Lipidomic landscape of lipokines in adipose tissue derived extracellular vesicles

Introduction: Adipose tissue-derived extracellular vesicles (EVs-AT) are recognized as critical mediators of metabolic alterations in obesity-related diseases. However, few studies have focused on the role of lipids within EVs-AT in the development of obesity-related diseases.Methods: In this study, we performed a targeted lipidomic analysis to compare the lipidome of EVs secreted by inguinal white adipose tissue (EVs-iWAT), epididymal white adipose tissue (EVs-eWAT), and interscapular brown adipose tissue (EVs-BAT) in lean and obese mice.Results: We uncovered a comprehensive lipidomic map, revealing the diversity and specific lipid sorting in EVs-iWAT, EVs-eWAT, and EVs-BAT in obesity. Biological function analyses suggested that lipids encapsulated within EVs-AT of obese individuals might correlate with metabolism, pro-inflammatory response, and insulin resistance. These effects were particularly pronounced in EVs-eWAT and EVs-BAT.Conclusion: Our findings indicated that EVs-AT serves as novel carriers for lipokines, thereby mediating the biological functions of EVs-AT. This study holds promise for the identification of new biomarkers for obesity-related diseases and the development of new strategies to combat metabolic diseases

Non-Coding Transcriptome Provides Novel Insights into the Escherichia coli F17 Susceptibility of Sheep Lamb

SIMPLE SUMMARY: Diarrhea and vomiting caused by Escherichia coli (E. coli) F17 are considered significant threats to animal farming. In the present study, RNA-Seq was performed to investigate the potential circRNA and miRNA biomarkers for E. coli F17-antagonism (AN) and -sensitive (SE) lambs. The results indicated that circRNA and miRNA expression is closely associated with the susceptibility of E. coli F17 in lambs. Numbers of circRNAs and miRNAs may serve as potential biomarkers for intestinal inflammatory response against E. coli F17 infection. Our study can provide a preliminary understanding of the underlying mechanisms of intestinal immunity. ABSTRACT: It has long been recognized that enterotoxigenic Escherichia coli (ETEC) is the major pathogen responsible for vomiting and diarrhea. E. coli F17, a main subtype of ETEC, is characterized by high morbidity and mortality in young livestock. However, the transcriptomic basis underlying E. coli F17 infection has not been fully understood. In this study, RNA sequencing was performed to explore the expression profiles of circRNAs and miRNAs in the jejunum of E. coli F17-antagonism (AN) and -sensitive (SE) lambs. A total of 16,534 circRNAs and 271 miRNAs (125 novel miRNAs and 146 annotated miRNAs) were screened, and 214 differentially expressed (DE) circRNAs and 53 DE miRNAs were detected between the AN and SE lambs (i.e., novel_circ_0025840, novel_circ_0022779, novel_miR_107, miR-10b). Functional enrichment analyses showed that source genes of DE circRNAs were mainly involved in metabolic-related pathways, while target genes of DE miRNAs were mainly enriched in the immune response pathways. Then, a two-step machine learning approach combining Random Forest (RF) and XGBoost (candidates were first selected by RF and further assessed by XGBoost) was performed, which identified 44 circRNAs and 39 miRNAs as potential biomarkers (i.e., novel_circ_0000180, novel_circ_0000365, novel_miR_192, oar-miR-496-3p) for E. coli infection. Furthermore, circRNA-related and lncRNA-related ceRNA networks were constructed, containing 46 circRNA-miRNA-mRNA competing triplets and 630 lncRNA-miRNA-mRNA competing triplets, respectively. By conducting a serious of bioinformatic analyses, our results revealed important circRNAs and miRNAs that could be potentially developed as candidate biomarkers for intestinal inflammatory response against E. coli F17 infection; our study can provide novel insights into the underlying mechanisms of intestinal immunity

Utilizing metagenomic next-generation sequencing for diagnosis and lung microbiome probing of pediatric pneumonia through bronchoalveolar lavage fluid in pediatric intensive care unit: results from a large real-world cohort

BackgroundMetagenomic next-generation sequencing (mNGS) is a powerful method for pathogen detection in various infections. In this study, we assessed the value of mNGS in the pathogen diagnosis and microbiome analysis of pneumonia in pediatric intensive care units (PICU) using bronchoalveolar lavage fluid (BALF) samples.MethodsA total of 104 pediatric patients with pneumonia who were admitted into PICU between June 2018 and February 2020 were retrospectively enrolled. Among them, 101 subjects who had intact clinical information were subject to parallel comparison of mNGS and conventional microbiological tests (CMTs) for pathogen detection. The performance was also evaluated and compared between BALF-mNGS and BALF-culture methods. Moreover, the diversity and structure of all 104 patients’ lung BALF microbiomes were explored using the mNGS data.ResultsCombining the findings of mNGS and CMTs, 94.06% (95/101) pneumonia cases showed evidence of causative pathogenic infections, including 79.21% (80/101) mixed and 14.85% (15/101) single infections. Regarding the pathogenesis of pneumonia in the PICU, the fungal detection rates were significantly higher in patients with immunodeficiency (55.56% vs. 25.30%, P =0.025) and comorbidities (40.30% vs. 11.76%, P=0.007). There were no significant differences in the α-diversity either between patients with CAP and HAP or between patients with and without immunodeficiency. Regarding the diagnostic performance, the detection rate of DNA-based BALF-mNGS was slightly higher than that of the BALF-culture although statistically insignificant (81.82% vs.77.92%, P=0.677) and was comparable to CMTs (81.82% vs. 89.61%, P=0.211). The overall sensitivity of DNA-based mNGS was 85.14% (95% confidence interval [CI]: 74.96%-92.34%). The detection rate of RNA-based BALF-mNGS was the same with CMTs (80.00% vs 80.00%, P>0.999) and higher than BALF-culture (80.00% vs 52.00%, P=0.045), with a sensitivity of 90.91% (95%CI: 70.84%-98.88%).ConclusionsmNGS is valuable in the etiological diagnosis of pneumonia, especially in fungal infections, and can reveal pulmonary microecological characteristics. For pneumonia patients in PICU, the mNGS should be implemented early and complementary to CMTs

Diagnosis of mixed infection and a primary immunodeficiency disease using next-generation sequencing: a case report

Major Histocompatibility Complex Class II (MHC II) deficiency is a rare primary immunodeficiency disorder (PID) with autosomal recessive inheritance pattern. The outcome is almost fatal owing to delayed diagnosis and lacking of effective therapy. Therefore, prompt diagnosis, timely and effective treatment are critical. Here, we report a 117-day-old boy with diarrhea, cough, cyanosis and tachypnea who was failed to be cured by empiric antimicrobial therapy initially and progressed to severe pneumonia and respiratory failure. The patient was admitted to the pediatric intensive care unit (PICU) immediately and underwent a series of tests. Blood examination revealed elevated levels of inflammatory markers and cytomegalovirus DNA. Imaging findings showed signs of severe infection of lungs. Finally, the diagnosis was obtained mainly through next-generation sequencing (NGS). We found out what pathogenic microorganism he was infected via repeated conventional detection methods and metagenomic next-generation sequencing (mNGS) of sputum and bronchoalveolar lavage fluid (BALF). And his whole exome sequencing (WES) examination suggested that CIITA gene was heterozygous mutation, a kind of MHC II deficiency diseases. After aggressive respiratory support and repeated adjustment of antimicrobial regimens, the patient was weaned from ventilator on the 56th day of admission and transferred to the immunology ward on the 60th day. The patient was successful discharged after hospitalizing for 91 days, taking antimicrobials orally to prevent infections post-discharge and waiting for stem cell transplantation. This case highlights the potential importance of NGS in providing better diagnostic testing for unexplained infection and illness. Furthermore, pathogens would be identified more accurately if conventional detection techniques were combined with mNGS

Whole exome sequencing identifies frequent somatic mutations in cell-cell adhesion genes in chinese patients with lung squamous cell carcinoma

Lung squamous cell carcinoma (SQCC) accounts for about 30% of all lung cancer cases. Understanding of mutational landscape for this subtype of lung cancer in Chinese patients is currently limited. We performed whole exome sequencing in samples from 100 patients with lung SQCCs to search for somatic mutations and the subsequent target capture sequencing in another 98 samples for validation. We identified 20 significantly mutated genes, including TP53, CDH10, NFE2L2 and PTEN. Pathways with frequently mutated genes included those of cell-cell adhesion/Wnt/Hippo in 76%, oxidative stress response in 21%, and phosphatidylinositol-3-OH kinase in 36% of the tested tumor samples. Mutations of Chromatin regulatory factor genes were identified at a lower frequency. In functional assays, we observed that knockdown of CDH10 promoted cell proliferation, soft-agar colony formation, cell migration and cell invasion, and overexpression of CDH10 inhibited cell proliferation. This mutational landscape of lung SQCC in Chinese patients improves our current understanding of lung carcinogenesis, early diagnosis and personalized therapy

RSSI Enhanced Microkernel-Based LBS Design

Geographical Information System (GIS) always plays an integral role in LBS systems. But it comes with technology problems, such as less flexible, low efficiency, no redundancy of existing geographic information of application configuration which has high entry cost. At same time, indoors positioning is attracting more and more attention from research domain where GPS-like systems do not work. By RSSI location fingerprint data that sampling from the actual WSN environment, this article analyzed RF signal propagation characteristics in indoor from the point of view of the indoor positioning, and analyzed some factors that may affect the positioning error, which provided a theoretical basis for the positioning algorithm design and positioning system deployment. The aim of this paper is also to present a lightweight, efficient and scalable microkernel plug-in geospatial information application system and its implementation method for GIS in LBS design and practice. In this paper a software model called Resource loading manager (RLM) is designed. Through the RLM efficient allocation of geographic information resources and security management could be achieved

Calculation on Bending Stiffness of RC Short Beam Strengthened by CFRP

Based on the bending tests of seven reinforced concrete (RC) short beams strengthened with carbon fiber reinforced polymer (CFRP), the bending stiffness curves of the whole process of the short beams strengthened with CFRP were obtained. The variation law of bending stiffness curve of short beam in the whole loading process was analyzed. Based on the reasonable calculation assumption, the calculation method of flexural rigidity of short reinforced concrete beams strengthened with CFRP sheets in the whole loading process was put forward. The comparison between the calculated value and the test value of bending stiffness showed that the calculation method of bending stiffness was reasonable and had high calculation accuracy. This calculation method can be used not only in the calculation of flexural rigidity of short reinforced concrete beams strengthened with CFRP sheets but also in the calculation of flexural rigidity of ordinary short reinforced concrete beams. The calculation method in this paper can provide a theoretical basis for the deformation calculation of reinforced concrete short beams strengthened with CFRP sheets

Seismic Behavior Analysis of Damaged Steel Fiber-Reinforced High-Strength Concrete Frame Joints Strengthened by FRP

In this paper, the seismic behavior of fiber-reinforced polymer (FRP) strengthened and unstrengthened steel fiber-reinforced high-strength concrete frame joints under low cyclic loading was tested. Then, the nonlinear finite element program was used to simulate the seismic behavior of FRP strengthened and unstrengthened steel fiber-reinforced high-strength concrete frame joints under low cyclic repeated load. The influence of FRP bond direction on the seismic behavior of steel fiber-reinforced high-strength concrete frame joints was studied. Through the comparison of the test values and numerical simulation values of the hysteretic curve, skeleton curve, energy dissipation capacity, displacement ductility, bearing capacity degradation, stiffness degradation, and other performance indexes of frame joints, the rule was obtained. The results showed that the 45° bonding direction of carbon fiber cloth is better than the 0° bonding direction, and the digital simulation results are in good agreement with the test results. Therefore, the constitutive model, element, end constraint, and loading method used in the finite element numerical simulation of this paper were reasonable, which can provide reference for the similar research in the future

A MODIFIED FOUR-QUADRANT FREQUENCY DISCRIMINATOR FOR CARRIER FREQUENCY ACQUISITION OF GPS RECEIVERS

ITC/USA 2005 Conference Proceedings / The Forty-First Annual International Telemetering Conference and Technical Exhibition / October 24-27, 2005 / Riviera Hotel & Convention Center, Las Vegas, NevadaThe four-quadrant frequency discriminator (FQFD) plays an important role in GPS receivers for carrier synchronization. This paper presents a detailed study of the operating principle of the FQFD, and the acquisition performance degradation due to the gain fluctuation of the FQFD is discussed. A modified FQFD called the enveloped-four-quadrant frequency discriminator (Enveloped-FQFD) is proposed, which introduces an envelope calculator on the basis of the FQFD. Performance comparison of the FQFD and the Enveloped-FQFD is given through theoretical analysis and computer simulation. Simulation results show that by employing the Enveloped-FQFD, a quicker pull-in process and a wider threshold than the FQFD can be achieved, while the additional hardware costs are trivial.International Foundation for TelemeteringProceedings from the International Telemetering Conference are made available by the International Foundation for Telemetering and the University of Arizona Libraries. Visit http://www.telemetry.org/index.php/contact-us if you have questions about items in this collection