Discovery of serum biomarkers of alcoholic fatty liver in a rodent model: C-reactive protein

<p>Abstract</p> <p>Background</p> <p>Excessive consumption of alcohol contributes to alcoholic liver disease. Fatty liver is the early stage of alcohol-related liver disease. The aim of this study was to search for specific serological biomarkers of alcoholic fatty liver (AFL) compared to healthy controls, non-alcoholic fatty liver (NAFL) and liver fibrosis in a rodent model.</p> <p>Methods</p> <p>Serum samples derived from animals with AFL, NAFL, or liver fibrosis were characterized and compared using two-dimensional differential gel electrophoresis. A matrix-assisted laser desorption ionization-time of flight tandem mass spectrometer in conjunction with mascot software was used for protein identification. Subsequently, Western blotting and flexible multi-analyte profiling were used to measure the expressions of the putative biomarkers present in the serum of animals and clinical patients.</p> <p>Results</p> <p>Eight differential putative biomarkers were identified, and the two most differentiated proteins, including upregulated C-reactive protein (CRP) and downregulated haptoglobin (Hp), were further investigated. Western blotting validated that CRP was dramatically higher in the serum of AFL compared to healthy controls and other animals with liver disease of NAFL or liver fibrosis (<it>p </it>< 0.05). Moreover, we found that CRP and Hp were both lower in liver fibrosis of TAA-induced rats and clinical hepatitis C virus-infected patients.</p> <p>Conclusion</p> <p>The results suggest that increased levels of CRP are an early sign of AFL in rats. The abnormally elevated CRP induced by ethanol can be used as a biomarker to distinguish AFL from normal or otherwise diseased livers.</p

A stability study of impregnated LSCF–GDC composite cathodes of solid oxide fuel cells

The performance degradation of composite cathodes of La0.6Sr0.4Co0.2Fe0.8O3−δ and Gd-doped ceria (LSCF–GDC), prepared by impregnating the porous GDC scaffold with a nitrate solution containing La, Sr, Co and Fe in desired composition, is investigated at 750 °C and open circuit in air for 500 h. The performance of the impregnated LSCF–GDC composite cathodes deteriorates after testing at 750 °C for 500 h; the electrode polarization resistance (Rp) increases from 0.38 to 0.83 Ω cm2, and the electrode ohmic resistance (Ro) increases from 1.79 to 2.14 Ω cm2. The grain growth and coarsening of impregnated LSCF nanoparticles are responsible for the performance degradation of the cathodes. XPS analysis shows the enrichment of cobalt on the surface of the infiltrated LSCF–GDC cathodes and such surface segregation could also contribute to the degradation of the electrocatalytic activity of the cathodes. Introducing MgO and LaNi0.6Fe0.4O3 phases can effectively suppress the coarsening of LSCF nanoparticles and enhance the stability of the cathodes. However, the enhancing effect is related to the conductivity and electrocatalytic activity of the introduced phases

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

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

[[alternative]]The synthesis and reactivity research of iron carbonyl cluster

[[abstract]]當 K2TeO3 與 Fe(CO)5 在鹼性的環境下, 以甲醇為溶劑在室溫下反應 後, 再以大陽離子團 [PhCH2NMe3]+ 當配對離子 , 可以產生 [PhCH2NMe3 ]2[Te6Fe8(CO)24] 與次要產物 [PhCH2NMe3]2[Te4Fe5(CO)14]。它門可以 利用對溶劑有不同的溶解渡來分離, [PhCH2NMe3]2[Te4Fe5(CO)14] 並使 用光譜分析法以及 X-ray 繞射解析鑑定其結構。起始物 [Te6Fe8(CO)24 ]2- 與有機雙鹵化物 BrCH2CH2Br, BrCH2CH2Cl, ClCH2CH2CH2Cl 在 THF 環境下反應, 分別可以得到 [BrTe2Fe2(CO)6]-, Fe2(CO)6(u-TeCH2CH2 Te), 與 Fe2(CO)6(u-TeCH2CH2CH2Te)。而產物之結構可以利用 X-ray繞 射解析得到明確的鑑定。此外, 利用 NaBiO3 與 Mo(CO)6 在甲醇中反應 後, 以大陽離子團 [Et4N]+ 當配對離子, 再利用 CH2Cl2 將其萃取可以 產生新的混合金屬簇化合物 [Et4N]2[BiMo4(CO)12(u3-OMe)3].CH2Cl2, 其結構也可由 X-ray 繞射解析得到明確的鑑定。 The reaction of K2TeO3 with Fe(CO)5/KOH in MeOH followed by the treatment with [PhCH2NMe3]Cl produces [PhCH2NMe3]2[Te6Fe8(CO)24 ] and the minor product [PhCH2NMe3]2[Te4Fe5(CO)14]. [PhCH2NMe3]2 [Te4Fe5(CO)14] has been isolated and structrually characterized by ingle-crystal X-ray diffraction and spectroscopic methods. Treatment of [Te6Fe8(CO)24]2- with BrCH2CH2Br, BrCH2CH2Cl or ClCH2CH2CH2Cl in THF produces [BrTe2Fe2(CO)6]-, Fe2(CO)6(u-TeCH2 CH2Te) or Fe2(CO)6(u-TeCH2CH2CH2Te), respectively. The structures of [BrTe2Fe2(CO)6]-, Fe2(CO)6(u-TeCH2CH2Te) and Fe2( CO)6(u-TeCH2CH2CH2Te) have been performed by single -crystal X- ray diffraction method. Besides, the reaction of NaBiO3 with Mo( CO)6 in MeOH followed by the treatment with [Et4N]Br produces [Et4N]2[BiMo4(CO)12(u3-OMe)3].CH2Cl2. It has been structurally characterized by single-crystal X-ray diffraction method and spectroscopic methods. The reaction of K2TeO3 with Fe(CO)5 KOH in MeOH followed by the

Activity-derived model for water and salt transport in reverse osmosis membranes: A combination of film theory and electrolyte theory

status: publishe

Surface-Enhanced Raman Scattering-Active Au/SiO₂ Nanocomposites Prepared Using Sonoelectrochemical Pulse Deposition Methods

For improving signals, reproducibility, and stabilities of surface-enhanced Raman scattering (SERS), numerous technologies have recently been reported in the literature. However, the fabrication processes are usually complicated. It is well-known that nanoparticles (NPs) of Au and SiO₂ are SERS active and inactive materials, respectively. In this work, a simple synthesis route based on sonoelectrochemical pulse deposition (SEPD) methods has been developed to synthesize effectively SERS-active Au/SiO₂ nanocomposites (NCs) with an enhancement factor of 5.4 × 10⁸. Experimental results indicate that pH value of solution and addition of SiO₂ NPs before and after oxidation–reduction cycles (ORCs) can significantly influence the corresponding SERS activities. Encouragingly, the SERS of Rhodamine 6G (R6G) adsorbed on the developed Au/SiO₂ NCs exhibits a higher intensity by more than 1 order of magnitude, as compared with that of R6G adsorbed on Au NPs synthesized using the same method. Moreover, this improved SERS activity is successfully verified from the mechanisms of electromagnetic (EM) and chemical (CHEM) enhancements

Human Neutrophil Peptides 1–3 as Gastric Cancer Tissue Markers Measured by MALDI-Imaging Mass Spectrometry: Implications for Infiltrated Neutrophils as a Tumor Target

Objective: Human neutrophil peptides (HNPs) -1, -2 and -3 are significantly upregulated and were reported as biomarkers in gastric cancer (GC). However, the tissue location and function of HNPs 1-3 are still unclear in GC, and the spatial distribution of the triad needs to be disclosed. The aims of this study were to investigate the distribution and relationships among HNPs-1, -2 and -3, and assess whether infiltrated neutrophils accumulate in gastric tumor