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The study uses Sequential Window Acquisition of All Theoretical Fragment Ion Mass Spectra (SWATH)-MS in conjunction with secretome proteomics to identify key proteins that Pseudomonas aeruginosa secretes against methicillin-resistant Staphylococcus aureus (MRSA). Variations in the inhibition zones indicated differences in strain resistance. Multivariate statistical methods were applied to filter the proteomic results, revealing five potential protein biomarkers, including Peptidase M23. Gene ontology (GO) analysis and sequence alignment supported their antibacterial activity. Thus, SWATH-MS provides a comprehensive understanding of the secretome of P. aeruginosa in its action against MRSA, guiding future antibacterial research.
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Chlorinated polyfluorinated ether sulfonate, commercially known as F-53B, has been associated with adverse birth outcomes. However, the reproductive toxicology of F-53B on the placenta remains poorly understood. To address this gap, we examined the impact of F-53B on placental injury and its underlying molecular mechanisms in vivo. Pregnant C57BL/6â¯J female mice were randomly allocated to three groups: the control group, F-53B 0.8⯵g/kg/day group, and F-53B 8⯵g/kg/day group. After F-53B exposure through free drinking water from gestational day (GD) 0.5-14.5, the F-53B 8⯵g/kg/day group exhibited significant increases in placental weights and distinctive histopathological alterations, including inflammatory cell infiltration, heightened syncytiotrophoblast knots, and a loosened trophoblastic basement membrane. Within the F-53B 8⯵g/kg/day group, placental tissue exhibited increased apoptosis, as indicated by increased caspase3 activation. Furthermore, F-53B potentially induced the NF-κB signaling pathway activation through IκB-α phosphorylation. Subsequently, this activation upregulated the expression of inflammatory cytokines and components of the NLRP3 inflammasome, including activated caspase1, IL-1ß, IL-18, and cleaved gasdermin D (GSDMD), ultimately leading to pyroptosis in the mouse placenta. Our findings reveal a pronounced inflammatory injury in the placenta due to F-53B exposure, suggesting potential reproductive toxicity at concentrations relevant to the human population. Further toxicological and epidemiological investigations are warranted to conclusively assess the reproductive health risks posed by F-53B.
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Inflamassomos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR , Placenta , Animais , Feminino , Gravidez , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Placenta/efeitos dos fármacos , Placenta/patologia , Camundongos , Inflamassomos/efeitos dos fármacos , Inflamação/induzido quimicamente , Inflamação/patologia , Apoptose/efeitos dos fármacos , NF-kappa B/metabolismo , Fluorocarbonos/toxicidade , Transdução de Sinais/efeitos dos fármacosRESUMO
The early detection of cognitive decline in Parkinson's disease is important for providing drug therapy and non-pharmacological management. The circulating microRNAs present in plasma are promising biomarkers of PD with dementia (PDD) due to their critical roles in synaptic plasticity and the regulation of neurodegeneration-associated proteins. In this study, we aimed to identify plasma microRNAs that may differentiate PD with or without cognitive impairment. Global microRNA expression was obtained from a discovery set of 123 participants who were divided into four groups, namely normal controls (HC), PD with no dementia (PDND), PD with mild cognitive impairment (PD-MCI), and PDD, using next-generation sequencing. The BOLD selector was used for microRNA candidate selection. Six miRNAs, namely miR-203a-3p, miR-626, miR-662, miR-3182, miR-4274, and miR-4295, were clustered as potential candidates for use in identifying PDND from PD-MCI. Another independent cohort of 120 participants was further recruited in a validation step in order to detect candidate microRNAs via droplet digital PCR (ddPCR), which was used for its high sensitivity in detecting low miRNA concentrations. Our results show that the ratio of miR-203a-3p/miR-16-5p, in which miR-16-5p was used as a reference control miRNA, was significantly increased in PDD compared to that seen in PD-MCI and PDND individually, and was negatively correlated with the MoCA scores (r = -0.237, p = 0.024) in patients with PD. However, there was no significant difference in the ratio of miR-203a-3p/miR-16-5p between HC and PDND, PD-MCI, or PDD individually. The ROC curve of the logistic regression model, factoring in the variables of age, the ratio of miR-203a-3p/miR-16-5p, and the UPDRS III score, demonstrated an AUC of 0.883. Our findings suggest that the ratio of miR-203a-3p/miR-16-5p, used with age and motor score, could be a predictor of dementia among PD patients.
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MicroRNA Circulante , Demência , MicroRNAs , Doença de Parkinson , Humanos , Doença de Parkinson/diagnóstico , MicroRNAs/metabolismo , Biomarcadores , Demência/diagnóstico , Demência/genéticaRESUMO
RAD23 (RADIATION SENSITIVE23) proteins are a group of UBL-UBA (ubiquitin-like-ubiquitin-associated) proteins that shuttle ubiquitylated proteins to the 26S proteasome for breakdown. Drought stress is a major environmental constraint that limits plant growth and production, but whether RAD23 proteins are involved in this process is unclear. Here, we demonstrated that a shuttle protein, MdRAD23D1, mediated drought response in apple plants (Malus domestica). MdRAD23D1 levels increased under drought stress, and its suppression resulted in decreased stress tolerance in apple plants. Through in vitro and in vivo assays, we demonstrated that MdRAD23D1 interacted with a proline-rich protein MdPRP6, resulting in the degradation of MdPRP6 by the 26S proteasome. And MdRAD23D1 accelerated the degradation of MdPRP6 under drought stress. Suppression of MdPRP6 resulted in enhanced drought tolerance in apple plants, mainly because the free proline accumulation is changed. And the free proline is also involved in MdRAD23D1-mediated drought response. Taken together, these findings demonstrated that MdRAD23D1 and MdPRP6 oppositely regulated drought response. MdRAD23D1 levels increased under drought, accelerating the degradation of MdPRP6. MdPRP6 negatively regulated drought response, probably by regulating proline accumulation. Thus, "MdRAD23D1-MdPRP6" conferred drought stress tolerance in apple plants.
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Malus , Ubiquitina , Ubiquitina/metabolismo , Proteínas de Transporte , Malus/genética , Proteínas de Plantas/genética , Secas , Regulação da Expressão Gênica de Plantas , Estresse Fisiológico , Plantas Geneticamente Modificadas/metabolismoRESUMO
In this article, COD, volatile phenol and ammonia nitrogen concentrations of the wastewater from semicarbon are reported as 38,000; 6,400 and 5,700 mg/L, respectively. According to the field test, when the pH of the wastewater is 9, the field test temperature is 20 °C, the adsorption time is 30 min and the optimal dosing ratio of nitrogen-doped gasification slag (HX-NGS) to the wastewater is 1:4, HX-NGS has the best removal effect on COD, volatile phenol and ammonia nitrogen in the wastewater from the semicarbon. The removal rates of COD, volatile phenol and ammonia nitrogen are 94, 91 and 85%, respectively, and the concentrations of the remaining COD, volatile phenol and ammonia nitrogen are 2,280, 576 and 855 mg/L, respectively, after regeneration, the material HX-NGS has a good effect on the treatment of the wastewater from the semicarbon. The reuse rate of the adsorption material is at least eight times. The adsorption effect of the material HX-NGS conforms to the mechanism law of dynamics and thermodynamics.
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Carbono , Águas Residuárias , Adsorção , Amônia , Fenol , Fenóis , Nitrogênio , Reatores BiológicosRESUMO
OBJECTIVE: Immunotherapy plus etoposide and platinum (EP)-based chemotherapy is the standard of care for patients with extensive stage-small cell lung carcinoma (ES-SCLC). In the era of immunotherapy, the role of thoracic radiotherapy for ES-SCLC remains unclear. METHODS: We retrospectively included ES-SCLC patients treated with first-line EP-based chemotherapy plus atezolizumab or durvalumab at Taichung Veterans General Hospital to evaluate the prognostic role and safety of thoracic radiotherapy. RESULTS: A total of 22 patients were included. The median age was 64 years and most of them were male and smokers. Sixteen patients (72.7%) received durvalumab, while the other 6 patients (27.3%) underwent atezolizumab treatment. Among these patients, 11 (50.0%) had a history of thoracic radiotherapy. There was no significant difference in baseline characteristics between patients with and without thoracic radiotherapy. In the overall population, the objective response rate to immunotherapy plus chemotherapy was 73.7%. The progression-free survival and overall survival were 6.0 months (95% CI: 4.0-7.9) and 13.8 months (95% CI: 8.0-19.6), respectively. The overall survival was significantly longer in patients with thoracic radiotherapy (not-reached [NR] [95% CI NR-NR] vs. 9.6 months [95% CI 2.5-16.6]), respectively ( P value by log-rank test <0.001). Both multivariate analysis and subgroup analysis specifically comparing patients with consolidative thoracic radiotherapy and patients with clinical benefits to systemic therapy who did not undergo thoracic radiotherapy indicated that thoracic radiotherapy improved survival. CONCLUSION: The real-world efficacy of EP-based chemotherapy plus atezolizumab or durvalumab was comparable with that of clinical trials. Thoracic radiotherapy may improve the outcome of ES-SCLC.
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Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Etoposídeo , Feminino , Humanos , Imunoterapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Masculino , Pessoa de Meia-Idade , Platina , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/radioterapiaRESUMO
BACKGROUND: Nasopharyngeal carcinoma (NPC), an Epstein-Barr virus (EBV) associated cancer, exhibits an extremely high incidence in southern Chinese. Given that human leukocyte antigen (HLA) plays critical roles in antigen presentation and relates to NPC susceptibility, it is speculated that certain HLA variants may affect EBV reactivation, which is a key pathogenic factor of NPC. Therefore, we attempted to identify HLA alleles associated with the indicator of EBV reactivation, Zta-IgA, in healthy males from NPC endemic area. METHODS: HLA alleles of 1078 healthy males in southern China from the 21-RCCP study were imputed using genome-wide single nucleotide polymorphism data. EBV Zta-IgA in blood samples were measured using an enzyme-linked immunosorbent assay. Multiple logistic regression analysis was used to evaluate the effect of HLA allele on Zta-IgA serological status and its potential joint association with smoking. The binding affinity for Zta-peptide was predicted using NetMHCIIpan 4.0. RESULTS: HLA-DRB1*09:01 was found to be associated with a higher risk of Zta-IgA seropositivity (odds ratio = 1.80, 95% confidence interval = 1.32-2.45; p = 1.82 × 10-4 ). Compared with non-smokers without HLA-DRB1*09:01, the effect size increased to 2.19- and 3.70-fold for the light and heavy smokers carrying HLA-DRB1*09:01, respectively. Furthermore, HLA-DRB1*09:01 showed a stronger binding affinity to Zta peptide than other HLA-DRB1 alleles. CONCLUSIONS: Our study highlighted the pivotal role of genetic HLA variants in EBV reactivation and the etiology of NPC. Smokers with HLA-DRB1*09:01 have a significantly higher risk of being Zta-IgA seropositive, which indicates the necessity of smoking cessation in certain high-risk populations and also provide clues for further research on the etiology of NPC.
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Infecções por Vírus Epstein-Barr/imunologia , Antígenos HLA/genética , Herpesvirus Humano 4/imunologia , Imunoglobulina A/imunologia , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/imunologia , Transativadores/imunologia , Adulto , Alelos , Anticorpos Antivirais/imunologia , Povo Asiático/genética , Infecções por Vírus Epstein-Barr/virologia , Estudo de Associação Genômica Ampla/métodos , Genótipo , Voluntários Saudáveis , Humanos , Imunoglobulina A/sangue , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/imunologia , Fumar/efeitos adversos , Proteínas Virais/imunologiaRESUMO
Most persimmon (Diospyros kaki) cultivars are astringent and require post-harvest deastringency treatments such as 95% CO2 (high-CO2 treatment) to make them acceptable to consumers. High-CO2 treatment can, however, also induce excessive softening, which can be reduced by adding 1-methylcyclopropene (1-MCP). Previous studies have shown that genes encoding the ETHYLENE RESPONSE FACTORS (ERFs) DkERF8/16/19 can trans-activate xyloglucan endotransglycosylase/hydrolase (DkXTH9), which encodes the cell wall-degrading enzyme associated with persimmon fruit softening. In this study, RNA-seq data between three treatments were compared, namely high-CO2, high-CO2+1-MCP, and controls. A total of 227 differentially expressed genes, including 17 transcription factors, were predicted to be related to persimmon post-deastringency softening. Dual-luciferase assays indicated that DkNAC9 activated the DkEGase1 promoter 2.64-fold. Synergistic effects on transcription of DkEGase1 that involved DkNAC9 and the previously reported DkERF8/16 were identified. Electrophoretic mobility shift assay indicated that DkNAC9 could physically bind to the DkEGase1 promoter. Bimolecular fluorescence complementation and firefly luciferase complementation imaging assays indicated protein-protein interactions between DkNAC9 and DkERF8/16. Based on these findings, we conclude that DkNAC9 is a direct transcriptional activator of DkEGase1 that can co-operate with DkERF8/16 to enhance fruit post-deastringency softening.
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Diospyros , Dióxido de Carbono/metabolismo , Diospyros/genética , Diospyros/metabolismo , Frutas/metabolismo , Regulação da Expressão Gênica de Plantas , Hipóxia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMO
Long noncoding RNAs (LncRNAs) lncRNA H19 has been shown to be involved in the chemotherapy resistance of cancer cells. However, the role of lncRNA H19 in chemotherapy resistance of melanoma cells remains unknown. Here, we determined lncRNA H19, miR-18b, and insulin-like growth factor 1 (IGF1) expression by utilizing quantitative real-time PCR. Cell proliferation ability and chemosensitivity were assessed by colony formation assay and MTT assay. Flow cytometry assay was applied to detect cell apoptosis. We discovered that lncRNA H19 was upregulated, but miR-18b was downregulated in melanoma tissues and cisplatin (DDP)-resistant melanoma cells. The overall survival for the group with lower lncRNA H19 was significantly better than the group with higher H19. IGF1 mRNA level was higher in melanoma tissues than that in normal tissues. miR-18b expression level A negative correlation was observed between the expression levels of miR-18b, lncRNA H19, and IGF1 mRNA. Functionally, knockdown of lncRNA H19 sensitized resistant A375/DDP and M8/DDP cells to DDP. Silencing lncRNA H19 inhibited colony formation ability and promoted apoptosis of DDP-resistant melanoma cells, which was abrogated by miR-18b inhibition and IGF1 upregulation. Mechanistically, lncRNA H19 directly interacted with miR-18b to regulate its expression. IGF1 was identified as a target of miR-18b. These findings highlight the fact that lncRNA H19 could influence DDP-resistance by modulating the miR-18b/IGF axis in melanoma cells, suggesting a new potential therapeutic target for melanoma patient treatment.
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Biomarcadores Tumorais/metabolismo , Cisplatino/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Fator de Crescimento Insulin-Like I/metabolismo , Melanoma/tratamento farmacológico , MicroRNAs/genética , RNA Longo não Codificante/genética , Antineoplásicos/farmacologia , Apoptose , Biomarcadores Tumorais/genética , Proliferação de Células , Regulação para Baixo , Humanos , Fator de Crescimento Insulin-Like I/genética , Melanoma/genética , Melanoma/metabolismo , Melanoma/patologia , Prognóstico , Células Tumorais CultivadasRESUMO
Hypoxic environments are generally undesirable for most plants, but for astringent persimmon, high CO2 treatment (CO2 > 90%), also termed artificial high-CO2 atmosphere (AHCA), causes acetaldehyde accumulation and precipitation of soluble tannins and could remove astringency. The multiple transcriptional regulatory linkages involved in persimmon fruit deastringency have been advanced significantly by characterizing the ethylene response factors (ERFs), WRKY and MYB; however, the involvement of zinc finger proteins for deastringency has not been investigated. In this study, five genes encoding C2H2-type zinc finger proteins were isolated and designed as DkZF1-5. Phylogenetic and sequence analyses suggested the five DkZFs could be clustered into two different subgroups. qPCR analysis indicated that transcript abundances of DkZF1/4 were significantly upregulated during AHCA treatment (1% O2 and 95% CO2) at day 1, DkZF2/5 at both day 1 and 2, while DkZF3 at day 2. Dual-luciferase assay indicated DkZF1 and DkZF2 as the activators of deastringency-related structural genes (DkPDC2 and DkADH1) and transcription factors (DkERF9/10). Moreover, combinative effects between various transcription factors were investigated, indicating that DkZF1 and DkZF2 synergistically showed significantly stronger activations on the DkPDC2 promoter. Further, both bimolecular fluorescence complementation (BiFC) and yeast two hybrid (Y2H) assays confirmed that DkZF2 had protein-protein interactions with DkZF1. Thus, these findings illustrate the regulatory mechanisms of zinc finger proteins for persimmon fruit deastringency under AHCA.
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Diospyros/genética , Frutas/genética , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Dióxido de Carbono/metabolismo , Hipóxia Celular , Diospyros/citologia , Diospyros/metabolismo , Frutas/citologia , Frutas/metabolismo , Filogenia , Proteínas de Plantas/metabolismo , Regiões Promotoras Genéticas , Estresse Fisiológico , Dedos de ZincoRESUMO
Armillaria gallica is a facultative parasitic fungus which is the only nutrient source of Gastrodia elata during its cultivation.Chitinase,as a glycosidic hydrolytic enzyme,plays an important role in the growth,development,stress tolerance and symbiotic signal transduction of A. gallica. There were 22 chitinase genes in A. gallica. Bioinformatics analysis of amino acid sequence of these chitinase genes revealed that 12 chitinase genes contained glycosidase 18 family( GH18) domain. Chitinase amino acid sequences of A. gallica,A. ostoyae,G. elata,Saccharomyces cerevisiae and Trichoderma harzianum were analyzed byclustering trees,so as to further predict the gene function of chitinase in A. gallica. Induction of A. gallica branching with strigolactone analogue GR24,high-throughput sequencing technology based on the induction of branch group( MHJ1),uninduced branch group( MHJ2) and blank control group( MHJ3) is used to detect the expression quantity,the transcription level data of 22 chitinase genes were obtained and the heat map was generated for expression pattern analysis. It was found that 8 genes may be involved in physiological processes such as A. gallica branching,cell wall degradation and remodeling. In this paper,the function of chitinase gene in A. gallica was just preliminarily analyzed and predicted.
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Armillaria , Trichoderma , Sequência de Aminoácidos , Quitinases , Biologia ComputacionalRESUMO
Medicinal Polyporus umbellatus is the dry sclerotia of P. umbellatus, with the effect of diuresis; Armillaria mellea is a parasitic fungus which can infect plants up to 300 genera, with sedative, anticonvulsant and some other biological activities. As the medicinal value of P. umbellatus and A. mellea is increasingly wide concerned, the market quantity demanded of them is gradually increased and the demand outstrips the supply. The symbiotic A. mellea and P. umbellatus are both the medicinal and edible fungi with diverse activities, including hypoglycemic action, improve immunity and antitumor and so on. The growth of the sclerotia forming from the mycelium of P. umbellatus is related to the infection of the symbiotic A. mellea and their secondary products. In this study, by comparing the chemical constituents of the mycelium and sclerotia of P. umbellatus and A. mellea, we found that they all produced steroids and nitrogen-containing heterocycles. The sclerotia of P. umbellatus and A. mellea also produced triterpenes secondary metabolites. In addition, the mycelium and infected sclerotia of P. umbellatus mainly produced different steroids, and the sclerotia produced some other special secondary metabolites, such as long-chain fatty acids, ceramides, phenol and so on. By analyzing above all kinds of differences, speculated that these may be caused by the infection of the symbiotic A. mellea which mainly produced sesquiterpenes, diterpenes and other secondary metabolites. The contents and types of compounds of P. umbellatus and A. mellea are closely related to their symbiosis and reproduction, therefore, many symbiosis mechanisms should be found by utilizing more molecular biology technology to elucidate this complex symbiotic infection and provide scientific basis for improving the yield and quality of P. umbellatus and A. mellea.
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Armillaria/química , Produtos Biológicos/química , Polyporus/química , Micélio/químicaRESUMO
OBJECTIVE: This study aimed to investigate the reasons behind the lower survival rates in male lung cancer patients than in female lung cancer patients. METHODS: Through various techniques, such as Argonaute immunoprecipitation, luciferase assays, and ChIP, this study confirmed the positive effects of androgen receptor (AR) on lung cancer cell invasion across different in vitro cell lines and in vivo mouse models. RESULTS: The findings suggest that AR enhanced the invasion of lung cancer cells by modifying EPHB2 signals at the protein expression level, which in turn required changes in miRNA-23a-3p. Restoring miRNA-23a-3p could counteract the intensified invasion of lung cancer cells mediated by AR. CONCLUSION: This study revealed that AR may facilitate the lung cancer matastasis by modulating miRNA-23a-3p/EPHB2 signaling and that targeting this signaling pathway could provide new approaches to inhibit lung cancer metastasis.
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Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares , MicroRNAs , Receptor EphB2 , Receptores Androgênicos , Transdução de Sinais , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Receptores Androgênicos/metabolismo , Receptores Androgênicos/genética , Animais , Camundongos , Masculino , Transdução de Sinais/genética , Receptor EphB2/genética , Receptor EphB2/metabolismo , Linhagem Celular Tumoral , Feminino , Metástase Neoplásica , Movimento Celular/genética , Invasividade Neoplásica/genéticaRESUMO
In this paper, we explore the challenges associated with biomarker identification for diagnosis purpose in biomedical experiments, and propose a novel approach to handle the above challenging scenario via the generalization of the Dantzig selector. To improve the efficiency of the regularization method, we introduce a transformation from an inherent nonlinear programming due to its nonlinear link function into a linear programming framework under a reasonable assumption on the logistic probability range. We illustrate the use of our method on an experiment with binary response, showing superior performance on biomarker identification studies when compared to their conventional analysis. Our proposed method does not merely serve as a variable/biomarker selection tool, its ranking of variable importance provides valuable reference information for practitioners to reach informed decisions regarding the prioritization of factors for further investigations.
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Biomarcadores , ProbabilidadeRESUMO
BACKGROUND: Accurate segmentation of lung tumors on chest computed tomography (CT) scans is crucial for effective diagnosis and treatment planning. Deep Learning (DL) has emerged as a promising tool in medical imaging, particularly for lung cancer segmentation. However, its efficacy across different clinical settings and tumor stages remains variable. METHODS: We conducted a comprehensive search of PubMed, Embase, and Web of Science until November 7, 2023. We assessed the quality of these studies by using the Checklist for Artificial Intelligence in Medical Imaging and the Quality Assessment of Diagnostic Accuracy Studies-2 tools. This analysis included data from various clinical settings and stages of lung cancer. Key performance metrics, such as the Dice similarity coefficient, were pooled, and factors affecting algorithm performance, such as clinical setting, algorithm type, and image processing techniques, were examined. RESULTS: Our analysis of 37 studies revealed a pooled Dice score of 79 % (95 % CI: 76 %-83 %), indicating moderate accuracy. Radiotherapy studies had a slightly lower score of 78 % (95 % CI: 74 %-82 %). A temporal increase was noted, with recent studies (post-2022) showing improvement from 75 % (95 % CI: 70 %-81 %). to 82 % (95 % CI: 81 %-84 %). Key factors affecting performance included algorithm type, resolution adjustment, and image cropping. QUADAS-2 assessments identified ambiguous risks in 78 % of studies due to data interval omissions and concerns about generalizability in 8 % due to nodule size exclusions, and CLAIM criteria highlighted areas for improvement, with an average score of 27.24 out of 42. CONCLUSION: This meta-analysis demonstrates DL algorithms' promising but varied efficacy in lung cancer segmentation, particularly higher efficacy noted in early stages. The results highlight the critical need for continued development of tailored DL models to improve segmentation accuracy across diverse clinical settings, especially in advanced cancer stages with greater challenges. As recent studies demonstrate, ongoing advancements in algorithmic approaches are crucial for future applications.
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Aprendizado Profundo , Neoplasias Pulmonares , Tomografia Computadorizada por Raios X , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/patologia , Tomografia Computadorizada por Raios X/métodos , AlgoritmosRESUMO
This study aimed to explore the isomer-specific, sex-specific, and joint associations of PFAS and red blood cell indices. We used data of 1,238 adults from the Isomers of C8 Health Project in China. Associations of PFAS isomers and red blood cell indices were explored using multiple linear regression models, Bayesian Kernel Machine Regression models and subgroup analysis across sex. We found that serum concentration of linear (n-) and branched (Br-) isomers of perfluorooctane sulfonate (PFOS) and perfluorohexanesulfonic acid (PFHxS) were significantly associated with red blood cell indices in single-pollutant models, with stronger associations observed for n-PFHxS than Br-PFHxS, in women than in men. For instance, the estimated percentage change in hemoglobin concentration for n-PFHxS (3.65%; 95% CI: 2.95%, 4.34%) was larger than that for Br-PFHxS (0.96%; 95% CI: 0.52%, 1.40%). The estimated percentage change in red blood cell count for n-PFHxS in women (2.55%; 95% CI: 1.81%, 3.28%) was significantly higher than that in men (0.12%; 95% CI: -1.04%, 1.29%) (Pinter < 0.001). Similarly, sex-specific positive association of PFAS mixture and outcomes was observed. Therefore, the structure, susceptive population, and joint effect of PFAS isomers should be taken into consideration when evaluating the health risk of chemicals.
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Ácidos Alcanossulfônicos , Poluentes Ambientais , Índices de Eritrócitos , Fluorocarbonos , Humanos , Feminino , Masculino , China , Fluorocarbonos/sangue , Ácidos Alcanossulfônicos/sangue , Adulto , Pessoa de Meia-Idade , Poluentes Ambientais/sangue , Isomerismo , Ácidos Sulfônicos/sangue , Exposição Ambiental/análise , Fatores SexuaisRESUMO
Evidence from animal experiments has shown that chlorinated polyfluoroalkyl ether sulfonic acids (Cl-PFESAs) can induce vision dysfunction in zebrafish. However, environmental epidemiological evidence supporting this hypothesis remains limited. In our case-control study, samples collected from 270 individuals (135 controls and 135 cases) from the Isomers of C8 Health Project data were analyzed for Cl-PFESAs. We also repeated our analysis on zebrafish to support our findings in humans and to decipher the mechanism underlying Cl-PFESA eye toxicity. The serum levels of per- and polyfluoroalkyl substances (PFASs) and alternatives were significantly higher in the cases than in the controls. Higher serum Cl-PFESA levels were associated with greater odds of eye diseases, and the trend showed a statistically significant dose-dependent relationship. The Shapley additive explanations (SHAP) value indicated that 8:2 Cl-PFESA was the dominant eye disease risk factor among the 13 studied PFASs. In zebrafish experiments, Cl-PFESAs induced eye toxicity in adult zebrafish by oxidative damage and cell apoptosis. Compared to the control group, there was significantly reduced thicknesses of the inner plexiform layer (IPL), outer plexiform layer (OPL), and retinal tissue in the zebrafish exposed to Cl-PFESAs. Our study provides human clinical and animal experimental data, showing that exposure to PFASs increases the odds of the development of eye toxicity.
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Evidence on the link of long-term exposure to ozone (O3) with childhood asthma, rhinitis, conjunctivitis and eczema is inconclusive. We did a population-based cross-sectional survey, including 177,888 children from 173 primary and middle schools in 14 Chinese cities. A satellite-based spatiotemporal model was employed to assess four-year average O3 exposure at both residential and school locations. Information on asthma, allergic rhinitis, eczema and conjunctivitis was collected by a standard questionnaire developed by the American Thoracic Society. We used generalized non-linear and linear mixed models to test the associations. We observed linear exposure-response associations between O3 and all outcomes. The odds ratios of doctor-diagnosed asthma, rhinitis, eczema, and conjunctivitis associated with per interquartile increment in home-school O3 concentration were 1.31 (95 % confidence interval [CI]: 1.28, 1.34), 1.25 (95 %CI: 1.23, 1.28), 1.19 (95 %CI: 1.16, 1.21), and 1.28 (95 %CI: 1.21, 1.34), respectively. Similar associations were observed for asthma-related outcomes including current asthma, wheeze, current wheeze, persistent phlegm, and persistent cough. Moreover, stronger associations were observed among children who were aged > 12 years, physically inactive, and exposed to higher temperature. In conclusion, long-term O3 exposure was associated with higher risks of asthma, allergic rhinitis, conjunctivitis and eczema in children.
Assuntos
Poluentes Atmosféricos , Asma , Cidades , Conjuntivite , Eczema , Ozônio , Rinite , Humanos , Ozônio/análise , Ozônio/toxicidade , Criança , China/epidemiologia , Asma/epidemiologia , Asma/induzido quimicamente , Eczema/epidemiologia , Eczema/induzido quimicamente , Masculino , Feminino , Rinite/epidemiologia , Rinite/induzido quimicamente , Poluentes Atmosféricos/toxicidade , Poluentes Atmosféricos/análise , Conjuntivite/induzido quimicamente , Conjuntivite/epidemiologia , Estudos Transversais , Exposição Ambiental/efeitos adversos , AdolescenteRESUMO
Contaminants may induce immune response polarization, leading to immune diseases, such as allergic diseases. Evidence concerning the effects of chlorinated paraffins (CPs), an emerging persistent organic pollutant, on immune system is scarce, particularly for epidemiological evidence. This study explores the association between CPs exposure and allergic diseases (allergic rhinitis, atopic eczema, and allergic conjunctivitis) in children and adolescents in the Pearl River Delta (PRD) in China. Herein, 131,304 children and adolescents from primary and secondary schools in the PRD were included and completed the questionnaire survey. The particulate matter (PM) samples were collected in the PRD and the PM2.5-bound CP concentrations were analyzed. In the multivarious adjustment mixed effect model (MEM), an IQR increase in ∑CPs was significantly associated with allergic diseases (rhinitis, eczema, and conjunctivitis) with the estimated odds ratios (ORs) for 1.11 (95% CI: 1.10, 1.13), 1.17 (95% CI: 1.15, 1.19), and 1.82 (95% CI: 1.76, 1.88), respectively. Interaction analysis indicated that overweight and obese individuals might have greater risk. Similar effect estimates were observed in several sensitivity analyses. This study provided epidemiological evidence on the immunotoxicity of CPs. More studies to confirm our findings and investigate mechanisms are needed.
Assuntos
Parafina , Humanos , Adolescente , Criança , Masculino , Feminino , China/epidemiologia , Parafina/toxicidade , Parafina/análise , Hipersensibilidade/epidemiologia , Exposição Ambiental/efeitos adversos , Hidrocarbonetos Clorados/toxicidade , Hidrocarbonetos Clorados/análise , Poluentes Atmosféricos/toxicidade , Poluentes Atmosféricos/análise , Material Particulado/toxicidade , Material Particulado/análise , Dermatite Atópica/epidemiologia , Dermatite Atópica/induzido quimicamente , Rinite Alérgica/epidemiologia , Rinite Alérgica/induzido quimicamenteRESUMO
Excessive nitrogen (N) deposition causes a series of environmental problems, including biodiversity loss. Therefore, assessing current N deposition thresholds of natural ecosystems is critical for regional N management and pollution control. In this study, the critical loads of N deposition in mainland China were estimated using the steady-state mass balance method, and the spatial distribution of ecosystems that exceeded the critical load was evaluated. The results showed that areas with critical loads of N deposition higher than 56, in the range of 14-56, and lower than 14 kg·(hm2·a)-1 accounted for 6%, 67%, and 27% of that in China, respectively. The areas with higher critical loads of N deposition were mainly distributed in the eastern Tibetan Plateau, northeastern Inner Mongolia, and parts of south China. Lower critical loads of N deposition were mainly distributed in the western Tibetan Plateau, northwest China, and parts of southeast China. Moreover, the areas where N deposition exceeded the critical loads accounted for 21% of that in mainland China, being mainly distributed in southeast and northeast China. The exceedances of critical loads of N deposition in northeast China, northwest China, and the Qinghai-Tibet Plateau were generally lower than 14 kg·(hm2·a)-1. Therefore, the management and control of N in these areas that exceeded the critical load of deposition is more worthy of future attention.