Identification of Regulatory RNA-Binding Proteins Associated with Immune Infiltration in Laryngeal Squamous Cell Carcinoma.

We analyzed bulk RNA sequencing and single-cell RNA sequencing (scRNA-seq) data to identify alternative splicing (AS) events and regulatory RNA-binding proteins (RBPs) associated with immune infiltration in human laryngeal squamous cell carcinoma (LSCC). Whole-transcriptome sequencing data of 20 human laryngeal cancer and paracancerous tissues were downloaded from the Gene Expression Omnibus public database, using newly published splicing-site usage variation analysis software to obtain highly conserved regulated AS (RAS) events, and scientific reverse convolution algorithm analysis was used to identify significantly different immune cells and perform a correlation analysis between the two. The software package edgeR was used to identify differentially expressed RBPs and the immune infiltration-related LSCC-RAS they may regulate. Finally, we present the expression profiles and survival curves of 117 human laryngeal cancer samples from The Cancer Genome Atlas dataset for the identified RBPs and LSCC-RAS. We also downloaded the gene set enrichment 150321 scRNA-seq data for two human LSCC tissue samples. The RBP expression pattern and the expression of prophase RBP genes were analyzed in different LSCC cell populations. RNA-binding motif protein 47 (RBM47) and filamin A, as well as the RBP-RAS events that were screened in both the fibulin 2 and fibronectin 1 genes, were all significantly associated with the prognosis, and the RBM47 gene was upregulated in myeloid cells. Because the prognosis was significantly associated with two RBP regulators and two LSCC-RAS events, they may be critical regulators of immune cell survival during laryngeal cancer progression, and RBM47 may regulate macrophage-associated AS and affect immunity.

NAT10 Is Involved in Cardiac Remodeling Through ac4C-Mediated Transcriptomic Regulation.

BACKGROUND: Heart failure, characterized by cardiac remodeling, is associated with abnormal epigenetic processes and aberrant gene expression. Here, we aimed to elucidate the effects and mechanisms of NAT10 (N-acetyltransferase 10)-mediated N4-acetylcytidine (ac4C) acetylation during cardiac remodeling. METHODS: NAT10 and ac4C expression were detected in both human and mouse subjects with cardiac remodeling through multiple assays. Subsequently, acetylated RNA immunoprecipitation and sequencing, thiol-linked alkylation for the metabolic sequencing of RNA (SLAM-seq), and ribosome sequencing (Ribo-seq) were employed to elucidate the role of ac4C-modified posttranscriptional regulation in cardiac remodeling. Additionally, functional experiments involving the overexpression or knockdown of NAT10 were conducted in mice models challenged with Ang II (angiotensin II) and transverse aortic constriction. RESULTS: NAT10 expression and RNA ac4C levels were increased in in vitro and in vivo cardiac remodeling models, as well as in patients with cardiac hypertrophy. Silencing and inhibiting NAT10 attenuated Ang II-induced cardiomyocyte hypertrophy and cardiofibroblast activation. Next-generation sequencing revealed ac4C changes in both mice and humans with cardiac hypertrophy were associated with changes in global mRNA abundance, stability, and translation efficiency. Mechanistically, NAT10 could enhance the stability and translation efficiency of CD47 and ROCK2 transcripts by upregulating their mRNA ac4C modification, thereby resulting in an increase in their protein expression during cardiac remodeling. Furthermore, the administration of Remodelin, a NAT10 inhibitor, has been shown to prevent cardiac functional impairments in mice subjected to transverse aortic constriction by suppressing cardiac fibrosis, hypertrophy, and inflammatory responses, while also regulating the expression levels of CD47 and ROCK2 (Rho associated coiled-coil containing protein kinase 2). CONCLUSIONS: Therefore, our data suggest that modulating epitranscriptomic processes, such as ac4C acetylation through NAT10, may be a promising therapeutic target against cardiac remodeling.

Nuclear import of Mas-related G protein-coupled receptor member D induces pathological cardiac remodeling.

Alamandine (Ala), a ligand of Mas-related G protein-coupled receptor, member D (MrgD), alleviates angiotensin II (AngII)-induced cardiac hypertrophy. However, the specific physiological and pathological role of MrgD is not yet elucidated. Here, we found that MrgD expression increased under various pathological conditions. Then, MrgD knockdown prevented AngII-induced cardiac hypertrophy and fibrosis via inactivating Gαi-mediacted downstream signaling pathways, including the phosphorylation of p38 (p-P38), while MrgD overexpression induced pathological cardiac remodeling. Next, Ala, like silencing MrgD, exerted its cardioprotective effects by inhibiting Ang II-induced nuclear import of MrgD. MrgD interacted with p-P38 and promoted its entry into the nucleus under Ang II stimulation. Our results indicated that Ala was a blocking ligand of MrgD that inhibited downstream signaling pathway, which unveiled the promising cardioprotective effect of silencing MrgD expression on alleviating cardiac remodeling. Video Abstract.

Predictive value of ACEF II score for adverse prognosis in patients with coronary heart disease after percutaneous coronary intervention.

OBJECTIVE: To investigate the predictive value of age, creatinine and ejection fraction (ACEF) II score for the incidence of major adverse cardiovascular and cerebrovascular events (MACCEs) in patients with coronary heart disease (CHD) after percutaneous coronary intervention (PCI). METHODS: A total of 445 patients with CHD who underwent PCI were consecutively enrolled. The receiver operating characteristic (ROC) curve was used to analyse the power of the ACEF II score in predicting MACCE. Kaplan-Meier survival curves and log-rank tests were chosen for survival analysis of adverse prognosis between groups. Finally, multivariate Cox proportional risk regression analysis was used to investigate independent risk factors for MACCEs in patients with CHD after PCI. RESULTS: There was a significantly higher incidence of MACCEs in patients with high ACEF II scores. The area under the ROC curve of ACEF II score was 0.718, suggesting it had ideal predictive value for MACCE risks. The ACEF II score had a best cut-off value of 1.461 (sensitivity 79.4%, specificity 53.7%). Survival analysis indicated that patients in the high-score group had a significantly lower cumulative MACCE-free survival rate. Multivariate Cox regression analysis showed that ACEF II scores ≥1.461, Gensini scores ≥61.5, age, cardiac troponin I and previous PCI were independent risk factors of MACCE in patients with CHD after PCI, while the utilisation of statins was an independent protective factor. CONCLUSIONS: The ACEF II score has an ideal capacity for risk stratification in patients with CHD undergoing PCI and offers good predictive value for MACCE in the long term.

Combined lifestyle factors are associated with the risk of ischaemic stroke in a Chinese population.

PURPOSE: Lifestyle plays an important role in the development of ischaemic stroke (IS). The objective of this study was to evaluate the association between combined lifestyle factors and the risk of IS in an eastern Chinese population. METHODS: We collected lifestyle information from 191 patients with IS admitted to the second affiliated hospital of Soochow University and 575 control subjects from community clinics using a structured questionnaire. After division into training and test datasets, regularised stepwise logistic regression, least absolute shrinkage and selection operator regression and genetic algorithm models were used to identify lifestyle factors associated with IS. The improved discriminative ability by adding the lifestyle factors was determined by c-index and reclassification analysis. The final model was validated in the test dataset. RESULTS: After controlling for conventional cardiovascular disease (CVD) risk factors, preferences for fruits (OR (95% CI): 0.29 (0.18-0.46), p<0.001) and soy products (0.47 (0.29-0.75), p=0.002) were negatively associated with IS, while lower life satisfaction (mildly satisfied: 2.15 (1.27-3.63), p=0.004; not satisfied: 6.39 (1.76-25.44), p=0.006) was positively associated with IS. Adding these factors to a basic CVD risk model improved the c-index (0.825 vs 0.753, p<0.001) and reclassification for IS (net reclassification index (95% CI): 18.49% (7.90%-29.08%), integrated discrimination index (95% CI): 0.11% (0.08%-0.14%), p<0.001). The model with lifestyle factors achieved a c-index of 0.813 and good calibration in the test dataset. CONCLUSIONS: Our results showed that combined lifestyle factors including dietary pattern and life satisfaction are independently associated with the risk of IS.

Involvement of circHIPK3 in the pathogenesis of diabetic cardiomyopathy in mice.

AIMS/HYPOTHESIS: In a mouse model of diabetic cardiomyopathy (DCM) the expression of the circular RNA circHIPK3 was found to be significantly increased. This study aimed to discover the molecular mechanisms linking circHIPK3 to the pathogenesis of DCM. METHODS: The diabetic mouse model was established by i.p. injection of streptozotocin, which led to the development of DCM. Echocardiographic measurements were used to evaluate cardiac structure and function, and histological staining was applied to detect myocardial fibrosis in mice. 5-Ethynyl-2'-deoxyuridine incorporation was performed to determine cell proliferation and RNA fluorescent in situ hybridisation was employed to examine circHIPK3 expression in cardiac fibroblasts. RNA immunoprecipitation and luciferase reporter assay were conducted to explore the pathological mechanism of circHIPK3 in myocardial fibrosis. RESULTS: Knockdown of circHIPK3 was found to attenuate myocardial fibrosis and enhance cardiac function in DCM mice. In addition, silencing of circHIPK3 could suppress proliferation of cardiac fibroblasts treated with angiotensin II. Furthermore, RNA immunoprecipitation and luciferase reporter assay revealed a circHIPK3-miR-29b-3p-Col1a1-Col3a1 regulatory network in the pathogenesis of myocardial fibrosis. CONCLUSIONS/INTERPRETATION: circHIPK3 contributes to increased myocardial fibrosis during DCM by functioning as a competing endogenous RNA that upregulates Col1a1 and Col3a1 expression through suppressing miR-29b-3p.

m6A RNA Methylation in Cardiovascular Diseases.

Cardiovascular diseases (CVDs) remain the leading cause of death and disability worldwide, despite marked improvements in prevention, diagnosis, and early intervention. There is an urgent need to discover more effective therapeutic strategies, which would be facilitated by a more in-depth understanding of CVDs and their underlying molecular mechanisms. Recent advances in knowledge about epigenetic mechanisms, especially RNA methylation, have revealed a close relationship between epigenetic modifications and CVDs and have brought to potential novel targets for diagnosis and treatment. Here, we provide a review of recent studies exploring RNA N6-methyladenosine (m6A) modification, with particular emphasis on its role in CVDs, such as coronary heart disease, hypertension, cardiac hypertrophy, and heart failure. We also introduce the "life cycle" of m6A and its dominant function in several biological processes. Finally, we highlight the prospects of treatment based on interfering with m6A, which could have a transformative effect on clinical medicine.

The link of depression, untreated hypertension, and diabetes with mortality in postmenopausal women: A cohort study.

OBJECTIVE: To explore the association of depression, as well as untreated hypertension or diabetes with all-cause death in community-based postmenopausal women in Beijing. METHODS: A cohort of 863 community-based postmenopausal women with no history of cardiovascular heart disease (CHD), stroke, cancer, or dementia was investigated on 20 July-28 September 2009 at baseline. Depression was diagnosed using the 30-item Center for Epidemiologic Studies Depression (CES-D) scale with CES-D ≥ 11. Meanwhile, data on health behavior, physical comorbidity, and social support at baseline were collected. These individuals were followed up from 20 July to 30 August 2014. All-cause mortality and cause of death were surveyed. RESULTS: After a median follow-up of 4.97 years, 120 subjects died of all-cause. Twenty-four died of stroke, 19 died of myocardial infarction, 21 died of cancer. The others died of aging, infection, and accident. Depression and untreated HP were significantly associated with all-cause mortality in Cox models after full adjustment for all of the potential confounders (Depression HR: 2.16, 95%CI: 1.35-3.46; Untreated hypertension HR: 1.84, 95%CI: 1.12-3.02). However, negative correlation of untreated diabetes on all-cause mortality was observed in this population (HR: 1.36, 95%CI: 0.75-2.49). When depression was co-existing with hypertension/diabetes, the HR for mortality elevated significantly (Depression co-existing with hypertension HR = 3.87, 95% CI: 2.07-7.23; Depression co-existing with diabetes HR = 5.02, 95% CI: 1.5-16.79). CONCLUSIONS: It is suggested we should take sufficient care of postmenopausal females with depression and control blood pressure and glucose more effectively. Abbreviations: HP: Hypertension; DM: Diabetes; TC: Cholesterol; TG: Triglyceride; BMI: Body-Mass Index; CES-D: Center for Epidemiologic Studies Depression; CDC: Centers for Disease Control and Prevention; HR: Hazard Ratio; CI: Confidence Interval; ADL: Activities of daily living scale.

Computer Vision-Based Bridge Damage Detection Using Deep Convolutional Networks with Expectation Maximum Attention Module.

Cracks and exposed steel bars are the main factors that affect the service life of bridges. It is necessary to detect the surface damage during regular bridge inspections. Due to the complex structure of bridges, automatically detecting bridge damage is a challenging task. In the field of crack classification and segmentation, convolutional neural networks have offer advantages, but ordinary networks cannot completely solve the environmental impact problems in reality. To further overcome these problems, in this paper a new algorithm to detect surface damage called EMA-DenseNet is proposed. The main contribution of this article is to redesign the structure of the densely connected convolutional networks (DenseNet) and add the expected maximum attention (EMA) module after the last pooling layer. The EMA module is obviously helpful to the bridge damage feature extraction. Besides, we use a new loss function which considers the connectivity of pixels, it has been proved to be effective in reducing the break point of fracture prediction and improving the accuracy. To train and test the model, we captured many images from multiple bridges located in Zhejiang (China), and then built a dataset of bridge damage images. First, experiments were carried out on an open concrete crack dataset. The mean pixel accuracy (MPA), mean intersection over union (MIoU), precision and frames per second (FPS) of the EMA-DenseNet are 87.42%, 92.59%, 81.97% and 25.4, respectively. Then we also conducted experiments on a more challenging bridge damage dataset, the MIoU, where MPA, precision and FPS were 79.87%, 86.35%, 74.70% and 14.6, respectively. Compared with the current state-of-the-art algorithms, the proposed algorithm is more accurate and robust in bridge damage detection.

Automatic Pixel-Level Pavement Crack Recognition Using a Deep Feature Aggregation Segmentation Network with a scSE Attention Mechanism Module.

Pavement crack detection is essential for safe driving. The traditional manual crack detection method is highly subjective and time-consuming. Hence, an automatic pavement crack detection system is needed to facilitate this progress. However, this is still a challenging task due to the complex topology and large noise interference of crack images. Recently, although deep learning-based technologies have achieved breakthrough progress in crack detection, there are still some challenges, such as large parameters and low detection efficiency. Besides, most deep learning-based crack detection algorithms find it difficult to establish good balance between detection accuracy and detection speed. Inspired by the latest deep learning technology in the field of image processing, this paper proposes a novel crack detection algorithm based on the deep feature aggregation network with the spatial-channel squeeze & excitation (scSE) attention mechanism module, which calls CrackDFANet. Firstly, we cut the collected crack images into 512 × 512 pixel image blocks to establish a crack dataset. Then through iterative optimization on the training and validation sets, we obtained a crack detection model with good robustness. Finally, the CrackDFANet model verified on a total of 3516 images in five datasets with different sizes and containing different noise interferences. Experimental results show that the trained CrackDFANet has strong anti-interference ability, and has better robustness and generalization ability under the interference of light interference, parking line, water stains, plant disturbance, oil stains, and shadow conditions. Furthermore, the CrackDFANet is found to be better than other state-of-the-art algorithms with more accurate detection effect and faster detection speed. Meanwhile, our algorithm model parameters and error rates are significantly reduced.

[Association of RAGE gene polymorphisms with MHR ratio and heart rate variability among patients with coronary heart disease].

OBJECTIVE: To assess the association of polymorphisms of receptor of advanced glycation end products (RAGE) gene, monocyte to high-density lipoprotein cholesterol ratio (MHR) and variability of heart rate among patients with coronary heart disease (CHD). METHODS: 120 patients with CHD and 120 healthy individuals were respectively selected as the observation group and the control group. Allelic and genotypic differences of -429T>C, 1704G>T, 82G>S, MHR ratio and heart rate variability between the two groups and patients with different severity were analyzed. The correlation between their genotypes and MHR ratio and heart rate variability was analyzed. RESULTS: The 82G>S polymorphism of the RAGE gene and the allelic difference between the two groups and patients with different severity were statistically significant (P< 0.05). Compared with the control group and patients with mild to moderate phenotype, monocyte, total cholesterol, triglyceride, low density lipoprotein, MHR, low frequency in the observation group and patients with severe symptoms were significantly higher, while their high density lipoprotein, standard deviation of NN intervals (SDNN), standard deviation average of NN intervals (SDANN), root mean square successive differences, percentage of differences exceeding 50ms between adjacent normal number of intervals (PMN50), high frequency (HF) were significantly lower. The gene frequencies of G-Gly-T, T-Gly-T, G-Ser-T and G-Gly-C were correlated with SDNN, SDANN, rMSSD, PMN50, HF and MHR, but negatively correlated with low frequency. CONCLUSION: Polymorphisms of the RAGE gene in patients with coronary heart disease are associated with the MHR ratio and heart rate variability, which can be used as markers for the diagnosis and efficacy evaluation.

miR-188-5p inhibits apoptosis of neuronal cells during oxygen-glucose deprivation (OGD)-induced stroke by suppressing PTEN.

The miRNAs and mRNAs are found to play a crucial role in modulating different diseases including stroke, according to the recent evidence. The current study is aimed at assessing the functional role played by miR-188-5p in the regulation of cell apoptosis and viability in OGD-induced human neural cell line HNC. With the help of RT-qPCR, the authors determined miR-188-5p as well as its putative target PTEN among OGD-treated cells in different treatment times. The cell viability was assessed through CCK-8 assay while the cell transfection either upregulated or may have silenced the genes. Both Western Blot as well as RT-qPCR found the proliferation biomarkers such as Ki87 and PCNA in addition to apoptosis biomarkers such as caspase-8 and caspase-3. The luciferase activity was tracked by conducting luciferase assay. The researchers observed an elevation in the expression of miR-188-5p while the PTEN got downregulated in Human Neural Cell line HNC with increase in the time span. The expressions of miR-188-5p and PTEN got increased with increasing OGD treatment time while the Luciferase reassured the binding site. The cell viability was suppressed by the overexpression of miR-188-5p which further inhibited the apoptosis biomarkers too. Meanwhile, it was understood that the results could be reversed to some extent with the inhibition of PTEN. The study findings from in vitro investigations yielded promising results and provided excellent insights about the fundamental molecular mechanisms of miR-188-5p involved in stroke via PTEN. This could be considered as a potential therapeutic axis among stroke patients in the near future.

Photo-excited carrier relaxation dynamics in two-dimensional InSe flakes.

Carrier relaxation dynamics of InSe flakes is investigated by using time-resolved pump-probe reflectivity measurement. The photocarriers associated with the P xy orbital band-edge transition at 2.40 eV, which is coupled to the in-plane polarized light, is observed to possess a lifetime of ∼19 ps at room temperature and ∼99 ps at 10 K. The temperature and power dependent carrier lifetime suggests that Shockley-Read-Hall process is the dominant nonradiative recombination mechanism responsible for the carrier relaxation. In addition, the electron scattering with a 14.5 meV optical phonon plays an active role in the carrier relaxation with increasing temperatures. A broad absorption around 1.65-1.90 eV is observed. The photocarriers associated with this broad transition show a long lifetime of ∼200 ps that is nearly independent of temperature and photon energy. This is indicative of bound carriers by defects. Our experimental results provide essential information for the characteristics of carrier dynamics and defects in InSe flakes. The experimental findings are fundamentally important for further development of microelectronics and optoelectronics based on InSe.

Kidney dysfunction is associated with risk of cardiovascular events in middle-aged and elderly population with hypertension: A 5-year community-based cohort study in China
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AIM: To evaluate the association between kidney dysfunction and cardiovascular disease (CVD) events in a middle-aged and elderly population in China. MATERIALS AND METHODS: In July 2009, a baseline survey of health status was performed in adults aged 55 years and older from Beijing, China. Occurrence of CVD events and mortality in subjects free of CVD at baseline was recorded in a 5-year follow-up period until December 2014. The association of mild (eGFRCKD-EPI 45 - 59 mL/min/1.73m2) and moderate to severe (eGFRCKD-EPI < 45 mL/min/1.73m2) kidney dysfunction with adverse outcomes were analyzed with Cox regression analysis. RESULTS: A total of 1,257 subjects were included in the final analysis. The risk of CVD events in those with mild kidney dysfunction increased by 65% (HR: 1.65, 95% CI: 1.04 - 2.62) as compared to those with normal kidney function. Subjects with both hypertension and CKD experienced more significantly increased risk of CVD events (adjusted HR = 1.87, 95% CI 1.17 - 2.97) and stroke (adjusted HR = 2.24, 95% CI 1.24 - 4.04). Pulse pressure (PP) ≥ 60 mmHg was the strongest risk factor for stroke in patients with CKD, with the adjusted HR value of 1.98 (95% CI 1.08 - 3.64). CONCLUSION: Moderate to severe kidney dysfunction was an independent risk predictor of CVD events. Among subjects with hypertension or poorly controlled blood pressure level, the presence of CKD significantly increased the risks of CVD events and stroke.

Dynamic Cerebral Autoregulation in Preclinical Atherosclerotic Cardiovascular Disease.

OBJECTIVE: The influence of atherosclerotic cardiovascular disease (ASCVD) on cerebral blood flow control is not well known. The aim of this study was to investigate the association between cardiovascular function and dynamic cerebral autoregulation (dCA) in patients with preclinical ASCVD. METHODS: A total of 44 participants aged 26-76 years were divided into low- and high-risk groups according to the China assessment of ASCVD risk. The cardiac function was assessed by echocardiography. The beat-to-beat blood pressure and cerebral blood flow velocity were measured at rest. Spectral and transfer function analyses were used to calculate cerebral and systemic hemodynamic variability and to estimate dCA metrics. RESULTS: There were no group differences in beat-to-beat heart rate, blood pressure, and cerebral blood flow velocity variability nor the ejection fraction, E/A and E'/A'. The dCA phase at very low frequency was reduced in the high-risk group (P = .03). Moreover, the dCA phase and E'/A' were negatively correlated with age, and dCA phase was positively correlated with E'/A' within the high-risk group (r2 = .517, P < .01). CONCLUSIONS: These findings suggest that advancing age, particularly in the high-risk ASCVD group, impairs cerebral blood flow control and cardiac diastolic function which are correlated with each other and may interplay under the effects of ASCVD risk factors.

LncRNA MALAT1 protects cardiomyocytes from isoproterenol-induced apoptosis through sponging miR-558 to enhance ULK1-mediated protective autophagy.

Investigating the molecular mechanisms of myocardial infarction (MI) and subsequent heart failure have gained considerable attention worldwide. Long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been previously demonstrated to regulate the proliferation and metastasis of several tumors. However, little is known about the effects of MALAT1 in MI and in regulating the cell date after MI. In our study, first, it was shown that the expression levels of MALAT1 were increased in the MI samples compared with normal tissues using quantitative reverse-transcription polymerase chain reaction. Then, MALAT1 knockdown could significantly decrease the cell viability and increase the apoptotic rates in isoproterenol (ISO)-treated H9C2 cells. In addition, we screened the possible target and found that miR-558 is its direct target using dual luciferase reporter assay, indicating that MALAT1 functioned as decoys sponging miR-558. Transfection of miR-558 mimic decreased the cell viability and enhanced the apoptosis. Furthermore, we revealed that miR-558 could downregulate ULK1 expression and suppressed ISO-induced protective autophagy. Activation of MALAT1/miR-558/ULK1 pathway protected H9C2 cells from ISO-induced mitochondria-dependent apoptosis. Finally, we used MALAT1-knockout mice to further demonstrated that MALAT1 protected cardiomyocytes from apoptosis and partially improved the cardiac functions upon ISO treatment. In conclusion, we elucidated that lncRNA MALAT1 protected cardiomyocytes from ISO-induced apoptosis by sponging miR-558 thus promoting ULK1-dependent autophagy. Targeting lncRNA MALAT1 might become a potential strategy in protecting cardiomyocytes during MI.

Metabolic syndrome and risks of carotid atherosclerosis and cardiovascular events in community-based older adults in China.

BACKGROUND AND OBJECTIVES: Previous studies on the importance of metabolic syndrome (MS) as a cardiovascular risk factor had not focused on older Chinese adults. The present study analyzed the association of MS with carotid atherosclerosis and the risk of cardiovascular events in Chinese adults. METHODS AND STUDY DESIGN: Data of a representative cohort study with 5-year follow-up were used. Community-dwelling people (n=1257) aged ≥55 years without cardiovascular disease (CVD) at baseline were followed up from 2009 to 2014. MS was defined based on the Chinese Diabetes Society criteria under the Chinese Medical Association. Multiple regression analyses were performed to examine the associations of MS with atherosclerosis and CVD events, with adjustment for confounding factors. RESULTS: In a multivariate logistic regression model with adjustment, MS was closely related to common carotid artery intima-media thickness (CCA-IMT) (1.62; 95% CI: 1.19-2.21) and carotid plaque presence (1.38; 95% CI: 1.01-1.89), but not with carotid artery stenosis. At the end of the 5-year follow- up, compared with subjects without MS, hazard ratios and 95% confidence intervals for the different risks in subjects with MS were 1.86 (1.02-3.29) for myocardial infarction (MI), 1.39 (1.01-2.05) for stroke, 1.52 (1.02- 2.37) for CVD death, and 1.13 (0.62-2.58) for total death, after adjusting for age, gender, smoking, drinking, physical activity, uric acid, high-sensitivity C-reactive protein, dietary factors and carotid atherosclerosis status. CONCLUSIONS: MS was significantly associated with IMT and the presence of carotid plaque and with positively increased risks of MI, stroke, and CVD mortality independent of CVD risk factors in older Chinese adults.

Utility of dominant epitopes derived from cell-wall protein LppZ for immunodiagnostic of pulmonary tuberculosis.

BACKGROUND: Serological antibodies tests for tuberculosis (TB) are widely used in developing countries. They appear to have some advantages- faster, simple and could be used for extrapulmonary TB. However, most of current commercial TB serological tests are failed to provide sufficient sensitivity and specificity. Improved serological biomarkers were essential. In this study, we present an approach using peptide array to discover new immunodiagnostic biomarkers based on immunodominant epitopes of TB antigens. RESULTS: The Probable conserved lipoprotein LppZ, which is difficult to express and purify in vivo was selected as the model antigen. We use two-step screening for dominant epitope selection. Based on peptide array data from 170 TB patients and 41 control samples, two dominant epitopes were identified to have diagnostic value for TB patients. Truncation assay was used to identify the core reactive sequence. Peptide- based ELISA was used to evaluate the diagnostic ability of pep-LppZ-1 and pep-LppZ-13. Pep-LppZ-1 has a sensitivity of 49.2% and a specificity of 83.3% in TB diagnose. Pep-LppZ-13 has a sensitivity of 43.3% and a specificity of 88.5% in TB diagnose. CONCLUSIONS: Our result demonstrated that peptide array screening would be an advantage strategy of screening TB diagnostic peptides.

Genetic mapping and validation of the loci controlling 7S α' and 11S A-type storage protein subunits in soybean [Glycine max (L.) Merr.].

KEY MESSAGE: Four soybean storage protein subunit QTLs were mapped using bulked segregant analysis and an F2 population, which were validated with an F5 RIL population. The storage protein globulins ß-conglycinin (7S subunit) and glycinin (11S subunits) can affect the quantity and quality of proteins found in soybean seeds and account for more than 70% of the total soybean protein. Manipulating the storage protein subunits to enhance soymeal nutrition and for desirable tofu manufacturing characteristics are two end-use quality goals in soybean breeding programs. To aid in developing soybean cultivars with desired seed composition, an F2 mapping population (n = 448) and an F5 RIL population (n = 180) were developed by crossing high protein cultivar 'Harovinton' with the breeding line SQ97-0263_3-1a, which lacks the 7S α', 11S A1, 11S A2, 11S A3 and 11S A4 subunits. The storage protein composition of each individual in the F2 and F5 populations were profiled using SDS-PAGE. Based on the presence/absence of the subunits, genomic DNA bulks were formed among the F2 plants to identify genomic regions controlling the 7S α' and 11S protein subunits. By utilizing polymorphic SNPs between the bulks characterized with Illumina SoySNP50K iSelect BeadChips at targeted genomic regions, KASP assays were designed and used to map QTLs causing the loss of the subunits. Soybean storage protein QTLs were identified on Chromosome 3 (11S A1), Chromosome 10 (7S α' and 11S A4), and Chromosome 13 (11S A3), which were also validated in the F5 RIL population. The results of this research could allow for the deployment of marker-assisted selection for desired storage protein subunits by screening breeding populations using the SNPs linked with the subunits of interest.

Implications of a school outbreak of multidrug-resistant tuberculosis in Northern China.

In this study, we identified a multidrug-resistant tuberculosis (MDR-TB) outbreak in a high school in northern China. The aim of this work was to describe TB transmission, drug resistance and treatment outcomes for this patient cluster. In January 2017, pulmonary TB was identified in a 17-year-old boy in northern China. Subsequently, a total of 11 TB cases were identified during 6-month follow-up of attendees of the same school. Of five students with latent TB infection (LTBI) receiving isoniazid preventive therapy (IPT), two pulmonary TB cases (40.0%) emerged in March and April, for an active case rate not significantly different from that of the non-IPT group (4/16, 25.0%, P = 0.598). All TB patients were first treated with a standardised first-line treatment regimen administered by the local TB hospital, with 11 of 12 active TB patients exhibiting poor treatment outcomes. Further data demonstrated that all nine patient isolates collected during this outbreak were MDR-TB and shared a common genotypic profile. In conclusion, our data demonstrate that diagnostic delay for the index MDR-TB case of this outbreak played a primary role in transmission of MDR-TB infection within a school setting. Importantly, IPT failed to prevent progression of MDR-TB from LTBI to active TB.