Validation of the Antineutrophil Cytoplasmic Antibody Renal Risk Score and Modification of the Score in a Chinese Cohort With a Majority of Myeloperoxidase-Positive Patients.

OBJECTIVE: We aimed to validate and modify the renal risk score for antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (AAGN) in a Chinese cohort with a majority of myeloperoxidase (MPO)-positive patients. METHODS: A total of 285 patients with biopsy-proven AAGN in our center were retrospectively included. Patients were randomly assigned to the development set (n = 201) and the validation set (n = 84). We calculated the renal risk score and analyzed the clinicopathological characteristics and follow-up data. The nomogram was constructed based on the independent prognostic factors identified by the multivariable Cox regression and then compared with the renal risk score. RESULTS: Over a median follow-up period of 41.3 (range 20.0-63.8) months, 84 (29.5%) patients reached end-stage kidney disease (ESKD). In the development set, hypertension (hazard ratio [HR] 2.16, 95% CI 1.08-4.32, P = 0.03), high serum creatinine (HR 1.002, 95% CI 1.001-1.003, P < 0.001), high daily urine protein (HR 1.34, 95% CI 1.15-1.57, P < 0.001), high glomerular sclerosis (HR 13.98, 95% CI 3.50-55.92, P < 0.001), and interstitial fibrosis > 50% (HR 4.18, 95% CI 1.90-9.19, P < 0.001) were independent risk factors for ESKD, and these indicators were included in the nomogram. The C-indices of the nomogram model in the development set, validation set, and all-data set were 0.838 (range 0.785-0.891), 0.794 (range 0.774-0.814), and 0.822 (range 0.775-0.869), respectively, which were higher than those of the renal risk score model, 0.801 (range 0.748-0.854), 0.746 (range 0.654-0.838) and 0.783 (range 0.736-0.830), respectively. The net reclassification improvement and the integrated discrimination improvement further illustrated the higher predictive ability of the nomogram. CONCLUSION: We present a nomogram as a practical tool to predict renal outcomes in Chinese patients with MPO-ANCA glomerulonephritis.

A novel defined cuproptosis-related gene signature for predicting the prognosis of colon adenocarcinoma.

The prognosis of colon adenocarcinoma (COAD) needs to be improved. Cuproptosis is a recently discovered cell death caused by intracellular overload of copper ions. There have been no reports about the cuproptosis-related prognostic model in COAD. First, we screened 30 differentially expressed genes (DEGs) from patients with COAD using The Cancer Genome Atlas (TCGA) database. Gene Expression Omnibus (GEO) database was used as a validation set to establish a risk model of five cuproptosis-related genes (CKDN2A, SDHB, CCS, ULK1, and CMC1) by least absolute shrinkage and selection operator (LASSO) Cox regression analysis. In both TCGA and GEO cohorts, we could see that overall survival of COAD patients of the low-risk group was longer. Combined with the clinical characteristics, the risk score was found to be an independent prognostic factor. Furthermore, single-sample Gene Set Enrichment Analysis (ssGSEA) showed that the levels of Th1 and Treg immune cells changed both in TCGA and GEO databases. Finally, clinical samples were used to verify the mRNA and protein levels of five risk-model genes. In conclusion, this model could predict the prognosis of COAD patients, and the mechanism may be related to the changes in immune cells in the tumor microenvironment (TME).

A circular RNA, circPTPN14, increases MYC transcription by interacting with FUBP1 and exacerbates renal fibrosis.

Fibrosis is a relentlessly progressive and irreversible cause of organ damage, as in chronic kidney disease (CKD), but its underlying mechanisms remain elusive. We found that a circular RNA, circPTPN14, is highly expressed in human kidneys with biopsy-proved chronic interstitial fibrosis, mouse kidneys subjected to ischemia/reperfusion (IR) or unilateral ureteral obstruction (UUO), and TGFß1-stimulated renal tubule epithelial cells (TECs). The intrarenal injection of circPTPN14 shRNA alleviated the progression of fibrosis in kidneys subjected to IR or UUO. Knockdown of circPTPN14 in TECs inhibited TGFß1-induced expression of profibrotic genes, whereas overexpressing circPTPN14 increased the profibrotic effect of TGFß1. The profibrotic action of circPTPN14 was ascribed to an increase in MYC transcription. The binding of circPTPN14 to the KH3 and KH4 domains of far upstream element (FUSE) binding protein 1 (FUBP1) enhanced the interaction between FUBP1 and FUSE domain, which was required for the initiation of MYC transcription. In human kidneys (n = 30) with biopsy-proved chronic interstitial fibrosis, the expression of circPTPN14 positively correlated with MYC expression. Taken together these studies show a novel mechanism in the pathogenesis of renal fibrosis, mediated by circPTPN14, which can be a target in the diagnosis and treatment of CKD.

Tough and Antifreezing MXene@Au Hydrogel for Low-Temperature Trimethylamine Gas Sensing.

Trimethylamine (TMA) is one of the important chemical indexes to judge the freshness of marine fish. It is necessary to develop a low temperature TMA sensor to help the monitoring and prediction of the quality of marine fish in cold chain. Herein, a flexible low temperature TMA gas sensor featuring antifreezing and superior mechanical properties was developed based on the Au nanoparticle-modified MXene (MXene@Au) composite. MXene@Au was synthesized and then polymerized with a hydrogel composed of acrylamide (AM), N,N'-methylenebisacrylamide (BIS), sodium carboxymethyl cellulose (CMC), and EG, and the resultant MXene@Au hydrogel was found to exhibit excellent antifreezing performance even at extremely low temperature as well as high tensile strength, ultrastretchability, and toughness, which enabled an efficient gas sensing platform for TMA detection at low temperature. The TMA sensing properties of the flexible MXene@Au DN hydrogel sensor at 25 °C and a low temperature of 0 °C were studied, and a linear relationship between TMA sensitivity and concentration was built. The excellent sensing properties were maintained even under deformation. The application of the MXene@Au DN hydrogel sensor in detection of fish freshness at 0 °C was investigated. The result indicated the potential application of the flexible MXene@Au DN hydrogel gas sensor in dynamic quality monitoring and prediction of marine fish products during its transportation and storage in the cold chain.