Background
The IL‐13 receptor α2 (IL‐13Rα2) is a receptor for IL‐13 which has conflicting roles in mediating IL‐13 responses in the lower airway, with little known about its impact on upper airway ...diseases. We sought to investigate the expression of IL‐13 receptors, IL‐13Rα1 and IL‐13Rα2, in chronically inflamed nasal epithelium, and explore IL‐13‐induced signaling pathways in an in vitro model of human nasal epithelial cells (hNECs).
Methods
The protein and mRNA expression levels of IL‐13 and its receptors in nasal biopsies of patients with nasal polyps (NP) and healthy controls were evaluated. We investigated goblet cell stimulation with mucus hypersecretion induced by IL‐13 (10 ng/mL, 72 hours) treatment in hNECs using a pseudostratified epithelium in air‐liquid interface (ALI) culture.
Results
There were significant increases in IL‐13, IL‐13Rα1, and IL‐13Rα2 mRNA and protein levels in NP epithelium with healthy controls as baseline. MUC5AC mRNA positively correlated with IL‐13Rα2 (r = .5886, P = .002) but not with IL‐13Rα1 in primary hNECs. IL‐13 treatment resulted in a significant increase in mRNA and protein levels of IL‐13Rα2 only in hNECs. IL‐13 treatment induced an activation of extracellular signal‐regulated kinases (ERK)1/2 and an upregulation of C‐JUN, where the IL‐13‐induced effects on hNECs could be attenuated by ERK1/2 inhibitor (50 μmol/L) or dexamethasone (10−4‐10−7 mol/L) treatment.
Conclusions
IL‐13Rα2 has a potential role in IL‐13‐induced MUC5AC and ciliary changes through ERK1/2 signal pathway in the nasal epithelium. IL‐13Rα2 may contribute to airway inflammation and aberrant remodeling which are the main pathological features of CRSwNP.
The increase in IL‐13Rα2 with IL‐13 treatment activates ERK1/2, which is associated with IL‐13‐induced MUC5AC upregulation and impaired ciliary function in hNECs. IL‐13‐induced effects on hNECs could be attenuated either by ERK1/2 inhibitor PD98059 or by dexamethasone treatment. IL‐13Rα2 has a potential role in airway inflammation and aberrant remodeling.
The hyperinduction of proinflammatory cytokines and chemokines such as TNF-alpha, IFN-beta, and CCL2/MCP-1 in primary human macrophages and respiratory epithelial cells by the highly pathogenic avian ...influenza H5N1 is believed to contribute to the unusual severity of human H5N1 disease. Here we show that TNF-alpha, IFN-beta, and IFN-lambda1 are the key mediators directly induced by the H5N1 virus in primary human macrophages. In comparison with human influenza (H1N1), the H5N1 virus more strongly activated IFN regulatory factor 3 (IRF3). IRF3 knockdown and p38 kinase inhibition separately and in combination led to a substantial reduction of IFN-beta, IFN-lambda1, and MCP-1 but only to a partial reduction of TNF-alpha. IRF3 translocation was independent of p38 kinase activity, indicating that IRF3 and p38 kinase are distinct pathways leading to cytokine production by H5N1 virus. We conclude that IRF3 and p38 kinase separately and predominantly contribute to H5N1-mediated induction of IFN-beta, IFN-lambda1, and MCP-1 but only partly control TNF-alpha induction. A more precise identification of the differences in the regulation of TNF-alpha and IFN-beta could provide novel targets for the design of therapeutic strategies for severe human H5N1 influenza and also for treating other causes of acute respiratory distress syndrome.
Abstract We report the timing analysis of PSR J1846−0513, a pulsar discovered by the Five-hundred-meter Aperture Spherical radio Telescope (FAST) in Commensal Radio Astronomy FAST Survey. The pulsar ...possesses a spin period of 23.36 ms and a spin-down rate ( P ̇ ) of 1.0106(3) × 10 −18 s s −1 , and it is located in an eccentric orbit ( e ∼0.208) with an orbital period of 0.61 days. The characteristic age and surface magnetic field of the pulsar are found to be 366.62 Myr and 4.9178 × 10 9 G, respectively, indicating that it is a recycled pulsar. Using over two years of timing data, we measure the periastron advance ω ̇ = 0.8956(8) deg yr −1 . By assuming that this effect is purely relativistic, we have estimated the total mass M = 2.6287(35) M ⊙ and obtained an upper limit for the pulsar mass and a lower limit for the companion’s mass. Our results indicate that this is a double neutron star system.
Summary
Background
Pemphigus is a group of rare life‐threatening mucocutaneous autoimmune diseases, presenting mainly as two subtypes: pemphigus vulgaris (PV) and pemphigus foliaceus (PF). Inherited ...predispositions to pemphigus have long been speculated but they remain poorly understood.
Objectives
To identify common and specific nongenetic and genetic factors associated with pemphigus and its subtypes in the Chinese population.
Methods
A genome‐wide association study (GWAS) was performed in 496 unrelated patients with pemphigus (including 365 with PV and 104 with PF) and 1105 controls without pemphigus.
Results
A sex preference was observed only in PV (57·5% female) and not in PF (47·1% female). For male patients only, the mean age at diagnosis was significantly lower for PV than for PF (P < 0·001). The strongest associated single‐nucleotide polymorphisms are in the human leucocyte antigen (HLA) region: rs70993900 (PV; P = 1·5 × 10−45) and rs9469220 (PF; P = 1·1 × 10−8). HLA‐DQB1*05:03 ranks at the top (P = 4·7 × 10−40; odds ratio 12·4) in both subtypes, with significantly different risk allele frequency (RAFPV = 34·2% vs. RAFPF = 18·8% vs. RAFcontrol = 4·4%), whereas HLA‐DRB1*14:01 and HLA‐DRB1*04:06 are PV specific. HLA‐DQB1*03:03 and HLA‐DQB1*03:02 show significant subtype specificity in opposite directions. All of these associations were validated in the replication series with 147 cases of pemphigus and 604 controls. Multiple novel non‐HLA susceptibility loci were also identified in the GWAS.
Conclusions
This study represents the largest GWAS on pemphigus in the Chinese population published to date, and has allowed us to identify HLA haplotypes significantly shared between or specific to the two main subtypes of pemphigus.
What's already known about this topic?
Pemphigus is a group of autoimmune mucocutaneous diseases.
It has multiple subtypes associated with certain human leucocyte antigen (HLA) haplotypes in an ethnicity‐specific manner.
What does this study add?
This is the largest genome‐wide association study published on pemphigus to date.
We identified, for the first time, more than 100 single‐nucleotide polymorphisms (SNPs; six independent) at the HLA locus, with associations reaching genome‐wide significance.
Some of these SNPs are strongly associated with specific subtypes of pemphigus.
What is the translational message?
The identified new haplotypes can potentially serve as genetic markers to improve investigation of the epidemiology and pathogenesis of pemphigus and its specific subtypes.
Linked Comment: Geller. Br J Dermatol 2019; 180:713–714.
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Breast cancer is the most common cancer in reproductive age women. The aim of this study is to assess the knowledge, attitude and intention on fertility preservation among women diagnosed to have ...breast cancer. This is a multi-centre cross-sectional questionnaire study. Reproductive age women diagnosed with breast cancer attending Oncology, Breast Surgery and Gynaecology Clinics and support groups were invited to participate. Women filled in paper or electronic form of the questionnaire. 461 women were recruited and 421 women returned the questionnaire. Overall, 181/410 (44.1%) women had heard of fertility preservation. Younger age and higher education level were significantly associated with increased awareness of fertility preservation. Awareness and acceptance of the different fertility preservation methods in reproductive age women with breast cancer was suboptimal. However, 46.1% women felt that their fertility concerns affected their decision for cancer treatment in some way.
Gastric cancer is one of the most aggressive cancers and is the second leading cause of cancer death worldwide. Approximately 40% of global gastric cancer cases occur in China, with peritoneal ...metastasis being the prevalent form of recurrence and metastasis in advanced disease. Currently, there are limited clinical approaches for predicting and treatment of peritoneal metastasis, resulting in a 6-month average survival time. By comprehensive genome analysis will uncover the pathogenesis of peritoneal metastasis. Here we describe a comprehensive whole-genome and transcriptome sequencing analysis of one advanced gastric cancer case, including non-cancerous mucosa, primary cancer and matched peritoneal metastatic cancer. The peripheral blood is used as normal control. We identified 27 mutated genes, of which 19 genes are reported in COSMIC database (ZNF208, CRNN, ATXN3, DCTN1, RP1L1, PRB4, PRB1, MUC4, HS6ST3, MUC17, JAM2, ITGAD, IREB2, IQUB, CORO1B, CCDC121, AKAP2, ACAN and ACADL), and eight genes have not previously been described in gastric cancer (CCDC178, ARMC4, TUBB6, PLIN4, PKLR, PDZD2, DMBT1and DAB1).Additionally,GPX4 and MPND in 19q13.3-13.4 region, is characterized as a novel fusion-gene. This study disclosed novel biological markers and tumorigenic pathways that would predict gastric cancer occurring peritoneal metastasis.
The evolutions of MHD instability behaviors and enhancement of both electrostatic and electromagnetic turbulence towards the plasma disruption have been clearly observed in the HL-2A plasmas. Two ...types of plasma disruptive discharges have been investigated for similar equilibrium parameters: one with a distinct stage of a small central temperature collapse (Formula: see text 5-10%) around 1 millisecond before the thermal quench (TQ), while the other without. For both types, the TQ phase is preceded by a rotating 2/1 tearing mode, and it is the development of the cold bubble from the inner region of the 2/1 island O-point along with its inward convection that causes the massive energy loss. In addition, the micro-scale turbulence, including magnetic fluctuations and density fluctuations, increases before the small collapse, and more significantly towards the TQ. Also, temperature fluctuations measured by electron cyclotron emission imaging enhances dramatically at the reconnection site and expand into the island when approaching the small collapse and TQ, and the expansion is more significant close to the TQ. The observed turbulence enhancement near the X-point cannot be fully interpreted by the linear stability analysis by GENE. Evidences suggest that nonlinear effects, such as the reduction of local Formula: see text shear and turbulence spreading, may play an important role in governing turbulence enhancement and expansion. These results imply that the turbulence and its interaction with the island facilitate the stochasticity of the magnetic flux and formation of the cold bubble, and hence, the plasma disruption.
A compact laser plasma accelerator (CLAPA) that can stably produce and transport proton ions with different energies less than 10 MeV,<1%energy spread, several to tens of pC charge, is demonstrated. ...The high current proton beam with continuous energy spectrum and a large divergence angle is generated by using a high contrast laser and micron thickness targets, which later is collected, analyzed and refocused by an image-relaying beam line using a combination of quadrupole and bending electromagnets. It eliminates the inherent defects of the laser-driven beams, realizes precise manipulation of the proton beams with reliability, availability, maintainability and inspectability (RAMI), and takes the first step towards applications of this new generation of accelerator. With the development of high-rep rate Petawatt (PW) laser technology, we can now envision a new generation of accelerator for many applications in the near future soon.
In this work, we report the in-orbit demonstration of X-ray pulsar navigation with Insight-Hard X-ray Modulation Telescope (Insight-HXMT) Satellite, which was launched on 2017 June 15. The new pulsar ...navigation method "Significance Enhancement of Pulse-profile with Orbit-dynamics" is adopted to determine the orbit with observations of only one pulsar. In this test, the Crab pulsar is chosen and observed by Insight-HXMT from 2017 August 31 to September 5. Using the five-day long observation data, the orbit of Insight-HXMT is determined successfully with the three telescopes onboard: High Energy X-ray Telescope, Medium Energy X-ray Telescope, and Low Energy X-ray Telescope, respectively. By combining all the data, the position and velocity of the Insight-HXMT are pinpointed to within 10 km (3 ) and 10 m s−1 (3 ), respectively.
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