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Motivation We explored how explainable artificial intelligence (XAI) can help to shed light into the inner workings of neural networks for protein function prediction, by extending the widely used XAI method of integrated gradients such that latent representations inside of transformer models, which were finetuned to Gene Ontology term and Enzyme Commission number prediction, can be inspected too. Results The approach enabled us to identify amino acids in the sequences that the transformers pay particular attention to, and to show that these relevant sequence parts reflect expectations from biology and chemistry, both in the embedding layer and inside of the model, where we identified transformer heads with a statistically significant correspondence of attribution maps with ground truth sequence annotations (e.g. transmembrane regions, active sites) across many proteins. Availability and Implementation Source code can be accessed at https://github.com/markuswenzel/xai-proteins. [ABSTRACT FROM AUTHOR]

Mastoparans are cationic peptides with multifunctional pharmacological properties. Mastoparan-R1 and mastoparan-R4 were computationally designed based on native mastoparan-L from wasps and have improved therapeutic potential for the control of bacterial infections. Here, we evaluated whether these peptides maintain their activity against Escherichia coli strains under a range of salt concentrations. We found that mastoparan- R1 and mastoparan-R4 preserved their activity under the conditions tested, including having antibacterial activities at physiological salt concentrations. The overall structure of the peptides was investigated using circular dichroism spectroscopy in a range of solvents. No significant changes in secondary structure were observed (random coil in aqueous solutions and a-helix in hydrophobic and anionic environments). The three-dimensional structures of mastoparan-R1 and mastoparan-R4 were elucidated through nuclear magnetic resonance spectroscopy, revealing amphipathic a-helical segments for Leu3-Ile13 (mastoparan-R1) and Leu3-Ile14 (mastoparan- R4). Possible membrane-association mechanisms for mastoparan-R1 and mastoparan-R4 were investigated through surface plasmon resonance and leakage studies with synthetic POPC and POPC/POPG (4:1) lipid bilayers. Mastoparan-L had the highest affinity for both membrane systems, whereas the two analogs had weaker association, but improved selectivity for lysing anionic membranes. This finding was also supported by molecular dynamics simulations, in which mastoparan-R1 and mastoparan-R4 were found to have greater interactions with bacteria-like membranes compared with model mammalian membranes. Despite having a few differences in their functional and structural profiles, the mastoparan-R1 analog stood out with the highest activity, greater bacteriostatic potential, and selectivity for lysing anionic membranes. This study reinforces the potential of mastoparan-R1 as a drug candidate. [ABSTRACT FROM AUTHOR]

Simple Summary: Louse-borne diseases have caused millions of deaths around the world and are currently re-emerging in some countries. Implementing a simple and accessible lice-rearing system would significantly advance research on the louse–pathogen cycle and vectorial capacities. Several in vivo and in vitro lice-rearing methods have been developed. However, these approaches have drawbacks, making lice production more difficult. Here, we aimed to adapt the Orlando (Or) strain of body lice on an artificial membrane. The Hemotek system and a Petri dish system covered with a Parafilm membrane were tested on newly hatched first-stage larvae (L1). Rearing follow-up consisted of recording dead, fed and moulted specimens throughout the experiments. In addition, microscopic ultra-structures, blood meal digestion and sterility were evaluated and compared to those of larvae being reared on rabbit hosts. When using heparinised blood on a Petri dish, we were able to maintain one generation of body lice. Development into adulthood was recorded 21 days after hatching, and 52 eggs were deposited. Inspection of the blood meal revealed a colour difference among lice fed in vitro and in vivo, while microscopic investigations did not show any differences. The in vitro lice-rearing experiments were conducted in accordance with animal welfare requirements and therefore have the potential to replace animal models in various biological assays. Human lice are the only hematophagous ectoparasites specific to human hosts. They transmit epidemic typhus, trench fever and relapsing fever, diseases which have already caused millions of deaths worldwide. In order to further investigate lice vectorial capacities, laboratory-controlled live lice colonies are essential. Previously developed lice-rearing methods significantly advanced research on louse-borne diseases and louse biology. In this study, we aimed to develop a rearing technique for the Orlando (Or) strain of body lice on an artificial membrane. We tested two systems, namely the Hemotek feeding system and a Petri dish with the lice being fed through a Parafilm membrane. Lice longevity and development were drastically affected by the blood anticoagulant. Additionally, heparinised human blood on a Petri dish was the best candidate when compared to the control group (reared on a rabbit). Therefore, this strategy was applied to 500 lice. Development into adulthood was recorded after 21 days (17 days for the rabbits), and 52 eggs were deposited (240 for the rabbits). In this study, we were able to maintain one generation of body lice on an artificial membrane with comparable feeding and longevity rates to those fed on live rabbits. However, lice fecundity decreased on the artificial membrane. In vitro lice-rearing experiments will enable pathogen infection assays and pesticide bioassays to be carried out in accordance with animal welfare requirements. [ABSTRACT FROM AUTHOR]

The Von Neumann architecture has been the foundation of modern computing systems. Still, its limitations in processing large amounts of data and parallel processing have become more apparent as computing requirements increase. Neuromorphic computing, inspired by the architecture of the human brain, has emerged as a promising solution for developing next-generation computing and memory devices with unprecedented computational power and significantly lower energy consumption. In particular, the development of optoelectronic artificial synaptic devices has made significant progress toward emulating the functionality of biological synapses in the brain. Among them, the potential to mimic the function of the biological eye also paves the way for advancements in robot vision and artificial intelligence. This review focuses on the emerging field of optoelectronic artificial synapses and memristors based on low-dimensional nanomaterials. The unique photoelectric properties of these materials make them ideal for use in neuromorphic and optoelectronic storage devices, with advantages including high carrier mobility, size-tunable optical properties, and low resistor–capacitor circuit delay. The working mechanisms, device structure designs, and applications of these devices are also summarized to achieve truly sense-storage-computer integrated optoelectronic artificial synapses. [ABSTRACT FROM AUTHOR]

Pathogenic Rhodococcus equi release the virulence‐associated protein A (VapA) within macrophage phagosomes. VapA permeabilizes phagosome and lysosome membranes and reduces acidification of both compartments. Using biophysical techniques, we found that VapA interacts with model membranes in four steps: (i) binding, change of mechanical properties, (ii) formation of specific membrane domains, (iii) permeabilization within the domains, and (iv) pH‐specific transformation of domains. Biosensor data revealed that VapA binds to membranes in one step at pH 6.5 and in two steps at pH 4.5 and decreases membrane fluidity. The integration of VapA into lipid monolayers was only significant at lateral pressures <20 mN m−1 indicating preferential incorporation into membrane regions with reduced integrity. Atomic force microscopy of lipid mono‐ and bilayers showed that VapA increased the surface heterogeneity of liquid disordered domains. Furthermore, VapA led to the formation of a new microstructured domain type and, at pH 4.5, to the formation of 5 nm high domains. VapA binding, its integration and lipid domain formation depended on lipid composition, pH, protein concentration and lateral membrane pressure. VapA‐mediated permeabilization is clearly distinct from that caused by classical microbial pore formers and is a key contribution to the multiplication of Rhodococcus equi in phagosomes. [ABSTRACT FROM AUTHOR]

Kymograph analysis is employed across the biological atomic force microscopy (AFM) community to boost temporal resolution. The method is well suited for revealing protein dynamics at the single molecule level in near-native conditions. Yet, kymograph analysis comes with limitations that depend on several factors including protein geometry and instrumental drift. This work focuses on conformational dynamics of difficult-to-study sparse distributions of membrane proteins. We compare and contrast AFM kymograph analysis for two proteins, one of which (SecDF) exhibits conformational dynamics primarily in the vertical direction (normal to the membrane surface) and the other (Pgp) exhibits a combination of lateral dynamics and vertical motion. Common experimental issues are analyzed including translational and rotational drift. Conformational transition detection is evaluated via kymograph simulations followed by state detection algorithms. We find that kymograph analysis is largely robust to lateral drift. Displacement of the AFM line scan trajectory away from the protein center of mass by a few nanometers, roughly half of the molecule diameter, does not significantly affect transition detection nor generate undue dwell time errors. On the other hand, for proteins like Pgp that exhibit significant azimuthal maximum height dependence, rotational drift can potentially produce artifactual transitions. Measuring the height of a membrane protein protrusion is generally superior to measurement of width, confirming intuition based on vertical resolution superiority. In low signal-to-noise scenarios, common state detection algorithms struggle with transition detection as opposed to infinite hidden Markov models. AFM kymography represents a valuable addition to the membrane biophysics toolkit; continued hardware and software improvements are poised to expand the method's impact in the field. [ABSTRACT FROM AUTHOR]

Manufacturing industries require the efficient and voluminous production of high-quality finished goods. In the context of Industry 4.0, visual anomaly detection poses an optimistic solution for automatically controlled product quality with high precision. In general, automation based on computer vision is a promising solution to prevent bottlenecks at the product quality checkpoint. We considered recent advancements in machine learning to improve visual defect localization, but challenges persist in obtaining a balanced feature set and database of the wide variety of defects occurring in the production line. Hence, this paper proposes a defect localizing autoencoder with unsupervised class selection by clustering with k-means the features extracted from a pretrained VGG16 network. Moreover, the selected classes of defects are augmented with natural wild textures to simulate artificial defects. The study demonstrates the effectiveness of the defect localizing autoencoder with unsupervised class selection for improving defect detection in manufacturing industries. The proposed methodology shows promising results with precise and accurate localization of quality defects on melamine-faced boards for the furniture industry. Incorporating artificial defects into the training data shows significant potential for practical implementation in real-world quality control scenarios. [ABSTRACT FROM AUTHOR]

Most logging businesses in the US South are owned by White males, many of whom are approaching retirement. The purpose of this study was to evaluate the characteristics of logging businesses with a young owner, beginning (new) business owner, and businesses owned by members of a minority group (YBM). In-person interviews were conducted with twelve YBM logging business owners in Florida and Georgia to gather information on business characteristics and perceived barriers to the formation of these businesses. The YBM business owners were more educated, employed more workers, and had similar capital investments relative to other logging business owners. These owners stated that difficulty recruiting quality employees, high startup costs, lack of industry connections, and high insurance premiums were unique obstacles to establishing YBM businesses. Purposeful actions by the forest industry, policymakers, and other stakeholders may encourage the formation and retention of YBM logging businesses. Study Implications: As the current generation of logging business owners leaves the industry, it is important to develop new businesses. New businesses will likely be owned by young owners, mid-career professionals starting new logging businesses (beginning businesses), and businesses owned by members of a minority group (YBM). Targeted efforts by loggers' associations, the forest industry, and other stakeholders that provide business management training, develop a skilled workforce of equipment operators and log truck drivers, and promote policies that result in affordable insurance may encourage the establishment and retention of YBM businesses. [ABSTRACT FROM AUTHOR]

Research on van der Waals heterostructures based on stacked two‐dimensional atomic thickness crystals has received considerable attention because of their unique characters and great potential applications in flexible transparent electronics and optoelectronics. In this study, a nonvolatile memory device with a few‐layer bipolar material WS2 as channel and charge‐trapping layers is designed with a floating‐gate structure in which charges (electrons and holes) can be stored in the charge‐trapping layer using a dual‐mode processing program by changing the metal–semiconductor contact type. The device exhibits different programming currents during programming, in particular, the device has a low programming current for programming voltages ˂20 V. Moreover, the heterostructure exhibits a remarkable long retention time (≈10,000 s), with no apparent degradation and a strong endurance, retaining its original performance even after 1,000 programming/erasing cycles. This study proposes a novel method for reducing power consumption while programming to facilitate artificial synapse applications. [ABSTRACT FROM AUTHOR]

The objective of this article is to provide a theoretical framework for the structure and function of the retina. The first focus of this article is the examination of the physiological aspects of the retina. The given study proposes a model that utilizes artificial neural networks to create the model's structure. This approach is motivated by the resemblance between the behavior of the model and that of retinal cells. The neural network receives as input the intensity of light that is incident on the retina and produces as output the activity of the retinal ganglion cells. A comparison has been conducted between the data derived by the model and the biological data. This comparative analysis demonstrates that neural networks can adequately simulate the behavior of ganglion cells. However, the effectiveness of the network is contingent upon its architectural configuration, the number of hidden layers used, and the specific learning method utilized. The experimental findings demonstrate that including the output from earlier iterations as input to the neural network results in the system exhibiting memory. This approach enhances the model's efficiency and mitigates the occurrence of periodic behavior. The model, as mentioned above, has potential applications in the development of artificial retinas, serving as a hardware implementation to restore some visual capabilities in individuals with visual impairments. [ABSTRACT FROM AUTHOR]

Data-driven simulations are gaining popularity in mechanics of biomaterials since they do not require explicit form of constitutive relations. Data-driven modeling based on neural networks lacks interpretability. In this study, we propose an interpretable data-driven finite element modeling for hyperelastic materials. This approach employs the Laplace stretch as the strain measure and utilizes response functions to define constitutive equations. To validate the proposed method, we apply it to inflation of anisotropic membranes on the basis of synthetic data for porcine skin represented by Holzapfel-Gasser-Ogden model. Our results demonstrate applicability of the method and show good agreement with reference displacements, although some discrepancies are observed in the stress calculations. Despite these discrepancies, the proposed method demonstrates its potential usefulness for simulation of hyperelastic biomaterials. [ABSTRACT FROM AUTHOR]

This study presents a one-stage technique for horizontal guided bone regeneration and transmucosal implant placement in the presence of hard and soft tissue defects. The proposed technique uses autologous bone particles, deproteinized bovine bone matrix, collagen membranes, and concentrated growth factor membranes to create a multilayer barrier and enhance tissue regeneration. Four patients were treated with a total of seven implants. Digital analyses of intraoral scan data taken at baseline and at 6 months postsurgery showed a mean increase in tissue volume of 157.4 mm³. The patient satisfaction was high, and no complications were observed. [ABSTRACT FROM AUTHOR]

Allografts have been routinely used for immediate grafting of extraction sites as modalities of alveolar ridge preservation (ARP). Solvent-dehydrated bone allograft (SDBA), which is commonly utilized for socket grafting, exists in the form of cortical and cancellous particles. This study aims to provide a histologic comparison of cortical and cancellous SDBA for ARP. A total of 35 extraction sockets were allocated to receive either a cortical (17 sites) or cancellous (18 sites) SDBA, followed by application of a resorbable collagen wound dressing in both groups. At approximately 4 months, a bone core biopsy sample was obtained during implant placement. Histomorphometric assessment was then conducted to compare the differences between both forms of SDBA. Within its limitations, a higher percentage of vital bone was observed in the cortical bone group compared to the cancellous bone group (28.6% vs 20.1%, respectively, P = .042), while there was a lack of statistically significant differences among other fractions of the bone biopsy sample (residual graft particles and nonmineralized tissues such as connective tissue or other components). [ABSTRACT FROM AUTHOR]

Antimicrobial resistance presents a pressing challenge to public health, which requires the search for novel antimicrobial agents. Various experimental and theoretical methods are employed to understand drug-target interactions and propose multistep solutions. Nonetheless, efficient screening of drug databases requires rapid and precise numerical analysis to validate antimicrobial efficacy. Diptool addresses this need by predicting free energy barriers and local minima for drug translocation across lipid membranes. In the current study employing Diptool free energy predictions, the thermodynamic commonalities between selected antimicrobial molecules were characterized and investigated. To this end, various clustering methods were used to identify promising groups with antimicrobial activity. Furthermore, the molecular fingerprinting and machine learning approach (ML) revealed common structural elements and physicochemical parameters in these clusters, such as long carbon chains, charged ammonium groups, and low dipole moments. This led to the establishment of guidelines for the selection of effective antimicrobial candidates based on partition coefficients (logP) and molecular mass ranges. These guidelines were implemented within the Reinforcement Learning for Structural Evolution (ReLeaSE) framework, generating new chemicals with desired properties. Interestingly, ReLeaSE produced molecules with structural profiles similar to the antimicrobial agents tested, confirming the importance of the identified features. In conclusion, this study demonstrates the ability of molecular fingerprinting and AI-driven methods to identify promising antimicrobial agents with a broad range of properties. These findings deliver substantial implications for the development of antimicrobial drugs and the ongoing battle against antibiotic-resistant bacteria. [ABSTRACT FROM AUTHOR]

Implementation of tunable digital and analog resistive switching (RS) behaviors for memristors is crucial toward their development in data storage and energy-efficient computations. Herein, the CsPbBr3 film-based RS memristors with different switching film thickness and adaptable electrodes are constructed, which are implemented by the solution processed method. All the constructed memristors demonstrate stable bipolar switching behaviors, and in special, the gradual analog RS behavior with multi-level conductance is observed for the thin memristor, making it as the promising artificial synapse. As a comparison, the thick memristor demonstrates digital abrupt RS behavior, accompanying with a high memory window (>103), which can be applied in data storage field. Furthermore, the evolution of conductive filaments, stemming from synergetic bromine vacancies and aluminum atoms, is proposed to clarify the distinguished dynamic changes in the RS process. This work provides an optimization strategy to tune RS behavior for CsPbBr3-based RS memristors and paves the way for both data storage and artificial synapse applications. [ABSTRACT FROM AUTHOR]

The main techniques, approaches, methods, and information products used in recent years for the identification of chemical compounds are summarized. The methodology used in target analysis has largely remained unchanged; only the identification criteria have undergone some adjustments. The scope of research in non-target analysis has been significantly expanded. In this case, the main problems lie in revealing candidates for identification. These versions are tested against typical criteria of target analysis. Effective search for suitable candidate compounds has become possible with the apearance of modern high-resolution chromatography–mass spectrometers and progress in informatics. The latter includes the development of algorithms and programs for processing chromatographic and mass spectrometric data; comparing them with reference values; and predicting mass spectra, retention parameters, and other quantities. Chemical databases enable the assessment of the prevalence of chemical compounds and, correspondingly, their potential as candidates for identification. [ABSTRACT FROM AUTHOR]

Purpose: Significant resources are spent on developing robust liquid chromatography (LC) methods with optimum conditions for all project in the pipeline. Although, data-driven computer assisted modelling has been implemented to shorten the method development timelines, these modelling approaches require project-specific screening data to model retention time (RT) as function of method parameters. Sometimes method re-development is required, leading to additional investments and redundant laboratory work. Cheminformatics techniques have been successfully used to predict the RT of metabolites & other component mixtures for similar use cases. Here we will show that these techniques can be used to model structurally diverse molecules and predictions of these models trained on multiple LC conditions can be used for downstream data-driven modelling. Methods: The Molecular Operating Environment (MOE) was used to calculate over 800 descriptors using the strucutres of the analytes. These descriptors were used to model the RT of the analytes under four chromatographic conditions. These models were then used to create data-driven models using LC-SIM. Results: A structural-based Random Forest (RF) model outperformed other techniques in cross-validation studies and predicted the RTs of a randomized test set with a median percentage error less than 4% for all LC conditions. RTs predicted by this structure-based model were used to fit a data-driven model that identifies optimum LC conditions without any additional experimental work. Conclusions: These results show that small training sets yield pharmaceutically relevant models when used in a combination of structure-based and data-driven model. [ABSTRACT FROM AUTHOR]

Excess cortisol release is associated with numerous health concerns, including psychiatric issues (i.e., anxiety, insomnia, and depression) and nonpsychiatric issues (i.e., osteoporosis). The aim of this study was to assess the in vitro inhibition of cortisol release, bioaccessibility, and bioavailability exerted by a chemically characterized Scutellaria lateriflora L. extract (SLE). The treatment of H295R cells with SLE at increasing, noncytotoxic, concentrations (5–30 ng/mL) showed significant inhibition of cortisol release ranging from 58 to 91%. The in vitro simulated gastric, duodenal, and gastroduodenal digestions, induced statistically significant reductions (p < 0.0001) in the bioactive polyphenolic compounds that most represented SLE. Bioavailability studies on duodenal digested SLE, using Caco-2 cells grown on transwell inserts and a parallel artificial membrane permeability assay, indicated oroxylin A glucuronide and oroxylin A were the only bioactive compounds able to cross the Caco-2 cell membrane and the artificial lipid membrane, respectively. The results suggest possible applications of SLE as a food supplement ingredient against cortisol-mediated stress response and the use of gastroresistant oral dosage forms to partially prevent the degradation of SLE bioactive compounds. In vivo studies and clinical trials remain necessary to draw a conclusion on the efficacy and tolerability of this plant extract. [ABSTRACT FROM AUTHOR]

In order to study the effect of the interaction between different inertial channels and decoupler membrane channels on the hydraulic mount characteristic. Firstly, the effect of the single inertia channel and decoupler membrane channel interaction on the hydraulic mount characteristic is analyzed. Secondly, a multi-inertia channel hydraulic mount model with nine structures and four combination schemes is proposed. Among them, the mount's structure includes long inertia channels, short inertia channels, different inertia channel cross-sectional areas, and the number of inertia channels. And then, the number of inertia channels, the cross-sectional area, and the interaction between long and short inertia channels and decoupler membrane channels are analyzed for their effects on the hydraulic mount characteristics. Finally, the effect of the interaction between the inertial and decoupler membrane channels on the time-domain characteristics of the hydraulic mount at different excitation amplitudes. The results show that the number of inertia channels, cross-sectional area, and the interaction between the number of long and short inertia channels and decoupler membrane channels directly affect the vibration isolation performance of hydraulic mounts at high and low frequencies. [ABSTRACT FROM AUTHOR]

Cystinosis is a low-prevalence lysosomal storage disease. The pathomechanism involves abnormal functioning of the cystinosine lysosomal cystine transporter (CTNS), causing intraliposomal accumulation of the amino acid cysteine disulfide, which crystallizes and deposits in several parts of the body. The most common ophthalmic complication of cystinosis is the deposition of "gold dust" cystine crystals on the cornea, which already occurs in infancy and leads to severe photosensitivity and dry eyes as it gradually progresses with age. In the specific treatment of cystinosis, preparations containing cysteamine (CYA) are used. The availability of commercialized eyedrops for the targeted treatment is scarce, and only Cystadrops® are commercially available with strong limitations. Thus, magistral CYA-containing compounded eyedrops (CYA-CED) could have a key role in patient care; however, a rationally designed comprehensive study on the commercialized and magistral products is still missing. This work aims to build up a comprehensive study about commercialized and magistral CYA eye drops, involving pharmacokinetic and physicochemical characterization (applying mucoadhesivity, rheology test, investigation of drug release, and parallel artificial membrane permeability assays), as well as ex vivo tests, well supported by statistical analysis. [ABSTRACT FROM AUTHOR]

Microcephaly is a rare neurodevelopmental disorder characterized by reduced skull circumference and brain volume that occurs sporadically in farm animals. We investigated an early‐onset neurodegenerative disorder observed in seven lambs of purebred Kerry Hill sheep. Clinical signs included inability to stand or severe ataxia, convulsions, and early death. Diagnostic imaging and brain necropsy confirmed microcephaly. The pedigree of the lambs suggested monogenic autosomal recessive inheritance. We sequenced the genome of one affected lamb, and comparison with 115 control genomes revealed a single private protein‐changing variant. This frameshift variant, MFSD2A: c.285dupA, p.(Asp96fs*9), represents a 1‐bp duplication predicted to truncate 80% of the open reading frame. MFSD2A is a transmembrane protein that is essential for maintaining blood–brain barrier homeostasis and plays a key role in regulating brain lipogenesis. Human MFSD2A pathogenic variants are associated with a neurodevelopmental disorder with progressive microcephaly, spasticity, and brain imaging abnormalities (NEDMISBA, OMIM 616486). Here we present evidence for the occurrence of a recessively inherited form of microcephaly in sheep due to a loss‐of‐function variant in MFSD2A (OMIA 002371‐9940). To the best of our knowledge, this is the first report of a spontaneous MFSD2A variant in domestic animals. [ABSTRACT FROM AUTHOR]

Future decarbonisation scenarios will make carbon capture and storage (CCS) a viable solution for organisations that use a lot of energy. Nevertheless, due to current technology's high energy and financial costs, CCS systems are challenging to deploy, making researchers prioritise novel solutions based upon new/improved methods such as chemical absorption, adsorption and solutions like solvents, sorbents, membranes, and new process designs. Mitigating CO2 using water is a potential and cost-effective method; hence, this paper presents a simulation analysis of CO2 absorption technology in a spray column scrubber with a novel helical sparger (NHS). In this context, a model was developed using the computational fluid dynamics (CFD) technique where a spray column scrubber with two different spargers (a conventional sparger and a novel helical sparger (NHS)) was designed to absorb CO2. The turbulent kinetic energy, the volume fraction of CO2, and hydrodynamics for both the spargers were determined. The results showed significant improvement in CO2 absorption in the novel helical scrubber as it shows a CO2 absorption efficiency of 52.64% while the conventional sparger shows it of 29.34% during experiments in aqueous medium. However, the simulations results show a higher absorption efficiencies of 50.945%, and 70.628% for conventional sparger, and novel helical sparger, respectively. This work shows that a properly designed CFD simulation can help to optimise the scrubber design and improve absorption performance. [ABSTRACT FROM AUTHOR]

The combination of 5-fluorouracil/leucovorin (5-FU/LV) plus oxaliplatin (FOLFOX) is widely acknowledged as the standard regimen for second-line treatment in patients with advanced biliary tract cancer. Nanoliposomal irinotecan (nal-IRI) has demonstrated its activity in patients with advanced pancreatic cancer. Recent studies have investigated the activity of nal-IRI in combination with 5-FU/LV for biliary tract cancer. However, the results have been contradictory. We conducted a meta-analysis to assess survival outcomes and response rates in randomised trials investigating the activity of nal-IRI in previously treated biliary tract cancer patients. We systematically collected potentially relevant findings from PubMed/Medline, the Cochrane library and EMBASE. Abstracts presented at major international oncological meetings were also reviewed. We extracted hazard ratios and 95% confidence intervals for progression-free survival and overall survival, as well as odds ratios and 95% confidence intervals for objective response rate. The outcomes of the accessible randomised studies evaluating the activity of nal-IRI plus 5-FU/LV were analysed. The combination therapy exhibited a statistically significant decrease in the risk of progression (hazard ratio 0.70; 95% confidence interval 0.50–0.97) when compared with 5-FU/LV alone. Additionally, the dual regimen yielded longer overall survival and a higher objective response rate. Our meta-analysis showed that nal-IRI plus 5-FU/LV had a superior activity in comparison with 5-FU/LV. Further investigations are required to elucidate the role of nal-IRI in this setting and to identify subgroups of patients who could derive the greatest benefit from its administration. • No evidence that doublet therapy is more effective than monotherapy in second-line treatment of biliary tract cancer. • FOLFOX demonstrated higher activity compared with active symptom control. • Two studies showed conflicting results assessing the activity of 5-FU/LV ± nal-IRI. • Our meta-analysis supports the role of nal-IRI in biliary tract cancer. [ABSTRACT FROM AUTHOR]

Summary: This study aimed to prepare SLC7A5 transporters targeted liposomes of Ribociclib (RB) by stear(o)yl conjugation of Phe, Asp, Glu amino acids to liposomes as targeting moieties. The liposomes were optimized for their formulations. Cell analysis on two cell lines of MCF-7 and NIH-3T3 were done including; cell viability test by MTT assay, cellular uptake, and cell cycle arrest by flow cytometry. The optimal liposomes showed the particle size of 123.6 ± 1.3 nm, drug loading efficiency and release efficiency of 83.87% ± 1.33% and 60.55% ± 0.46%, respectively. The RB loaded liposomes showed no hemolysis activity. Targeted liposomes increased cytotoxicity on MCF-7 cells more significantly than NIH-3T3 cells. Cell flow cytometry indicated that targeted liposomes uptake was superior to plain (non-targted) liposomes and free drug. Free drug and RB-loaded liposomes interrupted cell cycle in G1. However, amino acid-targeted liposomes arrested cells more than the free drug at this stage. Targeted liposomes reduced cell cycle with more interruption in the G2/M phase compared to the negative control. [ABSTRACT FROM AUTHOR]

Photonic solar sails are a class of advanced propellantless propulsion systems that use thin, large, lightweight membranes to convert the momentum of light from the Sun into thrust for space navigation. The conceptually simple nature of such a fascinating propulsion system requires, however, advances in materials, packaging, deployment, and control of a very large space structure. In this context, the finite element method (FEM), implemented in a robust and flexible software such as the commercial software Abaqus, represents a fundamental instrument to progress with the practical study of this promising propulsion system concept. In particular, in a typical (medium-size) square solar sail design process, the FEM-based analyses are used to better understand fundamental aspects of structural design, such as, for example, membrane pre-tensioning, deformations induced by Solar Radiation Pressure (SRP), and the buckling of reinforcing booms. The aim of this study is to describe an effective procedure to model a classical square solar sail structure into a typical commercial software for finite element analysis, such as the well-known suite Abaqus. In particular, we compare various membrane pre-tensioning techniques (useful for increasing the membrane's bending stiffness) and describe possible approaches to applying the SRP-induced load in a realistic way. Additionally, the flexibility of the structure under the solar sail loads and the criticality of section shape and boom size are taken into account, with particular regard to the problem of structural instability. In this context, performance and critical issues of different structural solutions are discussed and compared, allowing an improvement in the preliminary design phase of solar sails to be obtained. [ABSTRACT FROM AUTHOR]

A significant contributor to retaining wall structural failure occurs due to inadequate drainage in the backfill. A numerical model based on a computational fluid dynamics and discrete element method (CFD-DEM) coupled approach was developed to simulate particle movement in the graded filter zone and piping through the geotextiles. The model was used for conventional as well conical geotextile filter systems that use a series of woven geotextiles filtering a coarse-grained backfill soil. The model results were compared with laboratory results to verify the accuracy. The results indicated that conical filter systems contribute to higher soil piping rates but provide higher permeability than conventional geotextile filtration system counterparts. The model predictions compared with the laboratory measurements indicated that the movement of particles (i.e. suffusion) influenced the soil-geotextile contact zone permeabilities and caused a decrease in system permeabilities. A retention ratio, α sl , successfully predicted piping rates for different types of woven geotextiles with a percent error range of 13–29%. Overall, the model predictions matched the laboratory results within an order of magnitude or less, indicating the predictive capability of the model. [ABSTRACT FROM AUTHOR]

The unique anatomical and physiological connections between the nasal cavity and brain provide a pathway for bypassing the blood--brain barrier to allow for direct brain-targeted drug delivery through nasal administration. There are several advantages of nasal administration compared with other routes; for example, the first-pass effect that leads to the metabolism of orally administered drugs can be bypassed, and the poor compliance associated with injections can be minimized. Nasal administration can also help maximize brain-targeted drug delivery, allowing for high pharmacological activity at lower drug dosages, thereby minimizing the likelihood of adverse effects and providing a highly promising drug delivery pathway for the treatment of central nervous system diseases. The aim of this review article was to briefly describe the physiological structures of the nasal cavity and brain, the pathways through which drugs can enter the brain through the nose, the factors affecting brain-targeted nasal drug delivery, methods to improve brain-targeted nasal drug delivery systems through the application of related biomaterials, common experimental methods used in intranasal drug delivery research, and the current limitations of such approaches, providing a solid foundation for further in-depth research on intranasal brain-targeted drug delivery systems (see Graphical Abstract). [ABSTRACT FROM AUTHOR]

In some laboratories, mosquitoes' direct blood-feeding on live animals has been replaced with various membrane blood-feeding systems. The selection of blood meal sources used in membrane feeding is crucial in vector mass rearing as it influences the mosquitoes' development and reproductive fitness. Therefore, this scoping review aimed to evaluate the existing literature on the use of different blood sources and components in artificial membrane feeding systems and their effects on blood-feeding and the fecundity rate of Ae. aegypti. A literature review search was conducted by using PubMed, Scopus, and Web of Science databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA-ScR). The EndNote version 20 software was used to import all searched articles. Relevant information was retrieved for analysis into a Microsoft Excel Spreadsheet. A total of 104 full-text articles were assessed for eligibility criteria, whereby the articles should include the comparison between different types of blood source by using the membrane feeding systems. Only 16 articles were finally included in the analysis. Several studies had reported that human blood was superior in blood-feeding Ae. aegypti as compared to sheep blood which resulted in lower fecundity due to accumulation of free fatty acids (FFA) in the cuticles. In contrast, cattle whole blood and pig whole blood showed no significant differences in the blood-feeding and fecundity rate as compared to human blood. This review also indicated that bovine whole blood and pig whole blood enhanced Ae. aegypti's vitellogenesis and egg production as compared to plasma and blood cells. In addition, human blood of up to 10 days after the expiration date could still be used to establish Ae. aegypti colonies with good blood-feeding rates and number of eggs produced. Thus, future studies must consider the importance of selecting suitable blood sources and components for membrane blood feeding especially in mosquito colonisation and control measure studies. [ABSTRACT FROM AUTHOR]

We present FreeDTS software for performing computational research on biomembranes at the mesoscale. In this software, a membrane is represented by a dynamically triangulated surface equipped with vertex-based inclusions to integrate the effects of integral and peripheral membrane proteins. Several algorithms are included in the software to simulate complex membranes at different conditions such as framed membranes with constant tension, vesicles and high-genus membranes with various fixed volumes or constant pressure differences and applying external forces to membrane regions. Furthermore, the software allows the user to turn off the shape evolution of the membrane and focus solely on the organization of proteins. As a result, we can take realistic membrane shapes obtained from, for example, cryo-electron tomography and backmap them into a finer simulation model. In addition to many biomembrane applications, this software brings us a step closer to simulating realistic biomembranes with molecular resolution. Here we provide several interesting showcases of the power of the software but leave a wide range of potential applications for interested users. In this work, the authors report the FreeDTS software to simulate biomembranes at the mesoscale. The software provides various membrane simulations, focusing on protein organization and shape remodeling. A versatile tool propelling realistic membrane studies and diverse applications. [ABSTRACT FROM AUTHOR]

Summary: Heat stress interrupts physiological thermostability and triggers biochemical responses that are essential for plant survival. However, there is limited knowledge on the speed plants adjust to heat in hours and days, and which adjustments are crucial.Tropical–subtropical rainforest tree species (Polyscias elegans) were heated at 40°C for 5 d, before returning to 25°C for 13 d of recovery. Leaf heat tolerance was quantified using the temperature at which minimal chl a fluorescence sharply rose (Tcrit). Tcrit, metabolites, heat shock protein (HSP) abundance and membrane lipid fatty acid (FA) composition were quantified.Tcrit increased by 4°C (48–52°C) within 2 h of 40°C exposure, along with rapid accumulation of metabolites and HSPs. By contrast, it took > 2 d for FA composition to change. At least 2 d were required for Tcrit, HSP90, HSP70 and FAs to return to prestress levels.The results highlight the multi‐faceted response of P. elegans to heat stress, and how this response varies over the scale of hours to days, culminating in an increased level of photosynthetic heat tolerance. These responses are important for survival of plants when confronted with heat waves amidst ongoing global climate change. [ABSTRACT FROM AUTHOR]

A mixed‐dimensional heterostructure comprising nanomaterials with varying dimensions provides a promising structure for an artificial synapse for reconfigurable neuromorphic functions. In this study, an 8 × 8 memristor crossbar array based on a mixed‐dimensional heterostructure comprising Cs1−xFAxPbBr3 (0.00 ≤ x ≤ 0.15) quantum dots (QDs) and different dimensional interfacial nanomaterial layers between the Al and ITO electrodes is designed and fabricated. This array device exhibits a high yield and reliable self‐rectifying analog switching characteristics with low synaptic‐coupling (SC, up to 5.19 × 10−5) and light emission, facilitating stimuli response visualization and preventing undesired pathways in the network array. Furthermore, because the formamidinium (FA) concentration alters the QD size, thereby engineering interfacial band alignment in the heterostructure, the essential synaptic properties such as dynamic range, SC, and nonlinearity can be improved. Especially, as x increases from 0 to 0.11, the recognition accuracy for the MNIST patterns increases significantly, from 68.97% to 89.08%, even for single‐layer ANNs. The energy consumption required for a specific accuracy level is reduced by a factor of 25.15. The utilization of mixed‐dimensional perovskite QD‐based heterostructures in neural networks may provide desirable neuromorphic electronic functions with enhanced learning capability and energy efficiency, while preventing unwanted neural signals. [ABSTRACT FROM AUTHOR]

The continuous growth in artificial intelligence and high-performance computing has necessitated the development of efficient optoelectronic artificial synapses crucial for neuromorphic computing (NC). Ga2O3 is an emerging wide-bandgap semiconductor with high deep ultraviolet absorption, tunable persistent photoconductivity, and excellent stability toward electric fields, making it a promising component for optoelectronic artificial synapses. Currently reported Ga2O3 optoelectronic artificial synapses often suffer from complex fabrication processes and potential room for improvement due to plasticity. To address the issue of low device plasticity and practical application scenarios, we present an amorphous Ga2O3 (α-GaOx) flexible optoelectronic artificial synapse. This synapse modulates light stimulus signals using electron/oxygen vacancies and optical stimulation and operates as a visual storage device for information processing. We investigate the improvement of the optoelectronic synapses' plasticity by controlling the number of oxygen vacancies via a plasma treatment method and demonstrate its effective application in a three-layer backpropagation neural network for handwritten digit classification. Under the same stimulus conditions, the synaptic weight of samples treated with Ar plasma exhibits a higher rate of change, with the current levels increasing by 2–3 orders of magnitude, achieving greater plasticity. The improved optoelectronic synapses achieved an accuracy of 93.34%/94%, demonstrating their potential as efficient computing solutions and insights for future applications in NC chips. [ABSTRACT FROM AUTHOR]

There has been increasing interest in methods to generate synthetic lipid membranes as key constituents of artificial cells or to develop new tools for remodeling membranes in living cells. However, the biosynthesis of phospholipids involves elaborate enzymatic pathways that are challenging to reconstitute in vitro. An alternative approach is to use chemical reactions to non‐enzymatically generate natural or non‐canonical phospholipids de novo. Previous reports have shown that synthetic lipid membranes can be formed in situ using various ligation chemistries, but these methods lack biocompatibility and/or suffer from slow kinetics at physiological pH. Thus, it would be valuable to develop chemoselective strategies for synthesizing phospholipids from water‐soluble precursors that are compatible with synthetic or living cells Here, we demonstrate that amide‐forming ligations between lipid precursors bearing hydroxylamines and α‐ketoacids (KAs) or potassium acyltrifluoroborates (KATs) can be used to prepare non‐canonical phospholipids at physiological pH conditions. The generated amide‐linked phospholipids spontaneously self‐assemble into cell‐like micron‐sized vesicles similar to natural phospholipid membranes. We show that lipid synthesis using KAT ligation proceeds extremely rapidly, and the high selectivity and biocompatibility of the approach facilitates the in situ synthesis of phospholipids and associated membranes in living cells. [ABSTRACT FROM AUTHOR]

The elution by imidazole is used in the purification process of non-alpha IL-2 mutein, specifically in the immobilized metal chelates affinity chromatography step (IMAC). In order to demonstrate that a new elution process is possible using cheaper solutions, changes were made in the former capture step. These changes consist on separate the size exclusion chromatography and the controlled oxidation stage which are currently performed together, as well as changing the elution solution. To achieve this, a 22 factorial design of experiments was performed to evaluate the effect of pH and molar concentration on recovery, purity, and particle diameter. The best results were obtained with the solution of sodium acetate 20 mmol L-1 pH 4 being similar to those obtained in the industry nowadays: 29 % recovery, 90 % of purity, and particle diameter 18,40 nm. The first contribution of this paper is to demonstrate the feasibility of using the new elution methodology. Moreover, by using the academic software SuperPro Designer, the actual capture step of the purification process (elution by Imidazole) was simulated, validated, and verified. To demonstrate the relationship between costs and benefits, the CH SFF matrix gel volume was incremented. This change increased costs at this stage. However, the productivity obtained grew to 109 mg h-1, 2.78 times greater than the current productivity. Therefore, the gross net increased by 879 325, 00 $. This result constitutes the second contribution of this paper. [ABSTRACT FROM AUTHOR]

Topical treatments for onychomycosis are of interest to those seeking to avoid systemic drug interactions and to improve systemic safety. This work aimed to develop aqueous-based, simple, and cost-effective vehicles that provide high solubility for ciclopirox and enable the delivery of an active through channels created by nail microporation. Following solubility tests, aqueous gels and thermogels based on hydroxypropylmethylcellulose and poloxamer 407, respectively, were loaded with 8% and 16% ciclopirox. Their performance was then compared to the marketed lacquer Micolamina® in in vitro release tests with artificial membranes and in in vitro permeation tests with human nail clippings with and without poration. Finally, a microbiological assay compared the best gel formulations and the reference product. Little correlation was observed between the in vitro release and the permeation data, and the drug release was highly membrane-dependent. Ciclopirox nail retention in single-dose, porated nails tests was larger than in daily-dosing, non-porated nail conditions. The series of new gel and thermogel vehicles delivered ciclopirox more effectively than Micolamina® in single-dose, porated nail experiments. The inhibition of Trichophyton rubrum activity was significantly increased with microporated nails when the gel formulations were applied but not with Micolamina®. Overall, the results suggest that the new vehicles could be successfully combined with nail microporation to improve the drug delivery and efficacy of topical antifungal medication while reducing the dosing frequency, facilitating patients' adherence. [ABSTRACT FROM AUTHOR]

The endoplasmic reticulum (ER) is a dynamic organelle that is amenable to major restructuring. Introduction of recombinant ER-membrane-resident proteins that form homo oligomers is a known method of inducing ER proliferation: interaction of the proteins with each other alters the local structure of the ER network, leading to the formation large aggregations of expanded ER, sometimes leading to the formation of organized smooth endoplasmic reticulum (OSER). However, these membrane structures formed by ER proliferation are poorly characterized and this hampers their potential development for plant synthetic biology. Here, we characterize a range of ER-derived membranous compartments in tobacco and show how the nature of the polyproteins introduced into the ER membrane affect the morphology of the final compartment. We show that a cytosol-facing oligomerization domain is an essential component for compartment formation. Using fluorescence recovery after photobleaching, we demonstrate that although the compartment retains a connection to the ER, a diffusional barrier exists to both the ER and the cytosol associated with the compartment. Using quantitative image analysis, we also show that the presence of the compartment does not disrupt the rest of the ER network. Moreover, we demonstrate that it is possible to recruit a heterologous, bacterial enzyme to the compartment, and for the enzyme to accumulate to high levels. Finally, transgenic Arabidopsis constitutively expressing the compartment-forming polyproteins grew and developed normally under standard conditions. [ABSTRACT FROM AUTHOR]

Background: Collagen is a major component of the extracellular matrix that supports the epidermal layers of the skin; thus, many strategies have been made to enhance the topical delivery of collagen for antiaging purposes. In addition, our previous study indicated that liposome can help the penetration of active ingredients into the skin. Aims: To produce stable collagen‐encapsulated liposomes to improve the topical delivery of collagen. Methods: Collagen‐encapsulated liposomes were fabricated using high‐pressure homogenization method. The colloidal stability and adhesion ability were confirmed using dynamic light scattering, and spectrofluorophotometer, respectively. Keratinocyte differentiations of 3D skin before and after treatment with collagen‐encapsulated liposomes were confirmed by real‐time PCR. Results: In comparison with native collagen, collagen‐encapsulated liposomes enhanced collagen retention in artificial membranes by twofold, even after repeated washings with water. In addition, real‐time PCR results indicated that 3D skin treated with collagen‐encapsulated liposomes exhibited higher levels of collagen, keratin, and involucrin, even after ethanol treatment. Conclusion: Liposomes could serve as efficient delivery vehicles for collagen, thereby enhancing its antiaging effects. [ABSTRACT FROM AUTHOR]

New functional materials for engineering gingival tissue are still in the early stages of development. Materials for such applications must maintain volume and have advantageous mechanical and biological characteristics for tissue regeneration, to be an alternative to autografts, which are the current benchmark of care. In this work, methacrylated gelatin (GelMa) was photocrosslinked with synthetic immunomodulatory methacrylated divinyl urethanes and defined monomers to generate composite scaffolds. Using a factorial design, with the synthetic monomers of a degradable polar/hydrophobic/ionic polyurethane (D-PHI) and GelMa, composite materials were electrospun with polycarbonate urethane (PCNU) and light-cured in-flight. The materials had significantly different relative hydrophilicities, with unique biodegradation profiles associated with specific formulations, thereby providing good guidance to achieving desired mechanical characteristics and scaffold resorption for gingival tissue regeneration. In accelerated esterase/collagenase degradation models, the new materials exhibited an initial rapid weight loss followed by a more gradual rate of degradation. The degradation profile allowed for the early infiltration of human adipose-derived stromal/stem cells, while still enabling the graft's structural integrity to be maintained. In conclusion, the materials provide a promising candidate platform for the regeneration of oral soft tissues, addressing the requirement of viable tissue infiltration while maintaining volume and mechanical integrity. There is a need for the development of more functional and efficacious materials for the treatment of gingival recession. To address significant limitations in current material formulations, we sought to investigate the development of methacrylated gelatin (GelMa) and oligo-urethane/methacrylate monomer composite materials. A factorial design was used to electrospin four new formulations containing four to five monomers. Synthetic immunomodulatory monomers were crosslinked with GelMa and electrospun with a polycarbonate urethane resulting in unique mechanical properties, and resorption rates which align with the original design criteria for gingival tissue engineering. The materials may have applications in tissue engineering and can be readily manufactured. The findings of this work may help better direct the efforts of tissue engineering and material manufacturing. [Display omitted] [ABSTRACT FROM AUTHOR]

Due to nonspecific pathological changes and the rapid degradation of insulin in postmortem blood samples, the identification of the cause of death during insulin overdose has always been a difficulty in forensic medicine. At present, there is a lack of studies on the toxicological changes and related mechanisms of an insulin overdose, and the specific molecular markers of insulin overdose are still unclear. In this study, an animal model of insulin overdose was established, and 24 SD rats were randomly divided into a control group, insulin overdose group, and a recovery group (n = 8). We detected the biochemical changes and analyzed the toxicological mechanism of an insulin overdose. The results showed that after insulin overdose, the rats developed irregular convulsions, Eclampsia, Opisthotonos, and other symptoms. The levels of glucose, glycogen, and C-peptide in the body decreased significantly, while the levels of lactate, insulin, and glucagon increased significantly. The decrease in plasma K+ was accompanied by the increase in skeletal muscle K+. The PI3K-AKT signaling pathway was significantly activated in skeletal muscle, and the translocation of GLUT4/Na+-K+-ATPase to sarcolemma was significantly increased. Rare glycogenic hepatopathy occurred in the recovery group after insulin overdose. Our study showed that insulin overdose also plays a role in skeletal muscle cells, mainly through the PI3K-Akt signaling pathway. Therefore, the detection of signaling pathway proteins of the skeletal muscle cell membrane GLUT4 and Na+-K+-ATPase has a certain auxiliary diagnostic value for forensic insulin overdose identification. Glycogen detection in the liver and skeletal muscle is important for the diagnosis of insulin overdose, but it still needs to be differentiated from other causes of death. Skeletal muscle has great potential for insulin detection, and the ratio of insulin to the C-peptide (I:C) can determine whether an exogenous insulin overdose is present. [ABSTRACT FROM AUTHOR]

Conventional remediation techniques have become outdated and insufficient to treat the influx of pollution from different fronts (air, water, and soil). Green synthesis of nanoparticles is an eco-friendly approach to remediate these contaminants and Membrane technology is increasingly becoming popular for the treatment of wastewater due to their efficiency and versatility against a wide array of contaminants. Cellulose acetate (CA) is a polymer obtained from cellulose and hence considered biodegradable, making it a more environmentally friendly option over other conventional polymers. In this present study, silver nanoparticles were synthesized using Staphylococcus aureus and characterized by UV-vis Spectrometer, Scanning Electron Microscopy (SEM) and Energy Dispersive X-ray Analysis (EDAX). The synthesized green silver nanoparticles were assimilated onto synthesized CA membrane films to fabricate nanocomposite membranes (CA-X, CA-X1 and CA-X2). EDAX results showed higher counts of silver at 3keV on the CA-X, confirming that silver nanoparticles were properly embedded on the membrane. Physio-chemical tests performed on the collected sewage, showed that the total dissolved solids (TDS) were found to decrease significantly during the first hour of treatment, CA-X1 showed 16.2% decrease and 21.95% decrease was observed by CA-X2. A decrease in total nitrogen content by 38.88% and 41.36% for CA-X1 and CA-X2 respectively was recorded after a week's treatment. Therefore, the work displayed the capability of cellulose acetate nanocomposite membrane for leachate treatment, since it displayed its potential in remediating leachate in a short span of time and scalability could be achieved for a larger volume of leachate with larger nanocomposite membranes. [ABSTRACT FROM AUTHOR]

N‐Alkyl‐thio glycolipids (TGL) are proposed as fundamental components in the production of synthetic outer membrane vesicles (S‐OMVs). A small but representative library of glycolipids was prepared by thiol‐ene coupling (TEC), using unprotected thiols in acceptable to good yields (63‐96 %). Multilamellar giant vesicles (GVs) of varying sizes were assembled from mixtures of TGL and 1‐palmitoyl‐2‐oleoyl‐sn‐glycero‐3‐phosphate (POPC). Our results mark an important advancement for the development of synthetic anticancer vaccines, supramolecular adjuvants and drug delivery systems based on glycolipid/phospholipid formulations (10 % mol/mol in 0.1 mm solution). [ABSTRACT FROM AUTHOR]

1,3-β-d-Glucan (BDG) is commonly used for diagnosing invasive fungal infections (IFIs). While exposure to cellulose-based hemodialyzers is known to cause false-positive BDG results, the impact of modern hemofilters used in continuous renal replacement therapy (CRRT) remains unclear. This retrospective, single-center cohort study aimed to evaluate the effect of CRRT on BDG levels in critically ill patients. We included adult intensive care unit (ICU) patients with ≥1 BDG measurement between December 2019 and December 2020. The primary outcome was the rate of false-positive BDG results in patients exposed to CRRT compared to unexposed patients. Propensity score analysis was performed to control for confounding factors. A total of 103 ICU patients with ≥1 BDG level were identified. Most (72.8%) were medical ICU patients. Forty patients underwent CRRT using hemofilter membranes composed of sodium methallyl sulfonate copolymer (AN 69 HF) (82.5%) and of polyarylethersulfone (PAES) (17.5%). Among the 91 patients without proven IFI, 31 (34.1%) had false-positive BDG results. Univariable analysis showed an association between CRRT exposure and false-positive BDG results. However, the association between CRRT exposure and false-positive BDG results was no longer significant across three propensity score models employed: 1:1 match (n = 32) (odds ratio (OR) 1.65, p = .48), model-adjusted (n = 91) (OR 1.75, p = .38), quintile-adjusted (n = 91) (OR 1.78, p = .36). In this single-center retrospective analysis, exposure to synthetic CRRT membranes did not independently increase the risk of false-positive BDG results. Larger prospective studies are needed to further evaluate the association between CRRT exposure and false-positive BDG results in critically ill patients with suspected IFI. [ABSTRACT FROM AUTHOR]

In modern times, any disturbances caused by natural or artificial factors to technological systems must be identified and eliminated promptly. Space weather has been acknowledged for more than ten years as a key cause of breakdowns in numerous ground- and space-based technology systems that are essential to human life. Thus, this article about research interest trends related to space weather events (SWEs), from all around the world was analyzed through bibliometric analysis using Scopus publications from 1994 until 2022. Initially, 2779 journal articles on SWE were collected over the course of 28 years, but only 1713 were retained when review articles were omitted. The study also presents the trends of co-authorships in correspondence to countries/academic institutions and co-occurrences of author keywords. Since 2005, the number of publications regarding SWE has steadily increased, resulting in a substantial library of publications until 2022. The three top-ranked nations that produced the most papers with the highest levels of international collaboration and networking are the United States, the United Kingdom, and China. [ABSTRACT FROM AUTHOR]

Periodontal disease is one of the most common oral diseases with the highest incidence world-wide. In particular, the treatment of periodontal bone defects caused by periodontitis has attracted extensive attention. Guided bone regeneration (GBR) has been recognized as advanced treatment techniques for periodontal bone defects. GBR technique relies on the application of barrier membranes to protect the bone defects. The commonly used GBR membranes are resorbable and non-resorbable. Resorbable GBR membranes are divided into natural polymer resorbable membranes and synthetic polymer resorbable membranes. Each has its advantages and disadvantages. The current research focuses on exploring and improving its preparation and application. This review summarizes the recent literature on the application of GBR membranes to promote the regeneration of periodontal bone defects, elaborates on GBR development strategies, specific applications, and the progress of inducing periodontal bone regeneration to provide a theoretical basis and ideas for the future application of GBR membranes to promote the repair of periodontal bone defects. [ABSTRACT FROM AUTHOR]

Background: Person-specific computational models can estimate transcranial direct current stimulation (tDCS) current dose delivered to the brain and predict treatment response. Artificially created electrode models derived from virtual 10-20 EEG measurements are typically included in these models as current injection and removal sites. The present study directly compares current flow models generated via artificially placed electrodes ("artificial" electrode models) against those generated using real electrodes acquired from structural MRI scans ("real" electrode models) of older adults. Methods: A total of 16 individualized head models were derived from cognitively healthy older adults (mean age = 71.8 years) who participated in an in-scanner tDCS study with an F3-F4 montage. Visible tDCS electrodes captured within the MRI scans were segmented to create the "real" electrode model. In contrast, the "artificial" electrodes were generated in ROAST. Percentage differences in current density were computed in selected regions of interest (ROIs) as examples of stimulation targets within an F3-F4 montage. Main results: We found significant inverse correlations (p < 0.001) between median current density values and brain atrophy in both electrode pipelines with slightly larger correlations found in the artificial pipeline. The percent difference (PD) of the electrode distances between the two models predicted the median current density values computed in the ROIs, gray, and white matter, with significant correlation between electrode distance PDs and current density. The correlation between PD of the contact areas and the computed median current densities in the brain was found to be non-significant. Conclusions: This study demonstrates potential discrepancies in generated current density models using real versus artificial electrode placement when applying tDCS to an older adult cohort. Our findings strongly suggest that future tDCS clinical work should consider closely monitoring and rigorously documenting electrode location during stimulation to model tDCS montages as closely as possible to actual placement. Detailed physical electrode location data may provide more precise information and thus produce more robust tDCS modeling results. [ABSTRACT FROM AUTHOR]

Membrane proteins are critical mediators for tumor progression and present enormous therapeutic potentials. Although gene profiling can identify their cancer-specific signatures, systematic correlations between protein functions and tumor-related mechanisms are still unclear. We present here the CrMP-Sol database (https://bio-gateway.aigene.org.cn/g/CrMP), which aims to breach the gap between the two. Machine learning was used to extract key functional descriptions for protein visualization in the 3D-space, where spatial distributions provide function-based predictive connections between proteins and cancer types. CrMP-Sol also presents QTY-enabled water-soluble designs to facilitate native membrane protein studies despite natural hydrophobicity. Five examples with varying transmembrane helices in different categories were used to demonstrate the feasibility. Native and redesigned proteins exhibited highly similar characteristics, predicted structures and binding pockets, and slightly different docking poses against known ligands, although task-specific designs are still required for proteins more susceptible to internal hydrogen bond formations. The database can accelerate therapeutic developments and biotechnological applications of cancer-related membrane proteins. [ABSTRACT FROM AUTHOR]

The hydrogen in the vent gas stream of the hydrocracker (used to produce bio-jet fuel) cannot be reused since it has many impurities. The metal membrane can be a potential candidate for recovering hydrogen from this vent gas. In this work, the authors report the development of a composite palladium membrane and its application, for the first time, in the recovery of hydrogen from a simulated vent gas environment. A dense thin film (thickness ~3 µm) of Pd metal was coated on a ceramic support tube by the sputter deposition technique. The hydrogen permeance of the Pd membrane was found to be 18.75 × 10-6 mol·m-2·h-1·Pa-1, which was reduced to 3.25 × 10-6 mol·m-2·h-1·Pa-1, with an exposure of 100 h in the simulated bio-jet fuel environment. To avoid the loss of permeability, a thin layer of Pt can be coated over the Pd membrane. The present study used MATLAB software to simulate the Pt-coated Pd composite membrane performance in the bio-jet fuel production environment. Simulation studies confirmed that a membrane area of ~95 cm² (250 mm length and 12 mm OD) is sufficient for the complete recovery of hydrogen from the vent gas stream of hydrocracker at a feed velocity of 0.075 m/s. [ABSTRACT FROM AUTHOR]

In this study, we use machine learning algorithms with QM-derived COSMO-RS descriptors, along with Morgan fingerprints, to predict the absolute solubility of drug-like compounds. The QM-derived descriptors account for the molecular properties of the solute, i.e., the solute–solute interactions in an artificial-liquid-state (super-cooled liquid), and the solute–solvent interactions in solution. We employ two main approaches to predict solubility: (i) a hypothetical pathway that involves melting the solute at room temperature T = T¯ ( Δ fus G A ⊖ ) and mixing the artificially liquid solute into the solvent ( Δ m G A : B ⊖ ). In this approach Δ fus G A ⊖ is predicted using machine learning models, and the Δ m G A : B ⊖ is obtained from COSMO-RS calculations; (ii) direct solubility prediction using machine learning algorithms. The models were trained on a large number of Bayer in-house compounds for which water solubility data is available at physiological pH of 6.5 and ambient temperature. We also evaluated our models using external datasets from a solubility challenge. Our models present great improvements compared to the absolute solubility prediction with the QSAR model for the artificial liquid state as implemented in the COSMOtherm software, for both in-house and external datasets. We are furthermore able to demonstrate the superiority of QM-derived descriptors compared to cheminformatics descriptors. We finally present low-cost alternative models using fragment-based COSMOquick calculations with only marginal reduction in the quality of predicted solubility. [ABSTRACT FROM AUTHOR]

Compartmentalization is crucial for the functioning of cells. Membranes enclose and protect the cell, regulate the transport of molecules entering and exiting the cell, and organize cellular machinery in subcompartments. In addition, membraneless condensates, or coacervates, offer dynamic compartments that act as biomolecular storage centers, organizational hubs, or reaction crucibles. Emerging evidence shows that phase‐separated membraneless bodies in the cell are involved in a wide range of functional interactions with cellular membranes, leading to transmembrane signaling, membrane remodeling, intracellular transport, and vesicle formation. Such functional and dynamic interplay between phase‐separated droplets and membranes also offers many potential benefits to artificial cells, as shown by recent studies involving coacervates and liposomes. Depending on the relative sizes and interaction strength between coacervates and membranes, coacervates can serve as artificial membraneless organelles inside liposomes, as templates for membrane assembly and hybrid artificial cell formation, as membrane remodelers for tubulation and possibly division, and finally, as cargo containers for transport and delivery of biomolecules across membranes by endocytosis or direct membrane crossing. Here, recent experimental examples of each of these functions are reviewed and the underlying physicochemical principles and possible future applications are discussed. [ABSTRACT FROM AUTHOR]

A novel, simple, and rapid method is demonstrated for measuring the pore size and pore size distribution of filtration membranes (FMs) used in aqueous applications with fluorescence probes. Because the selected fluorescent probes are mixable and have strong signals, combined with the operation of dead-end filtration, this method only requires small amounts of reagents; additionally, it is time-efficient by avoiding multiple rounds of filtration. This method detects the size of a FM pore throat (i.e., the narrowest position of a pore tunnel), which is more consistent with the actual filtration situation. The conditions, such as probe concentration, temperature, transmembrane pressure difference, and types of surfactants, have been optimized. The experimental results show that the fluorescence probe method has good accuracy and reproducibility for measuring the pore size and pore size distribution of both organic and inorganic FMs. The method is particularly suitable for rapid testing of the filtration performance (nominal pore size≥0.02 μm) of purchased or synthetic membranes in the laboratory. [ABSTRACT FROM AUTHOR]