Plasma Components Research Articles

Applicability of Electron-Beam and Hybrid Plasmas for Polyethylene Terephthalate Processing to Obtain Hydrophilic and Biocompatible Surfaces.

The applicability of beam-plasma chemical reactors generating cold hybrid plasma for the production of noncytotoxic polymeric surfaces with high hydrophilicity and good biocompatibility with human fibroblast culture and human red blood cells was studied. Oxygen hybrid plasma was excited by the joint action of a continuous scanning electron beam and a capacity-coupled RF-gas discharge. Experiments showed that hybrid plasma treatment caused polar oxygen-containing functional group formation in the surface layer of poly (ethylene terephthalate) films. No thermal or radiative damage in tested polymer samples was found. The plasma-modified polymers turned out to be noncytotoxic and revealed good biocompatibility with human fibroblasts BJ-5ta as well as lower hemolytic activity than untreated poly (ethylene terephthalate). Experiments also demonstrated that no phenomena caused by the electrostatic charging of polymers occur in hybrid plasma because the electron beam component of hybrid plasma eliminates the item charge when it is treated. The electron beam can effectively control the reaction volume geometry as well as the fluxes of active plasma particles falling on the item surface. This provides new approaches to the production of abruptly structured patterns or smooth gradients of functionalities on a plane and 3D polymeric items of complicated geometry.

Western diet consumption by host vertebrate promotes altered gene expression on Aedes aegypti reducing its lifespan and increasing fertility following blood feeding

BackgroundThe high prevalence of metabolic syndrome in low- and middle-income countries is linked to an increase in Western diet consumption, characterized by a high intake of processed foods, which impacts the levels of blood sugar and lipids, hormones, and cytokines. Hematophagous insect vectors, such as the yellow fever mosquito Aedes aegypti, rely on blood meals for reproduction and development and are therefore exposed to the components of blood plasma. However, the impact of the alteration of blood composition due to malnutrition and metabolic conditions on mosquito biology remains understudied.MethodsIn this study, we investigated the impact of whole-blood alterations resulting from a Western-type diet on the biology of Ae. aegypti. We kept C57Bl6/J mice on a high-fat, high-sucrose (HFHS) diet for 20 weeks and followed biological parameters, including plasma insulin and lipid levels, insulin tolerance, and weight gain, to validate the development of metabolic syndrome. We further allowed Ae. aegypti mosquitoes to feed on mice and tracked how altered host blood composition modulated parameters of vector capacity.ResultsOur findings identified that HFHS-fed mice resulted in reduced mosquito longevity and increased fecundity upon mosquito feeding, which correlated with alteration in the gene expression profile of nutrient sensing and physiological and metabolic markers as studied up to several days after blood ingestion.ConclusionsOur study provides new insights into the overall effect of alterations of blood components on mosquito biology and its implications for the transmission of infectious diseases in conditions where the frequency of Western diet-induced metabolic syndromes is becoming more frequent. These findings highlight the importance of addressing metabolic health to further understand the spread of mosquito-borne illnesses in endemic areas.Graphical

Integrated ultra-high-performance liquid chromatography coupled with quadrupole-orbitrap mass spectrometry-based components analysis and network pharmacology strategy of Gancao Xiexin Decoction in treating gastric ulcer.

Gancao Xiexin Decoction (GCXXD) is a traditional Chinese decoction that is often used in treating gastric ulcers. However, the substance basis and mechanism of action remain unclear. In this study, in vivo and in vitro components of GCXXD were analyzed by ultra-high-performance liquid chromatography coupled with quadrupole-orbitrap mass spectrometry. The compound Discover platform was used to ultimately enable rapid identification of compounds. Acquire X intelligent data acquisition technology software was innovatively adopted. In the process of collecting drug-containing plasma, all components detected in blank plasma samples were excluded to eliminate the interference and influence of endogenous components in plasma, making the analysis results more accurate and reliable. At the same time, the possibility of selecting precursor parent ions with low concentration levels within the chromatographic peak can be increased, improving the coverage and integrality of the detection of components in vivo. Also, the targeted network pharmacology strategy combined with molecular docking was established to explore the mechanism of GCXXD in treating gastric ulcers. As a result, 113 components were identified, 41 of which could enter the bloodstream and exert therapeutic effects in vivo. The main effective components are glycyrrhizic acid, 6-gingerol, jatrorrhizine, wogonin, palmatine, and liquiritigenin, main targets in vivo were related to ALB, IL6, and VEGF, which play an important role in anti-inflammatory and promoting angiogenesis. In summary, this study adopted a comprehensive analysis strategy to reveal the pharmacodynamic material basis and mechanism of GCXXD against gastric ulcers, providing a scientific basis for its clinical application.

Review of haemovigilance at the Rabat Regional Blood Transfusion Centre in Morocco (2017-2021).

blood transfusion remains an essential therapeutic intervention, but the occurrence of transfusion reactions makes its administration even more complex. Vigilant reporting of such reactions by recipients of blood products is essential for effective haemovigilance. This study aimed to determine the frequency and nature of transfusion reactions. conducted over five years (2017-2021) at the Haemovigilance Department of the Rabat Regional Blood Transfusion Centre, this retrospective study exploited incident forms notified by health establishments and data from the regional blood transfusion centre's computer system. from 1 January 2017 and 31 December 2021, the Rabat Regional Blood Transfusion Centre distributed 435,651 labile blood products to various healthcare establishments, which reported 191 transfusion reactions involving 191 patients. The median age of the patients was 44.3 years, with an overall cumulative incidence of transfusion reactions of 0.44 per 1000 labile blood products delivered. The predominant reactions were non-haemolytic febrile and allergic reactions, accounting for 41.36% and 35.60% respectively. Grade 1 reactions accounted for 87% of all reactions recorded. During the study period, three deaths were recorded, with ABO incompatibility and transfusion-related acute lung injury (TRALI) accounting for two and one case respectively. Transfusion reactions involving erythrocyte components were significantly more frequent than those involving platelet and plasma components. this study revealed a relatively low incidence of transfusion reactions (0.44%), dominated by non-haemolytic febrile and allergic reactions. Several levels of failure were identified, in particular under-reporting of reactions and inadequate training in transfusion practices and haemovigilance, as well as the need for an effective electronic transfusion reaction reporting system to facilitate reporting and identification of underlying problems and risk factors to improve the quality of transfusion care provided to patients.

Relationship between seminal plasma composition and sperm quality parameters of the catfish Pseudoplatystoma reticulatum

Abstract Sperm quality is a fundamental parameter for the effective reproduction of fish in captivity and the development of reproductive techniques, such as semen cryopreservation. This study aimed to determine the composition of the seminal plasma of Pseudoplatystoma reticulatum and analyze the relationships between plasma components and sperm characteristics. Nine males were induced to spermiation with carp pituitary extract in the reproductive period of the species (November and December/2019). Semen characteristics were evaluated: subjective sperm motility, motility, duration, released sperm volume, sperm concentration, pH, osmolality, and seminal plasma composition, including levels of calcium, chloride, sodium, magnesium, potassium, glucose, fructosamine, triglycerides, and total protein. To determine the relationship between seminal plasma components and sperm motility parameters, a principal component analysis (PCA) was performed. The seminal plasma of P. reticulatum is composed mainly of the Na+ ion and organic components such as protein and glucose. Through PCA, it was observed that sperm motility had a strong positive correlation with motility time, sperm concentration, and total protein and a negative correlation with osmolality and fructosamine.

Method for prediction and control by uncertain microsatellite magnetic cleanliness based on calculation and compensation magnetic field spatial harmonics

Aim. Development of method for prediction and control the microsatellite magnetic cleanliness taking into account the uncertainties of the magnetic characteristics of the microsatellite, based on calculation the magnetic field spatial spherical harmonics in the area of the onboard magnetometer installation and using compensating multipoles. Methodology. Spatial spherical harmonics of microsatellite magnetic field in the area of the onboard magnetometer installation calculated as solution of nonlinear minimax optimization problem based on near field measurements for prediction far spacecraft magnetic field magnitude. Nonlinear objective function calculated as the weighted sum of squared residuals between the measured and predicted magnetic field. Values of the compensating dipoles, quadrupoles and octupoles and coordinates of them placement inside the spaceship for compensation of the dipoles, quadrupoles and octupoles components of the microsatellite initial magnetic field also calculated as solution of nonlinear minimax optimization problem. Both solutions of this nonlinear minimax optimization problems calculated based on particle swarm nonlinear optimization algorithms. Results. Results of prediction spacecraft far magnetic field magnitude based on spacecraft spatial spherical harmonics of the magnetic field using near field measurements and compensation of the dipoles, quadrupoles and octupoles components of the initial magnetic field with consideration of spacecraft magnetic characteristics uncertainty for ensuring the microsatellite magnetic cleanliness. Originality. The method for prediction and control by spacecraft magnetic cleanliness based on calculation spatial spherical harmonics of the magnetic field in the area of the onboard magnetometer installation using compensation of the dipoles, quadrupoles and octupoles components of the initial magnetic field with consideration of magnetic characteristics uncertainty is developed. Practical value. The important practical problem of ensuring the magnetic cleanliness of the «Sich-2» microsatellite family based on the spatial spherical harmonics of the magnetic field model using the compensation of the dipole, quadrupole and octupole components of the output magnetic field of the sensor for the kinetic parameters of the neutral component of the space plasma at the point of installation of the on-board magnetometer LEMI-016 by setting the compensating dipole, quadrupole and octupole with consideration of spacecraft magnetic characteristics uncertainty solved.

Anti-thermal Quenching in Blue Phosphor Ba3YAl2O7.5: Tm3+

Blue-emitting phosphors are essential components of the color plasma display panel (PDP), white light-emitting diodes (W-LEDs), and liquid crystal display (LCD) backlights. However, the thermal quenching effect of the phosphor is a serious problem in practice. In this work, a new kind of blue phosphor Ba3YAl2O7.5: xTm3+ was prepared and the luminescent characteristic and thermal stability were studied. Under 358 nm excitation, the phosphors produced a blue emission peak centered at 461 nm, which is due to the transition of Tm3+ from level 1D2 to 3F4. Moreover, the optimal sample Ba3YAl2O7.5: 0.03Tm3+ shows an anti-thermal quenching effect in which the emission intensity at 210 °C rises to 120 % of that at 30 °C , attributable to the presence of oxygen vacancy defects. The result indicates that the Ba3YAl2O7.5: Tm3+ with excellent thermal stability is a promising blue phosphor for lighting and display fields.

Two fluid dynamics in solar prominences

Aims. Solar prominences contain a significant number of neutral species. The dynamics of the ionised and neutral fluids composing the prominence plasma can be slightly different if the collisional coupling is not strong enough. The differential dynamics can be discerned by tracing line-of-sight velocities using observational techniques. Large-scale velocities can be quantified by measuring the global local and instantaneous displacement of spectral lines by the Doppler effect. Small-scale velocities leave their imprint on the width of spectral lines. In addition, these small-scale velocities can have a thermal (pure stochastic motion) nature or a non-thermal (small-scale unresolved instabilities, high-frequency waves, etc.) origin. For this work, we used one spectral line of ionised and two spectral lines of neutral elements to measure the resolved and unresolved velocities in a prominence with the aim to investigate the possible decoupling of the observed charged and neutral species. Methods. A faint prominence was observed with the German Vacuum Tower Telescope (VTT) on June 17, 2017. Time series consisting of repeated ten-position scans over the prominence were performed while simultaneously recording the intensity spectra of the Ca II IR 854.2 nm, Hα 656.28 nm, and He I D3 587.56 nm lines. The line-of-sight velocities and the Doppler width of the three spectral lines were determined at every spatial position and temporal moment. To make sure all spectral lines were sampling the same plasma volume, we applied selection criteria to identify locations with optically thin plasma. In addition, asymmetric or double-peaked profiles were also excluded for the analysis, since (even in an optically thin regime) they are indicative of the presence of strong velocity gradients or multiple components in the line of sight. Thus, only optically thin, symmetric, single-lobed profiles were retained for this study. As an additional reliability test of the selection criteria, we have also compared our results with optical thickness calculations. Results. After the application of all the selection criteria, only a region close to the prominence border met all requirements. The velocities of the three spectral lines turned out to be very similar over this region, with the ionised Ca II IR showing velocity excursions systematically larger compared to those of the neutral lines of Hα and He I at some moments. The latter was found to be much closer to each other. Most of the velocity differences were below 1 km s−1. The analysis of the Doppler widths indicated that the Ca II IR line shows an excess of unresolved motions. We cannot establish whether these velocities are related to a different temperature of the ions or to unresolved small-scale motions due to any non-thermal mechanism. Conclusions. The dynamics of the ionised and neutral plasma components in the observed prominence were very close to one another. The differences found may indicate that a localised decoupling between ions and neutrals may appear at particular spatial locations or instants of time. Indications of different unresolved motions between those species have also been obtained.

Plasmapheresis as an Adjunctive Section Therapy for Yellow Phosphorus Poisoning: A Case Report

Yellow Phosphorus (YP) poisoning is an infrequent, yet severe medical condition characterised by multi-systemic toxicity. The ingestion or inhalation of YP can lead to gastrointestinal irritation, hepatic injury, and Acute Liver Failure (ALF). Plasmapheresis, a therapeutic intervention involving the removal and replacement of plasma components, is a potential adjunctive treatment for YP poisoning. This case report aims to explore the mechanistic rationale, clinical efficacy, and safety considerations of plasmapheresis in the management of this toxicological emergency. Here, a 16-year-old female reported to the Emergency Department (ED), having consumed 1-2 g of Ratol poison at two different times of the day. She came to the hospital on day 4 post-consumption. On admission, the patient was jaundiced and Arterial Blood Gas (ABG) analysis was suggestive of respiratory alkalosis with hypokalemia. Treatment focused on fluid therapy, vitamin K therapy, and N-Acetyl Cysteine (NAC). She developed angioedema and urticaria with no airway compromise, in response to intravenous NAC. A diagnosis of acute liver injury secondary to YP poisoning was made. Close monitoring of liver function and coagulation parameters, and bleeding complications was done. Plasmapheresis was considered as NAC reinitiating was not feasible due to potential anaphylaxis. The patient responded well to the treatment and was discharged on day 7 of hospitalisation.

Protective effects of Huang-Qi-Ge-Gen decoction against diabetic liver injury through regulating PI3K/AKT/Nrf2 pathway and metabolic profiling

Ethnopharmacological relevanceHuang-Qi-Ge-Gen decoction (HGD) is a traditional Chinese medicine prescription that has been used for centuries to treat “Xiaoke” (the name of diabetes mellitus in ancient China). However, the ameliorating effects of HGD on diabetic liver injury (DLI) and its mechanisms are not yet fully understood. Aim of the studyTo elucidate the ameliorative effect of HGD on DLI and explore its material basis and potential hepatoprotective mechanism. Materials and methodsA diabetic mice model was induced by feeding a high-fat diet and injecting intraperitoneally with streptozotocin (40 mg kg−1) for five days. After the animals were in confirmed diabetic condition, they were given HGD (3 or 12 g kg−1, i. g.) for 14 weeks. The effectiveness of HGD in treating DLI mice was evaluated by monitoring blood glucose and blood lipid levels, liver function, and pathological conditions. Furthermore, UPLC-MS/MS was used to identify the chemical component profile in HGD and absorption components in HGD-treated plasma. Network pharmacology and molecular docking were performed to predict the potential pathway of HGD intervention in DLI. Then, the results of network pharmacology were validated by examining biochemical parameters and using western blotting. Lastly, urine metabolites were analyzed by metabolomics strategy to explore the effect of HGD on the metabolic profile of DLI mice. ResultsHGD exerted therapeutic potential against the disorders of glucose metabolism and lipid metabolism, liver dysfunction, liver steatosis, and fibrosis in a DLI model mice induced by HFD/STZ. A total of 108 chemical components in HGD and 18 absorption components in HGD-treated plasma were preliminarily identified. Network pharmacology and molecular docking results of the absorbed components in plasma indicated PI3K/AKT as a potential pathway for HGD to intervene in DLI mice. Further experiments verified that HGD markedly reduced liver oxidative stress in DLI mice by modulating the PI3K/AKT/Nrf2 signaling pathway. Moreover, 19 differential metabolites between normal and DLI mice were detected in urine, and seven metabolites could be significantly modulated back by HGD. ConclusionsHGD could ameliorate diabetic liver injury by modulating the PI3K/AKT/Nrf2 signaling pathway and urinary metabolic profile.

Ranolazine Quantification in Human Plasma: A QbD-Guided LC-MS Method Development and Validation

The present research outlines a comprehensive and systematic approach for the development and validation of a bioanalytical Liquid chromatography–mass spectrometry (LC-MS) method to quantify ranolazine in human plasma. The study employs principles of quality by design (QbD) to enhance method robustness, precision, and accuracy. The primary goals of this research were to create a reliable LC-MS method for the accurate quantification of ranolazine in human plasma and to validate this approach in accordance with established standards set by regulatory bodies. A secondary objective was to explore the application of QbD principles to optimize method performance. The study resulted in the successful development of an LC-MS method that exhibits exceptional specificity, sensitivity, accuracy, and precision in the quantification of ranolazine in human plasma. Specificity tests revealed no interference from endogenous plasma components. The method demonstrated good sensitivity with limit of quantitation (LoQ) of 5 ng/mL and limit of detection (LoD) of 2 ng/mL. Accuracy, as assessed through recovery studies, showed mean recoveries of 98, 99, and 101% for three different spiked concentrations. Precision, expressed as RSD, was below 5% for both intra-day and inter-day analyses. Linearity studies resulted in a calibration curve with an R² value of 0.9998. By employing QbD principles, the method demonstrated improved robustness, thus minimizing the impact of variability during sample analysis. Robustness experiments revealed minimal effects on precision and accuracy when varying critical parameters. This research not only presents a reliable LC-MS method for ranolazine quantification but also underscores the importance of incorporating QbD principles in bioanalytical method development. The validated method holds significant implications for clinical research, pharmacokinetic studies, and therapeutic drug monitoring. By enhancing the accuracy and robustness of ranolazine quantification, this method contributes to the advancement of pharmaceutical and clinical research, ultimately benefiting patient care and treatment outcomes.

Investigating the Effects of Cold Plasma on Cancer Cell Migration in the Presence of a Static Magnetic Field

Cold plasma is used in a wide range of applications [1]–[3] One of the primary uses of plasma is in the field of medicine. Moreover, many techniques have been suggested to enhance plasma performance, among which the inclusion of an external static magnetic field is one [4], [5]. This paper used a low-power (20-watt) RF 13.56 MHz plasma to investigate the effect of cold plasma on cancer cells' migration rate in the presence of a static magnetic field. The result of the scratch healing assay is shown in Figure 1 (Ⅰ and Ⅱ). The results are evaluated after 24 hours. Figure 1 (Ⅰ-A) is before plasma treatment (control), (Ⅰ-B) is without treatment, (Ⅰ-C) is 15 seconds of plasma treatment, and (Ⅰ-D) is plasma and SMF treatment. The area of free space in the created gap has been evaluated by image processing software. The percentage of free space compared to the total space is specified in the diagram (Figure1-Ⅱ). As shown in the figure, the empty space for the state where the plasma is combined with the magnetic field is twice the state of the plasma alone. One of the main components of plasma that changes the presence of a magnetic field is the density and temperature of electrons in cold plasma. The electron temperature was evaluated based on the Boltzmann plot method, and the electron density measurement was calculated using the Saha-Boltzmann equation (figure 1-Ⅲ). The Boltzmann diagram is drawn using the used plasma spectrum, which was used in the previous work [6]. The calculation indicates that the electron temperature Te and electron density ne is estimated as 1.04 eV and for the absence of SMF, and 1.24 eV and for the presence of SMF, respectively Although several factors are involved in the effect of plasma, in this work, the temperature and electron density of the plasma were evaluated. Because apart from the direct impact on the target, the electron also affects the density of the ions. The findings indicate that the presence of a stationary magnetic field in close proximity to a plasma significantly regulated the migratory rate of cancer cells.Figure 1. (Ⅰ) scratch healing assay, (Ⅱ) percentage of gap for treatments, (Ⅲ) electron temperature calculation with Boltzmann plot.[1] S. Padureanu et al., “Non-Thermal Plasma-Activated Water: A Cytogenotoxic Potential on Triticum aestivum,” Agronomy, vol. 13, no. 2, 2023, doi: 10.3390/agronomy13020459.[2] V. Ioannou and S. Laizet, “Numerical investigation of plasma-controlled turbulent jets for mixing enhancement,” Int. J. Heat Fluid Flow, vol. 70, no. October 2017, pp. 193–205, 2018, doi: 10.1016/j.ijheatfluidflow.2018.02.008.[3] L. Guo et al., “Mechanism of virus inactivation by cold atmospheric-pressure plasma and plasmaactivated water,” Appl. Environ. Microbiol., vol. 84, no. 17, 2018, doi: 10.1128/AEM.00726-18.[4] X. Cheng et al., “Enhancing cold atmospheric plasma treatment of cancer cells by static magnetic field,” Bioelectromagnetics, vol. 38, no. 1, pp. 53–62, 2017, doi: 10.1002/bem.22014.[5] R. Mehrabifard, H. Mehdian, K. Hajisharifi, and E. Amini, “Improving Cold Atmospheric Pressure Plasma Efficacy on Breast Cancer Cells Control-Ability and Mortality Using Vitamin C and Static Magnetic Field,” Plasma Chem. Plasma Process., vol. 40, no. 2, pp. 511–526, Nov. 2020, doi: 10.1007/s11090-019-10050-5.[6] R. Mehrabifard, Z. Kabarkouhi, F. Rezaei, K. Hajisharifi, H. Mehdian, and E. Robert, “Physical understanding of the static magnetic field’s synergistic enhancement of cold atmospheric pressure plasma treatment,” Apr. 2023, Accessed: Sep. 21, 2023. [Online]. Available: https://arxiv.org/abs/2304.05833v1 Figure 1

Purified Versus Plasma Alpha-1 Antitrypsin Effects on Cellular Activities.

By adding purified exogenous alpha-1 antitrypsin (AAT) to peripheral blood mononuclear cells in 20% autologous serum and measuring AAT-induced cellular adherence, it was determined that purified AAT differs from plasma AAT. The known association of AAT with lipoproteins and the negative feedback between AAT and low-density lipoprotein (LDL) suggest that purification may separate AAT from a plasma component such as LDL that participates in their normal plasma functions.

Absorption, Distribution, Metabolism, and Excretion of [14C]BS1801, a Selenium-Containing Drug Candidate, in Rats.

BS1801 is a selenium-containing drug candidate with potential for treating liver and lung fibrosis. To fully elucidate the biotransformation of BS1801 in animals and provide sufficient preclinical drug metabolism data for human mass balance study, the metabolism of BS1801 in rats was investigated. We used radiolabeling techniques to investigate the mass balance, tissue distribution, and metabolite identification of BS1801 in Sprague-Dawley/Long-Evans rats after a single oral dose of 100 mg/kg (100 μCi/kg) [14C]BS1801: 1. The mean recovery of radioactive substances in urine and feces was 93.39% within 168 h postdose, and feces were the main excretion route. 2. Additionally, less than 1.00% of the dose was recovered from either urine or bile. 3. BS1801-related components were widely distributed throughout the body. 4. Fifteen metabolites were identified in rat plasma, urine, feces, and bile, and BS1801 was detected only in feces. 5. BS1801-M484, the methylation product obtained via a N-Se bond reduction in BS1801, was the most abundant drug-related component in plasma. The main metabolic pathways of BS1801 were reduction, amide hydrolysis, oxidation, and methylation. Overall, BS1801 was distributed throughout the body, and excreted mainly as an intact BS1801 form through feces. No differences were observed between male and female rats in distribution, metabolism, and excretion of BS1801.

An integrated strategy to evaluate active substances of Astragali Radix-Carthami Flos combination on the treatment of cerebral ischemia reperfusion injury based on TQSM polypharmacokinetics and pharmacodynamics.

As a classic herb pair, Astragali Radix-Carthami Flos (AR-CF) has revealed good biological activity in the treatment of cerebral ischemia/reperfusion injury (CI/RI), which remained to be further clarified together with the underlying efficacy related compounds for material basis. In this study, the nine formulations were obtained by L9 (34) orthogonal array design of four active fractions (saponin and flavonoid extracted from AR, safflower yellow and safflower red extracted from CF). The concentrations of eleven components and the levels of four biochemical indicators in rat plasma were continuously detected after intragastric administration of nine formulations, respectively. The collected data were analyzed by sigmoid-Emax function to understand the polypharmacokinetics and pharmacodynamics (PK-PD) behaviors of multi-components. Using the total quantum statistic moment polypharmacokinetics and its similarity method, the importance of four active fractions from AR-CF in relieving CI/RI was discussed and the Q-markers were screened. The results represented that a reliable and robust liquid chromatography tandem mass spectrometry method been successfully established to simultaneously determine the concentrations of eleven components in rat plasma. The AUC and MRT values of components from flavonoid fraction had the greatest contribution to AUCT and MRTT values. The transitivity in vivo of calycosin-7-O-β-Dglucoside (CG), astragaloside IV (AIV) and hydroxysafflor yellow A (HYA) was closer to polypharmacokinetics behavior. All formulations up/down-regulated the levels of GSH-Px and ATP/ET and LDH to varying degrees, among which formulation 7 had the best regulating effect. By drawing the time-concentration-effect curve, clockwise hysteresis loops were presented in the time-concentration-effect relationships between eleven components and LDH/ET, while the relationship between eleven components and ATP/GSH-Px expressed as anticlockwise hysteresis loops. In conclusion, the combination based on the combination principle of formulation 7 produced the best alleviation effect on CI/RI, and flavonoid fraction might played key role in this process. The CG, AIV and HYA were identified as Q-markers. This research offered a novel strategy for exploring the active substances, and provided further understanding regarding the development of drugs for the treatment of cerebral ischemia-reperfusion injury.

Influence of a Secondary Plasma Cloud on the Ablation of Pellets in Magnetic Confinement Devices

The analysis of experimental data on the structure of hydrocarbon pellet clouds on the LHD stellarator has allowed one to estimate the relative contributions of neutral and plasma shielding at the ablation of macroparticles (pellets) in a high-temperature magnetized toroidal plasma. A method for the self-consistent calculation of the pellet ablation rate, the characteristic size of the pellet cloud, and the electron density in its singly ionized part including neutral gas and plasma shielding is described. This calculation for polystyrene pellets injected into the LHD plasma gives the results that agree with the experimental data obtained during the early ablation phase, when the ablation rate is determined by thermal electrons and the contribution of the superthermal component of the hot plasma to ablation can be neglected.

High-sensitivity C-reactive protein/albumin (hs-CRP/albumin) ratio as a predictor of deterioration of clinical outcome in central nervous system infections

Central nervous system (CNS) infections such as encephalitis, meningitis, or myelitis have high morbidity and mortality in Indonesia. High sensitivity C-reactive protein (hs-CRP) is a sensitive marker of acute inflammation, while albumin is the most abundant protein component in plasma and cerebrospinal fluid (CSS). Infection triggers an inflammatory response so that an increase in the hs-CRP/albumin ratio (CAR) can be a predictor of worsening clinical outcome in patients with CNS infections. However, studies examining the predictor value of serum and CSF CAR on worsening clinical outcomes of patients are limited, particularly in CNS infections. The purpose of this study was to prove the CAR as a predictor of worsening clinical outcome in patients with CNS infections. It was an observational study using a prospective cohort design. Fifty subjects recruited until October 2021 at Dr. Sardjito General Hospital were involved. The multivariate regression analysis showed that serum CAR (OR=3.604; 95%CI=1.487-8.736; p =0.005) could be a single predictor. However, by combining three variables, namely serum CAR, CSF CAR, and decreased consciousness at admission, could be a stronger predictor of worsening clinical outcome in patients with CNS infection (AUC = 97.1%; 95%CI = 0.929-1.00; p <0.001). The optimal cut-off value for serum CAR was 1.35 (Youden index = 0.88, sensitivity = 96%, specificity = 92%) while for CSF CAR was 0.14 (Youden index = 0.60, sensitivity = 76%, specificity = 84%). In conclusion, a combination predictive model of three variables, namely serum CAR, CSF CAR, and awareness at admission can be a stronger predictor of clinical outcome in patients with CNS infection than serum CAR alone.

A Systematic Study of Yiqi Qubai Standard Decoction for Treating Vitiligo Based on UPLC-Q-TOF/MS Combined with Chemometrics, Molecular Docking, and Cellular and Zebrafish Assays.

The Yiqi Qubai (YQ) formula is a hospital preparation for treating vitiligo in China that has had reliable efficacy for decades. The formula consists of four herbs; however, the extraction process to produce the formula is obsolete and the active ingredients and mechanisms remain unknown. Therefore, in this paper, fingerprints were combined with the chemometrics method to screen high-quality herbs for the preparation of the YQ standard decoction (YQD). Then, the YQD preparation procedure was optimized using response surface methodology. A total of 44 chemical constituents, as well as 36 absorption components (in rat plasma) of YQD, were identified via UPLC-Q-TOF/MS. Based on the ingredients, the quality control system of YQD was optimized by establishing the SPE-UPLC-Q-TOF/MS identification method and the HPLC quantification method. Network pharmacological analysis and molecular docking showed that carasinaurone, calycosin-7-O-β-d-glucoside, methylnissolin-3-O-glucoside, genkwanin, akebia saponin D, formononetin, akebia saponin B, and apigenin may be the key active components for treating vitiligo; the core targets associated with them were AKT1, MAPK1, and mTOR, whereas the related pathways were the PI3K-Akt, MAPK, and FoxO signaling pathways. Cellular assays showed that YQD could promote melanogenesis and tyrosinase activity, as well as the transcription and expression of tyrosinase-associated proteins (i.e., TRP-1) in B16F10 cells. In addition, YQD also increased extracellular tyrosinase activity. Further efficacy validation showed that YQD significantly promotes melanin production in zebrafish. These may be the mechanisms by which YQD improves the symptoms of vitiligo. This is the first systematic study of the YQ formula that has optimized the standard decoction preparation method and investigated the active ingredients, quality control, efficacy, and mechanisms of YQD. The results of this study lay the foundations for the clinical application and further development of the YQ formula.

Clinical outcomes in hospitalized plasma and platelet transfusion recipients prior to and following widespread blood donor SARS-CoV-2 infection and vaccination.

The safety of transfusion of SARS-CoV-2 antibodies in high plasma volume blood components to recipients without COVID-19 is not established. We assessed whether transfusion of plasma or platelet products during periods of increasing prevalence of blood donor SARS-CoV-2 infection and vaccination was associated with changesin outcomes in hospitalized patients without COVID-19. We conducted a retrospective cohort study of hospitalized adults who received plasma or platelet transfusions at 21 hospitals during pre-COVID-19 (3/1/2018-2/29/2020), COVID-19 pre-vaccine (3/1/2020-2/28/2021), and COVID-19 post-vaccine (3/1/2021-8/31/2022) study periods. We used multivariable logistic regression with generalized estimating equations to adjust for demographics and comorbidities to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Among 21,750 hospitalizations of 18,584 transfusion recipients without COVID-19, there were 697 post-transfusion thrombotic events, and oxygen requirements were increased in 1751 hospitalizations. Intensive care unit length of stay (n = 11,683) was 3 days (interquartile range 1-5), hospital mortality occurred in 3223 (14.8%), and 30-day rehospitalization in 4144 (23.7%). Comparing the pre-COVID, pre-vaccine and post-vaccine study periods, there were no trends in thromboses (OR 0.9 [95% CI 0.8, 1.1]; p = .22) or oxygen requirements (OR 1.0 [95% CI 0.9, 1.1]; p = .41). In parallel, there were no trends across study periods for ICU length of stay (p = .83), adjusted hospital mortality (OR 1.0 [95% CI 0.9-1.0]; p = .36), or 30-day rehospitalization (p = .29). Transfusion of plasma and platelet blood components collected during the pre-vaccine and post-vaccine periods of the COVID-19 pandemic was not associated with increased adverse outcomes in transfusion recipients without COVID-19.

Mass Balance and Metabolic Pathways of Eliapixant, a P2X3 Receptor Antagonist, in Healthy Male Volunteers.

Overactive adenosine triphosphate signaling via P2X3 homotrimeric receptors is implicated in multiple conditions. To fully understand the metabolism and elimination pathways of eliapixant, a study was conducted to assess the pharmacokinetics, mass balance, and routes of excretion of a single oral dose of the selective P2X3 receptor antagonist eliapixant, in addition to an invitro characterization. In this single-center open-label non-randomized non-placebo-controlled phase I study, healthy male subjects (n=6) received a single dose of 50mg eliapixant blended with 3.7MBq [14C]eliapixant as a PEG 400-based oral solution. Total radioactivity and metabolites excreted in urine and feces, and pharmacokinetics of total radioactivity, eliapixant, and metabolites in plasma were assessed via liquid scintillation counting and high-performance liquid chromatography-based methods coupled to radiometric and mass spectrometric detection. Metabolite profiles of eliapixant in human invitro systems and metabolizing enzymes were also investigated. After administration as an oral solution, eliapixant was rapidly absorbed, reaching maximum plasma concentrations within 2h. Eliapixant was eliminated from plasma with a mean terminal half-life of 48.3h. Unchanged eliapixant was the predominant component in plasma (72.6% of total radioactivity area under the curve). The remaining percentage of drug-related components in plasma probably represented the sum of many metabolites, detected in trace amounts. Mean recovery of total radioactivity was 97.9% of the administered dose (94.3-99.4%) within 14 days, with 86.3% (84.8-88.1%) excreted via feces and 11.6% (9.5-13.1%) via urine. Excretion of parent drug was minimal in feces (0.7% of dose) and urine (≈0.5%). In feces, metabolites formed by oxidation represented > 90% of excreted total radioactivity. The metabolites detected in the invitro experiments were similar to those identified invivo. Complete recovery of administered eliapixant-related radioactivity was observed in healthy male subjects with predominant excretion via feces. Eliapixant was almost exclusively cleared by oxidative biotransformation (>90% of dose), with major involvement of cytochrome P450 3A4. Excretion of parent drug was of minor importance (~1% of dose). ClinicalTrials.gov: NCT04487431 (registered 27 July 2020)/EudraCT number: 2020-000519-54 (registered 3 February 2020), NCT02817100 (registered 26 June 2016), NCT03310645 (registered 16 October 2017).