Intermittent hypoxia training does not change erythrocyte aggregation indicators in young, healthy men.

Background: The increasing popularity of hypoxic training as a training method to improve physical performance indicates the need to study the effects of this type of intervention on blood morphological and rheological indices, since the adaptive changes that follow such training mainly affect blood indices. In this study, the effects of a 4 weeks of intermittent hypoxic training on blood morphological and rheological indicators in physically active men were assessed. Methods: Forty-eight young, physically active men, participated in the study. Participants were randomly divided into three groups: two training groups and a control group without intervention (CTRL). Each group consisted of 16 participants. Training groups performed interval training (three times per week, 4 weeks, 12 workouts) under different conditions: in hypoxia (IHT; fraction of inspired oxygen (FiO2) = 14.4%) or in normoxia (NT; FiO2 = 20.9%). The control group performed only two workouts 4 weeks apart. Blood was taken during the first and last training session at rest, and 3 minutes after training. Results: After the last training session, there was a significant increase in mean corpuscular volume and a decrease in mean corpuscular haemoglobin concentration measured at rest only in the IHT group. There was also a significant decrease in resting aggregation amplitude for the IHT and CTRL groups. There was no difference in change of post-exercise plasma volume between first and last training session. Conclusion: The applied intermittent interval training in conditions of normoxia and hypoxia had no significant impact on resting aggregation parameters. This suggest that training under hypoxic conditions does not cause adverse rheological changes.

Differential phagocytic expression of IC-21 macrophages and their scavenging receptors during inflammatory induction by oxysterol: A microscopic approach.

Phagocytosis by macrophages dates back to a long history in science, this present study deals with new approaches that have been analyzed and standardized towards the interesting aspects of primary and secondary macrophages. The distinct morphological differences in primary and secondary phagocytic cells were observed and the phagocytic response of secondary macrophages under the influence of 7-ketocholesterol and lipopolysaccharide was analyzed. The primary peritoneal and secondary IC-21 cells unveiled explicit differences in nuclear numbers shapes and sizes of the granules present within the cytoplasmic region. Further, potent inducers 7KCh and LPS influenced an effective activation of IC-21 macrophages and resulted in ROS generation, irregulated protein expressions of CD86, CD68, and CD206 with enhanced phagocytic responses towards goat, cow, and human RBC targets with significant phagocytic rate and index were observed. Moreover, a remarkable observation of target specificity and aggregations with IC-21 phagocytic macrophages revealed the notion that specific membrane receptors and secretory molecules (lysosomes) are primarily involved in their phagocytic mechanism. RESEARCH HIGHLIGHTS: IC-21 macrophages are peritoneal origin from mice but the primary peritoneal macrophages and cell line show distinct differences. IC-21 macrophages express target-specific phagocytosis. Phagocytosis in IC-21 macrophages is regulated by CD markers (68, 86, and 206).

Spatiotemporal fate of nanocarriers-embedded dissolving microneedles: the impact of needle dissolving rate.

OBJECTIVE: Dissolving microneedles (DMNs) have shown great potential for transdermal drug delivery due to their excellent skin-penetrating ability and combination with nanocarriers (NCs) can realize targeted drug delivery. The objective of this study was to investigate the impact of microneedle dissolving rate on the in vivo fate of NC-loaded DMNs, which would facilitate the clinical translation of such systems. METHODS: Solid lipid nanoparticles (SLNs) were selected as the model NC for loading in DMNs, which were labeled by P4 probes with aggregation-quenching properties. Sodium hyaluronate acid (HA) and chitosan (CS), with different aqueous dissolving rates, were chosen as model tip materials. The effects of needle dissolving rate on the in vivo fate of NC-loaded DMNs was investigated by tracking the distribution of fluorescence signals after transdermal exposure. RESULTS: P4 SLNs achieved a deeper diffusion depth of 180 µm in DMN-HA with a faster dissolution rate, while the diffusion depth in DMN-CS with a slower dissolution rate was lower (140 µm). The in vivo experiments demonstrated that P4 SLNs had a T1/2 value of 12.14 h in DMN-HA, whilst a longer retention time was found in DMN-CS, with a T1/2 of 13.12 h. CONCLUSIONS: This study confirmed that the in vivo diffusion rate of NC-loaded DMNs was determined by the dissolving rate of DMNs materials and provided valuable guidance for the design and development of NC-loaded DMNs in the future.

The formation of aggregated chromatin/chromosomes in mouse oocytes treated with high concentration of IBMX as a model for a chromosome transfer in human.

The presence of cyclic adenosine monophosphate (cAMP) has been considered to be a fundamental factor in ensuring meiotic arrest prior to ovulation. cAMP is regarded as a key molecule in the regulation of oocyte maturation. However, it has been reported that increased levels of intracellular cAMP can result in abnormal cytokinesis, with some MI oocytes leading to symmetrically cleaved 2-cell MII oocytes. Consequently, we aimed to investigate the effects of elevated intracellular cAMP levels on abnormal cytokinesis and oocyte maturation during the meiosis of mouse oocytes. This study found that a high concentration of isobutylmethylxanthine (IBMX) also caused chromatin/chromosomes aggregation (AC) after the first meiosis. The rates of AC increased the greater the concentration of IBMX. In addition, AC formation was found to be reversible, showing that the re-formation of the spindle chromosome complex was possible after the IBMX was removed. In human oocytes, the chromosomes aggregate after the germinal vesicle breakdown and following the first and second polar body extrusions (the AC phase), while mouse oocytes do not have this AC phase. The results of our current study may indicate that the AC phase in human oocytes could be related to elevated levels of intracytoplasmic cAMP.

A peptide strategy for inhibiting different protein aggregation pathways.

Protein aggregation correlates with many human diseases. Protein aggregates differ in structure and shape. Strategies to develop effective aggregation inhibitors that reach the clinic failed so far. Here, we developed a family of peptides targeting early aggregation stages for both amorphous and fibrillar aggregates of proteins unrelated in sequence and structure. They act on dynamic precursors before mechanistic differentiation takes place. Using peptide arrays, we first identified peptides inhibiting the amorphous aggregation of a molten globular, aggregation-prone mutant of the Axin tumor suppressor. Optimization revealed that the peptides activity did not depend on their sequences but rather on their molecular determinants: a composition of 20-30% flexible, 30-40% aliphatic and 20-30% aromatic residues, a hydrophobicity/hydrophilicity ratio close to 1, and an even distribution of residues of different nature throughout the sequence. The peptides also suppressed fibrillation of Tau, a disordered protein that forms amyloids in Alzheimer's disease, and slowed down that of Huntingtin Exon1, an amyloidogenic protein in Huntington's disease, both entirely unrelated to Axin. Our compounds thus target early aggregation stages of different aggregation mechanisms, inhibiting both amorphous and amyloid aggregation. Such cross-mechanistic, multi-targeting aggregation inhibitors may be lead compounds for developing drug candidates against various protein aggregation diseases.

Solvent-Assisted Structural Modifications of Sulfur Dots Followed by Time-Dependent Emergence of a New Emissive State and Long-Lived Afterglow.

Sulfur dots are a new class of recently developed nonmetallic luminescent nanomaterials with various potential applications. Herein, we synthesized sulfur dots using a mild chemical etching method and then modified the structural features of the as-synthesized sulfur dots using a slow and defined solvent-assisted aggregation process. This increases the particle size and overall crystallinity along with the modifications of the surface functional groups, which eventually show a new emission band at longer wavelengths. Detailed photophysical and temperature-dependent luminescence studies confirmed that the new emissive state evolves due to interparticle interactions in the excited state. Furthermore, the occurrence of a new emissive state in a longer-wavelength region helped reduce the energy gap between the lowest excited singlet state and the lowest excited triplet state in modified sulfur dots, resulting in an aqueous stable room-temperature phosphorescence/afterglow emission through efficient intersystem crossing. This typical efficacious afterglow emission directly shows the potential applicability of structurally modified sulfur dots in encryption devices and can also be potentially effective in light emitting diodes (LED) and sensing devices.

Phase Separation and Aggregation of α-Synuclein Diverge at Different Salt Conditions.

The coacervation of alpha-synuclein (αSyn) into cytotoxic oligomers and amyloid fibrils are considered pathological hallmarks of Parkinson's disease. While aggregation is central to amyloid diseases, liquid-liquid phase separation (LLPS) and its interplay with aggregation have gained increasing interest. Previous work shows that factors promoting or inhibiting aggregation have similar effects on LLPS. This study provides a detailed scanning of a wide range of parameters, including protein, salt and crowding concentrations at multiple pH values, revealing different salt dependencies of aggregation and LLPS. The influence of salt on aggregation under crowding conditions follows a non-monotonic pattern, showing increased effects at medium salt concentrations. This behavior can be elucidated through a combination of electrostatic screening and salting-out effects on the intramolecular interactions between the N-terminal and C-terminal regions of αSyn. By contrast, this study finds a monotonic salt dependence of LLPS due to intermolecular interactions. Furthermore, it observes time evolution of the two distinct assembly states, with macroscopic fibrillar-like bundles initially forming at medium salt concentration but subsequently converting into droplets after prolonged incubation. The droplet state is therefore capable of inhibiting aggregation or even dissolving aggregates through heterotypic interactions, thus preventing αSyn from its dynamically arrested state.

Discovery of Fluorescent Naturally-occurring Inhibitor of SARS-CoV-2 Main Protease By AIE Fluorescent Probe.

Target-based high-throughput screening (HTS) is an efficient way to identify potent drugs. However, the accuracy of HTS could be affected by Pan-Assay Interference Compounds (PAINS). One reason for the generation of PAINS is that the inherent photophysical property of screened compounds could interfere with typically used assay signals including absorption and fluorescence. Our previous studies indicate that the fluorescent probe based on the fluorophore with characteristics of aggregation-induced emission (AIE) could provide high accuracy of HTS, especially for the fluorescent natural products. Herein, we report an AIE-based fluorescent probe for the main protease (Mpro) of SARS-CoV-2. We designed and synthesized an AIE fluorescent probe ZLHG5, which has a site that can be specifically cleaved by Mpro to produce a light-up fluorescence. Thanks to the large Stokes shift of AIE fluorophore (~300 nm), the probe could be effectively used for HTS of Mpro inhibitors. After screening a library of fluorescent natural products with ZLHG5, we obtained two coumarin-originated natural compounds with potent inhibitory activity towards Mpro protease. This study provides both useful fluorescent HTS probe and potent inhibitors for Mpro protease.

Type I Hsp40s/DnaJs aggregates exhibit features reminiscent of amyloidogenic structures.

A rise in temperature triggers a structural change in the human Type I 40 kDa heat shock protein (Hsp40/DnaJ), known as DNAJA1. This change leads to a less compact structure, characterized by an increased presence of solvent-exposed hydrophobic patches and ß-sheet-rich regions. This transformation is validated by circular dichroism, thioflavin T binding, and Bis-ANS assays. The formation of this ß-sheet-rich conformation, which is amplified in the absence of zinc, leads to protein aggregation. This aggregation is induced not only by high temperatures but also by low ionic strength and high protein concentration. The aggregated conformation exhibits characteristics of an amyloidogenic structure, including a distinctive X-ray diffraction pattern, seeding competence (which stimulates the formation of amyloid-like aggregates), cytotoxicity, resistance to SDS, and fibril formation. Interestingly, the yeast Type I Ydj1 also tends to adopt a similar ß-sheet-rich structure under comparable conditions, whereas Type II Hsp40s, whether human or from yeast, do not. Moreover, Ydj1 aggregates were found to be cytotoxic. Studies using DNAJA1- and Ydj1-deleted mutants suggest that the zinc-finger region plays a crucial role in amyloid formation. Our discovery of amyloid aggregation in a C-terminal deletion mutant of DNAJA1, which resembles a spliced homolog expressed in the testis, implies that Type I Hsp40 co-chaperones may generate amyloidogenic species in vivo.

Synthesis, crystal structure and photophysical properties of a dinuclear MnII complex with 6-(di-ethyl-amino)-4-phenyl-2-(pyridin-2-yl)quinoline.

A new quinoline derivative, namely, 6-(di-ethyl-amino)-4-phenyl-2-(pyridin-2-yl)quinoline, C24H23N3 (QP), and its MnII complex aqua-1κO-di-µ-chlorido-1:2κ4 Cl:Cl-di-chlorido-1κCl,2κCl-bis-[6-(di-ethyl-amino)-4-phenyl-2-(pyridin-2-yl)quinoline]-1κ2 N 1,N 2;2κ2 N 1,N 2-dimanganese(II), [Mn2Cl4(C24H23N3)2(H2O)] (MnQP), were synthesized. Their compositions have been determined with ESI-MS, IR, and 1H NMR spectroscopy. The crystal-structure determination of MnQP revealed a dinuclear complex with a central four-membered Mn2Cl2 ring. Both MnII atoms bind to an additional Cl atom and to two N atoms of the QP ligand. One MnII atom expands its coordination sphere with an extra water mol-ecule, resulting in a distorted octa-hedral shape. The second MnII atom shows a distorted trigonal-bipyramidal shape. The UV-vis absorption and emission spectra of the examined compounds were studied. Furthermore, when investigating the aggregation-induced emission (AIE) properties, it was found that the fluorescent color changes from blue to green and eventually becomes yellow as the fraction of water in the THF/water mixture increases from 0% to 99%. In particular, these color and intensity changes are most pronounced at a water fraction of 60%. The crystal structure contains disordered solvent mol-ecules, which could not be modeled. The SQUEEZE procedure [Spek (2015 ▸). Acta Cryst. C71, 9-18] was used to obtain information on the type and qu-antity of solvent mol-ecules, which resulted in 44 electrons in a void volume of 274 Å3, corresponding to approximately 1.7 mol-ecules of ethanol in the unit cell. These ethanol mol-ecules are not considered in the given chemical formula and other crystal data.

An outer membrane vesicle specific lipoprotein promotes Porphyromonas gingivalis aggregation on red blood cells.

Porphyromonas gingivalis uses a variety of mechanisms to actively interact with and promote the hydrolysis of red blood cells (RBCs) to obtain iron in the form of heme. In this study, we investigated the function of lipoprotein PG1881 which was previously shown to be up-regulated during subsurface growth and selectively enriched on outer membrane vesicles (OMVs). Our results show that wildtype strain W83 formed large aggregates encompassing RBCs whereas the PG1881 deletion mutant remained predominately as individual cells. Using a PG1881 antibody, immunofluorescence revealed that the wildtype strain's aggregation to RBCs involves an extracellular matrix enriched with PG1881. Our findings discover that RBCs elicit cell aggregation and matrix formation by P. gingivalis and that this process is promoted by an OMV-specific lipoprotein. We propose this strategy is advantageous for nutrient acquisition as well as dissemination from the oral cavity and survival of this periodontal pathogen.

Hierarchical Self-Aggregation of Multifunctional Steviol Glycosides in Aqueous Solutions.

Steviol glycosides (SGs) are a natural sweetener widely used in the food and beverage industry, but the low solubility and stability of SG aqueous solutions greatly limit their application performance, especially in liquid formulations. In this work, we explore the solubility behavior of rebaudioside A (Reb A) in water, a major component of SGs, with the aim of clarifying the underlying mechanisms of the solubility and stability constraints of SGs, as well as the impact on their multifunctional properties. We demonstrate for the first time that Reb A exhibits hierarchical self-assembly in solutions, forming spherical micelles first when the concentration exceeds its critical micelle concentration (5.071 mg/mL), which then further assemble into large rod-like aggregates. The formation of such large Reb A aggregates is mainly dominated by hydrogen bonding and short-range Coulomb interaction energy, thus leading to the low solubility and precipitation of Reb A solutions. Surprisingly, aggregated Reb A structures display significantly improved organoleptic properties, revealing that self-aggregation can be developed as a simple, efficient, and green strategy for improving the taste profile of SGs. Additionally, the self-aggregation of Reb A at high concentrations impairs active encapsulation and also affects its interfacial and emulsifying properties.

Highly Efficient Multicolor-Emitting Tetraphenylethylene-Based Organic Salts with Commercialization Prospects.

Since the discovery of aggregation-induced emission from tetraphenylethylene derivatives, various methods have been explored to prepare highly efficient multicolored luminescent materials. Herein, we report a simple and efficient strategy for constructing luminescent organic salts of the tetracationic luminogen, tetrapyridinium-tetraphenylethylene (T4Py-TPE4+), combined with seven di- and tetra-anionic aromatic sulfonate ligands. When aqueous solutions of the cationic luminogen and the anionic ligands were mixed, they rapidly aggregated into organic salts within seconds to minutes, giving yields of up to >90%. This was accompanied by an increase in the emission efficiency from ∼58% to almost 100%, and the ability to tune the emission color between 511 and 586 nm. These improvements were mainly attributed to the strong electrostatic attractions between the cation and anions, which resulted in the formation of a rigid hydrophobic network of the T4Py-TPE4+ luminogen with various π-conjugation lengths. Because these compounds are commercially available, this method opens the possibility of fabricating novel light-emitting materials for device fabrication and research.

Pyrenetetrasulfonate-grafted 2D ultrathin metal-organic layer as new electrochemiluminescence emitters for ultrasensitive microRNA-21 assay.

The exploration of novel electrochemiluminescence (ECL) luminophores with excellent ECL properties is a current research hotspot in the ECL field. Herein, a novel high-efficiency Ru-complex-free ECL emitter PyTS-Zr-BTB-MOL has been prepared by using porous ultrathin Zr-BTB metal-organic layer (MOL) as carrier to coordinatively graft the cheap and easily available polycyclic aromatic hydrocarbon (PAH) derivative luminophore PyTS whose ECL performance has never been investigated. Gratifyingly, the ECL intensity and efficiency of PyTS-Zr-BTB-MOL were markedly enhanced compared to both PyTS monomers and PyTS aggregates. The main reason was that the distance between pyrene rings was greatly expanded after the PyTS grafting on the Zr6 clusters of Zr-BTB-MOL, which overcame the aggregation-caused quenching (ACQ) effect of PyTS and thus enhanced the ECL emission. Meanwhile, the porous nanosheet structure of PyTS-Zr-BTB-MOL could distinctly increase the exposure of PyTS luminophores and shorten the diffusion paths of coreactants and electrons/ions, which effectively promoted the electrochemical excitation of more PyTS luminophores and thus achieved a further ECL enhancement. In light of the remarkable ECL property of PyTS-Zr-BTB-MOL, it was employed as an ECL indicator to build a novel high-sensitivity ECL biosensor for microRNA-21 determination, possessing a satisfactory response range (100 aM to 100 pM) and an ultralow detection limit (10.4 aM). Overall, this work demonstrated that using MOLs to coordinatively graft the PAH derivative luminophores to eliminate the ACQ effect and increase the utilization rate of the luminophores is a promising and efficient strategy to develop high-performance Ru-complex-free ECL materials for assembling ultrasensitive ECL biosensing platforms.

A rapid method to monitor structural perturbations of High-Concentrated therapeutic antibody solutions using Intrinsic tryptophan fluorescence emission spectroscopy.

Drug product development of therapeutic antibody formulations is still dictated by the risk of protein particle formation during processing or storage, which can lead to loss of potency and potential immunogenic reactions. Since structural perturbations are the main driver for irreversible protein aggregation, the conformational integrity of antibodies should be closely monitored. The present study evaluated the applicability of a plate reader-based high throughput method for intrinsic tryptophan fluorescence emission (ITFE) spectroscopy to detect protein aggregation due to protein unfolding in high-concentrated therapeutic antibody samples. The impact of fluorophore concentration on the ITFE signal in microplate readers was investigated by analysis of dilution series of two therapeutic antibodies and pure tryptophan. At low antibody concentrations (<5 mg/mL, equivalent to 0.8 mM tryptophan), the low inner filter effect suggests a quasi-linear relationship between antibody concentration and ITFE intensity. In contrast, the constant ITFE intensity at high protein concentrations (>40 mg/mL, equivalent to 6.1 mM tryptophan) indicate that ITFE spectroscopy measurements of IgG1 antibodies are feasible in therapeutically relevant concentrations (up to 223 mg/mL). Furthermore, the capability of the method to detect low levels of unfolding (around 1 %) was confirmed by limit of detection (LOD) determination with temperature-stressed antibody samples as degradation standards. Change of fluorescence intensity at the maximum (ΔIaM) was identified as sensitive descriptor for protein degradation, providing the lowest LOD values. The results demonstrate that ITFE spectroscopy performed in a microplate reader is a valuable tool for high-throughput monitoring of protein degradation in therapeutic antibody formulations.

A Snake Venom Peptide and Its Derivatives Prevent Aß42 Aggregation and Eliminate Toxic Aß42 Aggregates In Vitro.

Over a century has passed since Alois Alzheimer first described Alzheimer's disease (AD), and since then, researchers have made significant strides in understanding its pathology. One key feature of AD is the presence of amyloid-ß (Aß) peptides, which form amyloid plaques, and therefore, it is a primary target for treatment studies. Naturally occurring peptides have garnered attention for their potential pharmacological benefits, particularly in the central nervous system. In this study, nine peptide derivatives of Crotamine, a polypeptide from Crotalus durissus terrificus Rattlesnake venom, as well as one d-enantiomer, were evaluated for their ability to modulate Aß42 aggregation through various assays such as ThT, QIAD, SPR, and sFIDA. All tested peptides were able to decrease Aß42 aggregation and eliminate Aß42 aggregates. Additionally, all of the peptides showed an affinity for Aß42. This study is the first to describe the potential of crotamine derivative peptides against Aß42 aggregation and to identify a promising d-peptide that could be used as an effective pharmacological tool against AD in the future.

Marine bacteria Alteromonas spp. require UDP-glucose-4-epimerase for aggregation and production of sticky exopolymer.

The physiology and ecology of particle-associated marine bacteria are of growing interest, but our knowledge of their aggregation behavior and mechanisms controlling their association with particles remains limited. We have found that a particle-associated isolate, Alteromonas sp. ALT199 strain 4B03, and the related type-strain A. macleodii 27126 both form large (>500 µm) aggregates while growing in rich medium. A non-clumping variant (NCV) of 4B03 spontaneously arose in the lab, and whole-genome sequencing revealed a partial deletion in the gene encoding UDP-glucose-4-epimerase (galEΔ308-324). In 27126, a knock-out of galE (ΔgalE::kmr) resulted in a loss of aggregation, mimicking the NCV. Microscopic analysis shows that both 4B03 and 27126 rapidly form large aggregates, whereas their respective galE mutants remain primarily as single planktonic cells or clusters of a few cells. Strains 4B03 and 27126 also form aggregates with chitin particles, but their galE mutants do not. Alcian Blue staining shows that 4B03 and 27126 produce large transparent exopolymer particles (TEP), but their galE mutants are deficient in this regard. This study demonstrates the capabilities of cell-cell aggregation, aggregation of chitin particles, and production of TEP in strains of Alteromonas, a widespread particle-associated genus of heterotrophic marine bacteria. A genetic requirement for galE is evident for each of the above capabilities, expanding the known breadth of requirement for this gene in biofilm-related processes. IMPORTANCE: Heterotrophic marine bacteria have a central role in the global carbon cycle. Well-known for releasing CO2 by decomposition and respiration, they may also contribute to particulate organic matter (POM) aggregation, which can promote CO2 sequestration via the formation of marine snow. We find that two members of the prevalent particle-associated genus Alteromonas can form aggregates comprising cells alone or cells and chitin particles, indicating their ability to drive POM aggregation. In line with their multivalent aggregation capability, both strains produce TEP, an excreted polysaccharide central to POM aggregation in the ocean. We demonstrate a genetic requirement for galE in aggregation and large TEP formation, building our mechanistic understanding of these aggregative capabilities. These findings point toward a role for heterotrophic bacteria in POM aggregation in the ocean and support broader efforts to understand bacterial controls on the global carbon cycle based on microbial activities, community structure, and meta-omic profiling.

Research Priorities on the Role of α-Synuclein in Parkinson's Disease Pathogenesis.

Various forms of Parkinson's disease, including its common sporadic form, are characterized by prominent α-synuclein (αSyn) aggregation in affected brain regions. However, the role of αSyn in the pathogenesis and evolution of the disease remains unclear, despite vast research efforts of more than a quarter century. A better understanding of the role of αSyn, either primary or secondary, is critical for developing disease-modifying therapies. Previous attempts to hone this research have been challenged by experimental limitations, but recent technological advances may facilitate progress. The Scientific Issues Committee of the International Parkinson and Movement Disorder Society (MDS) charged a panel of experts in the field to discuss current scientific priorities and identify research strategies with potential for a breakthrough. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Dimerization of Full-length Aß -42 Peptide: A Comparison of Different Force Fields and Water Models.

Among the two isoforms of amyloid- i.e., Aß-40 and Aß-42, Aß-42 is more toxic due to its increased aggregation propensity. The oligomerization pathways of amyloid-ß may be investigated by studying its dimerization process at an atomic level. Intrinsically disordered proteins (IDPs) lack well-defined structures and are associated with numerous neurodegenerative disorders. Molecular dynamics simulations of these proteins are often limited by the choice of parameters due to inconsistencies in the empirically developed protein force fields and water models. To evaluate the accuracy of recently developed force fields for IDPs, we study the dimerization of full-length Aß-42 in aqueous solution with three different combinations of AMBER force field parameters and water models such as ff14SB/TIP3P, ff19SB/OPC, and ff19SB/TIP3P using classical MD and Umbrella Sampling method. This work may be used as a benchmark to compare the performance of different force fields for the simulations of IDPs.

Characterization of TEMPO-Oxidized Cellulose Nanofiber From Biowaste and Its Influence on Molecular Behavior of Fluorescent Rhodamine B Dye in Aqueous Suspensions.

Cellulose nanofiber (CNFs) obtained through TEMPO oxidation was structurally characterized using FT-IR (Fourier Transformed Infrared) and SEM (Scanning Electron Microscopy) spectroscopy. The molecular aggregation and spectroscopic properties of Rhodamine B (Rh-B) in CNFs suspension were investigated using molecular absorption and steady-state fluorescence spectroscopy techniques. The interaction between CNFs particles in the aqueous suspension and the cationic dye compound was examined in comparison to its behavior in deionized water. This interaction led to significant changes in the spectral features of Rh-B, resulting in an increase in the presence of H-dimer and H-aggregate in CNFs suspension. The H-type aggregates of Rh-B in CNFs suspensions were defined by the observation of a blue-shifted absorption band compared to that of the monomer. Even at diluted dye concentrations, the formation of Rh-B's H-aggregate was observed in CNFs suspension. The pronounced aggregation in suspensions originated from the strong interaction between negatively charged carboxylate ions and the dye. The aggregation behavior was discussed with deconvoluted absorption spectra. Fluorescence spectroscopy studies revealed a significant reduction in the fluorescence intensity of the dye in CNFs suspension due to H-aggregates. Furthermore, the presence of H-aggregates in the suspensions caused a decrease in the quantum yield of Rh-B compared to that in deionized water.