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Gram-positive S. aureus is one of the leading pathogens for death associated with antimicrobial resistance. The ß-lactamase (Bla) secreted by methicillin-resistant S. aureus (MRSA) hydrolyzes nearly all ß-lactam antibiotics, leaving only a few antibiotics available for the clinical treatment of MRSA infections. Thereby, a Bla-responsive peptide (BLAP) is designed here with the capacity of inhibiting MRSA infection through mimicking the host defense mechanism of human defensin-6. The BLAP comprising a self-assembling peptide sequence can respond specifically to the secreted Bla and assemble in situ surrounding MRSA. The assembled nanofibrous network is able to trap MRSA, preventing its invasion into the host cells effectively. As a consequence, the intramuscular injection of BLAP significantly restricted bacterial infection and abscess formation in mice. The biomimetic BLAP holds great potential for the efficient treatment of drug-resistant gram-positive bacterial infections.
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Inflammatory bowel disease (IBD) is a chronic and recurrent inflammatory disease of the gastrointestinal tract, including two subtypes: Crohn's disease (CD) and ulcerative colitis (UC). Metabolic disorders are important factors in the development of IBD. However, the evidence for the causal relationship between blood metabolites and IBD remains limited. A two-sample MR analysis was applied to evaluate relationships between 486 blood metabolites and IBD. The inverse variance weighted method was chosen as the primary MR analysis method. False discovery rate correction was used to control for false positives in multiple testing. Following complementary and sensitivity analyses were conducted using methods such as weight median, MR-egger, weighted mode, simple mode, Cochran Q test, and MR-PRESSO. Moreover, we performed replication, meta-analysis, Steiger test, and linkage disequilibrium score regression to enhance the robustness of the results. Additionally, we performed metabolic pathway analysis to identify potential metabolic pathways. As a result, we identified four significant causal associations between four blood metabolites and two IBD subtypes. Specifically, one metabolite was identified as being associated with the development of CD (mannose: odds ratio (OR) = 0.19, 95% confidence interval (CI) 0.08-0.43, P = 8.54 × 10-5). Three metabolites were identified as being associated with the development of UC (arachidonate (20:4n6): OR = 0.18, 95% CI 0.11-0.30, P = 2.09 × 10-11; 1, 5-anhydroglucitol: OR = 2.21, 95% CI 1.47-3.34, P = 1.50 × 10-4; 2-stearoylglycerophosphocholine: OR = 2.66, 95% CI 1.53-4.63, P = 5.30 × 10-4). The findings of our study suggested that the identified metabolites and metabolic pathways can be considered as useful circulating metabolic biomarkers for the screening and prevention of IBD in clinical practice, as well as candidate molecules for future mechanism exploration and drug target selection.
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Doenças Inflamatórias Intestinais , Análise da Randomização Mendeliana , Humanos , Doenças Inflamatórias Intestinais/sangue , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/metabolismo , Doença de Crohn/sangue , Doença de Crohn/genética , Polimorfismo de Nucleotídeo Único , Colite Ulcerativa/sangue , Colite Ulcerativa/genética , Biomarcadores/sangue , MetabolomaRESUMO
Peptide stapling, by employing a stable, preformed alpha-helical conformation, results in the production of peptides with improved membrane permeability and enhanced proteolytic stability, compared to the original peptides, and provides an effective solution to accelerate the rapid development of peptide drugs. Various reviews present peptide stapling chemistries, anchoring residues and one- or two-component cyclization, however, therapeutic stapled peptides have not been systematically summarized, especially focusing on various disease-related targets. This review highlights the latest advances in therapeutic peptide drug development facilitated by the application of stapling technology, including different stapling techniques, synthetic accessibility, applicability to biological targets, potential for solving biological problems, as well as the current status of development. Stapled peptides as therapeutic drug candidates have been classified and analysed mainly by receptor- and ligand-based stapled peptide design against various diseases, including cancer, infectious diseases, inflammation, and diabetes. This review is expected to provide a comprehensive reference for the rational design of stapled peptides for different diseases and targets to facilitate the development of therapeutic peptides with enhanced pharmacokinetic and biological properties.
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Peptídeos , Humanos , Animais , Peptídeos/uso terapêutico , Peptídeos/química , Peptídeos/farmacologia , Desenho de FármacosRESUMO
Antimicrobial photodynamic therapy (PDT) is a promising alternative to antibiotics for eradicating pathogenic bacterial infections. It holds advantage of not inducing antimicrobial resistance but is limited for the treatment of gram-negative bacterial infection due to the lack of photosensitizer (PS) capable of targeted permeating the outer membrane (OM) of gram-negative bacteria. To facilitate the targeted permeability of PS, cyclic polymyxin b nonapeptide that can specifically bind to the lipopolysaccharide on OM, is conjugated to an FDA approved PS chlorin e6 via variable linkers. Based on structure to activity study, C6pCe6 with aminohexanoic linker and P2pCe6 with amino-3, 6-dioxaoctanoic linker are identified to preferentially image gram-negative bacteria. These two conjugates also exhibit improved aqueous dispersity and enhanced ROS generation, consequently enabled their selective bactericidal activities against gram-negative bacteria upon 660 nm light irradiation. The effective photobactericidal ability of P2pCe6 is further validated on P. aeruginosa infected G. mellonella. Moreover, it is demonstrated to effectively treat the P. aeruginosa infection and accelerate the healing process at the wound site of mouse. Owing to the light irradiation triggered targeted imaging and enhanced bactericidal capacities, P2pCe6 hold great potential to serve as a potent PS for mediating the phototheranostics of gram-negative bacterial infection.
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Anti-Infecciosos , Infecções por Bactérias Gram-Negativas , Fotoquimioterapia , Animais , Camundongos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/química , Peptídeos Cíclicos/farmacologia , Peptídeos Cíclicos/uso terapêutico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Fotoquimioterapia/métodos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Antibacterianos/química , Anti-Infecciosos/farmacologia , Bactérias Gram-NegativasRESUMO
PURPOSE: We aimed to develop and validate a deep learning (DL) model to automatically segment posterior fossa ependymoma (PF-EPN) and predict its molecular subtypes [Group A (PFA) and Group B (PFB)] from preoperative MR images. EXPERIMENTAL DESIGN: We retrospectively identified 227 PF-EPNs (development and internal test sets) with available preoperative T2-weighted (T2w) MR images and molecular status to develop and test a 3D nnU-Net (referred to as T2-nnU-Net) for tumor segmentation and molecular subtype prediction. The network was externally tested using an external independent set [n = 40; subset-1 (n = 31) and subset-2 (n =9)] and prospectively enrolled cases [prospective validation set (n = 27)]. The Dice similarity coefficient was used to evaluate the segmentation performance. Receiver operating characteristic analysis for molecular subtype prediction was performed. RESULTS: For tumor segmentation, the T2-nnU-Net achieved a Dice score of 0.94 ± 0.02 in the internal test set. For molecular subtype prediction, the T2-nnU-Net achieved an AUC of 0.93 and accuracy of 0.89 in the internal test set, an AUC of 0.99 and accuracy of 0.93 in the external test set. In the prospective validation set, the model achieved an AUC of 0.93 and an accuracy of 0.89. The predictive performance of T2-nnU-Net was superior or comparable to that of demographic and multiple radiologic features (AUCs ranging from 0.87 to 0.95). CONCLUSIONS: A fully automated DL model was developed and validated to accurately segment PF-EPNs and predict molecular subtypes using only T2w MR images, which could help in clinical decision-making.
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Aprendizado Profundo , Ependimoma , Humanos , Estudos Retrospectivos , Área Sob a Curva , Tomada de Decisão Clínica , Ácido Fenilfosfonotioico, 2-Etil 2-(4-Nitrofenil) Éster , Ependimoma/diagnóstico por imagem , Ependimoma/genética , Imageamento por Ressonância MagnéticaRESUMO
Proteolysis-targeting chimeras (PROTACs) have recently emerged as a promising technology for drug development. However, poor water solubility, limited tissue selectivity, and inadequate tumor penetration pose significant challenges for PROTAC-based therapies in cancer treatment. Herein, we developed an iRGD-PROTAC conjugation strategy utilizing tumor-penetrating cyclic peptide iRGD (CRGDK/RGPD/EC) to deliver PROTACs deep into breast cancer tissues. As a conceptual validation study, iRGD peptides were conjugated with a bromodomain-containing protein 4 (BRD4) PROTAC through a GSH-responsive linker. The resulting iRGD-PROTAC conjugate iPR showed enhanced water solubility, tumor-targeting capability, and penetration within tumor tissues, resulting in increased antibreast cancer efficacy in animal models and patient-derived organoids. This study demonstrates the advantages of combining iRGD and PROTACs in improving drug delivery and highlights the importance of tissue selectivity and penetration ability in PROTAC-based therapeutics.
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Neoplasias da Mama , Animais , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Proteólise , Quimera de Direcionamento de Proteólise , Proteínas Nucleares , Linhagem Celular Tumoral , Fatores de Transcrição , Água , Proteínas que Contêm Bromodomínio , Proteínas de Ciclo CelularRESUMO
BACKGROUND AND PURPOSE: Conventional MR imaging is not sufficient to discern the H3 K27-altered status of spinal cord diffuse midline glioma. This study aimed to develop a radiomics-based model based on preoperative T2WI to determine the H3 K27-altered status of spinal cord diffuse midline glioma. MATERIALS AND METHODS: Ninety-seven patients with confirmed spinal cord diffuse midline gliomas were retrospectively recruited and randomly assigned to the training (n = 67) and test (n = 30) sets. One hundred seven radiomics features were initially extracted from automatically-segmented tumors on T2WI, then 11 features selected by the Pearson correlation coefficient and the Kruskal-Wallis test were used to train and test a logistic regression model for predicting the H3 K27-altered status. Sensitivity analysis was performed using additional random splits of the training and test sets, as well as applying other classifiers for comparison. The performance of the model was evaluated through its accuracy, sensitivity, specificity, and area under the curve. Finally, a prospective set including 28 patients with spinal cord diffuse midline gliomas was used to validate the logistic regression model independently. RESULTS: The logistic regression model accurately predicted the H3 K27-altered status with accuracies of 0.833 and 0.786, sensitivities of 0.813 and 0.750, specificities of 0.857 and 0.833, and areas under the curve of 0.839 and 0.818 in the test and prospective sets, respectively. Sensitivity analysis confirmed the robustness of the model, with predictive accuracies of 0.767-0.833. CONCLUSIONS: Radiomics signatures based on preoperative T2WI could accurately predict the H3 K27-altered status of spinal cord diffuse midline glioma, providing potential benefits for clinical management.
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Glioma , Humanos , Glioma/diagnóstico por imagem , Glioma/patologia , Imageamento por Ressonância Magnética/métodos , Estudos Prospectivos , Estudos Retrospectivos , Medula Espinal/diagnóstico por imagem , Medula Espinal/patologiaRESUMO
OBJECTIVES: To evaluate the utility of amide proton transfer-weighted (APTw) MRI imaging and its derived radiomics in classifying adult-type diffuse glioma. MATERIALS AND METHODS: In this prospective study, APTw imaging was performed on 129 patients with adult-type diffuse gliomas. The mean APTw-related metrics (chemical exchange saturation transfer ratio (CESTR), CESTR normalized with the reference value (CESTRnr), and relaxation-compensated inverse magnetization transfer ratio (MTRRex)) and radiomic features within 3D tumor masks were extracted. APTw-radiomics models were developed using a support vector machine (SVM) classifier. Sensitivity analysis with tumor area of interest, different histogram cutoff values, and other classifiers were conducted. RESULTS: CESTR, CESTRnr, and MTRRex in glioblastomas were all significantly higher (p < 0.0003) than those of oligodendrogliomas and astrocytomas, with no significant difference between oligodendrogliomas and astrocytomas. The APTw-related metrics for IDH-wildtype and high-grade gliomas were significantly higher (p < 0.001) than those for the IDH-mutant and low-grade gliomas, with area under the curve (AUCs) of 0.88 for CESTR. The CESTR-radiomics models demonstrated accuracies of 84% (AUC 0.87), 83% (AUC 0.83), 90% (AUC 0.95), and 84% (AUC 0.86) in predicting the IDH mutation status, differentiating glioblastomas from astrocytomas, distinguishing glioblastomas from oligodendrogliomas, and determining high/low grade prediction, respectively, but showed poor performance in distinguishing oligodendrogliomas from astrocytomas (accuracy 63%, AUC 0.63). The sensitivity analysis affirmed the robustness of the APTw signal and APTw-derived radiomics prediction models. CONCLUSION: APTw imaging, along with its derived radiomics, presents a promising quantitative approach for prediction IDH mutation and grading adult-type diffuse glioma. CLINICAL RELEVANCE STATEMENT: Amide proton transfer-weighted imaging, a quantitative imaging biomarker, coupled with its derived radiomics, offers a promising non-invasive approach for predicting IDH mutation status and grading adult-type diffuse gliomas, thereby informing individualized clinical diagnostics and treatment strategies. KEY POINTS: ⢠This study evaluates the differences of different amide proton transfer-weighted metrics across three molecular subtypes and their efficacy in classifying adult-type diffuse glioma. ⢠Chemical exchange saturation transfer ratio normalized with the reference value and relaxation-compensated inverse magnetization transfer ratio effectively predicts IDH mutation/grading, notably the first one. ⢠Amide proton transfer-weighted imaging and its derived radiomics holds potential to be used as a diagnostic tool in routine clinical characterizing adult-type diffuse glioma.
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Numerous studies have focused on the classification of N6-methyladenosine (m6A) modification sites in RNA sequences, treating it as a multi-feature extraction task. In these studies, the incorporation of physicochemical properties of nucleotides has been applied to enhance recognition efficacy. However, the introduction of excessive supplementary information may introduce noise to the RNA sequence features, and the utilization of sequence similarity information remains underexplored. In this research, we present a novel method for RNA m6A modification site recognition called M6ATMR. Our approach relies solely on sequence information, leveraging Transformer to guide the reconstruction of the sequence similarity matrix, thereby enhancing feature representation. Initially, M6ATMR encodes RNA sequences using 3-mers to generate the sequence similarity matrix. Meanwhile, Transformer is applied to extract sequence structure graphs for each RNA sequence. Subsequently, to capture low-dimensional representations of similarity matrices and structure graphs, we introduce a graph self-correlation convolution block. These representations are then fused and reconstructed through the local-global fusion block. Notably, we adopt iteratively updated sequence structure graphs to continuously optimize the similarity matrix, thereby constraining the end-to-end feature extraction process. Finally, we employ the random forest (RF) algorithm for identifying m6A modification sites based on the reconstructed features. Experimental results demonstrate that M6ATMR achieves promising performance by solely utilizing RNA sequences for m6A modification site identification. Our proposed method can be considered an effective complement to existing RNA m6A modification site recognition approaches.
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Adenosina , Nucleotídeos , Sequência de Bases , RNA/genéticaRESUMO
Chronic and recurrent inflammatory disorders of the gastrointestinal tract caused by a complex interplay between genetics and intestinal dysbiosis are called inflammatory bowel disease. As a result of the interaction between the liver and the gut microbiota, bile acids are an atypical class of steroids produced in mammals and traditionally known for their function in food absorption. With the development of genomics and metabolomics, more and more data suggest that the pathophysiological mechanisms of inflammatory bowel disease are regulated by bile acids and their receptors. Bile acids operate as signalling molecules by activating a variety of bile acid receptors that impact intestinal flora, epithelial barrier function, and intestinal immunology. Inflammatory bowel disease can be treated in new ways by using these potential molecules. This paper mainly discusses the increasing function of bile acids and their receptors in inflammatory bowel disease and their prospective therapeutic applications. In addition, we explore bile acid metabolism and the interaction of bile acids and the gut microbiota.
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Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Animais , Humanos , Ácidos e Sais Biliares , Intestinos , Fígado , Doenças Inflamatórias Intestinais/tratamento farmacológico , Disbiose , MamíferosRESUMO
BACKGROUND: Assessing the dairy consumption and psychological symptoms of Chinese college students as a reference for the mental health of Chinese college students. METHODS: A three-stage stratified whole-group sampling method was used to investigate dairy consumption and psychological symptoms among 5904 (2554 male students, accounting for 43.3% of the sample) college students in the Yangtze River Delta region. The mean age of the subjects was 20.13 ± 1.24 years. Psychological symptoms were surveyed using the Brief Questionnaire for the Assessment of Adolescent Mental Health. The detection rates of emotional problems, behavioral symptoms, social adaptation difficulties and psychological symptoms among college students with different dairy consumption habits were analyzed using chi-square tests. The association between dairy consumption and psychological symptoms was assessed using a logistic regression model. RESULTS: College students from the "Yangtze River Delta" region of China participated in the study, of which 1022 (17.31%) had psychological symptoms. The proportions of participants with dairy consumption of ≤2 times/week, 3-5 times/week, and ≥6 times/week were 25.68%, 42.09%, and 32.23%, respectively. Using dairy consumption ≥6 times/week as a reference, multifactor logistic regression analysis showed that college students with dairy consumption ≤2 times/week (OR = 1.42, 95% CI: 1.18, 1.71) were at higher risk of psychological symptoms (p < 0.001). CONCLUSION: During the COVID-19 pandemic, Chinese college students with lower dairy consumption exhibited higher detection rates of psychological symptoms. Dairy consumption was negatively associated with the occurrence of psychological symptoms. Our study provides a basis for mental health education and increasing knowledge about nutrition among Chinese college students.
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COVID-19 , Adolescente , Humanos , Masculino , Adulto Jovem , Adulto , Estudos Transversais , COVID-19/epidemiologia , Pandemias , Saúde Mental , Estudantes/psicologia , China/epidemiologiaRESUMO
BACKGROUND: Determination of H3 K27M mutation in diffuse midline glioma (DMG) is key for prognostic assessment and stratifying patient subgroups for clinical trials. MRI can noninvasively depict morphological and metabolic characteristics of H3 K27M mutant DMG. PURPOSE: This study aimed to develop a deep learning (DL) approach to noninvasively predict H3 K27M mutation in DMG using T2-weighted images. STUDY TYPE: Retrospective and prospective. POPULATION: For diffuse midline brain gliomas, 341 patients from Center-1 (27 ± 19 years, 184 males), 42 patients from Center-2 (33 ± 19 years, 27 males) and 35 patients (37 ± 18 years, 24 males). For diffuse spinal cord gliomas, 133 patients from Center-1 (30 ± 15 years, 80 males). FIELD STRENGTH/SEQUENCE: 5T and 3T, T2-weighted turbo spin echo imaging. ASSESSMENT: Conventional radiological features were independently reviewed by two neuroradiologists. H3 K27M status was determined by histopathological examination. The Dice coefficient was used to evaluate segmentation performance. Classification performance was evaluated using accuracy, sensitivity, specificity, and area under the curve. STATISTICAL TESTS: Pearson's Chi-squared test, Fisher's exact test, two-sample Student's t-test and Mann-Whitney U test. A two-sided P value <0.05 was considered statistically significant. RESULTS: In the testing cohort, Dice coefficients of tumor segmentation using DL were 0.87 for diffuse midline brain and 0.81 for spinal cord gliomas. In the internal prospective testing dataset, the predictive accuracies, sensitivities, and specificities of H3 K27M mutation status were 92.1%, 98.2%, 82.9% in diffuse midline brain gliomas and 85.4%, 88.9%, 82.6% in spinal cord gliomas. Furthermore, this study showed that the performance generalizes to external institutions, with predictive accuracies of 85.7%-90.5%, sensitivities of 90.9%-96.0%, and specificities of 82.4%-83.3%. DATA CONCLUSION: In this study, an automatic DL framework was developed and validated for accurately predicting H3 K27M mutation using T2-weighted images, which could contribute to the noninvasive determination of H3 K27M status for clinical decision-making. EVIDENCE LEVEL: 2 Technical Efficacy: Stage 2.
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Neoplasias Encefálicas , Aprendizado Profundo , Glioma , Neoplasias da Medula Espinal , Masculino , Humanos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Histonas/genética , Estudos Retrospectivos , Estudos Prospectivos , Mutação , Glioma/diagnóstico por imagem , Glioma/genética , Imageamento por Ressonância Magnética , Neoplasias da Medula Espinal/diagnóstico por imagem , Neoplasias da Medula Espinal/genéticaRESUMO
BACKGROUND: Hepatocellular carcinoma (HCC) is a leading cancer worldwide. miRNA has been linked to cancer processes. We want to figure out what the underlying mechanism and functions of miR-3682-3p are in HCC. METHODS: Thirty pairs of tumor tissues and adjacent tissues were obtained from HCC patients. mRNA and protein expressions were detected by quantitative real-time PCR and Western blot, respectively. The migration and invasion were measured using transwell or wound-healing assays. Dual luciferase and ChIP assays were utilized to detect gene interactions. RESULTS: miR-3682-3p was highly expressed in HCC tissues and cell lines. Silencing of miR-3682-3p inhibited cell migration and invasion, increased E-cadherin expression, and decreased N-cadherin, vimentin, and snail expressions, as well as the SOX2, OCT4, and Bmi1 expression, thereby restraining EMT and stemness of HCC in vitro. miR-3682-3p was positively activated by c-Myc and could directly target PTEN to activate PI3K/AKT/ß-catenin pathway. In addition, inhibition of PTEN weakened the anti-migration and anti-stemness effects of miR-3682-3p downregulation in HCC cells. CONCLUSION: miR-3682-3p promoted HCC migration and stemness through PTEN/PI3K/AKT/ß-catenin signaling, implying that miR-3682-3p might be a promising target for HCC clinical treatment.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Humanos , Carcinoma Hepatocelular/patologia , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Neoplasias Hepáticas/patologia , beta Catenina/genética , beta Catenina/metabolismo , Linhagem Celular Tumoral , MicroRNAs/genética , MicroRNAs/metabolismo , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismoRESUMO
Purpose: To investigate and evaluate the value of thoracic low dose computed tomography (LDCT) scan in the diagnosis of anemia. Materials and methods: 661 patients who received thoracic computed tomography (CT) examination and underwent a peripheral blood examination were retrospectively included. 341 patients underwent conventional dose CT (CDCT), and 320 patients underwent LDCT. Regions of interest (ROI) were placed on the left ventricular cavity (LV), descending aorta (DAo), and interventricular septum (IVS). The corresponding CT attenuation was measured, and the CT attenuation difference between LV and IVS (IVS-LV) and between DAo and IVS (IVS-DAo) was calculated, respectively. One-way analysis of variance (ANOVA) and linear regression were performed to analyze the relationship between these indicators and Hb levels. The receiver operating characteristic (ROC) curve was used to evaluate prediction performance. Results: Both attenuation on LDCT and CDCT showed significant differences between the healthy group and the anemic group (P < 0.05). In the LDCT group, the LV and DAo were more relevant with the hemoglobin (Hb) level (correlation coefficient 0.618 and 0.602) than other indicators, with AUCs of 0.815 (95% CI: 0.763-0.868) and 0.803 (95% CI: 0.747-0.859), respectively. The linear regression formulas for Hb level with the LV and DAo were 19.14 + 0.15 × HU [95% CI: (16.52, 21.75) + (0.12, 0.17) × HU] and 19.46 + 0.16 × HU [95% CI: (16.55, 22.36) + (0.13, 0.18) × HU], respectively. Youden's index indicated that 37.5 HU and 38.5 HU were the best thresholds to diagnose anemia for LV and DAo, respectively. In the CDCT group, the LV and IVS-LV got obviously higher correlation coefficients (0.813 and 0.812), with AUCs of 0.831 (95% CI: 0.786-0.877) and 0.851 (95% CI: 0.808-0.894), respectively. The optimal thresholds for LV and IVS-LV were 40.5 HU and 9.5 HU, respectively. Conclusion: In LDCT examinations, an approximation of Hb level and detecting of anemia can be conducted based on simple attenuation measurements.
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Peach diseases seriously affect peach yield and people's health. The precise identification of peach diseases and the segmentation of the diseased areas can provide the basis for disease control and treatment. However, the complex background and imbalanced samples bring certain challenges to the segmentation and recognition of lesion area, and the hard samples and imbalance samples can lead to a decline in classification of foreground class and background class. In this paper we applied deep network models (Mask R-CNN and Mask Scoring R-CNN) for segmentation and recognition of peach diseases. Mask R-CNN and Mask Scoring R-CNN are classic instance segmentation models. Using instance segmentation model can obtain the disease names, disease location and disease segmentation, and the foreground area is the basic feature for next segmentation. Focal Loss can solve the problems caused by difficult samples and imbalance samples, and was used for this dataset to improve segmentation accuracy. Experimental results show that Mask Scoring R-CNN with Focal Loss function can improve recognition rate and segmentation accuracy comparing to Mask Scoring R-CNN with CE loss or comparing to Mask R-CNN. When ResNet50 is used as the backbone network based on Mask R-CNN, the segmentation accuracy of segm_mAP_50 increased from 0.236 to 0.254. When ResNetx101 is used as the backbone network, the segmentation accuracy of segm_mAP_50 increased from 0.452 to 0.463. In summary, this paper used Focal Loss on Mask R-CNN and Mask Scoring R-CNN to generate better mAP of segmentation and output more detailed information about peach diseases.
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The vinyl phytic acid (GPA) was prepared using biophytic acid (PA) and glycidyl methacrylate (GMA), in which double bonds were introduced into the phytic acid molecule to increase the active groups in the phytic acid molecule. Furthermore, itaconic acid (IA) containing two unsaturated double bonds and GPA was polymerized in situ and crosslinked on the surface of cotton fabrics, and flame retardant and crease-proofed fabrics were obtained. The effects of GPA, IA, and the initiator on the flame-retardant and crease-proofing properties of the fabrics were analyzed by a single-factor and double-dip double-nip experiment. A flame-retardant and wrinkle-resistant fabric was obtained when the limiting oxygen index (LOI) and wrinkle recovery angle (WRA) were 28% and 270°, respectively. During combustion, the thermal properties of the fabrics changed; typically, the extrapolated initial temperature (Te) decreased, and moisture release increased. After burning, the fabrics had good shape retention, and the carbon residue content increased to 48%, which effectively inhibited or slowed down the combustion and heat release of the textiles. However, the whiteness, mechanical properties, and washability of the products need to be further improved.
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Colorectal cancer (CRC) has been the third leading cause of cancer-associated deaths. LncRNA SNHG16 is reported to be involved in metastasis of CRC cells. However, the mechanism by which SNHG16 regulates CRC progression is poorly understood. The proliferation of CRC cells was examined by MTT. Wound healing and transwell assay were used to measure migration and invasion ability. RT-qPCR and western blot were used to examine gene expression. Immunofluorescence was conducted to evaluate the EMT of CRC cells. Luciferase reporter assay were used to confirm direct interaction between miR-124-3p and SNHG16 or MCP-1. The interaction between miR-124-3p and SNHG16 was detected by RIP and RNA pull down assay. H&E staining was used to test the histomorphological changes of hepatic metastatic nodules. Finally, xenograft tumor experiment was utilized to determine tumor growth in vivo. SNHG16 and miR-124-3p were dysregulated in human colorectal tumors or cells. Knockdown of SNHG16 led to attenuate cell proliferation, migration, invasion, and EMT of CRC cells. And xenograft tumor experiment showed that SNHG16 might influence tumor growth. In contrast, miR-124-3p exerted the antitumor effects. Knockdown of miR-124-3p can reverse the effect of sh-SNHG16 on CRC cells. miR-124-3p could directly bind to SNHG16 or MCP-1. More importantly, MCP-1 acts as a critical effector mediating the role of SNHG16/ miR-124-3p in CRC cells. In summary, our data suggest that SNHG16 plays a contributory role in proliferation, migration, and EMT of CRC cells via miR-124-3p/MCP-1 axis, which offers a rationale for targeting SNHG16 and developing therapeutic drugs to treat CRC.
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Neoplasias Colorretais , MicroRNAs , RNA Longo não Codificante , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Transição Epitelial-Mesenquimal/genética , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismoRESUMO
OBJECTIVE: Hyperlipidemia is a main reason of pancreatitis. Baicalein can ameliorate the pathological manifestations of pancreatitis. This study evaluated underlying molecular mechanism of baicalein in hyperlipidemic pancreatitis (HP). METHODS: HP rat model was successfully established and treated with baicalein. Amylase (AMY) activity and concentrations of triglyceride (TG) and total cholesterol (TC) were detected. Levels of pyroptosis-related proteins (GSDMD, IL-1ß, IL-18) were detected by Western blot. Expressions of inflammatory factors (IL-6, TNF-α, IL-4) were detected by ELISA. Toxicity of baicalein on pancreatic acinar cells (PACs) was detected by MTT assay. HP cell model was established by 0.1 mM palmitic acid and CCK-8 stimulation. Target relation of miR-192-5p and TXNIP was predicted and verified by RNA22 v2 database and dual-luciferase reporter assay. Expressions of miR-192-5p and TXNIP were detected by RT-qPCR. Pyroptosis and inflammation in PACs were detected after baicalein treatment combined with silencing miR-192-5p or TXNIP overexpression. Protein levels of NLRP3/Caspase-1 pathway in vivo and vitro were detected. RESULTS: Baicalein reduced concentrations of TG and TC, AMY activity, and pathological scores in HP rat model, reduced LDH activity, pyroptosis and alleviated inflammation in vivo and in vitro. Mechanically, miR-192-5p targeted TXNIP, and baicalein inhibited pyroptosis and inflammation by up-regulating miR-192-5p and down-regulating TXNIP. Silencing miR-192-5p or TXNIP overexpression partially abolished the anti-pyroptosis and anti-inflammatory effect of baicalein on PACs. Baicalein attenuated HP by inhibiting the NLRP3/Caspase-1 pathway. CONCLUSION: Baicalein alleviated pyroptosis and inflammation in HP by inhibiting the NLRP3/Caspase-1 pathway through miR-192-5p upregulation and TXNIP inhibition.
Assuntos
Piroptose/efeitos dos fármacos , Animais , Proteínas de Transporte , Caspase 1/metabolismo , Regulação para Baixo , Flavanonas , Inflamassomos/metabolismo , Inflamação , Interleucina-18/metabolismo , Interleucina-1beta , MicroRNAs/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Pancreatite , RNA Longo não Codificante/metabolismo , Ratos , Transdução de Sinais , Regulação para CimaRESUMO
Glioblastoma (GBM) is a fatal brain tumor with poor prognosis. Blood-brain barrier (BBB) prevents the effective delivery of chemotherapeutic agents to GBM. Herein, we developed a pH/reduction-sensitive carboxymethyl chitosan nanogel (CMCSN) modified by targeting peptide angiopep-2 (ANG) and loaded with doxorubicin (DOX). The multifunctional nanogel (DOX-ANG-CMCSN) exhibited good pH and reduction sensitivity, ideal stability, and biocompatibility. Its hydrodynamic diameter was 190 nm, drug loading was 12.7%, and the cumulative release rate of 24 h was 82.3% under the simulated tumor microenvironment. More importantly, the modification of ANG significantly enhanced BBB penetration and tumor targeting ability both in vivo and in vitro. DOX-ANG-CMCSN achieved 2-3-fold higher uptake and an enhanced antitumor activity compared with nontargeted DOX-CMCSN. Therefore, the targeted nanogels with the pH/reduction dual-stimuli response may provide a promising platform for GBM-targeted chemotherapy.
Assuntos
Quitosana , Glioblastoma , Linhagem Celular Tumoral , Doxorrubicina , Glioblastoma/tratamento farmacológico , Humanos , Concentração de Íons de Hidrogênio , Nanogéis , Peptídeos , Microambiente TumoralRESUMO
OBJECTIVES: To retrospectively investigate whether radiological and clinicopathological characteristics were associated with the presence of stage IA-IIA lung adenocarcinoma in patients at high risk for a postoperative recurrence. MATERIALS AND METHODS: Three hundred twelve patients with biopsy-proven node-negative early-stage (IA-IIA) lung adenocarcinoma met the inclusion criteria for this study. Demographics data and histopathological findings were collected from medical records. Computed tomography (CT) performed approximately 1 month before surgery was manually scored using 23 CT descriptors. Univariate analyses were applied to demonstrate an association between clinicopathological and radiological features and 2-/5-year recurrences. Multivariate logistic regression was performed to assess the ability of radiological and clinicopathological features to discriminate low and high-risk factors for recurrence. A ROC curve was used to evaluate prediction performance. RESULTS: Univariate analysis revealed that the 2-year recurrence was associated with six radiological features and two clinicopathological features, while 5-year recurrence was associated with five radiological features and two clinicopathological features. A multivariate logistic regression model of combined clinicopathological and radiological features showed that stage IIA (OR = 2.87), solid texture (solid part > 50 %: OR = 4.81; solid part = 100 %: OR = 3.61), pleural attachment (OR = 3.97) and bronchovascular bundle thickening (OR = 2.16) were associated with the independent predictors of 2-year recurrence, and stage IIA (OR = 3.52), solid texture (solid part > 50 %: OR = 3.56; solid part = 100 %: OR = 2.44) and pleural attachment (OR = 4.57) were associated with 5-year recurrence. Combined radiological and clinicopathological features could be significant indicators of 2- and 5-year recurrences (AUC = 0.784 and AUC = 0.815, respectively). CONCLUSIONS: The combination of radiological and clinicopathological features has the potential to help predict postoperative recurrence in patients with stage IA-IIA lung adenocarcinomas and guide oncologists and patients whether to undergo additional treatment after surgery.