Search

Hepatocellular carcinoma (HCC) is a common malignant tumor of the digestive system, and its early asymptomatic characteristic increases the difficulty of diagnosis and treatment. This study is aimed at obtaining some novel biomarkers with diagnostic and prognostic meaning and may find out potential therapeutic targets for HCC. We screen differentially expressed genes (DEGs) from the HCC gene expression profile GSE14520 using GEO2R. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were conducted by using the clusterProfiler software while a protein-protein interaction (PPI) network was performed based on the STRING database. Then, prognosis analysis of hub genes was conducted using The Cancer Genome Atlas (TCGA) database. Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to further verify the expression of hub genes and explore the correlation between gene expression and clinicopathological parameters. A total of 1053 DEGs were captured, containing 497 upregulated genes and 556 downregulated genes. GO and KEGG analysis indicated that the downregulated DEGs were mainly enriched in the fatty acid catabolic process while upregulated DEGs were primarily enriched in the cell cycle. Simultaneously, ten hub genes (CYP3A4, UGT1A6, AOX1, UGT1A4, UGT2B15, CDK1, CCNB1, MAD2L1, CCNB2, and CDC20) were identified by the PPI network. Five prognosis-related hub genes (CYP3A4, CDK1, CCNB1, MAD2L1, and CDC20) were uncovered by the survival analysis based on TCGA database. The ten hub genes were further validated by qRT-PCR using samples obtained from our hospital. The prognosis-related hub genes such as CYP3A4, CDK1, CCNB1, MAD2L1, and CDC20 could be considered potential diagnosis biomarkers and prognosis targets for HCC. We also use Oncomine for further verification, and we found CCNB1, CCNB2, CDK1, and CYP3A4 which were highly expressed in HCC. Meanwhile, CCNB1, CCNB2, and CDK1 are highly expressed in almost all cancer types, which may play an important role in cancer. Still, further functional study should be conducted to explore the underlying mechanism and biological effect in the near future. [ABSTRACT FROM AUTHOR]

High-frequency synchronization has been found in many real neural systems and is confirmed by excitatory/inhibitory (E/I) network models. However, the functional role played by it remains elusive. In this paper, it is found that high-frequency synchronization in E/I neuronal networks could improve the firing rate contrast of the whole network, no matter if the network is fully connected or randomly connected, with noise or without noise. It is also found that the global firing rate contrast enhancement can prevent the number of spikes of the neurons measured within the limited time window from being confused by noise, thereby enhancing the information encoding efficiency (quantified by entropy theory here) of the neuronal system. The mechanism of firing rate contrast enhancement is also investigated. Our work implies a possible functional role in information transmission of high-frequency synchronization in neuronal systems. [ABSTRACT FROM AUTHOR]

Epoxyeicosatrienoic acids (EETs) are derived from arachidonic acid and metabolized by soluble epoxide hydrolase (sEH). The role of EETs in synaptic function in the central nervous system is still largely unknown. We found that pharmacological inhibition of sEH to stabilize endogenous EETs and exogenous 14,15-EET significantly increased the field excitatory postsynaptic potential (fEPSP) response in the CA1 area of the hippocampus, while additionally enhancing high-frequency stimulation- (HFS-) induced long-term potentiation (LTP) and forskolin- (FSK-) induced LTP. sEH inhibitor (sEHI) N-[1-(oxopropyl)-4-piperidinyl]-N’-[4-(trifluoromethoxy) phenyl)-urea (TPPU) and exogenous 14,15-EET increased HFS-LTP, which could be blocked by an N-methyl-D-aspartate (NMDA) receptor subunit NR2B antagonist. TPPU- or 14,15-EET-facilitated FSK-mediated LTP can be potentiated by an A1 adenosine receptor antagonist and a phosphodiesterase inhibitor, but is prevented by a cAMP-dependent protein kinase (PKA) inhibitor. sEHI and 14,15-EET upregulated the activation of extracellular signal-regulated kinases (ERKs) and Ca2+/calmodulin- (CaM-) dependent protein kinase II (CaMKII). Phosphorylation of synaptic receptors NR2B and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluR1 was increased by TPPU and 14,15-EET administration. These results indicated that EETs increased NMDAR- and FSK-mediated synaptic potentiation via the AC-cAMP-PKA signaling cascade and upregulated the ERKs and CaMKII, resulting in increased phosphorylation of NR2B and GluR1 in the hippocampus. [ABSTRACT FROM AUTHOR]

Rhythmic oscillations of neuronal network are actually kind of synchronous behaviors, which play an important role in neural systems. In this paper, the properties of excitement degree and oscillation frequency of excitatory bursting Hodkin-Huxley neuronal network which incorporates a synaptic learning rule are studied. The effects of coupling strength, synaptic learning rate, and other parameters of chemical synapses, such as synaptic delay and decay time constant, are explored, respectively. It is found that the increase of the coupling strength can weaken the extent of excitement, whereas increasing the synaptic learning rate makes the network more excited in a certain range; along with the increasing of the delay time and the decay time constant, the excitement degree increases at the beginning, then decreases, and keeps stable. It is also found that, along with the increase of the synaptic learning rate, the coupling strength, the delay time, and the decay time constant, the oscillation frequency of the network decreases monotonically. [ABSTRACT FROM AUTHOR]

Magnetic liquid double suspension bearing (MLDSB) includes electromagnetic system and hydrostatic system, and the bearing capacity and stiffness can be greatly improved. It is very suitable for the occasions of medium speed, heavy load, and starting frequently. Due to the mutual coupling and interaction between electromagnetic system and hydrostatic system, the probability and degree of static bifurcation are greatly increased and the operation stability is reduced. And flow of bearing cavity, coil current, oil film thickness, and galvanized layer thickness are the key parameters to ensure operation safe and stable, which has an important influence on the static bifurcation behavior. So this article intends to establish the coupling model of MLDSB to reveal the range of parameter combination in the case of static bifurcation. The influences of different parameter groups on the singularity characteristics, phase trajectory, x − t curves, and suction basin of the single DOF bearing system are analyzed. The result shows that there are nonzero singularities and static bifurcation occurs when ε 2 > 0 or δ 2 > 0. As the flow of bearing cavity, coil current, oil film thickness, and galvanized layer thickness changes in turn, the singularities will convert between stable focus, unstable focus, stable node, and saddle point, and then the stable limit cycle may be generated. The attractiveness of singularity will change greatly with the flow of the bearing cavity and coil current changes slightly in the case of small current or large flow. The minimal change of galvanized layer thickness will lead to the fundamental change of the final stable equilibrium point of the rotor, while the final equilibrium point is slightly affected by the oil film thickness. This study can provide a reference for the supporting stability of MLDSB. [ABSTRACT FROM AUTHOR]

Objective. To investigate the clinical study of intravitreal injection of anti-VEGF drugs combined with intravitreal injection of tretinoin for the treatment of Coats disease. Methods. The medical records of 90 patients (120 eyes) with Coats disease admitted to our hospital from April 2010 to June 2021 were selected as retrospective study subjects and divided into control and treatment groups according to the numerical table method. There were 45 cases and 60 eyes in each group. Among them, intravitreal tretinoin drug was injected into the control group, and anti-VEGF drug was injected into the vitreous sclera of the treatment group on the basis of the control group. Results. Before treatment, the differences in visual acuity changes between the two groups were not statistically significant (P > 0.05). After treatment, the light perception, manipulation, and indexes of both groups were significantly improved, and the treatment group was significantly better than the control group. This difference was statistically significant (P < 0.05) for statistical study comparison. The effective rate of 95.56% in the treatment group was significantly higher than that of 86.67% in the control group, and the complication rate was significantly lower than that of the control group, with statistically significant differences (P < 0.05). Conclusion. Intravitreal injection of anti-VEGF drugs combined with tretinoin injection can significantly improve the clinical efficacy of patients with Coats disease and improve visual acuity and central retinal thickness, which has certain reference value for the clinical treatment of Coats disease. [ABSTRACT FROM AUTHOR]

Blade icing problems are ubiquitous for wind turbines located in cold climate zones. Data-driven indirect icing detection methods based on supervisory control and data acquisition system have shown strong potential recently. However, the supervisory control and data acquisition data is annotated through manual observation, which will cause the data between normal condition and icing condition to be unlabeled. In addition, the amount of normal data is far more than icing data. The above two issues restrict the performance of most current data-driven models. In order to solve the label missing problem, this article proposes a Pearson correlation coefficient–based algorithm for measuring the degree of blade icing, which calculates the similarity between the unlabeled data and the icing data as its label. Aiming at the class-imbalance problem, this article constructs multiple class-balanced subsets from the original dataset by under-sampling the normal data. Temporal convolutional networks are trained to extract features and make predictions on each subset. The final prediction result is obtained by ensembling the prediction results of all temporal convolutional network models. The proposed model is validated using the actual supervisory control and data acquisition data collected from a wind farm in northern China, and the results indicate that ensuring the consecutiveness and class-balance of the data are quite advantageous for improving the detection accuracy. [ABSTRACT FROM AUTHOR]

Background and Aim. Heme oxygenase-1 (HO-1) has been verified to play an important role in nonalcoholic steatohepatitis (NASH), but the mechanism remains unclear. In this study, we aimed to clarify whether induction of HO-1 reverses steatofibrosis via suppression of the Wnt signaling pathway and to explore the potential mechanism of HO-1 on NASH-related liver fibrosis. Methods. Mice were fed with a methionine-choline-deficient (MCD) diet for 8 weeks to induce steatohepatitis-related liver fibrosis and were treated with HO-1 inducer Hemin and inhibitor ZnPP. Mouse sera were collected for the biochemical analysis, and livers were obtained for further histological observation and gene expression analysis. HSC-T6 cells were cultured for the in vitro study and were administrated with Hemin and si-HO-1 to induce or inhibit the expression of HO-1. qPCR and Western blot were used to assess the mRNA and protein levels of genes. Results. MCD-fed mice developed marked macrovesicular steatosis, focal necrosis, and inflammatory infiltration and pericellular fibrosis in liver sections. Administration of Hemin could significantly ameliorate the severity of steatosis, inflammation, and fibrosis and also could decrease the serum ALT and AST. We demonstrated that HO-1 induction was able to downregulate the key regulator of the canonical Wnt pathway Wnt1 and the noncanonical Wnt pathway Wnt5a. The downstream factors of the Wnt pathway β-catenin and NFAT5 were inhibited by Hemin, but GSK-3β was upregulated compared to the MCD group, which were consistent with the in vitro study. Hemin markedly inhibited the TGF-β1/Smad signaling pathway in both in vivo and in vitro studies. Conclusion. Our study demonstrated that HO-1 inhibited the activation of canonical and noncanonical Wnt signaling pathways in NASH-related liver fibrosis. Thus, these results may suggest a new therapeutic strategy for NASH-related liver fibrosis. [ABSTRACT FROM AUTHOR]

With the rise in the aging global population, stroke comorbidities have become a serious health threat and a tremendous economic burden on human society. Current therapeutic strategies mainly focus on protecting neurons from cytotoxic damage at the acute phase upon stroke onset, which not only is a difficult way to ameliorate stroke symptoms but also presents a challenge for the patients to receive effective treatment in time. The brain-derived neurotrophic factor (BDNF) is the most abundant neurotrophin in the adult brain, which possesses a remarkable capability to repair brain damage. Recent promising preclinical outcomes have made BDNF a popular late-stage target in the development of novel stroke treatments. In this review, we aim to summarize the latest progress in the understanding of the cellular/molecular mechanisms underlying stroke pathogenesis, current strategies and difficulties in drug development, the mechanism of BDNF action in poststroke neurorehabilitation and neuroplasticity, and recent updates in novel therapeutic methods. [ABSTRACT FROM AUTHOR]

An 8-week trial was conducted to compare the efficacy of a chelated copper (Cu) with the inorganic Cu (CuSO4), in the diet of Japanese sea bass ( Lateolabrax japonicus). Six diets were prepared based on two basal diets (semi-purified or practical) at two Cu inclusion levels (0 and 4 mg kg−1 from or chelated-Cu), accordingly named as S0, SI4, SM4, P0, PI4 and PM4 respectively. Each diet was fed to quadruplicate groups of Japanese sea bass (initial weight: 65.0 ± 0.03 g) during the trial. Fish fed practical diets had higher feed intake, specific growth rate, protein efficiency rate ( PER), liver Cu accumulation, liver Na+K+- ATPase and plasma alkaline phosphatase, but lower hepatosomatic index than the groups fed semi-purified diets ( P < 0.05). Higher PER was exhibited by fish fed chelated-Cu diets than that of fish fed CuSO4 diets ( P < 0.05). Although liver Cu accumulation was significantly higher in fish fed practical diets,, liver Cu content increased significantly with increasing dietary copper levels only in fish fed semipurified diets. Chelated-Cu has higher efficiency than CuSO4 when fed in practical diets. Poor growth performance of fish fed semipurified diets might induce underestimating the nutrient requirement of Japanese sea bass. [ABSTRACT FROM AUTHOR]