Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality in the world.
We downloaded the mRNA profiles and clinical information of 371 HCC patients from The Cancer Genome ...Atlas (TCGA) database. The consensus clustering analysis with the mRNA levels of 48 nuclear receptors (NRs) was performed by the "ConsensusClusterPlus." The univariate Cox regression analysis was performed to predict the prognostic significance of NRs on HCC. The risk score was calculated by the prognostic model constructed based on eight optimal NRs. Then multivariate Cox regression analysis was performed to determine whether the risk score is an independent prognostic signature. Finally, the nomogram based on multiple independent prognostic factors was used to predict the long-term survival of HCC patients.
The prognostic model constructed based on the eight optimal NRs (NR1H3, ESR1, NR1I2, NR2C1, NR6A1, PPARD, PPARG, and VDR) could effectively predict the prognosis of HCC patients as an independent prognostic signature. Moreover, the nomogram was constructed based on multiple independent prognostic factors including risk score and tumor node metastasis (TNM) stage and could better predict the long-term survival for 3- and 5-year of HCC patients.
Our results provided novel evidences that NRs could act as the potential prognostic signatures for HCC patients.
Introduction Oxidative and antioxidant pathways play essential roles in the development of alcohol-induced brain injury. The Nrf2 pathway is an endogenous antioxidant response pathway, but there has ...been little research on the role of Nrf2 in alcohol-related diseases. Thus, we examined the effects of alcohol and an Nrf2 agonist (TBHQ) on astrocyte function, mRNA expression, and metabolite content to further explore the protective mechanisms of Nrf2 agonists in astrocytes following alcohol exposure. Methods CTX TNA2 astrocytes were cultured with alcohol and TBHQ and then subjected to transcriptome sequencing, LC-MS/MS analysis, quantitative reverse transcription polymerase chain reaction (qRT-PCR), and malondialdehyde (MDA) and superoxide dismutase (SOD) activity assays. Results Alcohol exposure significantly increased malondialdehyde (MDA) levels while decreasing superoxide dismutase (SOD) levels in astrocytes. Treatment with TBHQ effectively reversed these effects, demonstrating its protective role against oxidative stress induced by alcohol. Transcriptome sequencing and qRT-PCR analysis revealed that TBHQ specifically upregulates genes involved in glutathione metabolism, including a notable increase in the expression of the glutathione S-transferase A5 (GSTA5) gene, which was suppressed by alcohol exposure. Additionally, metabolomic analysis showed that TBHQ regulates key components of ether lipid metabolism in alcohol-exposed astrocytes, with significant reductions in the levels of lysophosphatidylcholine (18:0) (LysoPC (18:0)) and 2-acetyl-1-alkyl-sn-glycero-3-phosphocholine, both of which are critical markers in the ether lipid metabolic pathway. Discussion The findings underscore the role of TBHQ as an Nrf2 agonist in mitigating alcohol-induced oxidative damage in astrocytes by modulating glutathione metabolism and ether lipid metabolism. The regulation of GSTA5 gene expression emerges as a key mechanism through which Nrf2 agonists confer neuroprotection against oxidative stress and lipid oxidation. These insights pave the way for potential therapeutic strategies targeting the Nrf2 pathway to protect astrocytes from alcohol-induced damage.
Alcohol dependence is a chronic, relapsing encephalopathy characterized by compulsive craving for alcohol, loss of control over alcohol use, and the presence of negative emotions and physical ...discomfort when alcohol is unavailable. Harmful use of alcohol is one of the greatest risk factors for death, illness, and disability. Rho kinase inhibitors have neuroprotective effects. This study used metabonomics analysis to assess untreated astrocytes, astrocytes exposed to 75 mmol/L of alcohol, and astrocytes exposed to 75 mmol/L of alcohol and treated with 15 µg/mL fasudil for 24 h. One of the clearest differences between the alcohol-exposed and fasudil-treated alcohol-exposed groups was the abundance of lipids and lipid-like molecules, although glycerophospholipid metabolism was comparable in both groups. Our findings show that fasudil may alleviate alcohol-induced astrocyte damage by modifying lipid metabolism, providing a new approach for preventing and treating alcohol dependence.
By comparing with traditional L-shaped plate, to explore the effectiveness of new Pilon plate in the treatment of type C Pilon fracture.
A clinical data of 57 patients with type C Pilon fractures who ...met the selection criteria between May 2018 and January 2020 was analyzed retrospectively. Thirty-two patients were treated with new Pilon plate (trial group) and 25 patients with traditional L-shaped plate (control group). There was no significant difference in gender, age, cause of injury, fracture side and type, the interval between injury and operation between the two groups (
>0.05). The operation time and complications of the two groups were recorded. X-ray films were taken after operation to assess the quality of fracture reduction according to the Burwell-Charnley classification and fracture healing. Ankle function was evaluated according to Johner-Wruhs scoring standard and American Orthopaedic Foot and Ankle Society (AOFAS) score.
The operations of the two groups were completed successfully, and the ope
A lot of important information about the working state of hydraulic components can be reflected by wear debris in hydraulic oil, the detection of debris can prevent hydraulic system failures. Due to ...the weak ability of inductive pulse sensor to detect non-ferromagnetic metal particles, an integrated wear debris sensor, which includes a capacitive pulse sensor and an inductive pulse sensor, is proposed in this paper. The frequency characteristics of the capacitive sensor were explored through experiments, and optimal detection frequency is 0.5MHz. Capacitive sensor can detect and distinguish between air bubbles and metal debris. Inductive sensor can detect and distinguish ferromagnetic and non-ferromagnetic metal debris. By comparing and analyzing the results of two sensors, the integrated sensor with <inline-formula> <tex-math notation="LaTeX">300~\mu \text{m} </tex-math></inline-formula> channel can detect air bubbles larger than <inline-formula> <tex-math notation="LaTeX">80~\mu \text{m} </tex-math></inline-formula>, 30-300<inline-formula> <tex-math notation="LaTeX">\mu \text{m} </tex-math></inline-formula> iron particles and 45-300<inline-formula> <tex-math notation="LaTeX">\mu \text{m} </tex-math></inline-formula> copper particles, and effectively distinguish the properties of particles.
Prefrontal cortex (PFC) and striatal neurotransmitter homeostasis is affected by alcohol dependence. In this study, the microarray dataset from the Gene Expression Omnibus (GEO) database were ...downloaded. The prefrontal and striatum data were cross-analyzed to reveal the co-effects of alcohol dependence on the two brain regions of mice.
The GSE123114 microarray profile was downloaded from the GEO database, and differentially expressed genes (DEGs) between the two groups were acquired by GEO2R. KEGG analyses were performed to identify the pivotal pathways of these DEGs. Key differential gene expressions and their mechanism associated with alcohol exposure were investigated by an intraperitoneal alcohol model.
A total of 13 overlapping DEGs from the PFC and striatal datasets of the GSE123114 microarray profile were identified, and they were significantly enriched in the morphine addiction pathway. The transcript levels and protein expression of Gabrb3 were consistent with the microarray data both in the PFC and striatum. The transcript levels of HMGB1, TLR4, TNFα and IL-1β were upregulated in the PFC and striatum of mice in the alcohol group. The HMGB1 inhibitor decreased Gabrb3 transcript and protein levels as well as TNFα and IL-1β transcript levels both in the PFC and striatum in the intraperitoneal alcohol model mice.
Through the reanalysis of GSE123114 microarray profile, we found that Gabrb3 is a key gene associated with alcohol exposure. In further experiments, our findings suggest that alcohol exposure modulates Gabrb3 expression through the HMGB1/TLR4 pathway. Moreover, inflammation-associated factors, such as IL-1β and TNFα, may be related to the HMGB1/TLR4-mediated regulation of
expression in alcohol exposure.
Soft open points (SOPs) offer real-time power flows control, the rapid self-healing of faults, and the balance of feeder load, which are widely applied in the distribution networks (DNs). However, ...distribution networks based on SOP often suffer from large signal disturbances such as grid voltage dips (GVDs) during operation, and their stability needs to be further improved to ensure the safe and stable operation of the SOP system. This article proposes a stable control strategy based on virtual capacitors and verifies the effectiveness of this method through theoretical analysis using mixed potential theory (MPT). Firstly, the virtual capacitor control strategy proposed in this article that can enhance the stability of SOP systems is stated. Secondly, a nonlinear average model of SOP was established, and based on MPT, the large signal stability criteria (LSSC) for the SOP system using virtual capacitor control strategy were derived. Based on this criterion, the impact of DC side capacitance on system stability was analyzed, and the effectiveness of virtual capacitance strategy to enhance the system's stable operation capability was verified. Finally, the correctness of the obtained criteria and the feasibility and effectiveness of the virtual capacitor strategy were verified through Matlab/Simulink time-domain simulation.
Inadequate water quality can mean that water is unsuitable for a variety of human uses, thus exacerbating freshwater scarcity. Previous large-scale water scarcity assessments mostly focused on the ...availability of sufficient freshwater quantity for providing supplies, but neglected the quality constraints on water usability. Here we report a comprehensive nationwide water scarcity assessment in China, which explicitly includes quality requirements for human water uses. We highlight the necessity of incorporating water scarcity assessment at multiple temporal and geographic scales. Our results show that inadequate water quality exacerbates China's water scarcity, which is unevenly distributed across the country. North China often suffers water scarcity throughout the year, whereas South China, despite sufficient quantities, experiences seasonal water scarcity due to inadequate quality. Over half of the population are affected by water scarcity, pointing to an urgent need for improving freshwater quantity and quality management to cope with water scarcity.
A new dynamic event-triggered control (ETC) scheme is proposed to address the practical fixed-time consensus (FTC) problem for multi-agent systems (MASs) with nonlinear dynamics. For the dynamic ETC ...scheme, the dynamic parameters are taken into account to reduce the number of triggering instants and save limited resources, and the triggering condition is based on a new dynamic variable that is obtained online rather than a constant. Moreover, the consensus of the nonlinear MASs can be obtained in a finite time for any initial conditions by the above-mentioned protocol. Finally, an example of Chua's circuit is given to demonstrate the feasibility of the proposed control algorithms.
•Key application areas of deep learning are identified in urban water and wastewater management.•Popular application areas include anomaly detection, system state forecasting, asset monitoring and ...assessment.•Industrial application of deep learning is still at an early stage with few implementations reported.•Research challenges include data privacy, algorithm development, explainability, multi-agent system and digital twin.•Deep learning should drive urban water systems towards high intelligence and autonomy.
Deep learning techniques and algorithms are emerging as a disruptive technology with the potential to transform global economies, environments and societies. They have been applied to planning and management problems of urban water systems in general, however, there is lack of a systematic review of the current state of deep learning applications and an examination of potential directions where deep learning can contribute to solving urban water challenges. Here we provide such a review, covering water demand forecasting, leakage and contamination detection, sewer defect assessment, wastewater system state prediction, asset monitoring and urban flooding. We find that the application of deep learning techniques is still at an early stage as most studies used benchmark networks, synthetic data, laboratory or pilot systems to test the performance of deep learning methods with no practical adoption reported. Leakage detection is perhaps at the forefront of receiving practical implementation into day-to-day operation and management of urban water systems, compared with other problems reviewed. Five research challenges, i.e., data privacy, algorithmic development, explainability and trustworthiness, multi-agent systems and digital twins, are identified as key areas to advance the application and implementation of deep learning in urban water management. Future research and application of deep learning systems are expected to drive urban water systems towards high intelligence and autonomy. We hope this review will inspire research and development that can harness the power of deep learning to help achieve sustainable water management and digitalise the water sector across the world.
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