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Objectives: Iatrogenic ureteral injury is a severe surgical complication, with a highest incidence of 1.5% in gynecological surgeries. The purpose of this report is to document our initial experience with using methylene blue (MB) to label the ureter in gynecological laparoscopic surgeries and to explore its effectiveness and safety. This is also a novel description of simultaneously visualizing ureteral MB fluorescence and sentinel lymph nodes (SLN's) Indocyanine Green (ICG) fluorescence using the same camera. Methods: This study included patients undergoing gynecological laparoscopic surgeries, with the same surgeon performing all cases. During the early stages of each surgery, rapid intravenous infusion of MB was administered. For cases requiring SLN imaging, we also injected ICG solution into the cervix. Assessment of the included cases was conducted both intraoperatively and postoperatively. The group that had MB fluorescence (Group A) was compared to a control group that did not have it (Group B). Results: A total of 25 patients (Group A) received MB during surgery, demonstrating 45 ureters clearly, with an imaging success rate of 90%. Continuous and clearer fluorescence imaging was achieved in cases with ureteral hydronephrosis. In most patients, ureteral fluorescence was visible 15-20â min after intravenous infusion of MB, and 64% still exhibited fluorescence at the end of the surgery. In patients who had both ICG and MB, dual fluorescence imaging was achieved clearly. Among the included cases, there were no iatrogenic ureteral injuries (0%), which we observed to be lower than in patients who did not receive MB (1.3%). The rate of adverse events was similar in both groups. Conclusion: Using MB fluorescence is an effective and safe method of visualizing the ureters during gynecological surgeries, and can diminish iatrogenic ureteral injury without increased associated adverse events. It therefore may offer promising prospects for clinical application.
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Background: Several prospective studies have found that local surgical resection did not improve the survival of patients with de novo metastatic breast cancer (dnMBC). However, a significant portion of dnMBC patients still undergo local surgery, and the role of axillary lymph node dissection (ALND) in dnMBC patients remains unclear. This study aimed to investigate the effect of ALND in patients with dnMBC. Methods: We included patients diagnosed with dnMBC between 2010 and 2020 using the data from the Surveillance, Epidemiology, and End Results program. The Chi-square test, binomial logistic regression, propensity score matching (PSM), Kaplan-Meier method, and multivariate Cox proportional models were employed for statistical analysis. Results: A total of 6,838 patients were identified, with 5,562 (81.3%) in the ALND group and 1,276 (18.7%) in the non-ALND group. Being diagnosed in later years emerged as an independent predictive factor related to the receipt of ALND (P=0.003). Before PSM, the 5-year breast cancer-specific survival (BCSS) was 51.1% and 38.2% in those with and without ALND, respectively (P<0.001). The 5-year overall survival (OS) was 45.9% and 32.3% in those with and without ALND, respectively (P<0.001). ALND was identified as an independent prognostic factor related to better BCSS (P<0.001) and OS (P<0.001) compared to the non-ALND group. Similar findings were observed after PSM. The outcomes were significantly better in the ALND group than in the non-ALND group in most subgroups. However, the number of removed lymph nodes did not show a significant association with BCSS (P=0.27) and OS (P=0.29). Conclusions: Our study suggests that ALND is associated with improved survival outcomes in dnMBC patients. These findings advocate for a re-evaluation of the role of surgical interventions in dnMBC, emphasizing the need for personalized treatment strategies that consider the potential benefits of ALND.
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Urban vacant land (UVL) has been an important issue in the urbanization process, especially for shrinking cities. Identifying UVL and analyzing its spatiotemporal characteristics are the foundation for coping with this issue. This study identified UVL in 497 shrinking cities on the globe (10 % of shrinking cities in total) in 2016 and 2021 using manual labeling and deep learning to reflect the distribution patterns of UVL and its spatiotemporal changes. The results reveal that a global expansion of UVL from 2016 to 2021 in 497 shrinking cities, with diverse distribution patterns and varying changes across different regions. As for socioeconomic factors, UVL is related to population shrinkage, and the UVL ratio presents a phased change with the increase of the urbanization rate, revealing an inverted U-shaped relationship between the UVL ratio and the urbanization rate. The distribution patterns of UVL also vary globally in different urbanization phases. This study can provide theoretical and practical insights for improving urban planning and promoting sustainable urbanization.
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Osteoarthritis (OA), a chronic joint disease affecting over 500 million individuals globally, is characterized by the destruction of articular cartilage and joint inflammation. Conventional treatments are insufficient for repairing damaged joint tissue, necessitating novel therapeutic approaches. Mesenchymal stem cells (MSCs), with their potential for differentiation and self-renewal, hold great promise as a treatment for OA. However, challenges such as MSC viability and apoptosis in the ischemic joint environment hinder their therapeutic effectiveness. Hydrogels with biocompatibility and degradability offer a three-dimensional scaffold that support cell viability and differentiation, making them ideal for MSC delivery in OA treatment. This review discusses the pathological features of OA, the properties of MSCs, the challenges associated with MSC therapy, and methods for hydrogel preparation and functionalization. Furthermore, it highlights the advantages of hydrogel-based MSC delivery systems while providing insights into future research directions and the clinical potential of this approach.
Subject(s)
Hydrogels , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Osteoarthritis , Humans , Osteoarthritis/therapy , Osteoarthritis/pathology , Hydrogels/chemistry , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cell Transplantation/methods , Animals , Cell Differentiation , Cartilage, Articular/pathologyABSTRACT
MicroRNAs (miRNAs) are a class of small RNA genes with important roles in cancer biology regulation. There are considerable studies regarding the roles of microRNA-505-3p (miR-505-3p) in cancer development and progression, but the function of miR-505-3p in epithelial ovarian cancer (EOC) has not been fully clarified. Comparative analysis of miRNA expression data set was used to select differentially expressed miRNAs. Quantitative real-time polymerase chain reaction was applied to detect expression levels of RNAs, while western blot and immunofluorescence staining were performed to detect expression levels of proteins of interest. The motility of EOC cells was assessed by wound healing and transwell assays. The binding and regulating relationship between miRNA and its direct target gene was investigated by dual-luciferase assay. Our results show that miR-505-3p was upregulated in recurrent EOC, which significantly inhibits EOC cell motility via modulating cell epithelial-mesenchymal transition. Furthermore, our results indicated that PEAK1 expression was inhibited by direct binding of miR-505-3p into its 3'-URT in EOC cells. Importantly, knockdown of PEAK1 attenuated the effect of mi-505-3p inhibitor on EOC cell migration and invasion. In conclusion, our findings indicate that miRNA-505-3p inhibits EOC cell motility by targeting PEAK1.
Subject(s)
Carcinoma, Ovarian Epithelial , Cell Movement , Epithelial-Mesenchymal Transition , Gene Expression Regulation, Neoplastic , MicroRNAs , Ovarian Neoplasms , MicroRNAs/genetics , MicroRNAs/metabolism , Humans , Female , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , Ovarian Neoplasms/metabolism , Carcinoma, Ovarian Epithelial/genetics , Carcinoma, Ovarian Epithelial/metabolism , Carcinoma, Ovarian Epithelial/pathology , Cell Line, Tumor , Epithelial-Mesenchymal Transition/geneticsABSTRACT
Multiple myeloma (MM) denotes a cancerous growth characterized by abnormal proliferation of plasma cells. Growing evidence suggests that the complexity in addressing MM lies in the presence of minimal residual disease (MRD) within the body. MRD assessment is becoming increasingly important for risk assessment in patients with MM. Similarly, the levels of serum free protein light chain and their ratio play a crucial role in assessing the disease burden and changes in MM. In this paper, we review and explore the utilization of MRD and serum free light chain ratio in the treatment of MM, delving into their respective characteristics, advantages, disadvantages, and their interrelation.
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The UN (United Nations) collects global data on the country-level Percentage of Population Residing in Urban Area (PPRUA). However, variations in urban definitions make these data incomparable across countries. This study assesses national defined PPRUA within UN statistics against estimates we derived using global comparable definitions. Refer to the UN's Degree of Urbanization framework, we propose 90 global harmonized methods for estimating PPRUA by combining different configurations of three global population datasets, six urban total population thresholds, and five urban population density thresholds. This approach demonstrated significant variations in country-level PPRUA estimations, with wide 95% confidence intervals using the Z score method. Most national defined PPRUA fall between the upper 95% CI and the median of the estimations, underscoring the need for globally harmonious PPRUA estimates. This study advocates for a reassessment of datasets and thresholds in the future and for investigating urbanization on a scale beyond the country level.
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Modifications at different positions on the aloperine molecule were performed to improve its anticancer activity and develop anticancer drugs. The in vitro anticancer activities of 44 synthesized compounds were evaluated. The effect of modification positions on anticancer activity was discussed and a structure-activity relationship analysis was established. A novel series of compounds with modifications at the N12 position showed much higher cytotoxicity than aloperine. Among them, compound 22 displayed promising in vitro anticancer activity against PC9 cells with a median inhibitory concentration (IC50) of 1.43 µM. The mechanism studies indicated that compound 22 induced cell apoptosis and cell cycle arrest in PC9 cells. These results demonstrate the potential of aloperine thiourea derivatives in anticancer activity.
Subject(s)
Antineoplastic Agents , Apoptosis , Drug Screening Assays, Antitumor , Piperidines , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Humans , Structure-Activity Relationship , Molecular Structure , Apoptosis/drug effects , Piperidines/pharmacology , Piperidines/chemistry , Piperidines/chemical synthesis , Drug Design , Quinolizidines/pharmacology , Quinolizidines/chemistry , Quinolizidines/chemical synthesis , Cell Line, Tumor , Cell Cycle Checkpoints/drug effectsABSTRACT
Background: The 18-24 age group has a much higher rate of depression risk than other age groups, and this age group has the highest proportion among users of mobile social media. The relationship between the use of mobile social media and depressive mood is inconsistent and the mechanism of action is controversial. Purpose: This study explored the relationship among the intensity of social media use, upward social comparison, cognitive overload and depressive mood. Methods: In this research, we used the Brief Self-rating Depression Scale (PHQ-9), the Social Media Usage Intensity Questionnaire, the Social Comparison Scale on Social Networking Sites and the Social Networking Site Cognitive Overload Scale to investigate the depressive mood and mobile social media use of 568 college students. Results: The intensity of mobile social media use, social networking site upward social comparison, and social networking site cognitive overload are all positively correlated with depressive mood. The intensity of mobile social media use has a positive predictive effect on depressive mood, with upward social comparison and cognitive overload acting as independent mediators in the relationship between mobile social media use intensity and depressive symptoms, as well as exhibiting a chained mediating effect of upward social comparison-cognitive overload. Conclusion: The upward social comparison and cognitive load that occur during the use of mobile social media are important predictive factors for the occurrence of depressive mood. This study is a supplement to the mechanism of the relationship between mobile social media use and depression, providing more evidence-based evidence and intervention directions for university teachers, mobile social media developers, and psychologists.
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BACKGROUND: The oral cavity is home to various ecological niches, each with its own unique microbial composition. Understanding the microbial communities and gene composition in different ecological niches within the oral cavity of oral cancer (OC) patients is crucial for determining how these microbial populations contribute to disease progression. METHODS: In this study, saliva and dental plaque samples were collected from patients with OC. Metagenomic sequencing was employed to analyze the microbial community classification and functional composition of the different sample groups. RESULTS: The results of the study revealed significant differences in both the function and classification of microbial communities between saliva and dental plaque samples. The diversity of microbial species in saliva was found to be higher compared to that in plaque samples. Notably, Actinobacteria were enriched in the dental plaque of OC patients. Furthermore, the study identified several inter-group differential marker species, including Prevotella intermedia, Haemophilus parahaemolyticus, Actinomyces radius, Corynebacterium matruchitii, and Veillonella atypica. Additionally, 1,353 differential genes were annotated into 23 functional pathways. Interestingly, a significant correlation was observed between differentially labeled species and Herpes simplex virus 1 (HSV-1) infection, which may be related to the occurrence and development of cancer. CONCLUSIONS: Significant differences in the microbial and genetic composition of saliva and dental plaque samples were observed in OC patients. Furthermore, pathogenic bacteria associated with oral diseases were predominantly enriched in saliva. The identification of inter-group differential biomarkers and pathways provide insights into the relationship between oral microbiota and the occurrence and development of OC.
Subject(s)
Dental Plaque , Mouth Neoplasms , Humans , Saliva/microbiology , Dental Plaque/microbiology , Bacteria/genetics , RNA, Ribosomal, 16S/geneticsABSTRACT
The development of efficient, accurate, and high-throughput technology for gut microbiota sensing holds great promise in the maintenance of health and the treatment of diseases. Herein, we developed a rapid fluorescent sensor array based on surface-engineered silver nanoparticles (AgNPs) and vancomycin-modified gold nanoclusters (AuNCs@Van) for gut microbiota sensing. By controlling the surface of AgNPs, the recognition ability of the sensor can be effectively improved. The sensor array was used to successfully discriminate six gut-derived bacteria, including probiotics, neutral, and pathogenic bacteria and even their mixtures. Significantly, the sensing system has also been successfully applied to classify healthy individuals and colorectal cancer (CRC) patients rapidly and accurately within 30 min, demonstrating its clinically relevant specificity.
Subject(s)
Colorectal Neoplasms , Gastrointestinal Microbiome , Gold , Metal Nanoparticles , Silver , Colorectal Neoplasms/microbiology , Colorectal Neoplasms/diagnosis , Humans , Silver/chemistry , Metal Nanoparticles/chemistry , Gold/chemistry , Vancomycin/pharmacology , Surface Properties , Fluorescent Dyes/chemistryABSTRACT
The infected wounds pose one of the major threats to human health today. To address this issue, it is necessary to develop innovative wound dressings with superior antibacterial activity and other properties. Due to its potent antibacterial, antioxidant, and immune-boosting properties, epigallocatechin gallate (EGCG) has been widely utilized. In this study, a multifunctional curdlan hydrogel loading EGCG (Cur-EGCGH3) was designed. Cur-EGCGH3 exhibited excellent physicochemical properties, good biocompatibility, hemostatic, antibacterial, and antioxidant activities. Also, ELISA data showed that Cur-EGCGH3 stimulated macrophages to secrete pro-inflammatory and pro-regenerative cytokines. Cell scratch results indicated that Cur-EGCGH3 promoted the migration of NIH3T3 and HUVECs. In vivo experiments confirmed that Cur-EGCGH3 could inhibit bacterial infection of the infected wounds, accelerate hemostasis, and promote epithelial regeneration and collagen deposition. These results demonstrated that Cur-EGCGH3 holds promise for promoting healing of the infected wounds.
Subject(s)
Anti-Bacterial Agents , Catechin , Catechin/analogs & derivatives , Hemostatics , Hydrogels , Wound Healing , beta-Glucans , Catechin/pharmacology , Catechin/chemistry , Animals , Wound Healing/drug effects , Mice , beta-Glucans/chemistry , beta-Glucans/pharmacology , Hydrogels/chemistry , Hydrogels/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Humans , NIH 3T3 Cells , Hemostatics/pharmacology , Hemostatics/chemistry , Wound Infection/drug therapy , Wound Infection/microbiology , Antioxidants/pharmacology , Antioxidants/chemistry , Human Umbilical Vein Endothelial Cells/drug effectsABSTRACT
BACKGROUND: During the brewing of soy sauce, the conversion of multiple substances is driven by various microorganisms and their secreted enzyme systems. Soy sauce mash is an important source of enzyme systems during moromi fermentation, but the changes of enzyme systems in soy sauce mash during moromi fermentation are poorly understood. In order to explore the predominant enzyme systems existing during moromi fermentation and to explain the characteristics of the enzyme system changes, an enzymatic activities assay and 4D-label-free proteomics analysis were conducted on soy sauce mash at different stages of fermentation. RESULTS: The activities of hydrolytic enzymes in soy sauce mash decreased continuously throughout the fermentation process, while most of the characteristic physicochemical substances in soy sauce mash supernatant had already accumulated at the early stage of fermentation. Four hydrolytic enzymes were found to be positively correlated with important physicochemical indexes by principal component analysis and Pearson correlation analysis. The proteomics analysis revealed three highly upregulated enzymes and two enzymes that were present in important metabolic pathways throughout the fermentation process. Furthermore, it was found that Aspergillus oryzae was able to accumulate various nutrients in the soy sauce mash by downregulating most of its metabolic pathways. CONCLUSION: Enzymes present with excellent properties during the moromi fermentation period could be obtained from these results. Meanwhile, the characterization of the metabolic pathways of microorganisms during the moromi fermentation period was revealed. The results provide a basis for more scientific and purposeful improvement of moromi fermentation in the future. © 2024 Society of Chemical Industry.
Subject(s)
Fermentation , Proteomics , Soy Foods , Soy Foods/analysis , Soy Foods/microbiology , Fungal Proteins/metabolism , Aspergillus oryzae/metabolism , Aspergillus oryzae/enzymologyABSTRACT
BACKGROUND: Human amniotic mesenchymal stem cells (hAMSCs) derived from amniotic membrane have multilineage differentiation, immunosuppressive, and anti-inflammation which makes them suitable for the treatment of various diseases. OBJECTIVE: This study aimed to explore the therapeutic effect and molecular mechanism of hAMSCs in ventricular remodeling (VR). METHODS: hAMSCs were characterized by a series of experiments such as flow cytometric analysis, immunofluorescence, differentiative induction and tumorigenicity. Mouse VR model was induced by isoproterenol (ISO) peritoneally, and the therapeutic effects and the potential mechanisms of hAMSCs transplantation were evaluated by echocardiography, carboxy fluorescein diacetate succinimidyl ester (CFSE) labeled cell tracing, histochemistry, qRT-PCR and western blot analysis. The co-culturing experiments were carried out for further exploring the mechanisms of hAMSCs-derived conditioned medium (CM) on macrophage polarization and fibroblast fibrosis in vitro. RESULTS: hAMSCs transplantation significantly alleviated ISO-induced VR including cardiac hypertrophy and fibrosis with the improvements of cardiac functions. CFSE labeled hAMSCs kept an undifferentiated state in heart, indicating that hAMSCs-mediated the improvement of ISO-induced VR might be related to their paracrine effects. hAMSCs markedly inhibited ISO-induced inflammation and fibrosis, seen as the increase of M2 macrophage infiltration and the expressions of CD206 and IL-10, and the decreases of CD86, iNOS, COL3 and αSMA expressions in heart, suggesting that hAMSCs transplantation promoted the polarization of M2 macrophages and inhibited the polarization of M1 macrophages. Mechanically, hAMSCs-derived CM significantly increased the expressions of CD206, IL-10, Arg-1 and reduced the expressions of iNOS and IL-6 in RAW264.7 macrophages in vitro. Interestingly, RAW264.7-CM remarkably promoted the expressions of anti-inflammatory factors such as IL-10, IDO, and COX2 in hAMSCs. Furthermore, the CM derived from hAMSCs pretreated with RAW264.7-CM markedly inhibited the expressions of fibrogenesis genes such as αSMA and COL3 in 3T3 cells. CONCLUSION: Our results demonstrated that hAMSCs effectively alleviated ISO-induced cardiac hypertrophy and fibrosis, and improved the cardiac functions in mice, and the underlying mechanisms might be related to inhibiting the inflammation and fibrosis during the ventricular remodeling through promoting the polarization of CD206hiIL-10hi macrophages in heart tissues. Our study strongly suggested that by taking the advantages of the potent immunosuppressive and anti-inflammatory effects, hAMSCs may provide an alternative therapeutic approach for prevention and treatment of VR clinically.
Subject(s)
Fluoresceins , Interleukin-10 , Mesenchymal Stem Cells , Succinimides , Mice , Humans , Animals , Interleukin-10/pharmacology , Amnion , Isoproterenol , Ventricular Remodeling , Macrophages , Inflammation/chemically induced , Inflammation/therapy , Anti-Inflammatory Agents/therapeutic use , Anti-Inflammatory Agents/pharmacology , Fibrosis , CardiomegalyABSTRACT
Introduction. Inappropriate use of antibiotics and inadequate therapeutic regimens for early-stage pulmonary infections are major contributors to increased prevalence of complications and mortality. Moreover, due to the limitations in sensitivity of conventional testing, there is an urgent need for more diagnostically efficient methods for the detection and characterization of pathogens in pulmonary infections.Hypothesis/Gap Statement. Metagenomic next-generation sequencing (mNGS) can contribute to the diagnosis and management of pulmonary infections.Aim. This study aimed to evaluate the clinical application and value of mNGS in the diagnosis of clinically suspected pulmonary infections by comparing with conventional testing.Methodology. In this study, the diagnosis performance of mNGS was evaluated using bronchoalveolar lavage fluid (BALF) samples from 143 patients with suspected lung infections. First, we conducted a prospective study on 31 patients admitted to Yuebei People's Hospital Affiliated to Shantou University Medical College to investigate the clinical value. Then a retrospective analysis was performed by including more patients (n=112) to reduce the random error. Pathogens were detected by mNGS and conventional methods (culture and PCR). Then, the types and cases of detected pathogens, as well as the specificity and sensitivity, were compared between the two methods. We evaluated the performance of mNGS in detecting bacterial, fungal, viral and mixed infections in BALF. The effect of disease severity in pulmonary infections on the integrity of mNGS pathogen detection was also explored.Results. The mNGS provided an earlier and more comprehensive pathogen profile than conventional testing, which in turn prompted a change in clinical medication, which led to improvement in eight patients (8/31=25.81â%) in the presence of other serious comorbidities. In a retrospective analysis, mNGS was much more sensitive than conventional testing in the diagnosis of pulmonary infections (95.33â% vs. 55.56â%; P<0.001), with a 39.77â% increase in sensitivity. The detection rate of mNGS for mixed infections was significantly higher than that of conventional testing methods for both common and severe pneumonia (48/67=71.64â% vs. 12/52=23.08â%, P<0.001; 44/59=74.58â% vs. 11/59=18.64â%, P<0.0001).Conclusion. The sensitivity of mNGS in the diagnosis of pathogenic microorganisms in pulmonary infections far exceeds that of conventional culture tests. As a complementary method to conventional methods, mNGS can help improve the diagnosis of pulmonary infections. In addition, mNGS pathogen integrity detection rate was similar in common and severe pneumonia. We recommend the prompt use of mNGS when mixed or rare pathogen infections are suspected, especially in immunocompromised individuals and/or critically ill individuals.
Subject(s)
Bacteriophages , Coinfection , Pneumonia , Humans , Bronchoalveolar Lavage Fluid , Prospective Studies , Retrospective Studies , High-Throughput Nucleotide Sequencing , Metagenomics , Sensitivity and SpecificityABSTRACT
The cultivated diploid Brassica oleracea is an important vegetable crop, but the genetic basis of its domestication remains largely unclear in the absence of high-quality reference genomes of wild B. oleracea. Here, we report the first chromosome-level assembly of the wild Brassica oleracea L. W03 genome (total genome size, 630.7 Mb; scaffold N50, 64.6 Mb). Using the newly assembled W03 genome, we constructed a gene-based B. oleracea pangenome and identified 29 744 core genes, 23 306 dispensable genes, and 1896 private genes. We re-sequenced 53 accessions, representing six potential wild B. oleracea progenitor species. The results of the population genomic analysis showed that the wild B. oleracea populations had the highest level of diversity and represents the most closely related population to modern-day horticultural B. oleracea. In addition, the WUSCHEL gene was found to play a decisive role in domestication and to be involved in cauliflower and broccoli curd formation. We also illustrate the loss of disease-resistance genes during selection for domestication. Our results provide new insights into the domestication of B. oleracea and will facilitate the future genetic improvement of Brassica crops.
Subject(s)
Brassica , Crops, Agricultural , Domestication , Genome, Plant , Brassica/genetics , Crops, Agricultural/genetics , Chromosomes, Plant/geneticsABSTRACT
Alzheimer's disease (AD) is a progressive neurodegenerative disease. Early detection and intervention are crucial in preventing the progression of AD. To achieve efficient and scalable AD auto-detection based on structural Magnetic Resonance Imaging (sMRI), a lightweight neural network using multi-slice sMRI is proposed in this paper. The backbone for feature extraction is based on ShuffleNet V1 architecture, which is effective for overcoming the limitations posed by limited sMRI data and resource-restricted devices. In addition, we incorporate Efficient Channel Attention (ECA) to capture cross-channel interaction information, enabling us to effectively enhance features of disease associated brain regions. To optimize the model, we employ both cross entropy loss and triplet loss functions to constrain the predicted probabilities to the ground-truth labels, and to ensure appropriate representation of distances between different classes in the learned features. Experimental results show that the classification accuracies of our method for AD vs. CN, AD vs. MCI, and MCI vs. CN classification tasks are 95.00%, 87.50%, and 85.62% respectively. Our method utilizes only 3.42 M parameters and 6.08G FLOPs, while maintaining a comparable level of performance compared to the other 5 latest lightweight methods. This model design is computationally efficient, allowing it to process large amounts of data quickly and accurately in a timely manner. Additionally, it has the potential to advance the intelligent detection of Alzheimer's disease on devices with limited computing capabilities.
Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Neurodegenerative Diseases , Humans , Alzheimer Disease/diagnostic imaging , Alzheimer Disease/pathology , Magnetic Resonance Imaging/methods , Neural Networks, ComputerABSTRACT
Cytokines are essential components of the immune system and are recognized as significant biomarkers. However, detection of a single cytokine is not precise and reliable enough to satisfy the requirements for diagnosis. Herein, we developed a pattern recognition-based method for the multiplexed sensing of cytokines, which involves three-color-emitting boronic acid-decorated carbon dots (BCDs) and arginine-modified titanium carbide (Ti3C2 MXenes) as the sensor array. Initially, the fluorescence signals of the three BCDs were quenched by Ti3C2 MXenes. In the presence of cytokines, the fluorescence intensity of the BCDs was restored or further quenched by different cytokines. The fluorescence response occurs in two steps: first, boronic acid interacts with cis-diol functional groups of cytokines, and second, arginine headgroup selectively interacts with glycans. By exploiting the different competing binding of the BCDs and the cytokines toward Ti3C2 MXenes, seven cytokines and their mixtures can be effectively discriminated at a concentration of 20 ng mL-1. Furthermore, our sensor array demonstrated an excellent performance in classifying human oral cancer saliva samples from healthy individuals with clinically relevant specificity. The noninvasive method offers a rapid approach to cytokine analysis, benefiting early and timely clinical diagnosis and treatment.
Subject(s)
Cytokines , Mouth Neoplasms , Humans , Carbon , Boronic Acids , Mouth Neoplasms/diagnosis , ArginineABSTRACT
IMPORTANCE: Gene mutations cannot explain all drug resistance of Mycobacterium tuberculosis, and the overexpression of efflux pump genes is considered another important cause of drug resistance. A total of 46 clinical isolates were included in this study to analyze the overexpression of efflux pump genes in different resistant types of strains. The results showed that overexpression of efflux pump genes did not occur in sensitive strains. There was no significant trend in the overexpression of efflux pump genes before and after one-half of MIC drug induction. By adding the efflux pump inhibitor verapamil, we can observe the decrease of MIC of some drug-resistant strains. At the same time, this study ensured the reliability of calculating the relative expression level of efflux pump genes by screening reference genes and using two reference genes for the normalization of quantitative PCR. Therefore, this study confirms that the overexpression of efflux pump genes plays an important role in the drug resistance of clinical isolates of Mycobacterium tuberculosis.