To cite this article: Kim YH, Yang TY, Park C‐S, Ahn S‐H, Son BK, Kim JH, Lim DH, Jang TY. Anti‐IL‐33 antibody has a therapeutic effect in a murine model of allergic rhinitis. Allergy 2012; 67: ...183–190.
Background: Interleukin (IL)‐33 is involved in the Th2 immune response and could play an essential role in nasal allergy. Therefore, we aimed to investigate the therapeutic potential of anti‐IL‐33 for allergic rhinitis (AR).
Methods: Twenty‐four BALB/c mice were used. In group A (control group, n = 6), mice were sensitized and challenged with saline. Group B ovalbumin (OVA) group, n = 6 mice received intraperitoneal and intranasal OVA challenge. In group C (control IgG group, n = 6), mice were injected intraperitoneally with rabbit control IgG before OVA challenge. In group D (anti‐IL‐33 group, n = 6), anti‐IL‐33 was injected before challenge. We evaluated the number of nose‐scratching events and external morphology; serum total and OVA‐specific IgE; number of eosinophils, neutrophils, and lymphocytes in bronchoalveolar lavage (BAL) fluid; histopathologic examination of nasal cavity; and IL‐4, IL‐5, and IL‐13 in BAL fluid.
Results: Anti‐IL‐33 treatment significantly reduced the nose‐scratching events and ameliorated skin denudation. Serum total and OVA‐specific IgE was significantly decreased in group D. The number of eosinophils in BAL fluid was also significantly decreased. Eosinophilic infiltration in the nasal cavity was significantly decreased in group D. IL‐4, IL‐5, and IL‐13 in BAL fluid were also significantly decreased after treatment.
Conclusions: Anti‐IL‐33 antibody has a therapeutic potential for experimental AR.
The authors provide an epidemiologic analysis of the first 425 confirmed cases of infection with the novel coronavirus in Wuhan, China. This analysis provides estimates of the epidemic doubling time ...and the basic reproductive number and shows clear evidence of sustained human-to-human transmission.
Objective
This systematic review and meta‐analysis of randomized controlled trials (RCTs) examined the efficacy and safety of adjunctive N‐acetylcysteine (NAC), an antioxidant drug, in treating major ...depressive disorder (MDD), bipolar disorder, and schizophrenia.
Methods
The PubMed, Cochrane Library, PsycINFO, CNKI, CBM, and WanFang databases were independently searched and screened by two researchers. Standardized mean differences (SMDs), risk ratios, and their 95% confidence intervals (CIs) were computed.
Results
Six RCTs (n = 701) of NAC for schizophrenia (three RCTs, n = 307), bipolar disorder (two RCTs, n = 125), and MDD (one RCT, n = 269) were identified and analyzed as separate groups. Adjunctive NAC significantly improved total psychopathology (SMD = −0.74, 95% CI: −1.43, −0.06; I2 = 84%, P = 0.03) in schizophrenia, but it had no significant effect on depressive and manic symptoms as assessed by the Young Mania Rating Scale in bipolar disorder and only a small effect on major depressive symptoms. Adverse drug reactions to NAC and discontinuation rates between the NAC and control groups were similar across the three disorders.
Conclusions
Adjunctive NAC appears to be a safe treatment that has efficacy for schizophrenia, but not for bipolar disorder or MDD. Further higher quality RCTs are warranted to determine the role of adjunctive NAC in the treatment of major psychiatric disorders.
Geological sequestration of atmospheric carbon dioxide (CO2) can be achieved by the erosion of organic carbon (OC) from the terrestrial biosphere and its burial in long-lived marine sediments. Rivers ...on mountain islands of Oceania in the western Pacific have very high rates of OC export to the ocean, yet its preservation offshore remains poorly constrained. Here we use the OC content (Corg, %), radiocarbon (Δ 14Corg) and stable isotope (δ13Corg) composition of sediments offshore Taiwan to assess the fate of terrestrial OC, using surface, sub-surface and Holocene sediments. We account for rock-derived OC to assess the preservation of OC eroded from the terrestrial biosphere and the associated CO2 sink during flood discharges (hyperpycnal river plumes) and when river inputs are dispersed more widely (hypopycnal). The Corg, Δ14Corg and δ 13Corg of marine sediment traps and cores indicate that during flood discharges, terrestrial OC can be transferred efficiently down submarine canyons to the deep ocean and accumulates offshore with little evidence for terrestrial OC loss. In marine sediments fed by dispersive river inputs, the Corg, Δ14Corg and δ 13Corg are consistent with mixing of terrestrial OC with marine OC and suggest that efficient preservation of terrestrial OC (>70%) is also associated with hypopycnal delivery. Sub-surface and Holocene sediments indicate that this preservation is long-lived on millennial timescales. Re-burial of rock-derived OC is pervasive. Our findings from Taiwan suggest that erosion and offshore burial of OC from the terrestrial biosphere may sequester >8 TgC yr−1 across Oceania, a significant geological CO2 sink which requires better constraint. We postulate that mountain islands of Oceania provide a strong link between tectonic uplift and the carbon cycle, one moderated by the climatic variability which controls terrestrial OC delivery to the ocean.
Standard heat treatment (HT1) for Inconel 718 superalloy is solutionizing at 1095
°C, 1
h/AC, then aging at 955
°C, 1
h/AC
+
720
°C, 8
h/FC 57
K/h to 620
°C, 8
h/AC. In order to study the aging ...effects of the δ phase, two more conditions HT2 (no aging condition 955
°C) and HT3 (955
°C, 3.5
h/AC) were studied in this research. Lever arm creep tests were performed at 650
°C under constant stress 625
MPa. Since HT2 produces no δ phase, the stress rupture life, creep elongation to failure and steady state creep rate of HT2 are largest among these three aging conditions. However, increasing the 955
°C aging time, the stress rupture life, creep elongation and steady state creep rate raise slightly as compared to HT1, because platelet δ phase is more uniformly nucleated and more direction oriented at grain boundaries. Fractographs show ductile fracture patterns mostly and, small portion of inter-granular fracture in the HT2 specimens. Generally only inter-granular fracture is observed in the other two cases of HT1 and HT3. Besides twinning and dislocation mechanisms, grain boundary sliding is also activated, so that creep elongation to failure of HT2 specimens could reach 5.6%, whereas 1% for the other two schemes.
Successful commercialization of perovskite solar cells (PSCs) in the near future will require the fabrication of cells with high efficiency and long-term stability. Despite their good processability ...at low temperatures, the majority of organic conductors employed in the fabrication of high-efficiency PSCs e.g. , 2,2′,7,7′-tetrakis( N , N -di- p -methoxyphenylamine)-9,9′-spirobifluorene (spiro-OMeTAD) and poly(triaryl amine) (PTAA) have low thermal stability. In order to fabricate PSCs with excellent thermal stability, both the constituent material itself and the interface between the constituents must be thermally stable. In this work, we focused on copper phthalocyanine (CuPC) as a model hole-transporting material (HTM) for thermally stable PSCs since CuPC is known to possess excellent thermal stability and interfacial bonding properties. The CuPC-based PSCs recorded a high power conversion efficiency (PCE) of ∼18% and maintained 97% of their initial efficiency for more than 1000 h of thermal annealing at 85 °C. Moreover, the device was stable under thermal cycling tests (50 cycles, −45 to 85 °C). The high PCE and high thermal stability observed in the CuPC-PSCs were found to arise as a result of the strong interfacial and conformal coating present on the surface of the perovskite facets, located between CuPC and the perovskite layer. These results will provide an important future direction for the development of highly efficient and thermally stable PSCs.
Reinforced concrete (RC) buildings are commonly used around the world. With recent earthquakes worldwide, rapid structural damage inspection and repair cost evaluation are crucial for building owners ...and policy makers to make informed risk management decisions. To improve the efficiency of such inspection, advanced computer vision techniques based on convolutional neural networks have been adopted in recent research to rapidly quantify the damage state (DS) of structures. In this article, an advanced object detection neural network, named YOLOv2, is implemented, which achieves 98.2% and 84.5% average precision in training and testing, respectively. The proposed YOLOv2 is used in combination with the classification neural network, which improves the identification accuracy for critical DS of RC structures by 7.5%. The improved classification procedures allow engineers to rapidly and more accurately quantify the DSs of the structure, and also localize the critical damage features. The identified DS can then be integrated with the state‐of‐the‐art performance evaluation framework to quantify the financial losses of critical RC buildings. The results can be used by the building owners and decision makers to make informed risk management decisions immediately after the strong earthquake shaking. Hence, resources can be allocated rapidly to improve the resiliency of the community.
Glycogen synthase kinase 3 beta (GSK3β) is highly inactivated in epithelial cancers and is known to inhibit tumor migration and invasion. The zinc-finger-containing transcriptional repressor, Slug, ...represses E-cadherin transcription and enhances epithelial-mesenchymal transition (EMT). In this study, we find that the GSK3β-pSer9 level is associated with the expression of Slug in non-small cell lung cancer. GSK3β-mediated phosphorylation of Slug facilitates Slug protein turnover. Proteomic analysis reveals that the carboxyl terminus of Hsc70-interacting protein (CHIP) interacts with wild-type Slug (wtSlug). Knockdown of CHIP stabilizes the wtSlug protein and reduces Slug ubiquitylation and degradation. In contrast, nonphosphorylatable Slug-4SA is not degraded by CHIP. The accumulation of nondegradable Slug may further lead to the repression of E-cadherin expression and promote cancer cell migration, invasion and metastasis. Our findings provide evidence of a de novo GSK3β-CHIP-Slug pathway that may be involved in the progression of metastasis in lung cancer.
Summary
Background
Drug reaction with eosinophilia and systemic symptoms (DRESS) is a condition caused by a drug‐induced immune response. Previous reports have found that CXCL10, also known as ...interferon‐γ‐induced protein (IP)‐10, may participate in the pathogenesis of cutaneous adverse drug reactions. However, the exact role of IP‐10 in DRESS and Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) has remained unknown.
Objectives
This comparative prospective cohort study aimed to ascertain the roles of the IP‐10/CXCR3 axis in DRESS and SJS/TEN.
Methods
Plasma IP‐10 levels were analysed, and univariate analyses were conducted to assess the relationship between IP‐10, human herpesvirus (HHV)‐6 reactivation and the development of long‐term sequelae. We also performed immunohistochemical staining using skin specimens and flow cytometry to determine the expression of CXCR3 in peripheral blood mononuclear cells (PBMCs).
Results
Significantly higher plasma IP‐10 levels were observed in patients with DRESS with long‐term sequelae (effect size 0·81) and also in those with HHV‐6 reactivation (effect size 0·83). By immunohistochemistry, more abundant IP‐10+ and CXCR3+ cells were demonstrated in the skin lesions of patients with DRESS with HHV‐6 reactivation. The percentages of CLA+ CXCR3+ CD4+ cells and CLA+ CXCR3+ CD8+ cells were also higher in the PBMCs of HHV‐6‐reactivated patients with DRESS than in those of patients with SJS/TEN.
Conclusions
Higher plasma IP‐10 levels are associated with the development of long‐term sequelae in DRESS. Higher IP‐10/CXCR3 expression in skin and more abundant CLA+ CXCR3+ CD4+ cells and CLA+ CXCR3+ CD8+ cells were observed in patients with DRESS with HHV‐6 reactivation. The IP‐10/CXCR3 axis is associated with HHV‐6 reactivation and development of long‐term sequelae in DRESS.
What is already known about this topic?
Elevated levels of interferon‐γ‐induced protein‐10 (IP‐10) have been observed in patients with drug reaction with eosinophilia and systemic symptoms (DRESS) and Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN).
Patients with DRESS tend to develop long‐term autoimmune sequelae, including type 1 diabetes and autoimmune thyroiditis. IP‐10 has been associated with these autoimmune diseases in previous studies.
What does this study add?
The patients with DRESS with HHV‐6 reactivation exhibited higher levels of IP‐10 in the plasma and skin than the patients with DRESS without HHV‐6 reactivation and the patients with SJS/TEN.
Patients with DRESS with higher plasma IP‐10 levels tended to develop sequelae during long‐term follow‐up.
What is the translational message?
IP‐10 is a useful biomarker to predict the development of long‐term sequelae in patients with DRESS.
Linked Comment: Belloón and Kardaun. Br J Dermatol 2020; 183:804–805.
What is already known about this topic?
Elevated levels of interferon‐γ‐induced protein‐10 (IP‐10) have been observed in patients with drug reaction with eosinophilia and systemic symptoms (DRESS) and Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN).
Patients with DRESS tend to develop long‐term autoimmune sequelae, including type 1 diabetes and autoimmune thyroiditis. IP‐10 has been associated with these autoimmune diseases in previous studies.
What does this study add?
The patients with DRESS with HHV‐6 reactivation exhibited higher levels of IP‐10 in the plasma and skin than the patients with DRESS without HHV‐6 reactivation and the patients with SJS/TEN.
Patients with DRESS with higher plasma IP‐10 levels tended to develop sequelae during long‐term follow‐up.
What is the translational message?
IP‐10 is a useful biomarker to predict the development of long‐term sequelae in patients with DRESS.
Linked Comment: Belloón and Kardaun. Br J Dermatol 2020; 183:804–805.
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