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Correlations between pain phenotypes and psychiatric traits such as depression and the personality trait of neuroticism are not fully understood. In this study, we estimated the genetic correlations of eight pain phenotypes (defined by the UK Biobank, n = 151,922–226,683) with depressive symptoms, major depressive disorders and neuroticism using the the cross-trait linkage disequilibrium score regression (LDSC) method integrated in the LD Hub. We also used the LDSC software to calculate the genetic correlations among pain phenotypes. All pain phenotypes, except hip pain and knee pain, had significant and positive genetic correlations with depressive symptoms, major depressive disorders and neuroticism. All pain phenotypes were heritable, with pain all over the body showing the highest heritability (h2 = 0.31, standard error = 0.072). Many pain phenotypes had positive and significant genetic correlations with each other indicating shared genetic mechanisms. Our results suggest that pain, neuroticism and depression share partially overlapping genetic risk factors.

Myopia, or nearsightedness, is a worldwide common type of refractive error. It is a non-life-threatening disorder with huge social and economic consequences due to its increasing prevalence. Axial length (AL) is the primary determinant of non-syndromic myopia. It is a parameter representing the combination of anterior chamber depth, lens thickness and vitreous chamber depth of the eye. AL can also be treated as an endophenotype of myopia and may provide extra advantages in the investigation of its genetic basis. The study of AL will not only identify the determinants of eye elongation, but also provide aetiological evidence for myopia. The purpose of this review is to outline the current state of AL research. Epidemiological evidence, genetic determinants, the relationship with other eye components and relative animal models of AL are summarised.

TiAl alloys are widely used in aerospace applications due to their low density and good mechanical properties. However, their pronounced mechanical anisotropy resulting from the preferred orientations of lamellar crystals remains an important issue. This study investigates the plastic anisotropy of TiAl alloys under various stress states using full-field crystal plasticity modeling based on electron backscatter diffraction data. The crystal plasticity simulations successfully reproduce the experimental mechanical anisotropy in uniaxial and biaxial tests. The research combines crystal plasticity simulations with Yld2004-18p anisotropic yield function to develop a predictive model that accurately characterizes the anisotropic yielding behavior of the TiAl alloys under various stress states. The findings demonstrate that the Yld2004-18p anisotropic yield function effectively describes the macroscopic anisotropic response obtained from crystal plasticity simulations, providing an important theoretical foundation for predicting the anisotropic behavior of TiAl alloys in engineering structures.

Hip pain is a common musculoskeletal complaint that leads many people to seek medical attention. We conducted a primary genome-wide association study (GWAS) on the hip pain phenotype within the UK Biobank cohort. Sex-stratified GWAS analysis approach was also performed to explore sex specific variants associated with hip pain. We found seven different loci associated with hip pain at GWAS significance level, with the most significant single nucleotide polymorphism (SNP) being rs77641763 within the EXD3 ( p value = 2.20 × 10 –13 ). We utilized summary statistics from the FinnGen cohort and a previous GWAS meta-analysis on hip osteoarthritis as replication cohorts. Four loci (rs509345, rs73581564, rs9597759, rs2018384) were replicated with a p value less than 0.05. Sex-stratified GWAS analyses revealed a unique locus within the CUL1 gene (rs4726995, p  = 2.56 × 10 –9 ) in males, and three unique loci in females: rs1651359966 on chromosome 7 ( p  = 1.15 × 10 –8 ), rs552965738 on chromosome 9 ( p  = 2.72 × 10 –8 ), and rs1978969 on chromosome 13 ( p  = 2.87 × 10 –9 ). This study has identified seven genetic loci associated with hip pain. Sex-stratified analysis also revealed sex specific variants associated with hip pain in males and females. This study has provided a foundation for advancing research of hip pain and hip osteoarthritis.

High-resolution multi-spectral images are desired for applications in remote sensing. However, multi-spectral images can only be provided in low resolutions by optical remote sensing satellites. The technique of pan-sharpening wants to generate high-resolution multi-spectral (MS) images based on a panchromatic (PAN) image and the low-resolution counterpart. The conventional deep learning based pan-sharpening methods process the panchromatic and the low-resolution image in a feedforward manner where shallow layers fail to access useful information from deep layers. To make full use of the powerful deep features that have strong representation ability, we propose a two-path network with feedback connections, through which the deep features can be rerouted for refining the shallow features in a feedback manner. Specifically, we leverage the structure of a recurrent neural network to pass the feedback information. Besides, a power feature extraction block with multiple projection pairs is designed to handle the feedback information and to produce power deep features. Extensive experimental results show the effectiveness of our proposed method.

Background Stem cell therapies have emerged as transformative therapeutic strategies for neurological disorders. However, neurons derived from transplanted stem cells often exhibit low survival rates and remain in an immature state. While pulsed electromagnetic fields (PEMF) may enhance neuronal differentiation, the extent of this effect and its molecular mechanisms remain poorly characterized. Method Human induced pluripotent stem cells (iPSCs) induced cortical neurons received daily PEMF stimulation (1 mT, 15 Hz, 3.75 ms pulse duration) for 7 days during differentiation. Neuronal differentiation and synaptic maturation were assessed using immunocytochemistry, qPCR, western blotting, and live-cell imaging to evaluate neurite outgrowth. Functional maturation was analyzed through calcium imaging and patch-clamp electrophysiology. Transcriptomic profiling identified key pathways involved in PEMF-modulated neuronal maturation, with the role of FDFT1-mediated cholesterol biosynthesis mechanistically validated through pharmacological inhibition and genetic knockdown. Result PEMF accelerated early-stage neuronal differentiation without altering neurite outgrowth and enhanced synaptic maturation after sustained stimulation. PEMF-treated neurons displayed heightened spontaneous calcium signaling and improved functional maturation, including enhanced excitability, action potential kinetics, and voltage-gated ion channel activity. Transcriptomics revealed significant upregulation of cholesterol biosynthesis pathways, with FDFT1 (squalene synthase) as a central regulator. Pharmacological inhibition or genetic knockdown of FDFT1 abolished PEMF-induced neuronal differentiation and synaptic maturation. Conclusion PEMF accelerates early-stage differentiation of human cortical neurons and enhances synaptic maturation following sustained stimulation. These effects are mechanistically linked to the activation of FDFT1-mediated cholesterol biosynthesis. This non-invasive PEMF stimulation approach represents a promising strategy to optimize stem cell-based therapies for neurological disorders.

Background Current human retina studies predominantly utilize post-mortem tissue, and the sample accessibility constraints make the characterization of the living human retina at single-cell resolution a challenge. Although single-nucleus RNA-seq expands the utility of frozen samples, it provides a nuclear-centric view, potentially missing key cytoplasmic information and transient biological processes. Thus, it is important to generate resources directly from living human retinal tissue to complement existing datasets. Methods We profiled 106,829 single cells from nine unfrozen human retina samples. Living samples were collected within 10 min of therapeutic enucleation and four postmortem samples were collected within 6 h. After standardized dissociation, single-cell transcriptomes were generated using 10x Genomics 3’ RNA-seq and applied scVI to generate batch-corrected integrated atlas. Major cell types and subtypes were annotated through iterative Leiden clustering, canonical markers. Subsequent analyses included differential expression comparisons between cell states and regulon activity profiling to further characterize cellular identities and regulatory networks. Transcriptional dynamics were assessed using RNA velocity, and cell-cell signaling pathways were inferred with CellChat. Key findings were validated in independent samples from two additional donors (four samples) using the identical workflow. Results We contribute to establishing a reference for retinal cell type proportions and cellular states. Our analysis revealed ELF1-mlCone, a distinct cluster of mlCone photoreceptors identified by distinct transcriptional features. The presence and transcriptional features of this cluster were validated in independent samples. Additionally, by comparing living and post-mortem samples, our study highlights differences in transcriptional dynamics: living tissue preserved coherent RNA velocity streams, enabling clear dynamic state transitions, while post-mortem tissue exhibited disorganized patterns. These findings suggest that using living tissue can improve the capture of active cellular states and transitions. Conclusions Our atlas provides a single-cell reference contrasting living versus early postmortem human retina, integrating cell type composition, transcriptional diversity, and functional insights. It may serve as a useful resource for retinal research and for understanding aspects of human retinal biology, particularly given its inclusion of living tissue and diverse pathological states.

Chronic pain is highly prevalent and a significant source of disability, yet its genetic and environmental risk factors are poorly understood. Its relationship with major depressive disorder (MDD) is of particular importance. We sought to test the contribution of genetic factors and shared and unique environment to risk of chronic pain and its correlation with MDD in Generation Scotland: Scottish Family Health Study (GS:SFHS). We then sought to replicate any significant findings in the United Kingdom Biobank study. Using family-based mixed-model analyses, we examined the contribution of genetics and shared family environment to chronic pain by spouse, sibling, and household relationships. These analyses were conducted in GS:SFHS (n = 23,960), a family- and population-based study of individuals recruited from the Scottish population through their general practitioners. We then examined and partitioned the correlation between chronic pain and MDD and estimated the contribution of genetic factors and shared environment in GS:SFHS. Finally, we used data from two independent genome-wide association studies to test whether chronic pain has a polygenic architecture and examine whether genomic risk of psychiatric disorder predicted chronic pain and whether genomic risk of chronic pain predicted MDD. These analyses were conducted in GS:SFHS and repeated in UK Biobank, a study of 500,000 from the UK population, of whom 112,151 had genotyping and phenotypic data. Chronic pain is a moderately heritable trait (heritability = 38.4%, 95% CI 33.6% to 43.9%) that is significantly concordant in spouses (variance explained 18.7%, 95% CI 9.5% to 25.1%). Chronic pain is positively correlated with depression (ρ = 0.13, 95% CI 0.11 to 0.15, p = 2.72x10-68) and shows a tendency to cluster within families for genetic reasons (genetic correlation = 0.51, 95%CI 0.40 to 0.62, p = 8.24x10-19). Polygenic risk profiles for pain, generated using independent GWAS data, were associated with chronic pain in both GS:SFHS (maximum β = 6.18x10-2, 95% CI 2.84 x10-2 to 9.35 x10-2, p = 4.3x10-4) and UK Biobank (maximum β = 5.68 x 10-2, 95% CI 4.70x10-2 to 6.65x10-2, p < 3x10-4). Genomic risk of MDD is also significantly associated with chronic pain in both GS:SFHS (maximum β = 6.62x10-2, 95% CI 2.82 x10-2 to 9.76 x10-2, p = 4.3x10-4) and UK Biobank (maximum β = 2.56x10-2, 95% CI 1.62x10-2 to 3.63x10-2, p < 3x10-4). Limitations of the current study include the possibility that spouse effects may be due to assortative mating and the relatively small polygenic risk score effect sizes. Genetic factors, as well as chronic pain in a partner or spouse, contribute substantially to the risk of chronic pain for an individual. Chronic pain is genetically correlated with MDD, has a polygenic architecture, and is associated with polygenic risk of MDD.

In this paper, we propose a new tritrophic food chain model. We address the conditions for the coexistence of two different zooplankton species and one phytoplankton species. The results of the numerical and analytical studies of the model show that the most relevant parameters influencing the plankton ecosystem, to maintain a stable coexistence equilibrium, are the: carrying capacity and the constant intrinsic growth rate of the phytoplankton population, and the conversion rate with a mortality rate of carnivorous zooplankton. We prove the existence and direction of Hopf bifurcation in non delay system. To account for the time delay in the conversion of herbivorous consumption to carnivorous zooplankton, we incorporate a discrete delay into the consume response function. Furthermore, we establish some adequate conditions to prove the occurrence of Hopf bifurcation induced by delay in the delayed model. We also plot two-parameter bifurcation diagrams. The numerical results support the analytical findings.

PurposeNeuropathic pain is a common disorder of the somatosensory system that affects 7%–10% of the general population. The disorder places a large social and economic burden on patients as well as healthcare services. However, not everyone with a relevant underlying aetiology develops corresponding pain. DOLORisk Dundee, a European Union-funded cohort, part of the multicentre DOLORisk consortium, was set up to increase current understanding of this variation in onset. In particular, the cohort will allow exploration of psychosocial, clinical and genetic predictors of neuropathic pain onset.ParticipantsDOLORisk Dundee has been constructed by rephenotyping two pre-existing Scottish population cohorts for neuropathic pain using a standardised ‘core’ study protocol: Genetics of Diabetes Audit and Research in Tayside Scotland (GoDARTS) (n=5236) consisting of predominantly type 2 diabetics from the Tayside region, and Generation Scotland: Scottish Family Health Study (GS:SFHS; n=20 221). Rephenotyping was conducted in two phases: a baseline postal survey and a combined postal and online follow-up survey. DOLORisk Dundee consists of 9155 participants (GoDARTS=1915; GS:SFHS=7240) who responded to the baseline survey, of which 6338 (69.2%; GoDARTS=1046; GS:SFHS=5292) also responded to the follow-up survey (18 months later).Findings to dateAt baseline, the proportion of those with chronic neuropathic pain (Douleur Neuropathique en 4 Questions questionnaire score ≥3, duration ≥3 months) was 30.5% in GoDARTS and 14.2% in Generation Scotland. Electronic record linkage enables large scale genetic association studies to be conducted and risk models have been constructed for neuropathic pain.Future plansThe cohort is being maintained by an access committee, through which collaborations are encouraged. Details of how to do this will be available on the study website (http://dolorisk.eu/). Further follow-up surveys of the cohort are planned and funding applications are being prepared to this effect. This will be conducted in harmony with similar pain rephenotyping of UK Biobank.