Search Results (23,492)

With the continuous increase in train running speeds and the rapid complexity of operation environments, running stability of the high-speed train is facing significant challenges. A series of abnormal vibration issues, caused by hunting instability, have emerged, including bogie instability alarm, carbody swaying, and carbody shaking, posing a significant threat to the safe and stable operation of high-speed trains. Therefore, the monitoring and diagnosis of hunting instability have become important research topics in rail transit. This review follows the development of fault diagnosis for bogie hunting instability and carbody hunting instability. It first summarizes the existing evaluation standards and innovative diagnostic methods. Due to the current limitation of hunting instability evaluation standards, which can only detect large-amplitude hunting, this paper addresses the gap in evaluation criteria for early-stage, small amplitude hunting instability diagnosis. A thorough overview of the progress made by researches in this field of research is given, emphasizing three primary facets: diagnostic signal sources, diagnostic features, and diagnostic targets. Furthermore, given that existing methods only classify faults into small and large amplitudes, which does not meet the practical need for quickly and accurately identifying fault types and severity during operation, this review introduces existing works on the detailed assessment and fault tracing of hunting instability, as well as the mechanisms underlying its occurrence, with the aim of achieving a comprehensive diagnosis of hunting instability. Finally, the limitations of current methods and the future development trends in hunting instability diagnostics are discussed and summarized. This paper provides readers with a framework for the research process of hunting instability diagnosis, offering valuable references and innovative perspectives for their future research efforts. Full article

Burkholderia is the second largest source of natural product bacteria after Actinomyces and can produce many secondary metabolites including pyrrolnitrin (PRN). Natural products of microbial origin are usually found in trace amounts, so in metabolic engineering, promoter engineering is often used to regulate gene expression to increase yield. In this study, an endogenous strong promoter was identified based on RNA-seq to overexpress biosynthetic genes to increase the production of PRN. By analyzing the transcriptomic data of the antagonistic bacterium Burkholderia sp. JP2-270 in three different development periods, we screened 50 endogenous promoters with high transcriptional activity, nine of which were verified by an obvious fluorescent signal via fluorescence observation. Then, combined with RT-qPCR analysis, P_hp, the promoter of a hypothetical protein, was found to be significantly expressed in all three periods. In order to increase the suitability of endogenous promoters, the promoter P_hp was shortened at different lengths, and the results show that a sequence length of 173 bp was necessary for its activity. Moreover, this promoter was used to overexpress the PRN biosynthesis genes (prnA, prnB, prnC and prnD) in JP2-270, resulting in a successful increase in gene expression levels by 40–80 times. Only the overexpression of the prnB gene successfully increased PRN production to 1.46 times that of the wild type. Overall, the endogenous strong promoters screened in this study can improve gene expression and increase the production of secondary metabolites in JP2-270 and other strains. Full article

With the rapid development of the digital new infrastructure industry, the energy demand for communication base stations in smart grid systems is escalating daily. The country is vigorously promoting the communication energy storage industry. However, the energy storage capacity of base stations is limited and widely distributed, making it difficult to effectively participate in power grid auxiliary services by only implementing the centralized control of base stations. Aiming at this issue, an interactive hybrid control mode between energy storage and the power system under the base station sleep control strategy is delved into in this paper. Grounded in the spatiotemporal traits of chemical energy storage and thermal energy storage, a virtual battery model for base stations is established and the scheduling potential of battery clusters in multiple scenarios is explored. Then, based on the time of use electricity price and user fitness indicators, with the maximum transmission signal and minimum operating cost as objective functions, a decentralized control device is used to locally and quickly regulate the communication system. Furthermore, a multi-objective joint peak shaving model for base stations is established, centrally controlling the energy storage system of the base station through a virtual battery management system. Finally, a simulation analysis was conducted on data from different types of base stations in the region, designing two distinct scheduling schemes for four regional categories. The analysis results demonstrate that the proposed model can effectively reduce the power consumption of base stations while mitigating the fluctuation of the power grid load. Full article

Lipopolysaccharide (LPS) triggers a severe systemic inflammatory reaction in mammals, with the dimerization of TLR₄/MD-2 upon LPS stimulation serving as the pivotal mechanism in the transmission of inflammatory signals. Ginsenoside Rh₂ (G-Rh₂), one of the active constituents of red ginseng, exerts potent anti-inflammatory activity. However, whether G-Rh₂ can block the TLR₄ dimerization to exert anti-inflammatory effects remains unclear. Here, we first investigated the non-cytotoxic concentration of G-Rh₂ on RAW 264.7 cells, and detected the releases of pro-inflammatory cytokines in LPS-treated RAW 264.7 cells, and then uncovered the mechanisms involved in the anti-inflammatory activity of G-Rh₂ through flow cytometry, fluorescent membrane localization, Western blotting, co-immunoprecipitation (Co-IP), molecular docking and surface plasmon resonance (SPR) analysis in LPS-stimulated macrophages. Our results show that G-Rh₂ stimulation markedly inhibited the secretion of LPS-induced interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and nitric oxide (NO). Additionally, G-Rh₂ blocked the binding of LPS with the membrane of RAW264.7 cells through direct interaction with TLR₄ and MD-2 proteins, leading to the disruption of the dimerization of TLR₄ and MD-2, followed by suppression of the TLR₄/NF-κB signaling pathway. Our results suggest that G-Rh₂ acts as a new inhibitor of TLR₄ dimerization and may serve as a promising therapeutic agent against inflammation. Full article

Transcranial magnetic stimulation (TMS) has been widely used to study the mechanisms that underlie motor output. Yet, the extent to which TMS acts upon the cortical neurons implicated in volitional motor commands and the focal limitations of TMS remain subject to debate. Previous research links TMS to improved subject performance in behavioral tasks, including a bias in phoneme discrimination. Our study replicates this result, which implies a causal relationship between electro-magnetic stimulation and psychomotor activity, and tests whether TMS-facilitated psychomotor activity recorded via electroencephalography (EEG) may thus serve as a superior input for neural decoding. First, we illustrate that site-specific TMS elicits a double dissociation in discrimination ability for two phoneme categories. Next, we perform a classification analysis on the EEG signals recorded during TMS and find a dissociation between the stimulation site and decoding accuracy that parallels the behavioral results. We observe weak to moderate evidence for the alternative hypothesis in a Bayesian analysis of group means, with more robust results upon stimulation to a brain region governing multiple phoneme features. Overall, task accuracy was a significant predictor of decoding accuracy for phoneme categories (F(1,135) = 11.51, p < 0.0009) and individual phonemes (F(1,119) = 13.56, p < 0.0003), providing new evidence for a causal link between TMS, neural function, and behavior. Full article

Propagation of cuttings is the primary method of rose multiplication. Aux/IAA, early response genes to auxin, play an important role in regulating the process of adventitious root formation in plants. However, systematic research on the identification of RhAux/IAA genes and their role in adventitious root formation in roses is lacking. In this study, 34 RhAux/IAA genes were identified by screening the rose genome, distributed on seven chromosomes, and classified into three clades based on the evolutionary tree. An analysis of the cis-acting elements in the promoters of RhAux/IAA genes revealed the presence of numerous elements related to plant hormones, the light signal response, the growth and development of plants, and abiotic stress. RNA-seq analysis identified a key RhIAA25 gene that may play an important role in the generation of adventitious roots in roses. Subcellular localization, yeast self-activation, and tissue-specific expression experiments indicated that RhIAA25 encoded a nuclear protein, had no yeast self-activated activity, and was highly expressed in the stem. The overexpression of RhIAA25 promoted the elongation of the primary root in Arabidopsis but inhibited adventitious root formation. This study systematically identified and analyzed the RhAux/IAA gene family and identified a key gene, RhIAA25, that regulates adventitious root generation in roses. This study offers a valuable genetic resource for investigating the regulatory mechanism of adventitious root formation in roses. Full article

Hyperlipidemia is a metabolic disorder characterized by abnormal lipid metabolism, resulting in lipid accumulation in the plasma. According to reports, medicinal and edible plants can reduce the risk of metabolic diseases such as hyperlipidemia. This study investigates the effects and mechanisms of Astragalus membranaceus extract (AME), Hippophae rhamnoides L. extract (HRE), and Taraxacum mongolicum Hand. Mazz extract (TME) on hyperlipidemia. Active compounds and potential gene targets of AME, HRE, and TME were screened using LC-MS and TCMSP databases, and hyperlipidemia targets were detected from the OMIM and DisGeNet databases. A drug-target pathway disease network was constructed through protein interactions, GO enrichment, and KEGG pathway analysis. Finally, the lipid-lowering effects of three extracts were validated through in vitro HepG2 cell and in vivo animal experiments. The results show that LC-MS and network pharmacology methodologies identified 41 compounds and 140 targets. KEGG analysis indicated that the PI3K-Akt and MAPK signaling pathways significantly treat hyperlipidemia with AHT. In vitro experiments have shown that AHT is composed of a ratio of AME:HRE:TME = 3:1:2. HepG2 cell and animal experiments revealed that AHT exhibits strong lipid-lowering and antioxidant properties, significantly regulating the levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC). It is worth noting that AHT can effectively downregulate the protein expression levels of p-AKT/AKT and p-PI3K/PI3K and upregulate the protein expression levels of p-AMPK/AMPK and SIRT1, verifying the results predicted by network pharmacology. This study presents a novel approach to utilizing these natural plant extracts as safe and effective treatments for hyperlipidemia. Full article

The oscillation synchronization analysis in biological systems will expand our knowledge about the response of living systems to changes in environmental conditions. This knowledge can be used in medicine (diagnosis, therapy, monitoring) and agriculture (increasing productivity, resistance to adverse effects). Currently, the search is underway for an informative, accurate and sensitive method for analyzing the synchronization of oscillatory processes in cell biology. It is especially pronounced in analyzing the concentration oscillations of intracellular signaling molecules in electrically nonexcitable cells. The bispectral analysis method could be applied to assess the characteristics of synchronized oscillations of intracellular mediators. We chose endothelial cells from mouse microvessels as model cells. Concentrations of well-studied calcium and nitric oxide (NO) were selected for study in control conditions and well-described stress: heating to 40 °C and hyperglycemia. The bispectral analysis allows us to accurately evaluate the proportion of synchronized cells, their synchronization degree, and the amplitude and frequency of synchronized calcium and NO oscillations. Heating to 40 °C increased cell synchronization for calcium but decreased for NO oscillations. Hyperglycemia abolished this effect. Heating to 40 °C changed the frequencies and increased the amplitudes of synchronized oscillations of calcium concentration and the NO synthesis rate. The first part of this paper describes the principles of the bispectral analysis method and equations and modifications of the method we propose. In the second part of this paper, specific examples of the application of bispectral analysis to assess the synchronization of living cells in vitro are presented. The discussion compares the capabilities of bispectral analysis with other analytical methods in this field. Full article

Cancer research has advanced tremendously with the identification of causative genes, proteins, and signaling pathways. Numerous antitumor drugs have been designed and screened for cancer therapeutics; however, designing target-specific drugs for malignant cells with minimal side effects is challenging. Recently, energy-sensing- and homeostasis-associated molecules and signaling pathways playing a role in proliferation, apoptosis, autophagy, and angiogenesis have received increasing attention. Energy-metabolism-based studies have shown the contribution of energetics to cancer development, where tumor cells show increased glycolytic activity and decreased oxidative phosphorylation (the Warburg effect) in order to obtain the required additional energy for rapid division. The role of energy homeostasis in the survival of normal as well as malignant cells is critical; therefore, fuel intake and expenditure must be balanced within acceptable limits. Thus, energy-sensing enzymes detecting the disruption of glycolysis, AMP, ATP, or GTP levels are promising anticancer therapeutic targets. Here, we review the common energy mediators and energy sensors and their metabolic properties, mechanisms, and associated signaling pathways involved in carcinogenesis, and explore the possibility of identifying drugs for inhibiting the energy metabolism of tumor cells. Furthermore, to corroborate our hypothesis, we performed meta-analysis based on transcriptomic profiling to search for energy-associated biomarkers and canonical pathways. Full article

The analysis of utilising unmanned aerial vehicles (UAVs) to form flying networks in obstacle conditions and various algorithms for obstacle avoidance is conducted. A planning scheme for deploying a flying LiFi network based on UAVs in a production facility with obstacles is developed and described. Such networks are necessary to ensure reliable data transmission from sensors or other sources of information located in dangerous or hard-to-reach places to the crisis centre. Based on the planning scheme, the following stages are described: (1) laying the LiFi signal propagation route in conditions of interference, (2) placement of the UAV at the specified points of the laid route for the deployment of the LiFi network, and (3) ensuring the reliability of the deployed LiFi network. Strategies for deploying UAVs from a stationary depot to form a flying LiFi network in a room with obstacles are considered, namely the strategy of the first point for the route, the strategy of radial movement, and the strategy of the middle point for the route. Methods for ensuring the uninterrupted functioning of the flying LiFi network with the required level of reliability within a given time are developed and discussed. To implement the planning stages for deploying the UAV flying LiFi network in a production facility with obstacles, the “Simulation Way” and “Reliability Level” software tools are developed and described. Examples of utilising the proposed software tools are given. Full article

Functional neuroimaging analysis takes noisy multidimensional measurements as input and produces statistical inferences regarding the functional properties of brain regions as output. Such inferences are most commonly model-based, in that they assume a model of how neural activity translates to the measured signal (blood oxygenation level-dependent signal in the case of functional MRI). The use of models increases statistical sensitivity and makes it possible to ask fine-grained theoretical questions. However, this comes at the cost of making theoretical assumptions about the underlying data-generating process. An advantage of model-free approaches is that they can be used in cases where model assumptions are known not to hold. To this end, we introduce a randomization-based, model-free approach to functional neuroimaging. TWISTER randomization makes it possible to infer functional selectivity from correlations between experimental runs. We provide a proof of concept in the form of a visuomotor mapping experiment and discuss the possible strengths and limitations of this new approach in light of our empirical results. Full article

Proteins are the most common types of biomarkers used in breast cancer (BC) theranostics and management. By definition, a biomarker must be a relevant, objective, stable, and quantifiable biomolecule or other parameter, but proteins are known to exhibit the most variate and profound structural and functional variation. Thus, the proteome is highly dynamic and permanently reshaped and readapted, according to changing microenvironments, to maintain the local cell and tissue homeostasis. It is known that protein posttranslational modifications (PTMs) can affect all aspects of protein function. In this review, we focused our analysis on the different types of PTMs of histological biomarkers in BC. Thus, we analyzed the most common PTMs, including phosphorylation, acetylation, methylation, ubiquitination, SUMOylation, neddylation, palmitoylation, myristoylation, and glycosylation/sialylation/fucosylation of transcription factors, proliferation marker Ki-67, plasma membrane proteins, and histone modifications. Most of these PTMs occur in the presence of cellular stress. We emphasized that these PTMs interfere with these biomarkers maintenance, turnover and lifespan, nuclear or subcellular localization, structure and function, stabilization or inactivation, initiation or silencing of genomic and non-genomic pathways, including transcriptional activities or signaling pathways, mitosis, proteostasis, cell–cell and cell–extracellular matrix (ECM) interactions, membrane trafficking, and PPIs. Moreover, PTMs of these biomarkers orchestrate all hallmark pathways that are dysregulated in BC, playing both pro- and/or antitumoral and context-specific roles in DNA damage, repair and genomic stability, inactivation/activation of tumor-suppressor genes and oncogenes, phenotypic plasticity, epigenetic regulation of gene expression and non-mutational reprogramming, proliferative signaling, endocytosis, cell death, dysregulated TME, invasion and metastasis, including epithelial–mesenchymal/mesenchymal–epithelial transition (EMT/MET), and resistance to therapy or reversal of multidrug therapy resistance. PTMs occur in the nucleus but also at the plasma membrane and cytoplasmic level and induce biomarker translocation with opposite effects. Analysis of protein PTMs allows for the discovery and validation of new biomarkers in BC, mainly for early diagnosis, like extracellular vesicle glycosylation, which may be considered as a potential source of circulating cancer biomarkers. Full article

Following the acute phase of SARS-CoV-2 infection, certain individuals experience persistent symptoms referred to as long COVID. This study analyzed the patients categorized into three distinct groups: (1) individuals presenting rheumatological symptoms associated with long COVID, (2) patients who have successfully recovered from COVID-19, and (3) donors who have never contracted COVID-19. A notable decline in the expression of miR-200c-3p, miR-766-3p, and miR-142-3p was identified among patients exhibiting rheumatological symptoms of long COVID. The highest concentration of miR-142-3p was found in healthy donors. One potential way to reduce miRNA concentrations is through antibody-mediated hydrolysis. Not only can antibodies possessing RNA-hydrolyzing activity recognize the miRNA substrate specifically, but they also catalyze its hydrolysis. The analysis of the catalytic activity of plasma antibodies revealed that antibodies from patients with long COVID demonstrated lower hydrolysis activity against five fluorescently labeled oligonucleotide sequences corresponding to the Flu-miR-146b-5p, Flu-miR-766-3p, Flu-miR-4742-3p, and Flu-miR-142-3p miRNAs and increased activity against the Flu-miR-378a-3p miRNA compared to other patient groups. The changes in miRNA concentrations and antibody-mediated hydrolysis of miRNAs are assumed to have a complex regulatory mechanism that is linked to gene pathways associated with the immune system. We demonstrate that all six miRNAs under analysis are associated with a large number of signaling pathways associated with immune response-associated pathways. Full article

This work reports on the development of an analyte sampling strategy on a plasmonic substrate to amplify the detection capability of a dual analytical system, paper spray ionization–mass spectrometry (PSI-MS) and surface-enhanced Raman spectroscopy (SERS). While simply applying only an analyte solution to the plasmonic paper results in a limited degree of SERS enhancement, the introduction of plasmonic gold nanoparticles (AuNPs) greatly improves the SERS signals without sacrificing PSI-MS sensitivity. It is initially revealed that the concentration of AuNPs and the type of analytes highly influence the SERS signals and their variations due to the “coffee ring effect” flow mechanism induced during sampling and the degree of the interfacial interactions (e.g., van der Waals, electrostatic, covalent) between the plasmonic substrate and analyte. Subsequent PSI treatment at high voltage conditions further impacts the overall SERS responses, where the signal sensitivity and homogeneity significantly increase throughout the entire substrate, suggesting the ready migration of adsorbed analytes regardless of their interfacial attractive forces. The PSI-induced notable SERS enhancements are presumably associated with creating unique conditions for local aggregation of the AuNPs to induce effective plasmonic couplings and hot spots (i.e., electromagnetic effect) and for repositioning analytes in close proximity to a plasmonic surface to increase polarizability (i.e., chemical effect). The optimized sampling and PSI conditions are also applicable to multi-analyte analysis by SERS and MS, with greatly enhanced detection capability and signal uniformity. Full article

Calcium (Ca²⁺) functions as a universal signal messenger in eukaryotes but in bacteria, the physiological roles for Ca²⁺ are limited. Here, we examine the role of Ca²⁺ in Streptococcus pneumoniae during manganese (Mn²⁺) intoxication. S. pneumoniae mntE mutants, lacking the Mn²⁺ efflux transporter, exhibit impaired growth due to accumulation of Mn²⁺ when exposed to elevated exogenous Mn²⁺. This Mn²⁺-sensitive growth defect is restored to wild-type growth level by exogenous Ca²⁺, in a Ca²⁺-dependent manner. Despite growth restoration of the mntE mutant to wild-type levels, cellular Mn²⁺ remains elevated in this strain. Bacterial capsule production is also increased for the mntE mutant, resulting in reduced adherence capacity to surfaces and poor biofilm formation, which is consistent with it experiencing Mn²⁺ intoxication. Ca²⁺ presence did not significantly impact bacterial capsule production or biofilm formation. Further analysis of the cell morphology demonstrates that Ca²⁺ contributes to cell division and reduces cell chain lengths. Together, these data describe the first role of Ca in S. pneumoniae that has potential implications in bacterial virulence since Ca affects cell division and likely Mn²⁺-associated cellular processes. Full article