Membrane Transport Research Articles

In situ growth of covalent organic framework on graphene oxide nanosheet enable proton-selective transport in flow battery membrane

Perfluorosulfonic acid (PFSA) is the most widely used membrane material for all-vanadium redox flow batteries (VRFB). However, severe vanadium ion permeation of PFSA membranes remains to be solved. In this work, a series of PFSA-based composite membranes are prepared by introducing two-dimensional continuous covalent organic framework (COF) to achieve enhanced performance. Two dimensional continuous Schiff base network-type COFs (GO/SNW) are synthesized by using the two-dimensional multi-functionalized surface of graphene oxide (GO) as a reaction site. Compared to the original form of agglomerated particles, two-dimensional continuous structure obtained a larger vanadium resistance area. Comparing to conventional PFSA membranes, the special pores of COF have a size sieving mechanism for selectively proton transfer, leading to simultaneously enhancement of proton conductivity and vanadium barrier property. VRFB assembled with PFSA-GO/SNW-7 showed high Coulombic efficiency (CE: 97.47%–98.18 % VS PFSA: 80.73%–91.92 %) and energy efficiency (EE: 93.04%–85.71 % VS PFSA: 77.53%–81.78 %) at 40–120 mA cm−2. In addition, there is no significant decrease in the efficiency of battery assembled with PFSA-GO/SNW-7 after 800 cycle (than 650 h) tests. This work provides a new direction in the design of fillers for mixed matrix membranes.

Perfect confinement of crown ethers in MOF membrane for complete dehydration and fast transport of monovalent ions.

Fast transport of monovalent ions is imperative in selective monovalent ion separation based on membranes. Here, we report the in situ growth of crown ether@UiO-66 membranes at a mild condition, where dibenzo-18-crown-6 (DB18C6) or dibenzo-15-crown-5 is perfectly confined in the UiO-66 cavity. Crown ether@UiO-66 membranes exhibit enhanced monovalent ion transport rates and mono-/divalent ion selectivity, due to the combination of size sieving and interaction screening effects toward the complete monovalent ion dehydration. Specifically, the DB18C6@UiO-66 membrane shows a permeation rate (e.g., K+) of 1.2 mol per square meter per hour and a mono-/divalent ion selectivity (e.g., K+/Mg2+) of 57. Theoretical calculations and simulations illustrate that, presumably, ions are completely dehydrated while transporting through the DB18C6@UiO-66 cavity with a lower energy barrier than that of the UiO-66 cavity. This work provides a strategy to develop efficient ion separation membranes via integrating size sieving and interaction screening and to illuminate the effect of ion dehydration on fast ion transport.

Decoding Organelle Interactions: Unveiling Molecular Mechanisms and Disease Therapies.

Organelles, substructures in the cytoplasm with specific morphological structures and functions, interact with each other via membrane fusion, membrane transport, and protein interactions, collectively termed organelle interaction. Organelle interaction is a complex biological process involving the interaction and regulation of several organelles, including the interaction between mitochondria-endoplasmic reticulum, endoplasmic reticulum-Golgi, mitochondria-lysosomes, and endoplasmic reticulum-peroxisomes. This interaction enables intracellular substance transport, metabolism, and signal transmission, and is closely related to the occurrence, development, and treatment of many diseases, such as cancer, neurodegenerative diseases, and metabolic diseases. Herein, the mechanisms and regulation of organelle interactions are reviewed, which are critical for understanding basic principles of cell biology and disease development mechanisms. The findings will help to facilitate the development of novel strategies for disease prevention, diagnosis, and treatment opportunities.

Size and Polarizability of Boron Cluster Carriers Modulate Chaotropic Membrane Transport

Perhalogenated closo‐borates represent a new class of membrane carriers. They owe this activity to their chaotropicity, which enables the transport of hydrophilic molecules across model membranes and into living cells. The transport efficiency of this new class of cluster carriers depends on a careful balance between their affinity to membranes and cargo, which varies with chaotropicity. However, the structure‐activity parameters that define chaotropic transport remain to be elucidated. Here, we have studied the modulation of chaotropic transport by decoupling the halogen composition from the boron core size. The binding affinity between perhalogenated decaborate and dodecaborate clusters carriers was quantified with different hydrophilic model cargos, namely a neutral and a cationic peptide, phalloidin and (KLAKLAK)2. The transport efficiency, membrane‐lytic properties, and cellular toxicity, as obtained from different vesicle and cell assays, increased with the size and polarizability of the clusters. These results validate the chaotropic effect as the driving force behind the membrane transport propensity of boron clusters. This work advances our understanding of the structural features of boron cluster carriers and establishes the first set of rational design principles for chaotropic membrane transporters.

Size and Polarizability of Boron Cluster Carriers Modulate Chaotropic Membrane Transport.

Perhalogenatedcloso-borates represent a new class of membrane carriers. They owe this activity to their chaotropicity, which enables the transport of hydrophilic molecules across model membranes and into living cells. The transport efficiency of this new class of cluster carriers depends on a careful balance between their affinity to membranes and cargo, which varies with chaotropicity. However, the structure-activity parameters that define chaotropic transport remain to be elucidated. Here, we have studied the modulation of chaotropic transport by decoupling the halogen composition from the boron core size. The binding affinity between perhalogenated decaborate and dodecaborate clusters carriers was quantified with different hydrophilic model cargos, namely a neutral and a cationic peptide, phalloidin and (KLAKLAK)2. The transport efficiency, membrane-lytic properties, and cellular toxicity, as obtained from different vesicle and cell assays, increased with the size and polarizability of the clusters. These results validate the chaotropic effect as the driving force behind the membrane transport propensity of boron clusters. This work advances our understanding of the structural features of boron cluster carriers and establishes the first set of rational design principles for chaotropic membrane transporters.

Genomic insights into the cellular specialization of predation in raptorial protists

BackgroundPredation is a fundamental mechanism for organisms to acquire energy, and various species have evolved diverse tools to enhance their hunting abilities. Among protozoan predators, raptorial Haptorian ciliates are particularly fascinating as they possess offensive extrusomes known as toxicysts, which are rapidly discharged upon prey contact. However, our understanding of the genetic processes and specific toxins involved in toxicyst formation and discharge is still limited.ResultsIn this study, we investigated the predation strategies and subcellular structures of seven Haptoria ciliate species and obtained their genome sequences using single-cell sequencing technology. Comparative genomic analysis revealed distinct gene duplications related to membrane transport proteins and hydrolytic enzymes in Haptoria, which play a crucial role in the production and discharge of toxicysts. Transcriptomic analysis further confirmed the abundant expression of genes related to membrane transporters and cellular toxins in Haptoria compared to Trichostomatia. Notably, polyketide synthases (PKS) and l-amino acid oxidases (LAAO) were identified as potentially toxin genes that underwent extensive duplication events in Haptoria.ConclusionsOur results shed light on the evolutionary and genomic adaptations of Haptorian ciliates for their predation strategies in evolution and provide insights into their toxic mechanisms.

Screening mitochondria-related biomarkers in skin and plasma of atopic dermatitis patients by bioinformatics analysis and machine learning

BackgroundThere is a significant imbalance of mitochondrial activity and oxidative stress (OS) status in patients with atopic dermatitis (AD). This study aims to screen skin and peripheral mitochondria-related biomarkers, providing insights into the underlying mechanisms of mitochondrial dysfunction in AD.MethodsPublic data were obtained from MitoCarta 3.0 and GEO database. We screened mitochondria-related differentially expressed genes (MitoDEGs) using R language and then performed GO and KEGG pathway analysis on MitoDEGs. PPI and machine learning algorithms were also used to select hub MitoDEGs. Meanwhile, the expression of hub MitoDEGs in clinical samples were verified. Using ROC curve analysis, the diagnostic performance of risk model constructed from these hub MitoDEGs was evaluated in the training and validation sets. Further computer-aided algorithm analyses included gene set enrichment analysis (GSEA), immune infiltration and mitochondrial metabolism, centered on these hub MitoDEGs. We also used real-time PCR and Spearman method to evaluate the relationship between plasma circulating cell-free mitochondrial DNA (ccf-mtDNA) levels and disease severity in AD patients.ResultsMitoDEGs in AD were significantly enriched in pathways involved in mitochondrial respiration, mitochondrial metabolism, and mitochondrial membrane transport. Four hub genes (BAX, IDH3A, MRPS6, and GPT2) were selected to take part in the creation of a novel mitochondrial-based risk model for AD prediction. The risk score demonstrated excellent diagnostic performance in both the training cohort (AUC = 1.000) and the validation cohort (AUC = 0.810). Four hub MitoDEGs were also clearly associated with the innate immune cells’ infiltration and the molecular modifications of mitochondrial hypermetabolism in AD. We further discovered that AD patients had considerably greater plasma ccf-mtDNA levels than controls (U = 92.0, p< 0.001). Besides, there was a significant relationship between the up-regulation of plasma mtDNA and the severity of AD symptoms.ConclusionsThe study highlights BAX, IDH3A, MRPS6 and GPT2 as crucial MitoDEGs and demonstrates their efficiency in identifying AD. Moderate to severe AD is associated with increased markers of mitochondrial damage and cellular stress (ccf=mtDNA). Our study provides data support for the variation in mitochondria-related functional characteristics of AD patients.

Identification and characterization of a new potent inhibitor targeting CtBP1/BARS in melanoma cells

BackgroundThe C-terminal-binding protein 1/brefeldin A ADP-ribosylation substrate (CtBP1/BARS) acts both as an oncogenic transcriptional co-repressor and as a fission inducing protein required for membrane trafficking and Golgi complex partitioning during mitosis, hence for mitotic entry. CtBP1/BARS overexpression, in multiple cancers, has pro-tumorigenic functions regulating gene networks associated with “cancer hallmarks” and malignant behavior including: increased cell survival, proliferation, migration/invasion, epithelial-mesenchymal transition (EMT).Structurally, CtBP1/BARS belongs to the hydroxyacid-dehydrogenase family and possesses a NAD(H)-binding Rossmann fold, which, depending on ligands bound, controls the oligomerization of CtBP1/BARS and, in turn, its cellular functions.Here, we proposed to target the CtBP1/BARS Rossmann fold with small molecules as selective inhibitors of mitotic entry and pro-tumoral transcriptional activities.MethodsStructured-based screening of drug databases at different development stages was applied to discover novel ligands targeting the Rossmann fold. Among these identified ligands, N-(3,4-dichlorophenyl)-4-{[(4-nitrophenyl)carbamoyl]amino}benzenesulfonamide, called Comp.11, was selected for further analysis. Fluorescence spectroscopy, isothermal calorimetry, computational modelling and site-directed mutagenesis were employed to define the binding of Comp.11 to the Rossmann fold. Effects of Comp.11 on the oligomerization state, protein partners binding and pro-tumoral activities were evaluated by size-exclusion chromatography, pull-down, membrane transport and mitotic entry assays, Flow cytometry, quantitative real-time PCR, motility/invasion, and colony assays in A375MM and B16F10 melanoma cell lines. Effects of Comp.11 on tumor growth in vivo were analyzed in mouse tumor model.ResultsWe identify Comp.11 as a new, potent and selective inhibitor of CtBP1/BARS (but not CtBP2). Comp.11 directly binds to the CtBP1/BARS Rossmann fold affecting the oligomerization state of the protein (unlike other known CtBPs inhibitors), which, in turn, hinders interactions with relevant partners, resulting in the inhibition of both CtBP1/BARS cellular functions: i) membrane fission, with block of mitotic entry and cellular secretion; and ii) transcriptional pro-tumoral effects with significantly hampered proliferation, EMT, migration/invasion, and colony-forming capabilities. The combination of these effects impairs melanoma tumor growth in mouse models. ConclusionsThis study identifies a potent and selective inhibitor of CtBP1/BARS active in cellular and melanoma animal models revealing new opportunities to study the role of CtBP1/BARS in tumor biology and to develop novel melanoma treatments.

Two-phase flow in the gas diffusion layer with different perforation of proton exchange membrane fuel cell

ABSTRACT Gas diffusion layer (GDL) is an important pathway for water transport in the proton exchange membrane fuel cell. The presence of excessive liquid water in the cathode GDL will cause “water flooding” and block the reactant transport path to catalyst sites. Therefore, it’s critical to understand water transfer mechanism in GDL and propose novel strategy to improve water management. In this study, the effect of GDL with different perforation holes on liquid water transport behavior are investigated by volume of fluid method. The simulation model is validated by comparing with the reported data. The results show that the GDL with perforation holes will accelerate the liquid water breakthrough. Specially, the GDL with cylindrical perforation achieves the lowest breakthrough pressure, and most excellent water drainage capacity under various pressure drops. The gradient hydrophobic distribution in GDL will improve the water breakthrough path and drainage capacity. However, gradient hydrophobic treatment in GDL with conical perforations will result more water leakage along the though-plane direction. The simulation results will provide significant guidance for designing high performance GDL and improving the water management in proton exchange membrane fuel cell.

Proteomic characterization of the different stages of seed germination in Cupressus gigantea

Abstract Seed germination is a pivotal period of plant growth and development. This process can be divided into four major stages, swelling absorption, seed coat dehiscence, radicle emergence and radicle elongation. Cupressus gigantea, a tree native to Tibet, China, is characterized by its resistance to stresses such as cold, and drought, and has a high economic and ecological value. Nevertheless, given its unique geographic location, its seeds are difficult to germinate. Therefore, it is crucial to explore the mechanisms involved in seed germination in this species to improve the germination efficiency of its seeds, thereby protecting this high-quality resource. Here, our findings indicate that seed germination was enhanced when exposed to a 6-h/8-h light/dark photoperiod, coupled with a temperature of 20°C. Furthermore, the application of exogenous GA3 (1 mg/ml, about 2.9 mM) stimulated the germination of C. gigantea seeds. Subsequently, proteomics was used to detect changes in protein expression during the four stages of seed germination. We identified 34 differentially expressed proteins (DEPs), including 13 at the radicle pre-emergence stage, and 17 at the radicle elongation stage. These DEPs were classified into eight functional groups, cytoskeletal proteins, energy metabolism, membrane transport, stress response, molecular chaperones, amino acid metabolism, antioxidant system and ABA signalling pathway. Most of them were found to be closely associated with amino acid metabolism. Combined, these findings indicate that, along with temperature and light, exogenous GA3 can increase the germination efficiency of C. gigantea seeds. Our study also offers insights into the changes in protein expression patterns in C. gigantea seeds during germination.

Ecotoxicological effects of polyethylene microplastics and lead (Pb) on the biomass, activity, and community diversity of soil microbes

Microplastics and heavy metals are ubiquitous and persistent contaminants that are widely distributed worldwide, yet little is known about the effects of their interaction on soil ecosystems. A soil incubation experiment was conducted to investigate the individual and combined effects of polyethylene microplastics (PE-MPs) and lead (Pb) on soil enzymatic activities, microbial biomass, respiration rate, and community diversity. The results indicate that the presence of PE-MPs notably reduced soil pH and elevated soil Pb bioavailability, potentially exacerbated the combined toxicity on the biogeochemical cycles of soil nutrients, microbial biomass carbon and nitrogen, and the activities of soil urease, sucrase, and alkaline phosphatase. Soil CO2 emissions increased by 7.9% with PE-MPs alone, decreased by 46.3% with single Pb, and reduced by 69.4% with PE-MPs and Pb co-exposure, compared to uncontaminated soils. Specifically, the presence of PE-MPs and Pb, individually and in combination, facilitated the soil metabolic quotient, leading to reduced microbial metabolic efficiency. Moreover, the addition of Pb and PE-MPs modified the composition of the microbial community, leading to the enrichment of specific taxa. Tax4Fun analysis showed the effects of Pb, PE-MPs and their combination on the biogeochemical processes and ecological functions of microbes were mainly by altering amino acid metabolism, carbohydrate metabolism, membrane transport, and signal transduction. These findings offer valuable insights into the ecotoxicological effects of combined PE-MPs and Pb on soil microbial dynamics, reveals key assembly mechanisms and environmental drivers, and highlights the potential threat of MPs and heavy metals to the multifunctionality of soil ecosystems.

Antibacterial activity of Angelica essential oil, its mechanism against Pseudomonas fluorescens, and its application in the preservation of chilled fresh beef

The mechanism by which Angelica essential oil (AEO) can act as an antimicrobial agent at cellular and metabolic levels to inhibit Pseudomonas fluorescens (P. fluorescens), and its effectiveness in beef preservation, were investigated and evaluated in this study. Our results showed that the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of AEO to P. fluorescens were 12.5 μL/mL and 25 μL/mL, respectively, at which AEO could effectively inhibit P. fluorescens reproduction and retard its growth (p < 0.05). Severe morphological damage to the AEO-treated cells of the microorganism, including cell walls and membranes, were observed via scanning electron microscopy (SEM). AEO treatment was also seen to lead to an increase in alkaline phosphatase (AKPase) activity and conductivity, and a significant leakage of intracellular macromolecular components (such as nucleic acids and proteins), providing further evidence of damage to the integrity of cell wall and cell membrane. Metabolomics analysis revealed that the differential metabolites in the AEO hindered nucleic acid synthesis and expression in the P. fluorescens, leading to tricarboxylic acid (TCA) cycle blockage and amino acid restriction, energy metabolism disorders and membrane damage, mainly through nucleotide metabolism, amino acid metabolism, carbohydrate metabolism and membrane transport. Moreover, application testing demonstrated the efficacy of AEO in slowing the increase of beef pH and total volatile basic nitrogen (TVB-N), extending the shelf life of chilled beef by 5.39 d, and effectively maintaining the organoleptic quality of beef. These results lay a foundation for the development of AEO as a natural bacteriostatic agent.

Bio-inspired superhydrophobic fiber membrane for oil-water separation and non-destructive transport of liquids in corrosive environments

Conventional polymer separation membranes or coatings suffer from poor separation performance and serious failure in highly corrosive environments, due to their low chemical and mechanical stability. Herein, a simple electrospraying and electrospinning strategy was used to prepare flexible superhydrophobic carbon fiber membranes (FSCFM). The wettability of FSCFM was improved by forming a lotus leaf-like hierarchical rough structure on its surface. The FSCFM exhibited an excellent permeation flux of immiscible oil-water mixtures (up to 15,800 L m-2 h-1) and water-in-oil emulsions (over 5,500 L m-2 h-1), while the separation efficiencies were always kept at more than 99% after 25 consecutive separations. Even in corrosive environments, its separation performance did not show any degradation. Notably, except for recovering floating oil under external driving forces with excellent cyclic stabilities, FSCFM was also able to transport various corrosive solutions with high efficiencies (99.9%). After multiple mechanical damages and bending cycles, the FSCFM remained superhydrophobic. It could also maintain its repellency in strong acids/bases, high salt solutions and even under high-temperature environments (94.5 °C). These superior properties make it a strong candidate for oil-water/emulsion separation and non-destructive transport of highly corrosive fluids.

Transglutaminase-mediated stiffening of the glomerular basement membrane mitigates pressure-induced reductions in molecular sieving coefficient by reducing compression

Proteinuria, the presence of high molecular weight proteins in the urine, is a primary indicator of chronic kidney disease. Proteinuria results from increased molecular permeability of the glomerular filtration barrier combined with saturation or defects in tubular protein reabsorption. Any solute that passes into the glomerular filtrate traverses the glomerular endothelium, the glomerular basement membrane, and the podocyte slit diaphragm. Damage to any layer from the filter has reciprocal effects on other layers to increase glomerular permeability. The GBM is thought to act as a compressible ultrafilter that has increased molecular selectivity with increased pressure due to compression that reduced the porosity of the GBM with increased pressure. In multiple forms of chronic kidney disease, crosslinking enzymes are upregulated and may act to increase GBM stiffness. Here we show that enzymatically crosslinking porcine GBM with transglutaminase increases the stiffness of the GBM and mitigates pressure-dependent reductions in molecular sieving coefficient. This was modeled mathematically using a modified membrane transport model accounting for GBM compression. Changes in the mechanical properties of the GBM may contribute to proteinuria through pressure-dependent effects on GBM porosity.

Atomic insight into the transport mechanism of CO2/N2 molecules passing through UiO-66/PDMS membranes

Mixed matrix membranes (MMM) prepared by adding MOF filler to polymeric membranes are expected to overcome the trade-off effect inherent in membranes and improved the efficiency of separation and CO2 capture. In this work, concentration-gradient-driven molecular dynamics (CGD-MD) was employed to explore gas permeability of pure CO2/N2 and their mixture in PDMS membrane, UiO-66 membrane and UiO-66/PDMS membrane, respectively. The transport mechanism of gas molecules in the membranes was illustrated from molecular level. Moreover, the simulated permeability and predict permeability were compared to investigate the effect of the porosity at the UiO-66/PDMS interface on gas transport in mixed matrix membrane. The competitive effect between CO2 and N2 molecules in mixture could explain their different permeability in different membranes. The pore sizes distribution map and pore connectivity diagrams within UiO-66/PDMS membrane shown that the relative larger pore size and interconnectivity voids are formed in the interfacial region, and the interfacial porosity formed in UiO-66/PDMS membrane shown a positive effect on pure N2 transport and almost no effect on pure CO2 permeability. While the selectivity of UiO-66/PDMS membrane for the mixed gas case is improved because CO2 increases the retention time of N2 in the membrane and decreases the N2 permeability. This work provides a worthwhile perspective on the design of high-performance membranes for separation.

The Effects of the Coating and Aging of Biodegradable Polylactic Acid Membranes on In Vitro Primary Human Retinal Pigment Epithelium Cells

Age-related macular degeneration (AMD) is the most frequent cause of blindness in developed countries. The replacement of dysfunctional human retinal pigment epithelium (hRPE) cells by the transplantation of in vitro-cultivated hRPE cells to the affected area emerges as a feasible strategy for regenerative therapy. Synthetic biomimetic membranes arise as powerful hRPE cell carriers, but as biodegradability is a requirement, it also poses a challenge due to its limited durability. hRPE cells exhibit several characteristics that putatively respond to the type of membrane carrier, and they can be used as biomarkers to evaluate and further optimize such membranes. Here, we analyze the pigmentation, transepithelial resistance, genome integrity, and maturation markers of hRPE cells plated on commercial polycarbonate (PC) versus in-house electrospun polylactide-based (PLA) membranes, both enabling separate apical/basolateral compartments. Our results show that PLA is superior to PC-based membranes for the cultivation of hRPEs, and the BEST1/RPE65 maturation markers emerge as the best biomarkers for addressing the quality of hRPE cultivated in vitro. The stability of the cultures was observed to be affected by PLA aging, which is an effect that could be partially palliated by the coating of the PLA membranes.

P155 Gene expression in hypermobility and the role of inflammation

Abstract Background/Aims Hypermobile conditions, including Ehlers-Danlos syndrome and joint hypermobility syndrome, encompass a broad spectrum of heterogenous clinical entities characterised by excessive range of joint movements and variable extra-articular features. The etiological basis of these conditions is thought to relate to abnormal collagen assembly, which impairs the structural integrity of connective tissue, although precise mechanisms remain both debated and incompletely understood. Despite the established strong heritability of hypermobility, a definitive genetic cause remains unidentifiable in most hypermobile patients, highlighting the need to further characterize the genetic landscape of hypermobile conditions. In this study, we therefore employ transcriptomic analysis as an alternate means of elucidating the genetic basis of hypermobility. Methods We tested for the effects of hypermobility on gene expression, at baseline and following an inflammatory challenge, by re-analysing existing transcriptomic data gathered from healthy subjects and patients with fibromyalgia and chronic fatigue using total RNA sequencing of blood samples (Illumina NextSeq 500). From each participant, two blood samples were taken on separate occasions: one after a saline injection and the other after an inflammatory challenge, the typhoid vaccination, in a cross-over design. Participants were assigned to hypermobile or non-hypermobile conditions in accordance with criterion 1: generalized joint hypermobility of the Diagnostic Criteria for Hypermobile Ehlers-Danlos Syndrome (hEDS) produced by the International Consortium on Ehlers-Danlos Syndromes &amp; Related disorders. Differential gene expression analysis comparing hypermobile and non-hypermobile participants was performed using EdgeR software in R studio. Baseline differences were determined by comparing post-saline samples between groups. Differential responses to the inflammatory challenge were detected by comparison of post-typhoid samples between groups. Gene ontology on differentially expressed genes was performed using DAVID’s Functional Annotation Clustering tool. Results We found 288 differentially expressed genes post-saline (i.e at baseline) and 1113 post-typhoid at p &amp;lt; 0.05 although none passed false discovery rate. At baseline, differentially expressed genes were significantly enriched for nuclear, endoplasmic reticulum, and microtubular genes (enrichment score = 2.96, 2.02, 1.3 respectively); and post-typhoid, for 24 clusters, the three most significant being synaptic, ion transport, and plasma membrane genes (enrichment score = 11.34, 8.71, and 7.3 respectively). Conclusion These data demonstrate distinct patterns of gene expression, both at baseline and during inflammation, which implicate potential biological pathways in the pathophysiology of hypermobility. These results also contribute to a growing understanding of the genetic basis of hypermobility and may inform future higher-powered studies to validate our findings. Disclosure J. Porter: None. M. Amato: None. K. Themelis: None. H. Critchley: None. S. Newbury: None. K. Davies: None. N. Harrison: None. B. Towler: None. J. Eccles: Grants/research support; J.E. has received funding from Versus Arthritis, National Institute for Health Research and the Fibroduck Foundation.

Metal-phenolic network as precursor complex coating for forward osmosis membrane with enhanced antifouling property

ABSTRACT In this study, a multi-functional layer was developed based on the commercially available cellulose triacetate (CTA) forward osmosis (FO) membrane to improve its antifouling property. Tannic acid/ferric ion (TA/Fe3+) complexes were firstly coated as a precursor layer on the membrane surface via self-assembly. Afterwards, the tannic acid/diethylenetriamine (TA/DETA) hydrophilic functional layer was further coated, following Ag/polyvinylpyrrolidone (PVP) anti-bacterial layer was formed in situ through the reducibility of TA to obtain TA/Fe3+-TA/DETA-Ag/PVP-modified membrane. The optimized precursor layer was acquired by adjusting the buffer solution pH to 8, TA/Fe3+ ratio to 4 and the number of self-assembled layers to 5. The permeability testing results illustrated that the functional layer had an insignificant effect on the membrane transport parameters. The TA/Fe3+-TA/DETA-Ag/PVP-modified membrane simultaneously exhibited excellent physical and chemical stability. The coated membrane also demonstrated enhanced anti-bacterial properties, achieving 98.63 and 97.30% inhibition against Staphylococcus aureus and Escherichia coli, respectively. Furthermore, the dynamic fouling experiment showed a 12% higher water flux decrease for the TA/Fe3+-TA/DETA-Ag/PVP CTA membrane compared to the nascent CTA membrane, which proved its excellent antifouling performance. This work provides a feasible strategy to heighten the antifouling property of the CTA FO membrane.

Effects of Lactobacillus plantarum (L) and molasses (M) on nutrient composition, aerobic stability, and microflora of alfalfa silage in sandy grasslands.

The objective of this experiment was to investigate the effects of Lactobacillus plantarum and molasses on the nutrient composition, fermentation quality, bacterial count, aerobic stability, and microflora of alfalfa silage in sandy grasslands. The experimental treatments included control (CK), 106 CFU/g Lactobacillus plantarum (L), 5% molasses (M), and 106 CFU/g Lactobacillus plantarum + 5% molasses (LM). The nutrient composition, fermentation quality, bacterial count, aerobic stability, and microflora were determined after 14 days and 56 days of ensiling, respectively. The results showed that the addition of L, M, and LM reduced dry matter loss (DM), neutral detergent fiber (NDF), and acid detergent fiber (ADF) content, and increased water-soluble carbohydrates (WSC) and ether extract (EE) content, compared to the CK group. Meanwhile, more lactic acid (LA) and accelerated fermentation were observed, causing the pH value to drop below 4.5 in the L, M, and LM groups after 56 days of ensiling. The addition of L, M, and LM promoted lactic acid bacteria (LAB), and inhibited yeast. The addition of L significantly increased the content of acetic acid (AA). In terms of microflora, the addition of L, M, and LM made Firmicutes become the dominant bacterial phylum earlier, while Lactobacillus, Weissella, and Pediococcus had a higher abundance. According to the result of Pearson's correlation, there is a very significant negative correlation between pH value and Lactobacillus (P < 0.01) and a very significant positive correlation between pH value and Lactococcus, Enterobacter, Enterococcus, and Leuconostoc (P < 0.01), which may be inhibited by Lactobacillus under the decreased pH value. The results of the prediction of microbial genes indicated that the addition of M could enhance the carbohydrate metabolism and membrane transport metabolism, which may contribute to LA production by LAB metabolism. In general, L, M and LM all improved the fermentation quality and reduced the loss of nutrients to varying degrees, but considering the fermentation quality, the overall effects of M and LM were better than L. M and LM are recommended to be used as silage additives in the process of alfalfa silage in sandy grasslands to improve the quality.

Inhibition of human drug transporter activities by succinate dehydrogenase inhibitors

Succinate dehydrogenase inhibitors (SDHIs) are widely-used fungicides, to which humans are exposed and for which putative health risks are of concern. In order to identify human molecular targets for these environmental chemicals, the interactions of 15 SDHIs with activities of main human drug transporters implicated in pharmacokinetics were investigated in vitro. 5/15 SDHIs, i.e., benzovindiflupyr, bixafen, fluxapyroxad, pydiflumetofen and sedaxane, were found to strongly reduce activity of the renal organic anion transporter (OAT) 3, in a concentration-dependent manner (with IC50 values in the 1.0–3.9 μM range), without however being substrates for OAT3. Moreover, these 5/15 SDHIs decreased the membrane transport of estrone-3 sulfate, an endogenous substrate for OAT3, and sedaxane was predicted to inhibit in vivo OAT3 activity in response to exposure to the acceptable daily intake (ADI) dose. In addition, pydiflumetofen strongly inhibited the renal organic cation transporter (OCT) 2 (IC50 = 2.0 μM) and benzovindiflupyr the efflux pump breast cancer resistance protein (BCRP) (IC50 = 3.9 μM). Other human transporters, including organic anion transporting polypeptide (OATP) 1B1 and OATP1B3 as well as multidrug and toxin extrusion protein (MATE) 1 and MATE2-K were moderately or weakly inhibited by SDHIs, whereas P-glycoprotein, multidrug resistance-associated protein (MRP), OCT1 and OAT1 activities were not or only marginally impacted. Then, some human drug transporters, especially OAT3, constitute molecular targets for SDHIs. This could have toxic consequences, notably with respect to levels of endogenous compounds and metabolites substrates for the considered transporters or to potential SDHI-drug interactions. This could therefore contribute to putative health risk of these fungicides.