Bupivacaine (BP) is a commonly clinically used local anesthetic (LA). Current studies suggest that neurological complications are increased in diabetic patients after LA application, but the ...molecular mechanism is poorly understood. LA-induced autophagy and neuronal injury have been reported. We hypothesized that a high-glucose environment aggravates BP-induced autophagic damage. Mouse dorsal root ganglion (DRG) neurons were treated with BP in a high-glucose environment, and the results showed that reactive oxygen species (ROS) levels increased, autophagy was activated, autophagy flux was blocked, and cell viability decreased. Pretreatment with the ROS scavenger N-acetyl-cysteine (NAC) attenuated ROS-mediated autophagy regulation. Moreover, the expression of the long noncoding RNA (lncRNA) taurine upregulated gene 1 (TUG1) increased, and NAC and TUG1 siRNA inhibited the expression of TUG1/mammalian target of rapamycin (mTOR) in DRGs treated with BP in a high-glucose environment. Intriguingly, contrary to previous reports on a positive effect on neurons, we found that rapamycin, an autophagy activator, and chloroquine, an autophagy and lysosome inhibitor, both exacerbated autophagic damage. These data suggest that a high-glucose environment exacerbated BP induced ROS-dependent autophagic damage in DRG neurons through the TUG1/mTOR signaling pathway, which provides a theoretical basis and target for the clinical prevention and treatment of BP neurotoxicity in diabeties.
•High glucose causes an increase in cell toxicity induced by BP.•High glucose aggravated BP-induced DNA damage and apoptosis.•High glucose aggravated BP-induced DNA damage through inhibit DNA-PK/Ku70 ...protein.
Bupivacaine (BP) is commonly used as a local anaesthetic(LA) in the clinic, but it can also cause neurotoxicity, especially in patients with diabetes. Previous studies have found that high-glucose environments can aggravate BP-induced DNA damage in nerve cells. Ku70 is subunit of the DNA damage repair enzyme DNA-PK. This study was designed to determine whether high-glucose conditions enhance BP neurotoxicity and DNA damage by inhibiting Ku70 expression.
We examined the effect of BP on apoptosis and DNA damage in murine dorsal root ganglion (DRG) neurons under hyperglycaemic conditions. Untreated DRG cells and DRG cells pretreated with NU7441, a DNA-PK inhibitor, were cultured for 3 days under normal culture conditions or with 50 mM glucose, and the cells were then treated with BP for 3 h. DNA damage was investigated via comet assays, the ratio of early to late apoptotic cells was assessed by Annexin V-FITC/PI staining, and cell viability was measured by CCK-8 assays. The protein expression levels of DNA-PK, Ku70, Bax, Bcl-2 and γH2ax were measured by immunofluorescence or Western blotting.
Compared to its effect under normal culture conditions, BP treatment led to decreased cell viability and increased DNA damage in DRG cells grown under high-glucose conditions. The rate of DRG cell apoptosis and the expression of γH2ax, the ratio of Bax to Bcl-2 also increased under the high-glucose conditions. Furthermore, Ku70 expression was inhibited. The DNA-PK inhibitor, NU7441, could significantly inhibit DNA-PK and Ku70 expression, simultaneously further aggravating BP-induced apoptosis and DNA damage under high-glucose conditions.
These data indicate that hyperglycaemia may enhance BP-induced neurotoxicity and DNA damage by inhibiting the DNA repair protein Ku70.
To investigate the role of poly(ADP-ribose) polymerases-1 (PARP-1)-mediated blockade of autophagic flow in myocardial ischemia-reperfusion injury.
H9c2 cells, a rat cardiac myocyte line, were divided ...into control group, hypoxia/ reoxygenation model group (H/R group), PARP-1 inhibitor (PJ34) group, and PJ34 + H/R group. The total protein was extracted from the cells in each group to detect the expressions of pADPr, Bax, the DNA damage marker protein p-YH2ax, and autophagic flow-associated proteins LC3BⅡ/LC3Ⅰ, Beclin-1, and P62 using Western blotting.
Compared with the control cells, the cells with H/R exhibited significantly increased expressions of pADPr, Bax and p-YH2ax (
< 0.05). The expressions of LC3B Ⅱ, beclin-1 and p62 were also increased significantly in the cells with H/R (
< 0.05), indicating the block of the autophagic flow. The application of PARP-1 inhibitor PJ34 in the cells with H/R significantly inhibited the expressions of pADPr (
< 0.05) and Bax (
< 0.01), and alleviated DNA damage in the cel
Taking only the mean value of cover transmittance and cover absorbance would lead to a large error in estimating the thermal performance of a greenhouse. This paper discusses an innovative dynamic ...energy balance model of a glass greenhouse, incorporating dynamic cover absorbance and transmittance. Different cover absorbances and transmittances for diffuse, beam, and ground-reflected radiation are used. The model primarily comprises nine differential energy conservation equations for indoor air, seven layers of soil, and the greenhouse’s cover. Greenhouse temperature trends are acquired by solving the unsteady-state equations with MATLAB. The model was verified using experimental data recorded during three non-continuous periods of 15 days each in northern China (36.08°N, 116.95°E), during which the daily maximum outdoor solar radiation flux intensity fell between 191 and 894 Wm-2, the outdoor air temperature fell between −12.3 °C and 24.5 °C, the ground surface temperature fell between 0.6°C and 44.3 °C, and the indoor air temperature fell between −9.0 °C and 51.8 °C. The estimates agree well with the measurements, suggesting that the dynamic model is valid. Meanwhile, the dynamic cover absorbance and transmittance, the solar radiation absorbed by the cover, the solar radiation transmitted into the glass greenhouse and the proportion of solar radiation from each surface are discussed.
•The model considers dynamic cover absorbance and transmittance with an improved performance.•Use of a sub-model of seven-layer soil resulted in an improved performance.•The solar radiation transmitted into the greenhouse from side walls was studied.•Study of the dynamic absorbance and transmittance of various greenhouse surfaces.•Analysis of solar radiation absorbed by cover and solar radiation transmitted into the greenhouse.
•Under natural ventilation, the wind speed has the least impact on the microenvironment in the greenhouse.•Side vent opening and crop height significantly affect the microenvironment in the ...greenhouse, and they have the best matching relationship.•When only the inter valley vent is opened, the HREs are the smallest and close under various crop height and wind speed.•When the side vent openings are the same, the height of the horizontal layer of the lowest temperature increases with the increase of crop height.
Multi-span arched plastic greenhouse is an important horticultural facilities structure. The main problem to be faced is ventilation and cooling in summer. Therefore, 3-span arched plastic greenhouse with better adjustable performance were used as a research object. The effects of vent opening, wind speed and crop height on the microenvironment under natural ventilation were studied by means of in-situ observation and computational fluid dynamics (CFD) analysis. By analyzing the space-time evolution of microenvironment and ventilation efficiency in the greenhouse, this paper aims to explore the change process of microenvironment and the reasonable matching relationship between various factors. The results show that side vent opening and crop height significantly affect the microenvironment in the greenhouse, and they have the optimum matching relationship. When the crop height is 1.0 m and the wind speeds are 0 m/s, 1.0 m/s and 2.0 m/s respectively in the dynamic stability stage, the temperatures of point Q2 under the condition that the side vent opening is 0.8 m are 3.00 °C, 1.49 °C and 0.51 °C lower than temperatures under the condition that only the inter valley vent is opened. When the crop height is 1.8 m and the wind speed is 0 m/s, the difference of temperature of point Q3 is 3.50 °C, 0.97 °C and 2.15 °C respectively. The larger the opening of the side vent, the better the ventilation and cooling effect. Compared with the influence of the size of the side vent opening on the microclimate in the greenhouse, the influence of wind speed on it is weak. When side and inter valley vent are opened at the same time, the horizontal layer height of the lowest temperature at the crop height of 1.0 m is lower than that of 1.8 m. The influence of side vent opening on heat removal efficiencies (HREs) takes precedence over the influence of wind speed. When only the inter valley vent is opened, the HREs are the smallest and close at various crop heights and wind speeds. These results provided a control strategy with lower energy consumption and higher efficiency for 3-span arched greenhouses.
Purpose
Central nervous system (CNS) is the prevalent site for metastases in epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)-relapsed NSCLC patients. To understand the
EGFR
...mutation status in paired cerebrospinal fluid (CSF) and plasma samples after EGFR-TKI treatment failure might be useful to guide the treatment of intra- and extracranial tumors in those patients.
Methods
Paired CSF and plasma samples were collected from seven NSCLC patients with CNS metastases after EGFR-TKI failure.
EGFR
mutations were tested by amplification refractory mutation system (ARMS) and droplet digital PCR (ddPCR) methods. Gefitinib concentrations were evaluated by high-performance liquid chromatography–mass spectrometry (HPLC–MS/MS).
Results
EGFR
mutations were detected in all seven CSF samples, including three of E19-Del, three of L858R and one of E19-Del&T790M by both methods. On the other hand, majority of the matched plasma samples (5/7) were negative for
EGFR
mutations by both methods. The other two plasma samples were positive for E19-Del&T790M by ddPCR, and one of them had undetectable T790M by ARMS. Gefitinib concentration in CSF was much lower than that in plasma (mean CSF/plasma ratio: 1.8 %).
Conclusions
After EGFR-TKI failure, majority of the NSCLC patients with CNS metastases remained positive detection of
EGFR
sensitive mutations in CSF, but much less detection in the matched plasma. Significantly low exposure of gefitinib in CSF might explain the intracranial protection of the
EGFR
sensitive mutation positive tumor cells.
As the core process of natural gas purification plant, natural gas sweetening directly affects the production efficiency and product quality of the purification plant. However, process modeling based ...on sulfur content prediction presents challenges in adaptability and accuracy. To tackle this, a machine learning‐based modeling approach is proposed that integrates an adaptive immune genetic algorithm with random forest (RF) to intelligently select process features as input variables for RF modeling. The industrial result indicates that the proposed method is able to remove interfering variables and adaptively achieve optimal model precision for different scenarios. It offers a novel research instrument for product quality monitoring in natural gas sweetening plants.
A machine learning‐based modeling approach is proposed that integrates an adaptive immune genetic algorithm with random forest to intelligently select process features as input variables for natural gas sweetening process modeling. This model can adaptively execute physical feature selection and possesses the advantages of strong predictive performance and tolerance to outliers and noise.
This paper proposes a fertilizer mixing device that combines pressure relief return and mechanical agitation to address the issues in the current water-fertilizer integration equipment related to ...limited fertilizer mixing methods and inconvenient irrigation pressure regulation. The device employs different mixing modes for various fertilizer forms and uses pressure relief return to adjust irrigation pressure, thereby enhancing the efficiency of water-fertilizer mixing and optimizing energy consumption. The experimental results indicate that the reflux mode is suitable for liquid-type fertilizers which are fast dissolving and easy to diffuse, and its EC value is stable at about 6.60 mS/cm, which is close to the calibrated value of 6.80 mS/cm. The stirring paddle mode compensates for the reflux mode's weak mixing effect, making it suitable for solid powder-type fertilizers' mixing operation. The EC value remains stable at approximately 8.60 mS/cm when calibrated at 8.70 mS/cm. The “stirring paddle + two-way reflux” mode demonstrates the most robust mixing effect and is suitable for mixing solid granular fertilizers. When calibrated at 8.20 mS/cm, it stabilizes at approximately the calibration value after 105 s. This research provides technical support and a theoretical basis to accomplish efficient, energy-saving, and rational application of water-fertilizer integration across diverse fertilizer forms.
To evaluate the insulin receptor isoform mRNA expression status in non-small cell lung cancer (NSCLC) patients.
RNA-seq data from 614 NSCLC 355 adenocarcinomas (LUAD) and 259 squamous cell carcinomas ...(LUSC) and 92 normal lung specimens were obtained from The Cancer Genome Atlas (TCGA) to evaluate the mRNA expression of insulin receptor isoform A (IR-A) and insulin receptor isoform B (IR-B). The differential expression status of the insulin receptor isoforms in NSCLC patients was confirmed using qRT-PCR assays with lung cancer cDNA arrays and primary tumor samples.
The mRNA expression levels of IR-B were significantly lower in some NSCLC samples compared to normal lung specimens, including both LUAD and LUSC. Notably, no IR-B transcripts were detected - only the IR-A isoform was expressed in 11% of NSCLC patients. This decrease in IR-B expression contributed to an elevated IR-A/IR-B ratio, which was also associated with lower epithelial-mesenchymal transition gene signatures in NSCLC and longer patient survival under standard of care in LUSC. In addition to NSCLC, RNA-seq data from TCGA revealed a similar increase in IR-A/IR-B ratio in many other cancer types, with high prevalence in acute myeloid leukemia, glioblastoma multiforme, and brain lower grade glioma.
Our results indicate a common reduction of the mRNA expression level of IR-B and an increased IR-A/IR-B mRNA ratio in NSCLC and other tumor types. The relationship of altered IR-A/IR-B ratios with cancer progression and patient survival should be prospectively explored in future studies.
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