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Drugs that target immune checkpoint have become the most popular weapon in cancer immunotherapy, yet only have practical benefits for a small percentage of patients. Tumor cells constantly interact with their microenvironment, which is made up of a variety of immune cells as well as endothelial cells and fibroblasts. Immune checkpoint expression and blocked signaling of immune cells in the tumor microenvironment (TME) are key to tumor progression. In this study, we perform deliberation convolution on the TCGA database for human lung, breast, and colorectal cancer to infer crosstalk between immune checkpoint receptors (ICRs) and ligands (ICLs) in TME of pan-carcinogenic solid tumor types, validated by flow cytometry. Analysis of immune checkpoints showed that there was little variation between different tumor types. It showed that CD160, LAG3, TIGIT were found to be highly expressed in CD8+ T cells instead of CD4+ T cells, PD-L1, PD-L2, CD86, LGALS9, TNFRSF14, LILRB4 and other ligands were highly expressed on macrophages, FVR, NECTIN2, FGL1 were highly expressed on Epithelial cells, CD200 was highly expressed in Endothelial cells, and CD80 was highly expressed in CD8 High expression on T cells. Overall, our study provides a new resource for the expression of immune checkpoints in TME on various types of cells. Significance: This study provides immune checkpoint expression of immune cells of multiple cancer types to infer immune mechanisms in the tumor microenvironment and provide ideas for the development of new immune checkpoint-blocking drugs.
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Nano-TiO2 is widely used in various fields such as industry, daily necessities, food and medicine. Previous studies have shown that it can enter mammalian tissues through the digestive tract or respiratory tract and have effects on various organs and systems. However, the effect of nano-TiO2 on the mammalian thyroid gland has not been reported. In this study, we fed SD rats with rutile nano-TiO2 at a dose of 5 mg/kg body weight for 3 weeks, and then examined the thyroid histology and thyroid function of the rats. In vitro experiments were conducted to determine the effects of nano-TiO2 on the viability, apoptosis, inflammatory factors, antioxidant enzymes, and oxidative stress of human thyroid follicular epithelial cells. Histological evidence showed abnormal morphology of rat thyroid follicles and organelle damage in follicular epithelial cells. Nano-TiO2 caused a decrease in the level of sodium/iodide symporter (NIS), an increase in the level of apoptotic protein cleaved-caspase 3, and an increase in the levels of pro-inflammatory factors IL-1ß and TNF-α in rat thyroid tissue. Nano-TiO2 also resulted in increased serum FT4 and TPO-Ab levels. In in vitro experiments, nano-TiO2 reduced the viability of human thyroid follicular cells, downregulated the levels and activities of antioxidant enzymes CAT, GPX1 and SOD, and increased the levels of ROS and MDA caused by oxidative stress. These results indicate that nano-TiO2 damages the structure and function of thyroid follicular epithelial cells through oxidative stress. Long-term exposure to nano-TiO2 could be a potential risk factor for thyroid dysfunction.
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OBJECTIVES: This cross-sectional correlational study aimed to understand nurses' perceived overqualification and work engagement, explore their effects on job satisfaction and provide a theoretical basis for hospital management policies in a public comprehensive tertiary hospital in China. DESIGN: Cross-sectional correlational study. SETTING: The study was conducted in a public comprehensive tertiary hospital in China. The specific location is not disclosed. PARTICIPANTS: 584 nurses participated in the study, with a completion rate of 97.3%. The average age of participants was 34.8±6.7 years, with 96.4% being women. 67.8% held a bachelor's degree or higher, and 71.6% had over 5 years of work experience. PRIMARY AND SECONDARY OUTCOME MEASURES: The Scale of Perceived Overqualification was used to assess nurses' perceptions of their qualifications, demonstrating a high level of reliability with a Cronbach's alpha coefficient of 0.832. Utrecht Work Engagement Scale was used to assess nurses' work engagement, showing internal consistency coefficients (Cronbach's alpha) of 0.683 for the vigour dimension, 0.693 for the dedication dimension and 0.834 for the absorption dimension. Minnesota Satisfaction Questionnaire was used to evaluate nurses' job satisfaction, with internal consistency coefficients (Cronbach's alpha) of 0.765 for the intrinsic satisfaction scale and 0.734 for the extrinsic satisfaction scale. The primary outcome measures included perceived overqualification, work engagement and job satisfaction. RESULTS: The average scores for perceived overqualification, work engagement and job satisfaction were 26.38±3.44, 65.36±14.92 and 74.29±15.04, respectively. Perceived overqualification showed negative correlations with work engagement (r=-0.562, p<0.05) and job satisfaction (r=-0.674, p<0.05). However, work engagement was positively correlated with job satisfaction (r=0.519, p<0.05). Path analysis indicated that perceived overqualification had both a direct (ß=-0.06, p<0.001) and an indirect effect (ß=-0.35, p=0.015) on job satisfaction, with work engagement partially mediating this relationship. CONCLUSION: The perception of overqualification among nurses shows a significant correlation with both their work engagement and job satisfaction. This finding suggests that hospital administrators should pay attention to nurses' perceptions of their qualifications and take measures to enhance their job satisfaction. Furthermore, work engagement acts as a mediator between the perception of overqualification and job satisfaction, emphasising the importance of increasing work engagement. Overall, hospitals can improve nurses' work engagement and job satisfaction by providing career development opportunities, establishing feedback mechanisms and fostering work-life balance. Comprehensive management measures focusing on nurses' career development opportunities and levels of work engagement are necessary. Future research could expand the sample size, employ more diverse research designs and integrate qualitative research methods to further explore the factors influencing nurses' job satisfaction and happiness.
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Satisfação no Emprego , Recursos Humanos de Enfermagem Hospitalar , Engajamento no Trabalho , Humanos , Estudos Transversais , Feminino , Adulto , Masculino , China , Recursos Humanos de Enfermagem Hospitalar/psicologia , Inquéritos e Questionários , Centros de Atenção Terciária , Atitude do Pessoal de SaúdeRESUMO
BACKGROUND: Ischemia-reperfusion (I/R) injury is a major factor in liver damage following hepatic resection and liver transplantation, with anesthetics demonstrating the ability to shield organs from this type of injury. METHODS: Hypoxia-reoxygenation (H/R) was used to create in vitro I/R hepatocyte cell injury models. The CCK-8 assay, flow cytometer, LDH assay, and ELSIA were utilized to assess hepatocyte injury. The in vivo I/R injury rat model was then built. HE and TUNEL staining were used to assess liver tissue damage. Western-blot was applied to assess the activation of the MAPK/ERK pathway. RESULTS: Remimazolam (RMZL) remarkably improved cell viability and decreased apoptosis in H/R-induced hepatocyte injury. RMZL reduced the release of H/R-induced inflammatory mediators (TNF-α and IL-6) as well as LDH levels. We also discovered that RMZL inhibited p38 and ERK1/2 phosphorylation in vivo and in vitro. The stimulation of MAPK/ERK, on the other hand, abolished RMZL's anti-inflammation effects in H/R-induced hepatocyte injury. Furthermore, RMZL reduced liver tissue injury in I/R rats. CONCLUSION: RMZL prevented hepatic I/R damage by inhibiting MAPK/ERK signaling.
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Hepatócitos , Fígado , Sistema de Sinalização das MAP Quinases , Ratos Sprague-Dawley , Traumatismo por Reperfusão , Animais , Traumatismo por Reperfusão/prevenção & controle , Traumatismo por Reperfusão/metabolismo , Ratos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/fisiologia , Masculino , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/metabolismo , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Sobrevivência Celular/efeitos dos fármacos , BenzodiazepinasRESUMO
Introduction: The aim of the study was to evaluate the risk factors for cervical instability in rheumatoid arthritis (RA). Material and methods: Computer searches were conducted in PubMed, Embase, Cochrane Library, the China National Knowledge Infrastructure (CNKI) database, the Wan Fang database, the Chinese Scientific Journal Databases (VIP) database, and the Chinese Biomedical Literature database (CBM) from their establishment until November 2022. Results: A total of 8 articles were included in this study, including 1 cross-sectional study, 5 case-control studies, and 2 cohort study, including 3078 patients with RA. Meta-analysis results showed that: male sex (OR = 1.70, 95% CI: 1.19-2.42), course of disease (OR = 1.72, 95% CI: 1.29-2.28), long-term glucocorticosteroid use (OR = 2.84, 95% CI: 1.97-2.40), Steinbrocker staging (OR = 2.30, 95% CI: 1.61-3.28), disability at baseline (OR = 24.57, 95% CI: 5.51-109.60), peripheral joint destruction (OR = 2.24, 95% CI: 1.56-3.21), Steinbrocker stage I-IV progression to disability (OR = 20.08, 95% CI: 4.18-96.53), and previous joint surgery (OR = 1.54, 95% CI: 1.06-2.26) are the main risk factors for cervical instability in RA. Conclusions: There are many risk factors for cervical instability in RA. In clinical practice, special attention should be paid to patients who are male, have a longer course of disease, have long-term glucocorticosteroid use, have previous joint surgery, have peripheral joint damage, and develop disability in Steinbrocker stage I-IV. Attention should be paid to the high-risk groups mentioned above, and effective measures such as early screening and full monitoring should be taken to prevent the occurrence of cervical instability in RA.
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Objective: The DEP domain-containing 1 (DEPDC1) gene is essential in the development and advancement of different types of cancer. This study is to examine the levels of DEPDC1 in lung adenocarcinoma (LUAD), and to determine its relationship with clinical results and immune response. The goal is to assess its potential as a biomarker and therapeutic target for LUAD. Methods: By comprehensively utilizing the Cancer Genome Atlas (TCGA), gene Expression Synthesis (GEO), UALCAN, cBioPortal, TISIDB databases and online platforms, we conducted a bioinformatics analysis to investigate DEPDC1 gene survival analysis, prognostic diagnosis, prognostic survival, immune cell infiltration, DNA methylation, and the correlation of genetic mutations in LUAD. The results were validated through cell assay and immunohistochemical staining. Results: DEPDC1 shows high levels of expression in the majority of tumors, with its expression being notably elevated in LUAD compablue to normal tissues. The expression of DEPDC1 varies based on the clinical characteristics of patients with LUAD. DEPDC1 expression affects the survival prognosis and prognostic model construction of LUAD patients. In addition, the presence of DEPDC1 is linked to immune infiltration. Various chemokines and chemokine receptors, immunoinhibitors and immune-stimulators in LUAD are significantly correlated with DEPDC1 methylation levels. Cell experiments confirmed through qPCR that the mRNA expression of DEPDC1 in LUAD was markedly elevated in comparison to the normal population, and immunohistochemistry showed positive DEPDC1 expression in LUAD pathological sections. Conclusion: Systematic analysis and experiments have verified that DEPDC1 serves as a biomarker for detecting early, prediction of survival, and evaluation of immune cell infiltration in LUAD.
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Objectives: To analyse the enhanced recovery after surgery approach combined with fine surgical nursing on recovery time, pain, sleep quality and satisfaction with care after lung cancer surgery. METHODS: The cross-sectional study was conducted at the Nanjing Chest Hospital, China, from October 2019 to March 2022, and comprised non-small cell lung cancer patients undergoing single-port video-assisted thoracoscopic surgery. Patients receiving fine surgical nursing in addition to conventional enhanced recovery after surgery formed the intervention group A, while those receiving the conventional enhanced recovery after surgery care alone formed control group B. Intraoperative blood loss, operative time, extubation time and length of stay values were noted for both the groups using standard scales. Nursing satisfaction and the incidence of adverse reactions in the two groups were also noted. Data was analysed using SPSS 23. RESULTS: Of the 99 patients, 46(46.5%) were in group A; 23(50%) males and 23(50%) females with mean age 70.3±4.8 years and mean body mass index 26.76±2.55kg/m2. There were 53(53.5%) patients in group B: 16(30.2%) males and 37(69.8%) females with mean age 69.9±4.4 years and mean body mass index 25.93±2.40kg/m2 (p>0.05). Intraoperative blood loss, operative time, postoperative extubation time and length of stay in group A were lower than those in group B (p<0.05). Pain and sleep quality values in group A were lower, while health status value was higher than group B (p<0.05). Group A had significantly higher nursing satisfaction compared to group B (p<0.05). Conclusion: The use of enhanced recovery after surgery combined with fine surgical nursing in patients with nonsmall cell lung cancer after video-assisted thoracoscopic surgery promoted postoperative recovery.
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Carcinoma Pulmonar de Células não Pequenas , Recuperação Pós-Cirúrgica Melhorada , Tempo de Internação , Neoplasias Pulmonares , Duração da Cirurgia , Cirurgia Torácica Vídeoassistida , Humanos , Masculino , Feminino , Neoplasias Pulmonares/cirurgia , Idoso , Estudos Transversais , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Tempo de Internação/estatística & dados numéricos , Dor Pós-Operatória , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Pessoa de Meia-Idade , Qualidade do Sono , Satisfação do Paciente/estatística & dados numéricos , Extubação , China/epidemiologia , Enfermagem Perioperatória/métodosRESUMO
Cell division cycle 42 (CDC42) regulates the progression of leukemia via mediating proliferation and immune evasion of malignant cells. The study aimed to investigate the correlation of CDC42 with clinical features, treatment response, event-free survival (EFS) and overall survival (OS) in adult Philadelphia chromosome negative acute lymphoblastic leukemia (Ph- ALL) patients. CDC42 expression in bone marrow mononuclear cells was detected in 78 adult Ph- ALL patients and 10 donors using real-time reverse transcriptase-polymerase chain reaction. CDC42 was increased in adult Ph- ALL patients compared with donors (p < .001). Besides, elevated CDC42 was linked with pro-B ALL or early-T ALL (p = .038) and white blood cell (WBC) elevation at diagnosis (p = .025). Fifty (64.1%) and 23 (29.5%) patients had complete remission (CR) at 1 month and minimal residual disease (MRD) after CR, respectively. CDC42 was inversely associated with CR at 1 month (p = .034), but not MRD after CR (p = .066). Concerning survival, patients with CDC42 ≥ 3.310 (cut by median value in patients) showed a shortened EFS (p = .006) and OS (p = .036) compared to those with CDC42 < 3.310. In detail, patients with CDC42 ≥ 3.310 and CDC42 < 3.310 had 5-year EFS rate of 29.9% and 45.4%, and 5-year OS rate of 39.4% and 63.6%, correspondingly. Further multivariate Cox's regression analyses revealed that CDC42 ≥ 3.310 was independently related to shorter EFS (hazard ratio = 2.933, p = .005). Elevated CDC42 is related with pro-B ALL or early-T ALL, WBC elevation at diagnosis, unfavorable treatment response and worse survival in adult Ph- ALL patients.
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Neoplasia Residual , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras , Proteína cdc42 de Ligação ao GTP , Humanos , Adulto , Feminino , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Pessoa de Meia-Idade , Proteína cdc42 de Ligação ao GTP/metabolismo , Proteína cdc42 de Ligação ao GTP/genética , Adolescente , Idoso , Adulto Jovem , Indução de Remissão , Prognóstico , Resultado do Tratamento , Intervalo Livre de DoençaRESUMO
Purpose: To investigate the knowledge, attitudes and practices (KAP) among college students toward physical literacy during COVID-19 school closure. Patients and Methods: This web-based cross-sectional study was conducted between December 9th, 2022 and December 24th, 2022 among college students during COVID-19 school closure. A self-designed questionnaire was developed to collect demographic information of the college students, and assess their KAP toward physical literacy. Results: A total of 969 students were recruited, with mean age of 18.73±0.97 years. The majority were male (54.70%), urban residents (78.02%), majoring in engineering (58.00%), and having exercise habits (61.09%). The mean KAP scores were 6.57±0.95, 32.63±4.07, and 27.06±7.23, respectively. Positive associations were identified between knowledge and attitude (OR = 2.01, 95% CI: 1.52-2.66, P < 0.001), and between attitude and practice (OR = 1.17, 95% CI: 1.12-1.22, P < 0.001). A bachelor's degree and being in the sophomore year were positively associated with knowledge (OR = 1.51-4.05, all P < 0.05). Urban residence and being in the sophomore year were negatively associated with attitude (OR = 0.43-0.59, all P < 0.05), while having daily exercise habits showed the opposite trend (OR = 1.85, 95% CI: 1.33-2.57, P < 0.001). Father's education level of high school and technical secondary school (OR = 0.58, 95% CI: 0.37-0.93, P = 0.023) and having daily exercise habits (OR = 3.88, 95% CI: 2.72-5.55, P < 0.001) were associated with practice. Conclusion: College students had sufficient knowledge, moderate attitudes and negative practices towards physical literacy during COVID-19 school closure. The findings hold significant potential for developing educational programs, fostering healthier lifestyles and promoting mental well-being among college students during public health outbreaks.
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BACKGROUND AND AIMS: We aimed to investigate the correlation and to explore which MAFLD subtypes have the greatest influence on progression of arterial stiffness risk. METHODS AND RESULTS: Using data from a health examination-based cohort, a total of 12,129 participants who underwent two repeated health examinations that included brachial-ankle pulse wave velocity (baPWV) from 2012 to 2020 were enrolled. Participants were separated into non-MAFLD, overweight/obese (OW-MAFLD), lean/normal weight (lean-MAFLD) and diabetes (DM-MAFLD) groups. Among the participants with a median follow-up of 2.17 years, 4511 (37.2%) participants had MAFLD at baseline, among which 3954 (87.7%), 123 (2.7%), and 434 (9.6%) were OW-, lean- and DM-MAFLD, respectively. Analyses using linear regression models confirmed that compared with the non-MAFLD group, the elevated baPWV change rates (cm/s/year) were 12.87 (8.81-16.94), 25.33 (7.84-42.83) and 38.49 (27.88-49.10) in OW, lean and DM-MAFLD, respectively, while the increased change proportions (%) were 1.53 (1.10-1.95), 3.56 (1.72-5.40) and 3.94 (2.82-5.05), respectively. Similar patterns were observed when these two baPWV parameters were transformed in the form of the greatest increase using Cox proportional hazards model analyses. Furthermore, the risk of arterial stiffness progression across MAFLD subtypes presented a significant, gradient, inverse relationship in the order of DM-, lean-, OW with metabolic abnormalities (MA)-, and OW without MA-MAFLD. CONCLUSION: MAFLD, especially DM-MAFLD and lean-MAFLD, was significantly associated with arterial stiffness progression, providing evidence that stratification screening and surveillance strategies for CVD risk have important clinical implications.
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Índice Tornozelo-Braço , Progressão da Doença , Hepatopatia Gordurosa não Alcoólica , Rigidez Vascular , Humanos , Masculino , Feminino , Estudos Prospectivos , Pessoa de Meia-Idade , Adulto , Medição de Risco , Fatores de Tempo , Fatores de Risco , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Análise de Onda de Pulso , Prognóstico , Magreza/fisiopatologia , Magreza/epidemiologia , Magreza/diagnóstico , Obesidade/fisiopatologia , Obesidade/epidemiologia , Obesidade/diagnóstico , IdosoRESUMO
Studying the regulatory mechanism and clinical application of G2 and S phase-expressed protein 1 (GTSE1) genes in lung adenocarcinoma (LUAD). LUAD data was obtained from The Cancer Genome Atlas (TCGA) database, and differentially expressed genes (DEGs) were derived by analyzing expression data using R software. Survival analysis was performed to identify genes associated with LUAD, and among them, a target gene for LUAD was identified. Further analysis of the gene expression profiling interactive analysis database revealed differences in gene expression between normal and tumor tissues of LUAD patients. Disease free survival (DFS) and overall survival (OS) of the GTSE1 genes in LUAD were compared. The study conducted a GSEA analysis of GTSE1 expression and further investigated the relationships between GTSE1 expression and the survival time of LUAD patients at different pathological stages. The correlations between OS and GTSE1 gene expression were explored based on different treatments. Additionally, the correlation between the GTSE1 gene and immune infiltration was analyzed. The results indicated that the expression of GTSE1 was significantly higher in tumor tissues of LUAD compared to normal tissues. Furthermore, patients with high GTSE1 expression had significantly lower survival rates for OS and DFS compared to patients with low expression of GTSE1. The GSEA analysis of GTSE1 revealed its involvement in LUAD through the Reactome unwinding of DNA and Biocarta ranms pathway. In patients with LUAD at the pathological T2 stage, low expression of GTSE1 was associated with longer survival time. Furthermore, LUAD patients with low GTSE1 expression who underwent surgery without chemotherapy exhibited a longer survival time. The GTST1 gene, identified as a target gene of LUAD, was validated through cell experiments and pathological sections. GTSE1 can be used as a marker and therapeutic target for LUAD. The survival of LUAD patients can be improved by reducing the expression of GTSE1.
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Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Fase S , Prognóstico , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Pulmonares/patologia , Proteínas Associadas aos Microtúbulos/metabolismoRESUMO
The deliberate pork adulteration with lymph nodes is a common adulteration phenomenon, and it poses a serious threat to public health and food safety. An untargeted metabolomics and lipidomics approach based on ultrahigh performance liquid chromatography coupled with linear ion trap quadrupole-Orbitrap high resolution mass spectrometry (MS) was used to distinguish lymph nodes from minced pork. The principal component analysis and orthogonal projection to latent structures discriminant analysis models were established with the good of fitness and predictivity. The results showed that there were significant differences in metabolites and lipids between lymph nodes and pork. A total of 16 significantly differentiated metabolites were identified, of which 1-palmitoylglycerophosphocholine, 12,13-dihydroxy-9-octadecenoic acid, and prostaglandin E2 (PGE2) were positively correlated with lymph node content and were identified as potential markers of lymph nodes. These three markers were combined to create a binary logistic regression model, and a combined-factor exceeding 0.75 was ultimately identified as a marker for pork adulteration with lymph nodes. The desorption electrospray ionization-MS images showed that PGE2 had a higher relative abundance in the lymph node region than in adjacent non-lymph node regions, indicating that PGE2 was a marker that contributed significantly for identifying lymph nodes adulteration into pork. Our results provide a theoretical basis for identifying lymph node adulteration, which will contribute to combating fraud in the meat industry.
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Carne de Porco , Carne Vermelha , Animais , Suínos , Cromatografia Líquida de Alta Pressão/métodos , Lipidômica , Cromatografia Líquida/métodos , Metabolômica/métodosRESUMO
Intestinal barrier integrity is essential for normal nutrient digestion and absorption and disease resistance. This study aims to investigate how fermentation affects the ameliorative effect of bee pollen on the intestinal barrier dysfunction stimulated by interferon-γ and tumor necrosis factor (IFN-γ/TNF-α) cytokines. The results indicated that fermentation enhances the alleviating effect of bee pollen on intestinal barrier dysfunction (including elevated trans epithelial electrical resistance and decreased paracellular permeability). In addition, fermented bee pollen (FBP) significantly decreased (p < 0.05) the secretion levels of interleukin (IL)-6, IL-8, and IL-1ß and expression of cyclooxygenase (COX)-2 protein in intestinal barrier cells. Furthermore, fermentation improved the ability of bee pollen to up-regulate the expression of tight junction proteins including zonula occludens (ZO)-1, occluding, and claudin-1. Notably, FBP showed stronger ability to inhibit the expression of nuclear factor kappa-B (NF-κB) mediated myosin light chain kinase (MLCK) and myosin light chain (MLC) signaling pathway associated with phosphorylated proteins. Overall, our results indicated that fermentation enhances the protective effect of bee pollen on the intestinal barrier, and FBP has promising potential to be used as a novel functional food to protect the intestinal barrier.
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Quinase de Cadeia Leve de Miosina , NF-kappa B , Humanos , Animais , Abelhas , NF-kappa B/metabolismo , Quinase de Cadeia Leve de Miosina/metabolismo , Células CACO-2 , Fermentação , Mucosa Intestinal/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Transdução de Sinais , PólenRESUMO
BACKGROUND AND AIM: Remnant cholesterol (remnant-C) mediates the progression of major adverse cardiovascular events. It is unclear whether remnant-C, and particularly cumulative exposure to remnant-C, is associated with nonalcoholic fatty liver disease (NAFLD). This study aimed to explore whether remnant-C, not only baseline but cumulative exposure, can be used to independently evaluate the risk of NAFLD. METHODS: This study included 1 cohort totaling 21,958 subjects without NAFLD at baseline who underwent at least 2 repeated health checkups and 1 sub-cohort totaling 2,649 subjects restricted to those individuals with at least 4 examinations and no history of NAFLD until Exam 3. Cumulative remnant-C was calculated as a timeweighted model for each examination multiplied by the time between the 2 examinations divided the whole duration. Cox regression models were performed to estimate the association between baseline and cumulative exposure to remnant-C and incident NAFLD. RESULTS: After multivariable adjustment, compared with the quintile 1 of baseline remnant-C, individuals with higher quintiles demonstrated significantly higher risks for NAFLD (hazard ratio [HR] 1.48, 95%CI 1.31-1.67 for quintile 2; HR 2.07, 95%CI 1.85-2.33 for quintile 3; HR 2.55, 95%CI 2.27-2.88 for quintile 4). Similarly, high cumulative remnant-C quintiles were significantly associated with higher risks for NAFLD (HR 3.43, 95%CI 1.95-6.05 for quintile 2; HR 4.25, 95%CI 2.44-7.40 for quintile 3; HR 6.29, 95%CI 3.59-10.99 for quintile 4), compared with the quintile 1. CONCLUSION: Elevated levels of baseline and cumulative remnant-C were independently associated with incident NAFLD. Monitoring immediate levels and longitudinal trends of remnant-C may need to be emphasized in adults as part of NAFLD prevention strategy.
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Hepatopatia Gordurosa não Alcoólica , Adulto , Humanos , Estudos de Coortes , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Colesterol , Modelos de Riscos Proporcionais , Fatores de RiscoRESUMO
Purpose: This study investigated the mechanism of TSF in treating DN through network pharmacology, molecular docking, and experimental validation. Methods: To identify critical active ingredients, targets, and DN genes in TSF, multiple databases were utilized for screening purposes. The drug-compound-target network was constructed using Cytoscape 3.9.1 software for network topological analysis. The protein interaction relationship was analyzed using the String database platform. Metascape database conducted enrichment analysis on the key targets using Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes. The renoprotective effect was evaluated using a mouse model of diabetic nephropathy (db/db mice) that occurred spontaneously. Validation of the associated targets and pathways was performed using Western Blot (WB), Polymerase Chain Reaction (PCR), and Immunohistochemical methods (IHC). Results: The network analysis showed that the TSF pathway network targeted 24 important targets and 149 significant pathways. TSF might have an impact by focusing on essential objectives such as TP53, PTEN, AKT1, BCL2, BCL2L1, PINK-1, PARKIN, LC3B, and NFE2L2, along with various growth-inducing routes. Our findings demonstrated that TSF effectively repaired the structure of mitochondria in db/db mice. TSF greatly enhanced the mRNA levels of PINK-1. WB and IHC findings indicated that TSF had a notable impact on activating the PINK-1/PARKIN signaling pathway in db/db mice, significantly increasing LC3 and NRF2 expression. Conclusion: Our results indicate that TSF effectively addresses DN by activating the PINK-1/PARKIN signaling pathway and enhancing Mitochondrion structure in experimental diabetic nephropathy.
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Systemic therapies-based combination treatments have been developed rapidly in patients with advanced hepatocellular carcinoma (HCC). However, there are still a few patients not applicable to any recommended therapies, making it considerable to try new therapeutic options. Among them, anlotinib, a new oral tyrosine kinase inhibitor, is being widely used for many advanced malignancies. We present the first case of the antitumor effect of complete remission by anlotinib combined with an anti-programmed cell death protein 1 antibody, sintilimab, in a patient with advanced HCC. In April 2020, a 51-year-old male patient was diagnosed with large HCC and underwent hepatectomy with R0 resection. Two months later, he was admitted to our hospital because of a tumor relapse with multiple liver and lung metastases. After the failure of comprehensive treatment containing sorafenib, camrelizumab and transhepatic arterial chemotherapy and embolization, 2 months after tumor relapse, the patient started to receive anlotinib and sintilimab. The multiple tumor nodules were remarkable repressed both in the liver and lung. Six months after anlotinib plus sintilimab treatment, there were no residual tumors, and the alpha-fetoprotein level was decreased from 2310.9â mg/L to normal. Also, the patient continued to receive anlotinib to date. In subsequent follow-up visits until now, there was no sign of recurrence found on imaging. Anlotinib is a promising alternative for patients insensitive to the first-line targeted drugs. More clinical studies should be conducted to further broaden the clinical indications of anlotinib and immunotherapy in patients with HCC.
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Anticorpos Monoclonais Humanizados , Carcinoma Hepatocelular , Indóis , Neoplasias Hepáticas , Quinolinas , Masculino , Humanos , Pessoa de Meia-Idade , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , RecidivaRESUMO
In potato, stolon swelling is a complex and highly regulated process, and much more work is needed to fully understand the underlying mechanisms. We identified a novel tuber-specific basic helix-loop-helix (bHLH) transcription factor, StbHLH93, based on the high-resolution transcriptome of potato tuber development. StbHLH93 is predominantly expressed in the subapical and perimedullary region of the stolon and developing tubers. Knockdown of StbHLH93 significantly decreased tuber number and size, resulting from suppression of stolon swelling. Furthermore, we found that StbHLH93 directly binds to the plastid protein import system gene TIC56 promoter, activates its expression, and is involved in proplastid-to-amyloplast development during the stolon-to-tuber transition. Knockdown of the target TIC56 gene resulted in similarly problematic amyloplast biogenesis and tuberization. Taken together, StbHLH93 functions in the differentiation of proplastids to regulate stolon swelling. This study highlights the critical role of proplastid-to-amyloplast interconversion during potato tuberization.
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Solanum tuberosum , Solanum tuberosum/genética , Solanum tuberosum/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Tubérculos/genética , Tubérculos/metabolismo , Transcriptoma , Plastídeos/metabolismo , Regulação da Expressão Gênica de PlantasRESUMO
Background/Objective: The aim of this study was to examine the effects of school-based intervention integrating physical literacy (PL) into active school recesses (ASR) on physical fitness (i.e., body composition, 20-m shuttle run, 50-m run, rope skipping, sit and reach, handgrip) and academic achievement (i.e., academic result of Chinese and Mathematics) in Chinese children. Methods: A total of 357 children (mean age: 7.8 ± 0.7 years; boys: 50.4%) were recruited from two schools and these two schools were randomly assigned as the intervention group (IG) and the control group (CG), respectively. The IG consisted of 155 children (mean age: 7.9 ± 0.7 years, boys: 51.0%), and 202 children (mean age: 7.8 ± 0.7 years; boys: 50%) were allocated to the CG. Children in the IG received a 10-week intervention integrating PL that was conducted during ASR. In the CG, children's regular school activity was remained during the intervention period. Generalized estimating equation was performed to compare the levels of physical fitness and academic achievement between the IG and the CG after intervention. Results: Regarding physical fitness, there was a significant group × time interaction on 20-m shuttle run (ß = -3.89, 95% CI [-5.08; -2.71], p < 0.001) and handgrip (ß = -0.70, 95% CI [-1.20; -0.20], p = 0.006). After intervention, children in the IG had a greater increase than the CG (p < 0.001) in terms of 20-m shuttle run and handgrip. In addition, the post-test analysis indicated that performance of children in the IG was significantly greater than those in the CG (20-m shuttle run: p < 0.001, handgrip: p = 0.002). There was a significant group × time interaction on academic result of Chinese (ß = -1.21, 95% CI [-1.91; -0.56], p = 0.001) and academic result of Mathematics (ß = 16.71, 95% CI [15.14; 18.143], p < 0.001). Statistically significant positive difference in post-test was observed in academic result of Mathematics between the IG and the CG (p = 0.012). Conclusion: The results of this intervention study indicate that intervention integrating PL into ASR could bring a promising effect on physical fitness and academic achievement in children. It is recommended that future studies are necessary to assess the effects of ASR-based PL intervention on physical and cognitive outcomes using a wide range of sample.
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China ranks first in the production and harvest area of walnut (Juglans regia L.) worldwide. Currently, the poor health and low yield of walnut caused by pathogen infection is of concern. In 2022, severe walnut leaf spot disease was observed on the seedlings of four walnut nurseries (0.08 to 0.23 ha) in Liaocheng, Shandong, China, with an average incidence of 48.6% (from 34.6% to 65.3% on the cultivar Xiangling). From August to October, leaf spots mainly appeared on the edges of the leaflets, and occasionally between veins. The lesions were initially soft and rotten, and then light brown, round to semi-circular. Subsequently, the adjacent lesions fused, and the edges of the leaflets and entire leaflets showed symptoms of browning and wilting. For pathogen isolation, five leaflets with representative symptoms from one of the nurseries were collected and wiped three times with sterile absorbent cotton dipped in 75% alcohol and washed with distilled water. Leaflet pieces at the junction of the lesion and healthy tissues were removed, crushed in a sterile mortar, and soaked in a small amount of distilled water for 10 min. The diseased tissue suspension was streaked on a nutrient agar medium (NA) with a sterile inoculation ring and incubated at 28°C for 24 to 72 h. The bacterial colonies obtained were further cultured on NA. The purified colonies were uniform in shape, round, and yellow, with a raised, shiny surface and smooth margin. The isolates were Gram-negative, and the electron microscope analysis showed that the pathogens were short rods (0.35 to 0.52 × 0.90 to 1.24 µm, average = 0.44 ± 0.05 × 1.08 ± 0.11 µm, n = 25). For bacterial species identification, a single-colony culture was subjected to genomic DNA extraction and gene amplification and sequencing of 16S rRNA, rpoD, and gyrB. The universal primers 27F/1492R (Lane 1991) were used to amplify the 16S rRNA gene and the specific primers 70F/70R and UP-1E/APrU (Yamamoto et al. 2000) were used to amplify the rpoD and gyrB genes, respectively. In the BLAST analysis, the 16S rRNA sequence (GenBank OR195734) of the isolate shared 99% similarity (1409/1410 bp) with Pseudomonas oryzihabitans strain IAM 1568T (AM262973.1), and the rpoD (OR709708) and gyrB (OR709707) sequences showed >98% identity to rpoD (707/717 bp; FN554494.1) and gyrB (787/801 bp; FN554210.1) of P. oryzihabitans strain LMG 7040T. Based on the above results, the isolated bacterium was identified as P. oryzihabitans. For the pathogenicity test, healthy leaflets from 10 two-year-old potted walnut seedlings (cv. Xiangling) were used as inoculation materials. The leaflets were punctured with a sterile inoculation needle of 0.4 mm, and three small holes on each leaflet at an interval of about 5 mm were covered with a piece of sterile cotton. A bacterial suspension (1 ml) at 107 CFU/ml was spread onto the cotton, and wrapped with plastic film for 24 h. Water was used as a negative control. The inoculations were performed five times. Plants were grown outdoors at a daily average temperature of 22°C with relative humidity over 45%. Two days after inoculation, the disease began to develop in the leaflets with similar symptoms to those observed in the field. In contrast, control plants remained healthy and symptomless. Bacteria were reisolated from the inoculated walnut plants, and the morphology and 16S rRNA gene sequences of the isolates were the same as those of the original strains. Since it was discovered as an opportunistic human pathogenic bacterium in the 1970s (Keikha et al. 2019), P. oryzihabitans has also been shown to cause certain plant diseases, such as panicle blight and grain discoloration on rice (Hou et al. 2020), fruit black rot on prickly ash (Liu et al. 2021), and stem and leaf rot on muskmelon (Li et al. 2021). As far as we know, this is the first report of P. oryzihabitans causing walnut leaf spot disease in China. Leaf spot caused by P. oryzihabitans may be a threat to walnut cultivation, and this report of its occurrence is the first step in determining potential spread and effective control measures.
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BACKGROUND: The purpose of this study was to construct a preterm birth prediction model based on electronic health records and to provide a reference for preterm birth prediction in the future. METHODS: This was a cross-sectional design. The risk factors for the outcomes of preterm birth were assessed by multifactor logistic regression analysis. In this study, a logical regression model, decision tree, Naive Bayes, support vector machine, and AdaBoost are used to construct the prediction model. Accuracy, recall, precision, F1 value, and receiver operating characteristic curve, were used to evaluate the prediction performance of the model, and the clinical application of the model was verified. RESULTS: A total of 5411 participants were included and were used for model construction. AdaBoost model has the best prediction ability among the five models. The accuracy of the model for the prediction of "non-preterm birth" was the highest, reaching 100%, and that of "preterm birth" was 72.73%. CONCLUSIONS: By constructing a preterm birth prediction model based on electronic health records, we believe that machine algorithms have great potential for preterm birth identification. However, more relevant studies are needed before its application in the clinic.