China’s Regional Innovation Environment Evaluation

On the base of monitoring China’s regional environmental quality and analyzing soft power of innovation environment, the authors make a comprehensive evaluation on China’s 31 provinces’ regional innovation environment in four levels: basic environment, organizational environment, cultural environment and information environment. The study shows that the innovation environment in East Coast is the best; the Central and Northeastern regions are moderate; while the innovation environment of the West is worse than the other three regions. Also, the policy recommendations to enhance innovation environment quality of the West have been proposed

Terror Management: The Effects of Mortality Salience on Desire for Money Among Singaporeans

Terror management theory has been used to explain our penchant for materialism. While materialism includes both the desire for products and the desire for money, research has generally examined the former. Consequently, this article aimed to examine the effects of mortality salience on desire for money in Singapore. Study 1 found that mortality salience did not increase self-reported desire for money but increased the size of a drawn coin. Study 2 found that mortality salience did not increase the preferred selling price of a used laptop. Finally, Study 3 found that mortality salience did not increase the willingness to listen to unpleasant sounds in exchange for money. Furthermore, attitudes toward money did not moderate the effects of mortality salience on desire for money. The nonsignificant results could be due to data collection during the coronavirus disease 2019 (COVID-19) pandemic and the use of a Singaporean sample. Future research directions include examining the effects of the pandemic on terror management theory research and examining both the desire for products and the desire for money concurrently as dependent variables

Tribological behaviors of vacuum hot-pressed ceramic composites with enhanced cyclic oxidation and corrosion resistance

Wear failure is a bottleneck restricting applications and developments of Ti3SiC2 ceramic. Particles reinforced composites provide an effective strategy to resist wear. In this work, Ti(C,N) particles are used as reinforcements, and Ti3SiC2/Ti(C,N) composite is fabricated by vacuum hot-pressing. Scanning electron microscopy (SEM), energy dispersive spectrometer (EDS) and X-ray diffract meter (XRD) are used to investigate composite morphologies, compositions and phases before and after hot-pressing. Meanwhile, high-temperature cyclic oxidations and tribological behaviors of composites under various loads, speeds and Ti(C,N) contents are characterized. Results show that as-prepared composite is relatively dense, and Ti(C,N) addition plays an important role in particle reinforcement of Ti3SiC2. Meanwhile, its hardness, wear resistance, cyclic oxidation resistance and corrosion resistance are significantly improved. In addition, wear characteristics and mechanisms of composites under different loads and speeds are analyzed in details. This work shows great potentials in developing engineering applications of ceramics, especially in high-temperature, oxidizing, frictional and corrosive environment

The circulating proteome and brain health:Mendelian randomisation and cross-sectional analyses

Decline in cognitive function is the most feared aspect of ageing. Poorer midlife cognitive function is associated with increased dementia and stroke risk. The mechanisms underlying variation in cognitive function are uncertain. Here, we assessed associations between 1160 proteins' plasma levels and two measures of cognitive function, the digit symbol substitution test (DSST) and the Montreal Cognitive Assessment in 1198 PURE-MIND participants. We identified five DSST performance-associated proteins (NCAN, BCAN, CA14, MOG, CDCP1), with NCAN and CDCP1 showing replicated association in an independent cohort, GS (N = 1053). MRI-assessed structural brain phenotypes partially mediated (8-19%) associations between NCAN, BCAN, and MOG, and DSST performance. Mendelian randomisation analyses suggested higher CA14 levels might cause larger hippocampal volume and increased stroke risk, whilst higher CDCP1 levels might increase intracranial aneurysm risk. Our findings highlight candidates for further study and the potential for drug repurposing to reduce the risk of stroke and cognitive decline.</p

Epigenetic scores for the circulating proteome as tools for disease prediction

Protein biomarkers have been identified across many age-related morbidities. However, characterising epigenetic influences could further inform disease predictions. Here, we leverage epigenome-wide data to study links between the DNA methylation (DNAm) signatures of the circulating proteome and incident diseases. Using data from four cohorts, we trained and tested epigenetic scores (EpiScores) for 953 plasma proteins, identifying 109 scores that explained between 1% and 58% of the variance in protein levels after adjusting for known protein quantitative trait loci (pQTL) genetic effects. By projecting these EpiScores into an independent sample (Generation Scotland; n = 9537) and relating them to incident morbidities over a follow-up of 14 years, we uncovered 137 EpiScore-disease associations. These associations were largely independent of immune cell proportions, common lifestyle and health factors, and biological aging. Notably, we found that our diabetes-associated EpiScores highlighted previous top biomarker associations from proteome-wide assessments of diabetes. These EpiScores for protein levels can therefore be a valuable resource for disease prediction and risk stratification

Integrated methylome and phenome study of the circulating proteome reveals markers pertinent to brain health

Characterising associations between the methylome, proteome and phenome may provide insight into biological pathways governing brain health. Here, we report an integrated DNA methylation and phenotypic study of the circulating proteome in relation to brain health. Methylome-wide association studies of 4058 plasma proteins are performed (N = 774), identifying 2928 CpG-protein associations after adjustment for multiple testing. These are independent of known genetic protein quantitative trait loci (pQTLs) and common lifestyle effects. Phenome-wide association studies of each protein are then performed in relation to 15 neurological traits (N = 1,065), identifying 405 associations between the levels of 191 proteins and cognitive scores, brain imaging measures or APOE e4 status. We uncover 35 previously unreported DNA methylation signatures for 17 protein markers of brain health. The epigenetic and proteomic markers we identify are pertinent to understanding and stratifying brain health

Hsa-miR-196a2 Rs11614913 Polymorphism Contributes to Cancer Susceptibility: Evidence from 15 Case-Control Studies

BACKGROUND: MicroRNAs (miRNAs) are a family of endogenous, small and noncoding RNAs that negatively regulate gene expression by suppressing translation or degrading mRNAs. Recently, many studies investigated the association between hsa-miR-196a2 rs11614913 polymorphism and cancer risk, which showed inconclusive results. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a meta-analysis of 15 studies that included 9,341 cancer cases and 10,569 case-free controls. We assessed the strength of the association, using odds ratios (ORs) with 95% confidence intervals (CIs). Overall, individuals with the TC/CC genotypes were associated with higher cancer risk than those with the TT genotype (OR=1.18, 95% CI=1.03-1.34, P<0.001 for heterogeneity test). In the stratified analyses, we observed that the CC genotype might modulate breast cancer risk (OR=1.11, 95%CI=1.01-1.23, Pheterogeneity=0.210) and lung cancer risk (OR=1.25, 95%CI=1.06-1.46, Pheterogeneity=0.958), comparing with the TC/TT genotype. Moreover, a significantly increased risk was found among Asian populations in a dominant model (TC/CC versus TT, OR=1.24, 95% CI=1.07-1.43, Pheterogeneity=0.006). CONCLUSIONS: These findings supported that hsa-miR-196a2 rs11614913 polymorphism may contribute to the susceptibility of cancers

Extensive Crosstalk between O-GlcNAcylation and Phosphorylation Regulates Akt Signaling

O-linked N-acetylglucosamine glycosylations (O-GlcNAc) and O-linked phosphorylations (O-phosphate), as two important types of post-translational modifications, often occur on the same protein and bear a reciprocal relationship. In addition to the well documented phosphorylations that control Akt activity, Akt also undergoes O-GlcNAcylation, but the interplay between these two modifications and the biological significance remain unclear, largely due to the technique challenges. Here, we applied a two-step analytic approach composed of the O-GlcNAc immunoenrichment and subsequent O-phosphate immunodetection. Such an easy method enabled us to visualize endogenous glycosylated and phosphorylated Akt subpopulations in parallel and observed the inhibitory effect of Akt O-GlcNAcylations on its phosphorylation. Further studies utilizing mass spectrometry and mutagenesis approaches showed that O-GlcNAcylations at Thr 305 and Thr 312 inhibited Akt phosphorylation at Thr 308 via disrupting the interaction between Akt and PDK1. The impaired Akt activation in turn resulted in the compromised biological functions of Akt, as evidenced by suppressed cell proliferation and migration capabilities. Together, this study revealed an extensive crosstalk between O-GlcNAcylations and phosphorylations of Akt and demonstrated O-GlcNAcylation as a new regulatory modification for Akt signaling

Behavioral Carry-Over Effects and Power Considerations in Crossover Trials

Thesis (Master's)--University of Washington, 2023The carry-over effect remains an outstanding concern in crossover trials when washout periods cannot sufficiently diminish their impacts. This can occur in comparative effectiveness research where carry-over effects are behavioral rather than biological. We first investigate crossover trials with and without carry-over effects under the potential outcome framework. We find that when carry-over effects exist and satisfy some sign condition, the classic estimator underestimates the treatment effect, which does not inflate the type I error of one-sided tests but decreases the power and leads to a power trade-off between crossover and parallel trials. We derive the condition under which crossover trials do not have type I error inflation and are more powerful than parallel trials. We further develop covariate adjustment methods for crossover trials and illustrate their performance using data from a real analgesic study and a hypothetical HIV prevention trial. We also compare the total investigation times and the total trial times of crossover and parallel trials