in metal–semiconductor (M–S) junctions has stimulated intensive research activities for sub-bandgap photodetection, in particular the development of ...silicon-based infrared photodetectors. Here, a copper–silicon heterojunction was investigated both theoretically and experimentally in comparison to the commonly used gold–silicon ones. A 1-order-of-magnitude higher responsivity and a longer cutoff wavelength over 2000 nm were observed in experiments in the sub-bandgap wavelength range of silicon with a copper–silicon junction. A phenomenological model was developed to analyze the dynamic processes of HCs and attributed the advanced photodetection performance of copper–silicon devices to the relatively higher electron density of state above the Fermi level and the higher ejection probability. Such a complementary metal–oxide–semiconductor-compatible and low-cost HC photodetection platform shows promising potential in silicon-based optoelectronic applications.
In recent years, nanomaterials have aroused extensive research interest in the world's material science community. Electrospinning has the advantages of wide range of available raw materials, simple ...process, small fiber diameter and high porosity. Electrospinning as a nanomaterial preparation technology with obvious advantages has been studied, such as its influencing parameters, physical models and computer simulation. In this review, the influencing parameters, simulation and models of electrospinning technology are summarized. In addition, the progresses in applications of the technology in biomedicine, energy and catalysis are reported. This technology has many applications in many fields, such as electrospun polymers in various aspects of biomedical engineering. The latest achievements in recent years are summarized, and the existing problems and development trends are analyzed and discussed.
Understanding how potent neutralizing antibodies (NAbs) inhibit SARS-CoV-2 is critical for effective therapeutic development. We previously described BD-368-2, a SARS-CoV-2 NAb with high potency; ...however, its neutralization mechanism is largely unknown. Here, we report the 3.5-Å cryo-EM structure of BD-368-2/trimeric-spike complex, revealing that BD-368-2 fully blocks ACE2 recognition by occupying all three receptor-binding domains (RBDs) simultaneously, regardless of their “up” or “down” conformations. Also, BD-368-2 treats infected adult hamsters at low dosages and at various administering windows, in contrast to placebo hamsters that manifested severe interstitial pneumonia. Moreover, BD-368-2’s epitope completely avoids the common binding site of VH3-53/VH3-66 recurrent NAbs, evidenced by tripartite co-crystal structures with RBDs. Pairing BD-368-2 with a potent recurrent NAb neutralizes SARS-CoV-2 pseudovirus at pM level and rescues mutation-induced neutralization escapes. Together, our results rationalized a new RBD epitope that leads to high neutralization potency and demonstrated BD-368-2’s therapeutic potential in treating COVID-19.
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•BD-368-2 blocks all three ACE2 binding sites regardless of RBD spatial conformations•BD-368-2 treats severely infected hamsters at low dosages and various dose windows•New cocktail design based on BD-368-2 neutralizes escaping SARS-CoV-2 mutants
Du et al. showed how a potent COVID-19 antibody, BD-368-2, interacts with the SARS-CoV-2 spike trimer to neutralize the virus and effectively treat severely infected hamsters. They further demonstrated how BD-368-2 can be paired with additional antibodies to form a cocktail that prevents the evolution of viral escape mutants.
The mitochondrial calcium uniporter (MCU)-a calcium uniporter on the inner membrane of mitochondria-controls the mitochondrial calcium uptake in normal and abnormal situations. Mitochondrial calcium ...is essential for the production of adenosine triphosphate (ATP); however, excessive calcium will induce mitochondrial dysfunction. Calcium homeostasis disruption and mitochondrial dysfunction is observed in many neurodegenerative disorders. However, the role and regulatory mechanism of the MCU in the development of these diseases are obscure. In this review, we summarize the role of the MCU in controlling oxidative stress-elevated mitochondrial calcium and its function in neurodegenerative disorders. Inhibition of the MCU signaling pathway might be a new target for the treatment of neurodegenerative disorders.
Alteration of immune status in the central nervous system (CNS) has been implicated in the development of post-traumatic stress disorder (PTSD). However, the nature of overall changes in brain ...immunocyte landscape in PTSD condition remains unclear.
We constructed a mouse PTSD model by electric foot-shocks followed by contextual reminders and verified the PTSD-related symptoms by behavior test (including contextual freezing test, open-field test, and elevated plus maze test). We examined the immunocyte panorama in the brains of the naïve or PTSD mice by using single-cell mass cytometry. Microglia number and morphological changes in the hippocampus, prefrontal cortex, and amygdala were analyzed by histopathological methods. The gene expression changes of those microglia were detected by quantitative real-time PCR. Genetic/pharmacological depletion of microglia or minocycline treatment before foot-shocks exposure was performed to study the role of microglia in PTSD development and progress.
We found microglia are the major brain immune cells that respond to PTSD. The number of microglia and ratio of microglia to immunocytes was significantly increased on the fifth day of foot-shock exposure. Furthermore, morphological analysis and gene expression profiling revealed temporal patterns of microglial activation in the hippocampus of the PTSD brains. Importantly, we found that genetic/pharmacological depletion of microglia or minocycline treatment before foot-shock exposure alleviated PTSD-associated anxiety and contextual fear.
Our results demonstrated a critical role for microglial activation in PTSD development and a potential therapeutic strategy for the clinical treatment of PTSD in the form of microglial inhibition.
Abstract
Background
Persistent inflammation dysregulation and cognitive decline have been associated with several trauma- and stress-related disorders such as posttraumatic stress disorder (PTSD) and ...anxiety disorder. Despite the abundant discoveries of neuroinflammation in such disorders, the underlying mechanisms still remain unclear.
Method
Wild-type and
Nlrp3
−/−
mice were exposed to the electric foot shocks in the contextual fear memory paradigm. Three hours after the electric foot shocks, activation of the NLRP3 inflammasome was investigated through immunoblotting and ELISA. Microglia were isolated and analyzed by quantitative real-time PCR. Hippocampal tissues were collected 3 h and 72 h after the electric foot shocks and subjected to RNA sequencing. MCC950 was administrated to mice via intraperitoneal (i.p.) injection. Interleukin-1 receptor antagonist (IL-ra) and interleukin-1β (IL-1β) were delivered via intracerebroventricular (i.c.v.) infusion. Contextual fear responses of mice were tested on 4 consecutive days (test days 1-4) starting at 48 h after the electric foot shocks. Anxiety-like behaviors were examined by elevated plus maze and open-field test.
Results
We demonstrated that, in the contextual fear memory paradigm, the NLRP3 inflammasome was activated 3 h after electric foot shocks. We also found an upregulation in toll-like receptor and RIG-I-like receptor signaling, and a decrease in postsynaptic density (PSD) related proteins, such as PSD95 and Shank proteins, in the hippocampus 72 h after the electric foot shocks, indicating an association between neuroinflammation and PSD protein loss after stress encounter. Meanwhile,
Nlrp3
knockout could significantly prevent both neuroinflammation and loss of PSD-related proteins, suggesting a possible protective role of NLRP3 deletion during this process. For further studies, we demonstrated that both genetic knockout and pharmaceutical inhibition of the NLRP3 inflammasome remarkably enhanced the extinction of contextual fear memory and attenuated anxiety-like behavior caused by electric foot shocks. Moreover, cytokine IL-1β administration inhibited the extinction of contextual fear memory. Meanwhile, IL-1ra significantly enhanced the extinction of contextual fear memory and attenuated anxiety-like behavior.
Conclusion
Taken together, our data revealed the pivotal role of NLRP3 inflammasome activation in the regulation of fear memory and the development of PTSD and anxiety disorder, providing a novel target for the clinical treatment of such disorders.
Rationale: It is known that neuroinflammation plays a critical and detrimental role in the development of cerebral ischemia/reperfusion (I/R), but the regulation of the cyclic GMP-AMP synthase ...(cGAS)-mediated innate immune response in I/R-induced neuroinflammation is largely unexplored. This study aimed to investigate the function and regulatory mechanism of cGAS in I/R-induced neuroinflammation and brain injury, and to identify possible strategies for the treatment of ischemic stroke. Methods: To demonstrate that microglial histone deacetylase 3 (HDAC3) regulates the microglial cGAS-stimulator of interferon genes (cGAS-STING) pathway and is involved in I/R-induced neuroinflammation and brain injury, a series of cell biological, molecular, and biochemical approaches were utilized. These approaches include transient middle cerebral artery occlusion (tMCAO), real-time polymerase chain reaction (PCR), RNA sequencing, western blot, co-immunoprecipitation, chromosome-immunoprecipitation, enzyme-linked immunosorbent assay (ELISA), dual-luciferase reporter assay, immunohistochemistry, and confocal imaging. Results: The microglial cGAS- STING pathway was activated by mitochondrial DNA, which promoted the formation of a pro-inflammatory microenvironment. In addition, we revealed that HDAC3 transcriptionally promoted the expression of cGAS and potentiated the activation of the cGAS-STING pathway by regulating the acetylation and nuclear localization of p65 in microglia. Our in vivo results indicated that deletion of cGAS or HDAC3 in microglia attenuated I/R-induced neuroinflammation and brain injury. Conclusion: Collectively, we elucidated that the HDAC3-p65-cGAS-STING pathway is involved in the development of I/R-induced neuroinflammation, identifying a new therapeutic avenue for the treatment of ischemic stroke.
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