An novel effective and safe model for the diagnosis of nonalcoholic fatty liver disease in China: gene excavations, clinical validations, and mechanism elucidation.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases. NAFLD leads to liver fibrosis and hepatocellular carcinoma, and it also has systemic effects associated with metabolic diseases, cardiovascular diseases, chronic kidney disease, and malignant tumors. Therefore, it is important to diagnose NAFLD early to prevent these adverse effects. METHODS: The GSE89632 dataset was downloaded from the Gene Expression Omnibus database, and then the optimal genes were screened from the data cohort using lasso and Support Vector Machine Recursive Feature Elimination (SVM-RFE). The ROC values of the optimal genes for the diagnosis of NAFLD were calculated. The relationship between optimal genes and immune cells was determined using the DECONVOLUTION algorithm CIBERSORT. Finally, the specificity and sensitivity of the diagnostic genes were verified by detecting the expression of the diagnostic genes in blood samples from 320 NAFLD patients and liver samples from 12 mice. RESULTS: Through machine learning we identified FOSB, GPAT3, RGCC and RNF43 were the key diagnostic genes for NAFLD, and they were further demonstrated by a receiver operating characteristic curve analysis. We found that the combined diagnosis of the four genes identified NAFLD samples well from normal samples (AUC = 0.997). FOSB, GPAT3, RGCC and RNF43 were strongly associated with immune cell infiltration. We also experimentally examined the expression of these genes in NAFLD patients and NAFLD mice, and the results showed that these genes are highly specific and sensitive. CONCLUSIONS: Data from both clinical and animal studies demonstrate the high sensitivity, specificity and safety of FOSB, GPAT3, RGCC and RNF43 for the diagnosis of NAFLD. The relationship between diagnostic key genes and immune cell infiltration may help to understand the development of NAFLD. The study was reviewed and approved by Ethics Committee of Tianjin Second People's Hospital in 2021 (ChiCTR1900024415).

Visible light sensing based on shadow features using multi-scale region convolutional neural network.

There are various production items in the industrial internet of things (IIoT) environment, such as pedestrians, robots, automated automated guided vehicles, etc. The practice industrial environment requires simultaneous communication and sensing of production items to achieve intelligent production and control. Thus, sensing methods not only require the integration of communication but also achieve sensing tasks such as recognition and positioning. Compared with traditional sensing media, visible light sensing has the advantages of high-speed communication, high sensing accuracy, and security, low energy consumption, and has become a potential sensing technology. Based on the strong directivity of visible light spatial radiation and the consistency of light intensity and position, this paper proposes a multi-scale visible light sensing-region convolutional neural network (VLS-RCNN) framework based on shadow features for multiple target sensing. The framework enables the recognition and positioning to use shared visible light shadow features to assist each other, and the multi-scale compensation strategy of the shadow region makes the framework more robust. The simulation results show that positioning results in the sensing area improve the recognition accuracy. The recognition results also reduce the positioning error without additional overhead. Therefore, this paper provides a new perspective for the sensing technology in the future IIoT, which should be considered to sense objects of interest by utilizing the inherent characteristics of visible light.

Association of impaired lung function with dementia, and brain magnetic resonance imaging indices: a large population-based longitudinal study.

OBJECTIVE: to examine the association between different patterns of impaired lung function with the incident risk of dementia and magnetic resonance imaging (MRI)-based brain structural features. METHODS: in UK Biobank, a total of 308,534 dementia-free participants with valid lung function measures (forced expiratory volume in 1 s [FEV1] and forced vital capacity [FVC]) were included. Association was assessed using Cox proportional hazards regression model. Furthermore, the association between impaired lung function and brain MRI biomarkers related to cognitive function was analysed among 30,159 participants. RESULTS: during a median follow-up of 12.6 years, 3,607 incident all-cause dementia cases were recorded. Restrictive impairment (hazard ratio [HR], 1.42; 95% confidence interval [CI], 1.27-1.60) and obstructive impairment (HR, 1.28; 95% CI, 1.15-1.42) were associated with higher risk of all-cause dementia. The restricted cubic splines indicated FEV1% predicted and FVC % predicted had reversed J-shaped associations with dementia. Participants with impaired lung function have higher risks of all-cause dementia across all apolipoprotein E (APOE) risk categories, whereas associations were stronger among those of low APOE risk (P for interaction = 0.034). In addition, restrictive and obstructive impairment were linked to lower total (ß: -0.075, SE: 0.021, Pfdr = 0.002; ß: -0.033, SE: 0.017, Pfdr = 0.069) and frontoparietal grey matter volumes, higher white matter hyperintensity, poorer white matter integrity, lower hippocampus (ß: -0.066, SE: 0.024, Pfdr = 0.017; ß: -0.051, SE: 0.019, Pfdr = 0.019) and other subcortical volumes. CONCLUSIONS: participants with restrictive and obstructive impairments had a higher risk of dementia. Brain MRI indices further supported adverse effects and provided insight into potential pathophysiology biomarkers.

Detection of Experimental and Clinical Immune Complexes by Measuring SHIP-1 Recruitment to the Inhibitory FcγRIIB.

Fc γ receptors (FcγR) are involved in multiple aspects of immune cell regulation, are central to the success of mAb therapeutics, and underpin the pathology of several autoimmune diseases. However, reliable assays capable of accurately measuring FcγR interactions with their physiological ligands, IgG immune complexes (IC), are limited. A method to study and detect IC interactions with FcγRs was therefore developed. This method, designed to model the signaling pathway of the inhibitory FcγRIIB (CD32B), used NanoLuc Binary Interaction Technology to measure recruitment of the Src homology 2 domain-containing inositol phosphatase 1 to the ITIM of this receptor. Such recruitment required prior cross-linking of an ITAM-containing activatory receptor, and evoked luciferase activity in discrete clusters at the cell surface, recapitulating the known biology of CD32B signaling. The assay detected varying forms of experimental IC, including heat-aggregated IgG, rituximab-anti-idiotype complexes, and anti-trinitrophenol-trinitrophenol complexes in a sensitive manner (≤1 µg/ml), and discriminated between complexes of varying size and isotype. Proof-of-concept for the detection of circulating ICs in autoimmune disease was provided, as responses to sera from patients with systemic lupus erythematosus and rheumatoid arthritis were detected in small pilot studies. Finally, the method was translated to a stable cell line system. In conclusion, a rapid and robust method for the detection of IC was developed, which has numerous potential applications including the monitoring of IC in autoimmune diseases and the study of underlying FcγR biology.

Effect of chip spacing on light extraction for light-emitting diode array.

GaN LED array in packaging is important for the demand of high optical flux. In order to tighten the whole packaging size, the spacing among LED chips becomes an important factor in the packaging design. This study is to investigate the change of the light extraction when a GaN LED chip array packaging is applied. The shielding effect with various spacing for the GaN LED array with or without silicon encapsulation is obtained. We apply the Monte Carlo ray-tracing method in the simulations to analyze the optical behavior of the two major types of the GaN LED array. The shielding effect is more dominant for bare chip packaging. When a silicone thin dispensing layer is applied, the shielding effect is not obvious because of more light extraction, the neighbor dies play an important role in photon recycling.

Antioxidative responses in zebrafish liver exposed to sublethal doses Aphanizomenon flos-aquae DC-1 aphantoxins.

Aphanizomenon flos-aquae secretes paralytic shellfish poisons (PSPs), termed aphantoxins, and endangers environmental and human health via eutrophication of water worldwide. Although the molecular mechanism of neuronal PSP toxicity has been well studied, several issues remain unresolved, notably the in vivo hepatic antioxidative responses to this neurotoxin. Aphantoxins extracted from a natural isolate of A. flos-aquae DC-1 were resolved by high performance liquid chromatography. The primary components were gonyautoxins 1 and 5 and neosaxitoxin. Zebrafish (Danio rerio) were treated intraperitoneally with either 5.3 or 7.61 (low and high doses, respectively) µg saxitoxin (STX) equivalents (eq)/kg of A. flos-aquae DC-1 aphantoxins. Antioxidative responses in zebrafish liver were examined at different timepoints 1-24h post-exposure. Aphantoxin administration significantly enhanced hepatic malondialdehyde (MDA) content 1-12h post-exposure, indicative of oxidative stress and lipid peroxidation. By contrast, levels of reduced glutathione (GSH) in zebrafish liver declined significantly after 3-24h exposure, suggesting that GSH participates in MDA metabolism. A significant upregulation of the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) was observed, suggesting that aphantoxins induce lipid peroxidation in zebrafish liver and are likely to be hepatotoxic. Hepatic levels of MDA and GSH, and of the three enzymes (SOD, CAT, and GPx), therefore provide potential biomarkers for studying environmental exposure to aphantoxins/PSPs from cyanobacterial blooms.

A comprehensive method for the conservation of mouse strains combining natural breeding, sperm cryopreservation and assisted reproductive technology.

The maintenance and preservation of strains of mice used in biomedical research presents a unique challenge to individual investigators and research institutions. The goal of this study was to assess a comprehensive system for mouse strain conservation through a combination of natural mating, sperm cryopreservation and assisted reproductive technology. Our strategy was based on the collection and cryopreservation of fresh epididymal sperm from male mice by semi-vasectomy; these mice were then naturally mated for breeding purposes. If no satisfactory results were obtained from natural breeding, then the cryopreserved sperm were used for in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI); resultant embryos were then transferred into pseudopregnant-recipient female mice. Our results show that some semi-vasectomized mouse strains can be conserved by natural breeding, and that sterile males can be compensated for through the use of IVF and ICSI technology. As such, we believe this system is suitable for the purpose of strain conservation, allowing the continuation of natural breeding with the safeguard of assisted reproduction available.

Differences in chimera formation and germline transmission between E14 and C2J embryonic stem cells in mice.

Summary The goal of this project was to determine whether the originating strain of mouse embryonic stem (ES) cells affects the maintenance of their pluripotency under uniform culture conditions. ES cells from two strains of mice, E14 and C2J, were tested. Both ES cell lines were cultured in KOSR + 2i medium and then injected into C57BL/6J blastocysts. Our results demonstrate that this medium could support both E14 and C2J ES cells to keep their pluripotency, though E14 ES cells were found to have a higher chimeric rate than C2J ES cells. However, analysis by backcrossing revealed that C2J and E14 ES cells have the same ability for germline transmission. Our results demonstrate that ES cells derived from E14 and C2J cells have the same capacity for germline transmission when injected into C57BL/6J blastocysts; however, due to the limitation of mixed genetic background between E14 cells and host C57BL/6J embryos, C2J ES cells are preferable to E14 ES cells for use in gene-targeting and should become the cell line of choice for the generation of genetically engineered mutant mouse lines.

Olfactory preference of the litchi fruit borer for oviposition on two litchi varieties.

BACKGROUND: The litchi fruit borer Conopomorpha sinensis Bradley is a major destructive pest of litchi and longan plants in China, India and South East Asia. Given its strong olfactory-based oviposition behaviour, interfering with the chemical communication between this insect pest and its host plant may serve as a potential control strategy. However, the chemical compounds associated with its egg-laying behaviour remain poorly understood. RESULTS: In this study, we investigated the olfactory preference of female C. sinensis for oviposition on intact mature fruits of the Feizixiao (FZX) and Guiwei (GW) varieties. Results showed that female C. sinensis preferred to lay eggs on FZX compared with GW fruits, and this preference was olfactory-induced. In addition, we identified differences in the chemical composition of the volatile blend and proportions between FZX and GW fruits, with terpenes being the main volatile components contributing to this divergence. Compounds that induced electrophysiological activity in female borers were subsequently screened from FZX. d-Limonene exhibited the strongest oviposition attraction among four candidates. Furthermore, this compound served as a volatile olfactory cue for recognition and orientation in female C. sinensis. CONCLUSION: The results of this study provide a deeper understanding of the olfactory preferences of female C. sinensis for oviposition on specific litchi varieties. © 2024 Society of Chemical Industry.

Advantages of diapause in Anastatus japonicus Ashmead mass production on eggs of the Chinese oak silkworm, Antheraea pernyi.

BACKGROUND: Anastatus japonicus Ashmead, a biological control agent utilized in China to control fruit bugs and forest caterpillars, is efficiently raised on large Chinese oak silkworm (Antheraea pernyi) eggs. Here, we investigated the biological parameters of non-diapaused and diapaused Anastatus japonicus after long-term storage within eggs of the host, Antheraea pernyi, under laboratory conditions. RESULTS: Diapaused mature larvae of Anastatus japonicus were more cold-tolerant than non-diapaused mature larvae, as reflected by a lower supercoiling point, lower freezing point, and higher survival rate at cold temperatures. Diapause induction enhanced the lifespan, fecundity and oviposition period of Anastatus japonicus than non-diapaused Anastatus japonicus when refrigerated for 6 months. However, after 12 months of refrigeration, the fecundity and oviposition period of Anastatus japonicus were significantly reduced with and without diapause. No difference in the progeny sex ratio of Anastatus japonicus was observed between diapause-induction treatment and those of non-diapaused. With the extension of refrigeration period from 6 months to 12 months, the lifespan, fecundity and oviposition period of Anastatus japonicus which were treated with diapause induction showed a sharp decrease. No significantly difference in the lifespan, fecundity and oviposition period of Anastatus japonicus was observed between diapause-induction treatment and those of non-diapaused when refrigerated for 12 months. CONCLUSION: These results suggest that the induction of diapause is an applicable technique to achieve mass production of Anastatus japonicus in long-term storage using eggs of the factitious host Antheraea pernyi, without compromising the quality of the parasitoid. The refrigeration period of diapaused Anastatus japonicus should not exceed 6 months. © 2023 Society of Chemical Industry.

Consumption of sugary beverages, genetic predisposition and the risk of depression: a prospective cohort study.

Background: The associations between sugary beverages and genetic predisposition to depression risk remain unclear. Aims: This study aimed to investigate the associations of sugar-sweetened beverages (SSBs), artificially sweetened beverages (ASBs) and natural juices (NJs) with depression and to assess whether these associations were modified by genetic predisposition. Methods: We used data from the UK Biobank of 180 599 individuals aged 39-72 years who were depression-free at baseline. Dietary intake of SSBs, ASBs and NJs was accessed by a 24-hour dietary recall between 2009 and 2012. The Polygenic Risk Score for depression was estimated and categorised as low (lowest tertile), intermediate (tertile 2) and high (highest tertile). Cox proportional hazard and substitution models were conducted to evaluate hazard ratios (HRs) and 95% CIs. Results: Over the 12-year follow-up, 4915 individuals developed depression. Higher consumption (>2 units/day) of SSBs (HR: 1.26, 95% CI 1.12 to 1.43) and ASBs (HR: 1.40, 95% CI 1.23 to 1.60) were both associated with an increased risk of depression. However, moderate consumption (>0-1 units/day) of NJs was associated with a lower risk of depression (HR: 0.89, 95% CI 0.83 to 0.95). Furthermore, genetic predisposition did not modify these associations (p interaction>0.05). In substitution models, the HRs for depression risk were 0.94 (95% CI 0.89 to 0.99) and 0.89 (95% CI 0.85 to 0.94), respectively, when 1 unit/day of SSBs or ASBs was replaced by an equivalent intake of NJs. Conclusions: Higher consumption of SSBs and ASBs was associated with an increased risk of depression; in contrast, moderate consumption of NJs was inversely associated with a lower risk of depression. In theory, substituting SSBs and ASBs with NJs would suppose a reduction of depression risk.

Associations of environmental factors with neurodegeneration: An exposome-wide Mendelian randomization investigation.

Neurodegenerative diseases (NDDs) remain a global health challenge. Previous studies have reported potential links between environmental factors and NDDs, however, findings remain controversial across studies and elusive to be interpreted as evidence of robust causal associations. In this study, we comprehensively explored the causal associations of the common environmental factors with major NDDs including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS), based on updated large-scale genome-wide association study data through two-sample Mendelian randomization (MR) approach. Our results indicated that, overall, 28 significant sets of exposure-outcome causal association evidence were detected, 12 of which were previously underestimated and newly identified, including average weekly beer plus cider intake, strenuous sports or other exercises, diastolic blood pressure, and body fat percentage with AD, alcohol intake frequency with PD, apolipoprotein B, systolic blood pressure, and forced expiratory volume in 1 s (FEV1) with ALS, and alcohol intake frequency, hip circumference, forced vital capacity, and FEV1 with MS. Moreover, the causal effects of several environmental factors on NDDs were found to overlap. From a triangulation perspective, our investigation provided insights into understanding the associations of environmental factors with NDDs, providing causality-oriented evidence to establish the risk profile of NDDs.

Artificial-intelligence-based risk prediction and mechanism discovery for atrial fibrillation using heart beat-to-beat intervals.

BACKGROUND: Early diagnosis of atrial fibrillation (AF) is important for preventing stroke and other complications. Predicting AF risk in advance can improve early diagnostic efficiency. Deep learning has been used for disease risk prediction; however, it lacks adherence to evidence-based medicine standards. Identifying the underlying mechanisms behind disease risk prediction is important and required. METHODS: We developed an explainable deep learning model called HBBI-AI to predict AF risk using only heart beat-to-beat intervals (HBBIs) during sinus rhythm. We proposed a possible AF mechanism based on the model's explainability and verified this conjecture using confirmed AF risk factors while also examining new AF risk factors. Finally, we investigated the changes in clinicians' ability to predict AF risk using only HBBIs before and after learning the model's explainability. FINDINGS: HBBI-AI consistently performed well across large in-house and external public datasets. HBBIs with large changes or extreme stability were critical predictors for increased AF risk, and the underlying cause was autonomic imbalance. We verified various AF risk factors and discovered that autonomic imbalance was associated with all these factors. Finally, cardiologists effectively understood and learned from these findings to improve their abilities in AF risk prediction. CONCLUSIONS: HBBI-AI effectively predicted AF risk using only HBBI information through evaluating autonomic imbalance. Autonomic imbalance may play an important role in many risk factors of AF rather than in a limited number of risk factors. FUNDING: This study was supported in part by the National Key R&D Program and the National Natural Science Foundation of China.

Microtubule organisation, pronuclear formation and embryonic development of mouse oocytes after intracytoplasmic sperm injection or parthenogenetic activation and then slow-freezing with 1, 2-propanediol.

The goal of this study was to investigate the effect of cryopreservation on oocytes at different times after intracytoplasmic sperm injection (ICSI) and parthenogenetic activation. The study was performed in mouse oocytes fertilised by ICSI, or in artificially-activated oocytes, which were cryopreserved immediately, one hour or five hours later through slow-freezing. After thawing, the rates of survival, fertilisation-activation, embryonic development of oocytes-zygotes and changes in the cytoskeleton and ploidy were observed. Our results reveal a significant difference in survival rates of 0-, 1- and 5-h cryopreserved oocytes following ICSI and artificial activation. Moreover, significant differences in two pronuclei (PN) development existed between the 0-, 1- and 5-h groups of oocytes frozen after ICSI, while the rates of two-PN development of activated oocytes were different between the 1-h and 5-h groups. Despite these initial differences, there was no difference in the rate of blastocyst formation from two-PN zygotes following ICSI or artificial activation. However, compared with ICSI or artificially-activated oocytes cryopreserved at 5h, many oocytes from the 0- and 1-h cryopreservation groups developed to zygotes with abnormal ploidy; this suggests that too little time before cryopreservation can result in some activated oocytes forming abnormal ploidy. However, our results also demonstrate that spermatozoa can maintain normal fertilisation capacity in frozen ICSI oocytes and the procedure of freeze-thawing did not affect the later development of zygotes.

Evaluation of predation abilities of Blattisocius dolichus (Acari: Blattisociidae) on a plant-parasitic nematode, Radopholus similis (Tylenchida: Pratylenchidae).

Predation and predatory behavior of Blattisocius dolichus on Radopholus similis were tested both in experimental arenas and on potted plants. Predation occurred in all active stages of B. dolichus. Blattisocius dolichus preferred live R. similis when offered together with Caneorhabditis elegans and dead R. similis in a choice test. Consumption rate was affected by temperature, prey density and duration of starvation. Maximum consumption rates were observed at 25 °C, for both adult males and females after being starved for 96 and 72 h, respectively. Consumption rate increased with increasing prey density until satiation was reached, when the predator-prey ratio was 1:250 for both male and female predators. Anthurium andraeanum seedlings, artificially infested with R. similis (1,000 per pot), were used to evaluate the biological control efficiency of B. dolichus. The nematode density decreased by 66 % 10 days after a release of 500 mites per pot.

Acupuncture Therapy on Dementia: Explained with an Integrated Analysis on Therapeutic Targets and Associated Mechanisms.

BACKGROUND: Dementia, mainly Alzheimer's disease (AD) and vascular dementia (VaD), remains a global health challenge. Previous studies have demonstrated the benefits of acupuncture therapy (AT) in improving dementia. Nevertheless, the therapeutic targets and integrated biological mechanisms involved remain ambiguous. OBJECTIVE: To identify therapeutic targets and biological mechanisms of AT in treating dementia by integrated analysis strategy. METHODS: By the identification of differentially expressed genes (DEGs) of AD, VaD, and molecular targets of AT active components, the acupuncture therapeutic targets associated with the biological response to AD and VaD were extracted. Therapeutic targets-based functional enrichment analysis was conducted, and multiple networks were constructed. AT-therapeutic crucial targets were captured by weighted gene co-expression network analysis (WGCNA). The interactions between crucial targets with AT active components were verified by molecular docking. RESULTS: Our results demonstrated that 132 and 76 acupuncture therapeutic targets were associated with AD and VaD. AT-therapeutic crucial targets including 58 for AD and 24 for VaD were captured by WGCNA, with 11 in shared, including NMU, GRP, TAC1, ADRA1D, and SST. In addition, 35 and 14 signaling pathways were significantly enriched by functional enrichment analysis, with 6 mutual pathways including neuroactive ligand-receptor interaction, GABAergic synapse, calcium signaling pathway, cAMP signaling pathway, chemokine signaling pathway, and inflammatory mediator regulation of TRP channels. CONCLUSION: The improvement of AD and VaD by AT was associated with modulation of synaptic function, immunity, inflammation, and apoptosis. Our study clarified the therapeutic targets of AT on dementia, providing valuable clues for complementing and combining pharmacotherapy.

Bidirectional Semi-Supervised Dual-Branch CNN for Robust 3D Reconstruction of Stereo Endoscopic Images via Adaptive Cross and Parallel Supervisions.

Semi-supervised learning via teacher-student network can train a model effectively on a few labeled samples. It enables a student model to distill knowledge from the teacher's predictions of extra unlabeled data. However, such knowledge flow is typically unidirectional, having the accuracy vulnerable to the quality of teacher model. In this paper, we seek to robust 3D reconstruction of stereo endoscopic images by proposing a novel fashion of bidirectional learning between two learners, each of which can play both roles of teacher and student concurrently. Specifically, we introduce two self-supervisions, i.e., Adaptive Cross Supervision (ACS) and Adaptive Parallel Supervision (APS), to learn a dual-branch convolutional neural network. The two branches predict two different disparity probability distributions for the same position, and output their expectations as disparity values. The learned knowledge flows across branches along two directions: a cross direction (disparity guides distribution in ACS) and a parallel direction (disparity guides disparity in APS). Moreover, each branch also learns confidences to dynamically refine its provided supervisions. In ACS, the predicted disparity is softened into a unimodal distribution, and the lower the confidence, the smoother the distribution. In APS, the incorrect predictions are suppressed by lowering the weights of those with low confidence. With the adaptive bidirectional learning, the two branches enjoy well-tuned mutual supervisions, and eventually converge on a consistent and more accurate disparity estimation. The experimental results on four public datasets demonstrate our superior accuracy over other state-of-the-arts with a relative decrease of averaged disparity error by at least 9.76%.

Association of time spent in outdoor light and genetic risk with the incidence of depression.

Depression is the consequence of both environment and genes working together. Genetic factors increase depression risk, but it is unclear whether this association can be offset by time spent in outdoor light. The study was undertaken to investigate the optimal time spent in outdoor light for lowering the risk of depression and the joint association of time spent in outdoor light and depression genetic risk. In UK Biobank, 380,976 depression-free individuals were included in this study. Polygenic risk score (PRS) was categorized into three groups in terms of tertiles. Time spent in outdoor light on a typical day in summer or winter originated from the questionnaire survey. Depression was defined as hospital admission. The potential dose-response relationship between time spent in outdoor light and depression risk was shown by a restricted cubic spline. Data were analyzed using Cox regressions and Laplace regression. After the median follow-up of 12.6 years, 13,636 individuals suffered from depression in the end. A nonlinear (J-shaped relationship) trend was observed between time spent in outdoor light and depression risk. On average, 1.5 h/day of outdoor light was related to the minimum risk of depression. Individuals below and above this optimal time both had elevated depression risk (below, HR = 1.09, 95% CI: 1.02-1.16; above, HR = 1.13, 95% CI: 1.07-1.20), and the time to incident depression were both shortened by 0.46 years (50th percentile differences [PD] = -0.46, 95% CI: -0.78, -0.14) and 0.63 years (50th PD = -0.63, 95% CI: -0.90, -0.35) years, respectively. In a comparison of individuals with the lowest tertile of PRS and average 1.5 h/day outdoor light, the HRs and 95% CIs of depression were 1.36 (1.21-1.53) and 1.43 (1.29-1.58) in those with the highest tertile of PRS and below/above this reference value, respectively. Significant multiplicative interactions were observed between intermediate genetic risks and longer time spent in outdoor light. We found that an average of 1.5 h/day spent in outdoor light was associated with a lower depression risk whatever the degree of depression genetic predisposition. Moderate time spent in outdoor light may contribute to a decreased depression risk even among people with a higher genetic risk of depression.

Cardiometabolic diseases, polygenic risk score, APOE genotype, and risk of incident dementia: A population-based prospective cohort study.

Objective We aimed to prospective investigate the association between cardiometabolic diseases (CMDs) with dementia, and to examine whether genetic factors and CMDs jointly contribute to the incidence of dementia. Methods We used data from the UK biobank of 204,646 adults aged 37-73 free of dementia at baseline. Genetic risk for dementia including APOE ε4 status and polygenic risk score (PRS) categorized as low, intermediate, and high. CMDs including ischemic heart disease (IHD), stroke, and type 2 diabetes (T2D) were confirmed by touchscreen questionnaires, medical examinations, and hospital inpatient records. Results Over the follow-up (median: 12.5 years), 5,750 participants developed dementia. The HRs (95% CI) of those with APOE ε4 carriers and high PRS were 3.16 (3.00-3.33) and 1.50 (1.41-1.60), respectively. The risk of dementia was 70% higher among those with CMDs (HR: 1.70; 95% CI: 1.60-1.82). In joint effect analyses, compared to no CMDs and APOE ε4 non-carriers, the HRs (95% CIs) of dementia were 3.53 (3.31-3.76)/2.06 (1.89-2.23) in participants with only APOE ε4 carriers and CMDs, and 5.06 (4.64-5.53) for those with APOE ε4 carriers plus CMDs. Compared to no CMDs and low PRS, the HRs (95% CIs) of dementia were 1.29 (1.19-1.40)/1.60 (1.48-1.73) in participants with only intermediate and high PRS, and 2.00 (1.79-2.23)/2.63 (2.38-2.92) for those with intermediate, and high PRS plus CMDs. Moreover, there were significant additive and multiplication interactions between CMDs and APOE ε4 carriers of dementia, but only multiplication interaction was observed for PRS. Conclusions CMDs were associated with higher risk of dementia regardless of genetic risk for dementia.