Influence of Ketotifen, Cromolyn Sodium, and Compound 48/80 on the survival rates after intestinal ischemia reperfusion injury in rats

<p>Abstract</p> <p>Background</p> <p>Mast cells were associated with intestinal ischemia-reperfusion injury, the study was to observe the influence of Ketotifen, Cromolyn Sdium(CS), and Compound 48/80(CP) on the survival rates on the third day after intestinal ischemia-reperfusion injury in rats.</p> <p>Methods</p> <p>120 healthy Sprague-Dawley rats were randomly divided into 5 groups, Sham-operated group (group S), model group (group M), group K, group C and group CP. Intestinal damage was triggered by clamping the superior mesenteric artery for 75 minutes, group K, C, and CP were treated with kotifen 1 mg·kg^-1, CS 50 mg·kg^-1, and CP 0.75 mg·kg^-1i.v. at 5 min before reperfusion and once daily for three days following reperfusion respectively. Survival rate in each group was recorded during the three days after reperfusion. All the surviving rats were killed for determining the concentration of serum glutamic-oxaloacetic transaminase(AST), glutamic pyruvic transaminase(ALT), the ratio of AST compare ALT(S/L), total protein(TP), albumin(ALB), globulin(GLB), the ratio of ALB compare GLB(A/G), phosphocreatine kinase(CK), lactate dehydrogenase(LDH), urea nitrogen(BUN) and creatinine(CRE) at the 3^rdday after reperfusion. And ultrastructure of IMMC, Chiu's score, lung histology, IMMC counts, the levels of TNF-α, IL-1β, IL-6 and IL-10 of the small intestine were detected at the same time.</p> <p>Results</p> <p>Intestinal ischemia-reperfusion injury reduced the survival rate. The concentrations of TP, ALB and level of IL-10 in intestine in group M decreased significantly while the concentrations of S/L, LDH and the levels of IL-6 and TNF-α in intestine increased significantly compared with group S (<it>P </it>< 0.05). Treatment with Ketotifen and CS increased the survival rate compared with group M (<it>P </it>< 0.05), attenuated the down-regulation or up-regulation of the above index (<it>P </it>< 0.05). Treatment with CP decreased the survival rate on the 3^rdday after reperfusion compared with group M(<it>P </it>< 0.05). Group K and C had better morphology in IMMC in the small intestine and in the lungs than in group M and CP, although the Chiu's score and IMMC counts remained the same in the five groups(<it>P </it>> 0.05).</p> <p>Conclusion</p> <p>Mast cell inhibition after ischemia prior to reperfusion and following reperfusion may decrease the multi-organ injury induced by intestine ischemia reperfusion, and increase the survival rates.</p

A Renewable and Ultrasensitive Electrochemiluminescence Immunosenor Based on Magnetic RuL@SiO2-Au∼RuL-Ab2 Sandwich-Type Nano-Immunocomplexes

An ultrasensitive and renewable electrochemiluminescence (ECL) immunosensor was developed for the detection of tumor markers by combining a newly designed trace tag and streptavidin-coated magnetic particles (SCMPs). The trace tag (RuL@SiO2-Au∼RuL-Ab2) was prepared by loading Ru(bpy)32+(RuL)-conjuged secondary antibodies (RuL-Ab2) on RuL@SiO2 (RuL-doped SiO2) doped Au (RuL@SiO2-Au). To fabricate the immunosensor, SCMPs were mixed with biotinylated AFP primary antibody (Biotin-Ab1), AFP, and RuL@SiO2-Au∼RuL-Ab2 complexes, then the resulting SCMP/Biotin-Ab1/AFP/RuL@SiO2-Au∼RuL-Ab2 (SBAR) sandwich-type immunocomplexes were absorbed on screen printed carbon electrode (SPCE) for detection. The immunocomplexes can be easily washed away from the surface of the SPCE when the magnetic field was removed, which made the immunosensor reusable. The present immunosensor showed a wide linear range of 0.05–100 ng mL−1 for detecting AFP, with a low detection limit of 0.02 ng mL−1 (defined as S/N = 3). The method takes advantage of three properties of the immunosensor: firstly, the RuL@SiO2-Au∼RuL-Ab2 composite exhibited dual amplification since SiO2 could load large amount of reporter molecules (RuL) for signal amplification. Gold particles could provide a large active surface to load more reporter molecules (RuL-Ab2). Accordingly, through the ECL response of RuL and tripropylamine (TPA), a strong ECL signal was obtained and an amplification analysis of protein interaction was achieved. Secondly, the sensor is renewable because the sandwich-type immunocomplexes can be readily absorbed or removed on the SPCE’s surface in a magnetic field. Thirdly, the SCMP modified probes can perform the rapid separation and purification of signal antibodies in a magnetic field. Thus, the present immunosensor can simultaneously realize separation, enrichment and determination. It showed potential application for the detection of AFP in human sera

TNFAIP1 contributes to the neurotoxicity induced by Aβ25–35 in Neuro2a cells

Background: Amyloid-beta (Aβ) accumulation is a hallmark of Alzheimer’s disease (AD) that can lead to neuronal dysfunction and apoptosis. Tumor necrosis factor, alpha-induced protein 1 (TNFAIP1) is an apoptotic protein that was robustly induced in the transgenic C. elegans AD brains. However, the roles of TNFAIP1 in AD have not been investigated. Results: We found TNFAIP1 protein and mRNA levels were dramatically elevated in primary mouse cortical neurons and Neuro2a (N2a) cells exposed to Aβ25–35. Knockdown and overexpression of TNFAIP1 significantly attenuated and exacerbated Aβ25–35-induced neurotoxicity in N2a cells, respectively. Further studies showed that TNFAIP1 knockdown significantly blocked Aβ25–35-induced cleaved caspase 3, whereas TNFAIP1 overexpression enhanced Aβ25–35-induced cleaved caspase 3, suggesting that TNFAIP1 plays an important role in Aβ25–35-induced neuronal apoptosis. Moreover, we observed that TNFAIP1 was capable of inhibiting the levels of phosphorylated Akt and CREB, and also anti-apoptotic protein Bcl-2. TNFAIP1 overexpression enhanced the inhibitory effect of Aβ25–35 on the levels of p-CREB and Bcl-2, while TNFAIP1 knockdown reversed Aβ25–35-induced attenuation in the levels of p-CREB and Bcl-2. Conclusion: These results suggested that TNFAIP1 contributes to Aβ25–35-induced neurotoxicity by attenuating Akt/CREB signaling pathway, and Bcl-2 expression

A genome-wide association study identifies GRK5 and RASGRP1 as type 2 diabetes loci in Chinese Hans.

Substantial progress has been made in identification of type 2 diabetes (T2D) risk loci in the past few years, but our understanding of the genetic basis of T2D in ethnically diverse populations remains limited. We performed a genome-wide association study and a replication study in Chinese Hans comprising 8,569 T2D case subjects and 8,923 control subjects in total, from which 10 single nucleotide polymorphisms were selected for further follow-up in a de novo replication sample of 3,410 T2D case and 3,412 control subjects and an in silico replication sample of 6,952 T2D case and 11,865 control subjects. Besides confirming seven established T2D loci (CDKAL1, CDKN2A/B, KCNQ1, CDC123, GLIS3, HNF1B, and DUSP9) at genome-wide significance, we identified two novel T2D loci, including G-protein-coupled receptor kinase 5 (GRK5) (rs10886471: P = 7.1 × 10(-9)) and RASGRP1 (rs7403531: P = 3.9 × 10(-9)), of which the association signal at GRK5 seems to be specific to East Asians. In nondiabetic individuals, the T2D risk-increasing allele of RASGRP1-rs7403531 was also associated with higher HbA(1c) and lower homeostasis model assessment of β-cell function (P = 0.03 and 0.0209, respectively), whereas the T2D risk-increasing allele of GRK5-rs10886471 was also associated with higher fasting insulin (P = 0.0169) but not with fasting glucose. Our findings not only provide new insights into the pathophysiology of T2D, but may also shed light on the ethnic differences in T2D susceptibility

Distinct 'Immuno-Allertypes' of Disease and High Frequencies of Sensitisation in Non-Cystic-Fibrosis Bronchiectasis

Rationale: Allergic sensitization is associated with poor clinical outcomes in asthma, chronic obstructive pulmonary disease, and cystic fibrosis; however, its presence, frequency, and clinical significance in non–cystic fibrosis bronchiectasis remain unclear. Objectives: To determine the frequency and geographic variability that exists in a sensitization pattern to common and specific allergens, including house dust mite and fungi, and to correlate such patterns to airway immune-inflammatory status and clinical outcomes in bronchiectasis. Methods: Patients with bronchiectasis were recruited in Asia (Singapore and Malaysia) and the United Kingdom (Scotland) (n = 238), forming the Cohort of Asian and Matched European Bronchiectasis, which matched recruited patients on age, sex, and bronchiectasis severity. Specific IgE response against a range of common allergens was determined, combined with airway immune-inflammatory status and correlated to clinical outcomes. Clinically relevant patient clusters, based on sensitization pattern and airway immune profiles (“immunoallertypes”), were determined. Measurements and Main Results: A high frequency of sensitization to multiple allergens was detected in bronchiectasis, exceeding that in a comparator cohort with allergic rhinitis (n = 149). Sensitization was associated with poor clinical outcomes, including decreased pulmonary function and more severe disease. “Sensitized bronchiectasis” was classified into two immunoallertypes: one fungal driven and proinflammatory, the other house dust mite driven and chemokine dominant, with the former demonstrating poorer clinical outcome. Conclusions: Allergic sensitization occurs at high frequency in patients with bronchiectasis recruited from different global centers. Improving endophenotyping of sensitized bronchiectasis, a clinically significant state, and a “treatable trait” permits therapeutic intervention in appropriate patients, and may allow improved stratification in future bronchiectasis research and clinical trials.Ministry of Education (MOE)Ministry of Health (MOH)National Medical Research Council (NMRC)Published versionSupported by the Singapore Ministry of Health’s National Medical Research Council under its Transition Award NMRC/TA/0048/2016 (S.H.C.) and Changi General Hospital Research grant CHF2016.03-P (T.B.L.). The work performed at NUS was supported by the Singapore Ministry of Education Academic Research Fund, SIgN, and National Medical Research Council grants N-154-000-038-001, R-154-000-404-112, R-154-000-553-112, R-154-000-565-112, R-154-000-630-112, R-154-000-A08-592, R-154-000-A27-597, SIgN-06-006, SIgN-08-020, and NMRC/1150/2008 (F.T.C.); J.D.C. is supported by the GSK/British Lung Foundation Chair of Respiratory Research

JUNO Conceptual Design Report

The Jiangmen Underground Neutrino Observatory (JUNO) is proposed to determine the neutrino mass hierarchy using an underground liquid scintillator detector. It is located 53 km away from both Yangjiang and Taishan Nuclear Power Plants in Guangdong, China. The experimental hall, spanning more than 50 meters, is under a granite mountain of over 700 m overburden. Within six years of running, the detection of reactor antineutrinos can resolve the neutrino mass hierarchy at a confidence level of 3-4$\sigma$, and determine neutrino oscillation parameters $\sin^2\theta_{12}$, $\Delta m^2_{21}$, and $|\Delta m^2_{ee}|$ to an accuracy of better than 1%. The JUNO detector can be also used to study terrestrial and extra-terrestrial neutrinos and new physics beyond the Standard Model. The central detector contains 20,000 tons liquid scintillator with an acrylic sphere of 35 m in diameter. $\sim$17,000 508-mm diameter PMTs with high quantum efficiency provide $\sim$75% optical coverage. The current choice of the liquid scintillator is: linear alkyl benzene (LAB) as the solvent, plus PPO as the scintillation fluor and a wavelength-shifter (Bis-MSB). The number of detected photoelectrons per MeV is larger than 1,100 and the energy resolution is expected to be 3% at 1 MeV. The calibration system is designed to deploy multiple sources to cover the entire energy range of reactor antineutrinos, and to achieve a full-volume position coverage inside the detector. The veto system is used for muon detection, muon induced background study and reduction. It consists of a Water Cherenkov detector and a Top Tracker system. The readout system, the detector control system and the offline system insure efficient and stable data acquisition and processing.Comment: 328 pages, 211 figure

Bacterial diversity in typical abandoned multi-contaminated nonferrous metal(loid) tailings during natural attenuation

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordAbandoned nonferrous metal(loid) tailings sites are anthropogenic, and represent unique and extreme ecological niches for microbial communities. Tailings contain elevated and toxic content of metal(loid)s that had negative effects on local human health and regional ecosystems. Microbial communities in these typical tailings undergoing natural attenuation are often very poorly examined. The diversity and inferred functions of bacterial communities were examined at seven nonferrous metal(loid) tailings sites in Guangxi (China), which were abandoned between 3 and 31 years ago. The acidity of the tailings sites rose over 31 years of site inactivity. Desulfurivibrio, which were always coupled with sulfur/sulfide oxidation to dissimilate the reduction of nitrate/nitrite, were specific in tailings with 3 years abandonment. However, genus beneficial to plant growth (Rhizobium), and iron/sulfur- oxidizing bacteria and metal(loid)-related genera (Acidiferrobacter and Acidithiobacillus) were specific within tailings abandoned for 23 years or more. The increased abundance of acid-generating iron/sulfur-oxidizing and metal(loid)-related bacteria and specific bacterial communities during the natural attenuation could provide new insights for understanding microbial ecosystem functioning in mine tailings. OTUs related to Sulfuriferula, Bacillus, Sulfurifustis, Gaiella, and Thiobacillus genera were the main contributors differentiating the bacterial communities between the different tailing sites. Multiple correlation analyses between bacterial communities and geochemical parameters indicated that pH, TOC, TN, As, Pb, and Cu were the main drivers influencing the bacterial community structures. PICRUSt functional exploration revealed that the main functions were related to DNA repair and recombination, important functions for bacterial adaptation to cope with the multi- contamination of tailings. Such information provides new insights to guide future metagenomic studies for the identification of key functions beyond metal- transformation/resistance. As well, our results offers novel outlooks for the management of bacterial communities during natural attenuation of multi-contaminated nonferrous metal(loid) tailings sites.International Key Project from National Natural Science Foundation of ChinaProjects of Natural Science Foundation of ChinaPublic welfare project of Chinese Ministry of Environmental Protectionnternational key project of Ministry of Science and Technology of ChinaS2016G2135Centre National de la Recherche ScientifiqueRoyal Society Newton Mobility GrantNational Natural Science Foundation International Joint collaboration China-Swede

The Interleukin 3 Gene (IL3) Contributes to Human Brain Volume Variation by Regulating Proliferation and Survival of Neural Progenitors

One of the most significant evolutionary changes underlying the highly developed cognitive abilities of humans is the greatly enlarged brain volume. In addition to being far greater than in most other species, the volume of the human brain exhibits extensive variation and distinct sexual dimorphism in the general population. However, little is known about the genetic mechanisms underlying normal variation as well as the observed sex difference in human brain volume. Here we show that interleukin-3 (IL3) is strongly associated with brain volume variation in four genetically divergent populations. We identified a sequence polymorphism (rs31480) in the IL3 promoter which alters the expression of IL3 by affecting the binding affinity of transcription factor SP1. Further analysis indicated that IL3 and its receptors are continuously expressed in the developing mouse brain, reaching highest levels at postnatal day 1–4. Furthermore, we found IL3 receptor alpha (IL3RA) was mainly expressed in neural progenitors and neurons, and IL3 could promote proliferation and survival of the neural progenitors. The expression level of IL3 thus played pivotal roles in the expansion and maintenance of the neural progenitor pool and the number of surviving neurons. Moreover, we found that IL3 activated both estrogen receptors, but estrogen didn’t directly regulate the expression of IL3. Our results demonstrate that genetic variation in the IL3 promoter regulates human brain volume and reveals novel roles of IL3 in regulating brain development

A review of thermal management for Li-ion batteries: Prospects, challenges, and issues

Li-ion batteries are essential component in the current generation of electric vehicles. However, further pushing electric vehicles are concerned with battery life. Since the temperature dictates battery lifetime, it is crucial to manage the heat and keep the temperature at an acceptable range within the battery pack. The benefit of a cooling system is to prevent the premature degradation of battery life. This paper provides a critical review of the so far thermal management strategy dealing with temperature within the cells, module, and packs. This paper reviews the advantages and disadvantages of state of the art (traditional) thermal cooling system. In this paper, we have reviewed separately cell, module, and pack level cooling system. The battery thermal modeling techniques and cooling system design challenges are also reviewed. This paper also reviews the future cooling system for future vehicles with rising fast charge rate and these techniques can improve the limitations of the traditional cooling system. This paper also suggests the best suitable and economically viable technology for the upcoming EVs issues