Sphingosylphosphorylcholine alleviates pressure overload-induced myocardial remodeling in mice via inhibiting CaM-JNK/p38 signaling pathway.

Apoptosis plays a critical role in the development of heart failure, and sphingosylphosphorylcholine (SPC) is a bioactive sphingolipid naturally occurring in blood plasma. Some studies have shown that SPC inhibits hypoxia-induced apoptosis in myofibroblasts, the crucial non-muscle cells in the heart. Calmodulin (CaM) is a known SPC receptor. In this study we investigated the role of CaM in cardiomyocyte apoptosis in heart failure and the associated signaling pathways. Pressure overload was induced in mice by trans-aortic constriction (TAC) surgery. TAC mice were administered SPC (10 µM·kg-1·d-1) for 4 weeks post-surgery. We showed that SPC administration significantly improved survival rate and cardiac hypertrophy, and inhibited cardiac fibrosis in TAC mice. In neonatal mouse cardiomyocytes, treatment with SPC (10 µM) significantly inhibited Ang II-induced cardiomyocyte hypertrophy, fibroblast-to-myofibroblast transition and cell apoptosis accompanied by reduced Bax and phosphorylation levels of CaM, JNK and p38, as well as upregulated Bcl-2, a cardiomyocyte-protective protein. Thapsigargin (TG) could enhance CaM functions by increasing Ca2+ levels in cytoplasm. TG (3 µM) annulled the protective effect of SPC against Ang II-induced cardiomyocyte apoptosis. Furthermore, we demonstrated that SPC-mediated inhibition of cardiomyocyte apoptosis involved the regulation of p38 and JNK phosphorylation, which was downstream of CaM. These results offer new evidence for SPC regulation of cardiomyocyte apoptosis, potentially providing a new therapeutic target for cardiac remodeling following stress overload.

Enhanced light output from deep ultraviolet light-emitting diodes enabled by high-order modes on a photonic crystal surface.

The authors demonstrate the enhanced light output from 275-nm AlGaN-based deep ultraviolet (DUV) light-emitting diode (LED) structures via the in-plane modulation of shallow photonic crystal (PC) patterns that were fabricated on the p-AlGaN contact layer surface. The employed PC lattice constants are in the range of 270-780 nm, much larger than the fundamental Bragg order lattice constant (∼95 nm). As compared to the unpatterned sample, the intensity of the top (or bottom) emission can be enhanced by up to 331% (or 246%), attributed to the high-order coherent diffraction of the internal trapped light and also the Purcell enhancement of spontaneous emission. The findings in this Letter suggest an easier way for the realization of more energy-efficient DUV LEDs which offer the advantage of high emission for various applications in disinfection and sterilization.

Notoginsenoside R1 protects against myocardial ischemia/reperfusion injury in mice via suppressing TAK1-JNK/p38 signaling.

Previous studies show that notoginsenoside R1 (NG-R1), a novel saponin isolated from Panax notoginseng, protects kidney, intestine, lung, brain and heart from ischemia-reperfusion injury. In this study we investigated the cardioprotective mechanisms of NG-R1 in myocardial ischemia/reperfusion (MI/R) injury in vivo and in vitro. MI/R injury was induced in mice by occluding the left anterior descending coronary artery for 30 min followed by 4 h reperfusion. The mice were treated with NG-R1 (25 mg/kg, i.p.) every 2 h for 3 times starting 30 min prior to ischemic surgery. We showed that NG-R1 administration significantly decreased the myocardial infarction area, alleviated myocardial cell damage and improved cardiac function in MI/R mice. In murine neonatal cardiomyocytes (CMs) subjected to hypoxia/reoxygenation (H/R) in vitro, pretreatment with NG-R1 (25 µM) significantly inhibited apoptosis. We revealed that NG-R1 suppressed the phosphorylation of transforming growth factor ß-activated protein kinase 1 (TAK1), JNK and p38 in vivo and in vitro. Pretreatment with JNK agonist anisomycin or p38 agonist P79350 partially abolished the protective effects of NG-R1 in vivo and in vitro. Knockdown of TAK1 greatly ameliorated H/R-induced apoptosis of CMs, and NG-R1 pretreatment did not provide further protection in TAK1-silenced CMs under H/R injury. Overexpression of TAK1 abolished the anti-apoptotic effect of NG-R1 and diminished the inhibition of NG-R1 on JNK/p38 signaling in MI/R mice as well as in H/R-treated CMs. Collectively, NG-R1 alleviates MI/R injury by suppressing the activity of TAK1, subsequently inhibiting JNK/p38 signaling and attenuating cardiomyocyte apoptosis.

High brightness and broad modulation bandwidth InGaN-based red micro-LEDs integrated with plasmonic gratings.

We propose red micro-LEDs integrated with plasmonic gratings, which demonstrate high efficiency and broad modulation bandwidth. The Purcell factor and external quantum efficiency (EQE) for an individual device can be improved up to 5.1 and 11%, respectively, due to the strong coupling between surface plasmons and multiple quantum wells. The cross talk effect between adjacent micro-LEDs can be efficiently alleviated as well, thanks to the high-divergence far-field emission pattern. Moreover, the 3-dB modulation bandwidth of the designed red micro-LEDs is predicted to be ∼ 528 MHz. Our results can be used to design high-efficiency and high-speed micro-LEDs for the applications of advanced light display and visible light communication.

Dapagliflozin attenuates pressure overload-induced myocardial remodeling in mice via activating SIRT1 and inhibiting endoplasmic reticulum stress.

Endoplasmic reticulum stress-mediated apoptosis plays a vital role in the occurrence and development of heart failure. Dapagliflozin (DAPA), a new type of sodium-glucose cotransporter 2 (SGLT2) inhibitor, is an oral hypoglycemic drug that reduces glucose reabsorption by the kidneys and increases glucose excretion in the urine. Studies have shown that DAPA may have the potential to treat heart failure in addition to controlling blood sugar. This study explored the effect of DAPA on endoplasmic reticulum stress-related apoptosis caused by heart failure. In vitro, we found that DAPA inhibited the expression of cleaved caspase 3, Bax, C/EBP homologous protein (CHOP), and glucose-regulated protein78 (GRP78) and upregulated the cardiomyoprotective protein Bcl-2 in angiotensin II (Ang II)-treated cardiomyocytes. In addition, DAPA promoted the expression of silent information regulator factor 2-related enzyme 1 (SIRT1) and suppressed the expression of activating transcription factor 4 (ATF4) and the ratios p-PERK/PERK and p-eIF2α/eIF2α. Notably, the therapeutic effect of DAPA was weakened by pretreatment with the SIRT1 inhibitor EX527 (10 µM). Simultaneous administration of DAPA inhibited the Ang II-induced transformation of fibroblasts into myofibroblasts and inhibited fibroblast migration. In summary, our present findings first indicate that DAPA could inhibit the PERK-eIF2α-CHOP axis of the ER stress response through the activation of SIRT1 in Ang II-treated cardiomyocytes and ameliorate heart failure development in vivo.

Vertically Emitting Indium Phosphide Nanowire Lasers.

Semiconductor nanowire (NW) lasers have attracted considerable research effort given their excellent promise for nanoscale photonic sources. However, NW lasers currently exhibit poor directionality and high threshold gain, issues critically limiting their prospects for on-chip light sources with extremely reduced footprint and efficient power consumption. Here, we propose a new design and experimentally demonstrate a vertically emitting indium phosphide (InP) NW laser structure showing high emission directionality and reduced energy requirements for operation. The structure of the laser combines an InP NW integrated in a cat's eye (CE) antenna. Thanks to the antenna guidance with broken asymmetry, strong focusing ability, and high Q-factor, the designed InP CE-NW lasers exhibit a higher degree of polarization, narrower emission angle, enhanced internal quantum efficiency, and reduced lasing threshold. Hence, this NW laser-antenna system provides a very promising approach toward the achievement of high-performance nanoscale lasers, with excellent prospects for use as highly localized light sources in present and future integrated nanophotonics systems for applications in advanced sensing, high-resolution imaging, and quantum communications.

Low-threshold ultraviolet stimulated emissions from large-sized single crystalline ZnO transferable membranes.

Wide-bandgap inorganic semiconductors based ultraviolet lasers bring versatile applications with significant advantages including low-power consumption, high-power output, robustness and long-term operation stability. However, flexible membrane lasers remain challenging predominantly due to the need for a lattice matched supporting substrate. Here, we develop a simple laser liftoff process to make freestanding single crystalline ZnO membranes that demonstrate low-threshold ultraviolet stimulated emissions together with large sized dimension (> 2 mm), ultralow-weight (m/A<15 g/m2) and excellent flexibility. The 2.6 µm-thick crack-free ZnO membrane exhibits well-retained single crystallinity and enhanced excitonic emissions while the defect-related emissions are completely suppressed. The inelastic exciton-exciton scattering stimulated emissions with increased spontaneous emission rate is obtained with a reduced threshold of 0.35 MW/cm2 in the ZnO membrane transferred onto a flexible polyethylene naphthalate substrate. Theoretical simulations reveal that it is a synergetic effect of the increased quantum efficiency via Purcell effect and the improved optical gain due to vertical directional waveguiding of the membrane, which functions as a Fabry-Perot photonic resonator due to the refractive index contrast at ZnO-air boundaries. With simple architecture, efficient exciton recombination and easy fusion with waveguide system, the ZnO membranes provide an alternative platform to develop compact low-threshold ultraviolet excitonic lasers.

Single nanowire green InGaN/GaN light emitting diodes.

Single nanowire (NW) green InGaN/GaN light-emitting diodes (LEDs) were fabricated by top-down etching technology. The electroluminescence (EL) peak wavelength remains approximately constant with an increasing injection current in contrast to a standard planar LED, which suggests that the quantum-confined Stark effect is significantly reduced in the single NW device. The strain relaxation mechanism is studied in the single NW LED using Raman scattering analysis. As compared to its planar counterpart, the EL peak of the NW LED shows a redshift, due to electric field redistribution as a result of changes in the cavity mode pattern after metallization. Our method has important implication for single NW optoelectronic device applications.

Bloch surface plasmon enhanced blue emission from InGaN/GaN light-emitting diode structures with Al-coated GaN nanorods.

InGaN/GaN light-emitting diode structures with Al-coated GaN nanorods were fabricated by using soft ultraviolet nanoimprint lithography. The intensity of light emission was found to be greatly enhanced due to the strong near-fields confined at the interface of Al/GaN and extended to the multiple quantum wells (MQWs) active region. The dynamics of carrier recombination and plasmon-enhanced Raman scattering were also investigated, providing a progressive view on the effective energy transfer between MQWs and surface plasmons.

Second-order surface-plasmon assisted responsivity enhancement in germanium nano-photodetectors with bull's eye antennas.

The enhancement of photo-response in nanometer-scale germanium photodetectors through bull's eye antennas capable of supporting 2nd-order Bloch surface plasmon modes is demonstrated in theory and experiment. A detailed numerical investigation reveals that the presence of surface wave and its constructive interference with the directly incident light are incorporated into the main mechanisms for enhancing transmission through the central nanoaperture. With a grating period of 1500 nm, the area-normalized responsivity can be enhanced up to 3.8 times at 2 V bias for a 780 nm laser. It provides an easier fabrication path for ultra-short wavelength operations especially in devices using optically denser materials.

Ga2O3 Bipolar Heterojunction-Based Optoelectronic Synapse Array with Visual Attention.

The human brain efficiently processes only a fraction of visual information, a phenomenon termed attentional control, resulting in energy savings and heightened adaptability. Translating this mechanism into artificial visual neurons holds promise for constructing energy-efficient, bioinspired visual systems. Here, we propose a self-rectifying artificial visual neuron (SEVN) based on a NiO/Ga2O3 bipolar heterojunction with attentional control on patterns with a target color. The device exhibits short-term potentiation (STP) with quantum point contact (QPC) traits at low bias and transitions to long-term potentiation (LTP) at high bias, particularly facilitated by electron capture in deep defects upon ultraviolet (UV) exposure. With the utilization of two wavelengths of light upon the target and interference part of CAPTCHA to simulate top-down attentional control, the recognition accuracy is enhanced from 74 to 84%. These findings have the potential to augment the visual capability of neuromorphic systems with implications for diverse applications, including cybersecurity, healthcare, and machine vision.

Aerobic Exercise Attenuates Pressure Overload-Induced Myocardial Remodeling and Myocardial Inflammation via Upregulating miR-574-3p in Mice.

BACKGROUND: Exercise training can promote cardiac rehabilitation, thereby reducing cardiovascular disease mortality and hospitalization rates. MicroRNAs (miRs) are closely related to heart disease, among which miR-574-3p plays an important role in myocardial remodeling, but its role in exercise-mediated cardioprotection is still unclear. METHODS: A mouse myocardial hypertrophy model was established by transverse aortic coarctation, and a 4-week swimming exercise training was performed 1 week after the operation. After swimming training, echocardiography was used to evaluate cardiac function in mice, and histopathologic staining was used to detect cardiac hypertrophy, myocardial fibrosis, and cardiac inflammation. Quantitative real-time polymerase chain reaction was used to detect the expression levels of miR-574-3p and cardiac hypertrophy markers. Western blotting detected the IL-6 (interleukin-6)/JAK/STAT inflammatory signaling pathway. RESULTS: Echocardiography and histochemical staining found that aerobic exercise significantly improved pressure overload-induced myocardial hypertrophy (n=6), myocardial interstitial fibrosis (n=6), and cardiac inflammation (n=6). Quantitative real-time polymerase chain reaction detection showed that aerobic exercise upregulated the expression level of miR-574-3p (n=6). After specific knockdown of miR-574-3p in mouse hearts with adeno-associated virus 9 using cardiac troponin T promoter, we found that the protective effect of exercise training on the heart was significantly reversed. Echocardiography and histopathologic staining showed that inhibiting the expression of miR-574-3p could partially block the effects of aerobic exercise on cardiac function (n=6), cardiomyocyte cross-sectional area (n=6), and myocardial fibrosis (n=6). Western blotting and immunohistochemical staining showed that the inhibitory effects of aerobic exercise on the IL-6/JAK/STAT pathway and cardiac inflammation were partially abolished after miR-574-3p knockdown. Furthermore, we also found that miR-574-3p exerts cardioprotective effects in cardiomyocytes by targeting IL-6 (n=3). CONCLUSIONS: Aerobic exercise protects cardiac hypertrophy and inflammation induced by pressure overload by upregulating miR-574-3p and inhibiting the IL-6/JAK/STAT pathway.

Spectrum broadening of high-efficiency second harmonic generation in cascaded photonic crystal microcavities.

An effective approach is proposed to broaden the spectrum of high-efficiency second harmonic generation in a one-dimensional photonic crystal based on the cascaded structure. By controlling the thickness of the joint layer, it is possible to realize a flat-top or quasiflat-top impurity band centered at the fundamental wavelength due to mode splitting effect in coupled cavities. Simulation results reveal that the spectrum of generated second harmonic exhibits a hump-like or multi-peak profile with wavelength tuning. It is a salient feature that the spectral stability of efficiency enhancement could be greatly improved compared to the conventional Lorentzian profile while maintaining an ultrahigh Q factor. Such merit of spectra re-shaping can significantly relax the stringent requirements for ultrahigh-Q microcavities in practical applications, e.g. fabrication inaccuracy, thermal variation, and wavelength detuning.

Cardiac-Specific Overexpression of Caveolin-1 in Rats With Ischemic Cardiomyopathy Improves Arrhythmogenicity and Cardiac Remodelling.

BACKGROUND: Ischemic cardiomyopathy (ICM) is associated with electrical and structural remodelling, leading to arrhythmias. Caveolin-1 (Cav1) is a membrane protein involved in the pathogenesis of ischemic injury. Cav1 deficiency has been associated with arrhythmogenicity. The current study aimed to determine how Cav1 overexpression inhibits arrhythmias and cardiac remodelling in ICM. METHODS: ICM was modelled using left anterior descending (LAD) artery ligation for 4 weeks. Cardiac-specific Cav1 overexpression in ICM on arrhythmias, excitation-contraction coupling, and cardiac remodelling were investigated using the intramyocardial injection of an adeno-associated virus serotype 9 (AAV-9) system, carrying a specific sequence expressing Cav1 (AAVCav1) under the cardiac troponin T (cTnT) promoter. RESULTS: Cav1 overexpression decreased susceptibility to arrhythmias by upregulating gap junction connexin 43 (CX43) and reducing spontaneous irregular proarrhythmogenic Ca2+ waves in ventricular cardiomyocytes. It also alleviated ischemic injury-induced contractility weakness by improving Ca2+ cycling through normalizing Ca2+-handling protein levels and improving Ca2+ homeostasis. Masson stain and immunoblotting revealed that the deposition of excessive fibrosis was attenuated by Cav1 overexpression, inhibiting the transforming growth factor-ß (TGF-ß)/Smad2 signalling pathway. Coimmunoprecipitation assays demonstrated that the interaction between Cav1 and cSrc modulated CX43 expression and Ca2+-handling protein levels. CONCLUSIONS: Cardiac-specific overexpression of Cav1 attenuated ventricular arrhythmia, improved Ca2+ cycling, and attenuated cardiac remodelling. These effects were attributed to modulation of CX43, normalized Ca2+-handling protein levels, improved Ca2+ homeostasis, and attenuated cardiac fibrosis.

An avalanche-and-surge robust ultrawide-bandgap heterojunction for power electronics.

Avalanche and surge robustness involve fundamental carrier dynamics under high electric field and current density. They are also prerequisites of any power device to survive common overvoltage and overcurrent stresses in power electronics applications such as electric vehicles, electricity grids, and renewable energy processing. Despite tremendous efforts to develop the next-generation power devices using emerging ultra-wide bandgap semiconductors, the lack of effective bipolar doping has been a daunting obstacle for achieving the necessary robustness in these devices. Here we report avalanche and surge robustness in a heterojunction formed between the ultra-wide bandgap n-type gallium oxide and the wide-bandgap p-type nickel oxide. Under 1500 V reverse bias, impact ionization initiates in gallium oxide, and the staggered band alignment favors efficient hole removal, enabling a high avalanche current over 50 A. Under forward bias, bipolar conductivity modulation enables the junction to survive over 50 A surge current. Moreover, the asymmetric carrier lifetime makes the high-level carrier injection dominant in nickel oxide, enabling a fast reverse recovery within 15 ns. This heterojunction breaks the fundamental trade-off between robustness and switching speed in conventional homojunctions and removes a key hurdle to advance ultra-wide bandgap semiconductor devices for power industrial applications.

Loss of USP22 alleviates cardiac hypertrophy induced by pressure overload through HiF1-α-TAK1 signaling pathway.

Ubiquitin-specific protease 22 (USP22) is a member of the ubiquitin specific protease family (ubiquitin-specific protease, USPs), the largest subfamily of deubiquitinating enzymes, and plays an important role in the treatment of tumors. USP22 is also expressed in the heart. However, the role of USP22 in heart disease remains unclear. In this study, we found that USP22 was elevated in hypertrophic mouse hearts and in angiotensin II (Ang II)-induced cardiomyocytes. The inhibition of USP22 expression with adenovirus significantly rescued hypertrophic phenotype and cardiac dysfunction induced by pressure overloaded. Consistent with in vivo study, silencing by USP22 shRNA expression in vitro had similar results. Molecular analysis revealed that transforming growth factor-ß-activating protein 1 (TAK1)-(JNK1/2)/P38 signaling pathway and HIF-1α was activated in the Ang II-induced hypertrophic cardiomyocytes, whereas HIF-1α expression was decreased after the inhibition of USP22. Inhibition of HIF-1α expression reduces TAK1 expression. Co-immunoprecipitation and ubiquitination studies revealed the regulatory mechanism between USP22 and HIF1α.Under hypertrophic stress conditions, USP22 enhances the stability of HIF-1α through its deubiquitination activity, which further activates the TAK1-(JNK1/2)/P38 signaling pathway to lead to cardiac hypertrophy. Inhibition of HIF-1α expression further potentiates the in vivo pathological effects caused by USP22 deficiency. In summary, this study suggests that USP22, through HIF-1α-TAK1-(JNK1/2)/P38 signaling pathway, may be potential targets for inhibiting pathological cardiac hypertrophy induced by pressure overload.

Split Bull's eye shaped aluminum antenna for plasmon-enhanced nanometer scale germanium photodetector.

Bull's eye antennas are capable of efficiently collecting and concentrating optical signals into an ultrasmall area, offering an excellent solution to break the bottleneck between speed and photoresponse in subwavelength photodetectors. Here, we exploit the idea of split bull's eye antenna for a nanometer germanium photodetector operating at a standard communication wavelength of 1310 nm. The nontraditional plasmonic metal aluminum has been implemented in the resonant antenna structure fabricated by standard complementary metal-oxide-semiconductor (CMOS) processing. A significant enhancement in photoresponse could be achieved over the conventional bull's eye scheme due to an increased optical near-field in the active region. Moreover, with this novel antenna design the effective grating area could be significantly reduced without sacrificing device performance. This work paves the way for the future development of low-cost, high-density, and high-speed CMOS-compatible germanium-based optoelectronic devices.

Activation of the Cholinergic Anti-inflammatory Pathway Attenuated Angiotension II-Dependent Hypertension and Renal Injury.

Background: Angiotensin II (AngII) induces renal fibrosis, characterized by fibroblast proliferation, inflammatory cell infiltration and excessive extracellular matrix deposition, all of which was relevant closely to hypertension. The vagus nerve-related cholinergic anti-inflammatory pathway (CAP) modulates local and systemic inflammatory responses. The aim of present study was to determine the effect of CAP on renal inflammation and fibrosis. Methods and Results: AngII-induced hypertension was induced in vivo by 14-days low-dose AngII infusion from osmotic minipumps. We used GTS-21 dihydrochloride, a selective nicotinic acetylcholine receptor agonist. Daily intraperitoneal GTS-21 injection and/or vagotomy started after hypertension was confirmed and continued for 4 weeks. The elevated blood pressure caused by AngII was significantly attenuated by GTS-21. Improved baroreflex sensitivity was observed after GTS-21 administration. Masson stain and immunoblotting revealed that deposition of excessive fibrosis and overexpression of inflammatory cytokines induced by AngII was reduced by GTS-21. To determine the role of autonomic control in CAP, unilateral vagotomy was performed. Vagotomy weakened the effect of CAP on AngII-induced hypertension. In vitro, GTS-21 suppressed NF-κB activation, attenuated AngII-induced epithelial-mesenchymal transition and reduced inflammation and fibrosis in NRK-52E cells; α-bungarotoxin (α-Bgt, an α7-nAChR selective antagonist) partly inhibited these effects. Conclusion: CAP protected against AngII-induced hypertension via improvement in autonomic control, suppression of NF-κB activation, and reduction of renal fibrosis and inflammatory response.

Second-harmonic generation in photonic crystals with a pair of epsilon-negative and mu-negative defects.

A conventional one-dimensional photonic crystal with a conjugated pair of epsilon-negative and mu-negative defects has been presented, and only the defects are presumed to possess quadratic nonlinearity. Large enhancement of second-harmonic generation is predicted in numerical simulation. Interface and volume nonlinearity are both utilized in the process of second-harmonic generation due to the strong localization of the fundamental wave.

Highly Narrow-Band Polarization-Sensitive Solar-Blind Photodetectors Based on ß-Ga2O3 Single Crystals.

To suppress noise from full daylight background or environmental radiation, a spectrally selective solar-blind photodetector is widely required in many applications that need detection of light within a specific spectral range. Here, we present highly narrow-band solar-blind photodetectors by light polarization engineering of the anisotropic transitions in ß-Ga2O3 single crystals. The polarized transmittance characteristics reveal that direct transitions from valance subbands to the conduction band minimum are tuned between 4.53 and 4.76 eV for the light polarized E// c and E// b. The polarization-dependent photoresponsivity verifies that the order of fundamental band-to-band transitions obeys well the selection rules in terms of the valence-band splitting in the ß-Ga2O3 monoclinic crystal band structure. By combining an orthogonally aligned identical ß-Ga2O3 (100) single crystal filter with a detector measured at a chopper frequency of 17 Hz, a highly narrow-band detection is produced with a peak responsivity of 0.23 A/W at 262 nm, an EQE of 110%, a bandwidth of 10 nm, a light rejection ratio over 800, and a response time of 0.86 ms. This provides a new paradigm for a narrow-band solar-blind photodetector with broad applications where background noise emission needs to be suppressed.