Semipermeable Research Articles

Physiological, biochemical, and global transcriptomic and metabolomic analyses of the effect of the antifungal compound isobavachalcone on Botrytis cinerea on cherry tomatoes

Botrytis cinerea is a major postharvest pathogen on cherry tomato (Solanum lycopersicum). In this study, isobavachalcone (IBC) exhibited inhibitory activity against fungus B. cinerea in vitro and in vivo. Morphological and ultrastructural observations were conducted revealing that IBC caused significant changes in B. cinerea, including rupturing of the cell membrane, loosening of the cell wall, swelling of mitochondria, and massive reductions in the number of ribosomes. Physiological and biochemical analyses confirmed that IBC increased the permeability of the cell wall and membrane which had led to decrease in mitochondrial membrane potential (MMP), while significant increase in reactive oxygen species (ROS) level. According to transcriptomic and metabolomic analysis, IBC inhibited the expression of chitin deacetylase (CDA), glucan 1,3-beta-glucosidase (EXG), and squalene monooxygenase (ERG1) genes, which may result in the degradation of cell wall and membrane components, ultimately increasing cell permeability. IBC also interfered with the expression of cytochrome P450 (CYP102A) and cytochrome-b5 reductase (CYB5R) genes, which had a negative impact on mitochondrial energy metabolism. Additionally, the structure of the ribosomal large subunit and small subunit were altered by IBC, thus, interfering with translation initiation and polypeptide extension. These results provide an effective alternative approach against B. cinerea on cherry tomato.

Peptidyl-prolyl isomerase F as a prognostic biomarker associated with immune infiltrates and mitophagy in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is among the most prevalent malignancies worldwide, with unfavorable treatment outcomes. Peptidyl-prolyl isomerase F (PPIF) is known to influence the malignancy traits of tumor progression by modulating the bioenergetics and mitochondrial permeability in cancer cells; however, its role in LUAD remains unclear. Our study seeks to investigate the clinical significance, tumor proliferation, and immune regulatory functions of PPIF in LUAD. The expression of PPIF in LUAD tissues and cells was assessed using bioinformatics analysis, immunohistochemistry (IHC), and Western blotting. Survival curve analysis was conducted to examine the prognostic association between PPIF expression and LUAD. The immunomodulatory role of PPIF in LUAD was assessed through the analysis of PPIF expression and immune cell infiltration. A series of gain- and loss-of-function experiments were conducted on PPIF to investigate its biological functions in LUAD both in vitro and in vivo. The mechanisms underlying PPIF's effects on LUAD were delineated through functional enrichment analysis and Western blotting assays. PPIF exhibited overexpression in LUAD tissues compared to normal controls. Survival curve analysis revealed that patients with LUAD exhibiting higher PPIF expression demonstrated decreased overall survival and a shorter progression-free interval. PPIF was implicated in modulating immune cell infiltration, particularly in regulating the T helper 1-T helper 2 cell balance. Functionally, PPIF was discovered to promote tumor cell proliferation and advance cell-cycle progression. Furthermore, PPIF could impede mitophagy by targeting the FOXO3a/PINK1-Parkin signaling pathway. The findings of this study indicate that the prognosis-related gene PPIF may have a significant role in the regulation of LUAD cell proliferation, tumor-associated immune cell infiltration, and mitophagy, and thus PPIF may be a promising therapeutic target of LUAD.

Probabilistic evaluation of the permeability of the rocks of the elementary cell of a geological model

The article proposes a new method for calculating the permeability of a geological model cell using probabilistic methods. It is proposed as an alternative to the generally accepted method, which is based on the use of empirical dependencies between porosity and permeability based on the results of laboratory core tests. The proposed method allows us to calculate the dependences of the probabilities of exceeding certain permeability values on porosity. These are of interest for studying the geological structure of oil and gas facilities in the process of their modeling. In this work, the boundary values of filtration properties corresponding to the boundaries of reservoir classes in the classification proposed by A. A. Khanin in 1969 were used. The article discusses the problems arising from the integration of different-scale levels. One of their solutions can be obtained by using the Monte Carlo method. In particular, its use helped to simulate the reservoir properties of rocks in a virtual cell of a geological model based on analyses of the results of previous studies of core samples in laboratory conditions. The approximation of the probabilities of exceeding the corresponding values of permeability from porosity allows us to calculate histograms of this parameter for each cell of the model. To do this, it is necessary to determine the differences in the probability functions that are used for neighboring permeability thresholds. In turn, this makes it possible to perform a differentiable assessment of hydrocarbon reserves for the corresponding reservoir classes in terms of permeability. The article discusses a methodology that allows you to perform all calculations in an automated mode. The text of the article provides the necessary description of the program for calculating the probabilities of exceeding the permeability thresholds, as well as a schematic diagram reflecting the main provisions of its work. The article substantiates the expediency of not using porosity thresholds for reservoir identification. Instead, permeability histograms are calculated for each cell. This methodological scheme makes it possible to calculate reserves associated with rocks of various permeability classes in an automatic mode. Keywords: bottomhole formation zone; asphalt-resin-paraffin deposits; nitrite composition; surfactants; enhanced oil recovery.

Sensitivity and Validation of Porous Membrane Electrical Cell Substrate Impedance Spectroscopy (PM-ECIS) for Measuring Endothelial Barrier Properties.

Measurement of endothelial and epithelial barrier integrity is important for a variety of in vitro models, including Transwell assays, cocultures, and organ-on-chip platforms. Barrier resistance is typically measured by trans-endothelial electrical resistance (TEER), but TEER is invasive and cannot accurately measure isolated monolayer resistance in coculture or most organ-on-chip devices. These limitations are addressed by porous membrane electrical cell-substrate impedance sensing (PM-ECIS), which measures barrier integrity in cell monolayers grown directly on permeable membranes patterned with electrodes. Here, we advanced the design and utility of PM-ECIS by investigating its sensitivity to working electrode size and correlation with TEER. Gold electrodes were fabricated on porous membrane inserts using hot embossing and UV lithography, with working electrode diameters of 250, 500, and 750 μm within the same insert. Sensitivity to resistance changes (4 kHz) during endothelial barrier formation was inversely proportional to electrode size, with the smallest being the most sensitive (p < 0.001). Similarly, smaller electrodes were most sensitive to changes in impedance (40 kHz) corresponding to cell spreading and proliferation (p < 0.001). Barrier disruption with both EGTA and thrombin was detectable by all electrode sizes. Resistances measured by PM-ECIS vs TEER for sodium chloride solutions were positively and significantly correlated for all electrode sizes (r > 0.9; p < 0.0001), but only with 750 μm electrodes for endothelial monolayers (r = 0.71; p = 0.058). These data inform the design and selection of PM-ECIS electrodes for specific applications and support PM-ECIS as a promising alternative to conventional TEER for direct, noninvasive, real-time assessment of cells cultured on porous membranes in conventional and organ-on-chip barrier models.

Novel CNT/MXene composite membranes with superior electrocatalytic efficiency and durability for sustainable wastewater treatment

Self-assembled composite membranes are increasingly acknowledged for their potential in wastewater treatment due to their superior selectivity, high operational efficiency, and environmental sustainability. Nonetheless, challenges such as inadequate removal efficiencies for low molecular weight dyes and significant membrane fouling restrict their broader industrial application. To address these challenges, a structurally stable composite membrane of sodium lignosulfonate carbon nanotubes/alkalized MXene (SLS-CNT/alk-MXene) has been engineered. This membrane employs a polyethersulfone substrate pretreated with dopamine for uniform nanoparticle assembly through a layer-by-layer self-assembly technique. The manufacturing process includes hydrophilic modification of carbon nanotubes with lignosulfonate, followed by alkalization of MXene using sodium hydroxide. Performance evaluation of the M2 composite membrane, with a content ratio of SLS-CNT to alk-MXene of 4:2 by weight, revealed outstanding membrane properties. It achieved high selective permeability, with over 99 % retention efficiency for Methyl Blue and Congo Red, and a permeation flux of 51.6 L m-2h−1 bar−1. This membrane efficiently degraded various organic dyes within 1h, including Methyl Orange, Methylene Blue, Malachite Green, and Rhodamine B, and thanks to the integration of electrocatalysis with membrane separation, while maintaining a low membrane resistance of only 813 Ω. After environmentally sustainable testing, the membrane displayed excellent stability and 80 % recovery capacity, presenting a novel approach and design blueprint for enhancing clean water resources and environmental protection.

Surface-Enhanced Raman Spectroscopy Combined with Multivariate Analysis for Fingerprinting Clinically Similar Fibromyalgia and Long COVID Syndromes.

Fibromyalgia (FM) is a chronic central sensitivity syndrome characterized by augmented pain processing at diffuse body sites and presents as a multimorbid clinical condition. Long COVID (LC) is a heterogenous clinical syndrome that affects 10-20% of individuals following COVID-19 infection. FM and LC share similarities with regard to the pain and other clinical symptoms experienced, thereby posing a challenge for accurate diagnosis. This research explores the feasibility of using surface-enhanced Raman spectroscopy (SERS) combined with soft independent modelling of class analogies (SIMCAs) to develop classification models differentiating LC and FM. Venous blood samples were collected using two supports, dried bloodspot cards (DBS, n = 48 FM and n = 46 LC) and volumetric absorptive micro-sampling tips (VAMS, n = 39 FM and n = 39 LC). A semi-permeable membrane (10 kDa) was used to extract low molecular fraction (LMF) from the blood samples, and Raman spectra were acquired using SERS with gold nanoparticles (AuNPs). Soft independent modelling of class analogy (SIMCA) models developed with spectral data of blood samples collected in VAMS tips showed superior performance with a validation performance of 100% accuracy, sensitivity, and specificity, achieving an excellent classification accuracy of 0.86 area under the curve (AUC). Amide groups, aromatic and acidic amino acids were responsible for the discrimination patterns among FM and LC syndromes, emphasizing the findings from our previous studies. Overall, our results demonstrate the ability of AuNP SERS to identify unique metabolites that can be potentially used as spectral biomarkers to differentiate FM and LC.

Effects of gossypol acetate on growth, serum biochemical parameters, and intestinal health of goslings

Free gossypol (FG), the primary antinutritional component in cottonseed meal, can adversely affect the growth and health of poultry. Although younger geese are particularly sensitive to FG, the precise effects of FG on geese remain elusive. This study aimed to investigate the effects of gossypol acetate (GA), a form of FG, on the growth, serum biochemical parameters, and intestinal health of goslings. Seventy-two healthy male goslings, aged 7-day-old with similar body weight (BW), were randomly divided into 3 groups: a control group and 2 GA-treated groups (GA25 and GA50), which were orally administered GA (25 and 50 mg/kg BW) daily for 14 d. The results showed that oral administration of GA significantly suppressed BW, altered serum parameters, and impaired intestinal health in a dose- and time-dependent manner. Specifically, GA adversely affected intestinal morphology, induced oxidative stress, and inflammation, diminished immune function, and increased intestinal permeability and apoptosis of intestinal cells, consequently impairing nutrient absorption and utilization of goslings. Overall, these data indicate that GA adversely affects the growth, serum parameters, and intestinal health of goslings, providing valuable information further to understand the toxic effects of gossypol on goslings.

Stretch-Induced Spin-Cast Membranes Based on Semi-Crystalline Polymers for Efficient Microfiltration.

Microfiltration membranes derived from semi-crystalline polymers face various challenges when synthesized through the extrusion-casting technique, including the use of large quantities of polymer, long casting times, and the generation of substantial waste. This study focuses on synthesizing these membranes using spin-casting, followed by stretch-induced pore formation. Recycled high-density polyethylene (HDPE) and virgin polyethylene powder, combined with a calcium carbonate filler, were used as the source materials for the membranes. The influence of the polymer-filler ratio with and without stretching on the morphology, tensile strength, and water flow rate was investigated. Optimal conditions were determined, emphasizing a balance between pore structure and mechanical integrity. The permeable membrane exhibited a water flow rate of 19 mL/min, a tensile strength of 32 MPa, and a water contact angle of 126°. These membranes effectively eliminated suspended particles from water, with their performance evaluated against that of commercially available membranes. This research, carried out utilizing the spin-casting technique, outlines a synthesis route for microfiltration membranes tailored to semi-crystalline polymers and their plastic forms.

Highly permeable carbon nanotube membranes for efficient surface water treatment through separation and adsorption–electrochemical regeneration

Membrane-based processes feature many advantages for surface water treatment over other technologies; however, the trade-off between membrane selectivity and permeability usually results in the failure to obtain high-quality filtrate at a high permeance. In this study, we report a highly permeable sodium alginate/glutaraldehyde cross-linked carbon nanotube (CNT/SA-GA) membrane with high adsorption ability for surface water treatment. The CNT/SA-GA membranes have a well-formed hollow fiber morphology and good conductivity of 166–261 S/m. They could reject >98 % of large-sized molecules (e.g., Alcian Blue 8GX and Congo Red) at high permeances of 137–227 L/(m2·h·bar). Moreover, they could remove ~100 % of smaller molecules (e.g., Rhodamine B (RhB)) through dynamic adsorption with a capacity of ~57.3 mg/g. Benefiting from their good conductivity, the CNT/SA-GA membranes could easily decompose the pollutants after adsorption saturation through electrochemical oxidation and then regenerated themselves. Though the switch between adsorption and electrochemical oxidation (2.0 V), the CNT/SA-GA membranes could remove ~100 % RhB at a high permeance of 342 L/(m2·h·bar), which is one order of magnitude higher than those of nanofiltration membranes. When used for surface water treatment, the CNT/SA-GA membranes exhibited a much higher TOC removal rate than commercial poly(acrylonitrile) (PAN) membranes (56.2 % vs. 7.2 %). LC-MS/MS analysis showed that many small molecules such as caffeine could be effectively removed by the CNT/SA-GA membranes. In addition, they exhibited a higher fouling resistance than PAN membranes, evidenced by their lower permeance decline ratio (10.1 % vs. 43.7 %). This study will promote the development and applications of the CNT-based membranes for water purification.

Prospects and limitations of cumate-inducible lentivirus as a tool for investigating VEGF-A-mediated pathology in diabetic retinopathy

Diabetic retinopathy (DR) is a multifactorial disease displaying vascular-associated pathologies, including vascular leakage and neovascularization, ultimately leading to visual impairment. However, animal models accurately reflecting these pathologies are lacking. Vascular endothelial growth factor A (VEGF-A) is an important factor in the development of micro- and macro-vascular pathology in DR. In this study, we evaluated the feasibility of using a cumate-inducible lentivirus (LV) mediated expression of vegf-a to understand DR pathology in vitro and in vivo. Retinal pigment epithelial cells (ARPE-19) were transduced with cumate-inducible LV expressing vegf-a, with subsequent analysis of vegf-a expression and its impact on cell proliferation, viability, motility, and permeability. Cumate tolerability in adult Wistar rat eyes was assessed as an initial step towards a potential DR animal model development, by administering cumate via intravitreal injections (IVT) and evaluating consequent effects by spectral domain optical coherence tomography (SD-OCT), flash electroretinography (fERG), ophthalmic examination (OE), and immunohistochemistry. Transduction of ARPE-19 cells with cumate-inducible LV resulted in ~ 2.5-fold increase in vegf-a mRNA and ~ threefold increase in VEGF-A protein secretion. Transduced cells displayed enhanced cell proliferation, viability, permeability, and migration in tube-like structures. However, IVT cumate injections led to apparent retinal toxicity, manifesting as retinal layer abnormalities, haemorrhage, vitreous opacities, and significant reductions in a- and b-wave amplitudes, along with increased microglial activation and reactive gliosis. In summary, while cumate-inducible LV-mediated vegf-a expression is valuable for in vitro mechanistic studies in cellular drug discovery, its use is not a feasible approach to model DR in in vivo studies due to cumate-induced retinal toxicity.

Evaluating the MDCK cell permeability of greenly synthesize bimetallic Ag/Zn Nanoparticles using leaf extract of Vallaris solanacea as a potential antipesticide-resistant agent.

Bimetallic nanoparticles, particularly Ag/Zn bimetallic nanoparticles, have gained increasing attention due to their unique properties, making them suitable for a variety of applications such as catalysis, water treatment, and environmental remediation. This study aimed to elucidate the use of bimetallic nanoparticles of Ag/Zn as an alternative to resistant pesticides for pest control. Furthermore, this research demonstrates that BNPs can target specific pollutants and degrade them through various mechanisms. BNP docking with the Nilaparvata lugens cytochrome P450 (CYP6ER1) protein exhibited the lowest binding energy of-7.5 kcal/mol. The cell permeability analysis of BNP in plant cells reveals that the BNP has 0 % permeability towards any cell at-10 kcal/mol energy, which is the lowest free energy translocation pathway. The harmful leftover residues of the pesticides have a higher chance of degradability in case of interaction with BNP validated by chemical-chemical interaction analysis. Additionally, MDCK permeability coefficient of small molecules based on the regression model was calculated for BNP which authenticated the efficiency of BNP. Moreover, Swiss ADMET simulated absorption using a boiled egg model with no blood-brain barrier and gastrointestinal crossing for the expected BNP molecule has been observed. Significantly, the findings indicate that employing bimetallic nanoparticles like Ag/Zn is a crucial strategy for bioremediation because they proficiently decompose pesticides while posing no risk to humans. Our results will facilitate the design of novel BNPs materials for environmental remediation and pest control ensuring human health safety that are predicated on bimetallic nanoparticles.

An electrochemical flow cell for operando XPS and NEXAFS investigation of solid–liquid interfaces

Suitable reaction cells are critical for operando near ambient pressure (NAP) soft x-ray photoelectron spectroscopy (XPS) and near-edge x-ray absorption fine structure (NEXAFS) studies. They enable tracking the chemical state and structural properties of catalytically active materials under realistic reaction conditions, and thus allow a better understanding of charge transfer at the liquid–solid interface, activation of reactant molecules, and surface intermediate species. In order to facilitate such studies, we have developed a top-side illuminated operando spectro-electrochemical flow cell for synchrotron-based NAP-XPS/-NEXAFS studies. Our modular design uses a non-metal (PEEK) body, and replaceable membranes which can be either of x-ray transparent silicon nitride (SiN x ) or of water permeable polymer membrane materials (e.g. NafionTM). The design allows rapid sample exchange and simultaneous measurements of total electron yield, Auger electron yield and fluorescence-yield. The developed system is highly modular and can be used in the laboratory or directly at the beamline for operando XPS/ x-ray absorption spectroscopy investigations of surfaces and interfaces. We present examples to demonstrate the capabilities of the flow cell. These include an operando NEXAFS study of the Cu-redox chemistry using a SiN x /Ti-Au/Cu working electrode assembly (WEA) and a NAP-XPS/-NEXAFS study of water adsorption on a NafionTM polymer membrane based WEA (NafionTM/C/IrO x catalyst). More importantly, the spectro-electrochemical flow cell is available for user community of B07 beamlines at Diamond Light Source.

Instability analysis of pressure drop and flow characteristics in mini-channel heat sink with phase-separated configuration

Improving flow boiling stability is crucial for ensuring the safety in fields such as thermal management and microfluidic technology. Based on vapor–liquid separation analysis, multiple-pore phase-separated configurations have been proven to effectively enhance the stability of flow boiling in mini-channels. However, these structures primarily focus on expelling vapor from the mini-channel outlet, and vapor–liquid separation between adjacent mini-channels has not been addressed. In order to enhance and quantitatively analyze the vapor–liquid separation effect of phase-separated configurations, three phase-separated configurations with porous permeable membranes are prepared and experimentally studied in counter-flow mini-channel heat sinks: multiple-pore phase-separated configuration, sparse-pore phase-separated configuration, and poreless phase-separated configuration. The study found that phase-separated configurations effectively achieve vapor–liquid separation between adjacent mini-channels, thereby improving vapor–liquid distribution within the channels. Compared to sparse-pore and poreless phase-separated configurations, the multiple-pore phase-separated configuration offers greater advantages in enhancing the flow stability of mini-channel systems. Among them, the multiple-pore phase-separated configuration shows a maximum reduction of 24.71 % in the two-phase flow pressure drop, and with the increase in heat flux, this reduction becomes more pronounced compared to the conventional poreless structure. Additionally, the vapor permeation parameter X for the multiple-pore phase-separated configuration is increased by 27.66 % compared to the sparse-pore phase-separated structure, indicating a higher vapor transfer rate per unit time for the multiple-pore phase-separated structure. Simultaneously, the potential physical mechanisms underlying the suppression of flow instability in mini-channels by phase-separated structures are discussed in this study.

Novel Therapies for ANCA-associated Vasculitis: Apilimod Ameliorated Endothelial Cells Injury through TLR4/NF-κB Pathway and NLRP3 Inflammasome.

Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is a rapidly progressive form of glomerulonephritis for which effective therapeutic drugs are currently lacking, and its underlying mechanism remains unclear. This study aimed to investigate new treatment options for AAV through a combination of bioinformatics analysis and cell molecular experiments. The research utilized integrated bioinformatics analysis to identify genes with differential expression, conduct enrichment analysis, and pinpoint hub genes associated with AAV. Potential therapeutic compounds for AAV were identified using Connectivity Map and molecular docking techniques. In vitro experiments were then carried out to examine the impact and mechanism of apilimod on endothelial cell injury induced by MPO-ANCA-positive IgG. The findings revealed a set of 374 common genes from differentially expressed genes and key modules of WGCNA, which were notably enriched in immune and inflammatory response processes. A proteinprotein interaction network was established, leading to the identification of 10 hub genes, including TYROBP, PTPRC, ITGAM, KIF20A, CD86, CCL20, GAD1, LILRB2, CD8A, and COL5A2. Analysis from Connectivity Map and molecular docking suggested that apilimod could serve as a potential therapeutic cytokine inhibitor for ANCA-GN based on the hub genes. In vitro experiments demonstrated that apilimod could mitigate tight junction disruption, endothelial cell permeability, LDH release, and endothelial activation induced by MPO-ANCA-positive IgG. Additionally, apilimod treatment led to a significant reduction in the expression of proteins involved in the TLR4/NF-κB and NLRP3 inflammasome-mediated pyroptosis pathways. This study sheds light on the potential pathogenesis of AAV and highlights the protective role of apilimod in mitigating MPO-ANCA-IgG-induced vascular endothelial cell injury by modulating the TLR4/ NF-kB and NLRP3 inflammasome-mediated pyroptosis pathway. These findings suggest that apilimod may hold promise as a treatment for AAV and warrant further investigation.

Towards the Targeted Protein Degradation of PRMT1.

Targeting the protein arginine methyltransferase 1 (PRMT1) has emerged as a promising therapeutic strategy in cancer treatment. The phase 1 clinical trial for GSK3368715, the first PRMT1 inhibitor to enter the clinic, was terminated early due to a lack of clinical efficacy, extensive treatment-emergent effects, and dose-limiting toxicities. The incidence of the latter two events may be associated with inhibition-driven pharmacology as a high and sustained concentration of inhibitor is required for therapeutic effect. The degradation of PRMT1 using a proteolysis targeting chimera (PROTAC) may be superior to inhibition as proceeds via event-driven pharmacology where a PROTAC acts catalytically at a low dose. PROTACs containing the same pharmacophore as GSK3368715, combined with a motif that recruits the VHL or CRBN E3-ligase, were synthesised. Suitable cell permeability and target engagement were shown for selected candidates by the detection of downstream effects of PRMT1 inhibition and by a NanoBRET assay for E3-ligase binding, however the candidates did not induce PRMT1 degradation. This paper is the first reported investigation of PRMT1 for targeted protein degradation and provides hypotheses and insights to assist the design of PROTACs for PRMT1 and other novel target proteins.

Bacteriocins attenuate Listeria monocytogenes–induced intestinal barrier dysfunction and inflammatory response

Bacteriocins have the potential to effectively improve food-borne infections or gastrointestinal diseases and hold promise as viable alternatives to antibiotics. This study aimed to explore the antibacterial activity of three bacteriocins (nisin, enterocin Gr17, and plantaricin RX-8) and their ability to attenuate intestinal barrier dysfunction and inflammatory responses induced by Listeria monocytogenes, respectively. Bacteriocins have shown excellent antibacterial activity against L. monocytogenes without causing any cytotoxicity. Bacteriocins inhibited the adhesion and invasion of L. monocytogenes on Caco-2 cells, lactate dehydrogenase (LDH), trans-epithelial electrical resistance (TEER), and cell migration showed that bacteriocin improved the permeability of Caco-2 cells. These results were attributed to the promotion of tight junction proteins (TJP) assembly, specifically zonula occludens-1 (ZO-1), occludin, and claudin-1. Furthermore, bacteriocins could alleviate inflammation by inhibiting the mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) pathways and reducing the secretion of interleukin-6 (IL-6), interleukin-1 β (IL-1β) and tumor necrosis factor α (TNF-α). Among three bacteriocins, plantaricin RX-8 showed the best antibacterial activity against L. monocytogenes and the most pronounced protective effect on the intestinal barrier due to its unique structure. Based on our findings, we hypothesized that bacteriocins may inhibit the adhesion and invasion of L. monocytogenes by competing adhesion sites. Moreover, they may further enhance intestinal barrier function by inhibiting the expression of L. monocytogenes virulence factors, increasing the expression of TJP and decreasing the secretion of inflammatory factors. Therefore, bacteriocins will hopefully be an effective alternative to antibiotics, and this study provides valuable insights into food safety concerns.Key points• Bacteriocins show excellent antibacterial activity against L. monocytogenes• Bacteriocins improve intestinal barrier damage and inflammatory response• Plantaricin RX-8 has the best protective effect on Caco-2 cells damageGraphical

Pyridopyrimidinones as a new chemotype of calcium dependent protein kinase 1 (CDPK1) inhibitors for Cryptosporidium

The protozoan protein kinase calcium-dependent protein kinase 1 (CDPK1) has emerged as a potential therapeutic target for the treatment of cryptosporidiosis. A focused screen of known kinase inhibitors identified a pyridopyrimidinone as a new chemotype of Cryptosporidium parvum (Cp) CDPK1 inhibitors. Structural comparison of CpCDPK1 to two representative human kinases, RIPK2 and Src, revealed differences in the positioning of the αC-helix that was used in the design of a potent pyridopyrimidinone-based CpCDPK1 inhibitor 7 (a.k.a. UH15–16, IC50 = 10 nM), which blocked the growth of three C. parvum strains (EC50 = 12–40 nM) as well as C. hominis (EC50 = 85 nM) in HCT-8 host cells. Pharmacokinetic and tissue distribution analyses indicated that 7 had low systemic exposure after oral administration, but high gastrointestinal concentration, as well as good Caco-2 cell permeability. Finally, 7 demonstrated partial efficacy in an IL-12 knock-out mouse model of acute cryptosporidiosis.

Entropy production for diffusion processes across a semipermeable interface

The emerging field of stochastic thermodynamics extends classical ideas of entropy, heat, and work to nonequilibrium systems. One notable finding is that the second law of thermodynamics typically only holds after taking appropriate averages with respect to an ensemble of stochastic trajectories. The resulting average rate of entropy production then quantifies the degree of departure from thermodynamic equilibrium. In this paper we investigate how the presence of a semipermeable interface increases the average entropy production of a single diffusing particle. Starting from the Gibbs-Shannon entropy for the particle probability density, we show that a semipermeable interface or membrane S increases the average rate of entropy production by an amount that is equal to the product of the flux through the interface and the logarithm of the ratio of the probability density on either side of the interface, integrated along S. The entropy production rate thus vanishes at thermodynamic equilibrium, but can be nonzero during the relaxation to equilibrium, or if there exists a nonzero stationary equilibrium state (NESS). We then give a probabilistic interpretation of the interfacial entropy production rate using so-called snapping out Brownian motion. This also allows us to construct a stochastic version of entropy production. Finally, we illustrate the theory using the example of diffusion with stochastic resetting on a circle, and find that the average rate of interfacial entropy production is a nonmonotonic function of the resetting rate and the permeability. Published by the American Physical Society 2024

A Bioswitchable MiRNA Delivery System: Tetrahedral Framework DNA-Based miRNA Delivery System for Applications in Wound Healing.

The human body's primary line of defense, the skin, is especially prone to harm. Although microRNA (miRNA)-based therapies have attracted increasing attention for skin wound healing, their applications remain limited owing to a range of issues. Tetrahedral framework DNA (tFNA), a nanomaterial possessing nucleic acid characteristics, exhibits an excellent biocompatibility, in addition to anti-inflammatory and transdermal delivery capabilities, and can accelerate skin wound healing. Due to its potential to exert synergistic action with therapeutic miRNA, tFNA has been considered an ideal vehicle for miRNA therapy. The design and synthesis of a bioswitchable miRNA delivery system (BiRDS) is reported, which contains three miRNAs as well as a nucleic acid core to maximize the loading capacity while preserving the characteristics of tFNA. A high stability, excellent permeability of cells as well as tissues and good biological compatibility are demonstrated. By selectively inhibiting heparin-binding epidermal growth factor (HB-EGF), the BiRDS can inhibit the NF-κB pathway while simultaneously controlling the PTEN/Akt pathway. As a result, the BiRDS helps wound healing go through the inflammation to the proliferative phase. This study demonstrates the advantages of the BiRDS in miRNA-based therapy and provides new research ideas for the treatment of skin-related diseases.

Secretome profiling of human epithelial cells exposed to cigarette smoke extract and their effect on human lung microvascular endothelial cells

Cigarette smoke (CS) is one of the leading causes of pulmonary diseases and can induce lung secretome alteration. CS exposure-induced damages to human pulmonary epithelial cells and microvascular endothelial cells have been extensively demonstrated; however, the effects of the secretome of lung epithelial cells exposed to CS extracts (CSE) on lung microvascular endothelial cells are not fully understood. In this study, we aimed to determine the effects of the secretome of lung epithelial cells exposed to CSE on lung microvascular endothelial cells. Human lung epithelial cells, A549, were exposed to CSE, and the secretome was collected. Human lung microvascular endothelial cells, HULEC-5a, were used to evaluate the effect of the secretome of A549 exposed to CSE. Secretome profile, endothelial cell death, inflammation, and permeability markers were determined. CSE altered the secretome expression of A549 cells, and secretome derived from CSE-exposed A549 cells caused respiratory endothelial cell death, inflammation, and moderately enhanced endothelial permeability. This study demonstrates the potential role of cellular interaction between endothelial and epithelial cells during exposure to CSE and provides novel therapeutic targets or beneficial biomarkers using secretome analysis for CSE-related respiratory diseases.