Molecular Size Research Articles

Dielectric and hydrogen bonding studies of butyronitrile with 1,4-dioxane using a time-domain reflectometry

Using time-domain reflectometry (TDR), the complex permittivity of binary mixture of butyronitrile (BTN) and 1,4-dioxane (1,4-DX) at various temperatures and solvent proportions was determined over the frequency range of 10 MHz to 30 GHz. The complex permittivity spectra (CPS) have been fitted to the Havrilik–Negami equation. The relaxation time (τ) and static dielectric constant (ε0) have been calculated for each concentration using the least squares fit method. The nonlinear behavior of dielectric parameters suggests a change in the molecular size and intermolecular bonding of BTN–1,4-DX mixtures. Theoretical static dielectric constants (ε0) have been determined using hydrogen bonded model suggested by Luzar for all solvent proportions and compared with experimental values obtained from TDR.

Development of a Molecular Dynamics Model to Assess the Possibility of Type II/III Porous Liquid Formation

The study of porous liquids (PLs) using molecular dynamics (MD) simulation is one of the most interesting and attractive research topics. The possibility of creating permanent porosity in a solvent and increasing its adsorption capacity is very practical. The purpose of the present study is to examine how an MD model can be developed to evaluate the possibility of PL formation. Additionally, the validation of the model was conducted by simulations using two metal–organic frameworks (MOFs) including zeolitic imidazolate framework-8 (ZIF-8) and Hong Kong University of Science and Technology-1 (HKUST-1) as porogens and water (H2O) and triethylene glycol (TEG) as solvents. The results revealed that H2O and TEG are incapable of penetrating the ZIF-8 pores due to their small size and unfavorable thermodynamics; however, both solvents easily penetrate through the large HKUST-1 pores. These observations aligned with findings from experimental literature studies, thus confirming the validity of the model. In order to expand the model’s scope, the developed model was used to assess the possibility of PL formation using ZIF-8 and HKUST-1 with different pore and window sizes and shapes, and a wide range of hydrocarbon liquids with different molecular sizes and shapes as solvents. It was found that ZIF-8 can form PLs with a more extensive range of sterically hindered solvents due to its smaller apertures and incompatible shape. In addition, only a few solvents (e.g., n-pentane, benzene, 1,3,5-trimethylbenzene, 1,3,5-triisopropylcyclohexane, and 1,3,5-triisopropylbenzene) can partially penetrate its ZIF-8 pores without steric hindrance. These privileged solvents typically have an aspect ratio far from 1, indicating a more elongated shape, and/or more linear branches. In contrast, HKUST-1, which has larger apertures and a compatible shape, allows for complete penetration of specific solvents (e.g., benzene, iso-octane, n-pentane), thereby preventing PL formation with such combinations. In addition, cyclohexane has the ability to partially penetrate the pores of HKUST-1. Therefore, in addition to the size of the solvent molecule, one of the most important properties for penetration is the compatibility of the shape of the porogen pore window with the shape of the solvent molecule. This research provides important new information on how PLs come to be by illuminating the role that solvent molecules and porogen play in promoting penetration and, in the end, impacting the process of PL formation.

Recent Advances in the Oral Delivery of Biologics

The majority of patients find that the oral route of drug administration is the most convenient, easy to follow, non- invasive, and physician-preferred method. However, oral biologic administration is not as beneficial as other routes because of mucosal permeability and various gastrointestinal barriers that limit the systemic absorption of complex macromolecules after ingestion. Because of their large molecular size, which results in extremely poor permeability across the intestinal mucosa, biologics are sensitive to the harsh environment of the gastrointestinal tract and thus play a significant role in the treatment of therapeutic interventions such as Chronic ailments, metabolic disease aging, and inflammatory disorders. Many drug delivery systems and pharmaceutical technologies, such as micelles, nano carriers, lipid-based carriers, and cyclodextrins, have been explored to enhance oral drug absorption. This article will first address the drug discovery, intensive research, and design that have enhanced the growth of biologics in recent decades and further accelerated the way we administer the medication in a clinical setting. physiological barriers to oral delivery of biologics and addresses various approaches to enhance the efficacy of oral delivery; furthermore, this conversation will encompass the diverse benefits and constraints of drug delivery systems as well as the general perception and promise of this emerging clinical area. Keywords: Absorption enhancers; biologics; drug delivery; Gastrointestinal barriers; insulin; microneedle pill; oral delivery.

Modeling of brain efflux: Constraints of brain surfaces

Fluid efflux from the brain plays an important role in solute waste clearance. Current experimental approaches provide little spatial information, and data collection is limited due to short duration or low frequency of sampling. One approach shows tracer efflux to be independent of molecular size, indicating bulk flow, yet also decelerating like simple membrane diffusion. In an apparent contradiction to this report, other studies point to tracer efflux acceleration. We here develop a one-dimensional advection-diffusion model to gain insight into brain efflux principles. The model is characterized by nine physiological constants and three efflux parameters for which we quantify prior uncertainty. Using Bayes' rule and the two efflux studies, we validate the model and calculate data-informed parameter distributions. The apparent contradictions in the efflux studies are resolved by brain surface boundaries being bottlenecks for efflux. To critically test the model, a custom MRI efflux assay measuring solute dispersion in tissue and release to cerebrospinal fluid was employed. The model passed the test with tissue bulk flow velocities in the range 60 to 190 [Formula: see text]m/h. Dimensional analysis identified three principal determinants of efflux, highlighting brain surfaces as a restricting factor for metabolite solute clearance.

The impact of ultrasonic-assisted extraction on the in vitro hypoglycemic activity of peach gum polysaccharide in relation to its conformational conversion.

Peach gum (PG) is an exudate of the peach tree (Prunus persica of the Rosaceae family), which consists primarily of polysaccharides with a large molecular weight and branching structure. Consequently, PG can only swell in water and not dissolve directly, which severely limits its application. Current conventional extraction methods for PG polysaccharide (PGPS) are time-consuming and inefficient. This study investigated the impact of ultrasonic-assisted extraction (UAE) on PGPS structure and conformation, as well as their relationship to hypoglycemic activity in vitro. Compared to conventional aqueous extraction, UAE enhanced PGPS yield from 28.07%-32.83% to 80.37%-84.90% (w/w) in 2 h. It drastically decreased the molecular size and conformational parameters of PGPS, including Mw, Mn, Rg, Rh and [η] values. PGPS conformation converted from extended molecules to flexible random coil chains or compact spheres with no obvious primary structure alteration. Furthermore, UAE altered the flow behaviour of PGPS solution from non-Newtonian fluid to Newtonian fluid. As a result, PGPS treated with ultrasonic displayed weaker inhibitory activity than those untreated, mostly because UAE weakens the binding strength of PGPS to α-glucosidase. However, this negative effect of UAE on PGPS activity was compensated by the increased solubility of polysaccharide. This enabled PGPS to achieve a wider range of doses. UAE is capable of degrading PGPS efficiently while preserving its primary structure, resulting in a Newtonian fluid solution. The degraded PGPS conformation display a consistent correlation with their inhibitory effect on α-glucosidase activity. This article is protected by copyright. All rights reserved.

Fluorescent BF2 Complexes Inspired by Ageladine A

Abstract. The pH‐dependent UV/Vis absorption and fluorescence of several analogs of the marine natural product ageladine A were investigated. Besides ageladine A itself, its BF2 complex, and the corresponding debrominated analogs were included, as were the chloro analog of the debromoageladine‐BF2 complex, an imidazolone analog, and a triazole derivative, which lack the free amino group. Importantly, the pH‐dependence of the fluorescence of the chloro analog closely resembles that of the natural product ageladine A, but with about 25‐fold higher fluorescence intensity and a maximum between pH 3 and 6. The imidazolone derivative behaves in a complementary manner and shows fluorescence only above pH 6, but with less intensity than ageladine A. The calculated Stokes shifts agrees well with the experiment, which underlines the accuracy of the DFT calculation method (ωB97XD/TApr‐cc‐pVDZ, water, PCM). The combination of BF2 units with arylated imidazo[4,5‐c]pyridine structural motifs encourages further research on more strongly fluorescent derivatives of comparable molecular size.

Evaluation of free radical‐induced structural changes and their effect on antioxidant and anti‐inflammatory activities of UV/H2O2‐degraded dextrans

AbstractAlthough ultraviolet (UV)/H2O2 treatment could effectively improve the bioactivities of polysaccharides, the relationship between free radical‐induced structural changes and the bioactivities of products remains unknown. Therefore, this work investigated the changes in the chemical characteristics and chain conformations of degraded dextrans by the UV/H2O2 system as well as their antioxidant and anti‐inflammatory activities. The apparent degradation efficiencies of dextrans under different UV/H2O2 parameters were first investigated. UV/H2O2 treatment effectively destroyed the pyranose rings and glycosidic bonds of dextrans and significantly improved their uronic acid and carboxy contents. Furthermore, conformational studies revealed that besides the rapid decrease in the molecular weight, the compact spherical conformation of dextrans was gradually depolymerized into the flexible random coil conformation. Moreover, the significant antioxidant and anti‐inflammatory activities of the degraded dextrans were mainly attributed to their more extended random coil chains, increased quantity of reducing groups, and lower molecular sizes. This study contributes to investigating the structure–activity relationship of polysaccharides prepared by free radicals‐mediated degradation.

Efficient removal of tizanidine and tetracycline from water: A single and competitive sorption approach using carboxymethyl cellulose granulated iron-pillared clay

This study deals with the development of a granulated Fe-pillared clay (Fe-PC) using carboxymethylcellulose (CMC) as a binder to present it as an innovative adsorbent for the individual and competitive adsorption of tetracycline (Tc) and tizanidine (Tz) from water. An optimum pH value of 7 was determined for both individual and multi-component adsorption. The optimal dosage of granulated Fe-PC was determined to be 1.5 g/L for Tz and 3 g/L for Tc, resulting in constant removal rates of 80 % for Tc and 90 % for Tz. Tizanidine showed a higher affinity for powdered or granulated Fe-PC compared to tetracycline, due to its smaller molecular size and increased amine functional groups. Consequently, Tz showed improved kinetic rates (initial pseudo-second order sorption rates of 170.79 and 25.62 mg/g.h for Tz and Tc, respectively) and equilibrium capacities (maximum monolayer adsorption capacity of granulated Fe-PC at room temperature over Tc and Tz, 54.89 mg/g and 66.40 mg/g). Granulation affected the kinetic rate for both adsorbates, albeit with a more pronounced effect for Tc. The adsorption of Tz was less sensitive to temperature changes, indicating a lower enthalpy change of adsorption (14.24 and 77.91 kJ/mol for Tz and Tc, respectively). HCl for Tc and NaCl for Tz were identified as optimal desorption eluents, confirming the involvement of cation exchange in Tz adsorption. Surface functional group analysis confirmed the proposed complexation mechanisms. Tz consistently showed a higher affinity for granular Fe-PC than Tc, especially at lower adsorbent dosages. This article provides a comprehensive insight into the characterization of the prepared adsorbents and their cyclic adsorption-desorption performance for Tc and Tz.

Molecular simulations of hydrogen diffusion in underground porous media: Implications for storage under varying pressure, confinement, and surface chemistry conditions

Assessing the feasibility of porous formations for hydrogen geo-storage demands a comprehensive understanding of hydrogen (H2) transport behavior in porous media at subsurface conditions. In this study, we employ molecular dynamics simulations to evaluate the effects of pressure (20–500 atm), pore size (2–20 nm), and surface composition on H2 diffusion and interactions within organic and inorganic slit pores. Our analysis of H2 density profiles and interaction energies reveals a distinct preference for H2 molecules to adsorb more readily onto graphene surfaces than kaolinite surfaces. However, self-diffusion results demonstrate that H2 molecules interact relatively weakly with both substrate types. Further insights are provided by velocity autocorrelation functions, emphasizing the occurrence of wall-mediated collisions as H2 molecules diffuse along the pore surfaces, particularly within kaolinite. This highlights the significance of surface roughness in mitigating H2 loss via diffusion in subsurface nanopores, given the small molecular size of H2 and its limited interactions with both organic and inorganic materials. Furthermore, the results demonstrate that self-diffusion coefficients in both pore types increase with pore size and decrease with pressure. Notably, surface composition plays a critical role in low-pressure environments, with self-diffusion coefficients beginning to converge beyond a pressure of 100 atm. Self-diffusion coefficients also become less sensitive to slit aperture beyond a pressure of 50 atm. In high-pressure environments, hydrogen transport is governed by thermal collisions between gas molecules, leading to negligible property variations between pore types. These findings hold significance in the investigation of efficient H2 storage within porous media and caprock formations.

Scalable Preparation of Ultraselective and Highly Permeable Fully Aromatic Polyamide Nanofiltration Membranes for Antibiotic Desalination

Membranes are important in the pharmaceutical industry for the separation of antibiotics and salts. However, its widespread adoption has been hindered by limited control of the membrane microstructure (pore architecture and free‐volume elements), separation threshold, scalability, and operational stability. In this study, 4,4',4'',4'''‐methanetetrayltetrakis(benzene‐1,2‐diamine) (MTLB) as prepared as a molecular building block for fabricating thin‐film composite membranes (TFCMs) via interfacial polymerization. The relatively large molecular size and rigid molecular structure of MTLB, along with its non‐coplanar and distorted conformation, produced thin and defect‐free selective layers (~27 nm) with ideal microporosities for antibiotic desalination. These structural advantages yielded an unprecedented high performance with a water permeance of 45.2 L m‐2 h‐1 bar‐1 and efficient antibiotic desalination (NaCl/adriamycin selectivity of 422). We demonstrated the feasibility of the industrial scaling of the membrane into a spiral‐wound module (with an effective area of 2.0 m2). This module exhibited long‐term stability and performance that surpassed those of state‐of‐the‐art membranes used for antibiotic desalination. This study provides a scientific reference for the development of high‐performance TFCMs for water purification and desalination in the pharmaceutical industry.

Scalable Preparation of Ultraselective and Highly Permeable Fully Aromatic Polyamide Nanofiltration Membranes for Antibiotic Desalination.

Membranes are important in the pharmaceutical industry for the separation of antibiotics and salts. However, its widespread adoption has been hindered by limited control of the membrane microstructure (pore architecture and free-volume elements), separation threshold, scalability, and operational stability. In this study, 4,4',4'',4'''-methanetetrayltetrakis(benzene-1,2-diamine) (MTLB) as prepared as a molecular building block for fabricating thin-film composite membranes (TFCMs) via interfacial polymerization. The relatively large molecular size and rigid molecular structure of MTLB, along with its non-coplanar and distorted conformation, produced thin and defect-free selective layers (~27 nm) with ideal microporosities for antibiotic desalination. These structural advantages yielded an unprecedented high performance with a water permeance of 45.2 L m-2 h-1 bar-1 and efficient antibiotic desalination (NaCl/adriamycin selectivity of 422). We demonstrated the feasibility of the industrial scaling of the membrane into a spiral-wound module (with an effective area of 2.0 m2). This module exhibited long-term stability and performance that surpassed those of state-of-the-art membranes used for antibiotic desalination. This study provides a scientific reference for the development of high-performance TFCMs for water purification and desalination in the pharmaceutical industry.

Next-Generation Anti-TNFα Agents: The Example of Ozoralizumab.

Biologic therapy involving anti-tumor necrosis factor-α (anti-TNFα) agents has fundamentally changed the management of patients with immune-mediated inflammatory diseases, including rheumatoid arthritis, thus benefiting many patients. Nevertheless, the inability of some patients to achieve low disease activity or clinical remission remains a major concern. To address such concerns, next-generation anti-TNFα agents that differ from the immunoglobulin G-format anti-TNFα agents that have been used to date are being developed using antibody-engineering technology. Their unique design employing novel molecular characteristics affords several advantages, such as early improvement of clinical symptoms, optimization of drug bioavailability, enhancement of tissue penetration, and a reduction in side effects. This holds promise for a new paradigm shift in biologic therapy via the use of next-generation anti-TNFα agents. Ozoralizumab, a next-generation anti-TNFα agent that was recently approved in Japan, comprises a variable region heavy-chain format. It has a completely different structure from conventional therapeutic antibodies, such as a small molecular size, an albumin-binding module, and a unique format that produces an avidity effect. Ozoralizumab exhibited rapid biodistribution into joints, provided attenuation of Fcγ receptor-mediated inflammatory responses, and had a high binding affinity to TNFα in non-clinical studies. In clinical trials, ozoralizumab yielded an early improvement in clinical symptoms, a sustained efficacy for up to 52 weeks, and an acceptable tolerability in patients with rheumatoid arthritis. This review focuses on the results of pre-clinical and clinical trials for ozoralizumab and outlines the progress in next-generation antibody development.

A study of size-selective renal elimination using a novel human model

The recently discovered selective glomerular hypofiltration syndromes have increased interest in the actual elimination of molecules in the human kidney. In the present study, a novel human model was introduced to directly measure the single-pass renal elimination of molecules of increasing size. Plasma concentrations of urea, creatinine, C-peptide, insulin, pro-BNP, β2-microglobulin, cystatin C, troponin-T, orosomucoid, albumin, and IgG were analysed in arterial and renal venous blood from 45 patients undergoing Transcatheter Aortic Valve Implantation (TAVI). The renal elimination ratio (RER) was calculated as the arteriovenous concentration difference divided by the arterial concentration. Estimated glomerular filtration rate (eGFR) was calculated by the CKD-EPI equations for both creatinine and cystatin C. Creatinine (0.11 kDa) showed the highest RER (21.0 ± 6.3%). With increasing molecular size, the RER gradually decreased, where the RER of cystatin C (13 kDa) was 14.4 ± 5.3% and troponin-T (36 kDa) was 11.3 ± 4.6%. The renal elimination threshold was found between 36 and 44 kDa as the RER of orosomucoid (44 kDa) was −0.2 ± 4.7%. The RER of creatinine and cystatin C showed a significant and moderate positive linear relationship with eGFR (r = 0.48 and 0.40). In conclusion, a novel human model was employed to demonstrate a decline in renal elimination with increasing molecular size. Moreover, RERs of creatinine and cystatin C were found to correlate with eGFR, suggesting the potential of this model to study selective glomerular hypofiltration syndromes.

Balancing Solvent Polarity and Drying‐Kinetics for Processing Nonfullerene Acceptors Toward High‐Performance Organic Solar Cells

In recent years, the emergence of high‐efficiency nonfullerene acceptors (NFAs) has pushed the power conversion efficiency (PCE) beyond 19% in organic solar cells (OSCs). For solution processing of the photoactive layers, the study of solvent properties on device performance has become a hot research topic toward up‐scaling. Herein, the key roles of balancing solvent polarity and drying kinetics for processing of small molecular NFAs toward high‐performance OSCs are revealed. It is demonstrated that the synergistic effect of solvent polarity and drying kinetics significantly affects the multilength scale morphology of solid films and photovoltaic performance. Furthermore, the self‐assembly of NFAs in solution and the resulting thin film microstructures induced by electrostatic interactions with polarized additives are even more sensitive to solvent polarity and drying kinetics. Finally, the optimized devices achieve an outstanding PCE of 18.54% by fine‐tuning the microstructure with polar solvent and fast‐drying kinetics to form improved molecular packing and structure size. The work provides a novel view and deeper insights into the general selection rules of solvents toward the solution processing of high‐performance nonfullerene OSCs.

Exploring the Combined Action of Adding Pertuzumab to Branded Trastuzumab versus Trastuzumab Biosimilars for Treating HER2+ Breast Cancer.

The binding activity of various trastuzumab biosimilars versus the branded trastuzumab towards the glycosylated extracellular domain of the human epidermal growth factor receptor 2 (HER2) target in the presence of pertuzumab was investigated. We employed size exclusion chromatography with tetra-detection methodology to simultaneously determine absolute molecular weight, concentration, molecular size, and intrinsic viscosity. All trastuzumab molecules in solution exhibit analogous behavior in their binary action towards HER2 regardless of the order of addition of trastuzumab/pertuzumab. This analogous behavior of all trastuzumab molecules, including biosimilars, highlights the robustness and consistency of their binding activity towards HER2. Furthermore, the addition of HER2 to a mixture of trastuzumab and pertuzumab leads to increased formation of high-order HER2 complexes, up to concentrations of one order of magnitude higher than in the case of sequential addition. The observed increase suggests a potential synergistic effect between these antibodies, which could enhance their therapeutic efficacy in HER2-positive cancers. These findings underscore the importance of understanding the complex interplay between therapeutic antibodies and their target antigens, providing valuable insights for the development of more effective treatment strategies.

Novel sulfonated calixarenes derived crosslinker for reinforcing and toughening collagen: Relevance between structure and properties

AbstractCollagen is widely used in the development of new functional materials due to its high structural stability, good biocompatibility, and excellent hydrophilicity, but the collagen protein denatures easily, which makes its thermal stability and mechanical strength difficult to reach some of the parameters required in the application. To solve this, protein crosslinking is an effective way to better use collagen. In this paper, we compared the thermal stability and morphological stability of three kinds of sulfonated calixarenes crosslinked collagen before and after the treatment. The results showed that sulfonated calixarenes could significantly improve the thermal stability and morphological stability of dermal collagen. The reinforcing and toughening mechanism of the sulfonated calixarenes was revealed by scanning electron microscopy (SEM), infrared spectroscopy (FT‐IR), attenuated total reflection‐Fourier transform infrared spectroscopy (ATR‐FTIR), ultraviolet–visible–near‐infrared (UV–vis–NIR) spectrometer, X‐ray diffraction detection (XRD), atomic force microscopy (AFM), and circular dichroism (CD) detection. The results showed that sulfonated calixarenes were evenly distributed in collagen fibers and formed hydrogen bonds or electrovalent bonds with amino groups, peptide groups, or amide groups in collagen to improve the thermal stability of the collagen. Three kinds of sulfonated calixarenes enter collagen fiber to support the collagen, increase the three‐dimensional weave angle of collagen, and improve the physical and mechanical properties of collagen, thereby toughening and enhancing the collagen. Based on the above studies, the reinforcing and toughening mechanism of the sulfonated calixarenes crosslinked collagen was established. Confirmed the existence of hydrogen bonds between the three sulfonated calixarenes and collagen, and the nonchemical bond energy of the system was proportional to the molecular size of sulfonated calixarenes.

495 Optimizing Drug Delivery to the Brain for Breast Metastasis: A Novel Method for Tumor Targeting

INTRODUCTION: Brain metastases are difficult to treat due to the blood-brain barrier limiting delivery of therapeutic agents to the brain effectively. Intraventricular drug delivery has not been well studied for intra-axial pathologies. However, our prior work demonstrated that intraventricular drug delivery in a hyperosmolar vehicle showed preferential accumulation of drug within breast cancer tissue compared to surrounding brain parenchyma. METHODS: We used an intracerebral breast cancer tumor model in adult female nude rats divided into six experimental groups. We examined three iron labeled dextran molecules (3 KD, 5KD, and 10 KD) in 337 mOsm/L solution and three different osmolarities of delivery solution (307, 353, 368 mOsm/L) with 10 KD dextran. 7T MR imaging was used to analyze dextran distribution at different time points. All animals were sacrificed after 2 hours and quantity of dextran particles was determined by histopathology. RESULTS: Breast cancer tumor cells were successfully implanted in all rats. MRI quantification of dextran concentration was well corroborated by histopathology. Varying the molecular size of dextran resulted in the smallest molecule reaching peak levels in tumor tissue earlier than the larger molecules but the larger molecules remained concentrated in tumor tissue for a longer time. Varying the osmolarity of the delivery solution resulted in preferential accumulation of 10 KD dextran in tumor tissue except for when dextran was delivered in 368 mOsm/L solution where no preferential distribution was seen. CONCLUSIONS: Hyperosmolar intraventricular delivery of chemotherapeutic drugs could be effective in preferentially delivering drugs to abnormal tumor tissues.

Printing GelMA bioinks: a strategy for buildingin vitromodel to study nanoparticle-based minocycline release and cellular protection under oxidative stress.

Owing to its thermoresponsive and photocrosslinking characteristics, gelatin methacryloyl (GelMA)-based biomaterials have gained widespread usage as a novel and promising bioink for three-dimensional bioprinting and diverse biomedical applications. However, the flow behaviors of GelMA during the sol-gel transition, which are dependent on time and temperature, present significant challenges in printing thick scaffolds while maintaining high printability and cell viability. Moreover, the tunable properties and photocrosslinking capabilities of GelMA underscore its potential for localized drug delivery applications. Previous research has demonstrated the successful incorporation of minocycline (MH) into GelMA scaffolds for therapeutic applications. However, achieving a prolonged and sustained release of concentrated MH remains a challenge, primarily due to its small molecular size. The primary aim of this study is to investigate an optimal extrusion printing method for GelMA bioink in extrusion bioprinting, emphasizing its flow behaviors that are influenced by time and temperature. Additionally, this research seeks to explore the potential of GelMA bioink as a carrier for the sustained release of MH, specifically targeting cellular protection against oxidative stress. The material properties of GelMA were assessed and further optimization of the printing process was conducted considering both printability and cell survival. To achieve sustained drug release within GelMA, the study employed a mechanism using metal ion mediation to facilitate the interaction between MH, dextran sulfate (DS), and magnesium, leading to the formation of nanoparticle complexes (MH-DS). Furthermore, a GelMA-basedin vitromodel was developed in order to investigate the cellular protective properties of MH against oxidative stress. The experimental results revealed that the printability and cell viability of GelMA are significantly influenced by the printing duration, nozzle temperature, and GelMA concentrations. Optimal printing conditions were identified based on a thorough assessment of both printability and cell viability. Scaffolds printed under these optimal conditions exhibited exceptional printability and sustained high cell viability. Notably, it was found that lower GelMA concentrations reduced the initial burst release of MH from the MH-dextran sulfate (MH-DS) complexes, thus favoring more controlled, sustained release profiles. Additionally, MH released under these conditions significantly enhanced fibroblast viability in anin vitromodel simulating oxidative stress.

Optimal interfacial engineering with different bifunctional alkylamine sulfonates for efficient perovskite solar cells

Perovskite solar cells have gradually become the most attractive alternative for next-generation photovoltaic devices due to their excellent photovoltaic conversion efficiencies and low manufacturing costs. Defect engineering is an essential topic for improving the performance of perovskite devices. In this study, we utilize a bifunctional alkylamine sulfonate to modify the perovskite interfaces. The TsO− of sulfonates coordinates with Pb2+, while –NH2 of alkylamine forms hydrogen bonds with iodine, which reduces charge recombination and improves energy level arrangement. The molecular size and the alkylamine's dielectric constant significantly influence the interface modification performance. For the champion device with BATsO treatment, there is an enhancement in both the fill factor and the open-circuit voltage, resulting in a power conversion efficiency (PCE) of 23.53%. After 400 h of working condition, the device maintains roughly 90.40% of its initial efficiency. Therefore, this study postulates that modifying bifunctional alkylamine sulfonates could effectively enhance the PSC's performance.

A poisonous cocktail: interplay of cereulide toxin and its structural isomers in emetic Bacillus cereus.

Food intoxications evoked by emetic Bacillus cereus strains constitute a serious threat to public health, leading to emesis and severe organ failure. The emetic peptide toxin cereulide, assembled by the non-ribosomal peptide synthetase CesNRPS, cannot be eradicated from contaminated food by usual hygienic measures due to its molecular size and structural stability. Next to cereulide, diverse chemical variants have been described recently that are produced concurrently with cereulide by CesNRPS. However, the contribution of these isocereulides to the actual toxicity of emetic B. cereus, which produces a cocktail of these toxins in a certain ratio, is still elusive. Since cereulide isoforms have already been detected in food remnants from foodborne outbreaks, we aimed to gain insights into the composition of isocereulides and their impact on the overall toxicity of emetic B. cereus. The amounts and ratios of cereulide and isocereulides were determined in B. cereus grown under standard laboratory conditions and in a contaminated sample of fried rice balls responsible for one of the most severe food outbreaks caused by emetic B. cereus in recent years. The ratios of variants were determined as robust, produced either under laboratory or natural, food-poisoning conditions. Examination of their actual toxicity in human epithelial HEp2-cells revealed that isocereulides A-N, although accounting for only 10% of the total cereulide toxins, were responsible for about 40% of the total cytotoxicity. An this despite the fact that some of the isocereulides were less cytotoxic than cereulide when tested individually for cytotoxicity. To estimate the additive, synergistic or antagonistic effects of the single variants, each cereulide variant was mixed with cereulide in a 1:9 and 1:1 binary blend, respectively, and tested on human cells. The results showed additive and synergistic impacts of single variants, highlighting the importance of including not only cereulide but also the isocereulides in routine food and clinical diagnostics to achieve a realistic toxicity evaluation of emetic B. cereus in contaminated food as well as in patient samples linked to foodborne outbreaks. Since the individual isoforms confer different cell toxicity both alone and in association with cereulide, further investigations are needed to fully understand their cocktail effect.