Diabetic complications-coronary atherosclerosis is closely related to the increased reactive oxygen species (ROS) induced by hyperglycemia. ROS are reported to induce the abnormal proliferation of ...vascular smooth muscle cells (VSMCs) under high glucose conditions. Leaf and seed extracts from Moringa oleifera are found to exhibit antioxidant activity. However, few studies are evaluating the antioxidant activities of chemical compounds isolated from the M. oleifera especially in cardiovascular field.
The aim of this study is to explore the antioxidative effect during hyperglycemia of niazirin from M. oleifera.
A cell model was applied.
After the taking the in vitro antioxidant experiment including ferric reducing antioxidant power (FRAP), 2,2′-azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) assay and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. Cell viability was carried out using high glucose-induced VSMCs model. ROS production was tested by 2′,7′-dichlorofluorescein diacetate (DCF-DA) assay. The protein kinase C zeta (PKCζ) and NADPH oxidase 4 (Nox 4) expression in vitro and in vivo were measured by western blot analysis.
Niazirin showed good free radical scavenging activity. Niazirin significantly attenuated the proliferation of high glucose-induced VSMCs. Furthermore, it could decrease the ROS and malondialdehyde (MDA) productions, while increased total antioxidant capacity (T-AOC), superoxide dismutase (SOD) as well as glutathione peroxidase (GPx) levels in high glucose-induced VSMCs and streptozotocin-induced mice. In addition, niazirin could eliminate the high glucose-induced PKCζ activation, indicated by Thr410 phosphorylation and inhibition of the Nox4 protein expression in vitro and in vivo.
Niazirin from M. oleifera exhibited notably antioxidant activities and could be utilized as a potential natural antioxidant in preventing diabetic atherosclerosis.
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The rapid and accurate identification of rail surface defects is critical to the maintenance and operational safety of the rail. For the problems of large-scale differences in rail surface defects ...and many small-scale defects, this paper proposes a rail surface defect detection algorithm, RSDNet (Rail Surface Defect Detection Net), with YOLOv8n as the baseline model. Firstly, the CDConv (Cascade Dilated Convolution) module is designed to realize multi-scale convolution by cascading the cavity convolution with different cavity rates. The CDConv is embedded into the backbone network to gather earlier defect local characteristics and contextual data. Secondly, the feature fusion method of Head is optimized based on BiFPN (Bi-directional Feature Pyramids Network) to fuse more layers of feature information and improve the utilization of original information. Finally, the EMA (Efficient Multi-Scale Attention) attention module is introduced to enhance the network’s attention to defect information. The experiments are conducted on the RSDDs dataset, and the experimental results show that the RSDNet algorithm achieves a mAP of 95.4% for rail surface defect detection, which is 4.6% higher than the original YOLOv8n. This study provides an effective technical means for rail surface defect detection that has certain engineering applications.
Using multiple isotopes including 87Sr/86Sr in water, δ34SSO4, δ18OSO4, δ18OH2O and δ2HH2O, δ13CDIC and 14CDIC in water, we have investigated the origin and evolution of sulfate concentration ...(1472 mg/L) in the Tangquan Karst geothermal system in Nanjing, China. The sulfate has been found to be mainly derived from dissolution of gypsum and other evaporite minerals occurring in the carbonate reservoir. The dissolution of evaporite minerals is relatively easier than carbonate at elevated temperatures. We confirmed this differentiated dissolution process by reverse hydrogeochemical simulation using the PHREEQC code. The origin of sulfate is supported by 87Sr/86Sr isotope ratio (0.7088–0.709) with a typical marine signature. We further constrained the origin of sulfate with δ34S in aqueous SO4 (27.6‰–34.2‰) and δ18O in aqueous SO4 (14.3‰–18.4‰). Such sulfate-rich geothermal water usually occurs in open karst geothermal systems, favorable for Spa therapy in many places of the world.
•The source of sulfate in sulfate-rich water is identified to be evaporite dissolution, using the sulfur and oxygen isotope in sulfate and strontium isotope ratio as constraints.•The chemical thermodynamic simulation results by SOLVEQ show that the reason for the different hydrochemical types of cold water and geothermal water is due to the solubility difference between carbonate and gypsum minerals at different temperatures.
This paper proposes a modified iterative learning control (MILC) periodical feedback-feedforward algorithm to reduce the vibration of a rotor caused by coupled unbalance and parallel misalignment. ...The control of the vibration of the rotor is provided by an active magnetic actuator (AMA). The iterative gain of the MILC algorithm here presented has a self-adjustment based on the magnitude of the vibration. Notch filters are adopted to extract the synchronous (1 ×
Ω
) and twice rotational frequency (2 ×
Ω
) components of the rotor vibration. Both the notch frequency of the filter and the size of feedforward storage used during the experiment have a real-time adaptation to the rotational speed. The method proposed in this work can provide effective suppression of the vibration of the rotor in case of sudden changes or fluctuations of the rotor speed. Simulations and experiments using the MILC algorithm proposed here are carried out and give evidence to the feasibility and robustness of the technique proposed.
Acetaminophen (APAP)-induced liver injury (AILI) is the leading cause of acute liver failure in the United States, but its impact on metabolism, therapeutic efficacy, and adverse drug reactions ...(ADRs) of co- and/or subsequent administered drugs are not fully investigated. The current work explored this field with a focus on the AILI-mediated alterations of cytochrome P450-mediated drug metabolism. Various levels of liver injury were induced in mice by treatment with APAP at 0, 200, 400, and 600 mg/kg. Severity of liver damage was determined at 24, 48, 72, and 96 hours by plasma levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), microRNA miR122, and tissue staining. The expression and activities of CYP3A11, 1A2, 2B10, 2C29, and 2E1 were measured. Sedation efficacy and ADRs of midazolam, a CYP3A substrate, were monitored after APAP treatment. ALT, AST, and miR122 increased at 24 hours after APAP treatment with all APAP doses, whereas only groups treated with 200 and 400 mg/kg recovered back to normal levels at 72 and 96 hours. The expression and activity of the cytochromes P450 significantly decreased at 24 hours with all APAP doses but only recovered back to normal at 72 and 96 hours with 200 and 400, but not 600, mg/kg of APAP. The alterations of cytochrome P450 activities resulted in altered sedation efficacy and ADRs of midazolam, which were corrected by dose justification of midazolam. Overall, this work illustrated a low cytochrome P450 expression window after AILI, which can decrease drug metabolism and negatively impact drug efficacy and ADRs. SIGNIFICANCE STATEMENT: The data generated in the mouse model demonstrated that expression and activities of cytochrome P450 enzymes and correlated drug efficacy and ADRs are altered during the time course of liver repair and regeneration after liver is injured by treatment with APAP. Dose justifications based on predicted changes of cytochrome P450 activities can achieve desired therapeutic efficacy and avoid ADRs. The generated data provide fundamental knowledge for translational research to drug treatment for patients during liver recovery and regeneration who have experienced AILI.
Cytochrome P450 (P450) enzymes are responsible for metabolizing drugs. Expression of P450s can directly affect drug metabolism, resulting in various outcomes in therapeutic efficacy and adverse ...effects. Several nuclear receptors are transcription factors that can regulate expression of P450s at both basal and drug-induced levels. Some long noncoding RNAs (lncRNAs) near a transcription factor are found to participate in the regulatory functions of the transcription factors. The aim of this study is to determine whether there is a transcriptional regulatory network containing nuclear receptors and lncRNAs controlling both basal and drug-induced expression of P450s in HepaRG cells. Small interfering RNAs or small hairpin RNAs were applied to knock down four nuclear receptors hepatocyte nuclear factor 1
(HNF1
), hepatocyte nuclear factor 4
(HNF4
), pregnane X receptor (PXR), and constitutive androstane receptor (CAR) as well as two lncRNAs HNF1
antisense RNA 1 (HNF1
-AS1) and HNF4
antisense RNA 1 (HNF4
-AS1) in HepaRG cells with or without treatment of phenobarbital or rifampicin. Expression of eight P450 enzymes was examined in both basal and drug-induced levels. CAR and PXR mainly regulated expression of specific P450s. HNF1
and HNF4
affected expression of a wide range of P450s as well as other transcription factors. HNF1
and HNF4
controlled the expression of their neighborhood lncRNAs, HNF1
-AS1 and HNF4
-AS1, respectively. HNF1
-AS1 and HNF4
-AS1 was also involved in the regulation of P450s and transcription factors in diverse manners. Altogether, our study concludes that a transcription regulatory network containing the nuclear receptors and lncRNAs controls both basal and drug-induced expression of P450s in HepaRG cells.
Background
The successful application of Fish plasma model (FPM) will greatly simplify the risk assessment of drugs. At present, the FPM has been applied to the risk assessment of several human drugs ...with high hydrophobicity. However, its applicability to a wide variety of compounds needs to be tested. Field work about distribution characteristics of endocrine disrupting compounds (EDCs) in water and in fish plasma plays a key role in promoting the successful application of FPM. However, there are few reports on the distribution of EDCs in fish, especially in wild fish plasma.
Results
The distribution of 31 EDCs, including seven estrogens, eight androgens, six progesterones, five glucocorticoids, and five industrial compounds, in water and plasma of five categories of wild fishes in Taihu Lake was studied and the typical FPM was tested by the field data. The detected concentration of most compounds is relatively low (< 10 ng/L), and the industrial compounds are the predominant pollutants with the highest concentration up to 291.7 ng/L (Bisphenol A) in water. In general, glucocorticoids were detected at the highest concentrations in plasma of all kinds of fishes, followed by industrial compounds and estrogens. Except for glucocorticoids (up to 43.61 for Cortisone), the average concentrations of the other four categories of EDCs in fish plasma were generally low (< 10 μg/L). The available measured bioaccumulation factors (BAFs) of 20 kinds of EDCs were in the range of 0 to 5626. The bioaccumulation of EDCs in fish plasma is not only hydrophobicity-dependent, but is also both fish species-specific and compound-dependent. The classical FPM was tested and the results indicated that the good coincides of measured log BAFs and the theoretical log BCFs were only observed for limited EDCs (7 out of 20). The present available FPM generally underestimated the Log BAFs of most hydrophilic EDCs (log Kow < 3.87, 11 out of 20) whereas overestimated the Log BAFs of several high hydrophobic EDCs (Log Kow > 3.87) in fish plasma.
Conclusion
Although the present FPM is barely satisfactory, it is still promising for predicting the accumulation of EDCs in fish plasma and for further environmental risk assessment.
Ionic liquids (ILs) have been intensively studied as one promising candidate for an electrolyte in lithium ion batteries (LIBs). Structural analysis of interfaces between an IL-based electrolyte and ...a LIB electrode would provide beneficial information for improving LIBs. In this study, we investigated the interfacial structures between an IL, 1-ethyl-3-methylimidazolium bis (trifluoromethylsulfonyl)imide (EMI-TFSI), and a spinel-type lithium titanate (Li4Ti5O12) electrode in the presence and absence of Li-salt by frequency modulation atomic force microscopy (FM-AFM) utilizing a quartz tuning fork sensor. Solvation structures on the interface were successfully visualized by two-dimensional frequency shift mapping. Electrochemical impedance spectroscopy measurement was also performed to measure the rate of Li+-ion insertion/extraction on the interface and we found that the interfacial ion-transfer may prevent the formation of layered solvation structure.
Tip-enhanced Raman spectroscopy (TERS) is a nano-optical approach to extract spatially resolved chemical information with nanometer precision. However, in the case of direct-illumination TERS, which ...is often employed in commercial TERS instruments, strong fluorescence or far-field Raman signals from the illuminated areas may be excited as a background. They may overwhelm the near-field TERS signal and dramatically decrease the near-field to far-field signal contrast of TERS spectra. It is still challenging for TERS to study the surface of fluorescent materials or a bulk sample that cannot be placed on an Au/Ag substrate. In this study, we developed an indirect-illumination TERS probe that allows a laser to be focused on a flat interface of a thin-film waveguide located far away from the region generating the TERS signal. Surface plasmon polaritons are generated stably on the waveguide and eventually accumulated at the tip apex, thereby producing a spatially and energetically confined hotspot to ensure stable and high-resolution TERS measurements with a low background. With this thin-film waveguide probe, TERS spectra with obvious contrast from a diamond plate can be acquired. Furthermore, the TERS technique based on this probe exhibits excellent TERS signal stability, a long lifetime, and good spatial resolution. This technique is expected to have commercial potential and enable further popularization and development of TERS technology as a powerful analytical method.
The fish plasma model (FPM) facilitated the environmental risk assessment of human drugs by using existing data on human therapeutic plasma concentrations (HTPCs) and predicted fish plasma ...concentrations (FPCs). However, studies on carbamazepine (CMZ) with both the mode of action (MOA) based biological effects at molecular level (such as neurotransmitter and gene level) and measured FPCs are lacking. Bioconcentration of CMZ in adult zebrafish demonstrated that the FPM underestimated the bioconcentration factors (BCFs) in plasma at environmental CMZ exposure concentrations (1–100 μg/L). CMZ significantly increased Glu and GABA, decreased ACh and AChE as well as inhibited the transcription levels of gabra1, grin1b, grin2b, gad1b, and abat when the actual FPCs were in the ranges of 1/1000 HTPC to HTPC. It is the first read-across study of CMZ integrating MOA-based biological effects at molecular level and FPCs. This study facilitates model performance against a range of different drug classes.
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•The fish plasma model underestimated CMZ concentration at environmental levels•CMZ increased Glu and GABA, and decreased the levels of ACh and AChE•CMZ inhibited the transcription levels of gabra1, grin1b, grin2b, gad1b, and abat•CMZ showed a human-like biological effect on zebrafish at therapeutic plasma levels
Biological sciences; Biochemistry; Physiology; Animal physiology
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