Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial tissue inflammation and joint destruction associated with the activation of angiogenesis. Exosomes, which play a role in cell-to-cell communication as carriers of genetic information, transfer microRNAs (miRNAs or miRs) between cells and have been studied as delivery vehicles for therapeutic molecules. The aim of the current study was to investigate the therapeutic effect of mesenchymal stem cell (MSC)-derived miR-150-5p exosomes on joint destruction in RA. The expression and secretion of miR-150-5p, matrix metalloproteinase (MMP) 14, and vascular endothelial growth factor (VEGF) in RA patients and fibroblast-like synoviocytes (FLS) were examined by quantitative RT-PCR, ELISA, and Western blotting. Immunohistochemistry was used to assess angiogenesis. MSCs were transfected with an miR-150-5p expression plasmid, and MSC-derived exosomes were harvested. The effect of MSC-derived miR-150-5p exosomes (Exo-150) on MMP14 and VEGF expression was examined. The effects of Exo-150 on cell migration and invasion in cytokine-stimulated FLS from RA patients were examined by HUVEC tube formation and transwell assays. The effect of Exo-150 in vivo was examined in a collagen-induced arthritis mouse model. Exo-150 decreased migration and invasion in RA FLS and downregulated tube formation in HUVECs by targeting MMP14 and VEGF. Injection of Exo-150 reduced hind paw thickness and the clinical arthritic scores in collagen-induced arthritis mice. Exo-150 reduced joint destruction by inhibiting synoviocyte hyperplasia and angiogenesis. Exosomes facilitate the direct intracellular transfer of miRNAs between cells and represent a potential therapeutic strategy for RA.

We demonstrate a fiber optic surface plasmon resonance (SPR) biosensor based on smart phone platforms. The light-weight optical components and sensing element are connected by optical fibers on a phone case. This SPR adaptor can be conveniently installed or removed from smart phones. The measurement, control and reference channels are illuminated by the light entering the lead-in fibers from the phone’s LED flash, while the light from the end faces of the lead-out fibers is detected by the phone’s camera. The SPR-sensing element is fabricated by a light-guiding silica capillary that is stripped off its cladding and coated with 50-nm gold film. Utilizing a smart application to extract the light intensity information from the camera images, the light intensities of each channel are recorded every 0.5 s with refractive index (RI) changes. The performance of the smart phone-based SPR platform for accurate and repeatable measurements was evaluated by detecting different concentrations of antibody binding to a functionalized sensing element, and the experiment results were validated through contrast experiments with a commercial SPR instrument. This cost-effective and portable SPR biosensor based on smart phones has many applications, such as medicine, health and environmental monitoring.

Extracellular vesicles (EVs) are lipid‐bilayer membrane structures secreted by most cell types. EVs act as messengers via the horizontal transfer of lipids, proteins, and nucleic acids, and influence various pathophysiological processes in both parent and recipient cells. Compared to EVs obtained from body fluids or cell culture supernatants, EVs isolated directly from tissues possess a number of advantages, including tissue specificity, accurate reflection of tissue microenvironment, etc., thus, attention should be paid to tissue‐derived EVs (Ti‐EVs). Ti‐EVs are present in the interstitium of tissues and play pivotal roles in intercellular communication. Moreover, Ti‐EVs provide an excellent snapshot of interactions among various cell types with a common histological background. Thus, Ti‐EVs may be used to gain insights into the development and progression of diseases. To date, extensive investigations have focused on the role of body fluid‐derived EVs or cell culture‐derived EVs; however, the number of studies on Ti‐EVs remains insufficient. Herein, we summarize the latest advances in Ti‐EVs for cancers and non‐cancer diseases. We propose the future application of Ti‐EVs in basic research and clinical practice. Workflows for Ti‐EV isolation and characterization between cancers and non‐cancer diseases are reviewed and compared. Moreover, we discuss current issues associated with Ti‐EVs and provide potential directions.

Objective Osteoporosis is a prevalent and treatable condition, but it remains underdiagnosed. In this study, a deep learning-based system was developed to automatically measure bone mineral density (BMD) for opportunistic osteoporosis screening using lowdose chest computed tomography (LDCT) scans obtained for lung cancer screening. Methods First, a deep learning model was trained and tested with 200 annotated LDCT scans to segment and label all vertebral bodies (VBs). Then, the mean CT numbers of the trabecular area of target VBs were obtained based on the segmentation mask through geometric operations. Finally, a linear function was built to map the trabecular CT numbers of target VBs to their BMDs collected from approved software used for osteoporosis diagnosis. The diagnostic performance of the developed system was evaluated using an independent dataset of 374 LDCT scans with standard BMDs and osteoporosis diagnosis. Results Our deep learning model achieved a mean Dice coefficient of 86.6% for VB segmentation and 97.5% accuracy for VB labeling. Line regression and Bland-Altman analyses showed good agreement between the predicted BMD and the ground truth, with correlation coefficients of 0.964-0.968 and mean errors of 2.2-4.0 mg/cm 3. The area under the curve (AUC) was 0.927 for detecting osteoporosis and 0.942 for distinguishing low BMD. Conclusion The proposed deep learning-based system demonstrated the potential to automatically perform opportunistic osteoporosis screening using LDCT scans obtained for lung cancer screening. Key Points • Osteoporosis is a prevalent but underdiagnosed condition that can increase the risk of fracture. • A deep learning-based system was developed to fully automate bone mineral density measurement in low-dose chest computed tomography scans. • The developed system achieved high accuracy for automatic opportunistic osteoporosis screening using low-dose chest computed tomography scans obtained for lung cancer screening. Keywords Bone mineral density. Deep learning. Osteoporosis. Screening Abbreviations AUC Area under the curve BMD Bone mineral density CNN Convolutional neural network CT Computed tomography DL Deep learning DXA Dual-energy X-ray absorptiometry LDCT Low-dose chest computed tomography QA Quality assurance QCT Quantitative computed tomography VB Vertebral body VOI Volume of interest Yaling Pan and Dejun Shi contributed equally to this work.

The midbrain ventrolateral periaqueductal gray (VL-PAG) is a key component that mediates pain modulation. Although spinal cord glial cells appear to play an important role in chronic pain development, the precise mechanisms involving descending facilitation pathways from the PAG following nerve injury are poorly understood. This study shows that cellular events that occur during glial activation in the VL-PAG may promote descending facilitation from the PAG during neuropathic pain. Chronic constriction nerve injury (CCI) was induced by ligature construction of the sciatic nerve in male Sprague-Dawley rats. Behavioral responses to noxious mechanical (paw withdrawal threshold; PWT) and thermal (paw withdrawal latency; PWL) stimuli were evaluated. After CCI, immunohistochemical and Western blot analysis of microglia and astrocytes in the VL-PAG showed morphological and quantitative changes indicative of activation in microglia and astrocytes. Intra-VL-PAG injection of microglial or astrocytic inhibitors attenuated PWT and PWL at days 7 and 14, respectively, following CCI. We also evaluated the effects of intra-VL-PAG administration of the phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK) inhibitor SB 203580 at day 7 after CCI. This treatment abolished microglial activation and produced a significant time-dependent attenuation of PWT and PWL. Western blot analysis showed localized expression of p-p38 in the VL-PAG after CCI. P-p38 was expressed in labeled microglia of the VL-PAG but was not present in astrocytes and neurons on day 7 after CCI. These results demonstrate that CCI-induced neuropathic pain is associated with glial activation in the VL-PAG, which likely participates in descending pain facilitation through the p38 MAPK signaling pathway.

Objectives To automatically measure the Cobb angle and diagnose scoliosis on chest X-rays, a computer-aided method was proposed and the reliability and accuracy were evaluated. Methods Two Mask R-CNN models as the core of a computer-aided method were used to separately detect and segment the spine and all vertebral bodies on chest X-rays, and the Cobb angle of the spinal curve was measured from the output of the Mask R-CNN models. To evaluate the reliability and accuracy of the computer-aided method, the Cobb angles on 248 chest X-rays from lung cancer screening were measured automatically using a computer-aided method, and two experienced radiologists used a manual method to separately measure Cobb angles on the aforementioned chest X-rays. Results For manual measurement of the Cobb angle on chest X-rays, the intraclass correlation coefficients (ICC) of intra-and inter-observer reliability analysis was 0.941 and 0.887, respectively, and the mean absolute differences were < 3.5°. The ICC between the computer-aided and manual methods for Cobb angle measurement was 0.854, and the mean absolute difference was 3.32°. These results indicated that the computer-aided method had good reliability for Cobb angle measurement on chest X-rays. Using the mean value of Cobb angles in manual measurements > 10° as a reference standard for scoliosis, the computer-aided method achieved a high level of sensitivity (89.59%) and a relatively low level of specificity (70.37%) for diagnosing scoliosis on chest X-rays. Conclusion The computer-aided method has potential for automatic Cobb angle measurement and scoliosis diagnosis on chest X-rays.

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A new vinyl sulfone (VS) disulfide, 1,2-bis(11-(vinyl sulfonyl)undecyl)disulfane, was synthesized to enable the preparation of VS-presenting self-assembled monolayers (VS SAMs) on Au substrates. The VS SAMs were used as a model system to assess the reaction kinetics of bioactive ligands, i.e., glutathione (GSH), N-(5-amino-1-carboxypentyl)iminodiacetic acid (ab-NTA), and mannose, toward the VS groups on the SAM surface. The VS SAMs and the ligand immobilization were characterized by X-ray photoelectron spectroscopy (XPS), contact angle goniometry, and protein-binding experiments using a quartz crystal microbalance (QCM). Kinetic studies showed that the surface VS groups undergo pseudo-first-order reactions with various ligands, with the observed rate constant being 0.057 min(-1) for GSH at pH 7.5, 0.011 min(-1) for ab-NTA at pH 8.5, and 0.009 min(-1) for mannose at pH 10.5. This work advanced our understanding of the reactivity of VS-bearing functional surfaces and further demonstrated the versatile potential of VS chemistry to prepare ligand-immobilized bioactive surfaces.