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Abstract In clinical nursing, neonatal pain assessment is a challenging task for preventing and controlling the impact of pain on neonatal development. To reduce the adverse effects of repetitive painful treatments during hospitalization on newborns, we propose a novel method (namely pain concept-cognitive computing model, PainC3M) for evaluating facial pain in newborns. In the fusion system, we first improve the attention mechanism of vision transformer by revising the node encoding way, considering the spatial structure, edge and centrality of nodes, and then use its corresponding encoder as a feature extractor to comprehensively extract image features. Second, we introduce a concept-cognitive computing model as a classifier to evaluate the level of pain. Finally, we evaluate our PainC3M on various open pain data sets and a real clinical pain data stream, and the experimental results demonstrate that our PainC3M is very effective for dynamic classification and superior to other comparative models. It also provides a good approach for pain assessment of individuals with aphasia (or dementia).

Abstract Background The global prevalence of autoimmune hepatitis (AIH) is increasing due in part to the lack of effective pharmacotherapies. Growing evidence suggests that fibroblast growth factor 4 (FGF4) is crucial for diverse aspects of liver pathophysiology. However, its role in AIH remains unknown. Therefore, we investigated whether FGF4 can regulate M1 macrophage and thereby help treat liver inflammation in AIH. Methods We obtained transcriptome-sequencing and clinical data for patients with AIH. Mice were injected with concanavalin A to induce experimental autoimmune hepatitis (EAH). The mechanism of action of FGF4 was examined using macrophage cell lines and bone marrow-derived macrophages. Results We observed higher expression of markers associated with M1 and M2 macrophages in patients with AIH than that in individuals without AIH. EAH mice showed greater M1-macrophage polarization than control mice. The expression of M1-macrophage markers correlated positively with FGF4 expression. The loss of hepatic Fgf4 aggravated hepatic inflammation by increasing the abundance of M1 macrophages. In contrast, the pharmacological administration of FGF4 mitigated hepatic inflammation by reducing M1-macrophage levels. The efficacy of FGF4 treatment was compromised following the in vivo clearance of macrophage populations. Mechanistically, FGF4 treatment activated the phosphatidylinositol 3-kinase (PI3K)–protein kinase B (AKT)-signal pathway in macrophages, which led to reduced M1 macrophages and hepatic inflammation. Conclusion We identified FGF4 as a novel M1/M2 macrophage-phenotype regulator that acts through the PI3K–AKT-signaling pathway, suggesting that FGF4 may represent a novel target for treating inflammation in patients with AIH.

Background The prognosis of patients with coronary artery disease is adversely affected by elevated fasting plasma glucose (FPG) levels. However, the relationship between FPG levels and in-hospital cardiac arrest (IHCA) remains unclear.Objectives The objective of this study was to investigate the association between FPG levels and IHCA in patients diagnosed with acute coronary syndrome (ACS).Methods Data from a total of 31,726 ACS patients fitted with inclusion and exclusion criteria across 241 hospitals in the Improving Care for Cardiovascular Disease in China-ACS project from November 2014 to July 2019 were collected. Different logistic regression models were utilized to examine the associations of FPG levels with IHCA. Sensitivity analyses were then conducted to assess the robustness of the findings. Marginal effect analyses were also employed to evaluate the impact of different therapies.Results A total of 335 cases of IHCA and 293 in-hospital mortality were recorded throughout the study. A non-linear relationship between FPG levels and IHCA was identified after adjusting for the covariates. Specifically, a significant association was found between elevated FPG levels (≥6.1 mmol/L) and an increased risk of IHCA. These findings remained consistent across different subgroup analyses including both the diabetic and non-diabetic patients. Additionally, the marginal effect analyses revealed that percutaneous coronary intervention could lower the high FPG-related risk.Conclusions The study findings showed a positive correlation between FPG levels and a higher incidence of IHCA, irrespective of the presence of diabetes.

Background Research on food addiction has increased significantly in recent years. It has been demonstrated that food addiction can lead to impairments in physiological, psychological, and social functioning in individuals. However, there is a lack of studies investigating the influence of how individuals handle social situations on food addiction and the specific mechanisms involved. Method A cross-sectional survey was conducted with 1,151 university students, with a mean age of 21.44 (SD = 4.77) years. The sample comprised 74.46% female and 25.54% male students. Participants completed the Chinese version of the modified Yale Food Addiction Scale 2.0, the Social Physique Anxiety Scale, the Expressive Suppression Scale, and the Social Avoidance and Distress Scale. Statistical analyses were performed using SPSS 26.0 and the Process (Version 3.4) plug-in. Result The results of the study supported our hypothesis that the association between social physique anxiety and food addiction symptoms could be partially explained by expressive suppression and social avoidance and distress. This association remained significant even after adjusting for covariates such as gender, number of cigarettes smoked per day, bedtime, education, and BMI. Specifically, more severe social physique anxiety was found to be associated with frequent use of expressive suppression and social avoidance and distress, which in turn was associated with more severe food addiction symptoms. Conclusion This study explored the role of expression suppression and social avoidance and distress in the relationship between social physique anxiety and food addiction symptoms. The findings provide a theoretical basis for developing interventions for food addiction in college students. These interventions could include helping students develop a healthy perception of body image, encouraging emotional expression, and promoting active social participation to reduce food addiction symptoms.

Abstract. Background:. Oral anti-coagulants (OAC) are the intervention for the prevention of stroke, which consistently improve clinical outcomes and survival among patients with atrial fibrillation (AF). The main purpose of this study is to identify problems in OAC utilization among hospitalized patients with AF in China. Methods:. Using data from the Improving Care for Cardiovascular Disease in China-Atrial Fibrillation (CCC-AF) registry, guideline-recommended OAC use in eligible patients was assessed. Results:. A total of 52,530 patients with non-valvular AF were enrolled from February 2015 to December 2019, of whom 38,203 were at a high risk of stroke, 9717 were at a moderate risk, and 4610 were at a low risk. On admission, only 20.0% (6075/30,420) of patients with a diagnosed AF and a high risk of stroke were taking OAC. The use of pre-hospital OAC on admission was associated with a lower risk of new-onset ischemic stroke/transient ischemic attack among the diagnosed AF population (adjusted odds ratio: 0.54, 95% confidence interval: 0.43–0.68; P 70% of AF patients were at a high risk of stroke. Although poor performance on guideline-recommended OAC use was found in this study, over time the CCC-AF project has made progress in stroke prevention in the Chinese AF population.Registration:ClinicalTrials.gov, NCT02309398.

Abstract Background Whether a low-inflammatory diet relates to type 2 diabetes risk remains unclear. We examined the association between a low-inflammatory diet and risk of type 2 diabetes among normoglycemic and prediabetic participants. We also explored whether a low-inflammatory diet modifies genetic risk for type 2 diabetes. Methods Among 142,271 diabetes-free UK Biobank participants (aged 39–72 years), 126,203 were normoglycemic and 16,068 were prediabetic at baseline. Participants were followed for up to 15 years to detect incident type 2 diabetes. At baseline, dietary intake was assessed with a 24-h dietary record. An inflammatory diet index (IDI) was generated based on high-sensitivity C-reactive protein levels and was a weighted sum of 34 food groups (16 anti-inflammatory and 18 pro-inflammatory). Participants were grouped into tertiles corresponding to inflammatory level (low, moderate, and high) based on IDI scores. Prediabetes at baseline was defined as HbA1c 5.7–6.4% in diabetes-free participants. Incident type 2 diabetes and age of onset were ascertained according to the earliest recorded date of type 2 diabetes in the Primary Care and Hospital inpatient data. A diabetes-related genetic risk score (GRS) was calculated using 424 single-nucleotide polymorphisms. Data were analyzed using Cox regression and Laplace regression. Results During follow-up (median 8.40 years, interquartile range 6.89 to 11.02 years), 3348 (2.4%) participants in the normoglycemia group and 2496 (15.5%) in the prediabetes group developed type 2 diabetes. Type 2 diabetes risk was lower in normoglycemic (hazard ratio [HR] = 0.71, 95% confidence interval [CI] 0.65, 0.78) and prediabetic (HR = 0.81, 95% CI 0.73, 0.89) participants with low IDI scores compared to those with high IDI scores. A low-inflammatory diet may prolong type 2 diabetes onset by 2.20 (95% CI 1.67, 2.72) years among participants with normoglycemia and 1.11 (95% CI 0.59, 1.63) years among participants with prediabetes. In joint effect analyses, normoglycemic or prediabetes participants with low genetic predisposition to type 2 diabetes and low IDI scores had a significant 74% (HR = 0.26, 95% CI 0.21, 0.32) or 51% (HR = 0.49, 95% CI 0.40, 0.59) reduction in type 2 diabetes risk compared to those with high genetic risk plus high IDI scores. There were significant additive and multiplicative interactions between IDI and GRS in relation to type 2 diabetes risk in the normoglycemia group. Conclusions A low-inflammatory diet is associated with a decreased risk of type 2 diabetes and may delay type 2 diabetes onset among participants with normal blood glucose or prediabetes. A low-inflammatory diet might significantly mitigate the risk of genetic factors on type 2 diabetes development.

Introduction For individuals with mobility limitations, virtual exercise programmes can address the challenges of in-person participation in community exercise programmes. A synthesis of studies of virtual exercise programmes targeting mobility limitations provided outside of conventional rehabilitation services and strategies used to optimise equitable access and inclusivity in these programmes is lacking. We aim to characterise evaluations of virtual exercise programmes for adults with mobility limitations, and the nature of and extent to which equity, diversity and inclusion considerations are integrated in the research process.Methods and analysis A scoping review following a six-stage methodological framework, including a consultation exercise, is proposed. A comprehensive strategy will be used to search Medline, Embase, PEDro, CINAHL and Scopus to identify peer-reviewed studies evaluating virtual exercise programmes for adults with mobility limitations living in the community. Three trained reviewers will select studies independently. Data (eg, study methodology, programme structure and content, participant characteristics) will be extracted using a standardised form, and collated and summarised using quantitative and qualitative methods. The PROGRESS-Plus and International Classification of Functioning, Disability and Health frameworks will be used to classify participant characteristics and study outcomes, respectively. During the consultation exercise, key knowledge users, including exercise participants, programme providers and coordinators, and members of community organisations for persons living with disabilities and under-represented groups, will be asked to provide insights regarding the applicability of review findings. A directed content analysis of data from the consultation exercise will be performed.Ethics and dissemination The research ethics board at the University of Toronto approved the consultation exercise. Findings will be disseminated through peer-reviewed publications and conference presentations. Findings will enhance understanding of current research evaluating virtual exercise programmes and inform future research and strategies for promoting equitable access and outcomes for individuals with mobility limitations.Registration details https://doi.org/10.17605/OSF.IO/X5JMA.

Abstract. Background:. Previous studies have examined the bulk transcriptome of peripheral blood immune cells in acquired immunodeficiency syndrome patients experiencing immunological non-responsiveness. This study aimed to investigate the characteristics of specific immune cell subtypes in acquired immunodeficiency syndrome patients who exhibit immunological non-responsiveness. Methods:. A single-cell transcriptome sequencing of peripheral blood mononuclear cells obtained from both immunological responders (IRs) (CD4+ T-cell count >500) and immunological non-responders (INRs) (CD4+ T-cell count

Abstract TL-895 (formerly known as M7583) is a potent, highly selective, adenosine triphosphate (ATP)-competitive, second-generation, irreversible inhibitor of Bruton’s tyrosine kinase (BTK). We characterized its biochemical and cellular effects in in vitro and in vivo models. TL-895 was evaluated preclinically for potency against BTK using IC50 concentration–response curves; selectivity using a 270-kinase panel; BTK phosphorylation in Ramos Burkitt’s lymphoma cells by ProteinSimple Wes analysis of one study; anti-proliferative effects in primary chronic lymphocytic leukemia (CLL) blasts; cell viability effects in diffuse large B-cell lymphoma (DLBCL) and mantle-cell lymphoma (MCL) cell lines; effects on antibody-dependent cell-mediated cytotoxicity (ADCC) from Daudi cells and chromium-51 release from human tumor cell lines; and efficacy in vivo using four MCL xenograft model and 21 DLBCL patient-derived xenograft (PDX) models (subtypes: 9 ABC, 11 GCB, 1 Unclassified). TL-895 was active against recombinant BTK (average IC50 1.5 nM) and inhibited only three additional kinases with IC50 within tenfold of BTK activity. TL-895 inhibited BTK auto-phosphorylation at the Y223 phosphorylation site (IC50 1–10 nM). TL-895 inhibited the proliferation of primary CLL blasts in vitro and inhibited growth in a subset of activated DLBCL and MCL cell lines. TL-895 inhibited the ADCC mechanism of therapeutic antibodies only at supra-clinical exposure levels. TL-895 significantly inhibited tumor growth in the Mino MCL xenograft model and in 5/21 DLBCL PDX models relative to vehicle controls. These findings demonstrate the potency of TL-895 for BTK and its efficacy in models of B-cell lymphoma despite its refined selectivity.

Background Gastric cancer consists of solid tumors with a tendency for disseminated intravascular coagulation (DIC). DIC is rare in patients with stomach cancer, and there have been few studies on this condition. We aimed to perform comprehensive analyses of the prognosis and clinicopathologic characteristics of stomach cancer patients with DIC. Methods Between June 2006 and March 2020, 14,016 patients at Fujian Cancer Hospital were diagnosed with stomach cancer. We reviewed their medical records and found that 105 of these patients were diagnosed with DIC. After excluding patients who were lost to follow-up, 71 patients with DIC remained. The clinical data were retrospectively analyzed to observe clinical characteristics and prognostic factors, and the Kaplan–Meier survival analysis was performed. Prognostic variables were investigated by the Cox proportional hazards method. Results The median age was 54 (range, 21–83) years, and 38 patients (53.5%) were male. The histological category was poorly differentiated gastric cancer in 58 patients (81.7%). Eleven patients (15.5%) developed DIC after curative gastric resection. Sixty patients (84.5%) had DIC at the initial presentation of gastric cancer or developed DIC when the tumor progressed during treatment. Fifty-one patients (71.8%) had bleeding symptoms, and 43 (60.6%) patients had comorbidities at the time of DIC diagnosis. Among the 71 patients, 42 (59.2%) had multiple metastatic patterns. Twenty-one (29.6%) patients received chemotherapy. The median overall survival (OS) was 57.0 days (95% confidence interval [CI] [33.1–80.9] days). Tumor status (P = 0.000) and treatment (P = 0.003) were found to be significant variables associated with OS by univariate analysis. Multivariate analysis showed that tumor status (P = 0.000) and treatment (P = 0.000) had independent effects on OS. Conclusions Gastrointestinal bleeding, multiple metastatic patterns and comorbidities at diagnosis with DIC are common in patients with gastric cancer complicated with DIC. Patients with poorly differentiated gastric cancer are more likely to develop DIC. Treatment and tumor status are separate risk variables for the survival of gastric cancer patients with DIC.DIC patients without tumors have a good prognosis and can be cured by appropriate etiological correction and symptomatic treatment. Chemotherapy can improve the prognosis of DIC patients with tumors.

Abstract Genetic heterogeneity poses a challenge to research and clinical translation of autism spectrum disorder (ASD). In this study, we conducted a plasma proteomic and metabolomic study of children with ASD with and without risk genes (de novo mutation) and controls to explore the impact of genetic heterogeneity on the search for biomarkers for ASD. In terms of the proteomic and metabolomic profiles, the groups of children with ASD carrying and those not carrying de novo mutation tended to cluster and overlap, and integrating them yielded differentially expressed proteins and differential metabolites that effectively distinguished ASD from controls. The mechanisms associated with them focus on several common and previously reported mechanisms. Proteomics results highlight the role of complement, inflammation and immunity, and cell adhesion. The main pathways of metabolic perturbations include amino acid, vitamin, glycerophospholipid, tryptophan, and glutamates metabolic pathways and solute carriers‐related pathways. Integrating the two omics analyses revealed that L‐glutamic acid and malate dehydrogenase may play key roles in the pathogenesis of ASD. These results suggest that children with ASD may have important underlying common mechanisms. They are not only potential therapeutic targets for ASD but also important contributors to the study of biomarkers for the disease.

Objective To investigate the factors affecting the length of hospitalization after the Sun's procedure in patients with type A aortic coarctation. Methods From January 2018 to June 2023, the clinical data, related laboratory indicators and perioperative blood transfusion data of patients with type A aortic dissection who underwent Sun's procedure in the First Hospital of Lanzhou University were collected. LASSO regression was used to screen the characteristics related to the length of hospital stay, and linear regression analysis was used to determine the risk factors for prolonged length of hospital stay. Results The statistical analysis of 242 patients showed that the amount of red blood cell transfusion, plasma transfusion, platelet transfusion and autologous blood transfusion were the influencing factors of the length of hospital stay in patients with type A aortic dissection after operation. The total sum of squared deviations of the linear regression equation fitting the total length of hospital stay was statistically significant (F= 10.504, P

Abstract Pyroptosis is an inflammatory form of cell death, which plays a key role in the development of auto-inflammation and cancer. This study aimed to construct a pyroptosis and inflammasome-related genes for predicting prognosis of the pancreatic ductal adenocarcinoma (PDAC). This study was based primarily on the one-way analysis of variance, univariate Cox regression analysis, Least absolute shrinkage and selection operator (LASSO) Cox regression, a risk-prognostic signature, gene set variation analysis (GSVA), and immune microenvironment analysis, using PDAC data from The Cancer Genome Atlas and International Cancer Genome Consortium databases for the analysis of the role of 676 pyroptosis and inflammasome-related genes in PDAC retrieved from the Reactome and GeneCards databases. Lastly, we collected six paired PDAC and matched normal adjacent tissue samples to verify the expression of signature genes by quantitative real-time PCR (qRT-PCR). We identified 18 candidate pyroptosis and inflammasome-related genes that differed significantly between pathologic grades (stages) of PDAC patients. The univariate Cox and LASSO analyses pointed to six genes as the best variables for constructing a prognostic signature, including ACTA2, C1QTNF9, DNAH8, GATM, LBP, and NGF. The results of the risk prognostic model indicated that the AUCs at 1, 3, and 5 years were greater than 0.62. GSVA revealed that ‘GLYCOLYSIS’, ‘P53 PATHWAY’, ‘KRAS SIGNALING UP’, and ‘INFLAMMATORY RESPONSE’ hallmark gene sets were associated with the risk score. The high-risk group was associated with poor prognosis and was characterized by a lower infiltration of cells involved in anti-tumor immunity; whereas the low-risk group with higher T cells, NK cells, and macrophages showed relatively better survival and significantly higher upregulation of cytolytic scores and inflammation scores. Additionally, crucial pyroptosis and inflammasome-related genes were further validated by qRT-PCR. Our study revealed the prognostic role of the pyroptosis and inflammasome-related genes in PDAC for the first time. Simultaneously, the biological and prognostic heterogeneity of PDAC had been demonstrated, deepening our molecular understanding of this tumor.

Abstract. Background:. Pre-operative assessment with high-resolution magnetic resonance imaging (MRI) is useful for assessing the risk of local recurrence (LR) and survival in rectal cancer. However, few studies have explored the clinical importance of the morphology of the anterior mesorectum, especially in patients with anterior cancer. Hence, the study aimed to investigate the impact of the morphology of the anterior mesorectum on LR in patients with primary rectal cancer. Methods:. A retrospective study was performed on 176 patients who underwent neoadjuvant treatment and curative-intent surgery. Patients were divided into two groups according to the morphology of the anterior mesorectum on sagittal MRI: (1) linear type: the anterior mesorectum was thin and linear; and (2) triangular type: the anterior mesorectum was thick and had a unique triangular shape. Clinicopathological and LR data were compared between patients with linear type anterior mesorectal morphology and patients with triangular type anterior mesorectal morphology. Results:. Morphometric analysis showed that 90 (51.1%) patients had linear type anterior mesorectal morphology, while 86 (48.9%) had triangular type anterior mesorectal morphology. Compared to triangular type anterior mesorectal morphology, linear type anterior mesorectal morphology was more common in females and was associated with a higher risk of circumferential resection margin involvement measured by MRI (35.6% [32/90] vs. 16.3% [14/86], P = 0.004) and a higher 5-year LR rate (12.2% vs. 3.5%, P = 0.030). In addition, the combination of linear type anterior mesorectal morphology and anterior tumors was confirmed as an independent risk factor for LR (odds ratio = 4.283, P = 0.014). Conclusions:. The classification established in this study was a simple way to describe morphological characteristics of the anterior mesorectum. The combination of linear type anterior mesorectal morphology and anterior tumors was an independent risk factor for LR and may act as a tool to assist with LR risk stratification and treatment selection.

Abstract To establish a clinical-based nomogram for predicting the success rate of external cephalic version (ECV) through a prospective study. This was a single-center prospective study that collected eligible breech pregnant women. 152 participants were enrolled in the training cohort, who received ECV procedures performed by a single operator. We used the training cohort to establish regression equations and prediction models. These variables include maternal factors (age, operation gestational age, pre-pregnancy BMI (Body Mass Index), operation BMI, BMI increase, multipara), ultrasound factors (fetal weight estimation, amniotic fluid index, placental location, type of breech presentation, spinal position), and anesthesia. Univariate and multivariable analyses were used to screen the factors affecting the success of ECV. A nomogram scoring model was established based on these factors. And C-index, DCA (Decision Curve Analysis) and calibration curve, Hosmer–Lemeshow test was used to verify the prediction effect of the model. Finally, 33 participants were enrolled in the testing cohort who received ECV with an unrestricted operator. We used C-index, DCA (decision curve analysis), and Hosmer–Lemeshow to verify the application value of the prediction model. The calibration curves and ROC curves of both the training cohort and testing cohort are plotted for internal and external validation of the model. The ECV success rate of the training cohort was 62.5%. Univariate analysis showed that the predictors related to the success rate of ECV were age, BMI increase value, AFI (amniotic fluid index), breech type, placental location, spinal position, anesthesia, and multipara. The prediction thresholds of the corresponding indexes were calculated according to the Youden index. Multivariate logistic regression analysis showed that BMI increase ≥ 3.85 kg/m2, AFI ≥ 10.6 cm, anesthesia, multipara, and non-anterior placenta were independent predictors of ECV success. Through the internal and external validation, it is confirmed that the model has a good calibration and prediction ability. Our nomogram has a good ability to predict the success rate of ECV.

Abstract Floods and droughts are environmental phenomena that occur in Peninsular Malaysia due to extreme values of streamflow (SF). Due to this, the study of SF prediction is highly significant for the purpose of municipal and environmental damage mitigation. In the present study, machine learning (ML) models based on the support vector machine (SVM), artificial neural network (ANN), and long short-term memory (LSTM), are tested and developed to predict SF for 11 different rivers throughout Peninsular Malaysia. SF data sets for the rivers were collected from the Malaysian Department of Irrigation and Drainage. The main objective of the present study is to propose a universal model that is most capable of predicting SFs for rivers within Peninsular Malaysia. Based on the findings, the ANN3 model which was developed using the ANN algorithm and input scenario 3 (inputs consisting of previous 3 days SF) is deduced as the best overall ML model for SF prediction as it outperformed all the other models in 4 out of 11 of the tested data sets; and obtained among the highest average RMs with a score of 3.27, hence indicating that the model is very adaptable and reliable in accurately predicting SF based on different data sets and river case studies. Therefore, the ANN3 model is proposed as a universal model for SF prediction within Peninsular Malaysia.

Abnormal accumulation of alpha-synuclein (αSyn) in the remaining nigra dopaminergic neurons is a common neuropathological feature found in patients with Parkinson's disease (PD). Antibody-based immunotherapy has been considered a potential approach for PD treatment. This study aims to investigate the effectiveness of active immunization against αSyn in a mouse model of PD. Adult mice were immunized with or without a synthetic peptide containing the C-terminal residues of human αSyn and activation epitopes, followed by an intranigral injection of adeno-associated virus vectors for overexpressing human αSyn. Upon the peptide injection, αSyn-specific antibodies were raised, accompanied by degeneration of dopaminergic neurons and motor deficits. Furthermore, the induction of neuroinflammation was postulated by the elevation of astroglial and microglial markers in the immunized mice. Instead of lessening αSyn toxicity, this peptide vaccine caused an increase in the pathogenic species of αSyn. Our data demonstrated the potential adverse effects of active immunization to raise antibodies against the C-terminal fragment of αSyn. This drawback highlights the need for further investigation to weigh the pros and cons of immunotherapy in PD. Applying the αSyn C-terminal peptide vaccine for PD treatment should be cautiously exercised. This study provides valuable insights into the intricate interplay among immune intervention, αSyn accumulation, and neurodegeneration.

Abstract Superionic solid electrolytes are key to the development of advanced solid-state Li batteries. In recent years, various materials have been discovered, with ionic conductivities approaching or even exceeding those of carbonate-based liquid electrolytes used in high-performance Li-ion batteries. Among the different classes of inorganic solid electrolytes under study, lithium thiophosphates are one of the most promising due to their high Li-ion conductivity at room temperature and mechanical softness. Here, we report about the effect of synthesis parameters on the crystallization behavior and charge-transport properties of Li4PS4I. We show that thermally induced crystallization of Li4PS4I (P4/nmm), starting from the glassy phase 1.5Li2S–0.5P2S5–LiI, adversely affects the material’s conductivity. However, both conductivity and crystallization temperature can be significantly increased by applying pressure during the preparation.

Abstract Saliva has significant advantages as a test medium for detection of SARS-CoV-2 infection in patients, such as ease of collection, minimal requirement of supplies and trained personnel, and safety. Comprehensive validation in a large cohort of prospectively collected specimens with unknown SARS-CoV-2 status should be performed to evaluate the potential and limitations of saliva-based testing. We developed a saliva-based testing pipeline for detection of SARS-CoV-2 nucleic acids using real-time reverse transcription PCR (RT-PCR) and droplet digital PCR (ddPCR) readouts, and measured samples from 137 outpatients tested at a curbside testing facility and 29 inpatients hospitalized for COVID-19. These measurements were compared to the nasal swab results for each patient performed by a certified microbiology laboratory. We found that our saliva testing positively detects 100% (RT-PCR) and 93.75% (ddPCR) of curbside patients that were identified as SARS-CoV-2 positive by the Emergency Use Authorization (EUA) certified nasal swab testing assay. Quantification of viral loads by ddPCR revealed an extremely wide range, with 1 million-fold difference between individual patients. Our results demonstrate for both community screening and hospital settings that saliva testing reliability is on par with that of the nasal swabs in detecting infected cases, and has potential for higher sensitivity when combined with ddPCR in detecting low-abundance viral loads that evade traditional testing methods.

Abnormal heart rhythm is a common cardiac dysfunction in obese patients, and its pathogenesis is related to systemic lipid accumulation. The cardiomyocyte-derived apoLpp (homologous gene in Drosophila of the human apolipoprotein B) plays an important role in whole-body lipid metabolism of Drosophila under a high-fat diet (HFD). Knockdown of apoLpp derived from cardiomyocytes can reduce HFD-induced weight gain and abdominal lipid accumulation. In addition, exercise can reduce the total amount of apoLpp in circulation. However, the relationship between regular exercise, cardiomyocyte-derived apoLpp and abnormal heart rhythm is unclear. We found that an HFD increased the level of triglyceride (TG) in the whole-body, lipid accumulation and obesity in Drosophila. Moreover, the expression of apoLpp in the heart increased sharply, the heart rate and arrhythmia index increased and fibrillation occurred. Conversely, regular exercise or cardiomyocyte-derived apoLpp knockdown reduced the TG level in the whole-body of Drosophila. This significantly reduced the arrhythmia induced by obesity, including the reduction of heart rate, arrhythmia index, and fibrillation. Under HFD conditions, flies with apoLpp knockdown in the heart could resist the abnormal cardiac rhythm caused by obesity after receiving regular exercise. HFD-induced obesity and abnormal cardiac rhythm may be related to the acute increase of cardiomyocyte-derived apoLpp. Regular exercise and inhibition of cardiomyocyte-derived apoLpp can reduce the HFD-induced abnormal cardiac rhythm.

Objectives To investigate the prevalence of depression in college students and determine how social support and healthy lifestyle factors are associated with depression in this population.Design A cross-sectional design.Setting A comprehensive university in Changsha, Hunan, South China. The study was conducted from May to June 2019.Participants A total of 541 students at the comprehensive university.Primary and secondary outcome measures The Zung Self-Rating Depression Scale, Social Support Rating Scale and Health-Promoting Lifestyle Profile-II (HPLP-II) were used to evaluate depression, social support and lifestyles, respectively, and analyse the mutual relationships among them.Results Among the 541 participants, 161 (29.8%) experienced depressive symptoms, and there were significant gender-related and academic discipline-related differences in self-rated depression. The average social support score was 38.06 (38.06±7.52). The average HPLP-II score was 71.09 (71.09±11.47). A monofactor analysis showed that depression was correlated with social support and a healthy lifestyle. As demonstrated by logistic regression analysis, being a woman (OR=2.613, 95% CI: 1.541 to 4.43), inadequate social support (OR=0.912, 95% CI: 0.877 to 0.948), poor nutrition (OR=0.87, 95% CI: 0.775 to 0.977) and lack of self-actualisation (OR=0.644, 95% CI: 0.572 to 0.724) were significantly correlated with depression.Conclusions Owing to the high prevalence of depression among Chinese university students, educational institutions must take measures such as providing compulsory mental health education courses and improving the psychological counselling services available to students.

Abstract Background BRAF mutations occur in 2–4% non-small cell lung cancer (NSCLC) patients and can be categorized into three functional classes based on signaling mechanism and kinase activity: RAS-independent kinase-activating V600 monomers (class 1), RAS-independent kinase-activating dimers (class 2) and RAS-dependent kinase-inactivating heterodimers (class 3). The association between functional classes and clinical features in Chinese NSCLC patients remains unexplored. Our multi-center study aimed to survey the BRAF mutation rate and analyze the associated clinical features in this population. Methods Capture-based sequencing data of either plasma or tissue samples obtained from 8405 Chinese stage I–IV NSCLC patients were retrospectively analyzed. Results BRAF mutations were detected in 238 patients, revealing an overall mutation rate of 2.8%. Among them, 32%, 21% and 13% had BRAF mutant class 1, 2 and 3 respectively. The remaining 34% had other BRAF mutations. V600 (32%) and G469 (13%) were the two most predominant BRAF mutations. Patients with class 2 and 3 mutations were more likely to have concurrent KRAS mutations (P = 0.001). Collectively, BRAF mutations, including non-class 1–3 mutations, were more likely to occur in males (P

BackgroundThe COVID-19 pandemic has alarming implications for individual and population level mental health. Although the future of COVID-19 is unknown at present, more countries or regions start to ease restrictions. The findings from this study have provided the empirical evidence of prevalence and patterns of mental disorders in Chinese general population before and after easing most COVID-19 restrictions, and information of the factors associated with these patterns.MethodsA cross-sectional population-based online survey was carried out from February to March 2020 in the general population across all provinces in China. The 12-item General Health Questionnaire (GHQ-12) was incorporated in the survey. Latent class analyses were performed to investigate the patterns of mental disorders and multinomial logistic regressions were used to examine how individual and regional risk factors can predict mental disorder patterns.ResultsFour distinctive patterns of mental health were revealed in the general population. After the ease of most COVID-19 restrictions, the prevalence of high risk of mental disorders decreased from 25.8% to 20.9% and prevalence of being high risk of unhappiness and loss of confidence decreased from 10.1% to 8.1%. However, the prevalence of stressed, social dysfunction and unhappy were consistently high before and after easing restrictions. Several regional factors, such as case mortality rate and healthcare resources, were associated with mental health status. Of note, healthcare workers were less likely to have mental disorders, compared to other professionals and students.ConclusionsThe dynamic management of mental health and psychosocial well-being is as important as that of physical health both before and after the ease of COVID-19 restrictions. Our findings may help in mental health interventions in other countries and regions while easing COVID-19 restrictions.

Transcription factors regulate gene expression in response to various external and internal cues by activating or suppressing downstream genes. Significant progress has been made in identifying and characterizing the Cysteine3Histidine (C3H) gene family in several dicots and monocots. They are characterized by their signature motif of three cysteine and one histidine residues, and reportedly play important roles in regulation of plant growth, developmental processes and environmental responses. In this study, we performed genome-wide and deep analysis of putative C3H genes, and a total of 117 PbeC3H members, were identified in P. betulaefolia and classified into 12 groups. Results were supported by the gene structural characteristics and phylogenetic analysis. These genes were unevenly distributed on 17 chromosomes. The gene structures of the C3H genes were relatively complex but conserved in each group. The C3H genes experienced a WGD event that occurred in the ancestor genome of P. betulaefolia and apple before their divergence based on the synonymous substitutions (Ks) values. There were 35 and 37 pairs of paralogous genes in the P. betulaefolia and apple genome, respectively, and 87 pairs of orthologous genes between P. betulaefolia and apple were identified. Except for one orthologous pairs PbeC3H66 and MD05G1311700 which had undergone positive selection, the other C3H genes had undergone purifying selection. Expression profiles showed that high salinity stress could influence the expression level of C3H genes in P. betulaefolia. Four members were responsive to salt stress in roots, nine were responsive to salt stress in leaves and eight showed inhibited expression in leaves. Results suggested important roles of PbeC3H genes in response to salt stress and will be useful for better understanding the complex functions of the C3H genes, and will provide excellent candidates for salt-tolerance improvement.

Abstract Background Despite limited information on neonatal safety, the transfer of frozen-thawed cleavage-stage embryos with blastomere loss is common in women undergoing in vitro fertilization. We aimed to evaluate the pregnancy outcomes and safety of frozen-thawed cleavage-stage embryos with blastomere loss. Methods This prospective, multicenter, cohort study included all frozen-thawed cleavage-stage embryo transfer (FET) cycles between 2002 and 2012. Pregnancy outcomes and subsequent neonatal outcomes were compared between FET cycles with intact embryos and those with blastomere loss. Results A total of 12,105 FET cycles were included in the analysis (2259 cycles in the blastomere loss group and 9846 cycles in the intact embryo group). The blastomere loss group showed significantly poorer outcomes with respect to implantation, pregnancy, and live birth rates than the intact embryo group. However, following embryo implantation, the two groups were similar with respect to live birth rates per clinical pregnancy. Among multiple pregnancies (4229 neonates), neonates from the blastomere loss group were at an increased risk of being small for gestational age (aOR = 1.50, 95% CI 1.00–2.25) compared to those from the intact group. A similar trend was observed among singletons (aOR = 1.84, 95% CI 0.99–3.37). No associations were found between blastomere loss and the subsequent occurrence of congenital anomalies or neonatal mortality. However, neonates from the blastomere loss group were at an increased risk of transient tachypnea of the newborn (aOR = 5.21, 95% CI 2.42–11.22). Conclusions The transfer of embryos with blastomere loss is associated with reduced conception rates. Once the damaged embryos have implanted, pregnancies appear to have the same probability of progressing to live birth but with an increased risk of small for gestational age neonates and transient tachypnea of the newborn. Study registration This study was retrospectively registered at Chinese Clinical Trial Registry. Registration number: ChiCTR-OOC-16007753. Registration date: 13 January 2016.

Background: Patients with potential difficult mask ventilation (DV) and difficult intubation (DI) are often managed with awake intubation, which can be stressful for patients and anesthesiologists. This prospective randomized study evaluated a new approach, fast difficult airway evaluation (FDAE). We hypothesized that the FDAE approach would reduce the need for awake intubation. Methods: After obtaining informed consent, 302 patients with potential DV/DI undergoing elective surgeries were randomly assigned to the FDAE group (Group E) and the control group (Group C). In Group E, patients were gradually sedated, and adequacy of manual mask ventilation during spontaneous breathing was assessed at various sedation levels. Awake intubation was applied in those with inadequate mask ventilation. In Group C, DI was evaluated under local anesthesia. However, the care team could intubate under general anesthesia if the vocal cords were visible. The primary outcome was the rate of awake intubations in both groups and the induction efficiency assessed by the induction time. The secondary outcome was the incidence of serious complications. Results: The rate of awake intubation was significantly lower in Group E than that in Group C (5.81% vs. 36.05%, χ2 = 42.3, P < 0.001). The induction time was much shorter in Group E than in Group C (11.85 ± 4.82 min vs. 18.71 ± 7.85 min, t = 5.39, P < 0.001). There was no significant difference in the incidence of intubation related complications between the two groups. Patients in Group E had a much lower incidence of recall (9.68% vs. 44.90%, χ2 = 47.68, P < 0.001) of the induction process and higher satisfaction levels than patients in Group C (t = 15.36, P < 0.001). Conclusions: The FDAE significantly reduces the need for awake intubation and improves the efficiency of the intubation process without comprising safety in patients with potential difficult mask ventilation and DI. Trial Registration: No. ChiCTR-TRC-11001418; http://www.gctr.org/cn/proj/show.aspx?proj=1562.

(1) Background: The governance measures that governments deploy vary substantially across countries and even within countries; there is, however, limited knowledge of the responses of local governments or from different areas in the same country. (2) Methods: By using grounded theory and an automatic text processing method, this study analyses the pandemic governance measures, the pandemic governance pattern, and possible factors across 28 provinces in mainland China based on the text of 28 official provincial government Sina microblogs dating from 20 January to 1 July 2020. (3) Results and discussion: The provincial pandemic governance patterns in China are divided into a pathogen-control pattern, a diagnosis and treatment consolidation pattern, a balanced promotion pattern, a quick-adjustment response pattern, and a recovery-oriented pattern. The pandemic severity, economic development, public health service, and population structure may all have an impact on pandemic governance measures. (4) Conclusions: The conclusions of this study may help us to reconstruct governance systems related to global public health emergencies from the perspective of normalisation, as well as providing important clarification for management and a reference for countries seeking to curb the global spread of a pandemic.

Abstract Through a new hypothesis-driven and microRNA-pathway-based SNP (miR-SNP) association study we identified a novel miR-SNP (rs713065) in the 3′UTR region of FZD4 gene linked with decreased risk of death in early stage NSCLC patients. We determined biological function and mechanism of action of this FZD4-miR-SNP biomarker in a cellular platform. Our data suggest that FZD4-miR-SNP loci may significantly influence overall survival in NSCLC patients by specifically interacting with miR-204 and modulating FZD4 expression and cellular function in the Wnt-signaling-driven tumor progression. Our findings are bridging the gap between the discovery of epidemiological SNP biomarkers and their biological function and will enable us to develop novel therapeutic strategies that specifically target epigenetic markers in the oncogenic Wnt/FZD signaling pathways in NSCLC.

Abstract We report on the controllable synthesis of porous BN microfibers and explore their applications as adsorbent for removing dibenzothiophene (DBT) in model oil. The growth evolution of porous BN microfibers has been carefully investigated by correlating their structural characteristics with their synthesis conditions. The as-prepared BN microfibers exhibit very high adsorption capacity for DBT (86 mg S g−1 according to the Langmuir isotherm model), showing excellent adsorptive desulfurization performance. The porous BN after adsorption can be regenerated by a simply heat treatment. After four times recycling, the regenerated adsorption capacity still remains more than 83% of that at the first adsorption. The superb oxidation resistance and chemical inertness, high sulfur adsorption capacity, as well as excellent regeneration performance render the developed porous BN microfibers to be a decent adsorbent for sulfur removal from fuels.

Previous studies have found that high social class individuals are more dishonest than low social class ones. However, the underlying mechanism of this phenomenon is still unclear. The "ignoring negative consequences" hypothesis suggests that belonging to a high social class makes individuals ignore the negative consequences of dishonesty, whereas the "self-focused" hypothesis suggests that belonging to a high social class makes individuals focus more on the self and self-interests. The present study aims to examine these two hypotheses by measuring participants' subjective social class, narcissism, fear of negative evaluation, and tendency to be dishonest. To this end, an online survey was conducted. Results provide evidence for the self-focused hypothesis by showing that subjective social class positively predicts the tendency to be dishonest, and narcissism plays a mediating role in this relationship.

Physical space, clonal fragmentation and nutrient availability can each affect the growth of clonal plants, but their interactive effect has been little studied. We grew un-fragmented (connected) and fragmented (disconnected) ramet pairs of the floating, clonal plant Salvinia natans in cylindrical containers with different diameters and heights (volumes) filled with solutions of two nutrient levels (high vs. low). To simulate competition environments that are commonly confronted by S. natans, we also added two ramets of another floating plants Spirodela polyrrhiza in each container. Biomass (total biomass, floating biomass and submerged biomass) and number of ramets of S. salvinia were higher in the containers with a larger diameter. Compared to the low nutrient level, the high nutrient level increased number of ramets, and altered submerged to floating mass ratio of S. salvinia. The impacts of physical space on floating mass and number of ramets were stronger under the high than under the low nutrient level. Clonal fragmentation positively affected biomass in the containers with a smaller volume (a smaller height and diameter), but had little impact in the containers with a larger volume (a larger height or diameter). Our results suggest that physical space can interact with nutrients and clonal fragmentation to affect the performance of S. salvinia under competition.

The transforming growth factor-β (TGFβ) family plays an important role in many developmental processes and when mutated often contributes to various diseases. Marfan syndrome is a genetic disease with an occurrence of approximately 1 in 5,000. The disease is caused by mutations in fibrillin, which lead to an increase in TGFβ ligand activity, resulting in abnormalities of connective tissues which can be life-threatening. Mutations in other components of TGFβ signaling (receptors, Smads, Schnurri) lead to similar diseases with attenuated phenotypes relative to Marfan syndrome. In particular, mutations in TGFβ receptors, most of which are clustered at the C-terminal end, result in Marfan-like (MFS-like) syndromes. Even though it was assumed that many of these receptor mutations would reduce or eliminate signaling, in many cases signaling is active. From our previous studies on receptor trafficking in C. elegans, we noticed that many of these receptor mutations that lead to Marfan-like syndromes overlap with mutations that cause mis-trafficking of the receptor, suggesting a link between Marfan-like syndromes and TGFβ receptor trafficking. To test this hypothesis, we introduced three of these key MFS and MFS-like mutations into the C. elegans TGFβ receptor and asked if receptor trafficking is altered. We find that in every case studied, mutated receptors mislocalize to the apical surface rather than basolateral surface of the polarized intestinal cells. Further, we find that these mutations result in longer animals, a phenotype due to over-stimulation of the nematode TGFβ pathway and, importantly, indicating that function of the receptor is not abrogated in these mutants. Our nematode models of Marfan syndrome suggest that MFS and MFS-like mutations in the type II receptor lead to mis-trafficking of the receptor and possibly provides an explanation for the disease, a phenomenon which might also occur in some cancers that possess the same mutations within the type II receptor (e.g. colon cancer).

Circular RNAs (circRNAs) play important roles in miRNA function and transcriptional control. However, little is known regarding circRNAs in the pear. In this study, we identified circRNAs using deep sequencing and analyzed their expression under drought stress. We identified 899 circRNAs in total, among which 33 (23 upregulated, 10 downregulated) were shown to be dehydration-responsive. We performed GO and KEGG enrichment analysis to predict the functions of differentially expressed circRNAs. 309 circRNAs were predicted to act as sponges for 180 miRNAs. A circRNA-miRNA co-expression network was constructed based on correlation analysis between the differentially expressed circRNAs and their miRNA binding sites. Our study will provide a rich genetic resource for the discovery of genes related to drought stress, and can readily be applied to other fruit trees.

A method was developed for simultaneous determination of 15 amino acids and 7 alkyl amines. The method was based on the employment of high performance liquid chromatography/fluorescence detection and online derivatization with o-phthaldiadehyde. The 22 derivatives were separated within 30 min including the equilibration time and detected by a fluorescence detector at an excitation wavelength of 230 nm and emission wavelength of 450 nm. The analysis procedure was satisfactorily validated by the reproducibility, recovery, linearity and detection limit of the analytes. The relative standard deviations (RSDs) of retention time and peak area for individual amino acids and alkyl amines were consistently less than 0.30% and 2.35%, respectively. Good recovery values ranging from 70% to 109% were obtained. The proposed method showed good linearity (R2≥0.99) in the range of 0.125-125 μM/L for amino acids and 2.5-5000 ng/L for alkyl amines. The detection limit ranged from 0.13 pM to 0.37 pM for individual amino acids and from 0.9 ng to 7.2 ng for individual alkyl amines. The developed and validated method was successfully applied to the quantitative analysis of amino acids and alkyl amines in continental and marine aerosols in China. Among the identified organic nitrogen compounds, 7 amino acids and 6 alkyl amines were detected in every aerosol sample. Glycine was the dominant amino acid, with the average of 130.93 pmol/m3 (accounting for 83% of the total amino acids) and 137.22 pmol/m3 (accounting for 66% of the total amino acids) in continental and marine aerosols in China, respectively. Methylamine and ethanolamine were the most abundant alkyl amines, contributing 87% and 64% to the total alkyl amines in continental and marine aerosols in China, respectively. This work provided an accurate, sensitive and simple method to determine simultaneously amino acids and alkyl amines, and applied the proposed method to the first investigation of amino acids in Shanghai and amino acids and alkyl amines in Huaniao Island in China. The finding of considerable amino acids and alkyl amines in continental and marine aerosols may exert significant implications on nitrogen cycling and atmospheric chemistry.

Left ventricle (LV) assist, which refers to the use of a mini-pump or catheter implanted across the aortic valve connected to the pump, can promote myocardial recovery after left ventricle failure. However, conventional LV assist catheters compress the aortic valve, which can induce aortic insufficiency. Here we describe a novel LV assist catheter containing a retractable stent at its distal end that may prevent such insufficiency. The device was tested in six goats in which the coronary artery was ligated to induce acute LV failure, and then an LV assist was installed with a novel catheter in the left ventricle via the left subclavian artery. Inserting the catheter into the left ventricle caused mild to moderate aortic insufficiency. Releasing the stent maintained the catheter in the center of the three valve leaflets, which resolved the aortic insufficiency and, within a few minutes, led to significantly lower left ventricle end diastolic pressure (9.0±3.0 mmHg) than without stent release (17.6±5.0 mmHg, p = 0.012) as well as significantly higher left ventricle dP/dtmax (614±299 mmHg/s) than without stent release (343±245 mmHg/s, p = 0.03). Our results indicate that this novel drainage catheter with retractable stent can effectively prevent aortic insufficiency by maintaining the catheter in the center of the aortic valve leaflets, thereby lowering left ventricular end diastolic pressure and improving systolic function.

Background: It was believed that inflammatory response induced by cardiopulmonary bypass (CPB) was blamed for complications after cardiac surgery. To improve the outcome, many pharmacological interventions have been applied to attenuate inflammatory response during CPB. The objective of this study was to investigate the effect of ulinastatin (urinary trypsin inhibitor [UTI]) on outcome after CPB surgery. Methods: Totally, 208 patients undergoing elective valves replacement between November 2013 and September 2014 were divided into Group U (n = 70) and Group C (n = 138) based on they received UTI or not. Categorical variables were compared between groups using Fisher's exact test, and continuous variables using unpaired Student's t-test or Mann–Whitney U-test. One-way analysis of variance and Dunnett's or Tukey's tests were used to compare values at different time points within the same group. The risk of outcomes was estimated and adjusted by multivariable logistic regression, propensity scoring, and mixed-effect models for all measured variables. Results: Both the serious complications in total, including death, acute lung injury, acute respiratory distress syndrome and acute kidney injury, and the other complications, including hemodialysis, infection, re-incubation, and tracheotomy were similar between the two groups (P > 0.05). After adjusted by multivariable logistic regression and the propensity score, UTI still cannot be found any benefit to improve any outcomes after cardiac surgery. Also, no statistical differences with regard to duration of postoperative mechanical ventilation, the length of Intensive Care Unit and hospital stays (P > 0.05). Conclusion: UTI did not improve postoperative outcomes in our patients after cardiopulmonary bypass surgery.

Eicosanoids may play a role in ischemic stroke. However, the associations of variants in cyclooxygenase (COX) pathway genes and interaction among these variants with carotid plaque vulnerability are not fully understood. In present study, twelve variants in COX pathway genes were examined using matrix-assisted laser desorption ionization time-of-flight mass spectrometry method in 396 patients with ischemic stroke and 291 controls. Platelet aggregation, platelet-leukocyte aggregates, and urine 11-dehydrothromboxane B2 (11-dTxB2) were also measured. According to the results of carotid high-resolution B-mode ultrasound, the patients were stratified into the following groups [i.e., non-carotid plaque and carotid plaque. The carotid plaque was further classified into subgroups of echolucent plaque (ELP) and echogenic plaque (EGP)]. Additionally, gene-gene interactions were analyzed to assess whether there was any interactive role for assessed variants in affecting carotid plaque vulnerability, platelet activation and 11-dTxB2 levels. There were no significant differences in the frequencies of genotypes of the twelve variants between patients and controls. Among 396 patients, 294 cases (74.2%) had carotid plaques (106 had ELP, 188 had EGP). Frequency of PTGS2 rs20417CC, TXAS1 rs2267679TT, TXAS1 rs41708TT, PTGIS rs5602CC, and TXA2R rs1131882TT genotype was significantly higher in patients with plaque compared with patients without plaque, or in patients with ELP compared with patients with EGP. 11-dTxB2 levels, platelet aggregation and platelet-leukocyte aggregates were significantly higher in patients with ELP compared with patients without plaque or with EGP. Multivariate logistic regression analysis revealed that PTGS2 rs20417CC, TXA2R rs1131882TT, and high-risk interaction among variants in PTGS2 rs20417, TXA2R rs1131882 and TXAS1 rs41708 were independently associated with the risk of ELP after adjusting for confounding variables. The variants in COX pathway genes and the high-risk interactions among variants in PTGS2 rs20417, TXA2R rs1131882 and TXAS1 rs41708 were associated with high 11-dTxB2 and platelet activation, and independently associated with the risk of carotid plaque vulnerability. These variants might be potential markers for plaque instability.

The pear is an important temperate fruit worldwide that is produced by a group of species in the genus Pyrus. Callery pear (Pyrus calleryana Decne) is characterized by high resistance to multiple diseases, good adaptability, and high ornamental value, and is therefore widely planted in pear orchards for edible fruit production or as stock. Plant pathogens are a major threat to pear yield. Black spot disease, caused by the filamentous fungus Alternaria alternata, is one of the most serious diseases in pear. Elucidation of resistant genes to black spot disease is extremely important for understanding the underlying mechanisms as well as for the development of resistant cultivars. In this study, high-throughput single-strand RNA-sequencing was used to compare the transcriptome profiles of Callery pear leaves before and after A. alternata incubation for 7 days. The analysis yielded 73.3 Gb of clean data that were mapped onto the reference genome of the Chinese pear, and differentially expressed gene(DEG)s were identified with |log2FC| ≥ 1. Functional annotation demonstrated that black spot disease promoted great changes in the overall metabolism, and enrichment analysis of gene ontology terms showed that most of them are closely linked to signalling network and photosynthesis. Specifically, the genes included mainly transcription factors and genes involved in calcium signalling and ethylene and jasmonate pathways. Eight members of the ethylene response factor transcription factor gene family Group IX, including ERF1, ERF7, and ERF105, were up-regulated to 2.03-3.37-fold compared with CK, suggesting their role in the defence response to pathogen infection. Additionally, multiple transcription factors involved in biotic stresses, such as NAC78, NAC2, MYB44, and bHLH28, were up-regulated. Furthermore, we identified 144 long non-coding (lnc)RNAs, providing new insight into the involvement of lncRNAs in the response to black spot disease. Our study provides valuable data on the molecular genetics and functional genomic mechanisms of resistance to black spot disease in Callery pear. A good understanding of the molecular response to this disease will allow the development of durable and environmentally friendly control strategies.

The objective of this study is to observe whether cyclosporine A (CsA) inhibits the expression of dectin-1 in human corneal epithelial cells infected with Aspergillus fumigatus (A. fumigatus) and to investigate the molecular mechanisms of the inhibition.Immortalized human corneal epithelial cells (HCECs) were pretreated with 1,25(OH)2D3 and VDR inhibitor for 1 h, and then they were pretreated with CsA for 12h. After these pretreatments, the HCECs were stimulated with A. fumigatus and curdlan respectively, and the expression of dectin-1 and proinflammatory cytokines (IL-1β and TNF-α) were detected by RT-PCR, western blot and ELISA.Dectin-1 mRNA and dectin-1 protein expression increased when HCECs were stimulated with A. fumigatus or curdlan, and CsA inhibited the dectin-1 expression both in mRNA and protein levels specifically. Dectin-1 and proinflammatory cytokine expression levels were higher when HCECs were pretreated with VDR inhibitor and CsA compared to pretreatment with CsA alone, while dectin-1 and proinflammatory cytokine levels were lower when HCECs were pretreated with 1,25(OH)2D3 and CsA compared to pretreatment with CsA alone.These data provide evidence that CsA can inhibit the expression of dectin-1 and proinflammatory cytokines through dectin-1 when HCECs are stimulated by A. fumigatus or curdlan. The active form of vitamin D, 1,25(OH)2D3, and VDR signaling pathway regulate the inhibition of CsA. The inhibition is enhanced by 1,25(OH)2D3, and the VDR inhibitor suppresses the inhibition.

POTS is a global public-health disease, but predictor for therapeutic response to metoprolol in children with POTS is lacking. This study was designed to investigate predictive value of plasma C-type natriuretic peptide (CNP) in the therapeutic efficacy of metoprolol on postural tachycardia syndrome (POTS) in children. Totally 34 children with POTS and 27 healthy children were included in the study. The head-up test or head-up tilt test was used to check heart rate and blood pressure from supine to upright in subjects. A double antibody (competitive) sandwich immunoluminometric assay was used to detect plasma CNP. Metoprolol was used to treat children with POTS. The difference in plasma concentrations of CNP between responders and non-responders was compared. An ROC curve was used to analyze plasma CNP to predict efficacy of metoprolol on POTS in children. Plasma CNP in children with POTS was significantly higher than that of healthy children [(51.9 ± 31.4) vs. (25.1 ± 19.1) pg/ml, P 32.55 pg/ml yielded a sensitivity of 95.8% and specificity of 70% in predicting therapeutic efficacy of metoprolol on POTS children. Plasma CNP might serve as a useful predictor for the therapeutic efficacy of metoprolol on POTS in children.

Indoleamine 2,3-dioxygenase (IDO), which is mainly expressed in activated dendritic cells, is known as a regulator of immune responses. However, the role of IDO in immune responses against fungal corneal infection has not been investigated. To evaluate the regulatory mechanisms of IDO in fungal inflammation, we resorted to human corneal epithelial cells (HCECs), known as the first barrier of cornea against pathogenic microorganisms. We found that IDO was significantly up-regulated in corneal epithelium infected with Aspergillus fumigatus (A. fumigatus) and HCECs incubated with spores of A. fumigatus. Furthermore, IDO inhibitor (1-methyltryptophan, 1-MT) enhanced inflammatory cytokines IL-1β and IL-6 expression which were up-regulated by A. fumigatus spores infection. Dectin-1, as one of the important C-type lectin receptors, can identify β-glucan, and mediate fungal innate immune responses. In the present study, pre-treatment with curdlan, a Dectin-1 agonist, further enhanced IDO expression compared with A. fumigatus stimulation. While laminarin, the Dectin-1 specific inhibitor, partially inhibited IDO expression stimulated by A. fumigatus. Further studies demonstrated inhibition of IDO activity amplified the expressions of inflammatory cytokines IL-1β and IL-6 induced by activation of Dectin-1. These results suggested that IDO was involved in the immune responses of fungal keratitis. The activation of Dectin-1 may contribute to A. fumigatus spores-induced up-regulation of IDO.

To develop an index of the quality of nutritional care of premature infants based on the change in weight Z score from birth to discharge and to illustrate the use of this index in comparing the performance of different NICUs.Retrospective data analysis was performed to compare the growth of premature infants born in three perinatal centers. Infants with gestational age ≤ 32 weeks who survived to discharge from 2006 to 2010 were included. Weight Z scores at birth and discharge were calculated by the method of Fenton. Using data from one NICU as the reference, a multivariable linear regression model of change in weight Z score from birth to discharge was developed. Employing this model, a benchmark value of change in weight Z score was calculated for each baby. The difference between this calculated benchmark value and the baby's observed change in weight Z score was defined as the performance gap for that infant. The average value of the performance gaps in a NICU serves as its quality care index.1,714 infants were included for analysis. Change in weight Z score is influenced by birth weight Z score and completed weeks of gestation; thus the model for calculating the benchmark change in weight Z score was adjusted for these two variables. We found statistically significant differences in the average performance gaps for the three units.A quality care index was developed based on change in weight Z score from birth to discharge adjusted for two initial risk factors. This objective, easily calculated index may be used as a measurement of the quality of nutritional care to rank the performance of different NICUs.

BACKGROUND: Postural tachycardia syndrome (POTS) is prevalent in children and adolescents and has a great impact on health. But its risk factors have not been fully understood. This study aimed to explore possible risk factors for children and adolescents with POTS. METHODS AND FINDINGS: 600 children and adolescents (test group) aged 7-18 (11.9 ± 3.0) years old, 259 males and 341 females, were recruited for identifying its risk factors. Another 197 subjects aged from 7 to 18 (11.3 ± 2.3) years old were enrolled in the validation group. Heart rate (HR) and blood pressure (BP) were monitored during upright test. Risk factors were analyzed and sensitivity and specificity for predicting POTS were tested via receiver operating characteristic curve. Among 600 subjects, 41 were confirmed with POTS patients (6.8%) based on clinical manifestation and upright test. The results showed a significant difference in daily water intake, the daily sleeping hours, supine HR, HR increment and maximum HR during upright test between POTS and the unaffected children (P

An innovative logic tree, Failure Expansion Tree (FET), is proposed in this paper, which improves on traditional Fault Tree Analysis (FTA). It describes a different thinking approach for risk factor identification and reliability risk assessment. By providing a more comprehensive and objective methodology, the rather subjective nature of FTA node discovery is significantly reduced and the resulting mathematical calculations for quantitative analysis are greatly simplified. Applied to the Useful Life phase of a subsea pipeline engineering project, the approach provides a more structured analysis by constructing a tree following the laws of physics and geometry. Resulting improvements are summarized in comparison table form.

For reliability testing an Energy Expansion Tree (EET) and a companion Energy Function Model (EFM) are proposed and described in this paper. Different from conventional approaches, the EET provides a more comprehensive and objective way to systematically identify external energy factors affecting reliability. The EFM introduces energy loss into a traditional Function Model to identify internal energy sources affecting reliability. The combination creates a sound way to enumerate the energies to which a system may be exposed during its lifetime. We input these energies into planning an accelerated life test, a Multi Environment Over Stress Test. The test objective is to discover weak links and interactions among the system and the energies to which it is exposed, and design them out. As an example, the methods are applied to the pipe in subsea pipeline. However, they can be widely used in other civil engineering industries as well. The proposed method is compared with current methods.

Interleukin (IL) 33, a member of IL-1 cytokine family, is well known to promote Th2 type immune responses by signaling through its receptor ST2. However, it is not clear whether ST2 is expressed by mucosal epithelium, and how it responds to IL-33 to induce inflammatory mediators. This study was to identify the presence and function of ST2 and explore the role of IL-33/ST2 signaling in regulating the inflammatory cytokine production in corneal epithelial cells. Human corneal tissues and cultured primary human corneal epithelial cells (HCECs) were treated with IL-33 in different concentrations without or with different inhibitors to evaluate the expression, location and signaling pathways of ST2 in regulating production of inflammatory cytokine and chemokine. The mRNA expression was determined by reverse transcription and real time PCR, and protein production was measured by enzyme-linked immunosorbent assay (ELISA), immunohistochemical and immunofluorescent staining. ST2 mRNA and protein were detected in donor corneal epithelium and cultured HCECs, and ST2 signal was enhanced by exposure to IL-33. IL-33 significantly stimulated the production of inflammatory cytokines (TNF-α, IL-1β and IL-6) and chemokine IL-8 by HCECs at both mRNA and protein levels. The stimulated production of inflammatory mediators by IL-33 was blocked by ST2 antibody or soluble ST2 protein. Interestingly, the IκB-α inhibitor BAY11-7082 or NF-κB activation inhibitor quinazoline blocked NF-κB p65 protein phosphorylation and nuclear translocation, and also suppressed the production of these inflammatory cytokines and chemokine induced by IL-33. These findings demonstrate that ST2 is present in human corneal epithelial cells, and IL-33/ST2 signaling plays an important role in regulating IL-33 induced inflammatory responses in ocular surface.

Macrophage death in advanced lesion has been confirmed to play an important role in plaque instability. However, the mechanism underlying lesion macrophage death still remains largely unknown.Immunohistochemistry showed that caspase-1 activated in advanced lesion and co-located with macrophages and TUNEL positive reaction. In in-vitro experiments showed that ox-LDL induced caspase-1 activation and this activation was required for ox-LDL induced macrophages lysis, IL-1β and IL-18 production as well as DNA fragmentation. Mechanism experiments showed that CD36 and NLRP3/caspase-1/pathway involved in ox-LDL induced macrophage pyroptosis.Our study here identified a novel cell death, pyroptosis in ox-LDL induced human macrophage, which may be implicated in lesion macrophages death and play an important role in lesion instability.

Flowers of ethylene-sensitive ornamental plants transformed with ethylene-insensitive 1-1(etr1-1), a mutant ethylene receptor first isolated from Arabidopsis, are known to have longer shelf lives. We have generated petunia plants in which the etr1-1 gene was over-expressed under the control of a chemically-inducible promoter, which would allow expression of etr1-1 to be initiated at the desired time and stage of development. Here, we showed that transgenic plants grew and developed normally without a chemical inducer. Semi-quantitative RT-PCR demonstrated that the abundance of transcripts of Arabidopsis etr1-1 gene was substantially induced in flowers with 30 μM dexamethasone (DEX). Consequently, t he life of the flowers was almost doubled and the peak of ethylene production was delayed. We compared gene expression changes of petals with DEX to those without DEX at 24 h and 48 h by microarray. Our results indicated that transcripts of many putative genes encoding transcription factors were down-regulated by etr1-1 induced expression at the early stage. In addition, putative genes involved in gibberellin biosynthesis, response to jasmonic acid/gibberellins stimulus, cell wall modification, ethylene biosynthesis, and cell death were down-regulated associating with etr1-1 induced expression. We investigated time-course gene expression profiles and found two profiles which displayed totally opposite expression patterns under these two treatments. In these profiles, 'the regulation of transcription' was predominant in GO categories. Taking all results together, we concluded those transcription factors down-regulated at early stage might exert a major role in regulating the senescence process which were consequently characterized by cell wall modification and cell death.

Klotho (KL) expression is down-regulated in the renal tissues of chronic kidney disease (CKD) animal models and patients with end-stage renal disease. The putative role of KL promoter hypermethylation in the progression of CKD remains unclear. The present study aimed to determine renal and peripheral blood mononuclear cells (PBMC) levels of KL promoter methylation and analyze their relationship with clinical and histological severity in patients with CKD. Using bisulfite pyrosequencing, renal and PBMC levels of KL promoter methylation were quantified in 47 patients with CKD. 47 nephrectomy specimens of patients with renal cell carcinoma and 48 PBMC specimens of healthy volunteers were used as renal tissue and PBMC controls, respectively. Renal expression of KL protein was assayed by immunohistochemistry staining. Receiver operating characteristic (ROC) curve was used to identify the optimal cut-off value of PBMC KL promoter methylation level for renal KL promoter hypermethylation. Higher levels of KL promoter methylation were observed in renal tissue and PBMC in patients with CKD compared with controls (8.79±3.24 vs. 5.17±1.11%, P