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Molecular Psychiatry Jul 2024Current literature suggests that people with psychiatric disorders have a higher risk of COVID-19 infection and a worse prognosis of the disease. We aimed to study the...
Current literature suggests that people with psychiatric disorders have a higher risk of COVID-19 infection and a worse prognosis of the disease. We aimed to study the genetic contribution to these associations across seven psychiatric disorders as well as a general psychopathology factor (P-factor) and determine whether these are unique or shared across psychiatric disorders using statistical genetic techniques. Using the largest available genome-wide association studies (GWAS), we found a significant genetic overlap between depression, ADHD, PTSD, and the P-factor with both COVID-19 infection and hospitalization, and between anxiety and COVID-19 hospitalization. We used pairwise GWAS to examine this overlap on a fine-grained scale and identified specific regions of the genome shared between several psychiatric disorders, the P-factor, and COVID-19. Gene-based analysis in these genomic regions suggested possible links with immune-related pathways such as thyroid homeostasis, inflammation, and stress response. Finally, we show preliminary evidence for causal associations between depression, ADHD, PTSD, and the P-factor, and higher COVID-19 infection and hospitalization using Mendelian Randomization and Latent Causal Variable methods. Our results support the hypothesis that the relationship between psychiatric disorders and COVID-19 risk is likely due to shared alterations in immune-related pathways and is not a result of environmental factors alone, shedding light on potentially viable therapeutic targets.
PubMed: 38956374
DOI: 10.1038/s41380-024-02643-0 -
Communications Biology Jul 2024Gastric cancer (GC) is the 5 most prevalent cancer and the 4 primary cancer-associated mortality globally. As the first identified m6A demethylase for removing RNA...
Gastric cancer (GC) is the 5 most prevalent cancer and the 4 primary cancer-associated mortality globally. As the first identified m6A demethylase for removing RNA methylation modification, fat mass and obesity-associated protein (FTO) plays instrumental roles in cancer development. Therefore, we study the biological functions and oncogenic mechanisms of FTO in GC tumorigenesis and progression. In our study, FTO expression is obviously upregulated in GC tissues and cells. The upregulation of FTO is associated with advanced nerve invasion, tumor size, and LNM, as well as the poor prognosis in GC patients, and promoted GC cell viability, colony formation, migration and invasion. Mechanistically, FTO targeted specificity protein 1 and Aurora Kinase B, resulting in the phosphorylation of ataxia telangiectasia mutated and P38 and dephosphorylation of P53. In conclusion, the m6A demethylase FTO promotes GC tumorigenesis and progression by regulating the SP1-AURKB-ATM pathway, which may highlight the potential of FTO as a diagnostic biomarker for GC patients' therapy response and prognosis.
Topics: Humans; Alpha-Ketoglutarate-Dependent Dioxygenase FTO; Stomach Neoplasms; Cell Line, Tumor; Ataxia Telangiectasia Mutated Proteins; Sp1 Transcription Factor; Aurora Kinase B; Male; Female; Gene Expression Regulation, Neoplastic; Disease Progression; Middle Aged; Signal Transduction; Prognosis; Mice; Animals
PubMed: 38956367
DOI: 10.1038/s42003-024-06477-y -
Scientific Reports Jul 2024With the rapid advancement of educational technology, the flipped classroom approach has garnered considerable attention owing to its potential for enhancing students'...
With the rapid advancement of educational technology, the flipped classroom approach has garnered considerable attention owing to its potential for enhancing students' learning capabilities. This research delves into the flipped classroom teaching methodology, employing the Unified Theory of Acceptance and Use of Technology (UTAUT), learning engagement theory, and the 4C skills (comprising communication, collaboration, creativity, and critical thinking) to investigate its effects on learning capabilities. The research surveyed 413 students from three universities in Jiangxi Province, employing stratified random sampling. SPSS 24.0 and Amos were used for structural equation modeling and hypothesis testing analysis. The findings indicate that: (1) Performance expectancy, effort expectancy, and peer influence significantly enhance students' learning engagement in the flipped classroom. (2) Students' learning engagement in the flipped classroom notably promotes their learning capabilities. (3) Performance expectancy, effort expectancy, and peer influence can significantly boost learning capabilities by increasing learning engagement. (4) Personality traits significantly moderate the effect of peer influence on learning engagement, highlighting the crucial role of individual differences in learning. (5) The level of students' learning engagement is differentially influenced by performance expectancy and peer influence across various academic disciplines. Ultimately, this research provides valuable insights for educational policymakers and guides improvements in teaching practices, collectively advancing educational quality and equity.
Topics: Humans; Male; Female; Students; Learning; Teaching; Universities; Problem-Based Learning; Young Adult; Models, Educational; Educational Technology; Surveys and Questionnaires
PubMed: 38956355
DOI: 10.1038/s41598-024-66214-7 -
Nature Reviews. Chemistry Jul 2024The fact that ordered materials are rarely perfectly crystalline is widely acknowledged among materials scientists, but its impact is often overlooked or underestimated... (Review)
Review
The fact that ordered materials are rarely perfectly crystalline is widely acknowledged among materials scientists, but its impact is often overlooked or underestimated when studying how structure relates to properties. Various investigations demonstrate that intrinsic and extrinsic defects, and disorder generated by physicochemical reactions, are responsible for unexpectedly detrimental or beneficial functionalities. The task remains to modulate the disorder to produce desired properties in materials. As disorder is often correlated with local interactions, it is controllable. In this Review, we explore the structural disorder in cathode materials as a novel approach for improving their electrochemical performance. We revisit cathode materials for alkali-ion batteries and outline the origins and beneficial consequences of disorder. Focusing on layered, cubic rocksalt and other metal oxides, we discuss how disorder improves electrochemical properties of cathode materials and which interactions generate the disorder. We also present the potential pitfalls of disorder that must be considered. We conclude with perspectives for enhancing the electrochemical performance of cathode materials by using disorder.
PubMed: 38956354
DOI: 10.1038/s41570-024-00622-1 -
Nature Biotechnology Jul 2024Existing organoid models fall short of fully capturing the complexity of cancer because they lack sufficient multicellular diversity, tissue-level organization,...
Existing organoid models fall short of fully capturing the complexity of cancer because they lack sufficient multicellular diversity, tissue-level organization, biological durability and experimental flexibility. Thus, many multifactorial cancer processes, especially those involving the tumor microenvironment, are difficult to study ex vivo. To overcome these limitations, we herein implemented tissue-engineering and microfabrication technologies to develop topobiologically complex, patient-specific cancer avatars. Focusing on colorectal cancer, we generated miniature tissues consisting of long-lived gut-shaped human colon epithelia ('mini-colons') that stably integrate cancer cells and their native tumor microenvironment in a format optimized for real-time, high-resolution evaluation of cellular dynamics. We demonstrate the potential of this system through several applications: a comprehensive evaluation of drug effectivity, toxicity and resistance in anticancer therapies; the discovery of a mechanism triggered by cancer-associated fibroblasts that drives cancer invasion; and the identification of immunomodulatory interactions among different components of the tumor microenvironment. Similar approaches should be feasible for diverse tumor types.
PubMed: 38956326
DOI: 10.1038/s41587-024-02301-4 -
Nature Biotechnology Jul 2024Antigen discovery technologies have largely focused on major histocompatibility complex (MHC) class I-restricted human T cell receptors (TCRs), leaving methods for MHC...
Antigen discovery technologies have largely focused on major histocompatibility complex (MHC) class I-restricted human T cell receptors (TCRs), leaving methods for MHC class II-restricted and mouse TCR reactivities relatively undeveloped. Here we present TCR mapping of antigenic peptides (TCR-MAP), an antigen discovery method that uses a synthetic TCR-stimulated circuit in immortalized T cells to activate sortase-mediated tagging of engineered antigen-presenting cells (APCs) expressing processed peptides on MHCs. Live, tagged APCs can be directly purified for deconvolution by sequencing, enabling TCRs with unknown specificity to be queried against barcoded peptide libraries in a pooled screening context. TCR-MAP accurately captures self-reactivities or viral reactivities with high throughput and sensitivity for both MHC class I-restricted and class II-restricted TCRs. We elucidate problematic cross-reactivities of clinical TCRs targeting the cancer/testis melanoma-associated antigen A3 and discover targets of myocarditis-inciting autoreactive T cells in mice. TCR-MAP has the potential to accelerate T cell antigen discovery efforts in the context of cancer, infectious disease and autoimmunity.
PubMed: 38956325
DOI: 10.1038/s41587-024-02248-6 -
Nature Nanotechnology Jul 2024The Nernst effect, a transverse thermoelectric phenomenon, has attracted significant attention for its potential in energy conversion, thermoelectrics and spintronics....
The Nernst effect, a transverse thermoelectric phenomenon, has attracted significant attention for its potential in energy conversion, thermoelectrics and spintronics. However, achieving high performance and versatility at low temperatures remains elusive. Here we demonstrate a large and electrically tunable Nernst effect by combining the electrical properties of graphene with the semiconducting characteristics of indium selenide in a field-effect geometry. Our results establish a new platform for exploring and manipulating this thermoelectric effect, showcasing the first electrical tunability with an on/off ratio of 10. Moreover, photovoltage measurements reveal a stronger photo-Nernst signal in the graphene/indium selenide heterostructure compared with individual components. Remarkably, we observe a record-high Nernst coefficient of 66.4 μV K T at ultralow temperatures and low magnetic fields, an important step towards applications in quantum information and low-temperature emergent phenomena.
PubMed: 38956321
DOI: 10.1038/s41565-024-01717-y -
Nature Nanotechnology Jul 2024Neuromodulation technologies are crucial for investigating neuronal connectivity and brain function. Magnetic neuromodulation offers wireless and remote deep brain...
Neuromodulation technologies are crucial for investigating neuronal connectivity and brain function. Magnetic neuromodulation offers wireless and remote deep brain stimulations that are lacking in optogenetic- and wired-electrode-based tools. However, due to the limited understanding of working principles and poorly designed magnetic operating systems, earlier magnetic approaches have yet to be utilized. Furthermore, despite its importance in neuroscience research, cell-type-specific magnetic neuromodulation has remained elusive. Here we present a nanomaterials-based magnetogenetic toolbox, in conjunction with Cre-loxP technology, to selectively activate genetically encoded Piezo1 ion channels in targeted neuronal populations via torque generated by the nanomagnetic actuators in vitro and in vivo. We demonstrate this cell-type-targeting magnetic approach for remote and spatiotemporal precise control of deep brain neural activity in multiple behavioural models, such as bidirectional feeding control, long-term neuromodulation for weight control in obese mice and wireless modulation of social behaviours in multiple mice in the same physical space. Our study demonstrates the potential of cell-type-specific magnetogenetics as an effective and reliable research tool for life sciences, especially in wireless, long-term and freely behaving animals.
PubMed: 38956320
DOI: 10.1038/s41565-024-01694-2 -
Journal of Perinatology : Official... Jul 2024To assess the ideal time for caffeine administration in preterms, identifying its effects and safety. Study Design: Meta-analysis conducted including preterms <32 weeks... (Review)
Review
To assess the ideal time for caffeine administration in preterms, identifying its effects and safety. Study Design: Meta-analysis conducted including preterms <32 weeks GA or BW < 1500 g, comparing caffeine administration time: <24 x ≥24HOL, <48 x ≥48HOL, <72 x ≥72HOL. 18 studies included 76.998 patients. The median age of starting caffeine was the first 24 HOL. In the overall comparisons, there was reduction in patent ductus arteriosus (OR 0.71 [0.55, 0. 92]; low evidence), retinopathy of prematurity (OR 0.71 [0.54, 0.93]; moderate evidence), severe brain injury (OR 0.79 [0.70, 0.91]; moderate evidence), bronchopulmonary dysplasia (BPD) (OR 0.69 [0.59, 0.81]; moderate evidence), composite outcome of BPD or death (OR 0.76 [0.66, 0.88]; moderate evidence). Mortality increase was found (OR 1.20 [1.12, 1.29], very low evidence).Caffeine in the first 24 HOL has benefits in reducing morbidities associated with prematurity. Mortality finding is potentially due to survival bias.
PubMed: 38956314
DOI: 10.1038/s41372-024-02042-x -
Scientific Reports Jul 2024Influenza A virus subtype H1N1 can cause severe acute respiratory distress syndrome and death in young children and elderly individuals. H1N1 initiates inflammatory...
Influenza A virus subtype H1N1 can cause severe acute respiratory distress syndrome and death in young children and elderly individuals. H1N1 initiates inflammatory responses that aim to contain and eliminate microbial invaders. Various lipid mediators (LMs) are biosynthesized and play a critical role in fighting viruses during inflammation; thus, by profiling the LMs in patients, researchers can obtain mechanistic insights into diseases, such as the pathways disrupted. To date, the relationship between molecular alterations in LMs and the pathogenesis of H1N1 influenza in children is poorly understood. Here, we employed a targeted liquid chromatography coupled with tandem mass spectrometry (LC‒MS/MS) to profile LMs in serum from children with H1N1 influenza (H1N1 children) and recovered children. We found that 22 LM species were altered in H1N1 children with mild symptoms. Analysis of the LM profiles of recovered children revealed a decrease in the levels of thromboxane B2 (TxB) and thromboxane B3 (TxB) and an increase in the levels of other 8 altered LM species associated with H1N1 influenza, including cytochrome P450 (CYP) enzyme-derived dihydroxyeicosatrienoic acids (DiHETrEs) and hydroxyeicosatetraenoic acids (HETEs) from arachidonic acid (AA), and epoxyoctadecamonoenoic acids (EpOMEs) from linoleic acid (LA). Taken together, the results of this study revealed that serum LMs change dynamically in H1N1 children with mild symptoms. The dramatically altered LMs in H1N1 children could serve as a basis for potential therapeutics or adjuvants against H1N1 influenza.
Topics: Humans; Influenza A Virus, H1N1 Subtype; Influenza, Human; Child; Male; Female; Child, Preschool; Tandem Mass Spectrometry; Lipids; Chromatography, Liquid; Infant; Lipidomics
PubMed: 38956313
DOI: 10.1038/s41598-024-66190-y