Energy dependent chemical potentials of light hadrons and quarks based on transverse momentum spectra and yield ratios of negative to positive particles

We describe the transverse momentum (or mass) spectra of $\pi^\pm$, $K^\pm$, $p$, and $\bar{p}$ produced in central gold-gold (Au-Au), central lead-lead (Pb-Pb), and inelastic proton-proton ($pp$) collisions at different collision energies range from the AGS to LHC by using a two-component (in most cases) Erlang distribution in the framework of multi-source thermal model. The fitting results are consistent with the experimental data and the energy-dependent chemical potentials of light hadrons ($\pi$, $K$, and $p$) and quarks ($u$, $d$, and $s$) in central Au-Au, central Pb-Pb, and inelastic $pp$ collisions from the yield ratios of negative to positive particles obtained from the normalization constants are then extracted. The study shows that most types of energy-dependent chemical potentials decrease with increase of collision energy over a range from the AGS to LHC. The curves of all types of energy-dependent chemical potentials, obtained from the linear fits of yield ratios vs energy, have inflection points at the same energy of 3.526 GeV, which is regarded as the critical energy of phase transition from a hadron liquid-like state to a quark gas-like state in the collision system and indicates that the hadronic interactions play an important role in this period. At the RHIC and LHC, all types of chemical potentials become small and tend to zero at very high energy, which confirms that the collision system possibly changes completely from the hadron-dominant liquid-like state to the quark-dominant gas-like state and the partonic interactions possibly play a dominant role at the LHC

Clinical effect of toric designed orthokeratology and regular spherical orthokeratology on myopia patients with high difference in corneal surface

AIM: To explore whether there was a difference in clinical efficacy of toric design orthokeratology and regular spherical orthokeratology in myopia patients with high difference in corneal surface. METHODS: A retrospective analysis of 48 moderate myopia patients(94 eyes), who went to the optometry center of Ruikang Hospital Affiliated to Guangxi University of Chinese Medical form July 2016 to December 2017. The height difference between the horizontal axis and the vertical axis away from the central cornea at 4mm was ≥30μm calculated in all patients with corneal topography. In Group A, 25 cases(48 eyes)with toric design orthokeratology, Group B(23 cases, 46 eyes)with regular spherical. After wearing orthokeratology 1wk, 1, 3mo, the uncorrected visual acuity(UCVA), the changes of corneal astigmatism in 3mm corneal center, the eccentricity of corneal treatment area were observed. RESULTS: The UCVA was improved of both groups after operation, while was not significantly different between the two groups(P>0.05). The corneal regular astigmatism in 3mm corneal center were decreased after wearing orthokeratology 1wk, 1, 3mo, the changes were more obvious in Group A than Group B(PPCONCLUSION: For myopic patients with height difference between the horizontal axis and the vertical axis from the central cornea, the toric design orthokeratology is superior to regular spherical design orthokeratology in reducing astigmatism and stability of treatment area

mGluR5 antagonism inhibits cocaine reinforcement and relapse by elevation of extracellular glutamate in the nucleus accumbens via a CB1 receptor mechanism.

Metabotropic glutamate receptor 5 (mGluR5) antagonism inhibits cocaine self-administration and reinstatement of drug-seeking behavior. However, the cellular and molecular mechanisms underlying this action are poorly understood. Here we report a presynaptic glutamate/cannabinoid mechanism that may underlie this action. Systemic or intra-nucleus accumbens (NAc) administration of the mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) dose-dependently reduced cocaine (and sucrose) self-administration and cocaine-induced reinstatement of drug-seeking behavior. The reduction in cocaine-taking and cocaine-seeking was associated with a reduction in cocaine-enhanced extracellular glutamate, but not cocaine-enhanced extracellular dopamine (DA) in the NAc. MPEP alone, when administered systemically or locally into the NAc, elevated extracellular glutamate, but not DA. Similarly, the cannabinoid CB1 receptor antagonist, rimonabant, elevated NAc glutamate, not DA. mGluR5s were found mainly in striatal medium-spiny neurons, not in astrocytes, and MPEP-enhanced extracellular glutamate was blocked by a NAc CB1 receptor antagonist or N-type Ca++ channel blocker, suggesting that a retrograde endocannabinoid-signaling mechanism underlies MPEP-induced glutamate release. This interpretation was further supported by our findings that genetic deletion of CB1 receptors in CB1-knockout mice blocked both MPEP-enhanced extracellular glutamate and MPEP-induced reductions in cocaine self-administration. Together, these results indicate that the therapeutic anti-cocaine effects of mGluR5 antagonists are mediated by elevation of extracellular glutamate in the NAc via an endocannabinoid-CB1 receptor disinhibition mechanism

PPNet: Identifying functional association networks by phylogenetic profiling of prokaryotic genomes

Identification of microbial functional association networks allows interpretation of biological phenomena and a greater understanding of the molecular basis of pathogenicity and also underpins the formulation of control measures. Here, we describe PPNet, a tool that uses genome information and analysis of phylogenetic profiles with binary similarity and distance measures to derive large-scale bacterial gene association networks of a single species. As an exemplar, we have derived a functional association network in the pig pathogen Streptococcus suis using 81 binary similarity and dissimilarity measures which demonstrates excellent performance based on the area under the receiver operating characteristic (AUROC), the area under the precision-recall (AUPR), and a derived overall scoring method. Selected network associations were validated experimentally by using bacterial two-hybrid experiments. We conclude that PPNet, a publicly available (https://github.com/liyangjie/PPNet), can be used to construct microbial association networks from easily acquired genome-scale data. IMPORTANCE This study developed PPNet, the first tool that can be used to infer large-scale bacterial functional association networks of a single species. PPNet includes a method for assigning the uniqueness of a bacterial strain using the average nucleotide identity and the average nucleotide coverage. PPNet collected 81 binary similarity and distance measures for phylogenetic profiling and then evaluated and divided them into four groups. PPNet can effectively capture gene networks that are functionally related to phenotype from publicly prokaryotic genomes, as well as provide valuable results for downstream analysis and experiment testing

Ultrasound microbubble-mediated delivery of the siRNAs targeting MDR1 reduces drug resistance of yolk sac carcinoma L2 cells

<p>Abstract</p> <p>Background</p> <p>MDR1 gene encoding P-glycoprotein is an ATP-dependent drug efflux transporter and related to drug resistance of yolk sac carcinoma. Ultrasound microbubble-mediated delivery has been used as a novel and effective gene delivery method. We hypothesize that small interfering RNA (siRNA) targeting MDR1 gene (siMDR1) delivery with microbubble and ultrasound can down-regulate MDR1 expression and improve responsiveness to chemotherapeutic drugs for yolk sac carcinoma <it>in vitro</it>.</p> <p>Methods</p> <p>Retroviral knockdown vector pSEB-siMDR1s containing specific siRNA sites targeting rat MDR1 coding region were constructed and sequence verified. The resultant pSEB-siMDR1 plasmids DNA were encapsulated with lipid microbubble and the DNA release were triggered by ultrasound when added to culture cells. GFP positive cells were counted by flow cytometry to determine transfection efficiency. Quantitative real-time PCR and western blot were performed to determine the mRNA and protein expression of MDR1. P-glycoprotein function and drug sensitivity were analyzed by Daunorubicin accumulation and MTT assays.</p> <p>Results</p> <p>Transfection efficiency of pSEB-siMDR1 DNA was significantly increased by ultrasound microbubble-mediated delivery in rat yolk sac carcinoma L2 (L2-RYC) cells. Ultrasound microbubble-mediated siMDR1s delivery effectively inhibited MDR1 expression at both mRNA and protein levels and decreased P-glycoprotein function. Silencing MDR1 led to decreased cell viability and IC₅₀of Vincristine and Dactinomycin.</p> <p>Conclusions</p> <p>Our results demonstrated that ultrasound microbubble-mediated delivery of MDR1 siRNA was safe and effective in L2-RYC cells. MDR1 silencing led to decreased P-glycoprotein activity and drug resistance of L2-RYC cells, which may be explored as a novel approach of combined gene and chemotherapy for yolk sac carcinoma.</p

Induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma: A systematic review and meta-analysis

BackgroundAdding induction chemotherapy to concurrent platinum-based chemoradiotherapy has significantly prolonged the survival time of patients with locoregionally advanced nasopharyngeal carcinoma. In this study, we intend to evaluate the survival outcomes, responses, and incidences of toxicities of induction chemotherapy and the differences between different strategies.MethodsA comprehensive search was conducted in PubMed, Embase, Web of Science, and Cochrane CENTRAL on August 10, 2021. Single-arm or multi-arm prospective clinical trials on induction chemotherapy without targeted therapies or immune checkpoint inhibitors were included. Primary outcomes included survival outcomes, objective response rate, and disease control rate, and the secondary outcome was the rates of grade 3 or higher treatment-related adverse events.ResultsThe 39 studies included in the systematic review and meta-analysis comprised 36 clinical trials and 5389 patients. The estimates for 3-year overall and fail-free survival rates were 87% and 77%. The estimates for 5-year rates of overall and fail-free survival were 81% and 73%. Gemcitabine plus platinum and docetaxel combined with 5-fluorouracil plus platinum strategies were associated with the highest rates of 3-year and 5-year overall survival. The objective response and disease control rates were 85% and 98% after the completion of induction chemotherapy. Neutropenia (27%) and nausea/vomiting (7%) were the most common grade 3 or higher treatment-related hematological and non-hematological adverse events during the induction phase.ConclusionsDifferent induction chemotherapeutic strategies appear to have varying effects and risks; a comprehensive summary of the survival outcomes, responses, and toxicities in clinical trials may provide a crucial guide for clinicians

Haemophilus parasuis Infection Disrupts Adherens Junctions and Initializes EMT Dependent on Canonical Wnt/β-Catenin Signaling Pathway

In this study, animal experimentation verified that the canonical Wnt/β-catenin signaling pathway was activated under a reduced activity of p-β-catenin (Ser33/37/Thr41) and an increased accumulation of β-catenin in the lungs and kidneys of pigs infected with a highly virulent strain of H. parasuis. In PK-15 and NPTr cells, it was also confirmed that infection with a high-virulence strain of H. parasuis induced cytoplasmic accumulation and nuclear translocation of β-catenin. H. parasuis infection caused a sharp degradation of E-cadherin and an increase of the epithelial cell monolayer permeability, as well as a broken interaction between β-catenin and E-cadherin dependent on Wnt/β-catenin signaling pathway. Moreover, Wnt/β-catenin signaling pathway also contributed to the initiation of epithelial-mesenchymal transition (EMT) during high-virulence strain of H. parasuis infection with expression changes of epithelial/mesenchymal markers, increased migratory capabilities as well as the morphologically spindle-like switch in PK-15 and NPTr cells. Therefore, we originally speculated that H. parasuis infection activates the canonical Wnt/β-catenin signaling pathway leading to a disruption of the epithelial barrier, altering cell structure and increasing cell migration, which results in severe acute systemic infection characterized by fibrinous polyserositis during H. parasuis infection

Mesenchymal stromal cells-derived small extracellular vesicles modulate DC function to suppress Th2 responses via IL-10 in patients with allergic rhinitis

Mesenchymal stromal cells (MSCs) are well known for their immunoregulatory roles on allergic inflammation particularly by acting on T cells, B cells, and dendritic cells (DCs). MSC-derived small extracellular vesicles (MSC-sEV) are increasingly considered as one of the main factors for the effects of MSCs on immune responses. However, the effects of MSC-sEV on DCs in allergic diseases remain unclear. MSC-sEV were prepared from the induced pluripotent stem cells (iPSC)-MSCs by anion-exchange chromatography, and were characterized with the size, morphology, and specific markers. Human monocyte-derived DCs were generated and cultured in the presence of MSC-sEV to differentiate the so-called sEV-immature DCs (sEV-iDCs) and sEV-mature DCs (sEV-mDCs), respectively. The phenotypes and the phagocytic ability of sEV-iDCs were analyzed by flow cytometry. sEV-mDCs were co-cultured with isolated CD4+ T cells or peripheral blood mononuclear cells (PBMCs) from patients with allergic rhinitis. The levels of Th1 and Th2 cytokines produced by T cells were examined by ELISA and intracellular flow staining. And the following mechanisms were further investigated. We demonstrated that MSC-sEV inhibited the differentiation of human monocytes to iDCs with downregulation of the expression of CD40, CD80, CD86, and HLA-DR, but had no effects on mDCs with these markers. However, MSC-sEV treatment enhanced the phagocytic ability of mDCs. More importantly, using anti-IL-10 monoclonal antibody or IL-10Rα blocking antibody, we identified that sEV-mDCs suppressed the Th2 immune response by reducing the production of IL-4, IL-9, and IL-13 via IL-10. Furthermore, sEV-mDCs increased the level of Treg cells. Our study identified that mDCs treated with MSC-sEV inhibited the Th2 responses, providing novel evidence of the potential cell-free therapy acting on DCs in allergic airway diseases. Keywords: Allergic rhinitis; Dendritic cells; Interleukin-10; Mesenchymal stromal cells; Small extracellular vesicles