Single-cell sequencing reveals distinct immune cell features in cutaneous lesions of pemphigus vulgaris and bullous pemphigoid.

Bullous pemphigoid (BP) and pemphigus vulgaris (PV) are two common subtypes of autoimmune bullous disease (AIBD). The key role of circulating autoreactive immune cells contributing to skin damage of AIBD has been widely recognized. Nevertheless, the immune characteristics in cutaneous lesions remain unclear. Here, we performed single-cell RNA sequencing (scRNA-seq) and single-cell VDJ sequencing (scRNA-seq) to generate transcriptional profiles for cells and T/B cell clonetype in skin lesions of BP and PV. We found that the proportions of NK&T, macrophages/ dendritic cells, B cells, and mast cells increased in BP and PV lesions. Then, BP and PV cells constituted over 75% of all myeloid cell subtypes, CD4+ T cell subtypes and CD8+ T cell subtypes. Strikingly, CD8+ Trm was identified to be expanded in PV, and located in the intermediate state of the pseudotime trajectory from CD8+ Tm to CD8+ Tem. Interestingly, CD8+ Tem and CD4+ Treg highly expressed exhaustion-related genes, especially in BP lesions. Moreover, the enhanced cell communication between stromal cells and immune cells like B cells and macrophages/ dendritic cells was also identified in BP and PV lesions. Finally, clone expansion was observed in T cells of BP and PV compared with HC, while CD8+ Trm represented the highest ratio of hyperexpanded TCR clones among all T cell subtypes. Our study generally depicts a large and comprehensive single-cell landscape of cutaneous lesions and highlights immune cell features in BP and PV. This offers potential research targets for further investigation.

Sirt1 activation prevents high glucose-induced angiotensin converting enzyme 2 downregulation in renal tubular cells by regulating the TIMP3/ADAM17 pathway.

BACKGROUND: Angiotensin converting enzyme 2 (ACE2) exerts renoprotective effects in diabetic kidney disease (DKD) by converting angiotensin (Ang) II into Ang (1-7). Previous studies have demonstrated that ACE2 expression in renal tubules is downregulated in DKD, but the mechanism is not fully understood. Sirtuin-1 (Sirt1) is a protein deacetylase that may regulate the activity of the renin-angiotensin system. The present study investigated the effects of Sirt1 on ACE2 expression under high glucose (HG) conditions and the underlying signaling pathway. METHODS AND RESULTS: Rats with DKD and NRK-52E cells cultured with HG were employed in this study. Western blotting, immunohistochemistry detection and qRT-PCR were performed for protein and mRNA expression analyses. Rats subjected to DKD displayed downregulated expression of Sirt1 and ACE2 in kidneys. Resveratrol, an activator of Sirt1, restored ACE2 expression and ameliorated renal injuries. Similarly, pharmacological activation of Sirt1 with SRT1720 markedly upregulated ACE2 in NRK-52E cells cultured with HG, while Sirt1 small interfering RNA (siRNA) further suppressed ACE2 expression. In addition, A disintegrin and metalloproteinase (ADAM) 17 was observed to be upregulated, and its inhibitor, tissue inhibitor of metalloproteinase 3 (TIMP3), was downregulated in the kidneys of diabetic rats and NRK-52E cells incubated with HG. The TIMP3/ADAM17 pathway was involved in the regulation of ACE2 expression, as evidenced by decreased ACE2 expression levels after TIMP3-siRNA pretreatment. SRT1720 ameliorated the imbalance of TIMP3/ADAM17 induced by HG and consequently enhanced the expression of ACE2. Notably, the above effect of SRT1720 on ACE2 was interrupted by TIMP3-siRNA. CONCLUSIONS: Our findings suggest that Sirt1 activation may prevent HG-induced downregulation of renal tubular ACE2 by modulating the TIMP3/ADAM17 pathway. Sirt1 stimulation might be a potential strategy for the treatment of DKD.

Ecological assessment of stream water polluted by phosphorus chemical plant: Physiological, biochemical, and molecular effects on zebrafish (Danio rerio) embryos.

The rapid development of the phosphorus chemical industry has caused serious pollution problems in the regional eco-environment. However, understanding of their ecotoxic effects remains limited. This study aimed to investigate the developmental toxicity of a stream polluted by a phosphorus chemical plant (PCP) on zebrafish embryos. For this, zebrafish embryos were exposed to stream water (0, 25, 50, and 100% v/v) for 96 h, and developmental toxicity, oxidative stress, apoptosis, and DNA damage were assessed. Stream water-treated embryos exhibited decreased hatching rates, heart rates, and body lengths, as well as increased mortality and malformation rates. The general morphology score system indicated that the swim bladder and pigmentation were the main abnormal morphological endpoints. Stream water promoted antioxidant enzymes (superoxide dismutase (SOD), peroxidase (POD), and glutathione peroxidase (GPx)), lipid peroxidation, and DNA damage. It also triggered apoptosis in the embryos' heads, hearts, and spines by activating apoptotic enzymes (Caspase-3 and Caspase-9). Additionally, stream water influenced growth, oxidative stress, and apoptosis-related 19 gene expression. Notably, tyr, sod (Mn), and caspase9 were the most sensitive indicators of growth, oxidative stress, and apoptosis, respectively. The current trial concluded that PCP-polluted stream water exhibited significant developmental toxicity to zebrafish embryos, which was regulated by the oxidative stress-mediated activation of endogenous apoptotic signaling pathways.

A retrospective study of alveolar bone remodelling after anterior retraction in orthodontic tooth extraction cases with clear aligners and fixed appliances.

OBJECTIVES: To evaluate alveolar bone dimensions and its relationship with tooth movement (retraction, intrusion and torque) during orthodontic treatment with fixed appliance and clear aligners. METHODS: Thirty-two patients were included in this retrospective clinical study. Cone beam computed tomography (CBCT) was collected before and after treatment to measure the volume of dehiscence and fenestrations in the maxillary anterior region, anterior alveolar bone thickness and height and degree of tooth movement. Rank-sum tests were used to compare the differences in alveolar bone defect volumes between clear aligners and fixed appliance, multiple linear regression analysis was used for study evaluation, and kappa statistics were used to assess internal consistency and test-retest reliability. RESULTS: Post-operatively, most alveolar bone defects occurred on the labial side. The incidence of bone fenestration was 23.96% in the clear aligner group and 26.18% in the fixed appliance group, which was higher than the incidence of bone dehiscence (5.21%). The labial bone height decreased by 0.272 mm, and the palatal bone height increased by 0.617 mm for every 1 mm downward intrusion of the anterior tooth apex in the fixed appliance group. In the clear aligner group, there was no significant change in the labial bone height, and the palatal bone height decreased by 0.447 mm for every 1 mm of anterior tooth retraction coronally. CONCLUSIONS: In the fixed appliance group, anterior tooth intrusion and retraction may have led to alveolar bone resorption by its compression at the cervical level. This study provides a three-dimensional tooth movement evaluation method by using CBCT.

OsMFT1 Inhibits Seed Germination by Modulating Abscisic Acid Signaling and Gibberellin Biosynthesis under Salt Stress in Rice.

Seed dormancy and germination are regulated by endogenous gene expression as well as hormonal and environmental conditions, such as salinity, which greatly inhibits seed germination. MOTHER OF FT AND TFL1 (MFT), which encodes a phosphatidylethanolamine-binding protein, is a key regulator of seed germination in Arabidopsis thaliana. There are two orthologous genes of AtMFT in rice (Oryza sativa), namely, OsMFT1 and OsMFT2. However, the functions of these two genes in regulating rice seed germination under salt stress remain unknown. In this study, we found that seeds of loss-of-function osmft1 mutants germinated faster than wild-type (WT) seeds under salt stress, but this was not the case for loss-of-function osmft2 mutants. Overexpression of OsMFT1 (OsMFT1OE) or OsMFT2 increased the sensitivity to salt stress during seed germination. Transcriptome comparisons of osmft1 vs WT in the absence and presence of salt stress yielded several differentially expressed genes, which were associated with salt stress, plant hormone metabolism and signaling pathways, such as B-BOX ZINC FINGER 6, O. sativa bZIP PROTEIN 8 and GIBBERELLIN (GA) 20-oxidase 1. In addition, the sensitivity of OsMFT1OE seeds to GA and osmft1 seeds to abscisic acid (ABA) during seed germination increased under salt stress. Overall, our results indicate that ABA and GA metabolism and their signaling pathways are regulated by OsMFT1, modulating seed germination in rice under salt stress.

Alterations of fecal microbiome and metabolome in pemphigus patients.

The role of gut microbiome and metabolic substances in the development of autoimmune diseases has gradually been revealed. However, the relevant gut features in pemphigus have not been well clarified. We collected stool samples from pemphigus patients and healthy controls (HCs). Metagenomic sequencing and liquid chromatography-mass spectrometry (LC/MS) metabolome sequencing were performed to analyze the compositional and metabolic alternations of the gut microbiome in pemphigus patients and HCs. We observed the reduced richness and diversity and greater heterogeneity in pemphigus patients, which was characterized by a significant decrease in Firmicutes and an increase in Proteobacteria. At the species level, Intestinal pathogenic bacteria such as Escherichia coli and Bacteroides fragilis were significantly enriched, while anti-inflammatory bacteria and butyric acid-producing bacteria were significantly reduced, which were related to clinical indicators (Dsg1/3 and PDAI). 4 species were selected by the machine learning algorithm to better distinguish pemphigus patients from healthy people. Metabolomic analysis showed that the composition of pemphigus patients was different from that of HCs. PE (18:3 (6Z,9Z, 12Z)/14:1 (9Z)) was the main metabolic substance in pemphigus and involved in a variety of metabolic pathways. While Retinol, flavonoid compounds and various amino acids decreased significantly compared with HCs. Furthermore, we found that differences in the levels of these metabolites correlated with changes in the abundance of specific species. Our study provides a comprehensive picture of gut microbiota and metabolites in pemphigus patients and suggests a potential mechanism of the aberrant gut microbiota and metabolites in the pathogenesis of pemphigus.

Association between the triglyceride glucose index and in-hospital and 1-year mortality in patients with chronic kidney disease and coronary artery disease in the intensive care unit.

OBJECTIVE: This study aimed to explore the association between the triglyceride glucose index (TyG) and the risk of in-hospital and one-year mortality in patients with chronic kidney disease (CKD) and cardiovascular disease (CAD) admitted to the intensive care unit (ICU). METHODS: The data for the study were taken from the Medical Information Mart for Intensive Care-IV database which contained over 50,000 ICU admissions from 2008 to 2019. The Boruta algorithm was used for feature selection. The study used univariable and multivariable logistic regression analysis, Cox regression analysis, and 3-knotted multivariate restricted cubic spline regression to evaluate the association between the TyG index and mortality risk. RESULTS: After applying inclusion and exclusion criteria, 639 CKD patients with CAD were included in the study with a median TyG index of 9.1 [8.6,9.5]. The TyG index was nonlinearly associated with in-hospital and one-year mortality risk in populations within the specified range. CONCLUSION: This study shows that TyG is a predictor of one-year mortality and in-hospital mortality in ICU patients with CAD and CKD and inform the development of new interventions to improve outcomes. In the high-risk group, TyG might be a valuable tool for risk categorization and management. Further research is required to confirm these results and identify the mechanisms behind the link between TyG and mortality in CAD and CKD patients.

Comparing performance of iterative and non-iterative algorithms on various feature schemes for arrhythmia analysis.

To evaluate the performance of the classic machine learning algorithms and the effectiveness of various features, the iterative algorithms (i.e., support vector machine (SVM), and least-squares SVM (LS-SVM)) and non-iterative algorithms (i.e., random forest (RF) and naive bayes (NB)) for six feature schemes were performed to classify the ECG recordings. The ECG recordings were initially filtered with a 0.1 Hz - 12 Hz band pass filter. Then 80 features, including 48 time domain, 18 frequency domain, 12 time-frequency and two principle component analysis (PCA) features, were extracted to construct six feature schemes. The RF, SVM, LS-SVM and NB were employed to discern a binary-classification task (i.e., normal and AF ECG recordings) and a tri- classification task (i.e., the normal, AF and ST change ECG recordings) for the six feature schemes. The results revealed that time domain, frequency domain features and PCA features can provide relatively reliable feature combinations to the RF and SVM. In addition, the RF yielded the highest F1-scores (0.8908 and 0.7535) for the binary-classification task and the tri-classification task than the SVM, LS-SVM and NB.

Comparative Physiological and Transcriptome Analysis of Crossostephium chinense Reveals Its Molecular Mechanisms of Salt Tolerance.

Crossostephium chinense is a wild species with strong salt tolerance that has great potential to improve the salt tolerance of cultivated chrysanthemums. Conversely, the unique salt-tolerant molecular mechanisms of Cr. chinense are still unclear. This study performed a comparative physiological and transcriptome analysis of Cr. chinense, Chrysanthemum lavandulifolium, and three hybrids to investigate the salt-tolerant molecular mechanisms of Cr. chinense. The physiological results showed that Cr. chinense maintained higher superoxide dismutase (SOD) activity, alleviating oxidative damage to the membrane. KEGG enrichment analysis showed that plant hormone signaling transduction and the MAPK signaling pathway were mostly enriched in Cr. chinense and hybrids under salt stress. Further weighted gene co-expression network analysis (WGCNA) of DEGs suggested that abscisic acid (ABA) signaling transduction may play a significant role in the salt-tolerant mechanisms of Cr. chinense and hybrids. The tissue-specific expression patterns of the candidate genes related to ABA signaling transduction and the MAPK signaling pathway indicate that genes related to ABA signaling transduction demonstrated significant expression levels under salt stress. This study offers important insights into exploring the underlying salt-tolerant mechanisms of Cr. chinense mediated by ABA signaling transduction and broadens our understanding of the breeding strategies for developing salt-tolerant cultivars utilizing salt-tolerant chrysanthemum germplasms.

Determination of Volatile Organic Compounds and Endogenous Extracts and Study of Expression Patterns of TPS and BSMT in the Flowers of Seven Lilium Cultivars.

Lily is one of the most important cut flowers in the world, with a rich floral fragrance. To further explore the fragrance emission mechanisms of lily cultivars, headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) and organic solvent extraction-gas chromatography-mass spectrometry (OSE-GC-MS) were used to unveil the volatile organic compounds (VOCs) and endogenous extracts of seven lily cultivars. Furthermore, real-time quantitative PCR (qRT-PCR) was used to determine the expression levels of two key genes (TPS and BSMT) related to the biosynthesis of monoterpenoids and methyl benzoate. The results show that forty-five VOCs were detected in the petals of seven lily cultivars, and the main compounds were monoterpenoids and phenylpropanoids/benzenoids. Dichloromethane was the best solvent for extracting the endogenous extracts of Lilium 'Viviana' petals and eighteen endogenous extracts were detected using dichloromethane to extract the petals of seven lily cultivars. Each compound's emission ratio (natural logarithm of the ratio of VOC content to endogenous extract content) was calculated, and linear regression analyses between emission ratios and boiling points were conducted. Significant linear negative correlations existed between the emission ratios and boiling points of compounds, and the regression equations' coefficients of determination (R2) were all greater than 0.7. TPS was expressed highly in 'Viviana', 'Pink News', and 'Palazzo', and BSMT was expressed highly in 'Pink News' and 'Palazzo'. Correlation analyses between the gene expression levels and the monoterpenoids and methyl benzoate contents found that the TPS expression levels have strong positive correlations with monoterpenoids content, while no correlations were found between the expression levels of BSMT and the contents of methyl benzoate. This study lays the foundation for research on the release patterns of VOCs in the flowers of Lilium, and the breeding of lilies for their floral fragrance.

Metabolomics analysis of three Artemisia species in the Tibet autonomous region of China.

BACKGROUND: The Artemisia species are widely distributed around the world, and have found important usage in traditional medicinal practice. This study was designed to investigate the metabolites of Tibetan Artemisia species and understand the metabolic pathways. METHODS: The metabolites from three Artemisia species in Tibet, were analyzed using LC-MS/MS. The differential metabolites were classified and analyzed by principal component analysis (PCA), partial least squares analysis and hierarchical clustering. KEGG Pathway enrichment analysis was used to identify the key metabolic pathways involved in the differential metabolites of three Artemisia species. RESULT: The metabolites of three Artemisia species were analyzed. Under the positive ion mode in LC-MS/MS, 262 distinct metabolites were differentially detected from Artemisia sieversiana and Artemisia annua, 312 differential metabolites were detected from Artemisia wellbyi and Artemisia sieversiana, 306 differential metabolites were screened from Artemisia wellbyi and Artemisia annua. With the negative ion mode, 106 differential metabolites were identified from Artemisia sieversiana and Artemisia annua, 131 differential metabolites were identified from Artemisia wellbyi and Artemisia sieversiana,133 differential metabolites were differentially detected from Artemisia wellbyi and Artemisia annua. The selected differential metabolites were mainly organic acids and their derivatives, ketones, phenols, alcohols and coumarins. Among these natural compounds, artemisinin, has the highest relative content in Artemisia annua. CONCLUSIONS: This is the first reported attempt to comparatively determine the types of the metabolites of the three widely distributed Artemisia species in Tibet. The information should help medicinal research and facilitate comprehensive development and utilization of Artemisia species in Tibet.

Ischemia preconditioning alleviates ischemia/reperfusion injury-induced coronary no-reflow and contraction of microvascular pericytes in rats.

BACKGROUND: Ischemia preconditioning (IPC) ameliorates coronary no-reflow induced by ischemia/reperfusion (I/R) injury, and pericytes play an important role in microvascular function. However, it is unclear whether IPC exerts a protective effect on coronary microcirculation and regulates the pericytes. OBJECTIVE: The purpose of this study was to assess whether IPC improves coronary microvascular perfusion and reduces pericyte constriction after myocardial I/R injury. METHODS: Rats were randomly divided into three groups: the sham group, the I/R group, and the IPC + I/R group. The left anterior descending artery (LAD) of rats in the I/R group were ligated for 45 min, and the rats in the IPC + I/R group received 4 episodes of 6min occlusion followed by 6min reperfusion before the LAD was ligated. After 24 h of reperfusion, the area of no-reflow, and area at risk were evaluated with thioflavin-S and Evens blue staining, and infarct size with triphenyl tetrazolium chloride staining, respectively. Besides, fluorescent microspheres were perfused to enable visualization of the non-obstructed coronary vessels. Cardiac pericytes and microvascular were observed by immunofluorescence, and the diameter of microvascular at the site of the pericyte somata was analyzed. RESULTS: The infarct size, and area of no-reflow in the IPC + I/R group were significantly reduced compared with the I/R group (infarct size, 33.5% ± 11.9% vs. 49.2% ± 9.4%, p = 0.021；no-reflow, 12.7% ± 5.2% vs. 26.6% ± 5.0%, p < 0.001). IPC improved microvascular perfusion and reduced the percentage of the blocked coronary capillary. Moreover, we found that cardiac pericytes were widely distributed around the microvascular in various regions of the heart, and expressed the contractile protein α-smooth muscle actin. The microvascular lumen diameter at pericyte somata was reduced after I/R (4.3 ± 1.0 µm vs. 6.5 ± 1.2 µm, p < 0.001), which was relieved in IPC + I/R group compared with the I/R group (5.2 ± 1.0 µm vs. 4.3 ± 1.0 µm, p < 0.001). Besides, IPC could reduce the proportion of apoptotic pericytes compared to the I/R group (22.1% ± 8.4% vs. 38.5% ± 7.5%, p < 0.001). CONCLUSION: IPC reduced no-reflow and inhibited the contraction of microvascular pericytes induced by cardiac I/R injury, suggesting that IPC might play a protective role by regulating the pericyte function.

Effects of nicotinamide on follicular development and the quality of oocytes.

BACKGROUND: Nicotinamide (NAM) is an important antioxidant, which is closely related to female fertility, but its role has not been clearly elucidated. The purpose of the present study was to investigate the effects of NAM on follicular development at different stages and the quality of oocytes. METHODS: The concentration of NAM in follicular fluid (FF) of 236 women undergoing in vitro fertilization (IVF) was ascertained by enzyme-linked immunosorbent assay (ELISA), and the correlation between NAM and clinical indexes was analyzed. During the in vitro maturation (IVM) of mice cumulus-oocyte complexes (COCs), different concentrations of NAM were added to check the maturation rate and fertilization rate. The reactive oxygen species (ROS) levels in the oocytes treated with different hydrogen peroxide (H2O2) and NAM were assessed. Immunofluorescence staining was performed to measure the proportion of abnormal spindles. RESULTS: The level of NAM in large follicles was significantly higher than that in small follicles. In mature FF, the NAM concentration was positively correlated with the rates of oocyte maturation and fertilization. Five mM NAM treatment during IVM increased maturation rate and fertilization rate in the oxidative stress model, and significantly reduced the increase of ROS levels induced by H2O2 in mice oocytes. CONCLUSIONS: Higher levels of NAM in FF are associated with larger follicle development. The supplement of 5 mM NAM during IVM may improve mice oocyte quality, reducing damage caused by oxidative stress.

The triglyceride glucose index is associated with future cardiovascular disease nonlinearly in middle-aged and elderly Chinese adults.

OBJECTIVE: We aimed to investigate the association between triglyceride glucose index and cardiovascular disease (CVD) development in the Chinese middle-aged and elderly population using the China Health and Retirement Longitudinal Study dataset 2011-2018. METHODS: Basic characteristics of participants, including sociodemographic information, and health conditions, were acquired. Logistic regression analyses and restricted cubic spline regression analyses were conducted to investigate the association between the triglyceride glucose index and future CVD risks. Subgroup analyses were performed to evaluate potential interaction. RESULTS: Seven hundred fifty-three of 6114 (12.3%) participants have developed CVD in 2018 over an approximately 7-year follow-up. The logistic regression analysis exhibited that compared to the lowest triglyceride glucose index group, the multivariable OR for future CVD was 0.985 (95%CI 0.811-1.198) in the T2 triglyceride glucose index group and 1.288 (95%CI 1.068-1.555) in the T3 TyG index (P for trend 0.006). The restricted cubic spline regression analysis showed the nonlinear association between triglyceride glucose index and CVD incidence; the cut-off values were 8.07 and 8.57, respectively, after total adjustment. Gender, fast blood glucose, and triglycerides interacted with triglyceride glucose index and CVD except for BMI. CONCLUSION: The triglyceride glucose index was nonlinearly related to the risk of future cardiovascular disease in the middle-aged and elderly Chinese population.

Triglyceride glucose index exacerbates the risk of future cardiovascular disease due to diabetes: evidence from the China Health and Retirement Longitudinal Survey (CHARLS).

OBJECTIVE: We aimed to investigate the effect of the triglyceride glucose (TyG) index on the association between diabetes and cardiovascular disease (CVD). METHODS: Data from 6,114 individuals were extracted and analyzed from the China Health and Retirement Longitudinal Survey (CHARLS) from 2011 to 2018. Logistic regression analyses were conducted to assess the relationship between diabetes and CVD across the various TyG index groups. The statistical method of subgroup analysis was used to determine the correlation between diabetes and CVD for each TyG index group by sex, history of hypertension and dyslipidemia, smoking, and drinking. RESULTS: Diabetes was positively associated with CVD risk after adjustment in 2011(odds ratio (OR) 1.475, 95% CI 1.243-1.752, P < 0.001). There was a gradient increase in the OR for new-onset CVD in 2018 due to diabetes at baseline across the value of the TyG index based on a fully adjusted model (P for trend < 0.05). The ORs of diabetes at baseline for CVD in 2018 were 1.657 (95% CI 0.928-2.983, P = 0.098), 1.834(95% CI 1.064-3.188, P = 0.037) and 2.234(95% CI 1.349-3.673, P = 0.006) for T1, T2 and T3 of the TyG index respectively. The gradient of increasing risk of CVD still existed among those with hypertension and nondrinkers in the subgroup analysis. CONCLUSION: Elevated TyG index strengthens the correlation between diabetes mellitus and CVD in middle-aged and elderly Chinese adults.

Hemodynamic investigation and in vitro evaluation of a novel mixed-flow blood pump.

INTRODUCTION: Ventricular assist devices (VADs) are considered an effective treatment for patients with advanced heart failure, while complications associated with blood damage remain a burden. Structure design innovation has the potential to reduce hemolysis and improve hemocompatibility. METHODS: In this research, a novel mixed-flow blood pump that integrates structural features of the axial and centrifugal VADs was proposed. The pump consists of an inducer, a mixed impeller supported by two ceramic pivot bearings, and a volute. The flow field and laminar viscous shear stress were analyzed by the in silico simulation. The hydraulic and hemolytic performance were evaluated in vitro by using a 3D printed pump. RESULTS: The flow field distribution showed that streamlines in the connection area were smoothly transitioned through structural integration and no irregular flow occurred in the entire flow channel. The axial blades work as a fluid accelerator (generating 18.56% of the energy), and the centrifugal blades provide the main pressure head. The proportion of fluid inside the pump exposed to low laminar viscous shear stress (<50 Pa) and high laminar viscous shear stress (>150 Pa) was 99.02% and 0.03%, respectively. The in vitro hemolysis test results showed that the NIH (Normalized Index of Hemolysis) value of the mixed pump is 0.0079 ± 0.0039 g/100 L (n = 6). CONCLUSION: It can be concluded that the mixed flow structure is effective at improving hydraulic performance, eliminating flow disturbance, and minimizing shear stresses. This novel pump design is expected to provide a new direction for the development of next-generation VADs.

Generalized Eruptive Histiocytoma With S100 Protein-Positive Histiocytes and Prominent Eosinophilic Infiltration: A Rare Case Report.

ABSTRACT: Generalized eruptive histiocytoma (GEH) is a very rare benign disorder belonging to the group of non-Langerhans cell histiocytosis (non-LCH). GEH is characterized by a nearly uniform infiltrate of histiocytes with classic immunological phenotype (CD68+, S-100- and CD1a-). Prominent eosinophilic infiltration and S100-positive histiocytes are rarely associated in GEH. In this article, we reported a middle-age man presented with disseminated reddish papules distributed on the trunk and proximal extremities. A skin biopsy of the papule showed a dense histiocytic infiltration with prominent eosinophils. By immunohistochemistry, the histiocytes revealed strongly positive for CD68 and S100 protein and negative for CD1a and Langerin (CD207). Based on clinical and histopathological criteria, the diagnosis of GEH was established. We presented this rare case of GEH with such distinctive features to strengthen the awareness of this uncommon form of non-LCH. Classical histopathological and immunological features cannot reliably distinguish GEH from other non-LCH.

UHPLC-MS/MS-based method for quantification of verinurad in rat plasma and its application in a bioavailability study.

A rapid and sensitive UHPLC-MS/MS method was developed and fully validated for the quantification of verinurad in rat plasma. Lesinurad was used as an internal standard (IS), and simple protein precipitation was utilized to prepare the analytes from the matrix. Chromatographic separation was carried out on a Zorbax SB C18 column. The mobile phase consisted of water with 0.1% formic acid (A) and acetonitrile with 0.1% formic acid (B) at a flow rate of 0.3 mL/min. The short run time of 4 min made it possible to analyze more than 300 samples per day. The ion transitions were quantified in negative mode with multiple reaction monitoring (MRM) transitions of 347.1 â†’ 261.1 for verinurad and 404.2 â†’ 178.9 for the IS. The validated linear ranges of verinurad were 10-5000 ng/mL in rat plasma. The validated UHPLC-MS/MS method was further applied to the pharmacokinetic study of verinurad in rat plasma after intragastric (2 mg/kg) and intravenous (1 mg/kg) administrations. The pharmacokinetic study revealed that verinurad showed high clearance and high bioavailability (78.1%). To the best of our knowledge, this is the first report of the bioavailability study of verinurad.

SGDAN-A Spatio-Temporal Graph Dual-Attention Neural Network for Quantified Flight Delay Prediction.

There has been a lot of research on flight delays. But it is more useful and difficult to estimate the departure delay time especially three hours before the scheduled time of departure, from which passengers can reasonably plan their travel time and the airline and airport staff can schedule flights more reasonably. In this paper, we develop a Spatio-temporal Graph Dual-Attention Neural Network (SGDAN) to learn the departure delay time for each flight with real-time conditions at three hours before the scheduled time of departure. Specifically, it first models the air traffic network as graph sequences, what is, using a heterogeneous graph to model a flight and its adjacent flights with the same departure or arrival airport in a special time interval, and using a sequence to model the flight and its previous flights that share the same aircraft. The main contributions of this paper are using heterogeneous graph-level attention to learn the influence between the flight and its adjacent flight together with sequence-level attention to learn the influence between the flight and its previous flight in the flight sequence. With aggregating features from the learned influence from both graph-level and sequence-level attention, SGDAN can generate node embedding to estimate the departure delay time. Experiments on a real-world large-scale data set show that SGDAN produces better results than state-of-the-art models in the accurate flight delay time estimation task.