Microtube self-assembly leads to conformational freezing point depression.

HYPOTHESIS: Multi-walled tubular aggregates formed by hierarchical self-assembly of beta-cyclodextrin (ß-CD) and sodium dodecylsulfate (SDS) hold a great potential as microcarriers. However, the underlying mechanism for this self-assembly is not well understood. To advance the application of these structures, it is essential to fine-tune the cavity size and comprehensively elucidate the energetic balance driving their formation: the bending modulus versus the microscopic line tension. EXPERIMENTS: We investigated temperature-induced changes in the hierarchical tubular aggregates using synchrotron small-angle X-ray scattering across a broad concentration range. Detailed analysis of the scattering patterns enabled us to determine the structural parameters of the microtubes and to construct a phase diagram of the system. FINDINGS: The microtubes grow from the outside in and melt from the inside out. We relate derived structural parameters to enthalpic changes driving the self-assembly process on the molecular level in terms of their bending modulus and microscopic line tension. We find that the conformation of the crystalline bilayer affects the saturation concentration, providing an example of a phenomenon we call conformational freezing point depression. Inspired by the colligative phenomenon of freezing point depression, well known from undergraduate physics, we model this system by including the membrane conformation, which can describe the energetics of this hierarchical system and give access to microscopic properties without free parameters.

Sources of Discrepancy between Retinal Nerve Fiber Layer and Bruch's Membrane Opening-Minimum Rim Width Thickness in Eyes with Glaucoma.

Purpose: To compare the discrepancies between circumpapillary retinal nerve fiber layer (RNFL) and Bruch's membrane opening-minimum rim width (BMO-MRW) thickness in glaucoma eyes. Design: A cross-sectional observational study. Subjects: One hundred eighty-six eyes (118 patients) with glaucoma. Methods: OCT optic nerve head volume scans of patients enrolled in the Advanced Glaucoma Progression Study at the final available visit were exported. The RNFL and BMO-MRW measurements were averaged into corresponding 7.5° sectors, and the nasal sector data were excluded from analyses. A 2-stage screening process was used to identify true mismatches between the RNFL and BMO-MRW measurements, in which either the RNFL or BMO-MRW value was in the less than first percentile range while its counterpart was in the greater than first percentile range on the temporal-superior-nasal-inferior-temporal curve. The prevalence of these mismatches was mapped, and corresponding images were reviewed to determine the underlying cause of these discrepancies. Main Outcome Measures: Proportion of mismatches between RNFL and BMO-MRW, location of mismatches between RNFL and BMO-MRW, anatomical causes of mismatches between RNFL and BMO-MRW. Results: Mismatch analysis revealed true mismatches between RNFL and BMO-MRW in 7.7% of sectors. High BMO-MRW with low corresponding RNFL mismatches were most frequently located at the 45° and 322.5° sectors, whereas high RNFL with corresponding low BMO-MRW mismatches peaked at the 75° sector. Large blood vessels accounted for 90.9% of high RNFL with low BMO-MRW mismatches. Small to large blood vessels accounted for 62.9% of high BMO-MRW with low RNFL mismatches; the remaining mismatches could be attributed to retinoschisis or inclusion of outer retinal layers in BMO-MRW measurements. Conclusions: Although overall agreement between RNFL and BMO-MRW measurements is good in areas with advanced damage, blood vessels and other anatomical factors can cause discrepancies between the 2 types of structural measurements and need to be considered when evaluating the utility of such measurements for detection of change. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Characterization of Bacterial Membrane Fatty Acid Profiles for Biofilm Cells.

When submitted to environmental stresses, bacteria can modulate its fatty acid composition of membrane phospholipids in order to optimize membrane fluidity. Characterization of bacterial membrane fatty acid profiles is thus an interesting indicator of cellular physiological state. The methodology described here aims to improve the recovering of biofilm cells for the characterization of their fatty acid profiles. The saponification reagent is directly applied on the whole biofilm before the removal of cells from the inert surface. In this way, maximum of the cells and their fatty acids can be recovered from the deepest layers of the biofilm.

Human milk fat globule delivers entrapped probiotics to the infant's gut and acts synergistically to ameliorate oxidative and pathogenic stress.

The human milk fat globule membrane (hMFGM) and Lactobacillus modulate the infant's gut and benefit health. Hence, the current study assesses the probiotic potential of Lactiplantibacillus plantarum (MRK3), Limosilactobacillus ferementum (MK1) isolated from infant feces, and its interaction with hMFGM during conditions mimicking infant digestive tract. Both strains showed high tolerance to gastrointestinal conditions, cell surface hydrophobicity, and strong anti-pathogen activity against Staphylococcus aureus. During digestion, hMFGM significantly exhibited xanthine oxidase activity, membrane roughness, and surface topography. In the presence of hMFGM, survival of MRK3 was higher than MK1, and electron microscopic observation revealed successful entrapment of MRK3 in the membrane matrix throughout digestion. Interestingly, probiotic-membrane matrix interaction showed significant synergy to alleviate oxidative stress and damage induced by cell-free supernatant of Escherichia coli in Caco-2 cells. Our results show that a probiotic-encapsulated membrane matrix potentially opens the functional infant formula development pathway.

In-situ activation of biomimetic single-site bioorthogonal nanozyme for tumor-specific combination therapy.

Copper-catalyzed click chemistry offers creative strategies for activation of therapeutics without disrupting biological processes. Despite tremendous efforts, current copper catalysts face fundamental challenges in achieving high efficiency, atom economy, and tissue-specific selectivity. Herein, we develop a facile "mix-and-match synthetic strategy" to fabricate a biomimetic single-site copper-bipyridine-based cerium metal-organic framework (Cu/Ce-MOF@M) for efficient and tumor cell-specific bioorthogonal catalysis. This elegant methodology achieves isolated single-Cu-site within the MOF architecture, resulting in exceptionally high catalytic performance. Cu/Ce-MOF@M favors a 32.1-fold higher catalytic activity than the widely used MOF-supported copper nanoparticles at single-particle level, as first evidenced by single-molecule fluorescence microscopy. Furthermore, with cancer cell-membrane camouflage, Cu/Ce-MOF@M demonstrates preferential tropism for its parent cells. Simultaneously, the single-site CuII species within Cu/Ce-MOF@M are reduced by upregulated glutathione in cancerous cells to CuI for catalyzing the click reaction, enabling homotypic cancer cell-activated in situ drug synthesis. Additionally, Cu/Ce-MOF@M exhibits oxidase and peroxidase mimicking activities, further enhancing catalytic cancer therapy. This study guides the reasonable design of highly active heterogeneous transition-metal catalysts for targeted bioorthogonal reactions.

Evaluation of the shear stability of aerobic granular sludge from a pilot-scale membrane bioreactor: Establishment of a quantitative method.

This work established a quantitative method to access the shear stability of aerobic granular sludge (AGS) and validated its feasibility by using the mature AGS from a pilot-scale (50 tons/day) membrane bioreactor (MBR) for treating real municipal wastewater. The results showed that the changing rate (ΔS) of the peak area (S) of granule size distribution (GSD) exhibited an exponential relationship (R2≥0.76) with the shear time (y=a-b·cx), which was a suitable indicative index to reflect the shear stability of different AGS samples. The limiting granule size (LGS) was defined and proposed to characterize the equilibrium size for AGS after being sheared for a period of time, whose value in terms of Dv50 showed high correlation (R2=0.92) with the parameter a. The free Ca2+ (28.44-34.21 mg/L) in the influent specifically interacted with polysaccharides (PS) in the granule's extracellular polymeric substance (EPS) as a nucleation site, thereby inducing the formation of Ca precipitation to enhance its Young's modulus, while Ca2+ primarily interacted with PS in soluble metabolic product (SMP) during the initial granulation process. Furthermore, the Young's modulus significantly affected the parameter a related to shear stability (R2=0.99). Since the parameter a was more closely related (R2=1.00) to ΔS than that of the parameter b or c, the excellent correlation (R2=0.99) between the parameter a and the wet density further verified the feasibility of this method.

Enhancing levan biosynthesis by destroying the strongly acidic environment caused by membrane-bound glucose dehydrogenase (mGDH) in Gluconobacter sp. MP2116.

Levan produced by Gluconobacter spp. has great potential in biotechnological applications. However, Gluconobacter spp. can synthesize organic acids during fermentation, resulting in environmental acidification. Few studies have focused on the effects of environmental acidification on levan synthesis. This study revealed that the organic acids, mainly gluconic acid (GA) and 2-keto-gluconic acid (2KGA) secreted by Gluconobacter sp. MP2116 created a highly acidic environment (pH < 3) that inhibited levan biosynthesis. The levansucrase derived from strain MP2116 had high enzyme activity at pH 4.0 âˆ¼ pH 6.5. When the ambient pH was less than 3, the enzyme activity decreased by 67 %. Knocking out the mgdh gene of membrane-bound glucose dehydrogenase (mGDH) in the GA and 2KGA synthesis pathway in strain MP2116 eliminated the inhibitory effect of high acid levels on levansucrase function. As a result, the levan yield increased from 7.4 g/l (wild-type) to 18.8 g/l (Δmgdh) during fermentation without pH control. This study provides a new strategy for improving levan production by preventing the inhibition of polysaccharide synthesis by environmental acidification.

Photoswitchable detergents for light-controlled liposome lysis and channel gating.

Modulation of membrane properties via photoswitchable lipids has attracted attention due to the unparalleled spatiotemporal resolution of their functional control. Beside lipids, detergents are another prominent class for selective membrane perturbations owing to their ease of handling and spontaneous insertion in lipid bilayers. Herein, we describe the synthesis and characterization of three classes of visible light-sensitive surfactants with various azobenzene tail chain lengths. The photoswitchable detergents show water-solubility and micellization as well as undergo reversible isomerization under blue-/green light illumination. We demonstrate that the light-induced structural change of azobenzene can lead to vesicle rupture, making them a tool for controlled cargo release from vehicles. Via spontaneous insertion into the plasma membrane of mammalian cells transiently transfected with MscL, we used the azobenzene-derived detergents to optically activate the transmembrane mechanosensitive channel. This led to the rapid controlled uptake of membrane-impermeable molecules. Since detergents are extensively used in biochemistry and biotechnology, we propose that the photoswitchable detergents will be useful tools for the spatiotemporal modulation of membrane properties. Additionally, our work provides a design strategy for new detergents in membrane (protein) research.

Characterization of a membrane toxin-antitoxin system, tsaAT, from Staphylococcus aureus.

Bacterial toxin-antitoxin (TA) systems consist of a toxin that inhibits essential cellular processes, such as DNA replication, transcription, translation, or ATP synthesis, and an antitoxin neutralizing their cognate toxin. These systems have roles in programmed cell death, defense against phage, and the formation of persister cells. Here, we characterized the previously identified Staphylococcus aureus TA system, tsaAT, which consists of two putative membrane proteins: TsaT and TsaA. Expression of the TsaT toxin caused cell death and disrupted membrane integrity, whereas TsaA did not show any toxicity and neutralized the toxicity of TsaT. Furthermore, subcellular fractionation analysis demonstrated that both TsaA and TsaT localized to the cytoplasmic membrane of S. aureus expressing either or both 3xFLAG-tagged TsaA and 3xFLAG-tagged TsaT. Taken together, these results demonstrate that the TsaAT TA system consists of two membrane proteins, TsaA and TsaT, where TsaT disrupts membrane integrity, ultimately leading to cell death. Although sequence analyses showed that the tsaA and tsaT genes were conserved among Staphylococcus species, amino acid substitutions between TsaT orthologs highlighted the critical role of the 6th residue for its toxicity. Further amino acid substitutions indicated that the glutamic acid residue at position 63 in the TsaA antitoxin and the cluster of five lysine residues in the TsaT toxin are involved in TsaA's neutralization reaction. This study is the first to describe a bacterial TA system wherein both toxin and antitoxin are membrane proteins. These findings contribute to our understanding of S. aureus TA systems and, more generally, give new insight into highly diverse bacterial TA systems.

Osseodensification technique in crestal maxillary sinus elevation-A narrative review.

Osseodensification is a novel approach that has significantly advanced the field of implant dentistry, particularly in the context of transcrestal maxillary sinus floor elevation. This technique involves the use of specially designed burs that compact and densify bone along the osteotomy walls, thereby enhancing implant primary stability and facilitating osseointegration in low-density bone. This article reviews the historical evolution of implant site preparation, and the biomechanical, histological, and clinical evidence of osseodensification with a special focus on its application in sinus floor augmentation. The integration of this technique into contemporary practice represents a paradigm shift, offering a minimally invasive and efficient solution for addressing the challenges of posterior maxilla, with improved patient-reported outcomes and low complication rate. Three different protocols for sinus lift and implant placement using osseodensification burs are proposed based on available literature, and risk factors for Schneiderian membrane perforation based on residual bone height are discussed, along with implant-related outcomes and patient-reported outcome measures. The potential for osseodensification to become a standard practice in sinus floor augmentation is emphasized, highlighting key aspects such as surgical protocol and patient selection.

Cyclodextrin-Cholesterol Alone or in Combination With Cyclodextrin-Vitamin E Improves Bull Sperm Cryopreservation in a Soybean Lecithin Extender.

Combining cholesterol-loaded methyl-ß-cyclodextrin (CD-CHL) with vitamin E-loaded methyl-ß-cyclodextrin (CD-Vit E) to combat cold shock and oxidative stress during sperm cryopreservation in soybean lecithin extenders remains unexplored. Thus, the current study aimed to investigate the effect of treating bull sperm with CD-CHL and CD-Vit E prior to cryopreservation in a soybean lecithin extender. Sperm collected from eight fertile bulls were pooled and split into six aliquots. Five aliquots were treated, in a Tris-based extender, with CD-CHL (2 mg/120 × 106 cells/mL) and either 0, 0.5, 1.0, 1.5 or 2 mg CD-Vit E/120 × 106 cells/mL. The control aliquot was diluted in a Tris-based extender without further supplementation. After incubation at 22°C for 15 min and addition of a soybean lecithin extender, all aliquots were equilibrated for 2 h at 4°C and then cryopreserved in liquid nitrogen. Computer-assisted sperm analysis (CASA) was used to explore the different sperm motility parameters, hypo-osmotic swelling test to determine membrane functionality and fluorescein isothiocyanate-conjugated Aeachis hypogaea (peanut) agglutinin (FITC-PNA) to quantify acrosome integrity. The effect of oxidative stress on the sperm membrane was assessed through lipid peroxidation measurement. Compared to control, CD-CHL alone improved significantly (p < 0.05) all CASA motility parameters, membrane functionality and acrosome integrity of thawed sperm. The membrane functionality was more significantly (p < 0.05) improved when 0.5 mg CD-Vit E was combined with CD-CHL. Concerning lipid peroxidation, no significant differences (p > 0.05) in malondialdehyde (MDA) levels were registered between groups. In conclusion, the combination of CD-CHL and CD-Vit E demonstrated a significant positive effect on the cryopreservation of bull sperm in a soybean lecithin extender.

Artificial Compartments Encapsulating Enzymatic Reactions: Towards the Construction of Artificial Organelles.

Cells have used compartmentalization to implement complex biological processes involving thousands of enzyme cascade reactions. Enzymes are spatially organized into the cellular compartments to carry out specific and efficient reactions in a spatiotemporally controlled manner. These compartments are divided into membrane-bound and membraneless organelles. Mimicking such cellular compartment systems has been a challenge for years. A variety of artificial scaffolds, including liposomes, polymersomes, proteins, nucleic acids, or hybrid materials have been used to construct artificial membrane-bound or membraneless compartments. These artificial compartments may have great potential for applications in biosynthesis, drug delivery, diagnosis and therapeutics, among others. This review first summarizes the typical examples of cellular compartments. In particular, the recent studies on cellular membraneless organelles (biomolecular condensates) are reviewed. We then summarize the recent advances in the construction of artificial compartments using engineered platforms. Finally, we provide our insights into the construction of biomimetic systems and the applications of these systems. This review article provides a timely summary of the relevant perspectives for the future development of artificial compartments, the building blocks for the construction of artificial organelles or cells.

A Universal Strategy to Enhance Polarization Performance and Anode Reversal Tolerance by Polyaniline-Coated Carbon Support for Proton Exchange Membrane Fuel Cells.

Anode cell reversal typically leads to severe carbon corrosion and catalyst layer collapse, which significantly compromises the durability of proton exchange membrane fuel cells. Herein, three types of commercial carbon supports with various structures are facilely coated by polyaniline (PANI) and subsequently fabricated into reversal-tolerant anodes (RTAs). Consequently, the optimized PANI-coated catalyst RTAs demonstrate enhanced polarization performance and improved reversal tolerance compared to their uncoated counterparts, thus confirming the universality of this coating strategy. Essentially, the surface engineering introduced by PANI coating incorporates abundant N-groups and enhances coulombic interactions with ionomer side chains, which in turn reduces lower carbon exposure, promotes more uniform Pt deposition, and ensures better ionomer distribution. Accordingly, the membrane-electrode-assembly containing the Pt/PANI/XC-72R-1+IrO2 RTA presents a 100 mV (at 2500 mA cm-2) polarization performance improvement and 26-fold reduction in the degradation rate compared to the uncoated counterpart. This work provides a universal strategy for developing durable anodes and lays the groundwork for the practical fabrication of high-performance, low-degradation RTA.

Comprehensive secondary analysis of thrombotic events in pediatric patients receiving extracorporeal membrane oxygenation: A prospective cohort study.

INTRODUCTION: This study aims to describe laboratory and clinical factors associated with thrombotic events during prolonged pediatric extracorporeal membrane oxygenation. METHODS: A secondary analysis of a multi-center prospective study performed between 2012 and 2014. Patients under the age of 19 years that received extracorporeal membrane oxygenation for at least 4 days of therapy were included (n = 385). Univariable analysis and binomial regression were performed to evaluate predictive factors of single and multiple thrombotic events. A posteriori scoring tool was created to categorize thrombotic event severity. RESULTS: Over 39% of children receiving prolonged ECMO experienced a thrombotic event (TE). Binomial regression demonstrated an association between higher transfused platelet volume (mL/kg) (OR 1.04, CI: 95% 1.01-1.06, p = 0.003), Anti-Xa (OR 5.38, CI: 95% 1.22-23.8, p = 0.026) and aPTT (OR 1.01, CI: 95% 1.00-1.02, p = 0.032) the day prior to TE. Patients experiencing multiple TEs were associated with higher platelet transfusion volume (mL/kg) (OR 1.08, CI: 95% 1.05-1.12, p =< 0.001), antithrombin III (OR 1.03, CI: 95% 1.01-1.04, p = 0.001) and aPTT (OR 1.02, CI: 95% 1.01-1.03, p = 0.009). Patients experiencing multiple thrombotic events had a higher risk of 28-day mortality based on a cumulative clot severity score >4 (OR 2.37 (CI: 95% 1.32-4.24). CONCLUSIONS: Current lab tests show limited sensitivity to predict these events the day prior in a vulnerable patient group, leading to potential ECMO circuit failures. Patients with multiple thrombotic events during ECMO therapy face increased mortality risks, highlighting the need for dynamic reporting tools like clot severity scores and detailed documentation of interventions to enhance understanding and improve outcomes.

What determines transfer of carbon from plants to mycorrhizal fungi?

Biological Market Models are common evolutionary frameworks to understand the maintenance of mutualism in mycorrhizas. 'Surplus C' hypotheses provide an alternative framework where stoichiometry and source-sink dynamics govern mycorrhizal function. A critical difference between these frameworks is whether carbon transfer from plants is regulated by nutrient transfer from fungi or through source-sink dynamics. In this review, we: provide a historical perspective; summarize studies that asked whether plants transfer more carbon to fungi that transfer more nutrients; conduct a meta-analysis to assess whether mycorrhizal plant growth suppressions are related to carbon transfer; and review literature on cellular mechanisms for carbon transfer. In sum, current knowledge does not indicate that carbon transfer from plants is directly regulated by nutrient delivery from fungi. Further, mycorrhizal plant growth responses were linked to nutrient uptake rather than carbon transfer. These findings are more consistent with 'Surplus C' hypotheses than Biological Market Models. However, we also identify research gaps, and future research may uncover a mechanism directly linking carbon and nutrient transfer. Until then, we urge caution when applying economic terminology to describe mycorrhizas. We present a synthesis of ideas, consider knowledge gaps, and suggest experiments to advance the field.

[Pathogenesis of Fuchs endothelial corneal dystrophy, the fibrillar layer and individualized treatment]. / Pathogenese der Fuchs-Endotheldystrophie, die fibrilläre Schicht und individualisierte Therapie.

Fuchs endothelial corneal dystrophy (FECD) is a genetic and age-associated corneal disease characterized by an accelerated loss of corneal endothelial cells and an increased subendothelial deposition of extracellular matrix (ECM). Clinically, advanced disease leads to corneal edema with subsequent reduction in visual acuity. In the majority of patients with advanced FECD, a fibrillar layer (FL) appears on the posterior corneal surface. This FL is mostly localized in the inferotemporal corneal quadrant, marks areas with significantly reduced endothelial cell density and increased corneal thickness in the sense of edema and can be visualized and measured using Scheimpflug backscatter analysis due to increased backscatter. FECD is currently the most common indication for corneal transplantation worldwide, usually in the form of Descemet membrane endothelial keratoplasty (DMEK). New treatment approaches include variations of DMEK surgery such as hemi- or quarter DMEK with individualized and smaller grafts or Descemet membrane stripping only (DSO). In the future, clinical imaging of the FL as a particularly affected endothelial area could be important for FECD progression assessment and planning of surgical interventions. This article provides an overview of the current state of research on the clinical aspects, pathogenesis, fibrillar layer and individualized treatment of FECD.

Actin cytoskeleton and plasma membrane aquaporins are involved in different drought response of Arabidopsis rhd2 and der1 root hair mutants.

Actin cytoskeleton and reactive oxygen species are principal determinants of root hair polarity and tip growth. Loss of function in RESPIRATORY BURST OXIDASE HOMOLOG C/ROOT HAIR DEFECTIVE 2 (AtRBOHC/RHD2), an NADPH oxidase emitting superoxide to the apoplast, and in ACTIN 2, a vegetative actin isovariant, in rhd2-1 and der1-3 mutants, respectively, lead to similar defects in root hair formation and elongation Since early endosome-mediated polar localization of AtRBOHC/RHD2 depends on actin cytoskeleton, comparing the proteome-wide consequences of both mutations might be of eminent interest. Therefore, we employed a differential proteomic analysis of Arabidopsis rhd2-1 and der1-3 mutants. Both mutants exhibited substantial alterations in abundances of stress-related proteins. Notably, plasma membrane (PM)-localized PIP aquaporins showed contrasting abundance patterns in the mutants compared to wild-types. Drought-responsive proteins were mostly downregulated in rhd2-1 but upregulated in der1-3. Proteomic data suggest that opposite to der1-3, altered vesicular transport in rhd2-1 mutant likely contributes to the deregulation of PM-localized proteins, including PIPs. Moreover, lattice light sheet microscopy revealed reduced actin dynamics in rhd2-1 roots, a finding contrasting with previous reports on der1-3 mutant. Phenotypic experiments demonstrated a drought stress susceptibility in rhd2-1 and resistance in der1-3. Thus, mutations in AtRBOHC/RHD2 and ACTIN2 cause similar root hair defects, but they differently affect the actin cytoskeleton and vesicular transport. Reduced actin dynamics in rhd2-1 mutant is accompanied by alteration of vesicular transport proteins abundance, likely leading to altered protein delivery to PM, including aquaporins, thereby significantly affecting drought stress responses.

Sustainable control of microplastics in wastewater using the electrochemically enhanced living membrane bioreactor.

Wastewater treatment plant (WWTP) discharges are major contributors to the release of microplastics (MPs) into the environment. This research work aimed to assess the performance of the novel living membrane bioreactor (LMBR), which utilizes a biological layer as a membrane filter for the removal of polyethylene (PE) MPs from wastewater. The impact of an intermittently applied low current density (0.5 mA/cm2) on the reduction of MPs in the electrochemically enhanced LMBR (e-LMBR) has also been examined. The reactors were also compared to a conventional membrane bioreactor (MBR) and an electro-MBR (e-MBR). 1H nuclear magnetic resonance spectroscopy (1H NMR) was implemented for the MPs detection and quantification in terms of mass per volume of sample. The LMBR and MBR achieved comparable mean PE MPs reduction at 95% and 96%, respectively. The MPs mass reduction in the e-LMBR slightly decreased by 2% compared to that achieved in the LMBR. This potentially indicated the partial breakdown of the MPs due to electrochemical processes. Decreasing and inconsistent NH4-N and PO4-P removal efficiencies were observed over time due to the addition of PE MPs in the MBR and LMBR. In contrast, the integration of electric field in the e-MBR and e-LMBR resulted in consistently high values of conventional contaminant removals of COD (99.72-99.77 %), NH4-N (97.96-98.67%), and PO4-P (98.44-100.00%), despite the MPs accumulation. Integrating electrochemical processes in the e-LMBR led to the development of a stable living membrane (LM) layer, as manifested in the consistently low effluent turbidity 0.49 ± 0.33 NTU. Despite the increasing MPs concentration in the mixed liquor, applying electrochemical processes reduced the fouling rates in the e-LMBR. The e-LMBR achieved comparable efficiencies in contaminant reductions as those observed in the e-MBR, while using a low-cost membrane material.

Impact of Baseline Renal Insufficiency on Piflufolastat F-18 Performance and Investigation of Changes in Renal Function Following Piflufolastat F-18 Administration: Results From the OSPREY Trial.

INTRODUCTION: Piflufolastat F-18, a prostate-specific membrane antigen (PSMA)-targeted radiopharmaceutical, is predominantly eliminated via urinary excretion, and the kidneys have one of the highest absorbed doses. Therefore, this subgroup analysis aimed to investigate the impact of piflufolastat F-18 on renal function and its diagnostic performance in patients stratified by baseline renal function. PATIENTS AND METHODS: The OSPREY clinical trial enrolled 2 cohorts: A-high-risk patients undergoing radical prostatectomy with pelvic lymphadenectomy, and B-patients with suspected recurrent/metastatic prostate cancer on conventional imaging. Baseline estimated glomerular filtration rates were calculated, and patients were stratified by baseline chronic kidney disease (CKD) stage. Changes in serum creatinine within 28 days postdose and diagnostic performance of piflufolastat F-18 were assessed for each CKD stage group in both cohorts. RESULTS: 385 patients (cohort A, n = 268; cohort B, n = 117) underwent piflufolastat F-18-PET/CT. Baseline and postpiflufolastat F-18 median creatinine levels (mg/dL) were similar for patients in cohort A (0.95 [n = 264] vs. 0.95 [n = 252], respectively) and cohort B (0.93 [n = 116] vs. 0.96 [n = 84], respectively). Among 332 men (cohort A, n = 249; cohort B, n = 83) with baseline and postpiflufolastat creatinine measurements, there were minimal changes in creatinine across all baseline CKD stage groups (median change ranged from -0.02 to 0.023 in groups with >1 patient). The diagnostic performance of piflufolastat F-18 showed no meaningful differences when stratified by baseline CKD stage. CONCLUSION: Piflufolastat F-18 appears to be safe and effective for imaging prostate cancer, including men with mild/moderate renal insufficiency.

On the function of TRAP substrate-binding proteins: conformational variation of the sialic acid binding protein SiaP.

Tripartite ATP-independent periplasmic (TRAP) transporters are analogous to ABC transporters in that they use a substrate-binding protein to scavenge metabolites (e.g., N-acetylneuraminate) and deliver them to the membrane components for import. TRAP substrate-binding proteins are thought to bind the substrate using a two-state (open and closed) induced-fit mechanism. We solved the structure of the TRAP N-acetylneuraminate substrate-binding protein from Aggregatibacter actinomycetemcomitans (AaSiaP) in both the open ligand-free and closed liganded conformations. Surprisingly, we also observed an intermediate conformation, where AaSiaP is mostly closed and is bound to a non-cognate ligand, acetate, which hints at how N-acetylneuraminate binding stabilises a fully closed state. AaSiaP preferentially binds N-acetylneuraminate (KD = 0.4 µM) compared to N-glycolylneuraminate (KD = 4.4 µM), which is explained by the closed-N-acetylneuraminate bound structure. Small-angle X-ray scattering data alongside molecular dynamics simulations suggest the AaSiaP adopts a more open state in solution than in crystal. However, the open unliganded conformation can also sample closed conformations. Molecular dynamics simulations also demonstrate the importance of water molecules for stabilising the closed conformation. Although our data is consistent with an induced fit model of binding, we suggest that the open unliganded conformation may sample multiple states capable of binding substrate. The mechanism by which the ligand is released for import remains to be determined.