Human embryonic stem cell-derived mesenchymal stromal cells suppress inflammation in mouse models of rheumatoid arthritis and lung fibrosis by regulating T-cell function.

BACKGROUND AIMS: Rheumatoid arthritis (RA) is characterized by an overactive immune system, with limited treatment options beyond immunosuppressive drugs or biological response modifiers. Human embryonic stem cell-derived mesenchymal stromal cells (hESC-MSCs) represent a novel alternative, possessing diverse immunomodulatory effects. In this study, we aimed to elucidate the therapeutic effects and underlying mechanisms of hESC-MSCs in treating RA. METHODS: MSC-like cells were differentiated from hESC (hESC-MSCs) and cultured in vitro. Cell proliferation was assessed using Cell Counting Kit-8 assay and Ki-67 staining. Flow cytometry was used to analyze cell surface markers, T-cell proliferation and immune cell infiltration. The collagen-induced arthritis (CIA) mouse model and bleomycin-induced model of lung fibrosis (BLE) were established and treated with hESC-MSCs intravenously for in vivo assessment. Pathological analyses, reverse transcription-quantitative polymerase chain reaction and Western blotting were conducted to evaluate the efficacy of hESC-MSCs treatment. RESULTS: Intravenous transplantation of hESC-MSCs effectively reduced inflammation in CIA mice in this study. Furthermore, hESC-MSC administration enhanced regulatory T cell infiltration and activation. Additional findings suggest that hESC-MSCs may reduce lung fibrosis in BLE mouse models, indicating their potential to mitigate complications associated with RA progression. In vitro experiments revealed a significant inhibition of T-cell activation and proliferation during co-culture with hESC-MSCs. In addition, hESC-MSCs demonstrated enhanced proliferative capacity compared with traditional primary MSCs. CONCLUSIONS: Transplantation of hESC-MSCs represents a promising therapeutic strategy for RA, potentially regulating T-cell proliferation and differentiation.

Multilevel Spatial-Temporal Excited Graph Network for Skeleton-based Action Recognition.

The ability to capture joint connections in complicated motion is essential for skeleton-based action recognition. However, earlier approaches may not be able to fully explore this connection in either the spatial or temporal dimension due to fixed or single-level topological structures and insufficient temporal modeling. In this paper, we propose a novel multilevel spatial-temporal excited graph network (ML-STGNet) to address the above problems. In the spatial configuration, we decouple the learning of the human skeleton into general and individual graphs by designing a multilevel graph convolution (ML-GCN) network and a spatial data-driven excitation (SDE) module, respectively. ML-GCN leverages joint-level, part-level, and body-level graphs to comprehensively model the hierarchical relations of a human body. Based on this, SDE is further introduced to handle the diverse joint relations of different samples in a data-dependent way. This decoupling approach not only increases the flexibility of the model for graph construction but also enables the generality to adapt to various data samples. In the temporal configuration, we apply the concept of temporal difference to the human skeleton and design an efficient temporal motion excitation (TME) module to highlight the motion-sensitive features. Furthermore, a simplified multiscale temporal convolution (MS-TCN) network is introduced to enrich the expression ability of temporal features. Extensive experiments on the four popular datasets NTU-RGB+D, NTU-RGB+D 120, Kinetics Skeleton 400, and Toyota Smarthome demonstrate that ML-STGNet gains considerable improvements over the existing state of the art.

Phosphene object perception employs holistic processing during early visual processing stage.

Psychophysical studies have verified the possibility of recovering the visual ability by the form of low-resolution format of images, that is, phosphene-based representations. Our previous study has found that early visual processing for phosphene patterns is configuration based. This study further investigated the configural processing mechanisms of prosthetic vision by analyzing the event-related potential components (P1 and N170) in response to phosphene face and non-face stimuli. The results reveal that the coarse processing of phosphenes involves phosphene-specific holistic processing that recovers separated phosphenes into a gestalt; low-level feature processing of phosphenes is also enhanced compared with that of normal stimuli due to increased contrast borders introduced by phosphenes; while fine processing of phosphene stimuli is impaired reflected by reduced N170 amplitude because of the degraded detailed features in the low-resolution format representations. Therefore, we suggest that strategies that can facilitate the specific holistic processing stages of prosthetic vision should be considered in order to improve the performance when designing the visual prosthesis system.

Relations between BOLD fMRI-derived resting brain activity and cerebral blood flow.

Consistent resting brain activity patterns have been repeatedly demonstrated using measures derived from resting BOLD fMRI data. While those metrics are presumed to reflect underlying spontaneous brain activity (SBA), it is challenging to prove that association because resting BOLD fMRI metrics are purely model-free and scale-free variables. Cerebral blood flow (CBF) is typically closely coupled to brain metabolism and is used as a surrogate marker for quantifying regional brain function, including resting function. Assessing the correlations between resting BOLD fMRI measures and CBF correlation should provide a means of linking of those measures to the underlying SBA, and a means to quantify those scale-free measures. The purpose of this paper was to examine the CBF correlations of 3 widely used neuroimaging-based SBA measures, including seed-region based functional connectivity (FC), regional homogeneity (ReHo), and amplitude of low frequency fluctuation (ALFF). Test-retest data were acquired to check the stability of potential correlations across time. Reproducible posterior cingulate cortex (PCC) FC vs regional CBF correlations were found in much of the default mode network and visual cortex. Dorsal anterior cingulate cortex (ACC) FC vs CBF correlations were consistently found in bilateral prefrontal cortex. Both ReHo and ALFF were found to be reliably correlated with CBF in most of brain cortex. None of the assessed SBA measures was correlated with whole brain mean CBF. These findings suggest that resting BOLD fMRI-derived measures are coupled with regional CBF and are therefore linked to regional SBA.

Functional laser speckle imaging of cerebral blood flow under hypothermia.

Hypothermia can unintentionally occur in daily life, e.g., in cardiovascular surgery or applied as therapeutics in the neurosciences critical care unit. So far, the temperature-induced spatiotemporal responses of the neural function have not been fully understood. In this study, we investigated the functional change in cerebral blood flow (CBF), accompanied with neuronal activation, by laser speckle imaging (LSI) during hypothermia. Laser speckle images from Sprague-Dawley rats (n = 8, male) were acquired under normothermia (37°C) and moderate hypothermia (32°C). For each animal, 10 trials of electrical hindpaw stimulation were delivered under both temperatures. Using registered laser speckle contrast analysis and temporal clustering analysis (TCA), we found a delayed response peak and a prolonged response window under hypothermia. Hypothermia also decreased the activation area and the amplitude of the peak CBF. The combination of LSI and TCA is a high-resolution functional imaging method to investigate the spatiotemporal neurovascular coupling in both normal and pathological brain functions.

Motion-compensated noncontact imaging photoplethysmography to monitor cardiorespiratory status during exercise.

With the advance of computer and photonics technology, imaging photoplethysmography [(PPG), iPPG] can provide comfortable and comprehensive assessment over a wide range of anatomical locations. However, motion artifact is a major drawback in current iPPG systems, particularly in the context of clinical assessment. To overcome this issue, a new artifact-reduction method consisting of planar motion compensation and blind source separation is introduced in this study. The performance of the iPPG system was evaluated through the measurement of cardiac pulse in the hand from 12 subjects before and after 5 min of cycling exercise. Also, a 12-min continuous recording protocol consisting of repeated exercises was taken from a single volunteer. The physiological parameters (i.e., heart rate, respiration rate), derived from the images captured by the iPPG system, exhibit functional characteristics comparable to conventional contact PPG sensors. Continuous recordings from the iPPG system reveal that heart and respiration rates can be successfully tracked with the artifact reduction method even in high-intensity physical exercise situations. The outcome from this study thereby leads to a new avenue for noncontact sensing of vital signs and remote physiological assessment, with clear applications in triage and sports training.

Hippocampal synaptic metaplasticity requires the activation of NR2B-containing NMDA receptors.

The potential to exhibit synaptic plasticity itself is modulated by previous synaptic activity, which has been termed as metaplasticity. In this paper, we demonstrated that the activation of N-methyl-d-aspartate (NMDA) receptor 2B (NR2B) subunit in NNDA receptors was required for hippocampal metaplasticity at Schaffer collateral-commissural fiber-CA1 synapses. Brief 5 Hz priming stimulation did not cause long-term synaptic plasticity; however, it could result in the inhibition of subsequently evoked long-term potentiation (LTP). Meanwhile, the application of selective antagonists for NR2B subunit of NMDA receptors after delivering priming stimulation could block the metaplasticity. In contrast, LTP induction was not affected by NR2B antagonists in slices without pre-treatment of priming stimulation. These results indicated that the activation of NR2B-containing NMDA receptors was required for metaplasticity.

Influences of brain development and ageing on cortical interactive networks.

OBJECTIVE: To study the effect of brain development and ageing on the pattern of cortical interactive networks. METHODS: By causality analysis of multichannel electroencephalograph (EEG) with partial directed coherence (PDC), we investigated the different neural networks involved in the whole cortex as well as the anterior and posterior areas in three age groups, i.e., children (0-10 years), mid-aged adults (26-38 years) and the elderly (56-80 years). RESULTS: By comparing the cortical interactive networks in different age groups, the following findings were concluded: (1) the cortical interactive network in the right hemisphere develops earlier than its left counterpart in the development stage; (2) the cortical interactive network of anterior cortex, especially at C3 and F3, is demonstrated to undergo far more extensive changes, compared with the posterior area during brain development and ageing; (3) the asymmetry of the cortical interactive networks declines during ageing with more loss of connectivity in the left frontal and central areas. CONCLUSIONS: The age-related variation of cortical interactive networks from resting EEG provides new insights into brain development and ageing. SIGNIFICANCE: Our findings demonstrated that the PDC analysis of EEG is a powerful approach for characterizing the cortical functional connectivity during brain development and ageing.

Impaired neuronal synchrony after focal ischemic stroke in elderly patients.

OBJECTIVE: This study investigated whether cortical synchrony derived from electroencephalography (EEG) in elderly patients is impaired and if the impairment might reflect long-term functional recovery after stroke. METHODS: The scalp EEG signals of stroke patients (N=42) were collected within seven days after the onset of stroke and analyzed with phase synchronization (PS). Neurodeficit outcome was scored twice according to the National Institute of Health Stroke Scale (NIHSS): (1) at the same day of EEG recording and (2) two months after stroke. The correlation between cortical synchrony and NIHSS was analyzed. RESULTS: The level of synchronization between lesion and intact areas in the ipsilateral hemisphere was reduced significantly after stroke, while the synchronization among intact areas increased to 114% among the control subjects. Furthermore, the patients with lower inter-hemispheric synchrony after stroke were observed to have a higher NIHSS two months after stroke. CONCLUSIONS: Results indicated that the infarct broke down the cortical synchrony networks and affected large-scale neural communication. Inter-hemispheric synchrony was relevant to long-term functional recovery after stroke. SIGNIFICANCE: The prognostic value of PS for functional recovery after stroke might be helpful in understanding the alteration of cortical networks after ischemic injury.

Graphic patterns of cortical functional connectivity of depressed patients on the basis of EEG measurements.

Considerable evidences have shown a decrease of neuronal activity in the left frontal lobe of depressed patients, but the underlying cortical network is still unclear. The present study intends to investigate the conscious-state brain network patterns in depressed patients compared with control individuals. Cortical functional connectivity is quantified by the partial directed coherence (PDC) analysis of multichannel EEG signals from 12 depressed patients and 12 healthy volunteers. The corresponding PDC matrices are first converted into unweighted graphs by applying a threshold to obtain the topographic property in-degree (K(in)). A significantly larger K(in) in the left hemisphere is identified in depressed patients, while a symmetric pattern is found in the control group. Another two topographic measures, i.e., clustering coefficients (C) and characteristic path length (L), are obtained from the original weighted PDC digraphs. Compared with control individuals, significantly smaller C and L are revealed in the depression group, indicating a random network-like architecture due to affective disorder. This study thereby provides further support for the presence of a hemispheric asymmetry syndrome in the depressed patients. More importantly, we present evidence that depression is characterized by a loss of optimal small-world network characteristics in conscious state.

Influence of hypoxic-preconditioning on autonomic regulation following global ischemic brain injury in rats.

Experimental and clinical studies have shown that autonomic imbalance is associated with morbidity and mortality due to global ischemic brain injury following cardiac arrest (CA). Although hypoxic-preconditioning (HP) has shown promising neuro-protection in the subsequent ischemic brain injury, the underlying mechanisms and its influence on autonomic regulation have not yet well-understood. In this study, we utilized baroreflex sensitivity (BRS) to investigate the protective effect of HP on autonomic regulation. We investigated changes in heart rate, arterial blood pressure (BP), and BRS within 4h after CA in rats. The relationship between BRS and neurodeficit score (NDS) was analyzed. Although no significant differences were found in heart rate and BP before and after CA between the control and the preconditioned groups, both BRS and NDS of preconditioned rats were clearly higher than that of the control rats during recovery after CA. Furthermore, BRS in the first 4h after CA highly correlated with NDS 24h after CA. These results imply that treatment with HP improves autonomic regulation and protects the brain from ischemic injury. The correlation between BRS and NDS also suggests that BRS can be a prognostic criterion for the level of brain injury after CA.

Object recognition under distorted prosthetic vision.

Psychophysical studies have reported the efficacy of phosphene-based prosthetic vision in partly recovering the visual function of blind individuals. However, results by far have been based on evenly aligned phosphene arrays, which neglected the complicated visuotopy in the visual prosthesis system. In this study, we investigated how the objects were recognized under the stimuli with distorted phosphene arrays simulated by transformations of barrel distortion, rotation, or translation. The results revealed that distortions significantly decreased the accuracy of categorization (CA) and showed distinct interactive effects with the factors of object category and phosphene array density. Moreover, the CA changed differently with the increase of distortion levels. Regression analysis suggested a phosphene array of at least 10 × 10 be the essential for achieving a CA over the threshold value (CA(t)=62.5%) under distorted prosthetic vision. It is recommended that discriminative features be extracted to improve the performance of prosthetic vision.

Mental rotation differences between Chinese characters and English letters.

We investigated mental rotation and rotational uncertainty effect of Chinese characters and English letters, respectively by event-related potential (ERP) and behavior responses. The results indicated that subjects could mentally rotate Chinese characters and English letters at similar speed, but the total response time (RT) for Chinese characters was significantly longer. Rotational uncertainty effect was more prominent for Chinese characters than English letters in both behavior results and the amplitudes of P300 component. With the increase of orientation angle, the left-hemispheric dominance of P300 component was observed for English letters at parietal area, while Chinese characters did not show evident hemispheric asymmetry. Our results implied that significant difference of RT and ERP between different stimulus types is supposed to be in the sub-stages of the stimulus perceptual encoding and/or parity judgment.

[Auditory guidance systems for the visually impaired people].

Visually impaired people face many inconveniences because of the loss of vision. Therefore, scientists are trying to design various guidance systems for improving the lives of the blind. Based on sensory substitution, auditory guidance has become an interesting topic in the field of biomedical engineering. In this paper, we made a state-of-technique review of the auditory guidance system. Although there have been many technical challenges, the auditory guidance system would be a useful alternative for the visually impaired people.

Recent Progress on Computer-Aided Inhibitor Design of H5N1 Influenza A Virus.

Design of novel H5N1 inhibitors is currently a research topic of vital importance owing to both a recent pandemic threat by the worldwide spread of H5N1 avian influenza and the high resistance of H5N1 virus to the most widely used commercial drug, oseltamivir-OTV (Tamiflu). There has been much progress in this field recently. This review covers recent work on bioinformatics studies, structure based design, computer modeling and molecular dynamics simulations.

Configuration-based processing of phosphene pattern recognition for simulated prosthetic vision.

Visual prosthesis can elicit phosphenes by stimulating the retina, optic nerve, or visual cortex along the visual pathway. Psychophysical studies have demonstrated that visual function can be partly recovered with phosphene-based prosthetic vision. This study investigated the cognitive process of prosthetic vision through a face recognition task. Both behavioral response and the face-specific N170 component of event-related potential were analyzed in the presence of face and non-face stimuli with natural and simulated prosthetic vision. Our results showed that: (i) the accuracy of phosphene face recognition was comparable with that of the normal one when phosphene grid increased to 25 x 21 or more; (ii) shorter response time was needed for phosphene face recognition; and (iii) the N170 component was delayed and enhanced under phosphene stimuli. It was suggested that recognition of phosphene patterns employ a configuration-based holistic processing mechanism with a distinct substage unspecific to faces.

Neurophysiology study of early visual processing of face and non-face recognition under simulated prosthetic vision.

Behavioral researches have shown that the visual function can be partly restored by phosphene-based prosthetic vision for the non-congenital blinds. However, the early visual processing mechanisms of phosphene object recognition is still unclear. This paper aimed to investigate the electro-neurophysiology underlying the phosphene face and non-face recognition. The modulations of latency and amplitude of N170 component in the event-related potential (ERP) were analyzed. Our preliminary results showed that (1) both normal and phosphene face stimuli could elicit prominent N170; nevertheless, phosphene stimuli caused notable latency delay and amplitude suppression on N170 compared with normal stimuli and (2) under phosphene non-face stimuli, a slight but significant latency delay occurred compared with normal stimuli, while amplitude suppression was not observed. Therefore, it was suggested that (1) phosphene perception caused a disruption of the early visual processing for non-canonical images of objects, which was more profound in phosphene face processing; (2) the face-specific processing was reserved under prosthetic vision and (3) holistic processing was the major stage in early visual processing of phosphene face recognition, while part-based processing was attenuated due to the loss of the details.

SoundView: an auditory guidance system based on environment understanding for the visually impaired people.

Without visual information, the blind people live in various hardships with shopping, reading, finding objects and etc. Therefore, we developed a portable auditory guide system, called SoundView, for visually impaired people. This prototype system consists of a mini-CCD camera, a digital signal processing unit and an earphone, working with built-in customizable auditory coding algorithms. Employing environment understanding techniques, SoundView processes the images from a camera and detects objects tagged with barcodes. The recognized objects in the environment are then encoded into stereo speech signals for the blind though an earphone. The user would be able to recognize the type, motion state and location of the interested objects with the help of SoundView. Compared with other visual assistant techniques, SoundView is object-oriented and has the advantages of cheap cost, smaller size, light weight, low power consumption and easy customization.

Scaling exponents of EEG are related to the temporal process of the therapeutic hypothermia following ischemic brain injury.

Several markers based on quantitative electroencephalogram (qEEG) analysis have been associated with the neuroprotective effects of therapeutic hypothermia on hypoxic-ischemic encephalopathy (HIE) after cardiac arrest (CA). Nevertheless, the makers by far have not been linked to the temporal process of the ischemic neuronal death. In this study, we investigated the long-range correlations in EEG power in theta and alpha bands before and after CA by detrended fluctuation analysis (DFA). The scaling components by DFA showed that the short-term scaling exponent in alpha band (i.e. gamma(1)(alpha)) was well correlated with recovery of brain injury during the latent phase. While the short-term scaling exponent in theta band (i.e. gamma(1)(theta)) and the long-term scaling exponent in alpha band (i.e. gamma(2)(alpha)) were correlated with the delayed neuronal death after CA. Our preliminary results showed that the long-range correlations in theta and alpha bands could be related the detail temporal process of therapeutic hypothermia.

Influence of subcortical ischemic stroke on cortical neural network.

Stroke has remained as a leading cause of death and neurological disability worldwide in the past decades. Previous structural and functional studies reported little information regarding cortical neural network after stroke. Using the causality measure based on multi-channel electroencephalograph (EEG), i.e. partial directed coherence (PDC) in this paper, we investigated the different network patterns involved in pre-motor and parietal areas (F3, F4, C3, C4, P3 and P4) in three groups of patients who suffered unilateral or bilateral hemispheric stroke in basal ganglia with extension into corona radiate. Compared with the results in the control group, stroke patients showed: 1) more vulnerable long-distance intra- and inter-hemispheric interactions due to the ischemic injury; 2) strengthened short-distance interactions between the central areas in the intact hemisphere with the injured counterpart, which implied a functional compensation after unilateral stroke; 3) more suppression of cortical connections after bilateral hemispheric stroke than those with unilateral stroke. Causal interdependence by PDC analysis provides a new insight of cortical functional network following stroke.