Distinction of the object recognition and object identification in the brain-computer interfaces applications.

Object recognition is a complex cognitive process in which information is integrated and processed by various brain regions. Previous studies have shown that both the visual and temporal cortices are active during object recognition and identification. However, although object recognition and object identification are similar, these processes are considered distinct functions in the brain. Despite this, the differentiation between object recognition and identification has yet to be clearly defined for use in brain-computer interface (BCI) applications. This research aims to utilize neural features related to object recognition and identification and classify these features to differentiate between the two processes. The results demonstrate that several classifiers achieved high levels of accuracy, with the XGBoost classifier using a Linear Booster achieving the highest accuracy at 96% and a F1 score of 0.97. This ability to distinguish between object recognition and identification can be a beneficial aspect of a BCI object recognition system as it could help determine the intended target object for a user.

Ventral and Dorsal Stream EEG Channels: Key Features for EEG-Based Object Recognition and Identification.

Object recognition and object identification are multifaceted cognitive operations that require various brain regions to synthesize and process information. Prior research has evidenced the activity of both visual and temporal cortices during these tasks. Notwithstanding their similarities, object recognition and identification are recognized as separate brain functions. Drawing from the two-stream hypothesis, our investigation aims to understand whether the channels within the ventral and dorsal streams contain pertinent information for effective model learning regarding object recognition and identification tasks. By utilizing the data we collected during the object recognition and identification experiment, we scrutinized EEGNet models, trained using channels that replicate the two-stream hypothesis pathways, against a model trained using all available channels. The outcomes reveal that the model trained solely using the temporal region delivered a high accuracy level in classifying four distinct object categories. Specifically, the object recognition and object identification models achieved an accuracy of 89% and 85%, respectively. By incorporating the channels that mimic the ventral stream, the model's accuracy was further improved, with the object recognition model and object identification model achieving an accuracy of 95% and 94%, respectively. Furthermore, the Grad-CAM result of the trained models revealed a significant contribution from the ventral and dorsal stream channels toward the training of the EEGNet model. The aim of our study is to pinpoint the optimal channel configuration that provides a swift and accurate brain-computer interface system for object recognition and identification.

A general design of pyridinium-based fluorescent probes for enhancing two-photon microscopy.

Two-photon absorbing fluorescent probes have emerged as powerful imaging tools for subcellular-level monitoring of biological substances and processes, offering advantages such as deep light penetration, minimal photodamage, low autofluorescence, and high spatial resolution. However, existing two-photon absorbing probes still face several limitations, such as small two-photon absorption cross-section, poor water solubility, low membrane permeability, and potentially high toxicity. Herein, we report three small-molecule probes, namely MSP-1arm, Lyso-2arm, and Mito-3arm, composed of a pyridinium center (electron-acceptor) and various methoxystyrene "arms" (electron-donor). These probes exhibit excellent fluorescence quantum yield and decent aqueous solubility. Leveraging the inherent intramolecular charge transfer and excitonic coupling effect, these complexes demonstrate excellent two-photon absorption in the near-infrared region. Notably, Lyso-2arm and Mito-3arm exhibit distinct targeting abilities for lysosomes and mitochondria, respectively. In two-photon microscopy experiments, Mito-3arm outperforms a commercial two-photon absorbing dye in 2D monolayer HeLa cells, delivering enhanced resolution, broader NIR light excitation window, and higher signal-to-noise ratio. Moreover, the two-photon bioimaging of 3D human forebrain organoids confirms the successful deep tissue imaging capabilities of both Lyso-2arm and Mito-3arm. Overall, this work presents a rational design strategy in developing competent two-photon-absorbing probes by varying the number of conjugated "arms" for bioimaging applications.

Classifying Multi-Level Stress Responses From Brain Cortical EEG in Nurses and Non-Health Professionals Using Machine Learning Auto Encoder.

OBJECTIVE: Mental stress is a major problem in our society and has become an area of interest for many psychiatric researchers. One primary research focus area is the identification of bio-markers that not only identify stress but also predict the conditions (or tasks) that cause stress. Electroencephalograms (EEGs) have been used for a long time to study and identify bio-markers. While these bio-markers have successfully predicted stress in EEG studies for binary conditions, their performance is suboptimal for multiple conditions of stress. METHODS: To overcome this challenge, we propose using latent based representations of the bio-markers, which have been shown to significantly improve EEG performance compared to traditional bio-markers alone. We evaluated three commonly used EEG based bio-markers for stress, the brain load index (BLI), the spectral power values of EEG frequency bands (alpha, beta and theta), and the relative gamma (RG), with their respective latent representations using four commonly used classifiers. RESULTS: The results show that spectral power value based bio-markers had a high performance with an accuracy of 83%, while the respective latent representations had an accuracy of 91%.

Beyond vernacular: Measurement solutions to the lexical fallacy in disgust research.

Disgust may play an important role in several mental disorders, in part because disgust seems impervious to corrective information, a feature noted long before it was studied by clinical psychologists. A deeper understanding of disgust could improve not only the treatment of mental disorders, but also other societal problems involving this peculiar emotion. In this paper, we review the measurement of disgust and identify issues that hold back progress in understanding how to treat this emotion. First, self-report measures of disgust, although optimized in terms of reliability, are compromised in terms of validity due to the "lexical fallacy," that is, the assumption that vernacular usage of emotion terms reveals natural kinds. Improved self-report measures that parse disgust from neighboring states of discomfort and disapproval can address this limitation, but these approaches are absent in clinical psychology. Second, "objective" measures of disgust, although free of vernacular limitations, require greater psychometric scrutiny. In a critical review, we find that most instrument-based measures fail to demonstrate adequate reliability, rendering them unsuitable for the individual differences research crucial to clinical psychology. In light of this assessment, we provide several recommendations for improving the reliability and validity of disgust measurement, including renewed attention to theory.

Advances in the development of gene therapy, noncoding RNA, and exosome-based treatments for tendinopathy.

Tendinopathy is a common musculoskeletal disorder characterized by chronic low-grade inflammation and tissue degeneration. Tendons have poor innate healing ability and there is currently no cure for tendinopathy. Studies elucidating mechanisms underlying the pathogenesis of tendinopathy and mechanisms mediating the genesis of tendons during development have provided novel targets and strategies to enhance tendon healing and repair. This review summarizes the current understanding and treatments for tendinopathy. The review also highlights recent advances in gene therapy, the potential of noncoding RNAs, such as microRNAs, and exosomes, which are nanometer-sized extracellular vesicles secreted from cells, for the treatment of tendinopathy.

CITED2 mediates the cross-talk between mechanical loading and IL-4 to promote chondroprotection.

Osteoarthritis (OA) pathogenesis is mediated largely through the actions of proteolytic enzymes such as matrix metalloproteinase (MMP) 13. The transcriptional regulator CITED2, which suppresses the expression of MMP13 in chondrocytes, is induced by interleukin (IL)-4 in T cells and macrophages, and by moderate mechanical loading in chondrocytes. We tested the hypothesis that CITED2 mediates cross-talk between IL-4 signaling and mechanical loading-induced pathways that result in chondroprotection, at least in part, by downregulating MMP13. IL-4 induced CITED2 gene expression in human chondrocytes in a dose- and time-dependent manner through JAK/STAT signaling. Mechanical loading combined with IL-4 resulted in additive effects on inducing CITED2 expression and downregulating of MMP13 in human chondrocytes in vitro. In vivo, IL-4 gene knockout (KO) mice exhibited reduced basal levels of CITED2 expression in chondrocytes. While moderate treadmill running induced CITED2 expression and reduced MMP13 expression in wild-type mice, these effects were blunted (for CITED2) or abolished (for MMP13) in chondrocytes of IL-4 gene KO mice. Moreover, intra-articular injections of mouse recombinant IL-4 combined with regular cage activity mitigated post-traumatic OA to a greater degree compared to immobilized mice treated with IL-4 alone. These data suggest that using moderate loading to enhance IL-4 may be a potential therapeutic strategy for chondroprotection in OA.

CITED2 mediates the mechanical loading-induced suppression of adipokines in the infrapatellar fat pad.

Adipokines secreted from the infrapatellar fat pad (IPFP), such as adipsin and adiponectin, have been implicated in osteoarthritis pathogenesis. CITED2, a mechanosensitive transcriptional regulator with chondroprotective activity, may modulate their expression. Cited2 haploinsufficient mice (Cited2+/- ) on a high-fat diet (HFD) exhibited increased body weight and increased IPFP area compared to wild-type (WT) mice on an HFD. While an exercise regimen of moderate treadmill running induced the expression of CITED2, as well as PGC-1α, and reduced the expression of adipsin and adiponectin in the IPFP of WT mice on an HFD, Cited2 haploinsufficiency abolished the loading-induced expression of PGC-1α and loading-induced suppression of adipsin and adiponectin. Furthermore, knocking down or knocking out CITED2 in adipose stem cells (ASCs)/preadipocytes derived from the IPFP in vitro led to the increased expression of adipsin and adiponectin and reduced PGC-1α, and abolished the loading-induced suppression of adipsin and adiponectin and loading-induced expression of PGC-1α. Overexpression of PGC-1α in these ASC/preadipocytes reversed the effects caused by CITED2 deficiency. The current data suggest that CITED2 is a critical regulator in physiologic loading-induced chondroprotection in the context of an HFD and PGC-1α is required for the inhibitory effects of CITED2 on the expression of adipokines such as adipsin and adiponectin in the IPFP.

Epigallocatechin-3-gallate suppresses pain-related and proinflammatory mediators in the subacromial bursa in rotator cuff tendinopathy.

Rotator cuff tendinopathy is one of the leading causes of shoulder pain. However, the mechanisms involved in the development of rotator cuff tendinopathy pain are not fully understood. In this study, we first examined the histological features of subacromial bursa from patients with rotator cuff tendinopathy who had symptoms of pain, and investigated the expression of pain mediators, proinflammatory cytokines, metalloproteinases, growth factors, and alarmins in diseased tendon and bursa tissue by real-time PCR, western blot, and/or immunohistochemistry/immunofluorescence staining. Then we investigated whether epigallocatechin-3-gallate (EGCG) could reduce the expression of pain mediators and proinflammatory cytokines in human primary bursa cells and explored the paracrine effect of these EGCG-treated bursa cells on tenocytes in vitro. Neovascularization and infiltration of immune cells including monocytes/macrophages and mast cells were observed in diseased bursa tissue. Bursa from patients with pain had higher mRNA expression of pain mediators and proinflammatory cytokines, compared to the rotator cuff tendon of the same patients, as well as the bursa from asymptomatic patients. EGCG treatment significantly suppressed the interleukin 1 beta (IL-1ß)-induced elevation of mRNA expression of pain mediators, proinflammatory cytokines, and matrix metalloproteinases (MMPs) in bursa cells in vitro; conditioned medium from EGCG-treated bursa cells significantly reduced IL-1ß-induced expression in human primary tenocytes. Our study suggests that the subacromial bursa might serve as a local source of pain mediators and proinflammatory cytokines in rotator cuff tendinopathy. Moreover, EGCG treatment by primarily targeting the subacromial bursa may be a potential strategy to relieve rotator cuff tendinopathy-related pain and symptoms.

Correction to: Green tea polyphenol treatment is chondroprotective, anti-inflammatory and palliative in a mouse posttraumatic osteoarthritis model.

Following publication of the original article [1], the authors reported an error in Figs. 2C and 5C.

Retraction Note: The Role of Scleraxis in Fate Determination of Mesenchymal Stem Cells for Tenocyte Differentiation.

This paper has been retracted.

Nutraceuticals and osteoarthritis pain.

Arthritis is a chronic disease of joints. It is highly prevalent, particularly in the elderly, and is commonly associated with pain that interferes with quality of life. Because of its chronic nature, pharmacological approaches to pain relief and joint repair must be safe for long term use, a quality many current therapies lack. Nutraceuticals refer to compounds or materials that can function as nutrition and exert a potential therapeutic effect, including the relief of pain, such as pain related to arthritis, of which osteoarthritis (OA) is the most common form. Of interest, nutraceuticals have recently been shown to have potential in relieving OA pain in human clinical trials. Emerging evidence indicates nutraceuticals may represent promising alternatives for the relief of OA pain. In this paper, we will overview OA pain and the use of nutraceuticals in OA pain management, focusing on those that have been evaluated by clinical trials. Furthermore, we discuss the biologic and pharmacologic actions underlying the nutraceutical effects on pain relief based on the potential active ingredients identified from traditional nutraceuticals in OA pain management and their potential for drug development. The review concludes by sharing our viewpoints that future studies should prioritize elucidating the mechanisms of action of nutraceuticals in OA and developing nutraceuticals that not only relieve OA pain, but also mitigate OA pathology.

Exosomes: biology, therapeutic potential, and emerging role in musculoskeletal repair and regeneration.

Exosomes are nanovesicles secreted from cells that play key roles in intercellular communication. They carry unique content derived from parental cells and are capable of transferring this cargo between cells. The role and function of exosomes largely depends on the origin and functional status of the parental cells. Emerging evidence indicates that exosomes are associated with biological processes and pathogenesis of certain diseases. These nanovesicles offer great potential as biomarkers, enabling the monitoring and diagnosis of various diseases in a noninvasive manner. Furthermore, as an efficient vehicle of biomolecular intercellular transfer, exosomes are under intensive investigation for their potential for drug delivery and carriers for gene therapy. Here, we first summarize the basic biology and function of exosomes, followed by a discussion of their clinical potential, including the use of exosomes for disease diagnosis, treatment, and drug delivery. The review will highlight the potential of exosomes derived from stem cells in regenerative medicine, with a focus on musculoskeletal tissues. We conclude by sharing our views on the challenges, opportunities, and future directions for the use of exosomes as a therapeutic treatment for the repair and regeneration of musculoskeletal tissues.

Caveolae provide a specialized membrane environment for respiratory syncytial virus assembly.

Respiratory syncytial virus (RSV) is an enveloped virus that assembles into filamentous virus particles on the surface of infected cells. Morphogenesis of RSV is dependent upon cholesterol-rich (lipid raft) membrane microdomains, but the specific role of individual raft molecules in RSV assembly is not well defined. Here, we show that RSV morphogenesis occurs within caveolar membranes and that both caveolin-1 and cavin-1 (also known as PTRF), the two major structural and functional components of caveolae, are actively recruited to and incorporated into the RSV envelope. The recruitment of caveolae occurred just prior to the initiation of RSV filament assembly, and was dependent upon an intact actin network as well as a direct physical interaction between caveolin-1 and the viral G protein. Moreover, cavin-1 protein levels were significantly increased in RSV-infected cells, leading to a virus-induced change in the stoichiometry and biophysical properties of the caveolar coat complex. Our data indicate that RSV exploits caveolae for its assembly, and we propose that the incorporation of caveolae into the virus contributes to defining the biological properties of the RSV envelope.

Advances of stem cell based-therapeutic approaches for tendon repair.

Tendon injuries are significant clinical problems. Current treatments often result in incomplete repair or healing, which may lead to reduced function and rupture. Stem cell-based therapy is a promising intervention for tendon repair. In this article, we attempt to provide a brief overview on the recent progress in the field, current understanding of the underlying mechanisms of the approach, and the potential of stem cell-based therapies beyond cell implantation. We conclude the review by sharing our viewpoints on the challenges, opportunities, and future directions of this approach. The translational potential of this article: This paper reviews recent progress on stem cell-based therapeutic approaches for tendon repair, which highlights its translational potential and challenges.

Procyanidins Mitigate Osteoarthritis Pathogenesis by, at Least in Part, Suppressing Vascular Endothelial Growth Factor Signaling.

Procyanidins are a family of plant metabolites that have been suggested to mitigate osteoarthritis pathogenesis in mice. However, the underlying mechanism is largely unknown. This study aimed to determine whether procyanidins mitigate traumatic injury-induced osteoarthritis (OA) disease progression, and whether procyanidins exert a chondroprotective effect by, at least in part, suppressing vascular endothelial growth factor signaling. Procyanidins (extracts from pine bark), orally administered to mice subjected to surgery for destabilization of the medial meniscus, significantly slowed OA disease progression. Real-time polymerase chain reaction revealed that procyanidin treatment reduced expression of vascular endothelial growth factor and effectors in OA pathogenesis that are regulated by vascular endothelial growth factor. Procyanidin-suppressed vascular endothelial growth factor expression was correlated with reduced phosphorylation of vascular endothelial growth factor receptor 2 in human OA primary chondrocytes. Moreover, components of procyanidins, procyanidin B2 and procyanidin B3 exerted effects similar to those of total procyanidins in mitigating the OA-related gene expression profile in the primary culture of human OA chondrocytes in the presence of vascular endothelial growth factor. Together, these findings suggest procyanidins mitigate OA pathogenesis, which is mediated, at least in part, by suppressing vascular endothelial growth factor signaling.

Mesenchymal stem cells in tendon repair and regeneration: basic understanding and translational challenges.

Tendon injuries are common and present a clinical challenge because they often respond poorly to treatment and require prolonged rehabilitation. Current treatments often do not completely repair or regenerate the injured or diseased tendon to its native composition, structure, and mechanical properties. Stem cell-based therapies have brought new hope for tissue repair and regeneration, including that for tendon rupture and tendinopathy. Despite tremendous effort and progress, the success of stem cell-based studies on tendon repair and regeneration has mainly been limited to preclinical studies with few clinical applications. In this concise review, we discuss basic understanding and translational challenges of using mesenchymal stem cells (MSCs) for tendon repair and regeneration, with a focus on (1) tendon stem/progenitor cells (TSPCs) and therapeutic approaches using TSPCs and other MSCs, (2) regulation of fate determination in MSCs for tendon-lineage differentiation, (3) pretreatment and condition of stem/progenitor cells for transplantation, and (4) a treatment approach that involves stimulating endogenous stem cells to enhance tendon healing. The review concludes with discussion on future directions.

Curcumin slows osteoarthritis progression and relieves osteoarthritis-associated pain symptoms in a post-traumatic osteoarthritis mouse model.

BACKGROUND: Curcumin has been shown to have chondroprotective potential in vitro. However, its effect on disease and symptom modification in osteoarthritis (OA) is largely unknown. This study aimed to determine whether curcumin could slow progression of OA and relieve OA-related pain in a mouse model of destabilization of the medial meniscus (DMM). METHODS: Expression of selected cartilage degradative-associated genes was evaluated in human primary chondrocytes treated with curcumin and curcumin nanoparticles and assayed by real-time PCR. The mice subjected to DMM surgery were orally administered curcumin or topically administered curcumin nanoparticles for 8 weeks. Cartilage integrity was evaluated by Safranin O staining and Osteoarthritis Research Society International (OARSI) score, and by immunohistochemical staining of cleaved aggrecan and type II collagen, and levels of matrix metalloproteinase (MMP)-13 and ADAMTS5. Synovitis and subchondral bone thickness were scored based on histologic images. OA-associated pain and symptoms were evaluated by von Frey assay, and locomotor behavior including distance traveled and rearing. RESULTS: Both curcumin and nanoparticles encapsulating curcumin suppressed mRNA expression of pro-inflammatory mediators IL-1ß and TNF-α, MMPs 1, 3, and 13, and aggrecanase ADAMTS5, and upregulated the chondroprotective transcriptional regulator CITED2, in primary cultured chondrocytes in the absence or presence of IL-1ß. Oral administration of curcumin significantly reduced OA disease progression, but showed no significant effect on OA pain relief. Curcumin was detected in the infrapatellar fat pad (IPFP) following topical administration of curcumin nanoparticles on the skin of the injured mouse knee. Compared to vehicle-treated controls, topical treatment led to: (1) reduced proteoglycan loss and cartilage erosion and lower OARSI scores, (2) reduced synovitis and subchondral plate thickness, (3) reduced immunochemical staining of type II collagen and aggrecan cleavage epitopes and numbers of chondrocytes positive for MMP-13 and ADAMTS5 in the articular cartilage, and (4) reduced expression of adipokines and pro-inflammatory mediators in the IPFP. In contrast to oral curcumin, topical application of curcumin nanoparticles relieved OA-related pain as indicated by reduced tactile hypersensitivity and improved locomotor behavior. CONCLUSION: This study provides the first evidence that curcumin significantly slows OA disease progression and exerts a palliative effect in an OA mouse model.

Rho/Rock signal transduction pathway is required for MSC tenogenic differentiation.

Mesenchymal stem cell (MSC)-based treatments have shown promise for improving tendon healing and repair. MSCs have the potential to differentiate into multiple lineages in response to select chemical and physical stimuli, including into tenocytes. Cell elongation and cytoskeletal tension have been shown to be instrumental to the process of MSC differentiation. Previous studies have shown that inhibition of stress fiber formation leads MSCs to default toward an adipogenic lineage, which suggests that stress fibers are required for MSCs to sense the environmental factors that can induce differentiation into tenocytes. As the Rho/ROCK signal transduction pathway plays a critical role in both stress fiber formation and in cell sensation, we examined whether the activation of this pathway was required when inducing MSC tendon differentiation using rope-like silk scaffolds. To accomplish this, we employed a loss-of-function approach by knocking out ROCK, actin and myosin (two other components of the pathway) using the specific inhibitors Y-27632, Latrunculin A and blebbistatin, respectively. We demonstrated that independently disrupting the cytoskeleton and the Rho/ROCK pathway abolished the expression of tendon differentiation markers and led to a loss of spindle morphology. Together, these studies suggest that the tension that is generated by MSC elongation is essential for MSC teno-differentiation and that the Rho/ROCK pathway is a critical mediator of tendon differentiation on rope-like silk scaffolds.