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Although adolescent depression has been linked to individual chronic conditions, its broader role in shaping multimorbidity risk remains understudied.
Methods
A total of 87,562 UK Biobank participants were included, of whom 18,851 had documented adolescent depression. Cox proportional hazards models were applied to evaluate associations between adolescent depression and 24 chronic diseases, followed by stratified analyses by sex and age. Two-sample Mendelian randomization (MR) was then conducted to infer causality for diseases showing significant associations. Genomic colocalization analyses were performed using relevant GWAS data to identify shared causal variants. Mediation analyses were performed to detect possible mediating factors, including the frailty index, KDM biological age acceleration, allostatic load and 30 circulating biomarkers.
Results
Adolescent depression was associated with elevated risk for 12 chronic diseases, with strongest associations for hypothyroidism (HR = 1.29 [1.18–1.42]), diabetes (HR = 1.25 [1.13–1.38]) and chronic obstructive pulmonary disease (COPD) (HR = 1.74 [1.50–2.01]). Risks were notably higher among females and younger adults. MR confirmed likely causal relationships for hypothyroidism (OR = 1.45 [1.03–2.05]), diabetes (OR = 1.01 [1.01–1.02]) and COPD (OR = 1.04 [1.02–1.06]). Genomic colocalization revealed a shared genetic signal at the CDSN/PSORS1C1 locus between adolescent depression and hypothyroidism. Mediation analyses revealed disease-specific pathways: creatinine for hypothyroidism, testosterone for diabetes, KDM biological ageing for COPD and frailty index across all three conditions.
Conclusions
Adolescent depression confers systemic vulnerability through genetic and metabolic mechanisms, with amplified risks in females and individuals aged ≤55 years. These findings support early, integrated interventions to mitigate long-term multimorbidity.
The 4-DOF (four degrees of freedom) parallel manipulator, namely 2PPaRR-2PPaRU, offers three translations and one rotation capabilities, boasting an extensive rotation range, and a regular workspace. Moreover, its workspace can infinitely extend in conjunction with the extension of the driving joints. Nonetheless, the symmetric structure relying on Pa joint design presents performance challenges in the initial configuration and complicates the analytical solution of the forward kinematics, thereby increasing the complexity of dynamics and control. To address these limitations, the structure of the moving platform is modified by coaxially connecting the three joints at the ends of the three limbs to the moving platform. This improvement is followed by analyses of mobility, motion/force transmissibility, and stiffness. The overall reachable workspace area, good transmission workspace ratio, and global stiffness index are then chosen as key objectives for dimensional optimization, thereby achieving satisfactory performance for the new 3T1R PM. Finally, the CAD model with the selected parameters is presented, together with the distributions of motion/force transmission index and virtual stiffness index within the reachable workspace. The results validate the effectiveness of the optimization design.
The growing body of research on the effects of computerized dynamic assessment (C-DA) on second language (L2) learning underscores the need for a comprehensive research synthesis to identify future research directions and inform the application of C-DA in L2 educational contexts. This meta-analysis employed a three-level modeling approach to examine the effectiveness of C-DA in improving L2 learners’ performance. It synthesized 27 effect sizes from cake format designs, in which mediation is embedded within the test sequence, and 24 effect sizes from sandwich format designs, where mediation is delivered between a pretest and a posttest, across 35 studies published between 2000 and May 27, 2025. This study also investigated the key variables that moderate C-DA effectiveness. Findings reveal large, significant positive effects of both the cake and sandwich formats on L2 performance improvement (cake format: g = 2.120, p < .001; sandwich format: g = 1.676, p < .001), with the cake format tending to yield larger effect sizes. This may be because the cake format captures gains during mediation, whereas the sandwich format reflects post-mediation outcomes. Moderator analyses show that the number of items, test content, and learners’ first language affect C-DA effectiveness in promoting L2 performance. Drawing on the synthesized findings, this study contributes to theoretical, methodological, and technological understandings of C-DA and offers suggestions for future research in this domain.
Depression exhibits significant heterogeneity in its genetic underpinnings. The role of genetic components in the development of depression and its comorbidities remains insufficiently explored.
Methods
First, depression risk loci from a large-scale genome-wide meta-analysis were annotated to Gene Ontology (GO) terms by functional enrichment. GO-based polygenic risk scores (GO-PRS) were then calculated for individuals in the UK Biobank. Principal component analysis (PCA) was applied for dimensionality reduction, followed by cluster analysis to identify genetic subtypes of depression. Multistate models were applied to assess the impact of genetic patterns on the trajectory from healthy status to incident depression, and depression to 26 subsequent diseases, as well as the associations between environmental factors and disease trajectories across genetic subtypes.
Results
Participants were categorized into three genetic subtypes: immune-dominant, neuro-dominant, and comprehensive-risk. Significant differences in risk of depression and subsequent diseases, and susceptibility to environmental factors were observed across subtypes. Comprehensive-risk subtype showed higher risks of depression compared to immune-dominant (HR: 1.10, 95% CI: 1.05–1.15) and neuro-dominant subtype (HR: 1.12, 95% CI: 1.08–1.16). Comprehensive-risk subtype exhibited higher risks of transition from depression to subsequent diseases, such as anemia compared to immune-dominant subtype, and diseases of the digestive system compared to neuro-dominant subtype. Environmental factors were more strongly associated with the transition from depression to subsequent diseases in immune-dominant and comprehensive-risk subtypes, including cardiovascular, respiratory, and metabolic diseases.
Conclusions
Our findings highlight the genetic heterogeneity of depression and comorbidities, and shed light on how genetic components modulate responses to environmental factors.
Increasing evidences show that inflammation might be involved in bipolar disorder (BD), but the association between abnormal brain function and inflammation in BD is still unclear. In this study, we tried to explore the disrupted brain functional network topology, peripheral inflammatory cytokine levels, and their correlations in unmedicated bipolar II depression (BDII-D).
Methods
In this study, 65 individuals with unmedicated BDII-D and 50 healthy controls (HCs) underwent resting-state magnetic resonance imaging scans. Graph theory analysis was performed to investigate the topological properties of the whole-brain functional connectome at both global and nodal levels. Besides, serum levels of 17 inflammatory cytokines were measured in both BDII-D and HCs. Correlations between topological properties, clinical variables, and peripheral inflammatory cytokine levels in BDII-D were calculated.
Results
Compared with HCs, at the global level, BDII-D showed significantly higher $ \lambda $, decreased $ \gamma $, $ \sigma $, Eglo, and Eloc; at the nodal level, BDII-D showed decreased Enodal in the right olfactory cortex, left pallidum, and vermis. Besides, BDII-D showed higher levels of interleukin-8 (IL-8), interleukin-10 (IL-10), and granulocyte colony-stimulating factor (G-CSF) compared with the HCs. In BDII-D, $ \gamma $ and $ \sigma $ were significantly negatively correlated with the Hamilton Depression Rating Scale (HDRS) scores and number of episodes. Also, IL-8 level showed significant negative correlation with $ \gamma $, $ \sigma $, and Enodal of the left pallidum in BDII-D.
Conclusions
Reduced information segregation and integration, and lower nodal efficiency in the left pallidum were associated with proinflammatory cytokine IL-8 level and might contribute to severe depressive symptoms in unmedicated BDII-D.
The traditional design of laser drivers for inertial confinement fusion (ICF) is highly dependent on coherent laser light fields, which have significant advantages in achieving harmonic conversion and enhancing amplification efficiency. However, they also bring the core challenge of achieving uniform irradiation. This paper investigates the dynamic evolution process of uniform irradiation of multi-mode spatiotemporal light fields and analyzes the influence mechanism of spatiotemporal coherence on irradiation uniformity with different integration times. By balancing the relationship between the spatiotemporal coherence of the light field and uniform irradiation, we explore a possible scheme to alleviate the beam smoothing problem while satisfying the basic requirements of laser amplification and high-efficiency harmonic conversion. Based on this scheme, the overall architecture of the ICF laser driver is constructed.
Paleontology provides insights into the history of the planet, from the origins of life billions of years ago to the biotic changes of the Recent. The scope of paleontological research is as vast as it is varied, and the field is constantly evolving. In an effort to identify “Big Questions” in paleontology, experts from around the world came together to build a list of priority questions the field can address in the years ahead. The 89 questions presented herein (grouped within 11 themes) represent contributions from nearly 200 international scientists. These questions touch on common themes including biodiversity drivers and patterns, integrating data types across spatiotemporal scales, applying paleontological data to contemporary biodiversity and climate issues, and effectively utilizing innovative methods and technology for new paleontological insights. In addition to these theoretical questions, discussions touch upon structural concerns within the field, advocating for an increased valuation of specimen-based research, protection of natural heritage sites, and the importance of collections infrastructure, along with a stronger emphasis on human diversity, equity, and inclusion. These questions offer a starting point—an initial nucleus of consensus that paleontologists can expand on—for engaging in discussions, securing funding, advocating for museums, and fostering continued growth in shared research directions.
Little is known regarding the shared genetic architecture underlying the phenotypic associations between depression and preterm birth (PTB). We aim to investigate the genetic overlap and causality of depression with PTB.
Methods
Leveraging summary statistics from the largest genome-wide association studies for broad depression (Ntotal = 807,533), major depression (Ntotal = 173,005), bipolar disorder (Ntotal = 414,466), and PTB (Ntotal = 226,330), we conducted a large-scale genome-wide cross-trait analysis to assess global and local genetic correlations, identify pleiotropic loci, and infer potential causal relationships
Results
Positive genetic correlations were observed between PTB and broad depression (rg = 0.242), major depression (rg = 0.236), and bipolar disorder (rg = 0.133) using the linkage disequilibrium score regression, which were further verified by the genetic covariance analyzer. Local genetic correlation was identified at chromosome 11q22.3 (harbors NCAM1-TTC12-ANKK1-DRD2) for PTB with depression. Cross-trait meta-analysis identified two loci shared between PTB and broad depression, two loci shared with major depression, and five loci shared with bipolar disorder, among which three were novel (rs7813444, rs3132948 and rs9273363). Mendelian randomization demonstrated a significantly increased risk of PTB for genetic liability to broad depression (odds ratio [OR]=1.30; 95% confidence interval [CI]: 1.11-1.52) and major depression (OR=1.27; 95%CI: 1.08-1.49), and the estimates remained significant across the sensitivity analyses.
Conclusions
Our findings demonstrate an intrinsic link underlying depression and PTB and shed novel light on the biological mechanisms, highlighting an important role of early screening and effective intervention of depression in PTB prevention, and may provide novel treatment strategies for both diseases.
Danon disease is an X-linked disorder caused by variants in the lysosome-associated membrane protein-2 (LAMP2) gene located on Xq24. Due to its inheritance in an X-chromosome dominant manner, males typically experience more severe manifestations than females.
Method:
The whole exome sequencing was conducted on a cohort of 218 children diagnosed with hypertrophic cardiomyopathy; four children with hypertrophic cardiomyopathy carrying the LAMP2 variants were diagnosed at our centre. Variants in the LAMP2 gene were summarised, and their pathogenicity and conservation were analysed using bioinformatics methods. A retrospective analysis of genotype-phenotype associations was also conducted in conjunction with previously reported cases.
Results:
Four patients with Danon disease were diagnosed in our single centre by gene sequencing; they all presented with myocardial hypertrophy as the initial manifestation. Both male patients manifested symptoms from infancy, while disease onset in the two female cases occurred below the average age reported for females. Through gene sequencing, a total of four variants were identified in these four patients, including one splicing variant: c.865-1G>C, one loss of heterozygosity variant: loss1 exon:4-9), one frameshift variant: c.973delG(p.(L325Wfs×21)), and one stop codon variant: c.467T>G(p.(L156*)).
Conclusion:
This study identified four patients with LAMP2 gene variants, thereby enriching the documented genetic landscape of LAMP2-associated disorders. Bioinformatics analyses corroborated the pathogenicity of these variants. Additionally, we emphasised that women with suspected Danon disease should be thoroughly evaluated, and the possibility of implantable cardioverter defibrillator implantation and heart transplantation should be considered and discussed as early as possible.
Social determinants of health (SDHs) exert a significant influence on various health outcomes and disparities. This study aimed to explore the associations between combined SDHs and mortality, as well as adverse health outcomes among adults with depression.
Methods
The research included 48,897 participants with depression from the UK Biobank and 7,771 from the US National Health and Nutrition Examination Survey (NHANES). By calculating combined SDH scores based on 14 SDHs in the UK Biobank and 9 in the US NHANES, participants were categorized into favourable, medium and unfavourable SDH groups through tertiles. Cox regression models were used to evaluate the impact of combined SDHs on mortality (all-cause, cardiovascular disease [CVD] and cancer) in both cohorts, as well as incidences of CVD, cancer and dementia in the UK Biobank.
Results
In the fully adjusted models, compared to the favourable SDH group, the hazard ratios for all-cause mortality were 1.81 (95% CI: 1.60–2.04) in the unfavourable SDH group in the UK Biobank cohort; 1.61 (95% CI: 1.31–1.98) in the medium SDH group and 2.19 (95% CI: 1.78–2.68) in the unfavourable SDH group in the US NHANES cohort. Moreover, higher levels of unfavourable SDHs were associated with increased mortality risk from CVD and cancer. Regarding disease incidence, they were significantly linked to higher incidences of CVD and dementia but not cancer in the UK Biobank.
Conclusions
Combined unfavourable SDHs were associated with elevated risks of mortality and adverse health outcomes among adults with depression, which suggested that assessing the combined impact of SDHs could serve as a key strategy in preventing and managing depression, ultimately helping to reduce the burden of disease.
To fully understand resilience and to inform resilience-promoting interventions, it is important to explore how resilience develops and the factors that influence it. Using a multidimensional approach that considers both well-being resilience (higher than expected wellbeing after adversity) and depression resilience (lower than expected depression after adversity), this study examined resilience trajectories among Chinese 0adolescents and the associations of gratitude and perceived stress with resilience trajectories. Data from a four-wave longitudinal study were analyzed from 563 Chinese adolescents (mean age at Time 1 = 12.83 years, 51.87% boys). Parallel-process latent class growth modeling identified four distinct trajectories of resilience development: flourishing resilience (increasing resilience; 21.67%), increasing wellbeing resilience but decreasing depression resilience (28.24%), declining resilience (29.48%), and increasing depression resilience but decreasing wellbeing resilience (20.61%). Gratitude was associated with greater odds of being in the flourishing resilience group. Furthermore, perceived stress was associated with lower odds of being in the flourishing resilience group and higher odds of being in the declining resilience group. The findings suggest that resilience is a dynamic and multidimensional construct with highly heterogeneous developmental trajectories. Gratitude and perceived stress may be effective targets for interventions to enhance adolescent resilience.
The incorporation of trace metals into land snail shells may record the ambient environmental conditions, yet this potential remains largely unexplored. In this study, we analyzed modern snail shells (Cathaica sp.) collected from 16 sites across the Chinese Loess Plateau to investigate their trace metal compositions. Our results show that both the Sr/Ca and Ba/Ca ratios exhibit minimal intra-shell variability and small inter-shell variability at individual sites. A significant positive correlation is observed between the shell Sr/Ca and Ba/Ca ratios across the plateau, with higher values being recorded in the northwestern sites where less monsoonal rainfall is received. We propose that shell Sr/Ca and Ba/Ca ratios, which record the composition of soil solution, may be controlled by the Rayleigh distillation in response to prior calcite precipitation. Higher rainfall amounts may lead to a lower degree of Rayleigh distillation and thus lower shell Sr/Ca and Ba/Ca ratios. This is supported by the distinct negative correlation between summer precipitation and shell Sr/Ca and Ba/Ca ratios, enabling us to reconstruct summer precipitation amounts using the Sr/Ca and Ba/Ca ratios of Cathaica sp. shells. The potential application of these novel proxies may also be promising for other terrestrial mollusks living in the loess deposits globally.
The whitefly Bemisia tabaci (Hemiptera: Aleyrodidae) is economically one of the most threatening pests in tomato cultivation, which not only causes direct damage but also transmits many viruses. Breeding whitefly-resistant tomato varieties is a promising and environmentally friendly method to control whitefly populations in the field. Accumulating evidence from tomato and other model systems demonstrates that flavonoids contribute to plant resistance to herbivorous insects. Previously, we found that high flavonoid-producing tomato line deterred whitefly oviposition and settling behaviours, and was more resistant to whiteflies compared to the near-isogenic low flavonoid-producing tomato line. The objective of the current work is to describe in detail different aspects of the interaction between the whitefly and two tomato lines, including biochemical processes involved. Electrical penetration graph recordings showed that high flavonoid-producing tomato reduced whitefly probing and phloem-feeding efficiency. We also studied constitutive and induced plant defence responses and found that whitefly induced stronger reactive oxygen species accumulation through NADPH oxidase in high flavonoid-producing tomato than in low flavonoid-producing tomato. Moreover, whitefly feeding induced the expression of callose synthase genes and resulted in callose deposition in the sieve elements in high flavonoid-producing tomato but not in low flavonoid-producing tomato. As a consequence, whitefly feeding on high flavonoid-producing tomato significantly decreased uptake of phloem and reduced its performance when compared to low flavonoid-producing tomato. These results indicate that high flavonoid-producing tomato provides phloem-based resistance against whitefly infestation and that the breeding of such resistance in new varieties could enhance whitefly management.
Previous studies have suggested that nature contact is a protective factor for problem behavior in children. However, there remains a significant gap in research exploring the reciprocal relationship between nature contact and children’s problem behavior, as well as the underlying mechanisms driving this relationship. This study employed a longitudinal three-wave design involving 516 children in China (268 girls, Mage = 10.88 ± 0.66 years old at Time 3). Cross-lagged analyses indicated that nature contact and problem behavior negatively predicted each other over time, and prosocial behavior bidirectionally mediated the relationship between nature contact and problem behavior. These results provided evidence for the relationships among nature interaction, social development, and behavioral development in children. These findings suggested that promoting prosocial behavior could reduce problem behavior and enhance nature engagement, potentially serving as a strategy to foster comprehensive development in children.
Recent studies have increasingly utilized gradient metrics to investigate the spatial transitions of brain organization, enabling the conversion of macroscale brain features into low-dimensional manifold representations. However, it remains unclear whether alterations exist in the cortical morphometric similarity (MS) network gradient in patients with schizophrenia (SCZ). This study aims to examine potential differences in the principal MS gradient between individuals with SCZ and healthy controls and to explore how these differences relate to transcriptional profiles and clinical phenomenology.
Methods
MS network was constructed in this study, and its gradient of the network was computed in 203 patients with SCZ and 201 healthy controls, who shared the same demographics in terms of age and gender. To examine irregularities in the MS network gradient, between-group comparisons were carried out, and partial least squares regression analysis was used to study the relationships between the MS network gradient-based variations in SCZ, and gene expression patterns and clinical phenotype.
Results
In contrast to healthy controls, the principal MS gradient of patients with SCZ was primarily significantly lower in sensorimotor areas, and higher in more areas. In addition, the aberrant gradient pattern was spatially linked with the genes enriched for neurobiologically significant pathways and preferential expression in various brain regions and cortical layers. Furthermore, there were strong positive connections between the principal MS gradient and the symptomatologic score in SCZ.
Conclusions
These findings showed changes in the principal MS network gradient in SCZ and offered potential molecular explanations for the structural changes underpinning SCZ.
This study examined global trends in influenza-associated lower respiratory infections (LRIs) deaths from 1990 to 2019 using data from the GBD 2019. The annual percentage change (APC) and average annual percentage change (AAPC) were used to analyze age-standardized death rates (ASDR). Globally, the ASDR of influenza-associated LRIs was 3.29/100,000 in 2019, which was higher in the African region (6.57/100,000) and among adults aged 70 years and older (29.88/100,000). The ASDR of influenza-associated LRIs decreased significantly from 1990 to 2019 (AAPC = −1.88%, P < 0.05). However, it was significantly increased among adults aged 70 years and older during 2017–2019 (APC = 2.31%, P < 0.05), especially in Western Pacific Region and South-East Asia Regions. The ratio of death rates between adults aged 70 years and older and children aged under 5 years increased globally from 1.63 in 1990 to 5.34 in 2019, and the Western Pacific Region experienced the most substantial increase, with the ratio soaring from 1.83 in 1990 to 12.98 in 2019. Despite a decline in the global ASDR of influenza-associated LRIs, it continues to impose a significant burden, particularly in the African, Western Pacific regions and among the elderly population.
Optical fibers offer convenient access to a variety of nonlinear phenomena. However, due to their inversion symmetry, second-order nonlinear effects, such as second-harmonic generation (SHG), are challenging to achieve. Here, all-fiber in-core SHG with high beam quality is achieved in a random fiber laser (RFL). The fundamental wave (FW) is generated in the same RFL. The phase-matching condition is mainly achieved through an induced periodic electric field and the gain is enhanced through the passive spatiotemporal gain modulation and the extended fiber. The conversion needs no pretreatment and the average second-harmonic (SH) power reaches up to 10.06 mW, with a corresponding conversion efficiency greater than 0.04%. Moreover, a theoretical model is constructed to explain the mechanism and simulate the evolution of the SH and FW. Our work offers a simple method to generate higher brightness for in-fiber SHs, and may further provide new directions for research on all-fiber χ(2)-based nonlinear fiber optics and RFLs.
Systematically monitoring the baseline sensitivity of troublesome weeds to herbicides is a crucial step in the early detection of their market lifespan. Florpyrauxifen-benzyl is one of the most important herbicides used in rice production throughout the world, and has been used for 5 yr in China. Barnyardgrass is one of the main targeted weed species of florpyrauxifen-benzyl. In total, 114 barnyardgrass populations were collected from rice fields in Jiangsu Province, China, and using whole-plant bioassays they were screened for susceptibility to florpyrauxifen-benzyl. The GR50 values (representing the dose that causes a 50% reduction in fresh weight of aboveground parts) of florpyrauxifen-benzyl for all populations ranged from 1.0 to 34.5 g ai ha−1, with an average of 6.8 g ai ha−1, a baseline sensitivity dose of 3.3 g ai ha−1, and a baseline sensitivity index of 34.5. Twenty-one days after treatment with florpyrauxifen-benzyl at the labeled dose (36 g ai ha−1), 90% of the barnyardgrass populations exhibited >95% reductions in fresh weight of aboveground parts. Compared with the baseline sensitivity dose, 63, 44, and 7 populations had, respectively, no resistance (55%), low resistance (39%), and moderate resistance (6%) to florpyrauxifen-benzyl. Furthermore, the GR50 distribution of barnyardgrass populations did not show a significant correlation with collection location, planting method (direct-seeding or transplanting), or rice species (Oryza sativa L. ssp. indica or ssp. japonica) at any of rice fields where seeds had been collected (P > 0.05). In conclusion, florpyrauxifen-benzyl remains effective for barnyardgrass control in rice fields despite serious resistance challenges.