Search Results (384)

The encapsulation of bioactive compounds using proteins as wall materials has emerged as an effective strategy to enhance their stability, bioavailability, and controlled release. Proteins offer unique functional properties, including amphiphilic behavior, gel-forming ability, and interactions with bioactives, making them ideal candidates for encapsulation. Animal-derived proteins, such as whey and casein, exhibit superior performance in stabilizing lipophilic compounds, whereas plant proteins, including soy and pea protein, demonstrate greater affinity for hydrophilic bioactives. Advances in protein modification and the formation of protein–polysaccharide complexes have further improved encapsulation efficiency, particularly for heat- and pH-sensitive compounds. This review explores the physicochemical characteristics of proteins used in encapsulation, the interactions between proteins and bioactives, and the main encapsulation techniques, including spray drying, complex coacervation, nanoemulsions, and electrospinning. Furthermore, the potential applications of encapsulated bioactives in functional foods, pharmaceuticals, and nutraceuticals are discussed, highlighting the role of emerging technologies in optimizing delivery systems. Understanding the synergy between proteins, bioactives, and encapsulation methods is essential for developing more stable, bioavailable, and sustainable functional products. Full article

A novel brain positron emission tomography (PET) radioligand, [¹¹C]HY-2-15, has potential for imaging alpha-synuclein aggregations in multiple system atrophy and misfolded tau proteins in tauopathies, based on its high binding affinity in disease brain tissue homogenates. Here, we demonstrate that [³H]HY-2-15 has the capability to bind to aggregated alpha-synuclein in multiple system atrophy brain and tau aggregations in progressive supranuclear palsy and corticobasal degeneration brain tissues via in vitro autoradiography study. A first-in-human pilot multicenter clinical study recruited a total of 10 subjects including healthy controls and patients with Parkinson’s disease, multiple system atrophy, or progressive supranuclear palsy. The study revealed that [¹¹C]HY-2-15 has a relatively higher specific uptake in the pallidum and midbrain of patients with progressive supranuclear palsy. Total-body scans performed on the PennPET Explorer showed the radiotracer was cleared by renal excretion. However, the rapid metabolism and low brain uptake resulted in a limited signal of [¹¹C]HY-2-15 in brain. Full article

Background/Objectives: Opioid use disorder (OUD) remains a severe health problem globally, resulting in substantial social and economic challenges. While existing medications for managing OUD are proven to be effective, they also present certain challenges. A vaccine offers a promising therapeutic strategy to combat OUD and potentially reduce the risk of overdose death. The TT-6-AmHap heroin conjugate vaccine has effectively reduced heroin-induced pharmacological effects in behavioral assays as well as demonstrated the induction of high titer and high affinity antibody responses in mice and rats. In this GLP study conducted in rabbits, the potential local and systemic toxicity of the TT-6-AmHap heroin vaccine in combination with or without adjuvants ALF43 and Alhydrogel^® (ALFA) was investigated. Methods: Male and female New Zealand White rabbits were administered with vaccines or a saline control intramuscularly at two-week intervals over a 57-day study period. The presence, persistence or reversibility of any toxic effects of the vaccine was determined over a four-week recovery period. Results: Administration of TT-6-AmHap with or without the adjuvants induced high antibody-specific IgG in treatment groups compared to the controls. The study found no TT-6-AmHap-related effects on mortality, physical examinations, dermal Draize observations, body weights, body weight changes, food consumption, ophthalmology, clinical pathology (hematology, coagulation, clinical chemistry, and urinalysis), macroscopic pathology, or organ weights. Conclusions: Under the conditions of this study, these results demonstrate that the TT-6-AmHap vaccine with or without adjuvants was well tolerated, immunogenic, and the effects were not considered adverse in both male and female rabbits. Full article

Background: Sodium–glucose cotransporter 2 (SGLT2) inhibitors have transformed type 2 diabetes mellitus (T2DM) management by promoting glucosuria, lowering glycated hemoglobin (HbA1c), blood pressure, and weight; however, their use is limited by genitourinary infections and ketoacidosis. Phytocannabinoids—bioactive compounds from Cannabis sativa—exhibit multi-target pharmacology, including interactions with cannabinoid receptors, Peroxisome Proliferator-Activated Receptors (PPARs), Transient Receptor Potential (TRP) channels, and potentially SGLT2. Objective: To evaluate the potential of phytocannabinoids as novel modulators of renal glucose reabsorption via SGLT2 and to compare their efficacy, safety, and pharmacological profiles with synthetic SGLT2 inhibitors. Methods: We performed a narrative review encompassing the following: (1) the molecular and physiological roles of SGLT2; (2) chemical classification, natural sources, and pharmacokinetics/pharmacodynamics of major phytocannabinoids (Δ⁹-Tetrahydrocannabinol or Δ⁹-THC, Cannabidiol or CBD, Cannabigerol or CBG, Cannabichromene or CBC, Tetrahydrocannabivarin or THCV, and β-caryophyllene); (3) in silico docking and drug-likeness assessments; (4) in vitro assays of receptor binding, TRP channel modulation, and glucose transport; (5) in vivo rodent models evaluating glycemic control, weight change, and organ protection; (6) pilot clinical studies of THCV and case reports of CBD/BCP; (7) comparative analysis with established synthetic inhibitors. Results: In silico studies identify high-affinity binding of several phytocannabinoids within the SGLT2 substrate pocket. In vitro, CBG and THCV modulate SGLT2-related pathways indirectly via TRP channels and CB receptors; direct IC₅₀ values for SGLT2 remain to be determined. In vivo, THCV and CBD demonstrate glucose-lowering, insulin-sensitizing, weight-reducing, anti-inflammatory, and organ-protective effects. Pilot clinical data (n = 62) show that THCV decreases fasting glucose, enhances β-cell function, and lacks psychoactive side effects. Compared to synthetic inhibitors, phytocannabinoids offer pleiotropic benefits but face challenges of low oral bioavailability, polypharmacology, inter-individual variability, and limited large-scale trials. Discussion: While preclinical and early clinical data highlight phytocannabinoids’ potential in SGLT2 modulation and broader metabolic improvement, their translation is impeded by significant challenges. These include low oral bioavailability, inconsistent pharmacokinetic profiles, and the absence of standardized formulations, necessitating advanced delivery system development. Furthermore, the inherent polypharmacology of these compounds, while beneficial, demands comprehensive safety assessments for potential off-target effects and drug interactions. The scarcity of large-scale, well-controlled clinical trials and the need for clear regulatory frameworks remain critical hurdles. Addressing these aspects is paramount to fully realize the therapeutic utility of phytocannabinoids as a comprehensive approach to T2DM management. Conclusion: Phytocannabinoids represent promising multi-target agents for T2DM through potential SGLT2 modulation and complementary metabolic effects. Future work should focus on pharmacokinetic optimization, precise quantification of SGLT2 inhibition, and robust clinical trials to establish efficacy and safety profiles relative to synthetic inhibitors. Full article

Background/Objectives: PEGylated liposomes are widely recognized for their biocompatibility and capacity to extend systemic circulation via “stealth” properties. However, the PEG corona often limits tumor penetration and cellular internalization. Targeting matrix metalloproteinase-2 (MMP-2), frequently upregulated in breast cancer stroma, presents an opportunity to enhance tissue-specific drug delivery. In this study, we engineered MMP-2-responsive GPLGVRG peptide-modified cleavable PEGylated liposomes for targeted paclitaxel (PTX) delivery. Methods: Molecular docking simulations employed the MMP-2 crystal structure (PDB ID: 7XJO) to assess GPLGVRG peptide binding affinity. A cleavable, enzyme-sensitive peptide-PEG conjugate (Chol-PEG_2K-GPLGVRG-PEG_5K) was synthesized via small-molecule liquid-phase synthesis and characterized by ¹H NMR and MALDI-TOF MS. Liposomes incorporating this conjugate (S-Peps-PEG_5K) were formulated to evaluate whether MMP-2-mediated peptide degradation triggers detachment of long-chain PEG moieties, thereby enhancing internalization by 4T1 breast cancer cells. Additionally, the effects of tumor microenvironmental pH (~6.5) and MMP-2 concentration on drug release dynamics were investigated. Results: Molecular docking revealed robust GPLGVRG-MMP-2 interactions, yielding a binding energy of −7.1 kcal/mol. The peptide formed hydrogen bonds with MMP-2 residues Tyr A:23 and Arg A:53 (bond lengths: 2.4–2.5 Å) and engaged in hydrophobic contacts, confirming MMP-2 as the primary recognition site. Formulations containing 5 mol% Chol-PEG_2K-GPLGVRG-PEG_5K combined with 0.15 µg/mL MMP-2 (S-Peps-PEG_5K +MMP) exhibited superior internalization efficiency and significantly reduced clonogenic survival compared to controls. Notably, acidic pH (~6.5) induced MMP-2-mediated cleavage of the GPLGVRG peptide, accelerating S-Peps-PEG_5K dissociation and facilitating drug release. Conclusions: MMP-2-responsive, cleavable PEGylated liposomes markedly improve PTX accumulation and controlled release at tumor sites by dynamically modulating their stealth properties, offering a promising strategy to enhance chemotherapy efficacy in breast cancer. Full article

Atopic dermatitis (AD) is a chronic, multifactorial inflammatory skin disease characterized by persistent pruritus, immune system dysregulation, and an increased expression of cyclooxygenase-2 (COX-2), an enzyme that plays a central role in the production of prostaglandins and the promotion of inflammatory responses. In this study, we employed a comprehensive computational pipeline to identify phytocompounds capable of inhibiting COX-2 activity, offering an alternative to traditional non-steroidal anti-inflammatory drugs. The African and Traditional Chinese Medicine natural product databases were subjected to molecular screening, which identified six top compounds, namely, Tophit1 (−16.528 kcal/mol), Tophit2 (−10.879 kcal/mol), Tophit3 (−9.760 kcal/mol), Tophit4 (−9.752 kcal/mol), Tophit5 (−8.742 kcal/mol), and Tophit6 (−8.098 kcal/mol), with stronger binding affinities to COX-2 than the control drug rofecoxib (−7.305 kcal/mol). Molecular dynamics simulations over 200 ns, combined with MM/GBSA binding free energy calculations, consistently identified Tophit1 and Tophit2 as the most stable complexes, exhibiting exceptional structural integrity and a strong binding affinity to the target protein. ADMET profiling via SwissADME and pkCSM validated the drug-likeness, oral bioavailability, and safety of the lead compounds, with no Lipinski rule violations and favorable pharmacokinetic and toxicity profiles. These findings underscore the therapeutic potential of the selected phytocompounds as novel COX-2 inhibitors for the management of atopic-prone skin and warrant further experimental validation. Full article

We explore chaos, local dynamics, codimension-one, and codimension-two bifurcations of an asymmetric discrete predator–prey model. More precisely, for all the model’s parameters, it is proved that the model has two boundary fixed points and a trivial fixed point, and also under parametric conditions, it has an interior fixed point. We then constructed the linearized system at these fixed points. We explored the local behavior at equilibria by the linear stability theory. By the series of affine transformations, the center manifold theorem, and bifurcation theory, we investigated the detailed codimensions-one and two bifurcations at equilibria and examined that at boundary fixed points, no flip bifurcation exists. Furthermore, at the interior fixed point, it is proved that the discrete model exhibits codimension-one bifurcations like Neimark–Sacker and flip bifurcations, but fold bifurcation does not exist at this point. Next, for deeper understanding of the complex dynamics of the model, we also studied the codimension-two bifurcation at an interior fixed point and proved that the model exhibits the codimension-two 1:2, 1:3, and 1:4 strong resonances bifurcations. We then investigated the existence of chaos due to the appearance of codimension-one bifurcations like Neimark–Sacker and flip bifurcations by OGY and hybrid control strategies, respectively. The theoretical results are also interpreted biologically. Finally, theoretical findings are confirmed numerically. Full article

Ensuring the resilient navigation of unmanned aerial vehicles (UAVs) under conditions of limited or unstable sensor information is one of the key challenges of modern autonomous mobility within smart infrastructure and sustainable development. This article proposes an intelligent autonomous UAV control method based on the integration of geometric trajectory modeling, neural network-based sensor data filtering, and reinforcement learning. The geometric model, constructed using path coordinates, allows the trajectory tracking problem to be formalized as an affine control system, which ensures motion stability even in cases of partial data loss. To process noisy or fragmented GPS and IMU signals, an LSTM-based recurrent neural network filter is implemented. This significantly reduces positioning errors and maintains trajectory stability under environmental disturbances. In addition, the navigation system includes a reinforcement learning module that performs real-time obstacle prediction, path correction, and speed adaptation. The method has been tested in a simulated environment with limited sensor availability, variable velocity profiles, and dynamic obstacles. The results confirm the functionality and effectiveness of the proposed navigation system under sensor-deficient conditions. The approach is applicable to environmental monitoring, autonomous delivery, precision agriculture, and emergency response missions within smart regions. Its implementation contributes to achieving the Sustainable Development Goals (SDG 9, SDG 11, and SDG 13) by enhancing autonomy, energy efficiency, and the safety of flight operations. Full article

This paper presents a novel adaptive twisting sliding mode control strategy combined with a speed-sensorless cascade nonlinear observer for the high-performance control of linear induction motors (LIMs). The primary objective is to achieve accurate speed and rotor flux tracking without relying on mechanical sensors, thereby enhancing system reliability and reducing hardware complexity. For this purpose, a cascade nonlinear observer is designed and applied to the class of nonlinear affine systems representing LIM dynamics. Based on the interconnected form of the LIM mathematical model, the observer simultaneously reconstructs both the motor speed and rotor fluxes in real time. The stability of the proposed cascade observer is analyzed using Lyapunov theory, ensuring the convergence of the estimation errors under bounded disturbances. Complementing the observer, two adaptive gain twisting sliding mode controllers are developed: one for speed tracking and another for flux regulation. These controllers are robust against external disturbances and parameter uncertainties, even when the bounds of such disturbances are unknown. This feature significantly enhances the practical applicability of the control system in real-world industrial environments. To validate the performance and robustness of the proposed control scheme, a hardware-in-the-loop (HIL) experiment was conducted. Comparative studies with existing state-of-the-art sensorless control methods demonstrate that the proposed cascade nonlinear observer-based approach achieves faster convergence, higher estimation accuracy, and better disturbance rejection capabilities, while requiring less computational effort. Full article

The tomato leaf miner, Tuta absoluta (Lepidoptera: Gelechiidae), is a destructive pest of Solanaceae crops worldwide. Its olfactory system plays an important role in locating mating partners and recognizing host plants. Understanding its olfactory recognition mechanism, particularly the function of odorant-binding proteins (OBPs), may reveal potential targets for pest management. In this study, we characterized two antenna-specific OBPs, TabsOBP45 and TabsOBP46, which were identified from the T. absoluta genome. Sequence analysis revealed that both TabsOBPs belong to the classic OBP subfamily, which is characterized by the presence of six conserved cysteine residues and an N-terminal signal peptide. Both TabsOBPs showed predominant antennal expression in quantitative real-time PCR (qRT-PCR) assays, suggesting their key roles in olfactory perception. Fluorescence competitive binding assays with a total of 63 tested volatiles revealed that 13 compounds exhibited strong binding affinities (Ki < 22 µM) to TabsOBP45, with the highest binding affinity to β-ionone, β-caryophyllene, terpinolene, and cinnamaldehyde. Nine compounds showed strong binding affinities to TabsOBP46, with the strongest binding to 4-anisaldehyde, 4-methoxybenzaldehyde, cinnamaldehyde, and β-ionone. Molecular docking analysis revealed the key residues involved in β-ionone binding: TabsOBP45 interacted with ILE8, ALA9, PHE12, TRP37, ILE92, PHE94, THR115, and PHE118, while TabsOBP46 interacted with ILE8, PHE12, PHE36, TRP37, ILE92, LEU94, PHE118, and VAL134. These results provide new insights into the olfactory mechanism of T. absoluta and potential molecular targets for the development of olfactory-based pest control strategies. Full article

Aluminum, boron, and titanium microalloyed into high-strength low-alloy boron steel exhibit a complex interplay, competing for nitrogen, with titanium demonstrating the highest affinity, followed by boron and aluminum. This competition affects the formation and distribution of nitrides, impacting the microstructure and mechanical properties of the steel. Titanium protects boron from forming BN and facilitates the nucleation of acicular ferrite, enhancing toughness. The segregation of boron to grain boundaries, rather than its precipitation as boron nitride, promotes the formation of martensite and thus the through-hardenability. Aluminum nitride is critical in controlling grain size through a pronounced pinning effect. In this study, we employ energy- and wavelength-dispersive X-ray spectroscopy and computer-aided particle analysis to analyze the phase content of 12 high-purity vacuum induction-melted samples. The primary objective of this study is to correctly describe the microstructural evolution in the Fe-Al-B-Ti-C-N system using the Calphad approach, with special emphasis on correctly predicting the dissolution temperatures of nitrides. A multicomponent database is constructed through the incorporation of available binary and ternary descriptions, employing the Calphad approach. The experimental findings regarding the solvus temperature of the involved nitrides are employed to validate the accuracy of the thermodynamic database. The findings offer a comprehensive understanding of the relative phase stabilities and the associated interplay among the involved elements Al, B, and Ti in the Fe-rich corner of the system. The type and size distribution of the stable nitrides in microalloyed steel have been demonstrated to exert a substantial influence on the properties of the material, thereby rendering accurate predictions of phase stabilities of considerable relevance. Full article

Objective: This study aims to elucidate the potential mechanisms by which Fespixon cream promotes diabetic foot ulcer (DFU) healing using network pharmacology, molecular docking, and RT-qPCR validation in clinical tissue samples. Methods: Active components of Fespixon cream were screened from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and relevant literature, and their corresponding targets were standardized using the Universal Protein Resource (UniProt) database. Diabetic foot ulcer (DFU)-related targets were retrieved and filtered from the GeneCards database and the Online Mendelian Inheritance in Man (OMIM) database. The intersection of drug and disease targets was identified, and a protein–protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. The interaction network was visualized using Cytoscape version 3.7.2 software. The potential mechanisms of the shared targets were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis using R software packages, and results were visualized through Bioinformatics online tools. Molecular docking was performed to validate the binding between key active compounds of Fespixon cream and core DFU targets using AutoDock Vina version 1.1.2 and PyMOL software. Furthermore, RT-qPCR analysis was performed on wound edge tissue samples from DFU patients treated with Fespixon cream to experimentally verify the mRNA expression levels of predicted hub genes. Results: Network pharmacology analysis identified eight active compounds in Fespixon cream, along with 153 potential therapeutic targets related to diabetic foot ulcer (DFU). Among these, 21 were determined as core targets, with the top five ranked by degree value being RAC-αserine/threonine-protein kinase (AKT1), Cellular tumor antigen p53 (TP53), Tumor necrosis factor (TNF), Interleukin-6 (IL6), and Mitogen-activated protein kinase 1 (MAPK1). GO enrichment analysis indicated that the targets of Fespixon cream were primarily involved in various biological processes related to cellular stress responses. KEGG pathway enrichment revealed that these targets were significantly enriched in pathways associated with diabetic complications, atherosclerosis, inflammation, and cancer. Molecular docking confirmed stable binding interactions between the five major active compounds—quercetin, apigenin, rosmarinic acid, salvigenin, and cirsimaritin—and the five core targets (AKT1, TP53, TNF, IL6, MAPK1). Among them, quercetin exhibited the strongest binding affinity with AKT1. RT-qPCR validation in clinical DFU tissue samples demonstrated consistent expression trends with computational predictions: AKT1 was significantly upregulated, while TP53, TNF, IL6, and MAPK1 were markedly downregulated in the Fespixon-treated group compared to controls (p < 0.001), supporting the proposed multi-target therapeutic mechanism. Conclusions: Our study reveals the potential mechanisms by which Fespixon cream exerts therapeutic effects on DFUs. The efficacy of Fespixon cream in treating DFUs is attributed to the synergistic actions of its bioactive components through multiple targets and multiple signaling pathways. Full article

This study aimed to design dual-responsive chitosan–polylactic acid nanosystems (PLA@CS NPs) for controlled and targeted ledipasvir (LED) delivery to HepG2 liver cancer cells, thereby reducing the systemic toxicity and improving the therapeutic selectivity. Two formulations were developed utilizing ionotropic gelation and w/o/w emulsion techniques: LED@CS NPs with a size of 143 nm, a zeta potential of +43.5 mV, and a loading capacity of 44.1%, and LED-PLA@CS NPs measuring 394 nm, with a zeta potential of +33.3 mV and a loading capacity of 89.3%, with the latter demonstrating significant drug payload capacity. Since most drugs work through interaction with DNA, the in vitro affinity of DNA to LED and its encapsulated forms was assessed using stopped-flow and other approaches. They bind through multi-modal electrostatic and intercalative modes via two reversible processes: a fast complexation followed by a slow isomerization. The overall binding activation parameters for LED (cordination affinity, K_a = 128.4 M⁻¹, K_d = 7.8 × 10⁻³ M, ΔG = −12.02 kJ mol⁻¹), LED@CS NPs (K_a = 2131 M⁻¹, K_d = 0.47 × 10⁻³ M, ΔG = −18.98 kJ mol⁻¹) and LED-PLA@CS NPs (K_a = 22026 M⁻¹, K_d = 0.045 × 10⁻³ M, ΔG = −24.79 kJ mol⁻¹) were obtained with a reactivity ratio of 1/16/170 (LED/LED@CS NPs/LED-PLA@CS NPs). This indicates that encapsulation enhanced the interaction between the DNA and the LED-loaded nanoparticle systems, without changing the mechanism, and formed thermodynamically stable complexes. The drug release kinetics were assessed under tumor-mimetic conditions (pH 5.5, 10 mM GSH) and physiological settings (pH 7.4, 2 μM GSH). The LED@CS NPs and LED-PLA@CS NPs exhibited drug release rates of 88.0% and 73%, respectively, under dual stimuli over 50 h, exceeding the release rates observed under physiological conditions, which were 58% and 54%, thereby indicating that the LED@CS NPs and LED-PLA@CS NPs systems specifically target malignant tissue. Release regulated by Fickian diffusion facilitates tumor-specific payload delivery. Although encapsulation did not enhance the immediate cytotoxicity compared to free LED, as demonstrated by an in vitro cytotoxicity in HepG2 cancer cell lines, it significantly enhanced the therapeutic index (2.1-fold for LED-PLA@CS NPs) by protecting non-cancerous cells. Additionally, the nanoparticles demonstrated broad-spectrum antibacterial effects, suggesting efficacy in the prevention of chemotherapy-related infections. The dual-responsive LED-PLA@CS NPs allowed controlled tumor-targeted LED delivery with better selectivity and lower off-target toxicity, making LED-PLA@CS NPs interesting candidates for repurposing HCV treatments into safer cancer nanomedicines. Furthermore, this thorough analysis offers useful reference information for comprehending the interaction between drugs and DNA. Full article

Enhancing the energy management capabilities of modern smart buildings is essential for energy conservation, which is valuable for modern power networks maintaining a tight power balance under high renewable penetration. This study introduces a data-driven control strategy based on the model predictive control (MPC) for HVAC (heating, ventilation, and air conditioning) systems considering the time-of-use (ToU) electricity rates in Iraq. A multi-layer neural network is first constructed using time-delayed embedding for the modeling of building thermal dynamics, where the rectified linear unit (ReLU) is used as the activation function for the hidden layers. Based on such piecewise affine approximation, an optimization model is developed within the receding horizon control framework, which incorporates the data-driven model and is transformed into a mixed-integer linear programming facilitating efficient problem solving. To validate the efficiency of the proposed approach, a simulation model of the building’s thermal network is constructed using Simscape considering several thermal effects among the building components. Simulation results demonstrate that the proposed approach improves the economic performance of the building while maintaining thermal comfort levels within acceptable range. Full article

The molecular imaging of α-synuclein (α-syn) pathology in Parkinson’s disease (PD) and related movement disorders is a clinically unmet need. The aim of this study was to discover and characterize in vitro a radioligand for imaging α-syn pathology. A library of 78 small molecules was developed and screened using recombinant α-syn fibrils and brain homogenates from Alzheimer’s disease (AD) donors. The selection criteria were as follows: Ki_α-syn < 30 nM, Ki_tau and Ki_A-β > 200 nM. Three compounds, GMC-073 (K_iα-syn: 8 nM), GMC-098 (Ki_α-syn: 9.7 nM), and GMC-058 (Ki_α-syn: 22.5 nM), fulfilled the criteria and were radiolabeled with ³H. [³H]GMC-058 was the only compound with negligible binding in controls, and was further evaluated using tissue microarrays, autoradiography on fresh-frozen brain slices, and in vitro saturation binding assay on brain homogenates. [³H]GMC-058 binding co-localized with α-syn inclusions in Parkinson’s disease (PD) and multiple-system atrophy (MSA), with dense A-β plaques in cerebral amyloid angiopathy and AD and with p-tau inclusions in progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Specific binding was highest in PSP and CBD. In vitro K_D was highest in AD (5.4 nM), followed by PSP (41 nM) and CBD (75 nM). The K_D in MSA, PD, and controls was >100 nM. [³H]GMC-058 is a novel radioligand displaying a low affinity for aggregated α-syn in tissue, with an in vitro profile also suitable for detecting tau pathology in 4R tauopathies. Full article