This study explored the mechanism of l-lysine intervention in wheat gluten protein (WG) gel formation under a microwave (MW) field. The results showed that the MW treatment had higher ζ-potential values at the same heating rate. After adding l-lysine, the solution conductivity and dielectric loss were significantly increased. Moreover, the WG gel strength enhanced 4.40% under the MW treatment. The Fourier spectra showed that the α-helix content was decreased 13.78% with the addition of lysine. The ultraviolet absorption spectra and fluorescence spectra indicated that MW irradiation impacted the interactions between WG molecules more effectively than the water bath heating, promoting the denaturation and unfolding of the protein structure. In addition, scanning electron microscopy analysis showed that the incorporation of lysine promoted an ordered network structure formation of the protein, which enhanced the gel properties. This indicated that the zwitterion of l-lysine played a regulatory role in the aggregation of proteins in the MW field.

The coexistence of amyloid-β (Aβ) and human islet amyloid polypeptide (hIAPP) in the brain and pancreas is associated with an increased risk of Alzheimer\'s disease (AD) and type 2 diabetes (T2D) due to their coaggregation and cross-seeding. Despite this, the molecular mechanisms underlying their interaction remain elusive. Here, we systematically investigated the cross-talk between Aβ and hIAPP using atomistic discrete molecular dynamics (DMD) simulations. Our results revealed that the amyloidogenic core regions of both Aβ (Aβ10-21 and Aβ30-41) and hIAPP (hIAPP8-20 and hIAPP22-29), driving their self-aggregation, also exhibited a strong tendency for cross-interaction. This propensity led to the formation of β-sheet-rich heterocomplexes, including potentially toxic β-barrel oligomers. The formation of Aβ and hIAPP heteroaggregates did not impede the recruitment of additional peptides to grow into larger aggregates. Our cross-seeding simulations demonstrated that both Aβ and hIAPP fibrils could mutually act as seeds, assisting each other\'s monomers in converting into β-sheets at the exposed fibril elongation ends. The amyloidogenic core regions of Aβ and hIAPP, in both oligomeric and fibrillar states, exhibited the ability to recruit isolated peptides, thereby extending the β-sheet edges, with limited sensitivity to the amino acid sequence. These findings suggest that targeting these regions by capping them with amyloid-resistant peptide drugs may hold potential as a therapeutic approach for addressing AD, T2D, and their copathologies.

Surface chemistry of carriers plays a key role in enzyme loading capacity, structure rigidity, and thus catalyze activity of immobilized enzymes. In this work, the two model enzymes of horseradish peroxidase (HRP) and glucose oxidase (GOx) are co-immobilized on the lysozyme functionalized magnetic core-shell nanocomposites (LYZ@MCSNCs) to enhance their stability and activity. Briefly, the HRP and GOx aggregates are firstly formed under the crosslinker of trimesic acid, in which the loading amount and the rigidity of the enzyme can be further increased. Additionally, LYZ easily forms a robust anti-biofouling nanofilm on the surface of SiO2@Fe3O4 magnetic nanoparticles with abundant functional groups, which facilitate chemical crosslinking of HRP and GOx aggregates with minimized inactivation. The immobilized enzyme of HRP-GOx@LYZ@MCSNCs exhibited excellent recovery activity (95.6 %) higher than that of the free enzyme (HRP&GOx). Specifically, 85 % of relative activity was retained after seven cycles, while 73.5 % of initial activity was also remained after storage for 33 days at 4 °C. The thermal stability and pH adaptability of HRP-GOx@LYZ@MCSNCs were better than those of free enzyme of HRP&GOx. This study provides a mild and ecofriendly strategy for multienzyme co-immobilization based on LYZ functionalized magnetic nanoparticles using HRP and GOx as model enzymes.

GATM-related Fanconi renotubular syndrome 1 (FRTS1) is a form of renal Fanconi syndrome (RFS), which is a disorder of solute and water reabsorption caused by defects in the function of the entire proximal tubule. Recent findings reveal the molecular basis of FRTS1: Intramitochondrial fiber aggregation triggered by mutant GATM provides a starting point for proximal tubule damage and drives disease progression. As a rare and newly recognized inherited kidney disease, the complex manifestations of FRTS1 are easily underdiagnosed or misdiagnosed. We discuss the complex phenotype of a 26-year-old woman with onset in infancy and a long history of hypophosphatemic rickets. We also identified a novel heterozygous missense variant in the GATM gene in this patient. The novel variant and phenotype we report expand the disease spectrum of FRTS1. We recommend screening for GATM in children with RFS, especially in patients with resistant rickets who have previously had negative genetic testing. In addition, we found pathological deposition of mutant GATM proteins within mitochondria in the patient\'s urinary sediment cells by a combination of electron microscopy and immunofluorescence. This unique urine cytology experiment has the potential to be a valuable tool for identifying patients with RRTS1.

To counteract the increasing severity of water pollution and purify water sources, wastewater treatment materials are essential. In particular, it is necessary to improve the bonding strength between the adsorption material and the substrate in a long-term humid environment, and resist the invasion of microorganisms to prolong the service life. In this study, an amyloid-like aggregation method of lysozyme catalyzed by microbial transglutaminase (mTGase). Lysozyme self-assembles into an amyloid-like phase-transited lysozyme (PTL) in the presence of a reducing agent. Simultaneously, mTGase catalyzes acyl transfer reactions within lysozyme molecules or between lysozyme and keratin molecules, and driving PTL assembly on the wool fiber (TG-PTL@wool). This process enhances the grafting amount and fastness of PTL on the wool. Moreover, the tensile strength of wool fabric increased to 523 N. TG-PTL@wool achieves a 97.32 % removal rate of heavy metals, maintaining a removal rate of over 95 % after 5 cycles. TG-PTL@wool has excellent antibacterial property (99 %), and it remains above 90 % after 50 times of circulating washing. This study proved that mTGase can enhance the amyloid aggregation of lysozyme and enhance the bonding strength between PTL coating and substrate. Moreover, TG-PTL@wool provides a sustainable, efficient and cleaner solution for removing heavy metals from water.

The texture of soybean protein-based products is primarily influenced by the aggregation and gel morphology of the protein, which is modulated by manufacturing factors. Interactions involved in protein morphology changes include disulfide bonds, hydrophobic interactions, electrostatic interactions, and hydrogen bonds. Notably, an interaction perspective probably provides a new way to explaining the aggregation and gel morphology, which could help overcome the hurdle of developing a textured product. Based on the interaction perspective, this review provides detailed information and evidence on aggregation, conformational stability, and gel network morphology of soybean protein and its components induced by pH, NaCl, and temperature. pH-induced electrostatic interactions and hydrogen bonds, NaCl-induced electrostatic interactions, and temperature-induced hydrophobic interactions and disulfide linkages are the main motivations responsible for changes in soybean aggregation and gel morphology. By reducing the proportion of strong-interactions, such as disulfide linkages and hydrophobic interactions, and increasing the proportion of weak-interactions, such as electrostatic interactions and hydrogen bonds, the protein total surface area expands, indicating increased conformational stretching and decreased cohesion. This possibly results in reduced hardness and increased toughness of textured proteins. The opposite effect can be observed when the proportion of strong interactions is increased and that of weak interactions is decreased.

The accumulation of amyloid-β (Aβ) peptides is a major hallmark of Alzheimer\'s disease (AD) and plays a crucial role in its pathogenesis. Particularly, the structured oligomeric species rich in β-sheet formations were implicated in neuronal organelle damage. Addressing this formidable challenge requires identifying candidates capable of inhibiting peptide aggregation or disaggregating preformed oligomers for effective antiaggregation-based AD therapy. Here, we present a dual-functional nanoinhibitor meticulously designed to target the aggregation driving force and amyloid fibril spatial structure. Leveraging the exceptional structural stability and facile tailoring capability of endohedral metallofullerene Gd@C82, we introduce desired hydrogen-binding sites and charged groups, which are abundant on its surface for specific designs. Impressively, these designs endow the resultant functionalized-Gd@C82 nanoparticles (f-Gd@C82 NPs) with high capability of redirecting peptide self-assembly toward disordered, off-pathway species, obstructing the early growth of protofibrils, and disaggregating the preformed well-ordered protofibrils or even mature Aβ fibrils. This results in considerable alleviation of Aβ peptide-induced neuronal cytotoxicity, rescuing neuronal death and synaptic loss in primary neuron models. Notably, these modifications significantly improved the dispersibility of f-Gd@C82 NPs, thus substantially enhancing its bioavailability. Moreover, f-Gd@C82 NPs demonstrate excellent cytocompatibility with various cell lines and possess the ability to penetrate the blood-brain barrier in mice. Large-scale molecular dynamics simulations illuminate the inhibition and disaggregation mechanisms. Our design successfully overcomes the limitations of other nanocandidates, which often overly rely on hydrophobic interactions or photothermal conversion properties, and offers a viable direction for developing anti-AD agents through the inhibition and even reversal of Aβ aggregation.

The common belief that heat treatment enhances the gastric digestion of proteins is largely based on findings from animal proteins and may not apply to all proteins, particularly plant proteins. Here, we compared the digestion characteristics of soybean protein isolates (SPI) in an in vitro semi-dynamic digestion model and found distinct effects of heat treatment on the digestion properties of plant proteins. The results revealed that heat-treated SPIs formed clots during the early stages of digestion, although the clots gradually became smaller and looser as digestion progressed, the systems remained turbid at the end of gastric digestion, indicating the lag in their emptying. Furthermore, heat treatment altered the rheological properties of SPI, resulting in increased viscosity and slower gastric emptying. These effects became more pronounced with increasing heat treatment temperatures. The fluorescence spectrum analysis indicated that heat treatment altered its conformation. This led to protein unfolding and exposure of hydrophobic groups, facilitating the formation of larger aggregates during digestion. Additionally, heat treatment exposed more cleavage sites for gastric proteases, increasing the extent of hydrolysis. Elevated levels of free amino acids and a smaller molecular weight distribution further corroborated these findings. These findings contribute to a deeper understanding of the gastric digestion characteristics of plant proteins and the relationship between protein aggregation structure and the digestion process.

The deposition of α-synuclein (α-Syn) in Lewy bodies serves as a prominent pathological hallmark of Parkinson\'s disease (PD). Recent research has revealed that α-Syn can undergo liquid-liquid phase separation (LLPS) during its fibrillization. Over time, the maturation of the resulting condensates leads to a liquid-to-solid phase transition (LSPT) ultimately resulting in the amyloid deposition in cells which is linked to the pathogenesis and development of PD. Herein, we summarize the understanding of α-Syn aggregation which can be described by nucleation and elongation steps to obtain insights into the correlation of protein aggregation, structural polymorphism, and PD progression. Additionally, we discuss the LLPS phenomena of α-Syn and heterotypic cross-amyloid interactions with a focus on aberrant LSPT in the aggregation process. Exploring the underlying mechanisms and interplay between α-Syn aberrant aggregation, pathological phase transitions, and PD pathogenesis will shed light on potential therapeutic interventions.

As a consequence of somatosensory nervous system injury or disease, neuropathic pain is commonly associated with chemotherapies, known as chemotherapy-induced peripheral neuropathy (CIPN). However, the mechanisms underlying CIPN-induced proteome aggregation in neuronal cells remain elusive due to limited detection tools. Herein, we present series sensors for fluorescence imaging (AggStain) and proteomics analysis (AggLink) to visualize and capture aggregated proteome in CIPN neuronal cell model. The environment-sensitive AggStain imaging sensor selectively binds and detects protein aggregation with 12.3 fold fluorescence enhancement. Further, the covalent AggLink proteomic sensor captures cellular aggregated proteins and profiles their composition via LC-MS/MS analysis. This integrative sensor platform reveals the presence of proteome aggregation in CIPN cell model and highlights its potential for broader applications in assessing proteome stability under various cellular stress conditions.