Sirtuin1 Over-Expression Does Not Impact Retinal Vascular and Neuronal Degeneration in a Mouse Model of Oxygen-Induced Retinopathy

Proliferative retinopathy is a leading cause of blindness, including retinopathy of prematurity (ROP) in children and diabetic retinopathy in adults. Retinopathy is characterized by an initial phase of vessel loss, leading to tissue ischemia and hypoxia, followed by sight threatening pathologic neovascularization in the second phase. Previously we found that Sirtuin1 (Sirt1), a metabolically dependent protein deacetylase, regulates vascular regeneration in a mouse model of oxygen-induced proliferative retinopathy (OIR), as neuronal depletion of Sirt1 in retina worsens retinopathy. In this study we assessed whether over-expression of Sirtuin1 in retinal neurons and vessels achieved by crossing Sirt1 over-expressing flox mice with Nestin-Cre mice or Tie2-Cre mice, respectively, may protect against retinopathy. We found that over-expression of Sirt1 in Nestin expressing retinal neurons does not impact vaso-obliteration or pathologic neovascularization in OIR, nor does it influence neuronal degeneration in OIR. Similarly, increased expression of Sirt1 in Tie2 expressing vascular endothelial cells and monocytes/macrophages does not protect retinal vessels in OIR. In addition to the genetic approaches, dietary supplement with Sirt1 activators, resveratrol or SRT1720, were fed to wild type mice with OIR. Neither treatment showed significant vaso-protective effects in retinopathy. Together these results indicate that although endogenous Sirt1 is important as a stress-induced protector in retinopathy, over-expression of Sirt1 or treatment with small molecule activators at the examined doses do not provide additional protection against retinopathy in mice. Further studies are needed to examine in depth whether increasing levels of Sirt1 may serve as a potential therapeutic approach to treat or prevent retinopathy

Choroid Sprouting Assay: An Ex Vivo Model of Microvascular Angiogenesis

Angiogenesis of the microvasculature is central to the etiology of many diseases including proliferative retinopathy, age-related macular degeneration and cancer. A mouse model of microvascular angiogenesis would be very valuable and enable access to a wide range of genetically manipulated tissues that closely approximate small blood vessel growth in vivo. Vascular endothelial cells cultured in vitro are widely used, however, isolating pure vascular murine endothelial cells is technically challenging. A microvascular mouse explant model that is robust, quantitative and can be reproduced without difficulty would overcome these limitations. Here we characterized and optimized for reproducibility an organotypic microvascular angiogenesis mouse and rat model from the choroid, a microvascular bed in the posterior of eye. The choroidal tissues from C57BL/6J and 129S6/SvEvTac mice and Sprague Dawley rats were isolated and incubated in Matrigel. Vascular sprouting was comparable between choroid samples obtained from different animals of the same genetic background. The sprouting area, normalized to controls, was highly reproducible between independent experiments. We developed a semi-automated macro in ImageJ software to allow for more efficient quantification of sprouting area. Isolated choroid explants responded to manipulation of the external environment while maintaining the local interactions of endothelial cells with neighboring cells, including pericytes and macrophages as evidenced by immunohistochemistry and fluorescence-activated cell sorting (FACS) analysis. This reproducible ex vivo angiogenesis assay can be used to evaluate angiogenic potential of pharmacologic compounds on microvessels and can take advantage of genetically manipulated mouse tissue for microvascular disease research

Neuronal sirtuin1 mediates retinal vascular regeneration in oxygen-induced ischemic retinopathy

Regeneration of blood vessels in ischemic neuronal tissue is critical to reduce tissue damage in diseases. In proliferative retinopathy, initial vessel loss leads to retinal ischemia, which can induce either regrowth of vessels to restore normal metabolism and minimize damage, or progress to hypoxia-induced sight-threatening pathologic vaso-proliferation. It is not well understood how retinal neurons mediate regeneration of vascular growth in response to ischemic insults. In this study we aim to investigate the potential role of Sirtuin 1 (Sirt1), a metabolically-regulated protein deacetylase, in mediating the response of ischemic neurons to regulate vascular regrowth in a mouse model of oxygen-induced ischemic retinopathy (OIR). We found that Sirt1 is highly induced in the avascular ischemic retina in OIR. Conditional depletion of neuronal Sirt1 leads to significantly decreased retinal vascular regeneration into the avascular zone and increased hypoxia-induced pathologic vascular growth. This effect is likely independent of PGC-1α, a known Sirt1 target, as absence of PGC-1α in knockout mice does not impact vascular growth in retinopathy. We found that neuronal Sirt1 controls vascular regrowth in part through modulating deacetylation and stability of hypoxia-induced factor 1α and 2α, and thereby modulating expression of angiogenic factors. These results indicate that ischemic neurons induce Sirt1 to promote revascularization into ischemic neuronal areas, suggesting a novel role of neuronal Sirt1 in mediating vascular regeneration in ischemic conditions, with potential implications beyond retinopathy

Observation of a charged charmoniumlike structure in e+e−→(D∗Dˉ∗)±π∓e^+e^- \to (D^{*} \bar{D}^{*})^{\pm} \pi^\mp at s=4.26\sqrt{s}=4.26GeV

We study the process $e^+e^- \to (D^{*} \bar{D}^{*})^{\pm} \pi^\mp$ at a center-of-mass energy of 4.26GeV using a 827pb$^{-1}$ data sample obtained with the BESIII detector at the Beijing Electron Positron Collider. Based on a partial reconstruction technique, the Born cross section is measured to be $(137\pm9\pm15)$pb. We observe a structure near the $(D^{*} \bar{D}^{*})^{\pm}$ threshold in the $\pi^\mp$ recoil mass spectrum, which we denote as the $Z^{\pm}_c(4025)$. The measured mass and width of the structure are $(4026.3\pm2.6\pm3.7)$MeV/c$^2$ and $(24.8\pm5.6\pm7.7)$MeV, respectively. Its production ratio $\frac{\sigma(e^+e^-\to Z^{\pm}_c(4025)\pi^\mp \to (D^{*} \bar{D}^{*})^{\pm} \pi^\mp)}{\sigma(e^+e^-\to (D^{*} \bar{D}^{*})^{\pm} \pi^\mp)}$ is determined to be $0.65\pm0.09\pm0.06$. The first uncertainties are statistical and the second are systematic.Comment: 7 pages, 4 figures, 1 table; version accepted to be published in PR

Search for the Lepton Flavor Violation Process J/ψ→eμJ/\psi \to e\mu at BESIII

We search for the lepton-flavor-violating decay of the $J/\psi$ into an electron and a muon using $(225.3\pm2.8)\times 10^{6}$ $J/\psi$ events collected with the BESIII detector at the BEPCII collider. Four candidate events are found in the signal region, consistent with background expectations. An upper limit on the branching fraction of $\mathcal{B}(J/\psi \to e\mu)< 1.5 \times 10^{-7}$ (90% C.L.) is obtained

Search for Baryonic Decays of \psi(3770) and \psi(4040)

By analyzing data samples of 2.9 fb^{-1} collected at \sqrt s=3.773 GeV, 482 pb^{-1} collected at \sqrt s=4.009 GeV and 67 pb^{-1} collected at \sqrt s=3.542, 3.554, 3.561, 3.600 and 3.650 GeV with the BESIII detector at the BEPCII storage ring, we search for \psi(3770) and \psi(4040) decay to baryonic final states, including \Lambda\bar\Lambda\pi^+\pi^-, \Lambda \bar\Lambda\pi^0, \Lambda\bar\Lambda\eta, \Sigma^+ \bar\Sigma^-, \Sigma^0 \bar\Sigma^0, \Xi^-\bar\Xi^+ and \Xi^0\bar\Xi^0 decays. None are observed, and upper limits are set at the 90% confidence level.Comment: 9 pages, 3 figure

Retinal lipid and glucose metabolism dictates angiogenesis through the lipid sensor Ffar1

Tissues with high metabolic rates often use lipids, as well as glucose, for energy, conferring a survival advantage during feast and famine1. Current dogma suggests that high-energy–consuming photoreceptors depend on glucose2, 3. Here we show that the retina also uses fatty acid β-oxidation for energy. Moreover, we identify a lipid sensor, free fatty acid receptor 1 (Ffar1), that curbs glucose uptake when fatty acids are available. Very-low-density lipoprotein receptor (Vldlr), which is present in photoreceptors4 and is expressed in other tissues with a high metabolic rate, facilitates the uptake of triglyceride-derived fatty acid5, 6. In the retinas of Vldlr−/− mice with low fatty acid uptake6 but high circulating lipid levels, we found that Ffar1 suppresses expression of the glucose transporter Glut1. Impaired glucose entry into photoreceptors results in a dual (lipid and glucose) fuel shortage and a reduction in the levels of the Krebs cycle intermediate α-ketoglutarate (α-KG). Low α-KG levels promotes stabilization of hypoxia-induced factor 1a (Hif1a) and secretion of vascular endothelial growth factor A (Vegfa) by starved Vldlr−/− photoreceptors, leading to neovascularization. The aberrant vessels in the Vldlr−/− retinas, which invade normally avascular photoreceptors, are reminiscent of the vascular defects in retinal angiomatous proliferation, a subset of neovascular age-related macular degeneration (AMD)7, which is associated with high vitreous VEGFA levels in humans. Dysregulated lipid and glucose photoreceptor energy metabolism may therefore be a driving force in macular telangiectasia, neovascular AMD and other retinal diseases

Assessment of Vestibular-Evoked Myogenic Potentials in Parkinson&rsquo;s Disease: A Systematic Review and Meta-Analysis

(1) Background: The brainstem plays an essential role in the early stage of Parkinson&rsquo;s disease (PD), but it is not widely tested in clinical examinations of PD. Vestibular-evoked myogenic potentials (VEMPs) are recognized as fundamental tools in the assessment of brainstem function. The aim of our meta-analysis was to assess the abnormal findings of VEMPs in patients with PD. (2) Methods: Up to 14 February 2022, PubMed, Embase, and Web of Science were searched to evaluate VEMPs in patients with PD in comparison with respective controls. The study protocol was registered at PROSPERO (CRD42022311103). (3) Results: A total of 15 studies were finally included in our meta-analysis. The absence rates of VEMPs in patients with PD were significantly higher than those of control groups (cVEMP: OR = 6.77; oVEMP: OR = 13.9; mVEMP: OR = 7.52). A delayed P13 latency, a decreased peak-to-peak amplitude, and an increased AAR of cVEMP, and a delayed oVEMP P15 latency were also found in patients with PD. (4) Conclusions: Our meta-analysis indicates abnormal VEMP findings in patients with PD, revealing the dysfunction of the brainstem in PD. VEMP tests, especially cVEMP tests, could be a helpful method for the early detection of PD

An Adaptive Multi-Population Approach for Sphericity Error Evaluation in the Manufacture of Hemispherical Shell Resonators

The performance of a hemispherical resonant gyroscope (HRG) is directly affected by the sphericity error of the thin-walled spherical shell of the hemispherical shell resonator (HSR). In the production process of the HSRs, high-speed, high-accuracy, and high-robustness requirements are necessary for evaluating sphericity errors. We designed a sphericity error evaluation method based on the minimum zone criterion with an adaptive number of subpopulations. The method utilizes the global optimal solution and the subpopulations’ optimal solution to guide the search, initializes the subpopulations through clustering, and dynamically eliminates inferior subpopulations. Simulation experiments demonstrate that the algorithm exhibits excellent evaluation accuracy when processing simulation datasets with different sphericity errors, radii, and numbers of sampling points. The uncertainty of the results reached the order of 10−9 mm. When processing up to 6000 simulation datasets, the algorithm’s solution deviation from the ideal sphericity error remained around −3 × 10−9 mm. And the sphericity error evaluation was completed within 1 s on average. Additionally, comparison experiments further confirmed the evaluation accuracy of the algorithm. In the HSR sample measurement experiments, our algorithm improved the sphericity error assessment accuracy of the HSR’s inner and outer contour sampling datasets by 17% and 4%, compared with the results given by the coordinate measuring machine. The experiment results demonstrated that the algorithm meets the requirements of sphericity error assessment in the manufacturing process of the HSRs and has the potential to be widely used in the future

Selective oxidation of rare metal oxide insulation layers on particle substrates for optimizing the performance of FeSiCr-based soft magnetic composites

This study introduces an approach to fabricating soft magnetic composites (SMCs) that effectively address core loss while maintaining high magnetic conductivity. During the sintering process in a water vapor environment, the CeO2 insulation layer facilitates the selective oxidation of Si while simultaneously impeding the outward diffusion of Fe and Cr. Consequently, a CeO2·SiO2 composite insulation layer forms within the FeSiCr-based SMCs. The FeSiCr-based SMCs with the CeO2·SiO2 composite insulation layer achieve a saturation magnetization of 153.1 emu/g, which is 10.9% lower than that of FeSi3.7Cr4.5 compacts, and exhibits a deterioration rate lower than previously reported values. Moreover, the permeability of the FeSiCr-based SMCs remains highly stable, demonstrating outstanding insulation characteristics. The total core loss and core loss separation results further corroborate that incorporating a CeO2·SiO2 composite insulation layer leads to a more pronounced reduction in interparticle eddy current loss than using a CeO2 insulating layer alone. This performance enhancement can be attributed to the selective oxidation of a rare metal oxide insulation layer on a ferromagnetic metal particle substrate, a technique applied to SMCs for the first time. These findings hold significant implications for the design of high-performance SMCs in miniaturized and lightweight electromagnetic devices