FNIRS based study of brain network characteristics in children with cerebral palsy during bilateral lower limb movement.

BACKGROUND: Motor dysfunctions in children with cerebral palsy (CP) are caused by nonprogressive brain damage. Understanding the functional characteristics of the brain is important for rehabilitation. PURPOSE: This paper aimed to study the brain networks of children with CP during bilateral lower limb movement using functional near-infrared spectroscopy (fNIRS) and to explore effective fNIRS indices for reflecting functional brain activity. METHODS: Using fNIRS, cerebral oxygenation signals in the bilateral prefrontal cortex (LPFC/RPFC) and motor cortex (LMC/RMC) were recorded from fifteen children with spastic CP and seventeen children with typical development (CTDs) in the resting state and during bilateral lower limb movement. Functional connectivity matrices based on phase-locking values (PLVs) were calculated using Hilbert transformation, and binary networks were constructed at different sparsity levels. Network metrics such as the clustering coefficient, global efficiency, local efficiency, and transitivity were calculated. Furthermore, the time-varying curves of network metrics during movement were obtained by dividing the time window and using sparse inverse covariance matrices. Finally, conditional Granger causality (GC) was used to explore the causal relationships between different brain regions. RESULTS: Compared to CTDs, the connectivity between RMC-RPFC (p = 0.017) and RMC-LMC (p = 0.002) in the brain network was decreased in children with CP, and the clustering coefficient (p = 0.003), global efficiency (p = 0.034), local efficiency (p = 0.015), and transitivity (p = 0.009) were significantly lower. The standard deviation of the changes in global efficiency of children with CP during motion was also greater than that of CTDs. Using GC, it was found that there was a significant increase in causal strength from the RMC to the RPFC (p = 0.04) and from the RMC to the LMC (p = 0.042) in children with CP during motion. Additionally, there were significant negative correlations between the PLV of LMC-RMC (p = 0.002) and the Gross Motor Function Classification System (GMFCS) and between the GMFCS and the clustering coefficient (p = 0.01). CONCLUSIONS: During rehabilitation training of the lower limbs, there were significant differences in brain network indices between children with CP and CTDs. The indicators proposed in this paper are effective at evaluating motor function and the real-time impact of rehabilitation training on the brain network and have great potential for application in guiding clinical motor function assessment and planning rehabilitation strategies.

Zero-valent iron enhanced methane production of anaerobic digestion by reinforcing microbial electron bifurcation coupled with direct inter-species electron transfer.

Zero-valent iron (ZVI) can facilitate methanogens of anaerobic digestion (AD). However, the impact of ZVI on the micro-energetic strategies of AD microorganisms remains uncertain. This study aimed to elucidate the development of an energy conservation model involving direct interspecies electron transfer (DIET) and electron bifurcate (EB) by using four types of ZVI. Overall, the ZVI addition resulted in a substantial increase in methane production (1.26 to 2.18 times higher), and the effect of boron (B) doped ZVI was particularly pronounced. The underlying mechanism may be the formation of energy harvest pathway related to DIET. In detail, B-doped ZVI could enhance its interfacial binding to cytochrome c. Decreased polar solvation energy from 20.473 to 1.509 kJ/mol is beneficial for electron transfer, thereby augmenting the flavin-bounded Cytc activity and DIET process. Besides, ZVI-enhanced EB enzyme activity like HdrA2B2C2-MvhAGD could improve the EB process, which can couple with DIET for electron transfer and energy conservation. Energy analysis based on EB-coupled DIET metabolism pathways demonstrated that the ATP saved in this coupled model theoretically line in 0.25 to 0.5 mol ATP/mol substrate. Overall, this study offers valuable insights into microbial energetic strategies pertaining to the utilization of conductive materials, with the target of enhancing methane recovery efficiency from organic waste.

Generic design principles for antibody-based tumour necrosis factor (TNF) receptor 2 (TNFR2) agonists with FcγR-independent agonism.

Background: Selective TNFR2 activation can be used to treat immune pathologies by activating and expanding regulatory T-cells (Tregs) but may also restore anti-tumour immunity by co-stimulating CD8+ T-cells. Oligomerized TNFR2-specific TNF mutants or anti-TNFR2 antibodies can activate TNFR2 but suffer either from poor production and pharmacokinetics or in the case of anti-TNFR2 antibodies typically from the need of FcγR binding to elicit maximal agonistic activity. Methods: To identify the major factor(s) determining FcγR-independent agonism of anti-TNFR2 antibodies, we systematically investigated a comprehensive panel of anti-TNFR2 antibodies and antibody-based constructs differing in the characteristics of their TNFR2 binding domains but also in the number and positioning of the latter. Results: We identified the domain architecture of the constructs as the pivotal factor enabling FcγR-independent, thus intrinsic TNFR2-agonism. Anti-TNFR2 antibody formats with either TNFR2 binding sites on opposing sites of the antibody scaffold or six or more TNFR2 binding sites in similar orientation regularly showed strong FcγR-independent agonism. The affinity of the TNFR2 binding domain and the epitope recognized in TNFR2, however, were found to be of only secondary importance for agonistic activity. Conclusion: Generic design principles enable the generation of highly active bona fide TNFR2 agonists from nearly any TNFR2-specific antibody.

Abnormal Low-Frequency Corticokinematic Coherence in Stroke: An Electroencephalography and Acceleration Study.

Motor control is a complex process of coordination and information interaction among neural, motor, and sensory functions. Investigating the correlation between motor-physiological information helps to understand the human motor control mechanisms and is important for the assessment of motor function status. In this manuscript, we investigated the differences in the neuromotor coupling analysis between healthy controls and stroke patients in different movements. We applied the corticokinematic coherence (CKC) function between the electroencephalogram (EEG) and acceleration (ACC) data. First, we collected the EEG and ACC data from 10 healthy controls and 10 stroke patients under the task of movement execution (ear touch and knee touch) and movement maintenance (ear touch and knee touch). After the preprocessing of raw data, we used frequency domain coherence method to analyze the full-frequency EEG and ACC data, which could be concluded that the CKC intensity in the movement execution was higher than that in the movement maintenance. However, there was no significant difference between healthy subjects and stroke patients. Secondly, the coherence results in local frequency bands showed that low-frequency bands could better reflect the difference between movement execution and maintenance. The intensity of coherence in healthy subjects was significantly higher than that in other bands, but not in stroke patients. Further comparison of coherence results in local frequency bands showed that the intensity of theta band in healthy controls was significantly higher than other rhythms, especially in the knee touch phase. Therefore, we infer that neurodynamic coupling analysis based on EEG and ACC data can show the differences between healthy subjects and stroke patients. Such researches could add to the understanding of neuro-motor control mechanisms and provide new quantitative indicators on the motor function assessment.

Antibody-based soluble and membrane-bound TWEAK mimicking agonists with FcγR-independent activity.

Fibroblast growth factor (FGF)-inducible 14 (Fn14) activates the classical and alternative NFκB (nuclear factor 'kappa-light-chain-enhancer' of activated B-cells) signaling pathway but also enhances tumor necrosis factor (TNF)-induced cell death. Fn14 expression is upregulated in non-hematopoietic cells during tissue injury and is also often highly expressed in solid cancers. In view of the latter, there were and are considerable preclinical efforts to target Fn14 for tumor therapy, either by exploiting Fn14 as a target for antibodies with cytotoxic activity (e.g. antibody-dependent cellular cytotoxicity (ADCC)-inducing IgG variants, antibody drug conjugates) or by blocking antibodies with the aim to interfere with protumoral Fn14 activities. Noteworthy, there are yet no attempts to target Fn14 with agonistic Fc effector function silenced antibodies to unleash the proinflammatory and cell death-enhancing activities of this receptor for tumor therapy. This is certainly not at least due to the fact that anti-Fn14 antibodies only act as effective agonists when they are presented bound to Fcγ receptors (FcγR). Thus, there are so far no antibodies that robustly and selectively engage Fn14 signaling without triggering unwanted FcγR-mediated activities. In this study, we investigated a panel of variants of the anti-Fn14 antibody 18D1 of different valencies and domain architectures with respect to their inherent FcγR-independent ability to trigger Fn14-associated signaling pathways. In contrast to conventional 18D1, the majority of 18D1 antibody variants with four or more Fn14 binding sites displayed a strong ability to trigger the alternative NFκB pathway and to enhance TNF-induced cell death and therefore resemble in their activity soluble (TNF)-like weak inducer of apoptosis (TWEAK), one form of the natural occurring ligand of Fn14. Noteworthy, activation of the classical NFκB pathway, which naturally is predominately triggered by membrane-bound TWEAK but not soluble TWEAK, was preferentially observed with a subset of constructs containing Fn14 binding sites at opposing sites of the IgG scaffold, e.g. IgG1-scFv fusion proteins. A superior ability of IgG1-scFv fusion proteins to trigger classical NFκB signaling was also observed with the anti-Fn14 antibody PDL192 suggesting that we identified generic structures for Fn14 antibody variants mimicking soluble and membrane-bound TWEAK.

Electronic Bifurcation: A New Perspective on Fe Bio-Utilization in Anaerobic Digestion of Lactate.

Anaerobic microorganisms use flavin/quinone-based electronic bifurcation (EB) to gain a survival advantage at the thermodynamic limits. However, the contribution of EB to microscopic energy and productivity in the anaerobic digestion (AD) system is unknown. This study demonstrates for the first time that under limited substrate conditions, Fe-driven EB in AD leads to a 40% increase in specific methane production and contributes to 25% ATP accumulation, by analyzing the concentration of EB enzymes such as Etf-Ldh, HdrA2B2C2, and Fd, NADH and actual Gibbs free-energy changes. Differential pulse voltammetry and electron respiratory chain inhibition experiments detected that iron enhanced electron transport in EB by accelerating the activity of flavin, Fe-S clusters, and quinone groups. Other microbial and enzyme genes with EB potential closely related to iron transport have also been found in metagenomes. The potential of EB to accumulate energy and enhance productivity in AD systems was investigated, and metabolic pathways were proposed in the study.

Ru360 Alleviates Postoperative Cognitive Dysfunction in Aged Mice by Inhibiting MCU-Mediated Mitochondrial Dysfunction.

Purpose: Ru360, a selective inhibitor of mitochondrial calcium uptake, maintains mitochondrial calcium homeostasis. To evaluate whether mitochondrial calcium uniporter (MCU)-mediated mitochondrial function is associated with the pathological process of Postoperative cognitive dysfunction (POCD), elucidate its relationship with neuroinflammation, and observe whether the relevant pathological process can be improved with Ru360. Methods: Aged mice underwent experimental open abdominal surgery after anesthesia. Open field tests, Novel object recognition tests and Y Maze Tests were used to conduct behavioral experiments. The reactive oxygen species (ROS) content, the levels of inflammatory cytokines interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), intra-mitochondrial calcium, mitochondrial membrane potential (MMP) and the activity of antioxidant superoxide dismutase (SOD) in the hippocampus of mice were detected using kits. The expression of proteins was detected using Western blot. Results: After treatment with Ru360, MCU-mediated mitochondrial dysfunction was inhibited, neuroinflammation was reduced, and the learning ability of the mice was improved after surgery. Conclusion: Our study demonstrated that mitochondrial function plays a crucial role in the pathology of POCD, and using Ru360 to improve mitochondrial function may be a new and necessary direction for the treatment of POCD.

Novel Role of Hematite in Anaerobic Digestion: Manipulating Membrane-Bound Electron Transport Chain by the Construction of Biological Capacitors with Humic Acid.

Humic acid (HA) has attracted much attention for its electron-competitive effect of quinone groups on anaerobic methanogenesis. This study analyzed the biological "capacitor" to determine how it might effectively reduce electron competition. As biological capacitor-producing additives, three semiconductive materials, including magnetite, hematite, and goethite, were selected. The results showed that hematite and magnetite could significantly alleviate the inhibited methanogenesis caused by the HA model compound anthraquinone-2,6-disulfonate (AQDS). The electrons flowing to methane in hematite-AQDS, magnetite-AQDS, control, sole-AQDS, and goethite-AQDS groups accounted for 81.24, 77.12, 75.42, 70.55, and 56.32% of the total produced electrons, respectively. Hematite addition significantly accelerated the methane production rate (18.97%) compared with sole-AQDS. Electrochemical investigation showed that AQDS might have its oxidation potential reduced by adsorbing on hematite, which results in an energy band bending for hematite and the formation of a biological capacitor. The biological capacitor's integrated electric field helps with the transfer of electrons from reduced AQDS to anaerobic consortia via bulk hematite. Metagenomic and metaproteomic sequencing analyses revealed that the ferredoxin and Mph-reducing hydrogenase in hematite addition increased by 7.16 and 21.91%, respectively, compared to sole-AQDS addition. Accordingly, this research suggested that AH2QDS may re-transfer electrons to methanogens via the biological capacitor and the membrane's Mph-reducing hydrogenase, thus lowering the HA electron competition.

Stroke-Related Alterations in the Brain's Functional Connectivity Response Associated with Upper Limb Multi-Joint Linkage Movement.

Stroke is one of the primary causes of motor disorders, which can seriously affect the patient's quality of life. However, the assessment of the upper limb affected by stroke is commonly based on scales, and the characteristics of brain reorganization induced by limb movement are not clear. Thus, this study aimed to investigate stroke-related cortical reorganization based on functional near infrared spectroscopy (fNIRS) during upper limb multi-joint linkage movement with reference to the Fugl-Meyer Assessment of the upper extremities (FMA-UE). In total, 15 stroke patients and 15 healthy subjects participated in this study. The functional connectivity (FC) between channels and the regions of interest (ROI) was calculated by Pearson's correlation coefficient. The results showed that compared with the control group, the FC between the prefrontal cortex and the motor cortex was significantly increased in the resting state and the affected upper limb's multi-joint linkage movements, while the FC between the motor cortex was significantly decreased during the unaffected upper limb's multi-joint linkage movements. Moreover, the significantly increased ROI FC in the resting state showed a significantly positive correlation with FMA-UE in stroke patients (p < 0.05). This study highlights a new biomarker for evaluating the function of movement in stroke patients and provides guidance for rehabilitation training.

Cortical hemodynamic response and networks in children with cerebral palsy during upper limb bilateral motor training.

Understanding the characteristics of functional brain activity is important for motor rehabilitation of children with cerebral palsy (CP). Using the functional near-infrared spectroscopy (fNIRS) technology, the cortical response and networks of prefrontal (PFC) and motor cortices (MC) were analyzed for children with CP and typical development (CTD). Compared with CTD, the resting cortical response of dominant MC in children with CP increased, and the functional connectivity between cerebral areas decreased. In the motor state of children with CP, the coupling strength started from dominant MC increased compared with resting state, and the hemispherical autonomy index (HAI) of the dominant MC was higher than that in the CTD, which reflected the leading role of dominant MC in brain regulation during motor. The functional connectivity between bilateral MC was positively correlated with motor performance. This study provided effective indices for evaluating the motor function and real-time impact of motor on brain networks.

CD40- and 41BB-specific antibody fusion proteins with PDL1 blockade-restricted agonism.

Background: A strategy to broaden the applicability of checkpoint inhibitors is the combined use with antibodies targeting the immune stimulatory receptors CD40 and 41BB. However, the use of anti-CD40 and anti-41BB antibodies as agonists is problematic in two ways. First, anti-CD40 and anti-41BB antibodies need plasma membrane-associated presentation by FcγR binding to exert robust agonism but this obviously limits their immune stimulatory efficacy by triggering ADCC, CDC or anti-inflammatory FcγRIIb activities. Second, off tumor activation of CD40 and 41BB may cause dose limiting systemic inflammation. Methods: To overcome the FcγR-dependency of anti-41BB and anti-CD40 antibodies, we genetically fused such antibodies with a PDL1-specific blocking scFv as anchoring domain to enable FcγR-independent plasma membrane-associated presentation of anti-CD40- and anti-41BB antibodies. By help of GpL-tagged variants of the resulting bispecific antibodies, binding to their molecular targets was evaluated by help of cellular binding studies. Membrane PDL1-restricted engagement of CD40 and 41BB but also inhibition of PDL1-induced PD1 activation were evaluated in coculture assays with PDL1-expressing tumor cell lines and 41BB, CD40 and PD1 responsible cell lines or T-cells. Results: The binding properties of the bispecific antibody fusion proteins remained largely unchanged compared to their parental molecules. Upon anchoring to membrane PDL1, the bispecific antibody fusion proteins activated CD40/41BB signaling as efficient as the parental anti-CD40/anti-41BB antibodies when bound to FcγRs or cells expressing membrane-bound CD40L/41BBL. PD1 inhibition remained intact and the anti-41BB fusion protein thus showed PDL1-restricted costimulation of T-cells activated in vitro with anti-CD3 or a BiTe. Conclusions: Targeting of anti-CD40 and anti-41BB fusion proteins to membrane PDL1 with a blocking PDL1 scFv links PD1-PDL1 checkpoint blockade intrinsically with engagement of CD40 or 41BB.

A Comparative Study between A Protein Based Amorphous Formulation and Other Dissolution Rate Enhancing Approaches: A Case Study with Rifaximin.

Amorphous solid dispersions (ASDs) based on proteins as co-formers have previously shown promising potential to improve the solubility and bioavailability of poorly water-soluble drugs. In particular, whey proteins have shown to be promising co-formers and amorphous stabilizers in ASD formulations, including at high drug loading. In this study, the feasibility of the whey protein ß-lactoglobulin (BLG) as a co-former in ASDs was compared to the more traditional ASD co-formers based on synthetic polymers (hydroxypropyl methylcellulose acetate succinate and Eudragit® L) as well as to a nanocrystalline formulation. The poorly water-soluble drug rifaximin (RFX) was chosen as the model drug. All drug/co-former formulations were prepared as fully amorphous ASDs by spray drying at 50% (w/w) drug loading. The BLG-based ASD had the highest glass transition temperature and showed a faster dissolution rate and higher drug solubility in three release media with different pH values (1.2, 4.5, and 6.5) compared to the polymer-based ASDs and the nanocrystalline RFX. In conclusion, BLG is a promising co-former and amorphous stabilizer of RFX in ASD formulations, superior to the selected polymer-based ASD systems or the nanocrystalline formulation.

Correlation Between Gait and Near-Infrared Brain Functional Connectivity Under Cognitive Tasks in Elderly Subjects With Mild Cognitive Impairment.

Older adults with mild cognitive impairment (MCI) have a high risk of developing Alzheimer's disease. Gait performance is a potential clinical marker for the progression of MCI into dementia. However, the relationship between gait and brain functional connectivity (FC) in older adults with MCI remains unclear. Forty-five subjects [MCI group, n = 23; healthy control (HC) group, n = 22] were recruited. Each subject performed a walking task (Task 01), counting backward-walking task (Task 02), naming animals-walking task (Task 03), and calculating-walking task (Task 04). The gait parameters and cerebral oxygenation signals from the left prefrontal cortex (LPFC), right prefrontal cortex (RPFC), left motor cortex (LMC), right motor cortex (RMC), left occipital leaf cortex (LOL), and right occipital leaf cortex (ROL) were obtained simultaneously. Wavelet phase coherence was calculated in two frequency intervals: low frequency (interval I, 0.052-0.145 Hz) and very low frequency (interval II, 0.021-0.052 Hz). Results showed that the FC of RPFC-RMC is significantly lower in interval I in Task 03 compared with that in Task 02 in the MCI group (p = 0.001). Also, the right relative symmetry index (IDpsR) is significantly lower in Task 03 compared with that in Task 02 (p = 0.000). The IDpsR is positively correlated with the FC of RPFC-RMC in interval I in the MCI group (R = 0.205, p = 0.041). The gait symmetry such as left relative symmetry index (IDpsL) and IDpsR is significantly lower in the dual-task (DT) situation compared with the single task in the two groups (p < 0.05). The results suggested that the IDpsR might reflect abnormal change in FC of RPFC-RMC in interval I in the MCI population during Task 03. The gait symmetry is affected by DTs in both groups. The findings of this study may have a pivotal role in the early monitoring and intervention of brain dysfunction among older adults with MCI.

Hollow electrode capillary plasma ionization source for rapid online detection of gaseous samples.

RATIONALE: Gas chromatography mass spectrometry (GC-MS) with electron ionization (EI) is the most widely used analysis technique of gaseous samples, but it may be time-consuming for online monitoring of mixtures whose concentrations relatively change rapidly. On the contrary, current ionization methods, such as chemical ionization (CI) and proton transfer reaction (PTR), also have some disadvantages such as selectivity. Therefore, appropriate soft ionization sources are searched for rapid online detection. METHODS: Hollow electrode capillary plasma ionization (HECPI) is based on single electrode plasma. A hollow capillary was placed as both the electrode and the inlet of the gaseous samples. The ionization source is coupled with a mass spectrometer for performance evaluation. RESULTS: Several typical compounds have been tested with HECPI-mass spectrometer. In this process, the dominant ion peaks of all compounds can be indexed as molecular ion peaks, and the product ions of HECPI are less than that of dielectric barrier discharge ionization (DBDI). Three gaseous samples (linalool, triethylamine, and styrene) with various concentrations have been used to further confirm the performance of this source, and the detection limit of linalool is as low as 10 ppb. CONCLUSIONS: HECPI is simple in structure and shows good performance. The results also show that HECPI has the potential to be an effective tool for detecting online gaseous samples rapidly.

Food waste treating by biochar-assisted high-solid anaerobic digestion coupled with steam gasification: Enhanced bioenergy generation and porous biochar production.

A food waste treating system was proposed in this study by combining biochar-assisted high-solid anaerobic digestion and subsequent steam gasification of the digestate. The effect of solid level, biochar dosage in anaerobic digestion on the properties of biogas, syngas, and final biochar products were investigated. Results showed that at a high total solid level and biochar dosage of 25 g/L and 50 g/L, the accumulative methane yield reached 110.3 mL CH4/g VS and 126.7 mL CH4/g VS, respectively. From steam gasification of different digestates under 850 °C for 15 min, a maximum of 34.92 mmol/g for the hydrogen yield and 11.44 MJ/m3 for the higher heating value could be obtained for the syngas. Furthermore, the by-product produced from steam gasification was a nutrient-enriched porous biochar, which was suitable to be used as compost. This study demonstrated a pathway for food waste treating to produce methane-enriched biogas, hydrogen-enriched syngas, and nutrient-enriched biochar.

Membrane lymphotoxin-α2ß is a novel tumor necrosis factor (TNF) receptor 2 (TNFR2) agonist.

In the early 1990s, it has been described that LTα and LTß form LTα2ß and LTαß2 heterotrimers, which bind to TNFR1 and LTßR, respectively. Afterwards, the LTαß2-LTßR system has been intensively studied while the LTα2ß-TNFR1 interaction has been ignored to date, presumably due to the fact that at the time of identification of the LTα2ß-TNFR1 interaction one knew already two ligands for TNFR1, namely TNF and LTα. Here, we show that LTα2ß interacts not only with TNFR1 but also with TNFR2. We furthermore demonstrate that membrane-bound LTα2ß (memLTα2ß), despite its asymmetric structure, stimulates TNFR1 and TNFR2 signaling. Not surprising in view of its ability to interact with TNFR2, LTα2ß is inhibited by Etanercept, which is approved for the treatment of rheumatoid arthritis and also inhibits TNF and LTα.

Enhancement of methanogenic performance by gasification biochar on anaerobic digestion.

This work evaluates the performance of different biochar-amended anaerobic digestion systems. The Fourier Transform Infrared analysis showed that more ordered aromatic groups formed and the aromatization degree increased with the rise of gasification temperature. The biochar produced at 900 °C still showed an excellent ability to maintain the stability of anaerobic digestion performance, where the specific methane yield content steadily reached 742 mL CH4/g ethanol. Besides, the enzymatic activity test indicated an improved performance with the addition of biochar obtained at gasification temperature. The relationship between the microbial community and metabolism pathways result are signified due to the direct interspecies electron transfer among Pseudomonas or Candidatus cloacimonas and Methanosaeta via biochar. These links have promoted the methane metabolism pathway of acetate decarboxylation. Therefore, the current study helps better understand the influence of surface functional groups of biochar at different temperatures on anaerobic digestion performance.

Purinergic Signaling Mediates PTH and Fluid Flow-Induced Osteoblast Proliferation.

Both parathyroid hormone (PTH) and mechanical signals are able to regulate bone growth and regeneration. They also can work synergistically to regulate osteoblast proliferation, but little is known about the mechanisms how PTH and mechanical signals interact with each other during this process. In this study, we investigated responses of MC3T3-E1 osteoblasts to PTH and oscillatory fluid flow. We found that osteoblasts are more sensitive to mechanical signals in the presence of PTH according to ERK1/2 phosphorylation, ATP release, CREB phosphorylation, and cell proliferation. PTH may also reduce the osteoblast refractory period after desensitization due to mechanical signals. We further found that the synergistic responses of osteoblasts to fluid flow or ATP with PTH had similar patterns, suggesting that synergy between fluid flow and PTH may be through the ATP pathway. After we inhibited ATP effects using apyrase in osteoblasts, their synergistic responses to mechanical stimulation and PTH were also inhibited. Additionally, knocking down P2Y2 purinergic receptors can significantly attenuate osteoblast synergistic responses to mechanical stimulation and PTH in terms of ERK1/2 phosphorylation, CREB phosphorylation, and cell proliferation. Thus, our results suggest that PTH enhances mechanosensitivity of osteoblasts via a mechanism involving ATP and P2Y2 purinergic receptors.

Prospects for intelligent rehabilitation techniques to treat motor dysfunction.

More than half of stroke patients live with different levels of motor dysfunction after receiving routine rehabilitation treatments. Therefore, new rehabilitation technologies are urgently needed as auxiliary treatments for motor rehabilitation. Based on routine rehabilitation treatments, a new intelligent rehabilitation platform has been developed for accurate evaluation of function and rehabilitation training. The emerging intelligent rehabilitation techniques can promote the development of motor function rehabilitation in terms of informatization, standardization, and intelligence. Traditional assessment methods are mostly subjective, depending on the experience and expertise of clinicians, and lack standardization and precision. It is therefore difficult to track functional changes during the rehabilitation process. Emerging intelligent rehabilitation techniques provide objective and accurate functional assessment for stroke patients that can promote improvement of clinical guidance for treatment. Artificial intelligence and neural networks play a critical role in intelligent rehabilitation. Multiple novel techniques, such as brain-computer interfaces, virtual reality, neural circuit-magnetic stimulation, and robot-assisted therapy, have been widely used in the clinic. This review summarizes the emerging intelligent rehabilitation techniques for the evaluation and treatment of motor dysfunction caused by nervous system diseases.

Effects of fatigue on steady state motion visual evoked potentials: Optimised stimulus parameters for a zoom motion-based brain-computer interface.

BACKGROUND AND OBJECTIVE: In flicker-based steady-state visual evoked potentials (SSVEP) brain-computer interface (BCI), the system performance decreases due to prolonged repeated visual stimulation. To reduce the performance decrease due to visual fatigue, the zoom motion based steady-state motion visual evoked potentials (SSMVEPs) paradigm had been proposed. In this study, the stimulation parameters of the paradigm are optimised to mitigate the decrease in detection accuracy for SSMVEP due to visual fatigue. METHODS: Eight zoom motion-based SSMVEP paradigms with different stimulation parameters were compared. The graph size, luminance, colour, and shape, as well as the frequency range and interval of the stimulation and refresh rate of the screen was changed to determine the optimal paradigm with high recognition accuracy and reduced fatigue effects. The signal-to-noise ratio (SNR) of SSMVEP was also calculated for four fatigue levels. Moreover, the power spectral density of electroencephalograph (EEG) alpha and theta bands during ongoing activity was calculated for the stimulation experiment to evaluate fatigue at the start and end of the stimulation task. RESULTS: All stimulation SSMVEP paradigms exhibited high accuracies. Changes in luminance, colour, and shape did not impact the recognition accuracy, nor did a higher stimulation frequency or lower frequency interval of each stimulation block. However, the paradigm with smaller stimulus achieved the highest average target selection accuracy of 97.2%, compared to 94.9% for the standard paradigm. Furthermore, it exhibited almost zero reduction in recognition accuracy due to fatigue. From fatigue level 1 to level 4, the smaller zoom motion-based SSMVEP exhibited a lower decrease in the SNR of SSMVEP and a lower alpha/theta ratio decrease during ongoing stimulation activity compared to the standard paradigm. CONCLUSIONS: For a zoom motion-based SSMVEP paradigm, changing multiple stimulation parameters can lead to the same high performance as the standard paradigm. Moreover, using a smaller stimulus can reduce the accuracy decrease caused by fatigue because the SNR decrease in the evoked SSMVEP state was negligible and the alpha/theta index decrease during ongoing activity was lower than that for the standard paradigm.