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Usefulness of peripapillary nerve fiber layer thickness assessed by optical coherence tomography as a biomarker for Alzheimer’s disease
摘要： The use of optical coherence tomography (OCT) has been suggested as a potential biomarker for Alzheimer’s Disease based on previously reported thinning of the retinal nerve fiber layer (RNFL) in Alzheimer’s disease’s (AD) and Mild Cognitive Impairment (MCI). However, other studies have not shown such results. 930 individuals (414 cognitively healthy individuals, 192 probable amnestic MCI and 324 probable AD) attending a memory clinic were consecutively included and underwent spectral domain OCT (Maestro, Topcon) examinations to assess differences in peripapillary RNFL thickness, using a design of high ecological validity. Adjustment by age, education, sex and OCT image quality was performed. We found a non-significant decrease in mean RNFL thickness as follows: control group: 100,20 ± 14,60 μm, MCI group: 98,54 ± 14,43 μm and AD group: 96,61 ± 15,27 μm. The multivariate adjusted analysis revealed no significant differences in mean overall (p = 0.352), temporal (p = 0,119), nasal (p = 0,151), superior (p = 0,435) or inferior (p = 0,825) quadrants between AD, MCI and control groups. These results do not support the usefulness of peripapillary RNFL analysis as a marker of cognitive impairment or in discriminating between cognitive groups. The analysis of other OCT measurements in other retinal areas and layers as biomarkers for AD should be tested further.
关键词： retinal nerve fiber layer,optical coherence tomography,Alzheimer’s Disease,cognitive impairment,biomarker
更新于2025-09-23 15:21:21
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Highly Sensitive Room-Temperature Sensor Based on Nanostructured K2W7O22 for Application in the Non-Invasive Diagnosis of Diabetes
摘要： Diabetes is one of the most rapidly-growing chronic diseases in the world. Acetone, a volatile organic compound in exhaled breath, shows a positive correlation with blood glucose and has proven to be a biomarker for type-1 diabetes. Measuring the level of acetone in exhaled breath can provide a non-invasive, low risk of infection, low cost, and convenient way to monitor the health condition of diabetics. There has been continuous demand for the improvement of this non-invasive, sensitive sensor system to provide a fast and real-time electronic readout of blood glucose levels. A novel nanostructured K2W7O22 has been recently used to test acetone with concentration from 0 parts-per-million (ppm) to 50 ppm at room temperature. The results revealed that a K2W7O22 sensor shows a sensitive response to acetone, but the detection limit is not ideal due to the limitations of the detection system of the device. In this paper, we report a K2W7O22 sensor with an improved sensitivity and detection limit by using an optimized circuit to minimize the electronic noise and increase the signal to noise ratio for the purpose of weak signal detection while the concentration of acetone is very low.
关键词： non-invasive,biomarker,ferroelectric property,blood glucose,volatile organic compound,acetone,nanostructured K2W7O22,diabetes
更新于2025-09-23 15:21:21
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Localization of metabolites of human kidney tissue with infrared laser-based selected reaction monitoring mass spectrometry imaging and silver-109 nanoparticle-based surface assisted laser desorption/ionization mass spectrometry imaging
摘要： Infrared (IR) Laser Ablation-remote-Electrospray Ionization (LARESI) platform coupled to a tandem mass spectrometer (MS/MS) operated in selected reaction monitoring (SRM) or multiple reaction monitoring (MRM) modes was developed and employed for imaging of target metabolites in human kidney cancer tissue. SRM or MRM modes were employed to avoid artifacts that are present in full scan MS mode. Four tissue samples containing both cancerous and non-cancerous regions, obtained from three patients with renal cell carcinoma (RCC), were imaged. Sixteen endogenous metabolites that were reported in the literature as varying in abundance between cancerous and non-cancerous areas in various human tissues were selected for analysis. Target metabolites comprised ten amino acids, four nucleosides and nucleobases, lactate and vitamin E. For comparison purposes, images of the same metabolites were obtained with ultraviolet (UV) desorption/ionization mass spectrometry imaging (UV-LDI-MSI) using monoisotopic silver-109 nanoparticle-enhanced target (109AgNPET) in full-scan MS mode. The acquired MS images revealed differences in abundances of selected metabolites between cancerous and non-cancerous regions of the kidney tissue. Importantly, the two imaging methods offered similar results. This study demonstrates the applicability of the novel ambient LARESI SRM/MRM MSI method to both investigating and discovering cancer biomarkers in human tissue.
关键词： biomarker,cancer,chemical engineering,mass spectrometry,kidney,imaging,clear cell renal cell carcinoma
更新于2025-09-23 15:19:57
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Hierarchical Core-Shell Structure of 2D VS2@VC@N-Doped Carbon Sheets Decorated by Ultrafine Pd Nanoparticles: Assembled in 3D Rosette-like Array on Carbon Fiber Microelectrode for Electrochemical Sensing
摘要： The development of two-dimension (2D) nanohybrid materials with heterogeneous component in nanoscale and three-dimension (3D) well-ordered assembly in microscale has been regarded as an effective way to improve their overall performances by synergistic coupling of the optimized structure and composition. In this work, we reported the design and synthesis of a new type of hierarchically core-shell structure of 2D VS2@VC@N-doped carbon (NC) sheets decorated by ultrafine Pd nanoparticles (PdNPs), which were vertically grown on carbon fiber (CF) and assembled into a unique 3D rosette-like array. The resultant VS2@VC@NC-PdNPs modified CF microelectrode integrated the structural and electrochemical properties of the heterogeneous hybridization of core-shell VS2@VC@NC-PdNPs sheets with unique rosette-like array structure, and gave rise to a significant improvement in terms of electron transfer ability, electrocatalytic activity, stability and biocompatibility. Under the optimized conditions, the VS2@VC@NC-PdNPs modified CF microelectrode demonstrated excellent electrochemical sensing performance towards biomarker hydrogen peroxide (H2O2) including high sensitivity of 152.7 μA cm-2 mM-1, low detection limit of 50 nM (a signal-to-noise ratio of 3:1), as well as good reproducibility and anti-interference ability, which could be used for real-time in situ electrochemical detection of H2O2 in live cancer cells and cancer tissue. The remarkable performances of the proposed nanohybrid microelectrode will have a profound impact on the design of diverse 2D layered materials as promising candidate for electrochemical biosensing applications.
关键词： electrochemical sensing,hierarchical core-shell structure,three-dimension rosette-like sheets array,Two-dimension layered nanomaterials,cancer biomarker detection
更新于2025-09-23 15:19:57
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A Circulating MicroRNA Profile in a Laser-Induced Mouse Model of Choroidal Neovascularization
摘要： Choroidal neovascularization (CNV) is a pathological process in which aberrant blood vessels invade the subretinal space of the mammalian eye. It is a characteristic feature of the prevalent neovascular age-related macular degeneration (nAMD). Circulating microRNAs (cmiRNAs) are regarded as potentially valuable biomarkers for various age-related diseases, including nAMD. Here, we investigated cmiRNA expression in an established laser-induced CNV mouse model. Upon CNV induction in C57Bl/6 mice, blood-derived cmiRNAs were initially determined globally by RNA next generation sequencing, and the most strongly dysregulated cmiRNAs were independently replicated by quantitative reverse transcription PCR (RT-qPCR) in blood, retinal, and retinal pigment epithelium (RPE)/choroidal tissue. Our findings suggest that two miRNAs, mmu-mir-486a-5p and mmur-mir-92a-3p, are consistently dysregulated during CNV formation. Furthermore, in functional in vitro assays, a significant impact of mmu-mir-486a-5p and mmu-mir-92a-3p on murine microglial cell viability was observed, while mmu-mir-92a-3p also showed an impact on microglial mobility. Taken together, we report a robust dysregulation of two miRNAs in blood and RPE/choroid after laser-induced initiation of CNV lesions in mice, highlighting their potential role in pathology and eventual therapy of CNV-associated complications.
关键词： cmiRNA regulation,biomarker,laser-induced choroidal,neovascularization,age-related macular degeneration
更新于2025-09-23 15:19:57
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Amplified Fluorescence by ZnO Nanoparticles vs. Quantum Dots for Bovine Mastitis Acute Phase Response Evaluation in Milk
摘要： Bovine mastitis (BM) is a prominent inflammatory disease affecting the dairy industry worldwide, originated by pathogenic agent invasion onto the mammary gland. The early detection of new BM cases is of high importance for infection control within the herd. During inflammation, various biomarkers are released into the blood circulation, which are consequently found in milk. Herein, the lysosomal activity of N-acetyl-β-D-glucosaminidase (NAGase), a predominant BM indicator, was utilized for highly sensitive clinical state differentiation. The latter is achieved by the precise addition of tetraethyl orthosilicate-coated zinc oxide nanostructures (quantum dots or nanoparticles, individually) onto a conventional assay. Enhanced fluorescence due to the nanomaterial accumulative near-field effect is achieved within real milk samples, contaminated with Streptococcus dysgalactiae, favoring quantum dots over nanoparticles (> 7-fold and 3-fold, respectively), thus revealing significant differentiation between various somatic cell counts. The main advantage of the presented sensing concept, besides its clinically relevant concentrations, is the early bio-diagnostic detection of mastitis (subclinical BM) by using a simple and cost-effective experimental setup. Moreover, the assay can be adapted for BM recovery prognosis evaluation, and thus impact on udder health status, producing an alternative means for conventional diagnosis practices.
关键词： zinc oxide,quantum dots,signal enhancement,mastitis biomarker,nanoparticles,N-acetyl-β-D-glucosaminidase
更新于2025-09-23 15:19:57
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Combining multimodal imaging and treatment features improves machine learning-based prognostic assessment in patients with glioblastoma multiforme
摘要： Background: For Glioblastoma (GBM), various prognostic nomograms have been proposed. This study aims to evaluate machine learning models to predict patients’ overall survival (OS) and progression‐free survival (PFS) on the basis of clinical, pathological, semantic MRI‐based, and FET‐PET/CT‐derived information. Finally, the value of adding treatment features was evaluated. Methods: One hundred and eighty‐nine patients were retrospectively analyzed. We assessed clinical, pathological, and treatment information. The VASARI set of semantic imaging features was determined on MRIs. Metabolic information was retained from preoperative FET‐PET/CT images. We generated multiple random survival forest prediction models on a patient training set and performed internal validation. Single feature class models were created including "clinical," "pathological," "MRI‐based," and "FET‐PET/CT‐based" models, as well as combinations. Treatment features were combined with all other features. Results: Of all single feature class models, the MRI‐based model had the highest prediction performance on the validation set for OS (C‐index: 0.61 [95% confidence interval: 0.51‐0.72]) and PFS (C‐index: 0.61 [0.50‐0.72]). The combination of all features did increase performance above all single feature class models up to C‐indices of 0.70 (0.59‐0.84) and 0.68 (0.57‐0.78) for OS and PFS, respectively. Adding treatment information further increased prognostic performance up to C‐indices of 0.73 (0.62‐0.84) and 0.71 (0.60‐0.81) on the validation set for OS and PFS, respectively, allowing significant stratification of patient groups for OS. Conclusions: MRI‐based features were the most relevant feature class for prognostic assessment. Combining clinical, pathological, and imaging information increased predictive power for OS and PFS. A further increase was achieved by adding treatment features.
关键词： prognostic model,machine learning,VASARI,glioblastoma,FET‐PET,biomarker,MRI
更新于2025-09-23 15:19:57
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Stable Tb(III)-Based Metal–Organic Framework: Structure, Photoluminescence, and Chemical Sensing of 2-Thiazolidinethione-4-carboxylic Acid as a Biomarker of CS <sub/>2</sub>
摘要： A novel three-dimensional microporous framework, [Tb(pddb)phen(ox)0.5]n (Tb-MOF), was synthesized hydrothermally with V-shaped 4,4′-(pyridine-2,6-diyl)-dibenzoic acid (H2pddb), oxalate (ox), and 1,10-phenanthroline (phen). The framework of Tb-MOF features one-dimensional channels functionalized with pyridine-N Lewis base groups and the absence of coordinated and lattice water molecules in the structure. The Tb-MOF exhibits high thermostability (up to 385 °C) and chemical stability in a wide pH range (4?11) and common organic solvents as well as boiling water. The luminescence investigations of the Tb-MOF in common solvents, water with di?erent pH values, and inorganic ions were performed. Results show that the Tb-MOF has high luminescence stability and the ability to probe Fe3+ ions. Signi?cantly, the Tb-MOF with particularly high water stability can be ?rst developed as a highly selective and sensitive luminescent sensor for the biomarker 2-thiazolidinethione-4-carboxylic acid (TTCA) via ?uorescence quenching. The low detection limit (1 ppm), reusability, and high antidisturbance together make the Tb-MOF become a promising sensor for the practical detection of TTCA in urine systems, and for the ?rst time realize the detection of urinary TTCA through ?uorescence spectrometry based on an Ln-MOF sensor.
关键词： CS2 biomarker,urine detection,TTCA,luminescent sensor,Tb-MOF
更新于2025-09-23 15:19:57
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Quantitative imaging biomarkers for Yttrium-90 distribution on Bremsstrahlung single photon emission computed tomography after resin-based radioembolization
摘要： To identify baseline imaging features in patients with liver cancer that correlate with Yttrium-90 (90Y) distribution on post-procedural single photon emission computed tomography (SPECT) and predict tumor response to transarterial radioembolization (TARE). Methods: This retrospective study was approved by the institutional review board and included 38 patients with hepatocellular carcinoma (HCC) (n = 23, 18/23 males, mean age 62.39±8.62 years, 34 dominant tumors) and non-HCC hepatic malignancies (n = 15, 9/15 males, mean age 61.13±11.51 years, 24 dominant tumors) who underwent 40 resin-based TARE treatments (08/2012-01/2018). Multi-phasic contrast-enhanced MRI or CT was obtained prior to and Bremsstrahlung SPECT within two hours after TARE. Total (TTV, cm3) and enhancing tumor volume (ETV, cm3 and % of TTV), and total and enhancing tumor burden (%) were volumetrically assessed on baseline imaging. Up to two dominant tumors per treated lobe were analyzed. After multimodal image registration of baseline imaging and SPECT/CT (MIM Software Inc., Cleveland, OH), 90Y distribution was quantified on SPECT as tumor-to-normal-liver-ratio (TNR). Response was assessed according to RECIST1.1 and quantitative European Association for the Study of the Liver (qEASL) criteria. Clinical parameters were also assessed. Statistical tests included Mann-Whitney-U, Pearson correlation, and linear regression. Results: In HCC patients, high baseline ETV% significantly correlated with high TNR on SPECT, demonstrating greater 90Y uptake in the tumor relative to the liver parenchyma (p < 0.001). In non-HCC patients, a correlation between ETV% and TNR was observed as well (p = 0.039). Follow-up imaging for response assessments within one to four months post-TARE was available for 23 patients with 25 treatments. The change of ETV% significantly correlated with TNR in HCC (p = 0.039) but not in non-HCC patients (p = 0.886). Additionally, Child-Pugh class B patients demonstrated significantly more 90Y deposition in non-tumorous liver compared to Child-Pugh A patients (p = 0.021). Conclusion: This study identified ETV% as a quantifiable imaging biomarker on pre-procedural MRI and CT to predict 90Y distribution on post-procedural SPECT in HCC and non-HCC. However, the relationship between the preferential uptake of 90Y to the tumor with tumor response after radioembolization could only be validated for HCC.
关键词： imaging biomarker,Radioembolization,quantitative SPECT,Yttrium-90,contrast enhancement
更新于2025-09-19 17:15:36
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Cancer-Specific Biomarker hNQO1-Activatable Fluorescent Probe for Imaging Cancer Cells In Vitro and In Vivo
摘要： Human NAD(P)H quinone oxidoreductase-1 (hNQO1) is an important cancer-related biomarker, which shows significant overexpression in malignant cells. Developing an effective method for detecting NQO1 activity with high sensitivity and selectivity in tumors holds a great potential for cancer diagnosis, treatment, and management. In the present study, we report a new dicyanoisophorone (DCP) based fluorescent probe (NQ-DCP) capable of monitoring hNQO1 activity in vitro and in vivo in both ratiometric and turn-on model. NQ-DCP was prepared by conjugating dicyanoisophorone fluoroprobe with hNQO1 activatable quinone propionic acid (QPA), which remain non-fluorescent until activation by tumor-specific hNQO1. NQ-DCP featured a large Stokes shift (145 nm), excellent biocompatibility, cell permeability, and selectivity towards hNQO1 allowed to differentiate cancer cells from healthy cells. We have successfully employed NQ-DCP to monitor non-invasive endogenous hNQO1 activity in brain tumor cells in vitro and in xenografted tumors developed in nude mice.
关键词： NAD(P)H quinone oxidoreductase 1,cancer biomarker,tumor diagnosis,fluorescent probe,cancer imaging,large Stokes shift,dicyanoisophorone
更新于2025-09-19 17:15:36