Calcineurin suppresses rat H9c2 cardiomyocyteprotective autophagy under chronic intermittent hypoxia by downregulating the AMPK pathway.

Calcineurin plays a key role in cardiovascular pathogenesis by exerting pro-apoptotic effects in cardiomyocytes. However, whether calcineurin can regulate cardiomyocyte autophagy under conditions of chronic intermittent hypoxia (CIH) remains unclear. Here, we showed that CIH induced calcineurin activity in H9c2 cells, which attenuated adenosine monophosphate-activated protein kinase (AMPK) signaling and inhibited autophagy. In H9c2 cells, autophagy levels, LC3 expression, and AMPK phosphorylation were significantly elevated under conditions of CIH within 3 days. However, after 5 days of CIH, these effects were reversed and calcineurin activity and apoptosis were significantly increased. The calcineurin inhibitor 17-Allyl-1,14-dihydroxy-12-[2-(4-hydroxy-3-methoxycyclohexyl) -1-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo- [22.3.1.04,9]octacos-18- ene-2,3,10,16-tetrone (FK506) restored AMPK activation and LC3 expression and attenuated CIH-induced H9c2 cell apoptosis. In contrast, calcineurin overexpression significantly attenuated the increase in LC3 expression and enhanced H9c2 cell apoptosis under conditions of CIH. Calcineurin inhibition failed to induce autophagy or alleviate apoptosis in H9c2 cells expressing a kinase-dead K45R AMPK mutant. Autophagy inhibition abrogated the protective effects of FK506-mediated calcineurin inhibition. These results indicate that calcineurin suppresses adaptive autophagy during CIH by downregulating AMPK activation. Our findings reveal the underlying mechanism of calcineurin and autophagy regulation during H9c2 cell survival under conditions of CIH and may provide a new strategy for preventing CIH-induced cardiomyocyte damage.

High-precision angular rate detection based on an optomechanical micro hemispherical shell resonator gyroscope.

Cavity optomechanics with picometer displacement measurement resolution has shown vital applications in high-precision sensing areas. In this paper, an optomechanical micro hemispherical shell resonator gyroscope (MHSRG) is proposed, for the first time. The MHSRG is driven by the strong opto-mechanical coupling effect based on the established whispering gallery mode (WGM). And the angular rate is characterized by measuring the transmission amplitude changing of laser coupled in and out from the optomechanical MHSRG based on the dispersive resonance wavelength shift and/or dissipative losses varying. The detailed operating principle of high-precision angular rate detection is theoretically explored and the fully characteristic parameters are numerically investigated. Simulation results show that the optomechanical MHSRG can achieve scale factor of 414.8 mV/ (°/ s) and angular random walk of 0.0555 °/ h1/2 when the input laser power is 3 mW and resonator mass is just 98 ng. Such proposed optomechanical MHSRG can be widely used for chip-scale inertial navigation, attitude measurement, and stabilization.

Accuracy of a clinical decision support system based on the 3-minute diagnostic interview for CAM-defined delirium: A validation study✰.

OBJECTIVE: To evaluate the accuracy of the 3D-DST for delirium assessment in older adults by the nurse researcher. METHODS: The 3D-DST was administered by a trained nurse researcher to assess delirium among eligible older adults (aged ≥70 years). The criteria for identifying delirium was based on the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-V). RESULTS: A total of 95 older adults were enrolled in the current study, and 23 patients were identified as positive for delirium by the psychiatrist. The sensitivity and specificity of the 3D-DST were 96% and 94%, respectively. High sensitivities of the 3D-DST were also observed among patients with hypoactive delirium (95%) and those with cognitive impairment (93%). CONCLUSION: The 3D-DST was demonstrated as an appropriate instrument with highly acceptable sensitivities and specificities for delirium detection in hospitalized older patients.

Research on the reflection-type ELC-based optomechanical metamaterial.

In this paper, we propose a new kind of optomechanical metamaterial based on a planar ELC-type absorbing structure fabricated on the low-loss flexible substrate. The nonlinear coupling mechanism and nonlinear response phenomenon of the proposed optomechanical metamaterial driven by electromagnetic induced force are analyzed theoretically. The mechanical deformation/displacement and the mechanical resonance frequency shift of the metamaterial unit deposed on the flexible substrate are also numerically and experimentally demonstrated to reveal the coupling phenomenon of electromagnetic field and mechanical field. These results will help researchers to further understand the multi-physics interactions of optomechanical metamaterials and will promote the developments of new type of metasurface for high-efficiency dynamic electromagnetic wave controlling and formatting.

Immune Activation: A Link Between Food Insecurity and Chronic Disease in People Living With Human Immunodeficiency Virus.

Persistent immune activation is a hallmark of human immunodeficiency virus (HIV) infection and thought to play a role on chronic diseases in people with HIV (PWH). Food insecurity is disproportionately prevalent in PWH and is associated with adverse health outcomes. We determined whether food insecurity was associated with increased plasma levels of soluble CD14, CD27, and CD163 in 323 antiretroviral-treated PWH from the Miami Adult Studies on HIV cohort. Nearly half (42.7%) of participants were food insecure, and 85.5% were virally suppressed (<200 copies/mL). Food insecurity was independently associated with higher levels of soluble CD14 and soluble CD27. Very low food security was associated with increased soluble CD163 levels among those with lower CD4+ cell counts. Food insecurity may promote immune activation in PWH, suggesting a biological link between food insecurity and chronic disease among PWH. Improving financial security and access to high-quality diets could reduce the burden of disease in this highly vulnerable population.

Thermally tunable high-Q metamaterial and sensing application based on liquid metals.

Achieving a high Q-factor metamaterial unit for a precision sensing application is highly demanded in recent years, and most of the developed high-performance sensors based on the high-Q metamaterial units are due to the dielectric/magnetic property changes of the substrate/superstrate. In this paper, we propose a completely different sensing metamaterial unit configuration, with good sensing sensitivity and precision properties, based on the thermally tunable liquid metals. Specifically, a basic thermally tunable metamaterial unit, the mercury-inspired split ring resonator (SRR), is firstly presented to theoretically show the magnetic resonance and negative permeability frequency band shift properties under different background temperatures. Then, considering the radiation loss mechanism of the conventional SRR metamaterial unit and based on the physically reliable ability of liquid metals, the modified mercury-inspired Fano and toroidal resonators with a large frequency tuning range and high Q-factor are developed and discussed. The numerical demonstrations have shown that the designed Fano and toroidal resonators have much better sensing precision performances compared to the conventional SRR for the temperature sensing application. The experimental demonstrations have also been used to verify the proposed mercury-based toroidal resonators, and good agreements are achieved.

Role of Selenium in Viral Infections with a Major Focus on SARS-CoV-2.

Viral infections have afflicted human health and despite great advancements in scientific knowledge and technologies, continue to affect our society today. The current coronavirus (COVID-19) pandemic has put a spotlight on the need to review the evidence on the impact of nutritional strategies to maintain a healthy immune system, particularly in instances where there are limited therapeutic treatments. Selenium, an essential trace element in humans, has a long history of lowering the occurrence and severity of viral infections. Much of the benefits derived from selenium are due to its incorporation into selenocysteine, an important component of proteins known as selenoproteins. Viral infections are associated with an increase in reactive oxygen species and may result in oxidative stress. Studies suggest that selenium deficiency alters immune response and viral infection by increasing oxidative stress and the rate of mutations in the viral genome, leading to an increase in pathogenicity and damage to the host. This review examines viral infections, including the novel SARS-CoV-2, in the context of selenium, in order to inform potential nutritional strategies to maintain a healthy immune system.

Validation of the 3-minute diagnostic interview for CAM-defined Delirium in Chinese older adults.

Delirium is a common complication among older adults, but it is often unrecognized in routine practice. The 3-Minute Diagnostic Interview for CAM-defined Delirium (3D-CAM) was developed to identify delirium in the general unit. This prospective diagnostic study was conducted to validate the accuracy of the 3D-CAM Chinese version among older adults in the general units. A total of 204 hospitalized older adults from a geriatric hospital were enrolled in the study, of whom 54 were identified as positive for delirium. The sensitivity and specificity of the 3D-CAM Chinese version were 94% and 97%, respectively. The median duration of assessment using the 3D-CAM was about 3 minutes. The 3D-CAM had highly acceptable sensitivity and specificity when it was used by nurse researchers among Chinese older adults.

Anti-silencing factor 1A is associated with genome stability maintenance of mouse preimplantation embryos†.

Genome stability is critical for the normal development of preimplantation embryos, as DNA damages may result in mutation and even embryo lethality. Anti-silencing factor 1A (ASF1A) is a histone chaperone and enriched in the MII oocytes as a maternal factor, which may be associated with the maintenance of genome stability. Thus, this study was undertaken to explore the role of ASF1A in maintaining the genome stability of early mouse embryos. The ASF1A expressed in the preimplantation embryos and displayed a dynamic pattern throughout the early embryonic development. Inhibition of ASF1A expression decreased embryonic development and increased DNA damages. Overexpression of ASF1A improved the developmental potential and decreased DNA damages. When 293T cells that had been integrated with RGS-NHEJ were co-transfected with plasmids of pcDNA3.1-ASF1A, gRNA-NHEJ, and hCas9, less cells expressed eGFP, indicating that non-homologous end joining was reduced by ASF1A. When 293T cells were co-transfected with plasmids of HR-donor, gRNA-HR, hCas9, and pcDNA3.1-ASF1A, more cells expressed eGFP, indicating that homologous recombination (HR) was enhanced by ASF1A. These results indicate that ASF1A may be associated with the genome stability maintenance of early mouse embryos and this action may be mediated by promoting DNA damage repair through HR pathway.

Validation and Refinement of Noninvasive Methods to Assess Hepatic Fibrosis: Magnetic Resonance Elastography Versus Enhanced Liver Fibrosis Index.

BACKGROUND: Noninvasive fibrosis markers are routinely used in patients with liver disease. Magnetic resonance elastography (MRE) is recognized as a highly accurate methodology, but a reliable blood test for fibrosis would be useful. We examined performance characteristics of the Enhanced Liver Fibrosis (ELF) Index compared to MRE in a cohort including those with HCV, HIV, and HCV/HIV. METHODS: Subjects enrolled in the Miami Adult Studies on HIV (MASH) cohort underwent MRE and blood sampling. The ELF Index was scored and receiver-operator curves constructed to determine optimal cutoff levels relative to performance characteristics. Cytokine testing was performed to identify new markers to enhance noninvasive marker development. RESULTS: The ELF Index was determined in 459 subjects; more than half were male, non-white, and HIV-infected. MRE was obtained on a subset of 283 subjects and the group that had both studies served as the basis of the receiver-operator curve analysis. At an ELF Index of > 10.633, the area under the curve for cirrhosis (Metavir F4, MRE > 4.62 kPa) was 0.986 (95% CI 0.994-0.996; p < 0.001) with a specificity of 100%. For advanced fibrosis (Metavir F3/4), an ELF cutoff of 10 was associated with poor sensitivity but high specificity (98.9%, 95% CI 96.7-99.8%) with an AUC of 0.80 (95% CI 0.749-0.845). ELF Index performance characteristics exceeded FIB-4 performance. HCV and age were associated with increased fibrosis (p < 0.05) in a multivariable model. IP-10 was found to be a promising biomarker for improvement in noninvasive prediction algorithms. CONCLUSIONS: The ELF Index was a highly sensitive and specific marker of cirrhosis, even among HIV-infected individuals, when compared with MRE. IP-10 may be a biomarker that can enhance performance characteristics further, but additional validation is required.

Anatomical and Clinical Comparison of Small Free Flaps for Repairing Finger Skin Defects.

The reconstruction of finger defects requires improved functional outcomes and acceptable esthetic outcomes, and small free flaps present a good alternative technique for repairing finger skin defects. From January 2006 to December 2018, we investigated the number and diameter of proximal digital artery perforators, medial plantar artery perforators, and peroneal proper plantar digital arteries of the hallux by dissection and then transplanted free digital arterial perforator flaps, free medial plantar flaps, and free peroneal flaps from the hallux to repair small finger skin defects. The number (SD) of perforators from the medial plantar artery was approximately 2.2 (0.5), and these perforators measured 0.53 (0.20) mm in diameter. The diameter (SD) of the first metatarsal dorsal artery was approximately 1.16 (0.30) mm. A total of 25 patients were included in this study. The transplantation times (SD) for free digital arterial perforator flaps, free medial plantar flaps, and free peroneal flaps from the hallux were 3.5 (0.5) hours, 3.2 (0.7) hours, and 2.0 (0.4) hours, respectively. The follow-up period ranged from 8 to 15 months. All flaps survived and were appropriately shaped. The donor site was either covered with a free flap or directly sutured. Among these 3 types of small flaps, the free peroneal flap from the hallux can be recommended for clinical use because of the large diameter of the contributing vessels, the short operative time, the ease of access, and the improved appearance of the donor site.

Metamaterial perfect absorber with unabated size-independent absorption.

Metamaterial absorbers open a new door for the design of optical harvesting devices ranging from the microwave to optical regimes. The top resonator in these structures is critical for the function of metamaterial absorbers. The resonant frequency, bandwidth, and maximum absorption mainly depend on the choice of material, shape, and size of the top resonator. The maximum absorption is generally impaired as the size of the resonator changes, due to the high sensitivity of impedance matching with the medium. In this paper, we experimentally demonstrate a metamaterial perfect absorber with unabated absorption as its resonator's size changes. The perfect absorber is based on an array of metal squares inscribed with a hollow square. The absorption maxima stay above 98% as the size changes from 600 to 1500 nm in the mid-infrared region, agreeing with simulated results yielding an absorption of ~100%. The unabated absorption properties can be interpreted by the equivalent circuit theory. Moreover, the experimental absorption remains above 91% for incident angles change up to 50°, both for TE and TM polarization. Our work offers a method for achieving stable perfect absorption in sensing, filtering, and selective thermal emission.

Nonlinear coupling states study of electromagnetic force actuated plasmonic nonlinear metamaterials.

Electromagnetic force actuated plasmonic nonlinear metamaterials have attracted a great deal of interest from the scientific community over the past several years, owing to the abundant interactions between the electromagnetically induced Ampère's force and the stored mechanical force within the meta-atoms. Despite this interest, a comprehensive study of such metamaterials is still lacking, especially for the nonlinear coupling states analysis. Here we fill this gap by extensively studying the physics of electromagnetic force actuated plasmonic nonlinear metamaterials and presenting a number of new significant findings. Our study will help physicists and engineers to better understand this hot topic and stimulate rapid developments of this promising nonlinear metamaterials.

Bioinformatic analysis for the identification of key candidate genes and pathways in the substantia nigra in Parkinson's disease.

Parkinson's disease is one of the most common diseases in the elderly population, and the substantia nigra is generally involved in the disease process; however, the signaling pathways and related genes underlying Parkinson's disease remain unclear. This study integrated three cohorts of profile datasets to elucidate the potential key candidate genes and pathways in Parkinson's disease. The expression profiles of GSE8397, GSE20186 and GSE49036 were included 55 available substantia nigra tissue samples from individuals diagnosed with Parkinson's disease and 33 substantia nigra tissue samples from healthy controls. These samples were integrated and thoroughly analyzed. Differentially expressed genes (DEGs) were sorted, and candidate genes and pathway enrichments were analyzed. A DEG-associated protein-protein interaction network analysis was performed. 27 shared downregulated DEGs were identified from the three GSE datasets. The DEGs were clustered based on function and signaling pathway with significant enrichment analysis. 52 edges were identified from the DEG protein-protein interaction network complex, which included dopamine metabolism, nerve conduction, reduced neuronal toxicity and proliferation pathways. Using integrated bioinformatic analysis, we identified candidate genes and pathways in Parkinson's disease that could improve our understanding of underlying molecular events, which could be potential therapeutic targets for Parkinson's disease.

Controllable optomechanical coupling and Drude self-pulsation plasma locking in chip-scale optomechanical cavities.

We demonstrate the controllable optomechanical coupling and Drude self-pulsation plasma locking in chip-scale optomechanical cavities. The optomechanical coupling between the optical and mechanical degrees-of-freedom is dependent on the intracavity energy via the coupled fiber position. With the deterministic optomechanical stiffening, the interaction between optomechanical oscillation and self-pulsation can be controlled. Intracavity locking with 1/6 subharmonics is obtained over a wide optical detuning range of 190.01-192.23 THz. These results bring new insights into implementations of nonlinear dynamics at mesoscopic scale, with potential applications from photonic signal processing to nonlinear dynamic networks.

FTY-720P Suppresses Osteoclast Formation by Regulating Expression of Interleukin-6 (IL-6), Interleukin-4 (IL-4), and Matrix Metalloproteinase 2 (MMP-2).

BACKGROUND Osteoclast formation is closely related to the immune system. FTY720, a new immunosuppressive agent, has some functions in immune regulation. Its main active ingredients become FTY-720P in vivo by phosphorylation modification. The objective of this study was to determine the effects of FTY-720 with various concentrations on osteoclasts in vitro. MATERIAL AND METHODS RAW264.7 cells and bone marrow-derived mononuclear phagocytes (BMMs) were treated with RANKL to obtain osteoclasts in vitro. To investigate the role of FTY-720 in osteoclast formation, trap enzyme staining was performed and the number of osteoclasts was counted. Bone slices were stained with methylene blue, we counted the number of lacunae after bone slices were placed into dishes together with osteoclasts, and we observed the effect and function of FTY-720 in osteoclasts induced by RAW264.7 cells and BMMs. Then, we used a protein array kit to explore the effects of FTY-720P on osteoclasts. RESULTS The results of enzyme trap staining and F-actin staining experiments show that, with the increasing concentration of FTY-720P, the number of osteoclast induced by RAW264.7 cells and BMMs gradually decreased (P<0.05), especially when the FTY-720P concentration reached 1000 ng/ml, and the number of osteoclasts formed was the lowest (P<0.05). With bone lacuna toluidine blue staining, the results also show that, with the increasing concentration of FTY-720P, the number of bone lacuna gradually decreased (P<0.05), and the number of lacunae is lowest when the concentration reached 800 ng/ml. Finally, protein array results showed that IL-4, IL-6, IL-12, MMP-2, VEGF-C, GFR, basic FGF, MIP-2, and insulin proteins were regulated after FTY-720P treatment. CONCLUSIONS FTY-720P can suppress osteoclast formation and function, and FTY-720P induces a series of cytokine changes.

Numerical and theoretical analysis on the absorption properties of metasurface-based terahertz absorbers with different thicknesses.

In this paper, we numerically and theoretically discuss the novel absorption properties of a conventional metasurface-based terahertz (THz) electromagnetic (EM) absorber with different dielectric thicknesses. Two absorption modes are presented in the considered frequency band due to the increased dielectric thickness, and both modes can achieve near-unity absorptions when the dielectric layers reach additional nλ(d)/2 (n=1, 2) thicknesses, where λ(d) is the operating wavelength at the peak absorption in the dielectric slabs. The surface currents between the metasurface resonators and ground plane are not associated any longer, different from the conventional thin absorbers. Moreover, the EM wave energies are completely absorbed by the metasurface resonators and dielectric layer, and the main function of ground plane is to reflect the incident EM waves back to the resonators. The discussed novel absorption properties are analyzed and explained by classical EM theory and interference theory after numerical demonstrations. These findings can broaden the potential applications of the metasurface-based absorbers in the THz frequency range for different requirements.

Experimental demonstration of a magnetically tunable ferrite based metamaterial absorber.

We synthesize and systematically characterize a novel type of magnetically tunable metamaterial absorber (MA) by integrating ferrite as a substrate or superstrate into a conventional passive MA. The nearly perfect absorption and tunability of this device is studied both numerically and experimentally within X-band (8-12 GHz) in a rectangular waveguide setup. Our measurements clearly show that the resonant frequency of the MA can be shifted across a wide frequency band by continuous adjustment of a magnetic field acting on the ferrite. Moreover, the effects of substrate/superstrate's thickness on the MA's tunability are discussed. The insight gained from the generic analysis enabled us to design an optimized tunable MA with relative frequency tuning range as larger as 11.5% while keeping the absorptivity higher than 98.5%. Our results pave a path towards applications with tunable devices, such as selective thermal emitters, sensors, and bolometers.

Mechanical compression upregulates MMP9 through SMAD3 but not SMAD2 modulation in hypertrophic scar fibroblasts.

PURPOSE: Activation of transforming growth factor-ß (TGF-ß) signaling and matrix metalloproteinases are involved in hypertrophic scar (HS) formation. Compression therapy is known to be an effective approach for the treatment of hypertrophic scarring; however, the underlying molecular mechanisms remain poorly understood. We investigated the relationship between TGF-ß signaling activation and matrix metalloproteinases in HS fibroblasts during mechanical compressive stress. MATERIALS AND METHODS: Two groups of skin tissue from HS and the nearby normal tissue were obtained from surgical patients and analyzed. Primary fibroblasts from the HS tissue and normal fibroblasts were isolated. Pressure therapy was recapitulated in an in vitro three-dimensional culture model, using mechanical stress produced with the Flexcell FX-4000C Compression Plus System. Quantitative real-time PCR (qPCR) was used to analyze the gene expression profiles in skin tissue and cultured primary cells exposed to compressive stress. Knockdown of SMAD2 and SMAD3 was performed using their specific siRNA in HS and normal fibroblasts subjected to compressive stress, and gene expression was examined by qPCR and Western blot. RESULTS: There was a significant upregulation of the mRNA expression of matrix metalloproteinase-2 (MMP2) and MMP9 in primary HS fibroblasts in response to mechanical stress. In contrast, the mRNA levels of collagen I and collagen III were downregulated in primary HS fibroblasts compared with those in the control cells. SiRNA-mediated knockdown of SMAD3 in the primary fibroblasts exposed to mechanical stress resulted in a decrease in the expression of MMP9 compared to control cells. CONCLUSION: These results demonstrate that compressive stress upregulates MMP9 by SMAD3 but not by SMAD2.

Efficacy of combined therapy of periosteum and bone allograft in a critical-sized defect model in New Zealand white rabbits.

BACKGROUND: Large segmental bone defects caused by trauma, infection, or bone tumor resection are difficult to cure and have been a problem in the field of bone repair for decades. The objective of this study was to discuss the efficacy of combined therapy of free periosteum and bone allograft in treating bone defects and to provide a theoretical basis for clinical application of this therapy. MATERIAL/METHODS: A unilateral tibia cortical defect model in New Zealand white rabbits was established according to Girolamo method. Total 48 rabbits were randomized into 3 groups: a simple bone defect group (n=16), an autogenous bone graft group (n=16), and a periosteum and bone allograft combined therapy group (n=16). The efficacy was evaluated by imaging inspections and scoring, HE staining, and RT-PCR in postoperative weeks 2, 4, 8, and 12. RESULTS: The results of imaging and histopathological inspections in the study indicated that in postoperative weeks 4, 8, and 12 the experimental and control groups had statistically significant differences in Lane-Sandhu radiographic scoring and relative bone density when compared with the simple bone defect group (P<0.05). The RT-PCR results suggested that the expression of SPP-1, BMP-2, and VEGF in the experimental group was higher than in the control group (P<0.05) and the expression of Col Ia1 in the control group was higher than in the experimental group (P<0.05). CONCLUSIONS: Efficacies of the combined therapy (periosteum combined with bone allografting) and the criterion standard therapy (autogenous bone grafting) are equivalent in treating bone defects in New Zealand white rabbits.