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Although music learners’ metacognition could regulate and improve their practice and performance, respectively, metacognitive measurement tools for music domains remain scarce. Hence, this study aimed to develop and validate a Metacognitive Questionnaire for Music Learning (MQML). Through item analysis, exploratory factor analysis (EFA), and confirmatory factor analysis (CFA), two rounds of research were conducted on 513 valid questionnaires to analyze the item discrimination, reliability, and validity of the questionnaire. This study developed a questionnaire consisting of two subscales, eight factors, and 35 items. The MQML was explored and validated with a Cronbach’s alpha value of 0.960 for the overall scale, subscale Cronbach’s alpha values were 0.914 and 0.947. An eight-factor metacognitive structural model was validated for the first time in the music field. Essentially, MQML could provide empirical data for music students’ metacognition strategies and expand the current body of literature on music cognition.

In this paper, the total eclipsing binary WISE J185503.7+592234 (hereinafter J185503), whose mass ratio is around the mass ratio limit, was observed and investigated for the first time. The stellar atmospheric parameters of the primary (more massive) component were calculated by the spectral fitting, and the following results are obtained: Teff = 5747 ± 25 K, [Fe/H] = −0.16 ± 0.04 dex, logg = 4.78 ± 0.05 cm s−2. Although J185503 has a very small amplitude (∼ 0.17 mag in V band) and a short period (0.2800782 d), its light curves exhibit total eclipses (eclipse duration: ∼ 40 min, which is about 0.1 phase). The light curves derived from TESS exhibit some unusual behaviour, such as inversion of the O’Connell effect, exchange of occultation, and transit depths. Photometric solutions obtained from the multiband observations suggest that J185503 has a particularly low mass ratio (q = 0.0514) and a moderate contact degree of $26{{\ \rm per\ cent}}$. Based on 103 newly determined times of minimum spanning 14 yr, a secular period decrease was found, which is calculated to be dP/dt = −2.24 × 10−7 d yr−1. Through analysing the instability criterion, such as the instability separation, the instability mass ratio, and the ratio of spin angular momentum (Jspin) to the orbital angular momentum (Jorb), J185503 can be regarded as a progenitor of luminous red novae.

This paper takes the music class of Fuzhou Preschool Normal College, Jiangxi Province, China as a case study to analyze the different attitudes of students to the traditional Chinese opera—Fuzhou tea-picking opera which has been introduced into the music class of the school, thus affecting the cultural inheritance effect. A total of 150 non-music major local college students were selected from three classes to carry out the music course inheritance practice for four months in Fuzhou Preschool Normal College. This study was divided into three stages, (a) student assessment, (b) teaching the lesson, (c) feedback and assessment. The aim of this study was to study the perceptions of students from Fuzhou Preschool Normal College, Jiangxi Province, China towards the art from of Fuzhou tea-picking opera, and to explore the factors affecting the learning attitudes of these students. Mixed-methods design was employed within the study. The study found that the implementation of the course significantly improved students’ positive attitude towards Fuzhou tea-picking opera. The implementation of the course played a positive role in promoting the inheritance of the tea-picking opera. Although this is a study on the inheritance of traditional Chinese music course, the ideas of course design and research results are applicable to other traditional Chinese music, and even to other countries which have needs for the inheritance of traditional music.

Protonation, Fe2+ and solvent can induce different acidic structures and Lewis activity of Fe-IL by analyzing the slope of IA(X) ∼ n(Py).

The oxidation activity and solvation effect of iron-based ionic liquid (BmimFeCl4) are significantly affected by the structure and polarity of the added solvents.

The present study was designed to explore the potential regulatory mechanism between mitophagy and pyroptosis during sepsis-associated acute lung injury (ALI).In vitro or in vivo models of sepsis-associated ALI were established by administering lipopolysaccharide (LPS) or performing caecal ligation and puncture (CLP) surgery. Pyroptosis levels were detected by electron microscopy, immunofluorescence, flow cytometry, western blotting and immunohistochemistry. Dual-luciferase reporter gene assay was applied to verify the targeting relationship between miR-138-5p and NLRP3. Methylation-specific PCR and chromatin immunoprecipitation assays were used to determine methylation of the miR-138-5p promoter. Mitophagy levels were examined by transmission electron microscopy and western blotting.NLRP3 inflammasome silencing alleviated alveolar macrophage (AM) pyroptosis and septic lung injury. In addition, we confirmed the direct targeting relationship between miR-138-5p and NLRP3. Overexpressed miR-138-5p alleviated AM pyroptosis and the pulmonary inflammatory response. Moreover, the decreased expression of miR-138-5p was confirmed to depend on promoter methylation, while inhibition of miR-138-5p promoter methylation attenuated AM pyroptosis and pulmonary inflammation. Here, we discovered that an increased cytoplasmic mtDNA content in sepsis-induced ALI models induced the methylation of the miR-138-5p promoter, thereby decreasing miR-138-5p expression, which may activate the NLRP3 inflammasome and trigger AM pyroptosis. Mitophagy, a form of selective autophagy that clears damaged mitochondria, reduced cytoplasmic mtDNA levels. Furthermore, enhanced mitophagy might suppress miR-138-5p promoter methylation and relieve the pulmonary inflammatory response, changes that were reversed by treatment with isolated mtDNA.In summary, our study indicated that mitophagy induced the demethylation of the miR-138-5p promoter, which may subsequently inhibit NLRP3 inflammasome, AM pyroptosis and inflammation in sepsis-induced lung injury. These findings may provide a promising therapeutic target for sepsis-associated ALI.

Inflammatory bowel disease (IBD) is not only a chronic inflammatory disorder of the gastrointestinal tract but also accompanied by systemic inflammation. The onset of hypertension is closely related to systemic inflammation. However, the relationship between IBD and hypertension has not been investigated. We aimed to investigate the potential association between IBD and the incidence of hypertension.We retrieved IBD onset and the incidence of hypertension from a public database UK Biobank. The association between the onset of IBD and subsequent incidence of hypertension was analyzed using a multivariate Cox regression analysis, and propensity score matching was performed for sensitivity analysis.Of a total of 281,064 participants included in the study, 2376 (0.8%) were diagnosed with IBD at baseline, and 20,129 (7.2%) in the whole cohort developed hypertension with a median follow-up duration of 8.1 years (interquartile range [IQR] 7.3-8.8 years). Patients with IBD had a higher cumulative risk of hypertension compared with general population (10.9% in ulcerative colitis [UC], 7.7% in Crohn's disease [CD], and 9.3% in IBD unclassified [IBD-U] vs. 7.1% in non-IBD, p 0.001). Multivariate Cox regression analysis identified that UC, rather than CD or IBD-U, was independently associated with subsequent occurrence of hypertension (HR 1.30, 95% CI: 1.11-1.52, p = 0.001). In propensity matching analysis, UC also showed its robustness as a risk factor for the prediction of hypertension (HR 1.56, 95% CI: 1.21-2.03, p = 0.001).In IBD patients, UC rather than CD is associated with a higher risk for the incidence of hypertension compared with general population. Close monitoring of hypertension might be required in clinical practice.

The aim of this study was to examine the independent and joint associations of baseline coronary artery calcium score (CACS) and cystatin C (Cys-C) with the risk of major adverse cardiac and cerebrovascular events (MACCEs) and all-cause death in symptomatic populations.The study included 7140 patients with symptom of chest pain who underwent cardiac computerized tomography examinations to measure CACS. All of them had serum Cys-C results. Endpoints were set for MACCEs and all-cause death events.A total of 7140 participants were followed for a median of 1106 days. A total of 305 patients had experienced MACCEs and 191 patients had experienced all-cause death. CACS ≥ 100 and Cys-C ≥ 0.995 mg/L were independently associated with an increased risk of MACCEs (adjusted hazard ratio [HR]: 1.46; 95% confidence interval [CI]: 1.15-1.85; p = .002 and adjusted HR: 1.57; 95% CI: 1.24-2.00; p .001, respectively). Compared with CACS 100 and Cys-C 0.995 mg/L patients, CACS ≥ 100 and Cys-C ≥ 0.995 mg/L patients had the highest risk of MACCEs and all-cause death (adjusted HR: 2.33; 95% CI: 1.64-3.29; p .001 and adjusted HR: 2.85; 95% CI: 1.79-4.55; p .001, respectively). Even in patients with CACS 100, Cys-C ≥ 0.995 mg/L was also associated with a higher risk of MACCEs and all-cause death than Cys-C 0.995 mg/L (adjusted HR: 1.76; p = .003 and adjusted HR: 2.02; p = .007, respectively).The combined stratification of CACS and Cys-C showed an incremental risk of MACCEs and all-cause death, reflecting complementary prognostic value. Our results support the combination of the two indicators for risk stratification and event prediction.

Within the field of TESOL, language teacher identity (LTI) has been the focus of a myriad of studies in the previous two decades. Researchers need to trace back in order to move forward, it is an essential step towards a comprehensive understanding of what has been done in LTI research. This review article provides an overall literature review on conceptual approaches of how identity is defined and perceived in the context of recent history. It is then followed by an analysis of dominant trends on recent studies of Language Teacher Identity to profile what, why, when, and who constitute seminal works in LTI research by tracing scholarly literature from 1975 to the present. A dataset retrieved and analyzed from Scopus was further correlated using Vantage Point software. The findings not only revealed the conceptual approaches, dominant trends, and methodological development in LTI research, but also identified the underexplored areas in transnational teacher identities, teacher educator identities, and online teacher identities, which provided implications for future LTI research directions.

Endothelial apoptosis is the core pathological change in atherosclerotic cardiovascular disease, including coronary artery disease (CAD). Determining the molecular mechanisms underlying endothelial apoptosis is important. Nuclear factor kappa B (NF-κB) is a crucial transcription factor for controlling apoptosis. Our previous study demonstrated that the -94 ATTG ins/del mutant in the promoter of NFKB1 gene (rs28362491) is a risk factor for CAD. In the present study, we found that NFKB1 rs28362491 polymorphism was positively associated with increased major adverse cardiac and cerebrovascular events (MACCEs) in CAD patients. After adjusting for confounding factors including age, smoking, hypertension, glucose, and low-density lipoprotein cholesterol, the mutant DD genotype was an independent predictor of MACCEs ( OR = 2.578 , 95 % CI = 1.64 –4.05, P = 0.003 ). The in vitro study showed that mutant human umbilical vein endothelial cells (DD-mutant HUVECs) were more susceptible to high-glucose/palmitate-induced apoptosis, which was accompanied by decreased p50 expression and increased expression of cleaved caspase-3, Cytochrome c, and phospho-p65 ( P < 0.05 ). The mitochondrial membrane potential was significantly lower, while increasing levels of mtROS and more opening of the mPTP were observed in DD-mutant HUVECs ( P < 0.05 ). Furthermore, the percentage of cells with fragmented or spherical mitochondria was significantly higher in DD-mutant HUVECs than in wild-type cells (genotype II HUVECs) ( P < 0.05 ). In addition, after stimulation with high glucose/palmitate, the NFKB1 gene mutant significantly increased the expression of Drp1, which indicated that the NFKB1 gene mutant affected the expression of mitochondrial morphology-related proteins, leading to excessive mitochondrial fission. In conclusion, the mutant DD genotype of the NFKB1 gene was an independent predictor of worse long-term prognosis for CAD patients. DD-mutant HUVECs exhibited abnormal activation of the NF-κB pathway and increased Drp1 expression, which caused excessive mitochondrial fission and dysfunction, ultimately leading to increased apoptosis.

There are growing concerns that body mass index (BMI) is related to cancer risk at various anatomical sites, including the upper gastrointestinal tract, and the existence of a causal relationship remains unclear. The Mendelian randomization (MR) method uses instrumental genetic variables of risk factors to explore whether a causal relationship exists while preventing confounding. In our study, genome-wide association study (GWAS) data from the BioBank Japan (BBJ) project were used. Genetic variants were chosen as instrumental variables using inverse-variance weighting (IVW), MR-Egger regression and weighted-median methods to estimate the causal relationship between BMI and the risk of gastro-esophageal cancer. We found no evidence to support a causal association between BMI and risk of gastric cancer [odds ratio (OR) =0.99 per standard deviation (SD) increase in BMI; 95% confidence interval (CI): (0.76-1.30)

Salbutamol bronchodilator response (BDR) test and fractional exhaled nitric oxide (FeNO) have been recommended for the diagnosis of asthma in children, but FeNO levels is affected by many factors. Nonetheless, data of the effect on the FeNO values throughout the bronchodilator test and the differences in FeNO values between BDR positive (BDR+) and negative (BDR-) children with asthma are still limited. We aimed to evaluate the effect of the BDR test on FeNO and the differences in FeNO levels between BDR+ and BDR- children with asthma.This was a prospective, observational study performed over a 5-month period (December 2018 to April 2019) and involved 57 children with asthma. The FeNO levels at pre-spirometry, post-spirometry, and post-salbutamol BDR testing were estimated. Finally, the children were divided into two groups i.e., BDR+ and BDR-, and differences in the FeNO levels were compared between the two groups.The spirometry results were normal in 2 patients (3.5%). There were 53 (93%) patients with obstructive lung disease, including 40 (70.2%), 11 (19.3%), and 2 (3.5%) patients with mild, moderate, and severe obstruction, respectively. The remaining two patients had mixed lesions (3.5%), none of which were restrictive. The baseline median FeNO levels were significantly higher in the BDR+ group than in the BDR- group [33.00 (23.78, 46.73)This study revealed dynamic changes in the FeNO levels during the BDR test. The use of a bronchodilator results in a statistically significant difference in FeNO levels between BDR+ and BDR- children with asthma. Moreover, spirometry leads to a marked decrease in the FeNO levels. Our results will allow clinicians to better interpret FeNO, BDR and pulmonary function outcomes and better develop clinical protocols.

The treatment effect of myofunctional appliance therapy has remained debated. The aim of this study was to evaluate the skeletal and dentoalveolar effects in class II division I pediatric patients receiving Education Fonctionnelle (EF) myofunctional appliance therapy.Thirteen patients undergoing EF appliance treatment (9 boys and 4 girls；average 9.3years old) met the inclusion criteria and 13 untreated patients (9 boys and 4 girls；average 9.9 years old) served as controls. Initial and one-year follow-up lateral cephalometric measurement was used to assess skeletal and dentoalveolar changes. Gender ratio was analyzed using Chi-square test. Age and cephalometric measurement changes within and between the two groups were analyzed using Mann-Whitney U test and Wilcoxon signed rank test and Benjamini - Hochberg procedure.There were no significant differences in age, gender ratio, and initial cephalometric measurement data between the two groups. One-year follow-up skeletal findings revealed no significant differences between the two groups. Regarding the dentoalveolar changes, only the values of the upper incisor angle related parameters revealed significances between the two group (with adjusted p value).In this preliminary small sample size study, the EF group demonstrated significant upper incisor angle decrease, lower incisor angle increase, and lower incisor tip to mandibular plane distance decrease in comparison to the values measured in the control group. However, only the upper incisor angle changes were statistically significant after p-value adjustment. The skeletal effect of the EF appliance could not be verified in one-year follow-up of cephalometric data.

In a large multisite cohort of Veterans who underwent Roux-en-Y gastric bypass (RYGB) or laparoscopic sleeve gastrectomy (LSG), initiation of (ie, incident) and persistence of (ie, continuation of preoperative) depression treatment are compared with matched nonsurgical controls.Bariatric surgery has been associated with short-term improvements in depression but less is known about longer term outcomes.In a retrospective cohort study, we matched 1713 Veterans with depression treatment who underwent bariatric surgery in Veterans Administration bariatric centers from fiscal year 2001 to 2016 to 15,056 nonsurgical controls using sequential stratification and examined the persistence of depression treatment via generalized estimating equations. Incidence of depression treatment was compared using Cox regression models between 2227 surgical patients and 20,939 matched nonsurgical controls without depression treatment at baseline.In surgical patients with depression treatment at baseline, the use of postsurgical depression treatment declined over time for both surgical procedures, but postsurgical patients had greater use of depression treatment at 5 years [RYGB: odds ratio=1.24, 95% confidence interval (CI): 1.04-1.49; LSG: odds ratio=1.27, 95% CI: 1.04-1.56] compared with controls. Among those without depression treatment at baseline, bariatric surgery was associated with a higher incidence of depression treatment compared with matched controls (RYGB: hazard ratio=1.34, 95% CI: 1.17-1.53; LSG: hazard ratio at 1-5 years=1.27, 95% CI: 1.10-1.47).Bariatric surgery was associated with a greater risk of postoperative incident depression treatment and greater persistence of postoperative depression treatment. Depression may worsen for some patients after bariatric surgery, so clinicians should carefully monitor their patients for depression postoperatively.

Nutritional screening tools should be sensitive, simple, and easy to use. Differing opinions among clinicians concern the simplicity of the three tools-the Global Leadership Initiative on Malnutrition (GLIM) criteria, Nutritional Risk Screening 2002 (NRS-2002), and Patient-Generated Subjective Global Assessment (PG-SGA). For each tool, we estimated prediction of overall survival (OS) in tumor staging, sensitivity, and specificity. The NRS-2002 is favored by clinicians because it is simple to use. We compared its sensitivity and specificity with the GLIM and PG-SGA.This is an analysis of data from 1,358 adult colorectal cancer patients recruited in a multicenter from July 2013 to July 2018.In Kaplan-Meier models, each tool was found to be significantly predictive of OS: NRS-2002 (1.28), GLIM (1.49), and PG-SGA (1.42). Use of any tool improved prediction of survival at tumor staging. NRS-2002 has superior specificity (0.90) to diagnose patients without nutritional deficits (GLIM = 0.62 and PG-SGA = 0.82).This study provides evidence for the superiority of NRS-2002 to accurately identify colorectal cancer patients without nutritional limitations. Compared with the complexity of the other tools, NRS-2002 is the simplest tool to use in routine nutritional screening in busy clinical practice.

The problems of parallel two-sided assembly lines balancing (TALB) are nonpolynomial (NP-hard) problems that belong to the field of combinatorial optimization. In most cases, these problems can be resolved with algorithms. To this end, this research adopts colored Petri nets (CPN) and a minimal spanning tree (MST) to address the type I problems for two-sided assembly line balancing problem (TALBP). This research proposes a three-step method. In the first step, a reachability tree chart is built to show potential tasks order assignment. In the second step, the color firing mechanism is employed to determine if the colored conditions are satisfied. The final step uses a MST and a least-time prioritized rule to select the proper tasks for assignment efficiently. These steps will be performed repetitively until all the tasks are properly assigned. Since the whole assignment process is based on graphical and paradigm methods, it can be adopted to lessen the burdens of complex calculations. The end of the research will present the comparison results between the examples from the literature and the method proposed in this research. As indicated by the research findings, employing CPN and an MST for TALBPs (type-I) can obtain even favorable and consistent results over legacy methods, and further optimize workstation design and enhance balance efficiency.

Sesamin is a kind of fat-soluble lignan extracted from sesame seeds or other plants. It has attracted more and more attention because of its extensive pharmacological activities. In this study, we systematically summarized the pharmacological activities of sesamin including antioxidant, anti-inflammatory, anticancer, protection of liver and kidney, prevention of diabetes, hypertension, and atherosclerosis. Studies focus on the abilities of sesamin to attenuate oxidative stress by reducing the levels of ROS and MDA, to inhibit the release of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, etc.), and to induce apoptosis and autophagy in cancer cells through a variety of signaling pathways such as NF-κB, JNK, p38 MAPK, PI3K/AKT, caspase-3, and p53. By inhibiting the production of ROS, sesamin can also enhance the biological activities of NO in blood vessels, improve endothelial dysfunction and hypertension, and change the process of atherosclerotic lesion formation. In line with this, the various pharmacological properties of sesamin have been discussed in this review so that we can have a deeper understanding of the pharmacological activities of sesamin and clear the future development direction of sesamin.

The Veterans Community Care Program (VCCP) aims to address access constraints in the Veterans Health Administration (VA) by reimbursing care from non-VA community providers. Little existing research explores how veterans' choice of VA versus VCCP providers has evolved as a significant VCCP expansion in 2014 as part of the Veterans Access, Choice, and Accountability Act.We examined changes in reliance on VA for primary care (PC), mental health (MH), and specialty care (SC) among VCCP-eligible veterans.We linked VA administrative data with VCCP claims to retrospectively examine utilization during calendar years 2016-2018.1.78 million veterans enrolled in VA before 2013 and VCCP-eligible in 2016 due to limited VA capacity or travel hardship.We measured reliance as the proportion of total annual outpatient (VA+VCCP) visits occurring in VA for PC, MH, and SC.Of the 26.1 million total outpatient visits identified, 45.6% were for MH, 29.9% for PC, and 24.4% for SC. Over the 3 years, 83.2% of veterans used any VA services, 23.8% used any VCCP services, and 20.0% were dual VA-VCCP users. Modest but statistically significant declines in reliance were observed from 2016-2018 for PC (94.5%-92.2%), and MH (97.8%-96.9%), and a more significant decline was observed for SC (88.5%-79.8%).Veterans who have the option of selecting between VA or VCCP providers continued using VA for most of their outpatient care in the initial years after the 2014 VCCP expansion.

Anaerobic digestion and composting are attracting increasing attention due to the increased production of animal manure. It is essential to know about the fate and bioavailability of heavy metals (HMs) for further utilisation of animal manure. This review has systematically summarised the migration of HMs and the transformation of several typical HMs (Cu, Zn, Cd, As, and Pb) during anaerobic digestion and composting. The results showed that organic matter degradation increased the HMs content in biogas residue and compost (with the exception of As in compost). HMs migrated into biogas residue during anaerobic digestion through various mechanisms. Most of HMs in biogas residue and compost exceeded relevant standards. Then, anaerobic digestion increased the bioavailable fractions proportion in Zn and Cd, decreased the F4 proportion, and raised them more than moderate environmental risks. As (III) was the main species in the digester, which extremely increased As toxicity. The increase of F3 proportion in Cu and Pb was due to sulphide formation in biogas residue. Whereas, the high humus content in compost greatly increased the F3 proportion in Cu. The F1 proportion in Zn decreased, but the plant availability of Zn in compost did not reduce significantly. Cd and As mainly converted the bioavailable fractions into stable fractions during composting, but As (V) toxicity needs to be concerned. Moreover, additives are only suitable for animal manure treated with slightly HM contaminated. Therefore, it is necessary to combine more comprehensive methods to improve the manure treatment and make product utilisation safer.

In the background of the information age of “Internet+,” the traditional teaching mode of business English has many drawbacks in terms of curriculum, teaching content, teaching methods, and teachers’ backgrounds and cannot adapt to the needs of the times. Therefore, business English teaching should actively follow the trend of “Internet + education” and continue to innovate in a multimodal way. The multimodal teaching mode of “wireless network + business English” is in line with the background of “Internet+,” optimizing teaching resources to the maximum extent and truly realizing the effective combination of Internet and business English teaching. The Internet-based multimodal innovation can be carried out in the four elements of business English teaching: environment, task, learner, and guide teaching. The specialization and modernization of business English teaching can be promoted through the optimization of O2O multisituational classroom, the application of multimodal tasks in three-dimensional teaching materials, the communication of diversified categories of students, and the configuration of multilevel teachers across fields.

There are many studies and reviews of the relationship between the asthma disease in young individuals on the one hand and caries and dental erosion on the other. The causes of caries and dental erosion might be related to the asthmatic drugs, low pH and the sweeteners that the inhaled drug contains and perhaps even the lifestyle of children and adolescents with asthma. The main focus of this review is therefore to describe various preventive strategies, based on long experience of preventive dental care in Sweden. Two fact boxes are presented, one on fluoride toothpaste as a population-based intervention for different ages and one on diet counselling in children and adolescents with asthma. The most important thing is to introduce fluoride toothpaste early in the child's life and that the parents brush the child's teeth twice a day, in the morning after breakfast and at night before bedtime, up to the age of 10. Moreover, a high-risk approach with an additional fluoride supply at home is presented, together with the application of fluoride varnish at the clinic. Regarding diet counselling, it is important to make sure that the child has regular meals during the day, maximum five to six times a day, to allow the teeth to rest between meals and restrict sweets and soft drinks to once a week. It is important to identify children and adolescents with asthma as early as possible and to refer them to a dental team for preventive treatment.

Background Epigenetic dysregulation is essential to the tumorigenesis of oral squamous cell carcinoma (OSCC). SET and MYND domain-containing protein 3 (SMYD3), a histone lysine methyltransferase, is implicated in gene transcription regulation and tumor development. However, the roles of SMYD3 in OSCC initiation are not fully understood. The present study investigated the biological functions and mechanisms involved in the SMYD3-mediated tumorigenesis of OSCC utilizing bioinformatic approaches and validation assays with the aim of informing the development of targeted therapies for OSCC. Results 429 chromatin regulators were screened by a machine learning approach and aberrant expression of SMYD3 was found to be closely associated with OSCC formation and poor prognosis. Data profiling of single-cell and tissue demonstrated that upregulated SMYD3 significantly correlated with aggressive clinicopathological features of OSCC. Alterations in copy number and DNA methylation patterns may contribute to SMYD3 overexpression. Functional experimental results suggested that SMYD3 enhanced cancer cell stemness and proliferation in vitro and tumor growth in vivo. SMYD3 was observed to bind to the High Mobility Group AT-Hook 2 (HMGA2) promoter and elevated tri-methylation of histone H3 lysine 4 at the corresponding site was responsible for transactivating HMGA2. SMYD3 also was positively linked to HMGA2 expression in OSCC samples. Furthermore, treatment with the SMYD3 chemical inhibitor BCI-121 exerted anti-tumor effects. Conclusions Histone methyltransferase activity and transcription-potentiating function of SMYD3 were found to be essential for tumorigenesis and the SMYD3–HMGA2 is a potential therapeutic target in OSCC.

Promotors are those genomic regions on the upstream of genes, which are bound by RNA polymerase for starting gene transcription. Because it is the most critical element of gene expression, the recognition of promoters is crucial to understand the regulation of gene expression. This study aimed to develop a machine learning-based model to predict promotors in Agrobacterium tumefaciens (A. tumefaciens) strain C58. In the model, promotor sequences were encoded by three different kinds of feature descriptors, namely, accumulated nucleotide frequency, k-mer nucleotide composition, and binary encodings. The obtained features were optimized by using correlation and the mRMR-based algorithm. These optimized features were inputted into a random forest (RF) classifier to discriminate promotor sequences from non-promotor sequences in A. tumefaciens strain C58. The examination of 10-fold cross-validation showed that the proposed model could yield an overall accuracy of 0.837. This model will provide help for the study of promoters in A. tumefaciens C58 strain.

Objective The aim of this work was to evaluate the predictive value of FAR combined with CACS for MACCEs. Background The fibrinogen-albumin-ratio (FAR), a novel biomarker of inflammation, is associated with the severity of coronary artery disease (CAD). Coronary calcification score (CACS) is associated with the severity of coronary stenosis and is closely related to the prognosis of CAD patients. What is the prognostic value of FAR in patients with chest pain, which has not been reported. This study aims to evaluate the relationship between CACS and FAR and their impact on prognosis in patients with suspected CAD. Methods We used information from 12,904 individuals who had coronary computed tomography angiography (CTA) for chest pain and tracked down any significant adverse cardiac and cerebrovascular events (MACCEs). The following formula was used to calculate FAR: fibrinogen (g/L)/albumin (g/L). Patients were separated into groups with greater levels of FAR (FAR-H) and lower levels of FAR (FAR-L) in accordance with the ideal cut-off value of FAR for MACCEs prediction. In addition, patients were divided into three groups based on their CACS scores (CACS ≤ 100, 100 400). Results 4946 patients [62(55–71) years, 64.4% male] were ultimately enrolled in the present study. During follow-up, a total of 234 cases (4.7%) of MACCEs were documented. Linear regression analysis results showed that CACS (R2 = 0.004, Standard β = 0.066, P P = 0.019). Multivariate Cox regression showed that age (adjusted HR 1.015 95% CI 1.001–1.028;p = 0.03), FAR (adjusted HR 1.355 95% CI 1.042–1.763;p = 0.023),FBG (adjusted HR 1.043 95% CI 1.006–1.083;p = 0.024) and CACS (adjusted HR 1.470 95% CI 1.250–1.727;p P P Conclusion FAR was an independent risk factor for MACCEs. The results showed that CACS was positively associated with FAR in patients with suspected CAD. A higher level of FAR and heavier coronary calcification burden was associated with worse outcomes among patients with suspected CAD. FAR and CACS improved the risk identification of patients with suspected CAD, leading to a significant reclassification of MACCEs.

PDF - 207K, A: Untreated KLM-1 tumors stain strongly for mesothelin. B-D: Mesothelin expression is not affected by treatment with RG7787, paclitaxel or both. IHC was done by Histoserv, Inc. according to a standard protocol. Representative pictures (10X) are shown.

Supplementary Figure S1. AUY922 does not significantly affect viability of normal colon epithelial cells; Supplementary Figure S2. Sensitivity of colon cancer cells to AUY922 is not associated with the expression levels of HSP90; Supplementary Figure S3. The general caspase inhibitor z-VAD-fmk efficiently inhibits AUY922-mediated inhibition of mutant KRAS colon cancer cell survival; Supplementary Figure S4. AUY922 kills colon cancer cells by induction of apoptosis; Supplementary Figure S5. AUY922 triggers reduction in the mitochondrial membrane potential, release of mitochondrial apoptogenic proteins in sensitive but not resistant colon cells; Supplementary Figure S6. Inhibition of Bim does not alter sensitivity of Caco-2 cells to AUY922; Supplementary Figure S7. Knockdown of PUMA or p53 does not inhibit cell death induced by AUY922; Supplementary Figure S8. Upregulation of Bim by AUY922 in mutant KRAS colon cancer cells is due to a transcriptional increase; Supplementary Figure S9. Knockdown of CHOP inhibits cell death induced by AUY922; Supplementary Figure S10. BGP-15 and 4-PBA attenuate XBP-1 splicing induced by AUY922; Supplementary Figure S11. Overexpression of GRP78 reduces AUY922-induced upregulation of CHOP and Bim; Supplementary Figure S12. A schematic model comparing different responses of mutant and wild-type KRAS colon cancer cells to AUY922; Supplementary Figure S13. AUY922 does not cause any significant change in the expression of STK33 in mutant KRAS colon cancer cells; Supplementary Table 1. List of Antibodies; Supplementary Table 2. List of reagents; Supplementary Table 3. siRNAs

PDF - 950KB, Legends for Supplementary Figures 1 and 2; Supplementary Figure 1: Screening of TK siRNA library; Supplementary Figure2: Src knock down slightly increased SS1P toxicity; Supplementary Table 1: Oligos used in the study.

Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis, and new therapies are needed. RG7787 is a novel low-immunogenic antimesothelin recombinant immunotoxin (RIT), engineered to overcome the limitations of SS1P, a RIT now in clinical trials. In vitro activity was evaluated on five established PDAC cell lines (KLM-1, AsPC-1, BxPC-3, Panc 3.014, and PK-1) and on PDAC cells directly established from a patient tumor (GUMC108). RG7787 had subnanomolar IC50s in most cell lines, and was significantly more active than SS1P in GUMC108, KLM-1, and Panc 3.014 cells. GUMC108 was most sensitive, with RG7787 killing >99% of the cells. In a subcutaneous KLM-1 xenograft mouse model, two cycles of 3 × 2.5 mg/kg RG7787 QOD combined with two cycles of 1 × 50 mg/kg paclitaxel induced near-complete responses, with all tumors regressing below 5 mm3 within 30 days after therapy was initiated (>95% decrease) and no significant growth increase for at least another 3 weeks. RG7787 alone gave limited but significant regressions and paclitaxel by itself arrested tumor growth. Quantifying the uptake of Alexa Fluor 647–labeled RG7787 in tumors showed that the RIT reached only 45% of KLM-1 cells, accounting in part for the limited responses. Paclitaxel did not improve RG7787 uptake, which thus cannot explain the beneficial effect of the combination therapy. In conclusion, RG7787 has high cytotoxic activity on PDAC cell lines as well as on primary patient cells. In vivo, this novel RIT gives durable near-complete tumor responses when combined with paclitaxel. RG7787 merits further evaluation for the treatment of PDAC. Mol Cancer Ther; 13(8); 2040–9. ©2014 AACR.

PDF - 60K, Toxicity studies for RG7787 were performed in athymic nude mice. General health and weight was evaluated during therapy.

PDF - 261K, Supplementary methods related to the IHC protocol and supplementary figure legends.

Fos-related antigen-2 (Fra-2) is a transcription factor belonging to the activator protein 1 (AP-1) family, which is associated with many chronic airway diseases such as asthma. Alternatively activated (M2) macrophages are associated with Fra2 in airway diseases such as pulmonary fibrosis. However, there is no specific study that explores the relationship between M2 macrophages and Fra2 in asthma.We hypothesized that a potential mechanism of allergic asthma could be that Fra2 is highly expressed in M2 macrophages through JAK3-STAT5 and facilitates the production of downstream T-helper 2 (Th2) cytokines, thus promoting the pathogenesis of asthma.Peripheral venous blood and airway tissue samples of patients with asthma and controls were obtained. Moreover, a C57BL/6 mouse model of asthma was established. Fra2 expression was detected using immunohistochemistry and immunofluorescence. Macrophages were obtained by flow sorting, and expression of the JAK3-STAT5-Fra2 signaling pathway was determined using PCR and western blotting. Enzyme-linked immunosorbent assay was used to determine M2 macrophage-associated Th2-type cytokine levels.Fra2 was highly expressed in patients with asthma and asthmatic mice. The JAK3-STAT5 was a signal pathway related to the high expression of Fra2 in M2 macrophages. Moreover, we found that Fra2 could affect the production of Th2 cytokines downstream of M2 macrophages, including interleukin 4 (IL-4) and IL-13.M2 macrophages could promote airway inflammation through JAK3-STAT5-Fra2 to induce allergic asthma. Our study offers a new insight to further understand the pathogenesis of asthma and also provides a new direction for targeted treatment.

Acoustic emission is a nondestructive testing technology based on the propagation of transient elastic waves captured by acoustic emission sensors. The acoustic emission signal depends not only on the distance and quality of the propagation path of the transient elastic wave but also on the sensitivity and frequency bandwidth of the receiving sensor that converts the transient elastic wave into a voltage signal. The frequency range of damage signals in concrete materials is generally in the low-frequency band. If high-frequency sensors are used, the low sensitivity to low-frequency signals will cause measurement errors, while the bandwidth of general commercial acoustic emission sensors is relatively narrow. Therefore, a high-sensitivity, low-frequency acoustic emission sensor is proposed, whose bandwidth is almost four times that of commercial sensors. Based on the customized sensor, we quantitatively analyzed the influence of propagation distance on the characteristic parameters of acoustic waves propagating in concrete. The results show that the different propagation modes of acoustic waves in concrete have different attenuation with the propagation distance, related to the position relationship between the acoustic source and the sensor and the propagation path and path quality. This result gives us a better understanding of the propagation mechanism of acoustic emission signals in concrete materials.

Asthma is a heterogeneous inflammatory disorder of the airways, and multiple studies have addressed the vital role of the nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3)/caspase-1/interleukin-1β (IL-1β) pathway in asthma, but its impact on ovalbumin- (OVA-) induced neutrophilic asthma remains unclear. Here, we explored this pathway’s effect on airway inflammation in neutrophilic asthma to clarify whether blocking this signaling could alleviate asthmatic airway inflammation. Using an established OVA-induced neutrophilic asthma mouse model, we provided asthmatic mice with a highly selective NLRP3 inhibitor, MCC950, and a specific caspase-1 inhibitor, Ac-YVAD-cmk. Our results indicated that asthmatic mice exhibited increased airway hyperresponsiveness, neutrophil infiltration, and airway mucus hypersecretion, upregulated retinoid-related orphan receptor-γt (RORγt) mRNA expression, and downregulated fork head box p3 (Foxp3) mRNA expression, which was concurrent with NLRP3 inflammasome activation and upregulation of caspase-1, IL-1β, and IL-18 expression in lung. Treatment of NLRP3 inflammasome inhibitors significantly attenuated airway hyperresponsiveness, airway inflammation, and reversed T helper 17 (Th17)/regulatory T (Treg) cell imbalance in asthmatic mice. We propose that the NLRP3/caspase-1/IL-1β pathway plays an important role in the pathological process of neutrophilic asthma and provides evidence that blocking this pathway could potentially be a treatment strategy to ameliorate airway inflammation in asthma after validation with future experimental and clinical studies.

This study aimed to investigate serum levels of adiponectin, and the mRNA expression of forkhead box C2 (FOXC2) and glucose transporter-4 (GLUT4) in visceral adipose tissue obtained from patients with gestational diabetes mellitus (GDM) and healthy pregnant women.Venous blood samples were obtained from 60 pregnant women with gestational normal glucose tolerance (GNGT) and 21 patients with GDM. Visceral adipose tissues were obtained from 11 women with GDM and 30 with GNGT. Serum adiponectin levels were detected by enzyme-linked immunosorbent assay, and FOXC2 and GLUT4 mRNA expression were detected by quantitative polymerase chain reaction.Serum adiponectin concentrations were lower in the women with GDM than in the controls (Our results revealed that decreased adiponectin, FOXC2, and GLUT4 expression were associated with increased risk of GDM and the regulation mechanism of GLUT4 mediated by FOXC2 would be the focus of further studies.