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1.
Artículo en Inglés | MEDLINE | ID: mdl-39110558

RESUMEN

Multi-omics integration has demonstrated promising performance in complex disease prediction. However, existing research typically focuses on maximizing prediction accuracy, while often neglecting the essential task of discovering meaningful biomarkers. This issue is particularly important in biomedicine, as molecules often interact rather than function individually to influence disease outcomes. To this end, we propose a two-phase framework named GREMI to assist multi-omics classification and explanation. In the prediction phase, we propose to improve prediction performance by employing a graph attention architecture on sample-wise co-functional networks to incorporate biomolecular interaction information for enhanced feature representation, followed by the integration of a joint-late mixed strategy and the true-class-probability block to adaptively evaluate classification confidence at both feature and omics levels. In the interpretation phase, we propose a multi-view approach to explain disease outcomes from the interaction module perspective, providing a more intuitive understanding and biomedical rationale. We incorporate Monte Carlo tree search (MCTS) to explore local-view subgraphs and pinpoint modules that highly contribute to disease characterization from the global-view. Extensive experiments demonstrate that the proposed framework outperforms state-of-the-art methods in seven different classification tasks, and our model effectively addresses data mutual interference when the number of omics types increases. We further illustrate the functional- and disease-relevance of the identified modules, as well as validate the classification performance of discovered modules using an independent cohort. Code and data are available at https://github.com/Yaolab-fantastic/GREMI.

2.
J Colloid Interface Sci ; 677(Pt A): 577-586, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39111093

RESUMEN

The intriguing characteristics of two-dimensional (2D) heterostructures stem from their unique interfaces, which can improve ion storage capability and rate performance. However, there are still challenges in increasing the proportion of heterogeneous interfaces in materials and understanding the complex interaction mechanisms at these interfaces. Here, we have successfully synthesized confined CoSe2 within the interlayer space of Ti3C2Tx through a simple solvothermal method, resulting in the formation of a superlattice-like heterostructures of CoSe2@Ti3C2Tx. Both density functional theory (DFT) calculations and experimental results show that compared with CoSe2 and Ti3C2Tx, CoSe2@Ti3C2Tx can significantly improve adsorption of Na+ ions, while maintaining low volume expansion and high Na+ ions migration rate. The heterostructure formed by MXene and CoSe2 is a Schottky heterostructure, and its interfacial charge transfer induces a built-in electric field that promotes rapid ion transport. When CoSe2@Ti3C2Tx was used as an anode material, it exhibits a high specific capacity of up to 600.1 mAh/g and an excellent rate performance of 206.3 mAh/g at 20 A/g. By utilizing CoSe2@Ti3C2Tx as the anode and activated carbon (AC) as the cathode, the sodium-ion capacitor of CoSe2@Ti3C2Tx//AC exhibits excellent energy and power density (125.0 Wh kg-1 and 22.5 kW kg-1 at 300.0 W kg-1 and 37.5 Wh kg-1, respectively), as well as a long service life (86.3 % capacity retention over 15,300 cycles at 5 A/g), demonstrating its potential for practical applications.

3.
Platelets ; 35(1): 2379815, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39072584

RESUMEN

Previous studies have reported inconsistent associations between platelet count (PLT) and cancer survival. However, whether there is linear causal effect merits in-depth investigations. We conducted a cohort study using the UK Biobank and a two-sample Mendelian randomization (MR) analysis. PLT levels were measured prior to cancer diagnosis. We adopted overall survival (OS) as the primary outcome. Cox models were utilized to estimate the effects of PLTs on survival outcomes at multiple lag times for cancer diagnosis. We employed 34 genetic variants as PLT proxies for MR analysis. Linear and non-linear effects were modeled. Prognostic effects of gene expression harboring the instrumental variants were also investigated. A total of 65 471 cancer patients were included. We identified a significant association between elevated PLTs (per 100 × 109/L) and inferior OS (HR: 1.07; 95% CI: 1.04-1.10; p < .001). Similar significant associations were observed for several cancer types. We further observed a U-shaped relationship between PLTs and cancer survival (p < .001). Our MR analysis found null evidence to support a causal association between PLTs and overall cancer survival (HR: 1.000; 95% CI: 0.998-1.001; p = .678), although non-linear MR analysis unveiled a potential greater detrimental effect at lower PLT range. Expression of eleven PLT-related genes were associated with cancer survival. Early detection of escalated PLTs indicated possible occult cancer development and inferior subsequent survival outcomes. The observed associations could potentially be non-linear. However, PLT is less likely to be a promising therapeutic target.


What is the context? Previous studies have reported inconsistent associations between platelet counts (PLTs) and cancer survival. However, it is unclear whether there is a linear causal effect, as most studies measured PLTs at the time of cancer diagnosis, which could be influenced by the cancer itself.This study aimed to investigate the association and potential causality between pre-diagnostic PLTs and cancer survival outcomes using a large prospective cohort and genetic analysis.What is new? The observational cohort study found a significant association between elevated pre-diagnostic PLTs and poorer overall and cancer-specific survival. We also identified a U-shaped relationship between PLTs and cancer survival, suggesting that both high and low PLTs may be detrimental.The Mendelian randomization analysis did not support a causal effect of PLTs on overall cancer survival, although it hinted at potential non-linear effects at lower PLT ranges.The study also identified several genes (TPM4, PDIA5, PSMD13, TMCC2, ZFPM2, BAZ2A, CDKN2A, GP1BA, TAOK1, CABLES1, and THPO) related to PLTs that were associated with cancer survival.What is the impact? The findings suggest that early detection of elevated PLTs may indicate occult cancer development and poorer subsequent survival outcomes. However, PLTs are less likely to be a promising therapeutic target for improving cancer survival, as the observed associations could be influenced by confounding factors.The study highlights the need for further research into the complex relationship between PLTs and cancer prognosis, as well as the exploration of other platelet-related traits as potential drug targets.


Asunto(s)
Neoplasias , Humanos , Neoplasias/genética , Neoplasias/mortalidad , Neoplasias/sangre , Recuento de Plaquetas/métodos , Femenino , Masculino , Pronóstico , Análisis de la Aleatorización Mendeliana/métodos , Plaquetas/metabolismo , Persona de Mediana Edad
4.
Adv Sci (Weinh) ; : e2404968, 2024 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-39033539

RESUMEN

The feasibility of aqueous zinc-ion batteries for large-scale energy storage is hindered by the inherent challenges of Zn anode. Drawing inspiration from cellular mechanisms governing metal ion and nutrient transport, erythritol is introduced, a zincophilic additive, into the ZnSO4 electrolyte. This innovation stabilizes the Zn anode via chelation interactions between polysaccharides and Zn2+. Experimental tests in conjunction with theoretical calculation results verified that the erythritol additive can simultaneously regulate the solvation structure of hydrated Zn2+ and reconstruct the hydrogen bond network within the solution environment. Additionally, erythritol molecules preferentially adsorb onto the Zn anode, forming a dynamic protective layer. These modifications significantly mitigate undesirable side reactions, thus enhancing the Zn2+ transport and deposition behavior. Consequently, there is a notable increase in cumulative capacity, reaching 6000 mA h cm⁻2 at a current density of 5 mA cm-2. Specifically, a high average coulombic efficiency of 99.72% and long cycling stability of >500 cycles are obtained at 2 mA cm-2 and 1 mA h cm-2. Furthermore, full batteries comprised of MnO2 cathode and Zn anode in an erythritol-containing electrolyte deliver superior capacity retention. This work provides a strategy to promote the performance of Zn anodes toward practical applications.

5.
Cell Genom ; 4(8): 100607, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-38996479

RESUMEN

Chondrichthyes is an important lineage to reconstruct the evolutionary history of vertebrates. Here, we analyzed genome synteny for six chondrichthyan chromosome-level genomes. Our comparative analysis reveals a slow evolutionary rate of chromosomal changes, with infrequent but independent fusions observed in sharks, skates, and chimaeras. The chondrichthyan common ancestor had a proto-vertebrate-like karyotype, including the presence of 18 microchromosome pairs. The X chromosome is a conversed microchromosome shared by all sharks, suggesting a likely common origin of the sex chromosome at least 181 million years ago. We characterized the Y chromosomes of two sharks that are highly differentiated from the X except for a small young evolutionary stratum and a small pseudoautosomal region. We found that shark sex chromosomes lack global dosage compensation but that dosage-sensitive genes are locally compensated. Our study on shark chromosome evolution enhances our understanding of shark sex chromosomes and vertebrate chromosome evolution.


Asunto(s)
Evolución Molecular , Genómica , Cariotipo , Cromosomas Sexuales , Tiburones , Animales , Tiburones/genética , Genómica/métodos , Cromosomas Sexuales/genética , Masculino , Femenino , Sintenía/genética , Filogenia , Compensación de Dosificación (Genética) , Cromosoma X/genética , Genoma/genética
6.
BioData Min ; 17(1): 9, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38444019

RESUMEN

BACKGROUND: Integrating multi-omics data is emerging as a critical approach in enhancing our understanding of complex diseases. Innovative computational methods capable of managing high-dimensional and heterogeneous datasets are required to unlock the full potential of such rich and diverse data. METHODS: We propose a Multi-Omics integration framework with auxiliary Classifiers-enhanced AuToencoders (MOCAT) to utilize intra- and inter-omics information comprehensively. Additionally, attention mechanisms with confidence learning are incorporated for enhanced feature representation and trustworthy prediction. RESULTS: Extensive experiments were conducted on four benchmark datasets to evaluate the effectiveness of our proposed model, including BRCA, ROSMAP, LGG, and KIPAN. Our model significantly improved most evaluation measurements and consistently surpassed the state-of-the-art methods. Ablation studies showed that the auxiliary classifiers significantly boosted classification accuracy in the ROSMAP and LGG datasets. Moreover, the attention mechanisms and confidence evaluation block contributed to improvements in the predictive accuracy and generalizability of our model. CONCLUSIONS: The proposed framework exhibits superior performance in disease classification and biomarker discovery, establishing itself as a robust and versatile tool for analyzing multi-layer biological data. This study highlights the significance of elaborated designed deep learning methodologies in dissecting complex disease phenotypes and improving the accuracy of disease predictions.

7.
Int J Mol Sci ; 25(3)2024 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-38338932

RESUMEN

Advancing the domain of biomedical investigation, integrated multi-omics data have shown exceptional performance in elucidating complex human diseases. However, as the variety of omics information expands, precisely perceiving the informativeness of intra- and inter-omics becomes challenging due to the intricate interrelations, thus presenting significant challenges in the integration of multi-omics data. To address this, we introduce a novel multi-omics integration approach, referred to as TEMINET. This approach enhances diagnostic prediction by leveraging an intra-omics co-informative representation module and a trustworthy learning strategy used to address inter-omics fusion. Considering the multifactorial nature of complex diseases, TEMINET utilizes intra-omics features to construct disease-specific networks; then, it applies graph attention networks and a multi-level framework to capture more collective informativeness than pairwise relations. To perceive the contribution of co-informative representations within intra-omics, we designed a trustworthy learning strategy to identify the reliability of each omics in integration. To integrate inter-omics information, a combined-beliefs fusion approach is deployed to harmonize the trustworthy representations of different omics types effectively. Our experiments across four different diseases using mRNA, methylation, and miRNA data demonstrate that TEMINET achieves advanced performance and robustness in classification tasks.


Asunto(s)
MicroARNs , Multiómica , Humanos , Reproducibilidad de los Resultados , Aprendizaje , MicroARNs/genética , Procesamiento Proteico-Postraduccional
8.
BMC Genom Data ; 25(1): 11, 2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-38291423

RESUMEN

OBJECTIVES: A genome sequence of a threatened species can provide valuable genetic information that is important for improving the conservation strategies. The white-eared night heron (Gorsachius magnificus) is an endangered and poorly known ardeid bird. In order to support future studies on conservation genetics and evolutionary adaptation of this species, we have reported a de novo assembled and annotated whole-genome sequence of the G. magnificus. DATA DESCRIPTION: The final draft genome assembly of the G. magnificus was 1.19 Gb in size, with a contig N50 of 187.69 kb and a scaffold N50 of 7,338.28 kb. According to BUSCO analysis, the genome assembly contained 97.49% of the 8,338 genes in the Aves (odb10) dataset. Approximately 10.52% of the genome assembly was composed of repetitive sequences. A total of 14,613 protein-coding genes were predicted in the genome assembly, with functional annotations available for 14,611 genes. The genome assembly exhibited a heterozygosity rate of 0.49 heterozygosity per kilobase pair. This draft genome of G. magnificus provides valuable genomic resources for future studies on conservation and evolution.


Asunto(s)
Genoma , Genómica , Animales , Anotación de Secuencia Molecular , Genoma/genética , Especies en Peligro de Extinción , Aves/genética
9.
Small ; 20(6): e2305902, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37775329

RESUMEN

Rechargeable aqueous zinc-ion batteries are regarded as promising energy storage devices due to their attractive economic benefits and extraordinary electrochemical performance. However, the sluggish Zn2+ mass transfer behavior and water-induced parasitic reactions that occurred on the anode-electrode interface inevitably restrain their applications. Herein, inspired by the selective permeability and superior stability of plasma membrane, a thin UiO-66 metal-organic framework layer with smart aperture size is ex-situ decorated onto the Zn anode. Experimental characterizations in conjunction with theoretical calculations demonstrate that this bio-inspired layer promotes the de-solvation process of hydrated Zn2+ and reduces the effective contact between the anode and H2 O molecules, thereby boosting Zn2+ deposition kinetics and restraining interfacial parasitic reactions. Hence, the Zn||Zn cells could sustain a long lifespan of 1680 h and the Zn||Cu cells yielded a stable coulombic efficiency of over 99.3% throughout 600 cycles under the assistance of the bio-inspired layer. Moreover, pairing with δ-MnO2 cathode, the full cells also demonstrate prominent cycling stability and rate performance. From the bio-inspired design philosophy, this work provides a novel insight into the development of aqueous batteries.

10.
Chem Asian J ; 19(4): e202301031, 2024 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-38081784

RESUMEN

Dearomative intramolecular Diels-Alder/sulfur extrusion reaction of thiophenes with alkynes successfully afforded fluoranthenes in moderate to excellent yields. The proximity of both reactive sites fixed at the peri-position of naphthalene would play an important role in the progress of this reaction. Tri(o-tolyl)phosphine effectively suppressed the side reactions as a sulfur scavenger.

11.
Neurobiol Aging ; 134: 84-93, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38039940

RESUMEN

Although genome-wide association studies have identified multiple Alzheimer's disease (AD)-associated loci by selecting the main effects of individual single-nucleotide polymorphisms (SNPs), the interpretation of genetic variance in AD is limited. Based on the linear regression method, we performed genome-wide SNP-SNP interaction on cerebrospinal fluid Aß42 to identify potential genetic epistasis implicated in AD, with age, gender, and diagnosis as covariates. A GPU-based method was used to address the computational challenges posed by the analysis of epistasis. We found 368 SNP pairs to be statistically significant, and highly significant SNP-SNP interactions were identified between the marginal main effects of SNP pairs, which explained a relatively high variance at the Aß42 level. Our results replicated 100 previously reported AD-related genes and 5 gene-gene interaction pairs of the protein-protein interaction network. Our bioinformatics analyses provided preliminary evidence that the 5-overlapping gene-gene interaction pairs play critical roles in inducing synaptic loss and dysfunction, thereby leading to memory decline and cognitive impairment in AD-affected brains.


Asunto(s)
Enfermedad de Alzheimer , Humanos , Enfermedad de Alzheimer/diagnóstico , Polimorfismo de Nucleótido Simple/genética , Epistasis Genética/genética , Péptidos beta-Amiloides/líquido cefalorraquídeo , Estudio de Asociación del Genoma Completo , Proteínas tau/líquido cefalorraquídeo , Biomarcadores/líquido cefalorraquídeo , Fragmentos de Péptidos/líquido cefalorraquídeo
12.
Infect Med (Beijing) ; 2(3): 212-223, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38073882

RESUMEN

Background: West Nile virus is a severe zoonotic pathogen that can cause severe central nervous system symptoms in humans and horses, and is fatal for birds, chickens and other poultry. With no specific drugs or vaccines available, antibody-based therapy is a promising treatment. This study aims to develop neutralizing antibodies against West Nile virus and assess their cross-protective potential against Japanese encephalitis virus. Methods: Monoclonal antibodies against WNV and JEV were isolated by hybridoma technology. The therapeutic efficacy of these antibodies was evaluated using a mouse model, and a humanized version of the monoclonal antibody was generated for potential human application. Results: In this study, we generated eight monoclonal antibodies that exhibit neutralizing activity against WNV. Their therapeutic effects against WNV were validated both in vivo and in vitro. Among these antibodies, C9-G11-F3 also exhibited cross-protective activity against JEV. We also humanized the antibody to ensure that it could be used for WNV infection treatment in humans. Conclusion: This study highlights the importance of neutralizing antibodies as a promising approach for protection against West Nile virus infection and suggests their potential utility in the development of therapeutic interventions.

13.
J Phys Chem Lett ; 14(41): 9167-9175, 2023 Oct 19.
Artículo en Inglés | MEDLINE | ID: mdl-37797163

RESUMEN

Aqueous zinc ion batteries exhibit a promising application prospect for next-generation energy storage devices. However, the decomposition of active H2O molecules on the Zn anode induces drastic dendrite formation, thereby impairing the performance for entire devices. To solve this challenge, we introduce subnanocyclic molecules of 15-Crown-5 as an additive into ZnSO4 electrolyte to stabilize the Zn anode. Owing to the binding property of crown ethers with alkali metal ions and the size-fit rule, the 15-Crown-5 additives enable effective regulation of the solvation structure of hydrated Zn2+ and reduce the efficient contact between Zn anode and active H2O, which are validated by the experimental analysis and theoretical calculations. Under the assistance of the 15-Crown-5 additive, the as-assembled Zn-based batteries deliver superior performance compared with ZnSO4 and 18-Crown-6contaning ZnSO4 electrolytes. This work shows a bright direction toward progress in aqueous batteries.

14.
J Phys Chem Lett ; 14(41): 9150-9158, 2023 Oct 19.
Artículo en Inglés | MEDLINE | ID: mdl-37796231

RESUMEN

Aqueous zinc-ion batteries are considered promising energy storage devices due to their superior electrochemical performance. Nevertheless, the uncontrolled dendrites and parasitic side reactions adversely affect the stability and durability of the Zn anode. To cope with these issues, inspired by the chelation behavior between metal ions and amino acids in the biological system, glutamic acid and aspartic acid are selected as electrolyte additives to stabilize the Zn anode. Experimental characterizations in conjunction with theoretical calculation results indicate that these additives can simultaneously modify the solvation structure of hydrated Zn2+ and preferentially adsorb onto the Zn anode, thereby restricting the occurrence of interfacial side reactions and enhancing the performance of the Zn anode. Benefiting from these synergistic effects, the as-assembled Zn-based batteries containing additive electrolytes achieved admirable electrochemical performance. From the viewpoint of electrolyte regulation, this work provides a bright direction toward the development of aqueous batteries.

15.
Int J Mol Med ; 52(5)2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37800616

RESUMEN

Iron overload is a prevalent pathological factor observed among elderly individuals and those with specific hematological disorders, and is frequently associated with an elevated incidence of osteoporosis. Although arctiin (ARC) has been shown to possess antioxidant properties and the ability to mitigate bone degeneration, its mechanism of action in the treatment of iron overload­induced osteoporosis (IOOP) remains incompletely understood. To explore the potential molecular mechanisms underlying the effects of ARC, the MC3T3­E1 cell osteoblast cell line was used. Cell Counting Kit was used to assess MC3T3­E1 cell viability. Alkaline phosphatase staining and alizarin red staining were assessed for osteogenic differentiation. Calcein AM assay was used to assess intracellular iron concentration. In addition, intracellular levels of reactive oxygen species (ROS), lipid peroxides, mitochondrial ROS, apoptosis rate and mitochondrial membrane potential changes in MC3T3­E1 cells were examined using flow cytometry and corresponding fluorescent dyes. The relationship between ARC and the PI3K/Akt pathway was then explored by western blotting and immunofluorescence. In addition, the effects of ARC on IOOP was verified using an iron overload mouse model. Immunohistochemistry was performed to evaluate expression of osteogenesis­related proteins. Micro-CT and H&E were used to analyze bone microstructural parameters and histomorphometric indices in the bone tissue. Notably, ARC treatment reversed the decreased viability and increased apoptosis in MC3T3­E1 cells originally induced by ferric ammonium citrate, whilst promoting the formation of mineralized bone nodules in MC3T3­E1 cells. Furthermore, iron overload induced a decrease in the mitochondrial membrane potential, augmented lipid peroxidation and increased the accumulation of ROS in MC3T3­E1 cells. ARC not only positively regulated the anti­apoptotic and osteogenic capabilities of these cells via modulation of the PI3K/Akt pathway, but also exhibited antioxidant properties by reducing oxidative stress. In vivo experiments confirmed that ARC improved bone microarchitecture and biochemical parameters in a mouse model of iron overload. In conclusion, ARC exhibits potential as a therapeutic agent for IOOP by modulating the PI3K/Akt pathway, and via its anti­apoptotic, antioxidant and osteogenic properties.


Asunto(s)
Sobrecarga de Hierro , Osteoporosis , Humanos , Ratones , Animales , Anciano , Proteínas Proto-Oncogénicas c-akt/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Antioxidantes/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Osteogénesis , Sobrecarga de Hierro/complicaciones , Sobrecarga de Hierro/tratamiento farmacológico , Sobrecarga de Hierro/metabolismo , Osteoporosis/tratamiento farmacológico , Osteoporosis/etiología , Osteoblastos/metabolismo
16.
Commun Biol ; 6(1): 746, 2023 07 18.
Artículo en Inglés | MEDLINE | ID: mdl-37463976

RESUMEN

Conservation genomics often relies on non-invasive methods to obtain DNA fragments which limit the power of multi-omic analyses for threatened species. Here, we report multi-omic analyses based on a well-preserved great bustard individual (Otis tarda, Otidiformes) that was found dead in the mountainous region in Gansu, China. We generate a near-complete genome assembly containing only 18 gaps scattering in 8 out of the 40 assembled chromosomes. We characterize the DNA methylation landscape which is correlated with GC content and gene expression. Our phylogenomic analysis suggests Otidiformes and Musophagiformes are sister groups that diverged from each other 46.3 million years ago. The genetic diversity of great bustard is found the lowest among the four available Otidiformes genomes, possibly due to population declines during past glacial periods. As one of the heaviest migratory birds, great bustard possesses several expanded gene families related to cardiac contraction, actin contraction, calcium ion signaling transduction, as well as positively selected genes enriched for metabolism. Finally, we identify an extremely young evolutionary stratum on the sex chromosome, a rare case among birds. Together, our study provides insights into the conservation genomics, adaption and chromosome evolution of the great bustard.


Asunto(s)
Aves , Especies en Peligro de Extinción , Animales , Aves/genética , ADN Mitocondrial/genética , Genómica , Filogenia
17.
Genes (Basel) ; 14(7)2023 06 23.
Artículo en Inglés | MEDLINE | ID: mdl-37510227

RESUMEN

Alzheimer's disease (AD) is the main cause of dementia worldwide, and the genetic mechanism of which is not yet fully understood. Much evidence has accumulated over the past decade to suggest that after the first large-scale genome-wide association studies (GWAS) were conducted, the problem of "missing heritability" in AD is still a great challenge. Epistasis has been considered as one of the main causes of "missing heritability" in AD, which has been largely ignored in human genetics. The focus of current genome-wide epistasis studies is usually on single nucleotide polymorphisms (SNPs) that have significant individual effects, and the amount of heritability explained by which was very low. Moreover, AD is characterized by progressive cognitive decline and neuronal damage, and some studies have suggested that hyperphosphorylated tau (P-tau) mediates neuronal death by inducing necroptosis and inflammation in AD. Therefore, this study focused on identifying epistasis between two-marker interactions at marginal main effects across the whole genome using cerebrospinal fluid (CSF) P-tau as quantitative trait (QT). We sought to detect interactions between SNPs in a multi-GPU based linear regression method by using age, gender, and clinical diagnostic status (cds) as covariates. We then used the STRING online tool to perform the PPI network and identify two-marker epistasis at the level of gene-gene interaction. A total of 758 SNP pairs were found to be statistically significant. Particularly, between the marginal main effect SNP pairs, highly significant SNP-SNP interactions were identified, which explained a relatively high variance at the P-tau level. In addition, 331 AD-related genes were identified, 10 gene-gene interaction pairs were replicated in the PPI network. The identified gene-gene interactions and genes showed associations with AD in terms of neuroinflammation and neurodegeneration, neuronal cells activation and brain development, thereby leading to cognitive decline in AD, which is indirectly associated with the P-tau pathological feature of AD and in turn supports the results of this study. Thus, the results of our study might be beneficial for explaining part of the "missing heritability" of AD.


Asunto(s)
Enfermedad de Alzheimer , Humanos , Enfermedad de Alzheimer/patología , Proteínas tau/genética , Proteínas tau/líquido cefalorraquídeo , Péptidos beta-Amiloides/genética , Estudio de Asociación del Genoma Completo , Epistasis Genética
19.
Proc Natl Acad Sci U S A ; 120(8): e2216641120, 2023 02 21.
Artículo en Inglés | MEDLINE | ID: mdl-36780517

RESUMEN

Microchromosomes are prevalent in nonmammalian vertebrates [P. D. Waters et al., Proc. Natl. Acad. Sci. U.S.A. 118 (2021)], but a few of them are missing in bird genome assemblies. Here, we present a new chicken reference genome containing all autosomes, a Z and a W chromosome, with all gaps closed except for the W. We identified ten small microchromosomes (termed dot chromosomes) with distinct sequence and epigenetic features, among which six were newly assembled. Those dot chromosomes exhibit extremely high GC content and a high level of DNA methylation and are enriched for housekeeping genes. The pericentromeric heterochromatin of dot chromosomes is disproportionately large and continues to expand with the proliferation of satellite DNA and testis-expressed genes. Our analyses revealed that the 41-bp CNM repeat frequently forms higher-order repeats (HORs) at the centromeres of acrocentric chromosomes. The centromere core regions where the kinetochore attaches often encompass telomeric sequence (TTAGGG)n, and in a one of the dot chromosomes, the centromere core recruits an endogenous retrovirus (ERV). We further demonstrate that the W chromosome shares some common features with dot chromosomes, having large arrays of hypermethylated tandem repeats. Finally, using the complete chicken chromosome models, we reconstructed a fine picture of chordate karyotype evolution, revealing frequent chromosomal fusions before and after vertebrate whole-genome duplications. Our sequence and epigenetic characterization of chicken chromosomes shed insights into the understanding of vertebrate genome evolution and chromosome biology.


Asunto(s)
Centrómero , Pollos , Animales , Masculino , Pollos/genética , Centrómero/genética , Telómero , Heterocromatina , Secuencias Repetidas en Tándem
20.
Small ; 19(10): e2207502, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36650991

RESUMEN

Aqueous zinc-ion batteries hold attractive potential for large-scale energy storage devices owing to their prominent electrochemical performance and high security. Nevertheless, the applications of aqueous electrolytes have generated various challenges, including uncontrolled dendrite growth and parasitic reactions, thereby deteriorating the Zn anode's stability. Herein, inspired by the superior affinity between Zn2+ and amino acid chains in the zinc finger protein, a cost-effective and green glycine additive is incorporated into aqueous electrolytes to stabilize the Zn anode. As confirmed by experimental characterizations and theoretical calculations, the glycine additives can not only reorganize the solvation sheaths of hydrated Zn2+ via partial substitution of coordinated H2 O but also preferentially adsorb onto the Zn anode, thereby significantly restraining dendrite growth and interfacial side reactions. Accordingly, the Zn anode could realize a long lifespan of over 2000 h and enhanced reversibility (98.8%) in the glycine-containing electrolyte. Furthermore, the assembled Zn||α-MnO2 full cells with glycine-modified electrolyte also delivers substantial capacity retention (82.3% after 1000 cycles at 2 A g-1 ), showing promising application prospects. This innovative bio-inspired design concept would inject new vitality into the development of aqueous electrolytes.

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