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Sleep is a natural and essential physiological need for individuals. Our study aimed to research the associations between accumulated social risks and sleep disorders.

ABSTRACTBackgroundA 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.MethodsA 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.ResultsWe 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.ConclusionsOur results suggested that coffee consumption has a significant association on the relationship of CP with depression and anxiety.

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 (BSRH= 0.056, BMCP= 0.044, BTPA= −1.795), computer use (BSRH= 0.007, BTPA= −3.469), and computer gaming (BSRH= 0.055, BMCP= 0.058, BTPA= −6.076) were consistently associated with poorer health status (all P< 0.05). Contrastingly, earlier exposure to mobile phones (BSRH= −0.048, BTPA= 0.933, BMCP= 0.056) was inconsistent with health (all P< 0.05). Additionally, BMI (Bcomputer use-SRH= 0.0026, Bphone-SRH= 0.0049, BTV-MCP= 0.0031, and BTV-TPA= −0.0584) exacerbated the negative effects of electronics use, and male (Bphone-SRH= −0.0414, Bphone-MCP= −0.0537, Bphone-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.

A network of microchannels is formed at the interface between the cutting tool and the workpiece during machining due to their rough surface structures. The penetration of coolant into these microchannels has a great effect on the machined surface quality by changing the frictional behaviour and heat transfer characteristics of the interfaces. Most of the present studies focus on the macroscopic coolant delivery process but the mechanism of the microscopic penetration phenomena in the channels at the interface remains unclear. Thus, this study proposes a multi-scale and multi-phase comprehensive theoretical model by combining the machining process, coolant flowing in microchannels and lubrication process, to analyse the coolant transportation in the microchannels and investigate its lubrication effects and the friction mechanisms at the interface between the tool and the workpiece. Then, an orthogonal turning testing of Inconel 718 is designed to verify the proposed model. The cooling and lubrication effect of coolant in the microchannels on the reduction of tool wear, contact length, cutting force and temperature has been demonstrated. And the improvement of chip fragment and microstructure has also been revealed.

BRCA1 deficiencies cause breast, ovarian, prostate and other cancers, and render tumours hypersensitive to poly(ADP-ribose) polymerase (PARP) inhibitors. To understand the resistance mechanisms, we conducted whole-genome CRISPR–Cas9 synthetic-viability/resistance screens in BRCA1-deficient breast cancer cells treated with PARP inhibitors. We identified two previously uncharacterized proteins, C20orf196 and FAM35A, whose inactivation confers strong PARP-inhibitor resistance. Mechanistically, we show that C20orf196 and FAM35A form a complex, ‘Shieldin’ (SHLD1/2), with FAM35A interacting with single-stranded DNA through its C-terminal oligonucleotide/oligosaccharide-binding fold region. We establish that Shieldin acts as the downstream effector of 53BP1/RIF1/MAD2L2 to promote DNA double-strand break (DSB) end-joining by restricting DSB resection and to counteract homologous recombination by antagonizing BRCA2/RAD51 loading in BRCA1-deficient cells. Notably, Shieldin inactivation further sensitizes BRCA1-deficient cells to cisplatin, suggesting how defining the SHLD1/2 status of BRCA1-deficient tumours might aid patient stratification and yield new treatment opportunities. Highlighting this potential, we document reduced SHLD1/2 expression in human breast cancers displaying intrinsic or acquired PARP-inhibitor resistance. Through CRISPR–Cas9 screen, Dev et al. identified that SHLD1/2 inhibition contributes to PARP-inhibitor resistance. Mechanistically, SHLDs promote non-homologous end-joining and antagonize homologous recombination.

Gut microbiome and inflammatory bowel disease (IBD) are implicated in the development of depression, but the effect of their interactions on the risk of depression remains unclear. We aim to analyze the effect of interactions between gut microbiome and IBD on the risk of depression, and explore candidate genes involving the interactions.

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.