Vertical Graphene-Based Printed Electrochemical Biosensor for Simultaneous Detection of Four Alzheimer's Disease Blood Biomarkers.

Early detection and timely intervention play a vital role in the effective management of Alzheimer's disease. Currently, the diagnostic accuracy for Alzheimer's disease based on a single blood biomarker is relatively low, and the combined use of multiple blood biomarkers can greatly improve diagnostic accuracy. Herein, we report a printed electrochemical biosensor based on vertical graphene (VG) modified with gold nanoparticles (VG@nanoAu) for the simultaneous detection of four Alzheimer's disease blood biomarkers. The printed electrochemical electrode array was constructed by laser etching and inkjet printing. Then gold nanoparticles were modified onto the working electrode surface via electrodeposition to further improve the sensitivity of the sensor. In addition, the entire printed electrochemical sensing system incorporates an electrochemical micro-workstation and a smartphone. The customized electrochemical micro-workstation incorporates four electro-chemical control chips, enabling the sensor to simultaneously analyze four biomarkers. Consequently, the printed electrochemical sensing system exhibits excellent analytical performance due to the large surface area, biocompatibility, and good conductivity of VG@nanoAu. The detection limit of the sensing system for Aß40, Aß42, T-tau, and P-tau181 was 0.072, 0.089, 0.071, and 0.051 pg/mL, respectively, which meets the detection requirements of Alzheimer's disease blood biomarkers. The printed electrochemical sensing system also exhibits good specificity and stability. This work has great value and promising prospects for early Alzheimer's disease diagnosis using blood biomarkers.

Hollow-polydopamine-nanocarrier-based near-infrared-light/pH-responsive drug delivery system for diffuse alveolar hemorrhage treatment.

Introduction: Diffuse alveolar hemorrhage (DAH) is a serious complication caused by systemic lupus erythematosus (SLE). Tissue damage and changes in immune response are all associated with excessive free radical production. Therefore, removing excess reactive oxygen species are considered a feasible scheme for diffuse alveolar hemorrhage treatment. Cyclophosphamide is often used as the main therapeutic drug in clinics. However, CTX carries a high risk of dose-increasing toxicity, treatment intolerance, and high recurrence rate. The combination of therapeutic drugs and functional nanocarriers may provide an effective solution. PDA is rich in phenolic groups, which can remove the reactive oxygen species generated in inflammatory reactions, and can serve as excellent free radical scavengers. Methods: We developed a hollow polydopamine (HPDA) nanocarrier loaded with CTX by ionization to prepare the novel nanoplatform, CTX@HPDA, for DAH treatment. The monodisperse silica nanoparticles were acquired by reference to the typical Stober method. PDA was coated on the surface of SiO2 by oxidation self-polymerization method to obtain SiO2@PDA NPs. Then, HPDA NPs were obtained by HF etching. Then HPDA was loaded with CTX by ionization to prepare CTX@HPDA. Then we tested the photothermal effect, animal model therapeutics effect, and biosafety of CTX@HPDA. Results: Material tests showed that the CTX@ HPDA nanoplatform had a uniform diameter and could release CTX in acidic environments. The vitro experiments demonstrated that CTX@HPDA has good photothermal conversion ability and photothermal stability. Animal experiments demonstrated that the CTX@HPDA nanoplatform had good biocompatibility. The nanoplatform can dissociate in acidic SLE environment and trigger CTX release through photothermal conversion. Combining HPDA, which scavenges oxygen free radicals, and CTX, which has immunosuppressive effect, can treat pulmonary hemorrhage in SLE. Micro-CT can be used to continuously analyze DAH severity and lung changes in mice after treatment. The pulmonary exudation in the various treatment groups improved to varying degrees. Discussion: In this study, we report a photothermal/PH-triggered nanocarrier (CTX@HPDA) for the precise treatment of SLE-DAH. CTX@HPDA is a simple and efficient nanocarrier system for DAH therapy. This work provides valuable insights into SLE treatment.

Imaging diagnostic features of intracranial primary extranodal Rosai-Dorfman disease: Two case reports and literature review.

In this report, we describe 2 cases of rare intracranial extranodal Rosai-Dorfman disease. The occurrence of this type of non-Langerhans cell histiocytosis in the central nervous system is infrequent, with less than 5% of cases. The first patient was a 35-year-old male who presented with recurring headaches, and the second patient was a 50-year-old male who reported sudden onset of dizziness and vomiting. Computed tomography scans were performed in both cases, but magnetic resonance imaging played a crucial role in the characterization of the lesions and their locations in the thalamus, third ventricle, lateral ventricles, and cerebellopontine angle area. The final diagnosis was confirmed through pathological examination and immunohistochemistry following brain tumor resection. These cases underscore the significance of magnetic resonance imaging in the early diagnosis of intracranial extranodal Rosai-Dorfman disease.

Electrochemical immunosensor based on superwettable microdroplet array for detecting multiple Alzheimer's disease biomarkers.

Alzheimer's disease (AD) is a neurodegenerative disease caused by neurons damage in the brain, and it poses a serious threat to human life and health. No efficient treatment is available, but early diagnosis, discovery, and intervention are still crucial, effective strategies. In this study, an electrochemical sensing platform based on a superwettable microdroplet array was developed to detect multiple AD biomarkers containing Aß40, Aß42, T-tau, and P-tau181 of blood. The platform integrated a superwettable substrate based on nanoAu-modified vertical graphene (VG@Au) into a working electrode, which was mainly used for droplet sample anchoring and electrochemical signal generation. In addition, an electrochemical micro-workstation was used for signals conditioning. This superwettable electrochemical sensing platform showed high sensitivity and a low detection limit due to its excellent characteristics such as large specific surface, remarkable electrical conductivity, and good biocompatibility. The detection limit for Aß40, Aß42, T-tau, and P-tau181 were 0.064, 0.012, 0.039, and 0.041 pg/ml, respectively. This study provides a promising method for the early diagnosis of AD.

Multifunctional Polydopamine-Based Nanoparticles for Dual-Mode Imaging Guided Targeted Therapy of Lupus Nephritis.

Lupus nephritis (LN) is a common and refractory inflammation of the kidneys caused by systemic lupus erythematosus. Diagnosis and therapies at this stage are inefficient or have severe side effects. In recent years, nanomedicines show great potential for imaging diagnosis and controlled drug release. Herein, we developed a polydopamine (PDA)-based nanocarrier modified with Fe3O4 and Pt nanoparticles and loaded with necrostatin-1 (Nec-1) for the bimodal imaging and therapy of LN. Results demonstrate that Nec-1/PDA@Pt-Fe3O4 nanocarrier exhibits good biocompatibility. Nec-1, as an inhibitor of receptor-interacting protein 1 kinase, can be used to inhibit receptor-interacting protein 1 kinase activity and then reduces inflammation due to LN. Experiments in vitro and in the LN mouse model confirmed that the nanocarrier can reduce neutrophil extracellular traps (NETs) production by RIPK1 and alleviate the progression of inflammation. Previous studies proved that Pt nanoparticles can catalyze H2O2 to produce oxygen. A blood oxygen graph of mouse photoacoustic tomography confirmed that Nec-1/PDA@Pt-Fe3O4 can generate oxygen to fight against the hypoxic microenvironment of LN. PDA and Fe3O4 are used as photographic developers for photoacoustic or magnetic resonance imaging. The preliminary imaging results support Nec-1/PDA@Pt-Fe3O4 potential for photoacoustic/magnetic resonance dual-mode imaging, which can accurately and non-invasively monitor microscopic changes due to diseases. Nec-1/PDA@Pt-Fe3O4 combining these advantages exhibited outstanding performance in LN imaging and therapy. This work offers valuable insights into LN diagnosis and therapy.

Portable Vertical Graphene@Au-Based Electrochemical Aptasensing Platform for Point-of-Care Testing of Tau Protein in the Blood.

Alzheimer's disease (AD) is a long-term neurodegenerative disease that poses a serious threat to human life and health. It is very important to develop a portable quantitative device for AD diagnosis and personal healthcare. Herein, we develop a portable electrochemical sensing platform for the point-of-care detection of AD biomarkers in the blood. Such a portable platform integrates nanoAu-modified vertical graphene (VG@Au) into a working electrode, which can significantly improve sensitivity and reduce detection limit due to the large specific surface, excellent electrical conductivity, high stability, and good biocompatibility. The tau protein, as an important factor in the course of AD, is selected as a key AD biomarker. The results show that the linear range of this sensing platform is 0.1 pg/mL to 1 ng/mL, with a detection limit of 0.034 pg/mL (S/N = 3), indicating that this portable sensing platform meets the demand for the detection of the tau protein in the blood. This work offers great potential for AD diagnosis and personal healthcare.

Automatic segmentation model of intercondylar fossa based on deep learning: a novel and effective assessment method for the notch volume.

BACKGROUND: Notch volume is associated with anterior cruciate ligament (ACL) injury. Manual tracking of intercondylar notch on MR images is time-consuming and laborious. Deep learning has become a powerful tool for processing medical images. This study aims to develop an MRI segmentation model of intercondylar fossa based on deep learning to automatically measure notch volume, and explore its correlation with ACL injury. METHODS: The MRI data of 363 subjects (311 males and 52 females) with ACL injuries incurred during non-contact sports and 232 subjects (147 males and 85 females) with intact ACL were retrospectively analyzed. Each layer of intercondylar fossa was manually traced by radiologists on axial MR images. Notch volume was then calculated. We constructed an automatic segmentation system based on the architecture of Res-UNet for intercondylar fossa and used dice similarity coefficient (DSC) to compare the performance of segmentation systems by different networks. Unpaired t-test was performed to determine differences in notch volume between ACL-injured and intact groups, and between males and females. RESULTS: The DSCs of intercondylar fossa based on different networks were all more than 0.90, and Res-UNet showed the best performance. The notch volume was significantly lower in the ACL-injured group than in the control group (6.12 ± 1.34 cm3 vs. 6.95 ± 1.75 cm3, P < 0.001). Females had lower notch volume than males (5.41 ± 1.30 cm3 vs. 6.76 ± 1.51 cm3, P < 0.001). Males and females who had ACL injuries had smaller notch than those with intact ACL (p < 0.001 and p < 0.005). Men had larger notches than women, regardless of the ACL injuries (p < 0.001). CONCLUSION: Using a deep neural network to segment intercondylar fossa automatically provides a technical support for the clinical prediction and prevention of ACL injury and re-injury after surgery.

Bioinspired Synthesis of ZnO@polydopamine/Au for Label-Free Photoelectrochemical Immunoassay of Amyloid-ß Protein.

Amyloid-ß protein (Aß) is an important biomarker and plays a key role in the early stage of Alzheimer's disease (AD). Here, an ultrasensitive photoelectrochemical (PEC) sensor based on ZnO@polydopamine/Au nanocomposites was constructed for quantitative detection of Aß. In this sensing system, the ZnO nanorod array decorated with PDA films and gold nanoparticles (Au NPs) have excellent visible-light activity. The PDA film was used as a sensitizer for charge separation, and it also was used for antibody binding. Moreover, Au NPs were loaded on the surface of PDA film by in situ deposition, which further improved the charge transfer efficiency and the PEC activity in visible light due to the localized surface plasmon resonance effect of Au NPs. Therefore, in ZnO@polydopamine/Au nanocomposites, a significantly enhanced photocurrent response was obtained on this photoelectrode, which provides a good and reliable signal for early detection of AD. Under the optimized conditions, the PEC immunosensor displayed a wide linear range from 1 pg/mL to 100 ng/mL and a low detection limit of 0.26 pg/mL. In addition, this PEC immunosensor also presented good selectivity, stability, and reproducibility. This work may provide a promising point-of-care testing method toward advanced PEC immunoassays for AD biomarkers.

Computed tomography and photoacoustic imaging guided photodynamic therapy against breast cancer based on mesoporous platinum with insitu oxygen generation ability.

Photodynamic therapy (PDT) has been widely used in cancer treatment. However, hypoxia in most solid tumors seriously restricts the efficacy of PDT. To improve the hypoxic microenvironment, we designed a novel mesoporous platinum (mPt) nanoplatform to catalyze hydrogen peroxide (H2O2) within the tumor cells in situ without an extra enzyme. During the fabrication, the carboxy terminus of the photosensitizer chlorin e6 (Ce6) was connected to the amino terminus of the bifunctional mercaptoaminopolyglycol (SH-PEG-NH2) by a condensation reaction, and then PEG-Ce6 was modified onto the mPt moiety via the mercapto terminal of SH-PEG-NH2. Material, cellular and animal experiments demonstrated that Pt@PEG-Ce6 catalyzed H2O2 to produce oxygen (O2) and that Ce6 transformed O2 to generate reactive oxygen species (ROS) upon laser irradiation. The Pt@PEG-Ce6 nanoplatform with uniform diameter presented good biocompatibility and efficient tumor accumulation. Due to the high atomic number and good near-infrared absorption for Pt, this Pt@PEG-Ce6 nanoplatform showed computed tomography (CT) and photoacoustic (PA) dual-mode imaging ability, thus providing an important tool for monitoring the tumor hypoxic microenvironment. Moreover, the Pt@PEG-Ce6 nanoplatform reduced the expression of hypoxia-inducible factor-1α (HIF-1α) and programmed death-1 (PD-1) in tumors, discussing the relationship between hypoxia, PD-1, and PDT for the first time.

Deep Learning Approach for Anterior Cruciate Ligament Lesion Detection: Evaluation of Diagnostic Performance Using Arthroscopy as the Reference Standard.

BACKGROUND: MRI is the most commonly used imaging method for diagnosing anterior cruciate ligament (ACL) injuries. However, the interpretation of knee MRI is time-intensive and depends on the clinical experience of the reader. An automated detection system based on a deep-learning algorithm may improve interpretation time and reliability. PURPOSE: To determine the feasibility of using a deep learning approach to detect ACL injuries within the knee joint on MRI. STUDY TYPE: Retrospective. POPULATION: In all, 163 subjects with an ACL tear and 245 subjects with an intact ACL. There were 285, 81, and 42 volumes for training, validation, and test sets, respectively. FIELD STRENGTH/SEQUENCE: 2D sagittal proton density-weighted spectral attenuated inversion recovery sequences at 1.5T and 3.0T. ASSESSMENT: Based on the architecture of 3D DenseNet, we constructed a classification convolutional neural network. We tested this deep learning approach with different inputs and two other algorithms, including VGG16 and ResNet. Then we had both inexperienced radiologists and senior radiologists read the MR images. STATISTICAL TESTS: Using arthroscopic results as the reference standard, the performance of three different inputs and three different algorithms, the residents and senior radiologists assessed the classification accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the receiver operating characteristic curve (AUC). RESULTS: The accuracy, sensitivity, specificity, PPV, and NPV of our customized 3D deep learning architecture was 0.957, 0.976, 0.944, 0.940, and 0.976, respectively. The average AUCs were 0.946, 0.859, 0.960 for ResNet, VGG16, and our proposed network, respectively. The diagnostic accuracy of our model, residents, and senior radiologists was 0.957, 0.814, and 0.899, respectively. DATA CONCLUSION: Our study demonstrated the feasibility of using an automated deep-learning-based detection system to evaluate ACL injury. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 1 J. MAGN. RESON. IMAGING 2020;52:1745-1752.

Combining optical coherence tomography with magnetic resonance angiography and Doppler ultrasonography for clinical detection of scleroderma.

Scleroderma (SD) is a rare and agnogenic autoimmune disease whose progression can be modified by medical or surgical intervention if detected early. Multimodality imaging makes early detection of SD possible based on the structural and functional findings from different imaging methods. Combining optical coherence tomography (OCT) with magnetic resonance angiography (MRA) and Doppler ultrasonography (DUS) to identify the typical structural and functional features that can exhibit significant differences between SD patients and healthy controls. In this study, six participants (three healthy volunteers and three SD patients) were recruited and clinically examined by a rheumatologist. Participants' fingers were scanned by MRA, DUS, and OCT, respectively. MRA and DSU imaging results showed that SD patients exhibited thicker finger skin, a loss of blood vessels, and lower blood flow, whereas OCT captured the high-resolution morphology changes of the skin, epidermal, dermis, and subcutaneous layers, demonstrating a distinct loss of the dermo-epidermal junction in SD patients. Multimodal imaging techniques offer a more comprehensive characterization of the morphological and functional information of biological tissues, which can assist physicians to achieve a more accurate SD diagnosis.