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1.
Talanta ; 281: 126861, 2025 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-39260257

RESUMO

In clinical practice, owing to the comprehensive genetic insights they offer, haplotypes have attracted greater attention than individual single nucleotide polymorphisms (SNPs). Due to the long distances across SNP locations, detecting the haplotype using genomic DNA is challenging. Current haplotyping methods are either expensive and labor-intensive (high-throughput DNA sequencing), or haplotyping a single clinical sample (computational approach) is impossible. Herein, we propose using mRNA as a haplotyping target to minimize the distance among SNPs and employing allele-specific PCR (AS-PCR) to pick up a desired haplotype, followed by multiplex pyrosequencing to type the alleles at the SNP location of interest. AS-PCR was improved by combining an additional 3'-phosphorylated modified probe to achieve the specific separation of two closely similar templates. Only the sample with more than two heterozygotes needs to be haplotyped; therefore, we propose a stratification strategy to screen the samples for further haplotyping. This method was evaluated by associating ABCB1 haplotypes with the rivaroxaban-derived side effect in a cohort of 505 patients with nephrotic syndrome, focusing on the SNPs of ABCB1: rs1236C > T, rs2677G > T/A, and rs3435C > T. We successfully identified five bleeding-related haplotypes: rs1236T-rs2677T-rs3435T, rs1236C-rs2677G-rs3435T, rs1236T-rs2677G-rs3435C, rs1236C-rs2677G-rs3435C, and rs1236T-rs2677T-rs3435C. We compared the results with those from the conventional computational algorithm PHASE and observed that PHASE results dismissed the impact of rs1236C-rs2677G-rs3435C and rs1236C-rs2677G-rs3435T on bleeding risk and erroneously suggested a false positive association of rs1236C-rs2677A-rs3435T with increased bleeding risk.


Assuntos
Subfamília B de Transportador de Cassetes de Ligação de ATP , Haplótipos , Polimorfismo de Nucleotídeo Único , Rivaroxabana , Humanos , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Hemorragia/genética , Reação em Cadeia da Polimerase Multiplex/métodos , Alelos
2.
Adv Sci (Weinh) ; : e2410099, 2024 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-39412082

RESUMO

Developing strategies to systematically increase the critical current, the threshold current below which the superconductivity exists, is an important goal of materials science. Here, the concept of quantum phase transition is employed to enhance the critical current of a kagome superconductor CsV3Sb5, which exhibits a charge density wave (CDW) and superconductivity that are both affected by hydrostatic pressure. As the CDW phase is rapidly suppressed under pressure, a large enhancement in the self-field critical current (Ic, sf) is recorded. The observation of a peak-like enhancement of Ic, sf at the zero-temperature limit (Ic, sf(0)) centered at p* ≈ 20 kbar, the same pressure where the CDW phase transition vanishes, further provides strong evidence of a zero-temperature quantum anomaly in this class of pressure-tuned superconductor. Such a peak in Ic, sf(0) resembles the findings in other well-established quantum-critical superconductors, hinting at the presence of enhanced quantum fluctuations associated with the CDW phase in CsV3Sb5.

3.
Tomography ; 10(10): 1676-1693, 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-39453040

RESUMO

Accurate assessment of N staging in patients with non-small cell lung cancer (NSCLC) is critical for the development of effective treatment plans, the optimization of therapeutic strategies, and the enhancement of patient survival rates. This study proposes a hybrid model based on 3D convolutional neural networks (CNNs) and transformers for predicting the N-staging and survival rates of NSCLC patients within the NSCLC radiogenomics and Nsclc-radiomics datasets. The model achieved accuracies of 0.805, 0.828, and 0.819 for the training, validation, and testing sets, respectively. By leveraging the strengths of CNNs in local feature extraction and the superior performance of transformers in global information modeling, the model significantly enhances predictive accuracy and efficacy. A comparative analysis with traditional CNN and transformer architectures demonstrates that the CNN-transformer hybrid model outperforms N-staging predictions. Furthermore, this study extracts the one-year survival rate as a feature and employs the Lasso-Cox model for survival predictions at various time intervals (1, 3, 5, and 7 years), with all survival prediction p-values being less than 0.05, illustrating the time-dependent nature of survival analysis. The application of time-dependent ROC curves further validates the model's accuracy and reliability for survival predictions. Overall, this research provides innovative methodologies and new insights for the early diagnosis and prognostic evaluation of NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Estadiamento de Neoplasias , Redes Neurais de Computação , Tomografia Computadorizada por Raios X , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Tomografia Computadorizada por Raios X/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Taxa de Sobrevida , Pulmão/diagnóstico por imagem , Pulmão/patologia
4.
Artigo em Inglês | MEDLINE | ID: mdl-39442083

RESUMO

Hafnium-based binary oxides are essential for fabricating nanoscale high-density ferroelectric memory devices. However, effective strategies to control and improve their thin-film single crystallinity and metastable ferroelectricity remain elusive, hindering potential applications. Here, using NdGaO3 (NGO) substrates with four crystalline orientations, we report a systematic study of the structural characterizations and ferroelectric properties of epitaxial Hf0.5Zr0.5O2 (HZO) films, demonstrating orientation-controlled high crystallinity and enhanced ferroelectric properties. HZO films grown on NGO(001) and NGO(110) substrates exhibit relatively low crystallinity and a significant presence of the monoclinic phase. In contrast, HZO films grown on NGO(100) and NGO(010) possess high single crystallinity and a dominant ferroelectric phase. These differences are attributed to the surface symmetry of the NGO substrate, which favors the formation of 4- or 2-fold domain configurations. Moreover, the optimized HZO films exhibit a large polarization (2Pr) of ∼50 µC/cm2, enhanced fatigue behavior up to 1011 cycles, improved retention of 2Pr ∼ 40 µC/cm2 after 10 years, and characteristic polarization switching speeds in the submicrosecond range. Our results highlight the importance of modulating the single crystallinity and ferroelectric phase fraction of HfO2-based films to enhance ferroelectric properties, further revealing the potential of epitaxial symmetry engineering.

5.
Updates Surg ; 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-39126533

RESUMO

PURPOSE: Traditional anesthesia for video-assisted thoracoscopy (VATS) such as double-lumen tracheal intubation (DLT) and one-lung ventilation (OLV), may lead to post-operative pulmonary complications (PPCs). Non-intubation VATS (NIVATS) is an anesthetic technique that avoided DLT and OLV, maybe avoiding the PPCs. So we hypothesized that NIVATS would non-inferiority to intubation VATS (IVATS) in the risk of developing PPCs and some safety indicators. METHODS: This study is a randomised, controlled, double-blind, non-inferiority trial, 120 patients were randomly assigned to the NIVATS group and IVATS group according to 1:1. The primary outcome was the incidence of PPCs with a pre-defined non-inferiority margin of 10%. The second outcome was the safety indicators, including the incidence of cough/body movement, hypoxemia, malignant arrhythmia, regurgitation and aspiration, and transferring to endobronchial intubation intraoperatively (The malignant arrhythmia was defined as an arrhythmia that caused hemodynamic disturbances in a short period of time, resulting in persistent hypotension or even cardiac arrest in the patient). RESULTS: There was no significant difference in demographic indicators such as gender and age between the two groups. The incidence of PPCs in the NIVATS group was non-inferior to that in the IVATS group (1.67% vs. 3.33%, absolute difference: - 1.67%; 95%CI - 7.25 to 3.91). In additionan, no significant differences were found between the two groups for the incidence of cough/body movement (10.00% vs. 11.67%, p = 0.77), the incidence of hypoxemia (25% vs. 18.33%, p = 0.38), the incidence of malignant arrhythmia (1.67% vs. 6.67%, p = 0.36), the incidence of regurgitation and aspiration (0% vs. 0%, p > 0.999) and the incidence of transferring to endobronchial intubation intraoperatively (0% vs. 0%, p > 0.999). CONCLUSION: We conclude that when using the non-intubation anesthesia for VATS, the incidence of PPCs was not inferior to intubation anesthesia. Furthermore, NIVATS had little effect on perioperative safety.

6.
Bioengineering (Basel) ; 11(8)2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39199725

RESUMO

When dealing with small targets in lung cancer detection, the YOLO V8 algorithm may encounter false positives and misses. To address this issue, this study proposes an enhanced YOLO V8 detection model. The model integrates a large separable kernel attention mechanism into the C2f module to expand the information retrieval range, strengthens the extraction of lung cancer features in the Backbone section, and achieves effective interaction between multi-scale features in the Neck section, thereby enhancing feature representation and robustness. Additionally, depth-wise convolution and Coordinate Attention mechanisms are embedded in the Fast Spatial Pyramid Pooling module to reduce feature loss and improve detection accuracy. This study introduces a Minimum Point Distance-based IOU loss to enhance correlation between predicted and ground truth bounding boxes, improving adaptability and accuracy in small target detection. Experimental validation demonstrates that the improved network outperforms other mainstream detection networks in terms of average precision values and surpasses other classification networks in terms of accuracy. These findings validate the outstanding performance of the enhanced model in the localization and recognition aspects of lung cancer auxiliary diagnosis.

7.
Curr Opin Chem Biol ; 81: 102505, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39053236

RESUMO

Glutathione (GSH) is a pivotal tripeptide antioxidant essential for maintaining cellular redox homeostasis and regulating diverse cellular processes. Subcellular compartmentalization of GSH underscores its multifaceted roles across various organelles including the cytosol, mitochondria, endoplasmic reticulum, and nucleus, each exhibiting distinct regulatory mechanisms. Perturbations in GSH dynamics contribute to pathophysiological conditions, emphasizing the clinical significance of understanding its intricate regulation. This review consolidates current knowledge on subcellular GSH dynamics, highlighting its implications in drug development, particularly in covalent drug design and antitumor strategies targeting intracellular GSH levels. Challenges and future directions in deciphering subcellular GSH dynamics are discussed, advocating for innovative methodologies to advance our comprehension and facilitate the development of precise therapeutic interventions based on GSH modulation.


Assuntos
Desenvolvimento de Medicamentos , Glutationa , Humanos , Glutationa/metabolismo , Desenvolvimento de Medicamentos/métodos , Animais , Organelas/metabolismo , Mitocôndrias/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/metabolismo
8.
J Am Chem Soc ; 146(32): 22396-22404, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39079063

RESUMO

Although many redox signaling molecules are present at low concentrations, typically ranging from micromolar to submicromolar levels, they often play essential roles in a wide range of biological pathways and disease mechanisms. However, accurately measuring low-abundant analytes has been a significant challenge due to the lack of sensitivity and quantitative capability of existing measurement methods. In this study, we introduced a novel chemically induced amplifiable system for quantifying low-abundance redox signaling molecules in living cells. We utilized H2O2 as a proof-of-concept analyte and developed a probe that quantifies cellular peroxide levels by combining the NanoBiT system with androgen receptor dimerization as a reporting mechanism. Our system demonstrated a highly sensitive response to cellular peroxide changes induced both endogenously and exogenously. Furthermore, the system can be adapted for the quantification of other signaling molecules if provided with suitable probing chemistry.


Assuntos
Peróxido de Hidrogênio , Receptores Androgênicos , Peróxido de Hidrogênio/análise , Peróxido de Hidrogênio/química , Humanos , Receptores Androgênicos/metabolismo , Oxirredução
9.
J Assist Reprod Genet ; 41(8): 2145-2161, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38902567

RESUMO

PURPOSE: The objective of this study was to discern ferroptosis-related genes (FRGs) linked to non-obstructive azoospermia and investigate the associated molecular mechanisms. METHOD: A dataset related to azoospermia was retrieved from the Gene Expression Omnibus database, and FRGs were sourced from GeneCards. Ferroptosis-related differentially expressed genes (FRDEGs) were discerned. Subsequently, these genes underwent analyses encompassing Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, as well as protein-protein interaction (PPI) networks and assessments of functional similarity. Following the identification of hub genes, an exploration of immune infiltration, single-cell expression, diagnostic utility, and interactions involving hub genes, RNA-binding proteins (RBPs), transcription factors (TFs), microRNAs (miRNAs), and drugs was conducted. RESULTS: A total of 35 differentially expressed FRGs were discerned. These genes demonstrated enrichment in functions and pathways associated with ferroptosis. From the PPI network, eight hub genes were selected. Functional similarity analysis highlighted the potential pivotal roles of HMOX1 and GPX4 in azoospermia. Analysis of immune cell infiltration indicated a significant decrease in activated dendritic cells in the azoospermia group, with notable correlations between hub genes, particularly SAT1 and HMGCR, and immune cell infiltration. Unique expression patterns of hub genes across various cell types in the human testis were observed, with GPX4 prominently enriched in spermatid/sperm. Eight hub genes exhibited robust diagnostic value (AUC > 0.75). Lastly, a comprehensive hub gene-miRNA-TF-RBP-drug network was constructed. CONCLUSION: In summary, our investigation unveiled eight FRDEGs associated with azoospermia, which hold potential as biomarkers for the diagnosis and treatment of azoospermia.


Assuntos
Azoospermia , Biologia Computacional , Ferroptose , Redes Reguladoras de Genes , Mapas de Interação de Proteínas , Humanos , Azoospermia/genética , Azoospermia/patologia , Masculino , Ferroptose/genética , Biologia Computacional/métodos , Mapas de Interação de Proteínas/genética , Redes Reguladoras de Genes/genética , MicroRNAs/genética , Perfilação da Expressão Gênica , Ontologia Genética , Fatores de Transcrição/genética , Regulação da Expressão Gênica/genética
10.
Chin Herb Med ; 16(2): 248-262, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38706822

RESUMO

Traditional Chinese herbal medicines not only cure human diseases, but also play an important role as insecticides. Compared with conventional chemical agents, traditional Chinese herbal medicines are characterized by low toxicity, low residues, and being eco-friendly, and they have become a research hotspot. Traditional Chinese herbal medicines have tremendous flexibility and indefinite potential. Therefore, this paper reviewed the types of insecticides belonging to traditional Chinese herbal medicines in Inner Mongolia, China, including their traditional uses, secondary metabolites, biological activities, action mechanisms, application methods, and development status. In addition, the most relevant issues involved in the development of traditional Chinese herbal medicines was discussed. We believe that traditional Chinese herbal medicines can be better implemented and developed; such that its other advantages, such as an insect repellent, can be promoted. Moreover, this study lays a solid foundation for further research on traditional Chinese herbal medicines in Inner Mongolia, China.

11.
Int J Neurosci ; : 1-6, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38497414

RESUMO

OBJECTIVE: To evaluate the efficacy of graded nutrition intervention strategy in improving patients with different degrees of impaired swallowing function after stroke. METHODS: According to the way of nursing, the patients were divided into two group. The main outcome measure was Kota swallowing index (WSI) score, and the secondary outcome was complications during the intervention. SF-36 scale was used to evaluate the improvement of quality of life before and intervention. RESULTS: The WSI score in the control group was 62.34 ± 10.23 at 1 week after treatment, 70.52 ± 13.45 at 6 weeks after treatment, and 80.48 ± 9.87 at 12 weeks after treatment, while that in the intervention group was 71.45 ± 9.68 at 1 week after treatment, 75.81 ± 11.78 at 6 weeks after treatment, and 84.12 ± 14.32 at 12 weeks after treatment. The WSI scores of the intervention group were significantly higher than those of the control group (t = 5.634, p < 0.001), suggesting better swallowing function of the patients The incidence of pulmonary infection, malnutrition and gastroesophageal reflux in the intervention group was significantly lower than that in the control group (p < 0.05). There was no significant difference in throat inflammation and dehydration between the two groups (p > 0.05). In addition, graded nutrition interventions significantly improved patients' quality of life, including dimensions of physical functioning, role physics, physical pain, and social functioning. CONCLUSION: Compared with conventional treatment, personalized graded nutrition intervention can significantly improve the swallowing function and reduce the pulmonary infection rate in patients with swallowing disorders after stroke.

12.
Drug Des Devel Ther ; 18: 325-339, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38344256

RESUMO

Purpose: This study was conducted to assess whether ciprofol vs propofol could affect the incidence of postoperative delirium (POD) in elderly patients with lung cancer after thoracoscopic surgery. Patients and Methods: In this study, a total of 84 elderly patients undergoing thoracoscopic surgery for lung cancer were recruited and randomized into two groups to receive anesthesia with either ciprofol or propofol. The primary outcome was the incidence of POD within three days after surgery. Secondary outcomes included the Confusion Assessment Method (CAM) score, intraoperative indicators related to mean arterial pressure (MAP), and cerebral tissue oxygen saturation (SctO2). Moreover, MAP- and SctO2-related indicators associated with POD were analyzed. Results: The incidence of POD was 7.1% and 16.7%, respectively, in the ciprofol group and the propofol group (risk ratio [RR], 0.37; 95% confidence interval [CI], 0.07 to 2.03; risk difference [RD], -9.6%; 95% CI, -23.3% to 4.1%; p = 0.178). Compared with those in the propofol group, patients in the ciprofol group had lower CAM scores three days after surgery (13 (12, 15) vs 15 (14, 17); 12 (11, 13) vs 14 (13, 16); 12 (11, 12) vs 13 (12, 14), p<0.05). Besides, patients in the ciprofol group exhibited higher mean and minimum MAP (88.63 ± 6.7 vs 85 ± 8.3; 69.81 ± 9.59 vs 64.9 ± 9.43, p<0.05) and SctO2 (77.26 ± 3.96 vs 75.3 ± 4.49, 71.69 ± 4.51 vs 68.77 ± 6.46, p<0.05) and percentage of time for blood pressure stabilization (0.6 ± 0.14 vs 0.45 ± 0.14, p<0.05) than those in the propofol group. Furthermore, MAP and SctO2-related indicators were validated to correlate with POD. Conclusion: Anesthesia with ciprofol did not increase the incidence of POD compared with propofol. The results demonstrated that ciprofol could improve intraoperative MAP and SctO2 levels and diminish postoperative CAM scores.


Assuntos
Delírio , Delírio do Despertar , Neoplasias Pulmonares , Propofol , Humanos , Idoso , Propofol/efeitos adversos , Neoplasias Pulmonares/cirurgia , Estudos Prospectivos , Delírio/epidemiologia
13.
Aggress Behav ; 50(1): e22127, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38268390

RESUMO

The coevolution of bullying and friendship networks and the moderating effects of classroom bullying popularity norms were examined in a sample of 965 students (52.1% boys) in 22 fourth- and fifth-grade classes. Longitudinal social network analysis showed that children were more likely to bully their friends' victims (bully influence effect) and to be bullied by their friends' bullies (victim influence effect); two children bullying the same child were likely to be friends (bully selection effect), and two victims bullied by the same child were likely to be friends (victim selection effect). Bullying popularity norms served as moderators, and the bully selection effect was significant weaker in the context of low bullying popularity norms. This study adds understanding of bullying as a group process and provides implications for preventing school bullying.


Assuntos
Bullying , Amigos , Masculino , Criança , Humanos , Feminino , Processos Grupais , Instituições Acadêmicas , Estudantes
14.
Nano Lett ; 24(4): 1351-1359, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38251855

RESUMO

The anomalous Hall effect (AHE) is one of the most fascinating transport properties in condensed matter physics. However, the AHE magnitude, which mainly depends on net spin polarization and band topology, is generally small in oxides and thus limits potential applications. Here, we demonstrate a giant enhancement of AHE in a LaCoO3-induced 5d itinerant ferromagnet SrIrO3 by hydrogenation. The anomalous Hall resistivity and anomalous Hall angle, which are two of the most critical parameters in AHE-based devices, are found to increase to 62.2 µΩ·cm and 3%, respectively, showing an unprecedentedly large enhancement ratio of ∼10000%. Theoretical analysis suggests the key roles of Berry curvature in enhancing AHE. Furthermore, the hydrogenation concomitantly induces the significant elevation of Curie temperature from 75 to 160 K and 40-fold reinforcement of coercivity. Such giant regulation and very large AHE magnitude observed in SrIrO3 could pave the path for 5d oxide devices.

15.
Science ; 383(6681): 388-394, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38271502

RESUMO

Identifying a suitable water-soluble sacrificial layer is crucial to fabricating large-scale freestanding oxide membranes, which offer attractive functionalities and integrations with advanced semiconductor technologies. Here, we introduce a water-soluble sacrificial layer, "super-tetragonal" Sr4Al2O7 (SAOT). The low-symmetric crystal structure enables a superior capability to sustain epitaxial strain, allowing for broad tunability in lattice constants. The resultant structural coherency and defect-free interface in perovskite ABO3/SAOT heterostructures effectively restrain crack formation during the water release of freestanding oxide membranes. For a variety of nonferroelectric oxide membranes, the crack-free areas can span up to a millimeter in scale. This compelling feature, combined with the inherent high water solubility, makes SAOT a versatile and feasible sacrificial layer for producing high-quality freestanding oxide membranes, thereby boosting their potential for innovative device applications.

16.
Nat Commun ; 14(1): 8496, 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38129430

RESUMO

Designing a broad-spectrum gas sensor capable of identifying gas components in complex environments, such as mixed atmospheres or extreme temperatures, is a significant concern for various technologies, including energy, geological science, and planetary exploration. The main challenge lies in finding materials that exhibit high chemical stability and wide working temperature range. Materials that amplify signals through non-chemical methods could open up new sensing avenues. Here, we present the discovery of a broad-spectrum gas sensor utilizing correlated two-dimensional electron gas at a delta-doped LaAlO3/SrTiO3 interface with LaFeO3. Our study reveals that a back-gating on this two-dimensional electron gas can induce a non-volatile metal to insulator transition, which consequently can activate the two-dimensional electron gas to sensitively and quantitatively probe very broad gas species, no matter whether they are polar, non-polar, or inert gases. Different gas species cause resistance change at their sublimation or boiling temperature and a well-defined phase transition angle can quantitatively determine their partial pressures. Such unique correlated two-dimensional electron gas sensor is not affected by gas mixtures and maintains a wide operating temperature range. Furthermore, its readout is a simple measurement of electric resistance change, thus providing a very low-cost and high-efficient broad-spectrum sensing technique.

17.
PNAS Nexus ; 2(11): pgad365, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38024414

RESUMO

We consider complex multistage multiagent negotiation processes such as those occurring at climate conferences and ask ourselves how can an agent maximize its social power, intended as influence over the outcome of the negotiation. This question can be framed as a strategic game played over an opinion dynamics model, in which the action of an agent consists in stubbornly defending its own opinion. We show that for consensus-seeking opinion dynamics models in which the interaction weights are uniform, the optimal action obeys to an early mover advantage principle, i.e. the agents behaving stubbornly in the early phases of the negotiations achieve the highest social power. When looking at data collected from the climate change negotiations going on at the United Nations Framework Convention on Climate Change, we find evidence of the use of the early mover strategy. Furthermore, we show that the social powers computed through our model correlate very well with the perceived leadership roles assessed through independent survey data, especially when non-uniform weights incorporating economical and demographic factors are considered.

18.
Front Endocrinol (Lausanne) ; 14: 1186252, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37745713

RESUMO

Genome-wide association meta-analysis (GWAMA) by the Cortisol Network (CORNET) consortium identified genetic variants spanning the SERPINA6/SERPINA1 locus on chromosome 14 associated with morning plasma cortisol, cardiovascular disease (CVD), and SERPINA6 mRNA expression encoding corticosteroid-binding globulin (CBG) in the liver. These and other findings indicate that higher plasma cortisol levels are causally associated with CVD; however, the mechanisms by which variations in CBG lead to CVD are undetermined. Using genomic and transcriptomic data from The Stockholm Tartu Atherosclerosis Reverse Networks Engineering Task (STARNET) study, we identified plasma cortisol-linked single-nucleotide polymorphisms (SNPs) that are trans-associated with genes from seven different vascular and metabolic tissues, finding the highest representation of trans-genes in the liver, subcutaneous fat, and visceral abdominal fat, [false discovery rate (FDR) = 15%]. We identified a subset of cortisol-associated trans-genes that are putatively regulated by the glucocorticoid receptor (GR), the primary transcription factor activated by cortisol. Using causal inference, we identified GR-regulated trans-genes that are responsible for the regulation of tissue-specific gene networks. Cis-expression Quantitative Trait Loci (eQTLs) were used as genetic instruments for identification of pairwise causal relationships from which gene networks could be reconstructed. Gene networks were identified in the liver, subcutaneous fat, and visceral abdominal fat, including a high confidence gene network specific to subcutaneous adipose (FDR = 10%) under the regulation of the interferon regulatory transcription factor, IRF2. These data identify a plausible pathway through which variation in the liver CBG production perturbs cortisol-regulated gene networks in peripheral tissues and thereby promote CVD.


Assuntos
Doenças Cardiovasculares , Glucocorticoides , Transcortina , Humanos , Tecido Adiposo , Doenças Cardiovasculares/genética , Redes Reguladoras de Genes , Estudo de Associação Genômica Ampla , Fatores de Risco de Doenças Cardíacas , Hidrocortisona , Fígado , Receptores de Glucocorticoides/genética , Fatores de Risco , Transcortina/genética
19.
Nat Methods ; 20(9): 1368-1378, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37537351

RESUMO

Gene regulatory networks (GRNs) are key determinants of cell function and identity and are dynamically rewired during development and disease. Despite decades of advancement, challenges remain in GRN inference, including dynamic rewiring, causal inference, feedback loop modeling and context specificity. To address these challenges, we develop Dictys, a dynamic GRN inference and analysis method that leverages multiomic single-cell assays of chromatin accessibility and gene expression, context-specific transcription factor footprinting, stochastic process network and efficient probabilistic modeling of single-cell RNA-sequencing read counts. Dictys improves GRN reconstruction accuracy and reproducibility and enables the inference and comparative analysis of context-specific and dynamic GRNs across developmental contexts. Dictys' network analyses recover unique insights in human blood and mouse skin development with cell-type-specific and dynamic GRNs. Its dynamic network visualizations enable time-resolved discovery and investigation of developmental driver transcription factors and their regulated targets. Dictys is available as a free, open-source and user-friendly Python package.


Assuntos
Redes Reguladoras de Genes , Multiômica , Animais , Camundongos , Humanos , Reprodutibilidade dos Testes , Fatores de Transcrição/genética , Algoritmos
20.
Materials (Basel) ; 16(6)2023 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-36984162

RESUMO

The c-axis aligned crystalline indium-gallium-zinc-oxide field-effect transistor (CAAC-IGZO FET), exhibiting an extremely low off-state leakage current (~10-22 A/µm), has promised to be an ideal candidate for Dynamic Random Access Memory (DRAM) applications. However, the instabilities leaded by the drift of the threshold voltage in various stress seriously affect the device application. To better develop high performance CAAC-IGZO FET for DRAM applications, it's essential to uncover the deep physical process of charge transport mechanism in CAAC-IGZO FET. In this work, by combining the first-principles calculations and nonradiative multiphonon theory, the charge trapping and emission properties in CAAC-IGZO FET have been systematically investigated. It is found that under positive bias stress, hydrogen interstitial in Al2O3 gate dielectric is probable effective electron trap center, which has the transition level (ε (+1/-1) = 0.52 eV) above Fermi level. But it has a high capture barrier about 1.4 eV and low capture rate. Under negative bias stress, oxygen vacancy in Al2O3 gate dielectric and CAAC-IGZO active layer are probable effective electron emission centers whose transition level ε (+2/0) distributed at -0.73~-0.98 eV and 0.69 eV below Fermi level. They have a relatively low emission barrier of about 0.5 eV and 0.25 eV and high emission rate. To overcome the instability in CAAC-IGZO FET, some approaches can be taken to control the hydrogen concentration in Al2O3 dielectric layer and the concentration of the oxygen vacancy. This work can help to understand the mechanisms of instability of CAAC-IGZO transistor caused by the charge capture/emission process.

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