Search

The excessive and ectopic pulmonary artery smooth muscle cells (PASMCs) are crucial to the pathogenesis of pulmonary arteriole (PA) remodeling in pulmonary arterial hypertension (PAH). We previously found that microRNA (miR)-30a was significantly increased in acute myocardial infarction (AMI) patients and animals, as well as in cultured cardiomyocytes after hypoxia, suggesting that it might be strongly associated with hypoxia-related diseases. Here, we investigated the role of miR-30a in the PASMC remodeling of PAH. The expression of miR-30a was higher in the serum of PAH patients compared with healthy controls. miR-30a was mainly expressed in PAs and was increased in PASMCs after hypoxia, mediating the downregulation of p53 tumor suppressor protein (P53). Genetic knockout of miR-30a effectively decreased right ventricular (RV) systolic pressure (RVSP), PA, and RV remodeling in the Su5416/hypoxia-induced and monocrotaline (MCT)-induced PAH animals. Additionally, pharmacological inhibition of miR-30a via intratracheal liquid instillation (IT-L) delivery strategy showed high efficiency, which downregulated miR-30a to mitigate disease phenotype in the Su5416/hypoxia-induced PAH animals, and these beneficial effects could be partially reduced by simultaneous P53 inhibition. We demonstrate that inhibition of miR-30a could ameliorate experimental PAH through the miR-30a/P53 signaling pathway, and the IT-L delivery strategy shows good therapeutic outcomes, providing a novel and promising approach for the treatment of PAH., Graphical abstract, Inhibition of miRNA-30a alleviates vascular remodeling in pulmonary arterial hypertension (PAH) through the miR-30a/P53 signaling pathway, and the intratracheal liquid instillation (IT-L) delivery strategy shows good therapeutic outcomes, providing a novel and promising approach for the treatment of PAH.

Membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults. Idiopathic MN (IMN), one of the forms of MN, usually has an unknown etiology. IMN is described as an autoimmune disease, and its pathogenesis is quite complex. The discovery of the M-type phospholipase A2 receptor (PLA2R) plays an important role in promoting our understanding of IMN, although the exact mechanisms of its occurrence and development are still not completely clear. Other target antigens have been discovered one after another, as considerable progress has been made in the molecular pathomechanisms of IMN. Here, we review the findings about the target antigens associated with IMN in recent years. It is hoped that this article can provide researchers with some scientific issues or innovative ideas for future studies of IMN, which will provide clinicians with more knowledge about further improving their abilities to provide better medical care for IMN patients.

Sentiment analysis (SA) is an important research area in cognitive computation-thus in-depth studies of patterns of sentiment analysis are necessary. At present, rich resource data-based SA has been well developed, while the more challenging and practical multi-source unsupervised SA (i.e. a target domain SA by transferring from multiple source domains) is seldom studied. The challenges behind this problem mainly locate in the lack of supervision information, the semantic gaps among domains (i.e., domain shifts), and the loss of knowledge. However, existing methods either lack the distinguishable capacity of the semantic gaps among domains or lose private knowledge. To alleviate these problems, we propose a two-stage domain adaptation framework. In the first stage, a multi-task methodology-based shared-private architecture is employed to explicitly model the domain common features and the domain-specific features for the labeled source domains. In the second stage, two elaborate mechanisms are embedded in the shared private architecture to transfer knowledge from multiple source domains. The first mechanism is a selective domain adaptation (SDA) method, which transfers knowledge from the closest source domain. And the second mechanism is a target-oriented ensemble (TOE) method, in which knowledge is transferred through a well-designed ensemble method. Extensive experiment evaluations verify that the performance of the proposed framework outperforms unsupervised state-of-the-art competitors. What can be concluded from the experiments is that transferring from very different distributed source domains may degrade the target-domain performance, and it is crucial to choose the proper source domains to transfer from., Comment: 17 pages, 4 figures

Introduction. The modification of lysine crotonylation (Kcr) is another biological function of histone in addition to modification of lysine acetylation (Kac), which may play a specific regulatory role in diseases. Objectives. This study compared the expression levels of Kcr and proteome between patients with chronic obstructive pulmonary disease (COPD) combined with type II respiratory failure (RF) to study the relationship between Kcr, proteome, and COPD. Methods. We tested the Kcr and proteome of COPD combined with type II RF and normal control (NC) using croton acylation enrichment technology and liquid chromatography tandem mass spectrometry (LC-MS/MS) with high resolution. Results. We found that 32 sites of 23 proteins were upregulated and 914 sites of 295 proteins were downregulated. We performed Kyoto Encyclopedia of Genes and Genomes (KEGG), protein domain, and Gene Ontology (GO) analysis on crotonylated protein. In proteomics research, we found that 190 proteins were upregulated and 151 proteins were downregulated. Among them, 90 proteins were both modified by differentially expressed crotonylation sites and differentially expressed in COPD combined with type II RF and NC. Conclusion. Differentially expressed crotonylation sites may be involved in the development of COPD combined with type II RF. 90 proteins modified by crotonylation and differentially expressed in COPD combined with type II RF can be used as markers for the study of the molecular pathogenesis of COPD combined with type II RF.

The incidence and mortality of colon cancer in China are increasing each year. At present, treatment selection for colon cancer patients mainly depends on imaging results, which require a large number of radiologists to interpret. In China, there is a shortage and uneven distribution of experienced radiologists, which leads to delays and bias in the evaluation of imaging data. Based on these considerations, the Colorectal Surgery Group of the Surgery Branch of the Chinese Medical Association in collaboration with experts at Beihang University has independently developed an artificial intelligence (AI)-based recognition system for the preoperative determination of colon cancer stage to partially replace the work of and relieve the pressure on radiologists. These guidelines aim to standardize the use of AI-based recognition systems in the preoperative staging of colon cancer and guide their clinical application.

SINQ Target-11 was in operation in 2015 and 2016. It was shut down due to an incident in June 2016, during which the pressure drop in the cooling water loop increased significantly, and meanwhile, the activity of the cooling water also increased tremendously. The evidence indicated a serious failure of the target. As this is the first severe failure since SINQ came into operation in 1997, some post-irradiation examinations (PIE) were performed to analyze the failure mechanisms.

Background: Intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC) acts on the tumor and affects surrounding organs at risk (OARs). This study aimed to quantify the geometric changes in the parotid gland, the submandibular gland (SMG), and the thyroid, during the course of treatment. Methods: Twenty patients diagnosed with locally advanced NPC were consecutively enrolled, and received definitive chemoradiotherapy in 33 fractions over 6.5 weeks. Each patient underwent planning computed tomography (pCT) followed by six weekly repeat CTs (rCTs) without contrast enhancement. Each rCT was rigidly registered to its pCT. Changes in terms of volume, position, and shape of the OARs were assessed. Differences in left- and right-sided OARs were compared. Results: Radiation doses to the parotid, SMG, and thyroid were 32.12 ± 11.2 Gy (mean ± standard deviation SD), 25.46 ± 8.62 Gy, and 18.89 ± 10.24 Gy, respectively. Volume reductions of 28.6% ± 14.6% (mean ± SD), 26.6% ± 17.1%, and 12.3% ± 11.3% were observed in the parotid, SMG, and thyroid, respectively. Rate of volume loss for the parotid and SMG decreased from 1.6-1.7% per day in the first week to 0.5%-0.6% in the last week. Contrarily, not all thyroid lobes decreased in volume during treatment. The center of mass of the parotid shifted 2.0-2.6 mm medially; for the SMG and thyroid, a 0.1-0.5 mm medial shift was noted. The displacement in the anterior-posterior and cranial-caudal directions was < 0.6 mm. The 3-dimensional vector displacements of the parotid and SMG were 2.2-2.9 mm, and that of thyroid was 4.0-4.3 mm. The overlapping metrics of all three OARs decreased over time, and the shortest perpendicular distance increased from 1.5-1.8 mm in the first week to 2.4-2.5 mm in the last week. The geometric differences between weeks were statistically significant (P

This paper presents a secure communication access authentication technology for power wireless private network. At the physical layer, the device is identified based on physical radio frequency fingerprint authentication, which improves the security of device access. At the same time, the idea of distributed authentication is used to reduce the device authentication pressure of the gateway on the core network side and improve the speed of access device authentication.

Purpose This study aims to solve the problem of the existing metal foreign object (MFO) detecting systems, which are not sensitive to the small size MFO in wireless charging region of electric vehicle (EV) because of the extremely complex signal noise in the process of wireless charging of EV. Design/methodology/approach A method for MFO detection based on the principle that MFOs can cause mistuned resonance of detection coil resonant circuit is proposed. The general scheme of detecting system is proposed. The design method for detection coils which is effective to small MFOs detection in large-area region of wireless charging of EV is presented. The design of time-sharing driving circuit and amplifying circuit of high frequency exciting signal for detection coils is introduced. The design scheme of signal processing circuit (including filter and rectifier) of detection coil terminal voltage is also proposed. Findings The influence of exciting frequency of detection coils on detecting sensitivity and the anti-noise feature of system are analyzed according to the experiment results. Originality/value The experiment of MFO detection indicates that the proposed method can effectively detect the coin-sized small MFO in the process of wireless charging of EV.

The histone demethylase KDM4B functions as a key co-activator for the androgen receptor (AR) and plays a vital in multiple cancers through controlling gene expression by epigenetic regulation of H3K9 methylation marks. Constitutively active androgen receptor confers anti-androgen resistance in advanced prostate cancer. However, the role of KDM4B in resistance to next-generation anti-androgens and the mechanisms of KDM4B regulation are poorly defined. Here we found that KDM4B is overexpressed in enzalutamide-resistant prostate cancer cells. Overexpression of KDM4B promoted recruitment of AR to the c-Myc (MYC) gene enhancer and induced H3K9 demethylation, increasing AR-dependent transcription of c-Myc mRNA, which regulates the sensitivity to next-generation AR-targeted therapy. Inhibition of KDM4B significantly inhibited prostate tumor cell growth in xenografts, and improved enzalutamide treatments through suppression of c-Myc. Clinically, KDM4B expression was found upregulated and to correlate with prostate cancer progression and poor prognosis. Our results revealed a novel mechanism of anti-androgen resistance via histone demethylase alteration which could be targeted through inhibition of KDM4B to reduce AR-dependent c-Myc expression and overcome resistance to AR-targeted therapies. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

To verify reliability of antibody detection and investigate population immunity to severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) in the local Chinese population. A cross-sectional study was conducted in Shenzhen to detect anti-coronavirus antibodies including, immunoglobulin G (IgG), immunoglobulin M (IgM), and immunoglobulin A (IgA). In the COVID-19 group, nine patients were enrolled after diagnosis. In the control group, 1589 individuals without clinical symptoms (cough, fever, and fatigue) and returning from outside Shenzhen were enrolled. The first study enrollment occurred at the end of February 2020; the final study visit was 18 March 2020. In the COVID-19 group, the seven of nine patients were positive for IgM, IgG, and IgA. Meanwhile, six of the 1589 healthy individuals were found to be weakly positive for IgG. According to SARS-CoV-2 nucleic acid tests, the six individuals were all negative. Strong supplemental support for clinical information can be provided by antibody detection, especially for IgA. According to comparison with overseas reports, the infection rate of the Chinese population outside Shenzhen, China, is significantly low, so most of the population in China is still susceptible. Hence, social distancing measures are still inevitable until a vaccine is developed successfully.

The outbreak of a large plaque, novel coronavirus pneumonia (NCP), which also named Coronavirus Disease 2019 (COVID-19) by the WHO, has detrimentally affected the livelihood and health of people in China. During the spread of COVID-19, colleagues who have been working at the frontline have had to face many new challenges in the treatment and prevention of NCP. Therefore, we have provided suggestions for the diagnosis, treatment, and prevention of the novel coronavirus pneumonia in the current epidemic situation based on the latest reports and the experience of doctors treating COVID-19 in our hospital. We recommend lopinavir/ritonavir as the effective drugs for antiviral treatment according to our experience in administering lopinavir/ritonavir to COVID-19 patients and the successful cases of these drugs in treating MERS and SARS, but need more clinical data to prove their efficacy in treating COVID-19.

Transplantation is currently the best treatment for patients with end-stage renal disease. However, acute rejection (AR) is the major source of failure in renal transplantation. The current best practice for the diagnosis of AR involves renal biopsy, but it is invasive, time-consuming, costly and inconvenient. Sensitive and less invasive detection of AR episodes in renal transplant patients is essential to preserve allograft function. The present study applied isobaric tags for relative and absolute quantitation (iTRAQ) mass spectrometry to analyze serum protein expression in patients with AR and healthy controls. Overall, 1,399 proteins were identified. Using a cut-off of Q1.2 for the variation in expression, 109 proteins were identified to be differentially expressed between the AR and control groups, 72 of which were upregulated and 37 were downregulated. Several proteins, including properdin, keratin 1, lipoprotein(a) and vitamin D-binding protein, may have roles in the pathogenesis of AR. The present study focused on iTRAQ-based proteomic profiling of serum samples in AR. Insight from the present study may help advance the understanding of the molecular mechanisms of AR and identify potential novel biomarkers of AR for further characterization.

An outbreak of severe acute respiratory syndrome‐related coronavirus 2 infection has posed significant threats to international health and the economy. In the absence of specific treatment for this virus, there is an urgent need to learn from the experience and lessons in China. To reduce the case‐fatality rate among coronavirus disease 2019 patients, we should not ignore the complications, such as RNAaemia, acute respiratory distress syndrome, and multiple organ dysfunction. To help understand the advantages and limitations of differential treatments, we provide a timely review and discuss the complications and corresponding major treatments, especially controversial ones such as antiviral therapy (remdesivir, ribavirin, and chloroquine), glucocorticoid therapy, extracorporeal support including an artificial liver system, and extracorporeal membrane oxygenation based on available evidence. As a result, we suggest that antiviral therapy and organ function support are vital to reduce mortality for mild patients and critical patients, respectively.

Renal transplantation is the most effective treatment for end-stage renal disease, but the long-term prognosis of organs after transplantation is not ideal. In recent years, the importance of gut microbes and metabolites in the study of disease mechanisms has gradually received attention. However, the coordination between gut microbes and the metabolism of renal transplant patients needs further study. We integrated 16s sequencing and metabolomics data to describe the changes in the serum and fecal metabolites of renal transplant patients. Our data revealed that the gut microbial diversity decreased and the relative abundance of many bacteria, such as Enterococcus and Streptococcus, significantly changed after transplantation. In addition, a large number of amino acids and peptides in serum and feces significantly changed, suggesting an abnormal amino acid metabolism after transplantation. Spearman's correlation analysis revealed the changes in the co-metabolism pattern between gut microbes and the host metabolism after transplantation. Furthermore, Enterococcus was found to be correlated with renal functions and metabolites reflecting renal damage. This study provides potential gut microbes and metabolites impacting renal health, which helps in understanding the renal damage in patients with kidney transplantation.

BackgroundProficient mismatch repair (pMMR) colorectal adenocarcinoma (CRAC) metastasizes to a greater extent than MMR-deficient CRAC. Prognostic biomarkers are preferred in clinical practice. However, traditional biomarkers screened directly from sequencing are often not robust and thus cannot be confidently utilized.MethodsTo circumvent the drawbacks of blind screening, we established a new strategy to identify prognostic biomarkers in the conserved and specific oncogenic pathway and its regulatory RNA network. We performed RNA sequencing (RNA-seq) for messenger RNA (mRNA) and noncoding RNA in six pMMR CRAC patients and constructed a glycosylation-related RNA regulatory network. Biomarkers were selected based on the network and their correlation with the clinicopathologic information and were validated in multiple centers (n = 775).ResultsWe constructed a competing endogenous RNA (ceRNA) regulatory network using RNA-seq. Genes associated with glycosylation pathways were embedded within this scale-free network. Moreover, we further developed and validated a seven-glycogene prognosis signature, GlycoSig (B3GNT6, GALNT3, GALNT8, ALG8, STT3B, SRD5A3, and ALG6) that prognosticate poor-prognostic subtype for pMMR CRAC patients. This biomarker set was validated in multicenter datasets, demonstrating its robustness and wide applicability. We constructed a simple-to-use nomogram that integrated the risk score of GlycoSig and clinicopathological features of pMMR CRAC patients.ConclusionsThe seven-glycogene signature served as a novel and robust prognostic biomarker set for pMMR CRAC, highlighting the role of a dysregulated glycosylation network in poor prognosis.

Background Post-translational modifications (PTMs) are at the heart of many cellular signaling events, which changes the function of protein. Crotonylation, one of the most important and common PTMs, plays a crucial role in the regulation of various biological processes. However, no study has evaluated the role of lysine crotonylation modification in chronic renal failure (CRF) patients. Methods Here, we comparatively evaluated the crotonylation proteome of normal controls and chronic renal failure patients using liquid chromatography-tandem mass spectrometry (LC-MS/MS) coupled with highly sensitive immune-affinity purification. Results A total of 1109 lysine modification sites were identified, of which 772 sites were up-regulated and 69 sites were down-regulated. This suggested that crotonylation modification maintains high levels in the patients with chronic renal failure. Gene ontology(GO) enrichment analysis showed that the crotonylated proteins were significantly enriched in the platelet alpha granule lumen, platelet degradulation, and cell adhesion molecule binding. In addition, Kyoto Encyclopedia of Genes and Genomes (KEGG)-based functional enrichment analysis in the Kyoto encyclopedia showed that crotonylated protein was enriched in CD36, which is closely linked to renal failure. Conclusions This is the first report of the global crotonylation proteome in chronic renal failure patients. Crotonylation of histone and non-histone may play important roles in delaying the continuous deterioration of renal function in patients with chronic renal failure.

Most previous risk-prediction models for gastrointestinal stromal tumors (GISTs) were based on Western populations. In the current study, we collected data from 23 hospitals in Shandong Province, China, and used the data to examine prognostic factors in Chinese patients and establish a new recurrence-free survival (RFS) prediction model. Records were analyzed for 5285 GIST patients. Independent prognostic factors were identified using Cox models. Receiver operating characteristic curve analysis was used to compare a novel RFS prediction model with current risk-prediction models. Overall, 4216 patients met the inclusion criteria and 3363 completed follow-up. One-, 3-, and 5-year RFS was 94.6% (95% confidence interval [CI] 93.8–95.4), 85.9% (95% CI 84.7–87.1), and 78.8% (95% CI 77.0–80.6), respectively. Sex, tumor location, size, mitotic count, and rupture were independent prognostic factors. A new prognostic index (PI) was developed: PI = 0.000 (if female) + 0.270 (if male) + 0.000 (if gastric GIST) + 0.350 (if non-gastric GIST) + 0.000 (if no tumor rupture) + 1.259 (if tumor rupture) + 0.000 (tumor mitotic count 10 per 50 HPFs) + 0.096 × tumor size (cm). Model-predicted 1-, 3-, and 5-year RFS was S(12, X) = 0.9926exp(PI), S(36, X) = 0.9739exp(PI) and S(60, X) = 0.9471exp(PI), respectively. Sex, tumor location, size, mitotic count, and rupture were independently prognostic for GIST recurrence. Our RFS prediction model is effective for Chinese GIST patients.

Background Immune aberrations in end-stage renal disease (ESRD) are characterized by systemic inflammation and immune deficiency. The mechanistic understanding of this phenomenon remains limited. Methods We generated 12 981 and 9578 single-cell transcriptomes of peripheral blood mononuclear cells (PBMCs) that were pooled from 10 healthy volunteers and 10 patients with ESRD by single-cell RNA sequencing. Unsupervised clustering and annotation analyses were performed to cluster and identify cell types. The analysis of hallmark pathway and regulon activity was performed in the main cell types. Results We identified 14 leukocytic clusters that corresponded to six known PBMC types. The comparison of cells from ESRD patients and healthy individuals revealed multiple changes in biological processes. We noticed an ESRD-related increase in inflammation response, complement cascade and cellular metabolism, as well as a strong decrease in activity related to cell cycle progression in relevant cell types in ESRD. Furthermore, a list of cell type-specific candidate transcription factors (TFs) driving the ESRD-associated transcriptome changes was identified. Conclusions We generated a distinctive, high-resolution map of ESRD-derived PBMCs. These results revealed cell type-specific ESRD-associated pathways and TFs. Notably, the pooled sample analysis limits the generalization of our results. The generation of larger single-cell datasets will complement the current map and drive advances in therapies that manipulate immune cell function in ESRD.

Aim: To investigate the autophagy-related gene (ATG) expression and the associated noncoding RNAs (ncRNA) and transcription factors (TF) in digestive system tumors (DST). Methods: We systematically investigated the ATG expression in DST by weighted gene correlation network analysis, crosstalk connection, functional analysis and Pivot analysis. Results: ATGs were clustered into six modules with co-expression in DST. Functional analysis revealed that six ATG-related modules were enriched in biological pathways involved in tumorigenesis. Pivot analysis identified key ncRNAs and TFs, which are essential for the pathogenesis, clinical diagnosis and treatment of DST. Conclusion: Our study highlights the crucial roles of ncRNA and TFs in the identification of potential biomarkers or therapeutic targets for DST.

Purpose This paper aims to propose an identification method based on monocular vision for cylindrical parts in cluttered scene, which solves the issue that iterative closest point (ICP) algorithm fails to obtain global optimal solution, as the deviation from scene point cloud to target CAD model is huge in nature. Design/methodology/approach The images of the parts are captured at three locations by a camera amounted on a robotic end effector to reconstruct initial scene point cloud. Color signatures of histogram of orientations (C-SHOT) local feature descriptors are extracted from the model and scene point cloud. Random sample consensus (RANSAC) algorithm is used to perform the first initial matching of point sets. Then, the second initial matching is conducted by proposed remote closest point (RCP) algorithm to make the model get close to the scene point cloud. Levenberg Marquardt (LM)-ICP is used to complete fine registration to obtain accurate pose estimation. Findings The experimental results in bolt-cluttered scene demonstrate that the accuracy of pose estimation obtained by the proposed method is higher than that obtained by two other methods. The position error is less than 0.92 mm and the orientation error is less than 0.86°. The average recognition rate is 96.67 per cent and the identification time of the single bolt does not exceed 3.5 s. Practical implications The presented approach can be applied or integrated into automatic sorting production lines in the factories. Originality/value The proposed method improves the efficiency and accuracy of the identification and classification of cylindrical parts using a robotic arm.

Liver cancer is the second leading cause of cancer mortality worldwide. Safer and more effective diagnostic methods for liver cancer are desirable, and biomarkers represent a potentially alternative method for diagnosis. The present study was designed to identify liver cancer biomarkers. We quantified the changes in serum protein levels between liver transplantation and healthy (control) females using isobaric tags for relative and absolute quantitation (iTRAQ) as well as proteomic analysis. A total of 1399 proteins were identified; of these, three proteins showed significantly different concentrations between the before transplantation group and the control group. These proteins may thus be relevant to liver cancer and constitute potential liver cancer biomarkers.

ObjectiveFrailty is a common geriatric syndrome that is diagnosed and staged based mainly on symptoms. We aimed to evaluate frailty-related alterations of the intestinal permeability and profile fecal microbiota of healthy and frail older adults to identify microbial biomarkers of this syndrome.MethodsWe collected serum and fecal samples from 94 community-dwelling older adults, along with anthropometric, medical, mental health, and lifestyle data. Serum inflammatory cytokines IL-6 and HGMB1 and the intestinal permeability biomarker zonulin were measured using enzyme-linked immunosorbent assays. The 16S rRNA amplicon sequencing method was performed to determine the fecal composition of fecal microbiota. We analyzed the diversity and composition differences of the gut microbiota in the two groups and assessed the relationship between the changes in microbiota structure and clinical biomarkers.ResultsOlder adults with frailty showed higher concentrations of IL-6, HGMB1, and zonulin. Although there were no statistically significant differences in the diversity index and evenness indices or species richness of fecal microbiota between the two groups, we found significant microbiota structure differences. Compared with the control group, fecal samples from the frail group had higher levels of Akkermansia, Parabacteroides, and Klebsiella and lower levels of the commensal genera Faecalibacterium, Prevotella, Roseburia, Megamonas, and Blautia. Spearman’s correlation analysis showed that the intergenus interactions were more common in healthy controls than older adults with frailty. Escherichia/Shigella, Pyramidobacter, Alistipes, and Akkermansia were positively correlated with IL-6, while Faecalibacterium, Prevotella, and Roseburia were negatively correlated with IL-6. Alistipes were found to be positively correlated with HGMB1. Akkermansia and Alistipes were linked to the increased serum level of inflammatory factors and intestinal permeability.ConclusionsFrailty is associated with differences in the composition of fecal microbiota. These findings might aid in the development of probiotics or microbial-based therapies for frailty.

With the continuous construction and development of smart grid, the continuous introduction of new services, largescale access of new energy sources, energy storage and charging piles, and continuous growth of large-bandwidth services, traditional communication networks have been unable to meet the requirements of smart grid. FlexE technology adds FlexShim layer in MAC layer and PCS layer to achieve network flexibility, sub-rate, rigid interface and other characteristics, which can be well connected with IP/Ethernet technology to meet the higher requirements of network bandwidth, delay, slicing, reliability and other aspects. Therefore, it is necessary to develop a slicing network framework based on flexible Ethernet technology oriented to the communication requirements and trends of smart grid. Based on the analysis of the differentiated (deterministic time delay, large bandwidth, security isolation, etc.) requirements analysis of power communication services, we proposed a slice network framework based on flexible Ethernet technology and studied typical use cases based on FlexE technology for power services.

Background: Previously, we invented a therapeutic vaccine targeting the endothelin-A receptor (termed ETRQβ-002). ETRQβ-002 successfully prevented the remodeling of pulmonary arterioles (PAs) and right ventricle (RV) without significant immune-mediated damage in experimental pulmonary arterial hypertension (PAH) mice models.Objective: Here, we aim to further evaluate the long-term effects of ETRQβ-002.Methods: PAH mice model was induced by a combination of subcutaneous injection with Sugen5416 and chronic hypoxic conditions (10% O2). PAH mice were immunized with ETRQβ-002 at different time points, and the experiment lasted for 21 weeks. Hemodynamic, histological, and biochemical analyses were conducted to evaluate the long-term effects of ETRQβ-002.Results: We demonstrated that the titer of the specific antibody against ETR-002 could be maintained chronically after periodic booster immunization in PAH mice. Long-term reduction of right ventricular systolic pressure and amelioration of PA remodeling by ETRQβ-002 were confirmed. Moreover, we found that ETRQβ-002 also exerted antiproliferation, anti-inflammation, and antifibrosis effects in PA remodeling. Besides, ETRQβ-002 durably limited pathological RV hypertrophy and fibrosis. Finally, no immune-mediated damage was observed in hepatic or renal function or by pathology in liver and kidney during the long-term administration of ETRQβ-002.Conclusion: Our findings indicate that ETRQβ-002 provides long-term therapeutic effects in Sugen/hypoxia-induced PAH animals and offers a promising clinical prospect for PAH treatment.

Background: Systemic Lupus Erythematous (SLE) is a complex chronic autoimmune disease with productive autoantibodies and multiple organ systems damage. Currently, effective diagnosis and treatment for SLE are still challenged and the mechanism investigation of SLE will be helpful for developing the efficiency of disease diagnosis and treatment. Yet, the mechanism of SLE has not been clearly revealed. Thereafter, it needs more studies on the mechanism of SLE. We aim at investigating and verification critical signaling pathways underneath the molecular mechanism of SLE disease and constructing a systematic signaling network by integrating data from different omics. Methods: 20 pairs of experimental groups (the SLE patients and healthy people) were recruited in our study. Omics technologies and biomolecules included genomics (DNA), whole transcriptomics (miRNAs, lncRNAs, circRNAs and mRNAs), proteomics (proteins) were used for collecting high throughput data from peripheral blood mononuclear cells (PBMCs) of subjects in our study. Joint analysis method of Multi-omics was taken advantage of in our studies for investigating some disease-related regulatory signaling networks.Results: Potential biomolecules that contain unique expression patterns and disease related signaling pathways in SLE were identified in our study. These pathways and biomolecules include complement and coagulation cascades (C1q, C6), Systemic lupus erythematosus (HIST1H2BA, C1QC), Oxidation (NFYB, WFS1, ATXN3L), apoptotic (PIK3R3, GADD45G, CTSF), JAK-STAT (TYK2, STAT1/2), TNF signaling, Cell proliferation, cellular senescence et al. Signaling pathways identified by different omics were connected with each other by sharing some common molecules and constructed the potential systematic regulation networks in SLE.Conclusions: Multi-omics technologies and the integrative analysis method develop some novel potential biomarkers and systemic signaling networks, which promotes our understanding of SLE disease and extend information for improving studies of diagnosis and treatment.

Background Pulmonary artery hypertension (PAH) is an incurable disease with a high mortality rate. Current medications ameliorate symptoms but cannot target adverse vascular remodeling. New therapeutic strategies for PAH need to be established. Methods Using the weighted gene coexpression network analysis (WGCNA) algorithm, we constructed a coexpression network of dataset GSE117261 from the Gene Expression Omnibus (GEO) database. Key modules were identified by the relationship between module eigengenes and clinical traits. Hub genes were screened out based on gene significance (GS), module membership (MM), and mean pulmonary artery pressure (mPAP). External validations were conducted in GSE48149 and GSE113439. Functional enrichment and immune cell infiltration were analyzed using Metascape and CIBERSORTx. Results The WGCNA analysis revealed 13 coexpression modules. The pink module had the highest correlation with PAH in terms of module eigengene (r=0.79; P=2e-18) and module significance (MS =0.43). Functional enrichment indicated genes in the pink module contributed to the immune system process and extracellular matrix (ECM). In the pink module, ECM2 (GS =0.65, MM =0.86, ρ=0.407, P=0.0019) and GLT8D2 (GS =0.63, MM =0.85, ρ=0.443, P=0.006) were identified as hub genes. For immune cells infiltration in PAH lung tissue, hub genes were positively correlated with M2 macrophages and resting mast cells, and were negatively correlated with monocytes, neutrophils, and CD4-naive T cells. Conclusions Our research identified 2 hub genes ECM2 and GLT8D2 related to PAH. The functions of these hub genes were involved in the immune process and ECM, indicating that they might serve as candidate therapeutic targets for PAH.

NEURAP is a dedicated set-up at the Swiss neutron spallation source (SINQ) at the Paul Scherrer Institut (PSI), optionally implemented as a special configuration of the neutron-imaging station NEUTRA. It is one of very few instrumentations available worldwide enabling neutron-imaging of highly radioactive samples to be performed routinely, with special precautions and following a specific procedure. Since the relevant objects are strong γ-sources, dedicated techniques are needed to handle the samples and to perform neutron-imaging despite the radiation background. Dysprosium (Dy)-loaded imaging plates, effectively made sensitive to neutrons only, are employed. Neutrons are captured by Dy during neutron irradiation. Then the imaging plate is erased removing gamma detections. A subsequent relatively long self-exposure by the radiation from the intrinsic neutron-activated Dy within the imaging plate yields the neutron-only radiograph that is finally read out. During more than 20 years of NEURAP operation, images have been obtained for two major applications: (a) highly radioactive SINQ target components were investigated after long-term operation life; and (b) spent fuel rods and their cladding from Swiss nuclear power plants were characterized. Quantitative analysis of the image data demonstrated the accumulation of spallation products in the lead filled “Cannelloni” Zircaloy tubes of the SINQ target and the aggregation of hydrogen at specific sites in used fuel pins of power plants and their cladding, respectively. These results continue to help understanding material degradation and optimizing the operational regimes, which might lead to extending the safe lifetimes of these components.

Background The 15q11‐q13 region contains three breakpoints (BP1 to BP3), and copy number variations often occur in the region. Aims 15q11‐q13 microdeletion and microduplication are usually associated with Prader‐Willi and Angelman syndromes, respectively. It is not yet clear to what extent microdeletion and microduplication affect the physical health of the fetus and the child. In this study, we examined seven fetuses ranging in gestational age from 15 to 27 weeks. Materials & Methods Detailed prenatal screening and laboratory examinations were performed, while karyotype analysis and chromosomal microarray analysis (CMA) of the amniotic fluid and umbilical cord blood were applied for genetic analysis. Results CMA analysis showed that four fetuses harbored a microdeletion and one fetus showed a microduplication at 15q11.2 BP1‐BP2, two fetuses had a microdeletion at 15q11‐q13 BP2‐BP3, and one fetus had an additional microdeletion at 16p13.11. Discussion There is no clear standard for the clinical diagnosis of 15q11‐q13 microdeletion and microduplication, some of them have clinical phenotypes or are clinically affected. Conclusion Therefore, parents of such fetuses should be informed of the possibility of microdeletions or microduplications to mitigate the psychological burden, and medical consultation and assistance should be provided when communicating the results of the mid‐gestation screening., All seven fetal cases in this report have 15q11‐q13 microdeletions and microduplications of different sizes, but not all of them have clinical phenotypes or are clinically affected.

Background: Chromosome 22q11.2 deletion (CH22qD) syndrome is the most common human deletion syndrome. Competing endogenous RNAs (ceRNAs) have miRNA binding sites that are capable of competitively binding miRNAs and inhibiting miRNA regulation of target genes. Results: We identified differently expressed miRNAs, circRNAs, lncRNAs and mRNAs of CH22qD, and we analysed the results by using GO analysis, KEGG pathway analysis and network regulation analysis. Conclusions: These analyses may predict the effects of chromosomal microdeletions.

Part-of-speech tagging and named entity recognition (NER) are fundamental sequential labeling tasks in natural language processing (NLP), where joint learning of both tasks is an effective one-step solution. Limited efforts have been made by existing research to meet such needs for Sindhi language. As POS tagging and NER are highly correlative sequence tagging tasks, so most often, a word recognized by the NER system may be recognized as a noun by a POS tagger. Thus, in this paper, we propose a neural joint model based on a bidirectional long-short term memory (BiLSTM) network and adversarial transfer learning to incorporate syntactic information from two tasks by using task-shared information. The syntactic structure captures and provides the information of long-range dependencies among words. Moreover, the self-attention is employed to capture intra-sentence dependencies to the joint model explicitly. Empirical results on two benchmark datasets show that our proposed joint model consistently and significantly surpass the existing methods.

This study aimed to evaluate the therapeutic effect of IR-61, a novel mitochondrial heptamethine cyanine dye with antioxidant effects, on diabetes mellitus-induced erectile dysfunction (DMED). Eight-week-old male Sprague–Dawley rats were intraperitoneally injected with streptozotocin (STZ) to induce type 1 diabetes. Eight weeks after STZ injection, all rats were divided into three groups: the control group, DM group, and DM + IR-61 group. In the DM + IR-61 group, the rats were administered IR-61 (1.6 mg kg−1) twice a week by intravenous injection. At week 13, erectile function was evaluated by determining the ratio of the maximal intracavernous pressure to mean arterial pressure, and the penises were then harvested for fluorescent imaging, transmission electron microscopy, histological examinations, and Western blot analysis. Whole-body imaging suggested that IR-61 was highly accumulated in the penis after intravenous injection. IR-61 treatment significantly improved the maximal ICP of diabetic rats. Additionally, IR-61 ameliorated diabetes-induced inflammation, apoptosis, and phenotypic transition of corpus cavernosum smooth muscle cells (CCSMCs) in penile tissue. IR-61 also attenuated mitochondrial damage, reduced reactive oxygen species production in the corpus cavernosum and upregulated sirtuin1 (SIRT1), sirtuin3 (SIRT3), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and heme oxygenase expression in penile tissue. In conclusion, IR-61 represents a potential therapeutic option for DMED by protecting the mitochondria of CCSMCs, which may be mediated by activation of the SIRT1, SIRT3, and Nrf2 pathways.

BACKGROUND Most preventive ileostomy following colorectal surgery requires a closure procedure. The intervals between primary surgery and ileostomy closure remain controversial. OBJECTIVE This study aimed to compare early versus late closure of preventive ileostomy following colorectal surgery. DATA SOURCE A systematic literature search was performed in conference papers, MEDLINE, EMBASE, the Cochrane Library, and the Clinicaltrials.gov database. STUDY SELECTION Randomized clinical trials published through October 2019 comparing early versus late closure of ileostomy following colorectal surgery were selected. MAIN OUTCOME MEASURES Morbidity, leak of the primary anastomosis, reoperation, surgical site infection, small-bowel obstruction/postoperative ileus, total operative time, and postoperative length of hospital stay were measured. Results were synthesized using meta-analysis and were rated as firm or weak evidence by trial sequential analysis. RESULTS A total of 6 randomized controlled trials were included. Firm evidence from trial sequential analysis demonstrated that the early closure of ileostomy after colorectal surgery reduced the incidence of small-bowel obstruction/postoperative ileus and required less total operative time, but increased the incidence of surgical site infection, compared with late closure of ileostomy; postoperative length of hospital stay tended to be longer with early versus late closure of ileostomy. Weak evidence showed that there was no difference between early and late closure in morbidity, reoperation, or leak of the primary anastomosis. LIMITATIONS The study was limited by some evidence rated as weak from trial sequential analysis, combined analysis of small-bowel obstruction and postoperative ileus, and exclusion of the influence of chemo- or radiotherapy. CONCLUSIONS In selected patients, early closure of ileostomy after colorectal surgery can be considered, with a lower incidence of postoperative small-bowel obstruction/postoperative ileus and less total operative time, but a relatively high surgical site infection rate. PROSPERO registration number: CRD42020160989.

Background: IgA nephropathy (IgAN) is one of the most common forms of primary glomerulonephritis. Recent studies have indicated that small noncoding RNAs, such as tRNA-derived small RNAs (tsRNAs), might be novel biomarkers for glomerulonephritis. We therefore investigated the potential roles and possible functions of the tsRNAs in IgAN. Method: Peripheral blood mononuclear cells (PBMCs) were extracted from blood samples of the patients with IgAN and healthy control groups. The expression profiles of tsRNAs were assessed by small RNA sequencing (RNA-Seq) in PBMCs of the IgAN and control groups. Dysregulated tsRNAs were selected for validation by quantitative real-time polymerase chain reaction (qRT-PCR). Target gene prediction and enrichment were performed by bioinformatics analysis. Results: The results revealed that 143 significantly upregulated and 202 significantly downregulated tsRNAs were differentially altered in the IgAN group compared with the control group. Five upregulated tsRNAs (tRF-Val-AAC-007, tRF-Ala-AGC-063, tRF-Gln-CTG-010, tRF-Tyr-GTA-011 and tRF-Thr-AGT-007) and 3 downregulated tsRNAs (tiRNA-Val-TAC-004, tRF-Gly-CCC-005 and tRF-His-GTG-006) were selected for validation by qRT-PCR; the results were consistent with the sequencing data. Gene Ontology (GO) analysis revealed that the target genes predicted by upregulated tsRNAs were mostly enriched in “nucleic acid metabolic process," “intracellular part," and “ion binding," whereas the target genes predicted by downregulated tsRNAs were mostly enriched in “regulation of cellular component organization," “membrane-bound organelle," and “ion binding." Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the target genes predicted by upregulated tsRNAs were mostly enriched in “herpes simplex virus 1 infection," whereas the target genes predicted by downregulated tsRNAs were mostly enriched in “circadian rhythm Conclusions: The present study confirmed the differential expression of tsRNAs in patients with IgAN, and these dysregulated tsRNAs might be novel potential targets for the diagnosis and treatment of IgAN.

Background: Bladder cancer has a high rate of recurrence and drug resistance due to a lack of effective therapies. IR-780 iodide, a near-infrared (NIR) mitochondria-targeting fluorescent agent, has been demonstrated to achieve higher selectivity than other drugs in different tumor types. In the study, we aimed to investigate the anti-tumor effect of IR-780 combined with hyperbaric oxygen (HBO) on bladder cancer.Methods: Using in vitro cell line data, in vivo model data and clinical data, we tested the ability of IR-780 to selectively accumulate in bladder cancer. We also evaluated the anti-tumor effect of IR-780 combined or not with HBO both in vitro and in vivo, and explored the potential mechanism of its anti-tumor effect. Results: We revealed for the first time that IR-780 selectively accumulated in bladder cancer (bladder cancer cells, xenografts and bladder cancer samples from patients) and could induce cancer cell apoptosis by targeting the mitochondrial complex I protein NDUFS1. Further study displayed that the combination with HBO could significantly enhance the antitumor effect of IR-780 in vitro by promoting cancer cell uptake and inducing excessive mitochondrial reactive oxygen species (ROS) production, while suppressing tumor growth and recurrence in animal models without causing apparent toxicity. Moreover, this combination antitumor strategy was also demonstrated in drug-resistant bladder cancer cells (T24/DDP) and xenografts. Conclusions: These data identify for the first time a combination of IR-780 and HBO (IR-780+HBO), which exhibits mitochondria-targeting and therapeutic capabilities, as a novel treatment paradigm for bladder cancer.

The rapid rise of Multimedia Broadband Services(MBS) makes the network traffic grow rapidly, which brings great challenges to the construction of smart grid. IP + optical network architecture based on SDN is an effective solution to this problem. However, the coordination ability and resource utilization of each layer of the network are often low. Therefore, for MBS, this paper proposes a DRL-Driven Service Routing method in Software-defined IP+Optical Smart Grid Communication Networks. Aiming at delay, network risk and primary/alternate routes similarity, this paper a reasonable routes allocation model. Then, deep reinforcement learning algorithm is used to solve the model. The simulation results show that this method can not only make full use of the resources of IP + optical networks, but also reduce the network risk, which provides a theoretical guidance for the routing method of MBS in smart grid communication network.

Background Since December 2019, coronavirus disease (COVID-19) has affected over 50 000 people in Wuhan, China. However, the number of daily infection cases, hospitalization rate, lag time from onset to diagnosis date and their associations with measures introduced to slow down the spread of COVID-19 have not been fully explored. Methods This study recruited 6872 COVID-19 patients in the Wuchang district, Wuhan. All of the patients had an onset date from 21 December 2019 to 23 February 2020. The overall and weekly hospitalization rate and lag time from onset to diagnosis date were calculated. The number of daily infections was estimated by the back-projection method based on the number of daily onset cases. Their association with major government reactions and measures was analyzed narratively. Results The overall hospitalization rate was 45.9% (95% CI 44.7 to 47.1%) and the mean lag time from onset to diagnosis was 11.1±7.4 d. The estimated infection curve was constructed for the period from 14 December 2019 to 23 February 2020. Raising public awareness regarding self-protecting and social distancing, as well as the provision of timely testing and inpatient services, were coincident with the decline in the daily number of infections. Conclusion Early public awareness, early identification and early quarantine, supported by appropriate infrastructure, are important elements for containing the spread of COVID-19 in the community.

Background: Malaria remains a global health threat for centuries. In recent years, a rising resistance of Plasmodium falciparum to current standard artemisinin-based combination therapies (ACTs) leads to increasing treatment failures and requires for optimized treatment. Here, we intend to make a systematic review and meta-analysis of optimizing treatment for malaria, so as to find a potential optimal treatment. Methods: We will search electronic databases: the Cochrane Infectious Diseases Group (CIDG) Specialized Register, the Cochrane Central Register of Controlled Trials (CEN-TRAL), PubMed, Embase, Web of Science from their inception to 1 July, 2020. We will also search International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov, and contact with authors when necessary. Two authors will independently collect and select data, and the statistical analyses will be conducted by Revman V.5.3 software. Results: We will evaluate efficacy and safety of modified ACTs for uncomplicate malaria, comparing with standard ACTs in all eligible clinical studies. Conclusion: In this study, we will offer clinical evidence for optimizing treatment for malaria. Registration number: INPLASY202070115

Lysine 2-hydroxyisobutyrylation (Khib) is one of the newly identified post-translational modifications (PTMs) primitively identified by mass spectrometry (MS). Research in animals suggests that histone Khib is related to regulation of chromatin and cellular functions. However, there is no review to summarize and elaborate on the current understanding of Khib. In this review, we start with the basic description of Khib, such as sequence preference and subcellular localization. We then analyze the lysine 2-hydroxyisobutyrylated sites with the purpose of learning its functions and activities. We finally discuss the regulation toward Khib and the way it regulates, thus opening an avenue for us to illustrate the diverse cellular metabolites associated with (Khib).

Background: Acetylation has a vital role in the pathogenesis of end-stage renal disease (ESRD). Lysine 2-hydroxyisobutyrylation (Khib) is a novel type of acetylation. In this study, we aimed to reveal the key features of Khib in peripheral blood monocytes (PBMCs) of patients with ESRD. Method: We combined TMT labeling with LC-MS/MS analysis to compare Khib modification of PBMCs between 20 ESRD patients and 20 healthy controls. The pan 2-hydroxyisobutyrylation antibody-based affinity enrichment method was used to reveal the features of Khib, and the bioinformatics analysis was conducted to analyze the pathology of these Khib-modified proteins. Result: Compared to healthy controls, we identified 440 upregulated proteins and 552 downregulated proteins in PBMCs of ESRD, among which 579 Khib sites on 324 upregulated proteins and 287 Khib sites on 188 downregulated proteins were identified. The site abundance, distribution, and function of the Khib protein were further analyzed. The bioinformatics analysis revealed that the Rho/ROCK signaling pathway was highly enriched in ESRD, suggesting that it might contribute to renal fibrosis in ESRD patients. Conclusion: In this study, we found that Khib-modified proteins correlated with the occurrence and progression of ESRD.

Background Long noncoding RNA POU class 3 homeobox 3 (POU3F3) is upregulated in esophageal squamous-cell carcinomas. The present study aimed to investigate the role of POU3F3 in non-small cell lung cancer (NSCLC). Methods A total of 80 patients with NSCLC (adenocarcinoma) admitted by Guangdong Provincial Hospital of Integrated Traditional Chinese and Western Medicine between May 2016 and May 2018 were enrolled in this study. All patients were diagnosed by histopathological approaches. Expression levels of POU3F3 and microRNA-30d-5p (miR-30d-5p) in cancer and non-tumor tissues from these NSCLC patients were determined by qRT-PCR. Cell transfections were performed to assess interactions between miR-30d-5p and POU3F3. Cell proliferation, Transwell migration and invasion assays were performed to investigate the role of miR-30d-5p and POU3F3 in the regulation of cell proliferation, migration and invasion. Results POU3F3 was upregulated, while miR-30d-5p was downregulated in cancer tissues than in adjacent healthy tissues of NSCLC patients. Correlation analysis showed that expression levels of POU3F3 and miR-30d-5p were inversely correlated in tumor tissues. Overexpression of miR-30d-5p did not affect the expression of POU3F3, while overexpression of POU3F3 resulted in the suppression of miR-30d-5p in NSCLC cell lines. Overexpression of POU3F3 mediated enhanced proliferation, migration and invasion of NSCLC cells. In addition, overexpression of miR-30d-5p played an opposite role and attenuated the effects of overexpressing POU3F3 on cancer cell proliferation, migration and invasion. Conclusions POU3F3 might positively regulate NSCLC cell proliferation, migration and invasion through downregulation of miR-30d-5p.

In view of the frequent access problem of massive terminal equipment in the power wireless private network, it is necessary to develop more efficient access authentication mechanism and technology. This paper designs a new privacy-enhanced group authentication protocol for wireless networks based on the end-to-end identity authentication framework of massive power wireless private networks in groups. Compared with the traditional end-to-end authentication method, this protocol enhances the privacy protection function. At the same time. the protocol can meet the real-time requirements of group communication scenarios, and can also better meet the business requirements of power wireless private network.

LTE power wireless private network communication systems are widely adopted by the State Grid of China. In this paper, two improved security schemes for LTE power wireless private network communication system are proposed. Firstly, the security isolation scheme of wireless side network in LTE power wireless private network communication system is proposed. By setting two PLMNs in the power wireless communication system messages broadcast on the base station side, which corresponding to the production control area and management information area respectively, the two areas are identified to form a logical isolation. Secondly, by adding and assigning an access level to terminals of different services in the LTE power wireless private network communication system, the power service terminal realizes the access control of the network system, so as to achieve the access guarantee of some services under special conditions. These two improved schemes will be useful for the future in FDD system.

With the maturity of wireless communication technology, the ubiquitous power Internet of things (PIoT) has also been developed rapidly in recent years. Due to the wide variety of power services, different services have different requirements for communication networks. Therefore, the feasibility of network slicing technology in the PIoT needs to be considered. In this paper, we first introduce the key technologies of network slicing. Then, we analyze the power services and its requirements on wireless communication. And finally, we study the combination point of network slicing technology and different services of smart grid.

BACKGROUND There are many situations of abnormal metabolism influencing liver graft function. This study aims to provide data for the development of liver function recovery after liver transplantation by dynamically analyzing metabolites of bile acids pathway in serum. MATERIAL AND METHODS A comprehensive metabolomics profiling of serum of 9 liver transplantation patients before transplantation, on the 1st, 3rd, and 7th days after liver transplantation, and healthy individuals were performed by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Multivariate data and dynamic analysis were used to search for biomarkers between the metabolomics profiles present in perioperative liver transplantation and normal controls. RESULTS Thirty-three differential endogenous metabolites were screened by the threshold of variable importance in the projection (VIP) from an orthogonal partial least square discriminant analysis (OPLS-DA) greater than 1.0, q-value

Background and Aims Immunoglobulin A nephropathy (IgAN) is the most common form of primary glomerulonephritis. Intestinal bacteria and their metabolites have been implicated in various diseases. Improved understanding of the gut microbiota and its metabolic capabilities will facilitate development of diagnostic, therapeutic, and prognostic methods for IgAN Method We identified gut microbiota and metabolite biomarkers of IgAN by analyzing microbiomes and metabolomes of fecal and serum samples of IgAN patients and healthy controls using 16s ribosomal RNA gene sequencing and liquid chromatography-tandem mass spectrometry, respectively, and bioinformatics approaches Results We found that relative abundances of Streptococcus and Enterococcus were higher in IgAN patients, whereas Bacteroidetes and Bacteroides were lower. The changes in gut microbiota affected metabolism and absorbance of microbiota-associated metabolites of IgAN patients, in particular polyunsaturated fatty acids, free amino acids and oligopeptides, and activated the phenylalanine metabolism pathway. Also, 5-hydroxyeicosatetraenoic acid and 5-hydroxy-6E,8Z,11Z-eicosatrienoic acid were proved to be associated with the classification of segmental glomerular sclerosis but not 24h urine protein and estimated glomerular filtration rate. Conclusion Our findings demonstrate an interplay between intestinal bacteria and metabolites in IgAN. The identified metabolites may have diagnostic and therapeutic applications.