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Lipidomics and metabolomics are closely related to tumor phenotypes, and serum lipoprotein subclasses and small-molecule metabolites are considered as promising biomarkers for breast cancer (BC) diagnosis. This study aimed to explore potential biomarker models based on lipidomic and metabolomic analysis that could distinguish BC from healthy controls (HCs) and triple-negative BC (TNBC) from non-TNBC.Blood samples were collected from 114 patients with BC and 75 healthy controls (HCs). A total of 112 types of lipoprotein subclasses and 30 types of small-molecule metabolites in the serum were detected byWe developed a valid discriminant model based on three-biomarker panel (formic acid, TPA2, and L6TG) that could distinguish patients with BC from HCs. The area under the receiver operating characteristic curve (AUC) was 0.999 (95% confidence interval [CI]: 0.995-1.000) and 0.990 (95% CI: 0.959-1.000) in the training and validation sets, respectively. Based on the panel (D-dimer, CA15-3, CEA, L5CH, glutamine, and ornithine), a discriminant model was established to differentiate between TNBC and non-TNBC, with AUC of 0.892 (95% CI: 0.778-0.967) and 0.905 (95% CI: 0.754-0.987) in the training and validation sets, respectively.This study revealed lipidomic and metabolomic differences between BC versus HCs and TNBC versus non-TNBC. Two validated discriminatory models established against lipidomic and metabolomic differences can accurately distinguish BC from HCs and TNBC from non-TNBC.Two validated discriminatory models can be used for early BC screening and help BC patients avoid time-consuming, expensive, and dangerous BC screening. This article is protected by copyright. All rights reserved.

PurposeLong non-coding RNAs (lncRNAs) play an important role in the occurrence and development of bladder cancer, but the underlying molecular mechanisms remain largely unknown. In this study, we found that LINC00467 was significantly highly expressed in bladder cancer through bioinformatic analysis. The present study aimed to explore the role of LINC00467 in bladder cancer and its possible underlying molecular mechanisms.MethodsThe expression of LINC00467 was obtained from GEO (GSE31189), the TCGA database, and qRT-PCR. The role of LINC00467 in bladder cancer was assessed both in vitro and in vivo. RIP, RNA pulldown, and CO-IP were used to demonstrate the potential mechanism by which LINC00467 regulates the progression of bladder cancer.ResultsThrough the analysis of GEO (GSE133624) and the TCGA database, it was found that LINC00467 was highly expressed in bladder cancer tissues and that the expression of LINC00467 was significantly negatively correlated with patient prognosis. Cell and animal experiments suggest that LINC00467 promotes the proliferation and invasion of bladder cancer cells. On the one hand, LINC00467 can directly bind to NF-kb-p65 mRNA to stabilize its expression. On the other hand, LINC00467 can directly bind to NF-kb-p65 to promote its translocation into the nucleus to activate the NF-κB signaling pathway, which promotes the progression of bladder cancer.ConclusionsLINC00467 is highly expressed in bladder cancer and can promote the progression of bladder cancer by regulating the NF-κB signaling pathway. Therefore, targeting LINC00467 is very likely to provide a new strategy for the treatment of bladder cancer and for improving patient prognosis.

Tacr2, the gene encoding the NK2 receptor, belongs to G protein-coupled receptors. Accumulating evidence has indicated that the tachykinin receptors may contribute to the pathophysiology of depression. During the last decade, some studies have shown that Tacr2 activation is involved in the modulation of emotional processes. However, the extent, to which stress impacts Tacr2 expression remains unclear. The molecular mechanisms underlying depression also remain poorly understood. In this study, we subjected adult male Sprague Dawley (SD) rats to chronic unpredictable mild stress (CUMS) to induce a depression-like phenotype. We then measured the body weight and performed the sucrose preference test, forced swimming test (FST) and open field test to detect the effects of stress on anhedonia and activity. Western blotting and real-time PCR were used to study the protein and mRNA expression levels of Tacr2, respectively, in the hypothalamus. To explore DNA methylation of the Tacr2 gene, we used methylated DNA immunoprecipitation sequencing (MeDIP-seq). Additionally, we used the bisulfite sequencing PCR (BSP) to further verify the DNA methylation levels of the Tacr2 receptor gene in rats. We found that the CUMS-sensitive rats exhibited a decrease in body weight and sucrose preference, a decrease in the distance traveled, rearing frequency and velocity in the open field test, and an increase in immobility time in the FST. Compared with the expression in the control rats, Tacr2 protein and mRNA expression in the hypothalamus significantly increased in the CUMS-sensitive rats; however, the DNA methylation levels of the Tacr2 gene were significantly lower than in the control rats. In summary, according to our findings, the stress-induced increase in Tacr2 expression in the hypothalamus correlated with a specific decrease in DNA methylation of the Tacr2 gene. These results may enrich the understanding of the pathological processes of depression and provide insights into therapeutic approaches for its treatment.

Background Pancreatic ductal adenocarcinoma (PDAC) is the most lethal malignancy: it has a 5-year survival rate of less than 9%. Although surgical resection is an effective treatment for PDAC, only a small number of patients can have their tumors surgically removed. Thus, an urgent need to find new therapeutic targets for PDAC exists. Understanding the molecular mechanism of PDAC development is essential for the treatment of this malignancy. This research aimed to study the mechanisms of pancreatic stellate cells (PSCs), which regulate branched-chain amino acid (BCAA) metabolism in PDAC. Methods Differentially expressed proteins were detected via nanoliquid chromatography coupled to mass spectrometry (nano-LC-MS/MS). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment methods were used to find the valine-leucine-isoleucine (BCAA) degradation pathway. The levels of BCAAs in the sera and tissues of patients with PDAC were measured by using nuclear magnetic resonance (NMR). The functions of BCAA concentrations and the effects of activated pancreatic stellate cells (aPSCs) were also evaluated by performing Cell Counting Kit-8, colony formation, and wound healing assays. Results A total of 1,519 proteins with significantly differential expression were discovered in PDAC and adjacent tissues by using nano-LC-MS/MS. KEGG pathway enrichment analysis identified the BCAA degradation pathway. The content of BCAA in PDAC clinical samples was up-regulated. However, the addition of different concentrations of BCAA to PDAC cell culture medium failed to promote the proliferation and migration of PDAC cells. Given that analysis based on The Cancer Genome Atlas database showed that the number of aPSCs gradually increased with the progression of PDAC, the effects of aPSCs on PDAC cells were explored. After coculture with aPSCs, PDAC cell proliferation showed a significant increase, and the proteins involved in the BCAA degradation pathway in PDAC cells had also changed. Conclusions aPSCs could regulate BCAA metabolism to enhance the progression of PDAC, indicating that the regulation of BCAA metabolism may serve as a new therapeutic direction for PDAC.

In traditional centralized application construction and data storage modes, the application servers and the users are not in equal position in user information management. The application server can store and abuse the user's information under the circumstances that the users are not aware, and the user cannot revoke the authorization from the application server. Therefore, this paper proposes an identity management system combined with blockchain technology, which can return the management right of user information to users. This system adopts a three-layer architecture composed of blockchain layer, virtual chain layer and storage layer, and encapsulates all functions in each layer. It has good flexibility, and is easy to add new technologies, with good extensibility. The blockchain records the user's information state to realize the consensus and integrity of the user's data. The virtual chain layer is responsible for the main logical functions and encapsulates the user's request into a blockchain transaction, maintaining a good portability. The storage layer is responsible for the actual file storage and is responsible for file routing, backup, and query. Comprehensively speaking, based on the above three layers' architecture, the system implements the user's privacy granularity control, the user file's external storage, and combines the zero-knowledge proof to update the user's private key. In view of the application environment of this system, the access time delay and efficiency of the P2P storage system are simulated. It solves the problems of centralized application construction and data storage mode under which users cannot fully control personal information and privacy protection.

Fusobacterium necrophorum, a Gram-negative anaerobe, is an important bovine pathogen that causes hepatic abscesses, foot rot, mastitis and endometritis. We have previously shown that the 43 kDa outer membrane protein (43 K OMP) of F. necrophorum is a porin protein that plays an important role in bacterial infections; however, the molecular mechanisms by which this protein mediates adhesion remain unclear. In this study, we investigated the role of 43 K OMP in F. necrophorum adhesion to bovine epithelial cells using 43 K OMP-deficient mutants, and identified the protein that interacts with 43 K OMP by immunoprecipitation-mass spectrometry. Our results indicated that the native 43 K OMP and recombinant 43 K OMP could bind to the cell membrane of MAC-T or bovine endometrial epithelial cells (BEECs). When F. necrophorum was preincubated with antibodies against the recombinant 43 K OMP or bovine epithelial cells were preincubated with 43 K OMP, the adhesion of F. necrophorum to MAC-T or BEECs decreased significantly (P0.01). We successfully constructed a 43 K OMP-deficient strain (A25Δ43 K OMP) and bacterial attachment to MAC-T or BEECs was significantly higher with the F. necrophorum A25 strain than with mutant strain A25Δ43 K OMP (P0.01). The deficiency of 43 K OMP reduced the binding of F. necrophorum to bovine epithelial cells by 90.5 %-94.9 %. Among the 39 potential differential proteins, fibronectin, collagen and myosin were selected as the target proteins, and direct interaction between 43 K OMP of F. necrophorum and fibronectin was demonstrated. Taken together, these results suggest that 43 K OMP plays a key role in adhesion of F. necrophorum to bovine epithelial cells through its interaction with fibronectin. These findings provide a theoretical basis for the pathogenic mechanism of F. necrophorum.

Wayside acoustic system plays a crucial role in monitoring and diagnosing the status of train wheel bearings. However, due to the signal distortion caused by Doppler effect, the diagnosis accuracy will be seriously disturbed. In this manner, this paper proposes a model-driven Doppler distortion self-tuning method in theory, named as parametric Doppler correction analysis (PDCA). Different from traditional methods, such as instantaneous frequency tracking and Doppler distortion sparse representation, the proposed method aims to abstractly construct a physical model of acoustic signal distortion propagation based on Morse acoustic theory, where the acoustic forward propagation model and reverse reconstruction model are simultaneously built. The scheme consists of four basic steps. Firstly, the physical model with amplitude modulation operator and frequency shift operator is described for the distortion process. Secondly, the pseudo transition signal with the characteristics of energy accumulation and no distortion is obtained via a construction of frequency rearrangement operator and amplitude demodulation operator. Then, pseudo Doppler correction (PDC) is presented to solve the frequency distortion of the received signal, where a high energy accumulation for frequency distribution is designed as optimization function. Especially, quasi Newton algorithm L-BFGS is used to realize the adaptive learning for distortion parameters. Finally, through time-domain interpolation resampling (TIR) technique, the corrected signal can be analytically reconstructed with the optimal parameters. Applying the PDCA scheme to simulated signals and experimental signals, its validity is verified. The comparison with the instantaneous frequency ridge extraction approach further indicates the proposed model-driven method can reach a more accurate correction result in a faster and adaptive process.

Fusobacterium necrophorum is a Gram negative, spore-free, anaerobic bacterium that can cause pyogenic and necrotic infections in animals and humans. It is a major bovine pathogen and causes hepatic abscesses, foot rot, and necrotic laryngitis. The 43K OMP of F. necrophorum is an outer membrane protein with molecular weight of 43 kDa, exhibiting similarity to pore-forming proteins of other Fusobacterium species that plays an important role in bacterial infections. However, the role of 43K OMP in F. necrophorum adhesion remains unknown. In this study, we evaluated whether the 43K OMP of F. necrophorum mediates adhesion to BHK-21 cells and performed a preliminary screen of the proteins that interact with 43K OMP of F. necrophorum by immunoprecipitation-mass spectrometry. The results showed that the natural 43K OMP and recombinant 43K OMP could bind to BHK-21 cells, and preincubation of F. necrophorum with an antibody against the recombinant 43K OMP of F. necrophorum decreased binding to BHK-21 cells. Seventy differential interacting proteins were successfully screened by immunoprecipitation-mass spectrometry. Among these seventy differential interacting proteins, seven cell membrane proteins and four extracellular matrix proteins shown to be relevant to bacteria adhesion through subcellular localization and single-molecule function analysis. These data increase our understanding of the pathogenesis of F. necrophorum and provide a new theoretical basis for the design of antimicrobial drugs against F. necrophorum.

Early diagnosis is essential for improving the prognosis and survival of patients with hepatocellular carcinoma (HCC). This study aims to explore the clinical value of lipoprotein subfractions in the diagnosis of hepatitis B virus (HBV)-related HCC. Lipoprotein subfractions were detected by 1H-NMR spectroscopy, and the pattern-recognition method and binary logistic regression were performed to classify distinct serum profiles and construct prediction models for HCC diagnosis. Differentially expressed proteins associated with lipid metabolism were detected by LC-MS/MS, and the potential prognostic significance of the mRNA expression was evaluated by Kaplan–Meier survival analysis. The diagnostic panel constructed from the serum particle number of very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein (LDL-1~LDL-6) achieved higher accuracy for the diagnosis of HBV-related HCC and HBV-related benign liver disease (LD) than that constructed from serum alpha-fetoprotein (AFP) alone in the training set (AUC: 0.850 vs. AUC: 0.831) and validation set (AUC: 0.926 vs. AUC: 0.833). Furthermore, the panel achieved good diagnostic performance in distinguishing AFP-negative HCC from AFP-negative LD (AUC: 0.773). We also found that lipoprotein lipase (LPL) transcript levels showed a significant increase in cancerous tissue and that high expression was significantly positively correlated with the poor prognosis of patients. Our research provides new insight for the development of diagnostic biomarkers for HCC, and abnormal lipid metabolism and LPL-mediated abnormal serum lipoprotein metabolism may be important factors in promoting HCC development.

Manganese (Mn) pollution is an important environmental problem because of the potential toxicity to human and animal health. However, the effects of Mn on energy metabolism and autophagy are not clear. Consequently, we examined the effects of excessive and chronic exposure to Mn on liver function, oxidative stress, respiratory chain complex activity, and autophagy in chicken liver. Our results indicated that the accumulation of Mn in the liver and levels of AST and ALT in the serum of the Mn-exposed group were significantly higher (P < 0.05) than those in the control group at 90 days; the activities of GSH-Px, SOD, CAT, Na+-K+-ATPase, Mg2+-ATPase, Ca2+-ATPase, and respiratory chain complexes (I, II, III) in the Mn-exposed group were significantly decreased (P < 0.05) compared to the control group. However, the MDA content, NO content, iNOS activity, mRNA and protein levels of iNOS, and autophagy-related genes in the Mn-exposed group were significantly increased (P < 0.05) compared to the control group. In contrast, the mRNA level and protein expression of mTOR were significantly decreased (P < 0.05) compared to the control group. Furthermore, the characteristic autophagic vacuolar organelles were observed in the Mn-exposed group. These results suggested that excess Mn exposure can cause a disorder of energy metabolism by mitochondrial injury and induce oxidative stress and autophagy, which eventually lead to liver damage.

BACKGROUND: Pancreatic cancer (PC) has the lowest 5-year survival rate; therefore, new early screening methods and therapeutic targets are still urgently required. Emerging technologies such as metabolomic-based liquid biopsy may contribute to the field. We found aberrant lactate dehydrogenase A (LDHA) signaling to be an unfavorable biomarker for PC. METHODS: A total of 9 genes of the glycolysis pathway were detected by enrichment analysis in the PC Gene Expression Omnibus (GEO) dataset. The relationship between LDHA/pyruvate kinase (PKM)/fructose biphosphate aldolase A (ALDOA)/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and patient survival was analyzed by Kaplan-Meier plotting analysis of The Cancer Genome Atlas (TCGA). The detection of changing metabolites in the serum of PC patients was performed using a nuclear magnetic resonance (NMR) spectrometer. RESULTS: We found LDHA was an independent predictor of overall survival (OS) in PC patients (P

The aim of this study was to investigate the information-processing changes during an auditory oddball task among healthy controls (HCs), convalescent bipolar depression (BPC), and bipolar depression (BPD) patients. Thirty patients with BPD, 27 patients with BPC, and 30 HC were recruited in this study. The participants' performance (reaction time and accuracy) as well as P300 amplitude and latency during the tests were analyzed statistically. BPD and BPC showed poor task performance compared with HC. BPD had lower P300 amplitude and delayed P300 latency in the frontal, central, and parietal areas than HC. BPC had lower P300 amplitude, but no difference in P300 latency compared with the HC group. Further, P300 latency was significantly delayed over the right relative to the left region. In conclusion, bipolar patients had P300 abnormalities and deficits in cognitive processing of stimulus, and may be present even when emotional symptoms were relieved.

According as the composing and working theory of the taxing UAV, aim at the controlling for the takeoff and landing, the monitor software for the takeoff and landing is proposed. This software is based on Microsoft Visual C++6.0 and the virtual instrument. The software can real-time display flight attitude, track, parameters and the tracking divation. It showed the feasibility and necessarily of the softswar for the monitor and control system for the takeoff and landing for taxiing UAV.