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Abstract Deep learning analysis of electrocardiography (ECG) may predict cardiovascular outcomes. We present a novel multi-task deep learning model, the ECG-MACE, which predicts the one-year first-ever major adverse cardiovascular events (MACE) using 2,821,889 standard 12-lead ECGs, including training (n = 984,895), validation (n = 422,061), and test (n = 1,414,933) sets, from Chang Gung Memorial Hospital database in Taiwan. Data from another independent medical center (n = 113,224) was retrieved for external validation. The model’s performance achieves AUROCs of 0.90 for heart failure (HF), 0.85 for myocardial infarction (MI), 0.76 for ischemic stroke (IS), and 0.89 for mortality. Furthermore, it outperforms the Framingham risk score at 5-year MACEs and 10-year mortality prediction. Over 10-year follow-ups, the model-predicted-positive group exhibits significantly higher MACE incidences than the model-predicted-negative group (relative incidence ratio: HF: 15.28; MI: 7.87; IS: 4.74; mortality: 13.18). Using solely ECGs, ECG-MACE effectively predicts one-year events and exhibits long-term anticipation. It provides potential applications in preventive medicine.

Background: Electrocardiogram (ECG) abnormalities have demonstrated potential as prognostic indicators of patient survival. However, the traditional statistical approach is constrained by structured data input, limiting its ability to fully leverage the predictive value of ECG data in prognostic modeling. Methods: This study aims to introduce and evaluate a deep-learning model to simultaneously handle censored data and unstructured ECG data for survival analysis. We herein introduce a novel deep neural network called ECG-surv, which includes a feature extraction neural network and a time-to-event analysis neural network. The proposed model is specifically designed to predict the time to 1-year mortality by extracting and analyzing unique features from 12-lead ECG data. ECG-surv was evaluated using both an independent test set and an external set, which were collected using different ECG devices. Results: The performance of ECG-surv surpassed that of the Cox proportional model, which included demographics and ECG waveform parameters, in predicting 1-year all-cause mortality, with a significantly higher concordance index (C-index) in ECG-surv than in the Cox model using both the independent test set (0.860 [95% CI: 0.859–0.861] vs. 0.796 [95% CI: 0.791–0.800]) and the external test set (0.813 [95% CI: 0.807–0.814] vs. 0.764 [95% CI: 0.755–0.770]). ECG-surv also demonstrated exceptional predictive ability for cardiovascular death (C-index of 0.891 [95% CI: 0.890–0.893]), outperforming the Framingham risk Cox model (C-index of 0.734 [95% CI: 0.715–0.752]). Conclusion: ECG-surv effectively utilized unstructured ECG data in a survival analysis. It outperformed traditional statistical approaches in predicting 1-year all-cause mortality and cardiovascular death, which makes it a valuable tool for predicting patient survival.

Abstract Objectives The objectives of this study were to present an accessible C-shaped partial stapled hemorrhoidopexy (C-PSH) in the treatment of grade IV hemorrhoids and to assess long-term outcomes of this technique compared with circular stapled hemorrhoidopexy (CSH). Methods Conventional CSH kits combined with an intestinal spatula were used for performing C-PSH. A total of 256 patients with grade IV hemorrhoids referred to Hangzhou Third People's Hospital between January 2016 and June 2017 were obtained: 122 (47.7%) with C-PSH, and 134 (52.3%) with CSH. After propensity score matching, 222 patients (111 in C-PSH group and 111 in CSH group) were ultimately analyzed. The primary outcome was the five-year recurrence rate of hemorrhoids. Secondary outcomes included intraoperative outcomes, postoperative outcomes and complications. Results The operative time in the C-PSH group was slightly longer than that in the CSH group (p 0.05). Multivariate Cox regression analysis revealed that constipation was an independent prognostic factor for hemorrhoidal recurrence. Conclusions The accessible C-PSH seems to be a safe and effective technique in managing grade IV hemorrhoids. It has advantages in alleviating postoperative pain at first defecation, fecal urgency and major complications compared with CSH. It could be an alternative technique in the treatment of grade IV hemorrhoids.

The need for precise radio telescope pointing has driven great attention to investigating the effect of antenna local deformation or irregularity, such as unevenness in the azimuth track. Although the track-alidade interaction model is commonly used to investigate the pointing effect of track unevenness (such as the works on DSN 34 m antennas and the Green Bank Telescope), few experiments have been done to test the effectiveness of this model independently from the overall pointing model. To address this issue, a method utilizing an optical pointing telescope (OPT) for determining the impact of track unevenness on pointing is proposed. This method uses a group of reference pointing data collected by an OPT mounted at the bottom of the antenna alidade to extract the twist effect of the alidade from the radio telescope pointing data, thus compared with the predicted twist by the track-alidade model. This method was applied to the 26 meter Nanshan Radio Telescope (NSRT 26 m), achieving good agreement with the model-predicted values.

Abstract Background Abnormal miRNA and mRNA expression and dysregulated immune microenvironment have been found to frequently induce the progression of hepatocellular carcinoma (HCC) in recent reports. In particular, the immune-related competing endogenous RNAs (ceRNA) mechanism plays a crucial role in HCC progression. However, the underlying mechanisms remain unclear. Methods Differentially expressed immune-related genes were obtained from the Immport, GEO, and TCGA databases. The mRNA and protein expression levels in HCC tissues and adjacent normal tissues were confirmed, and we further investigated the methylation levels of these biomarkers to explore their function. Then, the TIMER and TISCH databases were used to assess the relationship between immune infiltration and hub genes. Survival analysis and univariate and multivariate Cox models were used to evaluate the association between hub genes and HCC diagnosis. Hub gene expression was experimentally validated in six HCC cell lines and 15 HCC samples using qRT-PCR and immunohistochemistry. The hub genes were uploaded to DSigDB for drug prediction enrichment analysis. Results We identified that patients with abnormal miRNAs (hsa-miR-125b-5p and hsa-miR-21-5p) and their targeted genes (NTF3, PSMD14, CD320, and SORT1) had a worse prognosis. Methylation analysis of miRNA-targeted genes suggested that alteration of methylation levels is also a factor in the induction of tumorigenesis. We also found that the development of HCC progression caused by miRNA-mRNA interactions may be closely correlated with the infiltration of immunocytes. Moreover, the GSEA, GO, and KEGG analysis suggested that several common immune-related biological processes and pathways were related to miRNA-targeted genes. The results of qRT-PCR, immunohistochemistry, and western blotting were consistent with our bioinformatics results, suggesting that abnormal miRNAs and their targeted genes may affect HCC progression. Conclusions Briefly, our study systematically describes the mechanisms of miRNA-mRNA interactions in HCC and predicts promising biomarkers that are associated with immune filtration for HCC progression.

Objective To establish an index system for the evaluation on regional health emergency response capability in digital environment and to provide a reference to decision makers in relevant management practice. MethodsAn index system for evaluating regional health emergency response capacity in digital environment was preliminarily established through literature research. Two rounds of Delphi expert consultation were conducted among 15 professionals to assess the 16 first, 61 second, and 138 third level indexes covering 3 dimensions of process, structure and outcome. All the indexes were screened with boundary value method based on the experts′ assessments and the weight of each index was calculated with analytic hierarchy process (AHP) and proportional distribution method. ResultsFor the two rounds of consultation, the positive coefficients of experts reached 100%; the authority coefficients of the experts were 0.823 and 0.840 and the coordination coefficients of expert opinions were 0.141 and 0.303 (all P < 0.05). The finally established index system includes 8 first, 32 second, and 172 third level indicators, with the highest weight of 0.1961 for ‘emergency support′, 0.5903 for ‘training′, and 1.0000 for ‘local health administrative department′s timely report of information on rapid manipulation of a regional health emergency to local government and to superior health administrative department′s among the first, second, third level indicators, respectively. ConclusionThe established index system for the evaluation on regional health emergency response capability in digital environment is of clear hierarchy, indicators with reasonable weights, and practicability and the index system could be used in the evaluation-related survey, management and decision-making.

Abstract Primary liver cancer (PLC) is a common gastrointestinal malignancy worldwide. While hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are two major pathologic types of PLC, combined HCC and ICC (cHCC-ICC) is a relatively rare subtype that shares both hepatocyte and cholangiocyte differentiation. However, the molecular feature of this unique tumor remains elusive because of its low incidence and lack of a suitable animal model. Herein, we generated a novel spontaneous cHCC-ICC model using a Sleeping Beauty-dependent transposon plasmid co-expressing oncogenic Myc and AKT1 and a CRISPR-Cas9 plasmid expressing single-guide RNA targeting p53 into mouse hepatocytes via in situ electroporation. The histological and transcriptional analysis confirmed that this model exhibits cHCC-ICC features and activates pathways committing cHCC-ICC formation, such as TGF-β, WNT, and NF-κB. Using this model, we further screened and identified LAMB1, a protein involved in cell adhesion and migration, as a potential therapeutic target for cHCC-ICC. In conclusion, our work presents a novel genetic cHCC-ICC model and provides new insights into cHCC-ICC.

Abstract Background Though circular RNAs (circRNAs) are the key regulators in tumor carcinogenesis, they remain largely unexplored in hepatocellular carcinoma (HCC). Methods The expression of RanGAP1-derived circRNAs (circ_0063531, circ_0063534, circ_0063513, circ_0063518, circ_0063507, circ_0063723) were evaluated in eight paired HCC and normal tissues, and the correlation between circRanGAP1 (circ_0063531) expression and clinicopathological characteristics in 40 HCC patients was determined. The association between miR-27b-3p and circRanGAP1 or NRAS was predicted using bioinformatics analysis. The expression of circRanGAP1, miR-27b-3p, and NRAS were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The potential oncogenic role of circ-RanGAP1 was assessed using CCK-8, colony formation, transwell assays in vitro, subcutaneous tumor mouse model, vein tail metastatic model, and orthotopically implanted intrahepatic HCC model in vivo. Luciferase reporter and RNA immunoprecipitation (RIP) assays were used to explore the binding site between miR-27b-3p and circ-RanGAP1 or NRAS. Protein expression was detected using western blotting. The localization of miR-27b-3p and circ-RanGAP1 was investigated using fluorescence in situ hybridization (FISH). The level of immune infiltration was assessed by bioinformatics analysis, flow cytometry, and orthotopically implanted intrahepatic HCC models. Results Here, we found elevated circRanGAP1 in the cells and clinical tissues of patients with HCC. Increased circRanGAP1 levels are associated with enlarged tumors and the advanced stage of TNM. CircRanGAP1 promotes the growth, migration, and HCC cell invasion, concurrently with the growth and metastasis of tumors in-vivo. Moreover, circRanGAP1 is mainly located inside the cytoplasm. Mechanistically, circRanGAP1 as an oncogene promotes HCC progression by miR-27b-3p/NRAS/ERK axis, furthermore, affects the infiltration level of tumor-associated macrophages probably by sponging miR-27b-3p. Immune infiltration analysis shows that NRAS is positively correlated with the levels of CD68+ tumor-associated macrophages in HCC samples and that NRAS and CD68 are related to the poor outcome of HCC. Conclusion These results reveal that circRanGAP1 is a HCC oncogene that function by the miR-27b-3p/NRAS/ERK axis and regulates the infiltration levels of tumor-associated macrophages by sponging miR-27b-3p. Therefore, circRANGAP1/ NRAS axis may be an important potential treatment target against HCC.

BackgroundThe risk of mortality is relatively high among patients who visit the emergency department (ED), and stratifying patients at high risk can help improve medical care. This study aimed to create a machine-learning model that utilizes the standard 12-lead ECG to forecast acute mortality risk in ED patients.MethodsThe database included patients who visited the EDs and underwent standard 12-lead ECG between October 2007 and December 2017. A convolutional neural network (CNN) ECG model was developed to classify survival and mortality using 12-lead ECG tracings acquired from 345,593 ED patients. For machine learning model development, the patients were randomly divided into training, validation and testing datasets. The performance of the mortality risk prediction in this model was evaluated for various causes of death.ResultsPatients who visited the ED and underwent one or more ECG examinations experienced a high incidence of 30-day mortality [18,734 (5.42%)]. The developed CNN model demonstrated high accuracy in predicting acute mortality (hazard ratio 8.50, 95% confidence interval 8.20–8.80) with areas under the receiver operating characteristic (ROC) curve of 0.84 for the 30-day mortality risk prediction models. This CNN model also demonstrated good performance in predicting one-year mortality (hazard ratio 3.34, 95% confidence interval 3.30–3.39). This model exhibited good predictive performance for 30-day mortality not only for cardiovascular diseases but also across various diseases.ConclusionsThe machine learning-based ECG model utilizing CNN screens the risks for 30-day mortality. This model can complement traditional early warning scoring indexes as a useful screening tool for mortality prediction.

Abstract Background Hepatocellular carcinoma (HCC) is one of the most malignant tumors to threaten human life, and the survival rate remains low due to delayed diagnosis. Meanwhile, lncRNAs have great potential for application in tumor prognosis, therefore relevant research in hepatocellular carcinoma is indispensable. Methods Based on the EZH2 expression, the differentially expressed lncRNAs DElncRNAs), miRNAs (DEmiRNAs), and mRNAs (DEmRNAs) were identified in hepatocellular carcinoma by using the TCGA database. Bioinformatics technology was utilized to determine the effect of key genes in HCC progression. The methylation and immune infiltration analyses were performed to explore the underlying function of hub genes. Finally, cellular function experiments were performed to investigate the association between identified genes and biological phenotypes in HCC. Results lncRNA-AC079061.1, hsa-miR-765, and VIPR1 were identified as independent factors that affect the prognosis of hepatocellular carcinoma. The immune infiltration analyses revealed that lncRNA-AC079061.1 can alter the immune microenvironment and thus inhibit the development of HCC by regulating the expression of an immune-related gene (VIPR1). Methylation analyses demonstrated that VIPR1 expression is negatively related to the methylation level in HCC. Experimental results suggested that lncRNA-AC079061.1 and VIPR1 were frequently downregulated in HCC cells, while hsa-miR-765 was significantly upregulated. Moreover, the lncRNA-AC079061.1/VIPR1 axis suppressed the proliferation and invasion of HCC cells. Conclusion The present study identified the lncRNA-AC079061.1/VIPR1 axis as a novel biomarker that inhibited the proliferation and invasion of hepatocellular carcinoma, affecting the ultimate disease outcome.

The aim of this research is to investigate lipid-lowering influence of dietary ginger (Zingier officinales Rocs) polysaccharides (GPS) on hyperlipidemia rats. Rat models with hyperlipidemia was established by high-fat food diet (HFD). Comparing to GP-negative model group, GPS attenuated several effects of HFD feeding, including the levels of blood lipid biochemistry, serum inflammatory markers (tumor necrosis factor TNF-a, interleukin IL-6), antioxidant capacity (superoxide dismutase SOD, glutathione peroxidase GSH-Px, total antioxidant capacity T-AOC, propylene dialdehyde MDA), uric acid and immune index. 16 S rDNA gene sequencing of fecal samples showed that GPS increased the growth of Akkermansia muciniphila and decreased the proportion of Firmicutes to Bacteroidetes; This changes in microbial community structure can help prevent diet-induced metabolic disease. These results suggest that GPs may act on the gut, changing the structure of the gut microbial community, thereby reducing intestinal and systemic inflammation, thus improved metabolic outcomes.

BackgroundLeft ventricular systolic dysfunction (LVSD) characterized by a reduced left ventricular ejection fraction (LVEF) is associated with adverse patient outcomes. We aimed to build a deep neural network (DNN)-based model using standard 12-lead electrocardiogram (ECG) to screen for LVSD and stratify patient prognosis.MethodsThis retrospective chart review study was conducted using data from consecutive adults who underwent ECG examinations at Chang Gung Memorial Hospital in Taiwan between October 2007 and December 2019. DNN models were developed to recognize LVSD, defined as LVEF

Abstract Background Tumor-associated macrophages (TAM) are immunosuppressive cells that contribute to impaired anti-cancer immunity. Iron plays a critical role in regulating macrophage function. However, it is still elusive whether it can drive the functional polarization of macrophages in the context of cancer and how tumor cells affect the iron-handing properties of TAM. In this study, using hepatocellular carcinoma (HCC) as a study model, we aimed to explore the effect and mechanism of reduced ferrous iron in TAM. Methods TAM from HCC patients and mouse HCC tissues were collected to analyze the level of ferrous iron. Quantitative real-time PCR was used to assess M1 or M2 signature genes of macrophages treated with iron chelators. A co-culture system was established to explore the iron competition between macrophages and HCC cells. Flow cytometry analysis was performed to determine the holo-transferrin uptake of macrophages. HCC samples from The Cancer Genome Atlas (TCGA) were enrolled to evaluate the prognostic value of transferrin receptor (TFRC) and its relevance to tumor-infiltrating M2 macrophages. Results We revealed that ferrous iron in M2-like TAM is lower than that in M1-like TAM. In vitro analysis showed that loss of iron-induced immunosuppressive M2 polarization of mouse macrophages. Further experiments showed that TFRC, the primary receptor for transferrin-mediated iron uptake, was overexpressed on HCC cells but not TAM. Mechanistically, HCC cells competed with macrophages for iron to upregulate the expression of M2-related genes via induction of HIF-1α, thus contributing to M2-like TAM polarization. We further clarified the oncogenic role of TFRC in HCC patients by TCGA. TFRC is significantly increased in varieties of malignancies, including HCC, and HCC patients with high TFRC levels have considerably shortened overall survival. Also, TFRC is shown to be positively related to tumor-infiltrating M2 macrophages. Conclusions Collectively, we identified iron starvation through TFRC-mediated iron competition drives functional immunosuppressive polarization of TAM, providing new insight into the interconnection between iron metabolism and tumor immunity.

Sorafenib resistance is often developed and impedes the benefits of clinical therapy in hepatocellular carcinoma (HCC) patients. However, the relationship between sorafenib resistance and tumor immune environment and adjuvant drugs for sorafenib-resistant HCC are not systemically identified. This study first analyzed the expression profiles of sorafenib-resistant HCC cells to explore immune cell infiltration levels and differentially expressed immune-related genes (DEIRGs). The prognostic value of DEIRGs was analyzed using Cox regression and Kaplan–Meier analysis based on The Cancer Genome Atlas. The primary immune cells infiltrated in sorafenib-resistant HCC mice were explored using flow cytometry (FCM). Finally, small-molecule drugs for sorafenib-resistant HCC treatment were screened and validated by experiments. The CIBERSORT algorithm and mice model showed that macrophages and neutrophils are highly infiltrated, while CD8+ T cells are downregulated in sorafenib-resistant HCC. Totally, 34 DEIRGs were obtained from sorafenib-resistant and control groups, which were highly enriched in immune-associated biological processes and pathways. NR6A1, CXCL5, C3, and TGFB1 were further identified as prognostic markers for HCC patients. Finally, nalidixic acid was identified as a promising antagonist for sorafenib-resistant HCC treatment. Collectively, our study reveals the tumor immune microenvironment changes and explores a promising adjuvant drug to overcome sorafenib resistance in HCC.

The Main Steam Valve Set (MSVS) is the key protection device for nuclear power plants, whose dynamic characteristics are directly related to the security of the secondary circuit system especially under overpressure conditions. Dynamic mesh technology is used in this work to capture the dynamic characteristics of the interconnected pilot valves on the MSVS with different inlet diameters. The research results show that increasing inlet diameter can significantly reduce the opening time of the pilot valves, but it will also increase the fluid force of valve stem during the opening process as well as the movement speed at the maximum opening. The pressure of the pilot valves during the opening process is then analyzed. It can be seen that changing the inlet diameter will affect the inlet annular throttling area, thereby changing the pressure rise speed in the external chamber of the valve stem and the inner cavity of the valve body, thereby affecting the total response time. This work provides a reference for the selection of the pilot valve diameter in MSVS and helps to improve the overpressure protection capability of MSVS.

Purpose: Blast lung injury (BLI) is the most common damage resulted from explosion-derived shock wave in military, terrorism and industrial accidents. However, the molecular mechanisms underlying BLI induced by shock wave are still unclear. Methods: In this study, a goat BLI model was established by a fuel air explosive power. The key genes involved in were identified. The goats of the experimental group were fixed on the edge of the explosion cloud, while the goats of the control group were 3 km far away from the explosive environment. After successful modeling for 24 h, all the goats were sacrificed and the lung tissue was harvested for histopathological observation and RNA sequencing. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analysis were performed to identify the main enriched biological functions of differentially expressed genes (DEGs). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the consistency of gene expression. Results: Of the sampled goat lungs, 895 genes were identified to be significantly differentially expressed, and they were involved in 52 significantly enriched GO categories. KEGG analysis revealed that DEGs were highly enriched in 26 pathways, such as cytokine-cytokine receptor interaction, antifolate resistance, arachidonic acid metabolism, amoebiasis and bile secretion, JAK-STAT, and IL-17 signaling pathway. Furthermore, 15 key DEGs involved in the biological processes of BLI were confirmed by qRT-PCR, and the results were consistent with RNA sequencing. Conclusion: Gene expression profiling provide a better understanding of the molecular mechanisms of BLI, which will help to set strategy for treating lung injury and preventing secondary lung injury induced by shock wave.

CO2-enhanced oil recovery (CO2-EOR) technology is the process of capturing CO2, transporting the captured CO2 to a storage site, and injecting the captured CO2 into an oil field to enhance oil recovery. CO2-EOR technology can greatly increase the profitability of oil fields. It is also a promising method for reducing CO2 emission and improving the environment. For these reasons, this technology has become increasingly important for the development of the global oil industry and has been widely explored. However, CO2 injection significantly increases the risk of corrosion failure of tubing steel. As such, the effect of CO2 on the stress corrosion behavior of tubing steel should be investigated. In this study, the effect of CO2 partial pressure (\begin{document}$P_{{\rm{CO}}_2} $\end{document}) on the stress corrosion behavior of N80 steel was examined using an immersion test, a surface analysis technique, and an electrochemical technology. Results reveal that the influence of \begin{document}$P_{{\rm{CO}}_2} $\end{document} on the corrosion rate has an inflection point of approximately 1 MPa. When \begin{document}$P_{{\rm{CO}}_2} $\end{document} is 1 MPa, the corrosion product film can form at a faster rate, and the corrosion current density of N80 steel decreases as \begin{document}$P_{{\rm{CO}}_2} $\end{document} increases. The pH of the solution decreases continuously when CO2 is dissolved in solution. Consequently, the stress corrosion cracking (SCC) of N80 tubing steel occurs in an annulus environment. The SCC mechanism of N80 steel in the annulus environment of CO2 injection wells is the combination of anodic dissolution (AD) and hydrogen embrittlement (HE). Localized AD (pitting) is dominant in SCC at the initiation stage, and SCC is most likely initiated at \begin{document}$P_{{\rm{CO}}_2} $\end{document} of 1 MPa. At the crack growth stage, HE has a stronger effect on SCC than AD, the SCC easily grows with a high \begin{document}$P_{{\rm{CO}}_2} $\end{document}, and SCC sensitivity further improves.

Resistance to powdery mildew is an important trait of interest in many wheat breeding programs. The information on genes conferring resistance to powdery mildew in wheat cultivars is useful in parental selection. Winter wheat breeding line DH51302 derived from Liangxing 99 and cultivar Shimai 26 derived from Jimai 22 showed identical infection patterns against 13 isolates of Blumeria graminis f. sp. tritici (Bgt) that causes wheat powdery mildew. DH51302 and Shimai 26 were crossed to a powdery mildew susceptible cultivar Zhongzuo 9504 and the F2:3 families were used in molecular localization of the resistance genes. Fourteen polymorphic markers, which were linked to Pm52 from Liangxing 99, were used to establish the genetic linkage maps for the resistance genes PmDH51302 and PmSM26 in DH51302 and Shimai 26, respectively. These genes were placed in the same genetic interval where Pm52 resides. Analysis of gene-linked molecular markers indicated that PmDH51302 and PmSM26 differed from other powdery mildew resistance genes on chromosome arm 2BL, such as Pm6, Pm33, Pm51, MlZec1, MlAB10, and Pm64. Based on the results of reaction patterns to different Bgt isolates and molecular marker localization, together with the pedigree information, DH51302 and Shimai 26 carried the same gene, Pm52, which confers their resistance to powdery mildew.

Abstract Background Periodontitis was reported to be associated with inflammatory bowel disease (IBD). However, the association between them has not been firmly established in the existing literature. Therefore, this meta-analysis was conducted to evaluate the relationship between periodontitis and IBD. Methods Electronic databases were searched for publications up to August 1, 2019 to include all eligible studies. The pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated to determine the association between periodontal disease and IBD using a random or fixed effects model according to heterogeneity. Results Six eligible studies involving 599 IBD patients and 448 controls were included. The pooled OR between periodontitis and IBD was 3.17 (95% CI: 2.09–4.8) with no heterogeneity observed (I 2 = 0.00%). The pooled ORs were 3.64 (95% CI: 2.33–5.67) and 5.37 (95% CI: 3.30–8.74) for the associations between periodontitis and the two sub-categories of IBD, Crohn’ s disease and ulcerative colitis, respectively. Conclusions The results demonstrated that periodontitis was significantly associated with IBD. However, the mechanisms underlying periodontitis and IBD development are undetermined. Further studies are needed to elucidate this relationship.

Hepatocellular carcinoma (HCC) accounts for the predominant form of liver malignancy and presents a leading cause of cancer-related death globally. Sorafenib (SOR), a first-line targeted drug for advanced HCC treatment, has a battery of untoward side effects. Photothermal therapy (PTT) has been utilized as an effective adjuvant in synergy with other approaches. However, little is known about the tumoricidal efficacy of combining SOR with PTT for HCC. Herein, a novel versatile nanoparticle, Cu2−xSe@SOR@PEG (CSP), that is based on a photothermal Cu2−xSe core and SOR for simultaneously reinforcing PTT and reducing the adverse effects of SOR was constructed. The synthesized CSP exhibited a remarkably enhanced therapeutic effect upon 808 nm laser irradiation via dampening HCC cell propagation and metastasis and propelling cell apoptosis. The intravenous administration of CSP substantially suppressed tumor growth in a xenograft tumor mouse model. It was noted that the CSP manifested low toxicity and excellent biocompatibility. Together, this work indicates a promising and versatile tool that is based on synergistic PTT and molecular-targeted therapy for HCC management.

BackgroundThere have been reports of increasing azole resistance in Candida tropicalis, especially in the Asia-Pacific region. Here we report on the epidemiology and antifungal susceptibility of C. tropicalis causing invasive candidiasis in China, from a 9-year surveillance study.MethodsFrom August 2009 to July 2018, C. tropicalis isolates (n = 3702) were collected from 87 hospitals across China. Species identification was carried out by mass spectrometry or rDNA sequencing. Antifungal susceptibility was determined by Clinical and Laboratory Standards Institute disk diffusion (CHIF-NET10–14, n = 1510) or Sensititre YeastOne (CHIF-NET15–18, n = 2192) methods.ResultsOverall, 22.2% (823/3702) of the isolates were resistant to fluconazole, with 90.4% (744/823) being cross-resistant to voriconazole. In addition, 16.9 (370/2192) and 71.7% (1572/2192) of the isolates were of non-wild-type phenotype to itraconazole and posaconazole, respectively. Over the 9 years of surveillance, the fluconazole resistance rate continued to increase, rising from 5.7 (7/122) to 31.8% (236/741), while that for voriconazole was almost the same, rising from 5.7 (7/122) to 29.1% (216/741), with no significant statistical differences across the geographic regions. However, significant difference in fluconazole resistance rate was noted between isolates cultured from blood (27.2%, 489/1799) and those from non-blood (17.6%, 334/1903) specimens (P-value < 0.05), and amongst isolates collected from medical wards (28.1%, 312/1110) versus intensive care units (19.6%, 214/1092) and surgical wards (17.9%, 194/1086) (Bonferroni adjusted P-value < 0.05). Although echinocandin resistance remained low (0.8%, 18/2192) during the surveillance period, it was observed in most administrative regions, and one-third (6/18) of these isolates were simultaneously resistant to fluconazole.ConclusionThe continual decrease in the rate of azole susceptibility among C. tropicalis strains has become a nationwide challenge in China, and the emergence of multi-drug resistance could pose further threats. These phenomena call for effective efforts in future interventions.

In the field of chemical engineering, when the regeneration recycling process is introduced into the water-using networks (WUNs), several parameters that affect the cost of WUN can be reduced: the consumptions of freshwater and the regenerated water, and the wastewater discharge. However, it is often difficult to design the WUNs involving regeneration recycling and multiple regeneration units. This article introduced a subnetwork-dividing method to design WUNs involving regeneration recycling and multiple regeneration units. This method minimizes the consumption of freshwater and reduces the consumption of regenerated water. The main steps of the proposed method include: dividing of the whole network as pre-regeneration subnetwork and regeneration subnetwork, and design of subnetworks to obtain the final results. The results of a literature example: the consumption of freshwater is 58 t/h and the consumption of regenerated water is 179.143 t/h, it can be seen that method proposed in this paper is simple and effective. The design results obtained by this work are comparable to that obtained in the literatures.

Wheat stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is a devastating disease that can cause severe yield losses. Identification and utilization of stripe rust resistance genes are essential for effective breeding against the disease. Wild emmer accession TZ-2, originally collected from Mount Hermon, Israel, confers near-immunity resistance against several prevailing Pst races in China. A set of 200 F6:7 recombinant inbred lines (RILs) derived from a cross between susceptible durum wheat cultivar Langdon and TZ-2 was used for stripe rust evaluation. Genetic analysis indicated that the stripe rust resistance of TZ-2 to Pst race CYR34 was controlled by a single dominant gene, temporarily designated YrTZ2. Through bulked segregant analysis (BSA) with SSR markers, YrTZ2 was located on chromosome arm 1BS flanked by Xwmc230 and Xgwm413 with genetic distance of 0.8 cM (distal) and 0.3 cM (proximal), respectively. By applying wheat 90K iSelect SNP genotyping assay, 11 polymorphic loci (consisting of 250 SNP markers) closely linked to YrTZ2 were identified. YrTZ2 was further delimited into a 0.8-cM genetic interval between SNP marker IWB19368 and SSR marker Xgwm413, and co-segregated with SNP marker IWB28744 (co-segregated with 28 SNP). Comparative genomics analyses revealed high level of collinearity between the YrTZ2 genomic region and the orthologous region of Aegilops tauschii 1DS. The genomic region between loci IWB19368 and IWB31649 harboring YrTZ2 is orthologous to a 24.5-Mb genomic region between AT1D0112 and AT1D0150, spanning 15 contigs on chromosome 1DS. The genetic and comparative maps of YrTZ2 provide a framework for map-based cloning and marker-assisted selection of YrTZ2.

Cereal cyst nematode (Heterodera avenae, CCN) distributes worldwide and has caused severe damage to cereal crops, and a model host will greatly aid in the study of this nematode. In this research, we assessed the sensitivity of 25 inbred lines of Brachypodium distachyon to H. avenae from Beijing, China. All lines of B. distachyon were infested by second-stage juveniles (J2s) of H. avenae from Daxing District of Beijing population, but only 13 inbred lines reproduced 0.2–3 cysts/plant, showing resistance. The entire root system of the infested B. distachyon appeared smaller and the fibrous roots were shorter and less numerous. We found that a dose of 1 000 J2s of H. avenae was sufficient for nematode infestation. We showed that Koz-1 of B. distachyon could reproduce more cysts than TR2A line. Line Koz-1 also supported the complete life cycles of 5 CCN geographical populations belonging to the Ha1 or Ha3 pathotype group. Our results suggest that B. distachyon is a host for CCN.

Powdery mildew, caused by Blumeria graminis f. sp. tritici (Bgt), is one of the most damaging diseases to wheat in the world. The cultivation of resistant varieties of wheat is essential for controlling the powdery mildew epidemic. Wheat landraces are important resources of resistance to many diseases. Mapping powdery mildew resistance genes from wheat landraces will promote the development of new varieties with disease resistance. The Chinese wheat landrace Baiyouyantiao possesses characteristic of disease resistance to powdery mildew. To identify the resistance gene in this landrace, Baiyouyantiao was crossed with the susceptible cultivar Jingshuang 16 and seedlings of parents and F1, BC1, F2, and F2:3 were tested with Bgt isolate E09. The genetic results showed that the resistance of Baiyouyantiao to E09 was controlled by a single recessive gene, tentatively designated PmBYYT. An Illumina wheat 90K single-nucleotide polymorphism (SNP) array was applied to screen polymorphisms between F2-resistant and F2-susceptible DNA bulks for identifying the chromosomal location of PmBYYT. A high percentage of polymorphic SNPs between the resistant and susceptible DNA bulks was found on chromosome 7B, indicating that PmBYYT may be located on this chromosome. A genetic linkage map of PmBYYT consisting of two simple sequence repeat markers and eight SNP markers was developed. The two flanking markers were SNP markers W7BL-8 and W7BL-15, with genetic distances of 3 and 2.9 cM, respectively. The results of this study demonstrated the rapid characterization of a wheat disease resistance gene and SNP marker development using the 90K SNP assay. The flanking markers of gene PmBYYT will benefit marker-assisted selection (MAS) and map-based cloning in breeding wheat cultivars with powdery mildew resistance.

Powdery mildew, caused by Blumeria graminis f. sp. tritici, is one of the most severe wheat diseases. Mining powdery mildew resistance genes in wheat cultivars and their appliance in breeding program is a promising way to control this disease. Genetic analysis revealed that a single dominant resistance gene named PmTm4 originated from Chinese wheat line Tangmai 4 confers resistance to prevailing isolates of B. graminis f. sp. tritici isolate E09. Detailed comparative genomics analyses helped to develop closely linked markers to PmTm4 and a fine genetic map was constructed using large F2 population, in which PmTm4 was located into a 0.66-cM genetic interval. The orthologous subgenome region of PmTm4 in Aegilops tauschii was identified, and two resistance gene analogs (RGA) were characterized from the corresponding sequence scaffolds of Ae. tauschii draft assembly. The closely linked markers and identified Ae. tauschii orthologs in the mapping interval provide an entry point for chromosome landing and map-based cloning of PmTm4.

Pre-harvest sprouting (PHS) occurs frequently in most of the wheat cultivation area worldwide, which severely reduces yield and end-use quality, resulting in substantial economic loss. In this study, quantitative trait loci (QTL) for PHS resistance were mapped using an available high-density single nucleotide polymorphism (SNP) and simple sequence repeat (SSR) genetic linkage map developed from a 269 recombinant inbred lines (RILs) population of Yanda 1817×Beinong 6. Using phenotypic data on two locations (Beijing and Shijiazhuang, China) in two years (2012 and 2013 harvesting seasons), five QTLs, designated as QPhs.cau-3A.1, QPhs.cau-3A.2, QPhs.cau-5B, QPhs.cau-4A, and QPhs.cau-6A, for PHS (GP) were detected by inclusive composite interval mapping (ICIM) (LOD≥2.5). Two major QTLs, QPhs.cau-3A.2 and QPhs.cau-5B, were mapped on 3AL and 5BS chromosome arms, explaining 6.29–21.65% and 4.36–5.94% of the phenotypic variance, respectively. Precise mapping and comparative genomic analysis revealed that the TaVp-1A flanking region on 3AL is responsible for QPhs.cau-3A.2. SNP markers flanking QPhs.cau-3A.2 genomic region were developed and could be used for introgression of PHS tolerance into high yielding wheat varieties through marker-assisted selection (MAS).

A new method is proposed in this article to design the property-based water-using networks with reuse. The operator potential concept and a linear programming approach are combined in the design procedure. The precedence order of demands is determined by the values of the operator potential of demands. The allocations of the sources to the demands are decided with a linear programming approach. The results of two literature examples obtained with the proposed method are comparable to that obtained with graphical or mathematical programming method in the literature. In addition, the proposed method can be applied to both single and multiple property systems.

This study aimed to determine the global distribution and molecular characteristics of carbapenemase-producing Pseudomonas aeruginosa isolates. A total of 328 (11.1%, 328/2953) carbapenemase-producing P. aeruginosa isolates from humans were obtained from public databases as of October 2019. Of which, the blaVIM and blaIMP genes were the most prevalent carbapenemases in the P. aeruginosa isolates. These carbapenemase-producing P. aeruginosa isolates possessed 34 distinct sequence types (STs) and six predominated: ST357, ST823, ST308, ST233, ST175 and ST111. The ST357 and ST823 isolates were primarily found detected in Asia and all ST175 isolates were found in Europe. The ST308, ST233 and ST111 isolates were spread worldwide. Further, all ST823 isolates and the majority of ST111, ST233 and ST175 isolates carried blaVIM but ST357 isolates primarily carried blaIMP. ST308 isolates provide a key reservoir for the spread of blaVIM, blaIMP and blaNDM. WGS analysis revealed that ST111 carried a great diversity of ARG types (n = 23), followed by ST357 (n = 21), ST308 (n = 19), ST233 (n = 18), ST175 (n = 14) and ST823 (n = 10). The ST175 isolates carried a more diversity and frequent of aminoglycoside ARGs, and ST233 isolates harbored more tetracycline ARGs. Our findings revealed that different carbapenem resistance genes were distributed primarily in variant STs of P. aeruginosa isolates, these isolates also possessed an extensive geographical distribution that highlights the need for surveillance studies that detect carbapenemase-producing P. aeruginosa isolates in humans.

Compared to integration of water networks of a few plants separately, the integration of interplant water network can save more freshwater. This paper proposed an iterative method for design of interplant water network of multiple contaminants with an interplant water main by using the Concentration Potential Concepts. The key for design procedure of an interplant water network is to classify all processes into two groups based on reusing the water of the interplant water main or not. Then the design can be simplified into a design of a conventional single plant water integration with a central water main. An example is shown that the design procedure is simple and effective.

Distributed wastewater treatment network (DWTN) has significant advantages over centralised one. This paper mainly reviews the methods proposed by our group for the design of DWTNs. Pinch analysis and mathematical programming methods are briefly discussed as well. By analysing the features of DWTNs, our group pointed out that it is very important to minimize unnecessary stream mixing to reduce the total treatment flowrate of a DWTN. Based on this insight, we proposed a series of design methods for both single and multiple contaminant systems. The constraints on the maximum inlet concentrations of treatment processes were considered as well. The methods of our group can handle complex problems with simple calculation and have clear engineering meaning.

Industrial sites spend a large quantity of energy and emit into the environment a considerable amount of Greenhouse gases (GHG). Heat recovery and power cogeneration at Site level provide important options for energy saving and emission reduction. In designing and optimising Total Site heat recovery and cogeneration, the base indicators related to heat recovery, cogeneration efficiency and operating costs can be advantageously extended to allow designers seeing the complete picture of the system performance. Such additional indicators are suggested in the current work, including capital cost, as well as GHG and Water Footprints. The case study showed that generating an additional 15 t/h of boiler steam (VHP) beyond the 33 t/h that was initially needed, increased power generation by 1.72 MW (112 %), and lowered key targeted intensity indicators of Capital Cost by 7.7 %, GHG Footprint by 31.6 %, and Water Footprint by 44.6 %. These results demonstrate the dynamic link between the Total Site cogeneration system and the extended indicators.

In this study, we investigated the essential criteria for late-onset hypogonadism (LOH) syndrome based on the presence of symptoms associated with low testosterone levels in Han Chinese men. Blood tests for total testosterone (TT) and sex hormone-binding globulin (SHBG) were performed, and the aging male symptoms (AMS) questionnaire was conducted in a randomly selected cohort composed of 944 Chinese men aged 40 to 79 years from nine urban communities. Three sexual symptoms (decreased ability/frequency of sexual activity, decreased number of morning erections, and decreased libido) were confirmed to be related to the total and free testosterone levels. The thresholds for TT were approximately 12.55 nmol l−1 for a decreased ability/frequency to perform sex, 12.55 nmol l−1 for decreased frequency of morning erections, and 14.35 nmol l−1 for decreased sexual desire. The calculated free testosterone (CFT) thresholds for these three sexual symptoms were 281.14, 264.90, and 287.21 pmol l−1 , respectively. TT

Powdery mildew, caused by Blumeria graminis f. sp. tritici, is one of the most devastating wheat diseases. Wild emmer wheat (Triticum turgidum ssp. dicoccoides) is a promising source of disease resistance for wheat. A powdery mildew resistance gene conferring resistance to B. graminis f. sp. tritici isolate E09, originating from wild emmer wheat, has been transferred into the hexaploid wheat line WE4 through crossing and backcrossing. Genetic analyses indicated that the powdery mildew resistance was controlled by a single dominant gene, temporarily designated MlWE4. By mean of comparative genomics and bulked segregant analysis, a genetic linkage map of MlWE4 was constructed, and MlWE4 was mapped on the distal region of chromosome arm 5BL. Comparative genetic linkage maps showed that genes MlWE4, Pm36 and Ml3D232 were co-segregated with markers XBD37670 and XBD37680, indicating they are likely the same gene or alleles in the same locus. The co-segregated markers provide a starting point for chromosome landing and map-based cloning of MlWE4, Pm36 and Ml3D232.

This paper addresses the multiple-input multiple-output (MIMO) control problem with an active deformation adjustment mechanism on a 5-metre deployable antenna panel. An adaptive reduced-dimension fuzzy decoupling (ARDFD) control strategy based on fusion functions is proposed to eliminate the effects uncertainties due to coupled subsystems by designing and incorporating a fuzzy decoupling disturbance observer. Moreover, the MIMO system can be decomposed into a number of single-input single-output (SISO) systems using the unit diagonal matrix decoupling theory. Based on Lyapunov stability theory, it was shown that the error of fuzzy interference observer and the error between the fuzzy rule post parameter matrix and optimal post parameter matrix converge to a small region. Results of the simulation also show that the ARDFD control strategy can significantly eliminate adverse effects of the coupled subsystems.

Underwater robot plays an important role in underwater perception and manipulation tasks. Vision information processing is essential for the intelligent perception of an underwater robot, in which image matching is a fundamental topic. Feature-based image matching is suitable for the underwater environment. However, current underwater image matching usually directly applies those methods with a general purpose or designed for images obtained from the land to underwater images. The problem is that the blurring appearance caused feature descriptor ambiguity, which may greatly deteriorate the performance of these methods on underwater images. Aiming at problem, this article provides an underwater image matching framework by incorporating structural constraints. By integrating the appearance descriptor and structural information by a graph model, the feature correspondence-based image matching is formulated and solved by a graph matching method. Particularly, to solve the outlier feature problem, the graph matching method is applicable to the case where outlier features exist in both underwater images. Experiments on both synthetic points and real-world underwater images validate the effectiveness of the proposed method.

A series of 3-amino-5-benzylphenol derivatives were designed and synthesized. Among them, (3-benzyl-5-hydroxyphenyl)carbamates were found to exert good inhibitory activity against M. tuberculosis H37Ra, H37Rv and clinically isolated multidrug-resistant M. tuberculosis strains (MIC = 0.625−6.25 μg/mL). The privileged compounds 3i and 3l showed moderate cytotoxicity against cell line A549. Compound 3l also exhibited potent in vivo inhibitory activity on a mouse infection model via the oral administration. The results demonstrated 3-hydroxyphenylcarbamates as a class of new antitubercular agents with good potential.

High-density genetic linkage maps are necessary for precisely mapping quantitative trait loci (QTLs) controlling grain shape and size in wheat. By applying the Infinium iSelect 9K SNP assay, we have constructed a high-density genetic linkage map with 269 F 8 recombinant inbred lines (RILs) developed between a Chinese cornerstone wheat breeding parental line Yanda1817 and a high-yielding line Beinong6. The map contains 2431 SNPs and 128 SSR & EST-SSR markers in a total coverage of 3213.2 cM with an average interval of 1.26 cM per marker. Eighty-eight QTLs for thousand-grain weight (TGW), grain length (GL), grain width (GW) and grain thickness (GT) were detected in nine ecological environments (Beijing, Shijiazhuang and Kaifeng) during five years between 2010-2014 by inclusive composite interval mapping (ICIM) (LOD ≥ 2.5). Among which, 17 QTLs for TGW were mapped on chromosomes 1A, 1B, 2A, 2B, 3A, 3B, 3D, 4A, 4D, 5A, 5B and 6B with phenotypic variations ranging from 2.62% to 12.08%. Four stable QTLs for TGW could be detected in five and seven environments, respectively. Thirty-two QTLs for GL were mapped on chromosomes 1B, 1D, 2A, 2B, 2D, 3B, 3D, 4A, 4B, 4D, 5A, 5B, 6B, 7A and 7B, with phenotypic variations ranging from 2.62% to 44.39%. QGl.cau-2A.2 can be detected in all the environments with the largest phenotypic variations, indicating that it is a major and stable QTL. For GW, 12 QTLs were identified with phenotypic variations range from 3.69% to 12.30%. We found 27 QTLs for GT with phenotypic variations ranged from 2.55% to 36.42%. In particular, QTL QGt.cau-5A.1 with phenotypic variations of 6.82-23.59% was detected in all the nine environments. Moreover, pleiotropic effects were detected for several QTL loci responsible for grain shape and size that could serve as target regions for fine mapping and marker assisted selection in wheat breeding programs.

Mutations in the TARDBP gene, which encodes the Tar DNA binding protein, have been shown to causes of both familial amyotrophic lateral sclerosis (FALS) and sporadic ALS (SALS). Recently, several novel TARDBP exon 6 mutants have been reported in patients with ALS in Europe and America but not in Asia. To further examine the spectrum and frequency of TARDBP exon 6 mutations, we investigated their frequency in ethnic Chinese patients with sporadic ALS. TARDBP exon 6 was screened by direct sequencing in 207 non-SOD1 SALS patients and 230 unrelated healthy controls but no mutations were identified. Our data indicate that exon 6 mutations in TARDBP are not a common cause of SALS in Han Chinese population from Southern Mainland China.