Molecular Recognition of Arginine by Supramolecular Complexation with Calixarene Crown Ether Based on Surface Plasmon Resonance

Arginine plays an important role in cell division and the functioning of the immune system. We describe a novel method by which arginine can be identified using an artificial monolayer based on surface plasmon resonance (SPR). The affinity of arginine binding its recognition molecular was compared to that of lysine. In fabrication of an arginine sensing interface, a calix[4]crown ether monolayer was anchored onto a gold surface and then characterized by Fourier Transform infrared reflection absorption spectroscopy, atomic force microscopy, and cyclic voltammetry. The interaction between arginine and its host compound was investigated by SPR. The calix[4]crown ether was found to assemble as a monolayer on the gold surface. Recognition of calix[4]crown monolayer was assessed by the selective binding of arginine. Modification of the SPR chip with the calix[4]crown monolayer provides a reliable and simple experimental platform for investigation of arginine under aqueous conditions

Prognostic value of the neutrophil to lymphocyte ratio in lung cancer: A meta-analysis

Recently, a series of studies explored the correlation between the neutrophil to lymphocyte ratio and the prognosis of lung cancer. However, the current opinion regarding the prognostic role of the neutrophil to lymphocyte ratio in lung cancer is inconsistent. We performed a meta-analysis of published articles to investigate the prognostic value of the neutrophil to lymphocyte ratio in lung cancer. The hazard ratio (HR) and its 95% confidence interval (CI) were calculated. An elevated neutrophil to lymphocyte ratio predicted worse overall survival, with a pooled HR of 1.243 (95%CI: 1.106-1.397; Pheterogeneity=0.001) from multivariate studies and 1.867 (95%CI: 1.487-2.344; Pheterogeneity=0.047) from univariate studies. Subgroup analysis showed that a high neutrophil to lymphocyte ratio yielded worse overall survival in non-small cell lung cancer (NSCLC) (HR=1.192, 95%CI: 1.061-1.399; Pheterogeneity=0.003) as well as small cell lung cancer (SCLC) (HR=1.550, 95% CI: 1.156-2.077; Pheterogeneity=0.625) in multivariate studies. The synthesized evidence from this meta-analysis of published articles demonstrated that an elevated neutrophil to lymphocyte ratio was a predictor of poor overall survival in patients with lung cancer

Estimation of ischemic core in acute ischemic stroke with CT angiography and non-contrast CT: Attenuation changes in ASPECTS regions vs. automated ASPECTS scoring

PurposeReperfusion therapies for acute ischemic stroke due to large-vessel occlusion (AIS-LVO) are highly time-dependent, and large infarction is related to poor outcomes and risk of symptomatic hemorrhage. It is of significance to investigate and optimize the screening means and selection criteria for reperfusion therapies to identify more appropriate patients with better outcomes. This study aimed to compare the performance of attenuation changes vs. automated Alberta Stroke Program Early CT Score (ASPECTS) and using CT angiography (CTA) source images vs. non-contrast CT (NCCT) in distinguishing the infarction extent of ischemic core volumes ≥ 70 ml within different time windows.MethodsA total of 73 patients with AIS-LVO who received multimodal CT were analyzed. The automated software was used to calculate ASPECTS. Attenuation change was defined as the sum of products of relative Hounsfield unit (rHU) values times weighting factors of all 10 ASPECTS regions. rHU value of each region was the HU of the ischemic side over that of the contralateral. The corresponding weighting factors were the regression coefficients derived from a multivariable linear regression model which was used to correlate regional rHU with ischemic core volumes, because each region in the ASPECTS template is weighted disproportionally in the ASPECTS system. Automated ASPECTS and attenuation changes were both calculated using CTA and NCCT, respectively.ResultsAttenuation changes were correlated with ischemic core volumes within different time windows (Rho ranging from 0.439 to 0.637). In classification of the ischemic core ≥ 70 ml, the performances of attenuation changes were comparable with ASPECTS (area under the curve [AUC] ranging from 0.799 to 0.891), with DeLong’s test (P = 0.079, P = 0.373); using CTA (AUC = 0.842) was not different from NCCT (AUC = 0.838).ConclusionAttenuation changes in ASPECTS regions were correlated with ischemic core volumes. In the classification of infarction volumes, attenuation changes had a high diagnostic ability comparable with automated ASPECTS. Measurement of attenuation changes is not involved in complicated scoring algorithms. This measurement can be used as an available, rapid, reliable, and accurate means to evaluate infarction extent within different time windows. The usefulness of infarction volumes measured by attenuation changes to identify more appropriate patients for reperfusion therapies can be validated in future clinical trials

Analysis of gut microbiotal diversity in healthy young adults in Sunan County, Gansu Province, China

ObjectiveTo examine gut microbiotal diversity in the Han Chinese and Yugur populations of Sunan County, Gansu Province, living in the same environmental conditions, and to analyze possible causes of differences in diversity.MethodsWe selected 28 people, ages 18–45 years old, all of whom were third-generation pure Yugur or Han Chinese from Sunan County. Fresh fecal samples were collected, and total bacterial deoxyribonucleic acid (DNA) was extracted. We performed 16S ribosomal ribonucleic acid (16S rRNA) high-throughput sequencing (HTS) and bioinformatics to study the relationships among between gut microbiota structure, genetics, and dietary habits in Yugur and Han Chinese subjects.ResultsWe found 350 differential operational taxonomic units (OTUs) in Han Chinese and Yugur gut microbiota, proving that gut microbiota differed between the two populations. That were less abundant among Yugurs than Han Chinese were Prevotella_9 and Alloprevotella. That were more abundant among Yugurs than Han Chinese were Anaerostipes and Christensenellaceae_R-7_group. And they were significantly associated with a high-calorie diet In addition. we found differences in predicted gut microbiota structural functions (The main functions were metabolic and genetic information) between the two populations.ConclusionYugur subjects demonstrated differences in gut microbiotal structure from Han Chinese subjects, and this difference influenced by dietary and may be influenced by genetic influences. This finding will provide a fundamental basis for further study of the relationships among gut microbiota, dietary factors, and disease in Sunan County

Large-scale genome-wide association studies and meta-analyses of longitudinal change in adult lung function.

BACKGROUND: Genome-wide association studies (GWAS) have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function. METHODS: We performed GWAS of the rate of change in forced expiratory volume in the first second (FEV1) in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci. As a secondary aim, we estimated the mean rate of decline in FEV1 by smoking pattern, irrespective of genotypes, across these 14 studies using meta-analysis. RESULTS: The overall meta-analysis produced suggestive evidence for association at the novel IL16/STARD5/TMC3 locus on chromosome 15 (P  =  5.71 × 10(-7)). In addition, meta-analysis using the five cohorts with ≥3 FEV1 measurements per participant identified the novel ME3 locus on chromosome 11 (P  =  2.18 × 10(-8)) at genome-wide significance. Neither locus was associated with FEV1 decline in two additional cohort studies. We confirmed gene expression of IL16, STARD5, and ME3 in multiple lung tissues. Publicly available microarray data confirmed differential expression of all three genes in lung samples from COPD patients compared with controls. Irrespective of genotypes, the combined estimate for FEV1 decline was 26.9, 29.2 and 35.7 mL/year in never, former, and persistent smokers, respectively. CONCLUSIONS: In this large-scale GWAS, we identified two novel genetic loci in association with the rate of change in FEV1 that harbor candidate genes with biologically plausible functional links to lung function

The role of collaboration in the UK green supply chains: an exploratory study of the perspectives of suppliers, logistics and retailers

Many companies around the world have started to realise that working alone will not be sufficient in their move towards a greener supply chain (SC). More specifically, recent UK government regulations on implementing strict CO2 reduction encourage SC operators to work collaboratively, in production and logistics or other operations, to achieve their green objectives. In this research, we look at some underlying factors of SC collaboration, focussing on suppliers, logistics and retailers, for the purpose of improving the environmental sustainability of companies’ SCs. To facilitate our study, we conduct case studies in two overseas supplier companies with the aim of providing a better understanding of how green issues imposed by European and UK customers influence the companies’ actions to meet agreed environmental goals. Based on the initial analysis of the case studies, we develop a conceptual framework which indicates that SC collaboration plays an important role in ensuring companies achieve environmental sustainability of their SCs. Subsequently, staff in middle-management and related roles in sixteen companies operating in the UK are interviewed. This allows us to understand their business practices in terms of SC collaboration with their suppliers and buyers to achieve the goal of CO2 reduction. Finally, drawing upon the information from company reports and websites, a number of UK leading retailers’ actions to reduce CO2 emissions are investigated. We develop a conceptual framework of SC collaboration for environmental sustainability to help companies improve their level of collaboration between suppliers and buyers in terms of meeting their environmental objectives. The proposed framework will serve as a base model for the companies using or considering SC collaboration to achieve their environmental agendas, in line with governmental green regulatory requirements

Safety and Immunogenicity of a Malaria Vaccine, Plasmodium falciparum AMA-1/MSP-1 Chimeric Protein Formulated in Montanide ISA 720 in Healthy Adults

The P. falciparum chimeric protein 2.9 (PfCP-2.9) consisting of the sequences of MSP1-19 and AMA-1 (III) is a malaria vaccine candidate that was found to induce inhibitory antibodies in rabbits and monkeys. This was a phase I randomized, single-blind, placebo-controlled, dose-escalation study to evaluate the safety and immunogenicity of the PfCP-2.9 formulated with a novel adjuvant Montanide ISA720. Fifty-two subjects were randomly assigned to 4 dose groups of 10 participants, each receiving the test vaccine of 20, 50, 100, or 200 µg respectively, and 1 placebo group of 12 participants receiving the adjuvant only.The vaccine formulation was shown to be safe and well-tolerated, and none of the participants withdrew. The total incidence of local adverse events (AEs) was 75%, distributed among 58% of the placebo group and 80% of those vaccinated. Among the vaccinated, 65% had events that were mild and 15% experienced moderate AEs. Almost all systemic adverse reactions observed in this study were graded as mild and required no therapy. The participants receiving the test vaccine developed detectable antibody responses which were boosted by the repeated vaccinations. Sixty percent of the vaccinated participants had high ELISA titers (>1∶10,000) of antigen-specific antibodies which could also recognize native parasite proteins in an immunofluorescence assay (IFA).This study is the first clinical trial for this candidate and builds on previous investigations supporting PfCP-2.9/ISA720 as a promising blood-stage malaria vaccine. Results demonstrate safety, tolerability (particularly at the lower doses tested) and immunogenicity of the formulation. Further clinical development is ongoing to explore optimizing the dose and schedule of the formulation to decrease reactogenicity without compromising immunogenicity.

Multi-ancestry genome-wide association study accounting for gene-psychosocial factor interactions identifies novel loci for blood pressure traits

Psychological and social factors are known to influence blood pressure (BP) and risk of hypertension and associated cardiovascular diseases. To identify novel BP loci, we carried out genome-wide association meta-analyses of systolic, diastolic, pulse, and mean arterial BP, taking into account the interaction effects of genetic variants with three psychosocial factors: depressive symptoms, anxiety symptoms, and social support. Analyses were performed using a two-stage design in a sample of up to 128,894 adults from five ancestry groups. In the combined meta-analyses of stages 1 and 2, we identified 59 loci (p value < 5e−8), including nine novel BP loci. The novel associations were observed mostly with pulse pressure, with fewer observed with mean arterial pressure. Five novel loci were identified in African ancestry, and all but one showed patterns of interaction with at least one psychosocial factor. Functional annotation of the novel loci supports a major role for genes implicated in the immune response (PLCL2), synaptic function and neurotransmission (LIN7A and PFIA2), as well as genes previously implicated in neuropsychiatric or stress-related disorders (FSTL5 and CHODL). These findings underscore the importance of considering psychological and social factors in gene discovery for BP, especially in non-European populations