Genetic correlation and causal associations between circulating C-reactive protein levels and lung cancer risk.

PURPOSE: We aimed to characterize genetic correlations and causal associations between circulating C-reactive protein (CRP) levels and the risk of lung cancer (LC). METHODS: Leveraging summary statistics from genome-wide association studies of circulating CRP levels among 575,531 individuals of European ancestry, and LC risk among 29,266 cases and 56,450 controls, we investigated genetic associations of circulating CRP levels with the risk of overall lung cancer and its histological subtypes, by using linkage disequilibrium score (LDSC) regression and Mendelian randomization (MR) analyses. RESULTS: Significant positive genetic correlations between circulating CRP levels and the risk of LC and its histological subtypes were identified from LDSC regression, with correlation coefficients ranging from 0.12 to 0.26, and all false discovery adjusted p < 0.05. Univariable MR demonstrated a nominal association between CRP levels and an increased risk of lung squamous cell carcinoma (SCC) (inverse variance-weighted OR = 1.15, 95% CI 1.01-1.30). However, this association disappeared when multivariable MR included cigarettes per day and/or body mass index. By using our recently developed constrained maximum likelihood-based MR method, we identified significant associations of CRP levels with the risk of overall LC (OR 1.06, 95% CI 1.03-1.09), SCC (OR 1.06, 95% CI 1.02-1.09), and small cell lung cancer (SCLC, OR 1.09, 95% CI 1.03-1.15). Moreover, most univariable and multivariable MR analyses also revealed consistent CRP-SCLC associations. CONCLUSION: There may be a genetic and causal association between circulating CRP levels and the risk of SCLC, which is in line with previous population-based observational studies.

Blidingia sp. extracts improve intestinal health and reduce diarrhoea in weanling piglets.

Blidingia sp. is a prominent fouling green macroalga and we previously found that extracts from Blidingia sp. alleviated intestinal inflammation in mice challenged with lipopolysaccharides. However, whether these extracts are effective in weanling piglets remains unknown. In the present study, Blidingia sp. extracts were supplemented in the diet and their effects on growth performance, incidence of diarrhoea and intestinal function in weanling piglets were explored. The results showed that diets supplemented with 0.1% or 0.5% Blidingia sp. extract significantly increased average daily body weight gain and feed intake in weanling piglets. Meanwhile, piglets supplemented with 0.5% Blidingia sp. extract showed decreased incidence of diarrhoea as well as reduced fecal water and Na+ content. Furthermore, the diet supplemented with 0.5% Blidingia sp. extracts improved intestinal morphology, as indicated by the results of hematoxylin and eosin staining. Diet supplemented with 0.5% Blidingia sp. extracts also improved tight junction function, as indicated by increased expression of Occludin, Claudin-1 and Zonula occludens-1, and alleviated the inflammatory response, as indicated by decreased tumor necrosis factor-α and interleukin-6 (IL6) contents and increased IL10 levels. Taken together, our results showed that Blidingia sp. extracts had beneficial effects in weanling piglets and we suggest that Blidingia sp. extracts could be potentially used as an additive for piglets.

Observation of π/2 Modes in an Acoustic Floquet System.

Topological phases of matter have remained an active area of research in the last few decades. Periodic driving is a powerful tool for enriching such exotic phases, leading to various phenomena with no static analogs. One such phenomenon is the emergence of the elusive π/2 modes, i.e., a type of topological boundary state pinned at a quarter of the driving frequency. The latter may lead to the formation of Floquet parafermions in the presence of interaction, which is known to support more computational power than Majorana particles. In this Letter, we experimentally verify the signature of π/2 modes in an acoustic waveguide array, which is designed to simulate a square-root periodically driven Su-Schrieffer-Heeger model. This is accomplished by confirming the 4T-periodicity (T being the driving period) profile of an initial-boundary excitation, which we also show theoretically to be the smoking gun evidence of π/2 modes. Our findings are expected to motivate further studies of π/2 modes in quantum systems for potential technological applications.

Impact of fetal expression quantitative trait loci on transcriptome-wide association study of childhood leukemia.

Transcriptome-wide association studies increase the yield of loci associated with disease phenotypes by focusing on expression quantitative trait loci (eQTL). The major source of eQTL data for is the Gene and Tissue Expression (GTEx) project, which is comprised entirely of adults, mainly those >50 years of age at death. Since gene expression levels differ by developmental stage, it is not clear whether eQTLs derived from adult data sources are best suited for use in young-onset diseases such as pediatric cancers. To fill in this knowledge gap, we performed a large-scale eQTL mapping analysis in the GenCord study with newborn samples and compared it with GTEx. Under matched conditions, we found around 80% of the eQTLs in one study can be replicated in the other. However, among all eQTLs identified in GenCord (GTEx), 584 (1045) showed statistically significant differences in effect sizes in GTEx (GenCord). We further investigated how using fetal eQTL data can facilitate the genetic association study of acute lymphoblastic leukemia. GenCord and GTEx identified the same genetic loci with statistical significance; however, the overall association pattern was only weakly correlated. Our paper demonstrates age-differential eQTLs and shows their potential influence on childhood leukemia research.

Total Syntheses and Biological Evaluation of Both Enantiomers of Several Hydroxylated Dimeric Nuphar Alkaloids.

Herein, we describe the first total syntheses of five members of the dimeric nuphar alkaloids: (+)-6,6'-dihydroxythiobinupharidine (+)-1 a, (+)-6-hydroxythiobinupharidine (+)-1 b, (-)-6,6'-dihydroxythionuphlutine (-)-2 a, (-)-6,6'-dihydroxyneothiobinupharidine (-)-3 a, and (+)-6,6'-dihydroxyneothionuphlutine (+)-4 a. The latter two have not been found in nature. We have also made each of their enantiomers (-)-1 a-b, (+)-2 a, (+)-3 a, and (-)-4 a. The key step in these syntheses was the dimerization of an α-aminonitrile (a hydrolytically stable surrogate for its corresponding hemiaminal) with chiral Lewis acid complexes. We have also reassigned the literature structures of (+)-1 a-1 b­for those instances in which the NMR spectra were obtained in CD3OD­to their corresponding CD3O-adducts. Our efforts provide for the first time apoptosis data for (-)-3 a, (+)-4 a, and all five non-natural enantiomers prepared. The data indicate high apoptotic activity regardless of the enantiomer or relative stereochemical configuration at C7 and C7'.