Yu He

Large-scale proteomics studies can refine our understanding of health and disease and enable precision medicine. Here, we provide a detailed atlas of 2,920 plasma proteins linking to diseases (406 prevalent and 660 incident) and 986 health-related traits in 53,026 individuals (median follow-up: 14.8 years) from the UK Biobank, representing the most comprehensive proteome profiles to date. This atlas revealed 168,100 protein-disease associations and 554,488 protein-trait associations. Over 650 proteins were shared among at least 50 diseases, and over 1,000 showed sex and age heterogeneity. Furthermore, proteins demonstrated promising potential in disease discrimination (area under the curve [AUC] > 0.80 in 183 diseases). Finally, integrating protein quantitative trait locus data determined 474 causal proteins, providing 37 drug-repurposing opportunities and 26 promising targets with favorable safety profiles. These results provide an open-access comprehensive proteome-phenome resource (https://proteome-phenome-atlas.com/) to help elucidate the biological mechanisms of diseases and accelerate the development of disease biomarkers, prediction models, and therapeutic targets.

This paper introduces, constructs and studies a new class of arrays, called strong orthogonal arrays, as suitable designs for computer experiments. A strong orthogonal array of strength <it>t</it> enjoys better space-filling properties than a comparable orthogonal array in all dimensions lower than <it>t</it> while retaining the space-filling properties of the latter in <it>t</it> dimensions. Latin hypercubes based on strong orthogonal arrays of strength <it>t</it> are more space-filling than comparable orthogonal array-based Latin hypercubes in all <it>g</it> dimensions for any 2 ≤ <it>g</it> ≤ <it>t</it> − 1.

Bmx/Etk non-receptor tyrosine protein kinase has been implicated in endothelial cell migration and tube formation in vitro. However, the role of Bmx in vivo is not known. Bmx is highly induced in the vasculature of ischemic hind limbs. We used both mice with a genetic deletion of Bmx (Bmx-KO mice) and transgenic mice expressing a constitutively active form of Bmx under the endothelial Tie-2 enhancer/promoter (Bmx-SK-Tg mice) to study the role of Bmx in ischemia-mediated arteriogenesis/angiogenesis. In response to ischemia, Bmx-KO mice had markedly reduced, whereas Bmx-SK-Tg mice had enhanced, clinical recovery, limb perfusion, and ischemic reserve capacity when compared with nontransgenic control mice. The functional outcomes in these mice were correlated with ischemia-initiated arteriogenesis, capillary formation, and vessel maturation as well as Bmx-dependent expression/activation of TNF receptor 2- and VEGFR2-mediated (TNFR2/VEGFR2-mediated) angiogenic signaling in both hind limb and bone marrow. More importantly, results of bone marrow transplantation studies showed that Bmx in bone marrow-derived cells plays a critical role in the early phase of ischemic tissue remodeling. Our study provides the first demonstration to our knowledge that Bmx in endothelium and bone marrow plays a critical role in arteriogenesis/angiogenesis in vivo and suggests that Bmx may be a novel target for the treatment of vascular diseases such as coronary artery disease and peripheral arterial disease.

The aim of the current study is to assess the association between the alleles of endothelial nitric oxide synthases (eNOS) gene 4b/a, G894T, T786C polymorphisms and diabetic nephropathy (DN) through meta-analyses. We also performed a subgroup analysis based on ethnicity (Caucasians, East-Asian and other populations). A total of 3793 patients (DN) and 3161 controls (diabetes without nephropathy) for 4b/a, 2654 patients and 1993 controls for G894T and 1348 patients and 1175 controls for T786C were included in our analysis. Overall, allele contrast (4a versus 4b) of 4b/a polymorphism produced significant results in the global population [random effects model (RE) odds ratio (OR) = 1.33; 95% confidence interval (CI) = 1.10-1.61, P = 0.003] and East-Asian population (RE OR = 1.68; 95% CI = 1.23-2.30, P = 0.001), but not in the Caucasian population. In allele contrast of G894T, an obvious significant result was observed in the East-Asian population [fixed effects model OR = 1.69; 95% CI = 1.37-2.08, P < 0.0001], but not in the Caucasian population. Sensitivity analyses generated similar results to those of the primary analyses. The evidence accumulated suggested that 4b/a and G894T polymorphisms in the eNOS gene were associated with susceptibility to DN in Asian populations, but not in Caucasian populations.

Our study aimed to analyze genotype-specific, age-specific prevalence, and year-on-year trend of cervical human papillomavirus (HPV) detection among women in Guangdong, China 2008 to 2017. A total of 199 963 women attending the gynecological department and 11 999 women attending the medical examination center at Guangdong Women and Children Hospital were included. Prevalent HPV detection significantly differed between these two groups of women (20.16% vs 17.25%; P < .001). HPV genotypes of these two populations have a large overlap, with HPV52, 16, 58, CP8304, and 53 being the dominant subtypes among gynecological outpatients and HPV52, CP8304, 58, 53, and 16 among women receiving physical examinations. The distribution of prevalent HPV detection showed a bimodal pattern across age groups among these two populations. However, prevalent HPV detection among these two populations exhibited different trends from 2008 to 2017. Our study demonstrated that prevalent HPV detection among women in Guangdong is associated with age and different from that among women from other regions of China. Our study may provide valuable data to inform cervical cancer screening and HPV vaccination programs for women in this province.