Bronchial epithelial gene expression and interstitial lung abnormalities.

INTRODUCTION: Interstitial lung abnormalities (ILA) often represent early fibrotic changes that can portend a progressive fibrotic phenotype. In particular, the fibrotic subtype of ILA is associated with increased mortality and rapid decline in lung function. Understanding the differential gene expression that occurs in the lungs of participants with fibrotic ILA may provide insight into development of a useful biomarker for early detection and therapeutic targets for progressive pulmonary fibrosis. METHODS: Measures of ILA and gene expression data were available in 213 participants in the Detection of Early Lung Cancer Among Military Personnel (DECAMP1 and DECAMP2) cohorts. ILA was defined using Fleischner Society guidelines and determined by sequential reading of computed tomography (CT) scans. Primary analysis focused on comparing gene expression in ILA with usual interstitial pneumonia (UIP) pattern with those with no ILA. RESULTS: ILA was present in 51 (24%) participants, of which 16 (7%) were subtyped as ILA with a UIP pattern. One gene, pro platelet basic protein (PPBP) and seventeen pathways (e.g. TNF-α signalling) were significantly differentially expressed between those with a probable or definite UIP pattern of ILA compared to those without ILA. 16 of these 17 pathways, but no individual gene, met significance when comparing those with ILA to those without ILA. CONCLUSION: Our study demonstrates that abnormal inflammatory processes are apparent in the bronchial airway gene expression profiles of smokers with and without lung cancer with ILA. Future studies with larger and more diverse populations will be needed to confirm these findings.

Grape seed proanthocyanidins regulate mitophagy of endothelial cells and promote wound healing in mice through p-JNK/FOXO3a/ROS signal pathway.

Skin wound healing is a dynamic and complex process that involves multiple physiological and cellular events. Grape seed proanthocyanidins (GSP) have strong anti-oxidation and elimination of oxygen free radicals, and have been shown to significantly promote wound healing, but the underlying mechanism remains unclear. Studies have indicated that reactive oxygen species (ROS) acts as an upstream signal to induce mitophagy, suggesting that GSP can regulate mitophagy through the signal pathway. This study aimed to investigate whether GSP regulates mitophagy by down-regulating oxidative stress to promote wound healing. In vivo, GSP treatment accelerated wound healing, granulation tissue formation, collagen deposition, and angiogenesis in mice. Moreover, GSP down-regulated ROS levels and promoted the expression of antioxidant proteins by up-regulating the expression of p-JNK/FOXO3a protein, thereby regulating the expression of mitophagy-related proteins. In vitro, 4 µg/mL GSP showed no apparent toxic effects on cells and effectively reduce the oxidative stress damage of cells induced by H2O2. Western blot and superoxide anion fluorescence probe further confirmed that GSP effectively reduced Dihydroethidium content and up-regulated the expression of antioxidant proteins by activation of p-JNK/FOXO3a protein expression, thereby regulating mitophagy. Taken together, the findings from in vitro and in vivo experiments provide new insights into the promotion of wound healing by GSP.

Underwater 3D reconstruction using a photometric stereo with illuminance estimation.

Underwater image sensing is directly affected by the change in illuminance towards a camera caused by the refraction of light in different media. In this study, the convergence of a near-field point light source in water is analyzed using a light propagation model. The photometric stereo (PS) formula is determined based on an accurate estimation of the illuminance entering the camera. An underwater PS system is designed to verify the proposed method's feasibility. The experimental results demonstrate improved accuracy in normal calculation. This helps achieve accurate underwater 3D reconstruction of objects that is suitable for underwater surface microdefect detection.

Eudragit S100 prepared pH-responsive liposomes-loaded betulinic acid against colorectal cancer in vitro and in vivo.

This study aimed to develop polymer Eudragit S100 for preparing pH-responsive liposomes-loaded betulinic acid (pH-BA-LP) to improve the therapeutic index of chemotherapy for colorectal cancer. BA-loaded liposomes were coated with Eudragit S100 by a thin film dispersion and easily scalable pH-driven method. The prepared liposomes were evaluated for size, surface morphology, entrapment efficiency, stability, in vitro drug release, and antitumor activity. In particular, pH-BA-LP showed advantages such as lower size (<100 nm), encapsulation efficiency of 90%, high stability, and stably cumulative release. By detecting the antitumor effects of pH-BA-LP in vivo, it showed that the tumor proliferation and cell migration were significantly inhibited in colorectal cancer. The pH-BA-LP also inhibited tumor growth via the regulation of Akt/TLR-mediated signalling and significantly down-regulated the expression of NFAT1 and NFAT4 proteins. It was found that pH-BA-LP can increase NK cells and CD3+ cells in tumor tissues, and the proportion of CD8+ cells in CD3+ cells was also increased, which proved that pH-BA-LP can play an antitumor effect by enhancing the autoimmunity level in tumor-bearing mice. The positive infiltration rates of CD8 and CD68 were increased and CD163 was relatively decreased by using pH-BA-LP, which proved that pH-BA-LP can regulate the immune infiltration levels in tumor-bearing mice. Therefore, the present work provides an effective method to prepare pH-responsive polymer-coated liposomes for colonic delivery with biologically active compounds.

Air quality characteristics in Wuhan (China) during the 2020 COVID-19 pandemic.

Understanding the relationship between air quality, pollution emission control measures, and meteorological conditions is important for developing effective air quality improvement policies. In this study, we used pollution monitoring and meteorological data from January to May 2020 to analyze the air quality characteristics during the COVID-19 lockdown in Wuhan, which lasted from January 23 to April 8, 2020. Compared with the same period in 2019, the air quality in 2020 was significantly better. The total excellent and good air quality rates increased by 17.58%-90.08% in 2020; concentrations of NO2, particulate matter with a diameter <10 µm (PM10) and <2.5 µm (PM2.5), and total volatile organic compounds (TVOCs) also decreased by 38.23%, 30.25%, 32.92%, and 39.80%, respectively. Moreover, the number of days with NO2, PM10, and PM2.5 as the primary pollutants decreased by approximately 10%, 9%, and 15%, respectively. We compared the wind direction, wind speed, temperature, and relative humidity in January-April 2020, 2019, 2018, and 2017 and found no obvious correlation between meteorological factors and improved air quality during the 2020 lockdown. The implementation of strict lockdown measures, such as home quarantining, traffic restrictions, and non-essential enterprise shutdowns, was the dominant cause for the substantial air quality improvement during the 2020 COVID-19 lockdown in Wuhan.

Genome Sequence of Verticillium dahliae Race 1 Isolate VdLs.16 From Lettuce.

Verticillium dahliae is a widespread fungal pathogen that causes Verticillium wilt on many economically important crops and ornamentals worldwide. Populations of V. dahliae have been divided into two distinct races based upon differential host responses in tomato and lettuce. Recently, the contemporary race 2 isolates were further divided into an additional race in tomato. Herein, we provide a high-quality reference genome for the race 1 strain VdLs.16 isolated from lettuce in California, U.S.A. This resource will contribute to ongoing research that aims to elucidate the genetic basis of V. dahliae pathogenicity and population genomic diversity.

Profiling and bioinformatics analyses reveal differential expression of circular RNA in tongue cancer revealed by high-throughput sequencing.

Circular RNAs (circRNA) are special noncoding RNAs. They are widely present, but with unknown functions. Recent studies have shown that many endogenous circRNAs have sponge function to absorb microRNAs (miRNA). They can regulate target gene messenger RNA expression and play important roles in many biological processes. However, expression profile and function of circRNAs in human tongue squamous cell carcinoma (TSCC) have not been reported. High-throughput sequencing was performed to identify and annotate from three TSCC tissues and adjacent tissues. A separate set (n = 20) of human TSCCs and corresponding adjacent tissues were subjected to reverse-transcription polymerase chain reaction (RT-PCR) for validation of circRNAs expression profile. Gene Ontology (GO) functional analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and circRNA-miRNA network analysis were also performed to predict the function of circRNA in TSCC. A total of 12 156 circRNAs were identified and annotated, most of the circRNAs were novel ( n = 6231) and exonic (62.09%). Statistical analysis revealed 322 differentially expressed (DE) circRNAs. RT-PCR results showed that circRNA expression in TSCC was higher than that in adjacent tissues. GO functional analysis, KEGG pathway analysis, and circRNA-miRNA network analysis all showed that circRNAs correlated with tumor development and progression to a certain extent. The current study is the first to systematically characterize and annotate circRNA expression in TSCC, the majority were novel circRNAs. Some host genes of the DE circRNAs were involved in tumor signaling pathway and had complicated correlations with tumor-relevant miRNAs, indicating that circRNAs might be promoted development and progression of TSCC.

Laser frequency noise characterization by self-heterodyne with both long and short delay.

We propose a novel approach to laser frequency noise characterization by delayed self-heterodyne. Compared with the traditional treatment, our method applies to both long and short delay, corresponding to uncorrelated and correlated self-heterodyne. In the case of long delay, it overcomes the influence of 1/f noise on the intrinsic linewidth extraction from a broadened spectrum, and the results are more accurate than Voigt profile fitting. For short delayed correlated heterodyne, it eliminates artifact peaks at multiples of the reciprocal of delay time introduced by transferring measured RF phase noise to laser phase noise, thus extending the measurement range. In addition, it calibrates the frequency noise overestimation caused by a finite noise floor. This method remains valid when the delay and the coherence time are comparable. Experimental results are presented to demonstrate the effectiveness of the proposed approach in characterizing lasers with intrinsic linewidth ranging from sub-100 Hz to megahertz.

Distinct but Spatially Overlapping Intestinal Niches for Vancomycin-Resistant Enterococcus faecium and Carbapenem-Resistant Klebsiella pneumoniae.

Antibiotic resistance among enterococci and γ-proteobacteria is an increasing problem in healthcare settings. Dense colonization of the gut by antibiotic-resistant bacteria facilitates their spread between patients and also leads to bloodstream and other systemic infections. Antibiotic-mediated destruction of the intestinal microbiota and consequent loss of colonization resistance are critical factors leading to persistence and spread of antibiotic-resistant bacteria. The mechanisms underlying microbiota-mediated colonization resistance remain incompletely defined and are likely distinct for different antibiotic-resistant bacterial species. It is unclear whether enterococci or γ-proteobacteria, upon expanding to high density in the gut, confer colonization resistance against competing bacterial species. Herein, we demonstrate that dense intestinal colonization with vancomycin-resistant Enterococcus faecium (VRE) does not reduce in vivo growth of carbapenem-resistant Klebsiella pneumoniae. Reciprocally, K. pneumoniae does not impair intestinal colonization by VRE. In contrast, transplantation of a diverse fecal microbiota eliminates both VRE and K. pneumoniae from the gut. Fluorescence in situ hybridization demonstrates that VRE and K. pneumoniae localize to the same regions in the colon but differ with respect to stimulation and invasion of the colonic mucus layer. While VRE and K. pneumoniae occupy the same three-dimensional space within the gut lumen, their independent growth and persistence in the gut suggests that they reside in distinct niches that satisfy their specific in vivo metabolic needs.

Tumor exosomes induce tunneling nanotubes in lipid raft-enriched regions of human mesothelioma cells.

Tunneling nanotubes (TnTs) are long, non-adherent, actin-based cellular extensions that act as conduits for transport of cellular cargo between connected cells. The mechanisms of nanotube formation and the effects of the tumor microenvironment and cellular signals on TnT formation are unknown. In the present study, we explored exosomes as potential mediators of TnT formation in mesothelioma and the potential relationship of lipid rafts to TnT formation. Mesothelioma cells co-cultured with exogenous mesothelioma-derived exosomes formed more TnTs than cells cultured without exosomes within 24-48 h; and this effect was most prominent in media conditions (low-serum, hyperglycemic medium) that support TnT formation (1.3-1.9-fold difference). Fluorescence and electron microscopy confirmed the purity of isolated exosomes and revealed that they localized predominantly at the base of and within TnTs, in addition to the extracellular environment. Time-lapse microscopic imaging demonstrated uptake of tumor exosomes by TnTs, which facilitated intercellular transfer of these exosomes between connected cells. Mesothelioma cells connected via TnTs were also significantly enriched for lipid rafts at nearly a 2-fold higher number compared with cells not connected by TnTs. Our findings provide supportive evidence of exosomes as potential chemotactic stimuli for TnT formation, and also lipid raft formation as a potential biomarker for TnT-forming cells.

A novel procedure for purification of uridine 5'-monophosphate based on adsorption methodology using a hyper-cross-linked resin.

The conventional ion exchange process used for recovery of uridine 5'-monophosphate (UMP) from the enzymatic hydrolysate of RNA is environmentally harmful and cost intensive. In this work, an innovative benign process, which comprises adsorption technology and use of a hyper-cross-linked resin as a stationary phase is proposed. The adsorption properties of this kind of resin in terms of adsorption equilibrium as well as kinetics were evaluated. The influences of the operating conditions, i.e., initial UMP concentration, feed flow rate, and bed height on the breakthrough curves of UMP in the fixed bed system were investigated. Subsequently, a chromatographic column model was established and validated for the prediction of the experimentally attained breakthrough curves of UMP and the main impurity component (phosphate ion) with a real enzymatic hydrolysate of RNA as a feed mixture. At the end of this paper, the crystallization of UMP was carried out. The purity of the final product (uridine 5'-monophosphate disodium, UMPNa2) of over 99.5 % was obtained.

Potentials of Ulva spp.-derived sulfated polysaccharides as gelling agents with promising therapeutic effects.

Ulvan, a sulfated polysaccharide extracted from Ulva spp., has garnered significant attention in the food and pharmaceutical industries due to its potential health benefits. These include immunomodulation, antiviral, anti-inflammatory, anti-hyperlipidemic, and anti-cancer effects. Nonetheless, practical applications in these fields remain limited due to an incomplete understanding of its gelation mechanisms. Additionally, the underlying mechanisms of its gelation have not been completely understood and thoroughly reviewed. The primary objective is to provide current insights into ulvan's gelling mechanisms and potential health impacts. This review also delves into the existing applications of ulvan polysaccharides. By unraveling these aspects, the information provided in this work is expected to deepen our understanding of ulvan's gelation mechanisms and its prospective role in enhancing health, holding promise for advancements in the fields of food science and disease prevention. This work's theoretical insights contribute significantly to a deeper understanding of these aspects, which holds paramount importance in unleashing the full potential of ulvan and elevating its scientific significance.

PBPK Modeling Approach to Predict the Behavior of Drugs Cleared by Metabolism in Pregnant Subjects and Fetuses.

This study aimed to develop a physiologically based pharmacokinetic (PBPK) model that simulates metabolically cleared compounds' pharmacokinetics (PK) in pregnant subjects and fetuses. This model accounts for the differences in tissue sizes, blood flow rates, enzyme expression levels, plasma protein binding, and other physiological factors affecting the drugs' PK in both the pregnant woman and the fetus. The PBPKPlus™ module in GastroPlus® was used to model the PK of metoprolol, midazolam, and metronidazole for both non-pregnant and pregnant groups. For each of the three compounds, the model was first developed and validated against PK data in healthy non-pregnant volunteers and then applied to predict the PK in the pregnant groups. The model accurately described the PK in both the non-pregnant and pregnant groups and explained well the differences in the plasma concentration due to pregnancy. When available, the fetal plasma concentration, placenta, and fetal tissue concentrations were also predicted reasonably well at different stages of pregnancy. The work described the use of a PBPK approach for drug development and demonstrates the ability to predict differences in PK in pregnant subjects and fetal exposure for metabolically cleared compounds.

Construction of a Nomogram Prediction Model for Prognosis in Patients with Large Artery Occlusion-Acute Ischemic Stroke.

BACKGROUND: Patients with large artery occlusion-acute ischemic stroke (LAO-AIS) can experience adverse outcomes, such as brain herniation due to complications. This study aimed to construct a nomogram prediction model for prognosis in patients with LAO-AIS in order to maximize the benefits for clinical patients. METHODS: Retrospective analysis of 243 patients with LAO-AIS from January 2019 to January 2022 with medical history data and blood examination at admission. Univariate and multivariate analyses were conducted through binary logistic regression equation analysis, and a nomogram prediction model was constructed. RESULTS: Results of this study showed that hyperlipidemia (odds ratio [OR] = 2.849, 95% confidence interval [CI] = 1.100-7.375, P = 0.031), right cerebral infarction (OR = 2.144, 95% CI = 1.106-4.156, P = 0.024), D-Dimer>500 ng/mL (OR = 2.891, 95% CI = 1.398-5.980, P = 0.004), and neutrophil-lymphocyte ratio >7.8 (OR = 2.149, 95% CI = 1.093-4.225, P = 0.027) were independent risk factors for poor early prognosis in patients with LAO-AIS. In addition, hypertension (OR = 1.947, 95% CI = 1.114-3.405, P = 0.019), hyperlipidemia (OR = 2.594, 95% CI = 1.281-5.252, P = 0.008), smoking (OR = 2.414, 95% CI = 1.368-4.261, P = 0.002), D-dimer>500 ng/mL (OR = 3.170, 95% CI = 1.533-6.553, P = 0.002), and neutrophil-lymphocyte ratio >7.8 (OR = 2.144, 95% CI = 1.231-3.735, P = 0.007) were independent risk factors for poor long-term prognosis. The early prognosis nomogram receiver operating characteristic curve area under the curve value was 0.688 for the training set and 0.805 for the validation set, which was highly differentiated. The mean error was 0.025 for the training set calibration curve and 0.016 for the validation set calibration curve. Both the training and validation set decision curve analyses indicated that the clinical benefit of the nomogram was significant. The long-term prognosis nomogram receiver operating characteristic curve area under the curve values was 0.697 for the training set and 0.735 for the validation set, showing high differentiation. The mean error was 0.041 for the training set calibration curve and 0.021 for the validation set calibration curve. Both of the training and validation set decision curve analyses demonstrated a substantial clinical benefit of the nomogram. CONCLUSIONS: The nomogram prediction model based on admission history data and blood examination are easy-to-use tools that provide an accurate individualized prediction for patients with LAO-AIS and can assist in early clinical decisions and in obtaining an early prognosis.

The tumor immune microenvironment of nasopharyngeal carcinoma after gemcitabine plus cisplatin treatment.

Gemcitabine plus cisplatin (GP) chemotherapy is the standard of care for nasopharyngeal carcinoma (NPC). However, the mechanisms underpinning its clinical activity are unclear. Here, using single-cell RNA sequencing and T cell and B cell receptor sequencing of matched, treatment-naive and post-GP chemotherapy NPC samples (n = 15 pairs), we show that GP chemotherapy activated an innate-like B cell (ILB)-dominant antitumor immune response. DNA fragments induced by chemotherapy activated the STING type-I-interferon-dependent pathway to increase major histocompatibility complex class I expression in cancer cells, and simultaneously induced ILB via Toll-like receptor 9 signaling. ILB further expanded follicular helper and helper type 1 T cells via the ICOSL-ICOS axis and subsequently enhanced cytotoxic T cells in tertiary lymphoid organ-like structures after chemotherapy that were deficient for germinal centers. ILB frequency was positively associated with overall and disease-free survival in a phase 3 trial of patients with NPC receiving GP chemotherapy ( NCT01872962 , n = 139). It also served as a predictor for favorable outcomes in patients with NPC treated with GP and immunotherapy combined treatment (n = 380). Collectively, our study provides a high-resolution map of the tumor immune microenvironment after GP chemotherapy and uncovers a role for B cell-centered antitumor immunity. We also identify and validate ILB as a potential biomarker for GP-based treatment in NPC, which could improve patient management.

[Pharmacokinetics and bioequivalence of domestic trimetazidine formulations].

OBJECTIVE: To compare the pharmacokinetics and bioequivalence between domestic hydrochloric trimetazidine capsules and imported hydrochloric trimetazidine tablets in healthy male Chinese volunteers after single oral administration. METHODS: A single oral dose (test and reference formulations) was given to 24 healthy male Chinese subjects according to an open randomized crossover design. The blood samples were collected before and after administration. Plasma trimetazidine concentration was determined by HPLC-MS/MS. The pharmacokinetic parameters were calculated by WinNonlin Ver 6.2.1 software. RESULTS: The main pharmacokinetic parameters of domestic and imported formulation of trimetazidine were similar: C(max) (70.9 ± 15.3), (66.4 ± 13.8) µg/ml; t(max) (1.70 ± 0.72), (1.85 ± 0.55) h; t(1/2z) (4.70 ± 1.75), (4.77 ± 1.96) h; AUC(0-24 h) (481 ± 176), (469 ± 171) µg×h×ml(-1); AUC(0-∞) (511 ± 189), (500 ± 188) µg×h×ml(-1). The estimated 90% CIs for the ratio of C(max) and AUC(0-24 h) were also similar: 101.9% - 112.5% and 99.4% - 104.9%. The relative bioavailability of domestic formulation was (102.2 ± 8.3)%. CONCLUSION: The results demonstrates that the domestic hydrochloric trimetazidine capsules and imported hydrochloric trimetazidine tablets are bioequivalent.

Ex Vivo Pharmacokinetics and Pharmacodynamics Modeling and Optimal Regimens Evaluation of Cefquinome Against Bovine Mastitis Caused by Staphylococcus aureus.

Cefquinome, the fourth-generation cephalosporin applied solely for veterinary medicine, is commonly used for bovine mastitis caused by Staphylococcus aureus. The present study aims to establish an optimal dose and provide a PK/PD Cutoff value (COPD) for cefquinome against S. aureus based on ex vivo pharmacokinetics and pharmacodynamics (PK/PD) integration. This study investigated the pharmacokinetics (PK) of cefquinome when administered as three consecutive intramammary (IMM) doses of cefquinome in three healthy dairy cows at 75 mg/gland. Drug concentration was determined by HPLC-MS/MS assay. The ex vivo pharmacodynamics (PD) of cefquinome were evaluated by using a milk sample from a PK experiment. The relationship between the AUC/ MIC of cefquinome and bacterial loading reduction was simulated using a Sigmoid Emax model. The cefquinome concentration in milk attained a maximum level of 1.55 ± 0.21 mg/mL at 1.8 h after the third administration. The mean value of the area under the concentration-time curve (AUC0-24) was 26.12 ± 2.42 mg·h/mL after the third administration. The elimination half-life was 10.6 h. For PD profile, the MICs of cefquinome in milk were 2-4 times higher than those in the broth. In vitro time-killing curve shows that initial bacterial concentration has a huge impact on antibacterial effect on three strains. The antibacterial effect was weakened with the initial bacterial concentration increasing from 106 to 108 CFU/mL. The AUC0-24h/MIC index correlated well with ex vivo efficacy both for the initial inoculum of 106 CFU/mL and 108 CFU/mL (R 2 > 0.84). According to the inhibitory sigmoid Emax model analysis, the PK/PD surrogate (AUC0-24/MIC) values were 8,638, 1,397, and 3,851 for bactericidal effect (E = -3) with an initial inoculum of 106 CFU/mL, while the corresponding values were 12,266, 2,295, and 5,337, respectively, with the initial inoculum of 108 CFU/mL. The ex vivo PK/PD based population dose prediction indicated a target attainment rate (TAR) of 90% of 55 mg/gland/12 h. The COPD for cefquinome against S. aureus was 2 µg/mL under the recommended dose of 55 mg/gland/12 h. However, it should be validated in clinical practice in future investigations. These results contribute to the rational use of cefquinome for mastitis treatment in clinical veterinary medicine.

Soluble CD14-associated DNA methylation sites predict mortality among men with HIV infection.

OBJECTIVES: Elevated plasma levels of sCD14 predict all-cause mortality in people with HIV (PWH). Epigenetic regulation plays a key role in infection and inflammation. To reveal the epigenetic relationships between sCD14, immune function and disease progression among PWH, we conducted an epigenome-wide association study (EWAS) of sCD14 and investigated the relationship with mortality. DESIGN AND METHODS: DNA methylation (DNAm) levels of peripheral blood samples from PWH in the Veterans Aging Cohort Study (VACS) were measured using the Illumina Infinium Methylation 450K (n = 549) and EPIC (850K) BeadChip (n = 526). Adjusted for covariates and multiple testing, we conducted an epigenome-wide discovery, replication, and meta-analysis to identify significant associations with sCD14. We then examined and replicated the relationship between the principal epigenetic sites and survival using Cox regression models. FINDINGS: We identified 118 DNAm sites significantly associated with sCD14 in the meta-analysis of 1075 PWH. The principal associated DNAm sites mapped to genes (e.g. STAT1, PARP9, IFITM1, MX1, and IFIT1) related to inflammation and antiviral response. Adjusting for multiple testing, 10 of 118 sCD14-associated DNAm sites significantly predicted survival time conditional on sCD14 levels. CONCLUSION: The identification of DNAm sites independently predicting survival may improve our understanding of prognosis and potential therapeutic targets among PWH.

Chord: an ensemble machine learning algorithm to identify doublets in single-cell RNA sequencing data.

High-throughput single-cell RNA sequencing (scRNA-seq) is a popular method, but it is accompanied by doublet rate problems that disturb the downstream analysis. Several computational approaches have been developed to detect doublets. However, most of these methods may yield satisfactory performance in some datasets but lack stability in others; thus, it is difficult to regard a single method as the gold standard which can be applied to all types of scenarios. It is a difficult and time-consuming task for researchers to choose the most appropriate software. We here propose Chord which implements a machine learning algorithm that integrates multiple doublet detection methods to address these issues. Chord had higher accuracy and stability than the individual approaches on different datasets containing real and synthetic data. Moreover, Chord was designed with a modular architecture port, which has high flexibility and adaptability to the incorporation of any new tools. Chord is a general solution to the doublet detection problem.

Association of shorter mean telomere length with large artery stiffness in patients with coronary heart disease.

BACKGROUND: Accumulating evidence implicates leukocyte telomere length (LTL) shortening as a potential risk predictor for cardiovascular disease. Arterial stiffness chronicles the cumulative burden of cardiovascular disease risk factors. Therefore, the capacity of LTL to predict arterial stiffness was examined. METHODS: A total of 275 unrelated Chinese males: 163 patients with coronary artery disease (CAD) and 112 healthy controls, 40-73 years of age were included in this study. The relative telomere length of leukocytes was determined by a real-time fluorescence quantitative polymerase chain reaction (PCR). Large artery stiffness was measured with carotid-femoral pulse wave velocity (PWV). RESULTS: The relative telomere length (T/S) ratio was significantly shorter in patients with CAD (0.79 +/- 0.26) than in control subjects (1.08 +/- 0.22) (p<0.001). The correlation between LTL and PWV in patients with CAD was stronger than that in the controls (r= -0.467, r(2)=0.227, p<0.001 for patients with CAD versus r= -0.223; r(2)=0.050; p=0.018 for controls). The log(e)-transformed T/S ratio was inversely correlated with age (r= -0.345; p<0.001), PWV (r= -0.326; p<0.001) and C-reactive protein ( r= -0.133; p=0.027). CONCLUSIONS: The data show an association of leukocyte telomere length shortening with increased arterial stiffness and cardiovascular burden, suggesting that telomere length is a biomarker of large artery elasticity and CAD. Further studies are warranted to study the role of LTL dynamics in the pathogenesis of atherosclerosis.