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Abstract Vascular smooth muscle cells (VSMCs) are the major contributor to vascular repair and remodeling, which showed high level of phenotypic plasticity. Abnormalities in VSMC plasticity can lead to multiple cardiovascular diseases, wherein alternative splicing plays important roles. However, alternative splicing variants in VSMC plasticity are not fully understood. Here we systematically characterized the long-read transcriptome and their dysregulation in human aortic smooth muscle cells (HASMCs) by employing the Oxford Nanopore Technologies long-read RNA sequencing in HASMCs that are separately treated with platelet-derived growth factor, transforming growth factor, and hsa-miR-221-3P transfection. Our analysis reveals frequent alternative splicing events and thousands of unannotated transcripts generated from alternative splicing. HASMCs treated with different factors exhibit distinct transcriptional reprogramming modulated by alternative splicing. We also found that unannotated transcripts produce different open reading frames compared to the annotated transcripts. Finally, we experimentally validated the unannotated transcript derived from gene CISD1, namely CISD1-u, which plays a role in the phenotypic switch of HASMCs. Our study characterizes the phenotypic modulation of HASMCs from an insight of long-read transcriptome, which would promote the understanding and the manipulation of HASMC plasticity in cardiovascular diseases.

Abstract It has been demonstrated that lactate/albumin (L/A) ratio is substantially relevant to the prognosis of sepsis, septic shock, and heart failure. However, there is still debate regarding the connection between the L/A ratio and severe acute myocardial infarction (AMI). The aim of this study is to determine the prognostic role of L/A ratio in patients with severe AMI. Our retrospective study extracted data from the Medical Information Mart for Intensive Care III (MIMIC-III) database, included 1,134 patients diagnosed with AMI. Based on the tertiles of L/A ratio, the patients were divided into three groups: Tertile1 (T1) group (L/A ratio0.6667, n =376). Uni- and multivariate COX regression model were used to analyze the relationship between L/A ratio and 14-day, 28-day and 90-day all-cause mortality. Meanwhile, the restricted cubic spline (RCS) model was used to evaluate the effect of L/A ratio as a continuous variable. Higher mortality was observed in AMI patients with higher L/A ratio. Multivariate Cox proportional risk model validated the independent association of L/A ratio with 14-day all-cause mortality [hazard ratio (HR) 1.813, 95% confidence interval (CI) 1.041-3.156 (T3 vs T1 group)], 28-day all-cause mortality [HR 1.725, 95% CI 1.035-2.874 (T2 vs T1 group), HR 1.991, 95% CI 1.214-3.266 (T3 vs T1 group)], as well as 90-day all-cause mortality [HR 1.934, 95% CI 1.176-3.183 (T2 vs T1 group), HR 2.307, 95% CI 1.426-3.733 (T3 vs T1 group)]. There was a consistent trend in subgroup analysis. The Kaplan-Meier (K-M) survival curves indicated that patients with L/A ratio>0.6667 had the highest mortality. Even after adjusting the confounding factors, RCS curves revealed a nearly linearity between L/A ratio and 14-day, 28-day and 90-day all-cause mortality. Meanwhile, the areas under the receiver operating characteristic (ROC) curve (AUC) of 14-day, 28-day and 90-day all-cause mortality were 0.730, 0.725 and 0.730, respectively. L/A ratio was significantly associated with 14-day, 28-day and 90-day all-cause mortality in critical patients with AMI. Higher L/A ratio will be considered an independent risk factor for higher mortality in AMI patients.

ABSTRACT Fusarium sacchari is one of the primary pathogens causing pokkah boeng disease in sugarcane in China. Common fungal extracellular membrane (CFEM) domain-containing proteins only exist in fungi and play a significant role in the interaction of pathogens and plants. However, the CFEM proteins in F. sacchari were not identified and functionally resolved. Of the 20 FsCFEM proteins identified from the genome of F. sacchari, 16 FsCFEM genes were cloned, while 4 FsCFEM proteins (Fs06761, Fs08184, Fs10706, and Fs13617) were identified as effector proteins that could suppress the programmed cell death triggered by BCL2-associated X protein in Nicotiana benthamiana. Subcellular localization analysis revealed that these four effectors could enter plant cells and are mainly located in the cell membrane and nucleus. By the yeast YTK12 secretion system, the signal peptides of four CFEM proteins were functionally verified. The expression levels of these four effector proteins were significantly increased in the F. sacchari-infected sugarcane plants. Through fungal gene knockout, three genes (Fs06761, Fs08184, and Fs13617) were found to be important pathogenic factors for pathogens. Our results support that the FsCFEM effector proteins were virulence effectors and might be involved in regulating plant immunity. IMPORTANCE Common fungal extracellular membrane (CFEM) domain-containing protein has long been considered an essential effector, playing a crucial role in the interaction of pathogens and plant. Strategies aimed at understanding the pathogenicity mechanism of F. sacchari are eagerly anticipated to ultimately end the spread of pokkah boeng disease. Twenty FsCFEM proteins in the genome of F. sacchari have been identified, and four FsCFEM effector proteins have been found to suppress BCL2-associated X protein-triggered programmed cell death in N. benthamiana. These four effector proteins have the ability to enter plant cells and inhibit plant immunity. Furthermore, the expression of these four FsCFEM effector proteins significantly increases during the infection stage, with the three of them playing an essential role in achieving full virulence. These study findings provide a direction toward further exploration of the immune response in sugarcane. By applying these discoveries, we can potentially control the spread of disease through techniques such as host-induced gene silencing.

A homeobox transcription factor is a conserved transcription factor, ubiquitous in eukaryotes, that regulates the tissue formation of structure, cell differentiation, proliferation, and cancer. This study identified the homeobox transcription factor family and its distribution in Phoma sorghina var. saccharum at the whole genome level. It elucidated the gene structures and evolutionary characteristics of this family. Additionally, knockout experiments were carried out and the preliminary function of these transcription factors was studied. Through bioinformatics approaches, nine homeobox transcription factors (PsHOX1–PsHOX9) were identified in P. sorghina var. saccharum, and these contained HOX-conserved domains and helix–turn–helix secondary structures. Nine homeobox gene deletion mutants were obtained using the homologous recombinant gene knockout technique. Protoplast transformation was mediated by polyethylene glycol (PEG) and the transformants were identified using PCR. The knockouts of PsHOX1, PsHOX2, PsHOX3, PsHOX4, PsHOX6, PsHOX8, and PsHOX9 genes resulted in a smaller growth diameter in P. sorghina var. saccharum. In contrast, the knockouts of the PsHOX3, PsHOX6, and PsHOX9 genes inhibited the formation of conidia and led to a significant decrease in the pathogenicity. This study’s results will provide insights for understanding the growth and development of P. sorghina var. saccharum. The pathogenic mechanism of the affected sugarcane will provide an essential theoretical basis for preventing and controlling sugarcane twisted leaf disease.

Abstract Low heart rate is a risk factor of mortality in many cardiovascular diseases. However, the relationship of minimum heart rate (MHR) with outcomes after cardiac surgery is still unclear, and the association between optimum MHR and risk of mortality in patients receiving cardiac surgery remains unknown. In this retrospective study using the Multi-parameter Intelligent Monitoring in Intensive Care (MIMIC-III) database, 8243 adult patients who underwent cardiac surgery were included. The association between MHR and the 30-day, 90-day, 180-day, and 1-year mortality of patients undergoing cardiac surgery was analyzed using multivariate Cox proportional hazard analysis. As a continuous variable, MHR was evaluated using restricted cubic regression splines, and appropriate cut-off points were determined. Kaplan–Meier curve was used to further explore the relationship between MHR and prognosis. Subgroup analyses were performed based on age, sex, hypertension, diabetes, and ethnicity. The rates of the 30-day, 90-day, 180-day, and 1-year mortalities of patients in the low MHR group were higher than those in the high MHR group (4.1% vs. 2.9%, P

ABSTRACT Fusarium sacchari is one of the primary pathogens causing Pokkah Boeng disease (PBD) in sugarcane in China. Pectate lyases (PL), which play a critical role in pectin degradation and fungal virulence, have been extensively studied in major bacterial and fungal pathogens of a wide range of plant species. However, only a few PLs have been functionally investigated. In this study, we analyzed the function of the pectate lyase gene, FsPL, from F. sacchari. FsPL is a key virulence factor of F. sacchari and can induce plant cell death. FsPL also triggers the pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) response in Nicotiana benthamiana, as reflected by increases in reactive oxygen species (ROS) production, electrolyte leakage, and callose accumulation, as well as the upregulation of defense response genes. In addition, our study also found that the signal peptide of FsPL was necessary for induced cell death and PTI responses. Virus-induced gene silencing showed that FsPL-induced cell death in Nicotiana benthamiana was mediated by leucine-rich repeat (LRR) receptor-like kinases BAK1 and SOBIR1. Thus, FsPL may not only be a critical virulence factor for F. sacchari but may also induce plant defense responses. These findings provide new insights into the functions of pectate lyase in host-pathogen interactions. IMPORTANCE Pokkah Boeng disease (PBD) is one of the main diseases affecting sugarcane in China, seriously damaging sugarcane production and economic development. Therefore, it is important to clarify the pathogenic mechanisms of this disease and to provide a theoretical basis for the breeding of PBD-resistant sugarcane strains. The present study aimed to analyze the function of FsPL, a recently identified pectate lyase gene from F. sacchari. FsPL is a key virulence factor of F. sacchari that induces plant cell death. Our results provide new insights into the function of pectate lyase in host-pathogen interactions.

This paper reports the detection of ferric ions (Fe ^3+ ) based on nitrogen and sulfur co-doped carbon quantum dots. These nitrogen and sulfur co-doped carbon quantum dots were synthesized via a hydrothermal route using northern Shaanxi potatoes as carbon sources and ammonium sulfate as nitrogen and sulfur sources. The quantum yields of the carbon quantum dots were found to be 16.96% and 4.23% with and without doping, respectively. The structural details, morphology, and optical properties of carbon quantum dots were analyzed using Fourier transform infrared spectroscopy (FT-IR), x-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), ultraviolet-visible absorption spectroscopy (UV–vis), and fluorescence spectroscopy. The as-prepared co-doped carbon quantum dots were utilized as a fluorescent probe for detecting Fe ^3+ ions, where the fluorescence intensity of carbon quantum dots was remarkably quenched in the presence of Fe ^3+ ions. A good linear relationship for Fe ^3+ ion detection was obtained from 0 to 500 μ mol/L with a detection limit as low as 0.26 μ mol/L. Furthermore, the proposed method also provided satisfactory results in the tap water.

Abstract Venous thromboembolism (VTE), clinically presenting as deep vein thrombosis (DVT) or pulmonary embolism (PE). Not all DVT patients carry the same risk of developing acute pulmonary embolism (APE). To develop and validate a prediction model to estimate risk of APE in DVT patients combined with past medical history, clinical symptoms, physical signs, and the sign of the electrocardiogram. We analyzed data from a retrospective cohort of patients who were diagnosed as symptomatic VTE from 2013 to 2018 (n = 1582). Among them, 122 patients were excluded. All enrolled patients confirmed by pulmonary angiography or computed tomography pulmonary angiography (CTPA) and compression venous ultrasonography. Using the LASSO and logistics regression, we derived a predictive model with 16 candidate variables to predict the risk of APE and completed internal validation. Overall, 52.9% patients had DVT + APE (773 vs 1460), 47.1% patients only had DVT (687 vs 1460). The APE risk prediction model included one pre-existing disease or condition (respiratory failure), one risk factors (infection), three symptoms (dyspnea, hemoptysis and syncope), five signs (skin cold clammy, tachycardia, diminished respiration, pulmonary rales and accentuation/splitting of P2), and six ECG indicators (SIQIIITIII, right axis deviation, left axis deviation, S1S2S3, T wave inversion and Q/q wave), of which all were positively associated with APE. The ROC curves of the model showed AUC of 0.79 (95% CI, 0.77–0.82) and 0.80 (95% CI, 0.76–0.84) in the training set and testing set. The model showed good predictive accuracy (calibration slope, 0.83 and Brier score, 0.18). Based on a retrospective single-center population study, we developed a novel prediction model to identify patients with different risks for APE in DVT patients, which may be useful for quickly estimating the probability of APE before obtaining definitive test results and speeding up emergency management processes.

IntroductionPlant-specific Class III peroxidases (PRXs) play a crucial role in lignification, cell elongation, seed germination, and biotic and abiotic stresses.MethodsThe class III peroxidase gene family in sugarcane were identified by bioinformatics methods and realtime fluorescence quantitative PCR.ResultsEighty-two PRX proteins were characterized with a conserved PRX domain as members of the class III PRX gene family in R570 STP. The ShPRX family genes were divided into six groups by the phylogenetic analysis of sugarcane, Saccharum spontaneum, sorghum, rice, and Arabidopsis thaliana. The analysis of promoter cis-acting elements revealed that most ShPRX family genes contained cis-acting regulatory elements involved in ABA, MeJA, light responsiveness, anaerobic induction, and drought inducibility. An evolutionary analysis indicated that ShPRXs was formed after Poaceae and Bromeliaceae diverged, and tandem duplication events played a critical role in the expansion of ShPRX genes of sugarcane. Purifying selection maintained the function of ShPRX proteins. SsPRX genes were differentially expressed in stems and leaves at different growth stages in S. spontaneum. However, ShPRX genes were differentially expressed in the SCMV-inoculated sugarcane plants. A qRT-PCR analysis showed that SCMV, Cd, and salt could specifically induce the expression of PRX genes of sugarcane.DiscussionThese results help elucidate the structure, evolution, and functions of the class III PRX gene family in sugarcane and provide ideas for the phytoremediation of Cd-contaminated soil and breeding new sugarcane varieties resistant to sugarcane mosaic disease, salt, and Cd stresses.

Abstract Objective Although the levels of plasma fibrinogen and albumin have been proven to be in relation to coronary heart disease (CHD), the association between fibrinogen-to-albumin ratio (FAR) and acute coronary syndrome (ACS) has not been adequately investigated. The aim of this study is to investigate the relationship between FAR and the presence and severity of CHD in patients with ACS. Methods and results A total of 1575 individuals who received coronary angiography (CAG) were enrolled. Patients were divided into the ACS group and the control group. The severity of ACS was determined by Gensini score, number of diseased coronary artery and the presence of myocardial infarction (MI). Data showed that the level of FAR in ACS group was higher than in the control group (81.20 ± 35.45 vs. 72.89 ± 20.24, P

BackgroundBase excess (BE) represents an increase or decrease of alkali reserves in plasma to diagnose acid-base disorders, independent of respiratory factors. Current findings about the prognostic value of BE on mortality of patients with acute myocardial infarction (AMI) are still unclear. The purpose of this study was to explore the prognostic significance of BE for short-term all-cause mortality in patients with AMI.MethodsA total of 2,465 patients diagnosed with AMI in the intensive care unit from the Medical Information Mart for Intensive Care III (MIMIC-III) database were included in our study, and we explored the association of BE with 28-day and 90-day all-cause mortality using Cox regression analysis. We also used restricted cubic splines (RCS) to evaluate the relationship between BE and hazard ratio (HR). The primary outcomes were 28-day and 90-day all-cause mortality.ResultsWhen stratified according to quantiles, low BE levels at admission were strongly associated with higher 28-day and 90-day all-cause mortality. Multivariable Cox proportional hazard models revealed that low BE was an independent risk factor of 28-day all-cause mortality [HR 4.158, 95% CI 3.203–5.398 (low vs. normal BE) and HR 1.354, 95% CI 0.896–2.049 (high vs. normal BE)] and 90-day all-cause mortality [HR 4.078, 95% CI 3.160–5.263 (low vs. normal BE) and HR 1.369, 95% CI 0.917–2.045 (high vs. normal BE)], even after adjustment for significant prognostic covariates. The results were also consistent in subgroup analysis. RCS revealed an “L-type” relationship between BE and 28-day and 90-day all-cause mortality, as well as adjusting for confounding variables. Meanwhile, Kaplan–Meier survival curves were stratified by combining BE with carbon dioxide partial pressure (PaCO2), and patients had the highest mortality in the group which had low BE (< 3.5 mEq/L) and high PaCO2 (> 45 mmHg) compared with other groups.ConclusionOur study revealed that low BE was significantly associated with 28-day and 90-day mortality in patients with AMI and indicated the value of stratifying the mortality risk of patients with AMI by BE.

Laser welding of lap-filet joints SUS301L austenitic stainless steel plates were carried out with filler wire. Results showed that the weld zone was composed of columnar austenite and a small amount of δ-ferrite. The effect of feed direction, wire distance (H), laser incident position (L) and laser incident angle on the wire melting mechanism, weld pool geometry, metal transfer modes and heat distribution were studied with the assistance of the high speed camera recording the welding process. Better weld quality was obtained under the circumstances of leading direction, wire distance 0.5 mm, laser incident position 0.5 mm, and laser incident angle 0̊. The fracture was always located in the weld where the thickness of it was the smallest. There was a linear relationship between the weld width and the smallest weld thickness. The maximum tensile-shear force was 24.46 kN. The fracture mode was ductile fracture with fracture surface dimples.

BackgroundProlonged QT intervals have been observed in pregnant women, which predispose them to a higher risk of potentially lethal ventricular arrhythmias. This study was designed to evaluate the prevalence of QTc prolongation in Chinese hospitalized parturient women with single and twin pregnancies, and to explore potential risk factors associated with QTc prolongation.MethodsThis retrospective study included 1,218 patients from a large Chinese population between January 2014 and October 2020. Data from parturient women with single and twin pregnancies without pre-pregnancy cardiac diseases were collected. QTc was corrected by the Fridericia formula [QTc = QT/RR(1/3)], and QTc ≥ 460 ms for females was defined as prolonged QTc, QTc ≥ 500 ms was defined as severely prolonged QTc. The prevalence and common risk factors of QTc prolongation during pregnancy were analyzed in this cohort. Uni- and multivariable logistic regression analysis were performed to identify clinical parameters associated with QTc prolongation in this population.ResultsThe prevalence of QTc prolongation was 48.19% among this population, 10.56% in single pregnancy, 89.44% in twin pregnancies. The prevalence of severely prolonged QTc was 23.48% among the total cohort, 0.49% in single pregnancy, and 46.47% in twin pregnancies. The mean QTc interval was significantly longer in twin pregnancies than in single pregnancy (498.65 ± 38.24 vs. 424.96 ± 27.67 ms, P < 0.001). Systolic blood pressure, diastolic blood pressure, total cholesterol, serum uric acid, gestational hypertension and twin pregnancies were associated with QTc prolongation in parturient women.ConclusionThis is the first study to assess the prevalence and risk factors of QTc prolongation between single and twin pregnancies. QTc prolongation is more prevalent, and QTc intervals are significantly longer in twin pregnancies as compared to single pregnancy.

The commercial application of genetically modified plants has been seriously impeded by public concern surrounding the potential risks posed by such plants to the ecosystem and human health. Previously, we have developed a ‘pollen- and seed-specific Gene Deletor’ system that automatically excised all transgenes from the pollen and seeds of greenhouse-grown transgenic Nicotiana tabacum. In this study, we conducted seven field experiments over three consecutive years to evaluate the stability of transgene excision under field conditions. Our results showed that transgenes were stably excised from transgenic Nicotiana tabacum under field conditions with 100% efficiency. The stability of transgene excision was confirmed based on PCR, as well as the GUS staining patterns of various organs (roots, leaves, petiole, stem, flower, fruit, and seeds) from transgenic N. tabacum. In six transgenic lines (D4, D10, D31, D56, and D43), the transgenes were stably deleted in the T0 and T1 generations. Thus, the ‘Gene Deletor’ system is an efficient and reliable method to reduce pollen- and seed-mediated unintentional gene flow. This system might help to alleviate the food safety concerns associated with transgenic crops.

Phoma sorghina var. saccharum is a fungal pathogen that causes sugarcane twisted leaf disease in China. Here, we report complete genome assemblies of the Phoma sorghina var. saccharum isolate BS2-1, generated using single-molecule real-time sequencing. We present a high-quality genome sequence of a Phoma isolate that was assembled into 22 contigs with an N50 length of 1.92 Mb, a total length of 33.12 Mb, and a GC content of 52.12%. A total of 7,870 genes were annotated, using a combination of gene prediction tools, including 281 noncoding RNAs, 515 genes encoding carbohydrate-active enzymes, 2,440 genes associated with pathogen-host interactions, and 583 genes encoding secreted proteins. The complete genome sequence will be useful for understanding host-pathogen interaction and for improving disease management strategies.

The ultra-wide band (UWB) radar sensor is useful in the field of mission critical sensors and sensor networks due to its short detection time, high penetration, and low energy consumption. To support critical missions such as search and rescue, this paper designs a non-contact detection system based on a UWB radar sensor module to obtain vital signs of human beings. There are noise and clutter due to non-contact detection, and therefore the coherent background noise removal and moving target display filter are applied. Then, the variational mode decomposition (VMD) algorithm is used to extract heartbeat signals and respiratory signals. In addition, the Hilbert transform is applied to heartbeat signals and respiratory signals to obtain the time-frequency information. The electrocardiogram is also employed to compare the results of the UWB radar sensor. We also detect the human target through-the-wall. It turns out that the system can obtain respiratory and heartbeat characteristics simultaneously in one measurement, saving cost with high accuracy.

One of the causative agents of pokkah boeng disease (PBD), which affects sugarcane crops globally, is the fungus Fusarium sacchari. These fungal infections reduce sugar quality and yield, resulting in severe economic losses. Effector proteins play important roles in the interactions between pathogenic fungi and plants. Here, we used bioinformatic prediction approaches to identify 316 candidate secreted effector proteins (CSEPs) in the complete genome of F. sacchari. In total, 95 CSEPs contained known conserved structures, representing 40 superfamilies and 18 domains, while an additional 91 CSEPs contained seven known motifs. Of the 130 CSEPs containing no known domains or motifs, 14 contained one of four novel motifs. A heterogeneous expression system in Nicotiana benthamiana was used to investigate the functions of 163 CSEPs. Seven CSEPs suppressed BAX-triggered programmed cell death in N. benthamiana, while four caused cell death in N. benthamiana. The expression profiles of these eleven CSEPs during F. sacchari infection suggested that they may be involved in sugarcane-F. sacchari interaction. Our results establish a basis for further studies of the role of effector molecules in pathogen–sugarcane interactions, and provide a framework for future predictions of pathogen effector molecules.

Abstract  The selectable marker system, which utilizes the pmi gene encoding for phosphomannose-isomerase that converts mannose-6-phosphate to fructose-6-phosphate, was adapted for Agrobacterium-mediated transformation of cucumber (Cucumis sativus L.). Only transformed cells were capable of utilizing mannose as a carbon source. The highest transformation frequency of 23% was obtained with 10 g/l mannose and 10 g/l sucrose in the medium. Molecular, genetic analysis, and PMI activity assay showed that the regenerated shoots contained the pmi gene and the gene was transmitted to the progeny in a Mendelian fashion. The results indicated that the mannose selection system, which is devoid of the disadvantages of antibiotic or herbicide selection, could be used for cucumber Agrobacterium-mediated transformation. [ABSTRACT FROM AUTHOR]