ABSTRACT
Severe fever with thrombocytopenia syndrome (SFTS) has a high mortality rate compared to other infectious diseases. SFTS is particularly associated with a high risk of mortality in immunocompromised individuals, while most patients who die of SFTS exhibit symptoms of severe encephalitis before death. However, the region of brain damage and mechanisms by which the SFTS virus (SFTSV) causes encephalitis remains unknown. Here, we revealed that SFTSV infects the brainstem and spinal cord, which are regions of the brain associated with respiratory function, and motor nerves in IFNAR1-/- mice. Further, we show that A1-reactive astrocytes are activated, causing nerve cell death, in infected mice. Primary astrocytes of SFTSV-infected IFNAR1-/- mice also induced neuronal cell death through the activation of A1-reactive astrocytes. Herein, we showed that SFTSV induces fatal neuroinflammation in the brain regions important for respiratory function and motor nerve, which may underlie mortality in SFTS patients. This study provides new insights for the treatment of SFTS, for which there is currently no therapeutic approach.
Subject(s)
Astrocytes , Bunyaviridae Infections , Mice, Knockout , Phlebovirus , Receptor, Interferon alpha-beta , Animals , Astrocytes/virology , Astrocytes/pathology , Mice , Receptor, Interferon alpha-beta/genetics , Receptor, Interferon alpha-beta/deficiency , Phlebovirus/genetics , Phlebovirus/physiology , Phlebovirus/pathogenicity , Bunyaviridae Infections/virology , Bunyaviridae Infections/pathology , Bunyaviridae Infections/immunology , Brain/virology , Brain/pathology , Brain/immunology , Spinal Cord/virology , Spinal Cord/pathology , Disease Models, Animal , Neurons/virology , Neurons/pathology , Mice, Inbred C57BL , Brain Stem/virology , Brain Stem/pathology , Cell DeathABSTRACT
Background: Data-driven digital learning could improve the diagnostic performance of novice students for thyroid nodules. Objective: To evaluate the efficacy of digital self-learning and artificial intelligence-based computer-assisted diagnosis (AI-CAD) for inexperienced readers to diagnose thyroid nodules. Methods: Between February and August 2023, a total of 26 readers (less than 1 year of experience in thyroid US from various departments) from 6 hospitals participated in this study. Readers completed an online learning session comprising 3,000 thyroid nodules annotated as benign or malignant independently. They were asked to assess a test set consisting of 120 thyroid nodules with known surgical pathology before and after a learning session. Then, they referred to AI-CAD and made their final decisions on the thyroid nodules. Diagnostic performances before and after self-training and with AI-CAD assistance were evaluated and compared between radiology residents and readers from different specialties. Results: AUC (area under the receiver operating characteristic curve) improved after the self-learning session, and it improved further after radiologists referred to AI-CAD (0.679 vs 0.713 vs 0.758, p<0.05). Although the 18 radiology residents showed improved AUC (0.7 to 0.743, p=0.016) and accuracy (69.9% to 74.2%, p=0.013) after self-learning, the readers from other departments did not. With AI-CAD assistance, sensitivity (radiology 70.3% to 74.9%, others 67.9% to 82.3%, all p<0.05) and accuracy (radiology 74.2% to 77.1%, others 64.4% to 72.8%, all p <0.05) improved in all readers. Conclusion: While AI-CAD assistance helps improve the diagnostic performance of all inexperienced readers for thyroid nodules, self-learning was only effective for radiology residents with more background knowledge of ultrasonography. Clinical Impact: Online self-learning, along with AI-CAD assistance, can effectively enhance the diagnostic performance of radiology residents in thyroid cancer.
Subject(s)
Artificial Intelligence , Diagnosis, Computer-Assisted , Thyroid Nodule , Humans , Thyroid Nodule/diagnosis , Thyroid Nodule/diagnostic imaging , Female , Male , Diagnosis, Computer-Assisted/methods , Clinical Competence , Adult , Ultrasonography/methods , Radiology/education , ROC Curve , Internship and Residency/methods , Middle AgedABSTRACT
Extracellular vesicles, particularly exosomes, have emerged as promising drug delivery systems owing to their unique advantages, such as biocompatibility, immune tolerability, and target specificity. Various engineering strategies have been implemented to harness these innate qualities, with a focus on enhancing the pharmacokinetic and pharmacodynamic properties of exosomes via payload loading and surface engineering for active targeting. This concise review outlines the challenges in the development of exosomes as drug carriers and offers insights into strategies for their effective clinical translation. We also highlight preclinical studies that have successfully employed anti-inflammatory exosomes and suggest future directions for exosome therapeutics. These advancements underscore the potential for integrating exosome-based therapies into clinical practice, heralding promise for future medical interventions.
Subject(s)
Drug Delivery Systems , Exosomes , Exosomes/metabolism , Humans , Drug Delivery Systems/methods , Animals , Drug Carriers/chemistryABSTRACT
While an association between Parkinson's disease (PD) and viral infections has been recognized, the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on PD progression remains unclear. Here, we demonstrate that SARS-CoV-2 infection heightens the risk of PD using human embryonic stem cell (hESC)-derived dopaminergic (DA) neurons and a human angiotensin-converting enzyme 2 (hACE2) transgenic (Tg) mouse model. Our findings reveal that SARS-CoV-2 infection exacerbates PD susceptibility and cellular toxicity in DA neurons pre-treated with human preformed fibrils (hPFFs). Additionally, nasally delivered SARS-CoV-2 infects DA neurons in hACE2 Tg mice, aggravating the damage initiated by hPFFs. Mice infected with SARS-CoV-2 display persisting neuroinflammation even after the virus is no longer detectable in the brain. A comprehensive analysis suggests that the inflammatory response mediated by astrocytes and microglia could contribute to increased PD susceptibility associated with SARS-CoV-2. These findings advance our understanding of the potential long-term effects of SARS-CoV-2 infection on the progression of PD.
Subject(s)
Angiotensin-Converting Enzyme 2 , COVID-19 , Disease Models, Animal , Dopaminergic Neurons , Mice, Transgenic , Parkinson Disease , SARS-CoV-2 , Animals , Dopaminergic Neurons/pathology , Dopaminergic Neurons/metabolism , Dopaminergic Neurons/virology , Humans , COVID-19/pathology , COVID-19/virology , Parkinson Disease/pathology , Parkinson Disease/virology , Mice , Angiotensin-Converting Enzyme 2/metabolism , Angiotensin-Converting Enzyme 2/genetics , Microglia/pathology , Microglia/metabolism , Microglia/virology , Human Embryonic Stem Cells/metabolism , Astrocytes/pathology , Astrocytes/virology , Astrocytes/metabolism , Brain/pathology , Brain/virologyABSTRACT
OBJECTIVES: This study aimed to screen oral squamous cell carcinoma (OSCC) diagnostic and prognostic candidates and investigate the potential functions and mechanisms of candidates in the chemoresistance of OSCC cell lines. MATERIALS AND METHODS: Differential expression profiling of lncRNA was performed in a large cohort of OSCC patients from the Cancer Genome Atlas database to identify OSCC diagnostic and prognostic candidates. Taxol resistance in OSCC cell lines was analyzed using MTT assay. OSCC cell lines transfected with EIF3J-DT pcDNA or siRNA were used to determine its regulatory effects on apoptosis, cell cycle distribution and autophagy using flow cytometry and western blot. RESULTS: We identified EIF3J-DT as a candidate for OSCC diagnosis and prognosis. The expression level of EIF3J-DT in OSCC cell lines correlates with taxol resistance. EIF3J-DT silencing attenuated taxol resistance, and EIF3J-DT overexpression enhanced taxol resistance in OSCC cell lines. Silencing of EIF3J-DT reduced taxol resistance by inducing apoptosis, cell cycle arrest, and ATG14-mediated autophagy inhibition in OSCC cell lines. CONCLUSIONS: We found that EIF3J-DT induced chemoresistance by regulating apoptosis, cell cycle, and autophagy in OSCC cell lines, which EIF3J-DT might provide a novel therapeutic approach for OSCC as well as a diagnostic and prognostic factor.
ABSTRACT
Ectopic breast tissue can develop along the mammary ridge from the axilla to the groin, and the most common site is the axillae. Primary carcinoma of ectopic breast tissue is extremely rare. We report a rare case of a 61-year-old woman with a palpable mass in her left axilla who had a history of surgical excision of accessory breast tissue in the same area. Mammography (MMG), including axillary tail view, ultrasound (US), and breast MRI were performed. We evaluated the extent and characteristics of the microcalcifications in the axillary tail view. A US-guided biopsy was done, and histopathology revealed an invasive ductal carcinoma. Enhanced abdominal CT revealed multiple hepatic masses consistent with metastases, and the patient received palliative chemotherapy. Herein, we present a rare case of breast cancer arising from accessory breast tissue in the axilla, best appreciated on the axillary tail view of the patient's MMG.
ABSTRACT
Docetaxel (DTX), a semi-synthetic analogue of paclitaxel (taxol), is known to exert potent anticancer activity in various cancer cells by suppressing normal microtubule dynamics. In this study, we examined how the anticancer effect of DTX is regulated by polyphenols extracted from Korean Artemisia annua L. (pKAL) in DU145 prostate cancer cells (mutant p53) and HCT116 colorectal cancer cells (wild-type p53). Here, we show that the anticancer effect of DTX was enhanced more significantly by pKAL in HCT116 cells than in DU145 cells via phase-contrast microscopy, CCK-8 assay, Western blot, and flow cytometric analysis of annexin V/propidium iodide-stained cells. Notably, mutant p53 was slightly downregulated by single treatment of pKAL or DTX in DU145 cells, whereas wild-type p53 was significantly upregulated by pKAL or DTX in HCT116 cells. Moreover, the enhanced anticancer effect of DTX by pKAL in HCT116 cells was significantly associated with the suppression of DTX-induced p53 upregulation, increase of DTX-induced phospho-p38, and decrease of DTX-regulated cyclin A, cyclin B1, AKT, caspase-8, PARP1, GM130, NF-κB p65, and LDHA, leading to the increased apoptotic cell death and plasma membrane permeability. Our results suggest that pKAL could effectively improve the anticancer effect of DTX-containing chemotherapy used to treat various cancers expressing wild-type p53.
ABSTRACT
The bluetongue virus (BTV) is a significant animal pathogen with economic implications in the ruminant industry. Despite global reports on BTV detection and epidemiologic investigations, limited studies have focused on the virus in the ROK. In this study, BTV epidemiological research was conducted on blood samples from cattle and goat farms across nine regions during 2013-2014. The results showed that 3.33% of bovine blood samples (194/5824) and 0.19% of goat blood samples (2/1075) tested positive for BTV antibodies using ELISA. In Jeju-do, BTV RNA amplification occurred in 51 of 422 samples (12.1%) using real-time reverse transcription (RT-qPCR). The isolation of one sample revealed it as serotype 3, as indicated by the sequence of segments 2 (Seg-2) and 6 (Seg-6), associated with the eastern BTV topotype. However, based on Seg-1, -3, -4, -5, -7, -8, -9, and -10 analyses, the BTV-3/JJBB35 strain is more closely related to distinct BTV strains. These findings imply BTV circulation and that the Korean-isolated BTV might originate from Asian BTV strains due to multiple reassortment events. This study provides foundational data for ongoing BTV monitoring and disease-control policies in the ROK.
ABSTRACT
Although most CD8+ T cells are equipped to kill infected or transformed cells, a subset may regulate immune responses and preserve self-tolerance. Here, we describe a CD8 lineage that is instructed to differentiate into CD8 T regulatory cells (Tregs) by a surprisingly restricted set of T cell receptors (TCRs) that recognize MHC-E (mouse Qa-1) and several dominant self-peptides. Recognition and elimination of pathogenic target cells that express these Qa-1-self-peptide complexes selectively inhibits pathogenic antibody responses without generalized immune suppression. Immunization with synthetic agonist peptides that mobilize CD8 Tregs in vivo efficiently inhibit antigraft antibody responses and markedly prolong heart and kidney organ graft survival. Definition of TCR-dependent differentiation and target recognition by this lineage of CD8 Tregs may open the way to new therapeutic approaches to inhibit pathogenic antibody responses.
Subject(s)
CD8-Positive T-Lymphocytes , T-Lymphocytes, Regulatory , Mice , Animals , Receptors, Antigen, T-Cell , Peptides , Immune Tolerance , Histocompatibility Antigens Class IABSTRACT
Recent studies suggest that the anticancer activity of ß-lapachone (ß-Lap) could be improved by different types of bioactive phytochemicals. The aim of this study was to elucidate how the anticancer effect of ß-Lap is regulated by polyphenols extracted from Korean Artemisia annua L. (pKAL) in parental HCT116 and oxaliplatin-resistant (OxPt-R) HCT116 colorectal cancer cells. Here, we show that the anticancer effect of ß-Lap is more enhanced by pKAL in HCT116-OxPt-R cells than in HCT116 cells via a CCK-8 assay, Western blot, and phase-contrast microscopy analysis of hematoxylin-stained cells. This phenomenon was associated with the suppression of OxPt-R-related upregulated proteins including p53 and ß-catenin, the downregulation of cell survival proteins including TERT, CD44, and EGFR, and the upregulation of cleaved HSP90, γ-H2AX, and LC3B-I/II. A bioinformatics analysis of 21 proteins regulated by combined treatment of pKAL and ß-Lap in HCT116-OxPt-R cells showed that the enhanced anticancer effect of ß-Lap by pKAL was related to the inhibition of negative regulation of apoptotic process and the induction of DNA damage through TERT, CD44, and EGFR-mediated multiple signaling networks. Our results suggest that the combination of pKAL and ß-Lap could be used as a new therapy with low toxicity to overcome the OxPt-R that occurred in various OxPt-containing cancer treatments.
Subject(s)
Antineoplastic Agents , Artemisia annua , Colorectal Neoplasms , Humans , Oxaliplatin/pharmacology , HCT116 Cells , Polyphenols/pharmacology , Colorectal Neoplasms/drug therapy , ErbB Receptors , Cell Line, Tumor , Antineoplastic Agents/pharmacologyABSTRACT
Low-grade myofibroblastic sarcoma (LGMFS) is a rare type of sarcoma, and its manifestation as a radiotherapy (RT)-induced sarcoma following RT for breast cancer is even more unusual. To date, only one case of RT-induced mammary myofibroblastic sarcoma (MFS) has been reported. Here we present the case of a 49-year-old woman with LGMFS after undergoing breast-conserving surgery for invasive ductal carcinoma (IDC), and with a history of RT 16 years prior. Due to the rarity of this disease, previous studies have focused primarily on the pathological findings of MFS. In this report however, we present the clinical and radiological features of LGMFS in the retro pectoral area as a rare type of RT-induced sarcoma.
ABSTRACT
PURPOSE: To identify effective factors predicting extraprostatic extension (EPE) in patients with prostate cancer (PCa). METHODS: This retrospective cohort study recruited 898 consecutive patients with PCa treated with robot-assisted laparoscopic radical prostatectomy. The patients were divided into EPE and non-EPE groups based on the analysis of whole-mount histopathologic sections. Histopathological analysis (ISUP biopsy grade group) and magnetic resonance imaging (MRI) (PI-RADS v2.1 scores [1-5] and the Mehralivand EPE grade [0-3]) were used to assess the prediction of EPE. We also assessed the clinical usefulness of the prediction model based on decision-curve analysis. RESULTS: Of 800 included patients, 235 (29.3%) had EPE, and 565 patients (70.7%) did not (non-EPE). Multivariable logistic regression analysis showed that the biopsy ISUP grade, PI-RADS v2.1 score, and Mehralivand EPE grade were independent risk factors for EPE. In the regression assessment of the models, the best discrimination (area under the curve of 0.879) was obtained using the basic model (age, serum PSA, prostate volume at MRI, positive biopsy core, clinical T stage, and D'Amico risk group) and Mehralivand EPE grade 3. Decision-curve analysis showed that combining Mehralivand EPE grade 3 with the basic model resulted in superior net benefits for predicting EPE. CONCLUSION: Mehralivand EPE grades and PI-RADS v2.1 scores, in addition to basic clinical and demographic information, are potentially useful for predicting EPE in patients with PCa.
ABSTRACT
Sepsis is a serious clinical condition characterized by a systemic inflammatory response, a leading cause of acute liver and kidney injury, and is associated with a high morbidity and mortality. Understanding the molecular mechanisms underlying the acute liver and kidney injury is crucial for developing an effective therapy. Golgi apparatus plays important roles and has various substrates mediating cellular stress responses. Golgi phosphoprotein 3 (GOLPH3), linking Golgi membranes to the cytoskeleton, has been identified as an important oncogenic regulator; however, its role in endotoxemia-induced acute liver and kidney injury remains elusive. Here, we found that upregulation of GOLPH3 was associated with endotoxemia-induced acute liver and kidney injury. Lipopolysaccharide (LPS) treatment increased Golgi stress and fragmentation, and associated pro-inflammatory mediator (Tnfα, IL-6, and IL-1ß) production in vivo and in vitro. Interestingly, the downregulation of GOLPH3 significantly decreased LPS-induced Golgi stress and pro-inflammatory mediators (Tnfα, IL-6, Mcp1, and Nos2), and reversed apoptotic cell deaths in LPS-treated hepatocytes and renal tubular cells. GOLPH3 knockdown also reduced inflammatory response in LPS-treated macrophages. The AKT/NF-kB signaling pathway was suppressed in GOLPH3 knockdown, which may be associated with a reduction of inflammatory response and apoptosis and the recovery of Golgi morphology and function. Taken together, GOLPH3 plays a crucial role in the development and progression of acute liver and kidney injury by promoting Golgi stress and increasing inflammatory response and apoptosis, suggesting GOLPH3 as a potential therapeutic target for endotoxemia-induced tissue injury.
Subject(s)
Endotoxemia , Tumor Necrosis Factor-alpha , Humans , Tumor Necrosis Factor-alpha/metabolism , Endotoxemia/complications , Endotoxemia/genetics , Interleukin-6/genetics , Interleukin-6/metabolism , Lipopolysaccharides/pharmacology , Lipopolysaccharides/metabolism , Golgi Apparatus/metabolism , Apoptosis , Liver , Kidney , Membrane Proteins/genetics , Membrane Proteins/metabolismABSTRACT
ß-lapachone (ß-Lap), a topoisomerase inhibitor, is a naturally occurring ortho-naphthoquinone phytochemical and is involved in drug resistance mechanisms. Oxaliplatin (OxPt) is a commonly used chemotherapeutic drug for metastatic colorectal cancer, and OxPt-induced drug resistance remains to be solved to increase chances of successful therapy. To reveal the novel role of ß-Lap associated with OxPt resistance, 5 µM OxPt-resistant HCT116 cells (HCT116-OxPt-R) were generated and characterized via hematoxylin staining, a CCK-8 assay and Western blot analysis. HCT116-OxPt-R cells were shown to have OxPt-specific resistance, increased aggresomes, upregulated p53 and downregulated caspase-9 and XIAP. Through signaling explorer antibody array, nucleophosmin (NPM), CD37, Nkx-2.5, SOD1, H2B, calreticulin, p38 MAPK, caspase-2, cadherin-9, MMP23B, ACOT2, Lys-acetylated proteins, COL3A1, TrkA, MPS-1, CD44, ITGA5, claudin-3, parkin and ACTG2 were identified as OxPt-R-related proteins due to a more than two-fold alteration in protein status. Gene ontology analysis suggested that TrkA, Nkx-2.5 and SOD1 were related to certain aggresomes produced in HCT116-OxPt-R cells. Moreover, ß-Lap exerted more cytotoxicity and morphological changes in HCT116-OxPt-R cells than in HCT116 cells through the downregulation of p53, Lys-acetylated proteins, TrkA, p38 MAPK, SOD1, caspase-2, CD44 and NPM. Our results indicate that ß-Lap could be used as an alternative drug to overcome the upregulated p53-containing OxPt-R caused by various OxPt-containing chemotherapies.
Subject(s)
Colorectal Neoplasms , Tumor Suppressor Protein p53 , Humans , Oxaliplatin/pharmacology , Oxaliplatin/therapeutic use , HCT116 Cells , Tumor Suppressor Protein p53/metabolism , Superoxide Dismutase-1/metabolism , Colorectal Neoplasms/pathology , Caspase 2/metabolism , p38 Mitogen-Activated Protein Kinases/metabolism , Nucleophosmin , Receptor Protein-Tyrosine Kinases/metabolism , Apoptosis , Cell Line, Tumor , Hyaluronan Receptors/metabolismABSTRACT
We previously reported that radiotherapyresistant (RTR) triple negative breast cancer (TNBC) cells upregulate the expression of endothelialspecific molecule1 (ESM1) compared with TNBC cells. In addition, ESM1 is involved in an increased proliferation and invasion of RTRTNBC cells compared with TNBC cells. It was further identified that, in RTRTNBC cells, P2Y2 purinergic receptor (P2Y2R)mediated activation of p21activated kinase 1 (PAK1), protein kinase C (PKC), cJun Nterminal kinase (JNK) and p38 MAPKs is related to ESM1 expression via forkhead box O1 (FoxO1) regulation. Notably, it has been reported that P2Y2R mediates the transactivation of vascular epithelial growth factor receptor 2 (VEGFR2), and VEGFR2 is known to be involved in ESM1 expression. Therefore, in the present study, the involvement of VEGFR2 in the P2Y2Rmediated ESM1 upregulation in RTRTNBC cells and the relationship between P2Y2R and VEGFR2 activation was further examined. Western blotting and reverse transcriptionPCR were used to monitor the expression of ESM1, and the results demonstrated that extracellular ATP treatment regulated the expression of ESM1 in a P2Y2Rdependent manner in RTRMDAMB231 cells. In addition, extracellular ATP activated Src and VEGFR2 after 5 min of incubation, which was abolished by knockdown of P2Y2R expression. VEGFR2 activation in response to ATP was also decreased by inhibiting Src activity, suggesting that ATPactivated P2Y2R regulates VEGFR2 phosphorylation via Src activation. Furthermore, ATPinduced ESM1 expression was decreased by transfection with VEGFR2 small interfering RNA (siRNA). ESM1related signaling molecules, PAK1, PKC, JNK and p38 MAPKs, and the transcriptional regulator, FoxO1, which were activated by ATP, were also decreased following transfection with VEGFR2 siRNA. These results suggest that P2Y2Rmediated transactivation of VEGFR2 through Src phosphorylation is associated with ESM1 overexpression in RTRTNBC cells.
Subject(s)
Receptors, Purinergic P2Y2 , Triple Negative Breast Neoplasms , Vascular Endothelial Growth Factor Receptor-2 , Humans , Adenosine Triphosphate/metabolism , Phosphorylation , Protein Kinase C/metabolism , Receptors, Growth Factor/metabolism , RNA, Small Interfering/metabolism , Transcriptional Activation , Triple Negative Breast Neoplasms/genetics , Triple Negative Breast Neoplasms/radiotherapy , Receptors, Purinergic P2Y2/metabolism , Vascular Endothelial Growth Factor Receptor-2/metabolismABSTRACT
Loss of the PTEN tumour suppressor is one of the most common oncogenic drivers across all cancer types1. PTEN is the major negative regulator of PI3K signalling. The PI3Kß isoform has been shown to play an important role in PTEN-deficient tumours, but the mechanisms underlying the importance of PI3Kß activity remain elusive. Here, using a syngeneic genetically engineered mouse model of invasive breast cancer driven by ablation of both Pten and Trp53 (which encodes p53), we show that genetic inactivation of PI3Kß led to a robust anti-tumour immune response that abrogated tumour growth in syngeneic immunocompetent mice, but not in immunodeficient mice. Mechanistically, PI3Kß inactivation in the PTEN-null setting led to reduced STAT3 signalling and increased the expression of immune stimulatory molecules, thereby promoting anti-tumour immune responses. Pharmacological PI3Kß inhibition also elicited anti-tumour immunity and synergized with immunotherapy to inhibit tumour growth. Mice with complete responses to the combined treatment displayed immune memory and rejected tumours upon re-challenge. Our findings demonstrate a molecular mechanism linking PTEN loss and STAT3 activation in cancer and suggest that PI3Kß controls immune escape in PTEN-null tumours, providing a rationale for combining PI3Kß inhibitors with immunotherapy for the treatment of PTEN-deficient breast cancer.
Subject(s)
Immune Evasion , Mammary Neoplasms, Animal , PTEN Phosphohydrolase , Phosphatidylinositol 3-Kinase , Animals , Mice , Immunotherapy , Phosphatidylinositol 3-Kinase/metabolism , Phosphoinositide-3 Kinase Inhibitors , PTEN Phosphohydrolase/deficiency , PTEN Phosphohydrolase/genetics , Signal Transduction , Mammary Neoplasms, Animal/enzymology , Mammary Neoplasms, Animal/genetics , Mammary Neoplasms, Animal/immunology , Mammary Neoplasms, Experimental/enzymology , Mammary Neoplasms, Experimental/genetics , Mammary Neoplasms, Experimental/immunologyABSTRACT
In the medical field, it is delicate to anticipate good performance in using deep learning due to the lack of large-scale training data and class imbalance. In particular, ultrasound, which is a key breast cancer diagnosis method, is delicate to diagnose accurately as the quality and interpretation of images can vary depending on the operator's experience and proficiency. Therefore, computer-aided diagnosis technology can facilitate diagnosis by visualizing abnormal information such as tumors and masses in ultrasound images. In this study, we implemented deep learning-based anomaly detection methods for breast ultrasound images and validated their effectiveness in detecting abnormal regions. Herein, we specifically compared the sliced-Wasserstein autoencoder with two representative unsupervised learning models autoencoder and variational autoencoder. The anomalous region detection performance is estimated with the normal region labels. Our experimental results showed that the sliced-Wasserstein autoencoder model outperformed the anomaly detection performance of others. However, anomaly detection using the reconstruction-based approach may not be effective because of the occurrence of numerous false-positive values. In the following studies, reducing these false positives becomes an important challenge.
Subject(s)
Deep Learning , Ultrasonography, Mammary , Female , Humans , Ultrasonography, Mammary/methods , Image Processing, Computer-Assisted/methods , Ultrasonography , Diagnosis, Computer-Assisted/methodsABSTRACT
We explore the variation of interband absorption spectra of GaAs spherical sector quantum dots (QDs) in response to a strong resonant laser, using the renormalized wave function method. Even though a spherical sector QD appears identical to a section cut from a spherical QD, it contains a controllable additional spatial parameter, the apical angle, which results in radically different wave functions and energy levels of particles, and is anticipated to exhibit novel optical properties. The obtained findings reveal that the apical angle of the dot has a considerable effect on the interband absorption spectrum. With the increase in the dot apical angle, a significant redshift of the interband absorption peaks has been identified. Increasing the pump laser detuning and dot radius yields similar results. Especially when a powerful resonant laser with tiny detuning is utilized, a dynamical coupling between electron levels arises, resulting in the formation of new interband absorption peaks. These new peaks and the former ones were similarly influenced by the aforementioned parameters. Furthermore, it is thought that the new peaks, when stimulated by a suitable laser, will produce the entangled states necessary for quantum information.
ABSTRACT
Alzheimer's disease (AD) is the most common form of incurable dementia and represents a critical public health issue as the world's population ages. Although microglial dysregulation is a cardinal feature of AD, the extensive heterogeneity of these immunological cells in the brain has impeded our understanding of their contribution to this disease. Here, we identify a pathogenic microglial subset which expresses the CD11c surface marker as the sole producer of Osteopontin (OPN) in the 5XFAD mouse model of AD. OPN production divides Disease-Associated Microglia (DAM) into two functionally distinct subsets, i.e., a protective CD11c+OPN- subset that robustly ingests amyloid ß (Aß) in a noninflammatory fashion and a pathogenic CD11c+OPN+ subset that produces proinflammatory cytokines and fails to ingest significant amounts of Aß. Genetic ablation of OPN or administration of monoclonal anti-OPN antibody to 5XFAD mice reduces proinflammatory microglia, plaque formation, and numbers of dystrophic neurites and results in improved cognitive function. Analysis of brain tissue from AD patients indicates that levels of OPN-producing CD11c+ microglia correlate strongly with the degree of cognitive deficit and AD neuropathology. These findings define an OPN-dependent pathway to disease driven by a distinct microglial subset, and identify OPN as a novel therapeutic target for potentially effective immunotherapy to treat AD.
Subject(s)
Alzheimer Disease , Mice , Animals , Alzheimer Disease/metabolism , Microglia/metabolism , Amyloid beta-Peptides/metabolism , Osteopontin/metabolism , Mice, Transgenic , Disease Models, Animal , Plaque, Amyloid/metabolismABSTRACT
Renal ischemia reperfusion (IR) injury is a major cause of acute kidney injury (AKI) that is often complicated by multiple organ failure of the liver and intestine. The mineralocorticoid receptor (MR) is activated in patients with renal failure associated with glomerular and tubular damage. We thus investigated whether canrenoic acid (CA), a mineralocorticoid receptor (MR) antagonist, protects against AKI-induced hepatic and intestinal injury, suggesting the underlying mechanisms. Mice were divided into five groups: sham mice, mice subjected to renal IR, and mice pretreated with canrenoic acid (CA; 1 or 10 mg/kg) 30 min prior to renal IR. At 24 h after renal IR, the levels of plasma creatinine, alanine aminotransferase and aldosterone were measured, and structural changes and inflammatory responses of the kidney, liver, and intestine were analyzed. We found that CA treatment reduced plasma creatinine levels, tubular cell death and oxidative stress induced by renal IR. CA treatment also decreased renal neutrophil infiltration and inflammatory cytokine expression and inhibited the release of high-mobility group box 1 induced by renal IR. Consistently, CA treatment reduced renal IR-induced plasma alanine transaminase, hepatocellular injury and neutrophil infiltration, and inflammatory cytokine expression. CA treatment also decreased small intestinal cell death, neutrophil infiltration and inflammatory cytokine expression induced by renal IR. Taken together, we conclude that MR antagonism by CA treatment protects against multiple organ failure in the liver and intestine after renal IR.