Cycling comfort on asphalt pavement: Influence of the pavement-tyre interface on vibration

Attainment of cycling comfort on urban roads encourages travelers to use bicycles more often, which has social and environment benefits such as to reduce congestion, air pollution and carbon emissions. Cycling vibration is responsible for the cyclists’ perception of (dis)comfort. How asphalt pavement's surface characteristics relate to cycling comfort, however, remains undiscovered. In this study, the cycling vibration intensity on 46 sections of 24 urban roads was tested using a dynamic cycling comfort measure system while the cyclists’ perception of vibration was identified via questionnaires; the cycling comfort was then defined based on the cycling vibration. To record the accurate pavement-tyre interface under a stable environment, a total of 19 pavement sections were scanned using a 3D digital camera. These 3D models were then 3D printed, which are used to conduct the pressure film test using a self-developed pavement-tyre interface test system. Three ranges of pressure films were adopted to characterize the pavement-tyre interface via 9 parameters, namely contact area (A c ), unit bearing area (B u ), stress intensity (S i ), stress uniformity (S u ), kurtosis (S ku ), spacing (Sp a ), maximum peak spacing (Sp max ), radius ratio (R r ) and fractal dimension (F d ), in consideration of the area characteristics, pressure amplitude, peak spacing and shape of the interface. Finally, the significant interface parameters were identified, and the regression model between interface parameters and cycling comfort was established. Results show that the cycling vibration was described to be ‘very comfortable’ when the human exposure to vibration level (a wv ) was less than 1.78 m/s 2 ; ‘comfortable’ when the a wv was between 1.78 m/s 2 and 2.20 m/s 2 ; and ‘uncomfortable’ when the a wv was greater than 2.20 m/s 2 . The average stress on rear wheel-pavement interface is higher than that of the front wheel. B u-0.6 , Sp a-0.6 , and F d-0.6 are significant to cycling vibration. The 2LW pressure film is recommended for use to measure the bicycle pavement-tyre interface. The recommended interface characteristics are less than 7 mm 2 of the unit bearing area, 6 mm of average spacing and 2.38 of fractal dimension. Finally, dense asphalt mixture performs better in providing cycling comfort than the gap-graded asphalt mixture. Results of this study contribute to current knowledge on bike lane comfort and pavement design, the findings should be interested in cyclists, transport planners, and road authorities

The role of autophagy in the treatment of type II diabetes and its complications: a review

Type II diabetes mellitus (T2DM) is a chronic metabolic disease characterized by prolonged hyperglycemia and insulin resistance (IR). Its incidence is increasing annually, posing a significant threat to human life and health. Consequently, there is an urgent requirement to discover effective drugs and investigate the pathogenesis of T2DM. Autophagy plays a crucial role in maintaining normal islet structure. However, in a state of high glucose, autophagy is inhibited, resulting in impaired islet function, insulin resistance, and complications. Studies have shown that modulating autophagy through activation or inhibition can have a positive impact on the treatment of T2DM and its complications. However, it is important to note that the specific regulatory mechanisms vary depending on the target organ. This review explores the role of autophagy in the pathogenesis of T2DM, taking into account both genetic and external factors. It also provides a summary of reported chemical drugs and traditional Chinese medicine that target the autophagic pathway for the treatment of T2DM and its complications

A Refined Study of FCRL Genes from a Genome-Wide Association Study for Graves’ Disease

To pinpoint the exact location of the etiological variant/s present at 1q21.1 harboring FCRL1-5 and CD5L genes, we carried out a refined association study in the entire FCRL region in 1,536 patients with Graves’ disease (GD) and 1,516 sex-matched controls by imputation analysis, logistic regression, and cis-eQTL analysis. Among 516 SNPs with P<0.05 in the initial GWAS scan, the strongest signals associated with GD and correlated to FCRL3 expression were located at a cluster of SNPs including rs7528684 and rs3761959. And the allele-specific effects for rs3761959 and rs7528684 on FCRL3 expression level revealed that the risk alleles A of rs3761959 and C of rs7528684 were correlated with the elevated expression level of FCRL3 whether in PBMCs or its subsets, especially in $CD19^+$ B cells and $CD8^+$ T subsets. Next, the combined analysis with 5,300 GD cases and 4,916 control individuals confirmed FCRL3 was a susceptibility gene of GD in Chinese Han populations, and rs3761959 and rs7528684 met the genome-wide association significance level ($P_{combined}$ = 2.27×$10^{−12}$ and 7.11×$10^{−13}$, respectively). Moreover, the haplotypes with the risk allele A of rs3761959 and risk allele C of rs7528684 were associated with GD risk. Finally, our epigenetic analysis suggested the disease-associated C allele of rs7528684 increased affinity for NF-KB transcription factor. Above data indicated that FCRL3 gene and its proxy SNP rs7528684 may be involved in the pathogenesis of GD by excessive inhibiting B cell receptor signaling and the impairment of suppressing function of Tregs

Molecular Cloning of the Genes Encoding the PR55/Bβ/δ Regulatory Subunits for PP-2A and Analysis of Their Functions in Regulating Development of Goldfish, Carassius auratus

The protein phosphatase-2A (PP-2A), one of the major phosphatases in eukaryotes, is a heterotrimer, consisting of a scaffold A subunit, a catalytic C subunit and a regulatory B subunit. Previous studies have shown that besides regulating specific PP-2A activity, various B subunits encoded by more than 16 different genes, may have other functions. To explore the possible roles of the regulatory subunits of PP-2A in vertebrate development, we have cloned the PR55/B family regulatory subunits: β and δ, analyzed their tissue specific and developmental expression patterns in Goldfish ( Carassius auratus). Our results revealed that the full-length cDNA for PR55/Bβ consists of 1940 bp with an open reading frame of 1332 nucleotides coding for a deduced protein of 443 amino acids. The full length PR55/Bδ cDNA is 2163 bp containing an open reading frame of 1347 nucleotides encoding a deduced protein of 448 amino acids. The two isoforms of PR55/B display high levels of sequence identity with their counterparts in other species. The PR55/Bβ mRNA and protein are detected in brain and heart. In contrast, the PR55/Bδ is expressed in all 9 tissues examined at both mRNA and protein levels. During development of goldfish, the mRNAs for PR55/Bβ and PR55/Bδ show distinct patterns. At the protein level, PR55/Bδ is expressed at all developmental stages examined, suggesting its important role in regulating goldfish development. Expression of the PR55/Bδ anti-sense RNA leads to significant downregulation of PR55/Bδ proteins and caused severe abnormality in goldfish trunk and eye development. Together, our results suggested that PR55/Bδ plays an important role in governing normal trunk and eye formation during goldfish development

Plasma equol concentration is not associated with breast cancer and fibrocystic breast conditions among women in Shanghai, China

Equol (a bacterial metabolite of the soy isoflavone daidzein) is produced by 30% to 50% of humans and may be associated with health outcomes. We hypothesized that plasma equol would be inversely associated with risks of fibrocystic breast conditions (FBC) and breast cancer (BC). Plasma from women in a breast self-examination trial in Shanghai with BC (n = 269) or FBC (n = 443), and age-matched controls (n = 1027) was analyzed for isoflavones. Equol was grouped into categories (= 45 nmol/L) and, among women with daidzein >= 20 nmol/L, the log(10) equol:daidzein ratio was grouped into tertiles. Where available, non-cancerous tissue (NCT) adjacent to the carcinomas from women with BC were classified as non-proliferative or proliferative (n = 130 and 172, respectively). The lesions from women with FBC were similarly classified (n = 99 and 92, respectively). Odds ratios (OR) and 95% confidence intervals (CI) were calculated across equol categories and tertiles of log(10) equol:daidzein ratio. Equol categories were not associated with FBC or BC >.05). For log(10) equol:daidzein, compared to controls there were positive associations in the mid tertile for proliferative FBC (OR 2.06, 95% CI 1.08-3.93), BC with proliferative NCT (OR 2.95, 95% CI 1.37-6.35), and all BC regardless of histology (OR 2.37, 95% CI 1.43-3.95). However, trends in ORs with increasing plasma equol values or equol:daidzein ratios were not observed (P >.05). The results of this study do not provide evidence that equol plays a role in the etiology of these breast conditions. However, further work is needed to confirm or refute this conclusion. (C) 2016 Elsevier Inc. All rights reserved.Peer reviewe

A phase 4 multicentre, 2×2 factorial randomised, double-blind, placebo-controlled trial to investigate the efficacy and safety of tobramycin inhalation solution for Pseudomonas aeruginosa eradication in bronchiectasis:Erase

Chronic Pseudomonas aeruginosa (PA) infection significantly contributes to morbidity and mortality in bronchiectasis patients. Initiating antibiotics early may lead to the eradication of PA. Here we outline the design of a trial (ERASE; NCT06093191) assessing the efficacy and safety of inhaled tobramycin, alone or with oral ciprofloxacin, in bronchiectasis patients with a new isolation of PA. This multicentre, 2×2 factorial randomised, double-blind, placebo-controlled, parallel-group trial includes a 2-week screening period, a 12-week treatment phase (with a combination of ciprofloxacin or a placebo at initial 2 weeks) and a 24-week follow-up. 364 adults with bronchiectasis and a new PA isolation will be randomly assigned to one of four groups: placebo (inhaled saline and ciprofloxacin placebo twice daily), ciprofloxacin alone (750 mg ciprofloxacin and inhaled saline twice daily), inhaled tobramycin alone (inhaled 300 mg tobramycin and ciprofloxacin placebo twice daily) or a combination of both drugs (inhaled 300 mg tobramycin and 750 mg ciprofloxacin twice daily). The primary objective of this study is to assess the proportion of patients successfully eradicating PA in each group by the end of the study. Efficacy will be evaluated based on the eradication rate of PA at other time points (12, 24 and 36 weeks), the occurrence of exacerbations and hospitalisations, time to first pulmonary exacerbations, patient-reported outcomes, symptom measures, pulmonary function tests and the cost of hospitalisations. To date no randomised trial has evaluated the benefit of different PA eradication strategies in bronchiectasis patients. The ERASE trial will therefore generate crucial data to inform future clinical guidelines.</p