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Renal cell carcinoma (RCC) is considered a "metabolic disease" characterized by elevated glycolysis in patients with advanced RCC. Tyrosine kinase inhibitor (TKI) therapy is currently an important treatment option for advanced RCC, but drug resistance may develop in some patients. Combining TKI with targeted metabolic therapy may provide a more effective approach for patients with advanced RCC. An analysis of 14 RCC patients (including three needle biopsy samples with TKI resistance) revealed by sing-cell RNA sequencing (scRNA-seq) that glycolysis played a crucial role in poor prognosis and drug resistance in RCC. TCGA-KIRC and glycolysis gene set analysis identified DEPDC1 as a target associated with malignant progression and drug resistance in KIRC. Subsequent experiments demonstrated that DEPDC1 promoted malignant progression and glycolysis of RCC, and knockdown DEPDC1 could reverse TKI resistance in RCC cell lines. Bulk RNA sequencing (RNA-seq) and non-targeted metabolomics sequencing suggested that DEPDC1 may regulate RCC glycolysis via AKT/mTOR/HIF1α pathway, a finding supported by protein-level analysis. Clinical tissue samples from 98 RCC patients demonstrated that DEPDC1 was associated with poor prognosis and predicted RCC metastasis. In conclusion, this multi-omics analysis suggests that DEPDC1 could serve as a novel target for TKI combined with targeted metabolic therapy in advanced RCC patients with TKI resistance.
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Carcinoma de Células Renales , Glucólisis , Subunidad alfa del Factor 1 Inducible por Hipoxia , Neoplasias Renales , Proteínas Proto-Oncogénicas c-akt , Serina-Treonina Quinasas TOR , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/tratamiento farmacológico , Humanos , Glucólisis/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Neoplasias Renales/metabolismo , Neoplasias Renales/patología , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Línea Celular Tumoral , Proteínas Activadoras de GTPasa/metabolismo , Proteínas Activadoras de GTPasa/genética , Transducción de Señal , Ratones , Animales , Masculino , Femenino , Ratones Desnudos , Resistencia a Antineoplásicos/efectos de los fármacos , Regulación Neoplásica de la Expresión GénicaRESUMEN
Selection of chemical-resistant predatory mites is a good alternative to balance the contradiction between chemical control and biological control. Previously, a resistant strain of Neoseiulus barkeri for chlorpyrifos was obtained. In the current study, two up-regulated (NbCYP3A6, NbCYP3A16) and one down-regulated (NbCYP3A24) P450s were screened through differential expression analysis and other detoxification-related genes such as CCEs, GST, etc. were not found. 3D modelling and molecular docking indicated that the chlorine at position 5 on the pyridine ring of chlorpyrifos, as well as a methyl group, were closest to the heme iron of the enzymes (less than 5 Å). Three active recombinant P450 proteins were heterologously expressed and metabolized with chlorpyrifos in vitro. HPLC assay showed that only NbCYP3A24 could metabolize chlorpyrifos, with a metabolism rate of 21.60 %. Analysis of the m/z of metabolites by LC-MS/MS showed that chlorine at the 5C position of chlorpyrifos was stripped and hydroxylated, whereas chlorpyrifos-oxon, a common product of oxidation by P450, was not found. Knockdown of the NbCYP3A24 gene in the susceptiblestrain did reduce the susceptibility of N. barkeri to chlorpyrifos, suggesting that the biological activity of the metabolite may be similar to chlorpyrifos-oxon, thus enhancing the inhibitory effect on the target.
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Cloropirifos , Sistema Enzimático del Citocromo P-450 , Insecticidas , Ácaros , Simulación del Acoplamiento Molecular , Cloropirifos/metabolismo , Cloropirifos/química , Cloropirifos/análogos & derivados , Animales , Ácaros/efectos de los fármacos , Sistema Enzimático del Citocromo P-450/metabolismo , Sistema Enzimático del Citocromo P-450/genética , Insecticidas/metabolismo , Insecticidas/química , Insecticidas/toxicidad , Regulación hacia Abajo , HidroxilaciónRESUMEN
Overexpression of carboxyl/cholinesterase (CCE) genes has been reported to be associated with many cases of pesticide resistance in arthropods. However, it has been rarely documented that CCE genes participate in spirodiclofen resistance in Panonychus citri. In previous research, we found that spirodiclofen resistance is related to increased P450 and CCE enzyme activities in P. citri. In this study, we identified two CCE genes, PcCCE3 and PcCCE5, which were significantly upregulated in spirodiclofen-resistant strain and after exposure to spirodiclofen. RNA interference of PcCCE3 and PcCCE5 increased the spirodiclofen susceptibility in P. citri. In vitro metabolism indicated that PcCCE3 and PcCCE5 could interact with spirodiclofen, but metabolites were detected only in the PcCCE3 treatment. Our results indicated that PcCCE3 participates in spirodiclofen resistance through direct metabolism, and PcCCE5 may be involved in the spirodiclofen resistance by passive binding and sequestration, which provides new insights into spirodiclofen resistance in P. citri.
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Proteínas de Artrópodos , Compuestos de Espiro , Animales , Compuestos de Espiro/farmacología , Compuestos de Espiro/metabolismo , Compuestos de Espiro/química , Proteínas de Artrópodos/genética , Proteínas de Artrópodos/metabolismo , Proteínas de Artrópodos/química , Resistencia a Medicamentos/genética , Carboxilesterasa/genética , Carboxilesterasa/metabolismo , 4-Butirolactona/análogos & derivados , 4-Butirolactona/metabolismo , 4-Butirolactona/farmacologíaRESUMEN
Realizing large materials models has emerged as a critical endeavor for materials research in the new era of artificial intelligence, but how to achieve this fantastic and challenging objective remains elusive. Here, we propose a feasible pathway to address this paramount pursuit by developing universal materials models of deep-learning density functional theory Hamiltonian (DeepH), enabling computational modeling of the complicated structure-property relationship of materials in general. By constructing a large materials database and substantially improving the DeepH method, we obtain a universal materials model of DeepH capable of handling diverse elemental compositions and material structures, achieving remarkable accuracy in predicting material properties. We further showcase a promising application of fine-tuning universal materials models for enhancing specific materials models. This work not only demonstrates the concept of DeepH's universal materials model but also lays the groundwork for developing large materials models, opening up significant opportunities for advancing artificial intelligence-driven materials discovery.
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BACKGROUND: Education in nursing has noticed a positive effect of simulation-based education. There are many studies available on the effects of simulation-based education, but most of those involve a single institution, nonrandomized controlled trials, small sample sizes and subjective evaluations of the effects. The purpose of this multicenter randomized controlled trial was to evaluate the effects of high-fidelity simulation, computer-based simulation, high-fidelity simulation combined with computer-based simulation, and case study on undergraduate nursing students. METHODS: A total of 270 nursing students were recruited from five universities in China. Participants were randomly divided into four groups at each institution: the high-fidelity simulation group, the computer-based simulation group, the high-fidelity simulation combined with computer-based simulation group, and the case study group. Finally, 239 participants completed the intervention and evaluation, with 58, 67, 57, and 57 participants in each group. The data were collected at three stages: before the intervention, immediately after the intervention, and three months after the intervention. RESULTS: The demographic data and baseline evaluation indices did not significantly differ among the four groups. A statistically significant difference was not observed between the four methods for improving knowledge, interprofessional collaboration, critical thinking, caring, or interest in learning. While skill improvement differed significantly among the different groups after the intervention (p = 0.020), after three months, no difference was observed (p = 0.139). The improvement in skill in the computer-based simulation group was significantly lower at the end of the intervention than that in the high-fidelity simulation group (p = 0.048) or the high-fidelity simulation combined with computer-based simulation group (p = 0.020). CONCLUSIONS: Nursing students benefit equally from four methods in cultivating their knowledge, interprofessional collaboration, critical thinking, caring, and interest in learning both immediately and over time. High-fidelity simulation and high-fidelity simulation combined with computer-based simulation improve skill more effectively than computer-based simulation in the short term. Nursing educators can select the most suitable teaching method to achieve the intended learning outcomes depending on the specific circumstances. TRIAL REGISTRATION: This clinical trial was registered at the Chinese Clinical Trial Registry (clinical trial number: ChiCTR2400084880, date of the registration: 27/05/2024).
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Insecticide susceptibility is mainly determined by the insect host, but symbiotic bacteria are also an important affecting factor. In this study, we investigate the relationship between the structure of gut bacterial symbionts and insecticide susceptibility in Diaphorina citri, the important carrier of Candidatus Liberibacter asiaticus (CLas), the causal agent of Huanglongbing (HLB). Our results indicated that antibiotic treatment significantly increased the susceptibility of D. citri to bifenthrin and thiamethoxam, and significantly decreased the relative abundance of Wolbachia and Profftella, enzyme activities of CarEs, and expression level of multiple CarE genes. The relative loads of Wolbachia and Profftella were positively correlated with DcitCCE13, DcitCCE14, DcitCCE15, and DcitCCE16. RNAi and prokaryotic expression revealed that DcitCCE15 is associated with bifenthrin metabolism. These results revealed that bacterial symbionts might regulate DcitCCE15 expression, which is involved in the susceptibility of D. citri to bifenthrin.
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Hemípteros , Insecticidas , Simbiosis , Animales , Insecticidas/farmacología , Hemípteros/microbiología , Hemípteros/genética , Hemípteros/efectos de los fármacos , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Resistencia a los Insecticidas/genética , Wolbachia/efectos de los fármacos , Wolbachia/genética , Piretrinas/farmacología , Bacterias/genética , Bacterias/efectos de los fármacos , Bacterias/clasificación , Bacterias/aislamiento & purificación , Bacterias/metabolismo , Inactivación Metabólica/genéticaRESUMEN
The regulatory mechanism of the transcription factor GATA3 in the differentiation and maturation process of extravillous trophoblasts (EVT) in early pregnancy placenta, as well as its relevance to the occurrence of pregnancy disorders, remains poorly understood. This study leveraged single-cell RNA sequencing data from placental organoid models and placental tissue to explore the dynamic changes in GATA3 expression during EVT maturation. The expression pattern exhibited an initial upregulation followed by subsequent downregulation, with aberrant GATA3 localization observed in cases of recurrent miscarriage (RM). By identifying global targets regulated by GATA3 in primary placental EVT cells, JEG3, and HTR8/SVneo cell lines, this study offered insights into its regulatory mechanisms across different EVT cell models. Shared regulatory targets among these cell types and activation of trophoblast cell marker genes emphasized the importance of GATA3 in EVT differentiation and maturation. Knockdown of GATA3 in JEG3 cells led to repression of GATA3-induced epithelial-mesenchymal transition (EMT), as evidenced by changes in marker gene expression levels and enhanced migration ability. Additionally, interference with GATA3 accelerated cellular senescence, as indicated by reduced proliferation rates and increased activity levels for senescence-associated ß-galactosidase enzyme, along with elevated expression levels for senescence-associated genes. This study provides comprehensive insights into the dual role of GATA3 in regulating EMT and cellular senescence during EVT differentiation, shedding light on the dynamic changes in GATA3 expression in normal and pathological placental conditions.
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The citrus red mite, Panonychus citri, is one of the most notorious and devastating citrus pests around the world that has developed resistance to multiple chemical acaricides. In previous research, we found that spirodiclofen-resistant is related to overexpression of P450, CCE, and ABC transporter genes in P. citri. However, the regulatory mechanisms of these detoxification genes are still elusive. This study identified all hormone receptor 96 genes of P. citri. 8 PcHR96 genes contained highly conserved domains. The expression profiles showed that PcHR96h was significantly upregulated in spirodiclofen resistant strain and after exposure to spirodiclofen. RNA interference of PcHR96h decreased expression of detoxification genes and increased spirodiclofen susceptibility in P. citri. Furthermore, molecular docking, heterologous expression, and drug affinity responsive target stability demonstrated that PcHR96h can interact with spirodiclofen in vitro. Our research results indicate that PcHR96h plays an important role in regulating spirodiclofen susceptibility and provides theoretical support for the resistance management of P. citri.
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Compuestos de Espiro , Animales , Compuestos de Espiro/farmacología , Compuestos de Espiro/metabolismo , Acaricidas/farmacología , Propionatos/farmacología , Propionatos/metabolismo , Tetranychidae/efectos de los fármacos , Tetranychidae/genética , Tetranychidae/metabolismo , Simulación del Acoplamiento Molecular , Proteínas de Artrópodos/genética , Proteínas de Artrópodos/metabolismo , Resistencia a Medicamentos/genética , 4-Butirolactona/análogos & derivadosRESUMEN
Root-associated microbiota provide great fitness to hosts under environmental stress. However, the underlying microecological mechanisms controlling the interaction between heavy metal-stressed plants and the microbiota are poorly understood. In this study, we screened and isolated representative amplicon sequence variants (strain M4) from rhizosphere soil samples of Trifolium repens L. growing in areas with high concentrations of heavy metals. To investigate the microecological mechanisms by which T. repens adapts to heavy metal stress in abandoned mining areas, we conducted potting experiments, bacterial growth promotion experiments, biofilm formation experiments, and chemotaxis experiments. The results showed that high concentrations of heavy metals significantly altered the rhizosphere bacterial community structure of T. repens and significantly enriched Microbacterium sp. Strain M4 was demonstrated to significantly increased the biomass and root length of T. repens under heavy metal stress. Additionally, L-proline and stigmasterol could promote bacterial growth and biofilm formation and induce chemotaxis for strain M4, suggesting that they are key rhizosphere secretions of T. repens for Microbacterium sp. recruitment. Our results suggested that T. repens adapted the heavy metal stress by reshaping rhizosphere secretions to modify the rhizosphere microbiota.
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Metales Pesados , Microbacterium , Minería , Raíces de Plantas , Rizosfera , Microbiología del Suelo , Contaminantes del Suelo , Trifolium , Trifolium/microbiología , Contaminantes del Suelo/toxicidad , Raíces de Plantas/microbiología , Microbacterium/fisiología , Microbiota/efectos de los fármacos , Plomo/toxicidad , ZincRESUMEN
Neoadjuvant tyrosine kinase inhibitor (TKI) therapy is an important treatment option for advanced renal cell carcinoma (RCC). Many RCC patients may fail to respond or be resistant to TKI therapy. We aimed to explore the key mechanisms of neoadjuvant therapy résistance. We obtained tumor samples from matched pre-treatment biopsy and post-treatment surgical samples and performed single-cell RNA sequencing. Sunitinib-resistant ccRCC cell lines were established. Ferroptosis was detected by ferrous ion and lipid peroxidation levels. Tumor growth and resistance to Sunitinib was validated in vitro and vivo. Immunohistochemistry was used to validate the levels key genes and lipid peroxidation. Multi-center cohorts were included, including TCGA, ICGC, Checkmate-025 and IMmotion151 clinical trial. Survival analysis was performed to identify the associated clinical and genomic variables. Intratumoral heterogeneity was first described in the whole neoadjuvant management. The signature of endothelial cells was correlated with drug sensitivity and progression-free survival. Ferroptosis was shown to be the key biological program in malignant cell resistance. We observed tissue lipid peroxidation was negatively correlated with IL6 and tumor response. TKI-resistant cell line was established. SLC7A11 knockdown promoted cell growth and lipid peroxidation, increased the ferroptosis level, and suppressed the growth of tumor xenografts significantly (P < 0.01). IL6 could reverse the ferroptosis and malignant behavior caused by SLC7A11 (-) via JAK2/STAT3 pathway, which was rescued by the ferroptosis inducer Erastin. Our data indicate that ferroptosis is a novel strategy for advanced RCC treatment, which activated by IL6, providing a new idea for resistance to TKIs.
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Sistema de Transporte de Aminoácidos y+ , Carcinoma de Células Renales , Resistencia a Antineoplásicos , Ferroptosis , Neoplasias Renales , Terapia Neoadyuvante , Sunitinib , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/metabolismo , Ferroptosis/efectos de los fármacos , Ferroptosis/genética , Humanos , Neoplasias Renales/patología , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/genética , Neoplasias Renales/metabolismo , Terapia Neoadyuvante/métodos , Sunitinib/farmacología , Animales , Línea Celular Tumoral , Ratones , Sistema de Transporte de Aminoácidos y+/genética , Sistema de Transporte de Aminoácidos y+/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto , Inhibidores de Proteínas Quinasas/farmacología , Peroxidación de Lípido/efectos de los fármacos , Factor de Transcripción STAT3/metabolismo , Factor de Transcripción STAT3/genética , Femenino , Masculino , Terapia Molecular Dirigida , Interleucina-6/metabolismo , Interleucina-6/genética , Progresión de la EnfermedadRESUMEN
Constipation is a common gastrointestinal condition, which may occur at any age and affects countless people. The search for new treatments for constipation is ongoing as current drug treatments fail to provide fully satisfactory results. In recent years, probiotics have attracted much attention because of their demonstrated therapeutic efficacy and fewer side effects than pharmaceutical products. Many studies attempted to answer the question of how probiotics can alleviate constipation. It has been shown that different probiotic strains can alleviate constipation by different mechanisms. The mechanisms on probiotics in relieving constipation were associated with various aspects, including regulation of the gut microbiota composition, the level of short-chain fatty acids, aquaporin expression levels, neurotransmitters and hormone levels, inflammation, the intestinal environmental metabolic status, neurotrophic factor levels and the body's antioxidant levels. This paper summarizes the perception of the mechanisms on probiotics in relieving constipation and provides some suggestions on new research directions.
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Elasticity, featured by a recoverable strain, refers to the ability that materials can return to their original shapes after deformation. Typically, the elastic strains of most metals are well-known 0.2%. In shape memory alloys and high entropy alloys, the elastic strains can be several percent, as called superelasticity, which are all triggered by external stresses. A superelasticity induced by magnetic field, termed as magneto-superelasticity, is extremely important for contactless work of materials and for developing brand-new large stroke actuators and high efficiency energy transducers. In magnetic shape memory alloys, the twin boundary motion driven by magnetic field can output a strain of several percent. However, this strain is unrecoverable when removing the magnetic field and hence it is not magneto-superelasticity. Here, a giant magneto-superelasticity of 5% in a Ni34Co8Cu8Mn36Ga14 single crystal is reported by introducing arrays of ordered dislocations to form preferentially oriented martensitic variants during the magnetically induced reverse martensitic transformation. This work provides an opportunity to achieve high performance in functional materials by defect engineering.
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OBJECTIVE: To evaluate the rabbit modle of frozen shoulder induced by persistent strain injuries and ice compression. METHODS: Twelve clean, healthy male New Zealand rabbits with a mass of (2 500±500) g were selected and randomly divided into a blank group and a control group with 6 rabbits in each group. In the control group, the rabbits were modeled with persistent strain injuries and ice compression, the general conditions of the rabbits and the active and passive activities of the shoulder joint were observed and their body weights were recorded. MRI was performed on the affected shoulder joints at 6 d and 29 d after modelling to observe the fluid and soft tissue;HE staining was used to observe the morphology of the rabbit biceps longus tendon and the synovial membrane of the joint capsule;Masson staining was used to observe the fibrous deposits of the rabbit biceps longus tendon and the synovial membrane of the joint capsule, and the fibrous deposits were analysed semi-quantitatively by Image J software. RESULTS: Six days after the end of modeling, the active movement of the shoulder joints in the control group was limited, the passive movement was not significantly limited, and they walked with a limp;29 days after the end of the modeling, the active and passive movements of the shoulder joints in the model group were severely limited. Compared with the blank group (2.50±0.14) kg, the body weight of the model group (2.20±0.17) kg was significantly reduced(P<0.01). MRI showed that 6 days after modelling, the muscles around the shoulder joint were not smooth in shape, the joint capsule structure was narrowed and a large amount of fluid was seen in the joint cavity;29 days after modelling, the muscles around the shoulder joint were rough in shape, structure of the joint capsule was unclear and the fluid in the joint cavity was reduced compared with 6 days after modelling. Pathological staining showed that the long-headed biceps tendon fibres in the control group were disorganised, curled or even broken, and the synovial tissue of the joint capsule was heavily vascularised, with collagen fibre deposits and severe inflammatory cell infiltration. The fiber deposition of the long head of biceps brachii in the model group [(23.58±3.41)%, (27.56±3.70)%] and synovial tissue [(41.78±5.59)%, (62.19±7.54)%] were significantly higher than those in the blank group [(1.79±1.03) %, (1.29±0.63) %] at 7 and 30 days after modeling and synovial tissue fiber deposition [(8.15±3.61) %, (11.29±7.10) %], as shown by the semi-quantitative analysis of Masson staining results by Image J software. And the longer the time, the more severe the fibrosis (P<0.01). CONCLUSION: The behavioral, imaging and pathological findings showed that the rabbit frozen shoulder model with persistent strain injuries and ice compression is consistent with the clinical manifestations and pathogenesis of periarthritis, making it an ideal method for periarthritis research.
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Bursitis , Modelos Animales de Enfermedad , Animales , Conejos , Masculino , Bursitis/fisiopatología , Hielo , Esguinces y Distensiones/fisiopatología , Articulación del Hombro/fisiopatología , Imagen por Resonancia MagnéticaRESUMEN
Cyetpyrafen is a recently developed acaricide. The citrus red mite, Panonychus citri (McGregor), has developed significant resistance to cyetpyrafen. However, the molecular mechanism underlying the cyetpyrafen resistance in P. citri remains unclear. Glutathione S-transferases (GSTs) play a critical role in arthropod pesticide resistance. This study showed that GSTs were potentially related to the resistance of P. citri to cyetpyrafen through synergistic experiments and enzyme activity analysis. An omega-family GST gene, PcGSTO1, was significantly up-regulated in the egg, nymph, and adult stages of the cyetpyrafen-resistant strain. Additionally, silencing of PcGSTO1 significantly increased the mortality of P. citri to cyetpyrafen and recombinant PcGSTO1 demonstrated the ability to metabolize cyetpyrafen. Our results indicated that the overexpression of PcGSTO1 is associated with cyetpyrafen resistance in P. citri, and they also provided valuable information for managing resistance in P. citri.
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Acaricidas , Tetranychidae , Animales , Glutatión Transferasa/genética , Glutatión Transferasa/metabolismo , Tetranychidae/genética , Tetranychidae/metabolismo , Acaricidas/farmacología , Acaricidas/metabolismoRESUMEN
OBJECTIVE: The aim of this study was to investigate risk factors for the severity of breast abscess during lactation. METHODS: A cross-sectional study was conducted using data from the Questionnaire survey of breast abscess patients. According to whether the maximum abscess diameter > 5 cm, the patients were divided into two groups for univariate and multivariate regression analysis. RESULTS: 1805 valid questionnaires were included. Univariate and Binary logistic regression analysis demonstrated that low education (OR = 1.5, 95% CI 1.1-2.0, P = 0.005), non-exclusive breastfeeding (OR = 0.7, 95% CI 0.6-0.9, P = 0.004), fever > 37.5 â (OR = 0.7, 95% CI 0.6-0.9, P = 0.003), flat or inverted nipples (OR = 0.7, 95% CI 0.6-0.9, P = 0.005), antibiotic used (OR = 0.7, 95% CI 0.6-0.9, P = 0.006), and non-medical massage (OR = 0.3, 95% CI 0.2-0.4, P < 0.001) were the effective independent influencing factors for the maximum breast abscess diameter > 5 cm. CONCLUSION: Low education, non-exclusive breastfeeding, fever > 37.5 â, inverted or flat nipples, antibiotic used, and non-medical massage history have adverse effects on the severity of breast abscess during lactation.
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Lactancia Materna , Mastitis , Femenino , Humanos , Absceso , Estudios Transversales , Lactancia , Antibacterianos/uso terapéuticoRESUMEN
Dental caries, a highly prevalent oral disease, impacts a significant portion of the global population. Conventional approaches that indiscriminately eradicate microbes disrupt the natural equilibrium of the oral microbiota. In contrast, biointervention strategies aim to restore this balance by introducing beneficial microorganisms or inhibiting cariogenic ones. Over the past three decades, microbial preparations have garnered considerable attention in dental research for the prevention and treatment of dental caries. However, unlike related pathologies in the gastrointestinal, vaginal, and respiratory tracts, dental caries occurs on hard tissues such as tooth enamel and is closely associated with localized acid overproduction facilitated by cariogenic biofilms. Therefore, it is insufficient to rely solely on previous mechanisms to delineate the role of microbial preparations in the oral cavity. A more comprehensive perspective should involve considering the concepts of cariogenic biofilms. This review elucidates the latest research progress, mechanisms of action, challenges, and future research directions regarding probiotics, prebiotics, synbiotics, and postbiotics for the prevention and treatment of dental caries, taking into account the unique pathogenic mechanisms of dental caries. With an enhanced understanding of oral microbiota, personalized microbial therapy will emerge as a critical future research trend.
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Caries Dental , Microbiota , Probióticos , Simbióticos , Femenino , Humanos , Prebióticos , Caries Dental/prevención & control , Probióticos/uso terapéutico , BocaRESUMEN
BACKGROUND: Adolescent non-suicidal self-injury (NSSI) is a major public health issue. Family factors are significantly associated with NSSI in adolescents, while studies on forecasting NSSI at the family level are still limited. In addition to regression methods, machine learning (ML) techniques have been recommended to improve the accuracy of family-level risk prediction for NSSI. METHODS: Using a dataset of 7967 students and their primary caregivers from a cross-sectional study, logistic regression model and random forest model were used to test the forecasting accuracy of NSSI predictions at the family level. Cross-validation was used to assess model prediction performance, including the area under the receiver operator curve (AUC), precision, Brier score, accuracy, sensitivity, specificity, positive predictive value and negative predictive value. RESULTS: The top three important family-related predictors within the random forest algorithm included family function (importance:42.66), family conflict (importance:42.18), and parental depression (importance:27.21). The most significant family-related risk predictors and protective predictors identified by the logistic regression model were family history of mental illness (OR:2.25) and help-seeking behaviors of mental distress from parents (OR:0.65), respectively. The AUCs of the two models, logistic regression and random forest, were 0.852 and 0.835, respectively. LIMITATIONS: The key limitation is that this cross-sectional survey only enabled the authors to examine predictors that were considered to be proximal rather than distal. CONCLUSIONS: These findings highlight the significance of family-related factors in forecasting NSSI in adolescents. Combining both conventional statistical methods and ML methods to improve risk assessment of NSSI at the family level deserves attention.
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Trastornos Mentales , Conducta Autodestructiva , Humanos , Adolescente , Estudios Transversales , Conducta Autodestructiva/diagnóstico , Conducta Autodestructiva/epidemiología , Análisis de Regresión , Factores de Riesgo , Aprendizaje AutomáticoRESUMEN
Ethyl acetate fraction of Toddalia asiatica was fractionated to yield fifteen previously undescribed prenylated coumarins, asiaticasics A-O (1-15) along with nine (16-24) known derivatives. The structures of these undescribed coumarins were established by spectroscopic analysis and reference data. Biological activity evaluation showed that compound 3 with the IC50 value of 2.830 µM and compound 12 with the IC50 value of 0.682 µM owned anti-inflammatory activity by detecting the rate of lactate dehydrogenase release in pyroptosis J774A.1 cells. The results showed that the expression of Caspase-1 and IL-1ß was decreased in a dose-dependent manner in the compound 12 treatment group, suggesting that compound 12 may reduce pyroptosis by inhibiting NLRP3 inflammasome. To further determine that compound 12 treatment can inhibit macrophage pyroptosis, morphological observation was performed and the results were consistent with the bioactivity evaluation.
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Cumarinas , Rutaceae , Cumarinas/química , Rutaceae/química , Extractos Vegetales/química , Antiinflamatorios/farmacología , Raíces de Plantas/químicaRESUMEN
BACKGROUND: This study examined the moderating role of outdoor time on the relationship between overweight and myopia. METHODS: The data for this study was obtained from a prospective study in Shanghai, where non-myopic children wore wristwear and were followed up for 1 year. Eye examinations were performed at each visit. The modification effect was assessed on the additive scale using multivariable logistic regression, and relative excess risk due to interaction was used to calculate the modification effect. RESULTS: A total of 4683 non-myopic children were included with 32.20% being overweight at baseline. Following a 1-year period, 17.42% of children had myopia. When compared to those who spent <90 minutes outdoors, children who spent >120 had a relative risk of myopia onset that was reduced to 0.61. As time spent outdoors decreased, more risks of myopia onset were identified among overweight children than among normal children, the modification effect on the additive scale was -0.007, with ~70% of this effect attributed to the modifying influence of outdoor time. CONCLUSIONS: Increasing outdoor time can reduce myopia more among overweight children than normal. Future interventions should focus on outdoor activities among overweight children to reduce myopia risks.
Asunto(s)
Miopía , Obesidad Infantil , Niño , Humanos , Preescolar , Estudios de Seguimiento , Estudios Prospectivos , Sobrepeso/complicaciones , Sobrepeso/epidemiología , Obesidad Infantil/epidemiología , Obesidad Infantil/etiología , Actividades Recreativas , China/epidemiología , Miopía/epidemiología , Miopía/etiología , Encuestas y CuestionariosRESUMEN
BACKGROUND: Virtual simulation and face-to-face simulation are effective for clinical judgment training. Rare studies have tried to improve clinical judgment ability by applying virtual simulation and face-to-face simulation together. This study aimed to evaluate the effect of an integrated non-immersive virtual simulation and high-fidelity face-to-face simulation program on enhancing nursing students' clinical judgment ability and understanding of nursing students' experiences of the combined simulation. METHODS: A sequential exploratory mixed-methods study was conducted in a nursing simulation center of a university in Central China. Third-year nursing students (n = 122) taking clinical training in ICUs were subsequentially assigned to the integrated non-immersive virtual simulation and high-fidelity face-to-face simulation program arm (n = 61) or the face-to-face simulation-only arm (n = 61) according to the order in which they entered in ICU training. Clinical judgment ability was measured by the Lasater Clinical Judgment Rubric (LCJR). Focus group interviews were conducted to gather qualitative data. RESULTS: Students in both arms demonstrated significant improvement in clinical judgment ability scores after simulation, and students in the integrated arm reported more improvement than students in the face-to-face simulation-only arm. The qualitative quotes provided a context for the quantitative improvement measured by the LJCR in the integrated arm. Most of the quantitative findings were confirmed by qualitative findings, including the domains and items in the LJCR. The findings verified and favored the effect of the combination of non-immersive virtual simulation and high-fidelity face-to-face simulation integrated program on enhancing nursing students' clinical judgment ability. CONCLUSIONS: The integrated virtual simulation and face-to-face simulation program was feasible and enhanced nursing students' self-reported clinical judgment ability. This integrated non-immersive virtual simulation and high-fidelity face-to-face simulation program may benefit nursing students and newly graduated nurses in the ICU more than face-to-face simulation only.