RESUMO
Perennial trees must maintain stem growth throughout their entire lifespan to progressively increase in size as they age. The overarching question of the molecular mechanisms that govern stem perennial growth in trees remains largely unanswered. Here we deciphered the genetic architecture that underlies perennial growth trajectories using genome-wide association studies (GWAS) for measures of growth traits across years in a natural population of Populus tomentosa. By analyzing the stem growth trajectory, we identified PtoP4H9, encoding prolyl 4-hydroxylase 9, which is responsible for the natural variation in the growth rate of diameter at breast height (DBH) across years. Quantifying the dynamic genetic contribution of PtoP4H9 loci to stem growth showed that PtoP4H9 played a pivotal role in stem growth regulation. Spatiotemporal expression analysis showed that PtoP4H9 was highly expressed in cambium tissues of poplars of various ages. Overexpression and knockdown of PtoP4H9 revealed that it altered cell expansion to regulate cell wall modification and mechanical characteristics, thereby promoting stem growth in Populus. We showed that natural variation in PtoP4H9 occurred in a BASIC PENTACYSTEINE transcription factor PtoBPC1-binding promoter element controlling PtoP4H9 expression. The geographic distribution of PtoP4H9 allelic variation was consistent with the modes of selection among populations. Altogether, our study provides important genetic insights into dynamic stem growth in Populus, and we confirmed PtoP4H9 as a potential useful marker for breeding or genetic engineering of poplars.
Assuntos
Populus , Estudo de Associação Genômica Ampla , Prolil Hidroxilases/genética , Prolil Hidroxilases/metabolismo , Genes de Plantas , FenótipoRESUMO
Wood formation, intricately linked to the carbohydrate metabolism pathway, underpins the capacity of trees to produce renewable resources and offer vital ecosystem services. Despite their importance, the genetic regulatory mechanisms governing wood fibre properties in woody plants remain enigmatic. In this study, we identified a pivotal module comprising 158 high-priority core genes implicated in wood formation, drawing upon tissue-specific gene expression profiles from 22 Populus samples. Initially, we conducted a module-based association study in a natural population of 435 Populus tomentosa, pinpointing PtoDPb1 as the key gene contributing to wood formation through the carbohydrate metabolic pathway. Overexpressing PtoDPb1 led to a 52.91% surge in cellulose content, a reduction of 14.34% in fibre length, and an increment of 38.21% in fibre width in transgenic poplar. Moreover, by integrating co-expression patterns, RNA-sequencing analysis, and expression quantitative trait nucleotide (eQTN) mapping, we identified a PtoDPb1-mediated genetic module of PtoWAK106-PtoDPb1-PtoE2Fa-PtoUGT74E2 responsible for fibre properties in Populus. Additionally, we discovered the two PtoDPb1 haplotypes that influenced protein interaction efficiency between PtoE2Fa-PtoDPb1 and PtoDPb1-PtoWAK106, respectively. The transcriptional activation activity of the PtoE2Fa-PtoDPb1 haplotype-1 complex on the promoter of PtoUGT74E2 surpassed that of the PtoE2Fa-PtoDPb1 haplotype-2 complex. Taken together, our findings provide novel insights into the regulatory mechanisms of fibre properties in Populus, orchestrated by PtoDPb1, and offer a practical module for expediting genetic breeding in woody plants via molecular design.
Assuntos
Populus , Populus/genética , Populus/metabolismo , Desequilíbrio de Ligação , Ecossistema , Melhoramento Vegetal , Celulose/metabolismo , Madeira/genética , Regulação da Expressão Gênica de Plantas/genéticaRESUMO
Drought stress limits woody species productivity and influences tree distribution. However, dissecting the molecular mechanisms that underpin drought responses in forest trees can be challenging due to trait complexity. Here, using a panel of 300 Chinese white poplar (Populus tomentosa) accessions collected from different geographical climatic regions in China, we performed a genome-wide association study (GWAS) on seven drought-related traits and identified PtoWRKY68 as a candidate gene involved in the response to drought stress. A 12-bp insertion and/or deletion and three nonsynonymous variants in the PtoWRKY68 coding sequence categorized natural populations of P. tomentosa into two haplotype groups, PtoWRKY68hap1 and PtoWRKY68hap2. The allelic variation in these two PtoWRKY68 haplotypes conferred differential transcriptional regulatory activities and binding to the promoters of downstream abscisic acid (ABA) efflux and signaling genes. Overexpression of PtoWRKY68hap1 and PtoWRKY68hap2 in Arabidopsis (Arabidopsis thaliana) ameliorated the drought tolerance of two transgenic lines and increased ABA content by 42.7% and 14.3% compared to wild-type plants, respectively. Notably, PtoWRKY68hap1 (associated with drought tolerance) is ubiquitous in accessions in water-deficient environments, whereas the drought-sensitive allele PtoWRKY68hap2 is widely distributed in well-watered regions, consistent with the trends in local precipitation, suggesting that these alleles correspond to geographical adaptation in Populus. Moreover, quantitative trait loci analysis and an electrophoretic mobility shift assay showed that SHORT VEGETATIVE PHASE (PtoSVP.3) positively regulates the expression of PtoWRKY68 under drought stress. We propose a drought tolerance regulatory module in which PtoWRKY68 modulates ABA signaling and accumulation, providing insight into the genetic basis of drought tolerance in trees. Our findings will facilitate molecular breeding to improve the drought tolerance of forest trees.
Assuntos
Arabidopsis , Populus , Resistência à Seca , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Populus/metabolismo , Alelos , Estudo de Associação Genômica Ampla , Regulação da Expressão Gênica de Plantas , Arabidopsis/metabolismo , Secas , Ácido Abscísico/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Estresse Fisiológico/genéticaRESUMO
STUDY QUESTION: Is there a relationship between serum uric acid and fructose levels in polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Elevated serum uric acid levels in women with PCOS positively correlate with serum fructose levels, and elevated serum fructose levels are an independent risk factor for hyperuricemia in women with PCOS. WHAT IS KNOWN ALREADY: Our previous study suggested a link between elevated serum fructose levels and PCOS. Fructose is unique as it generates uric acid during metabolism, and high uric acid levels are associated with metabolic disorders and an increased risk of anovulation. However, the relationship between serum uric acid and fructose levels in women with PCOS remains unclear. STUDY DESIGN, SIZE, DURATION: In a case-control study of 774 women (482 controls and 292 patients with PCOS) between May and October 2020 at the Shengjing Hospital of China Medical University, the relationship between uric acid and fructose levels in women with PCOS was examined. Participants were divided into subgroups based on various factors, including BMI, insulin resistance, dyslipidemia, metabolic syndrome, and hyperuricemia. PARTICIPANTS/MATERIALS, SETTING, METHODS: Serum uric acid concentrations were measured using enzymatic assays, and serum fructose levels were determined using a fluorescent enzyme immunoassay. Dietary fructose data were collected through a validated food-frequency questionnaire of 81 food items. We applied restricted cubic splines to a flexibly model and visualized the linear/nonlinear relationships between serum uric acid and fructose levels in PCOS. Multivariate logistic analysis was executed to assess the association between serum fructose levels and hyperuricemia in PCOS. Human granulosa cell and oocyte mRNA profile sequencing data were downloaded for mapping uric acid and fructose metabolism genes in PCOS. Further downstream analyses, including Gene Ontology, Kyoto Encyclopedia of Genes and Genomes analysis, and protein-protein interactions were then carried out on the differentially expressed genes (DEGs). The correlation between uric acid and fructose metabolism genes was calculated using the Pearson correlation coefficient. The GeneCards database was used to identify DEGs related to uric acid and fructose metabolism in PCOS, and then several DEGs were confirmed by quantitative real-time PCR. MAIN RESULTS AND THE ROLE OF CHANCE: Both serum fructose and uric acid levels were significantly increased in women with PCOS compared with the control women (P < 0.001), and there was no statistically significant difference in dietary fructose intake between PCOS and controls, regardless of metabolic status. There was a positive linear correlation between serum uric acid and fructose levels in women with PCOS (Poverall < 0.001, Pnon-linear = 0.30). In contrast, no correlation was found in control women (Poverall = 0.712, Pnon-linear = 0.43). Additionally, a non-linear association was observed in the obese subgroup of patients with PCOS (Poverall < 0.001, Pnon-linear = 0.02). Serum uric acid levels were linearly and positively associated with serum fructose levels in patients with PCOS with insulin resistance, dyslipidemia, and metabolic syndrome. Furthermore, even after adjusting for confounding factors, elevated serum fructose levels were an independent risk factor for hyperuricemia in patients with PCOS (P = 0.001; OR, 1.380; 95% CI, 1.207-1.577). There were 28 uric acid and 25 fructose metabolism genes which showed a significant correlation in PCOS. Seven upregulated genes (CAT, CRP, CCL2, TNF, MMP9, GCG, and APOB) related to uric acid and fructose metabolism in PCOS ovarian granulosa cells were ultimately successfully validated using quantitative real-time PCR. LIMITATIONS, REASONS FOR CAUTION: Due to limited conditions, more possible covariates (such as smoking and ethnicity) were not included, and the underlying molecular mechanism between fructose and uric acid levels in women with PCOS remains to be further investigated. WIDER IMPLICATIONS OF THE FINDINGS: The results of this study and our previous research indicate that the high uric acid status of PCOS may be mediated by fructose metabolism disorders, highlighting the importance of analyzing fructose metabolism, and especially its metabolic byproduct uric acid, during the clinical diagnosis of PCOS. These results suggest the adverse effects of high uric acid in PCOS, and the importance of taking early interventions regarding uric acid levels to reduce the occurrence and development of further clinical signs, such as metabolic disorders in women with PCOS. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by: the National Natural Science Foundation of China (No. 82371647, No. 82071607, and No. 32100691); LiaoNing Revitalization Talents Program (No. XLYC1907071); Fok Ying Tung Education Foundation (No. 151039); and Outstanding Scientific Fund of Shengjing Hospital (No. 202003). No competing interests were declared. TRIAL REGISTRATION NUMBER: N/A.
RESUMO
Coal generates almost 40% of the world's electricity with 80 countries throughout the world using coal power. An inherent part of this generation is the rail transport of coal in uncovered cars, often up to a mile long. Existing studies document the subsequent increments of PM2.5 to the near-rail populations, which typically include a large number of economically disadvantaged residents and/or people of color. However, to date there is no assessment of the health implications of this stage in the use of coal. The present study quantifies such impacts on a region in the San Francisco Bay Area. The analysis shows important effects on mortality, hospitalization for cardiovascular and respiratory disease, asthma exacerbation, work loss, and days of restricted activity. Several of these outcomes exhibited a one to six percent increase over baseline. As such, it delineates the implications for the global effects of the transport of coal.
Assuntos
Carvão Mineral , Material Particulado , São Francisco , Material Particulado/análise , Humanos , Poluentes Atmosféricos/análise , Avaliação do Impacto na Saúde , Exposição Ambiental , Ferrovias , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/mortalidade , Hospitalização/estatística & dados numéricos , Doenças Respiratórias/epidemiologia , Doenças Respiratórias/mortalidade , Doenças Respiratórias/induzido quimicamente , Asma/epidemiologiaRESUMO
Chronic lead (Pb) exposure causes neurodysfunction and contributes to the development of neurodegenerative disease. However, the mechanism of Pb-induced neurological dysfunction have yet to be fully elucidated. This study determined the role pyroptosis plays in Pb-induced neurodysfunction in neurons. We used both in vitro and in vivo approaches to explore whether Pb exposure induces caspase-1-mediated pyroptosis in neurons and its relationship to Pb-induced neurological disorders. Our findings showed that caspase-1-mediated pyroptosis in Pb-exposed neurons activated glycogen synthase kinase 3 protease activity by disrupting Ca2+/calmodulin-dependent protein kinase II/cAMP-response element binding protein pathway, leading to neurological disorders. Moreover, the caspase-1 inhibition VX-765 or the non-steroidal anti-inflammatory drug sodium para-aminosalicylic acid (PAS-Na) attenuated the Pb-induced neurological disorders by alleviating caspase-1 mediated neuronal pyroptosis. Our novel studies suggest that caspase-1-mediated pyroptosis in neurons represents a potential mechanism for Pb-induced neurodysfunction, identifying a putative target for attenuating the neurodegenerative effects induced by this metal.
Assuntos
Caspase 1 , Chumbo , Neurônios , Piroptose , Piroptose/efeitos dos fármacos , Animais , Caspase 1/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/patologia , Chumbo/toxicidade , Camundongos , Camundongos Endogâmicos C57BL , Masculino , Dipeptídeos , para-AminobenzoatosRESUMO
BACKGROUND: When unintentional pancreatic duct access occurs during difficult biliary cannulation, the double guidewire (DGW) or transpancreatic sphincterotomy (TPS) may be utilized. DGW can be easily switched to TPS due to the existing guidewire in the pancreatic duct. However, the efficacy of TPS after DGW, named sequential DGW-TPS technique, versus primary TPS has not been assessed. AIMS: Our aim was to compare the benefits and adverse events of sequential DGW-TPS technique and primary TPS. METHODS: We performed a comparative retrospective cohort study that enrolled a total of 117 patients with native papillae. The patients were divided into one of 2 groups according to the primary bile duct access technique (sequential DGW-TPS or primary TPS), both with pancreatic stenting. RESULTS: Between November 2017 and May 2023, a total of 84 patients were grouped into sequential DGW-TPS and 33 into primary TPS. The overall post-ERCP pancreatitis (PEP) rate was 4.3% in the entire cohort, with no statistical differences were observed between the groups in terms of PEP rates (P = 0.927), PEP severity (P = 1.000), first biliary cannulation success (P = 0.621), overall cannulation success (P = 1.000), hyperamylasemia incidence (P = 0.241), elevated amylase levels (P = 0.881), and postoperative hospital stay (P = 0.185). Furthermore, these results remained consistent in multivariable regression analysis. CONCLUSIONS: The sequential DGW-TPS technique showed a comparable safety and biliary cannulation success rate to primary TPS in difficult biliary cannulation. Given the potential long-term complications associated with TPS, DGW should be first if inadvertent pancreatic access occurs, with TPS serving as second only if DGW fails.
Assuntos
Colangiopancreatografia Retrógrada Endoscópica , Ductos Pancreáticos , Pancreatite , Esfinterotomia Endoscópica , Humanos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Esfinterotomia Endoscópica/métodos , Esfinterotomia Endoscópica/efeitos adversos , Colangiopancreatografia Retrógrada Endoscópica/métodos , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Pancreatite/etiologia , Pancreatite/epidemiologia , Ductos Pancreáticos/cirurgia , Cateterismo/métodos , Cateterismo/efeitos adversos , Cateterismo/instrumentação , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Resultado do Tratamento , Stents , AdultoRESUMO
BACKGROUND: Rectal indomethacin reduces pancreatitis following endoscopic retrograde cholangiopancreatography (ERCP). However, there is insufficient evidence regarding its added benefits in patients already receiving prophylactic pancreatic stenting. Our goal was to evaluate the impact of indomethacin in high-risk patients undergoing pancreatic stenting. METHODS: A cohort study was conducted on all patients who underwent the rescue cannulation technique for challenging bile duct cannulation (selected high-risk patients). Patients were split into two groups based on the prophylaxis method for post-ERCP pancreatitis (PEP): one receiving a combination of indomethacin and pancreatic stenting, while the other received pancreatic stenting alone. Comparative analyses were carried out on PEP, hyperamylasemia, gastrointestinal bleeding, and postoperative hospital stay among post-ERCP pancreatitis patients. RESULTS: Between November 2017 and May 2023, a total of 607 patients with native papillae were enrolled, with 140 grouped into the indomethacin plus stent group and 467 into the stent alone group. The overall PEP rate was 4.4% in the entire cohort, with no statistical differences observed between the groups in terms of PEP rates (P = 0.407), mild PEP (P = 0.340), moderate to severe PEP (P = 1.000), hyperamylasemia (P = 0.543), gastrointestinal bleeding (P = 0.392), and postoperative hospital stay (P = 0.521). Furthermore, sensitivity analysis using multivariable analysis also validated these findings. CONCLUSIONS: Indomethacin did not reduce the incidence or severity of PEP in high-risk patients who routinely received prophylactic pancreatic stent placement. Therefore, the additional administration of rectal indomethacin to further mitigate PEP appears to be not necessary.
Assuntos
Colangiopancreatografia Retrógrada Endoscópica , Indometacina , Pancreatite , Stents , Humanos , Indometacina/uso terapêutico , Indometacina/administração & dosagem , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Pancreatite/prevenção & controle , Pancreatite/etiologia , Pancreatite/epidemiologia , Feminino , Masculino , Pessoa de Meia-Idade , Stents/efeitos adversos , Idoso , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/uso terapêutico , Administração Retal , Estudos Retrospectivos , Tempo de Internação/estatística & dados numéricos , Fatores de Risco , Estudos de Coortes , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologiaRESUMO
This paper aims to explore the epidemiology, clinical characteristics, and prognosis of extracranial malignant rhabdoid tumors (eMRTs) in children. A systematic review and meta-analysis of studies published in PUBMED, MEDLINE, Web of Science, Embase, Cochrane, and China National Knowledge Infrastructure (CNKI) was conducted. The search was limited to studies published between Jan 1, 1990 to Dec 31, 2022, with the last search done on Jan 31, 2023. We identified 496 papers through the literature search, and 12 retrospective cohort studies with 398 patients were included. The pooled age at diagnosis for malignant rhabdoid tumor of the kidney (MRTK) was 10.009 months (95%CI (7.542-12.476)), while extracranial malignant rhabdoid tumor (EERT) was 25.917 months (95%CI (17.304-34.530)). Among the 398 patients with eMRTs, chemotherapy treatment rate (86.8% (95%CI (74.4-96.0%))) was more frequently than radiotherapy treatment (45.4% (95%CI (38.1-52.6%))). The rate of metastasis in all patients was 41.4% (95%CI (33.9-48.9%)), in which the lung metastasis was occupied 70.4% (95%CI (58.0-81.6%)). SMARCB1/INI1 mutation was up to 93.2% (95%CI (81.3-99.8%)). The rate of total surgical resection was 50.4% (95%CI (35.2-65.6%)), while pooled proportion of death in all patients was 68.7% (95%CI (56.9-79.5%)). Conclusion: EMRTs are highly malignant tumors associated with high mortality rates. The loss of SMARCB1/INI1 gene and the protein expression is observed in the vast majority of eMRTs patients. Patients that suffered MRTK are younger than patients with extrarenal EERT and are more prone to lung metastasis, but there is no significant difference in overall survival, possibly due to the higher rate of R0 resection of primary tumors in MRTK. Trial registration: The study was registered on PROSPERO with registration number CRD42023400985. What is Known: ⢠Malignant rhabdoid tumor (MRT) is a rare and highly malignant tumor that may originate from embryonic stem cells. The incidence of MRT is exceptionally low, estimated at 0.00006%. ⢠Malignant rhabdoid tumor of the kidney (MRTK) and extrarenal extra-cranial malignant rhabdoid tumor (EERT) tend to manifest between 11 to 18 months of age, with a 5-year survival rate of approximately 17%-36%. What is New: ⢠There is no comprehensive meta-analysis or large-scale case series that reported to systematically introduce the eMRTs clinic outcome and prog-nosis based on largely pooled data. ⢠This study performed a meta-analysis through an extensive literature search and clinical data analysis in order to mainly explore the clinical characteris-tics and prognosis of eMRTs, improving the understanding of eMRTs in children..
Assuntos
Neoplasias Renais , Neoplasias Pulmonares , Tumor Rabdoide , Neoplasias de Tecidos Moles , Criança , Humanos , Lactente , Neoplasias Renais/terapia , Neoplasias Renais/diagnóstico , Neoplasias Renais/genética , Estudos Retrospectivos , Tumor Rabdoide/diagnóstico , Tumor Rabdoide/terapia , Tumor Rabdoide/genética , Pré-EscolarRESUMO
Carriage of HLA-DQA1*05 is thought to increase the formation of anti-tumour necrosis factor alpha (TNF-α) antibodies, reducing the drug efficacy in Crohn's disease (CD) patients. However, little data are currently available for small-bowel Crohn's disease (SB-CD). A specific assessment of the impact of HLA-DQA1*05 on the clinical response to treatment with infliximab (IFX), a TNF-α antagonists, in SB-CD patients is necessary. We conducted a single-center retrospective study that included 106 SB-CD patients treated with IFX. The serum samples were collected for antibodies to infliximab (ATI) testing and HLA-DQA1*05 genotyping. Double-balloon enteroscopy (DBE) was performed following the IFX treatment, with endoscopic outcomes evaluated using the partial simple endoscopic score for CD (pSES-CD), whereas the clinical response was assessed with the Crohn's disease activity index (CDAI). Multivariate logistic regression and multivariate COX regression analyses were employed to analyze the correlation of the HLA-DQA1*05 genotypes with other clinical variables. In this study, 30.2% of SB-CD patients carried the HLA-DQA1*05 allele, which significantly increased their risk of ATI generation (odds ratio [OR] = 2.337, p = .043), but it was not associated with the clinical response to IFX and drug persistence (OR = 2.356, p = .145; OR = 0.457, p = .249). The endoscopic remission rates were 40.6% (13/32) and 55.4% (41/74) in HLA-DQA1*05 carriers and non-carriers, respectively. HLA-DQA1*05 was not associated with endoscopic remission (OR = 0.684, p = .414). The HLA-DQA1*05 variant is identified as a significant risk factor of ATI formation in Chinese patients with SB-CD, but is not associated with the clinical response of IFX treatment and endoscopic remission of SB lesions.
RESUMO
The increasing demand for free-form irregular optical components in both military and civilian sectors has made the inspection of such unique shapes a central challenge that hinders their production and use. In particular, the shape and thickness errors of low- and medium-precision components thermally pressed from flat optical materials are greater than those of hard brittle optical components fabricated by subtractive manufacturing, and the resulting impact on human vision is more severe. Reasonable, convenient, efficient, and accurate 3D scanning and data processing for surface reconstruction that combines application scenarios and batch manufacturing needs are urgently needed. Based on the principles of optical ray tracing and triangulation processing, the sampling and calculation of optical path thickness proposed in this paper effectively establish a theoretical model for macroscopic distortion, providing a reasonable solution for distortion correction, batch manufacturing of free-form surface pressing formed components, and defect repair.
RESUMO
BACKGROUND: Manganese (Mn) and iron (Fe) are essential trace elements for humans, yet excessive exposure to Mn or Fe can accumulate in the central nervous system (CNS) and cause neurotoxicity. The purpose of this study was to investigate the effects of Mn and Fe exposure, alone or in combination, on inducing oxidative stress-induced neurological damage in rat cortical and SH-SY5Y cells, and to determine whether combined exposure to these metals increases their individual toxicity. METHODS: SH-SY5Y cells and male Sprague-Dawley rats were used to observe the effects of oxidative stress-induced neurological damage induced by exposure to manganese and iron alone or in combination. To detect the expression of anti-oxidative stress-related proteins, Nrf2, HO-1, and NQO1, and the apoptosis-related proteins, Bcl2 and Bax, and the neurological damage-related protein, α-syn. To detect reactive oxygen species generation and apoptosis. To detect the expression of the rat cortical protein Nrf2. To detect the production of proinflammatory cytokines. RESULTS: We demonstrate that juvenile developmental exposure to Mn and Fe and their combination impairs cognitive performance in rats by inducing oxidative stress causing neurodegeneration in the cortex. Mn, Fe, and their combined exposure increased the expression of ROS, Bcl2, Bax, and α-syn, activated the inflammatory factors IL-6 and IL-12, inhibited the activities of SOD and GSH, and induced oxidative stress-induced neurodegeneration both in rats and SH-SY5Y cells. Combined Mn-Fe exposure attenuated the oxidative stress induced by Mn and Fe exposure alone by increasing the expression of antioxidant factors Nrf2, HO-1, and NQO1. CONCLUSION: In both in vivo and in vitro studies, manganese and iron alone or in combination induced oxidative stress, leading to neuronal damage. In contrast, combined exposure to manganese and iron mitigated the oxidative stress induced by exposure to manganese and iron alone by increasing the expression of antioxidant factors. Therefore, studies to elucidate the main causes of toxicity and establish the molecular mechanisms of toxicity should help to develop more effective therapeutic modalities in the future.
Assuntos
Manganês , Neuroblastoma , Humanos , Masculino , Ratos , Animais , Manganês/toxicidade , Antioxidantes/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Ferro/metabolismo , Proteína X Associada a bcl-2/metabolismo , Ratos Sprague-Dawley , Estresse Oxidativo , Apoptose , NAD(P)H Desidrogenase (Quinona)/genética , NAD(P)H Desidrogenase (Quinona)/metabolismo , NAD(P)H Desidrogenase (Quinona)/farmacologiaRESUMO
BACKGROUND: Using Artificial Intelligence (AI) for neonatal pain assessment has great potential, but its effectiveness depends on accurate data labeling. Therefore, precise and reliable neonatal pain datasets are essential for managing neonatal pain. PURPOSE: To develop and validate a comprehensive multimodal dataset with accurately labeled clinical data, enhancing AI algorithms for neonatal pain assessment. METHODS: An assessment team randomly selected healthy neonates for assessment using the Neonatal Pain, Agitation, and Sedation Scale. During painful procedures, 2 cameras recorded neonates' pain reactions on site. After 2 weeks, assessors labeled the processed pain data on the EasyDL platform in a single-anonymized setting. The pain scores from the 4 single-modal data types were compared to the total pain scores derived from multimodal data. The On-Site Neonatal Pain Assessment completed using paper quality scales is referred to as OS-NPA, while the modality-data neonatal pain labeling performed using labeling software is MD-NPL. RESULTS: The intraclass correlation coefficient among the 4 single-modal groups ranged from 0.938 to 0.969. The overall pain intraclass correlation coefficient score was 0.99, with a Kappa statistic for pain grade agreement of 0.899. The goodness-of-fit for the linear regression models comparing the OS-NPA and MD-NPL for each assessor was greater than 0.96. IMPLICATIONS FOR PRACTICE AND RESEARCH: MD-NPL represents a productive alternative to OS-NPA for neonatal pain assessment, and the validity of the data labels within the Multimodality Dataset for Neonatal Acute Pain has been validating. These findings offer reliable validation for algorithms designed to assess neonatal pain.
RESUMO
Lead is one of the heavy metals that is toxic and widely distributed in the environment, and children are more sensitive to the toxic effects of lead because the blood-brain barrier and immune system are not yet well developed. The objective of the study was to investigate the clinical characteristics of lead poisoning in children aged 0â¼6 years in a hospital in Guangxi, and to provide scientific basis for the prevention and treatment of lead poisoning. We collected and analyzed the clinical data of 32 children with lead poisoning admitted to a hospital in Guangxi from 2010 to 2018. The results showed that most of the 32 cases presented with hyperactivity, irritability, poor appetite, abdominal pain, diarrhea, or constipation. The hemoglobin (HGB), mean corpusular volume (MCV), mean corpuscular hemoglobin (MCH), and hematocrit (HCT) of the lead-poisoned children were all decreased to different degrees and were below normal acceptable levels. Urinary ß2-microglobulin was increased. Blood lead levels (BLL) decreased significantly after intravenous injection of the lead chelator, calcium disodium edetate (CaNa2-EDTA). In addition, HGB returned to normal levels, while MCV, MCH, and HCT increased but remained below normal levels. Urinary ß2-microglobulin was reduced to normal levels. Therefore, in this cohort of children, the high-risk factors for lead poisoning are mainly Chinese medicines, such as baby powder. In conclusion, lead poisoning caused neurological damage and behavioral changes in children and decreased erythrocyte parameters, leading to digestive symptoms and renal impairment, which can be attenuated by CaNa2-EDTA treatment.
Assuntos
Intoxicação por Chumbo , Chumbo , Criança , Lactente , Humanos , Chumbo/toxicidade , China/epidemiologia , Ácido Edético , Intoxicação por Chumbo/epidemiologia , Intoxicação por Chumbo/etiologia , Hematócrito , HemoglobinasRESUMO
Objective: To explore the clinical effect of various doses of Budesonide combined with Tiotropium bromide in the treatment of elderly patients with chronic obstructive pulmonary disease (COPD). Methods: Clinical data of elderly patients with COPD, admitted to Affiliated Hospital of Shaoxing University from April 2021 to February 2023, were retrospectively analyzed. Based on the dosage of Budesonide combined with Tiotropium bromide, patients were divided into Low-dose group (Budesonide = 1mg), Medium-dose group (Budesonide = 2mg), and High-dose group (Budesonide = 3mg). All groups were matched for age, gender, course of disease, and BMI. Patients treated with Tiotropium bromide alone were assigned to the Control group. The clinical effect, pulmonary function index level, symptom improvement, inflammatory factor index level and adverse reactions in all groups were analyzed and compared. Results: A total of 88 patients were included in this study with 22 patients in each group. The total efficacy of Medium-dose (90.91%) and High-dose group (90.91%) was significantly higher than that of Low-dose group (63.64%) and the Control group (59.09%) (P<0.05). After the treatment, levels of pulmonary function, symptom improvement and inflammatory factors in the High-dose and the Medium-dose groups were better than those in the Low-dose group and the Control group. Pulmonary function, symptom improvement and levels of inflammatory factors was significantly better in the Low-dose group compared to the Control group (P<0.05). Conclusions: Budesonide combined with tiotropium bromide is better than tiotropium bromide alone in the treatment of elderly patients with COPD. Compared with low (1mg) dosage, medium (2mg) and high (3mg) dosage of budesonide are more effective in improving lung function, alleviating symptoms, reducing inflammatory response,, and are not associated with increased rate of adverse reactions.
RESUMO
Simultaneous enhancement of free excitons (FEs) emission and self-trapped excitons (STEs) emission remains greatly challenging because of the radiative pathway competition. Here, a significant fluorescence improvement, associated with the radiative recombination of both FEs and STEs is firstly achieved in an unconventional ACI-type hybrid perovskite, (ACA)(MA)PbI4 (ACA=acetamidinium) crystals with {PbI6} octahedron units, through hydrostatic pressure processing. Note that (ACA)(MA)PbI4 exhibits a 91.5-fold emission enhancement and considerable piezochromism from green to red in a mild pressure interval of 1â atm to 2.5â GPa. The substantial distortion of both individual halide octahedron and the Pb-I-Pb angles between two halide octahedra under high pressure indeed determines the pressure-tuning localized excitons behavior. Upon higher pressure, photocurrent enhancement is also observed, which is attributed to the promoted electronic connectivity in (ACA)(MA)PbI4. The anisotropic compaction reduces the distance between neighboring organic molecules and {PbI6} octahedra, leading to the enhancement of hydrogen bonding interactions. This work not only offers a deep understanding of the structure-optical relationships of ACI-type perovskites, but also presents insights into breaking the limits of luminescent efficiency by pressure-suppressed nonradiative recombination.
RESUMO
BACKGROUND: The relationship between sleep duration and cancer in China remains inconclusive. The authors investigated the association between sleep duration and cancer from both static and dynamic perspectives. METHODS: This study was based on the China Health and Retirement Longitudinal Study. We first tested the hazard ratios (HRs) with 95% confidence intervals (CIs) between baseline sleep duration and incident cancer using Cox proportional hazards regression analysis. Sleep duration trajectories from 2011 to 2015 were identified using group-based trajectory modeling to examine the subsequent risk of incident cancer from 2015 to 2018 using Cox proportional hazards regression model. RESULTS: The risk of incident cancer increased by 69% (HR, 1.69; 95% CI, 1.19-2.39) in individuals who slept for <7 h per day (vs. 7 to ≤8 h), 41% (HR, 1.41; 95% CI, 1.01-1.95) in those who slept for <6 h per night (vs. 6 to ≤8 h), and 60% (HR, 1.60; 95% CI, 1.01-2.55) in those who did not take any naps during the day (vs. >60 min). Stratified by sex and body mass index, the risk of cancer was evident among women with night sleep of <6 h (vs. 6-8 h). However, the duration of <7 h of total sleep among men and overweight individuals was associated with cancer risk. Moreover, individuals with a short night sleep duration but no napping had a higher risk of cancer. Furthermore, cancer risk was only observed in individuals with short stable trajectory of night sleep (HR, 2.01; 95% CI, 1.07-3.80) and among women with short stable trajectory of total sleep (HR, 2.26; 95% CI, 1.13-4.52). CONCLUSIONS: Cancer incidence risk was observed in participants with sleep duration of <7 h and among women with short stable sleep trajectory. Short nights and total sleep duration were both associated with a high risk of incident cancer, but varied by sex. Interestingly, cancer risk was restricted to women with short stable sleep trajectory. PLAIN LANGUAGE SUMMARY: This study showed that short nights and total sleep duration were associated with a high risk of cancer incidence in middle-aged and elderly Chinese population, with implications for early effective cancer prevention. Habitual sleep is a modifiable and dynamic lifestyle behavior, and long-term short sleep trajectories among women can predict cancer outcomes. Future studies should examine the association between the trajectory of sleep parameters based on objective measures and specific cancer types.
Assuntos
Neoplasias , Duração do Sono , Masculino , Idoso , Pessoa de Meia-Idade , Humanos , Feminino , Estudos Longitudinais , Fatores de Risco , Índice de Massa Corporal , Sono , Neoplasias/epidemiologia , Neoplasias/etiologiaRESUMO
1D carbon nanotubes have been widely applied in many fields, such as catalysis, sensing and energy storage. However, the long tunnel-like pores and relatively low specific surface area of carbon nanotubes often restrict their performance in certain applications. Herein, a dual-silica template-mediated method to prepare nitrogen-doped mesoporous carbon nanotubes (NMCTs) through co-depositing polydopamine (both carbon and nitrogen precursors) and silica nanoparticles (the porogen for mesopore formation) on a silica nanowire template is proposed. The obtained NMCTs have a hierarchical pore structure of large open mesopores and tubular macropores, a high specific surface area (1037 m2 g-1 ), and homogeneous nitrogen doping. The NMCT-45 (prepared at an interval time of 45 min) shows excellent performance in supercapacitor applications with a high capacitance (373.6 F g-1 at 1.0 A g-1 ), excellent rate capability, high energy density (11.6 W h kg-1 at a power density of 313 W kg-1 ), and outstanding cycling stability (98.2% capacity retention after 10 000 cycles at 10 A g-1 ). Owing to the unique tubular morphology, hierarchical porosity and homogeneous N-doping, the NMCT also has tremendous potential in electrochemical catalysis and sensing applications.
RESUMO
Little information is known about DNA methylation variation in shaping environment-specific drought resistance and resilience for tree adaptation. In this study, we leveraged RNA sequencing and whole-genome bisulfite sequencing data to dissect the distinction of epigenetic regulation under drought stress and rewater condition of Populus tomentosa accessions from three geographical regions. We demonstrated low resistance and high resilience for accessions from South. Non-CG methylation levels in promoter regions of Southern accessions were lower than accessions from higher latitudes and negatively regulated gene expression. CHH context methylation was more sensitive to drought stress, and the geographical-specific differentially methylated regions were scarcely changed by environmental fluctuation. We identified 60 conserved hub genes within the co-expression networks that correlate with photosynthetic and stomatal morphological traits. Epigenome-wide association studies and genome-wide association studies of these 60 hub genes revealed the interdependency between genetic and epigenetic variation in GATA9 and LECRK-VIII.2, which was associated with stomatal morphology and chlorophyll content. The natural epigenetic variation in GATA9 was also faithfully transmitted to progenies in two family-based F1 populations. This study indicates a functional relationship of DNA methylation diversity with drought resistance and resilience which offers new insights into plants' local adaptation to a stressful environment.
Assuntos
Metilação de DNA , Populus , Metilação de DNA/genética , Epigênese Genética , Populus/genética , Resistência à Seca , Estudo de Associação Genômica AmplaRESUMO
A mono-DMSO cobalt meso-CF3 corrole, formulated as (CF3)3CorCo(DMSO), where (CF3)3Cor is the trianion of 5,10,15-tris(trifluoromethyl)corrole, was synthesized and characterized as to its spectral and electrochemical properties in nonaqueous media with a focus on its coordination chemistry and electronic structure. Cyclic voltammetric measurements showed more facile reductions and difficult oxidations compared to the cobalt triarylcorrole possessing p-CF3Ph units at the meso-positions, a result consistent with the enhanced inductive effect of the electron-withdrawing trifluoromethyl substituents linked directly at the meso-carbon atoms of the macrocycle. The effects of DMSO, pyridine, and cyanide anions (CN-) on the electrochemistry and spectral properties of the compound were investigated, and it was found that only two molar equivalents are needed to form the bis-CN adduct, which exhibited two 1-electron oxidations at 0.27 and 0.95 V vs saturated calomel electrode (SCE) in CH2Cl2/0.1 M TBAP. The sites of electron transfer in the first oxidation and reduction were investigated by spectroelectrochemistry and confirmed that the first electron addition affords a Cor3-CoII complex under all solution conditions independent of the initial coordination and/or electronic configuration (i.e., innocent Cor3-CoIII or noninnocent Corâ¢2-CoII). In contrast, data for the first oxidation suggests that the site of electron abstraction (ligand or metal) depended upon coordination of the neutral and in situ generated complexes under the various solution conditions, leading to a Co(IV)-corrole3- product for both the bis-pyridine and bis-cyanide adducts.