Comprehensive Urinary Proteome Profiling Analysis Identifies Diagnosis and Relapse Surveillance Biomarkers for Bladder Cancer.

Bladder cancer (BCa) is the predominant malignancy of the urinary system. Herein, a comprehensive urine proteomic feature was initially established for the noninvasive diagnosis and recurrence monitoring of bladder cancer. 279 cases (63 primary BCa, 87 nontumor controls (NT), 73 relapsed BCa (BCR), and 56 nonrelapsed BCa (BCNR)) were collected to screen urinary protein biomarkers. 4761 and 3668 proteins were qualified and quantified by DDA and sequential window acquisition of all theoretical mass spectra (SWATH-MS) analysis in two discovery sets, respectively. Upregulated proteins were validated by multiple reaction monitoring (MRM) in two independent combined sets. Using the multi-support vector machine-recursive feature elimination (mSVM-RFE) algorithm, a model comprising 13 proteins exhibited good performance between BCa and NT with an AUC of 0.821 (95% CI: 0.675-0.967), 90.9% sensitivity (95% CI: 72.7-100%), and 73.3% specificity (95% CI: 53.3-93.3%) in the diagnosis test set. Meanwhile, an 11-marker classifier significantly distinguished BCR from BCNR with 75.0% sensitivity (95% CI: 50.0-100%), 81.8% specificity (95% CI: 54.5-100%), and an AUC of 0.784 (95% CI: 0.609-0.959) in the test cohort for relapse surveillance. Notably, six proteins (SPR, AK1, CD2AP, ADGRF1, GMPS, and C8A) of 24 markers were newly reported. This paper reveals novel urinary protein biomarkers for BCa and offers new theoretical insights into the pathogenesis of bladder cancer (data identifier PXD044896).

The RNA-binding protein sorbin and SH3 domain-containing 2 are transcriptionally regulated by specificity protein 1 and function as tumor suppressors in bladder cancer by stabilizing tissue factor pathway inhibitor.

Sorbin and SH3 domain-containing 2 (SORBS2) is an RNA-binding protein and has been implicated in the development of some cancers. However, its role in bladder cancer (BC) is yet to be established. The expression of SORBS2 in BC tissues was determined from the Gene Expression Omnibus and Gene Expression Profiling Interactive Analysis databases and collected paired tumor/normal samples. The effects of SORBS2 on BC cells were detected by CCK-8, colony formation, Transwell, dual-luciferase, RNA immunoprecipitation, chromatin immunoprecipitation, and DNA pull-down assays. In vivo, BC cell growth and metastasis were studied by a xenograft subcutaneous model and a tail-vein metastasis model. The results showed that SORBS2 expression was significantly decreased in BC tissues and cells. SORBS2 overexpression inhibited cell proliferation, migration, invasion, and epithelial-mesenchymal transition in vitro and tumor growth and metastasis in vivo, while silencing SORBS2 produced the opposite effect. Mechanistically, we found that SORBS2 enhanced the stability of tissue factor pathway inhibitor (TFPI) mRNA via direct binding to its 3' UTR. Restoration of TFPI expression reversed SORBS2 knockdown-induced malignant phenotypes of BC cells. In addition, SORBS2 expression was negatively regulated by the transcription factor specificity protein 1 (SP1). Conversely, SORBS2 can be transcriptionally regulated by SP1 and inhibit BC cell growth and metastasis via stabilization of TFPI mRNA, indicating SORBS2 may be a promising therapeutic target for BC.

Down-regulation of miR-204-5p ameliorates sevoflurane-induced brain injury in neonatal rats through targeting VCAM1.

To confirm the regulation of miR-204-5p on VCAM1 and its effect on sevoflurane-induced brain injury in neonatal rats. We adopted the sevoflurane-induced brain injury model, and the double luciferase reporter gene assay was applied to explore the targeting relationship between vascular adhesion factor 1 (VCAM1) and miR-204-5p. RT-qPCR was applied to assess the levels of miR-204-5. VCAM1, LC3, P62 and cleaved-caspase 3 levels in the hippocampus were estimated by western blot. The number of autophagosomes in the cerebral cortex was assessed via Transmission electron microscopy (TEM), and histopathological changes within the hippocampus by HE staining. miR-204-5p levels were remarkably increased, but VCAM1 expression was decreased after neonatal rat brain injury. Furthermore, miR-204-5p directly targeted VCAM1. The escape latency, swimming distance, autophagosome number, neuronal apoptosis ratio, LC3 II and Cleaved-caspase 3 expression were reduced after miR-204-5p inhibition interference, whereas crossing times, and P62 expression increased in the sevoflurane-induced brain injury model. Furthermore, down-regulation of VCAM1 reversed the trend of these indices. These results suggest that down-regulation of miR-204-5p ameliorates sevoflurane-induced cognitive impairment and hippocampal pathology and inhibits neuronal autophagy and apoptosis by targeting VCAM1.

Effect of High Efficiency Digestion and Utilization of Organic Iron Made by Saccharomyces cerevisiae on Antioxidation and Caecum Microflora in Weaned Piglets.

Organic iron is expected to replace inorganic iron used in diets as an iron source. Organic iron possesses high absorption efficiency and low fecal iron excretion. This study aims to study the effect of organic iron produced by Saccharomyces cerevisiae (yeast iron) on digestion, utilization, antioxidation and caecum microflora in weaned piglets. In total, 20 piglets that had been weaned after 28 days were divided into 4 groups, each of which followed a different basal diet. The basal diet of each of these 4 groups contained, respectively, 104 mg/kg iron (ferrous sulfate, CON), 84 mg/kg iron (yeast iron, LSC), 104 mg/kg iron (yeast iron, MSC) or 124 mg/kg iron (yeast iron, HSC). This experiment lasted 35 d. The apparent digestibility of iron in LSC, MSC and HMS was higher than that in CON (p < 0.01) and the fecal iron content in LSC, MSC and HMS was lower than that in CON (p < 0.01). Serum iron contents in LSC, MSC and HMS were higher than that in CON (p < 0.01). The iron contents of the heart, lungs, liver, kidney and left gluteus muscle in the MSC and HMS groups were higher than that in CON and LSC (p < 0.05). Serum catalase, glutathione peroxidase, superoxide dismutase activity, superoxide anion, glutathione, hydroxyl free radical scavenging rate, total antioxidant capacity, and liver superoxide anion clearance rate and peroxidase in MSC and HMS were higher than that in CON and LSC (p < 0.05). The contents of nitric oxide and peroxide of the weaned piglets in MSC and HMS were lower than that in CON and LSC (p < 0.05). The abundance of Firmicutes, Blautia and Peptococcus in LSC, HSC and MSC was higher than that in CON (p < 0.01). The abundance of Lactobacillus in CON and LSC was higher than that in MSC and HSC (p < 0.01). The abundance of Acinetobacter, Streptococcus and Prevotella in LSC, MSC and HSC was lower than that in CON (p < 0.01). The results suggested that a diet containing 84 mg/kg iron of yeast iron has the same effect as a diet containing 104 mg/kg iron of ferric sulfate, and that a diet containing 104 or 124 mg/kg iron of yeast iron is superior to a diet containing 104 mg/kg iron of ferric sulfate.

Dietary Taurine Improves Growth Performance and Intestine Health via the GSH/GSSG Antioxidant System and Nrf2/ARE Signaling Pathway in Weaned Piglets.

Early weaning of piglets was prone to increase reactive oxygen species, disrupt the redox balance, decrease antioxidant capacity, cause oxidative stress and intestinal oxidative damage, and lead to diarrhea in piglets. This research aimed to study dietary taurine (Tau) supplementation at a level relieving intestinal oxidative damage in early-weaned piglets. A total of 48 piglets were assigned to four groups of 12 individuals and fed a basal diet with 0.0% Tau (CON), 0.2% Tau (L-Tau), 0.3% Tau (M-Tau), or 0.4% Tau (H-Tau), respectively. The animal experiment lasted 30 days. The final weight, weight gain, average daily gain, and feed conversion rate increased with the increase in dietary Tau (Linear, p < 0.05; Quadratic p < 0.05), while the diarrhea index of piglets decreased with the increase in dietary Tau (Linear, p < 0.05). Serum malondialdehyde, nitric oxide (NO), D-lactose, and oxidized glutathione (GSSG) concentrations decreased with the increase in dietary Tau (Linear, p < 0.05). The O2•- and •OH clearance rate in serum, liver, and jejunum mucosa increased with the increase in dietary Tau (Linear, p < 0.05). Serum superoxide dismutase (SOD) activity, glutathione peroxidase (GPX) activity, catalase (CAT) activity, and peroxidase (POD) activity and total antioxidant capacity increased with the increase in dietary Tau (Linear, p < 0.05). The serum glutathione (GSH) concentration and the ratio of GSH to GSSG increased with the increase in dietary Tau (Linear, p < 0.05). The POD and glutathione synthase activity in the liver and jejunum mucosa increased with the increase in dietary Tau (Linear, p < 0.05). The mRNA abundances of HO-1 and GPX1 in the H-Tau group were higher than that in the L-Tau, M-Tau, and CON groups (p < 0.05). The mRNA abundances of SOD1 and Nrf2 in the M-Tau and H-Tau groups were higher than in the L-Tau and CON groups (p < 0.05). The mRNA abundance of SOD2 in the L-Tau, M-Tau, and H-Tau groups was higher than in the CON group (p < 0.05). The VH and the ratio of VH to CD of jejunum and ileum increased with the increase in dietary Tau (Linear, p < 0.05). The mRNA abundances of occludens 1 and claudin 1 in the H-Tau group were higher than that in the CON, L-Tau, and M-Tau (p < 0.05). The mRNA abundance of occludin in the L-Tau, M-Tau, and H-Tau groups was higher than that in CON (p < 0.05). The abundance of Firmicutes increased with the increase in dietary Tau (Linear, p < 0.05), while Proteobacteria and Spirochaetota decreased with the increase in dietary Tau (Linear, p < 0.05). Collectively, dietary supplementation of 0.3% and 0.4% Tau in feed could significantly improve the growth performance and enhance the antioxidant capacity of piglets.

Investigation of an Output Voltage Harmonic Suppression Strategy of a Power Quality Control Device for the High-End Manufacturing Industry.

Due to the influence of nonlinear loads, power quality control devices under the traditional double closed-loop control strategy suffer from a large output voltage harmonic distortion rate and a slow harmonic suppression response and cannot meet the high-quality power supply requirements of high-end manufacturing. A compound control strategy based on voltage feedback and current feed-forward is proposed to solve the voltage quality problem under a nonlinear load. Firstly, based on the mathematical model of power quality control device, the working principle and voltage current coupling relationship are analyzed. Then, an output voltage compound control strategy based on feed-forward and feedback is proposed, and the harmonic suppression mechanisms are deduced and analyzed. Finally, simulation and experimental results are presented to show that, compared with the traditional double closed-loop control strategy, the harmonic suppression effect of the composite control strategy proposed in this paper can be increased by 2.2%, and the response time is decreased to 100 ms.

MRI Image Segmentation Model with Support Vector Machine Algorithm in Diagnosis of Solitary Pulmonary Nodule.

This study focused on the application value of MRI images processed by a Support Vector Machine (SVM) algorithm-based model in diagnosis of benign and malignant solitary pulmonary nodule (SPN). The SVM algorithm was constrained by a self-paced regularization item and gradient value to establish the MRI image segmentation model (SVM-L) for lung. Its performance was compared factoring into the Dice index (DI), sensitivity (SE), specificity (SP), and Mean Square Error (MSE). 28 SPN patients who underwent the parallel MRI examination were selected as research subjects and were divided into the benign group (11 patients) and malignant group (17 patients) according to different plans for diagnosis and treatment. The apparent diffusion coefficient (ADC) at different b values was analyzed, and the steepest slope (SS) and washout ratio (WR) values in the two groups were calculated. The result showed that the MSE, DI, SE, SP values, and operation time of the SVM-L model were (0.41 ± 0.02), (0.84 ± 0.13), (0.89 ± 0.04), (0.993 ± 0.004), and (30.69 ± 2.60)s, respectively, apparently superior to those of the other algorithms, but there were no statistic differences (P > 0.05) in the WR value between the two groups of patients. The SS values of the time-signal curve in the benign and malignant groups were (2.52 ± 0.69) %/s and (3.34 ± 00.41) %/s, respectively. Obviously, the SS value of the benign group was significantly lower than that of the malignant group (P < 0.01). The ADC value with different b values in the benign group was significantly lower than that of the malignant group (P < 0.01). It suggested that the SVM-L model significantly improved the quality of lung MRI images and increased the accuracy to differentiate benign and malignant SPN, providing reference for the diagnosis and treatment of SPN patients.

Effects of Multi-Bacteria Solid-State Fermented Diets with Different Crude Fiber Levels on Growth Performance, Nutrient Digestibility, and Microbial Flora of Finishing Pigs.

This study aimed to investigate the effects of multi-bacteria solid-state fermented diets with different crude fiber (CF) levels on growth performance, nutrient digestibility, and microbial flora of finishing pigs. The multi-bacteria solid-state fermented diets were made up of Lactobacillus amylovorus, Enterococcus faecalis, Bacillus subtilis, and Candida utilis. According to a 2 (factors) × 2 (levels) design, with the two factors being multi-bacteria solid-state fermentation (fed non-fermented diet or multi-bacteria fermentation) or CF levels (fed a basal diet containing 2.52% CF or 7.00% CF), a total of 36 finishing pigs (70.80 ± 5.75 kg) were divided into 4 treatments with 9 barrows per group: (1) pigs fed a diet containing 7.00% CF (HF), (2) pigs fed a multi-bacteria fermentation diet containing 7.00% CF (HFM), (3) pigs fed a diet containing 2.52% CF (LF), and (4) piglets fed a multi-bacteria fermentation diet containing 2.52% CF (LFM). This experiment lasted 28 days. The multi-bacteria solid-state fermented diet increased the backfat thickness (p < 0.05) and apparent total tract nutrient digestibility (ATTD) of CF, neutral detergent fiber (NDF), acid detergent fiber (ADF), crude protein (CP), 8 amino acids (Trp, Asp, Gly, Cys, Val, Met, Ile, and Leu), total essential amino acids (EAA), total non-essential amino acids (NEEA), and total amino acids (TAA) (p < 0.05). Multi-bacteria solid-state fermented diet increased serum concentrations of HDL-c, ABL, TP, and GLU, the serum enzyme activities of GSH-Px, T-AOC, SOD, and CAT (p < 0.05), the relative abundance of Lactobacillus, Oscillospira, and Coprococcus (p < 0.05), and the abundance of YAMINSYN3-PWY, PWY-7013, GOLPDLCAT-PWY, ARGORNPROST-PWY, and PWY-5022 pathways (p < 0.05). The multi-bacteria solid-state fermented diet reduced the digestion amount of CF, NDF, and ADF (p < 0.05), the serum concentrations of TC, TG, LDL-c, BUN, and MDA (p < 0.05), the relative abundance of Streptococcaceae (p < 0.05), and the abundance of PWY-6470, PWY0-862, HSERMETANA-PWY, LACTOSECAT-PWY, MET-SAM-PWY, PWY-6700, PWY-5347, PWY0-1061, and LACTOSECAT-PWY pathways (p < 0.05). The high-fiber diet increased average daily feed intake (p < 0.05), the serum concentrations of TC, TG, LDL-c, BUN, and MDA (p < 0.05), the relative abundance of Clostridiaceae_Clostridium and Coprococcus (p < 0.05), and the abundance of TCA-GLYOX-BYPASS, GLYCOLYSIS-TCA-GLYOX-BYPASS, and PWY-6906 pathways (p < 0.05). The high-fiber diet reduced chest circumference (p < 0.05) and ATTD of ether extract (EE), CF, NDF, ADF, Ca, CP, 18 amino acids (Trp, Thr, Val, Met, Ile, Leu, Phe, Lys, His, Arg Asp, Ser, Glu, Gly, Ala, Cys, Tyr, and Pro), EAA, NEAA, and TAA (p < 0.05). The high-fiber diet also reduced the serum concentrations of HDL-c, TP, ABL, and GLU, the serum enzyme activities of T-AOC, GSH-Px, SOD, and CAT (p < 0.05), and the relative abundance of Akkermansia and Oscillospira (p < 0.05). There was no significant effect of the interaction between multi-bacteria fermentation and dietary CF levels, except on the digestion amount of CF (p < 0.05). The 7.00% CF had a negative effect on the digestion of nutrients, but multi-bacteria solid-state fermentation diets could relieve this negative effect and increase backfat thickness. High-fiber diets and multi-bacteria solid-state fermentation improved the diversity and abundance of fecal microorganisms in finishing pigs.