Higher Aggregates Research Articles

High Glucose Treatment Induces Nuclei Aggregation of Microvascular Endothelial Cells via the foxo1a-klf2a Pathway.

Hyperglycemia is a major contributor to endothelial dysfunction and blood vessel damage, leading to severe diabetic microvascular complications. Despite the growing body of research on the underlying mechanisms of endothelial cell (EC) dysfunction, the available drugs based on current knowledge fall short of effectively alleviating these complications. Therefore, our endeavor to explore novel insights into the cellular and molecular mechanisms of endothelial dysfunction is crucial for the field. In this study, we performed a high-resolution imaging and time-lapse imaging analysis of the behavior of ECs in Tg(kdrl:ras-mCherry::fli1a:nGFP) zebra fish embryos upon high glucose treatment. Genetic manipulation and chemical biology approaches were utilized to analyze the underlying mechanism of high glucose-induced nuclei aggregation and aberrant migration of zebra fish ECs and cultured human ECs. Bioinformatical analysis of single-cell RNA-sequencing data and molecular biological techniques was performed to identify the target genes of foxo1a. In this study, we observed that the high glucose treatment resulted in nuclei aggregation of ECs in zebra fish intersegmental vessels. Additionally, the aberrant migration of microvascular ECs in high glucose-treated embryos, which might be a cause of nuclei aggregation, was discovered. High glucose induced aggregation of vascular endothelial nuclei via foxo1a downregulation in zebra fish embryos. Then, we revealed that high glucose resulted in the downregulation of foxo1a expression and increased the expression of its direct downstream effector, klf2a, through which the aberrant migration and aggregation of vascular endothelial nuclei were caused. High glucose treatment caused the nuclei of ECs to aggregate in vivo, which resembles the crowded nuclei of ECs in microaneurysms. High glucose suppresses foxo1a expression and increases the expression of its downstream effector, klf2a, thereby causing the aberrant migration and aggregation of vascular endothelial nuclei. Our findings provide a novel insight into the mechanism of microvascular complications in hyperglycemia.

Impact of Microplastics on Growth and Lipid Accumulation in Scenedesmus quadricauda

Microplastics (MPs), as frequent pollutants, persist in aquatic environments and have an impact on the growth and biomass production of microalgae. This study employed MPs of polyethylene (PE), polystyrene (PS), and polypropylene (PP) at concentrations of 250 mg/L with MP sizes of 50, 100, 300, and 500 µm to investigate their influences on the growth and bio-production of Scenedesmus quadricauda. The results revealed that MPs suppressed the growth of S. quadricauda and increased algal lipid production. The order of the MPs in terms of their inhibitory and lipid production effect was the following: PP > PS > PE. The order of their size sensitivity was 50 > 100 > 300 > 500 µm. In the 50 µm PP culture, the inhibition of microalgal growth (inhibition rate: 49.26%) and accumulation of lipids (total lipid content: 65.40%) were most significant, especially with neutral lipid content. Additionally, scanning electron microscopy (SEM) and Fourier-transform infrared spectroscopy (FTIR) analyses proved that the rough MP surface led to high aggregation of microalgae, reduced the intensities of the protein-, lipid-, and carbohydrate-related bands and affected the structure of the algal cells.

Strategy to mitigate aggregation during Protein A chromatography and low pH virus inactivation for a nivolumab biosimilar candidate.

Protein A chromatography represents the most prevalent methodology for the capture of monoclonal antibodies. The use of a low pH elution buffer from Protein A has been observed to contribute to product aggregation, particularly in the case of IgG4 antibodies, such as nivolumab. This paper presents a well-defined strategy for addressing this issue. Initial experiments were conducted at scale-down Protein A affinity chromatography to evaluate the use of glycine-HCL and sodium citrate as elution buffers at pH values of 3.25, 3.5, and 3.75. Subsequently, a scale-down screening was conducted to assess the efficacy of various additives in Protein A elution. These included 10 % (w/v) mannitol, 50 mM histidine, 50 mM sucrose, 10 % (v/v) sorbitol, 50 mM arginine, 50 mM trehalose, 0.02 % (v/v) polysorbate 80, 1.5 M urea, and 1 M MgCl2. The three most stabilizing additives were evaluated at the laboratory scale, and the one that demonstrated the greatest ability to maintain the minimum high molecular weight aggregate over time was selected. Lastly, the selected additive was subjected to testing at elevated IgG concentrations during purification. Nivolumab exhibits a markedly pH-dependent propensity for aggregation, and the relative efficacy of glycine-HCL and sodium citrate in mitigating anti-PD1 aggregation within the pH range of 3.25 to 3.75 is subject to variation. The use of buffer 100 mM sodium citrate, pH 3.5 was found to be beneficial. All additives evaluated contribute to reducing nivolumab aggregation, albeit in different ways and to varying degrees of effectiveness. Elution buffer with mannitol, polysorbate 80, or MgCl₂ resulted in a monomer control ratio of approximately twice that observed in the absence of additives. However, the stabilizing role of mannitol was confirmed to be particularly significant, as the ratio of aggregation formed at a low pH was reduced to ≤ 2 % from 15 % in all evaluated scales and at different protein concentrations, while maintaining high biological activity.

Small-area variation in child under-vaccination in India: a multilevel analysis of cross-sectional data from 36 states and Union Territories, 707 districts, and 22,349 small-area clusters

India has made exceptional advances in child immunisation, but subnational inequities in vaccination coverage impede attainment of key programmatic goals. Our study provides an up-to-date national portrait of local variations in child vaccination using a comprehensive set of indicators relevant to routine immunisation. Indicators representing unvaccinated (zero-dose) children, incomplete basic immunisation, and vulnerability to measles and polio, were constructed from India's 2019-2021 National Family Health Survey. We used four-level random effects logistic regression models to partition the total outcome variation over state, district and cluster levels, and produce precision-weighted estimates of prevalence across clusters. District-level prevalence and within-district variation using standard deviation measures were derived for each outcome. Boxplots graphically summarised the distribution of precision-weighted mean cluster prevalence by state. The analysis included 87,622 children aged 12-36 months. Clusters accounted for 67.6% (var: 1.36; SE: 0.127) of the variation among zero-dose children, and more than 50% for all indicators. Districts with a higher prevalence of under-vaccination tended to have higher within-district heterogeneity, interpretable as greater within-district child vaccination inequities. For vaccines administered in the first year of life, the northeastern states and Uttar Pradesh had the highest median under-vaccination. Despite India's high aggregate vaccine coverage, the distribution of small-area (cluster) mean prevalence highlighted pockets of low coverage in most states, suggesting ongoing vulnerability to measles and polio. Achieving India's vaccination goals requires a strategic shift towards identification and targeting of low-immunity clusters at the sub-district level. Canadian Institutes of Health Research.

Temporal control of acute protein aggregate turnover by UBE3C and NRF1-dependent proteasomal pathways

A hallmark of neurodegenerative diseases (NDs) is the progressive loss of proteostasis, leading to the accumulation of misfolded proteins or protein aggregates, with subsequent cytotoxicity. To combat this toxicity, cells have evolved degradation pathways (ubiquitin-proteasome system and autophagy) that detect and degrade misfolded proteins. However, studying the underlying cellular pathways and mechanisms has remained a challenge, as formation of many types of protein aggregates is asynchronous, with individual cells displaying distinct kinetics, thereby hindering rigorous time-course studies. Here, we merge a kinetically tractable and synchronous agDD-GFP system for aggregate formation with targeted gene knockdowns, to uncover degradation mechanisms used in response to acute aggregate formation. We find that agDD-GFP forms amorphous aggregates by cryo-electron tomography at both early and late stages of aggregate formation. Aggregate turnover occurs in a proteasome-dependent mechanism in a manner that is dictated by cellular aggregate burden, with no evidence of the involvement of autophagy. Lower levels of misfolded agDD-GFP, enriched in oligomers, utilizes UBE3C-dependent proteasomal degradation in a pathway that is independent of RPN13 ubiquitylation by UBE3C. Higher aggregate burden activates the NRF1 transcription factor to increase proteasome subunit transcription and subsequent degradation capacity of cells. Loss or gain of NRF1 function alters the turnover of agDD-GFP under conditions of high aggregate burden. Together, these results define the role of UBE3C in degradation of this class of misfolded aggregation-prone proteins and reveals a role for NRF1 in proteostasis control in response to widespread protein aggregation.

PROBIOTIC AND β-LACTAM SENSITIVITY ASSESSMENT OF LACTIC ACID BACTERIA ISOLATED FROM TRADITIONALLY FERMENTED PRODUCTS OF MEGHALAYA

Objective: The present study aimed to isolate, identify, and analyze the probiotic properties and β-lactam sensitivity in the Lactic Acid Bacteria (LAB) prevalent in Tungtap and Lung-seij, common traditionally fermented ethnic products throughout Meghalaya. Methods: Bacterial pure colonies were identified using conventional biochemical tests and 16S rRNA Sanger sequencing. Slightly modified standard protocols were followed for the assessment of different probiotic properties. Results: The selected LAB isolates were found Gram-positive, catalase, and oxidase-negative and exhibited resistance to most of the β-lactam antibiotics used in this study. No significant antibacterial activity was shown against tested strains. However, they showed strong bile salt and acid tolerance, as well as high auto aggregation and moderate hydrophobicity properties, which represent their probiotics properties. Extracellular Polymeric Substances (EPS) yield was highest for the TT2 isolate, while TT10 showed maximal siderophore production. Biofilm formation varied, with BS2 and BS5 showing strong adherence. Sequencing results confirm that the majority of the isolates belonged to the Lactiplantibacillus and Ligilactibacillus genera. Moreover, further genetic analysis confirmed the presence of β-lactamase genes in the selected isolates. Conclusion: The presence of these genes suggests that the isolates may become reservoirs for Antimicrobial Resistance Genes (ARG) in traditional fermented foods. Further study is required to establish whether the isolates are transmitting their antimicrobial resistance genes during co-culture under different stress conditions and transportation.

Enhancing concrete strength and durability through incorporation of rice husk ash and high recycled aggregate

Enhancing concrete strength and durability through incorporation of rice husk ash and high recycled aggregate

Effects of sectoral and aggregate uncertainty on corporate debt structure

PurposeThis paper investigates the differential and interactive effects of sectoral and aggregate uncertainty on the corporate debt structure of credit-constrained and credit-unconstrained firms in India.Design/methodology/approachThe panel fixed-effect model was used to examine the effect of sectoral and aggregate uncertainty on corporate debt structure using annual data of 2,405 firms from 1997 to 2020.FindingsAn increase in sectoral and aggregate uncertainty leads to a greater increase in total and short-term debt and a decrease in long-term debt for credit-constrained firms than in unconstrained ones. However, sectoral uncertainty affects firms’ debt maturity structure more than aggregate uncertainty. Credit-constrained firms use short-term debt to finance capital expenditure during periods of high sectoral uncertainty and working capital requirements during periods of high aggregate uncertainty. When both sectoral and aggregate uncertainty are high, credit-constrained firms decrease total and short-term debt usage more than credit-unconstrained firms do. Our results are robust to a variety of tests, such as different measures of uncertainty, the use of instrument variables and controlling for economic conditions and financial crises.Originality/valueThis study addresses the differential and interactive effects of sectoral and aggregate uncertainty on corporate debt structure.

Umbrella-Shaped m-Terphenyls for Highly π-Extended Planar Dyes toward High-Performance Dye-Sensitized Solar Cells.

Porphyrin dyes with π-extended structures, particularly those with aromatic fused designs, have garnered considerable attention as efficient sensitizers for dye-sensitized solar cells (DCCSs). However, their photovoltaic performance has often been limited due to high aggregation tendencies caused by strong π-π interactions and charge recombination processes. Since m-terphenyls can be used as effective sterically protecting groups, the incorporation of umbrella-shaped m-terphenyls on the top of porphyrin dyes could provide an effective approach to unlock the full potential of highly π-extended porphyrin dyes. In this study, we report new fused porphyrin dyes, T-Ph, T-tBuPh, TT-Ph, and TT-tBuPh, introducing m-terphenyl groups. This innovative design ensures both blocking effects on dye aggregation on TiO2 and charge recombination against redox shuttles. Under the optimized conditions, DSSCs using thiophene-fused porphyrins T-Ph and T-tBuPh achieved a remarkable power conversion efficiency (PCE) of 11.5%. This is high compared to those with reference porphyrins, GY50 possessing steric hindrance due to the orthogonal orientation of a V-shaped diarylamino group to the porphyrin plane and DfZnP without the bulky umbrella-shaped m-terphenyl, demonstrating the proof of our concept. More importantly, the cosensitized DSSC using T-tBuPh and the complementary dye XY1B afforded the highest PCE of 12.3% ever reported for DSSCs with fused porphyrin dyes. This demonstrates that the "umbrella-shaped m-terphenyl" design is an attractive methodology for enhancing the photovoltaic performance of DSSCs with highly π-extended planar dyes, especially fused porphyrin dyes.

Mechanisms behind the changes in zein colloidal composite nanoparticles under different mass ratios and pH conditions

The hydrophobicity of zein (Z) makes it a candidate for encapsulating hydrophobic compounds and stabilizing Pickering emulsions. However, the high aggregation tendency of Z colloidal particles has limited its applications. Using an available and low-cost hydrophilic biopolymer to coat Z colloidal particles is an efficient way to increase their applications. In this work, the aggregation of Z particles was modulated by incorporating Farsi gum (FG), an emerging hydrocolloid with attractive characteristics, into the colloidal particles. Z/water-soluble portion of FG (WFG) particles were fabricated at pH range of 3–7 and 10:1–1:2 mass ratios using an anti-solvent procedure and then characterized. Zeta potential values indicated that in the presence of WFG, the colloidal stability of the particles increased. At higher pH values (pH 7), the Z:WFG (1:1) colloidal particles were smaller than the Z particles. Although WFG incorporation decreased the interfacial adsorption rate of particles due to the higher molecular weight and viscosity of the system, both Z and Z:WFG particles could efficiently reduce interfacial tension. The interfacial layer films developed by Z (pH 4) and Z: WFG (pH 4) particles revealed non-Newtonian and dominant viscouse (G″>G′) characters. This work can help to design Pickering emulsions using alcohol-soluble-based particles.

Screening of a Fraction with Higher Amyloid β Aggregation Inhibitory Activity from a Library Containing 210 Mushroom Extracts Using a Microliter-Scale High-Throughput Screening System with Quantum Dot Imaging.

Alzheimer's disease (AD) is a highly prevalent neurodegenerative disease hallmarked by amyloid plaques and neurofibrillary tangles. Amyloid plaques are formed by the amyloid β (Aβ) aggregation, so substances that inhibit this aggregation are useful for preventing and treating AD. Mushrooms are widely used medicinal fungi with high edible and nutritional value. Mushrooms have a variety of biologically active ingredients, and studies have shown that they have certain effects in anti-bacterial, anti-oxidation, anti-inflammatory, anti-tumor, and immune regulation. Previously, we developed a microliter-scale high-throughput screening (MSHTS) system using quantum dot (QD) nanoprobes to screen Aβ aggregation inhibitors. In this study, we appraised the Aβ aggregation inhibitory activity of 210 natural mushrooms from Hokkaido (Japan) and found 11 samples with high activity. We then selected Elfvingia applanata and Fuscoporia obliqua for extraction and purification as these samples were able to suppress Aβ-induced neurocytotoxicity and were readily available in large quantities. We found that the ethyl acetate (EtOAc) extract of E. applanata has high Aβ aggregation inhibitory activity, so we performed silica gel column chromatography fractionation and found that fraction 5 (f5) of the EtOAc extract displayed the highest Aβ aggregation inhibitory activity among all mushroom samples. The half-maximal effective concentration (EC50) value was 2.30 µg/mL, higher than the EC50 of 10.7 µg/mL for rosmarinic acid, a well-known Aβ aggregation inhibitor. This inhibitory activity decreased with further purification, suggesting that some compounds act synergistically. The f5 fraction also inhibited the deposition of Aβ aggregates on the cell surface of human neuroblastoma SH-SY5Y cells. Our expectation is that f5, with additional tests, may eventually prove to be an inhibitor for the prevention of AD.

(Invited) Development of Fused Porphyrin Sensitizers for Efficient Dye-Sensitized Solar Cells

Dye-sensitized solar cells (DSSCs) have attracted considerable attention as an alternative to silicon-based solar cells due to their potential advantages in terms of power conversion efficiency, production cost, design flexibility, and indoor use. Because the photovoltaic performance of DSSCs strongly depends on sensitizers, various kinds of sensitizers have been developed. Among them, porphyrin sensitizers have made remarkable contribution to performance improvement in DSSCs. The push–pull type porphyrin sensitizers have displayed excellent light-harvesting ability and demonstrated high power conversion efficiencies more than 10% in DSSCs.Meanwhile, incorporation of aromatic-fused structure into a porphyrin core is a fascinating option for highly efficient DSSCs because of direct π-expansion of the porphyrin core and resultant red-shifted absorption. However, aromatic-fused porphyrin sensitizers have suffered rather low cell performances due to their mismatch of HOMO-LUMO levels, high aggregation tendency, and short lifetime of the excited states. Bearing these in mind, we envisioned that the introduction of methylene-bridged fused structure into a porphyrin core would overcome these drawbacks, boosting the cell performance. In this context, we designed and synthesized a series of methylene-bridged thiophene-fused porphyrin sensitizers and revealed that the DSSC of thiophene-fused porphyrin sensitizer achieved the highest power conversion efficiency ever reported for DSSCs with aromatic-fused porphyrin sensitizers. Furthermore, rational molecular design can realize further enhancement of the photovoltaic performance of the DSSCs with thiophene-fused porphyrin sensitizers.

Low-temperature CO2 Hydrogenation to Olefins on Anorthic NaCoFe Alloy Carbides.

The hydrogenation of carbon dioxide to olefins (CTO) represents an ideal pathway towards carbon neutrality. However, most current CTO catalysts require a high-temperature condition of 300-450 °C, resulting in high energy consumption and possible aggregation among active sites. Herein, we developed an efficient iron-based catalyst modified with high-sodium content (7 %) and low-cobalt content (2 %), achieving a CO2 conversion of 22.0 % and an olefin selectivity of 55.9 % at 240 °C and 1000 mL/g/h, and it is even active at 180 °C and 4000 mL/g/h with more than 25 % olefins in hydrocarbons. The catalyst was kept stable under continuous operating conditions of 500 hours. Numerous characterizations and calculations reveal high content of sodium as an electronic promoter enhances the stability of the active anorthic Fe5C2 phase at low temperatures. Further incorporating the above catalyst with cobalt, as a structural promoter, causes Fe species to form a FexCoy alloying phase, which in turn facilitates the formation of higher active anorthic (FexCoy)5C2 phase, different from the conventional carbides and alloy carbides. An in-depth investigation of the synergistic effects of structural and electronic promoters can improve catalyst performance, increase reaction efficiency and cost-effectiveness, and provide profound insights for understanding and optimizing CO2 hydrogenation reactions.

Analysis of Tuberculosis Epidemiological Distribution Characteristics in Fujian Province, China, 2005-2021: Spatial-Temporal Analysis Study.

Tuberculosis (TB) is a chronic infectious disease that harms human health for a long time. TB epidemiological distribution analysis can help governments to control TB in high TB incidence areas. The distribution trend of TB cases varies in different regions. The unbalanced temporal and spatial trends of pulmonary TB (PTB) risk at a fine level in Fujian Province remain unclear. The purpose was to analyze different distribution characteristics, explore the prevalence of TB in this region, and provide a scientific basis for further guidance of TB control work in Fujian Province, China. Prefectural-level and county-level notified PTB case data were collected in Fujian Province. A joinpoint regression model was constructed to analyze the unbalanced temporal patterns of PTB notification rates from 2005 to 2021 at prefecture-level city scales. The spatial clustering analysis and spatial autocorrelation analysis were performed to assess the inequality of the locations of PTB cases. Demographical characteristics were explored by the method of descriptive analysis. TB cases reported in Fujian showed an overall downward trend from 2005 to 2021 (in 2005: n=32,728 and in 2021: n=15,155). TB case numbers showed obvious seasonal changes. The majority of TB cases were middle-aged and older adult male patients (45 years and older; n=150,201, 42.6%). Most of the TB cases were farmers (n=166,186, 47.1%), followed by houseworkers and the unemployed (n=48,828, 13.8%) and workers (n=34,482, 9.8%). Etiologically positive TB cases continue to be the main source of TB cases (n=159,702, 45.3%). Spatially, the reported TB cases were mainly distributed in cities in southeastern Fujian, especially at the county level. TB case numbers showed 2 spatial groups; cases within each group shared similar case characteristics. In terms of geographical distribution, TB showed obvious spatial correlation, and local areas showed high aggregation. The TB incidence trend decreased annually in Fujian Province. TB cases distributed commonly in the male population, middle-aged and older people, and farmers. Etiologically positive cases are still the main source of Mycobacterium tuberculosis infection. TB incidence is higher in the cities with a developed economy and large population in the southeast. TB control should be strengthened in these populations and areas, such as via early screening of cases and management of confirmed cases.

Impact of primary sequence changes on the self-association properties of mammalian cystathionine beta-synthase enzymes.

Cystathionine beta-synthase (CBS) is an evolutionarily conserved enzyme that plays a key role in mammalian sulfur amino acid biochemistry, mutations in which are the cause of classical homocystinuria (HCU), an inborn error of metabolism. Although there is agreement in the literature that CBS is a homomultimer, its precise structure is a source of confusion. Here, we performed a series of experiments examining the quaternary structure of various wild-type and mutant CBS enzymes using a combination of native gel electrophoresis, in situ activity assays, analytical ultracentrifugation, and gel filtration. Our data show that recombinantly expressed and purified full-length wild-type human CBS enzyme (hCBS) and HCU-causing variants (p.P422L, p.I435T, and p.R125Q CBS) form high molecular weight assemblies that are consistent with the properties expected of a filament. The filament is enzymatically active, and its size is sensitive to protein concentration. This behavior contrasts sharply with hCBS enzymes containing small deletions within the Bateman domain, which form stable tetramers and octamers regardless of concentration. Examination of liver lysates from humans and mice confirms the existence of enzymatically active high molecular weight aggregates in vivo, but also shows that these aggregates are specific to human CBS and do not occur in mice. Molecular modeling using AlphaFold2 suggests that these experimentally observed differences may be explained by subtle differences in the interaction mediated by the Bateman domains. Our results show that small differences in amino acid sequence can cause large differences in the size and shape of CBS multimers.

Conjugated oligo (phenylene vinylene) covalently linked porphyrin for sonodynamic therapy

AbstractSonodynamic therapy (SDT) is garnering considerable attention as a promising treatment for deep‐seated tumors because of its strong tissue penetration ability, non‐invasiveness, and controllability. However, the SDT efficiency of traditional sonosensitizers including porphyrins and their derivatives are limited due to their poor water dissolubility, high aggregation, and low reactive oxygen species (ROS) production efficiency. Consequently, it is crucial to develop novel sonosensitizers with high yields of ROS, outstanding water solubility, and good biocompatibility. Herein, we constructed a new platform for SDT based on unimolecular porphyrin derivatives OPV‐C3‐TPP. The probe OPV‐C3‐TPP was synthesized by covalently linking conjugated oligomers (OPV) with 5, 10, 15, 20‐tetra (4‐aminophenyl) porphyrin (TAPP). The introduction of OPV greatly improves the water solubility of the porphyrins and reduces the self‐aggregation of the porphyrins. In addition, OPV‐C3‐TPP has good intramolecular energy transfer efficiency, thus enhancing the yield of ROS. The experimental results show that OPV‐C3‐TPP exhibits excellent ROS generation capacity under ultrasound (US) irradiation, which leads to apoptosis and necrosis of tumor cells. In vivo tumor growth is also significantly inhibited in the OPV‐C3‐TPP + US group, exhibiting better SDT effects than TAPP. Therefore, the unimolecular OPV‐C3‐TPP can be used as a potential sonosensitizer, providing a promising SDT for deep‐tissue tumors.

Structure formation in high moisture extrudates produced from soy protein fractions varying in 7S/11S globulin ratio

Soy proteins mainly comprise 7S and 11S globulins, which have distinct structural and physical properties. To investigate the impact of soy protein composition on structure formation during high moisture extrusion (HME), fractions enriched in 7S or 11S globulins were prepared and blended in different ratios for lab-scale HME processing. Extrudates prepared from the 11S globulin-enriched fraction were inhomogeneous, as opposed to all other extrudates. Differences in extrudate structure and texture by varying the raw material protein composition were limited. However, 11S globulin-enriched fraction based extrudate was mainly stabilized by disulfide bonds, while with increasing raw material 7S globulin content the importance of non-covalent interactions increased. Even after disrupting all (non-)covalent bonds, high MW aggregates were detected in all extrudates. Thus, the protein composition of soy protein ingredients clearly impacts the type of protein-protein interactions and bonds formed during HME processing. This may hold relevance for the occurrence of specific phenomena during HME, such as syneresis, or the digestibility of the obtained products, although this requires further investigation. Overall, the findings of this study have implications for the use of protein-rich ingredients, which may vary in protein composition as the result of biological variability or prior processing, in high moisture extrusion.

Identification of a Hidden, Highly Aggregation-Prone Intermediate of Full-Length TDP-43 That Triggers its Misfolding and Amyloid Aggregation.

In cells, TDP-43 is a crucial protein that can form harmful amyloid aggregates linked to fatal and incurable human neurodegenerative disorders. Normally, TDP-43 exists in a smaller soluble native state that prevents aggregation. However, aging and stress can destabilize this native state, leading to the formation of disease-causing amyloid aggregates via the formation of partially unfolded, high-energy intermediates with a greater tendency to aggregate. These intermediates are crucial in the early stages of amyloid formation and are challenging to study due to their low stability. Understanding the structure of these early aggregation-prone states of TDP-43 is essential for designing effective treatments for TDP-43 proteinopathies. Targeting these initial intermediates could be more effective than focusing on fully formed amyloid aggregates. By disrupting the aggregation process at this early stage, we may be able to prevent the progression of diseases related to TDP-43 aggregation. Hence, we decided to uncover the hidden, high-energy intermediates in equilibrium with the native states of TDP-43 by modulating the thermodynamic stability of the soluble native dimer (N form) and monomeric molten globular state (MG form) of full-length TDP-43. The thermodynamic modulation performed in the current study successfully revealed the highly aggregation-prone intermediate of full-length TDP-43, i.e., PUF. Moreover, we observed that along with high aggregation propensity, the aggregation kinetics and mechanisms of PUF differ from previously identified intermediates of full-length TDP-43 (the MG and I forms). The information regarding the initial aggregation-prone state of full-length TDP-43 could lead to therapies for amyloid diseases by halting early protein aggregation.

Regiospecific Incorporation of Fluorine Atoms in Polythiophene Derivatives for Efficient Organic Solar Cells.

Derivatives of polythiophene (PT) have garnered considerable attention in organic solar cells (OSCs) because of their relatively uncomplicated molecular structures and cost-effective synthesis. Herein, we have developed two regioisomeric fluorinated PT donors, PEI3T-FITVT and PEI3T-FOTVT, to realize efficient OSCs. PEI3T-FITVT and PEI3T-FOTVT are strategically designed with different fluorine atom arrangements on thiophene-vinyl-thiophene (TVT) units. Notably, PEI3T-FOTVT possesses enhanced backbone planarity induced by F···S noncovalent interactions between two constituent building blocks. Consequently, PEI3T-FOTVT with the higher aggregation and crystalline properties leads to a 2.5-fold increase in hole mobility over PEI3T-FITVT (from 1.4 × 10-4 to 3.6 × 10-4 cm2 V-1 s-1). Furthermore, PEI3T-FOTVT exhibits higher domain purity than PEI3T-FITVT, leading to faster charge transport and reduced charge recombination in OSC devices. These characteristics lead to a higher power conversion efficiency of 14.4% for PEI3T-FOTVT-based OSCs, compared to 12.9% for PEI3T-FITVT-based OSCs.

Market-level tenant default risk on residential REIT operational efficiency

ABSTRACT Selecting which geographical markets a REIT serves is an important managerial decision that is expected to significantly impact firm performance. This paper investigates whether holding properties in areas with greater incidence of evictions impacts REIT operational efficiency. Using a comprehensive database of eviction lawsuits in the United States in combination with a time-series of residential REIT portfolio holdings, we construct REIT-year eviction exposure scores to analyse whether more exposure to areas with high aggregate eviction rates is a risk factor affecting REIT efficiency. We posit that market-level tenant default risk captures a locational risk dimension that should be considered in REIT portfolio management. Our results show that REITs with more exposure to markets with high tenant default risk observe higher operational inefficiencies after controlling for relevant firm characteristics and local market factors. These results are robust to multiple model specifications that control for potential endogeneity and omitted variable biases. Our findings have significant implications for REIT managers and investors, suggesting that the choice of property locations should consider aggregate tenant default risk as a determinant factor in residential REIT performance.