Delayed and fast rising radio flares from an optical and X-ray detected tidal disruption event in the center of a dwarf galaxy

AT2018cqh is a unique tidal disruption event (TDE) candidate discovered in a dwarf galaxy. Both the light curve fitting and galaxy scaling relationships suggest a central black hole mass in the range of 5.9<logM_BH/M_sun<6.4. A delayed X-ray brightening was found around 590 days after the optical discovery, but shows unusual long-time rising to peak over at least 558 days, which could be coming from delayed accretion of a newly forming debris disk. We report the discovery of delayed radio flares around 1105 days since its discovery, characterized by an initial steep rise of ~>175 days, a flattening lasting about 544 days, and a phase with another steep rise. The rapid rise in radio flux coupled with the slow decay in the X-ray emission points to a delayed launching of outflow, perhaps due to a transition in the accretion state. However, known accretion models can hardly explain the origins of the secondary radio flare that is rising even more rapidly in comparison with the initial one. If confirmed, AT2018cqh would be a rare TDE in a dwarf galaxy exhibiting optical, X-ray and radio flares. We call for continued multi-frequency radio observations to monitor its spectral and temporal evolution, which may help to reveal new physical processes that are not included in standard TDE models.Comment: 11 pages, 5 figures, to appear in ApJ Letter

Analysis of the Accumulation of Major Aroma Components in Japanese Apricot Fruit (Prunus mume Siebold et Zucc.) during Ripening

The major characteristic aroma components of Japanese apricot fruit grown in Dayi county, Sichuan Province were determined by headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry (HS-SPME-GC-MS) based on odor activity values (OAVs). The pattern of accumulation of the major aroma components was investigated by analysis of aroma precursors and their correlation with climate factors was analyzed. The results showed that ethyl butyrate, β-myrcene, ethyl 3-methyl-butyrate, benzaldehyde and nonanal were the major characteristic aroma substances of Japanese apricot fruit, and C6 and C9 compounds were the major aroma components. C6 aroma substances had a high correlation with unsaturated fatty acid precursors. There was a positive correlation between the synthesis of C6 and C9 aroma substances. Climate significantly affected aroma accumulation during fruit ripening. Precipitation was the key factor affecting the content of C6 substances in the early ripening stage, mainly affecting the accumulation of bound hexenol. At the late stage of maturity, air temperature had a great influence on the content of free substances such as hexanol and hexanoic acid. These results provide a basis for follow-up research to analyze the flavor and quality of processed Japanese apricot fruit, explore the effects of climate factors on Japanese apricot fruit and its products, and identify the production region of raw materials and processed products for flavor evaluation

Smoking and coronary artery disease risk in patients with diabetes: A Mendelian randomization study

BackgroundPrevious observational studies have shown an association between smoking and coronary artery disease (CAD) in patients with diabetes. Whether this association reflects causality remains unestablished. This study aimed to explore the causal effect of smoking on CAD in patients with diabetes.MethodsGenetic signatures for smoking were extracted from a large genome-wide association study (GWAS), consisted of up to 1.2 million participants. Four smoking phenotypes were included: smoking initiation, cigarettes per day, age at initiation of regular smoking, and smoking cessation. Genetic associations with CAD in patients with diabetes were extracted from another GWAS, which included 15,666 participants (3,968 CAD cases and 11,696 controls). The analyses were performed using the univariable and multivariable Mendelian randomization (MR) method.ResultsMR analysis revealed that smoking initiation was positively related to CAD risk in patients with diabetes (OR = 1.322, 95% CI = 1.114 – 1.568, P = 0.001), but this association was attenuated when adjusted for cardiovascular risk factors (OR = 1.212, 95% CI = 1.008 – 1.457, P = 0.041). Age at initiation of regular smoking was negatively related to CAD in patients with diabetes (OR = 0.214, 95% CI = 0.070 – 0.656, P = 0.007), but this association became insignificant when adjusted for cardiovascular risk factors.ConclusionsThis study supported the effect of smoking initiation on the risk of CAD in patients with diabetes

Data_Sheet_1_Genetic effects of iron levels on liver injury and risk of liver diseases: A two-sample Mendelian randomization analysis.XLSX

Background and aimsAlthough iron homeostasis has been associated with liver function in many observational studies, the causality in this relationship remains unclear. By using Mendelian Randomization analyses, we aimed to evaluate the genetic effects of increased systemic iron levels on the risk of liver injury and various liver diseases. Moreover, in light of the sex-dependent iron regulation in human beings, we further estimated the sex-specific effect of iron levels in liver diseases.MethodsIndependent single nucleotide polymorphisms associated with systemic iron status (including four indicators) at the genome-wide significance level from the Genetics of Iron Status (GIS) Consortium were selected as instrumental variables. Summary data for six liver function biomarkers and five liver diseases were obtained from the UK Biobank, the Estonian Biobank, the eMERGE network, and FinnGen consortium. Mendelian Randomization assessment of the effect of iron on liver function and liver diseases was conducted.ResultsGenetically predicted iron levels were positively and significantly associated with an increased risk of different dimensions of liver injury. Furthermore, increased iron status posed hazardous effects on non-alcoholic fatty liver disease, alcoholic liver disease, and liver fibrosis/cirrhosis. Sex-stratified analyses indicated that the hepatoxic role of iron might exist in NAFLD and liver fibrosis/cirrhosis development among men. No significantly causal relationship was found between iron status and viral hepatitis.ConclusionOur study adds to current knowledge on the genetic role of iron in the risk of liver injury and related liver diseases, which provides clinical and public health implications for liver disease prevention as iron status can be modified.</p

Data_Sheet_2_Genetic effects of iron levels on liver injury and risk of liver diseases: A two-sample Mendelian randomization analysis.docx

Background and aimsAlthough iron homeostasis has been associated with liver function in many observational studies, the causality in this relationship remains unclear. By using Mendelian Randomization analyses, we aimed to evaluate the genetic effects of increased systemic iron levels on the risk of liver injury and various liver diseases. Moreover, in light of the sex-dependent iron regulation in human beings, we further estimated the sex-specific effect of iron levels in liver diseases.MethodsIndependent single nucleotide polymorphisms associated with systemic iron status (including four indicators) at the genome-wide significance level from the Genetics of Iron Status (GIS) Consortium were selected as instrumental variables. Summary data for six liver function biomarkers and five liver diseases were obtained from the UK Biobank, the Estonian Biobank, the eMERGE network, and FinnGen consortium. Mendelian Randomization assessment of the effect of iron on liver function and liver diseases was conducted.ResultsGenetically predicted iron levels were positively and significantly associated with an increased risk of different dimensions of liver injury. Furthermore, increased iron status posed hazardous effects on non-alcoholic fatty liver disease, alcoholic liver disease, and liver fibrosis/cirrhosis. Sex-stratified analyses indicated that the hepatoxic role of iron might exist in NAFLD and liver fibrosis/cirrhosis development among men. No significantly causal relationship was found between iron status and viral hepatitis.ConclusionOur study adds to current knowledge on the genetic role of iron in the risk of liver injury and related liver diseases, which provides clinical and public health implications for liver disease prevention as iron status can be modified.</p

Seven psychiatric traits and the risk of increased carotid intima-media thickness: a Mendelian randomization study

BackgroundNumerous observational studies have suggested an association between psychiatric traits and carotid intima-media thickness (cIMT). However, whether these associations have a causal relationship remains unknown, largely due to issues of reverse causality and potential confounders. This study aims to elucidate the potential causal role of psychiatric traits in the risk of arterial injury as measured by cIMT.MethodsWe utilized instrumental variables for attention deficit/hyperactivity disorder (ADHD, n = 226,534), bipolar disorder (n = 353,899), major depressive disorder (n = 142,646), post-traumatic stress disorder (n = 174,494), obsessive-compulsive disorder (n = 9,725), autism spectrum disorder (n = 173,773), and anxiety disease (n = 17,310), derived from the largest corresponding genome-wide association studies (GWAS). Summary statistics for cIMT associations were obtained from a meta-analysis combining GWAS data from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortia (n = 71,128) and the UK Biobank study (n = 45,185). The inverse-variance weighted method served as the primary analytical tool, supplemented by additional statistical methods in the secondary analyses to corroborate the findings. Adjustments were made according to the Bonferroni correction threshold.ResultsThe Mendelian randomization analyses indicated a suggestive causal link between genetically predicted ADHD and cIMT (beta = 0.05; 95% confidence interval, 0.01–0.09; p = 0.018). Sensitivity analyses largely concurred with this finding. However, no significant associations were found between other psychiatric traits and cIMT.ConclusionsThis study provides insights into the risk effect of ADHD on cIMT, suggesting that arteriopathy and potential associated complications should be considered during the treatment and monitoring of patients with ADHD

Genetic Liability to Rheumatoid Arthritis in Relation to Coronary Artery Disease and Stroke Risk.

Funder: NIHR Cambridge Biomedical Research Centre; Id: http://dx.doi.org/10.13039/501100018956OBJECTIVE: To assess the causality of the associations of rheumatoid arthritis (RA) with coronary artery disease (CAD) and stroke using the Mendelian randomization approach. METHODS: Independent single-nucleotide polymorphisms strongly associated with RA (n = 70) were selected as instrumental variables from a genome-wide association meta-analysis including 14,361 RA patients and 43,923 controls of European ancestry. Summary-level data for CAD, all stroke, any ischemic stroke and its subtypes, intracerebral hemorrhage (ICH), and subarachnoid hemorrhage were obtained from meta-analyses of genetic studies, international genetic consortia, the UK Biobank, and the FinnGen consortium. We obtained summary-level data for common cardiovascular risk factors and related inflammatory biomarkers to assess possible mechanisms. RESULTS: Genetic liability to RA was associated with an increased risk of CAD and ICH. For a 1-unit increase in log odds of RA, the combined odds ratios were 1.02 (95% confidence interval [1.01, 1.03]; P = 0.003) for CAD and 1.05 (95% confidence interval [1.02, 1.08]; P = 0.001) for ICH. Genetic liability to RA was associated with increased levels of tumor necrosis factor and C-reactive protein (CRP). The association with CAD was attenuated after adjustment for genetically predicted CRP levels. There were no associations of genetic liability to RA with the other studied outcomes. CONCLUSION: This study found that genetic liability to RA was associated with an increased risk of CAD and ICH and that the association with CAD might be mediated by CRP. The heightened cardiovascular risk should be actively monitored and managed in RA patients, and this may include dampening systemic inflammation

CD96, a new immune checkpoint, correlates with immune profile and clinical outcome of glioma

Abstract CD96 is a promising candidate for immunotherapy. However, its role and importance in glioma remains unknown. We thus aimed to genetically and clinically characterize CD96 expression in gliomas. For this, we extracted RNA-seq data of 699 glioma samples from the TCGA dataset and validated these findings using the CGGA dataset comprising 325 glioma samples. Clinical and isocitrate dehydrogenase (IDH) mutation status were also analyzed. Various packages in R language were mainly used for statistical analysis. CD96 expression was significantly up-regulated in high-grade, IDH-wildtype, and mesenchymal-molecular subtype gliomas based on TCGA data, which was validated using the CGGA dataset. Subsequent gene ontology analysis of both datasets suggested that genes relevant to CD96 are mainly involved in immune functions in glioma as such genes were positively correlated with CD96 expression. To further explore the relationship between CD96 and immune responses, we selected seven immune-related metagenes and found that CD96 expression was positively correlated with HCK, LCK, and MHC II in the CGGA and TCGA cohorts but negatively associated with IgG. Further, Pearson correlation analysis showed that CD96 is associated with TIGIT, CD226, CRTAM, TIM-3, PD-L1, CTLA-4, and STAT3, indicating the additive antitumoral effects of these checkpoint proteins. CD96 was also suggested to play an important role in immune responses and positively collaborate with other checkpoint members. These findings show that CD96 is promising candidate for immunotherapy, and that such agents could complement current immunotherapy strategies for glioma

Appraising the Effects of Metabolic Traits on the Risk of Glaucoma: A Mendelian Randomization Study

Metabolic traits are associated with the risk of developing glaucoma in observational studies. To assess whether theses associations reflect causality, we conducted a Mendelian randomization (MR) study. Our study included up to 20,906 glaucoma cases and 438,188 controls. Genetic instruments associated with the concerned 11 exposures at the genome-wide significance level were selected from corresponding genome-wide association studies. Summary-level data for glaucoma were obtained from the UK Biobank, the GERA study, and the FinnGen consortium. Univariable and multivariable MR analyses were conducted separately in two populations. Our results showed that higher genetic liability to type 2 diabetes (T2D) was causally and independently associated with an increased risk of glaucoma (odds ratio [OR], 1.11; 95% confidence interval [CI], 1.06–1.16; p = 4.4 × 10−6). The association for T2D persisted after multivariable adjustment. In addition, higher genetically predicted systolic blood pressure (SBP), fasting glucose (FG), and HbA1c, were also suggestively associated with glaucoma risk. The OR was 1.08 (95% CI, 1.01–1.16; p = 0.035) for SBP, 1.24 (95% CI, 1.05–1.47; p = 0.011) for FG, and 1.28 (95% CI, 1.01–1.61; p = 0.039) for HbA1c. No evidence was observed to support the causal effects of body mass index and blood lipids for glaucoma. This study suggests a causal role for diabetes, as well as possible roles for higher SBP, FG, and HbA1c in the development of glaucoma. Further validation is needed to assess the potential of these risk factors as pharmacological targets for glaucoma prevention

Proteomic insights into the associations between obesity, lifestyle factors, and coronary artery disease

BackgroundWe aimed to investigate the protein pathways linking obesity and lifestyle factors to coronary artery disease (CAD).MethodsSummary-level genome-wide association statistics of CAD were obtained from the CARDIoGRAMplusC4D consortium (60,801 cases and 123,504 controls) and the FinnGen study (R8, 39,036 cases and 303,463 controls). Proteome-wide Mendelian randomization (MR) analysis was conducted to identify CAD-associated blood proteins, supplemented by colocalization analysis to minimize potential bias caused by linkage disequilibrium. Two-sample MR analyses were performed to assess the associations of genetically predicted four obesity measures and 13 lifestyle factors with CAD risk and CAD-associated proteins' levels. A two-step network MR analysis was conducted to explore the mediating effects of proteins in the associations between these modifiable factors and CAD.ResultsGenetically predicted levels of 41 circulating proteins were associated with CAD, and 17 of them were supported by medium to high colocalization evidence. PTK7 (protein tyrosine kinase-7), RGMB (repulsive guidance molecule BMP co-receptor B), TAGLN2 (transgelin-2), TIMP3 (tissue inhibitor of metalloproteinases 3), and VIM (vimentin) were identified as promising therapeutic targets. Several proteins were found to mediate the associations between some modifiable factors and CAD, with PCSK9, C1S, AGER (advanced glycosylation end product-specific receptor), and MST1 (mammalian Ste20-like kinase 1) exhibiting highest frequency among the mediating networks.ConclusionsThis study suggests pathways explaining the associations of obesity and lifestyle factors with CAD from alterations in blood protein levels. These insights may be used to prioritize therapeutic intervention for further study