Self-assembled Abietic acid encapsulated nanoparticles to improve the stability of Proanthocyanin B2.

Procyanidin B2 (Pac B2) has attracted much attention due to its strong antioxidant activity, but poor in vivo stability limits its wide application in food and medicine. In this paper, composite nanoparticles (NPs) were constructed using abietic acid (AA) as a carrier, which significantly enhanced Pac B2 stability. A spherical morphology and average diameter of 396.05 nm were observed in AA-Pac B2 NPs synthesized by solvent co-precipitation. Pac B2 encapsulation was 11.28 %, and thermal stability is improved. Infrared, Ultraviolet spectrum, and MD (molecular dynamics) spectroscopy revealed hydrogen bonding and hydrophobic interaction between AA and Pac B2. For up to 2 h at 37 °C, Pac B2 can be sustainably released in simulated gastric and intestinal fluids. In vitro, AA-Pac B2 NPs at the same concentration exhibited higher bioavailability and uptake efficiency than free Pac B2. The data demonstrate the potential of AA NPs for improving polyphenol thermal stability and bioavailability.

Cross polarization stability in multidimensional NMR spectroscopy of biological solids.

Magic-angle spinning (MAS) solid-state nuclear magnetic resonance (SSNMR) spectroscopy is a powerful and versatile technique for probing structure and dynamics in large, insoluble biological systems at atomic resolution. With many recent advances in instrumentation and polarization methods, technology development in SSNMR remains an active area of research and presents opportunities to further improve data collection, processing, and analysis of samples with low sensitivity and complex tertiary and quaternary structures. SSNMR spectra are often collected as multidimensional data, requiring stable experimental conditions to minimize signal fluctuations (t1 noise). In this work, we examine the factors adversely affecting signal stability as well as strategies used to mitigate them, considering laboratory environmental requirements, configuration of amplifiers, and pulse sequence parameter selection. We show that Thermopad® temperature variable attenuators (TVAs) can partially compensate for the changes in amplifier output power as a function of temperature and thereby ameliorate one significant source of instability for some spectrometers and pulse sequences. We also consider the selection of tangent ramped cross polarization (CP) waveform shapes, to balance the requirements of sensitivity and instrumental stability. These findings collectively enable improved stability and overall performance for CP-based multidimensional spectra of microcrystalline, membrane, and fibrous proteins performed at multiple magnetic field strengths.

Aspects of quercetin stability and its liposomal enhancement in yellow onion skin extracts.

Quercetin is a flavonoid that occurs in many types of fruit and vegetables and is stable for no longer than 4.5 h in the investigated pH range (6.0-8.0), even at 4 °C in the dark. At higher temperatures, the degradation/oxidation process is much faster. Simple but effective proliposomal encapsulation was used to protect the quercetin from environmental conditions such as pH. With this approach, 65 to 90% of pure quercetin and quercetin-rich onion extract was kept after >60 days under conditions that favoured its oxidation (pH 7.4). In addition, the encapsulated quercetin decreases the lipid peroxidation induced by pulsed UV light by >50%. At a mass ratio of 1:100 quercetin to lipids (w/w), the liposomes remained intact in solutions for six months. Quercetin in lipid bilayers simultaneously protects the unsaturated lipids from peroxidation.

Phenylethylammonium bromide-assisted solution-phase ligand exchange in CsPbBr3 quantum dot solar cells.

CsPbBr3 quantum dots (QDs) have excellent optical properties and good phase stability, but the long-chain ligands on their surfaces affect the charge transfer between QDs. Here, we propose a simple ligand exchange strategy: solution-phase ligand exchange. By adding an acetone solution of phenylethylammonium bromide to the purification process of CsPbBr3 QDs, the long-chain ligands were effectively replaced and the electric coupling between QDs was improved. As a result, the power conversion efficiency of the solar cell was increased from 1.95% to 2.83%. Meanwhile, the stability of the devices was significantly improved in the unencapsulated case.

Two aspects of feed-forward control of action stability: effects of action speed and unexpected events.

We explored two types of anticipatory synergy adjustments (ASA) during accurate four-finger total force production task. The first type is a change in the index of force-stabilizing synergy during a steady state when a person is expecting a signal to produce a quick force change, which is seen even when the signal does not come (steady-state ASA). The other type is the drop in in the synergy index prior to a planned force change starting at a known time (transient ASA). The subjects performed a task of steady force production at 10% of maximal voluntary contraction (MVC) followed by a ramp to 20% MVC over 1 s, 3 s, and as a step function (0 s). In another task, in 50% of the trials during the steady-state phase, an unexpected signal could come requiring a quick force pulse to 20% MVC (0-surprise). Inter-trial variance in the finger force space was used to quantify the index of force-stabilizing synergy within the uncontrolled manifold hypothesis. We observed significantly lower synergy index values during the steady state in the 0-ramp trials compared to the 1-ramp and 3-ramp trials. There was also larger transient ASA during the 0-ramp trials. In the 0-surprise condition, the synergy index was significantly higher compared to the 0-ramp condition whereas the transient ASA was significantly larger. The finding of transient ASA scaling is of importance for clinical studies, which commonly involve populations with slower actions, which can by itself be associated with smaller ASAs. The participants varied the sharing pattern of total force across the fingers more in the task with "surprises". This was coupled to more attention to precision of performance, i.e., inter-trial deviations from the target as reflected in smaller variance affecting total force, possibly reflecting higher concentration on the task, which the participants perceived as more challenging compared to a similar task without surprise targets.

Suspensions of antibiotics in self-emulsifying oils as a novel approach to formulate eye drops with substances which undergo hydrolysis in aqueous environment.

The aim of this study was to develop eye-drops with cefuroxime (CEF) sodium or vancomycin (VAN) hydrochloride, antibiotics that are instable in water. Anhydrous self-emulsifying oils (SEO) are proposed as a carrier and antibiotics are suspended. In the contact with tear fluid, the formulation should transform into emulsion, with fast dissolution of an antibiotic. CEF or VAN (5% w/w) was suspended in SEO carriers prepared by dissolving surfactants (Tween 20 or Span 80 5% w/w) in Miglyol, castor oil, or olive oil. Formulations with or without sodium citrate (2% w/w) were compared. Six-months or 1-year stability tests were carried out at 40 °C. The content of CEF and VAN was evaluated using HPLC and the potency of the antibiotic was assessed with agar diffusion method. In contact with water, drug particles suspended in SEO dissolved rapidly and o/w emulsion was formed. After 1-year at 40 °C, the content of degradation products was at most 0.5% in CEF and 4.0% in VAN formulations. The agar diffusion assay has shown that CEF and VAN loaded into SEO retained its potency against the sensitive microorganisms comparable to an aqueous solution. Therefore, SEO can be used as a novel carrier for the active substances which may not require improved solubility or absorption but need to be protected from moisture. This is a formulation that can be produced on industrial scale, with no limitation of stability or drug concentration.

Flow shear force destabilizes carotid plaques by affecting CHOP and GRP78 proteins.

BACKGROUND: Various factors, including blood, inflammatory, infectious, and immune factors, can cause ischemic stroke. However, the primary cause is often the instability of cervical arteriosclerosis plaque. It is estimated that 18-25% of ischemic strokes are caused by the rupture of carotid plaque.1 Plaque stability is crucial in determining patient prognosis. Developing a highly accurate, non-invasive, or minimally invasive technique to assess carotid plaque stability is crucial for diagnosing and treating stroke.Previous research by our group has demonstrated that the expression levels of CHOP (C/EBP homologous protein) and GRP78 (glucose-regulated protein 78) are correlated with the stability of atherosclerotic plaques.2 OBJECT: This research assesses changes in GRP78 and CHOP expressions in human umbilical vein endothelial cells(HUVEC) following experiments within the hemodynamic influencing factors test system. Additionally, it includes conducting an empirical study on the impact of blood flow shear force on the stability of human carotid atherosclerotic plaques. The objective is to explore the implications of blood flow shear force on the stability of carotid atherosclerotic plaques. METHOD: The hemodynamic influencing factors test bench system was configured with low (Group A, 4 dyns/cm²), medium (Group B, 8 dyns/cm²), and high shear force groups (Group C, 12 dyns/cm²). Relative expression levels of GRP78 and CHOP proteins in human umbilical vein endothelial cells were measured using Western blot analysis, and quantitative analysis of GRP78 and CHOP mRNA was conducted using RT-qPCR. Meanwhile, plaques from 60 carotid artery patients, retrieved via Carotid Endarterectomy (CEA), were classified into stable (S) and unstable (U) groups based on pathological criteria. Shear force at the carotid bifurcation was measured preoperatively using ultrasound. Western blot and RT-qPCR were used to analyze the relative expression levels of GRP78 and CHOP proteins and mRNA, respectively, in the plaque specimens from both groups. RESULT: Expression levels of GRP78, CHOP proteins, and their mRNAs were assessed in groups A, B, and C via Western blot and RT-qPCR. Results showed that in the low-shear group, all markers were elevated in group A compared to groups B and C. Statistical analysis revealed significantly lower shear forces at the carotid bifurcation in group U compared to group S. In group U plaques, GRP78 and CHOP expressions were significantly higher in group U than in group S. CONCLUSION: Blood flow shear forces variably affect the expression of GRP78 and CHOP proteins, as well as their mRNA levels, in vascular endothelial cells. The lower the shear force and fluid flow rate, the higher the expression of GRP78 and CHOP, potentially leading to endoplasmic reticulum stress(ERS), which may destabilize the plaque.

Enhancing storage stability of pea peptides through encapsulation in maltodextrin and gum tragacanth via monitoring scavenge ability to free radicals.

Pea peptides can lead to degradation through oxidation, deamidation, hydrolysis, or cyclization during production, processing, and storage, which in turn limit their broader application. To stabilize pea peptides, this study employed spray drying technology to create a pea peptide micro-encapsule using maltodextrin, gum tragacanth, and pea peptides. Four key factors, including polysaccharide ratio, glycopeptide ratio, solid-liquid ratio, and inlet temperature, were optimized to enhance the antioxidant properties of the pea peptide micro-encapsule. The results indicated that the utilization of maltodextrin and gum tragacanth significantly improves the storage stability and antioxidant activity of pea peptides. Moreover, optimal storage stability for pea peptides was achieved with a polysaccharide ratio of 9:1, a glycopeptide ratio of 10:1, a solid-liquid ratio of 4:40, and an inlet temperature of 180 °C. After 60 days of storage, the encapsulated pea peptides maintained 70.22 %, 25.19 %, and 40.32 % for scavenging abilities to hydroxyl radical, superoxide anion, and ABTS radical, respectively. In contrast, the unencapsulated pea peptides showed a decline to 47.02 %, 0 %, and 24.46 % in the same antioxidant activities after storage. These findings underscore the potential of spray drying technology to enhance the functional properties of pea peptides for various applications.

High freeze-thaw stability of Pickering emulsion stabilized by SPI-maltose particles and its effect on frozen dough.

Pickering emulsions with good freeze-thaw stability are essential in frozen food applications. This study developed a high freeze-thaw stabilized soy protein isolate (SPI)-maltose (M) Pickering emulsion and applied it to frozen doughs to investigate and reveal its impacts on the processing properties of the frozen dough. The results showed that after the freeze-thaw cycle, with a volume ratio of 1:2 of SPI to M, the appropriate amount of M changed the structure of SPI. This resulted in the Pickering emulsion prepared by the SPI exhibiting the least droplet coalescence and the best freeze-thaw stability. The results of dough rheological properties, textural properties, and binding capacity with water demonstrated that Pickering emulsions effectively inhibited the loss of gluten protein network structure in the dough after freeze treatment and increased the binding capacity of gluten proteins with starch and water in the dough. The best results were obtained with the incorporation of 3 % SPI-M high freeze-thaw stability, where the amount of bound water following three freeze-thaw cycles was 4.27 times higher than in doughs without Pickering emulsion. Overall, this study is significant for enhancing the freeze-thaw stability of Pickering emulsions stabilized by proteins and providing a new application route for Pickering emulsions.

Biomechanical evaluation of different medial column fixation patterns for valgus pilon fractures.

BACKGROUND: The purpose of this study was to perform a biomechanical analysis to compare different medial column fixation patterns for valgus pilon fractures in a case-based model. METHODS: Based on the fracture mapping, 48 valgus pilon fracture models were produced and assigned into four groups with different medial column fixation patterns: no fixation (NF), K-wires (KW), intramedullary screws (IS), and locking compression plate (LCP). Each group contained wedge-in and wedge-out subgroups. After fixing each specimen on the machine, gradually increased axial compressive loads were applied with a load speed of one millimeter per minute. The maximum peak force was set at 1500 N. Load-displacement curves were generated and the axial stiffness was calculated. Five different loads of 200 N, 400 N, 600 N, 800 N, 1000 N were selected for analysis. The specimen failure was defined as resultant loading displacement over 3 mm. RESULTS: For the wedge-out models, Group-IS showed less displacement (p < 0.001), higher axial stiffness (p < 0.01), and higher load to failure (p < 0.001) than Group-NF. Group-KW showed comparable displacement under loads of 200 N, 400 N and 600 N with both Group-IS and Group-LCP. For the wedge-in models, no statistical differences in displacement, axial stiffness, or load to failure were observed among the four groups. Overall, wedge-out models exhibited less axial stiffness than wedge-in models (all p < 0.01). CONCLUSIONS: Functional reduction with stable fixation of the medial column is essential for the biomechanical stability of valgus pilon fractures and medial column fixation provides the enough biomechanical stability for this kind of fracture in the combination of anterolateral fixation. In detail, the K-wires can provide a provisional stability at an early stage. Intramedullary screws are strong enough to provide the medial column stability as a definitive fixation. In future, this technique can be recommended for medial column fixation as a complement for holistic stability in high-energy valgus pilon fractures.

Insulator Polymer Matrix Construction on All-Small-Molecule Photoactive Blend Towards Extrapolated 15000 Hour T80 Stable Devices.

To boost the stability of all-small-molecule (ASM) organic photovoltaic (OPV) blends, an insulator polymer called styrene-ethylene-butylene-styrene (SEBS) as morphology stabilizer is applied into the host system of small molecules BM-ClEH:BO-4Cl. Minor addition of SEBS (1 mg/ml in host solution) provides a significantly enhanced T80 value of 15000 hours (extrapolated), surpassing doping-free (0 mg/ml) and heavy doping (10 mg/ml) counterparts (900 hours, 30 hours). The material reproducibility and cost-effectiveness of the active layer will not be affected by this industrially available polymer, where the power conversion efficiency (PCE) can be well maintained at 15.02%, which is still a decent value for non-halogen solvent-treated ASM OPV. Morphological and photophysical characterizations clearly demonstrate SEBS's pivotal effect on suppressing the degradation of donor molecules and blend film's crystallization/aggregation reorganization, which protects the exciton dynamics effectively. This work pays meaningful attention to the ASM system stability, performs a smart strategy to suppress the film morphology degradation, and releases a comprehensive understanding of the mechanism of device performance reduction.

Impacts of storage conditions on the dissolution performance of commercial metronidazole tablets available in Saudi Arabia.

This study aimed to investigate the impact of storage conditions on the dissolution performance of commercial metronidazole (MTZ) tablets available in Saudi Arabia; these were coded as the reference and Test A, Test B, and Test C products. Moreover, the hardness and the disintegration time were measured. The UV spectrophotometrically analytical technique was utilized to quantify MTZ. All the control tablets, which were tested upon receipt, met the USP requirement as not less than 85 % of the labeled amount of MTZ was dissolved in 60 min. The MTZ reference released 91.79 % ± 1.23 after 60 min, while the products A, B, and C released 87.96 % ± 2.60, 93.26 % ± 2.01, and 88.61 % ± 2.04, respectively. The different dissolution parameters calculated for all the control tablets showed that the MTZ products A and B had optimal dissolution performances and were considered similar to the reference product. The product C showed a significantly reduced dissolution performance and was considered different from the reference. The in vitro dissolution of the MTZ tablets stored at 40oC ± 2 oC/75 % RH ± 5 % for 6 months indicated that the tablets maintained compliance with the USP requirement. The MTZ reference released 89.36 % ± 3.64 after 60 min, while the products A, B, and C released 95.79 % ± 3.91, 88.52 % ± 2.52, and 87.79 % ± 5.04, respectively. However, a slight reduction in the percentage released after 30 min (% DE30) and a slight increase in the mean dissolution time (MDT) were observed during the first 3 months of storage under stressed conditions. These changes were more obvious after 6 months of storage under the same conditions. Furthermore, in vitro dissolution of the product C stored at 40oC ± 2 oC/75 % RH ± 5 % for 3 months with further protection against high humidity revealed an improvement in the dissolution parameters due to the similar protective effects exerted by the two packaging forms. Furthermore, the study shows that storage conditions such as humidity and temperature affect in vitro dissolution of MTZ marketed tablets which may have an impact on efficiency and patient safety.

PBAT/lignin-ZnO composite film for food packaging: Photo-stability, better barrier and antibacterial properties.

When PBAT used as film, stability deteriorates under sunlight exposure, the poor barrier and antibacterial properties are also limiting its application. In this work, lignin-ZnO nanoparticles were prepared by hydrothermal method, as additives to fill the PBAT matrix. In addition, PBAT-lignin-ZnO composite films were successfully prepared by melting and hot-pressing method. It is found that lignin could well dispersed the ZnO when its implantation into PBAT films, and lignin-ZnO not only maintaining tensile strength and thermal stability, but also could prompt PBAT's crystallinity. Especially, P-L-ZnO-2 composite films have good photostability. After 60 h aging, it can still maintain good molecular weight, chemical structure and mechanical properties. Besides, these composite films have improved hydrophobicity, barrier and antibacterial properties, could prevent mildew and significantly reduce the weight loss rate, color difference and hardness changes of strawberries during storage. This work provides a potential film material for outdoor applications and food packaging.

Understand the Stabilization Engineering of Ascorbic Acid, Mapping the Scheme for Stabilization, and Advancement.

Vitamin C is extensively used in cosmetic formulation, howbeit stability is the supreme demerit that limits its use in beautifying products. Numerous techniques are being employed to inhibit the degradation of vitamin C caused by formulation components to facilitate the use in skin rejuvenating products. Diverse materials are being exercised in formulation to stabilize the ascorbic acid and ingredients selected in this formulation composition help for stabilization. The initial stable prototype is developed and further optimization is accomplished by applying the design of experiment tools. The stable pharmaceutical formulations were evaluated for the evaluation parameters and designated as two optimized formulations. The analytical method for the assay of ascorbic acid from the United States pharmacopeia and the related substance method from European pharmacopeia has been modified to be used for cream formulation. The DoE design exhibited that the stability of formulation is impacted by citric acid and tartaric acid but not by propylene glycol and glycerin. The analysis results of topical formulations for the evaluation parameter exhibited satisfactory results. The in-vitro release study method has been developed, optimized, and validated to fit the analysis. The in-vitro studies have been performed for selected compositions and both the formulation has similar kinds of release patterns. The stability study as per ICH guidelines exhibited that the product is stable for accelerated, intermediate, and room-temperature storage conditions. The optimized formulation shows constant release and permeation of ascorbic acid through the skin. The formulation with the combinations of citric acid, tartaric acid, and tocopherol is more stable and the degradation of vitamin C has been reduced significantly. The beaucoup strategies in the unique composition help to protect the degradation by inhibiting the multitudinous degradation pathways.

Stability of new psychoactive substances in crude wastewater.

Those involved in drug testing continue to grapple with the dynamic nature of emerging psychoactive substances (NPS) and their rapid infiltration into society. The challenge extends beyond merely detecting and measuring NPS using analytical tools; it also encompasses the complexities arising from the formation and presence of metabolites and degradation products. This study utilises liquid chromatography time-of-flight mass spectrometry to investigate the stability of new psychoactive substances in wastewater. Seven NPS compounds including 25C-NBOMe, 5F-APINACA 4-hydroxyphenyl, AB-PINACA, APINACA 4-hydroxyphenyl, fentanyl, norfentanyl and MDPV, along with their corresponding internal standard, were examined. Reference material for each NPS compound was introduced into a wastewater sample from a Wessex water treatment plant. The sample was then exposed to four different environments: room temperature, refrigerator temperature, acidification to pH 2, and the introduction of sodium metabisulfite. The findings highlight the critical dependence of storage conditions on target analytes, emphasizing the paramount importance of the time elapsed between collection and analysis for NPS wastewater analysis. Notably, synthetic cannabinoids exhibit limited stability in wastewater whereas cathinone-like substances demonstrate greater stability. Furthermore, metabolites prove to be more stable in wastewater than the parent drug, suggesting that focusing on metabolite detection may be more favourable for future analysis.

An Impressive Open-Circuit Voltage of 1.223 V and High Humidity Stability of Perovskite Solar Cells with MgO Buffer Layer Deposited by Low-Temperature Atomic Layer Deposition.

The performance of perovskite solar cells has been continuously improving. However, humidity stability has become a key problem that hinders its promotion in the process of commercialization. A buffer layer deposited by atomic layer deposition is a very helpful method to solve this problem. In this work, MgO film is deposited between Spiro-OMeTAD and electrode by low-temperature atomic layer deposition at 80 °C, which resists the erosion of water vapor, inhibits the migration of electrode metal ions and the decomposition products of perovskite, then finally improves the stability of the device. At the same time, the MgO buffer layer can passivate the defects of porous Spiro, thus enhancing carrier transport efficiency and device performance. The Cs0.05(FAPbI3)0.85(MAPbBr3)0.15 perovskite device with a MgO buffer layer has displayed PCE of 22.74%, also with a high Voc of 1.223 V which is an excellent performance in devices with same perovskite component. Moreover, the device with a MgO buffer layer can maintain 80% of the initial efficiency after 7200 h of storage at 35% relative humidity under room temperature. This is a major achievement for humidity stability in the world, providing more ideas for further improving the stability of perovskite devices.

LncRNA Snhg12/IGFBP3 axis is involved in liver fibrosis by promoting the proliferation and activation of mouse hepatic stellate cells.

Liver fibrosis is a persistent damage repair response triggered by various injury factors, which leads to an abnormal accumulation of extracellular matrix within liver tissue samples. The current clinical treatment of liver fibrosis is currently ineffective; therefore, elucidating the mechanism of liver fibrogenesis is of significant importance. Herein, the function and related mechanisms of lncRNA Snhg12 within hepatic fibrosis were investigated. Snhg12 expression was shown to be increased in mouse hepatic fibrotic tissue samples, and Snhg12 knockdown suppressed hepatic pathological injury and down-regulated the expression levels of fibrosis-associated proteins. Mechanistically, Snhg12 played a role in the early activation of mouse hepatic stellate cells (mHSCs) based on bioinformatics analysis, and Snhg12 was positively correlated with Igfbp3 expression. Further experimental results demonstrated that Snhg12 knockdown impeded mHSCs proliferation and activation and also downregulated the protein expression of Igfbp3. Snhg12 could interact with IGFBP3 and boost its protein stability, and overexpression of Igfbp3 partially reversed the inhibition of mHSCsproliferation and activation by the knockdown of Snhg12. In conclusion, LncRNA Snhg12 mediates liver fibrosis by targeting IGFBP3 and promoting its protein stability, thereby promoting mHSC proliferation and activation. Snhg12 has been identified as an underlying target for treating liver fibrosis.

Addressing bioreactor hiPSC aggregate stability, maintenance and scaleup challenges using a design of experiment approach.

BACKGROUND: Stem cell-derived therapies hold the potential for treatment of regenerative clinical indications. Static culture has a limited ability to scale up thus restricting its use. Suspension culturing can be used to produce target cells in large quantities, but also presents challenges related to stress and aggregation stability. METHODS: Utilizing a design of experiments (DoE) approach in vertical wheel bioreactors, we evaluated media additives that have versatile properties. The additives evaluated are Heparin sodium salt (HS), polyethylene glycol (PEG), poly (vinyl alcohol) (PVA), Pluronic F68 and dextran sulfate (DS). Multiple response variables were chosen to assess cell growth, pluripotency maintenance and aggregate stability in response to the additive inputs, and mathematical models were generated and tuned for maximal predictive power. RESULTS: Expansion of iPSCs using 100 ml vertical wheel bioreactor assay for 4 days on 19 different media combinations resulted in models that can optimize pluripotency, stability, and expansion. The expansion optimization resulted in the combination of PA, PVA and PEG with E8. This mixture resulted in an expansion doubling time that was 40% shorter than that of E8 alone. Pluripotency optimizer highlighted the importance of adding 1% PEG to the E8 medium. Aggregate stability optimization that minimizes aggregate fusion in 3D culture indicated that the interaction of both Heparin and PEG can limit aggregation as well as increase the maintenance capacity and expansion of hiPSCs, suggesting that controlling fusion is a critical parameter for expansion and maintenance. Validation of optimized solution on two cell lines in bioreactors with decreased speed of 40 RPM, showed consistency and prolonged control over aggregates that have high frequency of pluripotency markers of OCT4 and SOX2 (> 90%). A doubling time of around 1-1.4 days was maintained after passaging as clumps in the optimized medium. Controlling aggregate fusion allowed for a decrease in bioreactor speed and therefore shear stress exerted on the cells in a large-scale expansion. CONCLUSION: This study resulted in a control of aggregate size within suspension cultures, while informing about concomitant state control of the iPSC state. Wider application of this approach can address media optimization complexity and bioreactor scale-up challenges.

A rapid protocol for synthesis of chitosan nanoparticles with ideal physicochemical features.

In this research, an innovative protocol is introduced to address crucial deficiencies in the formulation of chitosan nanoparticles (Cs NPs). While NPs show potential in drug delivery systems (DDSs), their application in the clinic is hindered by various drawbacks, such as toxicity, high material costs, and time-consuming and challenging preparation procedures. Within polymer-based NPs, Cs is a plentiful natural substance derived from the deacetylation of chitin, which can be sourced from the shells of shrimp or crab. Cs NPs can be formulated using the ionic gelation technique, which involves the use of a negatively charged agent, such as tripolyphosphate (TPP), as a crosslinking agent. Even though Cs is a cost-effective and biocompatible material, the formulation of Cs NPs with the correct size and surface electrical charge (zeta potential) presents a persistent challenge. In this study, various techniques were employed to analyze the prepared Cs NPs. The size and surface charge of the NPs were evaluated using dynamic light scattering (DLS). Morphological analysis was conducted using field emission-scanning electron microscopy (FE-SEM). The chemical composition and formation of Cs NPs were investigated using Fourier transform infrared (FTIR). The stability analysis was confirmed through X-ray diffraction (XRD) analysis. Lastly, the biocompatibility of the NPs was assessed through cell cytotoxicity evaluation using the MTT assay. Moreover, here, 11 formulations with different parameters such as reaction pH, Cs:TPP ratio, type of Cs/TPP, and ultrasonication procedure were prepared. Formulation 11 was chosen as the optimized formulation based on its high stability of more than three months, biocompatibility, nanosize of 75.6 ± 18.24 nm, and zeta potential of +26.7 mV. To conclude, the method described here is easy and reproducible and can be used for facile preparation of Cs NPs with desirable physicochemical characteristics and engineering ideal platforms for drug delivery purposes.

Resilience of the slow component in timescale-separated synchronized oscillators.

Physiological networks are usually made of a large number of biological oscillators evolving on a multitude of different timescales. Phase oscillators are particularly useful in the modelling of the synchronization dynamics of such systems. If the coupling is strong enough compared to the heterogeneity of the internal parameters, synchronized states might emerge where phase oscillators start to behave coherently. Here, we focus on the case where synchronized oscillators are divided into a fast and a slow component so that the two subsets evolve on separated timescales. We assess the resilience of the slow component by, first, reducing the dynamics of the fast one using Mori-Zwanzig formalism. Second, we evaluate the variance of the phase deviations when the oscillators in the two components are subject to noise with possibly distinct correlation times. From the general expression for the variance, we consider specific network structures and show how the noise transmission between the fast and slow components is affected. Interestingly, we find that oscillators that are among the most robust when there is only a single timescale, might become the most vulnerable when the system undergoes a timescale separation. We also find that layered networks seem to be insensitive to such timescale separations.