Aggregation Tendency Research Articles

A novel human single-domain antibody-drug conjugate targeting CEACAM5 exhibits potent in vitro and in vivo antitumor activity.

Leveraging the specificity of antibody to deliver cytotoxic agent into tumor, antibody-drug conjugates (ADCs) have become one of the hotspots in the development of anticancer therapies. Although significant progress has been achieved, there remain challenges to overcome, including limited penetration into solid tumors and potential immunogenicity. Fully human single-domain antibodies (UdAbs), with their small size and human nature, represent a promising approach for addressing these challenges. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) is a glycosylated cell surface protein that rarely expressed in normal adult tissues but overexpressed in diverse cancers, taking part in tumorigenesis, progression, and metastasis. In this study, we investigated the therapeutic potential of UdADC targeting CEACAM5. We performed biopanning in our library and obtained an antibody candidate B9, which bound potently and specifically to CEACAM5 protein (KD = 4.84 nM) and possessed excellent biophysical properties (low aggregation tendency, high homogeneity, and thermal stability). The conjugation of B9 with a potent cytotoxic agent, monomethyl auristatin E (MMAE), exhibited superior antitumor efficacy against CEACAM5-expressing human gastric cancer cell line MKN-45, human pancreatic carcinoma cell line BxPC-3 and human colorectal cancer cell line LS174T with IC50 values of 38.14, 25.60, and 101.4 nM, respectively. In BxPC-3 and MKN-45 xenograft mice, administration of UdADC B9-MMAE (5 mg/kg, i.v.) every 2 days for 4 times markedly inhibited the tumor growth without significant change in body weight. This study may have significant implications for the design of next-generation ADCs.

Surface modification boosts dispersion stability of nanoparticles in dielectric fluids

Achieving stable dispersion of nanoparticles in dielectric fluids is a challenging task, as there are complex and diverse influencing factors, requiring molecular-level understanding of the nanoparticle aggregation. In this paper, we conducted long-time molecular simulations of dielectric nanofluids containing fifteen SiO2 nanoparticles, systematically varying the length of alky chains grafted onto their surface to explore their impact on the aggregation process. Our results reveal that appropriate surface modification can dramatically increase the dispersion stability of nanoparticles in dielectric fluids. SiO2 nanoparticles lacking alkyl chains exhibit a strong tendency to approach each other, and form aggregates in natural esters, because of the Coulombic energy from heteroatoms of SiO2 nanoparticles. Despite the differences in the length of grafted alkyl chains on the surface of SiO2 nanoparticles, all of them, regardless of their length, are capable of effectively shielding the Coulombic interactions and increasing the van der Waals interaction with natural esters, thereby reducing the aggregation tendency of nanoparticles. Furthermore, the smaller diffusion ability, caused by the steric hindrance effect, of surface-modified SiO2 nanoparticles also inhibits their collision and subsequent aggregation.

Dual-Activity Fluoroquinolone-Transportan 10 Conjugates offer alternative Leukemia therapy during Hematopoietic Cell Transplantation.

Hematopoietic cell transplantation (HCT) is often considered a last resort leukemia treatment, fraught with limited success due to microbial infections, a leading cause of mortality in leukemia patients. To address this critical issue, we explored a novel approach by synthesizing antileukemic agents containing antibacterial substances. This innovative strategy involves conjugating fluoroquinolone antibiotics, such as ciprofloxacin (CIP) or levofloxacin (LVX), with the cell-penetrating peptide (CPP) transportan 10 (TP10). Here, we demonstrate that the resultant compounds display promising biological activities in preclinical studies. These novel conjugates not only exhibit potent antimicrobial effects but are also selective against leukemia cells. The cytotoxic mechanism involves rapid disruption of cell membrane asymmetry leading to membrane damage. Importantly, these conjugates penetrated mammalian cells, accumulating within the nuclear membrane without significant effect on cellular architecture or mitochondrial function. Molecular simulations elucidated the aggregation tendencies of TP10 conjugates within lipid bilayers, resulting in membrane disruption and permeabilization. Moreover, mass spectrometry analysis confirmed efficient reduction of disulfide bonds within TP10 conjugates, facilitating release and activation of the fluoroquinolone derivatives. Intriguingly, these compounds inhibited human topoisomerases, setting them apart from traditional fluoroquinolones. Remarkably, TP10 conjugates generated lower intracellular levels of reactive oxygen species (ROS) compared to CIP and LVX. The combination of antibacterial and antileukemic properties, coupled with selective cytostatic effects and minimal toxicity towards healthy cells, positions TP10 derivatives as promising candidates for innovative therapeutic approaches in the context of antileukemic HCT. This study highlights their potential in search of more effective leukemia treatments. Significance Statement Fluoroquinolones are commonly used antibiotics, while TP10 is a CPP with anticancer properties. In HCT, microbial infections are the primary cause of illness and death. Combining TP10 with fluoroquinolones enhanced their effects on different cell types. The dual pharmacological action of these conjugates offers a promising proof-of-concept solution for leukemic patients undergoing HCT. Strategically designed therapeutics, incorporating CPPs with antibacterial properties, have the potential to reduce microbial infections in the treatment of malignancies.

Spectral response of sulfonated polystyrene photonic crystals with varying concentrations of ethanol

Modifying polystyrene (PS) spheres through sulfonation is a well-established method to enhance their hydrophilic properties, rendering them valuable in diverse applications. Fabrication of photonic crystals (PCs) with sulfonated polystyrene (SPS) spheres offers an important platform for sensing applications. The hydrophilic nature of such PC platform helps in improving the detection of water content. In the present work, monodispersed SPS spheres were synthesized by adjusting the duration of the sulfonation reaction on the PS spheres created via emulsifier-free emulsion polymerization. PC opal films were fabricated using self-assembled PS and SPS spheres. The opal films were characterized using various techniques, including Fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM), field emission scanning electron microscopy (FESEM), angle-resolved reflection spectroscopy (ARRS), zeta potential and dynamic light scattering, and the results were compared and analysed. The hydrophilicity of the opal films was investigated using the water contact angle measurement, and it was found to improved by sulfonation. The spectral response of the PC opal films was investigated by monitoring Bragg’s diffraction spectra from the films using UV–VIS spectrometer. As a demonstration of a specific application, the prepared PC opal films were used to measure the water content in ethanol. PS and SPS opal films exhibited a noticeable blue shift in their spectral response when the water content in ethanol was increased to 3.8% and 3.4%, respectively. The added hydrophilicity brought on by the attached sulfonic groups improved the SPS film’s sensitivity to the water in the ethanol. SPS spheres demonstrated an optical response over a significantly more extensive range of the water content in ethanol than PS, which has a limited response range of up to 50%. Sulfonating PS spheres enhances colloidal stability and minimizes the tendency for aggregation in solution. Sulfonation for more than 3 h is found to exhibit reduced mechanical strength. Though the sulfonation induces an increase in surface roughness, the quality of the ordered arrangement of the spheres remained the same in comparison with PS films. By taking advantage of SPS’s hydrophilicity, high reactivity, stability, and the possibility of attaching additional functional groups, the present study opens up new possibilities for sensing water content in ethanol.

Process monitoring of cobalt carbonate precipitation by reactions between cobalt sulfate and sodium carbonate solutions to control product morphology and purity

Recovering critical elements from EV batteries is challenging as the separation is a complex process which involves different processing parameters. Cobalt (Co) is one of the metals which ensures the life of EV batteries and here we have successfully precipitated cobalt carbonate (CoCO3) by semi-batch precipitation using cobalt sulfate and sodium carbonate as reactant solutions. The precipitation of cobalt carbonate was investigated by offline Raman spectroscopy, Powder X-ray diffraction analysis, inline Focused Beam Reflectance Measurement (FBRM), and pH measurements. In addition, the effects of various factors including pH, aging time, reactant addition time, mixing speed, and temperature on cobalt carbonate precipitation and the properties of the precipitated solids were investigated. In the process of precipitation, the carbonate ions in the initial electrolyte solution were converted to bicarbonate ions during the addition of acidic cobalt sulfate solution, which consequently decreased the pH in the suspension. When the pH was lower than 8, the carbon mainly existed as bicarbonate and the cobalt carbonate started to precipitate at a high efficiency. Cobalt initially precipitated as cobalt carbonate hydroxide (Co2CO3(OH)2) at a higher pH (9–11) and converted to cobalt carbonate at a lower pH (6.5–8). The crystallite size of cobalt carbonate calculated for the different reaction conditions shows that the growth response is high at longer reactant addition time and high temperature. The morphology of the final cobalt carbonate precipitate was small single spherical crystals and their aggregates. The purity of precipitates could be increased by reducing the aggregation tendency during the precipitation.

Superior dye degradation for wastewater treatment based on nanocomposites of cerium oxide, gadolinium oxide and graphene oxide

Despite the significant Progression in nanocomposites (NCs) tailoring for ecological purposes, optimizing NCs for water treatment is still a challenge. Moreover, organic coloring (dyes) agents like Congo red (CR) and methylene blue (MB) were included which have carcinogenic effects. In this regard, photo-catalytic activity utilizing NCs for organic pollutants (dyes) removal is a great concern due to its viability and low cost. In this regard, a combination of nanocomposites including cerium Oxide (CeO2), gadolinium oxide (Gd2O3), and graphene oxide (GO) could be suggested. X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR) were utilized for characterization in addition to EDX, and electron microscopes (TEM, and FESEM). TEM micrograph exhibits TNC as scattered lanthanides oxides (CeO2, and Gd2O3) grains upon GO sheets. It shows a clear decline in the average size to reach 25 nm for CeO2, and 40 nm for Gd2O3. Also, FESEM reports that GO reduces the lanthanide oxides aggregation tendency in TNC, besides forming shallow pores within its rough surface. Regarding the thermal study, It is clear that activation energy (E*) is the almost equal enthalpy of activation (ΔH). It could refer to the presence of the tested composition at a higher degree of temperature (thermally stable). Nano-composite powders exhibited improvement in photo-catalytic efficiency and inhibition of photo-corrosion as compared with pure lanthanide oxides. The MB degradation potential of CeO2/Gd2O3/GO drops from 94.4 % in the first usage to 82.1 % in the fifth.

Synthesis of copper-based nanoparticles confined in a pyridine N-containing COF and their catalytic applications

The main challenge of using non-noble metal copper nanoparticles (Cu NPs) as catalysts is to find or prepare suitable support platforms to anchor Cu NPs, thereby avoiding the aggregation tendency owing to their high surface energy. In this study, a novel pyridine N-containing covalent organic framework (COF) was designed and used as a template for the confined growth of Cu NPs. The prepared imine-connected TAPB-PCBA had abundant one-dimensional ordered channels, moderate specific surface area and good stability. The skeleton structure of TAPB-PCBA contained a large number of evenly distributed pyridine N, which can act as the nucleation site for Cu NPs. The well-defined pore structure confines the growth of Cu NPs and makes them controllable in size. The pores in TAPB-PCBA are completely independent and isolated from each other, minimizing the accumulation of Cu NPs. With the help of these factors, ultrafine Cu/Cu2O composite NPs (2.5 nm) with narrow size distribution anchored inside the cavity of the TAPB-PCBA were successfully prepared. The as-prepared Cu-containing COF, Cu@TAPB-PCBA, showed excellent catalytic capacity for dye degradation and nitrophenol reduction under mild conditions and low catalyst loads, respectively. In addition, Cu@TAPB-PCBA also has a good recyclability, multiple use without significant loss of catalytic activity. We expect this COF-supported growth-confined preparation of metal NPs to further facilitate the design and preparation of non-noble metal NPs@COF composites, replacing noble metals in certain catalytic applications.

Unveiling Medin Folding and Dimerization Dynamics and Conformations via Atomistic Discrete Molecular Dynamics Simulations.

Medin is a principal component of localized amyloid found in the vasculature of individuals over 50 years old. Its amyloid aggregation has been linked to endothelial dysfunction and vascular inflammation, contributing to the pathogenesis of various vascular diseases. Despite its significance, the structures of the medin monomer, oligomer, and fibril remain elusive, and the dynamic processes of medin aggregation are not fully understood. In this study, we comprehensively investigated the medin folding and dimerization dynamics and conformations using atomistic discrete molecular dynamics simulations. Our simulation results suggested that the folding initiation of the medin involved the formation of β-sheets around medin30-41 and medin42-50, with subsequent capping of other segments to their β-sheet edges. Medin monomers typically consisted of three or four β-strands, along with a dynamic N-terminal helix. Two isolated medin peptides readily aggregated into a β-sheet-rich dimer, displaying a strong aggregation propensity. Dimerization of medin not only enhanced the β-sheet conformations but also led to the formation of β-barrel oligomers. The aggregation tendencies of medin1-18 and medin19-29 were relatively weak. However, the segments of medin30-41 and medin42-50 played a crucial role as they primarily formed a β-sheet core and facilitated medin1-18 and medin19-29 to form intra- and interpeptide β-sheets. The findings highlight the critical role of the medin30-41 and medin42-50 regions in stabilizing the monomer structure and driving the medin amyloid aggregation. These regions could potentially serve as promising targets for designing antiamyloid inhibitors against amyloid aggregation of medin. Additionally, our study provides a full picture of the monomer conformations and dimerization dynamics for medin, which will help better understand the pathology of medin aggregation.

Exploring the Effects of Various Capping Agents on Zinc Sulfide Quantum Dot Characteristics and In-vitro Fate.

The choice of capping agents used during the synthesis process of quantum dots (QDs) can significantly influence their fate and fundamental properties. Hence, choosing an appropriate capping agent is a critical step in both synthesis and biomedical application of QDs. In this research, ZnS QDs were synthesized via chemical precipitation process and three commonly employed capping agents, namely mercaptoethanol (ME), mercaptoacetic acid (MAA), and cysteamine (CA), were used to stabilize the QDs. This study was aimed to examine how these capping agents impact the physicochemical and optical characteristics of ZnS QDs, as well as their interactions with biological systems. The findings revealed that the capping agents had considerable effects on the behavior and properties of ZnS QDs. MAA-QD exhibited superior crystal lattice, smaller size, and significant quantum yield (QY). In contrast, CA-QDs demonstrated the lowest QY and the highest tendency for aggregation. ME-QDs exhibited intermediate characteristics, along with an acceptable level of cytotoxicity, rapid uptake by cells, and efficient escape from lysosomes. Consequently, it is advisable to select capping agents in accordance with the specific objectives of the research.

Tumor‐pH‐value responsive non‐peripheral substituted phthalocyanines: Synthesis, investigation of photophysical and photochemical properties

Cancer is one of the diseases with the highest mortality rate worldwide. Although PDT has recently produced encouraging outcomes, there are still many areas that need to be improved. The first of these is the negative consequences faced by patients treated with the PDT method when exposed to sunlight. For this reason, a new PDT method has been developed in recent years, and it is aimed at using photosensitizer molecules that can be active in acidic conditions. Since the pH values of tumor tissues are more acidic than normal tissues, preparing molecules that act effectively in acidic conditions will allow for more effective results in treating cancer with PDT. In this context, within the scope of this study, 3‐(4‐propionylphenoxy)phthalonitrile (1) and its non‐peripheral tetra‐substituted phthalocyanine derivatives [(2), (3), and (4)] were prepared. With these phthalocyanine derivatives, the novel compounds (5), (6), and (7) were synthesized for the first time. The aggregation tendencies of newly synthesized phthalocyanines (5–7) were investigated in solvent media. The effects of pH changes upon UV–Vis and fluorescence spectra were performed. The electronic and emission spectra of synthesized phthalocyanine derivatives are highly sensitive to pH changes. Formation constant (LogK) values of mono‐ and di‐protonated phthalocyanine forms were calculated by the Henderson–Hasselback equation. The mono‐ and di‐protonated species' equilibrium constants (logK1 and logK2) were calculated as ~5.0. This value may be promising for pH‐sensitizing photosensitizers. Also, the photophysical and photochemical properties of synthesized metallophthalocyanine derivatives (2) and (5) were studied at different pH values. The singlet oxygen quantum yield of (2) and (5) was calculated to be 0.78 and 0.81 in DMSO, respectively. When pH = 6.4, that is, tumor‐pH‐values, this value for (5) has increased to 0.92. The newly synthesized phthalocyanines are suitable photosensitizers for PDT applications, especially with high singlet oxygen quantum yield at pH 6.4.

Pathways of hLL-3717-29 Aggregation Give Insight into the Mechanism of α-Amyloid Formation.

α-amyloids present a novel self-assembly principle that can be utilized to prepare functional biomaterials. Evidence of α-amyloid formation in the active core of the human LL-37 protein (comprising residues 17 to 29) was associated with this peptide's membranolytic property. Though mechanistic pathways of β-amyloid formation are known, such studies are scarce in α-amyloids. Modern computational techniques allow such mechanistic studies in molecular detail. Here, we propose aggregation pathways in hLL-3717-29 through molecular dynamics simulations. We first identified oligomers among peptides based on a distance criterion. The distribution of oligomers was then used to build Markov state models from which pathways were obtained using the framework of transition path theory. We checked the structural stability of the peptides during oligomerization, which is crucial from their functional point of view. We also investigated the key residues that participate in oligomer formation, the interactions between them, and the effect of residue mutations on the binding free energy of the peptides. Our findings suggest that larger oligomers are produced from the association of smaller and intermediate oligomers. The peptides retain their helical structure during aggregation with transient occurrences of 3-10 helix and turns. Hydrophobic interactions are vital in the aggregation of these peptides with Ile24 playing a crucial role. Mutation of this residue to alanine decreases the peptides' binding free energy, resulting in reduced aggregation tendency.

Proteolytically Stable ααγ-Hybrid Peptides Inhibit the Aggregation and Cytotoxicity of Aβ42.

The recent approval of antibody-based therapy for targeting the clearance of amyloid plaques fuels the research in designing small molecules and peptide inhibitors to target the aggregation of Aβ-peptides. Here, we report that the 15-residue ααγ-hybrid peptide not only inhibits the aggregation of soluble Aβ42 into fibrils but also disintegrates the aggregated Aβ42 fibrils into smaller assemblies. Further, the hybrid peptide completely rescues neuronal cells from the toxicity of Aβ42 at equimolar concentrations. The shorter 10- and 12-mer peptides showed weak aggregation inhibition activity, while the fully hydrophobic 15-mer ααγ-hybrid peptide analogue showed no aggregation inhibition activity. Further, the 15-mer ααγ-hybrid peptide showed resistance against trypsin digestion and also nontoxic to the neuronal cells. The CD revealed that the peptide upon interaction induces a helix-type conformation in the Aβ42. This is in sharp contrast to the β-sheet conformation of Aβ42 upon incubation. The two-dimensional-NMR (2D-NMR) analysis revealed a large perturbation in the chemical shifts of residues at the N-terminus. The presence of 15-mer peptide at an equimolar concentration of Aβ42 showed less tendency for aggregation and also exhibited nontoxicity to the neuronal cells. The results reported here may be useful in designing new therapeutics for Alzheimer's disease.

Potential use of garlic products in ruminant feeding: A review.

The addition of antibiotics as growth promoters to ruminant feed can result in bacterial resistance and antibiotic residues in ruminant products. Correspondingly, there is serious public concern regarding the presence of antibiotic residue in ruminant products and the consequent threat to human health. As a result, the addition of plants and their products to ruminant feeds, as an alternative to antibiotics, has received much attention recently. Garlic and its products are rich in organosulphur compounds, which have a variety of biological activities and have been widely used as natural additives in animal production. This review presents recent knowledge on the addition of garlic products (powder, skin, oil, leaf and extracts) to the diets of ruminants. In this paper, garlic products are evaluated with respect to their chemical composition, bioactive compounds, and their impacts on the rumen ecosystem, antioxidant status, immune response, parasitic infection, growth performance and product quality of ruminants. This review provides valuable guidance and a theoretical basis for the development of garlic products as green, highly efficient and safe additives, with the aims of promoting ruminant growth and health, reducing methane emissions and improving ruminant product quality. Garlic extracts have the potential to control parasite infections by decreasing the faecal egg count. Garlic powder, oil and allicin are able to reduce the methane emissions of ruminants. Organosulphur compounds such as allicin, which is present in garlic products, have the potential to inhibit membrane lipid synthesis of the archaeal community, thus influencing the population of methanogenic archaea and resulting in a reduction in methane emissions. Some garlic products are also able to increase the average daily gain (garlic skin, water extract, and leaf) and the feed conversion ratio (garlic skin and leaf) of ruminants. Garlic stalk silage fed to sheep has the potential to improve the nutritional value of mutton by increasing the concentrations of linoleic and linolenic acids and essential amino acids. Sheep fed a diet containing garlic powder or oil are able to produce milk with higher concentrations of the conjugated linoleic acids and n-3 fatty acids, which has health benefits for consumers, due to the widely recognized positive impact of n-3 polyunsaturated fatty acids and conjugated linoleic acids on human heart health, improving platelet aggregation, vasodilation and thrombotic tendency. Overall, garlic products have the potential to enhance growth performance and product quality and reduce parasite infections, as well as methane emissions of ruminants.

N doping porous carbon embedded in self-assembled three-dimensional reduced graphene oxide networks for electrochemical hydrogen storage

Electrochemical hydrogen storage can realize reversible hydrogen absorption and desorption at room temperature and pressure, which has attracted extensive attention recently. A nanosheet-like reduced graphene oxide (rGO)-porous carbon composite with N-doping defect is prepared via a facile annealing, followed by hydrothermal and freeze-drying process. After N-doping, the porous carbon materials exhibit rich pore structure, and high pyridine nitrogen and pyrrolic nitrogen content. Adding them into the graphene self-assembly process, the aggregation tendency of graphene sheets can be reduced, the composite shows a free-standing 3D porous structure. Benefit from the synthetic effect between the rGO conductive network, the hierarchical porous structure, and the doping of N atoms, the rGO-N800 delivers a high hydrogen storage capacity of 266.3 mAh g−1 at 200 mA g−1 after 100 cycles. Moreover, the reversible capacities of the composite can reach 288.4, and 267.1 mAh g−1 at 1000 mA g−1 and 2000 mA g−1, respectively. The outstanding electrochemical performance of the composite demonstrates a promising direction for design carbon-based hydrogen storage materials.

Carotenoids and Dermoaesthetic Benefits: Public Health Implications

Food technology, health, nutrition, dermatology, and aesthetics have focused on colorless carotenoids. Carotenoids are readily bioavailable and have demonstrated various health-promoting actions. This article reviews the recent literature concerning carotenoids with the aim to systematize the scattered knowledge on carotenoids and aesthetics. The applications of carotenoids in health-promoting and nutrient products and their potential health effects are discussed. The carotenoids, particularly phytoene and phytofluene, have the unique ability to absorb ultraviolet radiation. Their distinct structures and properties, oxidation sensitivity, stiffness, aggregation tendency, and even fluorescence in the case of phytofluene, contribute to their potential benefits. A diet rich in carotenoid-containing products can positively impact skin health, overall well-being, and the prevention of various diseases. Future studies should focus on generating more data about phytoene and phytofluene levels in the skin to accurately assess skin carotenoid status. This expanding area of research holds promise for the development of novel applications in the fields of health and cosmetics.

Introducing MR‐TADF Emitters into Light‐Emitting Electrochemical Cells for Narrowband and Efficient Emission

AbstractOrganic semiconductors that emit by the process of multi‐resonance thermally activated delayed fluorescence (MR‐TADF) can deliver narrowband and efficient electroluminescence while being processable from solvents and metal‐free. This renders them attractive for use as the emitter in sustainable light‐emitting electrochemical cells (LECs), but so far reports of narrowband and efficient MR‐TADF emission from LEC devices are absent. Here, this issue is addressed through careful and systematic material selection and device development. Specifically, the authors show that the detrimental aggregation tendency of an archetypal rigid and planar carbazole‐based MR‐TADF emitter can be inhibited by its dispersion into a compatible carbazole‐based blend host and an ionic‐liquid electrolyte, and it is further demonstrated that the tuning of this active material results in a desired balanced p‐ and n‐type electrochemical doping, a high solid‐state photoluminescence quantum yield of 91%, and singlet and triplet trapping on the MR‐TADF guest emitter. The introduction of this designed metal‐free active MR‐TADF material into a LEC, employing air‐stabile electrodes, results in bright blue electroluminescence of 500 cd m−2, which is delivered at a high external quantum efficiency of 3.8% and shows a narrow emission profile with a full‐width‐at‐half‐maximum of 31 nm.

Communal interaction of glycation and gut microbes in diabetes mellitus, Alzheimer's disease, and Parkinson's disease pathogenesis.

Diabetes and its complications, Alzheimer's disease (AD), and Parkinson's disease (PD) are increasing gradually, reflecting a global threat vis-à-vis expressing the essentiality of a substantial paradigm shift in research and remedial actions. Protein glycation is influenced by several factors, like time, temperature, pH, metal ions, and the half-life of the protein. Surprisingly, most proteins associated with metabolic and neurodegenerative disorders are generally long-lived and hence susceptible to glycation. Remarkably, proteins linked with diabetes, AD, and PD share this characteristic. This modulates protein's structure, aggregation tendency, and toxicity, highlighting renovated attention. Gut microbes and microbial metabolites marked their importance in human health and diseases. Though many scientific shreds of evidence are proposed for possible change and dysbiosis in gut flora in these diseases, very little is known about the mechanisms. Screening and unfolding their functionality in metabolic and neurodegenerative disorders is essential in hunting the gut treasure. Therefore, it is imperative to evaluate the role of glycation as a common link in diabetes and neurodegenerative diseases, which helps to clarify if modulation of nonenzymatic glycation may act as a beneficial therapeutic strategy and gut microbes/metabolites may answer some of the crucial questions. This review briefly emphasizes the common functional attributes of glycation and gut microbes, the possible linkages, and discusses current treatment options and therapeutic challenges.

Molecular dynamics simulation of Pt@Au nanoalloy in various solvents: Investigation of solvation, aggregation, and possible coalescence

In this study, a pair of core-shell Pt@Au nanoalloy particles with 309 atoms was simulated in various solvents, including water, benzene, ethanol, water + benzene, and 1-butyl-1,1,1-trimethylammonium methanesulfonate [N1114][C1SO3] ionic liquid (IL) at 300 K and 1 atm. We investigated the aggregation and possible coalescence of Au–Pt nanoalloys based on various thermodynamic, dynamic, and structural simulation results. The findings from our study demonstrated that the tendency for aggregation of nanoalloys is greater in water and benzene + water systems than in other solvents. This tendency is weaker in the solvents such as IL, ethanol, and benzene (weakest in benzene). Our results also showed that there is a very small change in the structure of the nanoalloys in the different solvents even after 100 ns of simulation time. Furthermore, coalescence does not occur between the two (Pt@Au)309 nanoalloys. Our results also indicated that the nanoalloys have lower solvation energy in water than in the other solvents. It is also found that IL has a higher solvation energy compared to other solvents. The dynamic results indicated that the (Pt@Au)309 nanoalloys have higher self-diffusion coefficients in benzene and lower diffusion values in IL. Furthermore, we examined the effects of nanocluster shape and core by simulating truncated octahedral (Au)374 and pure icosahedral (Au)309 nanoclusters in water. The results showed that despite the (Pt@Au)309 nanoalloy, the two pure icosahedral (Au)309 nanoclusters approached each other, and coalescence occurred.

Inside Back Cover: The effect of tailing lipidation on the bioactivity of antimicrobial peptides and their aggregation tendency

Inside Back Cover: The effect of tailing lipidation on the bioactivity of antimicrobial peptides and their aggregation tendency

FUN Azores: a FUNctional trait database for the meio-, macro-, and megafauna from the Azores Marine Park (Mid-Atlantic Ridge)

Trait-based approaches that complement taxonomy-based studies have increased in popularity among the scientific community over the last decades. The collection of biological and ecological characteristics of species (i.e., traits) provides insight into species and ecosystem vulnerability to environmental and anthropogenic changes, as well as ecosystem functioning. Here, we present the FUN Azores trait database, describe our approach, evaluate its scope, compare it to other marine trait databases, and explore the spatial distribution of its traits with “functional maps.” While most of the available trait databases to date contain essential information to understand the functional diversity of a taxonomic or functional group, our ecosystem-based approach provides a comprehensive assessment of diverse fauna (i.e., meio-, macro-, and megafauna) from benthic and pelagic environments in the Azores Marine Park; including ridges, seamounts, hydrothermal vents, and the overlying water column. We used a collaborative approach involving 30 researchers with different expertise to develop the FUN Azores database, which contains compiled data on 14 traits representing morphological, behavioral, and life history characteristics for 1,210 species across 10 phyla. The “functional maps” show a distinct distribution of the two most common size classes, suggesting different communities with different functionalities. The following traits had the best scoring coverage (i.e., >95% of the species scored): maximum body size, body form, skeleton material, feeding structure, motility, environmental position, substratum affinity, distribution, and depth range; while traits related to species behavior (e.g., sociability or aggregation tendencies) and life history (e.g., developmental mechanism) had lower scoring coverage, highlighting the need for further research to fill these knowledge gaps. We found a larger number of species in the benthic compared to the pelagic environment and differing species composition between areas within the Azores Marine Park resulting from varying biodiversity, ecosystem types, sampling effort, and methodologies used. The FUN Azores database will foster and facilitate trait-based approaches in the area, develop a framework for expansion of cross-ecosystem and cross-taxa trait databases elsewhere, and improve our ecological understanding of the Azores Marine Park and its conservation requirements.