Glycosylation plays a pivotal role in regulating diverse biological processes. However, the lack of tools capable of controlling the spatiotemporal dynamics of glycosylation has largely hindered its functional elucidation. Here, we introduce an optogenetic approach that employs red/far-red light to dynamically and reversibly control the plasma membrane localization of O-linked N-acetylglucosamine transferase (OGT) in living systems. Red-light-induced translocation of OGT suppresses insulin signaling in both cells and mice. Glycoproteomic and phosphoproteomic analyses reveal a global impact of OGT-mediated glycosylation on signal transduction. Moreover, using protein semisynthesis, cell-based assays, and molecular dynamics simulations, we demonstrate that red-light-induced O-GlcNAcylation of WNK1 at S1949 inhibits downstream cell volume response signaling pathways by suppressing WNK1 biomolecular condensate formation. Together, our findings provide a valuable tool to modulate subcellular O-GlcNAcylation and control cellular signaling in living systems, with broad applicability to the study of glycosylation in cells.
Despite the evident advantages of multifunctional integrated devices in compactness and integration density, achieving efficient coexistence of photodetection, synapse-like memory and red-light emission in one monolithic unit remains an extraordinary challenge due to profound conflicts in carrier recombination, separation, and storage. Here, we effectively mitigate these long-standing limitations by developing a wafer-scale gallium nitride (GaN)-based optoelectronic micro-synapse that integrates red light emission, self-powered photodetection, and bias-reconfigurable synaptic plasticity within a single micro-device. Red emission is realized through a simple quantum-dot color-conversion layer on a blue GaN micro-LED, avoiding the efficiency bottleneck of native red emitters while preserving device scalability and color stability. Beyond light emission, the same junction operates as a zero-bias self-powered photodetector. Under optical stimulation and global bias modulation, the device further demonstrates rich optoelectronic synaptic behaviors. The demonstrated platform provides a scalable and manufacturable route toward integrated neuromorphic vision systems.
The spectral composition of light in the red and far-red bands is an essential environmental factor regulating plant growth. The rate of PAR-saturated CO2 assimilation of the dark-adapted plants increased 2.7-fold after short-term red-light irradiation. Dark respiration decreased and the ratio photosynthesis/respiration increased from 2.7 to 12.4. The activity of the NAD-glyceraldehyde phosphate dehydrogenase decreased by 40%-50%, while the activity of the NADP-enzyme increased by 1.8-2.0-fold, and the carboxylase activity of Rubisco increased by 2.5-3.0-fold. The activities of both dehydrogenases were returned to control levels by plants being exposed to far red light. Rubisco activity was also returned to near control levels. The dose dependence of NADP-glyceraldehyde phosphate dehydrogenase activity increased linearly up to 17-20 kJ m-2 red light, and the NAD-dependent one decreased linearly up to 8-10 kJ m-2 red light. The fresh and dry weight of whole plants increased by 40%-45% when they were exposed to short-duration red light for 15 days. The results suggest that phytochrome is involved in switching from dark respiratory metabolism to photosynthetic metabolism and leads to the accumulation of additional plant biomass during ontogeny.
To suppress phase separation and improve fluorophore dispersion in physically blended white-light-emitting polymer materials, while also achieving stretchability and repairability, reversibly interlocked macromolecular networks (RILNs) are employed in this work. A stretchable, self-healable, and robust RILNs-based white-light material with adjustable multi-color fluorescence is synthesized from a Schiff base bond crosslinked single network containing red-light-emitting and green-light-emitting groups and a boronic ester bond crosslinked epoxy network carrying blue-light-emitting side chains. The interlocking network's phase separation suppression effect reduces aggregation-induced quenching of the incorporated luminophores, thereby improving white-light regulation convenience and achieving an ultra-high white-light quantum yield of 58.1% for polymer-based materials (photoluminescence luminance = 359 cd m-2 under 420 nm excitation). The resulting materials also show good mechanical properties (tensile strength = 5.5 MPa, elongation at break = 78.5%), stretchability, fatigue resistance, self-healability and recyclability. Benefited from the reversible exchange reactions of built-in reversible covalent bonds at moderate temperature, the mechanical and optical properties of the recycled materials remain nearly unchanged. The design provides a specific strategy for constructing multifunctional polymer white-light materials, with the potential to expand their scope and applications.
This study investigated the effects of red LED light exposure on boar semen quality, sperm metabolism, and reproductive performance in sows. A total of 60 semen samples were collected from Duroc boars and randomly assigned to six light treatment procedures and a control. Among these, Procedure #1 (red light for 13 min - dark for 10 min - red light for 13 min) significantly improved sperm motility indicators, particularly reducing the amplitude of lateral head displacement (ALH) and enhancing beat-cross frequency (BCF) over time (P < 0.05). Flow cytometry analysis revealed that this procedure preserved mitochondrial membrane potential and acrosome integrity. A large-scale field trial involving 1,499 sows across four breeds demonstrated that insemination using red light-treated semen (Procedure #1) significantly increased pregnancy and delivery rates in Large White and Yorkshire sows, along with higher litter birth weight (LBW), total number born (TNB), and number born alive (NBA) (P < 0.05). Untargeted LC-MS/MS metabolomics identified 60 differential metabolites and revealed distinct clustering between treated and control groups. Enrichment and ROC analyses highlighted key altered pathways, including retinol metabolism, fatty acid degradation, sphingolipid metabolism, and arachidonic acid metabolism. Metabolites such as vitamin A, palmitoylcarnitine, psychosine, and prostaglandin E2 showed potential as biomarkers of red-light exposure. These findings suggest that optimized red LED exposure enhances boar semen quality and sow reproductive outcomes by modulating sperm motility and metabolic profiles, offering a novel strategy to improve reproductive efficiency in swine production.
This study demonstrates the use of Ficus religiosa (FR) leaves as a natural, cost-effective, green stabilizing and capping agent for the synthesis of nickel oxide (NiO) nanoparticles (NPs) for the sequestration of anionic Congo Red (CR). Various techniques, including FTIR, XRD, field-emission scanning electron microscopy, dynamic light scattering, Brunauer-Emmett-Teller, HRTEM, and a UV-Vis spectrophotometer, were employed to demonstrate the efficiency of the synthesized NiO (FR) NPs as a biosorbent. The crystallite size of the NPs was found to be 5 nm for NiO NPs (control) and 2.8 nm for Ni (FR) NPs, calculated using XRD. The adsorption behavior of the biosorbent was examined by varying several parameters, such as pH, dye concentration, adsorbent amount, and equilibrium time. Adsorption isotherms and kinetic models were also fitted. The maximum adsorption capacity of CR on biogenically synthesized NiO NPs was found to be 17 mg g-1, achieved at 37 °C or 310.15 K. Isotherm and kinetic studies revealed that Langmuir and pseudo-first order were found to be the best fit. The recyclability of the adsorbent remains good after 5 cycles of regeneration, with the adsorbent achieving ∼83% removal using the real wastewater sample. Overall, NiO (FR) NPs, as a sorbent based on dried FR leaves, exhibit strong potential as an effective biosorbent for the adsorption of CR via contaminated water. In this study, waste leaves of Ficus religiosa (FR), commonly known as peepal, an indigenous plant. The leaves were used as a green reducing and stabilizing agent for the synthesis of nickel oxide (NiO) nanoparticles (NPs). The synthesized NiO NPs were then applied for the removal of Congo Red (CR) dye from aqueous solution through batch adsorption experiments.To the best of our knowledge, no previous study has reported the green synthesis of NiO NPs using FR waste leaves specifically for the sequestration of CR. The FR-mediated NiO NPs exhibited good removal performance compared with conventionally synthesized control NiO NPs, mainly due to their higher surface area and improved water stability. These properties make the synthesized nanomaterial efficient for anionic dye removal. Therefore, this work presents a novel, eco-friendly, facile, and potentially scalable alternative to conventional and costly adsorbents. This approach introduces a novel, eco-friendly, green, facile, and scalable alternative to conventional and more expensive adsorbents. It highlights its potential for real-world wastewater treatment applications.
Surface-initiated atom transfer radical polymerization (SI-ATRP) enables the fabrication of functional polymer brushes, yet achieving simultaneous oxygen tolerance and controlling polymer growth and compatibility to biological environments remains challenging. Here, we report a hemoglobin (Hb)-catalyzed, red light-mediated SI-ATRP (SI-bioATRP) that proceeds efficiently in open air. In the presence of methylene blue (MB+) as a photosensitizer and trace dimethyl sulfoxide (DMSO) as an oxygen scavenger, red light excitation provides the rapid reduction of Hb-(FeIII) to Hb-(FeII), which acts as activator for ATRP. This cooperative Hb/MB+/red light system promotes the controlled growth of chemically different brushes exceeding 300 nm in thickness, while analogous polymerizations in solution proceed in an uncontrolled manner. Mechanistic and calorimetric analyses reveal that the controlled behavior of SI-bioATRP arises from the intrinsic tendency of Hb to physisorb on initiator surfaces and dormant/propagating brush interfaces, ensuring an effective activation-deactivation equilibrium. The resulting process is fully oxygen-tolerant and cytocompatible and operates even in cell-culture media, enabling in situ polymer brush formation under biologically relevant conditions.
In this paper, we report an innovative compact photoacoustic (PA) sensing probe based on a surface-micromachined optical ultrasound transducer (SMOUT). Owing to its excellent optical transparency, the excitation light can propagate through the SMOUT to the target, enabling the use of a single optical fiber for both excitation and reception. In addition, the SMOUT provides high acoustic sensitivity and good optical uniformity. For demonstration, a prototype PA sensing probe using the SMOUT has been designed, fabricated, and experimentally characterized. Red-dye solutions with different concentrations and a piece of black tape embedded at various depths in biological tissue are used as sensing targets, and the probe performance is validated by the experimental results. Overall, the compact and sensitive SMOUT-based probe shows strong potential for a wide range of PA sensing applications, and its uniform mass production makes it amenable to be arranged into 1-D and 2-D planar or spherical arrays for imaging applications.
Cigarette smoke (CS) exposure disrupts bronchial epithelial redox homeostasis, serving as a primary etiology of chronic bronchitis; however, the specific mechanisms linking ion transport dysregulation to CS-induced cytotoxicity remain poorly understood. This study identifies a critical protective role for the voltage-gated chloride channel ClC-3, a Cl-/H+ exchanger, in maintaining airway epithelial integrity against oxidative insult. We report significant downregulation of ClC-3 in the bronchial epithelium of chronic bronchitis patients and CS-exposed mice. Using transgenic overexpression and conditional knockout mouse models, we demonstrate that ClC-3 deficiency exacerbates, while its overexpression mitigates, CS-induced airway inflammation, systemic oxidative stress (SOD/MDA), and lung injury. Mechanistically, we show that CS exposure suppresses AKT phosphorylation, leading to the inactivation of the transcription factor CREB1. We validate that CREB1 acts as a direct transcriptional activator of CLCN3 by binding to its promoter; thus, the CS-mediated inhibition of the AKT/CREB1 axis results in transcriptional silencing of ClC-3. At the cellular level, loss of ClC-3 disrupts lysosomal acidification, resulting in a blockade of autophagic flux. This impairment prevents the effective clearance of oxidative damage, thereby promoting epithelial cell death and amplifying inflammatory responses. Collectively, these findings delineate a novel "CS-AKT/CREB1-ClC-3-Lysosome" axis, suggesting that restoring ClC-3-mediated lysosomal function represents a promising therapeutic strategy to restore redox balance in chronic bronchitis.
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To determine whether ReacStick parameters can differentiate between recurrent fallers and non-fallers and compare its diagnostic precision with functional tests. Cross-sectional study SETTING: Outpatient Rehabilitation Clinic in a Tertiary Hospital PARTICIPANTS: Community-dwelling older adults were recruited using convenience sampling. Ninety participants were enrolled, with those having recurrent falls (> 1 time) in the prior year age- and sex-matched with non-fallers. Not applicable. Sensorimotor functions (visual acuity, vibratory sensation, knee extensor strength), cognition, Timed Up and Go (TUG), and Berg Balance Scale (BBS) were evaluated. ReacStick parameters, which assessed Simple Reaction Time (SRT) using ruler-drop method and Reaction Accuracy by requiring participants to grasp or release the device within 390 milliseconds based on a light cue, were collected. The percentage of correctly caught light on trials (ON Accuracy), correctly released light off trials (OFF Accuracy), and the combination (All Accuracy) were recorded. Group comparisons and Receiver Operating Characteristic (ROC) curves were used to assess the ability of the parameters to discriminate between fallers and non-fallers. Multivariate logistic regression identified independent variables for faller status. Recurrent fallers showed significantly worse SRT, OFF Accuracy, All Accuracy, and OFF accuracy/SRT. Highest area under the curves were observed for All Accuracy (0.80), OFF Accuracy/SRT (0.79), and OFF accuracy (0.76). OFF accuracy/SRT best predicted faller status [aOR=12.18, 95% CI: 3.75-39.53]. TUG and BBS showed non-significant trends, while knee extensor strength was protective (aOR=0.53, 95% CI: 0.29-0.97). Diminished short latency inhibitory control was the most accurate means to identify faller status, whereas good knee extensor strength showed a protective effect. ReacStick may offer potential as a sensitive tool for assessing short latency inhibitory control and processing speed related to faller status in older adults. When combined with strength assessment, incorporating ReacStick in clinical practice may improve the accuracy of fall-status classification. TCTR20240828002.
This study investigated the chemical composition and antibacterial and antibiofilm activities of Cymbopogon flexuosus essential oil (CFEO) against multidrug-resistant (MDR) bacteria within a One Health framework. The bacterial panel comprised four clinical isolates (n = 1 per source): a methicillin-resistant Mammaliicoccus sciuri (MR-M. sciuri) from bovine mastitis, a colistin-resistant ESBL-producing Escherichia coli (E. coli) from avian colibacillosis, and MR-Staphylococcus haemolyticus (MR-S. haemolyticus) and MDR Staphylococcus aureus (MDR S. aureus) from healthy farm personnel in contact with diseased animals. GC-MS analysis was performed to study the chemical composition of the CFEO. Antibacterial activities were evaluated via disk diffusion and broth microdilution assays. Disk diffusion was used exclusively as a qualitative screening tool to identify potential interactions; synergy was assessed definitively through the checkerboard assay by calculating the Fractional Inhibitory Concentration Index (FICI). The antibiofilm activity of CFEO was quantified via Congo red agar, crystal violet staining, and light microscopy. Molecular docking simulation was performed to assess the binding interactions of the CFEO constituents with key bacterial proteins. The major constituents of CFEO were geranial (α-citral; 32.98%), neral (β-citral; 28.62%), β-terpinene (11.50%), geraniol (5.42%), nerol acetate (3.40%), and linalool (2.31%). The inhibition zones ranged from 38 ± 2.00 to 56 ± 1.00 mm, while the MIC values spanned from 8 to 8192 µg/mL. CFEO demonstrated a synergistic effect with oxacillin against MR-M. sciuri (FICI = 0.28). Sub-MIC concentrations of CFEO significantly disrupted the biofilms of M. sciuri and E. coli. Bioinformatics analysis via molecular docking revealed favorable binding affinities between major compounds of CFEO and key bacterial proteins, including PBP2a, SarA, and AgrA. This study highlights the in vitro efficacy of CFEO against MDR, MR and biofilm-forming bacteria circulating at the animal-human interface, as well as its synergistic potential when combined with oxacillin against MR-M. sciuri. Molecular docking analyses suggest that the major compounds of CFEO may act as promising adjuvants in the development of new therapeutic strategies against MDR bacteria within a One Health framework.
Pyrophosphates have acquired considerable attention as a potential electrode material in energy storage devices owing to their strong covalent P-O bonds, which ensure structural stability, high electrochemical activity, and efficient ion migration. In this contribution, we synthesized copper pyrophosphate (Cu2P2O7) by using a simple co-precipitation method followed by calcination at 500 °C for 30 minutes. The monoclinic structure of the material with space group C12/c1 was confirmed by powder X-ray diffraction. The Cu2P2O7 bonds were confirmed using Raman spectroscopy, while Fourier transform infrared spectroscopy confirmed the bending vibration of P-O-P and P-O bonds. X-ray Photoelectron Spectroscopy validates the +2-oxidation state of copper and the +5-oxidation state of phosphorus. Field emission scanning electron microscope revealed that the interconnected porous morphology with a rough surface of the material provides abundant active sites for ion movements and facilitates electrolyte penetration. The symmetric supercapacitor device of Cu2P2O7 possesses an excellent specific capacity of 225 F g-1 with a power density and energy density of 3200 W kg-1 and 80 Wh/kg at a current density of 1 A g-1, respectively. The symmetric device retains about 90% of its initial capacity after 10 000 cycles at a current density of 1.5 A g-1. The symmetric device is capable to illuminate a single 3 V red light emitting diode continuously for 1 minute and 27 seconds. The electrochemical findings endorse the viability of Cu2P2O7 as a suitable electrode material for long-term energy storage applications.
Free flap reconstruction is a standard procedure in surgery, yet vascular thrombosis occurs in 3% to 5% of cases. Early detection within the first few hours is essential for successful salvage, as the success rate of surgical re-exploration decreases over time. Since current clinical assessment remains subjective and depends on experience, objective and continuous monitoring is required. Photoplethysmography (PPG), which monitors blood volume changes non-invasively, is a candidate for this application. However, the influence of specific waveform changes during early hemodynamic shifts is not fully understood.

Methods: This study evaluated the diagnostic capacity of PPG for detecting early vascular changes using a custom silicone phantom. Synthetic vessels mimicking human arterial and venous mechanics were embedded at depths of 3, 9, 15, and 21 mm. A perfusion system simulated normal, early ischaemic, and early congested states. Signal quality was assessed using the Signal-to-Noise Ratio (SNR), and only signals with SNR > 15 dB were used for morphological analysis. Over 50 parameters, including Time, Area, and Slope, were extracted from the waveforms to identify those that characteristically respond to each hemodynamic state.

Results: The custom-made free flap phantom was successfully validated. Signal quality assessments limited morphological evaluation to depths up to 15 mm. Analysis showed that Intensity and Area-based parameters were the most effective indicators at all depths. At shallow positions, Time-related features showed clear changes during ischaemia, while Slope and Second Derivative (SDPPG) features emerged as key indicators at depth. Red light was useful for superficial monitoring at 3 mm, whereas Infrared (IR) was necessary for assessing deeper states.

Conclusion: A custom phantom capable of replicating early hemodynamic compromise was developed. Identifying specific feature variations across depths provides a framework for objective, continuous monitoring. These findings suggest that combining multiple morphological features can improve the reliability of flap assessment.
Breast cancer survivors undergoing hormone therapy frequently experience vaginal pain and sexual dysfunction, which negatively affect quality of life. These symptoms are often undertreated, and new therapeutic approaches are needed. To evaluate the effects of photobiomodulation (PBM) on vaginal pain, sexual function, safety, and tolerability in women with breast cancer undergoing hormone therapy. A prospective, quasi-experimental clinical study was conducted with 24 women presenting hormone therapy-induced sexual dysfunction, who underwent four weekly intra- and extra-cavitary PBM sessions (blue LED-440 nm, 8 min; red LED-660 nm, 20 min). Eight eligible participants who declined the intervention due to embarrassment were followed as an untreated observational group. Assessments were performed before and after the intervention using the Female Sexual Quotient Questionnaire (QS-F) and the Visual Analog Scale (VAS) for vaginal pain. At baseline, 82.6% of participants reported maximum vaginal pain (VAS = 10), and 78.2% presented absent or severely impaired sexual function. After four PBM sessions, 79.1% of the women reported complete absence of pain, with mean VAS scores decreasing from 9.46 ± 0.98 to 1.04 ± 2.17 (p < 0.0001). Sexual function also improved significantly, with mean QS-F scores increasing from 23.25 ± 23.47 to 87.21 ± 17.93 (p < 0.0001), and 95.8% of participants reporting good to excellent sexual function after treatment. The intervention was well tolerated, with no adverse events reported. The observational group showed no changes in the evaluated outcomes. PBM proved to be safe, well tolerated, and clinically effective in reducing vaginal pain and improving sexual function in women with breast cancer undergoing hormone therapy, representing a promising therapeutic alternative.
High-resolution extracellular electrophysiology is the gold standard for recording spikes from distributed neural populations and is especially powerful when combined with optogenetics for manipulation of specific cell types with high temporal resolution. We integrated these approaches into prototype Neuropixels Opto probes, which combine electronic and photonic circuits. These devices pack 960 electrical recording sites and two sets of 14 light emitters onto a 70-μm-wide, 1-cm-long shank, allowing spatially addressable optogenetic stimulation with blue and red light. In mouse cortex, Neuropixels Opto probes delivered high-quality recordings together with spatially addressable optogenetics, differentially activating or silencing neurons at distinct cortical depths. In the mouse striatum and other deep structures, Neuropixels Opto probes delivered efficient optotagging, facilitating the identification of two cell types in parallel. Neuropixels Opto probes represent a promising tool for recording, identifying and manipulating neuronal populations.
In this Letter, we report on the demonstration of InGaN/AlGaN nanowire red light-emitting diodes, which exhibit high thermal robustness under extreme operating conditions. The devices emit at a wavelength of ~650 nm and maintain stable red electroluminescence over injection currents from 10 to 1000 mA. Temperature-dependent electroluminescence characterization reveals sustained emission from 25 °C to ~950 °C under ramped conditions with a minimal peak wavelength shift of ~3-5 nm and moderate spectral broadening of ~10 nm. The emission linewidth remains broad, with a full width at half maximum of ~94 nm across the entire temperature range. These results establish III-nitride nanowire LEDs as a robust platform for high-temperature red emission, with implications for optoelectronic systems operating in harsh environments, including aerospace, high-temperature industrial processes, and advanced sensing.
High-fidelity manikin scenarios for contaminated airway management and upper gastrointestinal bleeding (UGIB) depend on blood or hematemesis simulants that reliably occlude optics and reproduce the visual gestalt of real blood under high-intensity video laryngoscopy and flexible endoscopy lighting. Commercially available simulated blood products are frequently optimized for reusability, stain resistance, and compatibility with procedural trainers, and can be cost-prohibitive for repeated high-volume "soiling" curricula. However, many simulated blood products do not report optical opacity or camera-obscuration performance for this specific use case. We performed a targeted technical review of blood and bleeding simulant strategies used in manikin-based training and adjacent materials science literature, and we describe a low-cost, reproducible hematemesis analog composed of three packets of a raspberry-flavored powdered beverage mix - Crystal Light Sugar-Free Raspberry Ice Drink Mix (made from maltodextrin, citrate salts, calcium phosphate, organic acids, and FD&C dyes) - dispersed with 20 g of unsweetened cocoa powder - Hershey's Cocoa - in 1 L of water using an immersion blender. In preliminary qualitative bench use, this particulate suspension formulation produced a dark red-brown appearance and visually reduced light transmission compared with the dye-only beverage mixture. Objective optical, rheologic, and comparative performance testing was not performed in this introductory report. Direct material cost was approximately $1.66/L using representative U.S. retail pricing, compared with $7-$29/L for selected commercial powders and premixes, although this comparison reflects direct consumable cost only and does not establish performance equivalence. Limitations include sedimentation and phase separation over time (necessitating re-homogenization) and potential staining of the manikin; a spot test on non-critical surfaces is recommended prior to implementation. Because the formulation contains organic particulates, it should not be introduced into patient-care endoscope working channels or equipment intended for later clinical use unless local reprocessing staff verify complete clearance for the specific device. This report is intended as a preliminary formulation and microcosting analysis; future work should quantify viscosity (including shear-thinning behavior), density, spectral absorbance/scattering, and material compatibility to support standardization across simulation programs.
In Alzheimer's disease (AD), tau pathology is more strongly linked to neurodegeneration than amyloid-β and better predicts brain atrophy. The spatial extent of tauopathy (SEOT) has shown promise as an earlier and more sensitive marker of AD severity than tau load, but how these complementary dimensions relate to neurodegeneration remains unclear. Here, we compared the in vivo associations of tau-PET extent versus load with cross-sectional and longitudinal neurodegeneration. We studied 367 participants across the healthy-aging to AD continuum (mean age 69.3 years; 61% female) from the TRIAD cohort who underwent [18F]MK-6240 tau-PET. Tau load was quantified as regional standardized uptake value ratio (SUVR), and SEOT as the proportion of abnormal voxels, within a temporal meta-region of interest (ROI) and a full-cortex ROI. Neurodegeneration markers included cortical thickness, hippocampal volume (HCV), medial temporal atrophy (MTA) visual ratings, plasma neurofilament light (NfL), and CSF total tau (t-tau). Cross-sectional associations were evaluated using multiple linear regression or covariate-adjusted Spearman correlations. We also compared local correlations of tau load and extent with cortical thickness across all cortical regions. Longitudinal predictive value for neurodegeneration was tested using linear mixed-effects models. Cross-sectionally, all tau-PET metrics were significantly associated with neurodegeneration across imaging and fluid biomarkers. Full-cortex SEOT provided the best model fit for cortical thinning. SEOT outperformed tau load for associations with HCV and for predicting MTA, whereas SEOT and SUVR showed comparable associations with plasma NfL and CSF t-tau. Tau extent was equal or superior to tau load in its correlation with local cortical thickness across all cortical regions. Longitudinally, baseline full-cortex SEOT best predicted future cortical thinning, while temporal SEOT best predicted future hippocampal atrophy. Across cross-sectional and longitudinal analyses, tau extent provided superior predictive value for imaging-based neurodegeneration compared with tau load. By enabling a spatially unbiased, whole-brain assessment of tau burden that accommodates heterogeneous topographies, SEOT represents a promising complementary tau-PET metric for staging and tracking disease progression in AD.
Early detection and biological characterization of Alzheimer's disease (AD) remain challenging, as current diagnostic approaches rely on invasive cerebrospinal fluid (CSF) sampling or costly neuroimaging, limiting scalability. Sleep quantitative electroencephalography (qEEG) provides a non-invasive measure of brain function and may capture early AD-related neural alterations; however, the high dimensionality and complexity of these features limit interpretation with conventional approaches, requiring multivariate methods. The objective of this study is to assess whether sleep qEEG features are associated with biologically meaningful stratification of AD in accordance with the NIA-AA 2024 framework. Forty-two patients with mild-to-moderate AD underwent overnight polysomnography and CSF biomarker assessment, while 58 cognitively unimpaired controls provided sleep EEG recording. EEG signals from four channels were preprocessed, segmented by sleep stage, and characterized using linear, spectral, and non-linear features. Dimensionality reduction was performed using principal component analysis (PCA), guided by random forest-based relevance to CSF biomarkers (A β 42, p-tau181, t-tau, and neurofilament light chain (NfL). Gaussian mixture models (GMMs) were applied to patient-level representations, including derived hybrid ratios (p-tau181/A β 42), to identify biologically coherent subgroups. A reduced 30-component qEEG representation explaining 92.4% of the variance differentiated cognitively unimpaired individuals from patients with AD and identified three AD subclusters. These subgroups showed graded differences in CSF biomarker profiles, including p-tau181/A β 42 and NfL. Sleep qEEG features show structured associations with CSF biomarker profiles and capture variability across the AD continuum. These findings suggest that higher-level qEEG-based machine learning approaches may complement established biomarker-based methods for biological characterization of AD within a geroscience framework.