Multi-omics analysis revealed that the protein kinase MoKin1 affected the cellular response to endoplasmic reticulum stress in the rice blast fungus, Magnaporthe oryzae.

BACKGROUND: Previous studies have shown that protein kinase MoKin1 played an important role in the growth, conidiation, germination and pathogenicity in rice blast fungus, Magnaporthe oryzae. ΔMokin1 mutant showed significant phenotypic defects and significantly reduced pathogenicity. However, the internal mechanism of how MoKin1 affected the development of physiology and biochemistry remained unclear in M. oryzae. RESULT: This study adopted a multi-omics approach to comprehensively analyze MoKin1 function, and the results showed that MoKin1 affected the cellular response to endoplasmic reticulum stress (ER stress). Proteomic analysis revealed that the downregulated proteins in ΔMokin1 mutant were enriched mainly in the response to ER stress triggered by the unfolded protein. Loss of MoKin1 prevented the ER stress signal from reaching the nucleus. Therefore, the phosphorylation of various proteins regulating the transcription of ER stress-related genes and mRNA translation was significantly downregulated. The insensitivity to ER stress led to metabolic disorders, resulting in a significant shortage of carbohydrates and a low energy supply, which also resulted in severe phenotypic defects in ΔMokin1 mutant. Analysis of MoKin1-interacting proteins indicated that MoKin1 really took participate in the response to ER stress. CONCLUSION: Our results showed the important role of protein kinase MoKin1 in regulating cellular response to ER stress, providing a new research direction to reveal the mechanism of MoKin1 affecting pathogenic formation, and to provide theoretical support for the new biological target sites searching and bio-pesticides developing.

Regulation of Electronic Structures of the Urchin-Like NiCoP/CoP Nanocatalysts for Fast Hydrogen Evolution.

The exploration of stable, efficient, and low-cost catalysts toward ammonia borane hydrolysis is of vital significance for the practical implementation of this hydrogen production technology. Integrating interface engineering and nano-architecture engineering is a favorable strategy to elevate catalytic performance, as it can modify the electronic structure and provide sufficient active sites simultaneously. In this work, urchin-like NiCoP/CoP heterostructures are prepared via a three-step hydrothermal-oxidation-phosphorization synthesis route. It is demonstrated that the original Ni/Co molar ratio and the amount of phosphorus are crucial for adjusting the morphology, enhancing the exposed surface area, facilitating charge transfer, and modulating the adsorption and activation of H2O molecules. Consequently, the optimal Ni1Co2P heterostructure displays remarkable catalytic properties in the hydrolysis of ammonia borane with a turnover frequency (TOF) value of 30.3 molH2 ⋅ min-1 ⋅ molmetal -1, a low apparent activation energy of 25.89 kJ ⋅ mol-1, and good stability. Furthermore, by combining infrared spectroscopy and isotope kinetics experiments, a possible mechanism for the hydrolysis of ammonia borane was proposed.

Assessment of automatic rib fracture detection on chest CT using a deep learning algorithm.

OBJECTIVES: To evaluate deep neural networks for automatic rib fracture detection on thoracic CT scans and to compare its performance with that of attending-level radiologists using a large amount of datasets from multiple medical institutions. METHODS: In this retrospective study, an internal dataset of 12,208 emergency room (ER) trauma patients and an external dataset of 1613 ER trauma patients taking chest CT scans were recruited. Two cascaded deep neural networks based on an extended U-Net architecture were developed to segment ribs and detect rib fractures respectively. Model performance was evaluated with a 95% confidence interval (CI) on both the internal and external dataset, and compared with attending-level radiologist readings using t test. RESULTS: On the internal dataset, the AUC of the model for detecting fractures at per-rib level was 0.970 (95% CI: 0.968, 0.972) with sensitivity of 93.3% (95% CI: 92.0%, 94.4%) at a specificity of 98.4% (95% CI: 98.3%, 98.5%). On the external dataset, the model obtained an AUC of 0.943 (95% CI: 0.941, 0.945) with sensitivity of 86.2% (95% CI: 85.0%, 87.3%) at a specificity of 98.8% (95% CI: 98.7%, 98.9%), compared to the sensitivity of 70.5% (95% CI: 69.3%, 71.8%) (p < .0001) and specificity of 98.8% (95% CI: 98.7%, 98.9%) (p = 0.175) by attending radiologists. CONCLUSIONS: The proposed DL model is a feasible approach to identify rib fractures on chest CT scans, at the very least, reaching a level on par with attending-level radiologists. KEY POINTS: • Deep learning-based algorithms automatically detected rib fractures with high sensitivity and reasonable specificity on chest CT scans. • The performance of deep learning-based algorithms reached comparable diagnostic measures with attending level radiologists for rib fracture detection on chest CT scans. • The deep learning models, similar to human readers, were susceptible to the inconspicuity and ambiguity of target lesions. More training data was required for subtle lesions to achieve comparable detection performance.

Serum Human Epididymis Protein 4 as a Prognostic Predictor of New-Onset Heart Failure among Women after Acute Coronary Syndrome: A Single-Center Retrospective Study.

INTRODUCTION: Little is known about the prognostic factors among women with acute coronary syndrome (ACS), partly due to the small number of women included in heart failure (HF) clinical trials. Human epididymis protein 4 (HE4) has been proven to be a new biomarker for acute and chronic HF over the years. We hypothesize that HE4 could be a promising predictor. METHODS: This retrospective study analyzed data from Zhejiang Provincial People's Hospital. This study included 302 female patients with ACS between January 1, 2021, and December 1, 2021. The primary outcome was new-onset HF after ACS during the 12-month follow-up period. We used a logistic regression model to evaluate the association between serum HE4 levels and the incidence of HF. Serum HE4 levels were measured at baseline (within 24 h after admission). RESULTS: Of the 302 female patients, 70 (23.2%) developed new-onset HF within 12 months. Serum HE4 levels in patients with adverse events were significantly higher than those in patients without events (8.9 [7.3-11.5] pmol/dL versus 5.9 [5.0-6.8] pmol/dL, p < 0.001). The levels of HE4, troponin I peak, left ventricular ejection fraction (LVEF), and estimated glomerular filtration rate (eGFR) were validated as independent predictors, with HE4 being the best laboratory predictor (area under the curve, 0.863; 95% confidence interval, 0.817-0.909). Serum HE4 concentrations of >6.93 pmol/dL distinguished patients at risk of HF with 82.9% sensitivity and 78.0% specificity (maximum Youden index J, 0.609). Moreover, HE4 levels were associated with an increased risk of HF. DISCUSSION: We found a strong relationship between HE4 and the occurrence of HF after ACS among women, which might help identify patients at high risk of HF for whom close or intense management should be mandatory.

Effect of mechanical thrombectomy with and without intravenous thrombolysis on the functional outcome of patients with different degrees of thrombus perviousness.

PURPOSE: This study aimed to investigate the long-term functional outcome of patients with different degrees of thrombus perviousness (TP) undergoing mechanical thrombectomy alone and those undergoing combined intravenous thrombolysis (IVT) plus mechanical thrombectomy. METHODS: We conducted a retrospective analysis of consecutive patients with acute ischemic stroke due to large vessel occlusion who underwent mechanical thrombectomy alone or bridging therapy between January 2016 and October 2020. TP was quantified by thrombus attenuation increase (TAI) on admission computed tomography angiography compared with non-contrast computed tomography. After dichotomization of TAI as higher or lower perviousness, Fisher exact tests were performed to estimate the associations of different therapies with favorable functional outcomes [Modified Ranking Scale score at 90 days (90-day mRS) of 0 to 2]. RESULTS: A total of 73 patients were included in our study. 35 (47.9%) thrombi were classified as higher-perviousness clots with TAI of ≥ 24 HU, and the other 38 thrombi were lower-perviousness clots. A favorable outcome with a 90-day mRS of 0 to 2 was observed in 32 patients. In patients with thrombi of lower perviousness, favorable outcome was more common in the bridging therapy group than in the thrombectomy-alone group (p = 0.013), whereas in patients with thrombi of higher perviousness, the long-term neurological outcome did not significantly differ between two therapy groups (p = 0.094). CONCLUSION: Patients with thrombi of lower perviousness were recommended to undergo intravenous alteplase followed by endovascular thrombectomy, and those with thrombi of higher perviousness could undergo thrombectomy alone.

Serum fibrinogen-to-albumin ratio predicts new-onset atrial fibrillation risk during hospitalization in patients with acute myocardial infarction after percutaneous coronary intervention: a retrospective study.

BACKGROUND: New-onset atrial fibrillation (NOAF) is a common adverse outcome of percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI) and is closely correlated with hospital stay and prognosis. In recent years, serum fibrinogen-to-albumin ratio (FAR), a novel biomarker for inflammation and thrombosis, has been used to predict the severity and prognosis of coronary artery disease. Our study aimed to investigate the relationship between FAR and NOAF during hospitalization after PCI in patients with AMI. METHODS: We retrospectively analyzed the incidence of NOAF during hospitalization and follow-up in 670 patients with AMI after PCI. Data were collected on patient age, sex, body mass index, medical history, current medication, heart failure, laboratory tests, culprit blood vessels, echocardiographic characteristics, and AMI type. The enrolled patients were divided into NOAF and non-NOAF groups. The baseline characteristics of patients in the two groups were compared, and the predictive correlation between FAR and NOAF was evaluated using logistic regression analysis and the receiver operating characteristic curve. RESULTS: Fifty-three (7.9%) patients developed NOAF during hospitalization. The occurrence of NOAF was found to be independently associated with higher FAR besides older age, higher neutrophil count, greater left atrial size, worse Killip class upon admission, lower body mass index, lower platelet count, lower left ventricle ejection fraction, and target left circumflex artery disease. FAR exhibited a better predictive value for the occurrence of NOAF during hospitalization (area under the curve, 0.732; 95% confidence interval, 0.659-0.808). CONCLUSIONS: FAR is a robust tool for predicting NOAF risk during hospitalization in patients with AMI after PCI and has a better predictive value than serum fibrin and serum albumin levels alone.

Quantitative and qualitative analysis of Artemisiae Verlotori Folium and Artemisiae Argyi Folium by high-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry.

Artemisiae Argyi Folium (Aiye in Chinese) has been widely used since ancient times. In the Lingnan region (Southern China), the leaf of Artemisia verlotorum Lamotte, which is named Hongjiaoai (HJA) because the roots are red (Hongjiao means red foot in Chinese), has been used as a local substitute for Artemisiae Argyi Folium. The plant has a long medicinal and edible history that can be traced to the Jin Dynasty. However, there is no systematic and reliable method to control the quality of Artemisiae Verlotori Folium. In this study, a comprehensive method involving high-performance liquid chromatography coupled with diode array detection and quadrupole-time-of-flight high-definition mass spectrometry was established to identify and quantify eight constituents (including organic acids and flavonoids) in Artemisiae Verlotori Folium and Artemisiae Argyi Folium as well as high-performance liquid chromatography fingerprints of the two varieties. Moreover, dissimilarities of chemical compositions among the two varieties were further investigated by orthogonal partial least squares discrimination analysis and cluster analysis. This research not only explored the similarities and differences between Artemisiae Verlotori Folium and Artemisiae Argyi Folium in eight components but also provided a qualitative and quantitative analytical method that quickly, accurately, and comprehensively assesses the quality of Artemisiae Verlotori Folium.

The association between nutritional status and sleep quality of Chinese community-dwelling older adults.

BACKGROUND: Sleep disorders are a common syndrome and could affect the life quality of the older adults. AIMS: This study aimed to investigate the association between nutritional status and sleep quality in the Chinese community-dwelling older adults. METHODS: A total of 2,878 participants ≥ 65 years old from the Yiwu Elderly Cohort were included in the study. Nutritional status was assessed using the Mini Nutritional Assessment Short Form (MNA-SF). Participants were categorized as subjects with malnutrition, at risk of malnutrition or well-nourished based on their MNA-SF score. Pittsburgh Sleep Quality Index (PSQI) was used to identify sleep disorders. PSQI score ≥ 6 was categorized as poor sleep quality. RESULTS: Among the 2,878 participants (mean age 72.71 ± 5.79 years, 50.3% men), 31.5% (n = 906) were classified as having sleep disorders, and 25.5% were identified as malnutrition or at risk of malnutrition. We found a significantly relationship between nutritional status and sleep quality in older adults, and the results showed well-nourished decreased the risk of sleep disorders (OR = 0.32, 95% CI = 0.13, 0.75). And well-nourished status was significantly associated with less daytime dysfunction, adequate sleep duration, and good subjective sleep quality (all P < 0.05). CONCLUSION: There was a close association of nutritional status and sleep quality in older adults. We should pay more attention to the nutritional status of older people with sleep problems, as well as the sleep quality of older adults with malnutrition.

Evaluation and validation of the prognostic value of anti-MDA5 IgG subclasses in dermatomyositis-associated interstitial lung disease.

OBJECTIVE: To investigate the association between the anti-melanoma differentiation associated gene 5 (MDA5) IgG subclasses and prognosis of patients with dermatomyositis (DM)-associated interstitial lung disease (ILD). METHODS: This retrospective study included 122 anti-MDA5 positive DM-ILD patients admitted from October 2017 to October 2020 as training cohort, and additional 68 patients from August 2014 to September 2017 as validation cohort. The levels of anti-MDA5 total IgG and IgG subclasses were measured using in-house enzyme-linked immunosorbent assays, and analysed in association with the patient prognosis. RESULTS: In the training cohort, the concentrations of anti-MDA5 IgG1 and IgG3 in non-survivors were significantly higher than in survivors (P < 0.05), whereas there were no significant differences in the IgG2 and IgG4 levels. Kaplan-Meier survival analysis revealed that the levels of anti-MDA5 total IgG, IgG1 and IgG3 were associated with mortality (P < 0.05). Multivariate analysis revealed anti-MDA5 IgG1 >13 U/ml and anti-MDA5 IgG3 >11 U/ml were independent risk factors for death of DM-ILD patients (P < 0.05). Anti-MDA5 IgG1 was confirmed as an independent risk factor in the validation cohort, while anti-MDA5 IgG3 was not. Anti-MDA5 IgG1 showed greater discriminable power for patient prognosis (Youden index 0.494) than anti-MDA5 total IgG, IgG3, or the combination of IgG1 and IgG3 (Youden index 0.356, 0.32 and 0.447, respectively). CONCLUSION: Anti-MDA5 IgG1 and IgG3 are significantly associated with poor prognosis in DM-ILD patients, and anti-MDA5 IgG1 is more efficient as a prognostic biomarker in DM-ILD patients.

Coronary angiography causes Rumpel-Leede symptoms.

BACKGROUND: Rumpel Leede sign (RLS) is a clinical presentation observed at the extremities due to pressure applied externally. The appearance ranges from scattered pin-point rashes to an entire arm covered with petechial hemorrhage depending upon the severity. This phenomenon is relatively uncommon in clinical practice. CASE PRESENTATION: A 64 year old female patient developed a rash in the normal skin area below the compression area on the second day of single catheter coronary angiography. The patient's rash resolved without treatment after 3 days. CONCLUSIONS: We report a case of hypertension and hyperlipidemia with a petechial rash on the skin under the tourniquet compressed by the radial artery after coronary angiography, which is consistent with the Rumpel-Leede phenomenon. clinicians should be watchful of these symptoms.

First Report of Colletotrichum siamense Causing Anthracnose on Eriobotrya japonica in China.

Eriobotrya japonica (Thunb.) Lindl. is a subtropical evergreen tree with economic and medicinal value. In 2021-2022, leaf-spot symptoms were observed on the leaves of E. japonica in Nanchang city, Jiangxi Province, China (28°68'N, 115°95'E). The disease incidence was 30% (20 diseased plants/60 surveyed plants). Symptoms included brown spots that gradually turned dark brown. The lesions were ca. 3-8 mm, and coalescing into irregular or round large lesions. Black acervuli were observed within the lesions. The margin of the diseased tissues was cut and surface sterilized in 75% ethanol for 10 s and 0.1% (v/v) mercuric chloride for 1 min, followed by three rinses in sterile water. Thirteen single spore isolates were purified and deposited in the Mycological Herbarium of Jiangxi Agricultural University. After 7 days, the colonies were grey-white with dense aerial mycelium. Conidia were uni-celled, hyaline and cylindrical. The sizes of the conidia were 12.6 to 17.5 × 4.2 to 6.5 µm. Appressoria were oval to irregular in shape and dark brown in color. These characteristics were consistent with descriptions of Colletotrichum siamense Prihastuti, L. Cai & K.D. Hyde (Weir et al. 2012; Rodríguez-Palafox et al. 2021). The internal transcribed spacer (ITS) region, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), calmodulin (CAL), and actin (ACT) genes were amplified and sequenced (Diao et al. 2017). The sequences were submitted to GenBank with accession numbers ON631874, ON642546, ON642547 and ON642548, respectively. BLASTn searches confirmed high identity (>99%) with the type-strain of C. siamense (MH863513, KC297007, JX009702, JX009549). The concatenated sequences were used to construct a phylogenetic tree. The present isolate JXCS1 formed a single clade with the C. siamense. For pathogenicity, the leaves of two-year-old seedlings (cv. Dawuxing) were inoculated with 10 µL of spore suspension (1×106 conidia/mL). Leaves inoculated with sterile distilled water served as controls. Each treatment was replicated three times. Five days post-inoculation, water-soaked lesions appeared on the leaves, lesions gradually expanded into large round necrotic spots. No symptoms were observed on the control plants. C. siamense was reisolated from all inoculated samples, fulfilling Koch's postulates. To our knowledge, this is the first report of C. siamense causing anthracnose on E. japonica in China. The results further expand the range of plants that can be infected by C. siamense. This disease may decrease the value of plants and proper management strategies should be applied.

[Mechanism of moistening process of Rehmanniae Radix based on kinetic process].

The moistening process of Rehmanniae Radix was characterized quantitatively by moisture phase, texture properties, and component content based on water absorption kinetics and expansion kinetics. Non-linear fitting of water absorption kinetics and expansion kinetics in the moistening process of Rehmanniae Radix was carried out. Low-field nuclear magnetic resonance and imaging(LF-NMR/MRI) technology was used to investigate the phase state and distribution changes of water during the moistening process. The Texture Analyzer was used for the determination of texture properties. The correlations between water absorption rate, expansion rate, water phase state, hardness, and compression cycle work of Rehmanniae Radix at different moistening time were analyzed. The results showed that the water absorption kinetics and expansion kinetics of Rehmanniae Radix were in accordance with the first-order kinetics. Moreover, the water absorption rate and expansion rate increased with the increase in temperature but decreased with the increase in the size of the medicinal materials.In the moistening process, the moisture was transferred from the outside to the inside, and the proportion of the moisture phase changed significantly.Within 16 hours, free water increased from 0.825% to 97.7%,while bound water decreased from 99.2% to 2.33%.Within 28 hours, the texture properties, such as hardness and compression cycle work, decreased gradually with the prolongation in moistening time.At 32 hours, water was evenly distributed throughout the whole medicinal material, and the texture properties also tended to be stable.Pearson correlation bivariate analysis showed that moistening time, water absorption rate, expansion rate, the relative content of free water and bound water, hardness, and compression cycle work were significantly correlated, suggesting that water absorption kinetics and expansion kinetics, LF-NMR/MRI,and Texture Analyzer could directly and quantitatively characterize the moistening process.This study is expected to provide a scientific basis for clarifying the scientific connotation of the moistening process of Rehmanniae Radix.

[Herbalogical study on Liangmianzhen (Zanthoxyli Radix)].

Liangmianzhen(Zanthoxyli Radix) has long been used as medicine. The current medicinal parts are different from those in the ancient. As recorded in the Chinese Pharmacopeia, the medicinal part is root. However, in ancient works, the medicinal parts include root, stem, leaf, and fruit. In an attempt to find the historical basis that stem is a reasonable medicinal part, the herbalogical study was carried out on this medicinal based on the formal names, synonyms, original plant, medicinal parts, habitat of the medicinal plant, producing area, processing and preparation methods, efficacy, and indications recorded in ancient Chinese materia medica and local gazetteers. The results showed that Liangmianzhen was firstly recorded as a medicinal in Shennong's Classic of Materia Medica with the formal name of "Manjiao". "Manjiao" was adopted from the Han Dynasty to the Qing Dynasty when it was changed to "Rudijinniu", the name originating from the folk in the south of the Five Ridges. Now, the formal name is "Liangmianzhen", which was firstly recorded in Wuxuan County Gazetteer in 1914 and then as a synonym in the Updated Records of Picking Herbs in the South of the Five Ridges. According to the formal names, synonyms, and the descriptions of the original plant, the medicinal plants of Liang-mianzhen have the characteristics of shrub-like young seedlings, vine adult seedlings, corymbiform thyrsus, stems with thorns, amphitropous golden-yellow roots with horn-like branches, and thorns on both sides of the leaves. Thus, "Manjiao", "Rudijinniu", and "Liangmianzhen" were from the same species of Zanthoxylum nitidum(Rutaceae), which was also verified based on the growth environment, habitat, processing and preparation methods, efficacy, and indications. In ancient times, the stem and root were the main medicinal parts and leaves and fruits were also used. However, in the Chinese Pharmacopeia, root is recorded as the only medicinal part, which is obviously inconsistent with the records in the ancient classics. In light of the limited medicinal resources for Liang-mianzhen, other medicinal parts of Z. nitidum is recommended. This study clarified the medicinal parts of Z. nitidum in history. It is recommended that the stem be added to the medicinal parts of Z. nitidum in the next edition of Chinese Pharmacopeia.

Clinical significance of radiological patterns of HRCT and their association with macrophage activation in dermatomyositis.

OBJECTIVES: To evaluate the distribution of radiological characteristics stratified by different myositis-specific autoantibodies, identify prognostic value of high-resolution CT (HRCT) patterns in DM-associated interstitial lung disease (DM-ILD), and explore the possible mechanism associated with macrophage activation. METHODS: We enrolled 165 patients with PM/DM-ILD. The distribution of HRCT radiological types with different myositis-specific autoantibodies and the relationship between radiological features and ILD course and prognosis were analysed. Additionally, the potential role of macrophage activation in rapidly progressive ILD (RP-ILD) with DM was studied. RESULTS: The organizing pneumonia pattern was dominant in HRCT findings of patients with DM-ILD, especially those with anti-SAE (6/6, 100%) and anti-MDA5 (46/62, 74.2%) antibodies. The ratios of organizing pneumonia and nonspecific interstitial pneumonia patterns were almost equal in patients with aminoacyl tRNA synthetase antibodies, and nonspecific interstitial pneumonia pattern was associated with a mild clinical course. Lower lung zone consolidation in HRCT was related to RP-ILD in both anti-MDA5 and anti-aminoacyl tRNA synthetase antibody-positive groups. Ferritin levels of >1000 ng/ml (odds ratio (OR), 12.3; P=0.009), elevated carcinoembryonic antigen (OR, 5.8; P=0.046) and carbohydrate antigen 19-9 (OR, 7.8; P=0.018) were independent predictors of a lower lung zone consolidation pattern in anti-MDA5 antibody-positive DM. The infiltration of CD163-positive macrophages into alveolar spaces was significantly higher in the DM-RP-ILD group than in the chronic DM-ILD group. CONCLUSION: HRCT patterns are different among variable myositis-specific autoantibodies positive patients with ILD and lower zone consolidation in HRCT correlated with RP-ILD in DM. Activated macrophages may contribute to the pathogenesis of RP-ILD in DM.

Transcatheter Closure of Atrial Septal Defects with Cardiac Computed Tomography Sizing: Eight-Year Single-Center Practice.

INTRODUCTION: An accurate evaluation of atrial septal defect (ASD) is important for the success of interventional treatment. Cardiac computed tomography (CT) has unique advantages for ASD assessment, although transesophageal echocardiography (TEE) remains the accepted method. OBJECTIVE: This study aimed to evaluate the safety and feasibility of transcatheter closure of ASD with cardiac CT sizing but without TEE measurement. METHODS: Among 134 patients undergoing transcatheter closure, 13 underwent TEE in addition to a cardiac CT examination, and 121 underwent only cardiac CT. Propensity score matching was used to analyze the outcomes of the groups treated with (group 1) or without (group 2) TEE examinations. The success rate and complications among the 121 ASD patients with only cardiac CT sizing were recorded and analyzed. The maximal diameters of the defects remeasured on CT images were compared to the echocardiography results and correlated with the device size by Student t test and Pearson's linear regression analysis, respectively. RESULTS: No significant differences (p > 0.05) were found between groups 1 and 2 in the success rate, complications, or ratio of the device size to the maximum diameter of the defect measured by cardiac CT. In group 1, the maximum diameters of the ASD derived from cardiac CT and TEE were comparable (22.08 ± 9.68 vs. 21.50 ± 10.24; p = 0.351). The success rate among the 121 patients who underwent transcatheter closure with only cardiac CT sizing was 99.2%; however, within 1 month of follow-up, 2 patients had arrhythmia, 1 patient had residual shunting, 1 patient had an infection, and 1 patient had a hematoma, but all patients recovered within a short time. CONCLUSIONS: Cardiac CT seems to be comparable to TEE in the assessment of ASD, and transcatheter closure of ASD based on CT sizing alone is safe and feasible.

Identification of Long Non-Coding RNAs for Predicting Prognosis Among Patients with Thymoma.

BACKGROUND: Thymoma is the most common primary anterior mediastinal neoplasm with a high recurrence rate. Long noncoding RNAs (lncRNAs) have recently been indicated to be used as diagnostic and prognostic indicators for different cancers. The aim of this study was to identify new tumor-specific prognostic lncRNA markers that can improve the treatment and follow-up of patients with thymomas. METHODS: One hundred seventeen thymoma patients with clinical information and level 3 RNAseqv2 data were downloaded from The Cancer Genome Atlas. Prognostic lncRNAs were identified using Kaplan-Meier survival analyses and univariate Cox proportional hazards regression analyses. A predictive risk scoring model was subsequently created using independently significant lncRNAs from a multivariate Cox regression analysis. RESULTS: Masaoka stage and 13 lncRNAs were significantly associated with RFS among 117 thymoma patients, while 59 lncRNAs were significantly associated with OS (all p < 0.05). Multivariate analyses revealed that OS was only independently associated with one lncRNA (JPX) and that RFS was only independently associated with three lncRNAs (AFAP1-AS1, LINC00324, and VLDLR-AS1). A risk score model constructed by the three lncRNA expressions showed that the high-risk group was more likely to experience recurrence. CONCLUSIONS: The expression profile for three lncRNAs (AFAP1-AS1, LINC00324, and VLDLR-AS1) could be used to independently predict RFS among thymoma patients, which may be as prognostic biomarkers for thymoma.

Ordered macroporous quercetin molecularly imprinted polymers: Preparation, characterization, and separation performance.

Ordered macroporous molecularly imprinted polymers were prepared by a combination of the colloidal crystal templating method and the molecular imprinting technique by using SiO2 colloidal crystal as the macroporogen, quercetin as the imprinting template, acrylamide as the functional monomer, ethylene glycol dimethacrylate as the cross-linker and tetrahydrofuran as the solvent. Scanning electron microscopy and Brunauer-Emmett-Teller measurements show that the ordered macroporous molecularly imprinted polymers have a more regular macroporous structure, a narrower pore distribution and a greater porosity compared with the traditional bulk molecularly imprinted polymers. The kinetic and isothermal adsorption behaviors of the polymers were investigated. The results indicate that the ordered macroporous molecularly imprinted polymers have a faster intraparticle mass transfer process and a higher adsorption capacity than the traditional bulk molecularly imprinted polymers. The ordered macroporous molecularly imprinted polymers were further employed as a sorbent for a solid-phase extraction. The results show that the ordered macroporous molecularly imprinted polymers can effectively separate quercetin from the Gingko hydrolysate.

Total flavones of Abelmoschus manihot improve diabetic nephropathy by inhibiting the iRhom2/TACE signalling pathway activity in rats.

CONTEXT: Total flavones extracted from Abelmoschus manihot L. (Malvaceae) medic (TFA) have been proven clinically effective at improving renal inflammation and glomerular injury in chronic kidney disease (CKD). OBJECTIVE: This study evaluated the function of TFA as an inhibitor of iRhom2/TACE (tumour necrosis factor-α converting enzyme) signalling and investigated its anti-DN (diabetic nephropathy) effects in a DN rat model. MATERIALS AND METHODS: In vitro, cells were treated with 200 µg/mL advanced glycation end products (AGEs), and then co-cultured with 20 µg/mL TFA for 24 h. Real time PCR, western blotting and co-immunoprecipitation assays were performed. In vivo, DN was induced in 8 week old male Sprague-Dawley rats via unilateral nephrectomy and intraperitoneal injection of streptozotocin, then TFA were administered to rats by gavage for 12 weeks at three different doses (300, 135 and 75 mg/kg/d). 4-Phenylbutanoic acid (2.5 mg/kg/d) was used as a positive control. RESULTS: IC50 of TFA is 35.6 µM in HK2 and 39.6 µM in HRMC. TFA treatment (20 µM) inhibited the activation of iRhom2/TACE signalling in cultured cells induced by AGEs. LD50>26 g/kg and ED50=67 mg/kg of TFA in rat by gavage, TFA dose-dependently downregulated the expression of proinflammatory cytokines and exerted anti-inflammatory effects significantly though inhibiting the activation of iRhom2/TACE signalling. DISCUSSION AND CONCLUSIONS: Our results show that TFA could dose-dependently ameliorate renal inflammation by inhibiting the activation of iRhom2/TACE signalling and attenuating ER stress. These results suggest that TFA has potential therapeutic value for the treatment of DN in humans.

Interruption of CD40 Pathway Improves Efficacy of Transplanted Endothelial Progenitor Cells in Monocrotaline Induced Pulmonary Arterial Hypertension.

BACKGROUND/AIMS: Transplantation of endothelial progenitor cells (EPCs) plays a therapeutic role in pulmonary arterial hypertension (PAH). Meanwhile, recruitment of progenitors has potential inflammatory effects and exaggerates vascular injury. CD40 pathway is identified as a major player in vascular inflammatory events. In this study, we investigated the role of CD40 pathway in regulating early outgrowth EPC functions, and searched for improvements in PAH cell therapy. METHODS: EPCs were isolated from rat bone marrow and cultured for 7 days. After treatment with soluble CD40 ligand (sCD40L) for 24 hours, EPC migration, adhesion, proliferation, paracrine and vasculogenesis functions were tested. Rat PAH model was founded by subcutaneous injection of monocrotaline (MCT). Control EPCs or lentivirus vectors (Lv)-shRNA-CD40 EPCs were infused via tail vein at day 7, 14, and 21 after MCT injection. Therapeutic effects were evaluated at day 28. RESULTS: sCD40L dose-dependently impaired EPC migration, adhesion, proliferation, and vasculogenesis functions. However, paracrine effects of soluble intercellular adhesion molecule-1, vascular endothelial growth factor and interleukin-6 were dose-dependently improved by sCD40L. Control EPC-derived conditioned medium protected endothelial cell in vitro vasculogenesis, while sCD40L-pretreated ones showed detrimental effects. After MCT injection, sCD40L levels in rat serum increased gradually. Other than in vitro results, benefits of both two EPC treatments were obvious, even taken at day 21. Benefits of control EPCs wore off over time, but those of Lv-shRNA-CD40 EPCs were more effective and enduring, as characterized by both ameliorated rat hemodynamic and reversed vascular remodeling. Furthermore, Lv-shRNA-CD40 EPCs integrated into endothelium better, rather than into adventitia and media. CONCLUSION: sCD40L impaired protective effects of EPCs. Traditional EPC treatments were limited in PAH, while interruption of CD40 pathway of transplanted cells could apparently improve the therapeutic efficacy.

TRPV1 activation exacerbates hypoxia/reoxygenation-induced apoptosis in H9C2 cells via calcium overload and mitochondrial dysfunction.

Transient potential receptor vanilloid 1 (TRPV1) channels, which are expressed on sensory neurons, elicit cardioprotective effects during ischemia reperfusion injury by stimulating the release of neuropeptides, namely calcitonin gene-related peptide (CGRP) and substance P (SP). Recent studies show that TRPV1 channels are also expressed on cardiomyocytes and can exacerbate air pollutant-induced apoptosis. However, whether these channels present on cardiomyocytes directly modulate cell death and survival pathways during hypoxia/reoxygenation (H/R) injury remains unclear. In the present study, we investigated the role of TRPV1 in H/R induced apoptosis of H9C2 cardiomyocytes. We demonstrated that TRPV1 was indeed expressed in H9C2 cells, and activated by H/R injury. Although neuropeptide release caused by TRPV1 activation on sensory neurons elicits a cardioprotective effect, we found that capsaicin (CAP; a TRPV1 agonist) treatment of H9C2 cells paradoxically enhanced the level of apoptosis by increasing intracellular calcium and mitochondrial superoxide levels, attenuating mitochondrial membrane potential, and inhibiting mitochondrial biogenesis (measured by the expression of ATP synthase ß). In contrast, treatment of cells with capsazepine (CPZ; a TRPV1 antagonist) or TRPV1 siRNA attenuated H/R induced-apoptosis. Furthermore, CAP and CPZ treatment revealed a similar effect on cell viability and mitochondrial superoxide production in primary cardiomyocytes. Finally, using both CGRP(8-37) (a CGRP receptor antagonist) and RP67580 (a SP receptor antagonist) to exclude the confounding effects of neuropeptides, we confirmed aforementioned detrimental effects as TRPV1(-/-) mouse hearts exhibited improved cardiac function during ischemia/reperfusion. In summary, direct activation of TRPV1 in myocytes exacerbates H/R-induced apoptosis, likely through calcium overload and associated mitochondrial dysfunction. Our study provides a novel understanding of the role of myocyte TRPV1 channels in ischemia/reperfusion injury that sharply contrasts with its known extracardiac neuronal effects.