Effect of chronic noise exposure on glucose and lipid metabolism in mice via modulating gut microbiota and regulating CREB/CRTC2 and SREBP1/SCD pathway.

Chronic noise exposure is correlated with gut microbiota dysbiosis and glucose and lipid metabolism disorders. However, evidence on the mechanisms underlying of gut microbiota alterations in chronic noise induced glucose and lipid metabolism disorders is limited, and the potential aftereffects of chronic noise exposure on metabolic disorders remain unclear. In present study, we established chronic daytime and nighttime noise exposure mice models to explore the effects and underlying mechanism of gut microbiota on chronic noise-induced glucose and lipid metabolism disorders. The results showed that exposure to chronic daytime or nighttime noise significantly increased the fasting blood glucose, serum and liver TG levels, impaired glucose tolerance, and decreased serum HDL-C levels and liver TC levels in mice. However, after 4 weeks of recovery, only serum TG of mice in nighttime noise recovery group remained elevated. Besides, exposure to chronic noise reduced the intestinal tight junction protein levels and increased intestinal permeability, while this effect did not completely dissipate even after the recovery period. Moreover, chronic noise exposure changed the gut microbiota and significantly regulated metabolites and metabolic pathways, and further activate hepatic gluconeogenesis CRTC2/CREB-PCK1 signaling pathway and lipid synthesis SREBP1/SCD signaling pathway through intestinal hepatic axis. Together, our findings demonstrated that chronic daytime and nighttime noise exposure could cause the glucose and lipid metabolism disorder by modulating the gut microbiota and serum metabolites, and activating hepatic gluconeogenic CREB/CRTC2-PCK1 signaling and lipid synthesis SREBP1/SCD signaling pathway. The potential aftereffects of noise exposure during wakefulness on metabolic disorders are more significant than that of noise exposure during sleep.

Depression and the Risk of Dementia and All-Cause Mortality Among Japanese Older Adults: A 9-Year Longitudinal Study From JAGES.

BACKGROUND: This study aims to investigate the association and dose-response relationship between depression, dementia, and all-cause mortality based on a national cohort study of older adults in Japan. METHODS: We conducted a longitudinal study of 44,546 participants ≥65 years from 2010-2019 Japanese Gerontological Evaluation Study. The Geriatric Depression Scale-15 was used to assess depressive symptoms and the long-term care insurance was used to assess dementia. Fine-Gray models and Cox proportional hazard models were used to explore the effect of depression severity on the incidence of dementia and all-cause mortality, respectively. Causal mediation analysis were used to explore the extent of association between dementia-mediated depression and all-cause mortality. RESULTS: We found that both minor and major depressive symptoms were associated with the increased cumulative incidence of dementia and all-cause mortality, especially major depressive symptoms (p < .001). The multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for dementia were 1.25 (1.19-1.32) for minor depressive symptoms and 1.42 (1.30-1.54) for major depressive symptoms in comparison to non-depression; p for trend < .001. The multivariable-adjusted HRs and 95% CIs for all-cause mortality were 1.27 (1.21-1.33) for minor depressive symptoms and 1.51 (1.41-1.62) for major depressive symptoms in comparison to non-depression; p for trend < .001. Depression has a stronger impact on dementia and all-cause mortality among the younger group. In addition, dementia significantly mediated the association between depression and all-cause mortality. DISCUSSION: Interventions targeting major depression may be an effective strategy for preventing dementia and premature death.

Interactions of genetic variations in FAS, GJB2 and PTPRN2 are associated with noise-induced hearing loss: a case-control study in China.

BACKGROUND: This study aimed to screen and validate noise-induced hearing loss (NIHL) associated single nucleotide polymorphisms (SNPs), construct genetic risk prediction models, and evaluate higher-order gene-gene, gene-environment interactions for NIHL in Chinese population. METHODS: First, 83 cases and 83 controls were recruited and 60 candidate SNPs were genotyped. Then SNPs with promising results were validated in another case-control study (153 cases and 252 controls). NIHL-associated SNPs were identified by logistic regression analysis, and a genetic risk model was constructed based on the genetic risk score (GRS), and classification and regression tree (CART) analysis was used to evaluate interactions among gene-gene and gene-environment. RESULTS: Six SNPs in five genes were significantly associated with NIHL risk (p < 0.05). A positive dose-response relationship was found between GRS values and NIHL risk. CART analysis indicated that strongest interaction was among subjects with age ≥ 45 years and cumulative noise exposure ≥ 95 [dB(A)·years], without personal protective equipment, and carried GJB2 rs3751385 (AA/AB) and FAS rs1468063 (AA/AB) (OR = 10.038, 95% CI = 2.770, 47.792), compared with the referent group. CDH23, FAS, GJB2, PTPRN2 and SIK3 may be NIHL susceptibility genes. CONCLUSION: GRS values may be utilized in the evaluation of the cumulative effect of genetic risk for NIHL based on NIHL-associated SNPs. Gene-gene, gene-environment interaction patterns play an important role in the incidence of NIHL.

Interplay of heart rate variability and resting heart rate on mortality in type 2 diabetes.

AIMS: Heart rate variability (HRV) and resting heart rate (RHR) are usually analyzed and interpreted separately. We aimed to assess the interplay of HRV and RHR on mortality in type 2 diabetes. METHODS: The study included 7,529 participants from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. HRV metrics included standard deviation of all normal-to-normal intervals (SDNN) and root mean square of successive differences between normal-to-normal intervals (rMSSD). Abnormal values were defined based on <25th percentile for HRV and >75th percentile for RHR. Interactions of HRV status and RHR status were tested on multiplicative and additive scales. Results were validated in a subset of patients with type 2 diabetes (n = 745) from the Multi-Ethnic Study of Atherosclerosis. RESULTS: Low SDNN was associated with increased all-cause mortality in the high RHR group (HR 1.60; 95% CI 1.29-1.97), but not in the normal RHR group. Compared with those who had neither low SDNN nor high RHR, the presence of either low SDNN or high RHR was not significantly associated with an increased risk of all-cause mortality. In contrast, the combination of low SDNN and high RHR was associated with a significantly increased risk of all-cause mortality (HR 1.68; 95% CI 1.43-1.97). Significant multiplicative and additive interactions were found between HRV status and RHR status on risk of all-cause mortality (all Pinteraction < 0.05). Similar findings were observed for cardiovascular mortality, in analyses using rMSSD, and in the Multi-Ethnic Study of Atherosclerosis. CONCLUSIONS: The association between HRV and mortality risk is modified by RHR levels. Furthermore, low HRV and high RHR have interdependent and synergistic associations with mortality risk.

New Insights into Rate Control: Time in Target Range of Resting Heart Rate and Major Adverse Outcomes in Atrial Fibrillation.

Background: Few studies have examined the relationship between the fluctuation of heart rate control over time and cardiovascular outcomes in patients with atrial fibrillation. Our study sought to evaluate the independent association between time in target range (TIR) of resting heart rate and cardiovascular outcomes in the AFFIRM (Atrial Fibrillation Follow-Up Investigation of Rhythm Management) study. Methods: Target range of resting heart was defined as less than 80 beats per minute (bpm) for both rate and rhythm control groups. Time in target range was estimated over the first 8 months of follow-up using Rosendaal interpolation method. The association between TIR of resting heart rate and cardiovascular outcomes was estimated using adjusted Cox proportional hazards regression models. Results: Time in target range of resting heart rate (months 0 through 8) was 71 ± 34% in the rate control group and 83 ± 27% in the rhythm control group. Each 1-SD increase in TIR of resting heart rate was significantly associated with lower risk of major adverse cardiovascular events after full adjustment for demographics, medical history and history of prior heart surgery, as well as all-cause mortality. Conclusions: Time in target range of resting heart rate independently predicts the risk of cardiovascular outcomes in patients with atrial fibrillation. Long-term maintenance of heart rate on target is of great importance for patients with atrial fibrillation.

Genetically optimizing soybean nodulation improves yield and protein content.

Symbiotic nitrogen fixation in legume nodules requires substantial energy investment from host plants, and soybean (Glycine max (L.) supernodulation mutants show stunting and yield penalties due to overconsumption of carbon sources. We obtained soybean mutants differing in their nodulation ability, among which rhizobially induced cle1a/2a (ric1a/2a) has a moderate increase in nodule number, balanced carbon allocation, and enhanced carbon and nitrogen acquisition. In multi-year and multi-site field trials in China, two ric1a/2a lines had improved grain yield, protein content and sustained oil content, demonstrating that gene editing towards optimal nodulation improves soybean yield and quality.