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The rational design of a solid electrolyte interphase (SEI) with high ionic conductivity and high electrochemical stability is significantly important in improving the electrochemical performance of anode materials. Herein, lithium difluoro(oxalate)borate (LiDFOB) is used as an electrolyte additive to generate protective SEI films on Li3VO4 (LVO) anodes. The addition of LiDFOB is beneficial to form a dense, uniform, stable and LiF-richer SEI, which is helpful to boost the Li-ion storage kinetics. In addition, the generated SEI can inhibit the further decomposition of electrolytes and maintain the morphology of LVO anodes during charge/discharge processes. As a result, LVO-based anodes exhibit a much higher capacity (769.5 mA h g-1 at 0.5 A g-1), enhanced rate performance (243.3 mA h g-1 at 5.0 A g-1) and excellent long-term cycling stability (209.9 mA h g-1 after 5000 cycles) when cycled in 1 wt% LiDFOB addition electrolyte. This work confirms that LiDFOB is a promising multi-functional additive for LiPF6 electrolytes and provides new insights into SEI construction towards high-performance LVO anodes.
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Aldehyde dehydrogenase 2 (ALDH2) deficiency caused by genetic variant is present in more than 560 million people of East Asian descent, which can be identified by apparent facial flushing from acetaldehyde accumulation after consuming alcohol. Recent findings indicated that ALDH2 also played a critical role in detoxification of formaldehyde (FA). Our previous studies showed that FA could enhance macrophagic inflammatory responses through the induction of HIF-1α-dependent glycolysis. In the present study, pro-inflammatory responses and glycolysis promoted by 0.5 mg/m3 FA were found in mice with Aldh2 gene knockout, which was confirmed in the primary macrophages isolated from Aldh2 gene knockout mice treated with 50 µM FA. FA at 50 and 100 µM also induced stronger dose-dependent increases of pro-inflammatory responses and glycolysis in RAW264.7 murine macrophages with knock-down of ALDH2, and the enhanced effects induced by 50 µM FA was alleviated by inhibition of HIF-1α in RAW264.7 macrophages with ALDH2 knock-down. Collectively, these results clearly demonstrated that ALDH2 deficiency reinforced pro-inflammatory responses and glycolysis in macrophages potentiated by environmentally relevant concentration of FA, which may increase the susceptibility to inflammation and immunotoxicity induced by environmental FA exposure.
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Acetaldeído , Etanol , Humanos , Camundongos , Animais , Aldeído-Desidrogenase Mitocondrial/genética , Etanol/toxicidade , Acetaldeído/toxicidade , Formaldeído/toxicidade , Camundongos Knockout , MacrófagosRESUMO
The correlation between formaldehyde (FA) exposure and prevalence of asthma has been widely reported. However, the underlying mechanism is still not fully understood. FA exposure at 2.0â¯mg/m3 was found to exacerbate asthma in OVA-induced murine models. IFN-γ, the cytokine produced by T helper 1 (Th1) cells, was significantly induced by FA in serum and bronchoalveolar lavage fluid (BALF) of asthmatic mice, which was different from cytokines secreted by other Th cells. The observation was also confirmed by mRNA levels of Th marker genes in CD4+ T cells isolated from BALF. In addition, increased production of IFN-γ and expression of T-bet in Jurkat T cells primed with phorbol ester and phytohaemagglutinin were also observed with 100⯵M FA treatment in vitro. Upregulated STAT1 phosphorylation, T-bet expression and IFN-γ production induced by FA was found to be restrained by STAT1 inhibitor fludarabine, indicating that FA promoted Th1 commitment through the autocrine IFN-γ/STAT1/T-bet pathway in asthma. This work not only revealed that FA could bias Th lineage commitment to exacerbate allergic asthma, but also identified the signaling mechanism of FA-induced Th1 differentiation, which may be utilized as the target for development of interfering strategies against FA-induced immune disorders.
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Asma , Formaldeído , Interferon gama , Fator de Transcrição STAT1 , Proteínas com Domínio T , Asma/induzido quimicamente , Animais , Fator de Transcrição STAT1/metabolismo , Interferon gama/metabolismo , Camundongos , Proteínas com Domínio T/genética , Proteínas com Domínio T/metabolismo , Formaldeído/toxicidade , Inflamação/induzido quimicamente , Camundongos Endogâmicos BALB C , Humanos , Feminino , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/química , Linfócitos T Auxiliares-Indutores/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células JurkatRESUMO
KEY MESSAGE: Genomic analysis of upland cotton revealed that cold tolerance was associated with ecological distribution. GhSAL1 on chromosome D09 negatively regulated cold tolerance of upland cotton. Cotton can undergo low-temperature stress at the seedling emergence stage, which adversely affects growth and yield; however, the regulatory mechanism underlying cold tolerance remains nebulous. Here, we analyze the phenotypic and physiological parameters in 200 accessions from 5 ecological distributions under constant chilling (CC) and diurnal variation of chilling (DVC) stresses at the seedling emergence stage. All accessions were clustered into four groups, of which Group IV, with most germplasms from the northwest inland region (NIR), had better phenotypes than Groups I-III under the two kinds of chilling stresses. A total of 575 significantly associated single-nucleotide polymorphism (SNP) were identified, and 35 stable genetic quantitative trait loci (QTL) were obtained, of which 5 were associated with traits under CC and DVC stress, respectively, while the remaining 25 were co-associated. The accumulation of dry weight (DW) of seedling was associated with the flavonoid biosynthesis process regulated by Gh_A10G0500. The emergence rate (ER), DW, and total length of seedling (TL) under CC stress were associated with the SNPs variation of Gh_D09G0189 (GhSAL1). GhSAL1HapB was the elite haplotype, which increased ER, DW, and TL by 19.04%, 11.26%, and 7.69%, respectively, compared with that of GhSAL1HapA. The results of virus-induced gene silencing (VIGS) experiment and determination of metabolic substrate content preliminarily illustrated that GhSAL1 negatively regulated cotton cold tolerance through IP3-Ca2+ signaling pathway. The elite haplotypes and candidate genes identified in this study could be used to improve cold tolerance at the seedling emergence stage in future upland cotton breeding.
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Estudo de Associação Genômica Ampla , Gossypium , Gossypium/genética , Estudo de Associação Genômica Ampla/métodos , Mapeamento Cromossômico , Plântula/genética , Melhoramento Vegetal , Fenótipo , Polimorfismo de Nucleotídeo ÚnicoRESUMO
The mean residual life (MRL) function is an important and attractive alternative to the hazard function for characterizing the distribution of a time-to-event variable. In this article, we study the modeling and inference of a family of generalized MRL models for right-censored survival data with censoring indicators missing at random. To estimate the model parameters, augmented inverse probability weighted estimating equation approaches are developed, in which the non-missingness probability and the conditional probability of an uncensored observation are estimated by parametric methods or nonparametric kernel smoothing techniques. Asymptotic properties of the proposed estimators are established and finite sample performance is evaluated by extensive simulation studies. An application to brain cancer data is presented to illustrate the proposed methods.
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Neoplasias Encefálicas , Humanos , Simulação por Computador , Probabilidade , Modelos EstatísticosRESUMO
The development of lithium-ion batteries (LIBs) is still facing challenges due to the design and optimization of anode materials and their Li-ion storage mechanisms. In this study, we aimed to address this issue by constructing three-dimensional hierarchical heterojunction structures using a double needle electrospinning strategy. The heterostructure was composed of insertion-type Li3VO4 and conversion/alloying-type Ga2O3 embedded porous carbon nanofibers (Li3VO4-Ga2O3@PCNF). The designed heterostructured Ga2O3 and Li3VO4 materials were found to effectively enhance charge transfer dynamics, thereby improving capacity and rate capability. Additionally, the facilitated efficient contact between the electrode and electrolyte, enabling the diffusion of ions and electrons. When applied as an anode material in LIBs, the Li3VO4-Ga2O3@PCNF composite achieved a high capacity of 630.0 mA h g-1 at 0.5 A g-1, and full capacity recovery after 6 periods of rate testing over 480 cycles. When simulating the practical application under a high discharge current of 6.0 A g-1, the Li3VO4-Ga2O3@PCNF could still deliver a high discharge capacity of 322.0 mA h g-1 after 2000 cycles. Furthermore, the composite exhibited a remarkable capacity retention of 77.2% after 2000 cycles at 6.0 A g-1. This research provides valuable guidance for the design of high-performance Li3VO4-based anodes, particularly in addressing the issue of inferior electronic conductivity.
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BACKGROUND: High serum uric acid (SUA) is a risk factor of cardiovascular disease (CVD). Abnormal SUA have been correlated with a significant increase in mortality. Anemia is an independent predictor of mortality and CVD. To date, no study has investigated the relationship between SUA and anemia. Here, we explored the correlation between SUA and anemia in the American population. METHODS: The cross-sectional study involved 9205 US adults from NHANES (2011-2014). The relationship between SUA and anemia was explored using multivariate linear regression models. Two-piecewise linear regression model, generalized additive models (GAM) and smooth curve fitting were performed to explore the non-linear relationships between SUA and anemia. RESULTS: We found a U-shaped non-linear relationship between SUA and anemia. The inflection point of the SUA concentration curve was 6.2 mg/dL. The ORs (95% CIs) for anemia on the left and right of the inflection point were 0.86 (0.78-0.95) and 1.33 (1.16-1.52), respectively. The 95% CI of inflection point was 5.9-6.5 mg/dL. The findings showed that both genders presented a U-shaped correlation. Safe ranges of SUA in men and women were 6-6.5 and 4.3-4.6 mg/dL, respectively. CONCLUSIONS: Both high and low SUA levels were correlated with increased risk of anemia, and a U-shaped relationship was observed between SUA and anemia.
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Doenças Cardiovasculares , Ácido Úrico , Humanos , Masculino , Adulto , Feminino , Estudos Transversais , Inquéritos Nutricionais , Fatores de RiscoRESUMO
BACKGROUND: The job performance of individual employees determines the overall performance of an organization, and organizational support is known as an important resource at the organizational level to enhance job performance. Although nursing scholars have confirmed the crucial role of organizational support in enhancing job performance, there are no studies on whether psychological capital and organizational identification mediate the association between organizational support and job performance. The purpose of this study is to investigate the influence of organizational support, psychological capital, and organizational identification on nurses' job performance. METHODS: A cross-sectional survey was conducted among 455 nurses from 21 public hospitals in China. Instruments were perceived organizational support scale, task performance scale, contextual performance scale, Nurse Psychological Capital Questionnaire, and Organizational Identification Questionnaire. Survey data were analyzed using SPSS and AMOS, and hypotheses were tested using path model analysis. RESULTS: Nurses' perceived organizational support, psychological capital, organizational identification, and task/contextual performance were positively correlated in every two variables. Psychological capital played an important mediating role in perceived organizational support and task/contextual performance, as well as organizational identification. The multi-mediating effect of psychological capital and organizational identification on the relationship between organizational support and task/contextual performance were 0.14 and 0.25, respectively. CONCLUSIONS: There was a positive correlation between organizational support and job performance among nurses. Psychological support, organizational identification and contextual performance played a chain mediation role in the relationship between organizational support on task performance in nurses. Nursing managers should pay more attention to enhancing nurses' psychological capital and organizational identification through effective interventions to improve nurses' job performance.
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Enfermeiros Administradores , Enfermeiras e Enfermeiros , Recursos Humanos de Enfermagem Hospitalar , Desempenho Profissional , Humanos , Estudos Transversais , Análise de Classes Latentes , Recursos Humanos de Enfermagem Hospitalar/psicologia , Inquéritos e Questionários , Satisfação no EmpregoRESUMO
BACKGROUND: The process of education is mutual. The learning needs of students need to be paid attention to and can affect the learning outcome. In order to make nursing postgraduates' curriculum better, meet the learning needs of students, and help to achieve the learning objectives of students, this study based on Hutchinson's learning needs theory, aims to collect the learning experience of nursing graduates, as well as the gap between learning needs and target needs, and explore the benefits and barriers of nursing graduates in the curriculum learning. It may provide beneficial reference for further optimizing teaching content and improving teaching methods. METHODS: This study was designed as a qualitative research. Purposive sampling was used to recruit 17 nursing postgraduates in the only two universities in Chongqing, Southwest China, 2021. Semi-structured, in-depth individual interviews were conducted to explore how they subjectively experience the benefits and demands of the professional curriculum. Data was analyzed using Colaizzi's seven-step analysis. RESULTS: Three main themes "clear learning cognition and goals," "positive learning attitude," and "the gap between learning goals and actual needs" were identified from the original data. Respectively, Subthemes concerning the first theme included "improve scientific research capabilities, enlighten thinking and broaden your horizons, and learn new knowledge and new skills." Subthemes of the second theme were "improve abilities in practice and actively seek diversification of course content and format." Subthemes of the third theme included "the course has a certain depth and breadth, but the course study does not meet the needs of scientific research, the course contents are theoretical, not knowing how to use the research method in certain conditions." CONCLUSIONS: The learning needs of nursing postgraduates in Southwest China could be divided into two parts: benefits and barriers, among which the benefits were participants had clear learning goals and positive learning attitudes. When curriculum could not meet their needs, they actively sought methods (e.g., networks or off-campus resources) to close the gap between those needs and their goals. Follow-up educators should focus on learning needs and build curricula by optimizing the contents and methods of existing teaching resources.
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Bacharelado em Enfermagem , Estudantes de Enfermagem , Humanos , Aprendizagem , Pesquisa Qualitativa , Estudantes , Bacharelado em Enfermagem/métodos , ChinaRESUMO
In this work, we propose a longitudinal quantile regression framework that enables a robust characterization of heterogeneous covariate-response associations in the presence of high-dimensional compositional covariates and repeated measurements of both response and covariates. We develop a globally adaptive penalization procedure, which can consistently identify covariate sparsity patterns across a continuum set of quantile levels. The proposed estimation procedure properly aggregates longitudinal observations over time, and ensures the satisfaction of the sum-zero coefficient constraint that is needed for proper interpretation of the effects of compositional covariates. We establish the oracle rate of uniform convergence and weak convergence of the resulting estimators, and further justify the proposed uniform selector of the tuning parameter in terms of achieving global model selection consistency. We derive an efficient algorithm by incorporating existing R packages to facilitate stable and fast computation. Our extensive simulation studies confirm the theoretical findings. We apply the proposed method to a longitudinal study of cystic fibrosis children where the association between gut microbiome and other diet-related biomarkers is of interest.
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BACKGROUND: With the frequent occurrence of public health emergencies, conflicts and natural disasters around the world, mobile surgical teams are becoming more crucial. The competency of the operating room (OR) nurse has a substantial impact on the effectiveness and quality of the surgical team's treatment, still there is limited knowledge about OR nurse competencies in mobile surgical teams. This study aimed to explore the competencies of OR nurses in mobile surgical teams based on the Onion Model. METHODS: We conducted a qualitative descriptive study of participants from 10 mobile surgical teams in 2022. Twenty-one surgical team members were interviewed, including 15 OR nurses, four surgeons, and two anesthesiologists. Data were collected through semi-structured interviews. The data were analyzed using Mayring's content analysis. RESULTS: Twenty-eight competencies were found in the data analysis, which were grouped into four major domains using the Onion Model. From the outer layer to the inner layer were knowledge and skills, professional abilities, professional quality, and personal traits. The qualitative data revealed several novel competencies, including triage knowledge, self and mutual medical aid, outdoor survival skills, and sense of discipline. CONCLUSIONS: The application of the Onion Model promotes the understanding of competency and strengthens the theoretical foundations of this study. New competencies can enrich the content of the competencies of OR nurses. The results of this study can be used for clinical recruitment, evaluation and training of OR nurses in mobile surgical teams. This study encourages further research to develop competency assessment tools and training programs for OR nurses.
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BACKGROUND: With frequent conflicts, natural disasters, and public health emergencies globally, mobile medical teams (MMTs) are becoming increasingly critical. Importantly, the competency of critical care nurses in MMTs can substantially affect the effectiveness and quality of its rescue efforts. Yet, these nurses' competencies are not well understood. AIM: This study examined the competencies of critical care nurses in MMTs using the Onion Model. DESIGN: A qualitative descriptive method was used to describe the competencies of Chinese MMT critical care nurses. METHODS: From April to May 2022, a convenience sample of 18 participants (14 critical care nurses and 4 surgeons) from 10 MMTs was recruited for semi-structured interviews. Deductive and inductive coding methods were combined for content analysis. RESULTS: In total, 29 competencies were identified, which were grouped into four major domains using the Onion Model. From the outer to inner layers, these domains were knowledge and skills, professional abilities, professional quality, and personal traits. Several novel competencies emerged, including field medical equipment operation skills, on-site hazard identification and safety prevention skills, triage knowledge, and field survival skills. CONCLUSIONS: Using the Onion Model, this study furthers the understanding of the competency of critical care nurses in MMTs, especially by revealing the novel competencies. Further, the results can be used to recruit, evaluate, and train critical care nurses for MMTs. RELEVANCE TO CLINICAL PRACTICE: Understanding MMT critical care nurses' competencies can help managers plan and provide relevant training and education before deployment, which can improve nurses' performance, and especially reduce the mortalities and disabilities from trauma.
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Previous studies have shown that low birth weight (LBW) individuals are at higher risk of glucose metabolism disorders compared with normal birth weight (NBW) individuals under overnutrition conditions, but the mechanism remains unclear. To explore the underlying mechanism of glucose metabolism disorders induced by LBW under overnutrition in adulthood, the prenatal malnutrition method was applied to ICR mice to establish the LBW mice model and high-fat diets were used to mimic overnutrition conditions. Then the mechanism was further explored on Hepg2 cells treated with nutritional deprivation plus palmitic acid. The results showed that LBW plus high-fat interventions will cause glucose metabolism disorders and inhibit autophagy flux in adulthood. Moreover, the expression of TRPC5-regulated AMPK/mTOR autophagy pathway was downregulated by LBW with high-fat interventions. Collectively, LBW plus high-fat intervention increased the risk of glucose metabolism disorders, which may be related to the alteration of TRPC5 expression level and its regulation of the AMPKα/mTOR autophagy pathway. This study may provide a fundamental basis for the molecular mechanism of glucose metabolism disorders induced by LBW with high-fat diets in adulthood and a new target for the treatment of metabolic diseases in LBW individuals.
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Transtornos do Metabolismo de Glucose , Hipernutrição , Proteínas Quinases Ativadas por AMP , Animais , Autofagia , Peso ao Nascer/fisiologia , Feminino , Camundongos , Camundongos Endogâmicos ICR , Ácido Palmítico , Gravidez , Serina-Treonina Quinases TOR , Canais de Cátion TRPCRESUMO
Cold stress is a major environmental factor affecting plant growth and development. Although some plants have developed resistance to cold stress, the molecular mechanisms underlying this process are poorly understood. Using genome-wide association mapping with 200 cotton accessions collected from different regions, we identified variations in the short chain alcohol dehydrogenase gene, GhSAD1, that responds to cold stress. Virus-induced gene silencing and overexpression in Arabidopsis revealed that GhSAD1 fulfils important roles in cold stress responses. Ectopic expression of a haploid genotype of GhSAD1 (GhSAD1HapB) in Arabidopsis increased cold tolerance. Silencing of GhSAD1HapB resulted in a decrease in abscisic acid (ABA) content. Conversely, overexpression of GhSAD1HapB increased ABA content. GhSAD1HapB regulates cold stress responses in cotton through modulation of C-repeat binding factor activity, which regulates ABA signalling. GhSAD1HapB induces the expression of COLD-REGULATED (COR) genes and increases the amount of metabolites associated with cold stress tolerance. Overexpression of GhSAD1HapB partially complements the phenotype of the Arabidopsis ABA2 mutant, aba2-1. Collectively, these findings increase our understanding of the mechanisms underlying GhSAD1-mediated cold stress responses in cotton.
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Proteínas de Arabidopsis , Arabidopsis , Ácido Abscísico/metabolismo , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Temperatura Baixa , Regulação da Expressão Gênica de Plantas , Estudo de Associação Genômica Ampla , Plantas Geneticamente Modificadas/genética , Estresse FisiológicoRESUMO
Arsenite (As+3) is a group one human carcinogen, which has been associated with many diseases. Previous studies indicated that As+3 could inhibit wound healing and repair. M2a cells are known as tissue remodeling macrophages, which play an important role in wound repair process. Peroxisome proliferator-activated receptor gamma (PPAR-γ), a key regulator of lipid and glucose metabolism, was found to mediate the IL-4-dependent M2a polarization of macrophages. In the present study, As+3 induced dose-dependent inhibition of M2a polarization starting from 0.1 µM in THP-1-derived macrophages stimulated with 20 ng/mL IL-4. Increased lipid accumulation and decreased PPAR-γ expression were also observed in As+3-treated M2a macrophages. Rosiglitazone (RSG), a potent PPAR-γ agonist, alleviated the suppressions of PPAR-γ and M2a polarization induced by 2 µM As+3. Collectively, these results not only demonstrated that As+3 was able to inhibit polarization of M2a cells through PPAR-γ suppression, but also indicated that PPAR-γ could be utilized as a target for the prevention and treatment of As+3-induced immunotoxicity.
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Arsenitos , Tiazolidinedionas , Arsenitos/metabolismo , Arsenitos/toxicidade , Regulação para Baixo , Humanos , Interleucina-4/metabolismo , Lipídeos , Macrófagos/metabolismo , PPAR gama/metabolismoRESUMO
Myricetin is a flavonoid widely-distributed in foods with many beneficial health effects, which has been marketed in health products. Formaldehyde is an environmental carcinogen which can enhance the Warburg effect through the induction of human hypoxia-inducible factor 1 subunit alpha (HIF-1α), the primary regulator of cellular glycolysis. HIF-1α was verified as an important target in lung and ovarian tumors, which was also identified as a receptor for myricetin via molecular docking. The reinforced HIF-1α signaling, the Warburg effect and T cell suppression induced by 50 µM formaldehyde in both A549 and Caov-3 cells were dose-dependently attenuated by myricetin from 20 to 100 µM, and the attenuative effects were diminished by the stabilization of HIF-1α with deferoxamine. Exposure to 2.0 mg/m3 formaldehyde also stimulated tumor growth and elevated HIF-1α expression in tumor tissues of A549 xenograft mice, which were also alleviated by oral administration of 100 mg/kg myricetin. These results demonstrated that myricetin alleviated formaldehyde-enhanced Warburg effect in tumor cells through HIF-1α inhibition, which could be further developed as a therapeutic or complementary agent for formaldehyde-induced carcinogenesis.
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Carcinógenos Ambientais , Animais , Linhagem Celular Tumoral , Desferroxamina , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Formaldeído/toxicidade , Humanos , Fator 1 Induzível por Hipóxia , Subunidade alfa do Fator 1 Induzível por Hipóxia , Camundongos , Simulação de Acoplamento MolecularRESUMO
Environmental exposure to formaldehyde is known to be associated with cancers and many other diseases. Although formaldehyde has been classified as a group I carcinogen, the molecular mechanisms of its carcinogenicity are still not fully understood. Formaldehyde is also involved in the folate-driven onecarbon metabolism, and excess amount of formaldehyde was found to interfere with other metabolic pathways including glycolysis, which can enhance Warburg effect and induce immunosuppression in tumor microenvironment. Therefore, different tumor cells and THP-1 derived macrophages were utilized to explore the metabolism-related effects induced by formaldehyde at environmentally relevant concentrations. Significant increases of glucose uptake, glycolysis levels, HIF-1α signaling and methylglyoxal production were observed in tumor cells treated with 20 and 50 µM formaldehyde for 24 h, and the overproduced methylglyoxal in the conditioned medium collected from the tumor cells treated with formaldehyde triggered macrophage polarization towards M2 cells. Myricetin, a flavonol scavenging methylglyoxal, reversed the polarization of macrophages induced by methylglyoxal at 50 µM. These results not only provided essential evidences to reveal the molecular mechanisms of Warburg effect and metabolism-related immunosuppression related to formaldehyde exposure, but also indicated that methylglyoxal could be utilized as a target for therapeutic treatment or prevention of formaldehyde-induced immunotoxicity.
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Formaldeído/efeitos adversos , Aldeído Pirúvico/metabolismo , Macrófagos Associados a Tumor/efeitos dos fármacos , Efeito Warburg em Oncologia/efeitos dos fármacos , Células A549 , Linhagem Celular Tumoral , Glicólise/efeitos dos fármacos , Células HCT116 , Células HeLa , Humanos , Células Jurkat , Células MCF-7 , Ativação de Macrófagos/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Células Th1 , Microambiente Tumoral/efeitos dos fármacos , Macrófagos Associados a Tumor/metabolismoRESUMO
KEY MESSAGE: Two regions located at chromosome A05 and D04 were found to be significantly associated with 0-0.5 mm and 0.5-2 mm diameter roots, respectively, and two candidate genes related to root development were identified. Roots absorb water and nutrients, and play an important role in plant growth. However, there are few genetic developmental studies on cotton root structural traits. In this study, we used 200 upland cotton (Gossypium hirsutum L.) varieties to analyze the phenotypic variation of 43 traits. A total of 2001 related single-nucleotide polymorphism (SNP) sites located within or near 1046 genes were detected through a genome-wide association study (GWAS). The 32 root traits were linked to SNPs that corresponded to 317 nonrepetitive genes. For SNPs associated with root length and 0-0.5 mm diameter root traits, a significant peak appeared on chromosome A05 (between 21.91 and 22.24 Mb). For SNPs associated with root surface area, root volume and 0.5-2 mm diameter root traits, a significant peak appeared on chromosome D04 (between 7.35 and 7.70 Mb). Within these two key regions, SNPs were detected in the promoter and coding regions of two candidate genes, GhTRL1-A05 and GhPIN8-D04. The expression levels of these two genes also changed significantly according to transcriptome sequencing and quantitative real-time PCR (qRT-PCR). After silencing the GhTRL1 and GhPIN8 genes via virus-induced gene silencing (VIGS), we found that the plants expressing TRV2::GhTRL1 and TRV2::GhPIN8 had a reduced root length, surface area. Moreover, the contents of cis-12-oxo-phytodienoic acid (cis-OPDA), isopentenyl adenosine (iPR) and cis-zeatin (cZ) in the roots of the plants expressing TRV2::GhTRL1 decreased. This study contributes to the cultivation and improvement of cotton varieties.
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Estudo de Associação Genômica Ampla , Gossypium , Adenosina , Gossypium/genética , Água , ZeatinaRESUMO
Multivariate recurrent event data are frequently encountered in biomedical and epidemiological studies when subjects experience multiple types of recurrent events. In practice, the event type information may be missing due to a variety of reasons. In this article, we consider a semiparametric additive rates model for multivariate recurrent event data with missing event types. We develop the augmented inverse probability weighting technique to handle event types that are missing at random. The nonparametric kernel-assisted proposals for the missing mechanisms are studied. The resulting estimator is shown to be consistent and asymptotically normal. Extensive simulation studies and a real data application are provided to illustrate the validity and practical utility of the proposed method.
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Projetos de Pesquisa , Simulação por Computador , Humanos , ProbabilidadeRESUMO
BACKGROUND: Congenital adrenal hyperplasia (CAH), characterized by defective adrenal steroidogenesis, is transmitted in an autosomal recessive manner. Mutations in the steroid 21-hydroxylase gene CYP21A2 causing steroid 21-hydroxylase deficiency account for most cases of CAH. The c.145l-1452delGGinsC gene mutation is rare, and only one case has been reported, but the form of gene mutation is different from this case, resulting in different clinical phenotype. The most common pathogenic genotype of CAH is a homozygous or compound heterozygous mutation, but CAH patients homozygous for the p.I173N mutation and heterozygous for the c.1451-1452delGGinsC mutation have not been reported previously. We report herein a familial case of CAH, in which both siblings carry the rare homozygous p.I173N mutation and heterozygous c.1451-1452delGGinsC mutation. CASE PRESENTATION: The proband showed amenorrhea, infertility, polycystic ovaries, and increased levels of androgen, rather than the typical clinical manifestations of CAH such as an adrenal crisis or masculine vulva, so was misdiagnosed with polycystic ovary syndrome for many years. Following a correct diagnosis of CAH, she was given glucocorticoid treatment, her menstruation became more regular, and she became pregnant and delivered a healthy baby girl. CONCLUSIONS: The genotypes may be p.I173N homozygous or p.I173N/c.1451-1452delGGinsC heterozygous, both mutations could be pathogenic. This complex combination of mutations has not been reported or studied before. Through the report and analysis of this genotype, the content of CAH gene bank is enriched and the misdiagnosis rate of CAH is reduced.