Alpha-1-acid glycoprotein (AGP, also known as AAG or orosomucoid) is an important plasma protein involved in the binding and transport of many drugs, especially basic compounds. AGP has some unique ...drug-binding properties that differ from those of albumin. For example, the plasma concentration of AGP is relatively low and there is only one drug-binding site in each AGP molecule. Thus, binding to AGP is saturable and displaceable. This could have potential implications for drug-drug interactions or toxicological consequences. Furthermore, AGP is an acute phase protein and the concentration of AGP in plasma can significantly increase in various diseases (such as cancer and inflammatory diseases) or following trauma (burns, surgery). Changes in AGP concentration could potentially alter the free fraction of drugs in plasma or at their target sites and eventually affect their pharmacokinetic disposition and pharmacological action. Given that an increasing number of drugs have been shown to bind preferrentially to AGP, a better understanding of this unique interaction may provide great benefit for drug discovery and development. In this review, we will focus on the effect of altered AGP binding on the pharmacokinetics and pharmacodynamics (PK/PD) of drugs, as well as the species differences in AGP binding.
The water tree is one of the key factors leading to the insulation property deterioration in cross-linked polyethylene (XLPE) cables. An accelerated ageing experiment has been performed to produce ...water trees with the purpose of ageing the full-size XLPE cable under the high-frequency electric field. Based on Polarization and Depolarization Current (PDC) method, the diagnostic tests are employed to evaluate the ageing extent of the cable subjected to water tree at different ageing time. Results show that the average length of water trees is proportional to the ageing time, and thus the experiment is effective to accelerate the growth of water trees. Furthermore, such various diagnostic indicators as the I*t~lnt curves, the loss factor at different frequency, have their rules to assess the ageing condition of the cable with the duration of ageing time. Therefore, information obtained from PDC current can be used for determining the ageing extent of the cables.
The purpose of this study was to determine the effects of different concentrations of ligustrazine, an extract from Chinese herb, on ketamine requirement for hypnosis and analgesia in mice. In the ...hypnotic response study, mice were randomly allocated to receive saline or ligustrazine at 10, 20, 40, 80 or 160 mg·kg−1 by intraperitoneal injection. Ketamine was administrated 15 min after ligustrazine injection. The hypnotic response was determined by assessing loss of the righting reflex (LORR) after ketamine injection. The dose of ketamine was determined by modified Dixon’s up-and-down method in each group. In the analgesia study, different doses of ligustrazine were administrated 15 min before 50 mg·kg−1 ketamine injection. The analgesia effects (pain threshold) were determined by heat radiation-induced tail-flick latency and evaluated before ligustrazine administration or 5, 15, 30 and 60 min after ketamine administration. The ED50 95% confidence interval (CI) for hypnosis induced by ketamine was 54.1 (44.8, 65.3) mg·kg−1. Ligustrazine dose-dependently decreased the ED50 for ketamine to induce hypnosis, which was 31.6 (26.2, 38.1) mg·kg−1 with the addition of 80 mg·kg−1 ligustrazine and 27.7 (22.6, 33.7) mg·kg−1 with the addition of 160 mg·kg−1 ligustrazine, respectively (p<0.05). Ligustrazine at 160 mg·kg−1 also increased pain threshold in the presence of ketamine. Ligustrazine enhanced the hypnotic effect of ketamine in a dose-dependent manner. Ligustrazine at a large dose also increased the analgesic effect of ketamine.
This article discusses the main structure of HV cables as well as the characteristics of buffer layers and detection of ablation defects. To effectively detect ablation defects in the buffer layer, ...two approaches, terahertz time-domain measurements and commercial computed tomography (CT), were used in the laboratory to evaluate samples of cable with these defects and compare different preset conditions for detecting defects. The test results showed that the terahertz time domain measurement method was more sensitive than CT to moisture intrusion into the cable, but terahertz wave energy was reflected on the surface of the aluminum sheath of the cable and could not penetrate the sheath, thus, it was difficult to use this method to detect internal defects. The commercial CT method used X-rays to penetrate the aluminum sheath, and it could effectively obtain data for the three-dimensional reconstruction of each layer of material, other than the copper core. The structure of the cable was mapped through three-dimensional reconstruction using VGstudio Max software, and the three-dimensional map and gray value analysis were combined. The results confirmed that defects with different densities in the buffer layer could be detected by commercial CT. Thus, commercial CT detection methods provide an effective solution for identifying hidden defects in cables and have profound practical significance for the development of methods to detect defects when cables are in use.
General anesthetics interfere with dendritic development and synaptogenesis, resulting in cognitive impairment in the developing animals. RhoA signal pathway plays important roles in dendritic ...development by regulating cytoskeleton protein such as tubulin and actin. However, it’s not clear whether RhoA pathway is involved in inhaled general anesthetics sevoflurane-induced synaptic development abnormalities and long-term cognitive dysfunction. Rats at postnatal day 7 (PND7) were injected intraperitoneally with RhoA pathway inhibitor Y27632 or saline 20 min before exposed to 2.8% sevoflurane for 4 h. The apoptosis-related proteins and RhoA/CRMP2 pathway proteins in the hippocampus were measured 6 h after sevoflurane exposure. Cognitive functions were evaluated by the open field test on PND25 rats and contextual fear conditioning test on PND32-33 rats. The dendritic morphology and density of dendritic spines in the pyramidal neurons of hippocampus were determined by Golgi staining and the synaptic plasticity-related proteins were also measured on PND33 rats. Long term potentiation (LTP) from hippocampal slices was recorded on PND34-37 rats. Sevoflurane induced caspase-3 activation, decreased the ratio of Bcl-2/Bax and increased TUNEL-positive neurons in hippocampus of PND7 rats, which were attenuated by inhibition of RhoA. However, sevoflurane had no significant effects on activity of RhoA/CRMP2 pathway. Sevoflurane disturbed dendritic morphogenesis, reduced the number of dendritic spines, decreased proteins expression of PSD-95, drebrin and synaptophysin, inhibited LTP in hippocampal slices and impaired memory ability in the adolescent rats, while inhibition of RhoA activity did not rescue the changes above induced by sevoflurane. RhoA signal pathway did not participate in sevoflurane-induced dendritic and synaptic development abnormalities and cognitive dysfunction in developing rats.
This study aimed to evaluate the prevalence of human papillomavirus (HPV) infection and presence of licensed HPV vaccine genotypes among patients with genital warts in Foshan, China from 2015 to ...2022, to provide useful references for the detection, prevention and control of genital warts in Foshan.
The present study retrospectively analyzed the HPV detection rates in patients with genital warts. A total of 1,625 patients were seen at the Second People's Hospital of Foshan, Guangdong Province, China, from 2015 to 2022. Samples were collected from various lesions and genotyped for 21 genotypes of HPV by infusion hybridization. The classification principle of HPV genotypes in this study: (1) Based on the relationship between HPV and carcinogenicity; (2) Based on the number of HPV genotypes infected; (3) Based on the HPV genotypes of licensed HPV vaccines.
The detection rate of any HPV in patients with genital warts was 80.37% (1,306/1,625). The detection rates of HPV for low-risk infection, co-infection and high-risk infection were 49.48% (804/1,625), 24.92% (405/1,625) and 5.97% (97/1,625), respectively. Single infection was the predominant type (51.94%, 844/1625). HPV-6 and HPV-11 were the predominant types of single infection; HPV-6 and HPV-52 were the predominant types of paired combinations of multiple infection. 82.22% (1,336/1,625) of the cases had an age distribution of ≤ 24, 25-34, and 35-44. The distribution of some HPV genotypes had age specificity, annual specificity and gender specificity. The genotype detection rates of 2v, 4v and 9v showed a decreasing trend with ages (all
< 0.05). The genotype detection rates of 4v and 9v showed a decreasing trend over the 8-year period (both
< 0.05). The genotype detection rates of 4v and 9v in the male group were higher than those in the female group (both
< 0.05). The genotype detection rate of 9v was significantly higher than that of 2v and 4v in the female group (both
< 0.05).
Our study demonstrated that low-risk infection and single infection were the main types of HPV infection in patients with genital warts, mainly among young patients. Our study provides epidemiological data for the detection, prevention and control of genital warts in China.
Realizing the value of ecological products is the key point to realize the integration of the dual goals of ecological civilization construction and economic development in China, and is a powerful ...grip for promoting industrial transformation and upgrading and implementing high-quality development tactics. In the value realization mechanism of ecological products, it is most critical to coordinate the relationship among farmers, ecological product developers and the government. Based on the systematic analysis of the game relationship among three subjects, this study constructs a game model and uses evolutionary game and numerical simulation methods to analyze the model, obtains the conditions of pure strategy selection of three subjects and the evolutionary law of mixed strategy probability combinations. This study confirms the crowding-out effect and the effectiveness of combining incentive policies such as government subsidies, fines, and required loss compensation, providing a decision reference for building an eco-product value realization system from the perspective of organizational relationship governance and policy mechanism construction.
Analogues structurally related to anaplastic lymphoma kinase (ALK) inhibitor 1 were optimized for metabolic stability. The results from this endeavor not only led to improved metabolic stability, ...pharmacokinetic parameters, and in vitro activity against clinically derived resistance mutations but also led to the incorporation of activity for focal adhesion kinase (FAK). FAK activation, via amplification and/or overexpression, is characteristic of multiple invasive solid tumors and metastasis. The discovery of the clinical stage, dual FAK/ALK inhibitor 27b, including details surrounding SAR, in vitro/in vivo pharmacology, and pharmacokinetics, is reported herein.
This article uses a distributed optical fiber temperature measurement system (DTS, Distributed Temperature Sensing) to fix the temperature measurement optical fiber on the surface of the power cable, ...collect the real-time operating temperature of the power cable, conduct the ampacity test, and analyze the cable laying method and depth, soil temperature, Soil thermal resistance coefficient, cable spacing and irradiation strength and other test conditions, the impact on the current carrying capacity of power cables. According to the real-time monitoring temperature of the cable, the alarm can be made when the cable temperature is too high or the temperature rise speed is too fast. And on the basis of determining the working temperature and load operating conditions of the cable conductor core, dynamically calculate the current carrying capacity of the cable, which is conducive to improving the performance of the power cable and increasing the load capacity of the power cable.
In recent years, with the development of economy and the rapid growth of electricity consumption, the number and length of medium and high voltage cable lines have increased rapidly. As an important ...part of the power transmission and distribution network, to ensure the safe and reliable operation of cable lines and reduce unplanned power outages. Based on the field test and analysis of the abnormal ground current of the 110kV Luoyong line, it is found that the cross interconnection system has many defects such as phase sequence error and identification plate indication error. It is recommended that the cable cross interconnection system carry out a segmented insulation resistance test to exclude cables. Hidden dangers such as damage to the protective layer and damage to the protective layer.