•PM0.2 exposure induced the disorders of α-syn degradation in mice and astrocytes.•LAMP2-mediated autophagy-lysosome pathway was disturbed and underlied α-syn pathology induced by PM0.2 ...exposure.•PP242 improved the disorder of α-syn through TFEB/LAMP2 pathway.
Atmospheric particulate matter (PM) exacerbates the risk factor for Alzheimer's and Parkinson's diseases (PD) by promoting the alpha-synuclein (α-syn) pathology in the brain. However, the molecular mechanisms of astrocytes involvement in α-syn pathology underlying the process remain unclear. This study investigated PM with particle size <200 nm (PM0.2) exposure-induced α-syn pathology in ICR mice and primary astrocytes, then assessed the effects of mammalian target of rapamycin inhibitor (PP242) in vitro studies. We observed the α-syn pathology in the brains of exposed mice. Meanwhile, PM0.2-exposed mice also exhibited the activation of glial cell and the inhibition of autophagy. In vitro study, PM0.2 (3, 10 and 30 µg/mL) induced inflammatory response and the disorders of α-syn degradation in primary astrocytes, and lysosomal-associated membrane protein 2 (LAMP2)-mediated autophagy underlies α-syn pathology. The abnormal function of autophagy-lysosome was specifically manifested as the expression of microtubule-associated protein light chain 3 (LC3II), cathepsin B (CTSB) and lysosomal abundance increased first and then decreased, which might both be a compensatory mechanism to toxic α-syn accumulation induced by PM0.2. Moreover, with the transcription factor EB (TFEB) subcellular localization and the increase in LC3II, LAMP2, CTSB, and cathepsin D proteins were identified, leading to the restoration of the degradation of α-syn after the intervention of PP242. Our results identified that PM0.2 exposure could promote the α-syn pathological dysregulation in astrocytes, providing mechanistic insights into how PM0.2 increases the risk of developing PD and highlighting TFEB/LAMP2 as a promising therapeutic target for antagonizing PM0.2 toxicity.
Display omitted
Immune deficiency is a prevalent issue among kittens, severely threatening their health and development by increasing susceptibility to infections and diseases. This study investigates the effects of ...dietary supplements containing lactoferrin and Lactobacillus plantarum (L. plantarum) on the immune function, intestinal health, and microbiota composition of kittens. The results demonstrate that these supplements significantly enhance immune responses, with immunoglobulin A (IgA) levels increasing by 14.9% and IgG levels by 14.2%. Additionally, there was a notable 28.7% increase in catalase activity, indicating a reduction in oxidative stress. Gastrointestinal (GI) health improved markedly, evidenced by increased populations of beneficial bacteria such as Lactobacillus, which rose from 4.13% to 79.03% over the study period. The DNC group also showed significant reductions in pro-inflammatory cytokines, including decreases of 13.94% in IL-2, 26.46% in TNF-α, and 19.45% in IFN-γ levels. Furthermore, improvements in physical conditions were observed, including enhanced coat condition and mental status. These findings underline the potential of lactoferrin and L. plantarum as effective dietary interventions to improve kitten health, thereby reducing dependency on antibiotics and mitigating associated risks. This research provides a scientific foundation for optimizing nutritional management practices to enhance the overall vitality of kittens during their critical growth phases.
Gastrointestinal (GI) afflictions are prevalent among the feline population, wherein the intricacies of the gut microbiome exert a profound influence on their overall health. Alterations within this ...microbial consortium can precipitate a cascade of physiological changes, notably in immune function and antioxidant capacity. This research investigated the impact of Bifidobacterium lactis (B. lactis) and Lactobacillus plantarum (L. plantarum) on cats’ GI health, exploring the effects of probiotic supplementation on the intestinal ecosystem using 16S rRNA gene sequencing. The findings demonstrated a significant improvement in gut barrier function by reducing plasma concentrations of D-lactate (D-LA) by 30.38% and diamine oxidase (DAO) by 22.68%, while increasing the population of beneficial bacteria such as Lactobacillus. There was a notable 25% increase in immunoglobulin A (IgA) levels, evidenced by increases of 19.13% in catalase (CAT), 23.94% in superoxide dismutase (SOD), and 21.81% in glutathione peroxidase (GSH-Px). Further analysis revealed positive correlations between Lactobacillus abundance and IgA, CAT, and total antioxidant capacity (T-AOC) levels. These correlations indicate that B. lactis and L. plantarum enhance feline immune and antioxidant functions by increasing the abundance of beneficial Lactobacillus in the GI tract. These findings provide a foundation for probiotic interventions aimed at enhancing health and disease resistance in feline populations.
Sex-determining region Y-related high mobility group box 2 (SOX-2) is a key pluripotency-associated transcription factor and may be implicated in the pathogenesis of cervical squamous cell carcinoma ...(SCC). The aim of this study was to explore SOX-2 expression in cervical SCC tissues and to examine whether and how SOX-2 regulates the malignant behaviors of cervical SCC cells in vitro. We here found that SOX-2 expression in the examined cervical SCC tissues was higher than that in the normal cervical and cervical intraepithelial neoplasia (CIN) tissues. Higher protein level of SOX-2 (nuclear positive staining cells ≥50 %) was detected in 34.9 % (29 out of 83 cases) of cervical SCC patients. We also noted that 100 % of well-differentiated and 66.7 % of moderately differentiated cervical SCCs showed lower SOX-2 expression (nuclear positive staining cells <50 %), while 58.8 % of poorly differentiated tumors had higher SOX-2 expression (
P
< 0.05). Furthermore, the migratory and invasive capabilities of SiHa cervical cancer cells were enhanced when SOX-2 was upregulated whereas suppressed when SOX-2 was downregulated. Also, the phosphorylation levels of protein kinase B (Akt) and extracellular regulated protein kinases (ERK) 1/2 were increased in SOX-2-overexpressed cancer cells but decreased in SOX-2-depleted cells. Additionally, LY294002 (Akt pathway inhibitor) or U0126 (ERK pathway inhibitor) significantly suppressed SOX-2-overexpression-induced migration and invasion in SiHa cells. Our results indicate that differentially expressed SOX-2 is associated with tumor differentiation (
P
< 0.05) and that SOX-2 contributes to the migratory and invasive behaviors of cervical SCC in vitro.
The complete sequences of chloroplast genomes provide wealthy information regarding the evolutionary history of species. With the advance of next-generation sequencing technology, the number of ...completely sequenced chloroplast genomes is expected to increase exponentially, powerful computational tools annotating the genome sequences are in urgent need.
We have developed a web server CPGAVAS. The server accepts a complete chloroplast genome sequence as input. First, it predicts protein-coding and rRNA genes based on the identification and mapping of the most similar, full-length protein, cDNA and rRNA sequences by integrating results from Blastx, Blastn, protein2genome and est2genome programs. Second, tRNA genes and inverted repeats (IR) are identified using tRNAscan, ARAGORN and vmatch respectively. Third, it calculates the summary statistics for the annotated genome. Fourth, it generates a circular map ready for publication. Fifth, it can create a Sequin file for GenBank submission. Last, it allows the extractions of protein and mRNA sequences for given list of genes and species. The annotation results in GFF3 format can be edited using any compatible annotation editing tools. The edited annotations can then be uploaded to CPGAVAS for update and re-analyses repeatedly. Using known chloroplast genome sequences as test set, we show that CPGAVAS performs comparably to another application DOGMA, while having several superior functionalities.
CPGAVAS allows the semi-automatic and complete annotation of a chloroplast genome sequence, and the visualization, editing and analysis of the annotation results. It will become an indispensible tool for researchers studying chloroplast genomes. The software is freely accessible from http://www.herbalgenomics.org/cpgavas.
To improve vehicle path-following performance and to reduce driver workload, a human-centered feed-forward control (HCFC) system for a vehicle steering system is proposed. To be specific, a novel ...dynamic control strategy for the steering ratio of vehicle steering systems that treats vehicle speed, lateral deviation, yaw error, and steering angle as the inputs and a driver's expected steering ratio as the output is developed. To determine the parameters of the proposed dynamic control strategy, drivers are classified into three types according to the level of sensitivity to errors, i.e., low, middle, and high. The proposed HCFC system offers a human-centered steering system (HCSS) with a tunable steering gain, which can assist drivers in tracking a given path with smaller steering wheel angles and change rate of the angle by adaptively adjusting steering ratio according to driver's path-following characteristics, reducing the driver's workload. A series of experiments of tracking the centerline of double lane change (DLC) are conducted in CarSim and three different types of drivers are subsequently selected to test in a portable driving simulator under a fixed-speed condition. The simulation and experiment results show that the proposed HCSS with the dynamic control strategy, as compared with the classical control strategy of steering ratio, can improve task performance by about 7% and reduce the driver's physical workload and mental workload by about 35% and 50%, respectively, when following the given path.
With the development of ecological paradigm coupled with the relentless implementation of myriad environmental policies in China, the rapid development of carbon emission trading and carbon trading ...market has had a vital impact on the financial performance of enterprises at the microlevel. This study has sampled the A-share listed companies in China, from 2009 to 2018, and adopted the difference-in-difference (DID) method to investigate the effect of the carbon emission trading on corporate financial performance from the microlevel. Evidence showed that the implementation of carbon emission trading effectively improved the total asset-liability ratio of enterprises, though it reduced the value of the current capital market. Moreover, in the regions under strict legal environment, the enhancement effect of the total asset-liability ratio was more obvious, whereas in the regions under loose legal environment, the reduction effect of the value of the capital market was more obvious. Further analysis showed that the implementation of carbon emission trading could not promote Chinese enterprises to increase R&D investment. Hence the implementation of carbon emission trading has improved the level of non-business income of enterprises incorporated into the trading system, but its impact on the investment income of enterprises was not significant.
A major cause of gynecological cancer ‐related deaths worldwide, ovarian cancer is characterized by heterogeneity in both tumor cells and the tumor microenvironment (TME). Our study aimed to ...characterize tumor cell heterogeneity and the infiltration of M2 tumor‐associated macrophages (TAMs) in the ovarian cancer TME by single‐cell RNA‐Seq (scRNA‐Seq) analysis combined with bulk RNA sequencing (bulk RNA‐Seq). Several highly variable genes were identified in ovarian cancer tissues, and tumor cell heterogeneity and infiltrating immune tumor cell heterogeneity were characterized in ovarian cancer cells. M2 TAMs in the TME were the predominant phenotype of TAM. Further, M2 TAM infiltration in the TME was negatively correlated with poor prognosis of ovarian cancer patients. Four M2 TAM‐associated genes (SLAMF7, GNAS, TBX2‐AS1, and LYPD6) correlated with the prognostic survival of ovarian cancer patients. Knockdown of SLAMF7 or GNAS mRNA repressed malignancy and cisplatin resistance of ovarian cancer cells. ScRNA‐Seq combined with bulk RNA‐Seq identified the same four genes associated with M2 TAMs. The prognostic risk score model based on these four genes may hold favorable predictive value for the prognosis of ovarian cancer patients.
A major cause of gynecological cancer.related deaths worldwide, ovarian cancer is characterized by heterogeneity in both tumor cells and the tumor microenvironment (TME). Our study aimed to characterize tumor cell heterogeneity and the infiltration of M2 tumor‐associated macrophages (TAMs) in the TME in ovarian cancer by single‐cell RNA‐Seq (scRNA‐Seq) analysis, combined with bulk RNA sequencing (bulk RNA‐Seq).
Dual-inverter configuration has been attracting increasing attention, especially in motor drives, for its advantages in fault tolerance, multilevel modulation effect, dc voltage utilization, etc. ...However, its switch fault diagnosis is difficult due to the symmetry of the two sub-inverters. A signal processing approach is proposed in this paper to detect the switch open-circuit fault occurrence and further identify the specific faulty switch, benefiting maintenance and fault-tolerant operation. In this scheme, the faulty phase and the faulty switch pair, consisting of the faulty switch and the switch on its diagonal, are identified using the stator phase currents average values. Following that, the bridge of the faulty phase is forced into a unipolar mode by artificially turning off one switch in the healthy pair continuously. Through properly controlling the duty ratios of the other switches in this bridge, the faulty switch is allowed to be further identified from the faulty pair by analyzing the behavior of the induced current in this phase. This approach is independent of either the speed or the voltage information. The effectiveness is validated through experiments on a sensorless controlled open-end winding induction motor drive.
Rapid and accurate detection of nucleic acids is of paramount importance in many fields, including medical diagnosis, gene therapy and virus identification. In this work, by taking advantage of two ...DNA hybridization probes, one of which was immobilized on the surface of gold nanoparticles, while the other was free in solution, detection of short length nucleic acids was successfully achieved using a large size (20 nm tip diameter) polyethylene terephythalate (PET) nanopore. The sensor was sensitive and selective: DNA samples with concentrations at as low as 0.5 nM could be detected within minutes and the number of mismatches can be discerned from the translocation frequency. Furthermore, the nanopore can be repeatedly used many times. Our developed large-size nanopore sensing platform offers the potential for fieldable/point-of-care diagnostic applications.
Display omitted
•Short length nucleic acids are successfully detected by using a large size (20-nm tip diameter) conic PET nanopore.•DNA samples at concentrations as low as 0.5 nM are detected within minutes.•The number of mismatches can be discerned from the translocation frequency.•The nanopore sensor can be repeatedly used many times.
PDF
