Cu(I)-mediated Fenton-like catalytic performance has been extensively explored in chemodynamic therapy (CDT) due to its excellent reactive oxygen species (ROS) production. Integration of its specific Cu(I)-mediated CDT functions with customized aggregation-induced emission (AIE) luminogens to achieve efficient therapeutics and specific bioimaging of tumors is highly desirable but rarely studied. Herein, a novel triphenylamine (TPA)-modified AIE-active ligand and triphenylphosphine (TPP)-coordinated copper(I) complex (denoted as DPB-OD-Cu) was fabricated and accurately characterized. Owing to the restriction of the two rotatable parts of TPA and TPP units to motion in poor and high viscosity solvents, DPB-OD-Cu exhibits strong AIE behavior. Besides, the obtained DPB-OD-Cu exhibited high cytotoxicity and tumor suppression effect due to the conversion of intracellular hydrogen peroxide (H2O2) into cytotoxic hydroxyl radicals (˙OH) in the presence of Cu(I), thereby increasing oxidative stress, leading to the apoptosis of cancer cells. Furthermore, DPB-OD-Cu has shown specific mitochondrial imaging performance in NCI-H460 cancer cells. Therefore, the integration of Cu(I)'s Fenton-like reaction with functional AIEgens will advance the development of cell/subcellular-targeted CDT agents for image-guided therapy, opening new therapeutic opportunities.

Curdlan exhibits diverse biological activities. However, elucidating the structure-activity relationship of curdlan remains challenging owing to its conformational complexity and variability in well-defined systems. This study systematically examines the impact of temperature, sodium hydroxide (NaOH) concentration, and curdlan concentration on the single-helix conformation of curdlan. 1H and 13C nuclear magnetic resonance (NMR) spectroscopy, small-angle X-ray scattering, gel permeation chromatography, and dynamic light scattering analyses confirm that the single-helix conformation of curdlan is successfully formed in dilute (0.15 M-0.24 M) NaOH solutions within the temperature range of 35 °C-50 °C, whereas partial conversion to aggregated or mixed helical structures occurs at lower temperatures (5 °C-25 °C). 23Na NMR parameter variations reveal direct Na+ interactions with the random-coil or single-helix conformations of curdlan. NMR and ultraviolet-visible absorption spectroscopy experiments confirm that the single-helix structure of curdlan facilitates stable encapsulation of Congo red via supramolecular assembly at 35 °C-50 °C. This study provides new insights into the conformation-activity relationships of β-(1,3)-glucans.

Ramped heating from 50 °C to 90 °C was applied to elucidate how temperature regulates the gelation behavior and hydrogel properties of myofibrillar proteins-capsaicin (MPs-CAP) blends. The hydrogels were characterized in terms of macroscopic properties, water status, microstructure, intermolecular forces, and rheological behavior. The results showed non-monotonic trends in whiteness, hardness, springiness, and water-holding capacity, with an initial increase followed by a decrease as temperature rose, and optimal performance was observed at 70 °C. At 50-70 °C, heating unfolded MPs and facilitated the integration of CAP through hydrophobic interactions, which likely reinforced the network structure. CAP appeared to participate in network formation; this association, in combination with hydrogen bonding, created a dense and uniform three-dimensional network. This network converted free water into immobilized water via capillary effects, endowing the hydrogels with favorable water-holding capacity and thermal stability (Tp = 138.33 °C). Above 70 °C, excessive and disordered aggregation of MPs, along with increased release of CAP, was accompanied by pore enlargement, implying possible dissociation of CAP from the network. These results reveal the non-monotonic temperature-dependent behavior of MPs-CAP gelation, providing a theoretical basis for precise thermal processing of protein gels containing hydrophobic bioactive ingredients.

The upregulation of vascular cell adhesion molecule-1 (VCAM-1) by the transcription factor GATA-6 during inflammation of the brain is a key contributor to neuronal injury. Silencing GATA-6 expression in brain endothelial cells may provide an avenue for ameliorating blood-brain barrier (BBB) inflammation and slowing neurodegeneration. Cationic bicelles composed of DPPC/DC7PC/DOTAP at a molar ratio of 63.8/25.0/11.2 were designed for the targeted delivery of GATA-6 siRNA to the BBB. However, formulation processes such as sonication or lyophilization introduce stresses that may impact the structural stability of the bicelles and therapeutic efficacy of the siRNA cargo. Therefore, these processes must be optimized. A sonication time of 3 min was sufficient for achieving a narrow particle size distribution without mechanically damaging the siRNA. A trehalose concentration of 10% w/v was effective at protecting the siRNA-bicelle complexes from particle aggregation and loss of silencing efficiency after 3 cycles of freeze-thaw. By contrast, a sucrose concentration of 5% w/v was only able to protect the siRNA-bicelle complexes from particle aggregation. Moreover, the addition of sucrose partially hindered the cellular uptake of cationic bicelles in polarized human cerebral microvascular endothelial cell (hCMEC/D3) monolayers, suggesting that it is an inappropriate cryoprotectant for cationic bicelles. Optimization of these formulation parameters for siRNA-bicelle complexes contributes towards their efficacy during delivery and stability during storage, which are critical factors to consider in a clinical setting. Thus, these findings will aid in the translation of siRNA-loaded cationic bicelles from the bench to the bedside.

Impacts of wheat bran albumin (WBA) upon dough rheological properties alongside Chinese steamed bread quality were investigated, with emphasis on its interactions with gluten proteins and gluten network formation. WBA reduced dough viscoelasticity while significantly enhancing extensibility up to 85% with only 0.6% WBA addition, resulting in a 28.4% increase in specific volume of steamed bread. Molecular structure analysis revealed WBA induced gluten protein disaggregation by disrupting disulfide bonds in glutenin, and concomitantly promoted the aggregation through newly formed disulfide bonds and dityrosine cross-links involving gliadin subunits. These corresponded well with the increased endpoints rate and junction density of gluten network. At WBA addition ≤0.6%, protein aggregation predominated, accompanied by synergistically enhanced hydrophobic and hydrogen bonds interactions, together with super alterations in protein secondary and tertiary conformations. Overall, WBA, as a non-gluten protein, exhibited strong potential to regulate gluten network structure and improve flour processing performance.

Previous genome-wide association studies have identified more than 400 prostate cancer (PCa) susceptibility loci. However, the tissue and spatial epithelial contexts through which inherited PCa risk may operate in the normal prostate remain incompletely understood. We analyzed normal human prostate spatial transcriptomic data using a gsMap-based framework to localize PCa association signals across spatially resolved prostate compartments. Spatial spots were clustered using SpaGCN and then manually curated and annotated based on matched histological images and canonical prostate marker gene expression. Because individual spatial spots may contain multiple cells, annotations were interpreted as compartment-enriched dominants rather than pure cell-type identities. PCa genetic association scores were aggregated within annotated compartments using Cauchy-combined p value and median spot-level p value as a complementary descriptive summary. Gene-level spatial correspondence was further assessed using Pearson correlation coefficients (PCCs) between gene-expression patterns and spot-level PCa gsMap signal. We annotated normal prostate tissue into four major compartments: basal epithelium-enriched, luminal epithelium-enriched, smooth muscle-enriched, and fibroblast stroma-enriched compartments. Basal epithelium-enriched compartments showed the strongest and most consistent enrichment for PCa association, with a Cauchy-combined p of 1.85 × 10-8 and a median spot-level based p of 3.67 × 10-7. Luminal epithelium-enriched compartments also showed strong enrichment, with a Cauchy p of 3.79 × 10-7 and a median-based p of 1.45 × 10-6. In contrast, fibroblast stroma-enriched compartments showed no evidence of enrichment (Cauchy p = 0.52; median p = 0.42), while smooth muscle-enriched compartments showed only modest evidence in the Cauchy-based analysis that was accompanied by a weaker median spot-level association signal (Cauchy p = 8.95 × 10-4; median p = 0.18). PCC analysis showed that genes with the strongest spatial correspondence to PCa gsMap signal were predominantly epithelial-associated, including CDH1, VAMP8, GMNN, TSPAN1, and FOXA1. In normal human prostate tissue, inherited PCa association localizes preferentially to basal epithelium-enriched and luminal epithelial-enriched compartments rather than to smooth muscle-enriched or fibroblast stroma-enriched compartments. Gene-level PCC patterns further support spatial alignment between PCa-associated gsMap signal and epithelial transcriptional programs. These findings provide proof-of-concept evidence for the spatial localization of inherited PCa susceptibility through the integration of large-scale population-based genetic data and spatial transcriptomics.

A common goal of longitudinal research in psychology and related disciplines is the study of causal effects over time. An often overlooked assumption in this context is temporal alignment, referring to a match between the timescale at which a longitudinal process operates, the timescale at which data were collected, and the time frame in measurements. We present multiple scenarios, representing both the analysis of intensive longitudinal data and panel data, in which this assumption is violated due to time aggregation (i.e., aggregating scores over multiple occasions) and/or systematic undersampling (i.e., measurement intervals that are too long in relation to the longitudinal process). Our simulations demonstrate the large biases that can occur in estimates of lag-0 and lag-1 effects using various modeling approaches, even when there is no effect in the data. We discuss implications of these results and briefly consider future lines of methodological research to address this problem.

Acute painful vaso-occlusive episodes (VOEs) are the primary reason for emergency department visit by sickle cell disease (SCD) patients and contribute to significant morbidity in SCD. Crizanlizumab, a first-in-class humanized anti-P-selectin IgG2 monoclonal antibody, is approved in more than 40 countries for prevention of VOEs in 16 years or older SCD patients. Inclacumab, a fully human anti-P-selectin IgG4 mAb in clinical development is believed to have stronger affinity to P-selectin and greater maximal inhibition of cell-cell interactions than crizanlizumab. Using in vitro blinded experiments, we investigated whether crizanlizumab and inclacumab can be differentiated in terms of P-selectin binding affinity and inhibition of P-selectin-mediated cell adhesion in blood samples from healthy volunteers or SCD patients. Surface Plasmon Resonance revealed that inclacumab had higher P-selectin binding affinity than crizanlizumab, however, the inhibition of P-selectin-mediated cell adhesion was higher or comparable with crizanlizumab than inclacumab. Crizanlizumab and inclacumab were comparable in inhibiting leukocyte and erythrocyte adhesion to P-selection under vascular mimetic flow in microfluidic channels, leukocyte-platelet aggregation, and platelet aggregation in SCD patient or control human blood. In summary, these results suggest that comparable or higher inhibition of cell adhesion with crizanlizumab vs inclacumab does not correlate with P-selectin binding affinity. Ultimately, clinical trials are required to evaluate how crizanlizumab vs inclacumab translate into treatment outcomes in SCD patients.

The compressible Euler-Riesz equations are fundamental with wide applications in astrophysics, plasma physics, and mathematical biology. In this paper, we are concerned with the global existence and nonlinear stability of finite-energy solutions of the multidimensional Euler-Riesz equations with large initial data of spherical symmetry. We consider both attractive and repulsive interactions for a wide range of Riesz and logarithmic potentials for dimensions larger than or equal to two. This is achieved by the inviscid limit of the solutions of the corresponding Cauchy problem for the Navier-Stokes-Riesz equations. The strong convergence of the vanishing viscosity solutions is achieved through delicate uniform estimates in L p . It is observed that, even if the attractive potential is super-Coulomb, no concentration is formed near the origin in the inviscid limit. Moreover, we prove that the nonlinear stability of global finite-energy solutions for the Euler-Riesz equations is unconditional under a spherically symmetric perturbation around the steady solutions. Unlike the Coulomb case where the potential can be represented locally, the singularity and regularity of the nonlocal radial Riesz potential near the origin require careful analysis, which is a crucial step. We also establish uniform energy estimates of global solutions for not only the Riesz potential but also the limiting end-point case: the logarithmic potential. Finally, unlike the Coulomb case, a Grönwall type estimate is required to overcome the difficulty of the appearance of boundary terms in the sub-Coulomb case and the singularity of the super-Coulomb potential. Furthermore, we prove the nonlinear stability of global finite-energy solutions for the compressible Euler-Riesz equations around steady states by employing concentration compactness arguments. Steady states properties are obtained by variational arguments connecting to recent advances in aggregation-diffusion equations.

Understanding how small molecules modulate protein aggregation is pivotal for developing strategies against amyloid-related disorders. Polyphenols are promising modulators, yet the connection between their molecular photophysics and aggregation inhibition remains largely unresolved. In this article, femtosecond transient absorption spectroscopy has been employed to unravel the excited-state dynamics of some commonly used polyphenols, namely, Baicalein, EGCG, and Myricetin across varied environments-neat solvents, micelles and reverse micelles, and in the presence of globular and intrinsically disordered protein (in its native and aggregated forms). Excited-state intramolecular proton transfer (ESIPT) emerges to be highly sensitive to hydrogen-bonding, polarity, and local confinement, serving as a subpicosecond reporter of polyphenol-environment interactions. In protein systems, modulation of ESIPT dynamics signals environment-specific embedding of polyphenols within evolving protein landscapes. A unique tri-parameter correlation-linking binding affinities of the polyphenols to the native proteins, ESIPT lifetimes, and aggregation kinetics-reveals that inhibitory potency arises not from tight native binding but from selective engagement with aggregation-prone species. This work posits ESIPT as a sensitive molecular signature that links ultrafast photophysics to the functional inhibition of protein aggregation, providing new insights into how small molecules navigate complex biomolecular environments to regulate self-assembly pathways.

A 3-y-old rooster was submitted for postmortem evaluation following a 4-mo history of progressive ulcerative dermatitis affecting the right hock. Autopsy revealed 6 bilateral, discrete globoid masses along the caudoventral cervical musculature and extending into the proximal celomic cavity. Histologically, a neoplasm effaced and/or compressed residual thymic parenchyma and consisted of ill-defined aggregates of 2-3 primordial germ cell lineages (ectoderm, mesoderm, endoderm). Immunohistochemical and histochemical stains, including desmin, glial fibrillary acidic protein, pancytokeratin, and phosphotungstic acid hematoxylin, confirmed the presence of heterogeneous germ cell tissues, consistent with an extragonadal teratoma. Extragonadal teratomas are rare in non-human species, particularly in avian species, and reports of mediastinal involvement are limited. In our case, the teratoma was an incidental finding; the primary reason for submission was progressive necroulcerative bacterial dermatitis affecting the right leg.