Association between urinary sodium and circulating lipid levels: a Mendelian randomization study

BackgroundUrinary sodium was indicated to be associated with dyslipidemia, but inconsistent conclusions for this association exist across the present observational studies.ObjectivesThis study aimed to evaluate the causal association between urinary sodium and circulating lipid levels [low-density lipoprotein cholesterol (LDL-C), triglycerides, and high-density lipoprotein cholesterol (HDL-C)] through Mendelian randomization.MethodsUnivariable Mendelian randomization (UVMR) and multivariable Mendelian randomization (MVMR) with pleiotropy-resistant methods were performed. Data for urinary sodium were obtained from the genome-wide association study (GWAS) from 446,237 European individuals. Data for lipid profiles were extracted from GWAS based on the UK Biobank (for the discovery analysis) and the Global Lipids Genetics Consortium (for the replication analysis).ResultsIn the discovery analysis, UVMR provided evidence that per 1-unit log-transformed genetically increased urinary sodium was associated with a lower level of HDL-C level (beta = −0.32; 95% CI: −0.43, −0.20; p = 7.25E−08), but not with LDL-C and triglycerides. This effect was still significant in the further MVMR when considering the effect of BMI or the other two lipid contents. In contrast, higher genetically predicted triglycerides could increase urinary sodium in both UVMR (beta = 0.030; 95% CI: 0.020, −0.039; p = 2.12E−10) and MVMR analyses (beta = 0.029; 95% CI: 0.019, 0.037; p = 8.13E−10). Similar results between triglycerides and urinary sodium were found in the replication analysis.ConclusionIncreased urinary sodium may have weak causal effects on decreased circulating HDL-C levels. Furthermore, genetically higher triglyceride levels may have independent causal effects on increased urinary sodium excretion

Modeling the mid-piacenzian warm climate using the water isotope-enabled Community Earth System Model (iCESM1.2-ITPCAS)

The mid-Piacenzian Warm Period (MPWP, ~ 3.264–3.025 Ma) is the most recent example of a persistently warmer climate in equilibrium with atmospheric CO2 concentrations similar to today. Towards studying patterns and dynamics of a warming climate the MPWP is often compared to today. Following the Pliocene Model Intercomparison Project, Phase 2 (PlioMIP2) protocol we prepare a water isotope-enabled Community Earth System Model (iCESM1.2) simulation that is warmer and wetter than the PlioMIP2 multi-model ensemble (MME). While our simulation resembles PlioMIP2 MME in many aspects we find added insights. (1) Considerable warmth at high latitudes exceeds previous simulations. Polar amplification (PA) is comparable to proxies, enabled by iCESM1.2’s high climate sensitivity and a distinct method of ocean initialization. (2) Major driver of warmth is the downward component of clear-sky surface long-wave radiation. (3) In iCESM1.2 modulated dominance of dynamic (δDY) processes causes different low-latitude (~ 30 S°–10°N) precipitation response than the PlioMIP2 MME, where thermodynamic processes (δTH) dominate. (4) Modulated local condensation leads to lower δ18O across tropical Indian Ocean and surrounding Asian-African-Australian monsoon regions. (5) We find contrasting changes in tropical atmospheric circulations (Hadley and Walker cells). Anomalous regional meridional (zonal) circulation, forced by changes in tropical-subtropical (tropical) diabatic processes, presents a more comprehensive perspective than explaining weakened and expanded Hadley circulation (strengthened and westward-shifted Walker circulation) via static stability. (6) Enhanced Atlantic meridional overturning circulation owes to a closed Bering Strait

Microstructural alterations in white matter and related neurobiology based on the new clinical subtypes of Parkinson's disease

Background and objectivesThe advent of new clinical subtyping systems for Parkinson's disease (PD) has led to the classification of patients into distinct groups: mild motor predominant (PD-MMP), intermediate (PD-IM), and diffuse malignant (PD-DM). Our goal was to evaluate the efficacy of diffusion tensor imaging (DTI) in the early diagnosis, assessment of clinical progression, and prediction of prognosis of these PD subtypes. Additionally, we attempted to understand the pathological mechanisms behind white matter damage using single-photon emission computed tomography (SPECT) and cerebrospinal fluid (CSF) analyses.MethodsWe classified 135 de novo PD patients based on new clinical criteria and followed them up after 1 year, along with 45 healthy controls (HCs). We utilized tract-based spatial statistics to assess the microstructural changes of white matter at baseline and employed multiple linear regression to examine the associations between DTI metrics and clinical data at baseline and after follow-up.ResultsCompared to HCs, patients with the PD-DM subtype demonstrated reduced fractional anisotropy (FA), increased axial diffusivity (AD), and elevated radial diffusivity (RD) at baseline. The FA and RD values correlated with the severity of motor symptoms, with RD also linked to cognitive performance. Changes in FA over time were found to be in sync with changes in motor scores and global composite outcome measures. Furthermore, baseline AD values and their rate of change were related to alterations in semantic verbal fluency. We also discovered the relationship between FA values and the levels of α-synuclein and β-amyloid. Reduced dopamine transporter uptake in the left putamen correlated with RD values in superficial white matter, motor symptoms, and autonomic dysfunction at baseline as well as cognitive impairments after 1 year.ConclusionsThe PD-DM subtype is characterized by severe clinical symptoms and a faster progression when compared to the other subtypes. DTI, a well-established technique, facilitates the early identification of white matter damage, elucidates the pathophysiological mechanisms of disease progression, and predicts cognitively related outcomes. The results of SPECT and CSF analyses can be used to explain the specific pattern of white matter damage in patients with the PD-DM subtype

The role of N6-methyladenosine (m6A) in kidney diseases

Chemical modifications are a specific and efficient way to regulate the function of biological macromolecules. Among them, RNA molecules exhibit a variety of modifications that play important regulatory roles in various biological processes. More than 170 modifications have been identified in RNA molecules, among which the most common internal modifications include N6-methyladenine (m6A), n1-methyladenosine (m1A), 5-methylcytosine (m5C), and 7-methylguanine nucleotide (m7G). The most widely affected RNA modification is m6A, whose writers, readers, and erasers all have regulatory effects on RNA localization, splicing, translation, and degradation. These functions, in turn, affect RNA functionality and disease development. RNA modifications, especially m6A, play a unique role in renal cell carcinoma disease. In this manuscript, we will focus on the biological roles of m6A in renal diseases such as acute kidney injury, chronic kidney disease, lupus nephritis, diabetic kidney disease, and renal cancer

A Deep Insight into Ferroptosis in Renal Disease: Facts and Perspectives

Background: Ferroptosis, a newly recognized form of programmed cell death, is distinguished by its reliance on reactive oxygen species and iron-mediated lipid peroxidation, setting it apart from established types like apoptosis, cell necrosis, and autophagy. Recent studies suggest its role in exacerbating or mitigating diseases by influencing metabolic and signaling pathways in conditions such as tumors and ischemic organ damage. Evidence also links ferroptosis to various kidney diseases, prompting a review of its research status and potential breakthroughs in understanding and treating these conditions. Summary: In acute kidney disease (AKI), ferroptosis has been confirmed in animal kidneys after being induced by various factors such as renal ischemia-reperfusion and cisplatin, and glutathione peroxidase 4 (GPX4) is linked with AKI. Ferroptosis is associated with renal fibrosis in chronic kidney disease (CKD), TGF-β1 being crucial in this regard. In diabetic nephropathy (DN), high SLC7A11 and low nuclear receptor coactivator 4 (NCOA4) expressions are linked to disease progression. For polycystic kidney disease (PKD), ferroptosis promotes the disease by regulating ferroptosis in kidney tissue. Renal cell carcinoma (RCC) and lupus nephritis (LN) also have links to ferroptosis, with mtDNA and iron accumulation causing RCC and oxidative stress causing LN. Key Messages: Ferroptosis is a newly identified form of programmed cell death that is associated with various diseases. It targets metabolic and signaling pathways and has been linked to kidney diseases such as AKI, CKD, PKD, DN, LN, and clear cell RCC. Understanding its role in these diseases could lead to breakthroughs in their pathogenesis, etiology, and treatment

Microscopic optical model potential based on a Dirac Brueckner Hartree Fock approach and the relevant uncertainty analysis

A relativistic microscopic optical model potential, named CTOM, for nucleon-nucleus scattering is investigated in the framework of Dirac-Brueckner-Hartree-Fock approach. The microscopic feature of CTOM is guaranteed through rigorously adopting the isospin dependent DBHF calculation within the subtracted T matrix scheme. In order to verify its prediction power, a global study n, p+ A scattering are carried out. The predicted scattering observables coincide with experimental data within a good accuracy over a broad range of targets and a large region of energies only with two free items, namely the free-range factor t in the applied improved local density approximation and minor adjustments of the scalar and vector potentials in the low-density region. In addition, to estimate the uncertainty of the theoretical results, the deterministic simple least square approach is preliminarily employed to derive the covariance of predicted angular distributions, which is also briefly contained in this paper

Differences in health-related behaviors between middle school, high school, and college students in Jiangsu province, China

BACKGROUND AND OBJECTIVES: Increasing rates of obesity among Chinese adolescents has become a major public health concern in recent years. Studies have shown that factors such as food choices, physical activity, and screen time play important roles in fostering obesity. We examined a number of biological and social determinants that influence these factors. To determine whether dietary behavior, physical activity, and screen time varied among students in different stages of their education. METHODS AND STUDY DESIGN: Students in 13 cities across Jiangsu Province completed an anonymous survey assessing demographics and various health-related behaviors in a controlled setting. The survey population ranged from middle school students to undergraduates. 55,361 surveys were returned, and 46,611 (84.2%) were usable for the analysis. Multiple linear regression models were used to investigate the relationship between four behavioral factors (dietary behavior, screen time, physical activity, and moderate exercise) and seven predictors (gender, age, BMI, mother's education, nearsightedness, allowance, and geographic region). RESULTS: Baseline characteristics of the survey population analyzed by education level (middle school, high school, college and beyond) showed moderate differences in demographics among the three groups. Physical activity, moderate exercise, and dietary behavior decreased with educational level, while screen time increased. All predictors in the four considered regression models were statistically significant. CONCLUSIONS: This unique, large-scale survey of Chinese students in a region of contrasting economic development revealed numerous relationships between health-related diet and physical-activity, region, and education level. These findings can inform the development of measures to counteract the rise of obesity in China