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Sleep disturbances have been linked with Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS) in observational studies, and the comorbidity of PD and ALS has been reported in clinical case reports, but the causalities remain unclear. This study aims to examine bidirectional causal relationships between sleep traits, PD and ALS.Bidirectional two sample Mendelian randomisation (MR) analyses were conducted, with data from individuals of mainly European ancestry. Genetic instruments were obtained from the largest published genome-wide association studies (GWAS) concerning various sleep traits, PD and ALS. MR estimates from each genetic instrument were combined by inverse variance weighted method, with alternate methods (eg, weighted median, MR Egger, MR-PRESSO) and statistical graphs to assess horizontal pleiotropy and remove outliers.MR analysis failed to observe any causal association between sleep disorders and PD, but found a possible causal effect of PD risk on ALS risk (odds ratio [OR] = 1.07; 95% CI: 1.01-1.14, P 0.01), albeit with a horizontal pleiotropy. Furthermore, MR analyses indicated that excessive daytime sleepiness (EDS) (OR = 2.29; 95% CI: 1.04-5.03, P = 0.04) contributed to a modest increase in risk of ALS, but the reverse causalities were not significant. Higher risk of ALS may be associated with being a "morning person" (OR = 1.03, P = 0.02), a longer sleep duration (OR = 1.01, P 0.01), and a mean of 9 h or more total sleep duration (β = 0.02, P = 0.04).Aided by large-scale GWAS, a shortage of evidence supporting causal relationships of sleep traits and PD risk, while significant evidence supports that EDS, higher PD risk may causally influence ALS risk. Future researches are required to explore the underlying pathological mechanism as well as the clinically significance, and replicate our findings using independent samples when data become available.

Objective To identify whether there exists a genetic correlation and causal relationship between 25(OH)D and autism spectrum disorder (ASD). Methods Based on large-scale genome-wide association studies, a series of genetic approaches were adopted to obtain summary statistics. Using linkage disequilibrium score regression, we assessed the shared polygenic structure between traits and performed pleiotropic analysis under composite null hypothesis (PLACO) to identify pleiotropic loci between complex traits. A bidirectional Mendelian randomization (MR) analysis was applied to investigate whether there is a causal relationship between 25(OH)D and ASD. Results The linkage disequilibrium score regression (LDSC) showed a negative genetic correlation between 25(OH)D and ASD (rg = − 0.227, P < 0.05), and PLACO analysis identified 20 independent pleiotropic loci matched to 24 pleiotropic genes, of which the function reveals an underlying mechanism on 25(OH)D and ASD. In Mendelian randomization analysis, the inverse variance-weighted (IVW) method with OR = 0.941 (0.796, 1.112) and p Conclusion This study provides evidence for a shared genetic overlap between 25(OH)D and ASD. Bidirectional MR analysis also did not show a definite causal relationship between 25(OH)D and ASD.

Depression is a prevalent and disabling mental disorder that frequently co-occurs with a wide range of chronic conditions. Past evidence suggests that depression could be associated with the all-cause mortality and other disease mortality in Western populations, but little is known about the relationship in the Chinese population. Therefore, we investigated the associations between self-reported depression and all-cause and specific-cause mortality in Chinese adult populations.The Patient Health Questionnaire-9 (PHQ-9) was used to measure depressive symptoms among 8,151 adult participants drawn from the general population of Guizhou province, China. Participants death and cause of death were determined by linking with the official death records and certificates up to June 2021. Cause of death was coded according to ICD-10 then categorized as either cardiovascular disease (CVD, I00-I99), cancer (C00-C97) or other cause. Cox proportional hazard regression was used to examine the associations of self-reported depression with all-cause mortality and cause-specific mortality.With a median follow-up of 7.4 years, 8,151 participants (52.6% women) at baseline were included in the analysis. The multivariable cox hazard regression models showed that participants with moderate and major depression had the highest hazard ratio (HR) for risk of all-cause mortality (HR=5.65, 95% CI 3.09-10.33), CVD mortality (HR=5.66, 95% CI 2.02-15.84), and cancer mortality (HR=7.21, 95% CI 2.00-25.99), compared with participants had no or mild depression.Our findings suggested that depression was a risk factor for mortality, with greater risk for greater severity. Clinicians should be aware of the increased risk of mortality in populations with depression.

MicroRNAs (miRNAs), have been frequently reported to regulate various diseases including hypertension. However, the biological role and regulatory mechanism of miR-20b-5p are unclear in hypertension. The current study aimed to investigate the role of miR-20b-5p in hypertension.Bioinformatics analysis (starBase: http://starbase.sysu.edu.cn ) and a wide range of experiments including blood pressure detection, morphometric sampling by electron microscopy, real-time quantitative polymerase chain reaction (RT-qPCR), CCK-8, western blot, luciferase reporter, hematoxylin and eosin (HE) staining and Masson trichrome staining assays were used to explore the function and mechanism of miR-20b-5p in hypertension.MiR-20b-5p level was significantly upregulated in Spontaneously hypertensive rats' (SHRs') thoracic aortic vascular tissues. In function, miR-20b-5p silencing inhibited the proliferation and migration of aortic smooth muscle cells (ASMCs) of SHRs. In mechanism, we predicted 10 potential target mRNAs for miR-20b-5p. After prediction by bioinformatics, MAGI3 was validated to bind with miR-20b-5p. Rescue assays showed that MAGI3 silencing reversed the inhibitive influence of miR-20b-5p depletion on cell proliferation and migration.MiR-20b-5p contributed to the dysfunction of ASMCs by targeting MAGI3 in hypertension. This new discovery provided a potential novel insight for hypertension treatment.

Although a significant proportion of type 2 diabetes mellitus (T2DM) cases arose from normal-weight individuals, studies on indicators of T2DM in normal-weight people are limited. Accordingly, this study aims to investigate the predictive value of obesity indices and triglyceride glucose-related parameters (TyG-related parameters) in T2DM among normal-weight Chinese elderly. A total of 24,215 normal-weight Chinese elderly (age ≥ 60 years) [body mass index–BMI (18.5–23.9 kg/m2)] were included. Obesity indices and triglyceride glucose-related parameters (TyG-related parameters) included waist circumference (WC), waist-to-height ratio (WHtR), visceral adiposity index (VAI), lipid accumulation product (LAP), and TyG-related parameters (TyG, TyG-BMI, TyG-WC, and TyG-WHtR). Multivariate logistic regression analysis was performed to examine the associations between obesity- and TyG-related indices and T2DM. The areas under the curve (AUC) of the receiver-operating characteristic (ROC) curve analyses were used to evaluate and compare the predictive value of the different indices. The prevalence of T2DM was 14.2% in normal-weight individuals. Among the indices, TyG was significantly associated with T2DM among men and women, respectively, (adjusted odds ratio–aOR per SD 3.46; 95% CI 3.23–3.71) and (aOR per SD 3.64; 95% CI 3.43–3.86). Compared with other indices, TyG had the highest AUC value for T2DM in men (AUC: 0.818, 95% CI 0.810–0.825) and women (AUC: 0.824, 95% CI 0.814–0.833). TyG is an effective marker and outperforms other indices when predicting T2DM in the normal-weight Chinese elderly population. Level V: Opinions of authorities, based on descriptive studies, narrative reviews, clinical experience, or reports of expert committees.

Considering the inconsistent findings of research into the associations between serum levels of liver enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], and gamma-glutamyltransferase [GGT]) and mortality among elderly people, we aimed to investigate the associations of ALT, AST, GGT, and De-Ritis ratio (DRR, defined as AST/ALT) and all-cause or cause-specific mortality among the US elderly people using National Health and Nutrition Examination Surveys data.We included 6415 elderly participants (≥ 65 years). Exclusion criteria included positive test for hepatitis B virus, hepatitis C virus, and human immunodeficiency virus infection at baseline. Multivariable-adjusted Cox regression models calculating hazard ratios (HR) and 95% confidence intervals were developed for each of the liver enzyme measures.All-cause cumulative mortality was 33.8%, of which 23.8% were cardiovascular disease (CVD) deaths, 15.6% were cancer deaths, and 60.6% were other cause deaths. Adjusted Cox models found increased all-cause mortality risk for low ALT (HR: 1.70), low AST (HR: 1.13), high GGT (HR: 1.25), and high DRR (HR: 1.68). Low ALT and high DRR predicted CVD mortality. Low ALT (HR: 1.91), low AST (HR: 1.16), high GGT (HR: 1.40), and high DRR (HR: 1.76) predicted other cause mortality.Low ALT and high DRR were associated with increased CVD and cancer mortality. All serum liver enzyme measures were associated with all-cause mortality and other cause mortality in the US elderly population. Further studies may validate these findings in other elderly populations.

To investigate the impact of 10 common foods (including staple foods, fruits, vegetables, sugar, meat, fish, eggs, beans, salt-preserved vegetables, and garlic) on cognitive function in Chinese older adults.Cross-sectional data on demographic characteristics, lifestyle, and dietary habits were taken from the 2018 Chinese Longitudinal Healthy Longevity Survey (CLHLS). Cognition was assessed using the Mini-Mental State Examination (MMSE). Food consumption was measured by participants reporting the frequency of their food consumption. Association between food groups and cognitive function was evaluated using mixed-effect regression model analysis.Compared with those who rarely or never consumed vegetables, meat, fruits, beans, and garlic, older adults who consumed these foods almost daily were 56%, 30%, 23%, 34%, and 29% less likely to have cognitive impairment, respectively. No associations between staple foods, sugar, fish, and eggs consumption and cognitive impairment were found. Low-frequency consumption of salt-preserved vegetables may be associated with cognitive function. Regular vegetables consumption had the greatest associated risk reduction of all food types. Interactions indicated that the co-ingestion of vegetables and beans or sugar, meat and beans may have antagonistic effect, while the co-ingestion of salt-preserved vegetables and garlic may have synergistic effect. Subgroup analyses showed that sex and age were the significant effect modifiers for meat and fish, respectively.Cognitive function of Chinese older adults may be related to food groups. Future research should measure food types and consumption level with greater granularity.

This study used data from the Chinese Longitudinal Healthy Longevity Survey (n = 9765, age 65+) to investigate the impact of biomass fuels on the mortality of the Chinese elderly population. The association between biomass fuels and mortality was examined using a Cox proportional hazards model. We evaluated the difference in risk of death between those who switched fuel types from biomass to clean fuels and from clean to biomass fuels versus those who did not during the follow-up period. Participants who used biomass fuels had a higher risk of death than participants who used clean fuels (HR = 1.09, 95% CI: 1.01-1.17). For participants who switched cooking fuel types during the follow-up period, switching from biomass to clean fuels significantly reduced the risk of death (HR = 0.78, 95% CI: 0.67-0.91), while no evidence of an association between switching from clean to biomass fuels and risk of death was found (p > 0.05). Interactions and subgroup analyses indicated that effect estimates were greater for women and non-smokers. Biomass fuels may be associated with a higher risk of death among Chinese elderly. Research measuring personal exposure levels to indoor air pollution caused by biomass fuels combustion is required to confirm our results.

Previous studies show inconsistent associations between niacin supplementation and diabetes mellitus (DM) in high-risk population, but little is known about the relationship between dietary intake of niacin and DM in the generation population. Our study aimed to explore the associations of dietary niacin intake with the risk of DM in the United States (US) adult population.These data were derived from the National Health and Nutrition Examination Survey (NHANES) 2003-2018 of 35,606 individuals aged 20 years or older. Niacin intake and food sources were measured by two 24-h dietary recall interviews. The diagnosis of DM was established according to the American Diabetes Association (ADA) criteria. Binary logistic regression and restricted cubic spline models were applied to evaluate the association of dietary niacin intake and DM.Among the 35,606 individuals, the prevalence of DM was 11.47%. The full-adjusted odds ratio(aOR) of DM was 1.27(95%CI 1.06-1.52) for quartile (Q) 4 v. Q1 of dietary niacin intake. In the dose-response analysis, the shape of the association of niacin intake with the risk of DM was approximately J-shaped (non-linear, p 0.05). Energy-adjusted niacin of 26.08 mg/day was the optimal cut-off value for predicting DM.High dietary niacin intake was positively associated with DM among US adults.Level V: Opinions of authorities, based on descriptive studies, narrative reviews, clinical experience, or reports of expert committees.

The objective of this study is to investigate the dose-response relationship between antibiotic exposure in early life and the risk of subsequent overweight or obesity. Electronic databases were searched from inception to December 2020. Prospective studies that reported the odds ratios (ORs) of childhood overweight or obesity for three or more quantitative categories of antibiotic exposure were identified. A random-effect model was used to pool the ORs and 95% confidence intervals (CIs). Generalized least squares and restricted cubic splines were used to explore the dose-response association. A total of 12 sets of results from 10 articles involving 427,453 participants were included in this meta-analysis. The pooled OR for increased risk of overweight or obesity was 1.30 in high-level antibiotic exposure (95% CI: 1.20 to 1.41) and 1.06 in low-level antibiotic exposure (95% CI: 1.02 to 1.10), as compared with children who never exposed to antibiotics. There was a logarithmic-curve relationship between early-life antibiotic exposure and the risk of subsequent overweight or obesity. The OR was 1.08 (95% CI: 1.06 to 1.11) for one prescription, 1.16 (95% CI 1.11 to 1.21) for two prescriptions, 1.24 (95% CI: 1.16 to 1.32) for three prescriptions, 1.30 (95% CI: 1.20 to 1.41) for four prescriptions, and less than a 5% increase for more prescriptions. Early-life antibiotic exposure is associated with the risk of childhood overweight or obesity in a dose-response manner. Further studies are needed to confirm our results.

Purpose: Although a significant proportion of type 2 diabetes mellitus (T2DM) cases arose from normal-weight individuals, studies on indicators that can predict T2DM in normal-weight people are limited. Accordingly, this study aims to investigate the predictive value of obesity indices and triglyceride glucose related parameters (TyG-related parameters) in T2DM among normal-weight Chinese elderly.Methods: A total of 24,215 normal-weight Chinese elderly (age ≥ 60 years) [body mass index--BMI (18.5-23.9 kg/m2)] were included. Obesity indices and triglyceride glucose related parameters (TyG-related parameters) included waist circumference (WC), waist-to-height ratio (WHtR), visceral adiposity index (VAI), lipid accumulation product (LAP), and TyG-related parameters (TyG, TyG-BMI, TyG-WC, and TyG-WHtR). Multivariate logistic regression analysis was performed to examine the associations between obesity-and TyG-related indices and T2DM. The areas under the curve (AUC) of the receiver-operating characteristic (ROC) curve analyses were used to evaluate and compare the predictive value of the different indices. Results: The prevalence of T2DM was 14.2% in normal-weight individuals. Among the indices, TyG was significantly associated with T2DM among men and women, respectively (adjusted odds ratio--aOR 19.005; 95% CI 13.235–27.291) and (aOR 25.262; 95% CI 16.957–37.634). Compared with other indices, TyG had the highest AUC value for T2DM in men (AUC: 0.818, 95% CI 0.810–0.825) and women (AUC: 0.824, 95% CI 0.814–0.833).Conclusions: TyG is an effective marker and outperforms than other indices when predicting T2DM in the normal-weight Chinese elderly population.Level of evidence: Level V

We realized a 101 W single-frequency continuous wave (CW) all-solid-state 1064 nm laser by means of mode self-reproduction in this Letter. Two identical laser crystals were placed into a resonator to relax the thermal lens of the laser crystals, and an imaging system was employed to realize cavity mode self-reproduced at the places of the laser crystals. Single-frequency operation of the resonator was realized by employing a new kind of high extinction ratio optical diode based on the terbium scandium aluminum garnet crystal to realize a stable unidirectional operation of the laser, together with introducing a large enough nonlinear loss to the resonator to effectively suppress the multi-mode oscillation and mode hopping of the laser. As a result, a 101 W single-frequency 1064 nm laser in a single-ring resonator was achieved with 42.3% optical efficiency. The measured power stability for 8 h and the beam quality were better than ±0.73% and 1.2, respectively.

The relationship between the longitudinal-mode structure (LMS) of the laser and the relative intensity noise (RIN) properties was investigated in this paper after an all-solid-state continuous-wave (CW) single-frequency 1064 nm laser with output power of 50.3 W was achieved. The LMS of the laser was manipulated by controlling the temperature of the deliberately introduced nonlinear lithium triborate (LBO) crystal in the resonator. When the laser worked with single-longitudinal-mode (SLM) operation, the stable RIN spectrum was observed and measured. Moreover, with the decrease of the nonlinear conversion efficiency (NCE), the frequency and amplitude of the resonant-relaxation oscillation (RRO) peak regularly shifted to the higher frequencies and increased, respectively. However, with further decrease of the NCE, the laser began to work with the multi-longitudinalmode (MLM) or mode-hopping operation and the unstable RIN spectra of the laser were both observed not only at low frequencies but also at high frequencies. Once the NCE was moved away, the MLM or mode-hopping can only enhance the fluctuation of the laser RIN spectrum below the frequency of RRO. The experimental results definitely revealed that the key to achieve a stable high power laser with low intensity noise was to realize single-frequency operation of the laser with free MLM and mode-hopping.

We presented a 125 W single-frequency continuous-wave (CW) 1064 nm laser, where a homemade 50.3 W single-frequency CW high quality Nd:YVO4 laser and a two-stage dual-end-pumped master-oscillator power amplifier (MOPA) acted as the seed source and amplifier, respectively. As a result, a maximum output power of 125.2 W was achieved with the incident pump power of 200 W. The optical-to-optical conversion efficiency and the overall amplified power gain were 43.3% and 3.28%, respectively. The measured beam quality M 2 and the long-term power stability of the 1064 nm amplifier during 8 h were better than 1.28 and ±0.73%, respectively. Additionally, the power extraction efficiency of the designed MOPA system was further investigated and the results revealed that the key of improvement of the power extraction efficiency of the MOPA system was employing a high-power single-frequency CW laser as the master oscillator.

The influence of the longitudinal-mode structure (LMS) of the laser on the relative intensity noise (RIN) properties was investigated in this paper after an all-solid-state continuous-wave (CW) single-frequency 1064 nm laser with output power of 50.3 W was achieved. The LMS of the laser was manipulated by controlling the temperature of the nonlinear lithium triborate (LBO) crystal deliberately introduced to the resonator. When the laser worked with single-longitudinal-mode (SLM) operation, the stable RIN spectrum was observed and measured. Moreover, with the decrease of the nonlinear conversion efficiency (NCE), the frequency and amplitude of the resonant-relaxation oscillation (RRO) peak regularly shifted to the higher frequencies and increased, respectively. However, with further decrease of the NCE, the laser began to work with the multi-longitudinal-mode (MLM) or mode-hopping operation and the unstable RIN spectra of the laser were both observed not only at low frequencies but also at high frequencies. Once the NCE was moved away, the MLM or mode-hopping can only enhance the fluctuation of the laser RIN spectrum at the low frequencies (lower than the frequency of RRO). The experimental results directly revealed the relationship between the LMS of the laser and the RIN spectra, and confirmed definitely that the key to achieve a stable high power laser with low intensity noise was to realize single-frequency operation of the laser with free MLM and mode-hopping.