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The objectives of this study were to investigate the interaction of mitochondrial DNA (mtDNA) and lifestyle factors in the development of psychiatric disorders and to gain greater insight into their pathogenesis and comorbidity. We analyzed data from approximately 150,000 individuals from the UK Biobank. Mitochondrial gene-by-environment interaction studies (mtGEIS) were performed to assess the relationships between mtDNA and psychiatric disorders, such as anxiety, depression, and self-harm. These disorders were defined using diagnostic and severity indicators derived from the General Anxiety Disorder (GAD-7) and Patient Health Questionnaire (PHQ-9). Smoking and drinking behaviors were characterized based on UK Biobank criteria. For the mtGEIS, logistic and linear regression models from PLINK 2.0 were employed, accounting for covariates like age, sex, PC1-10, Townsend Deprivation Index (TDI), and educational attainment. We also conducted sex-stratified analyses to detect any gender-specific effects. Our findings highlighted significant associations between mtDNA and three psychiatric disorders. Moreover, the interplay between mtDNA and lifestyle factors showed significant associations with psychiatric disorders (all P values < 0.05). Specifically, two mutant loci, T5004C ( B Anx _ self = − 0.0026 , B Dep _ self = − 0.0024 , B Self − harm = − 0.0018) and G9123A ( B Anx _ self = − 0.0030 , B Dep _ self = − 0.0024 , B Self − harm = − 0.0017), were found to reduce the risk of three disorders after interacting with alcohol. Sex-specific differences were also observed. In summary, the expression of mitochondrial genes could be modulated by lifestyle factors like smoking and drinking, potentially affecting psychiatric disorders. These habits might influence mitochondrial respiratory chain activity and the replication and transcriptional regulation of mitochondrial genes, culminating in changes in mitochondrial functionality and subsequently psychiatric disorders. [ABSTRACT FROM AUTHOR]

A bidirectional relationship between chronic pain (CP) and mental disorders has been reported, and coffee was believed to be associated with both. However, the association of coffee in this bidirectional relationship remains unclear. We aim to analyze the association of coffee consumption on the relationship of CP with depression and anxiety. A total of 376,813 participants from UK Biobank were included. We collected data on anxiety, depression and CP from objects of our study population. The association of coffee consumption on the relationship of CP with depression and anxiety was assessed through logistic/linear regression models. Moreover, seemingly unrelated estimation test (SUEST) was used to compare whether the coefficients differed in two different groups. We observed significant associations of coffee consumption in the interaction of CP with depression and anxiety, such as the association of multisite chronic pain (MCP) on self-reported depression (βcoffee = 0.421, βnon-coffee = 0.488, PSUEST = 0.001), and the association of MCP on generalized anxiety disorder-7 (GAD-7) scores (βcoffee = 0.561, βnon-coffee = 0.678, PSUEST = 0.004) were significantly different between coffee drinking and non-coffee drinking groups. Furthermore, in analysis stratified by gender, we found headache (βmale = 0.392, βfemale = 0.214, PSUEST = 0.022) and hip pain (βmale = 0.480, βfemale = 0.191, PSUEST = 0.021) had significant associations with self-reported depression between males and females groups in coffee drinkers. Our results suggested that coffee consumption has a significant association on the relationship of CP with depression and anxiety. [ABSTRACT FROM AUTHOR]

Immune dysregulation has been widely observed in patients with psychiatric disorders. This study aims to examine the association between HLA alleles and depression and anxiety. Using data from the UK Biobank, we performed regression analyses to assess the association of 359 HLA alleles with depression and anxiety, as determined by Patient Health Questionnaire (PHQ) score (n = 120,033), self‐reported depression (n = 121,685), general anxiety disorder (GAD‐7) score (n = 120,590), and self‐reported anxiety (n = 108,310). Subsequently, we conducted gene environmental interaction study (GEIS) to evaluate the potential effects of interactions between HLA alleles and environmental factors on the risk of depression and anxiety. Sex stratification was implemented in all analysis. Our study identified two significant HLA alleles associated with self‐reported depression, including HLA‐C*07:01 (β = −0.015, p = 5.54 × 10−5) and HLA‐B*08:01 (β = −0.015, p = 7.78 × 10−5). Additionally, we identified four significant HLA alleles associated with anxiety score, such as HLA‐DRB1*07:01 (β = 0.084, p = 9.28 × 10−5) and HLA‐B*57:01 (β = 0.139, p = 1.22 × 10−4). GEIS revealed that certain HLA alleles interacted with environmental factors to influence mental health outcomes. For instance, HLA‐A*02:07 × cigarette smoking was associated with depression score (β = 0.976, p = 1.88 × 10−6). Moreover, sex stratification analysis revealed significant sex‐based differences in the interaction effects of certain HLA alleles with environmental factors. Our findings indicate the considerable impact of HLA alleles on the risks of depression and anxiety, providing valuable insights into the functional relevance of immune dysfunction in these conditions. [ABSTRACT FROM AUTHOR]

Metamaterials with multiple resonators have been widely investigated for the purpose of generating multiple stop bands or broadening the attenuation bandwidth. The multiple resonators could be connected end to end in a line, namely, in-series connection, or connected individually to the host structures, namely, in-parallel connection. This paper investigates the influence of the resonator connection methodology on the frequency response functions of metamaterial beams with multiple resonators and exhibits an approach for optimizing their resonator distribution over the structure. The receptance functions of metamaterial beams with various resonator connection architectures are calculated by a transfer matrix model, which is verified through finite element model results. It is demonstrated that resonator interconnection architectures have a great impact on the global dynamic properties of metamaterials. An optimization strategy is subsequently proposed to find out the optimal resonator connection architectures and mass distributions that could minimize the maximal receptance functions in targeted single and multiple frequency ranges. The objective functions within single targeted frequency ranges are solved by the adoption of the genetic algorithm method. The weighted sum method is used to gain an optimal solution for multi-frequency range optimization. The metamaterial beams with optimal resonator connection methods and mass distributions demonstrate greatly enhanced vibration attenuation at frequencies of interest compared with other beams. The work is expected to provide the necessary theoretical basis and incentive for future researchers working on the design of metamaterials with extended, tuned, and optimized stop bands. [ABSTRACT FROM AUTHOR]

In order to establish the joint interface elements more quickly, and to analyze the dynamic characteristics of machine tools under different states (such as headstock at different position), the CAD model of machine tool must be divided effectively, so that the hexahedron elements with specified size can be generated in the area of the joint interfaces, so that the nodes on the joint surfaces can be coincident. Using APDL technology, the linear spring-damped elements are quickly established on the fixed joint (bolt joint interface between the bed and base) and the moving joint (guideway-slider, screw-nut). The experimental and simulation results show that the method is effective.It has considerable accuracy, and can greatly speed up the machine tool modeling, especially the processing speed of the joint interfaces.

The dynamics of tilting table behaves differently during five-axis machining due to the constant changes of the position of its center of mass which leads to different forces acting on parts of the transmission system. In this research, the lumped parameter method is used to model the dynamics of tilting table driven by worm and worm wheel in the tilting direction, where the varying stiffness of the transmission system at different tilting angles is considered. The impact testing experiments of tilting table system with tilting angles from 0° to 90° are also performed to verify the analytical model. The results from sensitivity analysis show that the three stiffnesses have a great effect on the variation of system natural frequency in the tilting direction, including the equivalent tangential meshing stiffness of worm and worm wheel, the torsional stiffness of worm wheel shaft, and the axial stiffness of worm supporting bearings. Moreover, the variations of system natural frequency with the three stiffnesses at different tilting angles are further investigated. [ABSTRACT FROM AUTHOR]

Intelligence quotient is a vital index to evaluate the ability of an individual to think rationally, learn from experience and deal with the environment effectively. However, limited efforts have been paid to explore the potential associations of intelligence quotient traits with the tissue proteins from the brain, CSF and plasma. The information of protein quantitative trait loci was collected from a recently released genome-wide association study conducted on quantification data of proteins from the tissues including the brain, CSF and plasma. Using the individual-level genotypic data from the UK Biobank cohort, we calculated the polygenic risk scores for each protein based on the protein quantitative trait locus data sets above. Then, Pearson correlation analysis was applied to evaluate the relationships between intelligence quotient traits (including 120 330 subjects for 'fluid intelligence score' and 38 949 subjects for 'maximum digits remembered correctly') and polygenic risk scores of each protein in the brain (17 protein polygenic risk scores), CSF (116 protein polygenic risk scores) and plasma (59 protein polygenic risk scores). The Bonferroni corrected P -value threshold was P < 1.30 × 10 -4 (0.05/384). Finally, Mendelian randomization analysis was conducted to test the causal relationships between 'fluid intelligence score' and pre-specific proteins from correlation analysis results. Pearson correlation analysis identified significant association signals between the protein of macrophage-stimulating protein and fluid intelligence in brain and CSF tissues ( P brain = 1.21 × 10 -8 , P CSF = 1.10 × 10 -7 ), as well as between B-cell lymphoma 6 protein and fluid intelligence in CSF ( P CSF = 1.23 × 10 -4 ). Other proteins showed close-to-significant associations with the trait of 'fluid intelligence score', such as plasma protease C1 inhibitor ( P CSF = 4.19 × 10 -4 , P plasma = 6.97 × 10 -4 ), and with the trait of 'maximum digits remembered correctly', such as tenascin ( P plasma = 3.42 × 10 -4 ). Additionally, Mendelian randomization analysis results suggested that macrophage-stimulating protein (Mendelian randomization-Egger: β = 0.54, P = 1.64 × 10 -61 in the brain; β = 0.09, P = 1.60 × 10 -12 in CSF) had causal effects on fluid intelligence score. We observed functional relevance of specific tissue proteins to intelligence quotient and identified several candidate proteins, such as macrophage-stimulating protein. This study provided a novel insight to the relationship between tissue proteins and intelligence quotient traits., Competing Interests: The authors report no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Aims: To assess the alterations in cell-specific DNA methylation associated with chondroitin sulphate response using peripheral blood collected from Kashin-Beck disease (KBD) patients before initiation of chondroitin sulphate treatment., Methods: Peripheral blood samples were collected from KBD patients at baseline of chondroitin sulphate treatment. Methylation profiles were generated using reduced representation bisulphite sequencing (RRBS) from peripheral blood. Differentially methylated regions (DMRs) were identified using MethylKit, while DMR-related genes were defined as those annotated to the gene body or 2.2-kilobase upstream regions of DMRs. Selected DMR-related genes were further validated by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) to assess expression levels. Tensor composition analysis was performed to identify cell-specific differential DNA methylation from bulk tissue., Results: This study revealed 21,060 hypermethylated and 44,472 hypomethylated DMRs, and 13,194 hypermethylated and 22,448 hypomethylated CpG islands for differential global methylation for chondroitin sulphate treatment response. A total of 12,666 DMR-related genes containing DMRs were identified in their promoter regions, such as CHL1 (false discovery rate (FDR) = 2.11 × 10 -11 ), RIC8A (FDR = 7.05 × 10 -4 ), and SOX12 (FDR = 1.43 × 10 -3 ). Additionally, RIC8A and CHL1 were hypermethylated in responders, while SOX12 was hypomethylated in responders, all showing decreased gene expression. The patterns of cell-specific differential global methylation associated with chondroitin sulphate response were observed. Specifically, we found that DMRs located in TESPA1 and ATP11A exhibited differential DNA methylation between responders and non-responders in granulocytes, monocytes, and B cells., Conclusion: Our study identified cell-specific changes in DNA methylation associated with chondroitin sulphate response in KBD patients., Competing Interests: B. Cheng reports grants from Fundamental Research Funds for the Central Universities (xzy012023092) and the National Natural Science Foundation of China (82304265), related to this study., (© 2024 Cheng et al.)

Aim: Few previous studies have investigated the impact of multiple types of electronic devices on health status, and the moderating effects of gender, age, and BMI. Our aim is to examine the relationships between the use of four types of electronics and three health status indicators in a middle-aged and elderly population, and how these relationships varied by gender, age, and BMI., Subject and Methods: Using data from 376,806 participants aged 40-69 years in the UK Biobank, we conducted a multivariate linear regression to estimate the association between electronic device use and health status. Electronics use was categorized as TV watching, computer use, computer gaming, and mobile phone use, and health status included self-rated health (SRH), multisite chronic pain (MCP), and total physical activity (TPA). Interaction terms were utilized to assess whether the above associations were modified by BMI, gender, and age. Further stratified analysis was performed to explore the role of gender, age, and BMI., Results: Higher levels of TV watching (B SRH = 0.056, B MCP = 0.044, B TPA = -1.795), computer use (B SRH = 0.007, B TPA = -3.469), and computer gaming (B SRH = 0.055, B MCP = 0.058, B TPA = -6.076) were consistently associated with poorer health status (all P < 0.05). Contrastingly, earlier exposure to mobile phones (B SRH = -0.048, B TPA = 0.933, B MCP = 0.056) was inconsistent with health (all P < 0.05). Additionally, BMI (B computer use-SRH = 0.0026, B phone-SRH = 0.0049, B TV-MCP = 0.0031, and B TV-TPA = -0.0584) exacerbated the negative effects of electronics use, and male (B phone-SRH = -0.0414, B phone-MCP = -0.0537, B phone-TPA = 2.8873) were healthier with earlier exposure to mobile phones (all P < 0.05)., Conclusion: Our findings suggest that the adverse health effects associated with watching TV, computer use, and computer gaming were consistent and were moderated by BMI, gender, and age, which advances a comprehensive understanding of the association between multiple types of electronic devices and health status, and provides new perspectives for future research., Supplementary Information: The online version contains supplementary material available at 10.1007/s10389-023-01886-5., Competing Interests: Competing interestsThe authors report no financial interests or potential conflicts of interest., (© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Objective To investigate the effect of silencing of SOX9 gene on the apoptosis of laryngeal squamous cell carcinoma cells induced by As 2 O 3 . Methods The SOX9 specific siRNA (si-SOX9) was transfected into human laryngeal carcinoma Hep-2 cells, and Western blotting was used to detect the expression of SOX9 protein after cells were transfected for 48 hours. Hep-2 cells were randoimly divided into 4 treatment groups, namely, blank group, si-SOX9 group, As 2 O 3 group and si-SOX9 combined with As 2 O 3 group. The cells in all groups were treated for 48 hours, MTT assay was used to detect the proliferation of Hep-2 cells; flow cytometry was used to detect the apoptosis rate; ROS kit was used to detect the ROS content; Western blotting was used to detect the expression of proliferating cell nuclear antigen(PCNA), BAX, vascular endothelial growth factor(VEGF), phospoinositide 3-kinase(PI3K) and phosphorylated AKT(p-AKT) proteins. Results After transfection of si-SOX9, the level of SOX9 protein in Hep-2 cells was significantly reduced. The cell viability and the expression of PCNA, VEGF, PI3K and p-AKT in si-SOX9 group and As 2 O 3 group were significantly lower than that in the blank group, the apoptosis rate, the content of ROS and the expression of BAX protein were significantly higher than that in the blank group, while the cell viability and the expression of PCNA, VEGF, PI3K and p-AKT in the si-SOX9 combined with As 2 O 3 group were significantly lower than that in si-SOX9 group and As 2 O 3 group, the apoptosis rate, ROS content and BAX protein expression in the si-SOX9 ombined with As 2 O 3 group were significantly higher than that in si-SOX9 group and As 2 O 3 group. Conclusion silencing SOX9 gene expression enhances apoptosis of laryngeal squamous cell carcinoma cells induced by As 2 O 3 , which is related to increasing the intacellular ROS content and down-regulating the PI3K/AKT signaling pathway.