Decrease In Concentration Research Articles

Differential modulation of inflammatory cytokines by recombinant IL-10 in IL-1β and TNF-α ̶ stimulated equine chondrocytes and synoviocytes: impact of washing and timing on cytokine responses

Osteoarthritis (OA) remains a challenging joint disorder necessitating effective anti-inflammatory interventions. In this study, our primary objective was to establish an in vitro protocol that replicates the clinical investigation of anti-inflammatory drugs intended for OA management. Focusing on recombinant IL-10 (r.IL-10) as a potential anti-inflammatory treatment, we designed and implemented two distinct protocols to evaluate the efficacy of r.IL-10 in modulating chondrocyte and synoviocyte inflammation.The experimental design involved sequential stimulation with IL-1β and TNF-α for 24 h, followed by washing (model 1) or not washing (model 2) the cells before r.IL-10 treatment. Samples were collected after 6–24 h of treatment. Cellular responses were evaluated by quantifying gene expression and synthesis of key inflammatory cytokines and proteases.The expression and synthesis of inflammatory cytokines and proteases was significantly affected by washing and treatment time. The expression of IL-1β, TNF-α, IL-8, MMP-13, and ADAMTS5 were effectively reduced in r.IL-10-treated chondrocytes and synoviocytes in model 2 after 24 h, particularly at concentrations of 10 and 20 ng/mL. r.IL-10 treatment significantly increased IL-6 gene expression in chondrocytes at all time points. However, in synoviocytes, IL-6 expression was significantly lower in model 2 after 24 h of r.IL-10 treatment. r.IL-10 treatment significantly decreased IL-1β and TNF-α content in synoviocyte supernatants, particularly in model 2 at concentrations of 10 and 20 ng/mL after 6 and 24 h. r.IL-10 treatment in chondrocytes led to a significant decrease in IL-1β supernatant concentrations in model 2 after 24 h only.This study demonstrated that r.IL-10 treatment effectively reduces key inflammatory markers and matrix metalloproteinase activity in both chondrocytes and synoviocytes, particularly in model 2 where cells were not washed prior to treatment. These findings highlight r.IL-10’s potential as a robust anti-inflammatory agent for OA management and suggest its critical role in developing effective therapeutic strategies for OA.

Growth-dependent concentration gradient of the oscillating Min system in Escherichia coli.

Cell division in Escherichia coli is intricately regulated by the MinD and MinE proteins, which form oscillatory waves between cell poles. These waves manifest as concentration gradients that reduce MinC inhibition at the cell center, thereby influencing division site placement. This study explores the plasticity of the MinD gradients resulting from the interdependent interplay between molecular interactions and diffusion in the system. Through live cell imaging, we observed that as cells elongate, the gradient steepens, the midcell concentration decreases, and the oscillation period stabilizes. A one-dimensional model investigates kinetic rate constants representing various molecular interactions, effectively recapitulating our experimental findings. The model reveals the nonlinear dynamics of the system and a dynamic equilibrium among these constants, which underlie variable concentration gradients in growing cells. This study enhances quantitative understanding of MinD oscillations within the cellular environment. Furthermore, it emphasizes the fundamental role of concentration gradients in cellular processes.

The impact of CEO contract duration on corporate misconduct

CEOs play a crucial role in mitigating organisational misconduct. However, previous studies have mainly focused on the CEO characteristics that help firms choose an appropriate CEOs. Less is known about how to manage risk through contract design when appointing a chief executive to reduce misconduct. This study examines how CEO contract duration affects the likelihood of corporate misconduct. We bridge agency and upper echelon theories to hypothesise the impact of CEO contract duration on corporate misconduct. We also examine how CEO compensation and firm ownership concentration moderate this relationship. Using data collected from multiple sources, we analyse the impact of CEO contract duration on corporate misconduct in listed companies from 1994 to 2022. The results show a U-shaped relationship between CEO contract duration and misconduct. Initially, misconduct decreases with longer CEO contracts but begins to increase as the duration extends further. This relationship is strengthened when CEO compensation and ownership concentration decrease. We also investigate the relationship between CEO succession contract duration and the actual tenure situation, and the results are generally consistent with our hypothesis. Overall, CEO succession contract duration at an intermediate level is more effective in reducing corporate misconduct than other contract durations. Our conclusions contribute to the research on the relationship between CEO contract design and corporate misconduct.

Numerical and analytical investigation of Jeffrey nanofluid convective flow in magnetic field by FEM and AGM

In the present research, a numerical and analytical study on magnetohydrodynamic (MHD) convective flow of Jeffrey nanofluid has been presented. Investigation of mass and heat transfer phenomena has been done using mathematical modeling and considering thermal radiation. Solving and developing non-linear differential equations is done using finite element method (FEM) and Akbari-Ganji method (AGM). The novelty of this research lies in its application of these methods to investigate the effects of varying physical parameters on Jeffrey nanofluid flow, thereby filling a significant gap in the field of magnetohydrodynamics (MHD). Non-linear equations for energy, momentum and concentration are converted into dimensionless nonlinear equations by using appropriate variables. The main goal of this study is to determine the effect of various physical parameters on velocity, temperature and fluid concentration with the finite element model. This particular model was chosen because of the important role of magnetohydrodynamics and its wide applications in industry, engineering and medicine. The obtained results are presented graphically. It can be seen that with the increase of the mixed convection parameter, the velocity field increases, but the temperature and concentration decrease. Increasing the Hartmann number increases the speed and decreases the temperature in a certain range. When the Prandtl number increases, the temperature decreases. An increase in the Schmidt number results in a decrease in concentration. The results of the present study are in good agreement with the previous results, which shows the high accuracy and efficiency of the techniques used in this study.

The Impact of Methamphetamine on Liver Injury in Iraqi Male Addicts

Methamphetamine (METH) is a powerful stimulant that affects neurochemical processes controlling heart rate, appetite, blood pressure, body temperature, and wakefulness, making it highly susceptible to abuse. Liver enzymes such as ALT, AST, ALP, and GGT are crucial for liver function. Albumin, a protein synthesized by healthy liver cells, serves as an indicator of chronic liver disease. Additionally, hepatocytes produce bile acids, which are essential for the secretion of bile salts into the bile canaliculi. Disruption in this secretion results in the accumulation of bile salts in the canaliculi, leading to intrahepatic cholestasis. METH-induced liver toxicity involves disruptions in hepatic metabolism, oxidative stress, and increased body temperature, affecting cellular processes such as cell division and the cell cycle and potentially accelerating liver cell apoptosis. The study explores the link between liver toxicity and hepatocyte damage in Iraqi males suffering from addiction. This is a case-control study, conducted at Ibn-Rushed Psychiatric Hospital in Baghdad from July 2023 to February 2024, involved 196 males, with addiction durations exceeding 24 months with varying degrees of methamphetamine (METH) addiction. The study included 187 healthy male controls with no history of drug addiction. Participants were aged 18 to 40 years. Diagnosis was confirmed using a drug test screening card administered by a specialist. The study included liver function tests (ALT, AST, ALP, and GGT), total bilirubin, and albumin concentration assessments. Significant differences were observed between the addicts and controls, particularly a marked decrease in serum albumin concentration in the addicted males. The ROC curve classification model at various thresholds demonstrated that liver enzymes, especially ALT, ALP, and GGT, exhibited increased sensitivity to METH addiction. A histopathological examination was conducted on a deceased 38-year-old male who had a six-year history of chronic amphetamine addiction to confirm liver injury and the resulting elevation of liver enzymes. The findings of this study indicate that METH greatly affects liver function, suggested to the importance of following a preventative measures and effective treatment approaches for monitoring METH addiction progress.

Decadal changes in summer aerosol composition and secondary aerosol formation mechanisms in Beijing

Abstract Aerosol chemistry in China has undergone significant transformation due to stringent emission control measures, leading to great shifts in aerosol composition and formation mechanisms. This study investigates the summer chemical evolution of aerosol species in Beijing over the past decade based on two summertime measurements using aerosol chemical speciation monitors. The results reveal a substantial decrease in fine particulate matter concentrations by 72.7% in summer over the past decade, particularly primary species that dropped by 86.3-95.1%. However, this improvement in particulate matter was accompanied by a worsening of ozone pollution between 2011 and 2022. In contrast, secondary components such as sulfate and secondary organic aerosol (SOA) exhibited significant increases in their contributions, rising from 18.2-25.5% to 21.4-41%. The varying responses of aerosol species to emission reductions are closely tie to changes in emission sources, aerosol chemistry, and meteorology. By decoupling the influence of meteorology through machine learning, our analysis highlights the crucial role of emission reductions in improving air quality, though with different impacts on aerosol chemistry. The dominant formation mechanisms of secondary components varied between the two summers, likely influenced by shifts in aerosol liquid water content and atmospheric oxidation capacity due to NOx reductions. Compared to the summer of 2011, the formation of sulfate and SOA in summer 2022 was primarily driven by photochemical processes related to ozone, with less impacts from aqueous-phase formation, while nitrate was predominantly formed via N2O5 heterogeneous hydrolysis. Considering the complex nature of secondary aerosol formation, future summer pollution control strategies should prioritize stricter collaborative regulation of precursors for both secondary aerosol and ozone.

Hardness properties of calcium and magnesium ions in drinking water

The drinking water parameter - water hardness - is defined as the sum of calcium and magnesium ion concentrations. In this study, their precipitation during boiling was investigated, using water of different hardnesses, calcium to magnesium ratios, natural tap and bottled waters. During boiling, pH value, conductivity, and calcium and magnesium concentrations were measured. Further, the morphology and composition of precipitates were analyzed. Boiling tests with durations of 30 min showed only a decrease of calcium concentration by precipitation. Longer boiling of water with a high proportion of magnesium showed decreasing magnesium concentrations once the calcium precipitation was completed. Calcium carbonate precipitated as calcite and aragonite crystals with aragonite needles occurring in the presence of high magnesium concentrations. Magnesium hydroxide formed during precipitation was identified as hydromagnesite crystals with different crystallization morphologies. Unexpectedly, for a water with low and equimolar concentrations of calcium and magnesium only magnesium precipitated at the relatively low pH 8.7. In summary, calcium ions in drinking water are evaluated as being of considerably higher relevance for the hardness properties than the magnesium ions. However, the precipitation of both minerals depends on their concentrations and ratio as well as on the pH value and the water matrix.

Protective effect of Glycyrrhizic Acid against diclofenac-induced renal damage in male albino rats

Acute renal injury is a serious condition of severe damage to the kidney tissue resulting from various causes. Some medicinal plants have been used to treat certain renal injury. The purpose of the current investigation was to determine the protective effect of Glycyrrhizic acid (GA) on kidney function in rat models with induced kidney damage by Diclofenac sodium (Voltarene®, 50 mg coated tablets). Glycyrrhizic acid was given at doses of 200 and 400 mg/kg/day orally for 30 days. Its protective effect was evaluated by renal function tests . The result showed significant decreased the elevation of urea , serum creatinine and uric acid. Also, The result show significant decrease in total cholesterol, triglyceride concentration and low-density lipoprotein, and a significant increase in high-density lipoprotein concentration. Therefore, GA can be used for the prevention and treatment of renal damage and some kidney and liver disorders.

Computational study on entropy generation in Casson nanofluid flow with motile gyrotactic microorganisms using finite difference method

The present study reveals the phenomenon of flow and thermal variations of non-Newtonian nanofluids flow of Copper (Cu) nanoparticles through two orthogonal permeable porous discs. Additionally, the study delves into the significance of liquid solid interfacial layer and nanoparticle diameter is studied to optimize the thermal conductivity. Gyrotactic Microorganisms are also considered to optimize the nanoparticles stability inside the fluid, and the entropy generation caused to system disorder, so entropy analysis is also calculated. Using appropriate dimensionless variables, the controlling PDEs are converted into dimensionless forms. These dimensionless PDEs are solved using the Finite Difference technique, which yields very accurate and stable solutions. Higher values of the Rayleigh bio-convection and mixed convection terms enhance the flow velocity field in both porous discs. The less thickness of nanolayer has significance effect to optimize the temperature. Enhancing the values of bioconvection Lewis number leads to a decrease in motile microorganism concentration in both permeable discs, and entropy generation rate increases against rising power of Eckert number and thermal radiation rise. The finite difference method outcomes have been thoroughly validated against already published research, and showing an excellent correlation. This research holds significant potential for applications in the fabrication and electromagnetic control of advanced magnetic nanofluid materials, relevant to biomedical, energy, thermal management, and aerospace technologies.

Circulating Fetuin-A concentrations in rheumatic diseases: asystematic review and meta-analysis.

Rheumatic diseases (RDs) include a broad group of disabling conditions with different phenotypes, from autoimmune to autoinflammatory, degenerative, metabolic or mixed manifestations. With the continuous efforts to identify therapeutic targets for new biologic drugs to treat overt clinical manifestations, research is also focusing on the discovery of new biomarkers to diagnose and manage early disease stages. In this context, we conducted a systematic review and meta-analysis of Fetuin-A (FtA), a glycoprotein synthesized by the liver that participates in several biological processes and has been proposed as a biomarker for several disorders, including rheumatoid arthritis. A systematic search in PubMed, Scopus and Web of Science, from inception to the 24th of August 2024, led to the identification of 13 manuscripts from 219 records; six additional studies were identified through reference hand-search, for a total of 19 studies. There was a significant decrease in FtA concentrations in RD patients (standardized mean difference, SMD = -.91; 95% CI -1.43 to -.39, p = .001), with no substantial contribution from any individual study nor publication bias. The effect size was significantly associated with erythrocyte sedimentation rate, various lipid fractions, geographical area of study conduction, study design and specific type of RD. In conclusion, our study identified significant reductions in FtA concentrations in RD patients versus healthy controls. These alterations were significantly associated with specific study and patient characteristics. Further research is required to identify the exact pathophysiological mechanisms underlying these alterations and the possible utility of measuring FtA for the diagnosis and management of RDs.

Proteostasis collapse in rat’s lung tissue as one of the effects of European adder (Vipera berus subsp. berus and Vipera berus subsp. nikolskii) envenomation

Abstract Snakebites and their consequences are a growing concern around the globe. The mixture of enzymes, present in snake venom is a great challenge for a snakebite victim’s body. European adder (Vipera berus) is considered as not very harmful snake due to the mild clinical symptoms of envenomation and rare cases of cardiovascular or pulmonary failure. Nevertheless, at the molecular level, many details of V. berus bite (including proteostasis instability) remain unclear. This work was aimed to determine the effect of Eastern Europe typical adder species Vipera berus berus and Vipera berus nikolskii envenomation on the protein homeostasis of rat’s lung tissue. The decrease in total protein concentration, significant redistribution of main protein fractions (including proteolytically active), rise in middle-mass molecules and low molecular weight peptide concentration have been observed during V. b. berus and V. b. nikolskii envenomation, strongly indicating the proteostasis collapse and endogenous intoxication in lung tissue as an effect of European adder snakebite. Moreover, according to the results of experiments, the effect of V. b. nikolskii venom is more harmful to lung tissue protein homeostasis, comparing to V. b. berus, suggesting that the former may represent a greater danger to people. The results of this study may find applications in antivenom development and could be taken into consideration for proper snakebite treatment selection in order to avoid proteome complications in patients.

Risk factors for hemocoagulase-associated hypofibrinogenemia in patients with gastrointestinal bleeding

BACKGROUND With the widespread use of hemocoagulase in patients with gastrointestinal bleeding, clinicians have become increasingly concerned about coagulation disorders associated with this medication. Risk factors for hypofibrinogenemia associated with hemocoagulase are poorly understood. AIM To determine risk factors for hemocoagulase-associated hypofibrinogenemia in patients with gastrointestinal bleeding. METHODS We performed a retrospective analysis of the medical documentation of hospitalized patients treated with hemocoagulase for gastrointestinal bleeding. Hypofibrinogenemia was defined as a decrease in plasma fibrinogen concentration to less than 2.0 g/L. The included patients were divided into two groups: acquired hypofibrinogenemia group and non-hypofibrinogenemia group. We used logistic regression analysis to identify potential risk factors and established risk assessment criteria by employing a receiver operating characteristic curve. RESULTS There were 36 patients in the acquired hypofibrinogenemia group and 73 patients in the non-hypofibrinogenemia group. The hypofibrinogenemia group showed higher rates of intensive care unit admissions (P = 0.021), more female patients (P = 0.005), higher in-hospital mortality (P = 0.027), larger hemocoagulase doses (P = 0.026), more Packed Red Cells transfusions (P = 0.024), and lower baseline fibrinogen levels (P < 0.000). Binary logistic regression was employed to examine the risk factors associated with acquired hypofibrinogenemia. The analysis revealed that baseline fibrinogen [odds ratio (OR) 0.252, 95%CI: 0.137-0.464, P < 0.000], total hemocoagulase doses (OR 1.074, 95%CI: 1.015-1.137, P = 0.014), and female gender (OR 2.856, 95%CI: 1.015–8.037, P = 0.047) were statistically significant risk factors. CONCLUSION Higher doses of total hemocoagulase, female gender, and a lower baseline fibrinogen level were risk factors for hemocoagulase-associated hypofibrinogenemia in patients with gastrointestinal bleeding.

Virus Removal from Real Wastewater as an Environmental Management Approach

The increased presence of resistant microorganisms in water promotes the need for supplementary measures to mitigate the water source’s contamination. Traditional treatments are inefficient in wastewater management at removing some emerging contaminants. Corbicula fluminea, an invasive species, can be used in the treatment due to their resistance and biofiltration capacity, working as a pest management strategy. In this study, this bivalve was used to promote the virus disinfection from the municipal wastewater treatment plant (MWTP) that enters (influent) and after the secondary treatment (effluent leaving the plant). JC virus, norovirus (GI, GII), and hepatitis A (HAV) were identified. C. fluminea promoted norovirus GI and GII removal after 72 h and a slight decrease in the JC virus concentration. These results prove the potential of this pest management approach to be used in virus removal. Furthermore, infectivity assays using mengovirus confirmed the correlation between the presence of the genome detected by PCR and the infectious virus particles. This highlights the potential of PCR as a reliable indicator of the infectious virus’s presence. However, such an infectivity assay proved that even when PCR results are undetectable, a reduced number of viruses may remain viable and able to infect susceptible cells in culture.

Projected health benefits of air pollution reductions in a Swedish population.

A large part of the Swedish population is exposed to higher levels of air pollution than the health-centered air quality guidelines recommended by the World Health Organization (WHO). The aim of the study was to illustrate the potential health benefits of cleaner air in Sweden by conducting a comprehensive health impact assessment, using a population sample of 100,000 individuals representing the country's demographics. Exposure-response functions for various health outcomes were derived from epidemiological literature, mainly from systematic reviews and low-exposure settings. Two hypothetical scenarios were studied: a 1 µg/m3 decrease in particulate matter with an aerodynamic diameter <2.5µm (PM2.5) and nitrogen dioxide (NO2), and a reduction in PM2.5 or NO2 from average exposure corresponding to Sweden's Clean Air objectives to WHO's air quality guidelines. The findings demonstrated that even a modest decrease in air pollution concentrations can yield significant health benefits. For example, reducing PM2.5 by 1 µg/m3 was projected to correspond to a 1% to 2% decrease in mortality, a 2% reduction in myocardial infarction cases, a 4% decrease in stroke incidence, a 2% decline in chronic obstructive pulmonary disease, and a 1% decreases in lung cancer and type 2 diabetes annually. Moreover, this reduction is estimated to lower childhood asthma cases, incidences of hypertension during pregnancy, and premature births by 3%, 3% and 2%, respectively, each year. The results highlighted that even minor enhancements in air quality would lead to substantial improvements in public health.

Comparison of Homogeneous Anion-Exchange Membrane Based on Copolymer of N,N-Diallyl-N,N-dimethylammonium Chloride and Commercial Anion-Exchange Membranes in Electrodialysis Processing of Dilute Sodium Chloride Solutions

In this study, we investigated the electrodialysis process for treating a dilute sodium chloride solution using various anion exchange membranes – specifically, the commercial heterogeneous MA-41 and homogeneous Neosepta AMX, along with the experimental homogeneous membrane MA-1. We observed an increase in the desalting rate and the limiting current for the studied anion-exchange membranes in the series MA-41, MA-1, and AMX. We found that with commercial membranes, the decrease of the solution concnetration leads to the development of conjugated effects of concentration polarization. For the AMX membrane, useful mass transfer due to electroconvection increases, whereas for the MA-41 membrane, the flux of salt ions decreases due to the occurrence of the water dissociation reaction. For the MA-1 membrane, a decrease in the solution concentration leads to a transition of the system to the underlimiting current mode. This behavior may be associated with a significant contribution of equilibrium electroconvection to the process of ion transfer in dilute solutions in electromembrane systems with this membrane. Due to these differences in membrane properties, the mass transfer coefficients for the MA-1 membrane are higher compared to the AMX membrane at potential drops of 1 and 2 V. Our findings suggest that the most optimal operating mode for the MA-1 membrane is at a potential drop of 1 V in the electromembrane system, which results in a specific energy consumption of 0.24 kWh/mol. Contrastingly, under comparable conditions for the AMX membrane, the specific energy consumption is 0.34 kWh/mol.

Thermophoretic convection in porous atmosphere due to boosting temperature of plume: Climate change effects

A computational analysis of the impacts of thermophoretic convective heat transfer on climate change within a saturated porous atmosphere is predicted. A mathematical model is developed for the proposed problem, employing a Cartesian coordinate system for the source region, a cylindrical coordinate system for the plume region, and a spherical coordinate system for the atmospheric region. The temperature along the central axis of the plume is assumed to be variable, as is the surface temperature of the source region. In the source region, fossil fuel combustion releases thermophoretic particles that travel through the plume into the atmosphere. The climate impact of these particles is calculated via temperature difference across each region. Numerical simulations are performed to gain insights into the physical implications of the model, using the finite difference method to discretise and solve the governing partial differential equations. The effect of various parameters in the flow model, such as mixed convection parameter λT, modified mixed convection parameter λC, Schmidt number Sc, variable viscosity parameter γ, variable thermal conductivity parameter ε, porosity parameter ΩA thermophoretic parameter Nt and indexes of variable surface temperature, are analysed and presented graphically and in tabular form. The primary findings show that an increase in the porosity parameter ΩA results in increase in velocity and temperature profile, while the thermophoretic concentration decreases, potentially moderating climate impact. Further, the thermophoretic rate of heat transfer is maximum at α=1.5rad and minimum at α=πrad in the saturated porous atmosphere. The fundamental innovation of the current work is that three models from three regions are linked via trans-boundaries in terms of temperature differences. The accuracy of the obtained results is ensured by the prescribed boundary conditions and is highlighted graphically as well as in tabular form.

Development of a Photoelectrochemical Microelectrode Using an Organic Probe for Monitoring Hydrogen Sulfide in Living Brains.

Hydrogen sulfide (H2S) is an important bioactive molecule that plays a significant role in various functions, particularly in the living brain, where it is closely linked to cognition, memory, and several neurological diseases. Consequently, developing effective detection methods for H2S is essential for studying brain functions and the underlying mechanisms of these diseases. This study aims to construct a novel photoelectrochemical (PEC) microelectrode Ti/TiO2@HSP for the quantitative monitoring of H2S levels in the living brain. The PEC microelectrode Ti/TiO2@HSP is formed by covalently bonding a specifically designed organic PEC probe HSP, which possesses a D-π-A structure, to the surface of TiO2 nanotubes generated via in situ anodic oxidation of titanium wire. The PEC probe HSP can effectively react with H2S and generate significant photocurrent response under long-wavelength excitation light (560 nm), thereby achieving quantitative detection of H2S. The sensor demonstrates high sensitivity and good selectivity. In vivo experiments utilizing the PEC microelectrode Ti/TiO2@HSP enable the monitoring of dynamic changes in H2S levels across various regions of the mouse brain. The findings reveal that in normal mice, the concentration of H2S in the hippocampus is significantly higher than in the striatum and cerebral cortex. Additionally, following propargylglycine drug stimulation, H2S concentrations in different brain regions were observed to decrease, with the most substantial reduction noted in the hippocampus. This suggests that cystathionine γ-lyase (CSE) is the primary enzyme responsible for H2S production in this area, while the striatum exhibits a less pronounced decrease in H2S concentration, indicating a reliance on alternative enzymatic pathways for H2S production. Therefore, this study not only successfully develops a high-performance H2S detection sensor but also provides new experimental tools and theoretical foundations for further exploring the roles of H2S in neurophysiological and pathological processes.

Microplastics' impact on soil health and quality: Effect of incubation time and soil properties in soil fertility and pollution extent under the circular economy concept.

The aim of the present study is to highlight the effect of two commonly used plastics, polyethylene (PE) and polyethylene terephthalate (PET), on the quality and health indices of soil. To this end, a pot experiment was carried out using two soils, one acidic and one alkaline. The soil samples were collected from rural areas of central and Northern Greece and had similar particle size composition and almost equal copper (Cu), zinc (Zn), cadmium (Cd) and lead (Pb) concentrations. PE and PET microplastics (MPs) were added into the soil samples in two ratios (2% and 4% v/v) and remained in the soils for 20, 60 and 120 days. Then, the changes in the properties, nutrients, potentially toxic elements and health indicators of the soil samples were measured. PE addition at 4% v/v caused the maximum increase in trace element availability when it remained in the soil sample for 120 days. In contrast, PET addition caused a maximum decrease in the DTPA-extractable concentration of toxic elements (Cd and Pb), after 120 days of incubation in acid and alkaline soil. The present work provides a fresh perspective evaluating MPs from unwanted waste to materials with potential positive benefits, enhancing the circular economy approach to soil systems. Knowledge of the MPs present in soils, along with physicochemical soil properties, including their nutrient and toxic element content, are critical aspects that need to be addressed to ensure that soil quality and health are not adversely affected.

PBPK modelling for the evaluation of drug-drug interaction between meropenem and valproic acid.

The present study aimed to quantitatively investigate the potential drug-drug interaction (DDI) mechanism between meropenem (MEPM) and valproic acid (VPA). In the present study, we firstly developed a physiologically based pharmacokinetic (PBPK) model of MEPM and VPA. The verified PBPK model was then used to quantitatively investigate the potential DDI between MEPM and VPA. The effect of genetic polymorphisms of acylpeptide hydrolase (APEH) on DDI was also evaluated. In our simulation, the plasma concentration of hydrolysate of VPAG decreased to 63% when combined with MEPM. Total plasma concentration of VPA before carbapenem use was 53.61 mg/L, whereas it was 45.42 mg/L during carbapenem use. The inhibition of hydrolysis of VPAG by MEPM alone could not result in a rapid and substantial decrease in the plasma concentration of VPA. Parameter sensitivity analysis showed that the changes of absorption played an important role in the maximum plasma concentration (Cmax) of VPA, whereas area under the plasma concentration-time profile (AUC) was more susceptible to elimination changes. In addition, a decrease in APEH activity had little impact on the plasma pharmacokinetics of VPA. The DDI between MEPM and VPA might be a comprehensive result of multiple factors. On the basis of our simulation, interval medication of MEPM injection and VPA immediate release tablet at 4-6h timed interval was recommended, or intravenous administration of VPA solution was preferred when combination regimen was necessary in a clinical setting.

Effect of phenylbutazone administration on the enteroinsular axis in horses with insulin dysregulation.

Phenylbutazone is prescribed for laminitis-associated pain and decreases glucose and insulin responses to an oral glucose test (OGT) in horses with insulin dysregulation (ID). Investigate the effect of phenylbutazone administration on the enteroinsular axis in horses. Sixteen horses, including 7 with ID. Randomized cross-over study design, with horses assigned to treatment with phenylbutazone (4.4 mg/kg IV q24h) or placebo (5 mL 0.9% saline). On Day 9 of treatment, an OGT was conducted, followed by a 10-day washout period, administration of the alternative treatment, and repetition of the OGT. Glucose-dependent insulinotropic polypeptide (GIP), and active glucagon-like peptide 1 and 2 (aGLP-1 and GLP-2) concentrations were determined by ELISA. The effects of ID status and treatment on peptide concentrations were assessed using t tests and analyses of variance. Horses with ID had significantly higher maximum GIP concentrations (Cmax) than controls (median, 279.1; interquartile range [IQR], 117.5-319.4 pg/mL vs median, 90.12; IQR, 74.62-116.5 pg/mL; P = .01), but no significant effect of ID was detected on aGLP-1 and GLP-2 concentrations. In horses with ID, phenylbutazone treatment significantly decreased GIP Cmax compared with placebo (168.1 ± 59.26 pg/mL vs 242.8 ± 121.8 pg/mL; P = .04), but no significant effect of phenylbutazone was detected on aGLP-1 and GLP-2 concentrations. Glucose-dependent insulinotropic polypeptide, aGLP-1 and GLP-2 do not mediate the decrease in glucose and insulin concentrations observed after phenylbutazone administration. Only GIP was repeatedly associated with ID status, calling into question the role of the enteroinsular axis in ID.