Urinary complement profile in IgA nephropathy and its correlation with the clinical and pathological characteristics

Background and objectivesThe activated complement profile in IgA nephropathy (IgAN) is still unclear. Our study investigated the profile of urinary complements in IgAN patients and its correlations with clinical and pathological characteristics.MethodsUrinary protein abundance was detected by liquid chromatography-tandem mass spectrometry (LC–MS/MS) in 50 IgAN, 50 membranous nephropathy (MN), and 68 healthy controls (HC). Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to identify differentially expressed proteins in IgAN patients. The differentially expressed complement proteins were screened in IgAN patients, and their correlations with laboratory or pathological parameters were analyzed. Thereafter, 7 complement components were validated by enzyme-linked immunosorbent assay (ELISA) in the urine samples of 45 IgAN patients.ResultsThere were 786 differentially expressed proteins between IgAN and HC. KEGG analysis showed that differentially expressed urinary proteins in IgAN were enriched with complement. Of these, 67% of urinary complement protein abundance was associated with the estimated glomerular filtration rate. The urinary complement-related protein collectin12 (colec12), complement H factor (CFH), complement H factor-related protein 2 (CFHR2), and complement B factor (CFB) were positively correlated with serum creatinine; colec12, CFHR2, CFB, and C8g were positively correlated with glomerulosclerosis; CFH, CFHR2, C8g, and C9 were positively correlated with tubular atrophy/interstitial fibrosis.ConclusionAbnormally increased components of complement pathways significantly correlate with reduced renal function, proteinuria, and renal histological damage in IgAN. It could provide a potential biomarker panel for monitoring IgAN and provide clues for therapeutic choice targeting complement system of IgAN patients

Bloodstream infection, peritonitis, and pneumonia caused by Pasteurella multocida in a patient with liver cirrhosis despite no animal contact: case report and literature review

Pasteurella multocida is an opportunistic pathogen. Previously reported infections associated with P. multocida have often been linked to contact with cats, dogs, and other animals. Cases of systemic multiple-site infections following P. multocida infection are rare. This case study presents a 49-year-old middle-aged man with post-hepatitis B cirrhosis and no history of animal contact. The patient was admitted with symptoms of fever accompanied by diarrhea, abdominal distension, and cough. Blood tests showed elevated levels of CRP, PCT, and IL-6, and blood culture revealed the growth of P. multocida. CT scans revealed a large amount of abdominal effusion, a small amount of pleural effusion, and pulmonary infection foci. The patient’s condition improved after successive administration of ceftriaxone and levofloxacin to fight the infection, and abdominal puncture and drainage. Multiple-site infections caused by P. multocida are rarely encountered in patients with liver cirrhosis but without animal contact, which could be regarded as serious conditions warranting careful attention in terms of clinical diagnosis and treatment

A robust autoregressive long-term spatiotemporal forecasting framework for surrogate-based turbulent combustion modeling via deep learning

This paper systematically develops a high-fidelity turbulent combustion surrogate model using deep learning. We construct a surrogate model to simulate the turbulent combustion process in real time, based on a state-of-the-art spatiotemporal forecasting neural network. To address the issue of shifted distribution in autoregressive long-term prediction, two training techniques are proposed: unrolled training and injecting noise training. These techniques significantly improve the stability and robustness of the model. Two datasets of turbulent combustion in a combustor with cavity and a vitiated co-flow burner (Cabra burner) have been generated for model validation. The effects of model architecture, unrolled time, noise amplitude, and training dataset size on the long-term predictive performance are explored. The well-trained model can be applicable to new cases by extrapolation and give spatially and temporally consistent results in long-term predictions for turbulent reacting flows that are highly unsteady

Antibiotic resistance spectrum of E. coli strains from different samples and age-grouped patients: a 10-year retrospective study

Objective Escherichia coli (E. coli) is the most common opportunistic clinical micro-organism with high drug resistance. This study aimed to analyse the resistance pattern of E. coli according to patient age and clinical sample type.Design and setting This retrospective observational study was conducted in a tertiary hospital in southeastern China.Participants E. coli strains were isolated from blood, urine and sputum of infected inpatients. The patients were divided into four age groups: children (0–14 years old, including neonatal and non-neonatal groups), youths (15–40 years old), middle-aged (41–60 years old) and old (>60 years old).Results A total of 7165 E. coli strains were collected from all samples. Compared with urine and blood isolates, more sputum isolates were resistant against 12 tested antibiotics. Furthermore, urine isolates were more resistant to levofloxacin than sputum and blood isolates. Although the patients’ age was not associated with resistance rates of E. coli strains isolated from blood, a larger proportion of urine-derived strains from youths were resistant to sulfamethoxazole-trimethoprim and piperacillin-tazobactam than those from old people. The sputum strains from the elderly were more resistant to most of the tested antibiotics compared with sputum strains isolated from children.Conclusions The resistance profile of E. coli is different among age groups and specimen sources and should be considered during E. coli infection treatment

XRRA1 Targets ATM/CHK1/2-Mediated DNA Repair in Colorectal Cancer

X-ray radiation resistance associated 1 (XRRA1) has been found to regulate the response of human tumor and normal cells to X-radiation (XR). Although XRRA1 overexpression is known to be involved in cancer cell response to XR, there are no reports about whether the expression of XRRA1 in tumors can adjust radioresistance. It is widely known that cell cycle arrest could cause radioresistance. We found that blocked XRRA1 expression could lead to cell cycle G2/M arrest by the regulation of cyclin A, cyclin E, and p21 proteins in colorectal cancer (CRC) and expression of XRRA1 reduced cell cycle arrest and increased cell proliferation in CRC. However, whether regulation of the cell cycle by XRRA1 can influence radioresistance is poorly characterized. Correspondingly, DNA repair can effectively lead to radioresistance. In our study, when cancer cells were exposed to drugs and ionizing radiation, low expression of XRRA1 could increase the phosphorylation of DNA repair pathway factors CHK1, CHK2, and ATM and reduce the expression of γ-H2AX, which is believed to participate in DNA repair in the nucleus. Crucially, our results identify a novel link between XRRA1 and the ATM/CHK1/2 pathway and suggest that XRRA1 is involved in a DNA damage response that drives radio- and chemoresistance by regulating the ATM/CHK1/2 pathway

Metabolomics Mechanism and Lignin Response to Laxogenin C, a Natural Regulator of Plants Growth

Laxogenin C (LGC) is a natural spirostanol deriving from plant hormone which has shown growing regulation similar to those of brassinosteroids. In the present study, LGC showed a promoting effect on tomato seed germination and seedling growth in a dose-dependent manner. We applied LC-MS/MS to investigate metabolome variations in the tomato treated with LGC, which revealed 10 differential metabolites (DMs) related to KEGG metabolites, associated with low and high doses of LGC. Enrichment and pathway mapping based on the KEGG database indicated that LGC regulated expressions of 2-hydroxycinnamic acid and l-phenylalanine to interfere with phenylalanine metabolism and phenylpropanoids biosynthesis. The two pathways are closely related to plant growth and lignin formation. In our further phenotypic verification, LGC was confirmed to affect seedling lignification and related phenylpropanoids, trans-ferulic acid and l-phenylalanine levels. These findings provided a metabolomic aspect on the plant hormone derivates and revealed the affected metabolites. Elucidating their regulation mechanisms can contribute to the development of sustainable agriculture. Further studies on agrichemical development would provide eco-friendly and efficient regulators for plant growth control and quality improvement

Spatio-Temporal Variation and Influencing Factors of the Coupling Coordination Degree of Production-Living-Ecological Space in China

Territorial space is a multi-functional complex. The coordinated production-living-ecological space (PLES) effectively coordinates the man-land relationship, promotes regional sustainable development, and maximizes territorial space. How to build a high-quality national spatial layout and support system for development has become a hot topic of concern in all sectors of society. However, few studies have explored the coupling coordination considering the various production-living-ecological functions of land use type and its influencing factors of PLES at the county scale in China. To address the gap, based on the connotation of PLES theory, this study established a classification and evaluation system for PLES and analyzed the spatio-temporal characteristics, coupling coordination degree, spatial autocorrelation, and influencing factors of PLES in China from 2000 to 2020. The results are as follows: (1) The production space index and living space index in China showed a continuous increase tendency, while the ecological space index decreased continuously during the study period. The production space and living space were concentrated in the east of Hu Line, and the ecological space indexes in mountainous areas were significantly higher than those in plain areas during the study period. (2) The gravity centers of PLES all migrated to the west of China to different degrees during the study period. (3) From 2000 to 2020, the basically balanced category was the main coupling coordination type, and the number of seriously unbalanced categories accounted for the least. In the west of the Hu Line, the seriously unbalanced category was dominant, while in the east of the Hu Line were the moderately unbalanced categories and above. (4) During the study period, the low-low type was the main relationship type, widely distributed in western China, followed by the high-high type, mainly situated in the North China Plain, Yangtze River Delta, Pearl River Delta, Jianghan Plain, Chengdu Plain, Northeast China Plain, and some provincial capital cities. (5) Regression results showed that natural factors were the main reason restricting the coordinated development of PLES, and socioeconomic factors could effectively promote the coordinated development of PLES. Landscape pattern also significantly influenced the coordinated development of PLES, but varied greatly. The findings of this study can provide a scientific reference for the optimization of territorial space layout and the promotion of high-quality development of territorial space