Effect of Molecular Charge Asymmetry on Even-to-odd Ratio of High-order Harmonic Generation

Recently, asymmetric molecules, such as HeH$_2^+$, CO, OCS, HCl, have been evolved much attention since its rich information in the high-order harmonic generation (HHG), whose ratio of adjacent even and odd harmonics characterizes the asymmetry of molecules. In this paper, we study the dependence of even-to-odd ratio on the asymmetric parameters, in particular, the nuclear-charge ratio, and the permanent dipole, by exploiting a simple but general model of asymmetric molecules $Z_1Z_2$ subjected to an intense laser pulse. The HHG is simulated by the numerical method of solving the time-dependent Schrödinger equation. We find out that this even-to-odd ratio strongly depends on the nuclear-charge ratio. In particular, the even-to-odd ratio reaches its maximum when the nuclear-charge ratio is about from 0.5 to 0.7. Besides, the dependence on the permanent dipole of the even-to-odd ratio has a non-trivial law. To explain, we calculate the analytical ratio of the transition dipole according to the emission of even and odd harmonics, and this ratio is well consistent with the even-to-odd ratio of the HHG

CTLA-4 mediates inhibitory function of mesenchymal stem/stromal cells

Mesenchymal stem/stromal cells (MSCs) are stem cells of the connective tissue, possess a plastic phenotype, and are able to differentiate into various tissues. Besides their role in tissue regeneration, MSCs perform additional functions as a modulator or inhibitor of immune responses. Due to their pleiotropic function, MSCs have also gained therapeutic importance for the treatment of autoimmune diseases and for improving fracture healing and cartilage regeneration. However, the therapeutic/immunomodulatory mode of action of MSCs is largely unknown. Here, we describe that MSCs express the inhibitory receptor CTLA-4 (cytotoxic T lymphocyte antigen 4). We show that depending on the environmental conditions, MSCs express different isoforms of CTLA-4 with the secreted isoform (sCTLA-4) being the most abundant under hypoxic conditions. Furthermore, we demonstrate that the immunosuppressive function of MSCs is mediated mainly by the secretion of CTLA-4. These findings open new ways for treatment when tissue regeneration/fracture healing is difficult

Early Treatment with Imiquimod 5% Cream of Periungual Warts in Vietnam: The Poorer, the Better

AIM: To evaluate the efficacy of imiquimod 5% in periungual wart treatment. MATERIAL AND METHODS: A group of 40 patients were recruited to apply imiquimod 5 % cream once daily for 5 consecutive days per week in 8 weeks. They were classified into 3 levels: Mild (the total lesion area ≤ 25 mm2), moderate (25 mm2 <total lesion area ≤ 50 mm2), severe (total lesion area > 50 mm2). The outcome was evaluated at the 4th and the 8th week. The result was graded as excellent (complete clearance), good (≥ 50% clearance) and poor (< 50% clearance). RESULTS: The total area of the wart lesion got decreased significantly from the beginning to the 4th and the 8th week (36.7 mm2 vs 16.8 mm2, p = 0.0001 and 16.8 mm2 vs 8.8 mm2, p = 0.01). The complete clearance rate at the 4th week was lower than that at the 8th week significantly (22.5% vs 72.5%, p = 0.04). The clearance rate of patients suffering severe warts was lower significantly than that of mild/ moderate patients (82.8% vs 45.5%, p = 0.03). The duration of the disease in people who responded completely to imiquimod was shorter than that of patients partially responded (10.2 ± 14.1 months vs 22.3 ± 14.3 months, p = 0.02). Adverse effects were not common, mild and local only. Recurrence rate after 6 months of follow up was 3.5%. CONCLUSION: In conclusion, Imiquimod 5% cream is a safe and effective drug in the treatment of periungual warts

MicroRNA-31 Reduces the Motility of Proinflammatory T Helper 1 Lymphocytes

Proinflammatory type 1 T helper (Th1) cells are enriched in inflamed tissues and contribute to the maintenance of chronic inflammation in rheumatic diseases. Here we show that the microRNA- (miR-) 31 is upregulated in murine Th1 cells with a history of repeated reactivation and in memory Th cells isolated from the synovial fluid of patients with rheumatic joint disease. Knock-down of miR-31 resulted in the upregulation of genes associated with cytoskeletal rearrangement and motility and induced the expression of target genes involved in T cell activation, chemokine receptor– and integrin-signaling. Accordingly, inhibition of miR-31 resulted in increased migratory activity of repeatedly activated Th1 cells. The transcription factors T-bet and FOXO1 act as positive and negative regulators of T cell receptor (TCR)–mediated miR-31 expression, respectively. Taken together, our data show that a gene regulatory network involving miR-31, T-bet, and FOXO1 controls the migratory behavior of proinflammatory Th1 cells

Selective targeting of pro-inflammatory Th1 cells by microRNA-148a-specific antagomirs in vivo.

In T lymphocytes, expression of miR-148a is induced by T-bet and Twist1, and is specific for pro-inflammatory Th1 cells. In these cells, miR-148a inhibits the expression of the pro-apoptotic protein Bim and promotes their survival. Here we use sequence-specific cholesterol-modified oligonucleotides against miR-148a (antagomir-148a) for the selective elimination of pro-inflammatory Th1 cells in vivo. In the murine model of transfer colitis, antagomir-148a treatment reduced the number of pro-inflammatory Th1 cells in the colon of colitic mice by 50% and inhibited miR-148a expression by 71% in the remaining Th1 cells. Expression of Bim protein in colonic Th1 cells was increased. Antagomir-148a-mediated reduction of Th1 cells resulted in a significant amelioration of colitis. The effect of antagomir-148a was selective for chronic inflammation. Antigen-specific memory Th cells that were generated by an acute immune reaction to nitrophenylacetyl-coupled chicken gamma globulin (NP-CGG) were not affected by treatment with antagomir-148a, both during the effector and the memory phase. In addition, antibody titers to NP-CGG were not altered. Thus, antagomir-148a might qualify as an effective drug to selectively deplete pro-inflammatory Th1 cells of chronic inflammation without affecting the protective immunological memory

Antigen-driven PD-1+ TOX+ BHLHE40+ and PD-1+ TOX+ EOMES+ T lymphocytes regulate juvenile idiopathic arthritis in situ

T lymphocytes accumulate in inflamed tissues of patients with chronic inflammatory diseases (CIDs) and express pro-inflammatory cytokines upon re-stimulation in vitro. Further, a significant genetic linkage to MHC genes suggests that T lymphocytes play an important role in the pathogenesis of CIDs including juvenile idiopathic arthritis (JIA). However, the functions of T lymphocytes in established disease remain elusive. Here we dissect the transcriptional and the clonal heterogeneity of synovial T lymphocytes in JIA patients by single-cell RNA sequencing combined with T cell receptor profiling on the same cells. We identify clonally expanded subpopulations of T lymphocytes expressing genes reflecting recent activation by antigen in situ. A PD-1+ TOX+ EOMES+ population of CD4+ T lymphocytes expressed immune regulatory genes and chemoattractant genes for myeloid cells. A PD-1+ TOX+ BHLHE40+ population of CD4+ , and a mirror population of CD8+ T lymphocytes expressed genes driving inflammation, and genes supporting B lymphocyte activation in situ. This analysis points out that multiple types of T lymphocytes have to be targeted for therapeutic regeneration of tolerance in arthritis

Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial

Background Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population. Methods AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2–15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. Findings Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [<1%]; p=0·038) at 6 months. Interpretation Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke

Hypoxia promotes osteogenesis but suppresses adipogenesis of human mesenchymal stromal cells in a hypoxia-inducible factor-1 dependent manner.

BACKGROUND: Bone fracture initiates a series of cellular and molecular events including the expression of hypoxia-inducible factor (HIF)-1. HIF-1 is known to facilitate recruitment and differentiation of multipotent human mesenchymal stromal cells (hMSC). Therefore, we analyzed the impact of hypoxia and HIF-1 on the competitive differentiation potential of hMSCs towards adipogenic and osteogenic lineages. METHODOLOGY/PRINCIPAL FINDINGS: Bone marrow derived primary hMSCs cultured for 2 weeks either under normoxic (app. 18% O(2)) or hypoxic (less than 2% O(2)) conditions were analyzed for the expression of MSC surface markers and for expression of the genes HIF1A, VEGFA, LDHA, PGK1, and GLUT1. Using conditioned medium, adipogenic or osteogenic differentiation as verified by Oil-Red-O or von-Kossa staining was induced in hMSCs under either normoxic or hypoxic conditions. The expression of HIF1A and VEGFA was measured by qPCR. A knockdown of HIF-1α by lentiviral transduction was performed, and the ability of the transduced hMSCs to differentiate into adipogenic and osteogenic lineages was analyzed. Hypoxia induced HIF-1α and HIF-1 target gene expression, but did not alter MSC phenotype or surface marker expression. Hypoxia (i) suppressed adipogenesis and associated HIF1A and PPARG gene expression in hMSCs and (ii) enhanced osteogenesis and associated HIF1A and RUNX2 gene expression. shRNA-mediated knockdown of HIF-1α enhanced adipogenesis under both normoxia and hypoxia, and suppressed hypoxia-induced osteogenesis. CONCLUSIONS/SIGNIFICANCE: Hypoxia promotes osteogenesis but suppresses adipogenesis of human MSCs in a competitive and HIF-1-dependent manner. We therefore conclude that the effects of hypoxia are crucial for effective bone healing, which may potentially lead to the development of novel therapeutic approaches

Ce3+/Ce4+-Doped ZrO2/CuO Nanocomposite for Enhanced Photocatalytic Degradation of Methylene Blue under Visible Light

In recent years, photocatalysis has been used as an environmentally friendly method for the degradation of organic pigments in water. In this study, Ce3+/Ce4+-doped ZrO2/CuO as a mixed semiconductor oxide was successfully prepared by a one-step hydrothermal method. The Ce3+/Ce4+-doped ZrO2/CuO has shown high degradation efficiency of methylene blue (MB), and the maximum degradation percentage was observed to be 94.5% at 180 min under irradiation visible light. The photocatalytic activity increases significantly by doping Ce3+/Ce4+ in ZrO2/CuO for MB degradation. Ce3+/Ce4+ doping is shown to reduce the (e-/h+) recombination rate and improve the charge transfer, leading to enhanced photocatalytic activity of materials. The materials were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), FTIR, EDS, BET and diffuse reflectance spectroscopy (DRS)