Identification of Gut Microbiome Signatures Associated with Indole Pathway in Tryptophan Metabolism in Patients Undergoing Hemodialysis.

Microbiota tryptophan metabolism and the biosynthesis of indole derivatives play an important role in homeostasis and pathogenesis in the human body and can be affected by the gut microbiota. However, studies on the interplay between gut microbiota and tryptophan metabolites in patients undergoing dialysis are lacking. This study aimed to identify the gut microbiota, the indole pathway in tryptophan metabolism, and significant functional differences in ESRD patients with regular hemodialysis. We performed the shotgun metagenome sequencing of stool samples from 85 hemodialysis patients. Using the linear discriminant analysis effect size (LEfSe), we examined the composition of the gut microbiota and metabolic features across varying concentrations of tryptophan and indole metabolites. Higher tryptophan levels promoted tyrosine degradation I and pectin degradation I metabolic modules; lower tryptophan levels were associated with glutamate degradation I, fructose degradation, and valine degradation modules. Higher 3-indoxyl sulfate concentrations were characterized by alanine degradation I, anaerobic fatty acid beta-oxidation, sulfate reduction, and acetyl-CoA to crotonyl-CoA. Contrarily, lower 3-indoxyl sulfate levels were related to propionate production III, arabinoxylan degradation, the Entner-Doudoroff pathway, and glutamate degradation II. The present study provides a better understanding of the interaction between tryptophan, indole metabolites, and the gut microbiota as well as their gut metabolic modules in ESRD patients with regular hemodialysis.

Gene set correlation enrichment analysis for interpreting and annotating gene expression profiles.

Pathway analysis, including nontopology-based (non-TB) and topology-based (TB) methods, is widely used to interpret the biological phenomena underlying differences in expression data between two phenotypes. By considering dependencies and interactions between genes, TB methods usually perform better than non-TB methods in identifying pathways that include closely relevant or directly causative genes for a given phenotype. However, most TB methods may be limited by incomplete pathway data used as the reference network or by difficulties in selecting appropriate reference networks for different research topics. Here, we propose a gene set correlation enrichment analysis method, Gscore, based on an expression dataset-derived coexpression network to examine whether a differentially expressed gene (DEG) list (or each of its DEGs) is associated with a known gene set. Gscore is better able to identify target pathways in 89 human disease expression datasets than eight other state-of-the-art methods and offers insight into how disease-wide and pathway-wide associations reflect clinical outcomes. When applied to RNA-seq data from COVID-19-related cells and patient samples, Gscore provided a means for studying how DEGs are implicated in COVID-19-related pathways. In summary, Gscore offers a powerful analytical approach for annotating individual DEGs, DEG lists, and genome-wide expression profiles based on existing biological knowledge.

A urine extracellular vesicle lncRNA classifier for high-grade prostate cancer and increased risk of progression: A multi-center study.

To construct a urine extracellular vesicle long non-coding RNA (lncRNA) classifier that can detect high-grade prostate cancer (PCa) of grade group 2 or greater and estimate the risk of progression during active surveillance, we identify high-grade PCa-specific lncRNAs by combined analyses of cohorts from TAHSY, TCGA, and the GEO database. We develop and validate a 3-lncRNA diagnostic model (Clnc, being made of AC015987.1, CTD-2589M5.4, RP11-363E6.3) that can detect high-grade PCa. Clnc shows higher accuracy than prostate cancer antigen 3 (PCA3), multiparametric magnetic resonance imaging (mpMRI), and two risk calculators (Prostate Cancer Prevention Trial [PCPT]-RC 2.0 and European Randomized Study of Screening for Prostate Cancer [ERSPC]-RC) in the training cohort (n = 350), two independent cohorts (n = 232; n = 251), and TCGA cohort (n = 499). In the prospective active surveillance cohort (n = 182), Clnc at diagnosis remains a powerful independent predictor for overall active surveillance progression. Thus, Clnc is a potential biomarker for high-grade PCa and can also serve as a biomarker for improved selection of candidates for active surveillance.

Use of spatial panel-data models to investigate factors related to incidence of end-stage renal disease: a nationwide longitudinal study in Taiwan.

BACKGROUND: The assumptions of conventional spatial models cannot estimate the responses across space and over time. Here we propose new spatial panel data models to investigate the association between the risk factors and incidence of end-stage renal disease (ESRD). METHODS: A longitudinal (panel data) study was conducted using data from the National Health Insurance Database in Taiwan. We developed an algorithm to identify the patient's residence and estimate the ESRD rate in each township. Corresponding covariates, including patient comorbidities, history of medication use, and socio-environmental factors, were collected. Local Indicators of Spatial Association were used to describe local spatial clustering around an individual location. Moreover, a spatial panel data model was proposed to investigate the association between ESRD incidence and risk factors. RESULTS: In total, 73,995 patients with ESRD were included in this study. The western region had a higher proportion of high incidence rates than the eastern region. The proportion of high incidence rates in the eastern areas increased over the years. We found that most "social environmental factors," except average income and air pollution (PM 2.5 and PM10), had a significant influence on the incidence rate of ESRD when considering spatial dependences of response and explanatory variables. Receiving non-steroidal anti-inflammatory drugs and aminoglycosides within 90 days prior to ESRD had a significant positive effect on the ESRD incidence rate. CONCLUSION: Future comprehensive studies on townships located in higher-risk clusters of ESRD will help in designing healthcare policies for suitable action.

The Biomechanical Characteristics of Swallowing in Tracheostomized Patients with Aspiration following Acquired Brain Injury: A Cross-Sectional Study.

Objectives: Investigate the biomechanical characteristics in tracheostomized patients with aspiration following acquired brain injury (ABI) and further explore the relationship between the biomechanical characteristics and aspiration. Methods: This is a single-center cross-sectional study. The tracheostomized patients with aspiration following ABI and age-matched healthy controls were recruited. The biomechanical characteristics, including velopharynx (VP) maximal pressure, tongue base (TB) maximal pressure, upper esophageal sphincter (UES) residual pressure, UES relaxation duration, and subglottic pressure, were examined by high-resolution manometry and computational fluid dynamics simulation analysis. The penetration−aspiration scale (PAS) score was evaluated by a videofluoroscopic swallowing study. Results: Fifteen healthy subjects and fifteen tracheostomized patients with aspiration following ABI were included. The decreased VP maximal pressure, increased UES residual pressure, and shortened UES relaxation duration were found in the patient group compared with the control group (p < 0.05). Furthermore, the subglottic pressure significantly decreased in patients (p < 0.05), while no significant difference was found in TB maximal pressure between groups (p > 0.05). In addition, in the patient group, VP maximal pressure (rs = −0.439; p = 0.015), UES relaxation duration (rs = −0.532; p = 0.002), and the subglottic pressure (rs = −0.775; p < 0.001) were negatively correlated with the PAS score, while UES residual pressure (rs = 0.807; p < 0.001) was positively correlated with the PAS score (p < 0.05), the correlation between TB maximal pressure and PAS score (rs = −0.315; p = 0.090) did not reach statistical significance. Conclusions: The biomechanical characteristics in tracheostomized patients with aspiration following ABI might manifest as decreased VP maximal pressure and subglottic pressure, increased UES residual pressure, and shortened UES relaxation duration, in which VP maximal pressure, UES relaxation duration, subglottic pressure, and UES residual pressure were correlated with aspiration.

Plasma extracellular vesicle circRNA signature and resistance to abiraterone in metastatic castration-resistant prostate cancer.

BACKGROUND: We aimed to develop and validate a plasma extracellular vesicle circular RNA (circRNA)-based signature that can predict overall survival (OS) in first-line abiraterone therapy for metastatic castration-resistant prostate cancer (mCRPC) patients. METHODS: In total, 582 mCRPC patients undergoing first-line abiraterone therapy from four institutions were sorted by three phases. In the discovery phase, 30 plasma samples from 30 case-matched patients with or without early progression were obtained to generate circRNA expression profiles using RNA sequencing. In the training phase, differentially expressed circRNAs were examined using digital droplet PCR in a training cohort (n = 203). The circRNA signature was constructed using a least absolute shrinkage and selection operator Cox regression to predict OS. In the validation phase, the prognostic ability of this signature was prospectively validated in two external cohorts (Cohort I, n = 183; Cohort II, n = 166). RESULTS: We developed a five-circRNA signature, based on circCEP112, circFAM13A, circBRWD1, circVPS13C and circMACROD2, which successfully stratified patients into high-risk and low-risk groups. The prognostic ability of this signature was prospectively validated in two external cohorts (P < 0.0001, P < 0.0001). Patients with high-risk scores had shorter OS than patients with low-risk scores. CONCLUSION: This five-circRNA signature is a reliable predictor of OS for mCRPC patients undergoing abiraterone.

Multiple subtentorial metastasis in diffuse midline glioma receiving tumor treating fields: a case report and literature review.

Diffuse midline glioma (DMG) is one of fatal glioblastoma multiforme (GBM) with no proven medical therapies. Tumor treating fields (TTFields) is a new revolutionary therapy for GBM which prolongs the overall survival time obviously. However, we can observe more tumor growth phenomena (such as distant multiple metastases) than before. This report describes an adult patient who presented headache and dizziness, accompanied by left limb weakness, nausea, and vomiting following car accident trauma, following imaging examinations suggested thalamus GBM. He was treated with subtotal excision. Final pathology was diagnosed as DMG with H3F3A mutation, isocitrate dehydrogenase (IDH) wild type. Following concurrent chemoradiation therapy (CCRT) and adjuvant temozolomide (TMZ) chemotherapy + TTFields therapy were carried out. Supratentorial tumor has been exhibited a partial radiological response for nine months until TTFields was used irregularly or even discontinued in the later stage. Especially, subtentorial and spinal multiple metastasis occurred during this time. Both supratentorial and subtentorial tumors were treated with surgery, radiotherapy, chemotherapy, even targeted drugs, with the only difference being TTFields, but we could see different consequences for tumor growth. One conclusion might be drawn that TTFields can provide a longer survival time (14 vs. 8 months reported before) for DMG patients and improve survival benefits. However, we can observe that patients maybe die from subtentorial metastasis because TTFields could not cover the subtentorial tumors, which is the focal challenge at present. So further research on subtentorial tumors with TTFields is urgently needed.

Internal insulation condition identification for high-voltage capacitor voltage transformers based on possibilistic fuzzy clustering.

The internal insulation condition of capacitor voltage transformers (CVTs) is a key influence factor that affects their measurement performance and safe operation. However, the internal insulation would age along with long-time operation and degrade due to environmental factors, and once the insulation degradation grows, serious damage and even explosion may happen in CVTs; hence, it is necessary to monitor the internal insulation condition of CVTs, and the fault type and fault degree need to be identified. In this paper, a data-driven internal insulation condition identification method for CVTs is proposed. Both the amplitude and phase of the output voltage of CVTs are collected, and then, recognition models based on the combination of the output voltages and distribution topology of CVTs in substations are built. A possibilistic fuzzy clustering method is used to monitor the internal insulation condition of CVTs, and different types and different degrees of insulation faults could be identified effectively. Finally, the proposed method is verified in several cases; not only the preset typical faults in the method could be identified effectively but also the faults beyond the preset faults could be diagnosed.

Factorial two-stage analyses of parameters affecting the oil-gas interface and miscibility in bulk phase and nanopores.

In this paper, a factorial analysis approach is applied to characterize the potential single and interactive factors as well as their effects on the interface and miscibility of three light oil-CO2 systems under 32 different conditions. First, a modified Peng-Robinson equation of state coupled with the parachor model is applied to calculate the vapour-liquid equilibrium and interfacial tensions (IFTs) at a variation of pore radii and different pressures, based on which the MMPs are determined from the diminishing interface method. Second, by means of the factorial-analysis approach and calculated IFTs and minimum miscibility pressures (MMPs), the following five factors are specifically studied to evaluate their main and interactive effects on the IFTs and MMPs: temperature, initial oil and gas compositions, feed gas to oil ratio (feed GOR), and pore radius. It is found that the main and interactive effects of the five factors on the IFTs are inconsistent at different pressures. The effects of the five factors on the MMPs are evaluated quantitatively, which contribute to screen out significant factors, analyze interactions, and identify schemes for the miscible CO2 enhanced oil recovery. The most positive significant main and interactive effects on the MMPs are Factors C (gas composition) and AB (temperature and oil composition), whereas the most negative results are Factors E (pore radius) and AC (temperature and gas compositions). A three-factor analysis indicates that the MMP is substantially reduced in small pores by controlling the percentage of the CH4-dominated gas in the impure CO2 sample and lowering the feed GOR.

Revisiting the Role of Plant Transcription Factors in the Battle against Abiotic Stress.

Owing to diverse abiotic stresses and global climate deterioration, the agricultural production worldwide is suffering serious losses. Breeding stress-resilient crops with higher quality and yield against multiple environmental stresses via application of transgenic technologies is currently the most promising approach. Deciphering molecular principles and mining stress-associate genes that govern plant responses against abiotic stresses is one of the prerequisites to develop stress-resistant crop varieties. As molecular switches in controlling stress-responsive genes expression, transcription factors (TFs) play crucial roles in regulating various abiotic stress responses. Hence, functional analysis of TFs and their interaction partners during abiotic stresses is crucial to perceive their role in diverse signaling cascades that many researchers have continued to undertake. Here, we review current developments in understanding TFs, with particular emphasis on their functions in orchestrating plant abiotic stress responses. Further, we discuss novel molecular mechanisms of their action under abiotic stress conditions. This will provide valuable information for understanding regulatory mechanisms to engineer stress-tolerant crops.

Bacillus spore-based oral carriers loading curcumin for the therapy of colon cancer.

Oral drug delivery has attracted substantial attention due to its advantages over other administration routes. Bacillus spores, as oral probiotic agents, are applied widely. In this paper, a novel Bacillus spore-based oral colon targeted carrier loading curcumin was developed for colon cancer treatment. Curcumin was linked covalently with the outer coat of Bacillus spore and folate, respectively (SPORE-CUR-FA). Bacillus spores are capable of delivering drugs to the colon area through gastric barrier, taking the advantage of its tolerance to the harsh conditions and disintegration of the outer coat of spores after germination in the colon. The drug release in vitro and in vivo of SPORE-CUR-FA was investigated. Results showed that SPORE-CUR-FA had the characteristics of colon-targeted drug release. Pharmacokinetic studies confirmed that Bacillus spore-based carriers could efficiently improve the oral bioavailability of curcumin. In vitro and in vivo anti-tumor studies showed that SPORE-CUR-FA had substantial ability for inhibiting colon cancer cells. These findings suggest that this Bacillus spore-based oral drug delivery system has a great potential for the treatment of colon cancer.

Expressions and correlations of TLR2 ,TLR4 ,TLR7 and TLR9 in eosinophil-enriched blood cells from patients with allergic rhinitis / 西安交通大学学报(医学版)

Objective To investigate expressions and correlations of TLR2,TLR4,TLR7 and TLR9 in eosinophil-enriched cell populations from patients with allergic rhinitis (AR),and elucidate their roles in AR. Methods Peripheral venous blood samples were collected from healthy controls (HCs)and AR patients,and then incubated with crude extracts of Artemisia pollen,dust mite,and Platanus pollen,respectively.Levels of TLR2 , TLR4,TLR7 and TLR9 in blood eosinophil-enriched cells were detected by flow cytometry.Correlations between TLR2+,TLR4+,TLR7+and TLR9+eosinophils were analyzed by SPSS.Results Levels of TLR2+eosinophils from patients with AR were reduced by 4%,mean fluorescence intensity (MFI)of TLR4+eosinophil was elevated by 20%,and TLR7+eosinophils increased up to 4.8 folds compared with HCs when cultured with medium only (P＜0.05).Artemisia pollen extracts induced approximately 7 .8 % of increase in TLR2+eosinophils from AR patients.In addition,correlations between TLR2+and TLR4+eosinophils,TLR2+and TLR7+eosinophils,and TLR7+and TLR9+eosinophils were -0.670 (P＜0.01),-0.430 (P＜0.05)and 0.446 (P＜0.05),respectively. However,allergens had few effects on TLR2,TLR4,TLR7 and TLR9 expressions in HCs.Conclusion Eosinophil-derived TLR2 ,TLR4 and TLR7 are likely to play a key role in AR.TLR2 ,TLR4 and TLR7 might become the potential targets for AR treatment.

Packaging cordycepin phycocyanin micelles for the inhibition of brain cancer.

Cordycepin has been successfully used as a natural anti-cancer drug, but it is rapidly metabolized in vivo. Nanoencapsulation is thus a promising method to improve its bioavailability. In this study, we adopted a green synthesis process to develop novel self-assembling phycocyanin-dextran-cordycepin (Phy-Dex-Cord) micelles for efficient cordycepin encapsulation and delivery. We first used the Maillard reaction method to graft dextran onto phycocyanin, forming a phycocyanin-dextran complex. Through the self-assembly of the cordycepin parcel to the phycocyanin-dextran complex, the micelles were formed. Their physical and chemical properties and characterization results showed that Phy-Dex-Cord micelles have a spherical shape and consistent size distribution of about 60 nm. In addition, anti-cancer activities in vitro and in vivo revealed that the Phy-Dex-Cord micelles have a comparable or even stronger inhibitory effect against C6 cells than do free cordycepin and free phycocyanin and no side effects.

Nursing for patients with advanced hepatocellular carcinoma receiving transcatheter arterial ;chemoembolization combined with sorafenib：initial experience in 23 cases / 介入放射学杂志

Objective To discuss the nursing care for patients with advanced hepatocellular carcinoma (HCC) who are receiving transcatheter arterial chemoembolization (TACE) combined with sorafenib. Methods A total of 23 consecutive patients with advanced HCC who met the inclusion criteria were enrolled in this study. TACE was carried out in all patients. Three-five days after TACE the patients started to orally take sorafenib. During the treatment course, the patients were kept under close observation for adverse reactions and complications. After leaving the hospital the patients were followed up by the extended care team members, and health education as well as appropriate nursing intervention was carried out. Results All patients with advanced HCC took sorafenib orally after TACE. The major adverse events and complications were gastrointestinal adverse reactions (n = 22) and transient liver dysfunction (n = 23). After leaving the hospital all the patients received regular follow- up examination and extended nursing care. Conclusion Usually, the incidence of adverse reactions is higher in patients with advanced HCC after TACE combined with sorafenib treatment. Careful in-hospital observation and extended out-hospital nursing can reduce the incidence of adverse reactions and thus improve the patient’s quality of life.

Chaotic digital communication by encoding initial conditions.

We investigate the possibility to improve the noise performance of a chaotic digital communication scheme by utilizing further dynamical information. We show that by encoding the initial information of the chaotic carrier according to the transmitting bits, extra redundance can be introduced into the segments of chaotic signals corresponding to the consecutive bits. Such redundant information can be exploited effectively at the receiver end to improve the noise performance of the system. Compared to other methods (e.g., differential chaos shift keying), straightforward application of the proposed modulation/demodulation scheme already provides significant performance gain in the low signal-to-noise ratio (SNR) region. Furthermore, maximum likelihood precleaning procedure based on the Viterbi algorithm can be applied before the demodulation step to overcome the performance degradation in the high SNR region. The study indicates that it is possible to improve the noise performance of the chaotic digital communication scheme if further dynamics information is added to the system.