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Two Gram-stain-negative, straight rods, non-motile, asporogenous, catalase-negative and obligately anaerobic butyrate-producing strains, HLW78T and CYL33, were isolated from faecal samples of two healthy Taiwanese adults. Phylogenetic analyses of 16S rRNA and DNA mismatch repair protein MutL (mutL) gene sequences revealed that these two novel strains belonged to the genus Faecalibacterium. On the basis of 16S rRNA and mutL gene sequence similarities, the type strains Faecalibacterium butyricigenerans AF52-21T(98.3-98.1â% and 79.0-79.5â% similarity), Faecalibacterium duncaniae A2-165T(97.8-97.9â% and 70.9-80.1â%), Faecalibacterium hattorii APC922/41-1T(97.1-97.3â% and 80.3-80.5â%), Faecalibacterium longum CM04-06T(97.8-98.0% and 78.3â%) and Faecalibacterium prausnitzii ATCC 27768T(97.3-97.4â% and 82.7-82.9â%) were the closest neighbours to the novel strains HLW78T and CYL33. Strains HLW78T and CYL33 had 99.4â% both the 16S rRNA and mutL gene sequence similarities, 97.9â% average nucleotide identity (ANI), 96.3â% average amino acid identity (AAI), and 80.5â% digital DNA-DNA hybridization (dDDH) values, indicating that these two strains are members of the same species. Phylogenomic tree analysis indicated that strains HLW78T and CYL33 formed an independent robust cluster together with F. prausnitzii ATCC 27768T. The ANI, AAI and dDDH values between strain HLW78T and its closest neighbours were below the species delineation thresholds of 77.6-85.1â%, 71.4-85.2â% and 28.3-30.9â%, respectively. The two novel strains could be differentiated from the type strains of their closest Faecalibacterium species based on their cellular fatty acid compositions, which contained C18â:â1 ω7c and lacked C15â:â0 and C17â:â1 ω6c, respectively. Phenotypic, chemotaxonomic and genotypic test results demonstrated that the two novel strains HLW78T and CYL33 represented a single, novel species within the genus Faecalibacterium, for which the name Faecalibacterium taiwanense sp. nov. is proposed. The type strain is HLW78T (=BCRC 81397T=NBRC 116372T).
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Técnicas de Tipagem Bacteriana , DNA Bacteriano , Faecalibacterium , Ácidos Graxos , Fezes , Hibridização de Ácido Nucleico , Filogenia , RNA Ribossômico 16S , Análise de Sequência de DNA , Fezes/microbiologia , Humanos , RNA Ribossômico 16S/genética , Taiwan , DNA Bacteriano/genética , Ácidos Graxos/análise , Adulto , Faecalibacterium/genética , Faecalibacterium/isolamento & purificação , Faecalibacterium/classificação , Composição de Bases , Proteínas MutL/genéticaRESUMO
BACKGROUND: Recent advancements in deep learning models have demonstrated their potential in the field of medical imaging, achieving remarkable performance surpassing human capabilities in tasks such as classification and segmentation. However, these modern state-of-the-art network architectures often demand substantial computational resources, which limits their practical application in resource-constrained settings. This study aims to propose an efficient diagnostic deep learning model specifically designed for the classification of intracranial hemorrhage in brain CT scans. METHOD: Our proposed model utilizes a combination of depthwise separable convolutions and a multi-receptive field mechanism to achieve a trade-off between performance and computational efficiency. The model was trained on RSNA datasets and validated on CQ500 dataset and PhysioNet dataset. RESULT: Through a comprehensive comparison with state-of-the-art models, our model achieves an average AUROC score of 0.952 on RSNA datasets and exhibits robust generalization capabilities, comparable to SE-ResNeXt, across other open datasets. Furthermore, the parameter count of our model is just 3 % of that of MobileNet V3. CONCLUSION: This study presents a diagnostic deep-learning model that is optimized for classifying intracranial hemorrhages in brain CT scans. The efficient characteristics make our proposed model highly promising for broader applications in medical settings.
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Encéfalo , Aprendizado Profundo , Hemorragias Intracranianas , Tomografia Computadorizada por Raios X , Humanos , Tomografia Computadorizada por Raios X/métodos , Hemorragias Intracranianas/diagnóstico por imagem , Hemorragias Intracranianas/classificação , Encéfalo/diagnóstico por imagem , Redes Neurais de Computação , Bases de Dados FactuaisRESUMO
Objectives: This study aimed to identify predictors of remission or low disease activity (LDA) in patients with rheumatoid arthritis (RA) and low-ultrasound inflammation. Methods: A total of 80 patients with RA who fulfilled the 1987 ACR criteria for RA with a disease activity score of 28 joints (DAS28) > 3.2 were recruited. Over 1 year of therapy, we conducted blood tests every 6 months to examine erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), monocyte chemotactic protein-1 (MCP-1), neuraminidase 3 (Neu3), and α-2,3-sialyltrasnferse I (ST3Gal-1) levels in B cells and monocytes. Additionally, we evaluated physical function by using the Health Assessment Questionnaire-Disability Index (HAQ-DI). Data on demographic and clinical parameters were collected, and musculoskeletal ultrasonography was performed twice a year on 12 specific joints to assess synovial changes. One year later, we compared all collected data and laboratory or ultrasound results between patients achieving remission or LDA and those who did not in order to determine the predictors. Results: Age, the presence or absence of rheumatoid factor, and the number of conventional disease-modifying anti-rheumatic drugs used were not correlated with remission or LDA for DAS28 or Simplified Disease Activity Index formulas. However, male sex, low CRP levels, low ESR levels, and low HAQ-DI scores were associated with a higher likelihood of achieving remission or LDA for DAS28-ESR. Negative anticyclic citrullinated peptide (CCP) and low HAQ-DI scores were predictors of remission or LDA for DAS28-MCP-1. Interestingly, having less than two comorbidities is a good predictor of a combined remission/low disease activity state for SDAI and DAS28-MCP-1. Furthermore, Neu3 and ST3Gal-1 levels and ST3Gal-1/Neu3 ratios in B cells and monocytes had no significant correlation with total ultrasound scores. Nevertheless, monocyte ST3Gal-1 and Neu3 correlated significantly with DAS28-ESR >5.1 and DAS-MCP-1 >4.8 (both categories belong to high disease activity), respectively (rho = 0.609 with p = 0.012, and rho = 0.727 with p = 0.011, respectively). Monocyte ST3Gal-1/Neu3 ratios connected with DAS28-ESR >5.1 and 3.3 < SDAI ⦠11 (low disease activity), respectively (rho = 0.662 with p = 0.005, and rho = 0.342 with p = 0.048, respectively). Conclusions: In patients with RA in Taiwan, male sex, low CRP levels, low ESR levels, and low HAQ-DI scores are predictors of remission or LDA for DAS28-ESR, which differ from the predictors for DAS28-MCP-1. Moreover, monocyte ST3Gal-1, Neu3, and their ratios correlated with different disease activity categories of DAS28-ESR, DAS28-MCP-1, and SDAI scores.
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A novel coagulase-negative Staphylococcus strain (H164T) was isolated from soymilk in Taiwan. Comparative sequence analysis of the 16S rRNA gene revealed that the H164T strain is a member of the genus Staphylococcus. We used multilocus sequence analysis (MLSA) and phylogenomic analyses to demonstrate that the novel strain was closely related to Staphylococcus gallinarum, Staphylococcus nepalensis, Staphylococcus cohnii, and Staphylococcus urealyuticus. The average nucleotide identity and digital DNA-DNA hybridization values between H164T and its closest relatives were <95% and <70%, respectively. The H164T strain could also be distinguished from its closest relatives by the fermentation of d-fructose, d-maltose, d-trehalose, and d-mannitol, as well as by the activities of α-glucosidase and alkaline phosphatase. The major cellular fatty acids were C15:0 iso and C15:0 anteiso, and the predominant menaquinones were MK-7 and MK-8, respectively. The major cellular fatty acids and predominant menaquinones were C15:0 iso and C15:0 anteiso and MK-7 and MK-8, respectively. In conclusion, this strain represents a novel species, named Staphylococcus hsinchuensis sp. nov., with the type strain H164T (=BCRC 81404T = NBRC 116174T).
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BACKGROUND: Tongue diagnosis in traditional Chinese medicine (TCM) provides clinically important, objective evidence from direct observation of specific features that assist with diagnosis. However, the current interpretation of tongue features requires a significant amount of manpower and time. TCM physicians may have different interpretations of features displayed by the same tongue. An automated interpretation system that interprets tongue features would expedite the interpretation process and yield more consistent results. MATERIALS AND METHODS: This study applied deep learning visualization to tongue diagnosis. After collecting tongue images and corresponding interpretation reports by TCM physicians in a single teaching hospital, various tongue features such as fissures, tooth marks, and different types of coatings were annotated manually with rectangles. These annotated data and images were used to train a deep learning object detection model. Upon completion of training, the position of each tongue feature was dynamically marked. RESULTS: A large high-quality manually annotated tongue feature dataset was constructed and analyzed. A detection model was trained with average precision (AP) 47.67%, 58.94%, 71.25% and 59.78% for fissures, tooth marks, thick and yellow coatings, respectively. At over 40 frames per second on a NVIDIA GeForce GTX 1060, the model was capable of detecting tongue features from any viewpoint in real time. CONCLUSIONS/SIGNIFICANCE: This study constructed a tongue feature dataset and trained a deep learning object detection model to locate tongue features in real time. The model provided interpretability and intuitiveness that are often lacking in general neural network models and implies good feasibility for clinical application.
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Redes Neurais de Computação , Língua , Medicina Tradicional Chinesa/métodosRESUMO
Areca nut is a major contributor to the high prevalence of oral cancer in Asia. The precise mechanisms by which areca nut stimulates mucosal cells and contributes to the progression of oral cancer urgently require clarification. The current study aimed to assess the effects of arecoline on the normal human gingival epithelium cell line S-G. Cell viability, levels of reactive oxygen species (ROS), protein expression, cellular morphology, and gene expression were evaluated using the MTT test, flow cytometry, Western blot analysis, optical or confocal microscopy, and RT-qPCR. Keratin (KRT6) analysis involved matched normal and cancer tissues from clinical head and neck specimens. The results demonstrated that 12.5 µg/mL of arecoline induced ROS production, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) mRNA expression in S-G cells. This activation of the MAPK/ERK pathway increased KRT6 expression while limiting cell migration. In head and neck cancer tissues, KRT6B gene expression exceeded that of normal tissues. This study confirms that arecoline induces ROS accumulation in normal cells, leading to the secretion of proinflammatory factors and KRT6 expression. This impedes oral mucosal healing, thereby promoting the progression of oral cancer.
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Tumor necrosis factor α (TNFα), an inflammatory cytokine, induces lipolysis and increases circulating concentrations of free fatty acids. In addition, TNFα is the first adipokine produced by adipose tissue in obesity, contributing to obesity-associated metabolic disease. Given that benzyl isothiocyanate (BITC) is a well-known anti-inflammatory agent, we hypothesized that BITC can ameliorate TNFα-induced lipolysis and investigated the working mechanisms involved. We first challenged 3T3-L1 adipocytes with TNFα to induce lipolysis, which was confirmed by increased glycerol release, decreased protein expression of peroxisome proliferator-activated receptor γ (PPARγ) and perilipin 1 (PLIN1), and increased phosphorylation of ERK, protein kinase A (PKA), and hormone-sensitive lipase (HSL). However, inhibition of ERK or PKA significantly attenuated the lipolytic activity of TNFα. Meanwhile, pretreatment with BITC significantly ameliorated the lipolytic activity of TNFα; the TNFα-induced phosphorylation of ERK, PKA, and HSL; the TNFα-induced ubiquitination of PPARγ; the TNFα-induced decrease in PPARγ nuclear protein binding to PPAR response element; and the TNFα-induced decrease in PLIN1 protein expression. Our results indicate that BITC ameliorates TNFα-induced lipolysis by inhibiting the ERK/PKA/HSL signaling pathway, preventing PPARγ proteasomal degradation, and maintaining PLIN1 protein expression.
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Esterol Esterase , Fator de Necrose Tumoral alfa , Animais , Camundongos , Fator de Necrose Tumoral alfa/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Esterol Esterase/metabolismo , Lipólise , Células 3T3-L1 , PPAR gama/metabolismo , Transdução de Sinais , Fosforilação , Adipócitos/metabolismo , Obesidade/metabolismo , Perilipina-1/metabolismoRESUMO
BACKGROUND: Antimicrobial resistance (AMR) is a growing worldwide public health issue due to the overuse and inappropriate use of antibiotics. AMR has been more prevalent during the coronavirus pandemic of 2019 (COVID-19) compared to previous periods. Therefore, this study was conducted to evaluate the AMR profile of common bacteria that were isolated for routine analysis during the pandemic of COVID-19 in Central Taiwan. The main goal of this study was to examine and analyze the AMR patterns both before and after the start of the COVID-19 pandemic. METHODS: We conducted a retrospective analysis of clinical samples collected from two different time periods: the 1-year period before the onset of the COVID-19 pandemic (January 2019 to December 2019) and the 2-year period following the start of the pandemic (September 2020 to September 2022). The data for this study were obtained from clinical records, and both bacterial identification and antibiotic susceptibility testing were performed using the Phoenix identification system. RESULTS: Among the 8152 bacterial isolates obtained during the study period from September 2020 to September 2022, 4022 (49.3%) were Escherichia coli, 1346 (16.5%) were Klebsiella pneumoniae, 1156 (14.2%) were Staphylococcus aureus, 887 (10.9%) were Pseudomonas aeruginosa, 376 (4.6%) were Enterococcus faecium, and 365 (4.5%) were Acinetobacter baumannii. The overall prevalence of resistant bacteria during the COVID-19 pandemic was as follows: vancomycin-resistant Enterococcus, 69%; carbapenem-resistant A. baumannii, 65%; methicillin-resistant S. aureus, 49%; carbapenem-resistant K. pneumoniae, 29%; carbapenem-resistant P. aeruginosa, 17%; and carbapenem-resistant E. coli, 2%. Carbapenem-resistant A. baumannii, vancomycin-resistant Enterococcus, carbapenem-resistant K. pneumoniae, and carbapenem-resistant E. coli increased by 19%, 10%, 2%, and 1%, respectively. On the other hand, carbapenem-resistant P. aeruginosa and methicillin-resistant S. aureus decreased by 6%, respectively. CONCLUSION: This study provides a comprehensive assessment of AMR during the COVID-19 pandemic in Central Taiwan. Understanding the prevalence of AMR is crucial for preventing infection and formulating disease prevention policies. Further research is warranted to elucidate the correlation between AMR and the severity of infection in COVID-19 patients.
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COVID-19 , Staphylococcus aureus Resistente à Meticilina , Humanos , Estudos Retrospectivos , Vancomicina , Pandemias , Taiwan/epidemiologia , Escherichia coli , Farmacorresistência Bacteriana , COVID-19/epidemiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Carbapenêmicos , Bactérias , Klebsiella pneumoniae , Testes de Sensibilidade MicrobianaRESUMO
Motivation: ProbioMinServer is a platform designed to help researchers access information on probiotics regarding a wide variety of characteristics, such as safety (e.g. antimicrobial resistance, virulence, pathogenic, plasmid, and prophage genes) and functionality (e.g. functional classes, carbohydrate-active enzyme, and metabolite gene cluster profile). Because probiotics are functional foods, their safety and functionality are a crucial part of health care. Genomics has become a crucial methodology for investigating the safety and functionality of probiotics in food and feed. This shift is primarily attributed to the growing affordability of next-generation sequencing technologies. However, no integrated platform is available for simultaneously evaluating probiotic strain safety, investigating probiotic functionality, and identifying known phylogenetically related strains. Results: Thus, we constructed a new platform, ProbioMinServer, which incorporates these functions. ProbioMinServer accepts whole-genome sequence files in the FASTA format. If the query genome belongs to the 25 common probiotic species collected in our database, the server performs a database search and analyzes the core-genome multilocus sequence typing. Front-end applications were implemented in JavaScript with a bootstrap framework, and back-end programs were implemented using PHP, Perl, and Python. ProbioMinServer can help researchers quickly and easily retrieve information on the safety and functionality of various probiotics. Availability and implementation: The platform is available at https://probiomindb.imst.nsysu.edu.tw.
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Andrographolide (AND) is a bioactive component of the herb Andrographis paniculata and a well-known anti-inflammatory agent. Atherosclerosis is a chronic inflammatory disease of the vasculature, and oxidized LDL (oxLDL) is thought to contribute heavily to atherosclerosis-associated inflammation. The aim of this study was to investigate whether AND mitigates oxLDL-mediated foam cell formation and diet-induced atherosclerosis (in mice fed a high-fat, high-cholesterol, high-cholic acid [HFCCD] diet) and the underlying mechanisms involved. AND attenuated LPS/oxLDL-mediated foam cell formation, IL-1[Formula: see text] mRNA and protein (p37) expression, NLR family pyrin domain containing 3 (NLRP3) mRNA and protein expression, caspase-1 (p20) protein expression, and IL-1[Formula: see text] release in BMDMs. Treatment with oxLDL significantly induced protein and mRNA expression of CD36, lectin-like oxLDL receptor-1 (LOX-1), and scavenger receptor type A (SR-A), whereas pretreatment with AND significantly inhibited protein and mRNA expression of SR-A only. Treatment with oxLDL significantly induced ROS generation and Dil-oxLDL uptake; however, pretreatment with AND alleviated oxLDL-induced ROS generation and Dil-oxLDL uptake. HFCCD feeding significantly increased aortic lipid accumulation, ICAM-1 expression, and IL-1[Formula: see text] mRNA expression, as well as blood levels of glutamic pyruvic transaminase (GPT), total cholesterol, and LDL-C. AND co-administration mitigated aortic lipid accumulation, the protein expression of ICAM-1, mRNA expression of IL-1[Formula: see text] and ICAM-1, and blood levels of GPT. These results suggest that the working mechanisms by which AND mitigates atherosclerosis involve the inhibition of foam cell formation and NLRP3 inflammasome-dependent vascular inflammation as evidenced by decreased SR-A expression and IL-1[Formula: see text] release, respectively.
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Aterosclerose , Inflamassomos , Animais , Camundongos , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Macrófagos/metabolismo , Lipoproteínas LDL , Células Espumosas/metabolismo , Receptores Depuradores , Inflamação/metabolismo , Colesterol/metabolismo , Aterosclerose/tratamento farmacológico , Aterosclerose/etiologia , Aterosclerose/metabolismo , RNA Mensageiro/metabolismo , Interleucina-1/metabolismoRESUMO
Cardiovascular disease (CVD) is prevalent in patients with chronic kidney disease (CKD) and it is responsible for approximately half of all CKD-related deaths. CVDs are the primary cause of death in hemodialysis patients due to major adverse cardiovascular events. Therefore, better approaches for differentiating chronic hemodialysis patients at higher cardiovascular risk will help physicians improve clinical outcomes. Hence, there is an urgent need to discover feasible and reliable cardiac biomarkers to improve diagnostic accuracy, reflect myocardial injury, and identify high-risk patients. Numerous biomarkers that have significant prognostic value with respect to adverse CVD outcomes in the setting of mild to severe CKD have been identified. Therefore, a better understanding of the positive clinical impact of cardiac biomarkers on CVD patient outcomes is an important step toward prevention and improving treatment in the future. In this review, we address the relationship between cardiovascular biomarkers and CKD treatment strategies to elucidate the underlying importance of these biomarkers to patient outcomes.
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Doenças Cardiovasculares , Insuficiência Renal Crônica , Humanos , Doenças Cardiovasculares/diagnóstico , Diálise Renal , Insuficiência Renal Crônica/complicaçõesRESUMO
BACKGROUND: The breakdown of fibrinogen and fibrin during the process of fibrinolysis creates D-dimer. A D-dimer analysis is crucial for the diagnosis of pulmonary embolism, deep vein thrombosis, and disseminated intravascular coagulation. The aim of this study is to evaluate the validity of two different D-dimer assays. METHODS: To analyze the D-dimer, venous blood taken in a vacuette containing 3.2% sodium citrate was used. Peripheral whole blood specimens were collected from 89 subjects, and plasma was separated from these specimens. VIDAS® D-dimer Exclusion™ II and the Beckman Coulter D-dimer assays were used for the quantitative detection of D-dimer levels. The analytical performance of the two different D-dimer assays was compared. RESULTS: The plasma values of D-dimer ranged from 89.2 to 7,452.9 ng/mL (FEU) when tested on the VIDAS® platform and from 20 to 7,770 ng/mL (FEU) when tested on the Beckman Coulter platform. Our results showed that the agreement between the two methods was acceptable and Pearson's correlation coefficient (r) was 0.93 (p < 0.001). CONCLUSIONS: A high correlation exists between quantitative D-dimer measurements conducted with the VIDAS® D-dimer Exclusion™ II and the Beckman Coulter D-dimer assays.
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Coagulação Intravascular Disseminada , Produtos de Degradação da Fibrina e do Fibrinogênio , Humanos , Plasma , FibrinaRESUMO
The enzymes α-2,6-sialyltransferase 1 (ST6Gal1), neuraminidase 1 (Neu1), α-2,3-sialyltransferase 1 (ST3Gal1), and neuraminidase 3 (Neu3) are known to affect immune cell function. However, it is not known whether the levels of these enzymes relate to remission definitions or differentiate American College of Rheumatology (ACR), European League Against Rheumatism (EULAR), and Simplified Disease Activity Index (SDAI) responses in patients with rheumatoid arthritis (RA). We measured the ST6Gal1, Neu1, ST3Gal1, and Neu3 levels of B cells and monocytes in RA patients and correlated the cells' enzyme levels/ratios with the improvement in the ACR, EULAR and SDAI responses and with the two remission definitions. The difference in the B-cell Neu1 levels differed between the ACR 70% improvement and non-improvement groups (p = 0.043), between the EULAR good major response (improvement) and non-good response groups (p = 0.014), and also between the SDAI 50% or 70% improvement and non-improvement groups (p = 0.001 and 0.018, respectively). The same held true when the RA patients were classified by positive rheumatoid factor or the use of biologics. The B-cell Neu1 levels significantly indicated 2005 modified American Rheumatism Association and 2011 ACR/EULAR remission definitions (area under the curve (AUC) = 0.674 with p = 0.001, and AUC = 0.682 with p < 0.001, respectively) in contrast to the CRP and ESR (all AUCs < 0.420). We suggest that B-cell Neu1 is superior for discriminating ACR, EULAR, and SDAI improvement and is good for predicting two kinds of remission definitions.
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Artrite Reumatoide , Doenças Reumáticas , Humanos , Monócitos , Neuraminidase , Artrite Reumatoide/diagnóstico , Ácido N-Acetilneuramínico , SialiltransferasesRESUMO
BACKGROUND: The aim of this study was to optimize the mean volume of blood drawn by nurses to a level that is recommended by our hospital through the implementation of PDCA cycle management. The purpose of the current study was to match the mean volumes of blood drawn with the volume recommended by the manufacturer. METHODS: The adequacy of blood volume in a bottle of aerobic blood culture per venipuncture was evaluated for every month from January 2021 to March 2022 by using the Becton Dickinson BD blood volume monitoring system. Furthermore, the study compared changes in the mean blood volumes before and after the PDCA cycle management was implemented. RESULTS: The mean blood volumes calculated for Q1 2021 (January 2021 to March 2021) before the PDCA cycle management was 6.3 mL per culture bottle. After PDCA cycle management was implemented, the mean blood volumes for Q1 2022 (January 2022 to March 2022) were calculated as 8.6 mL (p < 0.01). In addition, the positive culture rate increased from 13% to 15%. CONCLUSIONS: Implementing the PDCA cycle management can improve the mean blood culture volumes effectively and match the volume recommended by the manufacturer. Additionally, our study indicated that a higher blood volume yielded a culture rate that was significantly positive.
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Hemocultura , Volume Sanguíneo , HumanosRESUMO
Andrographolide is the major bioactive component of the herb Andrographis paniculata and is a potent anti-inflammatory agent. Obesity leads to an excess of free fatty acids, particularly palmitic acid (PA), in the circulation. Obesity also causes the deposition of ectopic fat in nonadipose tissues, which leads to lipotoxicity, a condition closely associated with inflammation. Here, we investigated whether andrographolide could inhibit PA-induced inflammation by activating autophagy, activating the antioxidant defense system, and blocking the activation of the NLRP3 inflammasome. Bone marrow-derived macrophages (BMDMs) were primed with lipopolysaccharide (LPS) and then activated with PA. LPS/PA treatment increased both the mRNA expression of NLRP3 and IL-1[Formula: see text] and the release of IL-1[Formula: see text] in BMDMs. Andrographolide inhibited the LPS/PA-induced protein expression of caspase-1 and the release of IL-1[Formula: see text]. Furthermore, andrographolide attenuated LPS/PA-induced mtROS generation by first promoting autophagic flux and catalase activity, and ultimately inhibiting activation of the NLRP3 inflammasome. Our results suggest that the mechanisms by which andrographolide downregulates LPS/PA-induced IL-1[Formula: see text] release in BMDMs involve promoting autophagic flux and catalase activity. Andrographolide may thus be a candidate to prevent obesity- and lipotoxicity-driven chronic inflammatory disease.
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Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Animais , Camundongos , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Lipopolissacarídeos/efeitos adversos , Catalase/metabolismo , Macrófagos/metabolismo , Inflamação/metabolismo , Antioxidantes/metabolismo , Interleucina-1/metabolismo , Camundongos Endogâmicos C57BLRESUMO
An aerobic bacterium, designated as strain KD337-16T, was isolated from the fecal samples of a black pig. It exhibited spherical, non-motile and non−spore-forming, Gram-positive cells. KD337-16T was identified as a member of the genus Micrococcus through 16S rRNA gene sequencing, and its closest relatives were found to be Micrococcus endophyticus YIM 56238T (99.5% similarity), Micrococcus luteus NCTC 2665T (99.1%), Micrococcus yunnanensis YIM 65004T (99.1%), Micrococcus aloeverae AE-6T (99.1%), Micrococcus antarcticus T2T (98.9%), and Micrococcus flavus LW4T (98.7%). Phylogenomic trees were constructed, and strain KD337-16T was found to form its own cluster as an independent lineage of M. flavus LW4T. Between KD337-16T and its close relatives, the average nucleotide identity, average amino acid identity, and digital DNA−DNA hybridization were below the respective species delineation thresholds at 82.1−86.6%, 78.1−86.1%, and 24.4−34.9%. The major cellular fatty acids and polar lipids were anteiso-C15:0 and iso-C15:0, and DPG and PG, respectively. The predominant menaquinone was MK-8(H2). Taken together, the results indicate that strain KD337-16T is a novel species of the genus Micrococcus, for which the name Micrococcus porci sp. nov. is proposed. The type strain is KD337-16T (=BCRC 81318T = NBRC 115578T).
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Endometriosis is a common gynecological disease that affects approximately 5-10% of reproductive-aged women. However, the etiology and pathophysiology of endometriosis are currently unclear. The objective of this study was to identify a potential pathogenic gene of endometriosis using RNA sequencing (RNA-seq) analysis. Human endometrial stromal cells were isolated from four patients receiving surgical treatment for endometriosis during laparoscopic surgery, and RNA-seq was used to examine differentially expressed genes (DEGs) in eutopic and ectopic endometrial stromal cells. The functional significance of the differentially expressed genes was analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. A total of 1309 upregulated and 663 downregulated genes were identified through the analysis of the transcriptomes of eutopic and ectopic endometrial stromal cells. Furthermore, KEGG analysis indicated that these DEGs were mainly enriched in the PI3K-Akt signaling pathway, cytokine-cytokine receptor interaction, and MAPK signaling pathway. Our study identified differential gene expression in eutopic as compared to ectopic endometrial tissue stromal cells. We strongly believe that our findings can bring new insights into the underlying mechanisms of endometriosis. However, future research is necessary to clarify the roles of the identified genes.
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MOTIVATION: MIB2 (metal ion-binding) attempts to overcome the limitation of structure-based prediction approaches, with many proteins lacking a solved structure. MIB2 also offers more accurate prediction performance and more metal ion types. RESULTS: MIB2 utilizes both the (PS)2 method and the AlphaFold Protein Structure Database to acquire predicted structures to perform metal ion docking and predict binding residues. MIB2 offers marked improvements over MIB by collecting more MIB residue templates and using the metal ion type-specific scoring function. It offers a total of 18 types of metal ions for binding site predictions. AVAILABILITY AND IMPLEMENTATION: Freely available on the web at http://bioinfo.cmu.edu.tw/MIB2/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Computadores , Proteínas , Bases de Dados de Proteínas , Proteínas/química , Sítios de Ligação , Domínios Proteicos , Metais , SoftwareRESUMO
The new coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2) has been reported and spread globally. There is an urgent need to take urgent measures to treat and prevent further infection of this virus. Here, we use virtual drug screening to establish pharmacophore groups and analyze the ACE2 binding site of the spike protein with the ZINC drug database and DrugBank database by molecular docking and molecular dynamics simulations. Screening results showed that Venetoclax, a treatment drug for chronic lymphocytic leukemia, has a potential ability to bind to the spike protein of SARS-CoV-2. In addition, our in vitro study found that Venetoclax degraded the expression of the spike protein of SARS-CoV-2 through amino acids Q493 and S494 and blocked the interaction with the ACE2 receptor. Our results suggest that Venetoclax is a candidate for clinical prevention and treatment and deserves further research.