Physiological Effects of Superoxide Dismutase on Altered Visual Function of Retinal Ganglion Cells in db/db Mice

Background: The C57BLKS/J db/db (db/db) mouse is a widely used type 2 diabetic animal model, and this model develops early inner retinal neuronal dysfunction beginning at 24 weeks. The neural mechanisms that mediate early stage retinal dysfunction in this model are unknown. We evaluated visual response properties of retinal ganglion cells (RGCs) during the early stage of diabetic insult (8, 12, and 20 wk) in db/db mice and determined if increased oxidative stress plays a role in impaired visual functions of RGCs in 20 wk old db/db mice. Methodology/Principal Findings: In vitro extracellular single-unit recordings from RGCs in wholemount retinas were performed. The receptive field size, luminance threshold, and contrast gain of the RGCs were investigated. Although ONand OFF-RGCs showed a different time course of RF size reduction, by 20 wk, the RF of ON- and OFF-RGCs were similarly affected. The LT of ON-RGCs was significantly elevated in 12 and 20 wk db/db mice compared to the LT of OFF-RGCs. The diabetic injury also affected contrast gains of ON- and OFF-RGCs differently. The generation of reactive oxidative species (ROS) in fresh retina was estimated by dihydroethidium. Superoxide dismutase (SOD) (300 unit/ml) was applied in Ames medium to the retina, and visual responses of RGCs were recorded for five hours. ROS generation in the retinas of db/db mice increased at 8wk and continued to progress at 20 wk of ages. In vitro application of SOD improved visual functions in 20 wk db/db mice but the SOD treatment affected ON- and OFF-RGCs differently in db/m retina

PPARs and Female Reproduction: Evidence from Genetically Manipulated Mice

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated nuclear receptors controlling many important physiological processes, including lipid and glucose metabolism, energy homeostasis, inflammation, as well as cell proliferation and differentiation. In the past decade, intensive study of PPARs has shed novel insight into prevention and treatment of dyslipidemia, insulin resistance, and type 2 diabetes. Recently, a large body of research revealed that PPARs are also functionally expressed in reproductive organs and various parts of placenta during pregnancy, which strongly suggests that PPARs might play a critical role in reproduction and development, in addition to their central actions in energy homeostasis. In this review, we summarize recent findings elucidating the role of PPARs in female reproduction, with particular focus on evidence from gene knockout and transgenic animal model study

Comparative and phylogenetic analysis of the complete chloroplast genomes of six Polygonatum species (Asparagaceae)

Abstract Polygonatum Miller belongs to the tribe Polygonateae of Asparagaceae. The horizontal creeping fleshy roots of several species in this genus serve as traditional Chinese medicine. Previous studies have mainly reported the size and gene contents of the plastomes, with little information on the comparative analysis of the plastid genomes of this genus. Additionally, there are still some species whose chloroplast genome information has not been reported. In this study, the complete plastomes of six Polygonatum were sequenced and assembled, among them, the chloroplast genome of P. campanulatum was reported for the first time. Comparative and phylogenetic analyses were then conducted with the published plastomes of three related species. Results indicated that the whole plastome length of the Polygonatum species ranged from 154,564 bp (P. multiflorum) to 156,028 bp (P. stenophyllum) having a quadripartite structure of LSC and SSC separated by two IR regions. A total of 113 unique genes were detected in each of the species. Comparative analysis revealed that gene content and total GC content in these species were highly identical. No significant contraction or expansion was observed in the IR boundaries among all the species except P. sibiricum1, in which the rps19 gene was pseudogenized owing to incomplete duplication. Abundant long dispersed repeats and SSRs were detected in each genome. There were five remarkably variable regions and 14 positively selected genes were identified among Polygonatum and Heteropolygonatum. Phylogenetic results based on chloroplast genome strongly supported the placement of P. campanulatum with alternate leaves in sect. Verticillata, a group characterized by whorled leaves. Moreover, P. verticillatum and P. cyrtonema were displayed as paraphyletic. This study revealed that the characters of plastomes in Polygonatum and Heteropolygonatum maintained a high degree of similarity. Five highly variable regions were found to be potential specific DNA barcodes in Polygonatum. Phylogenetic results suggested that leaf arrangement was not suitable as a basis for delimitation of subgeneric groups in Polygonatum and the definitions of P. cyrtonema and P. verticillatum require further study

Ultrasonic metamaterials with negative modulus

The emergence of artificially designed subwavelength electromagnetic materials, denoted metamaterials1, 2, 3, 4, 5, 6, 7, 8, 9, 10, has significantly broadened the range of material responses found in nature. However, the acoustic analogue to electromagnetic metamaterials has, so far, not been investigated. We report a new class of ultrasonic metamaterials consisting of an array of subwavelength Helmholtz resonators with designed acoustic inductance and capacitance. These materials have an effective dynamic modulus with negative values near the resonance frequency. As a result, these ultrasonic metamaterials can convey acoustic waves with a group velocity antiparallel to phase velocity, as observed experimentally. On the basis of homogenized-media theory, we calculated the dispersion and transmission, which agrees well with experiments near 30 kHz. As the negative dynamic modulus leads to a richness of surface states with very large wavevectors, this new class of acoustic metamaterials may offer interesting applications, such as acoustic negative refraction and superlensing below the diffraction limit

DataSheet_1_Elucidating common pathogenic transcriptional networks in infective endocarditis and sepsis: integrated insights from biomarker discovery and single-cell RNA sequencing.docx

BackgroundInfective Endocarditis (IE) and Sepsis are two closely related infectious diseases, yet their shared pathogenic mechanisms at the transcriptional level remain unclear. This research gap poses a barrier to the development of refined therapeutic strategies and drug innovation.MethodsThis study employed a collaborative approach using both microarray data and single-cell RNA sequencing (scRNA-seq) data to identify biomarkers for IE and Sepsis. It also offered an in-depth analysis of the roles and regulatory patterns of immune cells in these diseases.ResultsWe successfully identified four key biomarkers correlated with IE and Sepsis, namely CD177, IRAK3, RNASE2, and S100A12. Further investigation revealed the central role of Th1 cells, B cells, T cells, and IL-10, among other immune cells and cytokines, in the pathogenesis of these conditions. Notably, the small molecule drug Matrine exhibited potential therapeutic effects by targeting IL-10. Additionally, we discovered two Sepsis subgroups with distinct inflammatory responses and therapeutic strategies, where CD177 demonstrated significant classification value. The reliability of CD177 as a biomarker was further validated through qRT-PCR experiments.ConclusionThis research not only paves the way for early diagnosis and treatment of IE and Sepsis but also underscores the importance of identifying shared pathogenic mechanisms and novel therapeutic targets at the transcriptional level. Despite limitations in data volume and experimental validation, these preliminary findings add new perspectives to our understanding of these complex diseases.</p

miR-301b-3p Regulates Breast Cancer Cell Proliferation, Migration, and Invasion by Targeting NR3C2

Objectives. Breast cancer is the most common malignant tumor among females, and miRNAs have been reported to play an important regulatory role in breast cancer progression. This study aimed to explore the function and underlying molecular mechanism of miR-301b-3p in breast cancer. Methods. Differential analysis and survival analysis were performed based on the data accessed from the TCGA-BRCA dataset for identification of the target miRNA. Bioinformatics analysis was conducted to predict the downstream target gene of the miRNA. Real-time quantitative PCR was carried out to detect the expression of miR-301b-3p and nuclear receptor subfamily 3 group C member 2 (NR3C2). Western blot was used to assess the protein expression of NR3C2. Cell counting kit-8 assay was performed to evaluate the proliferation of breast cancer cells. Transwell assay was conducted to determine the migratory and invasive abilities of breast cancer cells. Dual-luciferase reporter assay was employed to verify the targeting relationship between miR-301b-3p and NR3C2. Results. miR-301b-3p was elevated in breast cancer cell lines and promoted cell proliferation, migration, and invasion in terms of its biological function in breast cancer. NR3C2 was validated as a direct target of miR-301b-3p via bioinformatics analysis and dual-luciferase reporter assay, and NR3C2 was downregulated in breast cancer cell lines. The rescue experiment indicated that NR3C2 was involved in the mechanism by which miR-301b-3p regulated the malignant phenotype of breast cancer cells. Conclusion. The present study revealed for the first time that miR-301b-3p could foster breast cancer cell proliferation, migration, and invasion by targeting NR3C2, unveiling that miR-301b-3p is a novel carcinogen in breast cancer

Visual response properties of ON- and OFF-RGCs of 20 wk db/db mice after in vitro SOD application.

<p><b>Panel A:</b> Discharge patterns of two ON-center RGCs in response to 0.02 cyc/deg sinusoidal drifting gratings of different contrast levels. The top two traces exhibit discharge patterns of an ON-RGC (305-C3, top left) recorded from a db/m retina (eccentricity: 0.94 mm) and bottom two traces show discharge patterns of an ON-RGC (121-C3, bottom left) recorded from a db/db retina (eccentricity: 1.17 mm). Contrast levels are shown to the left of the response traces. <b>Panel B:</b> Discharge patterns of two OFF-RGCs. The top two traces exhibit discharge patterns of an OFF-RGC (307-C3, top right) recorded from a db/m retina (eccentricity: 1.71 mm) and bottom two traces show discharge patterns of an OFF-RGC (121-C4) recorded from a db/db retina (eccentricity: 1.21 mm). <b>Panel C:</b> contrast response profiles of the two ON cells exhibited in Panel A. The abscissa is contrast (%) and vertical coordinate depicts contrast response magnitude (spk/sec). The open triangles depict db/m ON; open squares represent db/db ON. <b>Panel D:</b> The contrast response profiles of two OFF-RGCs illustrated in Panel B. filled triangles: db/m OFF; and filled squares: db/db OFF. <b>Panel E:</b> Histogram comparing average contrast sensitivity of ON and OFF RGCs of within each group. For db/db mice, as a comparison was made between the control (without SOD treatment) and ON-RGCs that received SOD treatment, the average contrast gain of latter was significantly increased (p<0.05, n = 6). As a comparison was made between the control and OFF-RGCs that received SOD treatment, the average contrast sensitivity of latter was significantly improved (p<0.01, n = 6). For db/m mice, after the SOD treatment, the contrast gain of ON-RGCs was not significantly changed whereas that of OFF-RGCs was significantly suppressed (p<0.01, n = 7). <b>Panel F:</b> Histogram comparing the average RF size of RGCs after SOD treatment. Other conventions are as for <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0030343#pone-0030343-g004" target="_blank">Figure 4</a>.</p

Receptive field size reduction in ON- and OFF-RGCs.

<p>The abscissa is animal age (wk) and vertical coordinate depicts relative percentage of RF size reduction. Filled diamond and solid line represents ON-RGC while open circle and dashed line shows OFF-RGC RF size reduction.</p