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BACKGROUND: Breast cancer (BC) is one of the most prevalent malignant tumours that threatens women health worldwide. It has been reported that circular RNAs (circRNAs) play an important role in regulating tumour progression and tumour microenvironment (TME) remodelling. METHODS: Differentially expression characteristics and immune correlations of circRNAs in BC were verified using high-throughput sequencing and bioinformatic analysis. Exosomes were characterised by nanoparticle transmission electron microscopy and tracking analysis. The biological function of circ-0100519 in BC development was demonstrated both in vitro and in vivo. Western blotting, RNA pull-down, RNA immunoprecipitation, flow cytometry, and luciferase reporter were conducted to investigate the underlying mechanism. RESULTS: Circ-0100519 was significant abundant in BC tumour tissues and related to poor prognosis. It can be encapsulated into secreted exosomes, thereby promoting BC cell invasion and metastasis via inducing M2-like macrophages polarisation.Mechanistically, circ-0100519 acted as a scaffold to enhance the interaction between the deubiquitinating enzyme ubiquitin-specific protease 7 (USP7) and nuclear factor-like 2 (NRF2) in macrophages, inducing the USP7-mediated deubiquitination of NRF2. Additionally, HIF-1α could function as an upstream effector to enhance circ-0100519 transcription. CONCLUSIONS: Our study revealed that exosomal circ-0100519 is a potential biomarker for BC diagnosis and prognosis, and the HIF-1α inhibitor PX-478 may provide a therapeutic target for BC.
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Neoplasias de la Mama , Exosomas , Factor 2 Relacionado con NF-E2 , ARN Circular , Peptidasa Específica de Ubiquitina 7 , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Humanos , ARN Circular/genética , ARN Circular/metabolismo , Femenino , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/genética , Peptidasa Específica de Ubiquitina 7/genética , Peptidasa Específica de Ubiquitina 7/metabolismo , Exosomas/metabolismo , Exosomas/genética , Macrófagos/metabolismo , Ratones , Progresión de la Enfermedad , Animales , Línea Celular TumoralRESUMEN
MAF bZIP transcription factor G (MAFG)-driven astrocytes have been reported to promote inflammation in the CNS. However, its function in depression, the primary cause of disability worldwide, has not been well characterized. This study investigated the possible perturbation of heme oxygenase 1 (HMOX1, also known as HO1) by the transcription factor MAFG as an underlying mechanism of the development of depression. The GSE98793 dataset was included for gene expression analysis of whole blood from donors with major depressive disorder and controls, and the target of MAFG was predicted by multiple database mining. Mouse and cellular models of depression were established by chronic unpredictable mild stress (CUMS) and lipopolysaccharide (LPS) treatment of astrocytes, which were treated with MAFG and HMOX1 knockdown plasmids. MAFG was highly expressed in the hippocampal tissues of CUMS-challenged mice and LPS-induced astrocytes. MAFG knockdown alleviated depression-like behaviors in mice. MAFG bound to the HMOX1 promoter and repressed its transcription. Knockdown of HMOX1 exacerbated neuroinflammation in astrocytes and accelerated depression-like behavior in mice. In conclusion, MAFG knockdown attenuated CUMS-stimulated depression-like behaviors in mice by astrocyte-mediated neuroinflammation via restoration of HMOX1.
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Astrocitos , Depresión , Hemo-Oxigenasa 1 , Enfermedades Neuroinflamatorias , Animales , Astrocitos/metabolismo , Ratones , Hemo-Oxigenasa 1/metabolismo , Depresión/metabolismo , Masculino , Enfermedades Neuroinflamatorias/metabolismo , Proteínas de la Membrana/metabolismo , Lipopolisacáridos/farmacología , Hipocampo/metabolismo , Ratones Endogámicos C57BL , Proteínas Represoras/metabolismo , Proteínas Represoras/genética , Humanos , Modelos Animales de Enfermedad , Estrés Psicológico/metabolismo , Inflamación/metabolismoRESUMEN
Turbidity is a crucial indicator of water quality. The European Commission's Copernicus Land Monitoring Service Platform provides free turbidity data for large lakes to monitor the global water quality of lakes. However, the data were missing from April 2012 to April 2016, severely limiting long-term analysis. Based on MODIS and turbidity data, Random Forest and XGBoost models are used to invert Tonle Sap Lake's turbidity. Random Forest outperformed the XGBoost model. Based on Random Forest model, missing data were filled in to construct long-term series data of Tonle Sap Lake turbidity (2004-2021). Trend, persistence and correlation analyses were conducted to reveal spatiotemporal characteristics and driving mechanism of turbidity. The results showed that: (1) spatially, the average annual, monthly, and seasonal turbidity was higher in the north but lower in the south, with regions of higher turbidity exhibiting more significant changes; (2) temporally, the annual turbidity mean was 53.99 NTU and showed an increasing trend. Monthly, turbidity values were higher from March to August and lower from September to February, with the highest and lowest recorded in June and November at 110.06 and 5.82 NTU, respectively. Seasonally, turbidity was higher in spring and summer compared to autumn and winter, with mean turbidity values of 84.16, 93.47, 15.33 and 23.21 NTU, respectively; (3) In terms of sustainability, the Hurst exponent for annual turbidity was 0.23, indicating a reverse trend in the near future; (4) Dam construction's impact on turbidity was not significant. Compared with natural factors (permanent wetlands, grasslands, lake surface water temperature, and remote sensing ecological index), human activities (barren, urban and built-up lands, croplands and population density) had a more significant impact on turbidity. Turbidity was highly correlated with croplands (r = 0.76), followed by population density (r = 0.71), and urban and built-up lands (r = 0.69).
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Acoustic methods are often used for fisheries resource surveys to investigate fish stocks in a wide area. Commercial fisheries echo sounders, which are installed on most small fishing vessels, are used to record a large amount of data during fishing trips. Therefore, it can be used to collect the basic information necessary for stock assessment for a wide area and frequently. To carry out the quantification for the fisheries echo sounder, we devised a simple method using the backscattering strength of the seabed to perform calibration periodically and easily. In this study, seabed secondary reflections were used instead of primary reflection because the fisheries echo sounders were not equipped with a time-varied gain (TVG) function, and the primary backscattering strength of the seabed was saturated. It was also necessary to use standard values of seabed backscattering strength averaged over a certain area for calibration to eliminate some of the effects of differences in seabed sediment and vessel motions. By using standard values of the seabed secondary reflections, the fisheries echo sounder was calibrated accurately. Our study can provide a reliable framework to calibrate commercial fisheries echo sounders, to improve the estimation and management of fishery resources.
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Explotaciones Pesqueras , Calibración , Animales , Acústica/instrumentación , Peces/fisiología , Conservación de los Recursos Naturales/métodosRESUMEN
BACKGROUND: Cinnamomum cassia Presl, a traditional Chinese medicine recorded in "Shennong's Herbal Classic," has been historically used to treat respiratory diseases and is employed to address inflammation. The essential oil derived from Cinnamomum cassia bark is a primary anti-inflammatory agent. However, there remains ambiguity regarding the chemical composition of cinnamon bark essential oil (BCEO), its principal anti-inflammatory components, and their potential efficacy in typical inflammatory respiratory conditions, such as acute lung injury (ALI). PURPOSE: This study aimed to unveil the chemical composition of BCEO. In addition, the mechanism of action of BCEO in ameliorating ALI and regulating macrophage polarization through the TLR4/MyD88/NF-κB pathway was elucidated. METHODS: BCEO was extracted using supercritical fluid extraction (SFE) and characterized through gas chromatography-mass spectrometry (GC-MS) analysis. Acute oral toxicity was observed in C57BL/6 J mice. The pharmacological effects and underlying mechanisms of BCEO were evaluated in a mouse model of ALI, which was induced by administering 5 mg/kg of lipopolysaccharide (LPS) through intratracheal instillation. RESULTS: GC-MS analysis revealed 99.08% of the constituents of BCEO. The primary components of BCEO were trans-cinnamaldehyde, o-methoxycinnamaldehyde, (+)-α-muurolene, δ-cadinene, and copaene. Oral acute toxicity tests indicated that the maximum tolerated dose of BCEO was 12 g/kg/day. BCEO treatment significantly reduced lung W/D ratio, total protein concentration in BALF, levels of TNF-α, IL-6, and IL-1ß in BALF, WBC count and NEU% in peripheral blood, and lung histological damage. Pulmonary function, IL-10 levels, and LYM% in peripheral blood also showed improvement. BCEO effectively decreased the proportion of M1 phenotype macrophages in BALF, M1/M2 ratio, and apoptotic cells in the lung tissue while increasing the proportion of M2 phenotype macrophages in BALF. Furthermore, BCEO treatment led to reduced protein and mRNA levels of TLR4, MyD88, and p-p65, alongside increased p65 expression, suggesting its potential to impede the TLR4/MyD88/NF-κB signaling pathway. CONCLUSION: SFE-extracted BCEO or its major constituents could serve as a viable treatment for ALI by reducing lung inflammation, improving pulmonary function, and protecting against LPS-induced ALI in mice. This therapeutic effect is achieved by inhibiting M1 macrophage polarization, promoting M2 macrophage polarization, and suppressing the TLR4/MyD88/NF-κB signaling pathway.
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Lesión Pulmonar Aguda , Antiinflamatorios , Cinnamomum aromaticum , Macrófagos , Aceites Volátiles , Corteza de la Planta , Animales , Masculino , Ratones , Acroleína/análogos & derivados , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/inducido químicamente , Antiinflamatorios/farmacología , Cinnamomum aromaticum/química , Modelos Animales de Enfermedad , Lipopolisacáridos , Macrófagos/efectos de los fármacos , Ratones Endogámicos C57BL , Factor 88 de Diferenciación Mieloide/metabolismo , FN-kappa B/metabolismo , Aceites Volátiles/farmacología , Aceites Volátiles/química , Corteza de la Planta/química , Transducción de Señal/efectos de los fármacos , Receptor Toll-Like 4/metabolismoRESUMEN
Eelgrass beds provide a habitat for many high-value fishery resources, and provisioning services, one of the ecosystem services, need to be quantified. However, few examples have been evaluated spatially. We determined the distribution of eelgrass beds in Lake Notoro, a marine lagoon in Hokkaido, Japan, and quantified the provisioning services by the eelgrass beds in relation to Pandalus latirostris, a fishery resource. Acoustic measurement surveys of the eelgrass beds and catch surveys of the shrimp were conducted in July and August 2015. The relationship between catch per unit effort (CPUE) of shrimp and the distribution of eelgrass beds was shown. The estimated distribution area of eelgrass beds was 7.07 km2. Shrimp was frequently caught at water depths of 3-5 m, approximately 200 m from the edge of the eelgrass beds. The expected catch of shrimp in the fishing area of Lake Notoro in 2015 was 25.37 tons and US$ 463.6 thousand. Eelgrass beds were found to affect the fisheries production not only on the inside but also at the edge and outside. The entire coastal space should be evaluated, while considering the effect of the distribution of eelgrass beds, to quantify the provisioning services.
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Ecosistema , Pandalidae , Animales , Japón , Lagos , Explotaciones PesquerasRESUMEN
This paper introduces a solution to address the intricacy of the model employed in the deep learning-based diagnosis of musculoskeletal abnormalities and the limitations observed in the performance of a single deep learning network model. The proposed approach involves the integration of an improved EfficientNet-B2 model with MobileNetV2, resulting in the creation of FusionNet. First, EfficientNet-B2 is combined with coordinate attention (CA) to obtain CA-EfficientNet-B2. Furthermore, aiming to minimize the model parameter count, we further enhanced the mobile inverted residual bottleneck convolution module (MBConv) employed for feature extraction in EfficientNet-B2, resulting in the development of CA-MBC-EfficientNet-B2. Next, the features extracted from CA-MBC-EfficientNet-B2 and MobileNetV2 are fused. Finally, the final diagnosis of musculoskeletal abnormalities was performed by using fully connected layers. The experimental results demonstrate that, first, compared to EfficientNet-B2, CA-MBC-EfficientNet-B2 not only significantly improves the diagnostic performance of musculoskeletal abnormalities, it also reduces the parameter count and storage space by 17%. Moreover, as compared to other models, FusionNet demonstrates remarkable performance in the area of anomaly diagnosis, particularly on the elbow dataset, achieving a precision of 92.93%, an AUC of 93.89% and an accuracy of 87.10%.
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Anomalías Musculoesqueléticas , Humanos , Anomalías Musculoesqueléticas/diagnóstico , Aprendizaje ProfundoRESUMEN
BACKGROUND: Triple-negative breast cancer (TNBC) is a type of highly invasive breast cancer with a poor prognosis. According to new research, long noncoding RNAs (lncRNAs) play a significant role in the progression of cancer. Although the role of lncRNAs in breast cancer has been well reported, few studies have focused on TNBC. This study aimed to explore the biological function and clinical significance of forkhead box C1 promoter upstream transcript (FOXCUT) in triple-negative breast cancer. METHODS: Based on a bioinformatic analysis of the cancer genome atlas (TCGA) database, we detected that the lncRNA FOXCUT was overexpressed in TNBC tissues, which was further validated in an external cohort of tissues from the General Surgery Department of the First Affiliated Hospital of Nanjing Medical University. The functions of FOXCUT in proliferation, migration, and invasion were detected in vitro or in vivo. Luciferase assays and RNA immunoprecipitation (RIP) were performed to reveal that FOXCUT acted as a competitive endogenous RNA (ceRNA) for the microRNA miR-24-3p and consequently inhibited the degradation of p38. RESULTS: lncRNA FOXCUT was markedly highly expressed in breast cancer, which was associated with poor prognosis in some cases. Knockdown of FOXCUT significantly inhibited cancer growth and metastasis in vitro or in vivo. Mechanistically, FOXCUT competitively bounded to miR-24-3p to prevent the degradation of p38, which might act as an oncogene in breast cancer. CONCLUSION: Collectively, this research revealed a novel FOXCUT/miR-24-3p/p38 axis that affected breast cancer progression and suggested that the lncRNA FOXCUT could be a diagnostic marker and therapeutic target for breast cancer.
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MicroARNs , ARN Largo no Codificante , Neoplasias de la Mama Triple Negativas , Humanos , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica/genética , Sistema de Señalización de MAP Quinasas , MicroARNs/genética , MicroARNs/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/genética , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/patologíaRESUMEN
In the field of the Internet of Things, image acquisition equipment is the very important equipment, which will generate lots of invalid data during real-time monitoring. Analyzing the data collected directly from the terminal by edge calculation, we can remove invalid frames and improve the accuracy of system detection. SSD algorithm has a relatively light and fast detection speed. However, SSD algorithm do not take full advantage of both shallow and deep information of data. So a multiscale feature fusion attention mechanism structure based on SSD algorithm has been proposed in this paper, which combines multiscale feature fusion and attention mechanism. The adjacent feature layers for each detection layer are fused to improve the feature information expression ability. Then, the attention mechanism is added to increase the attention of the feature map channels. The results of the experiments show that the detection accuracy of the optimized model is improved, and the reliability of edge calculation has been improved.
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Cancer is still one of the major problems threatening human health and the therapeutical efficacies of available treatment choices are often rather low. Due to their favorable biocompatibility, simplicity of modification, and improved therapeutic efficacy, peptide-based self-assembled delivery systems have undergone significant evolution. Physical encapsulation and covalent conjugation are two common approaches to load drugs for peptide assembly-based delivery, which are always associated with drug leaks in the blood circulation system or changed pharmacological activities, respectively. To overcome these difficulties, a more elegant peptide-based assembly strategy is desired. Notably, peptide-mediated co-assembly with drug molecules provides a new method for constructing nanomaterials with improved versatility and structural stability. The co-assembly strategy can be used to design various nanostructures for cancer therapy, such as nanotubes, nanofibrils, hydrogels, and nanovesicles. Recently, these co-assembled nanostructures have gained tremendous attention for their unique superiorities in tumor therapy. This article describes the classification of assembled peptides, driving forces for co-assembly, and specifically, the design methodologies for various drug molecules in co-assembly. It also highlights recent research on peptide-mediated co-assembled delivery systems for cancer therapy. Finally, it summarizes the pros and cons of co-assembly in cancer therapy and offers some suggestions for conquering the challenges in this field.
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Nanoestructuras , Nanotubos , Neoplasias , Humanos , Péptidos/química , Nanoestructuras/química , Hidrogeles/química , Neoplasias/tratamiento farmacológico , Sistemas de Liberación de Medicamentos/métodosRESUMEN
Exposure to essential and toxic metals occurs simultaneously as a mixture in real-life. However, there is no consensus regarding the effects of co-exposure to multiple metal(loid)s (designated hereafter metals) on blood lipid levels. Thus, blood concentrations of six human essential metals and five toxic metals in 720 general populations from southeastern China were simultaneously determined as a measure of exposure. In addition, quantile g-computation, Bayesian kernel machine regression, elastic net regression, and generalized linear model were used to investigate both the joint and individual effects of exposure to this metal mixture on human blood lipid levels. The significant positive joint effect of exposure to this metal mixture on serum total cholesterol (TC) levels, rather than on serum triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, Castelli risk index I, Castelli risk index II, atherogenic coefficient, and non-HDL-C levels, was found. In addition, the positive effect may be primarily driven by selenium (Se), lead (Pb), and mercury (Hg) exposure. In addition, on the effect of TC levels, the synergistic effect between Pb and Hg and the antagonistic effect between Se and Pb were identified. Our finding suggests that combined exposure to this metal mixture may affect human blood lipid levels. Therefore, reducing exposure to heavy metals, such as Pb and Hg, should be a priority for the general population. In addition, Se supplementation should also be considered with caution.
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Background: Breast cancer (BRCA) ranks first among cancers in terms of incidence and mortality rates in women, primarily owing to metastasis, chemo-resistance, and heterogeneity. To predict long-term prognosis and design novel therapies for BRCA, more sensitive markers need to be explored. Methods: Data from 1089 BRCA patients were downloaded from TCGA database. Pearson's correlation analysis and univariate and multivariate Cox regression analyses were performed to assess the role of cell death-related genes (CDGs) in predicting BRCA prognosis. Kaplan-Meier survival curves were generated to compare the overall survival in the two subgroups. A nomogram was constructed using risk scores based on the five CDGs and other clinicopathological features. CCK-8, EdU incorporation, and colony formation assays were performed to verify the inhibitory effect of NFKBIA on BRCA cell proliferation. Transwell assay, flow cytometry, and immunohistochemistry analyses were performed to ascertain the biological function of NFKBIA. Results: Five differentially expressed CDGs were detected among 156 CDGs. The risk score for each patient was then calculated based on the expression levels of the five CDGs. Distinct differences in immune inï¬ltration, expression of immune-oncological targets, mutation status, and half-maximal inhibitory concentration values of some targeted drugs were observed between the high- and low-risk groups. Finally, in vitro cell experiments verified that NFKBIA overexpression suppresses the proliferation and migration of BRCA cells. Conclusions: Our study revealed that some CDGs, especially NFKBIA, could serve as sensitive markers for predicting the prognosis of patients with BRCA and designing more personalized clinical therapies.
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Background: The five major RNA methylation modifications (m6A, m1A, m6Am, m5C, and m7G) exert biological roles in tumorigenicity and immune response, mediated mainly by "writer" enzymes. Here, the prognostic values of the "writer" enzymes and the TCP1 role in drug resistance in breast cancer (BC) were explored for further therapeutic strategies. Methods: We comprehensively characterized clinical, molecular, and genetic features of subtypes by consensus clustering. RNA methylation modification "Writers" and related genes_risk (RMW_risk) model for BC was constructed via a machine learning approach. Moreover, we performed a systematical analysis for characteristics of the tumor microenvironment (TME), alisertib sensitivity, and immunotherapy response. A series of experiments in vitro were carried out to assess the association of TCP1 with drug resistance. Results: One "writer" (RBM15B) and two related genes (TCP1 and ANKRD36) were identified for prognostic model construction, validated by GSE1456, GSE7390, and GSE20685 cohorts and our follow-up data. Based on the patterns of the genes related to prognosis, patients were classified into RMW_risk-high and RMW_risk-low subtypes. Lower RMW_Score was associated with better overall survival and the infiltration of immune cells such as memory B cells. Further analysis revealed that RMW_Score presented potential values in predicting drug sensitivity and response for chemo- and immunotherapy. In addition, TCP1 was confirmed to promote BC alisertib-resistant cell proliferation and migration in vitro. Conclusion: RMW_Score could function as a robust biomarker for predicting BC patient survival and therapeutic benefits. This research revealed a potential TCP1 role regarding alisertib resistance in BC, providing new sights into more effective therapeutic plans.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Metilación , Microambiente Tumoral/genética , ARNRESUMEN
BACKGROUND: Triple-negative breast cancer (TNBC), a heterogeneous subtype of breast cancer (BC), had poor prognosis. Endoplasmic reticulum (ER) stress was responsible for cellular processes and played a crucial role in the cell function. ER stress is a complex and dynamic process that can induce abnormal apoptosis and death. However, the underlying mechanism of ER stress involved in TNBC is not well defined. METHODS: We identified ubiquitin-specific protease 19 (USP19) as a TNBC negative regulator for further investigation. The effects of USP19 on BC proliferation were assessed in vitro using proliferation test and cell-cycle assays, while the effects in vivo were examined using a mouse tumorigenicity model. Through in vitro flow cytometric analyses and in vivo TUNEL assays, cell apoptosis was assessed. Proteomics was used to examine the proteins that interact with USP19. RESULTS: Multiple in vitro and in vivo tests showed that USP19 decreases TNBC cell growth while increasing apoptosis. Then, we demonstrated that USP19 interacts with deubiquitinates and subsequently stabilises family molecular chaperone regulator 6 (BAG6). BAG6 can boost B-cell lymphoma 2 (BCL2) ubiquitination and degradation, thereby raising ER calcium (Ca2+ ) levels and causing ER stress. We also found that the N6 -methyladenosine (m6 A) "writer" methyltransferase-like 14 (METTL14) increased global m6 A modification. CONCLUSIONS: Our study reveals that USP19 elevates the intracellular Ca2+ concentration to alter ER stress via regulation of BAG6 and BCL2 stability and may be a viable therapeutic target for TNBC therapy.
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Calcio , Neoplasias de la Mama Triple Negativas , Humanos , Animales , Neoplasias de la Mama Triple Negativas/genética , Estrés del Retículo Endoplásmico , Modelos Animales de Enfermedad , Enzimas Desubicuitinizantes , Proteínas Proto-Oncogénicas c-bcl-2 , Chaperonas Moleculares , EndopeptidasasRESUMEN
BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that poses a significant threat to a patient's quality of life. Commonly used drugs include glucocorticoids, nonsteroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, and biological agents; however, there are associated side effects. Complementary and alternative medicines can play positive roles. Bibliometric analysis of herbal medicines for RA has been conducted, but current research trends in nonpharmaceutical traditional Chinese medicine (TCM) therapies for the treatment of RA have not been studied. Here, we conducted a bibliometric analysis of the application of nonpharmaceutical TCM therapies for RA over the last 20 years. METHODS: We retrieved relevant literature from the Web of Science Core Collection database and used VOSviewer and CiteSpace software for analysis. Visualized maps were then generated to display the relationships between the author, country, institution, and keywords. RESULTS: A total of 567 articles were included in the final analysis. The number of annual publications on nonpharmaceutical TCM interventions for RA increased over the study period. The journal with the highest number of publications on this topic was Evidence-based Complementary and Alternative Medicine; however, Cochrane Database of Systematic Reviews had the most citations. Collaborations were observed among worldwide institutions, with the People's Republic of China playing a dominant role in the research on treatment of RA using nonpharmaceutical TCM therapies. Ernst E was the most productive author, with 11 articles, whereas Green S had the highest number of citations (287) at the time of retrieval. Specific improvements in the efficacy and selection of nonpharmaceutical therapies were the main research hotspots based on citation burst analysis. CONCLUSION: This study characterizes the trends in the literature for nonpharmaceutical TCM therapy for RA over the past 20 years; showcasing the current research status for relevant researchers and their teams and providing a reference for future research directions.
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Artritis Reumatoide , Medicina Tradicional China , Humanos , Calidad de Vida , Revisiones Sistemáticas como Asunto , Bibliometría , Artritis Reumatoide/tratamiento farmacológicoRESUMEN
Male breast cancer (MBC) is a rare but aggressive malignancy with cellular and immunological characteristics that remain unclear. Here, we perform transcriptomic analysis for 111,038 single cells from tumor tissues of six MBC and thirteen female breast cancer (FBC) patients. We find that that MBC has significantly lower infiltration of T cells relative to FBC. Metastasis-related programs are more active in cancer cells from MBC. The activated fatty acid metabolism involved with FASN is related to cancer cell metastasis and low immune infiltration of MBC. T cells in MBC show activation of p38 MAPK and lipid oxidation pathways, indicating a dysfunctional state. In contrast, T cells in FBC exhibit higher expression of cytotoxic markers and immune activation pathways mediated by immune-modulatory cytokines. Moreover, we identify the inhibitory interactions between cancer cells and T cells in MBC. Our study provides important information for understanding the tumor immunology and metabolism of MBC.
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Neoplasias de la Mama Masculina , Humanos , Femenino , Masculino , Análisis de Expresión Génica de una Sola Célula , Terapia de Inmunosupresión , Metabolismo de los Lípidos/genética , Ácidos GrasosRESUMEN
Lead (Pb), cadmium (Cd), and mercury (Hg) are environmentally toxic heavy metals that can be simultaneously detected at low levels in the blood of the general population. Although our previous studies have demonstrated neurodevelopmental toxicity upon co-exposure to these heavy metals at these low levels, the precise mechanisms remain largely unknown. Dendritic spines are the structural foundation of memory and undergo significant dynamic changes during development. This study focused on the dynamics of dendritic spines during brain development following Pb, Cd, and Hg co-exposure-induced memory impairment. First, the dynamic characteristics of dendritic spines in the prefrontal cortex were observed throughout the life cycle of normal rats. We observed that dendritic spines increased rapidly from birth to their peak value at weaning, followed by significant pruning and a decrease during adolescence. Dendritic spines tended to be stable until their loss in old age. Subsequently, a rat model of low-dose Pb, Cd, and Hg co-exposure from embryo to adolescence was established. The results showed that exposure to low doses of heavy metals equivalent to those detected in the blood of the general population impaired spatial memory and altered the dynamics of dendritic spine pruning from weaning to adolescence. Proteomic analysis of brain and blood samples suggested that differentially expressed proteins upon heavy metal exposure were enriched in dendritic spine-related cytoskeletal regulation and axon guidance signaling pathways and that cofilin was enriched in both of these pathways. Further experiments confirmed that heavy metal exposure altered actin cytoskeleton dynamics and disturbed the dendritic spine pruning-related LIM domain kinase 1-cofilin pathway in the rat prefrontal cortex. Our findings demonstrate that low-dose Pb, Cd, and Hg co-exposure may promote memory impairment by perturbing dendritic spine dynamics through dendritic spine pruning-related signaling pathways.
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Cadmio , Mercurio , Humanos , Adolescente , Animales , Ratas , Cadmio/toxicidad , Mercurio/toxicidad , Espinas Dendríticas , Plomo/toxicidad , Proteómica , Factores Despolimerizantes de la Actina , Encéfalo , Trastornos de la Memoria/inducido químicamenteRESUMEN
Breast cancer (BRCA) is the most fatal malignancy of women. Immunotherapy has greatly improved the prognosis of advanced BRCA. Cellular senescence contributes to tumorigenesis and suppresses anti-cancer immunity. Identification of senescence-relevant long noncoding RNAs (SRlncRNAs) signature may benefit the predictions of prognosis and response to immunotherapy of BRCA. RNA-seq, mutation, and clinical data of BRCA were acquired from public databases. SRlncRNAs were screened using univariate Cox regression analysis. Consensus clustering classified BRCA patients into 2 clusters, and the differences of overall survival (OS) and immune status between the 2 clusters were analyzed by survival analysis, CIBERSORT, and ESITIMATE. The SRlncRNAs signature was constructed by least absolute shrinkage and selection operator (LASSO) regression analysis, and BRCA patients were divided into 2 risk groups. Enrichment analyses were performed to explore the cancer- and immunotherapy-relevant pathways. Transcriptome analysis was performed to investigate the differences of OS, immune infiltration, and ESITIMATE score of the 2 groups. Genome analysis was applied to investigate the differences of somatic mutation, tumor mutation burden (TMB) and microsatellite instability (MSI) between the 2 risk groups. A nomogram combined with calibration curves and decision curve analysis (DCA) was established for better clinical decision. Tumor Immune Dysfunction and Exclusion (TIDE) score and IMvigor-210 were applied for the predicting of response to immunotherapy. Profiling Relative Inhibition Simultaneously in Mixtures (PRISM) and the Cancer Therapeutics Response Portal resource (CTRP) databases were used for drug susceptibility analysis. Ten prognostic SRlncRNAs were identified and BRCA patients were divided into 2 clusters. Cluster 1 had better OS with anti-tumor immune microenvironment. The high-risk BRCA had poorer OS in the Cancer Genome Atlas (TCGA) training cohort, which was also verified by TCGA validation cohort and GSE20685 validation cohort. Low-risk patients also had anti-tumor immune microenvironment. Genome analysis demonstrated that the high-risk group had significant higher TMB. High-risk BRCA were more susceptive to immunotherapy according to the TIDE score and IMvigor-210. Finally, drug susceptibility analysis showed that 6 compounds were sensitive to high-risk BRCA patients. We developed and verified an original SRlncRNAs signature by multi-omics analysis, which could serve as a prognosis and immunotherapy predictor for BRCA.
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Neoplasias de la Mama , ARN Largo no Codificante , Humanos , Femenino , Neoplasias de la Mama/genética , Neoplasias de la Mama/terapia , ARN Largo no Codificante/genética , Multiómica , Inmunoterapia , Carcinogénesis , Pronóstico , Microambiente Tumoral/genéticaRESUMEN
Depression clinical interview corpora are essential for advancing automated depression diagnosis. While previous studies have used written speech material in controlled settings, these materials do not accurately represent spontaneous conversational speech. Additionally, self-reported measures of depression are subject to bias, making the data unreliable for training models for real-world scenarios. This study introduces a new corpus of depression clinical interviews collected directly from a psychiatric hospital, containing 113 recordings with 52 healthy and 61 depressive patients. The subjects were examined using the Montgomery-Asberg Depression Rating Scale (MADRS) in Chinese. Their final diagnosis was based on medical evaluations through a clinical interview conducted by a psychiatry specialist. All interviews were audio-recorded and transcribed verbatim, and annotated by experienced physicians. This dataset is a valuable resource for automated depression detection research and is expected to advance the field of psychology. Baseline models for detecting and predicting depression presence and level were built, and descriptive statistics of audio and text features were calculated. The decision-making process of the model was also investigated and illustrated. To the best of our knowledge, this is the first study to collect a depression clinical interview corpus in Chinese and train machine learning models to diagnose depression patients.
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Depresión , Trastorno Depresivo Mayor , Humanos , Depresión/diagnóstico , Pueblos del Este de Asia , Escalas de Valoración Psiquiátrica , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/psicología , ComunicaciónRESUMEN
Worldwide, breast cancer is the most common malignancy. LHX2, a member of the LIM homeobox gene family and a transcription factor, plays a crucial role in numerous tumors, but the function of LHX2 in breast cancer progression remains unknown. In this study, we show that LHX2 is upregulated in breast cancer tissues and positively correlated with breast cancer progression. Meanwhile, the clinical characteristics of breast cancer and LHX2 expression showed a strong correlation. GSEA showed that a high LHX2 expression may activate the T-cell activation pathway, PI3K/AKT/mTOR signaling pathway, and apoptosis pathway. Moreover, ssGSEA showed that Th1 cells and Th2 cells had a positive correlation with LHX2 expression in breast cancer. Experiments showed that LHX2 promotes the proliferation, colony formation, migration, and invasion of breast cancer cells. Immunohistochemistry and immunofluorescence assays helped to analyze LHX2-associated immune infiltration in breast cancer. A Western blot assay proved that LHX2 activated the PI3K/AKT/mTOR pathway and the apoptosis pathway. A TUNEL assay confirmed that LHX2 inhibited apoptosis. Taken together, LHX2 plays a vital role in breast cancer's progression and prognosis and could be an immune infiltration biomarker for breast cancer, and LHX2 activates the PI3K/AKT/mTOR pathway and apoptosis pathway in breast cancer.