Membrane Defects Research Articles

Sound insulation performance of double membrane-type acoustic metamaterials combined with a Helmholtz resonator

As one of the representatives of acoustic metamaterials, the membrane-type acoustic metamaterial has excellent sound insulation performance due to its locally resonant features, which makes an extremely broad development prospect in many fields such as aerospace, ship and civil engineering. At the same time, sandwich structures are widely used because of their great mechanical properties. In this paper, we designed a sandwich structure of double membrane-type acoustic metamaterials combined with a Helmholtz resonator, a new structure is presented with both pleasant mechanical nature and admirable acoustic insulation at low frequency. Based on theoretical derivation we calculated the resonant frequencies and out-of-plane displacements of membrane-type acoustic metamaterials. The sound transmission loss, dynamic response and negative characteristics of the new structure are amply analyzed through numerical simulation, and the accuracy of the simulation is verified through experiments. It can be concluded that the average sound insulation performance of this new sandwich structure at 50 Hz–1600 Hz is 30% higher than the single-membrane type sandwich structure. At the same time, the sound insulation performance is improved by 24.8% compared with the double-membrane type sandwich structure which does not increase the cavity height. To sum up, this sound insulation performance of the structure is significantly higher than that of a single membrane-type acoustic metamaterial, with the possibility of flexible changes in cavity height, additional block arrangement form and membrane defect location from multiple angles, and a variety of configurations can be designed according to the actual engineering requirements of both lightweight, load-bearing and sound insulation requirements.

Tethered Bilayer Lipid Membrane Platform for Screening Triton X-100 Detergent Replacements by Electrochemical Impedance Spectroscopy.

In light of regulatory considerations, there are ongoing efforts to identify Triton X-100 (TX-100) detergent alternatives for use in the biological manufacturing industry to mitigate membrane-enveloped pathogen contamination. Until now, the efficacy of antimicrobial detergent candidates to replace TX-100 has been tested regarding pathogen inhibition in endpoint biological assays or probing lipid membrane disruption in real-time biophysical testing platforms. The latter approach has proven especially useful to test compound potency and mechanism of action, however, existing analytical approaches have been limited to studying indirect effects of lipid membrane disruption such as membrane morphological changes. A direct readout of lipid membrane disruption by TX-100 detergent alternatives would be more practical to obtain biologically relevant information to guide compound discovery and optimization. Herein, we report the use of electrochemical impedance spectroscopy (EIS) to investigate how TX-100 and selected replacement candidates-Simulsol SL 11W (Simulsol) and cetyltrimethyl ammonium bromide (CTAB)-affect the ionic permeability of tethered bilayer lipid membrane (tBLM) platforms. The EIS results revealed that all three detergents exhibited dose-dependent effects mainly above their respective critical micelle concentration (CMC) values while displaying distinct membrane-disruptive behaviors. TX-100 caused irreversible membrane disruption leading to complete solubilization, whereas Simulsol caused reversible membrane disruption and CTAB induced irreversible, partial membrane defect formation. These findings establish that the EIS technique is useful for screening the membrane-disruptive behaviors of TX-100 detergent alternatives with multiplex formatting possibilities, rapid response, and quantitative readouts relevant to antimicrobial functions.

Influence of surface chemistry and channel shapes on the lithium-ion separation in metal-organic-framework-nanochannel membranes

Metal-organic-framework-based channel (MOFC) membranes have great potential in ion separation due to their high flexibility than polycrystalline MOF membranes. Although a few single-MOFC membranes with high ion selectivity and permeability have been reported, the scale-up of MOFC membranes from single-channel membranes to multichannel membranes remains a challenge as defects with the system are escalated, limiting their practical application. Minimizing defects in multichannel MOFC membranes is the key to solving this scale-up challenge. Herein, the surface chemistry of polyethylene terephthalate (PET) nanochannel substrate was firstly tuned by a chemical modification to enhance the binding between the PET nanochannel walls and UiO-66-(COOH)2 MOF crystals. Further investigation of the influences of PET nanochannels' size, shape, and channel density on the selectivity revealed that the cylindrical and ethylenediamine (EDA)-functionalized single PET-UiO-66-(COOH)2 MOFC membrane exhibited an ultrahigh Li+/Mg2+ selectivity of 3077-fold over those of previous single-MOFC works. Furthermore, cylindrical, EDA-functionalized, multichannel UiO-66-(COOH)2 MOFC membranes with a channel density of 106/cm2 have been fabricated to achieve 50-fold Li+/Mg2+ selectivity and a vast enhancement of Li + conductance for 6 orders of magnitude. As the first example of scaling up the MOFC membrane, this work provides a fundamental basis and experimental techniques for MOF membrane synthesis and lithium-ion extractions.

Five Years’ Experience with Gene Panel Sequencing in Hereditary Hemolytic Anemia Screened by Routine Peripheral Blood Smear Examination

Hereditary hemolytic anemia (HHA) is defined as a group of heterogeneous and rare diseases caused by defects of red blood cell (RBC) metabolism and RBC membrane, which leads to lysis or premature clearance. The aim of this study was to investigate individuals with HHA for potential disease-causing variants in 33 genes reported to be associated with HHA. A total of 14 independent individuals or families diagnosed with suspected HHA, and in particular, RBC membranopathy, RBC enzymopathy, and hemoglobinopathy, were collected after routine peripheral blood smear testing. A custom designed panel, including the 33 genes, was performed using gene panel sequencing on the Ion Torrent PGM™ Dx System. The best candidate disease-causing variants were confirmed by Sanger sequencing. Several variants of the HHA-associated genes were detected in 10 out of 14 suspected HHA individuals. After excluding those variants predicted to be benign, 10 pathogenic variants and 1 variant of uncertain significance (VUS) were confirmed in 10 individuals with suspected HHA. Of these variants, the p.Trp704Ter nonsense variant of EPB41 and missense p.Gly151Asp variant of SPTA1 were identified in two out of four hereditary elliptocytoses. The frameshift p.Leu884GlyfsTer27 variant of ANK1, nonsense p.Trp652Ter variant of the SPTB, and missense p.Arg490Trp variant of PKLR were detected in all four hereditary spherocytosis cases. Missense p.Glu27Lys, nonsense p.Lys18Ter variants, and splicing errors such as c.92 + 1G > T and c.315 + 1G > A within HBB were identified in four beta thalassemia cases. This study provides a snapshot of the genetic alterations in a cohort of Korean HHA individuals and demonstrates the clinical utility of using gene panels in HHA. Genetic results can provide precise clinical diagnosis and guidance regarding medical treatment and management for some individuals.

Parkinson's disease-associated mutants shift equilibrium bound state of alpha-synuclein towards the second helix.

α-synuclein regulates neurotransmitter release by binding to the outer lipid membrane of synaptic vesicles. Mutations within the lipid-binding region of α-synuclein are associated with protein aggregates and the progression of Parkinson's Disease (PD). However, the role of lipid-binding in α-synuclein's propensity to aggregate is not fully understood. Here, we explore how a mathematical framework reveals details in protein-membrane interactions that are disrupted by PD-associated mutants. Upon binding, α-synuclein forms two α-helices that insert into the lipid membrane - a process that is mediated by lipid membrane defects. A tryptophan fluorescence assay reveals how PD-associated mutants alter the equilibrium distribution of fully vs. partially bound protein. In unraveling the role of α-synuclein in the progression of PD, we reveal a unifying difference in protein behavior between wild-type α-synuclein and disease-associated mutants. Altogether, our results show that PD-associated point mutations uniformly shift the equilibrium bound state towards the second helix, suggesting that protein aggregation and eventual neurotoxicity may be linked to the equilibrium between the two helices.

The role of protein-protein interactions in Fluc dimerization stability and function.

Functional ion channel assembly often requires subunit oligomerization. Yet the molecular factors that define the stability of ion channel complexes in membranes remain to be delineated. Here we investigate this question by studying the dynamic dimerization reaction of the model system Fluc to map out the molecular and physical forces driving this reaction in membranes. Fluc is dual-topology homodimer, where dimerization confers the highly specific fluoride permeation pathway. Our previous analysis demonstrated that a sodium titratable mutant of Fluc participates in a two-step equilibrium dimerization reaction in membranes. First, membrane-dependent dimerization drives subunits to assemble and form a non-contact lipid-solvated stable dimer intermediate by burying a membrane defect imposed in the monomer. However, the fluoride conducting state requires the protein subunits to come closer and expel the lipids to form the fluoride permeation pathway. High resolution crystal structures of Fluc show numerous protein-protein interactions across the dimerization interface, suggesting these interactions might be involved in stabilizing the close-contact dimer state. Alternatively, these contacts may not play a major role in the overall dimer stability but may be important for conferring function. Here, we will investigate how disruption of these protein-protein interactions affects dimerization stability, channel activity or both. Site-directed mutagenesis was employed following four strategies of disruption: (1) reduction of van der Waals interactions by leucine-to-alanine substitutions; (2) removal of potential hydrogen bonds by threonine-to-valine substitutions; (3) decrease backbone flexibility by glycine-to-alanine mutations of the GxxxG dimerization motif; (4) and introduction of bulky tryptophan residues at the interface. Using single-molecule photobleaching analysis to investigate dimer stability in membranes combined with single channel bilayer recordings, these results will provide a quantitative characterization of the contribution of protein-protein interactions to Fluc dimer stability and activity.

Analysis of direct transmembrane permeability of mono-amino acids by the planar membrane system.

Amino acids are delivered to living cells by direct permeation, endocytosis, or assisted diffusion. Direct permeation does not require carriers or energy to deliver amino acids into the cytoplasm. Revealing how mono-amino acids permeate through the membrane will help to understand the permeation mechanism of cell-penetrating peptides and elucidate the way protocells take up amino acids. The relationship between the direct permeability of amino acids and their physicochemical properties is poorly understood, and their interactions with membranes remain controversial. In this study, we used the electrophysiological method, a label-free permeation measurement that avoids the influence of label molecules on the permeation, to analyze the transmembrane permeation through the planar lipid bilayer system. Considering the relationship between the shape of the current signal and the permeation models in the membrane, we attempt to estimate the membrane direct permeability of all twenty L-amino acids. As the result, the current signals were detected for amino acids at 20 mM. To confirm the transmembrane permeation of amino acids through the membrane, UV spectroscopy and chromogenic reaction were also measured. Three kinds of signals corresponding to the direct permeation (spike-like current) and the formation of membrane defects (erratic and multiple currents) were observed and assigned to each model. We analyzed the frequency and ratio of signal occurrence the spike-like signals and assessed the direct permeation of amino acids. The results show that hydrophobic amino acids exhibited higher current frequency and shorter duration, suggesting higher permeation. Through the relationship of current value and duration, we found differences in pore-forming ability and membrane permeation rate between amino acids. We will discuss factors that contribute to differences in membrane permeation.

The role of the membrane in driving CLC-ec1 dimerization.

Most membrane proteins oligomerize in the membrane. In the case of the bacterial chloride/proton antiporter CLC-ec1, the role of highly stable homodimers is not understood since individual CLC-ec1 protomers can maintain the chloride/proton transport stoichiometry. In a previous study, we used experimental and computational approaches to show that in C16:0/C18:1 palmitoyl-oleoyl lipid membranes, the monomeric state of CLC-ec1 creates a membrane defect that is ≈ 8 Å thinner than the bulk. However, in the dimer state, the membrane is restored to a near-native bilayer thickness and structure. We hence proposed that the dimerization is driven by the larger free-energy cost of lipid solvation of the dissociated monomers. Here, we carry out coarse-grained molecular dynamics simulations with umbrella sampling and free energy perturbation methods to quantify the membrane's contribution to free energy of dimerization. In the case of CLC-ec1, addition of 30% C12:0 di-lauryl chain lipids stabilizes the free energy of the monomeric state by ≈ 2 kcal/mole, in qualitative agreement with our experimental observations. Therefore, we have a physical model of how changes in lipid composition can regulate self-assembly reactions of membrane proteins in membranes. This work was partially performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344. LLNL-ABS-840782.

A Single-Cell Electroporation Model for Quantitatively Estimating the Pore Area Ratio by High-Frequency Irreversible Electroporation

The electroporation technique utilizes pulsed electric fields to induce porous defects in the cell membrane, and the technique can be used for delivering drugs into cells and killing cancer cells. To develop an electric pulse protocol in the clinic with this technique, the key issue is to understand the evolution of pores in the cell membrane during the process of electroporation. This paper presents a study to address this issue. Specifically, a mathematical model of single-cell electroporation (SCE) was developed, which includes pore area ratio (PAR) as an indicator of the electroporation dynamics and area weight for considering the 3D nature of cells. The model was employed to simulate the electroporation of a single cell with different high-frequency irreversible electroporation (H-FIRE) protocols. The simulation result has found that the change of PAR with respect to the time duration of electroporation follows a sigmoid pattern to increase under specific protocols, which is called the cumulative effect of PAR. Subsequently, the relationship between the protocol of H-FIRE, described by a set of pulse parameters such as pulse width, pulse delay, electric field strength, and pulse burst duration, and the cumulative effect of PAR was established, which thereby allows designing the protocol to kill cells effectively. The study concluded that the proposed SCE model, along with the cumulative effect of PAR, is useful in designing H-FIRE protocols for the ablation of cancer tumors in the clinic.

Myopic macular Bruch’s membrane defects

PurposeTo examine histologic characteristics of macular Bruchś membrane defects (BMD) in axially elongated eyes. DesignHistomorphometric study. MethodsUsing light microscopy, we examined enucleated human globes for BMDs. ResultsIn 247 eyes, BMDs were detected in 15 (6.1%) eyes (axial length:27.0–36.0 mm), in 10 of them in the macular region. Prevalence and size of BMDs (mean:1.93 ± 1.62 mm; range:0.22mm–6.24 mm) correlated with longer axial length (OR:1.52; 95%CI:1.19,1.94; P = 0.001) and higher prevalence of scleral staphylomas (OR:16.3; 95%CI:2.67,99.3; P < 0.001). The BMDs were smaller than corresponding gaps in the retinal pigment epithelium (RPE) (1.93 ± 1.62 mm versus 2.61 mm ± 1.73 mm; P = 0.003), and larger than corresponding gaps in the inner nuclear layer (0.43 ± 0.76 mm; P = 0.008) and inner limiting membrane bridges (0.13 ± 0.33 mm; P = 0.001). Choriocapillaris thickness, BM thickness and RPE cell density did not vary (all P > 0.05) between the BDM border and adjacent areas. In the BMD, choriocapillaris and RPE were absent. The sclera was thinner in the BDM area than in adjacent areas (0.28 ± 0.19 mm versus 0.36 ± 0.13 mm; P = 0.006). ConclusionsBMDs as hallmarks of myopic macular degeneration are characterized by longer gaps in the RPE and smaller gaps in the outer nuclear layer and inner nuclear layer, by localized scleral thinning, and by a spatial association with scleral staphylomas. Thickness of the choriocapillaris and density of the RPE cell layer, both absent within the BDMs, do not vary between the BMD border and adjacent regions. The results suggest an association between BDMs and absolute scotomas, stretching of the adjacent retinal nerve fiver layer, and an axial elongation-associated stretching effect on BM as etiology of the BDMs.

Atrophic, Tractional, and Neovascular Grading System in a Dome-Shaped Macula and Ridge-Shaped Macula Highly Myopic Cohort

Introduction: The aim of this study was to analyze the atrophic, tractional, and neovascular (ATN) components grading in highly myopic patients with dome-shaped macula (DSM) and ridge-shaped macula (RSM). Methods: This was a cross-sectional, noninterventional study. 57 eyes of 38 different patients were included. They were classified as DSM or RSM based on the number of radial scans that showed an inward protrusion ≥50 µm in the swept-source optical coherence tomography (SS-OCT) (12 = DSM; <12 = RSM). All patients underwent a complete ophthalmological examination in addition to SS-OCT. They were graded using the ATN system for myopic maculopathy by 2 masked retina specialists that assessed the atrophic (A), tractional (T), and neovascular (N) components in order to analyze the differences between the groups. As complementary measurements, age, axial length, and best-corrected visual acuity were collected. Height and orientation of the macular bulge and the presence of Bruch’s membrane defects, scleral perforating vessels, and staphyloma were recorded. Results: Out of total 57 eyes, 13 eyes (22.8%) were classified as DSM. Regarding the atrophic component (A), there were statistically significant differences between groups, with DSM group showing a greater stage of atrophy (predominantly stage A3 in 69.2% of the sample) compared to the RSM group (predominantly stage A2 in 61.3% of the sample) (p < 0.05). For the T and N components, there were no significant differences between groups. The presence of Bruch’s membrane defects was more frequently seen in DSM (p < 0.05). Conclusions: DSM group showed more Bruch’s membrane defects and a greater stage of the atrophy component, based on the ATN grading system, compared with RSM group. As Bruch’s membrane may have biomechanical properties in terms of strength, the defects found around the macula, added to the major atrophic component, may be a cause of a local relaxation that induce a central bulge forming the dome.

Status of the mucosa of the upper gastrointestinal tract in patients with acute viral hepatitis B

Introduction. Patients with acute viral hepatitis B (AVHB) during the peak may develop erosions and ulcers of the mucous membrane of the upper gastrointestinal tract, which are difficult to diagnose clinically. Aim. The differences in clinical and laboratory manifestations of acute viral hepatitis B, depending on the presence or absence of erosive and ulcerative defects of the mucous membrane of the upper gastrointestinal tract has studied. Materials and methods. The work used clinical and laboratory data and the results of endoscopic examination of 44 patients with AVHB. All patients underwent a comprehensive clinical and laboratory examination, supplemented by fibroesophagogastroduodenoscopy (FEGDS). Results. Among 44 patients with AVHB, complaints of a dyspeptic character occurred in 79.6% (35 patients) and did not depend on the severity of the course of AVHВ. FEGDS of patients with AVHB revealed various pathological changes in the mucous membrane from superficial gastritis and gastroduodenitis (61.4%) to erosive gastroduodenitis and acute ulcers of the mucous membrane of the duodenal bulb (38.6%). Erosive and ulcerative defects of the mucous membrane of the upper gastrointestinal tract (ММUGIT) were more often diagnosed in the first 9 days from the onset of AVHB and was acute. Еrosions and ulcers of the GIТ tract with AVHB were less often than non-erosive gastritis/gastroduodenitis accompanied by such dyspeptic complaints as epigastric pain, nausea, and vomiting, which excludes dyspeptic syndrome as an evidence-based clinical landmark in diagnosing the degree of damage to the mucous membrane of the upper gastrointestinal tract. However, patients with AVHB with erosive and ulcerative defects of the ММUGIT had a significantly higher level of ALT at admission than patients with EVHV with gastritis/gastroduodenitis (1860 U/l (1030.2889) vs. 910 U/l (325.1749), p< 0 .05). Conclusion: In order to identify erosive-ulcerative defects of the mucous membrane of the upper gastrointestinal tract in patients with AVHB the FEGDS should be performed in the first 9 days of the disease in the presence of high ALT activity, which will allow to correct the tactics of managing patients with AVHВ earlier.

Technology opportunity discovery of proton exchange membrane fuel cell from the perspective of papers-patents correlation analysis

Papers and patents can respectively present the latest progress of scientific research and technological development. Combining the two for correlation analysis has certain reference significance for technology opportunity discovery. Therefore, this paper proposes a method for technology opportunity discovery of proton exchange membrane fuel cell from the perspective of papers-patents correlation analysis. Firstly, papers and patent data are collected from papers and patent databases and the LDA model is applied to extract paper and patent topics. Secondly, the indicators of topic heat and novelty are calculated to select high-value paper topics. After that, the similarity analysis between high-value paper topics and all patent topics is considered to select the patent topics with development potential. Finally, the patent texts with high relevance to these patent topics with development potential are positioned. The technical keywords in them are extracted by text mining tool and classified into innovation dimensions according to their attributes and the TEMPEST model. After that, the innovation rules in the SCAMPER model are introduced to combine with the technical keywords in each innovation dimension to identify specific technology opportunities. An empirical study on the technology of proton exchange membrane fuel cell provides sufficient evidence of the method’s ability to discover technology opportunities. This paper contributes by generating four specific technology opportunities, which can make up for the existing defects of proton exchange membrane fuel cells and provide useful guidance for companies to carry out technological innovation.

In vivo Sealing of Fetoscopy-Induced Fetal Membrane Defects by Mussel Glue

Introduction: The benefits of fetal surgery are impaired by the high incidence of iatrogenic preterm prelabor rupture of the fetal membranes (iPPROM), for which chorioamniotic separation has been suggested as a potential initiator. Despite the urgent need to prevent iPPROM by sealing the fetoscopic puncture site after intervention, no approach has been clinically translated. Methods: A mussel-inspired biomimetic glue was tested in an ovine fetal membrane (FM) defect model. The gelation time of mussel glue (MG) was first optimized to make it technically compatible with fetal surgery. Then, the biomaterial was loaded in polytetrafluoroethylene-coated nitinol umbrella-shaped receptors and applied on ovine FM defects (N = 10) created with a 10 French trocar. Its sealing performance and tissue response were analyzed 10 days after implantation by amniotic fluid (AF) leakage and histological methods. Results: All ewes and fetuses recovered well after the surgery, and 100% ewe survival and 91% fetal survival were observed at explantation. All implants were tight at explantation, and no AF leakage was observed in any of them. Histological analysis revealed a mild tissue response to the implanted glue. Conclusion: MG showed promising properties for the sealing of FM defects and thereby the prevention of preterm birth. Studies to analyze the long-term tissue response to the sealant should be performed.

Morphological Characteristics of Catalyst Layer Defects in Catalyst-Coated Membranes in PEM Fuel Cells

Catalyst layer defects and irregularities in catalyst-coated membrane (CCM) electrodes affect the lifetime of polymer electrolyte membrane fuel cells (PEMFCs) during their operation. Thus, catalyst layer defects are important concerns for fuel cell manufacturers and prompt the development of quality control systems with the aim of fabricating defect-free electrodes. Consequently, the objective of this study is to gain a fundamental understanding of the morphological changes of real catalyst layer defects that have developed during CCM production. In this paper, missing catalyst layer defects (MCLD) formed during the decal transfer process are investigated through a nondestructive method using reflected light microscopy. The geometric features of the defects are quantified, and their growth is measured at regular time intervals from beginning-of-life (BOL) to end-of-life (EOL) until the OCV has dropped by 20% of its initial value as per a DOE-designed protocol. Overall, two types of degradation are observed: surface degradation caused by catalyst erosion and crack degradation caused by membrane mechanical deformation. Furthermore, catalyst layer defects formed during the decal transfer process were found to exhibit a higher growth rate at middle-of-life (MOL-1) and stabilize by EOL. This type of study will provide manufacturers with baseline information to allow them to select and reject CCMs, ultimately increasing the lifetime of fuel cell stacks.

Rise of the planet of rare anemias: An update on emerging treatment strategies.

Therapeutic options for rare congenital (hemoglobinopathies, membrane and enzyme defects, congenital dyserythropoietic anemia) and acquired anemias [warm autoimmune hemolytic anemia (wAIHA), cold agglutinin disease CAD, paroxysmal nocturnal hemoglobinuria (PNH), and aplastic anemia (AA)] are rapidly expanding. The use of luspatercept, mitapivat and etavopivat in beta-thalassemia and pyruvate kinase deficiency (PKD) improves transfusion dependence, alleviating iron overload and long-term complications. Voxelotor, mitapivat, and etavopivat reduce vaso-occlusive crises in sickle cell disease (SCD). Gene therapy represents a fascinating approach, although patient selection, the toxicity of the conditioning regimens, and the possible long-term safety are still open issues. For acquired forms, wAIHA and CAD will soon benefit from targeted therapies beyond rituximab, including B-cell/plasma cell targeting agents (parsaclisib, rilzabrutinib, and isatuximab for wAIHA), complement inhibitors (pegcetacoplan and sutimlimab for CAD, ANX005 for wAIHA with complement activation), and inhibitors of extravascular hemolysis in the reticuloendothelial system (fostamatinib and FcRn inhibitors in wAIHA). PNH treatment is moving from the intravenous anti-C5 eculizumab to its long-term analog ravulizumab, and to subcutaneous and oral proximal inhibitors (anti-C3 pegcetacoplan, factor D and factor B inhibitors danicopan and iptacopan). These drugs have the potential to improve patient convenience and ameliorate residual anemia, although patient compliance becomes pivotal, and long-term safety requires further investigation. Finally, the addition of eltrombopag significantly ameliorated AA outcomes, and data regarding the alternative agent romiplostim are emerging. The accelerated evolution of treatment strategies will need further effort to identify the best candidate for each treatment in the precision medicine era.

Computational investigation on lipid bilayer disruption induced by amphiphilic Janus nanoparticles: combined effect of Janus balance and charged lipid concentration.

Janus nanoparticles (NPs) with charged/hydrophobic compartments have garnered attention for their potential antimicrobial activity. These NPs have been shown to disrupt lipid bilayers in experimental studies, yet the underlying mechanisms of this disruption at the particle-membrane interface remain unclear. To address this knowledge gap, the present study conducts a computational investigation to systematically examine the disruption of lipid bilayers induced by amphiphilic Janus NPs. The focus of this study is on the combined effects of the hydrophobicity of the Janus NP, referred to as the Janus balance, defined as the ratio of hydrophilic to hydrophobic surface coverage, and the concentration of charged phospholipids on the interactions between Janus NPs and lipid bilayers. Computational simulations were conducted using a coarse-grained molecular dynamics (MD) approach. The results of these MD simulations reveal that while the area change of the bilayer increases monotonically with the Janus balance, the effect of charged lipid concentration in the membrane is not easy to be predicted. Specifically, it was found that the concentration of negatively charged lipids is directly proportional to the intensity of membrane disruption. Conversely, positively charged lipids have a negligible effect on membrane defects. This study provides molecular insights into the significant role of Janus balance in the disruption of lipid bilayers by Janus NPs and supports the selectivity of Janus NPs for negatively charged lipid membranes. Furthermore, the anisotropic properties of Janus NPs were found to play a crucial role in their ability to disrupt the membrane via the combination of hydrophobic and electrostatic interactions. This finding is validated by testing the current Janus NP design on a bacterial membrane-mimicking model. This computational study may serve as a foundation for further studies aimed at optimizing the properties of Janus NPs for specific antimicrobial applications.

Peters anomaly: An overview.

Peters anomaly (PA) is a rare, often bilateral, congenital corneal opacity, usually with a sporadic inheritance pattern, characterized by corneal opacities and irido-corneal or lenticular-corneal adhesions with a defect in the Descemet's membrane, occurring due to anterior segment dysgenesis during fetal development. Due to other ocular and systemic comorbidities, a team comprising pediatric cornea, glaucoma, and strabismus specialists in addition to a pediatrician and geneticist is necessary for the appropriate management of these children. Since the outcome of pediatric penetrating keratoplasty is variable and has a higher chance of failure when accompanied by additional procedures, such as lensectomy and vitrectomy, minimally invasive alternatives are increasingly being offered to these patients. Of note is the recently reported novel procedure: selective endothelialectomy for PA, which avoids the need for a corneal transplant and results in gradual clearing of the corneal opacity over time. In this overview, we aimed to describe the etiology, classification, pathophysiology, histopathology, clinical features, and management of PA.

Experience of laser myringoplasty in children with juvenile ideopathic arthritis

Surgeons' dissatisfaction with the surgical treatment for tympanic membrane perforations results leads to the constant improvement of the surgical technique and the emergence of new techniques. Difficulties arise in the surgical treatment of rheumatological patients treated with immunosuppressive drugs due to the high potential risk of postoperative complications. The most promising direction in this cohort of patients can be considered the use of laser exposure techniques under endoscopic control. The experience of performing endoscopic laser myringoplasty in 9 children aged from 6 to 16 years (mean age 10±3 years) with tympanic membrane perforation up to 6 mm in diameter and juvenile idiopathic arthritis treated with methotrexate and tocilizumab is presented. The effectiveness of the studied technique in relation to the closure of perforation of the tympanic membrane was 66.7%. Considering that in children, reconstructive ear surgery is considered less effective than in adults, and the presence of chronic systemic rheumatoid disease and immunosuppressive therapy are risk factors for recurrence of perforation after tympanoplasty, these results can be considered successful. The presented method is promising in this cohort of patients for the restoration of small tympanic membrane defects. However, further research is needed.

Facile self-repair of ultrathin palladium membranes

Pd membranes can play an important role in H2 separation and purification for the development of sustainable and renewable energies. By supporting on porous substrates, Pd layer thickness can be reduced to several micrometers, thus improving the H2 permeance by several orders of magnitude. However, the supported thin Pd membranes are concomitant with pinhole formation due to either fabrication (e.g., electroless-plating) or thermal treatment, which exist as a remarkable challenge for its widespread applications. This study presents a novel and facile approach for self-repair of Pd membrane defects by immersing the stainless-steel supported Pd membranes in PdCl2 solution. Three membranes were deliberately selected with a low selectivity of 152–1687 (400 ​°C, 0.1Mpa), for which disproportionation reactions between Pd2+ and Fe/Cr/Ni at the defect sites spontaneously occur leading to the formation of Pd particles at the exact point of defects. This self-repair process can be enhanced when applying a high pressure of 30–50 ​bar in the PdCl2 solution for 30 ​min, by overcoming the capillary resistance and penetrating through the pinholes. Interestingly, densely distributed hillocks were observed on the membrane surface probably due to reduction of PdCl2 under following H2 treatment, thus increasing the H2 permeance with a higher effective surface area. The H2/N2 selectivity can be improved by more than one order of magnitude (in the best case from 1687 to 8768) and a long-term stability test of 300 ​h was achieved for the repaired membranes, corroborating the application potential of this approach.