Association between monocyte lymphocyte ratio and abdominal aortic calcification in US adults: A cross-sectional study

Background This study aimed to evaluate the association between Monocyte Lymphocyte Ratio (MLR) and Abdominal Aortic Calcification (AAC) in adults over 40 years of age in the United States. Methods Data were collected from the 2013–2014 National Health and Nutrition Examination Survey (NHANES). AAC was quantified by the Kauppila score system based on dual-energy X-Ray absorptiometry. Severe AAC was defined as a total AAC score > 6. The lymphocyte count and monocyte count can be directly obtained from laboratory data files. Multivariable logistic regression models were used to determine the association between MLR and the AAC score and severe AAC. Results A total of 3,045 participants were included in the present study. After adjusting for multiple covariates, MLR was positively associated with higher AAC score (β = 0.21, 95% CI 0.07, 0.34, p = 0.0032) and the odds of severe AAC increased by 14% per 0.1 unit increase in the MLR (OR = 1.14, 95% CI 1.00, 1.31, p = 0.0541). The Odds Ratio (OR) (95% CI) of severe AAC for participants in MLR tertile 3 was 1.88 (1.02, 3.47) compared with those in tertile 1 (p for trend = 0.0341). Subgroup analyses showed that a stronger association was detected in the elderly compared with non-elderly (p for interaction = 0.0346) and diabetes compared with non-diabetes (borderline significant p for interaction = 0.0578). Conclusion In adults in the United States, MLR was associated with higher AAC scores and a higher probability of severe AAC. MLR may become a promising tool to predict the risk of AAC

Patterns of major depression and nonmedical use of prescription opioids in the United States

Introduction: Recent epidemiologic studies have shown that nonmedical use of prescription opioids (NMUPO) and major depression frequently co-occur. Comorbid forms of drug use and mental illness such as NMUPO and depression pose a greater disease burden than either condition alone. However, sociodemographic and substance use differences between individuals with either NMUPO or depression and those with comorbid conditions have not yet been fully investigated. Methods: Data came from the 2011 and 2012 National Survey on Drug Use and Health (NSDUH). Adolescents and adults were examined independently because of differences in screening for major depressive episodes (MDE). Weighted multinomial logistic regression investigated differences between persons with either past-year NMUPO (4.0%) or MDE (5.5%) and those with comorbid NMUPO and MDE (0.6%), compared to persons with neither condition. Results: Females were more likely than males to report either MDE-alone and comorbid NMUPO and MDE, whereas adult men were marginally more likely to report NMUPO-alone (not significant among adolescents). Polydrug use and alcohol use disorders were more pronounced among those with comorbid NMUPO and MDE than persons with either NMUPO-alone or MDE-alone. Persons with independent and comorbid NMUPO and MDE were more likely to report lower income and unemployment versus employment. Conclusions: This study found that independent and comorbid NMUPO and MDE were disproportionately clustered with burdens of lower socioeconomic position, suggesting that a population-based approach to address NMUPO would target these social determinants of health, whereas a high-risk approach to prevention should be tailored to females experiencing MDE symptoms and polydrug users

Amorphous shear bands in crystalline materials as drivers of plasticity

Traditionally, the formation of amorphous shear bands (SBs) in crystalline materials has been undesirable, because SBs can nucleate voids and act as precursors to fracture. They also form as a final stage of accumulated damage. Only recently SBs were found to form in undefected crystals, where they serve as the primary driver of plasticity without nucleating voids. Here, we have discovered trends in materials properties that determine when amorphous shear bands will form and whether they will drive plasticity or lead to fracture. We have identified the materials systems that exhibit SB deformation, and by varying the composition, we were able to switch from ductile to brittle behavior. Our findings are based on a combination of experimental characterization and atomistic simulations, and they provide a potential strategy for increasing toughness of nominally brittle materials

The honeysuckle genome provides insight into the molecular mechanism of carotenoid metabolism underlying dynamic flower coloration

Lonicera japonica is a wide-spread member of the Caprifoliaceae (honeysuckle) family utilized in traditional medical practices. This twining vine honeysuckle is also a much-sought ornamental, in part due to its dynamic flower coloration, which changes from white to gold during development. The molecular mechanism underlying dynamic flower coloration in L. japonica was elucidated by integrating whole genome sequencing, transcriptomic analysis, and biochemical assays. Here, we report a chromosome-level genome assembly of L. japonica, comprising nine pseudo-chromosomes with a total size of 843.2 Mb. We also provide evidence for a whole genome duplication event in the lineage leading to L. japonica, which occurred after its divergence from Dipsacales and Asterales. Moreover, gene expression analysis not only revealed correlated expression of the relevant biosynthetic genes with carotenoid accumulation, but also suggested a role for carotenoid degradation in L. japonica's dynamic flower coloration. The variation of flower color is consistent with not only the observed carotenoid accumulation pattern, but also with the release of volatile apocarotenoids that presumably serve as pollinator attractants. Beyond novel insights into the evolution and dynamics of flower coloration, the high-quality L. japonica genome sequence also provides a foundation for molecular breeding to improve desired characteristics

Real-time qPCR for the detection of puffer fish components from Lagocephalus in food: L. inermis, L. lagocephalus, L. gloveri, L. lunaris, and L. spadiceus

Puffer fish is a type of precious high-end aquatic product, is widely popular in Asia, especially in China and Japan, even though it naturally harbors a neurotoxin known as tetrodotoxin (TTX) that is poisonous to humans and causes food poisoning. With the increasing trade demand, which frequently exceeds existing supply capacities, fostering fraudulent practices, such as adulteration of processed products with non-certified farmed wild puffer fish species. To determine the authenticity of puffer fish processed food, we developed a real-time qPCR method to detect five common puffer fish species in aquatic products: Lagocephalus inermis, Lagocephalus lagocephalus, Lagocephalus gloveri, Lagocephalus lunaris, and Lagocephalus spadiceus. The specificity, cross-reactivity, detection limit, efficiency, and robustness of the primers and probes created for five species of puffer fish using TaqMan technology have been determined. No cross-reactivity was detected in the DNA of non-target sample materials, and no false-positive signal was detected; the aquatic products containing 0.1% of a small amount of wild puffer fish materials without certification can be reliably tracked; the statistical p-value for each method’s Ct value was greater than 0.05. The developed qPCR method was sensitive, highly specific, robust, and reproducibility, which could be used to validate the authenticity of wild puffer fish in aquatic products sold for commercial purposes

The Rose-comb Mutation in Chickens Constitutes a Structural Rearrangement Causing Both Altered Comb Morphology and Defective Sperm Motility

Rose-comb, a classical monogenic trait of chickens, is characterized by a drastically altered comb morphology compared to the single-combed wild-type. Here we show that Rose-comb is caused by a 7.4 Mb inversion on chromosome 7 and that a second Rose-comb allele arose by unequal crossing over between a Rose-comb and wild-type chromosome. The comb phenotype is caused by the relocalization of the MNR2 homeodomain protein gene leading to transient ectopic expression of MNR2 during comb development. We also provide a molecular explanation for the first example of epistatic interaction reported by Bateson and Punnett 104 years ago, namely that walnut-comb is caused by the combined effects of the Rose-comb and Pea-comb alleles. Transient ectopic expression of MNR2 and SOX5 (causing the Pea-comb phenotype) occurs in the same population of mesenchymal cells and with at least partially overlapping expression in individual cells in the comb primordium. Rose-comb has pleiotropic effects, as homozygosity in males has been associated with poor sperm motility. We postulate that this is caused by the disruption of the CCDC108 gene located at one of the inversion breakpoints. CCDC108 is a poorly characterized protein, but it contains a MSP (major sperm protein) domain and is expressed in testis. The study illustrates several characteristic features of the genetic diversity present in domestic animals, including the evolution of alleles by two or more consecutive mutations and the fact that structural changes have contributed to fast phenotypic evolution

TNFRSF10C methylation is a new epigenetic biomarker for colorectal cancer

Background Abnormal methylation of TNFRSF10C was found to be associated with different types of cancers, excluding colorectal cancer (CRC). In this paper, the performance of TNFRSF10C methylation in CRC was studied in two stages. Method The discovery stage was involved with 38 pairs of CRC tumor and paired adjacent non-tumor tissues, and 69 pairs of CRC tumor and paired adjacent non-tumor tissues were used for the validation stage. Quantitative methylation specific PCR (qMSP) method and percentage of methylated reference (PMR) were used to test and represent the methylation level of TNFRSF10C, respectively. A dual-luciferase reporter gene experiment was conducted to evaluate the promoter activity of TNFRSF10C fragment. Results A significant association of TNFRSF10C promoter hypermethylation with CRC was found and validated (discovery stage: 24.67 ± 7.52 vs. 3.36 ± 0.89; P = 0.003; validation stage: 31.21 ± 12.48 vs. 4.52 ± 1.47; P = 0.0005). Subsequent analyses of TCGA data among 46 pairs of CRC samples further confirmed our findings (cg23965061: P = 4E − 6; cg14015044: P = 1E − 7). Dual-luciferase reporter gene assay revealed that TNFRSF10C fragment was able to significantly promote gene expression (Fold change = 2.375, P = 0.013). Our data confirmed that TNFRSF10C promoter hypermethylation can predict shorter overall survival of CRC patients (P = 0.032). Additionally, bioinformatics analyses indicated that TNFRSF10C hypermethylation was significantly associated with lower TNFRSF10C expression. Conclusion Our work suggested that TNFRSF10C hypermethylation was significantly associated with the risk of CRC

Single-cell RNA sequencing highlights the role of PVR/PVRL2 in the immunosuppressive tumour microenvironment in hepatocellular carcinoma

IntroductionThe conflict between cancer cells and the host immune system shapes the immune tumour microenvironment (TME) in hepatocellular carcinoma (HCC). A deep understanding of the heterogeneity and intercellular communication network in the TME of HCC will provide promising strategies to orchestrate the immune system to target and eradicate cancers.MethodsHere, we performed single-cell RNA sequencing (scRNA-seq) and computational analysis of 35786 unselected single cells from 3 human HCC tumour and 3 matched adjacent samples to elucidate the heterogeneity and intercellular communication network of the TME. The specific lysis of HCC cell lines was examined in vitro using cytotoxicity assays. Granzyme B concentration in supernatants of cytotoxicity assays was measured by ELISA.ResultsWe found that VCAN+ tumour-associated macrophages (TAMs) might undergo M2-like polarization and differentiate in the tumour region. Regulatory dendritic cells (DCs) exhibited immune regulatory and tolerogenic phenotypes in the TME. Furthermore, we observed intensive potential intercellular crosstalk among C1QC+ TAMs, regulatory DCs, regulator T (Treg) cells, and exhausted CD8+ T cells that fostered an immunosuppressive niche in the HCC TME. Moreover, we identified that the TIGIT-PVR/PVRL2 axis provides a prominent coinhibitory signal in the immunosuppressive TME. In vitro, antibody blockade of PVR or PVRL2 on HCC cell lines or TIGIT blockade on immune cells increased immune cell-mediated lysis of tumour cell. This enhanced immune response is paralleled by the increased secretion of Granzyme B by immune cells.DiscussionCollectively, our study revealed the functional state, clinical significance, and intercellular communication of immunosuppressive cells in HCC at single-cell resolution. Moreover, PVR/PVRL2, interact with TIGIT act as prominent coinhibitory signals and might represent a promising, efficacious immunotherapy strategy in HCC

The honeysuckle genome provides insight into the molecular mechanism of carotenoid metabolism underlying dynamic flower coloration

Lonicera japonica is a wide-spread member of the Caprifoliaceae (honeysuckle) family utilized in traditional medical practices. This twining vine honeysuckle is also a much-sought ornamental, in part due to its dynamic flower coloration, which changes from white to gold during development. The molecular mechanism underlying dynamic flower coloration in L. japonica was elucidated by integrating whole genome sequencing, transcriptomic analysis, and biochemical assays. Here, we report a chromosome-level genome assembly of L. japonica, comprising nine pseudochromosomes with a total size of 843.2 Mb. We also provide evidence for a whole genome duplication event in the lineage leading to L. japonica, which occurred after its divergence from Dipsacales and Asterales. Moreover, gene expression analysis not only revealed correlated expression of the relevant biosynthetic genes with carotenoid accumulation, but also suggested a role for carotenoid degradation in L. japonica’s dynamic flower coloration. The variation of flower color is consistent with not only the observed carotenoid accumulation pattern, but also with the release of volatile apocarotenoids that presumably serve as pollinator attractants. Beyond novel insights into the evolution and dynamics of flower coloration, the high-quality L. japonica genome sequence also provides a foundation for molecular breeding to improve desired characteristics