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To explore the clinical characteristics of patients infected with SARS-CoV-2 nationwide, especially the effect factors of asymptomatic infection and disappearance of clinical symptoms. A total of 66,448 COVID-19 patients in China who have been diagnosed by nucleic acid test or rapid antigen test were surveyed online (December 24, 2022 to January 16, 2023). Our cross-sectional study used descriptive analyses and binary Logistics regression model to assess the correlation between the clinical characteristics and relative factors, including age, gender, pre-existing conditions, reinfection, vaccination and treatment. A total of 64,515 valid questionnaires were collected. Among included participants, 5969 of which were asymptomatic. The symptoms were mainly upper respiratory symptoms, including dry and itchy throat (64.16%), sore throat (59.95%), hoarseness (57.90%), nasal congestion (53.39%). In binary Logistics regression model, we found that male, no pre-existing conditions, reinfection and vaccination have positive correlations with the appearance of asymptomatic COVID-19 patients. In Cox proportional-hazards regression model, considering all clinical symptoms disappeared in 14 days as outcome, we found that ≤ 60 years old, male, no pre-existing conditions, vaccination and adopted treatment have positive correlations with rapid amelioration of clinical symptoms in COVID-19 patients. The clinical symptoms of the participants were mainly upper respiratory symptoms which were according with the infection of Omicron variant. Factors including age, gender, pre-existing conditions and reinfection could influence the clinical characteristics and prognosis of COVID-19 patients. Importantly, vaccination has positive significance for the prevention and treatment of COVID-19. Lastly, the use of Chinese medicine maybe beneficial to COVID-19 patients, however, reasonable guidance is necessary.
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Infections asymptomatiques , COVID-19 , SARS-CoV-2 , Humains , COVID-19/épidémiologie , COVID-19/diagnostic , COVID-19/virologie , Mâle , Femelle , Chine/épidémiologie , Études transversales , Adulte d'âge moyen , Adulte , Infections asymptomatiques/épidémiologie , SARS-CoV-2/isolement et purification , Sujet âgé , Jeune adulte , AdolescentRÉSUMÉ
Bromodomain-containing protein 4 (BRD4) has emerged as a promising therapeutic target in prostate cancer (PCa). Understanding the mechanisms of BRD4 stability could enhance the clinical response to BRD4-targeted therapy. In this study, we report that BRD4 protein levels are significantly decreased during mitosis in a PLK1-dependent manner. Mechanistically, we show that BRD4 is primarily phosphorylated at T1186 by the CDK1/cyclin B complex, recruiting PLK1 to phosphorylate BRD4 at S24/S1100, which are recognized by the APC/CCdh1 complex for proteasome pathway degradation. We find that PLK1 overexpression lowers SPOP mutation-stabilized BRD4, consequently rendering PCa cells re-sensitized to BRD4 inhibitors. Intriguingly, we report that sequential treatment of docetaxel and JQ1 resulted in significant inhibition of PCa. Collectively, the results support that PLK1-phosphorylated BRD4 triggers its degradation at M phase. Sequential treatment of docetaxel and JQ1 overcomes BRD4 accumulation-associated bromodomain and extra-terminal inhibitor (BETi) resistance, which may shed light on the development of strategies to treat PCa.
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Azépines , Protéines du cycle cellulaire , Docetaxel , Résistance aux médicaments antinéoplasiques , Mitose , , Tumeurs de la prostate , Protein-Serine-Threonine Kinases , Protéines proto-oncogènes , Facteurs de transcription , Triazoles , Humains , Protéines du cycle cellulaire/métabolisme , Mâle , Tumeurs de la prostate/métabolisme , Tumeurs de la prostate/anatomopathologie , Tumeurs de la prostate/traitement médicamenteux , Tumeurs de la prostate/génétique , Phosphorylation , Protéines proto-oncogènes/métabolisme , Mitose/effets des médicaments et des substances chimiques , Protein-Serine-Threonine Kinases/métabolisme , Facteurs de transcription/métabolisme , Résistance aux médicaments antinéoplasiques/effets des médicaments et des substances chimiques , Lignée cellulaire tumorale , Azépines/pharmacologie , Triazoles/pharmacologie , Docetaxel/pharmacologie , Protéolyse/effets des médicaments et des substances chimiques , Protéines nucléaires/métabolisme , Animaux , Protéine-kinase CDC2/métabolisme , Souris nude , Souris , Proteasome endopeptidase complex/métabolisme , Protéines contenant un bromodomaine , Protéines de répressionRÉSUMÉ
PLK1 (Polo-like kinase 1) plays a critical role in the progression of lung adenocarcinoma (LUAD). Recent studies have unveiled that targeting PLK1 improves the efficacy of immunotherapy, highlighting its important role in the regulation of tumor immunity. Nevertheless, our understanding of the intricate interplay between PLK1 and the tumor microenvironment (TME) remains incomplete. Here, using genetically engineered mouse model and single-cell RNA-seq analysis, we report that PLK1 promotes an immunosuppressive TME in LUAD, characterized with enhanced M2 polarization of tumor associated macrophages (TAM) and dampened antigen presentation process. Mechanistically, elevated PLK1 coincides with increased secretion of CXCL2 cytokine, which promotes M2 polarization of TAM and diminishes expression of class II major histocompatibility complex (MHC-II) in professional antigen-presenting cells. Furthermore, PLK1 negatively regulates MHC-II expression in cancer cells, which has been shown to be associated with compromised tumor immunity and unfavorable patient outcomes. Taken together, our results reveal PLK1 as a novel modulator of TME in LUAD and provide possible therapeutic interventions.
Sujet(s)
Adénocarcinome pulmonaire , Protéines du cycle cellulaire , Tumeurs du poumon , , Protein-Serine-Threonine Kinases , Protéines proto-oncogènes , Analyse sur cellule unique , Microenvironnement tumoral , Animaux , Humains , Souris , Adénocarcinome pulmonaire/génétique , Adénocarcinome pulmonaire/immunologie , Adénocarcinome pulmonaire/anatomopathologie , Présentation d'antigène/génétique , Protéines du cycle cellulaire/génétique , Protéines du cycle cellulaire/métabolisme , Lignée cellulaire tumorale , Chimiokine CXCL2/génétique , Chimiokine CXCL2/métabolisme , Régulation de l'expression des gènes tumoraux , Antigènes d'histocompatibilité de classe II/génétique , Antigènes d'histocompatibilité de classe II/métabolisme , Tumeurs du poumon/génétique , Tumeurs du poumon/immunologie , Tumeurs du poumon/anatomopathologie , Protein-Serine-Threonine Kinases/génétique , Protein-Serine-Threonine Kinases/métabolisme , Protéines proto-oncogènes/génétique , Protéines proto-oncogènes/métabolisme , Microenvironnement tumoral/immunologie , Microenvironnement tumoral/génétique , Macrophages associés aux tumeurs/immunologie , Macrophages associés aux tumeurs/métabolismeRÉSUMÉ
The tree shrew (Tupaia belangeri) is a promising emerging model organism in biomedical studies, notably due to their evolutionary proximity to primates. To enhance our understanding of how DNA methylation is implicated in regulation of gene expression and the X chromosome inactivation (XCI) in tree shrew brains, here we present their first genome-wide, single-base-resolution methylomes integrated with transcriptomes from prefrontal cortices. We discovered both divergent and conserved features of tree shrew DNA methylation compared to that of other mammals. DNA methylation levels of promoter and gene body regions are negatively correlated with gene expression, consistent with patterns in other mammalian brains studied. Comparing DNA methylation patterns of the female and male X chromosomes, we observed a clear and significant global reduction (hypomethylation) of DNA methylation across the entire X chromosome in females. Our data suggests that the female X hypomethylation does not directly contribute to the gene silencing of the inactivated X chromosome nor does it significantly drive sex-specific gene expression of tree shrews. However, we identified a putative regulatory region in the 5' end of the X inactive specific transcript (Xist) gene, a key gene for XCI, whose pattern of differential DNA methylation strongly relate to its differential expression between male and female tree shrews. We show that differential methylation of this region is conserved across different species. Moreover, we provide evidence suggesting that the observed difference between human and tree shrew X-linked promoter methylation is associated with the difference in genomic CpG contents. Our study offers novel information on genomic DNA methylation of tree shrews, as well as insights into the evolution of X chromosome regulation in mammals.
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Aims: This study aimed to evaluate the global research trend in the prevention and treatment of cardiotoxicity caused by anthracyclines from 2000 to 2023, and to explore international cooperation, research hotspots, and frontier trends. Methods: The articles on the prevention and treatment of anthracycline-induced cardiotoxicity published from 2000 to 2023 were searched by Web of Science. The bibliometrics software CiteSpace was used for visual analysis of countries, institutions, journals, authors, cited authors, cited references, and keywords. Results: This study analyzed the current status of global research on the prevention and treatment of cardiotoxicity caused by anthracyclines. A total of 3,669 papers were searched and 851 studies were included. The number of publications increased gradually throughout the years. Cardiovascular Toxicology (15) is the journal with the most publications. Circulation (547) ranked first among cited journals. In this field, the country with the most publications is the United States (229), and the institution with the most publications is Charles Univ Prague (18). In the analysis of the authors, Tomas S (10) ranked first. Cardinale D (262) ranked first among cited authors. In the ranking of cited literature frequency, the article ranked first is "Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy" (121). The keywords "heart failure" (215) and "oxidative stress" (212) were the most frequent. "Enalapril", "inflammation", "cell death", "NF-κB" and "Nrf2" were the advanced research contents in 2019-2023. Conclusions: This study provided valuable information for cardio-oncology researchers to identify potential collaborators and institutions, discover hot topics, and explore new research directions. The prevention and treatment of anthracycline-induced cardiotoxicity focuses on early detection and timely treatment. The results of the current clinical studies on the treatment of anthracycline-induced cardiotoxicity are contradictory, and more studies are needed to provide more reliable clinical evidence in the future.
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BACKGROUND: Patients with hepatocellular carcinoma (HCC) who undergo transarterial chemoembolization (TACE) may have varied outcomes based on their liver function and tumor burden diversity. This study aims to assess the prognostic significance of the tumor burden score (TBS) in these patients and develop a prognostic model for their overall survival. METHODS: The study involved a retrospective analysis of 644 newly diagnosed HCC patients undergoing TACE treatment. The individuals were assigned randomly to a training cohort (n = 452) and a validation cohort (n = 192). We utilized a multivariate Cox proportional risk model to identify independent preoperative predictive factors. We then evaluated model performance using the area under the curve (AUC), consistency index (c-index), calibration curve, and decision curve analysis (DCA) methods. RESULTS: The multivariate analysis revealed four prognostic factors associated with overall survival: Tumor Burden Score, Tumor Extent, Types of portal vein invasion (PVI), and Child-Pugh score. The total score was calculated based on these factors. The model demonstrated strong discriminative ability with high AUC values and c-index, providing high net clinical benefits for patients. Based on the model's scoring results, patients were categorized into high, medium, and low-risk groups. These results were validated in the validation cohort. CONCLUSIONS: The tumor burden score shows promise as a viable alternative prognostic indicator for assessing tumor burden in cases of HCC. The new prognostic model can place patients in one of three groups, which will estimate their individual outcomes. For high-risk patients, it is suggested to consider alternative treatment options or provide the best supportive care, as they may not benefit significantly from TACE treatment.
Sujet(s)
Carcinome hépatocellulaire , Chimioembolisation thérapeutique , Tumeurs du foie , Humains , Carcinome hépatocellulaire/thérapie , Tumeurs du foie/thérapie , Pronostic , Études rétrospectives , Charge tumoraleRÉSUMÉ
Cirrhosis is an aggressive disease, and over 80 % of liver cancer patients are complicated by cirrhosis, which lacks effective therapies. Transplantation of mesenchymal stem cells (MSCs) is a promising option for treating liver cirrhosis. However, this therapeutic approach is often challenged by the low homing ability and short survival time of transplanted MSCs in vivo. Therefore, a novel and efficient cell delivery system for MSCs is urgently required. This new system can effectively extend the persistence and duration of MSCs in vivo. In this study, we present novel porous microspheres with microfluidic electrospray technology for the encapsulation of bone marrow-derived MSCs (BMSCs) in the treatment of liver cirrhosis. Porous microspheres loaded with BMSCs (Mi-BMSCs) exhibit good biocompatibility and demonstrate better anti-inflammatory properties than BMSCs alone. Mi-BMSCs significantly increase the duration of BMSCs and exert potent anti-inflammatory and anti-fibrosis effects against CCl4 and TAA-induced liver cirrhosis by targeting the TGF-ß/Smad signaling pathway to ameliorate cirrhosis, which highlight the potential of Mi-BMSCs as a promising therapeutic approach for early liver cirrhosis.
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Despite continued advances in prevention and treatment strategies, cardiovascular diseases (CVDs) remain the leading cause of death worldwide, and more effective therapeutic methods are urgently needed. Polygonatum is a traditional Chinese herbal medicine with a variety of pharmacological applications and biological activities, such as antioxidant activity, anti-inflammation, antibacterial effect, immune-enhancing effect, glucose regulation, lipid-lowering and anti-atherosclerotic effects, treatment of diabetes and anticancer effect. There has also been more and more evidence to support the cardioprotective effect of Polygonatum in recent years. However, up to now, there has been a lack of comprehensive studies on the active ingredients and their pharmacotoxicological effects related to cardiovascular diseases. Therefore, the main active components of Polygonatum (including Polysaccharides, Flavonoids, Saponins) and their biological activities were firstly reviewed in this paper. Furthermore, we summarized the pharmacological effects of Polygonatum's active components in preventing and treating CVDs, and its relevant toxicological investigations. Finally, we emphasize the potential of Polygonatum in the prevention and treatment of CVDs.
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Metastasis of lung adenocarcinoma (LUAD) is a major cause of death in patients. Aryl hydrocarbon receptor (AHR), an important transcription factor, is involved in the initiation and progression of lung cancer. Polo-like kinase 1 (PLK1), a serine/threonine kinase, acts as an oncogene promoting the malignancy of multiple cancer types. However, the interaction between these two factors and their significance in lung cancer remain to be determined. In this study, we demonstrate that PLK1 phosphorylates AHR at S489 in LUAD, leading to epithelial-mesenchymal transition (EMT) and metastatic events. RNA-seq analyses reveal that type 2 deiodinase (DIO2) is responsible for EMT and enhanced metastatic potential. DIO2 converts tetraiodothyronine (T4) to triiodothyronine (T3), activating thyroid hormone (TH) signaling. In vitro and in vivo experiments demonstrate that treatment with T3 or T4 promotes the metastasis of LUAD, whereas depletion of DIO2 or a deiodinase inhibitor disrupts this property. Taking together, our results identify the AHR phosphorylation by PLK1 and subsequent activation of DIO2-TH signaling as mechanisms leading to LUAD metastasis. These findings can inform possible therapeutic interventions for this event.
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Adénocarcinome pulmonaire , Tumeurs du poumon , Humains , Phosphorylation , Iodide peroxidase/métabolisme , Récepteurs à hydrocarbure aromatique/génétique , Protein-Serine-Threonine Kinases/génétique , Protein-Serine-Threonine Kinases/métabolisme , Adénocarcinome pulmonaire/génétique , Hormones thyroïdiennes/génétique , Tumeurs du poumon/génétique , Tumeurs du poumon/anatomopathologie , Transition épithélio-mésenchymateuse/génétique , Prolifération cellulaire/physiologie ,RÉSUMÉ
Objective: To evaluate the changes in cardiac morphology of fetuses with congenital heart disease (CHD) using the fetal heart quantitative technique (fetalHQ).Methods: A total of 20 normal pregnant women (control group) and 20 pregnant women suspected of fetal CHD (case group) were included in this study. The dynamic images of the four-chamber view of the fetal heart were recorded and analyzed using fetalHQ. The global sphericity index (GSI) and 24-segment SI of the two groups were compared. The differences in the left and right ventricular 24-segment SI for each group were investigated.Results: There was no statistically significant difference in the GSI between the two groups (p > 0.05). The difference in the SI values of left ventricular segments 1-2 between the case group and control group was statistically significant (all p < 0.05), while the intergroup difference in SI of left ventricular segments 3-24 was not significant (all p > 0.05). The SI of the 24 segments of the right ventricle showed no significant intergroup difference (all p > 0.05). The difference in the left and right ventricular 24-segment SI in the case group did not reach statistical significance (all p > 0.05). In the control group, the SI values between the left and right ventricles were significantly different in segments 18-24 (all p < 0.05), and no significant difference was found in segments 1-17 (all p > 0.05). There was a statistically significant intergroup difference in the percentage of unusual left ventricular SI, determined based on Z-score (p < 0.05), and the percentage of outliers for the right ventricle between the two groups showed no significant difference (p > 0.05).Conclusion: The fetalHQ is regarded as a straightforward and reliable approach for assessing the cardiac GSI and 24-segment SI of left and right ventricles in fetuses diagnosed with CHD. While CHD may not significantly impact the overall shape of the fetal heart or the geometric shape of the right ventricle, in this study, a notable increase in SI values for the left ventricular 1-2 segments was observed, indicating a more flattened ventricular chamber. Additionally, the morphological distinctions between the left and right ventricles in fetuses with CHD are no longer discernible.
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Maladies foetales , Cardiopathies congénitales , Femelle , Humains , Grossesse , Échographie prénatale/méthodes , Coeur foetal/imagerie diagnostique , Cardiopathies congénitales/diagnostic , Ventricules cardiaques/imagerie diagnostique , Ventricules cardiaques/malformationsRÉSUMÉ
BACKGROUND: Whether intrauterine transmission of COVID-19 occurs remains uncertain, and it remains unclear whether the disease affects fetuses. We present a case of intrauterine transmission of SARS-CoV-2 infection and the prenatal ultrasonographic findings of the fetus in a pregnant woman with mild COVID-19. CASE PRESENTATION: A 30-year-old woman was admitted to our hospital for ultrasound examination in January 2023 at 26+ 3 weeks' gestation. Twenty-one days prior, her COVID-19 nucleic acid test was positive, and she had mild symptoms, including fever (38.3 °C), headache, chills, ankle pain and cough. After receiving symptomatic treatment, she fully recovered. Prenatal ultrasound revealed that the placenta was diffusely distributed with punctate echogenic foci, hepatomegaly, and the volume of bilateral lungs decreased significantly, with enhanced echo. In addition, we found that the surface of the fetal brain demonstrated widened gyri with a flattened surface. The prenatal MRI confirmed these fetal abnormalities. Amniotic fluid was tested for SARS-CoV-2, and the sample tested was positive for the virus. After careful consideration, the pregnant woman decided to terminate the pregnancy. CONCLUSION: The intrauterine transmission of COVID-19 is certain. Moreover, the intrauterine transmission of COVID-19 may cause abnormalities in various organs of the fetus.
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COVID-19 , Complications infectieuses de la grossesse , Femelle , Grossesse , Humains , Adulte , SARS-CoV-2 , Femmes enceintes , Complications infectieuses de la grossesse/diagnostic , Foetus , Placenta/imagerie diagnostique , Liquide amniotique , Transmission verticale de maladie infectieuse , Échographie prénataleRÉSUMÉ
PLK1 (Polo-like kinase 1) plays a critical role in the progression of lung adenocarcinoma (LUAD). Recent studies have unveiled that targeting PLK1 improves the efficacy of immunotherapy, highlighting its important role in the regulation of tumor immunity. Nevertheless, our understanding of the intricate interplay between PLK1 and the tumor microenvironment (TME) remains incomplete. Here, using genetically engineered mouse model and single-cell RNA-seq analysis, we report that PLK1 promotes an immunosuppressive TME in LUAD, characterized with enhanced M2 polarization of tumor associated macrophages (TAM) and dampened antigen presentation process. Mechanistically, elevated PLK1 coincides with increased secretion of CXCL2 cytokine, which promotes M2 polarization of TAM and diminishes expression of class II major histocompatibility complex (MHC-II) in professional antigen-presenting cells. Furthermore, PLK1 negatively regulates MHC-II expression in cancer cells, which has been shown to be associated with compromised tumor immunity and unfavorable patient outcomes. Taken together, our results reveal PLK1 as a novel modulator of TME in LUAD and provide possible therapeutic interventions.
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Metastasis of Lung adenocarcinoma (LUAD) is a major cause of death in patients. Aryl hydrocarbon receptor (AHR) is an important transcription factor involved in the initiation and progression of lung cancer. Polo-like kinase 1 (PLK1), a serine/threonine kinase, is an oncogene that promotes the malignancy of multiple cancer types. Nonetheless, the interaction between these two factors and significance in lung cancer remains to be determined. Here, we demonstrate that PLK1 phosphorylates AHR at S489 in LUAD, which leads to epithelial-mesenchymal transition (EMT) and metastatic events. RNA-seq analyses show that type 2 deiodinase (DIO2) is responsible for EMT and enhanced metastatic potential. DIO2 converts tetraiodothyronine (T4) to triiodothyronine (T3), which then activates thyroid hormone signaling. In vitro and in vivo experiments demonstrate that treatment with T3 or T4 promotes the metastasis of LUAD, whereas depletion of DIO2 or deiodinase inhibitor disrupts this property. Taken together, our results identify the phosphorylation of AHR by PLK1 as a mechanism leading to the progression of LUAD and provide possible therapeutic interventions for this event.
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BACKGROUND: The coronavirus disease 2019 (COVID-19) continues to spread worldwide. Integrated Chinese and Western medicine have had some successes in treating COVID-19. OBJECTIVE: This study aims to evaluate the efficacy and safety of three traditional Chinese medicine drugs and three herbal formulas (3-drugs-3-formulas) in patients with COVID-19. SEARCH STRATEGY: Relevant studies were identified from 12 electronic databases searched from their establishment to April 7, 2022. INCLUSION CRITERIA: Randomized controlled trials (RCTs), non-RCTs and cohort studies that evaluated the effects of 3-drugs-3-formulas for COVID-19. The treatment group was treated with one of the 3-drugs-3-formulas plus conventional treatment. The control group was treated with conventional treatment. DATA EXTRACTION AND ANALYSIS: Two evaluators screened and selected literature independently, then extracted basic information and assessed risk of bias. The treatment outcome measures were duration of main symptoms, hospitalization time, aggravation rate and mortality. RevMan 5.4 was used to analyze the pooled results reported as mean difference (MD) with 95% confidence interval (CI) for continuous data and risk ratio (RR) with 95% CI for dichotomous data. RESULTS: Forty-one studies with a total of 13,260 participants were identified. Our analysis suggests that compared with conventional treatment, the combination of 3-drugs-3-formulas might shorten duration of fever (MD = -1.39; 95% CI: -2.19 to -0.59; P < 0.05), cough (MD = -1.57; 95% CI: -2.16 to -0.98; P < 0.05) and fatigue (MD = -1.36; 95% CI: -2.21 to -0.51; P < 0.05), decrease length of hospital stay (MD = -2.62; 95% CI -3.52 to -1.72; P < 0.05), the time for nucleic acid conversion (MD = -2.92; 95% CI: -4.26 to -1.59; P < 0.05), aggravation rate (RR = 0.49; 95% CI: 0.38 to 0.64; P < 0.05) and mortality (RR = 0.34; 95% CI: 0.19 to 0.62; P < 0.05), and increase the recovery rate of chest computerized tomography manifestations (RR = 1.22; 95% CI: 1.14 to 1.3; P < 0.05) and total effectiveness (RR = 1.24; 95% CI: 1.09 to 1.42; P < 0.05). CONCLUSION: The 3-drugs-3-formulas can play an active role in treating all stages of COVID-19. No severe adverse events related to 3-drugs-3-formulas were observed. Hence, 3-drugs-3-formulas combined with conventional therapies have effective therapeutic value for COVID-19 patients. Further long-term high-quality studies are essential to demonstrate the clinical benefits of each formula. Please cite this article as: You LZ, Dai QQ, Zhong XY, Yu DD, Cui HR, Kong YF, Zhao MZ, Zhang XY, Xu QQ, Guan ZY, Wei XX, Zhang XC, Han SJ, Liu WJ, Chen Z, Zhang XY, Zhao C, Jin YH, Shang HC. Clinical evidence of three traditional Chinese medicine drugs and three herbal formulas for COVID-19: A systematic review and meta-analysis of the Chinese population. J Integr Med. 2023; 21(5): 441-454.
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Traitements médicamenteux de la COVID-19 , COVID-19 , Médicaments issus de plantes chinoises , Médecine traditionnelle chinoise , Humains , Asiatiques , Toux/étiologie , COVID-19/complications , COVID-19/thérapie , Fièvre/étiologie , Médecine traditionnelle chinoise/méthodes , Médicaments issus de plantes chinoises/usage thérapeutique , Traitements médicamenteux de la COVID-19/méthodes , Essais contrôlés randomisés comme sujetRÉSUMÉ
Fluorinated compounds are a class of organic substances resistant to degradation. Although zero-valent iron (Fe0) has a promising reducing capability, it still fails to degrade fluorine-containing antibiotics (i.e., florfenicol) efficiently. In this study, we applied a simple one-pot pyrolytic approach to synthesize nitrogen-doped biochar supported Fe0 and zero-valent copper (Cu0) composite (Fe/Cu@NBC) and investigated its performance on florfenicol removal. The results clearly showed that approximately 91.4% of florfenicol in the deionized water was removed by Fe/Cu@NBC within 8 h. As the reaction time was extended to 15 d, the total degradation rate of florfenicol reached 96.6%, in which the defluorination and dechlorination rates were 73.2% and 82.1%, respectively. Both experimental results and density functional theory calculation suggested that âOH and ·O2- triggered ß-fluorine elimination, resulting in defluorination prior to dechlorination. This new finding was distinct from previous viewpoints that defluorination was more difficult to occur than dechlorination. Fe/Cu@NBC also had a favorable performance for removal of florfenicol in surface water. This study provides a new insight into the degradation mechanism and pathway of florfenicol removal in the Fe/Cu@NBC system, which can be a promising alternative for remediation of fluorinated organic compounds in the environment.
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Antibactériens , Polluants chimiques de l'eau , Fer , Cuivre , Azote , Fluor , Eau , Polluants chimiques de l'eau/analyseRÉSUMÉ
Carbon quantum dots (CQDs) are considered promising metal-free green catalysts for the activation of persulfates, but direct experimental evidence to identify the true active sites on the surface of CQDs is still lacking. We prepared CQDs with different oxygen contents by controlling the carbonisation temperature, using a simple pyrolysis method. Photocatalytic activity experiments show that CQDs200 exhibits the best PMS activation performance. By investigating the relationship between the oxygen functional groups on CQDs surface and photocatalytic activity, it was postulated that the C=O groups might be the predominant active site, which was confirmed by selective chemical titrations of the C=O, C-OH and COOH groups. Furthermore, limited to the weak photocatalytic properties of the pristine CQDs, ammonia and phenylhydrazine were used to precisely nitrogen-modify the o-CQD surface. We found that phenylhydrazine-modified o-CQDs-PH promoted the absorption of visible light and the separation of photocarriers, thus enhancing the activation of PMS. Theoretical calculations provide more insights from different levels of the pollutant, fine-tuned CQDs, and their interactions.
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Skewed X chromosome inactivation (XCI-S) has been reported to be associated with some X-linked diseases. Several methods have been proposed to estimate the degree of XCI-S (denoted as γ) for quantitative and qualitative traits based on unrelated females. However, there is no method available for estimating γ based on general pedigrees. Therefore, in this paper, we propose a Bayesian method to obtain the point estimate and the credible interval of γ based on the mixture of general pedigrees and unrelated females (called mixed data for brevity), which is also suitable for only general pedigrees. We consider the truncated normal prior and the uniform prior for γ. Further, we apply the eigenvalue decomposition and Cholesky decomposition to our proposed methods to accelerate the computation speed. We conduct extensive simulation studies to compare the performances of our proposed methods and two existing Bayesian methods which are only applicable to unrelated females. The simulation results show that the incorporation of general pedigrees can improve the efficiency of the point estimation and the precision and the accuracy of the interval estimation of γ. Finally, we apply the proposed methods to the Minnesota Center for Twin and Family Research data for their practical use.
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Chromosomes X humains , Inactivation du chromosome X , Humains , Femelle , Théorème de Bayes , Inactivation du chromosome X/génétique , Pedigree , FamilleRÉSUMÉ
PURPOSE: To examine the relationship between Neutrophil-Lymphocyte Ratio (NLR) and Acute Kidney Injury (AKI) in patients undergoing noncardiac surgery, and subgroup analysis was performed for different types of non-cardiac surgery. METHODS: The present retrospective cohort study included 10,159 adult patients who underwent major noncardiac surgery at Nanfang Hospital, Southern Medical University, between 2008 and 2018. Postoperative AKI was defined as an increase in serum creatinine level of at least 0.3 mg/dl within 48 h, or 1.5 times higher than baseline within 7 days postoperatively according to the Kidney Disease Improving Global Outcome. The correlation between preoperative NLR and postoperative AKI was determined by stepwise multivariate logistic regression analysis, and the predictive value of NLR was evaluated by the receiver operating characteristics curve (ROC) analysis. RESULTS: Four hundred and eighty-five (4.77%) patients developed AKI postoperatively. Preoperative NLR was independently associated with postoperative AKI in all patients undergoing non-cardiac surgery (Odds ratio [OR], 1.03; 95% confidence interval [CI], 1.00-1.06). The optimal cut-off value of NLR was 2.12 according ROC analysis. The OR and 95% CI of AKI for NLR > 2.12 was 1.48 (1.21-1.81) compared with NLR ≤ 2.12. In addition, the positive association was mainly shown in patients undergone digestive system surgery with a cut-off value of 2.12 but not in neurological and musculoskeletal system surgeries. CONCLUSION: The present study confirmed the association of preoperative NLR with postoperative AKI in digestive system surgical patients. A NLR value of 2.12 may be a useful cut-off to evaluate the risk of AKI.
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Atteinte rénale aigüe , Granulocytes neutrophiles , Adulte , Humains , Études rétrospectives , Lymphocytes , Courbe ROC , Atteinte rénale aigüe/diagnostic , Atteinte rénale aigüe/étiologie , Complications postopératoires/étiologie , Facteurs de risqueRÉSUMÉ
Malignant ascites (MA) is a common symptom of peritoneal metastasis in liver cancer. Cancer immunotherapy can modulate immune cells to induce antitumor immune efficiency. Reprogramming tumor immune microenvironment (TIME) is a momentous strategy to overcome immunosuppression and achieve immune functional normalization. Inspired by the inherent apoptotic bodies and vesicles, we proposed and systematically studied engineered apoptosis-bioinspired nanoparticles (EBN) for cancer immunotherapy of MA. Using both in vitro and in vivo experimental validations, we elucidated that EBN could be efficiently engulfed by the tumor-associated macrophages (TAMs) and manipulate their polarization. Moreover, a boosted immune cascade response as a result of heightening cytotoxic T-lymphocytes (CTLs) activity was investigated. Based on these results, EBN was confirmed to have strong immune cascade activation capability. Remarkably, the injection of EBN further reduced ascites volume and reformed immune cell subtypes, compared to the injection of either PBS or free TMP195 alone. In short, this novel nanodrug delivery system (NDDS) represents a prospective immunotherapeutic approach for clinical therapeutics of hepatoma ascites and other malignant effusion.
Sujet(s)
Tumeurs du foie , Nanoparticules , Tumeurs du péritoine , Humains , Ascites/anatomopathologie , Études prospectives , Macrophages , Immunothérapie/méthodes , Tumeurs du foie/traitement médicamenteux , Apoptose , Microenvironnement tumoralRÉSUMÉ
Increased abundance of polo-like kinase 1 (PLK1) is observed in various tumor types, particularly in lung adenocarcinoma (LUAD). Here, we found that PLK1 accelerated the progression of LUAD through a mechanism that was independent of its role in mediating mitotic cell division. Analysis of human tumor databases revealed that increased PLK1 abundance in LUAD correlated with mutations in KRAS and p53, with tumor stage, and with reduced survival in patients. In a mouse model of KRASG12D-driven, p53-deficient LUAD, PLK1 overexpression increased tumor burden, decreased tumor cell differentiation, and reduced animal survival. PLK1 overexpression in cultured cells and mice indirectly increased the expression of the gene encoding the receptor tyrosine kinase RET by phosphorylating the transcription factor TTF-1. Signaling by RET and mutant KRAS in these tumors converged to activate the mitogen-activated protein kinase (MAPK) pathway. Pharmacological inhibition of the MAPK pathway kinase MEK combined with inhibition of either RET or PLK1 markedly suppressed tumor growth. Our findings show that PLK1 can amplify MAPK signaling and reveal a potential target for stemming progression in lung cancers with high PLK1 abundance.