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Despite the various treatments proposed with barrier membranes, one of the main challenges for guided bone regeneration (GBR) is maintaining space for large defects and ensuring an adequate blood supply. The presented feasibility case series aims to introduce an original titanium frame (TF) design, customized for each defect, as a modification of well-known principles and materials for GBR to achieve an enhanced and more predictable horizontal and vertical bone augmentation. Three patients with significant horizontal defects were treated with pre-trimmed TFs to create needed space, and then a 50/50 mixture of autograft and bovine xenograft was placed and covered with a collagen membrane. After 8 months of healing, the sites were reopened, and the titanium screws were removed with the frame. An average of 8.0 ± 1.0 mm of horizontal and 3.0 ± 0.0 mm of vertical bone gain were achieved at the time of reentry and implant placement surgery. Bone core biopsy sample was obtained during the implant placement. Histomorphometric analysis revealed that 42.8% of the sample was new vital bone, 18.8% was residual bone graft particles, and 38.4% was bone marrow-like structures. After 3 to 4 months from implant placement, the implants were restored with provisional crowns and then finalized with zirconia screw-retained crowns. This case series suggests that GBR utilizing TFs with or without collagen membranes can be considered a suitable approach for horizontal and vertical bone augmentation. However, based on only three reported cases, the results should be carefully interpreted. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the impact of different approaches to sinus membrane perforation (SMP) repair on bone formation, postoperative complications, and implant loss risk. Materials and Methods: Electronic searches on PubMed, Web of Science, Scopus, Embase, and Cochrane Library databases were conducted for publications up to February 2021. All included articles reported SMPs submitted for repair. The proportion of implant loss in repaired SMP sites was calculated using a random-effects model meta-analysis. Results: A total of 130 studies reporting SMP repair protocols were included in the systematic review, with 20 selected for meta-analysis. A total of 1,972 sinuses that were perforated and repaired during sinus elevation using different approaches were included in the qualitative analysis. The resorbable collagen membrane was the most commonly reported treatment. The presence of sinusitis was the most frequently described complication. Regarding bone parameters, the majority of studies described no differences between perforated and repaired sinuses and intact membranes. No difference in the implant loss proportion was observed between sites with repaired SMP compared to undetected SMP. The proportion of implant loss in repaired sinuses membrane sites (independent of the material or implant placement time) was 4% (95% CI: 2.0 to 8.0). In meta-regression analysis, no association was observed between the SMP size and implant loss proportion (P = .86). Conclusions: The materials and techniques indicated for SMP management seem to securely seal the maxillary sinus, without a negative effect on the ultimate survival of the implants placed in the affected sinuses. [ABSTRACT FROM AUTHOR]

The use of cellular nanovesicles (CNVs) is a groundbreaking innovation in biomedical applications. Both natural extracellular vesicles (EVs) and artificial cell membrane nanovesicles (AVs) have emerged as innovative CNVs, but they have limitations in therapeutic effects and targeting abilities. Challenges such as stability, immunogenicity, and drug payload capacity hinder their widespread application. Genetic engineering has matured as a widely employed modification strategy, leading to the development of genetically engineered extracellular vesicles (gEVs) and genetically engineered artificial cell membrane nanovesicles (gAVs). This review meticulously examines the diverse types and inherent characteristics of CNVs, alongside various surface engineering strategies for CNVs, with a specific focus on elucidating the attributes and detailing the preparation methods relevant to gEVs and gAVs. Furthermore, this exploration delves into the expansive landscape of biomedical applications, developmental prospects, and current challenges associated with the utilization of gEVs and gAVs. With a comprehensive approach, the primary objective is to provide insights that not only illuminate the nuanced intricacies of these nanovesicles but also pave the way for their seamless integration into clinical research and eventual translation into practical applications. [ABSTRACT FROM AUTHOR]

Given the toxicity of wastewater pollutants to both humans and the environment, it is critical to develop a new synthetic membrane with superior permeability and rejection. Herein, a novel asymmetric polyethersulfone (PES) composite filtration membrane was successfully prepared using a simple alternating vacuum‐deposition process with positively charged chitosan and negatively charged cellulose nanofibrils as polycations and polyanions, respectively. As expected, the produced PES composite filtration membranes had a compressed and negatively charged surface, which prevented the anionic dye methyl blue (MB) molecules from infiltrating into the membrane matrix. Consequently, the resulting PES composite filtration membranes exhibited an extremely high MB rejection (99.7%) and a satisfactory flux (37.47 L h−1 m−2 MPa−1). In addition, the composite membrane demonstrated extremely selective removal of anionic dyes in the presence of neutral dyes due to the Donnan effect. Furthermore, the developed PES composite filtration membranes displayed exceptional long‐term stability (99.8% rejection and 36.5 L h−1 m−2 MPa−1 flux after 50 h of filtration) and recycling properties (90.1% flux recovery rate after 3 cycles of running). In conclusion, the PES composite filtration membranes prepared in this study presented great potential in wastewater filtering. [ABSTRACT FROM AUTHOR]

The mammalian plasma membrane is known to contain domains with varying lipid composition and biophysical properties. However, studying these membrane lipid domains presents challenges due to their predicted morphological similarity to the bulk membrane and their scale being below the classical resolution limit of optical microscopy. To address this, we combine the solvatochromic probe di-4-ANEPPDHQ, which reports on its biophysical environment through changes in its fluorescence emission, with spectrally resolved single-molecule localisation microscopy. The resulting data comprises nanometre-precision localisation coordinates and a generalised polarisation value related to the probe's environment – a marked point pattern. We introduce quantification algorithms based on topological data analysis (PLASMA) to detect and map nano-domains in this marked data, demonstrating their effectiveness in both artificial membranes and live cells. By leveraging environmentally sensitive fluorophores, multi-modal single molecule localisation microscopy, and advanced analysis methods, we achieve nanometre scale mapping of membrane properties and assess changes in response to external perturbation with methyl-β-cyclodextrin. This integrated methodology represents an integrated toolset for investigating marked point pattern data at nanometre spatial scales. Studying lipid nano-domains within the mammalian cell plasma membrane remains a very challenging task. Here, the authors use the solvatochromic probe di-4-ANEPPDHQ, which is sensitive to its biophysical environment, to map membrane nano-environments via single-molecule localisation microscopy. [ABSTRACT FROM AUTHOR]

Simple Summary: STING agonists face challenges in breast cancer treatment due to their lower accumulation in tumors and rapid clearance from the body, resulting in a short duration of therapeutic effect. Novel phase-transitional liposomes loaded with STING agonists have been developed to overcome these limitations and are specifically designed for low-intensity focused ultrasound (LIFU)-assisted molecular imaging and precise treatment of breast cancer. With the assistance of LIFU, iRGD-modified liposomes (a targeting peptide) undergo a phase transition into microbubbles, leading to enhanced ultrasound molecular imaging of tumors and facilitating breast cancer immunotherapy by releasing STING agonists from the ultrasound-targeted liposomes. Background: Pharmacologically targeting the STING pathway offers a novel approach to cancer immunotherapy. However, small-molecule STING agonists face challenges such as poor tumor accumulation, rapid clearance, and short-lived effects within the tumor microenvironment, thus limiting their therapeutic potential. To address the challenges of poor specificity and inadequate targeting of STING in breast cancer treatment, herein, we report the design and development of a targeted liposomal delivery system modified with the tumor-targeting peptide iRGD (iRGD-STING-PFP@liposomes). With LIFU irradiation, the liposomal system exploits acoustic cavitation, where gas nuclei form and collapse within the hydrophobic region of the liposome lipid bilayer (transient pore formation), which leads to significantly enhanced drug release. Methods: Transmission electron microscopy (TEM) was used to investigate the physicochemical properties of the targeted liposomes. Encapsulation efficiency and in vitro release were assessed using the dialysis bag method, while the effects of iRGD on liposome targeting were evaluated through laser confocal microscopy. The CCK-8 assay was used to investigate the toxicity and cell growth effects of this system on 4T1 breast cancer cells and HUVEC vascular endothelial cells. A subcutaneous breast cancer tumor model was established to evaluate the tumor-killing effects and therapeutic mechanism of the newly developed liposomes. Results: The liposome carrier exhibited a regular morphology, with a particle size of 232.16 ± 19.82 nm, as indicated by dynamic light scattering (DLS), and demonstrated low toxicity to both HUVEC and 4T1 cells. With an encapsulation efficiency of 41.82 ± 5.67%, the carrier exhibited a slow release pattern in vitro after STING loading. Targeting results indicated that iRGD modification enhanced the system's ability to target 4T1 cells. The iRGD-STING-PFP@liposomes group demonstrated significant tumor growth inhibition in the subcutaneous breast cancer mouse model with effective activation of the immune system, resulting in the highest populations of matured dendritic cells (71.2 ± 5.4%), increased presentation of tumor-related antigens, promoted CD8+ T cell infiltration at the tumor site, and enhanced NK cell activity. Conclusions: The iRGD-STING-PFP@liposomes targeted drug delivery system effectively targets breast cancer cells, providing a new strategy for breast cancer immunotherapy. These findings indicate that iRGD-STING-PFP@liposomes could successfully deliver STING agonists to tumor tissue, trigger the innate immune response, and may serve as a potential platform for targeted immunotherapy. [ABSTRACT FROM AUTHOR]

Multi-heme cytochromes (MHCs), together with accessory proteins like porins and periplasmic cytochromes, enable microbes to transport electrons between the cytoplasmic membrane and extracellular substrates (e.g., minerals, electrodes, other cells). Extracellular electron transfer (EET) has been described in multiple systems; yet, the broad phylogenetic and mechanistic diversity of these pathways is less clear. One commonality in EET-capable systems is the involvement of MHCs, in the form of porin-cytochrome complexes, pililike cytochrome polymers, and lipid-anchored extracellular cytochromes. Here, we put forth MHCscan—a software tool for identifying MHCs and identifying potential EET capability. Using MHCscan, we scanned ∼60,000 bacterial and 2,000 archaeal assemblies, and identify a diversity of MHCs, many of which represent enzymes with no known function, and many found within organisms not previously known to be electroactive. In total, our scan identified ∼1,400 unique enzymes, each encoding more than 10 heme-binding motifs. In our analysis, we also find evidence for modularity and flexibility in MHC-dependent EET pathways, and suggest that MHCs may be far more common than previously recognized, with many facets yet to be discovered. [ABSTRACT FROM AUTHOR]

Sepsis-induced myopathy (SIM) has been recognized as a critical risk factor for the development of acquired muscle weakness among patients in the intensive care unit. These individuals frequently encounter inadequate dietary intake and malnutrition. With the aggravation of the severity of the person's condition, leading to increased skeletal muscle protein breakdown and reduced synthesis, which is an urgent problem to be solved in clinical nutritional treatment. Whole milk protein powder (WMPP) has promising bioactive nutrients and holds promising potential for enhancing skeletal muscle mass. The study was designed to delve into the potential effects and mechanisms of WMPP intervention for increaseing skeletal muscle mass on SIM mice. Our results clearly show that the intervention with WMPP can significantly improve the exercise capacity and skeletal muscle mass in SIM mice. It significantly increases the diameter and cross-sectional area (CSA) of skeletal muscle fibers, while effectively reducing the excessive aggregation of collagen fibers and the abnormal accumulation of adipose tissue in the skeletal muscle of SIM mice. Moreover, WMPP intervention also significantly alleviated the oxidative stress status of mitochondria, which subsequently enhanced the expression of mitochondrial metabolic enzymes. The mechanism may be associated with decreased AMPK phosphorylation in skeletal muscle tissue and simultaneously increased phosphorylation of mTOR, p70S6K1, and 4EBP-1 in SIM mice. In summary, the WMPP intervention significantly enhances exercise capacity and skeletal muscle mass while mitigating the oxidative stress status of mitochondria. Furthermore, it regulates skeletal muscle anabolism via the AMPK/mTOR signaling pathway in SIM mice. [ABSTRACT FROM AUTHOR]

Synthetic membrane technology plays an increasingly dominant role in modern industry, boasting remarkable efficiency and low carbon attributes. The ever-growing demand for molecular-level separation necessitates precise structures at the angstrom range with a concomitant low transport resistance, but it still remains a great challenge. Here, we demonstrate an enhanced separation performance towards monovalent cations of two-dimensional (2D) conjugated polymeric carbon nitride (PCN) membranes with angstrom pores, achieved through the strategic incorporation of multivalent ions. Based on the additional ions, the energy barrier of transmembrane transport for individual alkali metal ions could be effectively manipulated. Remarkably, the presence of LaCl3 substantially improves monovalent cation selectivity ratios, improving from 7 to 22 for K+/Li+ in mixtures. More importantly, under an initial concentration gradient, the transport rate of K+ was further enhanced over 1 kmol m−2 h−1, primarily attributed to the low ion transfer barrier. [ABSTRACT FROM AUTHOR]

Apolipoprotein-L1 (APOL1) is a membrane-interacting protein induced by inflammation, which confers human resistance to infection by African trypanosomes. APOL1 kills Trypanosoma brucei through induction of apoptotic-like parasite death, but two T. brucei clones acquired resistance to APOL1, allowing them to cause sleeping sickness. An APOL1 C-terminal sequence alteration, such as occurs in natural West African variants G1 and G2, restored human resistance to these clones. However, APOL1 unfolding induced by G1 or G2 mutations enhances protein hydrophobicity, resulting in kidney podocyte dysfunctions affecting renal filtration. The mechanism involved in these dysfunctions is debated. The ability of APOL1 to generate ion pores in trypanosome intracellular membranes or in synthetic membranes was provided as an explanation. However, transmembrane insertion of APOL1 strictly depends on acidic conditions, and podocyte cytopathology mainly results from secreted APOL1 activity on the plasma membrane, which occurs under non-acidic conditions. In this review, I argue that besides inactivation of APOL3 functions in membrane dynamics (fission and fusion), APOL1 variants induce inflammation-linked podocyte toxicity not through pore formation, but through plasma membrane disturbance resulting from increased interaction with cholesterol, which enhances cation channels activity. A natural mutation in the membrane-interacting domain (N264K) abrogates variant APOL1 toxicity at the expense of slightly increased sensitivity to trypanosomes, further illustrating the continuous mutual adaptation between host and parasite. [ABSTRACT FROM AUTHOR]

Artificial membranes with ion‐selective nanochannels for high‐efficiency mono/divalent ion separation are of great significance in water desalination and lithium‐ion extraction, but they remain a great challenge due to the slight physicochemical property differences of various ions. Here, the successful synthesis of two‐dimensional TpEBr‐based covalent organic framework (COF) nanosheets, and the stacking of them as consecutive membranes for efficient mono/divalent ion separation is reported. The obtained COF nanosheet membranes with intrinsic one‐dimensional pores and abundant cationic sites display high permeation rates for monovalent cations (K+, Na+, Li+) of ≈0.1–0.3 mol m−2 h−1, while the value of divalent cations (Ca2+, Mg2+) is two orders of magnitude lower, resulting in an ultrahigh mono/divalent cation separation selectivity up to 130.4, superior to the state‐of‐the‐art ion sieving membranes. Molecular dynamics simulations further confirm that electrostatic interaction controls the confined transport of cations through the cationic COF nanopores, where multivalent cations face i) strong electrostatic repulsion and ii) steric transport hindrance since the large hydrated divalent cations are retarded due to a layer of strongly adsorbed chloride ions at the pore wall, while smaller monovalent cations can swiftly permeate through the nanopores. [ABSTRACT FROM AUTHOR]

Background: Treatment of articular cartilage injury remains a challenging clinical problem in orthopedics. Chitosan-derived biomaterial could be a potential adjuvant treatment to improve cartilage repair. In the current study, we examined the effects of two potential chitosan-derived materials on cartilage regeneration of osteochondral defects in rabbits. Methods: An osteochondral defect was created over the rabbit knee and treated using three approaches: group A received no material (n = 24), group B received chitosan membranes with glucose absorption (CGA; n = 25), and group C received chitosan-glucose derivative membranes obtained via the Maillard reaction (CGMR; n = 25). Cartilage repair over the osteochondral defect was analyzed 12 weeks post-surgery via histological analysis, immunostaining, and reverse transcription-qualitative polymerase chain reaction (RT-qPCR) for type-I and type-II collagen mRNA. Results: According to histological analysis, CGMR-treated defects showed significantly improved modified O'Driscoll scoring when compared with no material- and CGA-treated defects (20.9 ± 4.3 vs. 13.00 ± 2.5 and 17.7 ± 4.6, p < 0.001). Moreover, group C exhibited higher intensity of type-II collagen immunohistochemical staining over the regenerated cartilage than groups A and B, along with increased expression of type-II collagen mRNA by RT-qPCR. Conclusions: CGMR might improve cartilage regeneration in osteochondral defects. [ABSTRACT FROM AUTHOR]

Background/Objectives: Physiologically based pharmacokinetic (PBPK) absorption models are instrumental for assessing drug absorption prior to clinical food effect studies, though discrepancies in predictive and actual outcomes are observed. This study focused on immediate release formulations of weakly basic water-insoluble compounds, namely rivaroxaban, ticagrelor, and PB-201, to investigate factors that could improve the predictive accuracy of PBPK models regarding food effects. Methods: Comprehensive in vitro experimental results provided the basis for the development of mechanistic absorption models, which were then combined with mechanistic disposition models to predict the systemic exposure of the model drugs in both fasted and fed states. Results: The developed PBPK models showed moderate to high predictive accuracy for food effects in Caucasian populations. For the Chinese population, the ticagrelor model's initial overestimation of fed-state absorption was addressed by updating the permeability parameters from Caco-2 cell assays to those derived from parallel artificial membrane permeability assays in FaSSIF and FeSSIF media. This refinement was also applied to the rivaroxaban and ticagrelor models, leading to a more accurate representation of absorption in Caucasians. Conclusions: This study highlights the importance of apparent permeability in enhancing the predictive accuracy of PBPK absorption models for weakly basic water-insoluble compounds. Furthermore, the precipitation of PB-201 in the two-stage transfer experiments suggests that precipitation may not be a universal phenomenon for such compounds in vivo. Consequently, the precipitation rate constant, a theoretically essential parameter, should be determined based on experimental evidence to avoid overparameterization and ensure robust predictive accuracy of PBPK models. [ABSTRACT FROM AUTHOR]

Indoor radon is one of the most significant contributors to lung cancer after smoking. Mitigation strategies based on protecting buildings with radon barrier materials, combined with home ventilation or room pressurization, are regularly used. A scale model room made from a porous ignimbrite rich in radon precursors was used as an analogue to test the efficiency of fifteen airtight membranes to reduce radon levels, also in combination with room pressurization. The results of these experiments were considered together with previous ones to propose the scale model room approach as a tool for rapidly evaluating the performance of specially designed radon barrier materials, and for radiation exposure assessment. Relative reduction of indoor radon (RIR) ranges from −20 to −94%. The most effective materials were FPO membrane, single-component silane-terminated polymer membranes and synthetic resins. The presence of additives likely modified the composition and structure of some products, improving their radon barrier capacity. The introduction of room pressurization further reduced radon levels in the model room where the membranes were applied. The overpressure necessary to reach RIRs of the order of 85–90% is very low for materials that powerfully stop radon even without ventilation, but necessarily higher for poorer membranes. [ABSTRACT FROM AUTHOR]

The dura mater is a barrier between the brain and the surrounding environment. Injuries to the dura can lead to serious complications, therefore, ensuring a hermetic closure of the dura is a primary task for a neurosurgeon. The aim of the study is to compare the effectiveness of applying the newly developed ViscollDURA collagen membrane (VDCM), with the commercially available Durepair (xenogeneic collagen) in animal model. A dural tear model was utilized in rats with membrane implantation using an application method. The sample size consisted of 24 rats. Group I underwent VDCM implantation, while Group II underwent Durepair implantation. Results were evaluated at 30, 60, and 90 days. The study was assessed using magnetic resonance imaging, histology, electron scanning microscopy, and immunohistochemistry. The obtained results underwent statistical analysis. In the clinical presentation, there were no difference between groups. Histologically, Group 1 showed comparable results to Group 2. The integration process of the membrane statistically differed between the groups. In Group 1, neovascularization and tissue replacement showed better results than in Group 2. Magnetic resonance imaging differences were observed at later stages, with group 2 showing adhesion and brain deformation in the implantation area. Both membranes showed safety and compatibility. The collagen membrane produced under sterile conditions demonstrated better regeneration with minimal inflammatory reaction. The study suggests that VDCM exhibits biocompatibility comparable to Durepair, providing prospects for potential applications in neurosurgery. [ABSTRACT FROM AUTHOR]

Gasdermin D (GSDMD) executes the cell death program of pyroptosis by assembling into oligomers that permeabilize the plasma membrane. Here, by single-molecule imaging, we elucidate the yet unclear mechanism of Gasdermin D pore assembly and the role of cysteine residues in GSDMD oligomerization. We show that GSDMD preassembles at the membrane into dimeric and trimeric building blocks that can either be inserted into the membrane, or further assemble into higher-order oligomers prior to insertion into the membrane. The GSDMD residues Cys39, Cys57, and Cys192 are the only relevant cysteines involved in GSDMD oligomerization. S-palmitoylation of Cys192, combined with the presence of negatively-charged lipids, controls GSDMD membrane targeting. Simultaneous Cys39/57/192-to-alanine (Ala) mutations, but not Ala mutations of Cys192 or the Cys39/57 pair individually, completely abolish GSDMD insertion into artificial membranes as well as into the plasma membrane. Finally, either Cys192 or the Cys39/Cys57 pair are sufficient to enable formation of GSDMD dimers/trimers, but they are all required for functional higher-order oligomer formation. Overall, our study unveils a cooperative role of Cys192 palmitoylation-mediated membrane binding and Cys39/57/192-mediated oligomerization in GSDMD pore assembly. This study supports a model in which Gasdermin D oligomerization relies on a two-step mechanism mediated by specific cysteine residues. Synopsis: Gasdermin D (GSDMD) permeabilizes the plasma membrane during pyroptosis. This work reveals a complex process of GSDMD pore assembly involving specific cysteine residues mediating its membrane targeting and oligomerization. GSDMD membrane targeting is promoted by the synergistic action of Cys192 S-palmitoylation and the presence of negatively-charged lipids. At the membrane, GSDMD preassembles into dimeric and trimeric building units from which higher-order oligomers are generated. Dimer and trimer formation is redundantly mediated by either Cys192 or the Cys39/Cys57 pair. Higher-order oligomerization requires the cooperative action of Cys39/Cys57 and Cys192. The cysteine residue pair Cys39/Cys57 and palmitoylation of Cys192 mediate Gasdermin D membrane targeting and oligomer formation. [ABSTRACT FROM AUTHOR]

Membrane separation has become an indispensable separation technology in social production, playing an important role in drug production, mineral exploitation, water purification, etc. The key core of membranes lies in achieving efficient and precise sieving between substances. As a result, a typical trade‐off arises: highly permeable membranes usually sacrifice selectivity and vice versa. To address this dilemma, long‐term research has focused on comprehensive understanding and modelling of synthetic membranes at various scales. A significant advancement in this arena is the advent of three‐dimensional covalent organic framework (3D COF) membranes, a novel category of long‐range ordered porous organic polymer materials. Characterized by an abundance of interconnected channels, diverse pore wall properties, tunable structures, and robust thermal and chemical resilience, 3D COF membranes offer a promising approach for efficient substance separation. This review undertakes a meticulous investigation of the synthesis and physicochemical properties of 3D COF membranes, accentuating the underlying design principles, fabrication methods, and application attempts. A comprehensive assessment of their research trajectory and current standing in the field of membrane processes is provided. The review culminates in a forward‐looking outlook, summarizing future research directions and highlighting the substantial potential of this innovative work to shape the future of efficient membrane separation processes. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Methods Results Conclusion While some labor interventions are essential in preventing maternal and neonatal morbidity, there is little evidence to support systematic early augmentation of labor (EAL). Our objective was to assess the association between EAL and cesarean delivery rate, postpartum hemorrhage and adverse neonatal outcomes.Population‐based study using data from the 2016 French Perinatal Survey. Women with a singleton cephalic fetus, delivering at term after a spontaneous labor were included. “EAL” was defined by artificial rupture of the membranes (AROM) and/or oxytocin within 1 h of admission and/or duration between interventions of less than 1 h. Women without EAL were women without labor augmentation or without EAL. The primary endpoint, cesarean delivery and the secondary endpoints were compared between women with and without EAL using univariate analysis. A multivariable logistic regression was adjusted on the suspected confounders and a propensity score approach was then performed.Among the 7196 women included, 1524 (21.2%) had EAL. Cesarean delivery rates were significantly higher in the EAL group compared with the no EAL group, 8.40% versus 6.15% (p < 0.01). EAL was associated with cesarean delivery in the multivariable analysis aOR 1.45 95% CI [1.15–1.82] and in the cohort matched on the propensity score, OR 1.56 [1.17–2.07]. EAL was not associated with severe postpartum hemorrhage, low 5‐min Apgar score, low neonatal cord pH or transfer to NICU.EAL is frequent, involving one in five spontaneous laboring women in France. This practice is associated with an increased cesarean delivery risk. [ABSTRACT FROM AUTHOR]

Despite longstanding excitement and progress toward understanding liquid-liquid phase separation in natural and artificial membranes, fundamental questions have persisted about which molecules are required for this phenomenon. Except in extraordinary circumstances, the smallest number of components that has produced large-scale, liquid-liquid phase separation in bilayers has stubbornly remained at three: a sterol, a phospholipid with ordered chains, and a phospholipid with disordered chains. This requirement of three components is puzzling because only two components are required for liquid-liquid phase separation in lipid monolayers, which resemble half of a bilayer. Inspired by reports that sterols interact closely with lipids with ordered chains, we tested whether phase separation would occur in bilayers in which a sterol and lipid were replaced by a single, joined sterol-lipid. By evaluating a panel of sterol-lipids, some of which are present in bacteria, we found a minimal bilayer of only two components (PChemsPC and diPhyPC) that robustly demixes into micron-scale, liquid phases. It suggests an additional role for sterol-lipids in nature, and it reveals a membrane in which tie-lines (and, therefore, the lipid composition of each phase) are straightforward to determine and will be consistent across multiple laboratories. [ABSTRACT FROM AUTHOR]

Phosvitin shows chelating abilities, an affinity for ACTH (corticotropin), growth factors, antioxidant properties, and acidic nature. An attempt was made to use this protein in hydrogels as a transporter of other protein substances: somatotropin (STH) and (ACTH). The aim of the study was to evaluate the effect of phosvitin on the permeation of ACTH and STH from semi-solid forms of the drug applied to the skin. Four hydrogel substrates were prepared using natural polymers: sodium alginate, methylcellulose, and starch. Based on the evaluation of physicochemical parameters, the hydrogel with the most favorable properties was selected and loaded with the active substances STH and ACTH, followed by the addition of phosvitin. A study of the permeation of STH and ACTH through the artificial cellulose membrane and through porcine skin was carried out without and with the addition of phosvitin. The effect of protein substances on rheological and textural parameters was studied. The evaluation of physicochemical parameters showed a favorable effect of STH and Phosvitin on the stability of the hydrogel with 4% methylcellulose and no effect of ACTH. All prepared formulations showed a reaction close to the natural pH of human skin. In the porcine skin permeation study, the addition of Phosvitin to the hydrogel with STH caused a slight increase in the amount of STH permeated and an increase in the time for STH to permeate porcine skin by 30 min. Phosvitin caused an increase in the amount of ACTH permeated through porcine skin almost twofold. Phosvitin may prove to be a promising permeation promoter for model protein-peptide substances when applied to the skin surface. [ABSTRACT FROM AUTHOR]

This study explores the incorporation of 10% 3-O-ethyl L-ascorbic acid (ETVC), a derivative of vitamin C, into two lipid gel systems: a hydrogel (HG) consisting exclusively of lipids and water and a bigel (BG) combining the hydrogel with an oleogel made from olive oil and beeswax. We investigated the ETVC release profiles from both materials using synthetic membranes and measured their permeation through porcine skin in vitro. Additionally, the interaction of these lipid gel systems with the stratum corneum (SC) was determined. Results from the release study indicate that the BG exhibited slower ETVC release compared to the HG. The permeation experiments showed that the presence of lipids in the formulations enhanced ETVC retention in the skin. The HG delivered a higher amount to the SC, while the BG achieved greater retention in the epidermis. This difference is attributed to the different lipophilic nature of each material. The structural analysis of SC lipids revealed that the organization of surface lipids remained unaltered by the application of the gels. Finally, an in vitro efficacy test in porcine skin using methylene blue indicated that our ETVC gels exhibited antioxidant activity. These findings provide valuable insights into the potential of lipid-based gels for topical applications. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the radiographic outcomes of lateral sinus floor elevation with simultaneous implant placement at sites without sinus membrane perforation (SMP) and sites with SMP managed with a resorbable membrane. Materials and Methods: One hundred and thirty‐nine patients and 170 implants (56 perforation, 114 non‐perforation) were included. Cone‐beam computed tomography (CBCT) images were taken before surgery (T0), immediately after surgery (T1) and 6 months after surgery (T2). Post‐operative augmentation parameters, including endo‐sinus bone gain (ESBG) along the implant axis, mean new bone height (NBH) surrounding the implant and augmentation volume (AV), were measured at T1 and T2. Results: At T1, there were no significant differences in ESBG, NBH and AV between the two groups. At T2, although ESBG did not significantly differ between the two groups, NBH (8.50 ± 1.99 mm vs. 9.99 ± 2.52 mm, p =.039) and AV (519.37 ± 258.38 mm3 vs. 700.99 ± 346.53 mm3, p <.001) were significantly lower in the perforation group. The shrinkage of graft material from T1 to T2, including ΔESBG (p =.002), ΔNBH (p <.001) and ΔAV (p <.001), was higher in the perforation group. Conclusions: SMP during LSFE with simultaneous implant placement is associated with greater resorption of the grafted area at a 6‐month follow‐up. [ABSTRACT FROM AUTHOR]

In this study, AlPO-18 zeolite has been synthesized at temperatures ranging from 140° to 180°C and varying synthesis time from 3 to 20 h using sonication mediated hydrothermal process. The characterization results of the synthesized powders and membranes revealed that phase pure AlPO-18 zeolite has been formed at 150°C for 15 h under sonication energy of 250 W. For comparison, the same has been synthesized by the conventional method for 200°C and 69 h. In the sonochemical process, H2O molecule splits into hydrogen radicals (H•) and hydroxyl (•OH) radicals with intense local heating and high pressure during the collapsing of cavitation, which initiates the formation of dihydrogen phosphite (H2PO3•) and dihydrogen phosphate (H2PO4•) radicals and facilitate the formation of AlPO-18 zeolite. Finally, the performance of the membranes has been studied with varying feed pressures for different binary gas mixtures and single gases, and simulated blast furnace (BF) gas has been used to study the separation efficiency of the membranes. The highest separation factors, calculated from BF mixture gas of H2/CO2 and H2/N2 have been achieved as 8.7 and 21, respectively. These results show the possibility of hydrogen recovery from BF flue gas to convert waste to wealth. [ABSTRACT FROM AUTHOR]

Magnetic skyrmions are particle-like topological protected spin structures that can be driven by electric current. We demonstrate a single skyrmion-based multilevel data storage device that could also work as the potential artificial synapse for neuromorphic computing. Four pinning sites are designed to situate the skyrmion in selective regions, whose resistances rise owing to the anisotropic magnetoresistance (AMR) induced by the skyrmion. Skyrmion's position could denote the data levels when the device works as a multilevel data storage device. Pinning sites' positions represent the synaptic weights when it functions as the artificial synapse. Multilevel data storage device's data level change or the synapse's potentiation and depression is realized by the electric current applied parallel to the track. Our work shows that the AMR could help to detect a single skyrmion without the magnetic tunnel junction. Moreover, the skyrmion manipulated by pinning provides an approach for precise control and helps realize skyrmion-based in-memory computing. [ABSTRACT FROM AUTHOR]

This pilot case series study reports the dimensional alveolar bone changes after reconstruction of severely resorbed postextraction sockets treated with a mixture of particulate bone allograft and xenograft in combination with titanium-reinforced dense polytetrafluoroethylene (Ti-d-PTFE) membranes. Ten subjects who required premolar or molar extraction were included. Bone grafts were protected with Ti-d-PTFE membranes, utilizing an open-healing environment; membranes were removed 4 to 6 weeks after extraction, and implants were placed 6.7 months mean) after extraction (T1). One patient required additional augmentation to correct an apical undercut of the alveolar process that was present preextraction. All implants integrated well and showed an implant stability quotient (ISQ) value between 71 and 83. The mean horizontal ridge width reduction from baseline extraction) to T1 was 0.8 mm. Throughout the study, the mean vertical bone gain increase ranged from 0.2 mm to 2.8 mm (mean keratinized tissue width increase: 5.8 mm). The ridge preservation/restoration technique showed good preservation and restoration of severely resorbed sockets as well as improved amounts of keratinized tissue. If implant therapy is required after tooth extraction and severely resorbed sockets are present, the use of a Ti-d-PTFE membrane is a realistic option. [ABSTRACT FROM AUTHOR]

A spiral‐artificial basilar membrane (S‐ABM) sensor is reported that mimics the basilar membrane (BM) of the human cochlea and can detect sound by separating it into 24 sensing channels based on the frequency band. For this, an analytical function is proposed to design the width of the BM so that the frequency bands are linearly located along the length of the BM. To fabricate the S‐ABM sensor, a spiral‐shaped polyimide film is used as a vibrating membrane, with maximum displacement at locations corresponding to specific frequency bands of sound, and attach piezoelectric sensor modules made of poly(vinylidene fluoride‐trifluoroethylene) film on top of the polyimide film to measure the vibration amplitude at each channel location. As the result, the S‐ABM sensor implements a characteristic frequency band of 96‐12,821 Hz and 24‐independent critical bands. Using real‐time signals from discriminate channels, it is demonstrated that the sensor can rapidly identify the operational noises from equipment processes as well as vehicle sounds from environmental noises on the road. The sensor can be used in a variety of applications, including speech recognition, dangerous situation recognition, hearing aids, and cochlear implants, and more. [ABSTRACT FROM AUTHOR]

Nanofluidic energy harvesting from salinity gradients is studied in 2D nanomaterials‐based membranes with promising performance as high ion selectivity and fast ion transport. In addition, moving forward to scalable, feasible systems requires environmentally friendly materials to make the application sustainable. Clay‐based membranes are attractive for being environmentally friendly, non‐hazardous, and easy to manipulate materials. However, achieving underwater stability for clay‐based membranes remains challenging. In this work, the synthetic clay Laponite is used to prepare clay‐based membranes with high stability and excellent performance for osmotic energy harvesting. The Laponite membranes (Lap‐membranes) are stabilized by low‐temperature annealing treatment to effectively reduce the interlayer space, achieving a continuous operation under salinity gradients. Furthermore, the Lap‐membranes conserve integrity while soaking in water for more than one month. The output power density improves from ≈4.97 W m−2 on the pristine membrane to ≈9.89 W m−2 in the membrane treated 12 h at 300 °C from a 30‐fold concentration gradient. Especially, It is found that the presence of interlayer water to be favorable for ion transport. Different mechanisms are proposed in the Lap‐membranes involved for efficient ion selectivity and the states found with varying annealing temperatures. This work demonstrates the potential application of Laponite based nanomaterials for nanofluidic energy harvesting. [ABSTRACT FROM AUTHOR]

Lithium (Li) metal is a promising next-generation anode material, but it suffers from dendrite growth and unstable solid electrolyte interphase (SEI). We developed a robust and continuous self-standing covalent organic framework (COF) membrane using a same-phase synthesis method and utilized the membrane as an artificial SEI. The membrane suppressed dendrite growth and enhanced the stability and longevity of Li metal anode cycling. [ABSTRACT FROM AUTHOR]

AbstractIn this study, in-vitro release experiments were performed using a Franz Diffusion Cell system for Terbinafine Hydrochloride, which is used in the treatment of various fungal infections in the skin caused by many susceptible dermatophytes. In order to evaluate TH transdermally, it was aimed to compare the permeability between polymeric membranes synthesized with polyvinyl alcohol and chitosan mixtures and commercial membranes. In the transdermal drug delivery system calculations, the Fick Diffusion Law was modified and the obtained data were compared. The study was evaluated according to the USP <1724> topical drug products in semisolid form - performance tests. A new high-performance liquid chromatography method was validated for the assay of TH released into the receptor medium in accordance with the ICH guideline. According to the results obtained during the validation process, the limit of detection value was calculated as 0.005 µg/mL and the limit of quantification value was 0.013 µg/mL. Since polymer-based synthetic membranes provide permeability according to molecular size, properties and the ideal environment for measuring and analyzing the diffusion rate of a compound, in experiments conducted using membranes of different structures, the permeability profiles of selected polymer synthetic membranes were statistically evaluated. It has been noted that the hydroxyl groups in PVA and the hydrophilic CS-g-PNDMAAm graft copolymer act at varying rates to enhance or reduce the permeability across the membrane by promoting its diffusion. NaY zeolite has been shown to function as an adsorbent against the medication, lessening the impact of hydrophilic PVA without supplying permeability. [ABSTRACT FROM AUTHOR]

Biological‐machine interface (BMI) devices represent a significant step toward adaptive and cognitive technologies. However, current BMI devices emphasize the analysis of electrophysiology and often overlook the chemical information of neurotransmitters in the process of signaling between neurons. To bridge this gap, a light‐gated artificial postsynaptic membrane (APM) is introduced, capable of reading dopamine (DA) released from rat pheochromocytoma cells and regulate neural signal transmission. Like the biological postsynaptic membrane, the APM is a porous membrane functionalized by DA‐specific aptamers and azobenzene (Azo) molecules in different regions. Azo molecules act as a light‐responsive trigger that controls DA release, while DA‐specific aptamers capture DA, which converts its concentration information into an ionic current signal. By light‐enhanced responses to DA exocytosis from rat pheochromocytoma (PC12) cells, the APM confirms its ability to communicate with biological systems, which lays the foundation for developing biological‐machine interaction systems with more advanced functionalities. [ABSTRACT FROM AUTHOR]

This article discusses the challenges and importance of accurately annotating transporters in metabolic modeling. It emphasizes the need for investment in accurate functional characterization to improve predictive tools and benefit fields such as personalized medicine, metabolic engineering, and microbial ecology. The text also discusses the types of errors that can occur in transporter annotations and the databases and tools available for transporter annotation. The document is a list of references to various scientific articles and databases related to protein subcellular localization, phenotypic testing, gene function, transporter systems, metabolic modeling, and microbial communities. These resources provide valuable information for researchers studying these areas of biology and can be used as references for further exploration. [Extracted from the article]

Motivation There has been a burgeoning interest in cyclic peptide therapeutics due to their various outstanding advantages and strong potential for drug formation. However, it is undoubtedly costly and inefficient to use traditional wet lab methods to clarify their biological activities. Using artificial intelligence instead is a more energy-efficient and faster approach. MuCoCP aims to build a complete pre-trained model for extracting potential features of cyclic peptides, which can be fine-tuned to accurately predict cyclic peptide bioactivity on various downstream tasks. To maximize its effectiveness, we use a novel data augmentation method based on a priori chemical knowledge and multiple unsupervised training objective functions to greatly improve the information-grabbing ability of the model. Results To assay the efficacy of the model, we conducted validation on the membrane-permeability of cyclic peptides which achieved an accuracy of 0.87 and R-squared of 0.503 on CycPeptMPDB using semi-supervised training and obtained an accuracy of 0.84 and R-squared of 0.384 using a model with frozen parameters on an external dataset. This result has achieved state-of-the-art, which substantiates the stability and generalization capability of MuCoCP. It means that MuCoCP can fully explore the high-dimensional information of cyclic peptides and make accurate predictions on downstream bioactivity tasks, which will serve as a guide for the future de novo design of cyclic peptide drugs and promote the development of cyclic peptide drugs. Availability and implementation All code used in our proposed method can be found at https://github.com/lennonyu11234/MuCoCP. [ABSTRACT FROM AUTHOR]

Accurate prediction of the phospholipidosis–induction risk of drugs at early stages is important in drug development. So far, discrimination models for predicting the induction risk of cationic drugs have been proposed, but it is still challenging to accurately predict the risk of cationic drugs with intermediate hydrophobicity (log P). In this study, we introduced a parameter (Δlog k 40) reflecting not only hydrophobic interaction but also interactions with the polar headgroup between cationic drugs and phospholipids, obtained with liquid chromatography using an immobilized artificial membrane column. The parameter was used along with other physicochemical properties as features to construct discrimination models. Linear discriminant analysis, the modified Mahalanobis discriminant analysis, support vector machine, and random forest were employed for model construction. The results showed that all discrimination models exhibited good predictive performance, with the modified Mahalanobis discriminant analysis and random forest providing the best results for cationic drugs, suggesting that the usefulness of the parameter reflecting complex interactions between cationic drugs and immobilized artificial membrane for constructing discrimination models to predict the induction risk. Furthermore, by applying the parameter as a feature in constructing discrimination models, we demonstrated an improvement in the predictive performance for drugs with intermediate hydrophobicity. [Display omitted] • Models to discriminate phospholipidosis induction risk of cationic drugs were made. • A feature representing interactions with immobilized artificial membrane are used. • The feature reflects both hydrophobic and ionic interactions with membrane. • A model allowed accurate prediction of drugs with intermediate hydrophobicity. • Considering complex interactions of drugs and membranes is useful for prediction. [ABSTRACT FROM AUTHOR]

Parallel artificial membrane permeability analysis (PAMPA) is used to determine the permeability of compounds through concentrated negatively charged phospholipid bilayer barriers. We employed MacroFlux (a scaled-up version of PAMPA) to test the permeation rate of terazosin hydrochloride (TH) tablets and predict in vivo bioequivalence. The dissolution profiles and permeability of one reference formulation, and seven generic TH tablets, were compared. The dissolution profiles of these generic tablets were equivalent to that of the reference drug in four different media. However, the flux and the total permeated amount of some generic TH tablets were below the lower limit of the confidence interval of the original acceptance range in MacroFlux, which implied risk in the bioequivalence test in vivo. We further evaluated potential factors responsible for this discrepancy by µFlux, including active pharmaceutical ingredient (API) permeability and excipient prescriptions. The analysis showed that different properties of API were a main factor leading to biological inequivalence in the MacroFlux assay, while excipient prescriptions did not have an impact on bioequivalence risk. These data indicated that the flux assay may be a helpful as an auxiliary method for predicting bioequivalence of generic drugs and analyze the factors responsible for bioequivalence risk. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Can a co-culture of three cell types mimic the in vivo layers of the uterine wall? SUMMARY ANSWER Three protocols tested for co-culture of endometrial epithelial cells (EEC), endometrial stromal cells (ESC), and myometrial smooth muscle cells (MSMC) led to formation of the distinct layers that are characteristic of the structure of the uterine wall in vivo. WHAT IS KNOWN ALREADY We previously showed that a layer-by-layer co-culture of EEC and MSMC responded to peristaltic wall shear stresses (WSS) by increasing the polymerization of F-actin in both layers. Other studies showed that WSS induced significant cellular alterations in epithelial and endothelial cells. STUDY DESIGN, SIZE, DURATION Human EEC and ESC cell lines and primary MSMC were co-cultured on a collagen-coated synthetic membrane in custom-designed wells. The co-culture model, created by seeding a mixture of all cells at once, was exposed to steady WSS of 0.5 dyne/cm2 for 10 and 30 min. PARTICIPANTS/MATERIALS, SETTING, METHODS The co-culture of the three different cells was seeded either layer-by-layer or as a mixture of all cells at once. Validation of the models was by specific immunofluorescence staining and confocal microscopy. Alterations of the cytoskeletal F-actin in response to WSS were analyzed from the 2-dimensional confocal images through the Z-stacks following a previously published algorithm. MAIN RESULTS AND THE ROLE OF CHANCE We generated three multi-cell in vitro models of the uterine wall with distinct layers of EEC, ESC, and MSMC that mimic the in vivo morphology. Exposure of the mixed seeding model to WSS induced increased polymerization of F-actin in all the three layers relative to the unexposed controls. Moreover, the increased polymerization of F-actin was higher (P -value < 0.05) when the length of exposure was increased from 10 to 30 min. Furthermore, the inner layers of ESC and MSMC, which are not in direct contact with the applied shearing fluid, also increased their F-actin polymerization. LARGE SCALE DATA N/A. LIMITATIONS, RESONS FOR CAUTION The mixed seeding co-culture model was exposed to steady WSS of one magnitude, whereas the uterus is a dynamic organ with intra-uterine peristaltic fluid motions that vary in vivo with different time-dependent magnitude. Further in vitro studies may explore the response to peristaltic WSS or other physical and/or hormonal perturbations that may mimic the spectrum of pathophysiological aspects. WIDER IMPLICATIONS OF THE FINDINGS Numerous in vitro models were developed in order to mimic the human endometrium and endometrium–myometrium interface (EMI) region. The present co-culture models seem to be the first constructed from EEC, ESC, and MSMC on a collagen-coated synthetic membrane. These multi-cell in vitro models better represent the complex in vivo anatomy of the EMI region. The mixed seeding multi-cell in vitro model may easily be implemented in controlled studies of uterine function in reproduction and the pathogenesis of diseases. STUDY FINDING/COMPETING INTEREST(S) This study was supported in part by Tel Aviv University funds. All authors declare no conflict of interest. [ABSTRACT FROM AUTHOR]

Aim: This study investigated the adjunctive effect of polydeoxyribonucleotide (PDRN) on bone formation in alveolar ridge preservation (ARP) sockets. Materials and Methods: Both mandibular second, third and fourth premolars of eight beagle dogs were randomly divided into ARP and ARP/PDRN groups. Following tooth extraction, ARP procedures were conducted using collagenized alloplastic graft material and bilayer collagen membrane soaked with normal saline (ARP group) or PDRN (ARP/PDRN group) for 10 min before application. Both groups were also randomly allocated to 2‐, 4‐ or 12‐week healing subgroups. The primary endpoint of this study was to compare histomorphometric differences between ARP and ARP/PDRN. The secondary endpoints of this study were to compare micro‐CT analysis and three‐dimensional volumetric measurement between the two groups. Results: In the histomorphometric analysis, the ARP/PDRN group exhibited greater new bone formation at coronal, middle and total position compared with the ARP group at 2‐week healing. The number of newly formed blood vessels was higher in the ARP/PDRN group than in the ARP group at 2‐ and 4‐week healing. In micro‐CT analysis, the mean new bone volume/total bone volume between ARP and ARP/PDRN was statistically significant at 2‐week healing. Ridge volume alterations were significantly decreased in the ARP/PDRN group during entire healing time compared with the ARP group, especially on the buccal side. Conclusions: The application of PDRN in ARP might provide additional benefits for early bone regeneration and maintenance of buccal ridge volume. [ABSTRACT FROM AUTHOR]

This study emphasizes the importance and application of bioinspired cellular membrane vesicles as smart drug delivery carriers. The lessons can be learned from nature for the smart drug delivery system. Biological membranes are essential to provide stable and functional compartments, preserve cellular architecture, and promote selective signaling and transportation, which are mediated by embedded integral or peripheral proteins. Bioinspired mimicking of natural components in organisms has demonstrated their potential to serve as an innovative system for theranostic applications. However, mimicking the cell membrane in an artificial system is complex because of the multifarious biological structures. The primary advantage of these bioinspired delivery systems is the systematic biodistribution that nonnative delivery systems could not possess. This review will present biomimics resulting from self-assembling amphiphilic polymers. The promising artificial self-assemblies tagged with biomolecules by encapsulation, hybridization, or insertion can serve as means for the development of a smart drug delivery system. Moreover, in case the developed system is stimuli-responsive, the system allows for the triggered or on demand release of payload with in situ specific reaction. In conclusion, cellular membrane vesicles offer an important approach to efficient drug-targeted treatments at the molecular and cellular levels. Here, bioinspired cellular membrane vesicles are discussed along with their applications. Relevant examples of bioinspired membrane mimics are included for an overview of drug delivery candidates. The advantages of using biomimetic membranes and current limitations for future improvements are also included. [ABSTRACT FROM AUTHOR]

The prefusion conformation of human metapneumovirus fusion protein (hMPV Pre-F) is critical for eliciting the most potent neutralizing antibodies and is the preferred immunogen for an efficacious vaccine against hMPV respiratory infections. Here we show that an additional cleavage event in the F protein allows closure and correct folding of the trimer. We therefore engineered the F protein to undergo double cleavage, which enabled screening for Pre-F stabilizing substitutions at the natively folded protomer interfaces. To identify these substitutions, we developed an AI convolutional classifier that successfully predicts complex polar interactions often overlooked by physics-based methods and visual inspection. The combination of additional processing, stabilization of interface regions and stabilization of the membrane-proximal stem, resulted in a Pre-F protein vaccine candidate without the need for a heterologous trimerization domain that exhibited high expression yields and thermostability. Cryo-EM analysis shows the complete ectodomain structure, including the stem, and a specific interaction of the newly identified cleaved C-terminus with the adjacent protomer. Importantly, the protein induces high and cross-neutralizing antibody responses resulting in near complete protection against hMPV challenge in cotton rats, making the highly stable, double-cleaved hMPV Pre-F trimer an attractive vaccine candidate. The authors report an efficacious vaccine for human metapneumovirus based on a prefusion-stabilized fusion protein trimer that does not require a trimerization domain, designed using an AI convolutional classifier trained to predict optimized complex polar interactions. [ABSTRACT FROM AUTHOR]

Natural membrane receptors are proteins that can report on changes in the concentration of external chemical messengers. Messenger binding to a receptor produces conformational changes that are relayed through the membrane into the cell; this information allows cells to adapt to changes in their environment. Artificial membrane receptors (R)‐1 and (S)‐1 are helical α‐aminoisobutyric acid (Aib) foldamers that replicate key parts of this information relay. Solution‐phase 19F NMR spectroscopy of zinc(II)‐capped receptor 1, either in organic solvent or in membrane‐mimetic micelles, showed messenger binding produced an enrichment of either left‐ or right‐handed screw‐sense; the chirality of the bound messenger was relayed to the other receptor terminus. Furthermore, in situ production of a chemical messenger in the external aqueous environment could be detected in real‐time by a racemic mixture of receptor 1 in micelles. The hydrolysis of insoluble anhydrides produced carboxylate in the aqueous phase, which bound to the receptors and gave a distinct 19F NMR output from inside the hydrophobic region of the micelles. [ABSTRACT FROM AUTHOR]

Canines are widely used for real-time detection of explosives and have proven to be on par with instrumental methods. Canines are thought to rely largely upon detection of volatile chemical constituents of the explosives, though not necessarily the explosive itself. Hence, it is crucial to understand the odor available to them as generated by training aids. Previous studies have established that the Training Aid Delivery Device (TADD) developed by SciK9 is a reliable training aid that reduces cross-contamination and doubles as a storage device. A TADD comprises a standardized container, a synthetic membrane, a membrane holder, and a lid. In the work presented, activated charcoal strips were placed above and below the TADD membrane to determine the relative amounts of volatiles emitted by dynamite (i.e., ethylene glycol dinitrate (EGDN) and trinitroglycerin (NG)). The strips were eluted and the extracts tested using gas chromatography–mass spectrometry in negative ion chemical ionization mode. A series of t-tests at 95% confidence level were performed to determine any differences in vapor composition above and below the membranes. Nine synthetic membranes and six glass fiber membranes were tested in this study. It was expected that the relative concentration of volatiles would remain the same on both sides of the membrane; however, selective removal of nitroglycerin by some membranes was observed. Synthetic membranes with larger pore sizes showed no alteration in the vapor composition. Both synthetic and glass fiber membranes did not show a significant change in relative concentration of the other volatile compound in dynamite, i.e., EGDN. Out of all the membranes tested, three synthetic membranes and four glass fiber membranes showed selective alteration in odor availability of nitroglycerin in dynamite. For training purposes, membranes that do not alter the vapor composition should be used in the training aid. [ABSTRACT FROM AUTHOR]

Objectives: Due to the complexity and importance of oral bone structure, oral bone regeneration materials differ from those used in other parts of the body. To study the research trends and hotspots of oral bone regeneration materials, this paper conducts a bibliometric analysis of related papers from 1991 to 2023 (retrieved on 27 September 2023). Materials and methods: Using bibliometric methods, two visualization metric software, Citespace and VOSviewer, were used to analyze 1217 papers in SCIE, including paper analysis, author analysis, country and institution analysis, keyword analysis, and cited literature analysis. Results: (Alavi et al., Oral Surgery Oral Medicine Oral Pathology Oral Radiology, 2023, 136 (5), 554-68) The number of papers is generally increasing and gradually stabilizing; (Xia et al., Bioactive Materials, 2021, 6 (11), 4186-208) Buser D is the most influential author, while Jung, Ronald E has the highest number of papers and total citations; (Wagner et al., Stem Cells Translational Medicine, 2019, 8 (10), 1084-91) The United States has the highest number of papers and citation frequency. The University of Bern and the University of Zurich in Switzerland are not only the institutions with the most papers but also the institutions with the most collaborations with other institutions. (Gallego et al., T Engineering Part A, 2010, 16 (4), 1179-87) Many research directions have persisted for decades since their inception. The field of oral bone regeneration materials is constantly developing and improving. In recent years, the research direction in this field may mainly focus on the role of blood cells and proteins in bone regeneration. (Wang et al., Japanese Dental Science Review, 2022, 58, 233-48). In recent years, the types of cited literature mainly include barrier membranes, alveolar ridge augmentation, bone graft materials, histological examination, and in vivo animal experimental models. Conclusion: The United States and Switzerland have a significant influence in the field of oral bone regeneration materials. The research hotspot in recent years is mainly on tissue engineering materials. However, traditional materials still occupy a large proportion in clinical treatment or research. In addition, the combined use of new and old materials has gradually become one of the research hotspots in this field. [ABSTRACT FROM AUTHOR]

Usutu virus (USUV) is an emerging flavivirus that is maintained in an enzootic cycle with mosquitoes as vectors and birds as amplifying hosts. In Europe, the virus has caused mass mortality of wild birds, mainly among Common Blackbird (Turdus merula) populations. While mosquitoes are the primary vectors for USUV, Common Blackbirds and other avian species are exposed to other arthropod ectoparasites, such as ticks. It is unknown, however, if ticks can maintain and transmit USUV. We addressed this question using in vitro and in vivo experiments and field collected data. USUV replicated in IRE/CTVM19 Ixodes ricinus tick cells and in injected ticks. Moreover, I. ricinus nymphs acquired the virus via artificial membrane blood-feeding and maintained the virus for at least 70 days. Transstadial transmission of USUV from nymphs to adults was confirmed in 4.9% of the ticks. USUV disseminated from the midgut to the haemocoel, and was transmitted via the saliva of the tick during artificial membrane blood-feeding. We further explored the role of ticks by monitoring USUV in questing ticks and in ticks feeding on wild birds in the Netherlands between 2016 and 2019. In total, 622 wild birds and the Ixodes ticks they carried were tested for USUV RNA. Of these birds, 48 (7.7%) carried USUV-positive ticks. The presence of negative-sense USUV RNA in ticks, as confirmed via small RNA-sequencing, showed active virus replication. In contrast, we did not detect USUV in 15,381 questing ticks collected in 2017 and 2019. We conclude that I. ricinus can be infected with USUV and can transstadially and horizontally transmit USUV. However, in comparison to mosquito-borne transmission, the role of I. ricinus ticks in the epidemiology of USUV is expected to be minor. Author summary: Usutu virus (USUV) is a virus primarily circulating between birds and mosquitoes. Other blood-feeding arthropods, such as ticks, feed on birds. However, it is unknown whether ticks can be infected with USUV and transmit the virus to birds or other animals. Therefore, we infected a tick cell line and ticks collected from the field with USUV. We showed that the virus replicates in tick cells, as well as in field-collected ticks. Moreover, we showed that USUV disseminated through the tick body and was excreted with the saliva of ticks during artificial feeding. We further investigated if ticks are infected with USUV while feeding on wild birds and when searching for a host in the vegetation. We found that 7.7% of tick-infested birds carried USUV positive ticks, while USUV was not detected in questing ticks. Our findings provide evidence that ticks can be infected with USUV and might transmit the virus to another host, but the role of ticks in the transmission of USUV is expected to be minor. [ABSTRACT FROM AUTHOR]

Glycosylation is the most common form of post‐translational modification in the brain. Aberrant glycosylation has been observed in cerebrospinal fluid and brain tissue of Alzheimer's disease (AD) cases, including dysregulation of terminal sialic acid (SA) modifications. While alterations in sialylation have been identified in AD, the localization of SA modifications on cellular or aggregate‐associated glycans is largely unknown because of limited spatial resolution of commonly utilized methods. The present study aims to overcome these limitations with novel combinations of histologic techniques to characterize the sialylation landscape of O‐ and N‐linked glycans in autopsy‐confirmed AD post‐mortem brain tissue. Sialylated glycans facilitate important cellular functions including cell‐to‐cell interaction, cell migration, cell adhesion, immune regulation, and membrane excitability. Previous studies have not investigated both N‐ and O‐linked sialylated glycans in neurodegeneration. In this study, the location and distribution of sialylated glycans were evaluated in three brain regions (frontal cortex, hippocampus, and cerebellum) from 10 AD cases using quantitative digital pathology techniques. Notably, we found significantly greater N‐sialylation of the Aβ plaque microenvironment compared with O‐sialylation. Plaque‐associated microglia displayed the most intense N‐sialylation proximal to plaque pathology. Further analyses revealed distinct differences in the levels of N‐ and O‐sialylation between cored and diffuse Aβ plaque morphologies. Interestingly, phosphorylated tau pathology led to a slight increase in N‐sialylation and no influence of O‐sialylation in these AD brains. Confirming our previous observations in mice with novel histologic approach, these findings support microglia sialylation appears to have a relationship with AD protein aggregates while providing potential targets for therapeutic strategies. [ABSTRACT FROM AUTHOR]

This paper investigates the efficacy of ultra-high-performance concrete (UHPC) jacketing as an option for seismic retrofit (repair or strengthening) of structural components that have been damaged by reinforcement corrosion. Previous work has illustrated that UHPC cover fully mitigates corrosion in the absence of service cracks and significantly reduces the corrosion rate in the case of preexisting cracks. In the present experimental study, cover replacement by UHPC is used to repair and strengthen corroded columns. Six lap-spliced columns designed based on pre-1970s design standards were constructed and subjected to artificial corrosion. Parameters of the investigation were: a) the aspect ratio of the specimens; b) the bar size (to account for the effect of bar diameter loss on bond); and c) the condition of the specimen (repair or strengthening after damage due to application of simulated seismic load to assess the effectiveness of retrofitting corroded components, even after having endured earthquake damage). The results show that thin UHPC jackets replacing conventional concrete cover suffice to impart a significant increase in strength and ductility of the columns. The jackets also endow the corroded and unconfined lap splices with significant force and deformation development capacity, thus alleviating a source of excessive column flexibility in existing construction. [ABSTRACT FROM AUTHOR]

The emergence of new protein functions is crucial for the evolution of organisms. This process has been extensively researched for soluble enzymes, but it is largely unexplored for membrane transporters, even though the ability to acquire new nutrients from a changing environment requires evolvability of transport functions. Here, we demonstrate the importance of environmental pressure in obtaining a new activity or altering a promiscuous activity in members of the amino acid-polyamine-organocation (APC)-type yeast amino acid transporters family. We identify APC members that have broader substrate spectra than previously described. Using in vivo experimental evolution, we evolve two of these transporter genes, AGP1 and PUT4, toward new substrate specificities. Single mutations on these transporters are found to be sufficient for expanding the substrate range of the proteins, while retaining the capacity to transport all original substrates. Nonetheless, each adaptive mutation comes with a distinct effect on the fitness for each of the original substrates, illustrating a trade-off between the ancestral and evolved functions. Collectively, our findings reveal how substrate-adaptive mutations in membrane transporters contribute to fitness and provide insights into how organisms can use transporter evolution to explore new ecological niches. [ABSTRACT FROM AUTHOR]

Temperature-responsive liquid chromatography (TRLC) offers a promising alternative to reversed-phase liquid chromatography (RPLC) for environmentally friendly analytical techniques by utilizing pure water as a mobile phase, eliminating the need for harmful organic solvents. TRLC columns, packed with temperature-responsive polymers coupled to silica particles, exhibit a unique retention mechanism influenced by temperature-induced polymer hydration. An investigation of the physicochemical parameters driving separation at high and low temperatures is crucial for better column manufacturing and selectivity control. Assessment of predictability using a dataset of 139 molecules analyzed at different temperatures elucidated the molecular descriptors (MDs) relevant to retention mechanisms. Linear regression, support vector regression (SVR), and tree-based ensemble models were evaluated, with no standout performer. The precision, accuracy, and robustness of models were validated through metrics, such as r and mean absolute error (MAE), and statistical analysis. At 45 ∘ C , logP predominantly influenced retention, akin to reversed-phase columns, while at 5 ∘ C , complex interactions with lipophilic and negative MDs, along with specific functional groups, dictated retention. These findings provide deeper insights into TRLC mechanisms, facilitating method development and maximizing column potential. [ABSTRACT FROM AUTHOR]

Proton Exchange Membrane Fuel Cells are a favorite technology for decarbonizing the transportation sector. However, their large-scale democratization is hampered by their high cost compounded by their unsatisfactory lifespan. To anticipate potential degradation while keeping improving performance, it is essential to maintain an acceptable humidity range inside the cells, especially at the membrane level. However, membrane humidity level is not directly measurable, alternative techniques must be considered to recover this key variable. Here, we develop a real-time software sensor of the membrane water content at the fuel cell's heart. We build a model describing the membrane water balance, electrochemical behavior, and species mass balance. We then reduce the model and perform an Adaptive Extended Kalman Filter. We perform sensitivity analyses in both steady-state and transient conditions. We validate the filter on a "Worldwide Harmonized Light Vehicles Test Cycles" test procedure. Finally, we obtain a fast and accurate model-based software sensor. • Real-time capable software sensor for PEMFC membrane water content. • Observer based on membrane model accounting for most of major transport phenomena. • Adaptive Extended Kalman filter applied to differential-algebraic equations. • Sensitivity analysis of membrane water content shows a 5% coefficient of variation.

In this study, based on ethnobotanical data recorded in Transylvania, the polyphenolic compounds and the permeability of the aerial part's extract of Tanacetum balsamita were investigated. Ultrahigh-performance liquid chromatography-tandem mass spectrometry was applied for the analysis of the extracts. Parallel artificial membrane permeability assay (PAMPA) for the gastrointestinal tract and the blood–brain barrier was conducted. In the ethanolic and aqueous extracts of the species traditionally used for wound, furuncle, and liver disorders, 92 polyphenols were characterized (e.g., flavonoid, hydroxycinnamic acid, catechin, dihydroxybenzoyl, lignan derivatives, and a monoterpene) including 54 compounds identified for the first time in the plant. In the PAMPA tests, eight components were shown to be capable of passive diffusion across the studied membranes. These include apigenin and seven methoxylated flavonoid derivatives. Based on these results, methoxylated flavonoids might promote the pharmacological potential of T. balsamita to be applied in the enhancement of novel remedies. [ABSTRACT FROM AUTHOR]

Introduction: Horizontal ridge augmentation of a deficient alveolar bone site is performed either simultaneously with implant placement or in a staged approach prior to implant insertion. There are several available strategies for the augmentation of alveolar ridge deficiencies, including guided bone regeneration (GBR) through the use of barrier membranes. The success of the GBR approach mainly depends on the exclusion of soft tissue cells during bone remodeling. Case presentation: A healthy 25-year-old male patient presented with a missing upper left central incisor after clinical and radiographic examination, the site showed a class III defect horizontal atrophy. The procedure performed was the horizontal alveolar ridge augmentation using resorbable pericardium membrane with double layer graft technique (DLT) where autogenous bone placed as a first layer of the graft followed by xenograft as a second layer, the membrane was fixed with titanium pins. A cone beam computed tomography (CBCT) was performed before, immediately and 6 month following the surgery. After 6 months during implant placement, a core biopsy specimen was retrieved, stored and prepared for histological evaluation, with assessment of primary implant stability. The radiographic analysis showed a horizontal width gain of about 4 mm, at 6 month following implant placement, the implant was successfully osteointegrated with stability assessment also done after 6 months from placement. Conclusion: DLT was successfully used for horizontal alveolar ridge augmentation, thus allowing a prosthetically driven implant placement. More cases assessing implant survival and success are needed to confirm the results of this case report. [ABSTRACT FROM AUTHOR]

Non-targeted analysis of high-resolution mass spectrometry (MS) can identify thousands of compounds, which also gives a huge challenge to their quantification. The aim of this study is to investigate the impact of mass spectrometry ionization efficiency on various compounds in food at different solvent ratios and to develop a predictive model for mass spectrometry ionization efficiency to enable non-targeted quantitative prediction of unknown compounds. This study covered 70 compounds in 14 different mobile phase ratio environments in positive ion mode to analyze the rules of the matrix effect. With the organic phase ratio from low to high, most compounds changed by 1.0 log units in log IE. The addition of formic acid enhanced the signal but also promoted the matrix effect, which often occurred in compounds with strong ionization capacity. It was speculated that the matrix effect was mainly in the form of competitive charge and charged droplet' gasification sites during MS detection. Subsequently, we present a log IE prediction method built using the COSMO-RS software and the artificial neural network (ANN) algorithm to address this difficulty and overcome the shortcomings of previous models, which always ignore the matrix effect. This model was developed following the principles of QSAR modeling recommended by the Organization for Economic Cooperation and Development (OECD). Furthermore, we validated this approach by predicting the log IE of 70 compounds, including those not involved in the log IE model development. The results presented demonstrate that the method we put forward has an excellent prediction accuracy for log IE (R2 pred = 0.880), which means that it has the potential to predict the log IE of new compounds without authentic standards. [ABSTRACT FROM AUTHOR]