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A proposal for the direct pure shear characterisation of steel-fibre-reinforced concrete specimens with two grooved shear planes is presented. In the first stage of work, crimped steel fibres (CSF) were used at volume fractions (Vf) of 0, 0.5, 1.0 and 1.5%, the concrete compressive strength was 35 MPa and the maximum coarse aggregate size (Dmax) was 9.5 mm. With these specifications, eight block specimens were subjected to the direct shear tests. A significant gain in shear strength was observed with an increase in fibre dosage – an increase of 90% when Vf = 1.5%. Based on this, three analytical expressions to compute the shear stress were formulated. The models were assessed by testing 15 blocks of smaller size and additional variables – hooked-end steel fibres (HSF), concrete compressive strength of 25 MPa and coarse aggregates with Dmax = 9.5, 19.0 and 25.0 mm. Better performance was obtained with the CSF rather than the HSF, with a strength gain of around 100% for Vf = 1.5% with the maximum coarse aggregate particle size of 25 mm and variability between the proposed analytical models of 2–7%. [ABSTRACT FROM AUTHOR]

Metaphysicians of composite objects commonly distinguish two types of composite objects: wholes and sums. The former can survive some changes of parts, while the latter cannot. This paper investigates how the distinction between wholes and sums can be respected, while denying that a sum is an individual composite object. In particular, the view presented here identifies wholes with the fusions of (extensional) mereology – hence going against a common tendency to identify sums with mereological fusions – and identifies sums with the pluralities of plural logic. It is argued that this view better captures the ideas behind the whole/sum-distinction while also avoiding various challenges the other accounts face. [ABSTRACT FROM AUTHOR]

The present opinion is the follow‐up of the conclusions and recommendations of the Scientific Opinion on the re‐evaluation of silicon dioxide (E 551) as a food additive relevant to the safety assessment for all age groups. In addition, the risk assessment of silicon dioxide (E 551) for its use in food for infants below 16 weeks of age is performed. Based on the newly available information on the characterisation of the SAS used as E 551 and following the principles of the 2021 EFSA Guidance on Particle‐TR, the conventional safety assessment has been complemented with nano‐specific considerations. Given the uncertainties resulting from the limitations of the database and in the absence of genotoxicity concern, the Panel considered that it is not appropriate to derive an acceptable daily intake (ADI) but applied the margin of exposure (MOE) approach for the risk assessment. The Panel concluded that the MOE should be at least 36 for not raising a safety concern. The calculated MOEs considering the dietary exposure estimates for all population groups using the refined non‐brand loyal scenario, estimated at the time of the 2018 re‐evaluation, were all above 36. The Panel concluded that E 551 does not raise a safety concern in all population groups at the reported uses and use levels. The use of E 551 in food for infants below 16 weeks of age in FC 13.1.1 and FC 13.1.5.1 does not raise a safety concern at the current exposure levels. The Panel also concluded that the technical data provided support an amendment of the specifications for E 551 laid down in Commission Regulation (EU) No 231/2012. The paucity of toxicological studies with proper dispersion protocol (with the exception of the genotoxicity studies) creates uncertainty in the present assessment of the potential toxicological effects related to the exposure to E 551 nanosize aggregates. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus (S. aureus) is the leading cause of surgical site infections (SSIs) and is capable of biofilm growth on implanted foreign devices. The use of surgical irrigation solutions has become a common strategy to combat bacterial contamination events that occur during surgery. Despite their antimicrobial activity, SSI rates remain consistent, suggesting that low-level contamination persists. In these cases, circulating neutrophils must traffic from the blood to contamination sites to aid in bacterial clearance. The influence of irrigation solutions on neutrophils' ability to engage with bacteria has not been explored. The effects of three commonly used irrigation solutions: Xperience (sodium lauryl sulfate), Irrisept (chlorhexidine gluconate), and Betadine® (povidone-iodine) on nascent S. aureus biofilms alone and in the presence of human neutrophils were assessed at manufactured and diluted concentrations. All three solutions, at a 10% dilution, inhibited bacterial growth as demonstrated by culture assays and confocal video microscopy of bacterial aggregate formation. The effects of 10% dilutions of each of these solutions on neutrophil membrane integrity (by flow cytometry and propidium iodide staining) and motility (by confocal video microscopy of neutrophil track length) were investigated with differing outcomes for each irrigation solution. At this concentration only Irrisept preserved neutrophil membrane integrity and motility. Together, this study examines an overlooked aspect of surgical irrigation solutions by investigating their impact on innate immunity and highlights the feasibility of formulations wherein solution effectiveness is complemented by neutrophil function to reduce risks of infection. [ABSTRACT FROM AUTHOR]

The effect of resveratrol (RESV) on α-lactalbumin (α-LA) thermal stability was evaluated using differential scanning calorimetry (DSC), circular dichroism (CD) and dynamic light scattering (DLS) measurements. Complementary information offered by molecular docking served to identify the binding site of the ligand on the native structure of protein and the type of interacting forces. DSC thermograms revealed a double-endotherm pattern with partial overlapping of the two components. The most relevant effect of RESV is manifested in the narrowing of the protein thermal fingerprint: the first process (peak temperature T1) is shifted to higher temperatures while the second one (peak temperature T2) to lower values. The CD data indicated partial conformational changes in the protein non-α-helix domain at T1, resulting in a β-sheet richer intermediate (BSRI) with an unaffected, native-like α-helix backbone. The RESV influence on this process may be defined as slightly demoting, at least within DSC conditions (linear heating rate of 1 K min−1). On further heating, unfolding of the α-helix domain takes place at T2, with RESV acting as a promoter of the process. Long time incubation at 333 K produced the same type of BSRI: no significant effect of RESV on the secondary structure content was detected by CD spectroscopy. Nevertheless, the size distribution of the protein population obtained from DLS measurements revealed the free (non-bound) RESV action manifested in the developing of larger size aggregates. [ABSTRACT FROM AUTHOR]

Organic fertilizers are essential for enhancing soil organic carbon (SOC) levels and promoting sustainable agriculture. The mechanisms of carbon sequestration in upland red soils using various organic materials are not well understood. Here, the impact of various organic fertilization strategies on SOC fractions, functional groups, iron oxides, and soil aggregates was investigated to clarify the protective mechanisms underlying SOC preservation. Six fertilization regimes were examined: no fertilization (CK), mineral fertilizer (CF), 60% mineral fertilizer (RF), RF + straw (RFS), RF + pig manure (RFP), and RF + vermicompost (RFV). The results demonstrated that SOC contents significantly increased by 62.5% in RFP and 63.1% in RFV compared to the CF treatment, with particulate organic carbon (POC) being the primary contributor. Scanning electron microscopy and X‐ray photoelectron spectroscopy demonstrated that RFP and RFV treatments induced the formation of denser flock‐like aggregates and increased aromatic C content, respectively. Fourier transform infrared spectroscopy analysis indicated that RFV treatment exhibited the highest abundance of functional groups among all treatments. SOC and POC were highly positively correlated with soil chemical properties, soil aggregates, poorly crystalline iron oxides, and aromatic rings. Structural equation models indicated that pig manure and vermicompost directly promoted POC accumulation, while straw provided physical protection for POC by enhancing aggregate formation. Furthermore, pig manure indirectly facilitated the development of POC and mineral‐associated organic carbon via soil biochemical properties and iron oxides, respectively. Overall, the application of organic fertilizers enhanced the physical protection, mineral immobilization, and recalcitrance (alkyl C, aromatic C) of organic carbon, facilitating C sequestration and stability. This study highlights the importance of organic management in upland red soils for increasing SOC storage and maintaining global C balance. [ABSTRACT FROM AUTHOR]

Lipases are hydrolytic enzymes which have significant potential for commercial applications, particularly in the breakdown of oil contaminants. Serratia marcescens EGHK-19 isolate exhibited considerable lipase activity. This study investigates the optimization, purification, and characterization of lipase from the Serratia marcescens EGHK-19 isolate. The optimized culture conditions revealed that maximal lipase activity was achieved after 24 hours at 30°C and pH 7, with continuous shaking at 150 rpm. Utilizing a 2% inoculum percentage with 1% diesel and 0.3% tryptone in the presence of Fe2+, Ca2+, Mg2+ salts, and Tween 80 resulted in the highest activity at 17.278 U/ml/min. The purification process involved acetone precipitation and DEAE-Sephadex column chromatography, revealing a molecular weight of approximately 60 kDa on SDS-PAGE. This method exhibited a 0.985-fold purification, and the final yield was limited to 2.097% due to lipase aggregates. Characterization of the purified lipase indicated optimal activity (8.765 U/mL/min) at 40°C a nd p H 7. T he K m a nd V max values w ere c alculated a s 6 .89 m M a nd 6 5.79 µmol/min, respectively. The presence of SDS, Tween 80, and Triton X-100 surfactants resulted in the inhibition of lipase activity. Despite these insuggestss, the biochemical characteristics of the purified lipase suggest its potential as an excellent candidate for various industrial applications. [ABSTRACT FROM AUTHOR]

The effects of aggregate type and size on the fresh characteristics and strength gains of ambient-cured self-consolidating geopolymer concrete (SCGC) were investigated in the present study. SCGC was made from three different types of aggregates: crushed gravel, crushed marble, and a combination of both. In addition, several aggregate sizes (9 mm, 12 mm, and 16 mm) were also examined. The first group included 100% ground granulated blast furnace slag (GGBS), whereas the second group included 50% GGBS and 50% fly ash (FA). Slump flow, L-Box, and V-funnel tests were used to conduct fresh state tests, whereas compressive strength improvements were investigated at ages of 7 days, 14 days, 28 days, and 90 days. The results indicated that, regardless of aggregate type, aggregate size had a significant effect on fresh state characteristics. The optimal size of aggregate was 12 mm and crushed gravel showed optimum performance when compared to other types of aggregate and mixing. However, aggregate had a considerably lower effect on fresh characteristics than basic materials, and using fly ash significantly improved fresh properties. The improvement was about 5/, 10, and 60% respectively for both type/size of aggregate and the use of fly ash. Moreover, the base materials and aggregate types sufficiently affected the compressive strength of SCGC at different ages. The improvement was determined to be 8, 15, and 50% respectively for both the type/size of aggregate and the use of 100% GGBS. It was revealed that the compressive strength of SCGC in an ambient environment had a superior improvement at the age of 90 days in comparison to the age of 7, 14, and 28 days. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) secreted by human brain cells have great potential as cell‐free therapies in various diseases, including stroke. However, because of the significant amount of EVs needed in preclinical and clinical trials, EV application is still challenging. Vertical‐Wheel Bioreactors (VWBRs) have designed features that allow for scaling up the generation of human forebrain spheroid EVs under low shear stress. In this study, EV secretion by human forebrain spheroids derived from induced pluripotent stem cells as 3D aggregates and on Synthemax II microcarriers in VWBRs were investigated with static aggregate culture as a control. The spheroids were characterized by metabolite and transcriptome analysis. The isolated EVs were characterized by nanoparticle tracking analysis, electron microscopy, and Western blot. The EV cargo was analyzed using proteomics and miRNA sequencing. The in vitro functional assays of an oxygen and glucose‐deprived stroke model were conducted. Proof of concept in vivo study was performed, too. Human forebrain spheroid differentiated on microcarriers showed a higher growth rate than 3D aggregates. Microcarrier culture had lower glucose consumption per million cells and lower glycolysis gene expression but higher EV biogenesis genes. EVs from the three culture conditions showed no differences in size, but the yields from high to low were microcarrier cultures, dynamic aggregates, and static aggregates. The cargo is enriched with proteins (proteomics) and miRNAs (miRNA‐seq), promoting axon guidance, reducing apoptosis, scavenging reactive oxygen species, and regulating immune responses. Human forebrain spheroid EVs demonstrated the ability to improve recovery in an in vitro stroke model and in vivo. Human forebrain spheroid differentiation in VWBR significantly increased the EV yields (up to 240–750 fold) and EV biogenesis compared to static differentiation due to the dynamic microenvironment and metabolism change. The biomanufactured EVs from VWBRs have exosomal characteristics and more therapeutic cargo and are functional in in vitro assays, which paves the way for future in vivo stroke studies. [ABSTRACT FROM AUTHOR]

The elongation of Caenorhabditis elegans embryos allows examination of mechanical interactions between adjacent tissues. Muscle contractions during late elongation induce the remodeling of epidermal circumferential actin filaments through mechanotransduction. Force inputs from the muscles deform circumferential epidermal actin filament, which causes them to be severed, eventually reformed, and shortened. This squeezing force drives embryonic elongation. We investigated the possible role of the nonmuscle myosins NMY-1 and NMY-2 in this process using nmy-1 and nmy-2 thermosensitive alleles. Our findings show these myosins act redundantly in late elongation, since double nmy-2(ts); nmy-1(ts) mutants immediately stop elongation when raised to 25°C. Their inactivation does not reduce muscle activity, as measured from epidermis deformation, suggesting that they are directly involved in the multistep process of epidermal remodeling. Furthermore, NMY-1 and NMY-2 inactivation is reversible when embryos are kept at the nonpermissive temperature for a few hours. However, after longer exposure to 25°C double mutant embryos fail to resume elongation, presumably because NMY-1 was seen to form protein aggregates. We propose that the two C. elegans nonmuscle myosin II act during actin remodeling either to bring severed ends or hold them. [ABSTRACT FROM AUTHOR]

Deep eutectic solvents (DESs) have emerged as viable alternatives to toxic organic solvents. The most intriguing aspect of these solvents is perhaps the widely varying physicochemical properties emerging from the changes in the constituents that form DESs along with their composition. Based on the constituents, a DES can be hydrophilic/polar or hydrophobic/non-polar, rendering a vastly varying spectrum of polarity a possibility. DESs formed by mixing urea (U) with hydrated lanthanide salts, lanthanum nitrate hexahydrate (La : U), cerium nitrate hexahydrate (Ce : U), and gadolinium nitrate hexahydrate (Gd : U), respectively, exhibit very high polarity as manifested via the probe-reported empirical parameters of dipolarity/polarizability (π*). The highest π* of 1.70 exhibited by the DES (Gd : U) in a 1 : 2 molar ratio is unprecedented. The π* ranges from 1.50 to 1.70 for these DESs, which is almost the highest reported for any solvent system. The π* decreases with an increasing amount of urea in the DES; however, the anomalous trends in H-bond donating acidity (α) and H-bond accepting basicity (β) appear to be due to the hydrated water of the lanthanide salt. The emission band maxima of the fluorescence probe of the "effective" dielectric constant (εeff) of the solubilizing media, pyrene-1-carboxaldehyde (PyCHO), in salt-rich DESs reflect higher cybotactic region dipolarity than that offered by water. Probe Nile red aggregates readily in these DESs to form non-fluorescent H-aggregates, which is a characteristic of highly polar solvents. The behavior of probe pyranine also corroborates these outcomes as the (lanthanide salt : urea) DES system supports the formation of the deprotonated form of the probe in the excited state. The (lanthanide salt : urea) DES system offers solubilizing media of exceptionally high polarity, which is bound to expand their application potential. [ABSTRACT FROM AUTHOR]

Studies across multiple soils find increasing pH decreases water repellency. In this study, water repellency and a range of other soil physical properties of bulk soils, aggregates and intact specimens were measured on a long-term pH field experiment on a single sandy loam soil under a ley-arable crop rotation, with soil pH adjustments occurring annually by adding FeSO4 or CaCO3, to lower or raise the pH, respectively. Crop impacts were investigated by comparing 3rd year grass-white clover to spring oats, at the beginning (May) and end (September) of the growing season to allow soil structure comparisons. As in previous research, increased CO2 microbial respiration (p<0.05) was found with increasing pH along the gradient, but in this study, we found only the aggregate and soil bulk density affected by soil pH. Soil-water contact angles differed between crops (p<0.05), as well as the repellency index of soil aggregates, however, there was no soil pH effect. Overall, differences in data were found to be a result of the various crops in the rotation rather than by soil pH, indicating only minor impacts on soil physical characteristics after > 55 years of chemical additions to amend soil pH. [ABSTRACT FROM AUTHOR]

The corrosion of metal not only produces serious economic losses and environmental pollution but also threatens equipment safety. Carbon dots (CDs) exhibit outstanding inhibition properties to availably retard the corrosion of metal. However, the present CDs-based corrosion inhibitors still fail to fully exert the environmentally friendly and low-cost merits of CDs. To address this issue, CD aggregates (CDAs) prepared by low-cost and eco-friendly CDs are developed as novel corrosion inhibitors for the first time, and their corrosion inhibition mechanism is disclosed. Specifically, CDAs with excellent long-term dispersion stability are synthesized by solvothermal treatment of CDs formed by citric acid and urea. CDAs at only 200 mg/L provide a corrosion inhibition effect of 90.38% for Q235 carbon steel in 1 mol/L HCl solution, approximately 1.53 times higher than that of CDs (59.21%). Moreover, the corrosion inhibition mechanism of CDAs is proposed through the analysis of adsorption isotherm, examination of corrosion morphologies, and theoretical calculations. That is, CDAs physically and chemically adsorb on the carbon steel surface, mainly hindering its anodic reaction, thus retarding the corrosion of carbon steel. This research firstly verifies the corrosion inhibition potential of green and low-cost CDAs and provides a novel strategy to promote the corrosion inhibition performance of CDs, promoting the progress of aggregate-based corrosion inhibitors.

The formulation of biopharmaceutical drugs is designed to eliminate chemical instabilities, increase conformational and colloidal stability of proteins, and optimize interfacial stability. Among the various excipients involved, buffer composition plays a pivotal role. However, conventional buffers like histidine and phosphate buffers may not always be the optimal choice for all monoclonal antibodies (mAbs). In this study, we investigated the effects of several alternative buffer systems on seven different mAbs, exploring various combinations of ionic strengths, concentrations of the main buffer component, mAb concentrations, and stress conditions. Protein stability was assessed by analyzing soluble aggregate formation through size exclusion chromatography. At low protein concentrations, protein instability after temperature stress was exclusively observed in the bis-TRIS/ glucuronate buffer. Conversely, freeze-thaw stress led to a significant increase in aggregate formation in tested formulations, highlighting the efficacy of several alternative buffers, particularly arginine/ citrate, in preserving protein stability. Under temperature stress, the introduction of arginine to histidine buffer systems provided additional stabilization, while the addition of lysine resulted in protein destabilization. Similarly, the incorporation of arginine into histi-dine/HCl buffer further enhanced protein stability during freeze--thaw cycles. At high protein concentrations, the histidine/citrate buffer emerged as one of the most optimal choices for addressing temperature and light-induced stress. The efficacy of histidine buffers in combating light stress might be attributed to the light-absorbing properties of histidine molecules. Our findings demonstrate that the development of biopharmaceutical formulations should not be confined to conventional buffer systems, as numerous alternative options exhibit comparable or even superior performance.

Aggregates created by a simple physical method promote the charge mobility between semiconductor nanoparticles and, combined with the selective photo-deposition of platinum, dramatically improve the hydrogen production when low loadings of Pt are used. [Display omitted] Photocatalysis has emerged as a promising and environmentally sustainable solution to produce high-purity hydrogen through ethanol photoreforming. It is commonly accepted that adding co-catalysts, especially noble metals, significantly enhances the catalytic activity of semiconductors. However, the high cost of noble metals such as Pt may limit the real application of this emerging technology. Here we evaluate the possibility of reducing the noble metal loading by creating the appropriate interface between pre-formed semiconductor nanoparticles. Commercial titania (P25) was selected as the semiconductor due to its commercial availability, facilitating the straightforward validation and corroboration of our results. Pt was selected as co-catalyst because one of the most efficient photocatalysts for the ethanol photo-reforming is still based on the use of P25 in combination with Pt. We report that the creation of induced aggregates dramatically improves the total hydrogen produced when very low loadings (≤0.05 wt%) of Pt are used. We have developed a pioneering reactor designed for conducting photoluminescence studies under authentic operational conditions of nanoparticle suspensions in the liquid phase. This approach allows us to obtain the average photoluminescence emission from the P25 agglomerates what it would be impossible to obtain by using standard solid samples holders. Thanks to this equipment, we can conclude that this remarkable improvement of the activity is mainly due to creation of an interface that favors the charge transfer between the particles of the aggregates. According to this, the titania nanoparticles of the agglomerates act as an antenna to collect the photons of the sun-light and produce the photo-excited electrons that will be transferred to the platinum nanoparticles located in the same agglomeration. In contrast, raw P25 with low loadings of Pt would have a high number of titania nanoparticles without platinum, and therefore, inactive. This result would be especially relevant in the case of immobilized photocatalytic systems for real future photocatalytic reactors because the immobilization of the semiconductors would generate similar interactions to the one created by our method. Consequently, the initial semiconductor immobilization followed by the subsequent photo-deposition of the co-catalyst emerges as a promising approach for a substantial reduction of the co-catalyst content. [ABSTRACT FROM AUTHOR]

The heating potential of microwave-heated bituminous mixtures depends on the heating characteristics of aggregates. This study focused on understanding the effect of mineral, chemical, and dielectric properties of aggregates on the rate of heating of aggregates, with special emphasis on the effect of the power level of microwave energy. Properties of the aggregates collected from 18 different sources were evaluated using X-ray diffraction, X-ray fluorescence spectroscopy, and a microwave vector network analyzer. Heating studies were conducted on the aggregates using a microwave oven at four different power levels (330, 525, 630, and 700 W). Thermal images, captured using a forward-looking infrared (FLIR) thermal camera, were used to obtain the heating characteristics, such as heating time, rate and nonuniformity of heating. The rate of heating of aggregates (0.212°C/s−1.007°C/s), nonuniformity of heating (0.059°C–0.218°C), and time of heating to 100°C (40–520 s) varied widely with the source of aggregate. In general, the heating rate and the degree of nonuniformity of the aggregates increased with increase in microwave power. Bulk mineralogy and chemical composition of aggregates significantly influenced the dielectric response of aggregates (adjusted R-squared values of 0.75 and 0.70, respectively) and the sensitivity of heating parameters to microwave power (adjusted R-squared values of 0.83 and 0.92, respectively). Two different predictive models were developed for estimation of heating rate of aggregates with (1) power, density, and dielectric loss factor, and (2) power, density, and aggregate chemical indices as independent variables. The adjusted R-squared values of these two predictive models were 0.84 and 0.92, respectively. [ABSTRACT FROM AUTHOR]

The frictional properties of aggregates play a significant role in determining pavement skid resistance. To preserve natural aggregates, reclaimed asphalt pavement (RAP) has been widely used for decades. However, its use in pavement surface courses is often limited due to its unknown frictional properties. Therefore, this research aimed to quantitatively investigate both aggregates and RAP to develop a quick evaluation method for frictional properties. Nine types of aggregates from Tennessee were selected for relative frictional tests. X-ray fluorescence was utilized to quantify the silica dioxide (SiO2) contents, establishing correlations with polish stone value (PSV), micro-Deval (MD) abrasion loss, and surface morphological characteristics of aggregates tested via the aggregate image measurement system. Subsequently, to develop a quick way to measure the SiO2 of RAP, laboratory-produced RAP and field-sampled RAP were compared. Laboratory-produced RAP was fabricated and compared with chemical trichloroethylene (TCE) and a hammer-crushed processing method to accurately measure the SiO2 content for the application of field-sampled RAP. Field pavement friction tests were conducted to correlate the laboratory findings to field measurements. Results show that the coefficients of determination (R2) of SiO2 from raw aggregates with PSV, MD loss, and texture loss are 0.81, 0.60, and 0.78, respectively. Field-sampled RAP washed by TCE three times could provide more accurate SiO2 content compared with hammer crushing. The field pavement friction test demonstrates that pavements with lower SiO2 contents exhibit reduced skid resistance due to texture loss caused by traffic polishing. These findings offer a straightforward method for evaluating pavement friction and selecting RAP with high skid resistance, where higher SiO2 content provides higher friction properties. As a result, this research provides a valuable strategy for the rapid evaluation of aggregates and RAP for skid resistance. [ABSTRACT FROM AUTHOR]

Abstract The primary challenge in today’s world of neuroscience is the search for new therapeutic possibilities for neurodegenerative disease. Central to these disorders lies among other factors, the aberrant folding, aggregation, and accumulation of proteins, resulting in the formation of toxic entities that contribute to neuronal degeneration. This review concentrates on the key proteins such as β-amyloid (Aβ), tau, and α-synuclein, elucidating the intricate molecular events underlying their misfolding and aggregation. We critically evaluate the molecular mechanisms governing the elimination of misfolded proteins, shedding light on potential therapeutic strategies. We specifically examine pathways such as the endoplasmic reticulum (ER) and unfolded protein response (UPR), chaperones, chaperone-mediated autophagy (CMA), and the intersecting signaling of Keap1-Nrf2-ARE, along with autophagy connected through p62. Above all, we emphasize the significance of these pathways as protein quality control mechanisms, encompassing interventions targeting protein aggregation, regulation of post-translational modifications, and enhancement of molecular chaperones and clearance. Additionally, we focus on current therapeutic possibilities and new, multi-target approaches. In conclusion, this review systematically consolidates insights into emerging therapeutic strategies predicated on protein aggregates clearance. Graphical Abstract

Various stress conditions, such as heat stress (HS) and oxidative stress, can cause biomolecular condensates represented by stress granules (SGs) via liquid-liquid phase separation. We have previously shown that Hsp90 forms aggregates in response to HS and that Hsp90 aggregates transiently co-localize with SGs as visualized by Pabp. Here, we showed that arsenite, one of the well-described SG-inducing stimuli, induces Hsp90 aggregates distinct from conventional SGs in fission yeast. Arsenite induced Hsp90 granules in a dose-dependent manner, and these granules were significantly diminished by the co-treatment with a ROS scavenger N-acetyl cysteine (NAC), indicating that ROS are required for the formation of Hsp90 granules upon arsenite stress. Notably, Hsp90 granules induced by arsenite do not overlap with conventional SGs as represented by eIF4G or Pabp, while HS-induced Hsp90 granules co-localize with SGs. Nrd1, an RNA-binding protein known as a HS-induced SG component, was recruited into Hsp90 aggregates but not to the conventional SGs upon arsenite stress. The non-phosphorylatable eIF2α mutants significantly delayed the Hsp90 granule formation upon arsenite treatment. Importantly, inhibition of Hsp90 by geldanamycin impaired the Hsp90 granule formation and reduced the arsenite tolerance. Collectively, arsenite stimulates two types of distinct aggregates, namely conventional SGs and a novel type of aggregates containing Hsp90 and Nrd1, wherein Hsp90 plays a role as a center for aggregation, and stress-specific compartmentalization of biomolecular condensates.

The primary challenge in today's world of neuroscience is the search for new therapeutic possibilities for neurodegenerative disease. Central to these disorders lies among other factors, the aberrant folding, aggregation, and accumulation of proteins, resulting in the formation of toxic entities that contribute to neuronal degeneration. This review concentrates on the key proteins such as β-amyloid (Aβ), tau, and α-synuclein, elucidating the intricate molecular events underlying their misfolding and aggregation. We critically evaluate the molecular mechanisms governing the elimination of misfolded proteins, shedding light on potential therapeutic strategies. We specifically examine pathways such as the endoplasmic reticulum (ER) and unfolded protein response (UPR), chaperones, chaperone-mediated autophagy (CMA), and the intersecting signaling of Keap1-Nrf2-ARE, along with autophagy connected through p62. Above all, we emphasize the significance of these pathways as protein quality control mechanisms, encompassing interventions targeting protein aggregation, regulation of post-translational modifications, and enhancement of molecular chaperones and clearance. Additionally, we focus on current therapeutic possibilities and new, multi-target approaches. In conclusion, this review systematically consolidates insights into emerging therapeutic strategies predicated on protein aggregates clearance. [ABSTRACT FROM AUTHOR]

Biomolecular aggregates ensure the optimum concentration and proximity required for biochemical processes to take place. Synthetic aggregating systems are becoming increasingly essential to study/mimic dynamic condensates in nature. Herein the ratiometric DNA aggregation of self‐assembled DNA constructs using lanthanide salts is reported. In addition, the aggregation is shown to be reversed by the addition of specific lanthanide‐binding ligands. The aggregate formation is confirmed by dynamic light scattering experiment, electrophoretic mobility shift assay, and field emission scanning electron microscope. This programmed DNA aggregation and its reversion are applied to evaluating the lanthanide‐DNA and lanthanide‐ligand binding constants, respectively. To achieve this, Forster resonance energy transfer (FRET) pair dyes at the 3′ or 5′ end of the DNA strands are strategically placed that generate unique fluorescence patterns upon interaction with the DNA constructs and different triggers such as lanthanides/ligands/monovalent cations, thus enabling the tracking of various states of binding. It also demonstrates a “fast method” to form and stabilize G‐quadruplex (GQ) using lanthanides which complements the existing slow formation of GQs with Na+/K+ ions. The formation of GQ by lanthanides is corroborated by FRET, circular dichroism (CD), and enzyme linked immunosorbent assay (ELISA) experiments. These DNA constructs, formed by lanthanides, have shown resistance to cleavage by DNase I, and distinctive binding to Protoporphyrin dyes and Thioflavin T. [ABSTRACT FROM AUTHOR]

AbstractLaccase has a wide range of substrates and the oxidation product is water, providing an ideal choice for the biological degradation and decolorization of dyeing wastewater. This study extracted laccase from the fruiting body of Agaricus bisporus, then used o-phthalaldehyde (OPA) as a cross-linking agent and added surface-aminated Fe3O4 nanoparticles (NH2-nanoFe3O4) to prepare magnetic cross-link enzyme aggregates (MCLEAs) of laccase, which was characterized by scanning electron microscope and vibrating sample magnetometer. The optimal temperature for the catalytic reaction of the MCLEAs was 35 °C, and the optimal pH was 3.0. The stability to temperature pH and storage stability were all enhanced. The immobilized laccase was utilized to treat amido black 10B solution, and the decolorization rate reached 92.48%. After five cycles of use, the MCLEAs of laccase could maintain 42.91% of the relative activity and 32.31% of the relative degradation ability to amido black 10B. [ABSTRACT FROM AUTHOR]

Prior research has demonstrated that incorporating solid waste from various sources, such as plastics, civil engineering waste, and industrial and mining waste, into pavement and civil works mixes has notable environmental benefits. This includes reducing the over-exploitation of aggregate banks and preventing waste materials from being deposited in open-pit landfills for extended periods. This review focuses on sustainable aggregates produced from solid waste with rheological or mechanical properties suitable for replacing conventional aggregates in asphalt or hydraulic concrete mixtures. The aim is to determine the optimal replacement percentage in the mixture to directly impact pavement performance. This review also delves into the impact on fatigue resistance and permanent deformation based on the type of waste material used in construction. Additionally, using sustainable aggregates presents added benefits for pavement binders, such as inhibiting reflection cracks, reducing traffic noise, and prolonging the service life of the pavement. However, it is crucial to study the percentage of replacement of sustainable aggregates in conjunction with other materials using mathematical models and simulations to ensure a substantial contribution to the sustainability of the construction industry. [ABSTRACT FROM AUTHOR]

Recent advancements in sustainable building practices include the integration of waste materials from various industries into construction materials. This approach is currently being evaluated, allowing us to view recycled material not as waste but as a valuable resource and raw material. Such an approach involves viewing this material as a separate resource with its own distinctive properties. This article investigates the use and environmental safety of perlite-based concrete. The research focuses on the properties of immobilizing potentially toxic elements (PTEs) in soil and plants, and it examines the impact of adding activated carbon to different types of perlite concrete on these properties. Initial tests varied the content of perlite concrete (3%, 5%, and 10%) to better understand the immobilization process in soil, roots, and aboveground plant parts. The results after adding 10% activated carbon provide insights into the nature and direction of the immobilization process and in determining the optimal amount of perlite concrete to enhance this process. The soil analysis revealed that the application of PPC at a rate of 10% led to a notable elevation in soil zinc content, reaching 96.6 mg/kg—a considerable 304% increase. Similarly, the amendment of PBFC at a rate of 10% resulted in a significant enhancement in copper content, reaching 21.7 mg/kg—an 112% increase. This study also evaluates the environmental safety of using perlite concrete and activated carbon in construction projects, such as earthworks and road subbases, where the materials interact with the water–soil environment. The novelty of this research lies in its examination of the remediation potential and environmental safety of modified perlite aggregate, offering a fresh perspective on the impacts of these modifications on previously studied materials. By applying varying concentrations of the amendments, the research provides a deeper understanding of their effects, yielding significant findings that support the advancement of sustainable construction practices. [ABSTRACT FROM AUTHOR]

Protein conformation is affected by interaction of several small molecules resulting either stabilization or disruption depending on the nature of the molecules. In our earlier communication, Hg2+ was known to disrupt the native structure of α-Cgn A leading to aggregation (Ansari, N.K., Rais, A. & Naeem, A. Methotrexate for Drug Repurposing as an Anti-Aggregatory Agent to Mercuric Treated α-Chymotrypsinogen-A. Protein J (2024). https://doi.org/10.1007/s10930-024-10187-z). Accumulation of β-rich aggregates in the living system is found to be linked with copious number of disorders. Here, we have investigated the effect of varying concentration of doxorubicin (DOX) i.e. 0-100 µM on the preformed aggregates of α-Cgn A upon incubation with 120 µM Hg2+. The decrease in the intrinsic fluorescence and enzyme activity with respect to increase in the Hg2+ concentration substantiate the formation of aggregates. The DOX showed the dose dependent decrease in the ThT fluorescence, turbidity and RLS measurements endorsing the dissolution of aggregates which were consistent with red shift in ANS, confirming the breakdown of aggregates. The α-Cgn A has 30% α-helical content which decreases to 3% in presence of Hg2+. DOX increased the α-helicity to 28% confirming its anti-aggregatory potential. The SEM validates the formation of aggregates with Hg2+ and their dissolution upon incubation with the DOX. Hemolysis assay checked the cytotoxicity of α-Cgn A aggregates. Docking revealed that the DOX interacted Lys203, Cys201, Cys136, Ser159, Leu10, Trp207, Val137 and Thr134 of α-Cgn A through hydrophobic interactions and Gly133, Thr135 and Lys202 forms hydrogen bonds. [ABSTRACT FROM AUTHOR]

Engineering applications including pervious concrete require effective packing of aggregates to optimize strength. Size and shape distribution of aggregates significantly affect the performance. Computational methods numerically represent shape of aggregates, from image analysis, the effectiveness of has not been compared and verified. This study aims to analyse the representability of shape aspects of aggregates by different computational methods. Crushed aggregates were grouped into 5 clusters, and each group was milled in a Los Angeles machine for different degrees (0–2000) to induce morphological changes on the aggregates. Aggregates ranging from 5 to 30mm in diameter were obtained (7191 in total). imageJTM, was used to compute dimensions and shape factors of aggregates from 14 computational methods. Statistical tests, Pearson's Correlations and Principal Components Analysis and machine learning classification tools, Decision-tree, Random-Forest, Naïve-Bayes, Support-Vector-Machines, K-Nearest-Neighbours and Perceptron were employed to assess. In conclusion, no shape factor could be singularly used to numerically represent the morphological changes on aggregate particles but a combination of shape factors is required. Data matrix had three primary dimensions. Combination of Circularity, Kumbrein-Solidity and Barksdale-Shape-Factor yield best representation of aggregate shape. Regression Tree classification method had the highest accuracy (0.9) in classifying milled and unmilled aggregates. [ABSTRACT FROM AUTHOR]

In this work, the implications of AAV9 capsid design and column reuse on AAV9 vector product quality were assessed with POROS CaptureSelect (PCS) AAVX and AAV9 resins using sf9 insect cell‐derived model AAV9 vectors with varying viral protein (VP) ratios. Chromatographic experiments with purified drug substance AAV9 model feeds indicated consistent vector elution profiles, independent of adeno‐associated virus (AAV) VP ratio, or cycle number. In contrast, the presence of process impurities in the clarified lysate feeds resulted in clear changes in the elution patterns. This included increased aggregate content in the vector eluates over multiple cycles as well as clear differences in the performance of these affinity resin systems. The AAV9‐serotype specific PCS AAV9 column, with lower vector elution pH, resulted in higher aggregate content over multiple cycles as compared to the serotype‐independent PCS AAVX column. Further, the results with vectors of varying VP ratio indicated that while one vector type eluate displayed higher aggregation in both affinity columns over column reuse, the eluate with the other vector type did not exhibit changes in the aggregation profile. Interestingly, vector aggregates in the affinity eluates also contained double‐stranded DNA impurities and histone proteins, with similar trends to the aggregate levels. This behavior upon column reuse indicates that these host cell impurities are likely carried over to subsequent runs due to incomplete clean‐in‐place (CIP). These results indicate that feed impurities, affinity resin characteristics, elution pH, column CIP, and vector stability can impact the reusability of AAV affinity columns and product quality. [ABSTRACT FROM AUTHOR]

The adverse aggregated‐caused quenching (ACQ) problem of most electroluminescent materials existing in highly doped thin films is one of the key factors impeding the commercialization of high‐efficiency organic light‐emitting diodes (OLEDs) panel. Whereas, by delicately constructing and modulating moderate intermolecular interactions, some aggregates have been demonstrated to present distinct luminescent properties such as tunable emission spectra, improved photoluminescence quantum yields, different emission mechanism and enhanced horizontal transition dipole ratio (Θ) of emitting layer, providing feasible solution for ACQ problem. The luminescence from newly generated emissive state in aggregates is different from the traditional "isolated" molecules in organic electronics and will possess novel properties and applications. Herein, we summarize the different types of intermolecular interactions within emitter aggregates exhibiting distinct luminescent mechanisms, as well as their effects on photoluminescent and electroluminescent properties, offering reliable reference for the advancement of highly efficient OLEDs utilizing aggregated emitters. [ABSTRACT FROM AUTHOR]

Biological systems evolve with minimum metabolic costs and use common components, and they represent guideposts toward a paradigm of manufacturing that is centered on minimum energy, local resources, and ecological integration. Here, a new method of metalworking that uses chitosan from the arthropod cuticle to aggregate colloidal suspensions of different metals into solid ultra‐low‐binder‐content composites is demonstrated. These composites, which can contain more than 99.5% metal, simultaneously show bonding affinity for biological components and metallic characteristics, such as electrical conductivity. This approach stands in contrast with existing metalworking methods, taking place at ambient temperature and pressure, and being driven by water exchange. Furthermore, all the nonmetallic components involved are metabolized in large amounts in every ecosystem. Under these conditions, the composites’ ability to be printed and cast into functional shapes with metallic characteristics is demonstrated. The affinity of chitometallic composites for other biological components also allows them to infuse metallic characteristics into other biomaterials. The findings and robust manufacturing examples go well beyond basic demonstrations and offer a generalizable new approach to metalworking. The potential for a paradigm shift toward biomaterials based on their unique characteristics and the principles of their manufacturing methods is highlighted. [ABSTRACT FROM AUTHOR]

Morphologies of nanoparticles and aggregates play an important role in their properties for a range of applications. In particular, significant synthesis efforts have been directed toward controlling nanoparticle morphology and aggregation behavior in biomedical applications, as their size and shape have a significant impact on cellular uptake. Among several techniques for morphological characterization, transmission electron microscopy (TEM) can provide direct and accurate characterization of nanoparticle/aggregate morphology details. Nevertheless, manually analyzing a large number of TEM images is still a laborious process. Hence, there has been a surge of interest in employing machine learning methods to analyze nanoparticle size and shape. In order to achieve accurate nanoparticle analysis using machine learning methods, reliable and automated nanoparticle segmentation from TEM images is critical, especially when the nanoparticle image contrast is weak and the background is complex. These challenges are particularly pertinent in biomedical applications. In this work, we demonstrate an efficient, robust, and automated nanoparticle image segmentation method suitable for subsequent machine learning analysis. Our method is robust for noisy, low-electron-dose cryo-TEM images and for TEM cell images with complex, strong-contrast background features. Moreover, our method does not require any a priori training datasets, making it efficient and general. The ability to automatically, reliably, and efficiently segment nanoparticle/aggregate images is critical for advancing precise particle/aggregate control in biomedical applications. [ABSTRACT FROM AUTHOR]

Novel self-assembled aggregates of stearic acid (SA)-modified burdock polysaccharide (BP) for loading lutein were constructed, and the release and absorption properties of lutein in the aggregates in simulated gastrointestinal fluid were investigated. Three different degrees of substitution (DS) of SA-BPs were used to embed lutein, resulting in the encapsulation efficiency exceeding 90%. The aggregates were uniformly spherical, with a particle size range of 227–341 nm. XRD analysis revealed that lutein was present in a non-crystalline state within the aggregates. FT-IR and FS analysis demonstrated that lutein was located in the hydrophobic domains of SA-BP. The highest bioavailability of lutein in these aggregates reached 4.36 times that in the unmodified samples. These aggregates were able to remain stable in gastric juice and enhance the release rate of lutein in intestinal fluid. The transport of lutein-loaded SA-BP aggregates in Caco-2 cells competed with P-glycoprotein inhibitors, mainly promoting the transmembrane absorption of lutein through caveolae (or lipid raft)-related and clathrin-dependent endocytosis pathways. The above results suggest that SA-BP aggregates have the potential to be promising carriers for the efficient delivery of hydrophobic lutein. [ABSTRACT FROM AUTHOR]

The construction sector generates a strong environmental impact every year as a result of the high consumption of raw materials and the large waste volumes associated with this productive activity. In this sense, the search for alternative and sustainable solutions that allow progress towards responsible economic growth has become a priority activity. This work presents an exhaustive characterisation of masonry mortars made with four different types of aggregates: standard sand, natural sand, concrete waste recycled sand and ceramic components recovered sand. Differently from other studies, this research addresses the previous characterisation of the aggregates as raw material for the manufacture of masonry mortars, and, afterwards, a study of the most relevant properties for these cement composites in the fresh and hardened state is carried out. The most relevant properties of the mortars made with these raw materials are presented, and the repercussion of aggregate washing on their physical-mechanical characteristics is analysed. The results show how mortars made with 100% recycled aggregate can be competitive in the industry, presenting excellent properties in the fresh state and achieving an optimal mechanical strength. In addition, it has been observed that the introduction of a previous washing step of the aggregates improves their physical-mechanical properties and results in a higher quality of the cement mortars finally produced. In this way, the most representative properties of this type of materials have been collected in a well-structured and complete way, thus showing their possibilities of application in the construction industry. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Moisture damage in asphalt mixtures is typically attributed to the loss of bond strength at the interface of the asphalt binder and aggregate matrix. Selecting an appropriate combination of materials that resist moisture-induced damage is therefore critical. This concern is of utmost importance when asphalt mixtures are prepared at lower temperatures (i.e. warm-mix asphalt (WMA) mixtures). An attempt was thus made to quantify the impact of moisture on asphalt mixtures prepared using four different WMA additives and two aggregates through bond strength tests. The results showed that WMA binders imparted similar or even higher bond strength than the base asphalt binder, regardless of the aggregate source and moisture exposure (wet or dry). The use of WMA additives improved the moisture sensitivity (evaluated through the bond strength ratio), despite lower production temperatures, compared with the base asphalt binder (VG30). Statistical analysis showed that the asphalt binder type significantly affected the bonding mechanism and moisture sensitivity. Based on the ranking protocol used in this study, use of the chemical-based WMA additive Rediset showed the best performance compared with other WMA additives in VG30. [ABSTRACT FROM AUTHOR]

15 soils were sampled in the present study to investigate the content of soil organic carbon (SOC) and soil aggregates, on the soil oxidant requirement (SOD) that used in the chemical oxidation remediation technology. Alkali-activated sodium persulfate was selected as the oxidant. The result showed that microaggregates (<250 μm) contained 70% of SOC. A significant positive correlation was found between the value of SOD and the content of SOC of the bulk soil. Furtherly, SOD was positively correlated with SOC content of three different aggregates of soils (2 000-250 μm, 250-53 μm and <53 μm), and the smaller the soil aggregates, the higher the significance value. Therefore, the SOC content, especially which in microaggregates was the key factor influencing the value of SOD. The results here could be useful for selection of the oxidant dosage and could also promote the efficiency oxidation remediation technology. [ABSTRACT FROM AUTHOR]

The present work analyses the physical characteristics of aggregates recovered with the waterjigging process from comminuted concrete. In this work, conventional concrete (C16/20) was crushed to a top size of 20 mm with a jaw crusher and classified in a size range of 5 to 20 mm. The densimetric distribution analysis was carried out in a densimetric range of 2.4 to 2.8 g/cm3, and the cement paste was dissolved from all granulometric ranges to analyze the composition (sand, cement paste, and aggregates) of each part and define the possibilities of materials to recover. A two-stage water jig concentration process was used, generating a cleaner material in the first stage and a re-cleaner material in the second jigging stage. The physical properties of the material inserted in the feed and the material generated in the first and second stages were analyzed to compare them with natural aggregates. The results indicate the viability of recovering 47.8% of the coarse aggregates present in the concrete feed in the re-cleaner material, with 84% of particles having a density higher than 2.6 g/cm3. These characteristics are similar to those found in natural aggregates. [ABSTRACT FROM AUTHOR]

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Lignin, a renewable aromatic polymer, has great potential as a synthetic building block for functional materials. The effects of quaternary ammonic methylation of alkali lignin (AL) on the morphologies and ofloxacin antibiotic (OA) removal application from water are investigated by using the dissipative particle dynamics (DPD) simulation method. Untreated AL can form spherical aggregates, but the phenylpropane units of untreated AL and loaded broad‐spectrum OA molecules are randomly distributed in aggregates. However, if quaternary ammonic groups are grafted onto all orthopositions of the phenolic hydroxyl groups (100‐QAMAL), then multilamellar spherical aggregates are obtained and OA molecules are entrapped in the aggregates. To prepare multilamellar spherical aggregates with an ordered and regular layered structure, <15 v% of 100‐QAMAL and low molecular weights of AL (≈4700–9400 Da) are suggested to be used. Lignin‐based multilamellar spherical aggregates can be adopted as potential functional carriers for removing pollutant OA from water. [ABSTRACT FROM AUTHOR]

In order to accurately understand the relationship between soil structure and climate feedback in the frozen soil area of Mu Us Sandy Land, China, and to explore the key control factors for the structural stability of soft rock and sand compound soil under freeze-thaw environment, the indoor freeze-thaw simulation experiment was applied. The results show that the freeze-thaw period, clay content, organic matter and their interactions have significant effects on the stability of composite soil aggregates. After 10 freeze-thaw cycles, the aggregate content in the 1:0, 1:1, 1:2, and 1:5 composite soil with a diameter greater than 1mm decreased by 55%, 34%, 44%, and 57%, while the aggregate content with a diameter less than 1mm increased by 91%, 70%, 66%, and 87%, and the aggregate composition of each particle size is mainly concentrated in the range of 0.25-0.5 mm. Under freeze-thaw conditions, the changes of clay and aggregate content in different proportions of composite soil is the same, all showing 1:1>1:2:>1:5, and 1:1 composite soil with >0.25mm aggregate content is the highest. Under freeze-thaw alternations, 1:1, 1:2 and 1:5 composite soil aggregates (<0.5 mm) showed a significant positive correlation with soil organic matter, while there is no significant correlation between large aggregates (>1 mm) and soil organic matter. In conclusion, the freeze-thaw cycle reduces the structural stability of composite soil aggregates, and clay are the key controlling factors for the formation and structural stability of composite soil aggregates. [ABSTRACT FROM AUTHOR]

Green mining and the formation of an effective and efficient development model have become key issues that aggregates enterprises around the world need to solve urgently. On the basis of analyzing the development status of aggregates industry in Xiluodu area, the paper studied the main problems faced in the construction of green aggregates mines at present, and proposed a "three-in-one" ecological, intelligent and efficient green mine construction model for "ecological development", "green logistics" and "solid waste recycling" of aggregates. The study has certain theoretical value and practical significance for the construction of green aggregates mine in Xiluodu area. [ABSTRACT FROM AUTHOR]

Nesprin proteins, which are components of the linker of nucleoskeleton and cytoskeleton (LINC) complex, are located within the nuclear envelope and play prominent roles in nuclear architecture. For example, LINC complex proteins interact with both chromatin and the cytoskeleton. Here, we report that the Drosophila Nesprin MSP300 has an additional function in autophagy within larval body wall muscles. RNAi-mediated MSP300 knockdown in larval body wall muscles resulted in defects in the contractile apparatus, muscle degeneration and defective autophagy. In particular, MSP300 knockdown caused accumulation of cytoplasmic aggregates that contained poly-ubiquitylated cargo, as well as the autophagy receptor ref(2)P (the fly homolog of p62 or SQSTM) and Atg8a. Furthermore, MSP300 knockdown larvae expressing an mCherry-GFP-tagged Atg8a transgene exhibited aberrant persistence of the GFP signal within these aggregates, indicating failure of autophagosome maturation. These autophagy deficits were similar to those exhibited by loss of the endoplasmic reticulum (ER) fusion protein Atlastin (Atl), raising the possibility that Atl and MSP300 might function in the same pathway. In support of this possibility, we found that a GFP-tagged MSP300 protein trap exhibited extensive localization to the ER. Alteration of ER-directed MSP300 might abrogate important cytoskeletal contacts necessary for autophagosome completion. [ABSTRACT FROM AUTHOR]

Biopharmaceutical products, in particular messenger ribonucleic acid (mRNA), have the potential to dramatically improve the quality of life for patients suffering from respiratory and infectious diseases, rare genetic disorders, and cancer. However, the quality and safety of such products are particularly critical for patients and require close scrutiny. Key product-related impurities, such as fragments and aggregates, among others, can significantly reduce the efficacy of mRNA therapies. In the present work, the possibilities offered by size exclusion chromatography (SEC) for the characterization of mRNA samples were explored using state-of-the-art ultra-wide pore columns with average pore diameters of 1000 and 2500 Å. Our investigation shows that a column with 1000 Å pores proved to be optimal for the analysis of mRNA products, whatever the size between 500 and 5000 nucleotides (nt). We also studied the influence of mobile phase composition and found that the addition of 10 mM magnesium chloride (MgCl2) can be beneficial in improving the resolution and recovery of large size variants for some mRNA samples. We demonstrate that caution should be exercised when increasing column length or decreasing the flow rate. While these adjustments slightly improve resolution, they also lead to an apparent increase in the amount of low-molecular-weight species (LMWS) and monomer peak tailing, which can be attributed to the prolonged residence time inside the column. Finally, our optimal SEC method has been successfully applied to a wide range of mRNA products, ranging from 1000 to 4500 nt in length, as well as mRNA from different suppliers and stressed/unstressed samples. [ABSTRACT FROM AUTHOR]

In the past few decades, there has been an evolution in our understanding of soil organic matter (SOM) dynamics from one of inherent biochemical recalcitrance to one deriving from plant‐microbe‐mineral interactions. This shift in understanding has been driven, in part, by influential conceptual frameworks which put forth hypotheses about SOM dynamics. Here, we summarize several focal conceptual frameworks and derive from them six controls related to SOM formation, (de)stabilization, and loss. These include: (a) physical inaccessibility; (b) organo‐mineral and ‐metal stabilization; (c) biodegradability of plant inputs; (d) abiotic environmental factors; (e) biochemical reactivity and diversity; and (f) microbial physiology and morphology. We then review the empirical evidence for these controls, their model representation, and outstanding knowledge gaps. We find relatively strong empirical support and model representation of abiotic environmental factors but disparities between data and models for biochemical reactivity and diversity, organo‐mineral and ‐metal stabilization, and biodegradability of plant inputs, particularly with respect to SOM destabilization for the latter two controls. More empirical research on physical inaccessibility and microbial physiology and morphology is needed to deepen our understanding of these critical SOM controls and improve their model representation. The SOM controls are highly interactive and also present some inconsistencies which may be reconciled by considering methodological limitations or temporal and spatial variation. Future conceptual frameworks must simultaneously refine our understanding of these six SOM controls at various spatial and temporal scales and within a hierarchical structure, while incorporating emerging insights. This will advance our ability to accurately predict SOM dynamics. Plain Language Summary: Soil organic matter, the remains of plants, animals, and microbes in the soil, performs many important functions for humans and ecosystems, providing habitat for animals, nutrients for plants, climate change buffering, and structure for soil animals and human structures. Thus, it is important to understand how soil organic matter is formed, stabilized, and lost. Here, we review conceptual frameworks that have contributed to our understanding of soil organic matter over the past 20 years. We evaluate their support in experiments and also how well represented they are in computer models. We find the least support and representation for controls of soil organic matter associated with properties of microbes and physical barriers between microbes and soil organic matter. These and novel soil organic matter controls require more research for better understanding of soil organic matter functions. Key Points: Soil organic matter (SOM) research has been advanced by conceptual frameworksConceptual frameworks are associated with different SOM controls with variable empirical support and model representationMicrobial physiology and morphology and physical inaccessibility, as SOM controls, require more empirical work and model representation [ABSTRACT FROM AUTHOR]

This study focusses on the scarce resources of high-quality silicated rock aggregates in Central Chad, a wide area almost devoid of hard rock outcrops. We provide an original study of the petrographic and mechanical characteristics of Alfallé massif together with a review of quarries in activity or potentially exploitable. The resistance to degradation of the prepared aggregates were evaluated using the standard test of Los Angeles and micro-Deval. The Alfallé massif is made up of three lithologies: alkali feldspar coarse granite, biotite-rich fine-grained quartz monzonite and biotite-rich fine-grained gneiss. The mechanical test results obtained indicate that the materials studied have excellent to satisfactory properties, and that the Alfallé massif provides the best characteristics among six different quarrying areas in Central Chad. Moreover, the three quarries that were once isolated islands in the mega-Chad paleolake yield on average higher resistance. We thus propose that these rare residual reliefs within the mega-Chad paleolake area reached optimal mechanical properties through a natural selection process, specific of the paleolake erosional conditions. [ABSTRACT FROM AUTHOR]

This review is devoted to the consideration of pathological intracellular mechanisms characteristic of Huntington's disease and the central role of huntingtin protein in these processes. The features of mutant huntingtin aggregates utilization by the ubiquitin–proteasome system and autophagy, as well as the possibilities of polyglutamine-containing substrates hydrolysis by proteasome are discussed. [ABSTRACT FROM AUTHOR]

Abstract The present opinion is the follow‐up of the conclusions and recommendations of the Scientific Opinion on the re‐evaluation of silicon dioxide (E 551) as a food additive relevant to the safety assessment for all age groups. In addition, the risk assessment of silicon dioxide (E 551) for its use in food for infants below 16 weeks of age is performed. Based on the newly available information on the characterisation of the SAS used as E 551 and following the principles of the 2021 EFSA Guidance on Particle‐TR, the conventional safety assessment has been complemented with nano‐specific considerations. Given the uncertainties resulting from the limitations of the database and in the absence of genotoxicity concern, the Panel considered that it is not appropriate to derive an acceptable daily intake (ADI) but applied the margin of exposure (MOE) approach for the risk assessment. The Panel concluded that the MOE should be at least 36 for not raising a safety concern. The calculated MOEs considering the dietary exposure estimates for all population groups using the refined non‐brand loyal scenario, estimated at the time of the 2018 re‐evaluation, were all above 36. The Panel concluded that E 551 does not raise a safety concern in all population groups at the reported uses and use levels. The use of E 551 in food for infants below 16 weeks of age in FC 13.1.1 and FC 13.1.5.1 does not raise a safety concern at the current exposure levels. The Panel also concluded that the technical data provided support an amendment of the specifications for E 551 laid down in Commission Regulation (EU) No 231/2012. The paucity of toxicological studies with proper dispersion protocol (with the exception of the genotoxicity studies) creates uncertainty in the present assessment of the potential toxicological effects related to the exposure to E 551 nanosize aggregates.

Abstract Extracellular vesicles (EVs) secreted by human brain cells have great potential as cell‐free therapies in various diseases, including stroke. However, because of the significant amount of EVs needed in preclinical and clinical trials, EV application is still challenging. Vertical‐Wheel Bioreactors (VWBRs) have designed features that allow for scaling up the generation of human forebrain spheroid EVs under low shear stress. In this study, EV secretion by human forebrain spheroids derived from induced pluripotent stem cells as 3D aggregates and on Synthemax II microcarriers in VWBRs were investigated with static aggregate culture as a control. The spheroids were characterized by metabolite and transcriptome analysis. The isolated EVs were characterized by nanoparticle tracking analysis, electron microscopy, and Western blot. The EV cargo was analyzed using proteomics and miRNA sequencing. The in vitro functional assays of an oxygen and glucose‐deprived stroke model were conducted. Proof of concept in vivo study was performed, too. Human forebrain spheroid differentiated on microcarriers showed a higher growth rate than 3D aggregates. Microcarrier culture had lower glucose consumption per million cells and lower glycolysis gene expression but higher EV biogenesis genes. EVs from the three culture conditions showed no differences in size, but the yields from high to low were microcarrier cultures, dynamic aggregates, and static aggregates. The cargo is enriched with proteins (proteomics) and miRNAs (miRNA‐seq), promoting axon guidance, reducing apoptosis, scavenging reactive oxygen species, and regulating immune responses. Human forebrain spheroid EVs demonstrated the ability to improve recovery in an in vitro stroke model and in vivo. Human forebrain spheroid differentiation in VWBR significantly increased the EV yields (up to 240–750 fold) and EV biogenesis compared to static differentiation due to the dynamic microenvironment and metabolism change. The biomanufactured EVs from VWBRs have exosomal characteristics and more therapeutic cargo and are functional in in vitro assays, which paves the way for future in vivo stroke studies.

Recombinant adeno-associated virus (rAAV)-based gene therapies are expanding in their application. Despite progress in manufacturing, current analytical methods for product quantification and characterization remain largely unchanged. Although critical for product and process development, in-process testing, and batch release, current analytical methods are labor-intensive, costly, and hampered by extended turnaround times and low throughput. The field requires more efficient, cost-effective analytical techniques capable of handling large sample quantities to accelerate product and process development. Here, we evaluated Stunner from Unchained Labs for quantifying and characterizing rAAVs and compared it with established analytical methods. Stunner is a combinatorial analytic technology platform that interpolates ultraviolet-visible (UV-Vis) absorption with static and dynamic light scattering (SLS/DLS) analysis to determine capsid and genomic titer, empty and full capsid ratio, and assess vector size and polydispersity. The platform offers empirical measurements with minimal sample requirements. Upon testing hundreds of rAAV vectors, comprising various serotypes and transgenes, the data show a strong correlation with established analytical methods and exhibit high reproducibility and repeatability. Some analyses can be applied to in-process samples from different purification stages and processes, fulfilling the demand for rapid, high-throughput analysis during development. In sum, the pipeline presented streamlines small- and large-batch analytics.