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The Mexico City Prospective Study is a prospective cohort of more than 150,000 adults recruited two decades ago from the urban districts of Coyoacán and Iztapalapa in Mexico City1. Here we generated genotype and exome-sequencing data for all individuals and whole-genome sequencing data for 9,950 selected individuals. We describe high levels of relatedness and substantial heterogeneity in ancestry composition across individuals. Most sequenced individuals had admixed Indigenous American, European and African ancestry, with extensive admixture from Indigenous populations in central, southern and southeastern Mexico. Indigenous Mexican segments of the genome had lower levels of coding variation but an excess of homozygous loss-of-function variants compared with segments of African and European origin. We estimated ancestry-specific allele frequencies at 142 million genomic variants, with an effective sample size of 91,856 for Indigenous Mexican ancestry at exome variants, all available through a public browser. Using whole-genome sequencing, we developed an imputation reference panel that outperforms existing panels at common variants in individuals with high proportions of central, southern and southeastern Indigenous Mexican ancestry. Our work illustrates the value of genetic studies in diverse populations and provides foundational imputation and allele frequency resources for future genetic studies in Mexico and in the United States, where the Hispanic/Latino population is predominantly of Mexican descent.
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Sequenciamento do Exoma , Genoma Humano , Genótipo , Hispânico ou Latino , Adulto , Humanos , África/etnologia , América/etnologia , Europa (Continente)/etnologia , Frequência do Gene/genética , Genética Populacional , Genoma Humano/genética , Técnicas de Genotipagem , Hispânico ou Latino/genética , Homozigoto , Mutação com Perda de Função/genética , México , Estudos ProspectivosRESUMO
Sweet osmanthus (Osmanthus fragrans) is famous in China for its flowers and contains four groups: Albus, Luteus, Aurantiacus, and Asiaticus. Understanding the relationships among these groups and the genetic mechanisms of flower color and aroma biosynthesis are of tremendous interest. In this study, we sequenced representative varieties from two of the four sweet osmanthus groups. Multiomics and phylogenetic analyses of varieties from each of the four groups showed that Asiaticus split first within the species, followed by Aurantiacus and the sister groups Albus and Luteus. We show that the difference in flower color between Aurantiacus and the other three groups was caused by a 4-bp deletion in the promoter region of carotenoid cleavage dioxygenase 4 (OfCCD4) that leads to expression decrease. In addition, we identified 44 gene pairs exhibiting significant structural differences between the multiseasonal flowering variety "Rixianggui" in the Asiaticus group and other autumn-flowering varieties. Through correlation analysis between intermediate products of aromatic components and gene expression, we identified eight genes associated with the linalool and α- and ß-ionone biosynthesis pathways. Overall, our study offers valuable genetic resources for sweet osmanthus, while also providing genetic clues for improving the flower color and multiseasonal flowering of osmanthus and other flowers.
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Flores , Oleaceae , Filogenia , Oleaceae/genética , Flores/genética , Regulação da Expressão Gênica de Plantas , Genoma de Planta , Genômica/métodos , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Genes de Plantas , MultiômicaRESUMO
BACKGROUND: The Rh blood group system is characterized by its complexity and polymorphism, encompassing 56 different antigens. Accurately predicting the presence of the C antigen using genotyping methods has been challenging. The objective of this study was to evaluate the accuracy of various genotyping methods for predicting the Rh C and to identify a suitable method for the Chinese Han population. METHODS: In total, 317 donors, consisting 223 D+ (including 20 with the Del phenotype) and 94 D- were randomly selected. For RHC genotyping, 48C and 109bp insertion were detected on the Real-time PCR platform and -292 substitution was analyzed via restriction fragment length polymorphism (RFLP). Moreover, the promoter region of the RHCE gene was sequenced to search for other nucleotide substitutions between RHC and RHc. Agreement between prediction methods was evaluated using the Kappa statistic, and comparisons between methods were conducted via the χ2 test. RESULTS: The analysis revealed that the 48C allele, 109bp insertion, a specific pattern observed in RFLP results, and wild-type alleles of seven single nucleotide polymorphisms (SNPs) were in strong agreement with the Rh C, with Kappa coefficients exceeding 0.8. However, there were instances of false positives or false negatives (0.6% false negative rate for 109bp insertion and 5.4-8.2% false positive rates for other methods). The 109bp insertion method exhibited the highest accuracy in predicting the Rh C, at 99.4%, compared to other methods (P values≤0.001). Although no statistical differences were found among other methods for predicting Rh C (P values>0.05), the accuracies in descending order were 48C (94.6%) > rs586178 (92.7%) > rs4649082, rs2375313, rs2281179, rs2072933, rs2072932, and RFLP (92.4%) > rs2072931 (91.8%). CONCLUSIONS: None of the methods examined can independently and accurately predict the Rh C. However, the 109bp insertion test demonstrated the highest accuracy for predicting the Rh C in the Chinese Han population. Utilizing the 109bp insertion test in combination with other methods may enhance the accuracy of Rh C prediction.
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Povo Asiático , Técnicas de Genotipagem , Polimorfismo de Nucleotídeo Único , Sistema do Grupo Sanguíneo Rh-Hr , Humanos , Sistema do Grupo Sanguíneo Rh-Hr/genética , Povo Asiático/genética , Técnicas de Genotipagem/métodos , China , Genótipo , Alelos , Polimorfismo de Fragmento de Restrição , Frequência do Gene , Regiões Promotoras Genéticas , População do Leste AsiáticoRESUMO
Drug resistance remains a challenge in ovarian cancer. In addition to aberrant activation of relevant signaling pathways, the adaptive stress response is emerging as a new spotlight of drug resistance in cancer cells. Stress granules (SGs) are one of the most important features of the adaptive stress response, and there is increasing evidence that SGs promote drug resistance in cancer cells. In the present study, we compared two types of ovarian cancer cells, A2780 and SKOV3, using the dual PI3K/mTOR inhibitor, PKI-402. We found that SGs were formed and SGs could intercept the signaling factor ATF5 and regulate the mitochondrial unfolded protein response (UPRmt) in A2780 cells. Therefore, exploring the network formed between SGs and membrane-bound organelles, such as mitochondria, which may provide a new insight into the mechanisms of antitumor drug functions.
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BACKGROUND AND OBJECTIVES: B(A) phenotype is usually formed by nucleotide mutations in the ABO*B.01 allele, with their products exhibiting glycosyltransferases (GTs) A and B overlapping functionality. We herein report a B(A) allele found in a Chinese family. MATERIALS AND METHODS: The entire ABO genes of the probands, including flanking regulatory regions, were sequenced through PacBio third-generation long-read single-molecule real-time sequencing. 3D molecular models of the wild-type and mutant GTB were generated using the DynaMut web server. The effect of the mutation on the enzyme function was predicted by PROVEAN and PolyPhen2. The predictions of stability changes were performed using DynaMut and SNPeffect. RESULTS: Based on serological and sequencing features, we concluded the two probands as possible cases of the B(A) phenotype. Crystallization analysis showed that Thr266 substitution does not disrupt the hydrogen bonds. However, some changes in interatomic contacts, such as loss of ionic interactions and hydrophobic contacts, and addition of weak hydrogen bonds, may have affected protein stability to some extent. This mutation was predicted to have a benign effect on enzyme function and slightly reduce protein stability. CONCLUSION: The probands had the same novel B(A) allele with a c.797T>C (p.Met266Thr) mutation on the ABO*B.01 backbone.
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Glicosiltransferases , Mutação de Sentido Incorreto , Humanos , Fenótipo , Mutação , Glicosiltransferases/química , Glicosiltransferases/genética , Alelos , China , Sistema ABO de Grupos Sanguíneos/genética , GenótipoRESUMO
BACKGROUND: Postoperative delirium (POD) represents a prevalent and noteworthy complication in the context of pediatric surgical interventions. In recent times, a hypothesis has emerged positing that cerebral ischemia and regional cerebral oxygen desaturation might serve as potential catalysts in the pathogenesis of POD. The primary aim of this study was to methodically examine the potential relationship between POD and regional cerebral oxygen saturation (rSO2) and to assess the predictive and evaluative utility of rSO2 in the context of POD. METHODS: This prospective observational study was conducted at the Children's Hospital, Zhejiang University School of Medicine, Zhejiang, China, spanning the period from November 2020 to March 2021. The research cohort comprised children undergoing surgical procedures within this clinical setting. To measure rSO2 dynamics, cerebral near-infrared spectroscopy (NIRS) was used to monitor rSO2 levels both before and after surgery. In addition, POD was assessed in the paediatric patients according to the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) criteria. The analysis of the association between the rSO2 index and the incidence of POD was carried out through the application of either the independent samples t-test or the nonparametric rank-sum test. To ascertain the threshold value of the adjusted rSO2 index for predictive and evaluative purposes regarding POD in the pediatric population, the Receiver Operating Characteristics (ROC) curve was employed. RESULTS: A total of 211 cases were included in this study, of which 61 (28.9%) developed POD. Participants suffering delirium had lower preoperative rSO2mean, lower preoperative rSO2min, and lower postoperative rSO2min, higher ∆rSO2mean, higher amount of ∆rSO2mean, lower ∆rSO2min (P < 0.05). Preoperative rSO2mean (AUC = 0.716, 95%CI 0.642-0.790), ∆rSO2mean (AUC = 0.694, 95%CI 0.614-0.774), amount of ∆rSO2mean (AUC = 0.649, 95%CI 0.564-0.734), preoperative rSO2min (AUC = 0.702, 96%CI 0.628-0.777), postoperative rSO2min (AUC = 0.717, 95%CI 0.647-0.787), and ∆rSO2min (AUC = 0.714, 95%CI 0.638-0.790) performed well in sensitivity and specificity, and the best threshold were 62.05%, 1.27%, 2.41%, 55.68%, 57.36%, 1.29%. CONCLUSIONS: There is a close relationship between pediatric POD and rSO2. rSO2 could be used as an effective predictor of pediatric POD. It might be helpful to measure rSO2 with NIRS for early recognizing POD and making it possible for early intervention.
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Delírio , Saturação de Oxigênio , Complicações Pós-Operatórias , Espectroscopia de Luz Próxima ao Infravermelho , Humanos , Estudos Prospectivos , Feminino , Masculino , Criança , Saturação de Oxigênio/fisiologia , Complicações Pós-Operatórias/metabolismo , Complicações Pós-Operatórias/diagnóstico , Pré-Escolar , Delírio/metabolismo , Delírio/diagnóstico , China , Adolescente , Encéfalo/metabolismo , Lactente , Oxigênio/metabolismo , Oxigênio/sangueRESUMO
OBJECTIVE: The aim of the study is to analyze microstate patterns in GLUT1-DS, both before and after the ketogenic diet (KD). METHODS: We conducted microstate analysis of a patient with GLUT-1 DS and 27 healthy controls. A systematic literature review and meta-analysis was done. We compared the parameters of the patients with those of healthy controls and the incorporating findings in literature. RESULTS: The durations of the patient were notably shorter, and the occurrence rates were longer than those of healthy controls and incorporating findings from the review. After 10 months of KD, the patient's microstate durations exhibited an increase from 53.05 ms, 57.17 ms, 61.80 ms, and 49.49 ms to 60.53 ms, 63.27 ms, 71.11 ms, and 66.55 ms. The occurrence rates changed from 4.0774 Hz, 4.9462 Hz, 4.8006 Hz, and 4.0579 Hz to 3.3354 Hz, 3.7893 Hz, 3.5956 Hz, and 4.1672 Hz. In healthy controls, the durations of microstate class A, B, C, and D were 61.86 ms, 63.58 ms, 70.57 ms, and 72.00 ms, respectively. CONCLUSIONS: Our findings suggest EEG microstates may be a promising biomarker for monitoring the effect of KD. Administration of KD may normalize the dysfunctional patterns of temporal parameters.
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Dieta Cetogênica , Eletroencefalografia , Humanos , Erros Inatos do Metabolismo dos Carboidratos/dietoterapia , Erros Inatos do Metabolismo dos Carboidratos/diagnóstico , Erros Inatos do Metabolismo dos Carboidratos/fisiopatologia , Biomarcadores/sangue , Feminino , Proteínas de Transporte de Monossacarídeos/deficiência , Masculino , Estudos ProspectivosRESUMO
OBJECTIVE: This systematic review of randomised controlled trials (RCTs) was conducted to assess the effect of repetitive transcranial magnetic stimulation (rTMS) on activities of daily living (ADLs) in Alzheimer's disease (AD) patients. DATA SOURCES: Ten databases were retrieved for pertinent Chinese and English literatures published up until January 2024. REVIEW METHODS: All RCTs of rTMS for ADLs in AD were included in this meta-analysis. Two researchers independently selected the literatures, retrieved the data of included literatures, accessed risk-of-bias of literatures with the Cochrane Collaboration's quality criteria and then cross-checked. Meta-analysis was carried out with Cochrane's Review Manager (RevMan, version 5.4). The PRISMA guidelines were followed in this systematic review. RESULTS: The 37 literatures involving 2461 patients with AD were included in this study. Compared with the control groups received the interventions such as routine pharmacotherapy, cognitive training, ect., with/without sham-rTMS, the experiment groups received the interventions of the control groups and rTMS. The findings were as follows: ADL scale [mean difference (MD) = -3.92, 95%CI (-4.93, -2.91), P < 0.00001]; Barthel Index (BI) [MD = 9.75, 95% CI (6.66, 12.85), P < 0.00001]; Modified Barthel Index (MBI) [MD = 5.43, 95% CI (3.13, 7.73), P < 0.00001]. The differences were statistically significant for all indicators. In 29 studies, rTMS stimulation sites were located in the dorsolateral prefrontal cortex (DLPFC). CONCLUSION: The rTMS could improve the ADLs in AD patients, and the DLPFC was a frequently used stimulation site of the rTMS for AD treatment.
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OBJECTIVE: To summarize the clinical characteristics and prognosis of febrile infection-related epilepsy syndrome with claustrum lesions (FIRES-C). METHOD: Clinical data of FIRES-C patients were collected retrospectively. The study reviewed and analyzed their clinical manifestations, treatment strategies, and prognosis. RESULT: Twenty patients were enrolled, including 13 females and 7 males, with a median onset age of 20.5 years. All patients developed seizures after fever, with a median interval of 5 days. Brain MRI showed symmetric lesions in the claustrum in all patients. The median interval from seizure onset to abnormal MRI signals detection was 12.5 days. All patients had negative results for comprehensive tests of neurotropic viruses and antineuronal autoantibodies. Seventy percent of cases had been previously empirically diagnosed with autoimmune encephalitis or viral encephalitis before. All patients received anti-seizure medicine. Eleven patients (55%) received antiviral therapy. All patients received immunotherapy, including glucocorticoids (100%), intravenous immunoglobulin (IVIg) (65%), plasma exchange (PLEX) (10%), tocilizumab (10%), rituximab (5%), and cyclophosphamide (5%). Sixty percent of patients received long-term immunotherapy (≥ 3 months). The median follow-up was 11.5 months;60% of patients were diagnosed with refractory epilepsy. CONCLUSION: Bilateral claustrum lesion on MRI is a distinctive neuroimage feature for FIRES, which may serve as an indication for the initial clinical assessments. FIRES-C should be classified as a type of inflammatory encephalopathy characterized by a monophasic nature. Some FIRES-C patients respond to immunotherapy and antiseizure treatments but most experience refractory epilepsy as a long-term outcome.
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Claustrum , Humanos , Masculino , Feminino , Adulto , Estudos Retrospectivos , Adolescente , Adulto Jovem , Claustrum/diagnóstico por imagem , Imageamento por Ressonância Magnética , Criança , Síndromes Epilépticas , Encefalite/diagnóstico por imagem , Encefalite/diagnóstico , Encefalite/complicações , Pré-Escolar , Pessoa de Meia-IdadeRESUMO
Three samples whose growth temperatures were 450°C, 500°C, and 560°C for S E S A M 1, S E S A M 2, and S E S A M 3, respectively, were tested by femto-second time-resolved transient absorption spectroscopy. The results indicate that the carrier dynamics of excited state absorption were dominant, and the lifetimes of carriers trapped by defect levels were about tens of pico-seconds. To further study the influence of carrier dynamics and recovery time of samples by ion-implantation, B + ions of 80 and 130 KeV were implanted into the samples with dose of 1014/c m 2. The modified samples showed a dominance of ultra-fast carrier dynamics of ground-state bleaching and direct recombination, which lasted for hundreds of femto-seconds, over excited state absorption. Additionally, carrier fast trapping was observed to be competitive with the excited state absorption process. After ion-implantation, the carrier dynamics of carrier trapping were enhanced, which contributed to forming an ultra-short laser, while the carrier dynamics of absorption of the excited state were suppressed. The conclusion that defect levels were partially eliminated by B + ion-implantation can be drawn.
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BACKGROUND: Children affected by tethered cord syndrome (TCS) encounter multifaceted challenges encompassing educational, familial and social spheres, underscoring the significance of a holistic comprehension of their subjective emotional well-being and life encounters. Nonetheless, healthcare professionals tend to prioritise the physical functionality of the afflicted individuals throughout the treatment and rehabilitation process, often neglecting the emotional experiences and requirements of these children as they transition into posthospitalization phases. AIM: To advance the subjective experiences and perceptions of children with TCS upon reintegration into their families, educational institutions and wider societal contexts subsequent to their discharge from medical facilities. METHODS: The study was conducted at the Children's Hospital in Zhejiang. Twelve children aged 8-15 with TCS were included in the study. The research design used an interpretative qualitative approach, utilising semi-structured interviews as the primary data collection method. Data analysis was performed using reflexive thematic analysis, facilitating a comprehensive exploration of emerging themes and patterns. RESULTS: Four major themes (and seven subthemes) were identified from the findings: (1) growing pains (a shameful secret, distance between ideal and reality); (2) inappropriate expressions of familial affection (knowing is not understanding, unspeakable guilt); (3) social estrangement (uncomfortable distinctions, familiar stranger) and (4) striving for independence and consistency. CONCLUSIONS: Children affected by TCS exhibit internal sensitivity and challenges in self-development, family dynamics and social interactions. They aspire to attain a future characterised by independence and freedom, akin to that of their typically developing peers. These findings can help health professionals, families and educators gain a deeper understanding of what it takes to be a child with TCS, and the findings can also serve as a platform for interventions that seek to promote self-expression in these children so that they can experience life as a meaningful and positive process. PATIENT OR PUBLIC CONTRIBUTION: This study received support from children with TCS and their guardians during data collection, as well as from the head nurse of the unit. Coresearchers also contributed to design, data collection, analysis and writing.
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Defeitos do Tubo Neural , Pesquisa Qualitativa , Humanos , Feminino , Criança , Masculino , Adolescente , Defeitos do Tubo Neural/psicologia , Entrevistas como Assunto , ChinaRESUMO
PURPOSE: To evaluate the influence of vertebral and disc wedging on the contribution of lumbar lordosis and the change of disc thickness before and after walking based on MRI. METHODS: Cross-sectional study. A total of 96 normally developing children, aged 5.7 ± 3.0 years old, 55 boys and 41 girls. They were divided into 3 groups: Pre-walking group, Walking group, and Post-walking group. PARAMETERS: lumbar lordosis Angle (LLA), the sum of the lumbar disc wedge Angle (∑D), the sum of the lumbar vertebral body wedge Angle (∑B), disc height (DH). RESULTS: (1) LLA, ∑D, ∑B, and DHL1-S1 were 33.2 ± 8.7°, 14.1 ± 8.6°, 11.9 ± 8.6°, and 6.9 ± 1.2 mm, 7.6 ± 1.4 mm, 8.2 ± 1.6 mm, 8.9 ± 1.7 mm, 8.5 ± 1.8 mm. (2) The difference in LLA values between the Pre-walking and the Post-walking group was statistically significant. DH were significantly different among the three groups. (3) In the Post-walking group, LLA value of girls was significantly higher than that of boys, and DHL3 - 4 and DHL4 - 5 values of girls were significantly lower than that of boys. (4) Age had a low positive correlation with LLA and ∑D and a moderate to strong positive correlation with DH; LLA showed a moderate positive correlation with ∑D, and a low positive correlation with ∑B and DH. CONCLUSION: Age and walking activity are the influencing factors of lumbar lordosis and disc thickening. Walking activity can significantly increase lumbar lordosis, and age is the main factor promoting lumbar disc thickening. DHL4-5 was the thickest lumbar intervertebral disc with the fastest intergroup thickening. Disc wedging contributes more to lumbar lordosis than vertebral wedging.
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BACKGROUND: To investigate the correlation between microinvasion and various features of hepatocellular carcinoma (HCC), and to clarify the microinvasion distance from visible HCC lesions to subclinical lesions, so as to provide clinical basis for the expandable boundary of clinical target volume (CTV) from gross tumor volume (GTV) in the radiotherapy of HCC. METHODS: HCC patients underwent hepatectomy of liver cancer in our hospital between July 2019 and November 2021 were enrolled. Data on various features and tumor microinvasion distance were collected. The distribution characteristics of microinvasion distance were analyzed to investigate its potential correlation with various features. Tumor size compared between radiographic and pathologic samples was analyzed to clarify the application of pathologic microinvasion to identify subclinical lesions of radiographic imaging. RESULTS: The average microinvasion distance was 0.6 mm, with 95% patients exhibiting microinvasion distance less than 3.0 mm, and the maximum microinvasion distance was 4.0 mm. A significant correlation was found between microinvasion and liver cirrhosis (P = 0.036), serum albumin level (P = 0.049). Multivariate logistic regression analysis revealed that HCC patients with cirrhosis had a significantly lower risk of microinvasion (OR = 0.09, 95%CI = 0.02 ~ 0.50, P = 0.006). Tumor size was overestimated by 1.6 mm (95%CI=-12.8 ~ 16.0 mm) on radiographic size compared to pathologic size, with a mean %Δsize of 2.96% (95%CI=-0.57%~6.50%). The %Δsize ranged from - 29.03% to 34.78%. CONCLUSIONS: CTV expanding by 5.4 mm from radiographic GTV could include all pathologic microinvasive lesions in the radiotherapy of HCC. Liver cirrhosis was correlated with microinvasion and were independent predictive factor of microinvasion in HCC.
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Carcinoma Hepatocelular , Hepatectomia , Neoplasias Hepáticas , Invasividade Neoplásica , Carga Tumoral , Humanos , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/diagnóstico por imagem , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Hepatectomia/métodos , Idoso , Seguimentos , Estudos Retrospectivos , Adulto , Planejamento da Radioterapia Assistida por Computador/métodos , Cirrose Hepática/patologiaRESUMO
Emerging evidence has suggested that exposure to PM2.5 is a significant contributing factor to the development of chronic obstructive pulmonary disease (COPD). However, the underlying biological effects and mechanisms of PM2.5 in COPD pathology remain elusive. In this study, we aimed to investigate the implication and regulatory effect of biomass fuels related-PM2.5 (BRPM2.5) concerning the pathological process of fibroblast-to-myofibroblast transition (FMT) in the context of COPD. In vivo experimentation revealed that exposure to biofuel smoke was associated with airway inflammation in rats. After 4 weeks of exposure, there was inflammation in the small airways, but no significant structural changes in the airway walls. However, after 24 weeks, airway remodeling occurred due to increased collagen deposition, myofibroblast proliferation, and tracheal wall thickness. In vitro, cellular immunofluorescence results showed that with stimulation of BRPM2.5 for 72â¯h, the cell morphology of fibroblasts changed significantly, most of the cells changed from spindle-shaped to star-shaped irregular, α-SMA stress fibers appeared in the cytoplasm and the synthesis of type I collagen increased. The collagen gel contraction experiment showed that the contractility of fibroblasts was enhanced. The expression level of TRPC1 in fibroblasts was increased. Specific siRNA-TRPC1 blocked BRPM2.5-induced FMT and reduced cell contractility. Additionally, specific siRNA-TRPC1 resulted in a decrease in the augment of intracellular Ca2+ concentration ([Ca2+]i) induced by BRPM2.5. Notably, it was found that the PI3K inhibitor, LY294002, inhibited enhancement of AKT phosphorylation level, FMT occurrence, and elevation of TRPC1 protein expression induced by BRPM2.5. The findings indicated that BRPM2.5 is capable of inducing the FMT, with the possibility of mediation by PI3K/AKT/TRPC1. These results hold potential implications for the understanding of the molecular mechanisms involved in BRPM2.5-induced COPD and may aid in the development of novel therapeutic strategies for pathological conditions characterized by fibrosis.
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Fibroblastos , Pulmão , Miofibroblastos , Material Particulado , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Canais de Cátion TRPC , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fibroblastos/efeitos dos fármacos , Ratos , Miofibroblastos/efeitos dos fármacos , Material Particulado/toxicidade , Pulmão/efeitos dos fármacos , Pulmão/patologia , Canais de Cátion TRPC/metabolismo , Masculino , Biomassa , Transdução de Sinais/efeitos dos fármacos , Ratos Sprague-Dawley , Doença Pulmonar Obstrutiva Crônica/patologiaRESUMO
Pyroptosis plays a critical role in the pathogenesis of mental disorders. However, its specific role and mechanism in arsenic (As)-induced generalized anxiety disorder (GAD) remain elusive. We utilized the data from CtdBbase, Phenopedia and DisGeNet to analyze genes that interact with arsenic poisoning and GAD. Subsequently KEGG and GO enrichment analysis were conducted to preliminatively predict the mechanism of inorganic arsenic-induced GAD. Male Wistar rats were administered water containing NaAsO2 (50, 100 µg/L) to evaluate GAD-like behavior through open field test and elevated plus maze. The expression of differential miRNAs including miR-425-3p, and pyroptosis in the prefrontal cortex of rats were detected. Furthermore, SKNSH cells were stimulated with NaAsO2 to examine the molecular changes, and then miR-425-3p mimic was transfected into SKNSH cells to detect pyroptosis in order to verify the function of miR-425-3p. Inorganic arsenic was confirmed to induce GAD-like behavior in rats, characterized by decreased locomotor activity and exploratory activities. Rats with inorganic arsenic-induced GAD exhibited reduced miR-425-3p expression levels in the prefrontal cortex and increased expression of pyroptosis-related proteins, including NF-κB, NLRP3, Caspase-1, GSDMD, IL-1ß, and IL-18. Treating with different concentrations of NaAsO2 showed that inorganic arsenic exposure downregulates miR-425-3p expression in SKNSH cells and upregulates the expression levels of pyroptosis-related proteins. Dual-luciferase reporter gene experiments demonstrated that miR-425-3p targets the NFKB1. Overexpressing miR-425-3p reversed the inorganic arsenic-induced pyroptosis in SKNSH cells by inhibiting the expression of NF-κB, NLRP3, Caspase-1, GSDMD, IL-1ß, and IL-18. Our findings suggest that inorganic arsenic exposure may induce GAD-like behavior in rats by downregulating miR-425-3p in prefrontal cortex, which targets NF-κB and regulates pyroptosis in neuronal cells.
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Transtornos de Ansiedade , Arsênio , MicroRNAs , Piroptose , Animais , Humanos , Masculino , Ratos , Transtornos de Ansiedade/induzido quimicamente , Arsênio/efeitos adversos , Arsênio/toxicidade , Caspase 1/metabolismo , Interleucina-18/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Piroptose/genética , Ratos WistarRESUMO
Heavy metal pollution in farmland soil threatens soil environmental quality. It is an important task to quickly grasp the status of heavy metal pollution in farmland soil in a region. Hyperspectral remote sensing technology has been widely used in soil heavy metal concentration monitoring. How to improve the accuracy and reliability of its estimation model is a hot topic. This study analyzed 440 soil samples from Sihe Town and the surrounding agricultural areas in Yushu City, Jilin Province. Considering the differences between different types of soils, a local regression model of heavy metal concentrations (As and Cu) was established based on projection pursuit (PP) and light gradient boosting machine (LightGBM) algorithms. Based on the estimations, a spatial distribution map of soil heavy metals in the region was drawn. The findings of this study showed that considering the differences between different soils to construct a local regression estimation model of soil heavy metal concentration improved the estimation accuracy. Specifically, the relative percent difference (RPD) of As and Cu element estimations in black soil increased the most, by 0.30 and 0.26, respectively. The regional spatial distribution map of heavy metal concentration derived from local regression showed high spatial variability. The number of characteristic bands screened by the PP method accounted for 10-13% of the total spectral bands, effectively reducing the model complexity. Compared with the traditional machine model, the LightGBM model showed better estimation ability, and the highest determination coefficients (R2) of different soil validation sets reached 0.73 (As) and 0.75 (Cu), respectively. In this study, the constructed PP-LightGBM estimation model takes into account the differences in soil types, which effectively improves the accuracy and reliability of hyperspectral image estimation of soil heavy metal concentration and provides a reference for drawing large-scale spatial distributions of heavy metals from hyperspectral images and mastering soil environmental quality.
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BACKGROUNDS: Moral distress significantly affects pediatric ICU nurses, leading to nurse burnout, increased turnover and reducing patient care quality. Despite its importance, there's a notable gap in knowledge on how to manage it effectively. AIMS: This review aimed to systematically identify and analyze coping strategies and interventions targeting moral distress among pediatric nurses in ICU, uncovering research gap and future studies directions. METHODS: A scoping review was conducted followed framework by Levac, Colquhoun, and O'Brien and Arksey and O'Malley. Searches were performed in 11 electrical databases, like PubMed and China Biology Medicine disc, within a timeframe of the database construction to November 2023, and performed literature screening and data extraction. RESULTS: Sixteen articles were ultimately included. Coping strategies adopted by pediatric ICUs nurses can be categorized into adaptive and maladaptive strategies, with the latter including passive acceptance, taking leave, and drinking, while the former involve pursuing interests outside of work, reflection and philosophizing, and communication. Nine articles described and evaluated the effectiveness of interventions for moral distress, categorizing them into individual and institutional levels. Individual-level interventions include Interprofessional Perspective-Taking, the PICU Resiliency Bundle, Ethics Education/Skills, and the Center for Caring. Institutional-level interventions encompasses Comprehensive Care Round, Goals of Care Conversations, Pediatric Ethics and Communication Excellence Rounds, Nursing Ethics Council, and Medical Ethical Decision-Making, though not all were effective in alleviating moral distress. CONCLUSIONS: Nurses often use self-adjustment strategies for moral distress, institutional ethical support focusing on enhancing nurses' moral resilience, promoting reflective thinking and improving communication remains crucial. Various interventions for moral distress are currently available, but nurse engagement is low and their effectiveness remained to be verified. Future studies should explore what aids or hinders these interventions. There's also a need for large, multicenter trials and ongoing evaluations to create effective support systems for pediatric ICU nurses.
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BACKGROUND: According to previous research, 2.8% of lesions clinically identified as endodontic pathosis were ultimately diagnosed as non-endodontic periapical lesions via histopathology, and 3.7% of these non-endodontic periapical lesions were malignant neoplasms. Rhabdomyosarcoma, a malignant tumor most commonly observed in children, is uncommon in the oral cavity. CASE PRESENTATION: This is a report of a rare case of embryonal rhabdomyosarcoma in a 41-year-old female, in which the lesion was in the maxillary gingiva. The biopsy reports confirmed the diagnosis of embryonal rhabdomyosarcoma. The wide excision of the tumor, free flap reconstruction, chemotherapy, and radiotherapy were performed. Clinical, radiological, and histopathological and management aspects of the neoplasm were also discussed. CONCLUSIONS: This case report aimed to create awareness that rhabdomyosarcoma is one of the differential diagnoses of periapical lesions.
Assuntos
Rabdomiossarcoma Embrionário , Rabdomiossarcoma , Adulto , Criança , Feminino , Humanos , Rabdomiossarcoma Embrionário/patologia , Gengiva/patologiaRESUMO
BACKGROUND: Head and neck cancer survivors suffer from xerostomia and sleep disturbances after radiotherapy, both of which affect their quality of life. This study aimed to explore the role of salivary flow in the oral health and sleep quality of head and neck cancer survivors. METHODS: We recruited 120 head and neck cancer survivors who were experiencing symptoms of dry mouth or sleep disturbances post-radiotherapy from a dental clinic. We gathered their socio-demographic and clinical data, measured their salivary flow rate, and recorded their dry mouth score using the summated xerostomia inventory. Additionally, a dentist collected the DMFT (Decayed, Missing, and Filled Teeth) index. The Pittsburgh Sleep Quality Index was employed to assess their sleep quality. RESULTS: In this study, xerostomia was observed in nearly 80% of the cancer survivors. The concurrent prevalence of sleep disturbance and xerostomia was at 55%. After five years post-radiotherapy, there was a significant improvement observed in both the quality of sleep (p = 0.03) and the stimulated salivary flow rate (p = 0.04). Additionally, these improvements were noted to have commenced from the third year onwards. A significant association was found between stimulated salivary flow and dry mouth scores with poor sleep quality (p < 0.05). CONCLUSIONS: We recommend that dental professionals prioritize managing both dental and mental health issues equally for head and neck cancer survivors who have undergone radiotherapy within the past 3 years.