Induction of mast cell accumulation, histamine release and skin edema by N49 phospholipase A2

<p>Abstract</p> <p>Background</p> <p>It has been recognized that phospholipase A₂(PLA₂) is a crucial component of snake venom, which contributes greatly to snake venom induced inflammation in man. However, the mechanisms through which N49 PLA₂provoke inflammation remain unclear. Recently, a N49 PLA₂, TM-N49 from <it>Protobothrops mucrosquamatus </it>crude venom was characterized in our laboratory. Since the purification procedure developed is able to supply us with relatively large quantity of highly purified TM-N49, we investigated the ability of TM-N49 in induction of inflammation.</p> <p>Results</p> <p>The results showed that TM-N49 provoked a dose dependent increase in microvascular leakage in the skin of rats. The potency of TM-N49 in induction of skin edema appeared similar potency of bradykinin and histamine. Pretreatment of rats with compound 48/80 diminished TM-N49 induced skin reaction and reduced mast cell numbers in rats. Ginkgolide B and cyproheptadine, but not terfenadine and quinacrine, inhibited TM-N49 elicited microvascular leakage when they were co-injected with the stimulus to rat skin. Moreover, TM-N49 was found to induce histamine release from human colon, lung and tonsil mast cells, and both metabolic inhibitors and pertussis toxin were capable of inhibiting TM-N49 elicited histamine release. TM-N49 induced mast cell accumulation in the peritoneum of mice, which was inhibited by co-injection of ginkgolide B, cyproheptadine and terfenadine. Intravenous injection of monoclonal antibodies against CD18, ICAM-1 and CD11a also blocked TM-N49 induced mast cell accumulation.</p> <p>Conclusion</p> <p>TM-N49 is a potent stimulus for skin edema, mast cell activation and accumulation.</p

Enhanced Chart Understanding in Vision and Language Task via Cross-modal Pre-training on Plot Table Pairs

Building cross-model intelligence that can understand charts and communicate the salient information hidden behind them is an appealing challenge in the vision and language(V+L) community. The capability to uncover the underlined table data of chart figures is a critical key to automatic chart understanding. We introduce ChartT5, a V+L model that learns how to interpret table information from chart images via cross-modal pre-training on plot table pairs. Specifically, we propose two novel pre-training objectives: Masked Header Prediction (MHP) and Masked Value Prediction (MVP) to facilitate the model with different skills to interpret the table information. We have conducted extensive experiments on chart question answering and chart summarization to verify the effectiveness of the proposed pre-training strategies. In particular, on the ChartQA benchmark, our ChartT5 outperforms the state-of-the-art non-pretraining methods by over 8% performance gains.Comment: Accepted by Findings of ACL 202

The X-Ray Variation of M81* Resolved by \u3cem\u3eChandra\u3c/em\u3e and \u3cem\u3eNuSTAR\u3c/em\u3e

Despite advances in our understanding of low-luminosity active galactic nuclei (LLAGNs), the fundamental details about the mechanisms of radiation and flare/outburst in hot accretion flow are still largely missing. We have systematically analysed the archival Chandra and NuSTAR X-ray data of the nearby LLAGN M81*, whose Lbol ∼ 10−5LEdd. Through a detailed study of X-ray light curve and spectral properties, we find that the X-ray continuum emission of the power-law shape more likely originates from inverse Compton scattering within the hot accretion flow. In contrast to Sgr A*, flares are rare in M81*. Low-amplitude variation can only be observed in soft X-ray band (amplitude usually ≲2). Several simple models are tested, including sinusoidal-like and quasi-periodical. Based on a comparison of the dramatic differences of flare properties among Sgr A*, M31*, and M81*, we find that, when the differences in both the accretion rate and the black hole mass are considered, the flares in LLAGNs can be understood universally in a magnetohydrodynamical model

Expressions of B7-H4 and B7-H3 Proteins and Effect of Sorafenib on their Expressions in Different Human Hepatoma Cell Lines

Purpose: To study whether B7-H3 and B7-H4 proteins can be candidate drug targets for preventing and treating hepatoma.Methods: Western blot assay was used to study the expressions of B7-H3 and B7-H4 proteins and the effect of sorafenib on their expressions in different human hepatoma cell lines (HepG2, Hep3B, BEL- 7402, BEL-7404, BEL-7405, QGY-7701, QGY-7703, SMMC-7721, MHCC97H, MHCC97L, HCCLM3 and HCCLM6). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to study the cytotoxicity of sorafenib against different human hepatoma cell lines.Results: The expressions of B7-H3 (0.26 - 0.84 μM) and B7-H4 (0.18 - 0.78 μM) proteins in different human hepatoma cell lines were significantly (p &lt; 0.01) up-regulated, compared with that of the normal human liver cell line (HL-7702) (0.09 and 0.08 μM). Sorafenib was cytotoxic on Hep3B, BEL-7404, MHCC97H, HCCLM3 and HCCLM6 cells with half-maximal inhibitory concentration (IC50) of 14.56, 9.14, 9.46, 17.21 and 9.29 μM, respectively. After treatment with sorafenib at concentrations of 5, 10 and 20 μM, the expressions of B7-H3 protein in MHCC97H, HCCLM3 and HCCLM6 cells and the expressions of B7-H4 protein in Hep3B, BEL-7404 and MHCC97H cells were significantly (p &lt; 0.01) down-regulated, compared with that of the control.Conclusion: Over-expression of B7-H3 and B7-H4 proteins is common in different human hepatoma cell lines and thus, B7-H3 and B7-H4 proteins may be regarded as candidate drug targets for preventing and treating hepatoma.Keywords: Hepatoma, B7-H3, B7-H4, Sorafenib, Over-expression, Cytotoxic activity, Down-regulatio

Photometric Variability in the CSTAR Field: Results From the 2008 Data Set

The Chinese Small Telescope ARray (CSTAR) is the first telescope facility built at Dome A, Antarctica. During the 2008 observing season, the installation provided long-baseline and high-cadence photometric observations in the i-band for 18,145 targets within 20 deg2 CSTAR field around the South Celestial Pole for the purpose of monitoring the astronomical observing quality of Dome A and detecting various types of photometric variability. Using sensitive and robust detection methods, we discover 274 potential variables from this data set, 83 of which are new discoveries. We characterize most of them, providing the periods, amplitudes and classes of variability. The catalog of all these variables is presented along with the discussion of their statistical properties.Comment: 38 pages, 11 figures, 4 tables; Accepted for publication in ApJ

Plasminogen Activator Inhibitor-1 in Cigarette Smoke Exposure and Influenza A Virus Infection-Induced Lung Injury

Parenchymal lung inflammation and airway and alveolar epithelial cell apoptosis are associated with cigarette smoke exposure (CSE), which contributes to chronic obstructive pulmonary disease (COPD). Epidemiological studies indicate that people exposed to chronic cigarette smoke with or without COPD are more susceptible to influenza A virus (IAV) infection. We found increased p53, PAI-1 and apoptosis in AECs, with accumulation of macrophages and neutrophils in the lungs of patients with COPD. In Wild-type (WT) mice with passive CSE (PCSE), p53 and PAI-1 expression and apoptosis were increased in AECs as was lung inflammation, while those lacking p53 or PAI-1 resisted AEC apoptosis and lung inflammation. Further, inhibition of p53-mediated induction of PAI-1 by treatment of WT mice with caveolin-1 scaffolding domain peptide (CSP) reduced PCSE-induced lung inflammation and reversed PCSE-induced suppression of eosinophil-associated RNase1 (EAR1). Competitive inhibition of the p53-PAI-1 mRNA interaction by expressing p53-binding 3\u27UTR sequences of PAI-1 mRNA likewise suppressed CS-induced PAI-1 and AEC apoptosis and restored EAR1 expression. Consistent with PCSE-induced lung injury, IAV infection increased p53, PAI-1 and apoptosis in AECs in association with pulmonary inflammation. Lung inflammation induced by PCSE was worsened by subsequent exposure to IAV. Mice lacking PAI-1 that were exposed to IAV showed minimal viral burden based on M2 antigen and hemagglutination analyses, whereas transgenic mice that overexpress PAI-1 without PCSE showed increased M2 antigen and inflammation after IAV infection. These observations indicate that increased PAI-1 expression promotes AEC apoptosis and exacerbates lung inflammation induced by IAV following PCSE

NRAV, a Long Noncoding RNA, Modulates Antiviral Responses through Suppression of Interferon-Stimulated Gene Transcription

SummaryLong noncoding RNAs (lncRNAs) modulate various biological processes, but their role in host antiviral responses is largely unknown. Here we identify a lncRNA as a key regulator of antiviral innate immunity. Following from the observation that a lncRNA that we call negative regulator of antiviral response (NRAV) was dramatically downregulated during infection with several viruses, we ectopically expressed NRAV in human cells or transgenic mice and found that it significantly promotes influenza A virus (IAV) replication and virulence. Conversely, silencing NRAV suppressed IAV replication and virus production, suggesting that reduction of NRAV is part of the host antiviral innate immune response to virus infection. NRAV negatively regulates the initial transcription of multiple critical interferon-stimulated genes (ISGs), including IFITM3 and MxA, by affecting histone modification of these genes. Our results provide evidence for a lncRNA in modulating the antiviral interferon response

Complications after radical gastrectomy following FOLFOX7 neoadjuvant chemotherapy for gastric cancer

<p>Abstract</p> <p>Background</p> <p>This study assessed the postoperative morbidity and mortality occurring in the first 30 days after radical gastrectomy by comparing gastric cancer patients who did or did not receive the FOLFOX7 regimen of neoadjuvant chemotherapy.</p> <p>Methods</p> <p>We completed a retrospective analysis of 377 patients after their radical gastrectomies were performed in our department between 2005 and 2009. Two groups of patients were studied: the SURG group received surgical treatment immediately after diagnosis; the NACT underwent surgery after 2-6 cycles of neoadjuvant chemotherapy.</p> <p>Results</p> <p>There were 267 patients in the SURG group and 110 patients in the NACT group. The NACT group had more proximal tumours (P = 0.000), more total/proximal gastrectomies (P = 0.000) and longer operative time (P = 0.005) than the SURG group. Morbidity was 10.0% in the NACT patients and 17.2% in the SURG patients (P = 0.075). There were two cases of postoperative death, both in the SURG group (P = 1.000). No changes in complications or mortality rate were observed between the SURG and NACT groups.</p> <p>Conclusion</p> <p>The FOLFOX7 neoadjuvant chemotherapy is not associated with increased postoperative morbidity, indicating that the FOLFOX7 neoadjuvant chemotherapy is a safe choice for the treatment of local advanced gastric cancer.</p

Host-Induced Gene Silencing of MoAP1 Confers Broad-Spectrum Resistance to Magnaporthe oryzae

Rice blast caused by Magnaporthe oryzae (M. oryzae) is a major threat to global rice production. In recent years, small interference RNAs (siRNAs) and host-induced gene silencing (HIGS) has been shown to be new strategies for the development of transgenic plants to control fungal diseases and proved a useful tool to study gene function in pathogens. We here tested whether in vitro feeding artificial siRNAs (asiRNAs) could compromise M. oryzae virulence and in vivo HIGS technique could improve rice blast resistance. Our data revealed that silencing of M. oryzae MoAP1 by feeding asiRNAs targeting MoAP1 (i.e., asiR1245, asiR1362, and asiR1115) resulted in inhibited fungal growth, abnormal spores, and decreased pathogenicity. Among the asiRNAs, asiR1115 was the most inhibitory toward the rice blast fungus. Conversely, the asiRNAs targeting three other genes (i.e., MoSSADH, MoACT, and MoSOM1) had no effect on fungal growth. Transgenic rice plants expressing RNA hairpins targeting MoAP1 exhibited improved resistance to 11 tested M. oryzae strains. Confocal microscopy also revealed profoundly restricted appressoria and mycelia in rice blast-infected transgenic rice plants. Our results demonstrate that in vitro asiRNA and in vivo HIGS were useful protection approaches that may be valuable to enhance rice blast resistance