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1.
Proc Natl Acad Sci U S A ; 121(21): e2317495121, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38753506

RESUMO

Myogenic regeneration relies on the proliferation and differentiation of satellite cells. TECRL (trans-2,3-enoyl-CoA reductase like) is an endoplasmic reticulum protein only expressed in cardiac and skeletal muscle. However, its role in myogenesis remains unknown. We show that TECRL expression is increased in response to injury. Satellite cell-specific deletion of TECRL enhances muscle repair by increasing the expression of EGR2 through the activation of the ERK1/2 signaling pathway, which in turn promotes the expression of PAX7. We further show that TECRL deletion led to the upregulation of the histone acetyltransferase general control nonderepressible 5, which enhances the transcription of EGR2 through acetylation. Importantly, we showed that AAV9-mediated TECRL silencing improved muscle repair in mice. These findings shed light on myogenic regeneration and muscle repair.


Assuntos
Proteína 2 de Resposta de Crescimento Precoce , Desenvolvimento Muscular , Músculo Esquelético , Regeneração , Animais , Camundongos , Músculo Esquelético/metabolismo , Proteína 2 de Resposta de Crescimento Precoce/metabolismo , Proteína 2 de Resposta de Crescimento Precoce/genética , Desenvolvimento Muscular/genética , Regeneração/genética , Regulação para Cima , Células Satélites de Músculo Esquelético/metabolismo , Fator de Transcrição PAX7/metabolismo , Fator de Transcrição PAX7/genética , Sistema de Sinalização das MAP Quinases , Camundongos Knockout , Diferenciação Celular
2.
J Am Chem Soc ; 146(9): 5834-5842, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38277793

RESUMO

Electrochemical conversion of CH4 to easily transportable and value-added liquid fuels is highly attractive for energy-efficient CH4 utilization, but it is challenging due to the low reactivity and solubility of CH4 in the electrolyte. Herein, we report a high-pressure electro-Fenton (HPEF) strategy to establish a hetero-homogeneous process for the electrocatalytic conversion of CH4 by O2 at room temperature. In combination with elevation of reactant pressure to accelerate reaction kinetics, it delivers an unprecedented HCOOH productivity of 11.5 mmol h-1 gFe-1 with 220 times enhancement compared to that under ambient pressure. Remarkably, an HCOOH Faradic efficiency of 81.4% can be achieved with an ultralow cathodic overpotential of 0.38 V. The elevated pressure not only promotes the electrocatalytic reduction of O2 to H2O2 but also increases the reaction collision probability between CH4 and •OH, which is in situ generated from the Fe2+-facilitated decomposition of H2O2.

3.
Planta ; 260(3): 58, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39039384

RESUMO

MAIN CONCLUSION: A genome-wide analysis had identified 642 ABA core component genes from 20 plant species, which were further categorized into three distinct subfamilies. The gene structures and evolutionary relationships of these genes had been characterized. PP2C_1, PP2C_2, and SnRK2_1 had emerged as key players in mediating the ABA signaling transduction pathway, specifically in rice, in response to abiotic stresses. The plant hormone abscisic acid (ABA) is essential for growth, development, and stress response, relying on its core components, pyrabactin resistance, pyrabactin resistance-like, and the regulatory component of ABA receptor (PYR/PYL/RCAR), 2C protein phosphatase (PP2C), sucrose non-fermenting-1-related protein kinase 2 (SnRK2). However, there's a lack of research on their structural evolution and functional differentiation across plants. Our study analyzed the phylogenetic, gene structure, homology, and duplication evolution of this complex in 20 plant species. We found conserved patterns in copy number and homology across subfamilies. Segmental and tandem duplications drove the evolution of these genes, while whole-genome duplication (WGD) expanded PYR/PYL/RCAR and PP2C subfamilies, enhancing environmental adaptation. In rice and Arabidopsis, the PYR/PYL/RCAR, PP2C, and SnRK2 genes showed distinct tissue-specific expression and responded to various stresses. Notably, PP2C_1 and PP2C_2 interacted with SnRK2_1 and were crucial for ABA signaling in rice. These findings offered new insights into ABA signaling evolution, interactions, and integration in green plants, benefiting future research in agriculture, evolutionary biology, ecology, and environmental science.


Assuntos
Ácido Abscísico , Evolução Molecular , Genoma de Planta , Oryza , Filogenia , Transdução de Sinais , Oryza/genética , Oryza/metabolismo , Oryza/fisiologia , Ácido Abscísico/metabolismo , Transdução de Sinais/genética , Genoma de Planta/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas , Duplicação Gênica , Estresse Fisiológico/genética , Reguladores de Crescimento de Plantas/metabolismo , Proteína Fosfatase 2C/genética , Proteína Fosfatase 2C/metabolismo , Arabidopsis/genética , Arabidopsis/fisiologia
4.
Phys Rev Lett ; 132(25): 250604, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38996251

RESUMO

As quantum circuits become more integrated and complex, additional error sources that were previously insignificant start to emerge. Consequently, the fidelity of quantum gates benchmarked under pristine conditions falls short of predicting their performance in realistic circuits. To overcome this problem, we must improve their robustness against pertinent error models besides isolated fidelity. Here, we report the experimental realization of robust quantum gates in superconducting quantum circuits based on a geometric framework for diagnosing and correcting various gate errors. Using quantum process tomography and randomized benchmarking, we demonstrate robust single-qubit gates against quasistatic noise and spatially correlated noise in a broad range of strengths, which are common sources of coherent errors in large-scale quantum circuits. We also apply our method to nonstatic noises and to realize robust two-qubit gates. Our Letter provides a versatile toolbox for achieving noise-resilient complex quantum circuits.

5.
Biometrics ; 80(1)2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38364801

RESUMO

A dynamic treatment regime (DTR) is a sequence of treatment decision rules that dictate individualized treatments based on evolving treatment and covariate history. It provides a vehicle for optimizing a clinical decision support system and fits well into the broader paradigm of personalized medicine. However, many real-world problems involve multiple competing priorities, and decision rules differ when trade-offs are present. Correspondingly, there may be more than one feasible decision that leads to empirically sufficient optimization. In this paper, we propose a concept of "tolerant regime," which provides a set of individualized feasible decision rules under a prespecified tolerance rate. A multiobjective tree-based reinforcement learning (MOT-RL) method is developed to directly estimate the tolerant DTR (tDTR) that optimizes multiple objectives in a multistage multitreatment setting. At each stage, MOT-RL constructs an unsupervised decision tree by modeling the counterfactual mean outcome of each objective via semiparametric regression and maximizing a purity measure constructed by the scalarized augmented inverse probability weighted estimators (SAIPWE). The algorithm is implemented in a backward inductive manner through multiple decision stages, and it estimates the optimal DTR and tDTR depending on the decision-maker's preferences. Multiobjective tree-based reinforcement learning is robust, efficient, easy-to-interpret, and flexible to different settings. We apply MOT-RL to evaluate 2-stage chemotherapy regimes that reduce disease burden and prolong survival for advanced prostate cancer patients using a dataset collected at MD Anderson Cancer Center.


Assuntos
Sistemas de Apoio a Decisões Clínicas , Medicina de Precisão , Masculino , Humanos , Medicina de Precisão/métodos , Algoritmos
6.
Appl Microbiol Biotechnol ; 108(1): 82, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38189955

RESUMO

Dunaliella salina is a high-quality industrial effector for carotenoid production. The mechanism by which red light regulates carotenoid synthesis is still unclear. In this study, a transcription factor of DsGATA1 with a distinct structure was discovered in D. salina. The recognition motif of DsGATA1 was comparable to that of plant and fungal GATA, despite its evolutionary proximity to animal-derived GATA. The expression of DsGATA1 in D. salina was still noticeably decreased when exposed to red light. Analysis of physiological and biochemical transcriptomic data from overexpressed, interfering, and wild-type strains of DsGATA1 revealed that DsGATA1 acts as a global regulator of D. salina carotenoid synthesis. The upregulated genes in the CBP pathway by DsGATA1 were involved in its regulation of the synthesis of carotenoids. DsGATA1 also enhanced carotenoid accumulation under red light by affecting N metabolism. DsGATA1 was found to directly bind to the promoter of nitrate reductase to activate its expression, promoting D. salina nitrate uptake and accelerating biomass accumulation. DsGATA1 affected the expression of the genes encoding GOGAT, GDH, and ammonia transporter proteins. Moreover, our study revealed that the regulation of N metabolism by DsGATA1 led to the production of NO molecules that inhibited carotenoid synthesis. However, DsGATA1 significantly enhanced carotenoid synthesis by NO scavenger removal of NO. The D. salina carotenoid accumulation under red light was elevated by 46% in the presence of overexpression of DsGATA1 and NO scavenger. Nevertheless, our results indicated that DsGATA1 could be an important target for engineering carotenoid production. KEY POINTS: • DsGATA1 with a distinct structure and recognition motif was found in D. salina • DsGATA1 enhanced carotenoid production and biomass in D. salina under red light • DsGATA1 is involved in the regulation of N metabolism and carotenoid synthesis.


Assuntos
Clorofíceas , Luz Vermelha , Animais , Amônia , Evolução Biológica , Carotenoides
7.
Oral Dis ; 30(2): 492-503, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36740958

RESUMO

OBJECTIVES: To explore the prognostic effects of previous cancer history on patients with major salivary gland cancer (SGC). SUBJECTS AND METHODS: SGC patients with (sec-SGC) and without (one-SGC) a previous cancer from the SEER database were identified. Cox proportional hazards regression (CoxPH) models were used to compare the prognosis between sec-SGC and one-SGC patients. Subgroup analyses for sec-SGC patients by gender, previous cancer types, previous cancer histology, and cancer diagnosis interval (CDI) were performed. Two CoxPH models were constructed to distinguish sec-SGC patients with different prognostic risks. RESULTS: 9098 SGC patients were enrolled. Overall, sec-SGC patients (adjusted HR [aHR] = 1.26, p < 0.001), especially those with a CDI ≤ 5 years (aHR = 1.47, p < 0.001), had worse overall survival (OS) than one-SGC patients. In subgroup analysis, only sec-SGC patients with a previous head and neck cancer who were female (aHR = 2.38, p = 0.005), with a CDI ≤ 5 years (aHR = 1.65, p = 0.007) or with a previous squamous cell carcinoma (aHR = 6.52, p < 0.001) had worse OS. Our models successfully differentiated all sec-SGC patients into high-, intermediate- and low-risk groups with different prognosis. CONCLUSIONS: Sec-SGC patients with different previous cancer types, gender, CDI and previous cancer histology had varied prognosis. The models we constructed could help differentiate the prognosis of sec-SGC patients with different risks.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias das Glândulas Salivares , Humanos , Feminino , Masculino , Prognóstico , Neoplasias das Glândulas Salivares/patologia , Carcinoma de Células Escamosas/patologia
8.
Ann Diagn Pathol ; 71: 152328, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38754357

RESUMO

BACKGROUND: The status of the lung adenocarcinoma (LUAD) grading system and the association between LUAD differentiation, driver genes, and clinicopathological features remain to be elucidated. METHODS: We included patients with invasive non-mucinous LUAD, evaluated their differentiation, and collected available clinicopathological information, gene mutations, and analyzed clinical outcomes. RESULTS: Among the 907 patients with invasive non-mucinous LUAD, 321 (35.4 %) were poorly differentiated, 422 (46.5 %) were moderately differentiated, and 164 (18.1 %) were well differentiated. EGFR mutation was more common in the LUADs accompanied without CGP (complex glandular pattern) than LUADs with CGP (p < 0.001). Correlation analysis between mutations and clinical characteristics showed that EGFR gene mutation (p < 0.001), KRAS gene mutation (p < 0.05), and ALK gene rearrangement (p < 0.001) were significantly related to the degree of tumor differentiation, and the KRAS and ALK gene mutation frequencies were higher in the low-differentiation group than in the high and medium differentiation groups. The EGFR mutation frequency was higher in the well/moderately differentiated adenocarcinoma group. CONCLUSIONS: Our study adds to the evidence regarding the role of the grading system in prognosis. EGFR, KRAS, and ALK are related to the degree of tumor differentiation.


Assuntos
Adenocarcinoma de Pulmão , Receptores ErbB , Neoplasias Pulmonares , Mutação , Gradação de Tumores , Proteínas Proto-Oncogênicas p21(ras) , Humanos , Masculino , Feminino , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Pessoa de Meia-Idade , Idoso , Gradação de Tumores/métodos , Proteínas Proto-Oncogênicas p21(ras)/genética , Receptores ErbB/genética , Adulto , Idoso de 80 Anos ou mais , Quinase do Linfoma Anaplásico/genética , Adenocarcinoma/genética , Adenocarcinoma/patologia , Biomarcadores Tumorais/genética
9.
J Adv Nurs ; 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38415959

RESUMO

AIM: This study intends to investigate whether, how and when service-oriented high-performance work systems (SHPWSs) drive nurses' extra-role service behaviour. DESIGN: This was a quantitative cross-sectional study conducted with matched nurse-patient participants. METHOD: We tested hypotheses using data from 284 nurses and their matched 566 patients. The data were collected in 2019. We conducted a set of hierarchical regression analyses to test our hypotheses. RESULTS: The results showed that SHPWSs have a positive impact on job crafting, which, in turn, mediates the link between SHPWSs and extra-role service behaviours. Additionally, the influence of professional identification moderates these relationships. Specifically, SHPWSs are significantly and positively associated with job crafting among highly professionally identified nurses. The indirect effect is significantly positive when nurses strongly identify with their profession but not significant when their professional identification is low. CONCLUSION: The results indicated that SHPWSs can elicit job crafting among higher professional identifiers, which further increases extra-role service behaviours towards patients. IMPACT: Our research emphasizes the significance of HRM themes in the healthcare service industry and their direct impact on healthcare personnel. Shifting from a management-centric to an individual-centric perspective, we focus on the proactive role of nurses. Furthermore, this study enhances the understanding of the boundary conditions for the effectiveness of SHPWSs. PATIENT OR PUBLIC CONTRIBUTION: Nurses and their mated patients from a Chinese hospital contributed to this study by completing the survey.

10.
Sensors (Basel) ; 24(13)2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-39000993

RESUMO

As a technical application in artificial intelligence, a social robot is one of the branches of robotic studies that emphasizes socially communicating and interacting with human beings. Although both robot and behavior research have realized the significance of social robot design for its market success and related emotional benefit to users, the specific design of the eye and mouth shape of a social robot in eliciting trustworthiness has received only limited attention. In order to address this research gap, our study conducted a 2 (eye shape) × 3 (mouth shape) full factorial between-subject experiment. A total of 211 participants were recruited and randomly assigned to the six scenarios in the study. After exposure to the stimuli, perceived trustworthiness and robot attitude were measured accordingly. The results showed that round eyes (vs. narrow eyes) and an upturned-shape mouth or neutral mouth (vs. downturned-shape mouth) for social robots could significantly improve people's trustworthiness and attitude towards social robots. The effect of eye and mouth shape on robot attitude are all mediated by the perceived trustworthiness. Trustworthy human facial features could be applied to the robot's face, eliciting a similar trustworthiness perception and attitude. In addition to empirical contributions to HRI, this finding could shed light on the design practice for a trustworthy-looking social robot.


Assuntos
Robótica , Confiança , Humanos , Robótica/métodos , Masculino , Feminino , Adulto , Face/anatomia & histologia , Face/fisiologia , Adulto Jovem , Inteligência Artificial
11.
Odontology ; 112(1): 100-111, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37043073

RESUMO

Diabetes mellitus (DM), characterized by production and accumulation of advanced glycation end products (AGEs), induces and promotes chronic inflammation in tissues, including periodontal tissue. Increasing amount of epidemiological and experimental evidence demonstrated that more extensive inflammatory reaction and bone resorption occurred in periodontal tissues in diabetic patients with periodontitis, which is speculated to be related to NLRP3 inflammasome. NLRP10 is the only NOD-like receptor protein lacking leucine-rich repeats, suggesting that NLRP10 may be a regulatory protein. The aim of this study was to investigate the regulatory role of NLRP10 on NLRP1 and NLRP3 inflammasome in human periodontal ligament cells (HPDLCs) under AGEs treatment. Expression of NLRP10 in HPDLCs stimulated with 100 ug/mL AGEs for 24 h was observed. Detection of TRIM31 is conducted, and in TRIM31-overexpressed HPDLCs, the interaction between NLRP10 with TRIM31 as well as NLRP10 with ubiquitination were explored by immunoprecipitation. Under AGEs stimulation, the activation of reactive oxidative stress (ROS) and inflammatory signaling pathway (NF-κB, MAPK pathway) was detected by biomedical microscope and western blot (WB), respectively. After stimulation with AGEs for 24 h with or without silencing NLRP10, inflammatory cytokines (IL-6 and IL-1ß), NF-κB, MAPK pathway, ROS, and components of inflammasome were assessed. In HPDLCs, we found AGEs induced NLRP10 and inhibited TRIM31. TRIM31 overexpression significantly enhanced interaction between TRIM31 and NLRP10, then induced proteasomal degradation of NLRP10. Moreover, under AGEs stimulation, NLRP10 positively regulates NLRP1, NLRP3 inflammasomes by activating NF-κB, MAPK pathway, and increasing ROS, finally promoting the expression of inflammatory cytokines. Together, we, for the first time, confirmed that NLRP10 could promote inflammatory response induced by AGEs in HPDLCs via activation of NF-κB, and MAPK pathway and increasing ROS.


Assuntos
Inflamassomos , NF-kappa B , Humanos , NF-kappa B/metabolismo , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Ligamento Periodontal , Estresse Oxidativo , Inflamação , Citocinas/metabolismo , Proteínas NLR/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Proteínas com Motivo Tripartido/metabolismo
13.
Methods ; 203: 125-138, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35436514

RESUMO

N6-methyladenosine (m6A) is the most abundant eukaryotic modification internal mRNA, which plays the crucial roles in the occurrence and development of cancer. However, current knowledge about m6A-mediated functional circuit and key genes targeted by m6A methylation in cancer is mostly elusive. Thus, here we proposed a novel network-based approach (called m6Acancer-Net) to identify m6A-mediated driver genes and their associated network in specific type of cancer, such as acute myeloid leukemia. m6A-mediated cancer driver genes are defined as genes mediated by m6A methylation, significantly mutated, and functionally interacted in cancer. m6Acancer-Net identified the m6A-mediated cancer driver genes by combining gene functional interaction network with RNA methylation, gene expression and mutation information. A cancer-specific gene-site heterogeneous network was firstly constructed by connecting the m6A site co-methylation network with the functional interaction pruned gene co-expression network generated from large scale gene expression profile of specific cancer. Then, the functional m6A-mediated genes were identified by selecting the m6A regulators as seed genes to perform the random walk with restart algorithm on the gene-site heterogeneous network. Finally, m6A-mediated cancer driver gene subnetworks were constructed by performing the heat diffusion of mutation frequency for functional m6A-mediated genes in protein-protein interaction networks. The experimental results of m6Acancer-Net on the acute myeloid leukemia (AML) and glioblastoma multiforme (GBM) data from TCGA project show that the m6A-mediated caner driver genes identified by m6Acancer-Net are targeted by m6A regulators, and mediate significant cancer-related pathways. They play crucial roles in development and prognostic stratification of cancer. Moreover, 15 m6A-mediated cancer driver genes identified in AML are validated by literatures to mediate AML progress, and 14 m6A-mediated cancer driver genes identified in GBM are validated by literatures to participate in development of GBM. m6Acancer-Net is reliable to identify the functionally significant m6A-mediated driver genes in specific cancer, and it can effectively facilitate the understanding of regulatory and therapeutic mechanism of cancer driver genes in epitranscriptome layer.


Assuntos
Redes Reguladoras de Genes , Glioblastoma , Algoritmos , Glioblastoma/genética , Humanos , Mutação , Mapas de Interação de Proteínas/genética
14.
Methods ; 203: 167-178, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35314342

RESUMO

N6-methyladenosine (m6A) is the most abundant form of mRNA modification and plays an important role in regulating gene expression. However, the mechanisms of m6A regulated gene expression in cell or condition specific, are still poorly understood. Even though, some methods are able to predict m6A regulated expression (m6A-reg-exp) genes in specific context, they don't introduce the m6A reader binding information, while this information can help to predict m6A-reg-exp genes and more clearly to explain the mechanisms of m6A-mediated gene expression process. Thus, by integrating m6A sites and reader binding information, we proposed a novel method (called m6Aexpress-Reader) to predict m6A-reg-exp genes from limited MeRIP-seq data in specific context. m6Aexpress-Reader adopts the reader binding signal strength to weight the posterior distribution of the estimated regulatory coefficients for enhancing the prediction power. By using m6Aexpress-Reader, we found the complex characteristic of m6A on gene expression regulation and the distinct regulated pattern of m6A-reg-exp genes with different reader binding. m6A readers, YTHDF2 or IGF2BP1/3 all play an important role in various cancers and the key cancer pathways. In addition, m6Aexpress-Reader reveals the distinct m6A regulated mode of reader targeted genes in cancer. m6Aexpress-Reader could be a useful tool for studying the m6A regulation on reader target genes in specific context and it can be freely accessible at: https://github.com/NWPU-903PR/m6AexpressReader.


Assuntos
Neoplasias , Proteínas de Ligação a RNA , Adenosina/genética , Adenosina/metabolismo , Regulação da Expressão Gênica , Humanos , Neoplasias/genética , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo
15.
Ear Hear ; 44(1): 53-60, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36194023

RESUMO

OBJECTIVES: Understanding the association between sleep traits and tinnitus could help prevent and provide appropriate interventions against tinnitus. Therefore, this study aimed to assess the relationship between different sleep patterns and tinnitus. DESIGN: A cross-sectional analysis using baseline data (2006-2010, n = 168,064) by logistic regressions was conducted to evaluate the association between sleep traits (including the overall health sleep score and five sleep behaviors) and the occurrence (yes/no), frequency (constant/transient), and severity (upsetting/not upsetting) of tinnitus. Further, a prospective analysis of participants without tinnitus at baseline (n = 9581) was performed, who had been followed-up for 7 years (2012-2019), to assess the association between new-onset tinnitus and sleep characteristics. Moreover, a subgroup analysis was also carried out to estimate the differences in sex by dividing the participants into male and female groups. A sensitivity analysis was also conducted by excluding ear-related diseases to avoid their confounding effects on tinnitus (n = 102,159). RESULTS: In the cross-sectional analysis, participants with "current tinnitus" (OR: 1.13, 95% CI: 1.04-1.22, p = 0.004) had a higher risk of having a poor overall healthy sleep score and unhealthy sleep behaviors such as short sleep durations (OR: 1.09, 95% CI: 1.04-1.14, p < 0.001), late chronotypes (OR: 1.09, 95% CI: 1.05-1.13, p < 0.001), and sleeplessness (OR: 1.16, 95% CI: 1.11-1.22, p < 0.001) than those participants who "did not have current tinnitus." However, this trend was not obvious between "constant tinnitus" and "transient tinnitus." When considering the severity of tinnitus, the risk of "upsetting tinnitus" was obviously higher if participants had lower overall healthy sleep scores (OR: 1.31, 95% CI: 1.13-1.53, p < 0.001). Additionally, short sleep duration (OR: 1.22, 95% CI: 1.12-1.33, p < 0.001), late chronotypes (OR: 1.13, 95% CI: 1.04-1.22, p = 0.003), and sleeplessness (OR: 1.43, 95% CI: 1.29-1.59, p < 0.001) showed positive correlations with "upsetting tinnitus." In the prospective analysis, sleeplessness presented a consistently significant association with "upsetting tinnitus" (RR: 2.28, p = 0.001). Consistent results were observed in the sex subgroup analysis, where a much more pronounced trend was identified in females compared with the males. The results of the sensitivity analysis were consistent with those of the cross-sectional and prospective analyses. CONCLUSIONS: Different types of sleep disturbance may be associated with the occurrence and severity of tinnitus; therefore, precise interventions for different types of sleep disturbance, particularly sleeplessness, may help in the prevention and treatment of tinnitus.


Assuntos
Otopatias , Distúrbios do Início e da Manutenção do Sono , Transtornos do Sono-Vigília , Zumbido , Humanos , Masculino , Feminino , Zumbido/terapia , Estudos Transversais , Bancos de Espécimes Biológicos , Estudos de Coortes , Sono , Transtornos do Sono-Vigília/complicações , Transtornos do Sono-Vigília/epidemiologia , Reino Unido/epidemiologia
16.
Nucleic Acids Res ; 49(20): e116, 2021 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-34417605

RESUMO

N6-methyladenosine (m6A) is the most abundant form of mRNA modification and controls many aspects of RNA metabolism including gene expression. However, the mechanisms by which m6A regulates cell- and condition-specific gene expression are still poorly understood, partly due to a lack of tools capable of identifying m6A sites that regulate gene expression under different conditions. Here we develop m6A-express, the first algorithm for predicting condition-specific m6A regulation of gene expression (m6A-reg-exp) from limited methylated RNA immunoprecipitation sequencing (MeRIP-seq) data. Comprehensive evaluations of m6A-express using simulated and real data demonstrated its high prediction specificity and sensitivity. When only a few MeRIP-seq samples may be available for the cellular or treatment conditions, m6A-express is particularly more robust than the log-linear model. Using m6A-express, we reported that m6A writers, METTL3 and METTL14, competitively regulate the transcriptional processes by mediating m6A-reg-exp of different genes in Hela cells. In contrast, METTL3 induces different m6A-reg-exp of a distinct group of genes in HepG2 cells to regulate protein functions and stress-related processes. We further uncovered unique m6A-reg-exp patterns in human brain and intestine tissues, which are enriched in organ-specific processes. This study demonstrates the effectiveness of m6A-express in predicting condition-specific m6A-reg-exp and highlights the complex, condition-specific nature of m6A-regulation of gene expression.


Assuntos
Adenosina/análogos & derivados , Processamento Pós-Transcricional do RNA , Análise de Sequência de RNA/métodos , Adenosina/metabolismo , Encéfalo/metabolismo , Células HeLa , Células Hep G2 , Humanos , Mucosa Intestinal/metabolismo
17.
Eur Arch Otorhinolaryngol ; 280(3): 1455-1465, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36348098

RESUMO

PURPOSE: We aimed to explore the clinicodemographic characteristics and prognosis of grey zone squamous cell cancer (GZSCC) located in the overlapping or ambiguous area of oral cavity and oropharynx and to identify valuable factors that would improve its differential diagnosis and prognosis. METHODS: Information of GZSCC patients in the Surveillance, Epidemiology, and End Results (SEER) database were compared to patients with oral cavity (OCSCC) and oropharyngeal (OPSCC) squamous cell carcinomas with corresponding HPV status, respectively. Kaplan-Meier method with log-rank test and multivariate Cox regression analysis were applied to assess associations between clinical characteristics and overall survival (OS). A predictive model integrating age, gender, marital status, HPV status and staging variables was conducted to classify GZSCC patients into three risk groups and verified internally by tenfold cross validation. RESULTS: A total of 3318 GZSCC, 10792 OPSCC and 6656 OCSCC patients were identified. HPV-positive GZSCC patients had the best 5-year OS as HPV-positive OPSCC (81% vs. 82%). However, the 5-year OS of HPV-negative/unknown GZSCC (43%/42%) were the worst among all groups, indicating that HPV status and the overlapping nature of tumors were valuable prognostic predictors in GZSCC patients. Compared with the strategy of dividing GZSCC into two groups by HPV status, the predictive model integrating more variables could additionally identify a unique high-risk GZSCC group with the lowest OS rate. CONCLUSIONS: GZSCC patients had distinct clinical characteristics and prognosis compared with OPSCC and OCSCC, integrating HPV status and other clinical factors could help distinguish GZSCC and predict their prognosis.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Humanos , Neoplasias Orofaríngeas/patologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Carcinoma de Células Escamosas/patologia , Prognóstico , Boca/patologia
18.
Molecules ; 28(16)2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37630313

RESUMO

Typically, the formation of vesicles requires the addition of salts or other additives to surfactant micelles. However, in the case of catanionic surfactants, unilamellar vesicles can spontaneously form upon dilution of the micellar solutions. Our study explores the intriguing spontaneous vesicle-to-micelle transition in catanionic surfactant systems, specifically cetyltrimethyl ammonium bromide (CTAB) and sodium octylsulfonate (SOS). To gain insights into the changes occurring at the interface, we employ a chemical trapping method to characterize variations in the molarities of sulfonate headgroups, water, and bromide ions during the transition. Our findings reveal the formation of ion pairs between the cationic component of CTAB and the anionic component of SOS, leading to tight interfacial packing in CTAB/SOS solutions. This interfacial packing promotes vesicle formation at low surfactant concentrations. Due to the significant difference in critical micelle concentration (cmc) between CTAB and SOS, an increase in the stoichiometric surfactant concentration results in a substantial rise in the SOS-to-CTAB ratio within the interfacial region. This enrichment of SOS in the aggregates triggers the transition from vesicles to micelles. Overall, our study may shed new light on the design of morphologies in catanionic and other surfactant systems.

19.
Bioinformatics ; 37(22): 4277-4279, 2021 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-33974000

RESUMO

MOTIVATION: N 6-methyladenosine (m6A) is the most abundant mammalian mRNA methylation with versatile functions. To date, although a number of bioinformatics tools have been developed for location discovery of m6A modification, functional understanding is still quite limited. As the focus of RNA epigenetics gradually shifts from site discovery to functional studies, there is an urgent need for user-friendly tools to identify and explore the functional relevance of context-specific m6A methylation to gain insights into the epitranscriptome layer of gene expression regulation. RESULTS: We introduced here Funm6AViewer, a novel platform to identify, prioritize and visualize the functional gene interaction networks mediated by dynamic m6A RNA methylation unveiled from a case control study. By taking the differential RNA methylation data and differential gene expression data, both of which can be inferred from the widely used MeRIP-seq data, as the inputs, Funm6AViewer enables a series of analysis, including: (i) examining the distribution of differential m6A sites, (ii) prioritizing the genes mediated by dynamic m6A methylation and (iii) characterizing functionally the gene regulatory networks mediated by condition-specific m6A RNA methylation. Funm6AViewer should effectively facilitate the understanding of the epitranscriptome circuitry mediated by this reversible RNA modification. AVAILABILITY AND IMPLEMENTATION: Funm6AViewer is available both as a convenient web server (https://www.xjtlu.edu.cn/biologicalsciences/funm6aviewer) with graphical interface and as an independent R package (https://github.com/NWPU-903PR/Funm6AViewer) for local usage. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Epigênese Genética , RNA , Animais , Metilação , Estudos de Casos e Controles , RNA/metabolismo , Redes Reguladoras de Genes , Adenosina/metabolismo , Mamíferos/genética
20.
J Biomech Eng ; 144(10)2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35420121

RESUMO

During respiration, the expansion and contraction of the chest and abdomen are coupled with each other, presenting a complex torso movement pattern. A finite element (FE) model of chest breathing based on the HUMOS2 human body model was developed. One-dimensional muscle units with active contraction functions were incorporated into the model based on Hill's active muscle model so as to generate muscle contraction forces that can change over time. The model was validated by comparing it to the surface displacement of the chest and abdomen during respiration. Then, the mechanism of the coupled motion of the chest and abdomen was analyzed. The analyses revealed that since the abdominal wall muscles are connected to the lower edge of the rib cage through tendons, the movement of the rib cage may cause the abdominal wall muscles to be stretched in both horizontal and vertical in a supine position. The anteroposterior and the right-left diameters of the chest will increase at inspiration, while the right-left diameter of the abdomen will decrease even though the anteroposterior diameter of the abdomen increases. The external intercostal muscles at different regions had different effects on the motion of the ribs during respiration. In particular, the external intercostal muscles at the lateral region had a larger effect on pump handle movement than bucket handle movement, and the external intercostal muscles at the dorsal region had a greater influence on bucket handle movement than pump handle movement.


Assuntos
Costelas , Tórax , Humanos , Músculos Intercostais , Movimento , Respiração , Costelas/fisiologia , Tórax/fisiologia
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