Search Results (753)

Disease-specific alpha-synuclein (αsyn) strains have been linked to different synucleinopathies. Current αsyn biomarkers are limited to binary detection of pathogenic αsyn in peripheral tissue biopsies or fluids, limiting differential diagnosis. Hence, there is an urgent need for methods that allow strain-specific detection and characterization of αsyn strain architecture. Notably, luminescent conjugated oligothiophenes (LCOs) have been successfully used to detect distinct protein strain conformers in prion diseases and Alzheimer’s disease, highlighting their utility in differentiating disease-specific amyloid structures. Species-dependent differences in αsyn structure are increasingly recognized as one of the critical aspects that shape how fibrils form, propagate and interact with molecular LCO probes. Here, we evaluate the potential of the LCO h-FTAA to differentiate species-specific αsyn strains and conduct a translational investigation using peripheral cardiac tissue of a gut-first synucleinopathy rodent model. Our in vitro data demonstrate strain-specific probe–fibril interactions, reflecting a differential strain architecture and cellular micro-environment. While h-FTAA binds with comparable efficiency to mouse (mo-) and human (hu-) pre-formed fibrils (PFFs), h-FTAA exhibits markedly lower quantum yield when bound to moPFFs versus huPFFs. Spectral imaging revealed h-FTAA-moPFF binding produces blue-shifted maxima (505–550 nm), contrasting with the red-shifted maxima (545–580 nm) of huPFFs. Fluorescence lifetime imaging microscopy confirmed h-FTAA’s intrinsic sensitivity to species-dependent variations through distinct temporal fluorescence signatures (moPFFs: ~0.60–1.5 ns vs. huPFFs: ~0.65–1.0 ns). Our translational investigation showed h-FTAA binding to peripheral cardiac pathology exhibits comparable red-shifted emission, but distinct fluorescence lifetimes of h-FTAA-bound aggregates in moPFF-injected (~1.0–1.4 ns) versus huPFF-injected (~0.69–0.8 ns) rats. Interestingly, we observed distinct blue-shifted emission profiles in a few selected regions of the heart of moPFF-injected rodents, further characterized by extra-long fluorescence decay shifts (~1.5–1.9 ns), reflecting differences in both aggregate conformation and maturity in moPFF-induced compared with huPFF-induced rats. Taken together, our findings underscore the potential of LCO ligands, like h-FTAA, to enable more precise disease staging and diagnosis through peripheral biopsies, complementing existing αsyn biomarker methods. Full article

Hair loss, particularly androgenetic alopecia (AGA) and alopecia areata (AA), is a prevalent condition with widespread psychosocial impact. Recently, low-level laser therapy (LLLT) has emerged as a promising non-invasive therapeutic alternative due to its bioregulatory effects and favorable safety profile compared to conventional pharmacological treatments. In this study, we employed fluorescence lifetime imaging microscopy (FLIM) to investigate the effects of red-light irradiation on hair follicle dynamics and the cutaneous microenvironment in a C57BL/6 mouse model. A hair regeneration model was established to evaluate the efficacy of 650 nm red-light irradiation (bandwidth ± 20 nm). Then, the skin tissue was stained with hematoxylin and eosin (H&E) and followed by FLIM analysis to provide a multidimensional assessment of tissue morphology and metabolic status. Results showed that red-light irradiation significantly increased hair follicle numbers and enhanced adenosine triphosphate (ATP) levels in the skin tissue. FLIM analysis further revealed prolonged fluorescence lifetime values across different epidermal and dermal layers in the irradiated group, indicating significant alterations in the skin metabolic microenvironment. Furthermore, phasor plot analysis enabled precise differentiation between hair follicles and their surrounding skin structures, highlighting FLIM’s high sensitivity and accuracy in evaluating hair growth. In conclusion, this study has provided novel imaging-based insights into the mechanisms of LLLT-induced hair regeneration, highlighting the potential of FLIM as a powerful tool for characterizing the cutaneous microenvironment and quantitatively evaluating phototherapeutic efficacy in future translational applications. Full article

The precise determination of highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energy levels is critical for understanding the photophysical and photochemical properties of carbon dots (C-dots), which directly govern their performance in optoelectronic, catalytic, and sensing applications. However, the lack of distinct redox peaks in cyclic voltammetry (CV) curves of C-dots poses a major challenge to conventional energy level calculation methods. Herein, we propose a novel strategy to calculate the HOMO–LUMO energy levels of C-dots by combining electron transfer (ET) kinetics with Marcus theory. A series of quinones (electron acceptors, EAs) and ferrocene derivatives (electron donors, EDs) were employed to quench the fluorescence of C-dots, and the ET rate constants (K) were derived from fluorescence lifetime measurements. The CV curves of EAs and EDs provided their respective oxidation and reduction potentials, which were used as reference energy levels. The UV–Vis absorption spectra confirmed that the fluorescence quenching mechanism was dominated by ET rather than energy transfer. Based on Marcus theory, the free energy change (ΔG) of ET reactions was correlated with K, and the HOMO and LUMO energy levels of C-dots were calculated to be −1.84 V (vs. SCE) and +1.60 V (vs. SCE), respectively. This study not only provides a reliable method for determining the energy levels of C-dots without distinct redox peaks but also deepens the understanding of ET mechanisms between C-dots and small molecules. The proposed strategy is expected to be extended to other fluorescent nanomaterials with similar CV limitations. Full article

A dual-mode electrical–optical nanocomposite hydrogel is developed by integrating carboxyl-modified upconversion nanoparticles (UCNPs-COOH) and quaternized chitosan (CQAS) into a polyacrylamide (PAAm) covalent network. The hydrogel exhibits high optical transparency (>90% in the visible region), excellent mechanical properties (fracture strain of 1742%, tensile strength of 0.85 MPa, toughness of 6.57 MJ/m³), and robust adhesion to various substrates. The synergistic covalent–noncovalent hybrid network enables efficient energy dissipation, while CQAS-enhanced dispersion of UCNPs significantly improves upconversion luminescence intensity and stability, as evidenced by prolonged fluorescence lifetime from 0.564 ms to 0.691 ms at 539 nm. Leveraging distinct electrical and optical signal transduction pathways, the hydrogel functions as a highly sensitive resistive strain sensor with multistage gauge factors up to 13.85 and excellent cyclic stability over 1200 loading–unloading cycles at 100% strain for human motion monitoring. It also serves as a ratiometric optical pH sensor over a broad range (pH 1–13) based on phenolphthalein-sensitized upconversion luminescence, with excellent repeatability. By integrating real-time resistance responses with optical readouts within a single soft material, this work demonstrates a reliable dual-mode sensing strategy for simultaneous mechanical and chemical monitoring, holding promise for wearable electronics, smart healthcare, and environment-responsive sensing systems. Full article

Neurodegenerative diseases feature diverse pathological protein aggregates, including Lewy bodies in Alzheimer’s disease (AD) and skein-like filaments in amyotrophic lateral sclerosis (ALS). The physical mechanisms underlying this morphological diversity remain unclear. Here, we demonstrate that aggregation of the prion-like domain of hnRNPA1 (A1PrD), implicated in AD and ALS, is driven by solution composition and phase transition dynamics. Utilizing 3D timelapse and fluorescence lifetime imaging microscopy, we show that solution conditions modulate phase separation, gelation, and fibrillation, resulting in distinct structures such as fibril, gel, and starburst morphologies. Homotypic and heterotypic interactions between A1PrD and RNA were observed to shift the balance between pathological and physiological condensates. Importantly, amyloid-rich starbursts displayed prion-like infection capabilities toward amyloid-poor condensates. Our findings highlight how the interplay between solution composition and kinetic balances of liquid-liquid phase separation, gelation, and fibrillation shapes the diverse pathological aggregate morphologies characteristic of neurodegenerative diseases. Full article

Background/Objectives: Early embryonic arrest during the cleavage stage (days 2–4) accounts for a substantial proportion of developmental failure in in vitro fertilization. This phenomenon remains poorly understood at the molecular level, even in chromosomally normal embryos identified by preimplantation genetic testing. This review aims to redefine cleavage-stage arrest from a passive energy deficit to a checkpoint-regulated endpoint caused by inadequate coordination among metabolism, transcriptome integrity, and stress-response pathways. Methods: We integrate evidence from long-read transcriptomics, metabolomics, epigenetics, and immunobiology relevant to pre-blastocyst development. These data are assembled into a unifying mechanistic framework and a clinically oriented stratification model, together with candidate multimodal readouts for early classification. Results: We propose a three-axis model linking: (i) metabolic–epigenetic insufficiency, including defective histone lactylation and impaired alpha-ketoglutarate-dependent DNA demethylation; (ii) isoform-level abnormalities, including intron retention and retrotransposon activation within a hidden transcriptomic landscape better resolved by long-read sequencing; and (iii) stress-related immune signaling, in which NLRP7 links alternative splicing and DNA-damage-response dysfunction with mitochondrial stress and p53-associated arrest. Within this framework, we distinguish three molecular arrest states: an early transition failure marked by defective maternal-to-embryonic reprogramming and severe splicing disruption; a metabolically quiescent state that may retain a limited rescue window; and a later stress-associated state characterized by senescence-like features, oxidative stress, and broad transcriptomic and genomic instability. Conclusions: Early embryo arrest should no longer be viewed as a nonspecific developmental failure, but as a mechanistically stratifiable condition with distinct metabolic, transcriptomic, and stress-associated trajectories. A diagnostic platform combining fluorescence lifetime imaging microscopy, long-read sequencing, and digital polymerase chain reaction may improve early mechanistic classification, help identify embryos with possible reversibility, and reduce uncertainty in embryo selection during in vitro fertilization. Full article

Molecular interactions underpin the functioning of the living cell. Molecules exist in distinct quaternary structural forms, associate with molecular partners in signaling cascades, form transient quinary interactions, localize in membrane domains, and cluster in membrane-less condensates. Measuring the concentration, size, and dynamics of these molecular assemblies remains an enduring biophysical challenge, particularly in cells, where heterogeneity is the rule rather than the exception. Orthogonal signals derived from fluorescence lifetime, fluorescence fluctuations, and fluorescence polarization provide valuable metrics for probing interactions and environments, concentration and size, and rotational dynamics, respectively. This paper combines fluorescence lifetime imaging microscopy with image correlation analysis and polarization to determine the concentrations, brightness, lifetime, and rotational correlation time of different fluorescent states. A two-population model is examined as a prototypical example of a heterogeneous system. The analysis is illustrated on a simple fluorescence model system, where cluster densities, relative brightnesses, lifetimes, and rotational correlation times are extracted. Full article

We present a modular building block strategy for synthesizing phosphonated polyaromatic systems as an alternative to the conventional late-stage phosphonation of prefabricated aromatic scaffolds, which often requires harsh conditions and has limited tolerance for functional groups. A monophosphonated biphenyl building block was obtained via nickel-catalyzed phosphonation of dibromobiphenyl at 170 °C for three hours. This synthesis is more economical and milder than typical high-temperature palladium systems. In parallel, a borated pyrene derivative was prepared by Suzuki–Miyaura borylation. The final palladium-catalyzed Suzuki cross-coupling reaction produced the target compound, octaethyl(pyrene-tetrakis(biphenyl))tetrakis(phosphonate), Et₈-PyTPPE. Single-crystal X-ray diffraction reveals a centrosymmetric molecule that crystallizes in the triclinic space group P–1, with the inversion center located at the central C–C bond of the pyrene core. The pyrene unit is essentially planar, while the biphenylphosphonate arms are highly twisted relative to the core and to each other. The crystal packing is dominated by weak intermolecular interactions, and no significant π–π stacking is observed. Hirshfeld surface analysis shows that H···H (60.5%) and C···H (22.5%) contacts predominate, while O···H interactions (14.4%) with phosphoryl oxygen atoms represent the most relevant directed contacts. From photophysical investigations, Et₈-PyTPPE exhibits blue fluorescence (λ_em. = 452 nm) in solution and aggregation-induced red-shifted emission with nanosecond lifetimes in the solid state, confirming purely fluorescent behavior. Full article

Most of the existing carbon dot (CD)-based afterglow materials are limited to a single emission mode of either room-temperature phosphorescence (RTP) or delayed fluorescence (DF), which makes it difficult to meet the application requirements of advanced anti-counterfeiting and multi-level information encryption. Therefore, the development of CD-based composite materials with multi-mode afterglow emission, long lifetime and high stability holds significant research significance and application value. In this study, long-afterglow manganese/nitrogen co-doped CDs@boric acid (BA) composites (Mn, N-CDs @BA) are successfully prepared, and their optical properties and emission mechanism are clarified. The results demonstrate that the Mn, N-CDs @BA composites exhibit wavelength-dependent dual-afterglow emission characteristics of RTP and DF. Under 254 nm ultraviolet (UV) light excitation, they exhibit DF emission with an average lifetime of 903.36 ms. Under 365 nm UV light excitation, RTP emission with an average lifetime of 354.43 ms is observed. Moreover, the afterglow color exhibits time dependence. Based on the triple emission modes (fluorescence, RTP and DF) of the Mn, N-CDs @BA composites, optical patterns were designed and fabricated, and counterfeit-resistant and unclonable anti-counterfeiting and high concealment information encryption were successfully achieved. This work develops a potentially feasible approach for next-generation advanced optical anti-counterfeiting and information encryption systems. Full article

Approximately 25% of the global population is estimated to have latent tuberculosis infection (LTBI), with a 5–10% lifetime risk of progression to active disease. Although interferon-gamma release assays (IGRAs) are widely used for LTBI diagnosis, their high cost and operational complexity limit large-scale implementation in resource-limited settings. This study evaluated the diagnostic performance of a low-complexity, rapid, fluorescence-based point-of-care assay, ichroma IGRA-TB, for LTBI detection. A total of 300 participants enrolled at TB Screening and Treatment Centers and the Dhaka Hospital of icddr,b were categorized as healthy controls (n = 130), household contacts of TB patients (n = 70), GeneXpert MTB/RIF Ultra-positive active TB patients (n = 80), or individuals with a previous history of TB (n = 20). ichroma IGRA-TB was compared with QuantiFERON-TB Gold Plus (QFT-Plus) across all groups. Overall agreement between ichroma IGRA-TB and QFT-Plus was 91.9%, with a Cohen’s kappa of 0.83, indicating almost perfect concordance. Using culture as a surrogate reference standard, QFT-Plus demonstrated higher sensitivity (74.6%) than ichroma IGRA-TB (69.0%). Overall, ichroma IGRA-TB demonstrates high agreement with QFT-Plus and acceptable sensitivity, supporting its potential as a near-point-of-care tool for LTBI screening in resource-constrained settings. Full article

The effect of the confinement of fluorophores (rhodamine 6G) in nano-cavities of porous 3D sculptured coatings made by glancing-angle deposition (GLAD) was investigated by fluorescence-lifetime imaging microscopy (FLIM). Shortening of fluorescence/ photoluminescence lifetime by ∼10% was observed from the dye-permeated (in liquid) structure; however, there was no rotational hindrance of dye molecules. When dried, a strong rotational hindrance $89\%$ was observed for the orientation along the ordinary optical axis (slow-axis), and the hindrance was smaller than $57\%$ for the extraordinary direction (fast axis). Light-intensity distribution inside the nano-structure with a form birefringence was numerically modeled using plane-wave illumination and a dipole source. Nanoscale localization of light intensity due to dipole nature $I\sim 1/radiu{s}^6$ and boundary conditions for E-field allows efficient energy deposition inside the region of lower refractive index (nanogaps). Full article

Polymer films and polymer blend films are widely used as functional materials; however, their photophysical behavior cannot be fully explained solely by bulk properties such as relative permittivity or glass transition temperature. In this study, we investigate how local polymer microenvironments regulate fluorescence responses by employing two strongly emissive solvatochromic dyes—FπPCM, a D–π–A-type π-conjugation-extended fluorene dye, and PK, a D–π–A-type pyrene dye—as molecular probes. The photophysical properties of these dyes were systematically examined in a series of transparent polymer matrices, including polystyrene, polycarbonate, poly(methyl methacrylate), poly(vinyl chloride), triacetylcellulose, poly(butyl methacrylate), and poly(2-ethyl-2-oxazoline). Polymer films containing the dyes were prepared by solution casting from homogeneous polymer–dye solutions onto quartz substrates followed by solvent evaporation. Both dyes exhibited polymer-dependent variations in fluorescence wavelength, quantum yield, and lifetime, reflecting not only differences in polymer polarity but also local chain packing and specific dye–polymer interactions. Fluorescence lifetime analysis of PS/POz blend films revealed microscopic heterogeneity even in miscible systems, quantitatively captured using averaged lifetime parameters. Temperature-dependent fluorescence measurements further demonstrated that thermal history and structural relaxation significantly influence local polymer environments. In particular, ratiometric fluorescence analysis of PMMA/PBMA blend films enabled reproducible temperature sensing over a wide range from 30 to 120 °C, despite an overall negative temperature response. These results establish solvatochromic dyes as versatile optical probes for evaluating local polymer microenvironments and highlight their potential for polymer-state monitoring and fluorescence-based temperature-sensing applications. Full article

Tb³⁺-doped CaF₂ single crystals are attractive materials for green photonic applications due to their low phonon energy, high optical transparency, and efficient Tb³⁺ emission. In this work, CaF₂ single crystals doped with different TbF₃ concentrations (1, 5, and 10 mol%) were grown and systematically investigated in order to clarify the concentration-dependent spectroscopic behavior of Tb³⁺ ions in a fluorite host. Optical absorption spectroscopy, Judd–Ofelt analysis, steady-state and time-resolved photoluminescence, colorimetric evaluation, and emission cross-section and gain calculations were employed. Judd–Ofelt intensity parameters typical of fluoride hosts were obtained, enabling the calculation of radiative transition probabilities and lifetimes. The emission spectra are dominated by intense green luminescence from the ⁵D₄ → ⁷F₅ transition, while the absence of ⁵D₃ emission is attributed to efficient cross-relaxation processes. Fluorescence lifetimes in the millisecond range show slight changes with Tb³⁺ concentration. Quantum efficiency increases from low to intermediate concentrations and tends to saturate at higher doping levels. CIE 1931 chromaticity coordinates confirm stable green emission, while emission cross-sections and gain parameters reveal a highest value for orange emission of 10 mol% TbF₃-doped CaF₂ crystal. These results indicate that CaF₂:Tb³⁺ single crystals are promising materials for photonic applications. Full article

Lignin from Phaleria macrocarpa (Mahkota Dewa) fruit, a bioactive-rich cultivated medicinal biomass, was employed as a renewable precursor for lignin quantum dots (LQDs). A simple, aqueous, catalyst-free two-step route (lignin to lignin nanoparticles to LQDs) is demonstrated, enabling the valorization of non-food lignin into photoluminescent nanomaterials. The resulting LQDs were predominantly amorphous with short-range graphitic ordering and a narrow particle size distribution (3–5 nm). Structural and chemical analyses indicated a partially graphitized carbon framework enriched with oxygenated surface functionalities, which is consistent with their bright blue–green emission (λ_em of 490 nm; average fluorescence lifetime of 4.51 ns). Hydrothermal carbonization induced a blue shift in the UV–Vis absorption profile, resulting in a main band at 288 nm with a shoulder at 312 nm. The LQDs exhibited high cytocompatibility toward L929 mouse fibroblasts (93.1 ± 6.5% viability at 24 h) and were readily internalized by cells, facilitating green fluorescence live-cell imaging as a proof-of-concept. Antibacterial activity was observed against both Gram-positive and Gram-negative strains, supporting dual biofunctional performance. Overall, this study established a green and scalable route for converting P. macrocarpa fruit lignin into multifunctional LQDs, with potential applications in circular-bioeconomy such as antimicrobial/active coatings and optical sensing in agro-industrial contexts. Full article

Culturing cells and micro-tissue samples in 3D bio-scaffolding structures is gaining popularity; however, precise control of tissue micro-environment in such systems remains challenging. We describe a family of new hybrid bio-scaffolds with 3D O₂-sensing ability, produced by simple means from readily available bio-scaffolding and O₂-sensing materials. Three different types of phosphorescent O₂-sensing materials—polymeric microparticles (MPs), supramolecular probe MitoXpress and nanoparticulate probes NanO2 and Nano-IR (NPs)—were integrated in Matrigel and agarose scaffolding materials and evaluated. Key working characteristics of such hybrid scaffolds, including heterogeneity, stability, cytotoxicity, optical signals and O₂-sensing properties, ease of fabrication and use, were compared. The results show superiority of the Matrigel hybrids with NanO2 and Nano-IR probes. Demonstration experiments were conducted with HCT116 cells and individual spheroids derived from these cells, culturing them in the Matrigel–NP hybrid scaffolds and monitoring oxygenation and local O₂ gradients on a time-resolved fluorescence plate reader and by phosphorescence lifetime imaging microscopy (PLIM). Full article