Modifiable pathways for longevity:A Mendelian randomization analysis

Background: A variety of factors, including diet and lifestyle, obesity, physiology, metabolism, hormone levels, psychology, and inflammation, have been associated with longevity. The specific influences of these factors, however, are poorly understood. Here, possible causal relationships between putative modifiable risk factors and longevity are investigated. Methods: A random effects model was used to investigate the association between 25 putative risk factors and longevity. The study population comprised 11,262 long-lived subjects (≥90 years old, including 3484 individuals ≥99 years old) and 25,483 controls (≤60 years old), all of European ancestry. The data were obtained from the UK Biobank database. Genetic variations were used as instruments in two-sample Mendelian randomization to reduce bias. The odds ratios for genetically predicted SD unit increases were calculated for each putative risk factor. Egger regression was used to determine possible violations of the Mendelian randomization model. Results: Thirteen potential risk factors showed significant associations with longevity (≥90th) after correction for multiple testing. These included smoking initiation (OR:1.606; CI: 1.112–2.319) and educational attainment (OR:2.538, CI: 1.685–3.823) in the diet and lifestyle category, systolic and diastolic blood pressure (OR per SD increase: 0.518; CI: 0.438–0.614 for SBP and 0.620; CI 0.514–0.748 for DBP) and venous thromboembolism (OR:0.002; CI: 0.000–0.047) in the physiology category, obesity (OR: 0.874; CI: 0.796–0.960), BMI (OR per 1-SD increase: 0.691; CI: 0.628–0.760), and body size at age 10 (OR per 1-SD increase:0.728; CI: 0.595–0.890) in the obesity category, type 2 diabetes (T2D) (OR:0.854; CI: 0.816–0.894), LDL cholesterol (OR per 1-SD increase: 0.743; CI: 0.668–0.826), HDL cholesterol (OR per 1-SD increase: 1.243; CI: 1.112–1.390), total cholesterol (TC) (OR per 1-SD increase: 0.786; CI: 0.702–0.881), and triglycerides (TG) (OR per 1-SD increase: 0.865; CI: 0.749–0.998) in the metabolism category. Both longevity (≥90th) and super-longevity (≥99th), smoking initiation, body size at age 10, BMI, obesity, DBP, SBP, T2D, HDL, LDL, and TC were consistently associated with outcomes. The examination of underlying pathways found that BMI indirectly affected longevity through three pathways, namely, SBP, plasma lipids (HDL/TC/LDL), and T2D (p &lt; 0.05). Conclusion: BMI was found to significantly affect longevity through SBP, plasma lipid (HDL/TC/LDL), and T2D. Future strategies should focus on modifying BMI to improve health and longevity.</p

Five-electrode direct current suppressor-detector combiner for ion chromatography: an integration of eluent suppression and resistance detection

An integration of eluent suppressor and resistance detector is proposed based upon the application of a common anode (or cathode), a common ion-exchange membrane, and two independent constant current sources.National Natural Science Foundation of China[20527005

Bondi-Sachs metrics and Photon Rockets

We study the Bondi-Sachs rockets with nonzero cosmological constant. We observe that the acceleration of the systems arises naturally in the asymptotic symmetries of (anti-) de Sitter spacetimes. Assuming the validity of the concepts of energy and mass previously introduced in asymptotically flat spacetimes, we find that the emission of pure radiation energy balances the loss of the Bondi mass in certain special families of the Bondi-Sachs rockets, so in these there is no gravitational radiation.Comment: 12 pages, to appear in General Relativity and Gravitatio

Transcriptome sequencing and phylogenomic resolution within Spalacidae (Rodentia)

BACKGROUND: Subterranean mammals have been of great interest for evolutionary biologists because of their highly specialized traits for the life underground. Owing to the convergence of morphological traits and the incongruence of molecular evidence, the phylogenetic relationships among three subfamilies Myospalacinae (zokors), Spalacinae (blind mole rats) and Rhizomyinae (bamboo rats) within the family Spalacidae remain unresolved. Here, we performed de novo transcriptome sequencing of four RNA-seq libraries prepared from brain and liver tissues of a plateau zokor (Eospalax baileyi) and a hoary bamboo rat (Rhizomys pruinosus), and analyzed the transcriptome sequences alongside a published transcriptome of the Middle East blind mole rat (Spalax galili). We characterize the transcriptome assemblies of the two spalacids, and recover the phylogeny of the three subfamilies using a phylogenomic approach. RESULTS: Approximately 50.3 million clean reads from the zokor and 140.8 million clean reads from the bamboo ratwere generated by Illumina paired-end RNA-seq technology. All clean reads were assembled into 138,872 (the zokor) and 157,167 (the bamboo rat) unigenes, which were annotated by the public databases: the Swiss-prot, Trembl, NCBI non-redundant protein (NR), NCBI nucleotide sequence (NT), Gene Ontology (GO), Cluster of Orthologous Groups (COG), and Kyoto Encyclopedia of Genes and Genomes (KEGG). A total of 5,116 nuclear orthologous genes were identified in the three spalacids and mouse, which was used as an outgroup. Phylogenetic analysis revealed a sister group relationship between the zokor and the bamboo rat, which is supported by the majority of gene trees inferred from individual orthologous genes, suggesting subfamily Myospalacinae is more closely related to subfamily Rhizomyinae. The same topology was recovered from concatenated sequences of 5,116 nuclear genes, fourfold degenerate sites of the 5,116 nuclear genes and concatenated sequences of 13 protein coding mitochondrial genes. CONCLUSIONS: This is the first report of transcriptome sequencing in zokors and bamboo rats, representing a valuable resource for future studies of comparative genomics in subterranean mammals. Phylogenomic analysis provides a conclusive resolution of interrelationships of the three subfamilies within the family Spalacidae, and highlights the power of phylogenomic approach to dissect the evolutionary history of rapid radiations in the tree of life

Electroacupuncture for psychogenic erectile dysfunction: A resting-state functional magnetic resonance imaging study exploring the alteration of fractional amplitude of low frequency fluctuation

BackgroundPsychogenic erectile dysfunction (PED) can seriously affect emotional and marital wellbeing. Electroacupuncture (EA) seems an effective method for treating PED. However, the central mechanisms underlying PED and the beneficial effects of EA treatment are unclear. The purpose of this study was to explore the central mechanisms of PED and to examine the impact of EA on erectile function.MethodsWe recruited 14 PED patients and 14 matched normal controls (NCs). PED patients underwent twice rs-fMRI scans, respectively, pre- and post-treatment. The NCs only completed one rs-fMRI scan. We used the fractional amplitude of low frequency fluctuation (fALFF) to compare spontaneous neural activity between the PED patients and NCs, and to examine the differences between the pre- and post-EA treatment scans in the PED patients.ResultsScores on the IIEF5, QEQ, and SEAR improved after EA treatment. Compared with the NCs, PED patients showed increased fALFF in the right posterior cingulate cortex (PCC), right dorsolateral prefrontal cortex (DLPFC), right supplementary motor area (SMA), and left middle occipital gyrus. Most of these regions are closely implicated in sexual inhibition. The results of the correlation analysis results indicated that the fALFF of the right PCC was negatively correlated with IIEF5 scores. After treatment, fALFF values were substantially lower in the left triangular part of the inferior frontal gyrus, right DLPFC, right SMA, bilateral PCC and the orbital part of the middle frontal gyrus, and higher in the left middle temporal gyrus and left caudate nucleus. These regions mainly belong to the default mode network (DMN), executive control network and primary sensory motor network. The results of the correlation analysis indicated a positive association between the changes in IIEF5 score and changes in the fALFF value in the right PCC after EA treatment.ConclusionIn conclusion, our study highlights that PED patients have abnormal patterns of activity in the right PCC, right DLPFC, and right SMA mainly involved in the DMN, executive central network, and sensory motor network which could lead to a higher levels of sexual inhibition. EA might regulate the process of sexual inhibition to improve erection function in PED patients probably by modulating spontaneous brain activity in the DMN, executive central network, and sensory motor network

The genetic correlation and causal association between key factors that influence vascular calcification and cardiovascular disease incidence

Background: Serum calcium (Ca), vitamin D (VD), and vitamin K (VK) levels are key determinants of vascular calcification, which itself impacts cardiovascular disease (CVD) risk. The specific relationships between the levels of these different compounds and particular forms of CVD, however, remain to be fully defined. Objective: This study was designed to explore the associations between these serum levels and CVDs with the goal of identifying natural interventions capable of controlling vascular calcification and thereby protecting against CVD pathogenesis, extending the healthy lifespan of at-risk individuals.Methods: Linkage disequilibrium score (LDSC) regression and a two-sample Mendelian randomization (MR) framework were leveraged to systematically examine the causal interplay between these serum levels and nine forms of CVD, as well as longevity through the use of large publically accessible Genome-Wide Association Studies (GWAS) datasets. The optimal concentrations of serum Ca and VD to lower CVD risk were examined through a restrictive cubic spline (RCS) approach.Results: After Bonferroni correction, the positive genetic correlations were observed between serum Ca levels and myocardial infarction (MI) (p = 1.356E–04), as well as coronary artery disease (CAD) (p = 3.601E–04). Negative genetic correlations were detected between levels of VD and CAD (p = 0.035), while elevated VK1 concentrations were causally associated with heart failure (HF) [odds ratios (OR) per 1-standard deviation (SD) increase: 1.044], large artery stroke (LAS) (OR per 1-SD increase: 1.172), and all stroke (AS) (OR per 1-SD increase: 1.041). Higher serum Ca concentrations (OR per 1-SD increase: 0.865) and VD levels (OR per 1-SD increase: 0.777) were causally associated with reduced odds of longevity. These findings remained consistent in sensitivity analyses, and serum Ca and VD concentrations of 2.376 mmol/L and 46.8 nmol/L, respectively, were associated with a lower CVD risk (p &lt; 0.001). Conclusion: Our findings support a genetic correlation between serum Ca and VD and CVD risk, and a causal relationship between VK1 levels and CVD risk. The optimal serum Ca (2.376 mmol/L) and VD levels (46.8 nmol/L) can reduce cardiovascular risk.</p

The genetic correlation and causal association between key factors that influence vascular calcification and cardiovascular disease incidence

Background: Serum calcium (Ca), vitamin D (VD), and vitamin K (VK) levels are key determinants of vascular calcification, which itself impacts cardiovascular disease (CVD) risk. The specific relationships between the levels of these different compounds and particular forms of CVD, however, remain to be fully defined. Objective: This study was designed to explore the associations between these serum levels and CVDs with the goal of identifying natural interventions capable of controlling vascular calcification and thereby protecting against CVD pathogenesis, extending the healthy lifespan of at-risk individuals.Methods: Linkage disequilibrium score (LDSC) regression and a two-sample Mendelian randomization (MR) framework were leveraged to systematically examine the causal interplay between these serum levels and nine forms of CVD, as well as longevity through the use of large publically accessible Genome-Wide Association Studies (GWAS) datasets. The optimal concentrations of serum Ca and VD to lower CVD risk were examined through a restrictive cubic spline (RCS) approach.Results: After Bonferroni correction, the positive genetic correlations were observed between serum Ca levels and myocardial infarction (MI) (p = 1.356E–04), as well as coronary artery disease (CAD) (p = 3.601E–04). Negative genetic correlations were detected between levels of VD and CAD (p = 0.035), while elevated VK1 concentrations were causally associated with heart failure (HF) [odds ratios (OR) per 1-standard deviation (SD) increase: 1.044], large artery stroke (LAS) (OR per 1-SD increase: 1.172), and all stroke (AS) (OR per 1-SD increase: 1.041). Higher serum Ca concentrations (OR per 1-SD increase: 0.865) and VD levels (OR per 1-SD increase: 0.777) were causally associated with reduced odds of longevity. These findings remained consistent in sensitivity analyses, and serum Ca and VD concentrations of 2.376 mmol/L and 46.8 nmol/L, respectively, were associated with a lower CVD risk (p &lt; 0.001). Conclusion: Our findings support a genetic correlation between serum Ca and VD and CVD risk, and a causal relationship between VK1 levels and CVD risk. The optimal serum Ca (2.376 mmol/L) and VD levels (46.8 nmol/L) can reduce cardiovascular risk.</p

The genetic correlation and causal association between key factors that influence vascular calcification and cardiovascular disease incidence

Background: Serum calcium (Ca), vitamin D (VD), and vitamin K (VK) levels are key determinants of vascular calcification, which itself impacts cardiovascular disease (CVD) risk. The specific relationships between the levels of these different compounds and particular forms of CVD, however, remain to be fully defined. Objective: This study was designed to explore the associations between these serum levels and CVDs with the goal of identifying natural interventions capable of controlling vascular calcification and thereby protecting against CVD pathogenesis, extending the healthy lifespan of at-risk individuals.Methods: Linkage disequilibrium score (LDSC) regression and a two-sample Mendelian randomization (MR) framework were leveraged to systematically examine the causal interplay between these serum levels and nine forms of CVD, as well as longevity through the use of large publically accessible Genome-Wide Association Studies (GWAS) datasets. The optimal concentrations of serum Ca and VD to lower CVD risk were examined through a restrictive cubic spline (RCS) approach.Results: After Bonferroni correction, the positive genetic correlations were observed between serum Ca levels and myocardial infarction (MI) (p = 1.356E–04), as well as coronary artery disease (CAD) (p = 3.601E–04). Negative genetic correlations were detected between levels of VD and CAD (p = 0.035), while elevated VK1 concentrations were causally associated with heart failure (HF) [odds ratios (OR) per 1-standard deviation (SD) increase: 1.044], large artery stroke (LAS) (OR per 1-SD increase: 1.172), and all stroke (AS) (OR per 1-SD increase: 1.041). Higher serum Ca concentrations (OR per 1-SD increase: 0.865) and VD levels (OR per 1-SD increase: 0.777) were causally associated with reduced odds of longevity. These findings remained consistent in sensitivity analyses, and serum Ca and VD concentrations of 2.376 mmol/L and 46.8 nmol/L, respectively, were associated with a lower CVD risk (p &lt; 0.001). Conclusion: Our findings support a genetic correlation between serum Ca and VD and CVD risk, and a causal relationship between VK1 levels and CVD risk. The optimal serum Ca (2.376 mmol/L) and VD levels (46.8 nmol/L) can reduce cardiovascular risk.</p

The genetic correlation and causal association between key factors that influence vascular calcification and cardiovascular disease incidence

Background: Serum calcium (Ca), vitamin D (VD), and vitamin K (VK) levels are key determinants of vascular calcification, which itself impacts cardiovascular disease (CVD) risk. The specific relationships between the levels of these different compounds and particular forms of CVD, however, remain to be fully defined. Objective: This study was designed to explore the associations between these serum levels and CVDs with the goal of identifying natural interventions capable of controlling vascular calcification and thereby protecting against CVD pathogenesis, extending the healthy lifespan of at-risk individuals.Methods: Linkage disequilibrium score (LDSC) regression and a two-sample Mendelian randomization (MR) framework were leveraged to systematically examine the causal interplay between these serum levels and nine forms of CVD, as well as longevity through the use of large publically accessible Genome-Wide Association Studies (GWAS) datasets. The optimal concentrations of serum Ca and VD to lower CVD risk were examined through a restrictive cubic spline (RCS) approach.Results: After Bonferroni correction, the positive genetic correlations were observed between serum Ca levels and myocardial infarction (MI) (p = 1.356E–04), as well as coronary artery disease (CAD) (p = 3.601E–04). Negative genetic correlations were detected between levels of VD and CAD (p = 0.035), while elevated VK1 concentrations were causally associated with heart failure (HF) [odds ratios (OR) per 1-standard deviation (SD) increase: 1.044], large artery stroke (LAS) (OR per 1-SD increase: 1.172), and all stroke (AS) (OR per 1-SD increase: 1.041). Higher serum Ca concentrations (OR per 1-SD increase: 0.865) and VD levels (OR per 1-SD increase: 0.777) were causally associated with reduced odds of longevity. These findings remained consistent in sensitivity analyses, and serum Ca and VD concentrations of 2.376 mmol/L and 46.8 nmol/L, respectively, were associated with a lower CVD risk (p &lt; 0.001). Conclusion: Our findings support a genetic correlation between serum Ca and VD and CVD risk, and a causal relationship between VK1 levels and CVD risk. The optimal serum Ca (2.376 mmol/L) and VD levels (46.8 nmol/L) can reduce cardiovascular risk.</p