35 research outputs found

    Power scaling of high-power linearly polarized fiber lasers with <10 GHz linewidth

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    In this work, an all-fiberized polarization-maintained (PM) fiber laser has been demonstrated with a near-top-hat-shaped spectrum. By optimizing the modulation signal to generate near-top-hat-shaped spectrums, a 3-kW PM fiber laser has been achieved at &lt;10 GHz linewidth with the polarization extinction ratio of 96% and beam quality of 1.156, which is the highest output power ever reported with approximately 10 GHz linewidth, and further scaling of output power is limited by stimulated Brillouin scattering. By decomposing the mode content, the proportion of the fundamental mode in the output laser is above 97%. The stimulated Raman scattering suppression ratio reaches 62 dB at the maximal output power

    The ORF7a Protein of SARS-CoV-2 Initiates Autophagy and Limits Autophagosome-Lysosome Fusion via Degradation of SNAP29 To Promote Virus Replication

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    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is closely related to various cellular aspects associated with autophagy. However, how SARS-CoV-2 mediates the subversion of the macroautophagy/autophagy pathway remains largely unclear. In this study, we demonstrate that overexpression of the SARS-CoV-2 ORF7a protein activates LC3-II and leads to the accumulation of autophagosomes in multiple cell lines, while knockdown of the viral ORF7a gene via shRNAs targeting ORF7a sgRNA during SARS-CoV-2 infection decreased autophagy levels. Mechanistically, the ORF7a protein initiates autophagy via the AKT-MTOR-ULK1-mediated pathway, but ORF7a limits the progression of autophagic flux by activating CASP3 (caspase 3) to cleave the SNAP29 protein at aspartic acid residue 30 (D30), ultimately impairing complete autophagy. Importantly, SARS-CoV-2 infection-induced accumulated autophagosomes promote progeny virus production, whereby ORF7a downregulates SNAP29, ultimately resulting in failure of autophagosome fusion with lysosomes to promote viral replication. Taken together, our study reveals a mechanism by which SARS-CoV-2 utilizes the autophagic machinery to facilitate its own propagation via ORF7a.Abbreviations: 3-MA: 3-methyladenine; ACE2: angiotensin converting enzyme 2; ACTB/β-actin: actin beta; ATG7: autophagy related 7; Baf A1: bafilomycin A1; BECN1: beclin 1; CASP3: caspase 3; COVID-19: coronavirus disease 2019; GFP: green fluorescent protein; hpi: hour post-infection; hpt: hour post-transfection; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MERS: Middle East respiratory syndrome; MTOR: mechanistic target of rapamycin kinase; ORF: open reading frame; PARP: poly(ADP-ribose) polymerase; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; shRNAs: short hairpin RNAs; siRNA: small interfering RNA; SNAP29: synaptosome associated protein 29; SQSTM1/p62: sequestosome 1; STX17: syntaxin 17; TCID50: tissue culture infectious dose; TEM: transmission electron microscopy; TUBB, tubulin, beta; ULK1: unc-51 like autophagy activating kinase 1

    miRNA-135a promotes breast cancer cell migration and invasion by targeting HOXA10

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    <p>Abstract</p> <p>Background</p> <p>miRNAs are a group of small RNA molecules regulating target genes by inducing mRNA degradation or translational repression. Aberrant expression of miRNAs correlates with various cancers. Although miR-135a has been implicated in several other cancers, its role in breast cancer is unknown. <it>HOXA10 </it>however, is associated with multiple cancer types and was recently shown to induce p53 expression in breast cancer cells and reduce their invasive ability. Because <it>HOXA10 </it>is a confirmed miR-135a target in more than one tissue, we examined miR-135a levels in relation to breast cancer phenotypes to determine if miR-135a plays role in this cancer type.</p> <p>Methods</p> <p>Expression levels of miR-135a in tissues and cells were determined by poly (A)-RT PCR. The effect of miR-135a on proliferation was evaluated by CCK8 assay, cell migration and invasion were evaluated by transwell migration and invasion assays, and target protein expression was determined by western blotting. GFP and luciferase reporter plasmids were constructed to confirm the action of miR-135a on downstream target genes including <it>HOXA10</it>. Results are reported as means Âą S.D. and differences were tested for significance using 2-sided Student"s t-test.</p> <p>Results</p> <p>Here we report that miR-135a was highly expressed in metastatic breast tumors. We found that the expression of miR-135a was required for the migration and invasion of breast cancer cells, but not their proliferation. <it>HOXA10</it>, which encodes a transcription factor required for embryonic development and is a metastasis suppressor in breast cancer, was shown to be a direct target of miR-135a in breast cancer cells. Our analysis showed that miR-135a suppressed the expression of <it>HOXA10 </it>both at the mRNA and protein level, and its ability to promote cellular migration and invasion was partially reversed by overexpression of <it>HOXA10</it>.</p> <p>Conclusions</p> <p>In summary, our results indicate that miR-135a is an onco-miRNA that can promote breast cancer cell migration and invasion. <it>HOXA10 </it>is a target gene for miR-135a in breast cancer cells and overexpression of <it>HOXA10 </it>can partially reverse the miR-135a invasive phenotype.</p

    Mulberry Leaf Dietary Supplementation Can Improve the Lipo-Nutritional Quality of Pork and Regulate Gut Microbiota in Pigs: A Comprehensive Multi-Omics Analysis

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    Mulberry leaves, a common traditional Chinese medicine, represent a potential nutritional strategy to improve the fat profile, also known as the lipo-nutrition, of pork. However, the effects of mulberry leaves on pork lipo-nutrition and the microorganisms and metabolites in the porcine gut remain unclear. In this study, multi-omics analysis was employed in a Yuxi black pig animal model to explore the possible regulatory mechanism of mulberry leaves on pork quality. Sixty Yuxi black pigs were divided into two groups: the control group (n = 15) was fed a standard diet, and the experimental group (n = 45) was fed a diet supplemented with 8% mulberry leaves. Experiments were performed in three replicates (n = 15 per replicate); the two diets were ensured to be nutritionally balanced, and the feeding period was 120 days. The results showed that pigs receiving the diet supplemented with mulberry leaves had significantly reduced backfat thickness (p p Muribaculaceae_norank, Prevotellaceae_NK3B31_group, and Limosilactobacillus. Simultaneously, the relative levels of L-tyrosine-ethyl ester, oleic acid methyl ester, 21-deoxycortisol, N-acetyldihydrosphingosine, and mulberrin were increased. Furthermore, we found that mulberry leaf supplementation significantly increased the mRNA expression of lipoprotein lipase, fatty acid-binding protein 4, and peroxisome proliferators-activated receptor Îł in muscle (p p p p p < 0.01). Collectively, this omic profile is consistent with an increased ratio of IMF to backfat in the pig model

    Nanostructured lipid carriers for MicroRNA delivery in tumor gene therapy

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    Abstract MicroRNAs (miRNAs), which are endogenous about 20–23 nucleotides non-coding RNAs, have been acted as post-transcriptional regulators of gene expression. Current studies demonstrated that miRNAs are promising candidates for tumor gene therapy because of their important biological functions in tumor cell proliferation, metastasis, apoptosis, and drug resistance. As an important delivery system, nanostructured lipid carriers (NLCs) have great potential in tumor gene therapy, particularly for miRNA delivery, due to low toxicity, low immunogenicity, long metabolic cycles, and easy modification. This article reviews recent research progress on NLCs for miRNA delivery in tumor gene therapy and prospective applications

    Adsorption Properties of Pb<sup>2+</sup> by Amino Group’s Functionalized Montmorillonite from Aqueous Solutions

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    The remediation of wastewater containing Pb<sup>2+</sup> has attracted much attention due to the harm of Pb<sup>2+</sup> to the environment and human health. A promising adsorbent, functionalized montmorillonite modified with a ligand diethylenetriamine (DETA) was prepared under mild reaction conditions. The modified montmorillonite (DETA-MMT) and nature montmorillonite (Na-MMT) were then characterized with the help of XRD, FTIR, TG/DTG, and BET. It was revealed that the modifier DETA was successfully inserted into interlayers of montmorillonite, as demonstrated by the characterizations. Batch adsorption experiments of Pb<sup>2+</sup> onto Na-MMT and DETA-MMT in solutions were studied as a function of various parameters, such as pH, contact time, initial concentration, and temperature. The maximum adsorption capacity of DETA-MMT was 61.1 mg g<sup>–1</sup>, which had more than doubled compared with that of Na-MMT. The adsorption thermodynamics of Pb<sup>2+</sup> by DETA-MMT was studied, and it showed a endothermic process. The adsorption kinetics of two samples both fit well with the pseudo-second-order model. The adsorption isotherms of Na-MMT and DETA-MMT can be well described by the Langmuir isotherm and Freundlich isotherm, respectively. Furthermore, the adsorbed Pb<sup>2+</sup> onto DETA-MMT can hardly be dissolved under weak acidic condition (pH >4) according to the desorption experiments of simulated acid rain and Tessier’s sequential extraction procedure

    Portable spirometer-based pulmonary function test willingness in China: A nationwide cross-sectional study from the “Happy Breathing Program”

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    Abstract. Background:. Understanding willingness to undergo pulmonary function tests (PFTs) and the factors associated with poor uptake of PFTs is crucial for improving early detection and treatment of chronic obstructive pulmonary disease (COPD). This study aimed to understand willingness to undergo PFTs among high-risk populations and identify any barriers that may contribute to low uptake of PFTs. Methods:. We collected data from participants in the “Happy Breathing Program” in China. Participants who did not follow physicians’ recommendations to undergo PFTs were invited to complete a survey regarding their willingness to undergo PFTs and their reasons for not undergoing PFTs. We estimated the proportion of participants who were willing to undergo PFTs and examined the various reasons for participants to not undergo PFTs. We conducted univariable and multivariable logistic regressions to analyze the impact of individual-level factors on willingness to undergo PFTs. Results:. A total of 8475 participants who had completed the survey on willingness to undergo PFTs were included in this study. Out of these participants, 7660 (90.4%) were willing to undergo PFTs. Among those who were willing to undergo PFTs but actually did not, the main reasons for not doing so were geographical inaccessibility (n = 3304, 43.1%) and a lack of trust in primary healthcare institutions (n = 2809, 36.7%). Among the 815 participants who were unwilling to undergo PFTs, over half (n = 447, 54.8%) believed that they did not have health problems and would only consider PFTs when they felt unwell. In the multivariable regression, individuals who were ≤54 years old, residing in rural townships, with a secondary educational level, with medical reimbursement, still working, with occupational exposure to dust, and aware of the abbreviation “COPD” were more willing to undergo PFTs. Conclusions:. Willingness to undergo PFTs was high among high-risk populations. Policymakers may consider implementing strategies such as providing financial incentives, promoting education, and establishing community-based programs to enhance the utilization of PFTs
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