Permeability Coefficient Values Research Articles

Various steaming durations alter digestion, absorption, and fermentation by human gut microbiota outcomes of Polygonatum cyrtonema Hua polysaccharides.

Different steaming durations dramatically alter the structure of Polygonatum cyrtonema polysaccharides (PCPs). This study aimed to compare characteristics of digestion, absorption, and fermentation by gut microbiota across four representative PCPs from different steaming durations (0, 4, 8, and 12 h), each with unique molecular weights and monosaccharide profiles. Chemical composition of the four PCPs was analyzed. Digestibility was evaluated using an in vitro saliva-gastrointestinal digestion model. Absorption characteristics were assessed with a Caco-2 monolayer model, and impacts on gut microbiota composition and short chain fatty acid (SCFA) levels were analyzed using in vitro fermentation with human gut microbiota. Longer steaming durations altered the chemical profiles of PCPs, reducing carbohydrate content (84.87-49.58%) and increasing levels of uronic acid (13.99-19.61%), protein (1.07-5.43%), and polyphenols (0.05-2.75%). Four PCPs were unaffected by saliva digestion but showed enhanced gastrointestinal digestibility, with reducing sugar content rising from 4.06% (P0) to 38.5% (P12). The four PCPs showed varying absorption characteristics, with P0 having the highest permeability coefficient value of 9.59 × 10-8 cm/s. However, all PCPs exhibited poor permeability, favoring gut microbiota fermentation. The four PCPs altered gut microbiota composition and elevated SCFA production, but levels declined progressively with longer steaming durations. All PCPs significantly increased the abundance of Bacteroidota, Firmicutes, and Actinobacteriota, making them the dominant bacterial phyla. Additionally, all PCPs significantly increased the abundance of Bifidobacterium, Prevotella, and Faecalibacterium compared to the control group, which, along with Bacteroides, became the dominant microbiota. Increasing the steaming duration led to a reduction in Prevotella levels, with PCPs from raw rhizomes showing the highest relative abundance at 24.90%. PCPs from moderately steamed rhizomes (4 h) led to a significant rise in Faecalibacterium (7.73%) among four PCPs. P8 and P12, derived from extensively steamed rhizomes (≥8 h), exhibited similar gut microbiota compositions, with significantly higher relative abundances of Bacteroides (20.23-20.30%) and Bifidobacterium (21.05-21.51%) compared to P0 and P4. This research highlights the importance of adjusting steaming durations to maximize the probiotic potential of P. cyrtonema polysaccharides, enhancing their effectiveness in modulating gut microbiota and SCFA levels.

Preparation and In vitro/Ex vivo Evaluation of Nanoemulsion-Based in Situ Gel for Intranasal Delivery of Lasmiditan

Lasmiditan (LAS) was formulated as a nanoemulsion based in situ gel (NEIG)with the aim of improving its oral bioavailability via application intranasally. The solubility of LAS in oils, emulsifiers, and co-emulsifiers was determined to identify nanoemulsion (NE)components. Phase diagrams were constructed to identify the area of nanoemulsification. LAS NE was formulated using the spontaneous nanoemulsification method. Four NEs (F19, F24, F31, and F34) containing 7-15 % oleic acid (OA) as an oily phase, 40-55% labrasol (LR), and transcutol (TC) as emulsifier mixture at (1:1), (2:1), (3:1), and (1:2) ratio with 30-53 % (w/w) aqueous phase, having suitable optical transparency of 95–98%, globule size of 104-140 nm and polydispersity of 0.253–0.382 were selected for ex vivo permeation study. F31 with the highest flux value (2.32 ± 0.01 mg/cm2.min) relative to the other NEs. It achieves an enhancement ratio of 3.3 as compared to LAS aqueous suspension (8% LAS) also it achieves a significantly higher value of permeability coefficient. F31 was selected for the incorporation of different percentages of pH-sensitive in situ gelling polymer (Carbopol 934) to prepare NEIGs 4,5 and 6. The gel strength, pH, gelation time, and viscosity were predicted for the prepared NEIGs. In vitro release and ex vivo, nasal permeation were determined for NEIG5, which exerts comparable release and permeation values as F31 with more residence time in order to overcome the normal nasal physiological clearance.

Kajian Setting Time dan Permeabilitas pada Beton Variasi Limbah Granit Sebagai Subtitusi Parsial Agregat Kasar

Currently, infrastructure development is a priority of the Indonesian government which aims to improve the quality of life of the community and equitable distribution of infrastructure development. The need for concrete material as a construction material also increases in line with the increase in infrastructure development. The use of recycled aggregate materials, especially granite waste, is a promising option in sustainable infrastructure development. This study was conducted with the aim of knowing the effect of partial substitution of coarse aggregates using granite waste variations on the binding time and permeability of concrete. Experimental method was chosen in this research. The levels of granite waste used were 0%; 15%; 30%; and 45% by weight of coarse aggregate or gravel. The test specimens used for the concrete bond time study were fresh concrete poured into cube molds measuring 20 cm x 20 cm x 20 cm with a minimum height of 15 cm. Testing concrete bond time using a penetrometer tool. The test specimen for concrete permeability is a cube measuring 15 cm x 15 cm x 15 cm, totaling 12 pieces and tested with a Permeability Test Apparatus (Water Permeabilty Apparatus).The results showed that partial substitution of coarse aggregate with granite waste variation did not affect the setting time of concrete up to a certain level. Based on the results of the research conducted, the initial setting time and final setting time values of 0%, 15%, 30%, and 45% granite content variations fluctuate and the coefficient of determination (R2) value in linear regression is only 0.5 and 0.3. Partial replacement of coarse aggregate with granite waste has an effect on the impermeability of concrete which meets the requirements for medium aggressive impermeable concrete. Water pressure of 5 kg/cm2 for 72 hours applied to the concrete partial replacement of coarse aggregate with granite waste variation resulted in permeability coefficient values of 4.11 x 10-12 cm/s; 3.48 x 10-12 cm/s; 2.17 x 10-12 cm/s; and 3.25 x 10-12 cm/s. The minimum coefficient value of concrete with partial substitution of coarse aggregate with granite waste is obtained at 30% by weight of coarse aggregate. Granite, whose specific gravity is greater than gravel, produces denser and more water-resistant concrete.

Evaluating intestinal absorption of peptide Met-Lys-Pro in casein hydrolysate using Caco-2 and human iPS cell-derived small intestinal epithelial cells

High blood pressure is a major risk factor for cardiovascular disease. Our previous study confirmed that daily intake of casein hydrolysate that contained Met-Lys-Pro (MKP) can safely lower mildly elevated blood pressure. The present study aimed to evaluate the intestinal absorption differences between peptide MKP as a casein hydrolysate and synthetic MKP alone using Caco-2 cells and human iPS cell-derived small intestinal epithelial cells (hiSIECs). MKP was transported intact through Caco-2 cells and hiSIECs with permeability coefficient (Papp) values of 0.57 ± 0.14 × 10-7 and 1.03 ± 0.44 × 10-7 cm/s, respectively. This difference in Papp suggests differences in the tight junction strength and peptidase activity of each cell. Moreover, the transepithelial transport and residual ratio of intact MKP after adding casein hydrolysate containing MKP was significantly higher than that after adding synthetic MKP alone, suggesting that other peptides in casein hydrolysate suppressed MKP degradation and increased its transport. These findings suggest that hiSIECs could be useful for predicting the human intestinal absorption of bioactive peptides; ingesting MKP as a casein hydrolysate may also improve MKP bioavailability.

Improving the Accuracy of Permeability Data to Gain Predictive Power: Assessing Sources of Variability in Assays Using Cell Monolayers.

The ability to predict the rate of permeation of new compounds across biological membranes is of high importance for their success as drugs, as it determines their efficacy, pharmacokinetics, and safety profile. In vitro permeability assays using Caco-2 monolayers are commonly employed to assess permeability across the intestinal epithelium, with an extensive number of apparent permeability coefficient (Papp) values available in the literature and a significant fraction collected in databases. The compilation of these Papp values for large datasets allows for the application of artificial intelligence tools for establishing quantitative structure-permeability relationships (QSPRs) to predict the permeability of new compounds from their structural properties. One of the main challenges that hinders the development of accurate predictions is the existence of multiple Papp values for the same compound, mostly caused by differences in the experimental protocols employed. This review addresses the magnitude of the variability within and between laboratories to interpret its impact on QSPR modelling, systematically and quantitatively assessing the most common sources of variability. This review emphasizes the importance of compiling consistent Papp data and suggests strategies that may be used to obtain such data, contributing to the establishment of robust QSPRs with enhanced predictive power.

Design Constant Head Permeability Meter Digital: A Project-Based Learning Media

The permeability coefficient value is one of the most important parameters in soil mechanics. Quick, simple, and digital direct soil permeability tests in the field are needed to obtain data representing conditions. This research aims to create a portable soil permeability test tool based on microcontroller automation used as a project-based learning for Transportation Cadets peculiarly Palembang Aviation Polytechnic Cadets for new experiences of new learning circumstances. This research method based on the principle of permeability testing using the constant-head method by analyzing the requirements quantitatively. This principle uses water change level parameters, which are used to test the infiltration rate in sample soil. Furthermore, measurements of changes in water level are used by water leveling sensors and processed using Arduino Uno based on fuzzy logic with access to results via the web, tool design, and simulation using SIMULINK software. The results of designing a digital measuring instrument for permeability using the constant head method have been validated for its schematic circuit using SIMULINK and can work without error. In conclusion, a model based on Darcy's Law equation and constant head to find the permeability coefficient can be generated, which can then be a prototype of the tool. It concluded the design of constant head permeability meter digital is useful as project-based leaning media for the Palembang aviation polytechnic. Furthermore, the equipment design will be the first digital measuring tool for permeability coefficient using the constant head method. The design has advantage to measure the soil permeability coefficient at the airport in the fastest way.

Separation of acetochlor through polymeric membrane system

In this study, an acetochlor belonging to the herbicide group was transported using a synthesized polymer inclusion membrane (PIM). Tricapryl-methylammonium chloride (Aliquat 366) and cellulose triacetate (CTA) were used as carrier and support material, respectively, in the membrane structure. The acetochlor samples taken during the transport from the donor phase containing 0.1 M HCl to the acceptor phase containing pure water were determined by Liquid Chromatography Mass Spectrometry (LC-MS/MS). The permeability coefficient (P), rate constant (k), and material flow rate (J) values were calculated at the end of the transportation processes. The recovery factor (%) was determined to be 91.2 % at the end of 240 min of transportation time. The effects of relative amounts of the target analyte, carrier, and acid type on the donor phase were determined, as well as those of the acceptor phase pH and stirring effect. The results achieved in this study suggest that a stable and environmentally sustainable polymer inclusion membrane system might be used to effectively transport acetochlor.

A Novel Calculation Model for the Permeability Coefficient of Soils Conditioned with Foam and Bentonite Slurry

Both foam and bentonite slurry are commonly employed in soil conditioning to prevent water spewing during earth pressure balance (EPB) shield tunnelling. A novel calculation model to estimate the permeability coefficient of soils conditioned with foam and bentonite slurry is developed. In this model, bentonite particles are assumed to adhere to the foam film in a monolayer of bridging particles, and the permeation channels within the conditioned soil are updated using the Kozeny-Carman equation. A series of permeability tests on conditioned soil, varying conditioning parameters and water heads, validate the accuracy of the model. The measured results that the value of permeability coefficient can be well captured by the calculation results, which indicates that the model can accurately predict the permeability of soil conditioning by foam and bentonite slurry. While there is a slight reduction in accuracy for conditioning states with high foam and bentonite slurry injection ratios, the model remains conservative for tunnelling engineering safety due to calculated values consistently exceeding measured ones. Furthermore, the model performs well in cases of foam-conditioned soil from previous studies. Additionally, the model underscores the significant influence of bentonite slurry on the permeability coefficient by altering soil grain gradation.

Study of Residual Soil Permeability Coefficient Post Addition of Coal Fly Ash

Residual soil is soil that is often used as barrier cover soil at the closure of B3 waste storage facilities. This is because the shear strength of the soil is quite good. The minimum value of the soil permeability coefficient (k) for barrier hoods at the closure of B3 waste storage facilities is 10-7 cm/sec. Many residual soils have a soil permeability coefficient (k) of less than 10-7 cm/sec. Because the dominant compound in coal fly ash is silica, mixing this fly ash with residual soil can reduce the value of the soil permeability coefficient (k) and is also expected to increase the shear strength value of the soil. In this study, residual soil samples were mixed with fly ash at 5%, 10%, 15%, 25% and 35% of the dry weight of the soil. This research aims to determine the effect of adding fly ash on the parameters of dry density, shear strength and soil permeability. The tests carried out were standard proctor testing, direct shear test, and Falling-Head permeability testing. The residual soil used in this research came from Hamlet I, Bintang Meriah Village, Pancur Batu District, Deli Serdang Regency. Based on standard proctor testing, the maximum density (gd max) of original soil is 1,410 gr/cm3. The largest maximum density (gd max) was obtained when adding 15% fly ash, namely 1.471 gr/cm3. In the direct shear test, the original soil cohesion value was 0.024 kg/cm² with an internal shear angle of 37.96º. In the variation of adding 15% fly ash, the cohesion value was 0.131 kg/cm² with an internal friction angle of 53.08º. Based on the Falling-Head permeability test, the original soil permeability coefficient value was 1.98 x 10-6 cm/s. The permeability coefficient value for variations in adding 15% fly ash was obtained at 8.02 x 10-8 cm/s.

Preparation, In-vitro, Ex-vivo, and Pharmacokinetic Study of Lasmiditan as Intranasal Nanoemulsion-based In Situ Gel.

Lasmiditan (LAS) is a recently developed antimigraine drug and was approved in October, 2019 for the treatment of acute migraines; however, it suffers from low oral bioavailability, which is around 40%. This study aimed to improve the LAS bioavailability via formulation as nanoemulsionbased in situ gel (NEIG) given intranasally and then compare the traditional aqueous-LASsuspension (AQS) with the two successful intranasal prepared formulations (NEIG 2 and NEIG 5) in order to determine its relative bioavailability (F-relative) via using rabbits. Two successfully prepared nanoemulsion (NE) formulas, a and b, were selected for the incorporation of different percentages of pH-sensitive in situ gelling polymer (Carbopol 934) to prepare NEIGs 1, 2, 3, 4, 5, and 6. The pH, gelation capacity, gel strength, and viscosity were predicted for the prepared NEIGs. The release (in vitro) and the nasal permeation (ex vivo) were determined for NEIG 2 and 5, and then both were subjected to pharmacokinetics in vivo studies. Eighteen male rabbits weighing 2.0 to 2.5 kg were employed in the parallel design study. The body surface area (BSA) normalization method was applied for LAS dose calculation. Serial blood samples were taken out and subjected to drug analysis using the HPLC method previously developed and validated by L. Santosh Kumar. Primary pharmacokinetics parameters, including maximum drug concentration in plasma (Cmax), time to reach C-max (T-max), and area under the concentration-time curve from time zero to affinity (AUCt0-∞) were calculated. Both NE (a and b), together with NEIG (2 and 5) formulas, were subjected to the stability study. Finally, a nasal ciliotoxicity study was carried out to evaluate the nasal toxicity of developed NEIGs 2 and 5. The results showed that NEIGs 2 and 5 could be selected as the optimized NEIGs as both achieved 100% permeation within 20 min and then released within 25 and 35 min, respectively, thus achieving 3.3 folds with higher permeation percentages as compared to the AQS. Both NEIGs 2 and 5 exerted comparable release and permeation values as the corresponding NE a and b with more residence time in order to overcome the normal nasal physiological clearance. The values of C-max, Tmax, and AUC0- ∞ for NEIG 2 and NEIG 5 were 8066±242 ng/ml, 0.75±0.05 h, 19616.86±589 ng. h/ml, and 7975.67±239 ng/ml, 1.0±0.05 h, 17912.36±537 ng. h/ml, respectively, compared to the traditional AQS, which is equal to 4181.09±125 ng/ml, 2±0.2 h, and 8852.27±266 ng. h/ml, respectively. It was discovered that NEIGs 2 and 5 had better intranasal delivery of LAS and could significantly (p<0.05) achieve a higher value of permeability coefficient (3.3 folds) and 2.5 folds improvement in bioavailability when compared to AQS. The NE a, NE b, NEIG2, and NEIG5 formulations showed good stability at various temperatures. According to the nasal ciliotoxicity study, the nasal mucosal membrane, which was treated with NEIG 5, showed irritation with a bit of damage. However, damage was not observed when it was treated with NEIG 2, indicating the biocompatibility of the last one to be selected as the optimum formula. NEIG 2 and NEIG 5 are promising new intranasal formulas with a faster onset of action and greater bioavailability than the oral dosage form (AQS). Finally, the selected optimum gold formula that will be ready for further clinical study is NEIG 2.

Protective effects of galacto-oligosaccharide and polydextrose on Caco-2 intestinal cell barrier injury model

To explore the protective effect of different ratios of galactose oligosaccharide(GOS) and polydextrose(PDX) on intestinal cell barrier damage model of Caco-2. The same batch of Caco-2 cells were cultured to form a cell barrier model and randomly divided into damaged model group without calcium, calcium-containing blank control group(1.8 mmol/L Ca~(2+)), low-ratio/low-dose group(1.8 mmol/L Ca~(2+)+2 mg/mL GOS+2 mg/mL PDX) and low-ratio/medium-dose group(1.8 mmol/L Ca~(2+)+4 mg/mL GOS+4 mg/mL PDX), low-ratio/high-dose group(1.8 mmol/L Ca~(2+)+8 mg/mL GOS+8 mg/mL PDX) and high-ratio/low-dose group(1.8 mmol/L Ca~(2+)+0.8 mg/mL GOS+3.2mg/mL PDX), high-ratio/medium-dose group(1.8 mmol/L Ca~(2+)+1.6 mg/mL GOS+6.4 mg/mL PDX), high-ratio/high-dose group(1.8 mmol/L Ca~(2+)+3.2mg/mL GOS+12.8 mg/mL PDX), a total of 8 groups, three parallel groups were performed in each group. The Trans Epithelial Electrical Resistance value and apparent permeability coefficient value of each group were determined after 4 d culture, and the morphology of tight junction proteins ZO-1, Occludin and Claudin-1 were observed by immunofluorescence method, and the expression levels of inflammatory related factors in each group were determined by protein microarray method. Compared with damaged model group, TEER ratio in calcium-containing blank control group was significantly increased(P&lt;0.05), while Papp value was significantly decreased(P&lt;0.05);Compared with calcium-containing blank control group, TEER ratio in low-ratio/medium-dose group and high-ratio/high-dose group was significantly increased(P&lt;0.05) while Papp value was significantly decreased(P&lt;0.05), and they could significantly down-regulate some inflammatory response related cytokines. The cell barrier was intact in all groups except for the compact junction protein structure in the model group. Compared with Ca~(2+) alone, the combination of two prebiotics can enhance the density of Caco-2 cell barrier and reduced the permeability of cell bypass. And it can significantly reduce the expression level of some inflammatory cytokines and effectively protect the intestinal cell barrier.

Permeabilitas Tanah Lanau Sebagai Temporary Landfill Cover yang Distabilisasi dengan Bakteri dan Larutan Sementasi

In the development of waste management, piles of rubbish can produce liquid waste called leachate. Leachate from landfills can affect human health and pollute the environment and aquatic biota because leachate contains various chemical compounds and many pathogenic bacteria. To minimize the impact of landfill waste on the surrounding environment, the waste is covered with material that can isolate it from the surrounding environment. This research aims to determine the optimal level of cementation solution addition to waste sludge as temporary landfill cover using the MICP method. The research results reveal that the sample permeability meets the criteria for a temporary cover landfill, where the permeability specification limits are between 10-4 to 10-5 cm/s. The research revealed that 0.25M cementation solution and Bacillus Subtilis bacteria had the lowest permeability. Soil without cementation solution has a permeability coefficient value of 5.04×10-4 cm/s, and decreases to 6.67×10-5 cm/s with a cementation solution concentration of 0.25M over a 28-day peram period. Variations in the 0.25M cementation solution showed its ability to reduce soil permeability by up to 86.7%. Permeability has decreased, which means the soil pores are getting smaller. Thus, this addition can reduce soil permeability and minimize the possibility of environmental damage by leachate.

ANN based-model for estimating the boron permeability coefficient as boric acid in SWRO desalination plants using ensemble-based machine learning

This study examines the relationship between input conditions and the prediction of boron rejection in full-scale seawater reverse osmosis (SWRO) desalination plants using ensemble-based machine learning. While reverse osmosis is the dominant desalination technology, limited research has focused on analyzing plant performance under actual operating conditions. To address this gap, we developed and implemented machine learning algorithms to forecast boron permeability coefficient values, which are indicative of boron rejection concentrations in the permeate. Our analysis utilizes data from a SWRO desalination plant in southeast Spain, examining various input variables and their influence on the prediction of these parameters. The results demonstrate that our ensemble-based machine learning approach can predict boron permeability coefficient values with a reasonable margin of error of 1 mgL−1, as evidenced by mean average error (MAE) and mean absolute percentage error (MAPE) values of 7.93·10–8 and 11.8 %, respectively. In conclusion, an innovative application of artificial intelligence algorithms in the field of water purification under real operational conditions has been introduced, thus introducing valuable insights into the use of machine learning algorithms for forecasting boron rejection concentrations in full-scale SWRO desalination plants. The findings lay the foundation for future researches exploring automated and deep-learning methods in water purification.

Determination of cell membrane permeability coefficients: Comparison of models in the case of oocytes

Values of cell membranes permeability coefficients for water and molecules of cryoprotective agents (CPAs) are the necessary characteristics for developing physical-mathematical models describing mass transfer processes through cell membranes in order to predict optimal cell cooling rates. We carried out a comparative analysis of the permeability coefficients of mouse oocyte membranes for molecules of water, ethylene glycol (EG), propane-1,2-diol (1,2-PD) and dimethyl sulfoxide (Me2SO), determined by applying the classical Kedem-Katchalsky model, which considers only the penetration of non-electrolyte molecules (water and CPA) through the membrane, and the model developed by us, which takes into account the transmembrane transfer of ions and the associated changes in the transmembrane electric potential. We shown that calculations based on the developed modified model provide lower values of the permeability coefficients of the oocyte membrane for water and CPA molecules. What is important that the obtained by our modified model permeability coefficients for water molecules do not depend on the type of cryoprotectant, while the application of the classical model both in our studies and works of other authors always gave different values of these coefficients in solutions with different cryoprotectants. Our modified model also makes it possible to determine the dynamics of the transmembrane electric potential of the cell under the conditions of transmembrane mass transfer and the duration of the membrane being influenced by the changes in electric potential, that is a parameter that can directly affect the viability of cells.

Анализ зависимости проницаемости от открытой пористости карбонатных пород коллектора в районах Астраханского газоконденсатного месторождения

At the present moment the fields reserves containing viscous and high-viscosity oil account for more than half of all the explored reserves of oil and gas fields. Carbonate deposits, in which oil and gas fluids are concentrated, are characterized by a complex structure of void space containing hydrocarbons. Due to the higher content of part of the oil in unrelated shallow cracks, the development of such reserves is difficult. For this reason, the main task of this study was to establish the dependence of the core-core permeability index on the porosity of carbonate reservoir rocks composing the Astrakhan Gas Condensate field (AGCM). Based on the characteristics of the Astrakhan arch and deposits in the AGCM areas, the paper presents the results of research work to determine the porosity of the rock by hydrostatic weighing based on the available information about the carbonate deposits of the formation, the physical properties of the rocks composing the formation, the characteristics of the geophysical values of porosity and permeability. The obtained values of the mass samples are given by weighing in various saturation states and calculating the permeability of the core samples. The linear dependence of the open porosity of carbonate rocks on permeability is revealed. The analysis of the results of studies on core samples obtained at the wells of the AGCM was carried out. The values of porosity and permeability coefficients are given. Based on the conclusion about the filtration-capacitance properties of the deposit the dependence of the permeability of the rock on the open porosity on the reservoir properties of the deposit was cocluded. The graph obtained on the basis of the calculated data is given, the equation of the “core-core” dependence or a linear regression equation is compiled.

Repurposing the in-house generated Alzheimer's disease targeting molecules through computational and preliminary in-vitro studies for the management of SARS-coronavirus-2.

Covid-19 was declared a world pandemic. Recent studies demonstrated that Covid-19 impairs CNS activity by crossing the blood-brain barrier and ensuing cognitive impairment. In this study, we have utilized Covid-19 main protease (Mpro) as a biological target to repurpose our previously reported multifunctional compounds targeting Alzheimer's disease. Molecular docking, spatial orientation, molecular dynamics simulation, MM-GBSA energy calculation, and DFT studies were carried out with these molecules. Among all the compounds, F27, F44, and F56 exhibited higher binding energy (-8.03, -8.65, and -8.68kcal/mol, respectively) over the co-crystal ligand O6K (-7.00kcal/mol). In MD simulation, compounds F27, F44, and F56 could make a stable complex with Mpro target throughout the simulation. The compounds were synthesized following reported methods and subjected for cytotoxicity, and assessment of their capability to cross the blood-brain barrier in PAMPA assay, and antioxidant property evaluation through DPPH assay. The compounds F27, F44, and F56 exhibited cytocompatibility with the SiHA cell line and also displayed significant antioxidant properties with IC50 = 45.80 ± 0.27μM, 44.42 ± 0.30μM, and 42.74 ± 0.23μM respectively. In the PAMPA assays, the permeability coefficient (Pe) value of F27, F44, and F56 lies in the acceptable range (Pe > 4). The results of the computational and preliminary in-vitro studies strongly corroborate the potential of F27, F44, and F56 as a lead for further optimization in treating the CNS complications associated with Covid-19.

Permeability coefficient of waterproof curtain by borehole packer test

Borehole packer testing is a commonly used method to obtain the in-situ permeability coefficients, which are closer to the actual subsurface conditions compared to indoor tests. Current methods for determining permeability coefficients through borehole packer testing are limited to semi-infinite spaces like rock masses, failing to accurately describe the permeability coefficient of domains with different shapes, such as waterproof curtains, thus leading to evaluation errors. This study proposed a novel approach that utilizes borehole packer tests on waterproof curtains for determination of in-situ permeability coefficients. Based on the assumption that seepage within the waterproof curtain obeys Darcy's law, and following the borehole packer testing procedures, the method derives specific formulas for different cross-sectional shapes of waterproof curtain, experimental parameters and groundwater levels. Applying this method to calculate domains with actual shapes has higher permeability coefficient values compared to the previous semi-infinite domain methods, which had underestimated the permeability coefficients of waterproof curtains. The study presents a calculation model for borehole packer tests on waterproof curtains under various geological formations and conditions, providing a more accurate approach to determine the in-situ permeability coefficients.

A Novel Method of Self-Healing Concrete to Improve Durability and Extend the Service Life of Civil Infrastructure

Concrete civil infrastructure often suffers severe damage to its internal structure due to insufficient durability in high and cold complex environments, affecting the service life of the infrastructure. Therefore, a novel method based on nanofillers for self-healing concrete is proposed to optimize the durability mix proportion of high-performance concrete in complex high and cold environments, which improves the strength recovery rate of concrete. Moreover, a concrete durability prediction model based on particle swarm optimization-least squares support vector machine (PSO-LSSVM) and improved NSGA-II (nondominated sorting genetic algorithm II) algorithm was proposed to quickly and accurately determine the optimization scheme of self-healing concrete mix proportion. First, the model employs PSO-LSSVM to achieve highly accurate predictions of relative dynamic elastic modulus and chloride ion permeability coefficient, which are key indicators of the concrete durability. Subsequently, the predicted regression functions for concrete durability are utilized as fitness functions, and the improved NSGA-II algorithm is employed to obtain the optimal mix ratio for durable concrete. Finally, the Pareto frontier solution set is processed using the ideal point method selection approach to determine the optimal concrete mix ratio scheme. To assess the self-healing ability of the proposed concrete, a concrete durability test study is conducted. Experimental research shows that the durability of the proposed self-healing concrete has been significantly improved. The optimized PSO-LSSVM model demonstrates excellent generalization capability. The coefficient of determination between the predicted and actual values in the test dataset is 0.9357, and the root-mean-square error is 0.10267. Building upon this, the enhanced concrete durability prediction model based on the NSGA-II algorithm proves to be highly effective in predicting the optimal concrete mix proportion scheme. The predicted values of chloride ion permeability coefficient and relative dynamic elastic modulus of the proposed model differ from the actual experimental values by 1.29% and 0.59%, significantly better than the other prediction models.

Utilization of endogenous albumin trafficking pathways in the lungs has potential to modestly increase the lung interstitial access and absorption of drug delivery systems after inhaled administration

ABSTRACT Objectives Drug delivery systems typically show limited access to the lung interstitium and absorption after pulmonary delivery. The aim of this work was to undertake a proof-of-concept investigation into the potential of employing endogenous albumin and albumin absorption mechanisms in the lungs to improve lung interstitial access and absorption of inhaled drug delivery systems that bind albumin. Methods The permeability of human albumin (HSA) through monolayers of primary human alveolar epithelia, small airway epithelia, and microvascular endothelium were investigated. The pulmonary pharmacokinetics of bovine serum albumin (BSA) was also investigated in efferent caudal mediastinal lymph duct-cannulated sheep after inhaled aerosol administration. Results Membrane permeability coefficient values (Papp) of HSA increased in the order alveolar epithelia<small airway epithelia<microvascular endothelium, where the permeability of HSA through small airway and microvascular endothelia were approximately 4- and 28-fold higher than alveolar epithelia, respectively. Only 6.5% of the delivered BSA aerosol dose was absorbed from the lungs of sheep over 5 days, although half of the absorbed dose was absorbed via the lung lymph. Conclusion Drug delivery systems that bind endogenous albumin may show a modest increase in lung permeability and absorption after inhaled delivery compared to systems that do not efficiently bind albumin.

Plasma non-transferrin-bound iron uptake by the small intestine leads to intestinal injury and intestinal flora dysbiosis in an iron overload mouse model and Caco-2 cells.

Iron overload often occurs during blood transfusion and iron supplementation, resulting in the presence of non-transferrin-bound iron (NTBI) in host plasma and damage to multiple organs, but effects on the intestine have rarely been reported. In this study, an iron overload mouse model with plasma NTBI was established by intraperitoneal injection of iron dextran. We found that plasma NTBI damaged intestinal morphology, caused intestinal oxidative stress injury and reactive oxygen species (ROS) accumulation, and induced intestinal epithelial cell apoptosis. In addition, plasma NTBI increased the relative abundance of Ileibacterium and Desulfovibrio in the cecum, while the relative abundance of Faecalibaculum and Romboutsia was reduced. Ileibacterium may be a potential microbial biomarker of plasma NTBI. Based on the function prediction analysis, plasma NTBI led to the weakening of intestinal microbiota function, significantly reducing the function of the extracellular structure. Further investigation into the mechanism of injury showed that iron absorption in the small intestine significantly increased in the iron group. Caco-2 cell monolayers were used as a model of the intestinal epithelium to study the mechanism of iron transport. By adding ferric ammonium citrate (FAC, plasma NTBI in physiological form) to the basolateral side, the apparent permeability coefficient (Papp) values from the basolateral to the apical side were greater than 3×10-6 cm s-1. Intracellular ferritin level and apical iron concentration significantly increased, and SLC39A8 (ZIP8) and SLC39A14 (ZIP14) were highly expressed in the FAC group. Short hairpin RNA (shRNA) was used to knock down ZIP8 and ZIP14 in Caco-2 cells. Transfection with ZIP14-specific shRNA decreased intracellular ferritin level and inhibited iron uptake. These results revealed that plasma NTBI may cause intestinal injury and intestinal flora dysbiosis due to the uptake of plasma NTBI from the basolateral side into the small intestine, which is probably mediated by ZIP14.