Search

In order to study the dynamic performance of coal samples with different length diameter ratio under impact load, this paper used an improved Hopkinson compression bar experimental device (ϕ75 mm), and carried out the impact compression experiments under 6 impact grades (4.18~8.03 m/s)and 4 aspect ratios(0.33~1.33).It analyzed the correlation between the dynamic parameters and the aspect ratio in combination with the gray correlation theory, and this study then established a 4-parameter uniaxial strength type statistical damage model of coal and rock based on the mechanical mechanism, Weibull distribution and D-P failure criterion.Results show that: ① The length diameter ratio of coal samples has a quadratic function relationship with the strain rate and dynamic compressive strength; The relationship between the dissipation energy and the aspect ratio is a quadratic function, and the dissipation energy decreases with the increase of the aspect ratio; The relationship between the electromagnetic energy and the aspect ratio is a linear function and keeps a positive correlation. ② According to the grey correlation theory, this study obtained the influence order of length diameter ratio of coal sample on dynamic parameters: electromagnetic energy(0.88)>dynamic compressive strength(0.84)>dissipation energy(0.81)>strain rate(0.78).③ The initial constitutive model is constructed based on Weibull distribution and D-P criterion, and the dynamic compressive strength σmax and strain rate、the relationship between length to diameter ratio n was corrected, and then the experimental stress-strain curves were compared to verify the reliability of the model(R2>0.91).

On the basis of designing and transforming the bench shock tube in the laboratory, a test system for coal sample damage and destruction under shock pressure was built, and shock step pressure characteristics under different driving gas conditions and different pressures, with or without bedding structure and different bedding structures were studied. The results show that: CO2 and air have obvious internal damage effect and similar damage degree at the same pressure; under different shock wave incident pressures, the damage degree of briquette without bedding structure increases with the increase of incident pressure; compared with the impact strength of briquette coal samples without bedding structure and the serious degree of destruction of the dense structure inside the coal samples, the degree of damage of the coal samples of any bedding structure changes little; the vertical bedding and parallel bedding raw coal samples show good consistency at medium and high-speed jet pressure impacts. At low speeds, parallel bedding is less resistant to compression than vertical bedding.

Bilirubin oxidation end products (BOXes) are associated with the late-developing neurological deficits after subarachnoid hemorrhage (SAH) possibly by direct constricting the cerebral arteries, but their specific impacts on neurons especially in the state of hypoxia, a prominent feature during the late stage of SAH, remain unclear. Here, we explored the effects of BOXes on the primary cortical neurons subjected to CoCl 2 -induced hypoxia by evaluating the morphological and apoptotic changes of neurons. The present study showed that Z-BOX B but not Z-BOX A greatly alleviated CoCl 2 -induced neuronal cell deterioration and apoptosis. Immunocytochemical staining assay showed Z-BOX B significantly increased neurite length, the numbers of both secondary and tertiary branches, and the protein level of Synaptophysin. Caspase 3/7 apoptosis assay and DAPI staining showed that Z-BOX B markedly reduced primary cortical neurons apoptosis. The expression of cleaved Caspase-3 was suppressed by Z-BOX B treatment, while the expression of Bcl-xL was upregulated. To further discover the mechanism of the neuroprotective effect observed in Z-BOX B, we found Z-BOX B increased the expression of p-mTOR, p-Akt, and p-p70S6K. In general, our results implicated Z-BOX B may prevent CoCl 2 -induced primary cortical neurons apoptosis by activating sAkt/mTOR/p70S6K signaling pathway. Hence, the present data may provide new insights into the pathophysiological mechanism of delayed neurological dysfunction after SAH and novel targets for treating SAH. • Z-BOX B, but not Z-BOX A, exerted neuroprotective effect on CoCl2-challenged primary cortical neurons. • Z-BOX B alleviated neuronal apoptosis induced by CoCl2. • Z-BOX B reduced the expression of CoCl2-induced apoptotic proteins. • Z-BOX B promoted Akt/mTOR/p70S6K signaling pathway. [ABSTRACT FROM AUTHOR]

Context: Almonertinib is primarily metabolized by CYP3A4, so it could interact with a variety of drugs metabolized by CYP3A4, leading to the changes of systemic exposure., Objective: For the purpose of this experiment, an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) assay with accuracy and simplicity was optimized and fully validated for the simultaneous quantitative determination of almonertinib and its metabolite HAS-719, and drug-drug interactions (DDI) between almonertinib and nicardipine in vivo and in vitro was researched., Materials and Methods: Detection of analytes was achieved by UPLC-MS/MS coupled with multiple reaction monitoring (MRM) in the positive ion mode with ion transitions of m/z 526.01 → 72.04 for almonertinib, m/z 512.18 → 455.08 for HAS-719 and m/z 447.16 → 128.11 for IS, respectively., Results: There was favourable linearity in the 0.5-200 ng/mL calibration range for almonertinib and 0.5-100 ng/mL for HAS-719. The lower limit of quantification (LLOQ) for both analytes was 0.5 ng/mL. The precision, accuracy, stability, matrix effect and extraction recovery required for methodological validation were consistent with the requirements of FDA guideline. Then, the UPLC-MS/MS assay was employed successfully on the interactions of almonertinib and nicardipine in vivo and in vitro . The half-maximal inhibitory concentration (IC 50 ) was 1.19 μM in rat liver microsomes (RLM), where nicardipine inhibited the metabolism of almonertinib with a mixed inhibitory mechanism. In pharmacokinetic experiments of rats, it was observed that nicardipine could significantly alter the pharmacokinetic profiles of almonertinib, including AUC (0-∞), AUC (0-t) and C max , but had no effect on the metabolism of HAS-719., Conclusion: According to the findings, it was indicated that nicardipine could inhibit the metabolism of almonertinib in vitro and in vivo .

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening lung diseases with high mortality rates, predominantly attributable to acute and severe pulmonary inflammation. Lomerizine (LMZ) is a calcium channel blocker previously used in preventing and treating migraine. Here, we found that LMZ inhibited inflammatory responses and lung pathological injury by reducing pulmonary edema, neutrophil infiltration and pro-inflammatory cytokine production in lipopolysaccharide (LPS)-induced ALI mice. In vitro experiments, upon treating with LMZ, the expression of interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α was attenuated in macrophages. The phosphorylation of p38 MAPK, ERK1/2, JNK, and NF-κB p65 was inhibited after LMZ treatment. Furthermore, LPS-induced Ca 2+ influx was reduced by treating with LMZ, which correlated with inhibition of pro-inflammatory cytokine production. And L-type Ca 2+ channel agonist Bay K8644 (BK) could restore cytokine generation. In conclusion, our study demonstrated that LMZ alleviates LPS-induced ALI and is a potential agent for treating ALI/ARDS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Song, Gou, Gao, Chen, Zhang, Zhao, Qian, Xu and Shen.)

Paraquat is a highly effective contact herbicide that is marketed worldwide as a fantastical, non-selective compound for broadleaf weed control. As compared to most pesticides, paraquat is extremely toxic to humans and the lack of strategies to manage paraquat poisoning has resulted in high fatality rates. The rats were randomly divided into acute paraquat poisoning group and control group. The paraquat group rats were given 36 mg/kg paraquat by intragastric administration. The influence of acute paraquat poisoning on the activities of CYP450 isoforms CYP2B6, CYP1A2, CYP2C9, CYP2D6, CYP3A4 and CYP2C19 were evaluated by cocktail method, they were responded by the changes of pharmacokinetic parameters of bupropion, phenacetin, tolbutamide, metoprolol, midazolam and omeprazole. The six probe drugs were given to rats through intragastric administration, and the plasma concentrations were determined by UPLC-MS/MS. In the results of paraquat group compared to control group, there was statistical pharmacokinetic difference for bupropion, tolbutamide, metoprolol, midazolam and omeprazole. Acute paraquat poisoning may induce the activities of CYP2C19, and inhibit of CYP2B6, CYP2C9, CYP2D6 and CYP3A4 in rats. This may give advising for reasonable drug use after acute paraquat poisoning.

Indocyanine Green is widely used in medical diagnosis and to evaluate liver function and other regional blood flows in clinical application or animal experiments. In this work, a sensitive and selective ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for determination of Indocyanine Green in rat plasma was developed and validated. After addition of rutin as an internal standard (IS), protein precipitation by acetonitrile-methanol (9:1, v/v) was used to prepare samples. Chromatographic separation was achieved on a UPLC BEH C18 column (2.1 mm × 100 mm, 1.7 μm) with 0.1% formic acid and acetonitrile as the mobile phase with gradient elution. An electrospray ionization source was applied and operated in positive ion mode; multiple reactions monitoring (MRM) mode was used for quantification using target fragment ions m/z 753.4→330.2 for Indocyanine Green, and m/z 611.1→303.1 for IS. Calibration plots were linear throughout the range 20-5000 ng/mL for Indocyanine Green in rat plasma. Mean recoveries of Indocyanine Green in rat plasma ranged from 79.5% to 85.4%. RSD of intra-day and inter-day precision were both < 12%. The accuracy of the method was between 95.9% and 113.9%. The method was successfully applied to pharmacokinetic study of Indocyanine Green after intravenous administration.