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Transcranial focused ultrasound stimulation (tFUS) has emerged as a promising neuromodulation technique that delivers acoustic energy with high spatial resolution for inducing long-term potentiation (LTP)- or depression (LTD)-like plasticity. The variability in the primary effects of tFUS-induced plasticity could be due to different stimulation patterns, such as intermittent versus continuous, and is an aspect that requires further detailed exploration. In this study, we developed a platform to evaluate the neuromodulatory effects of intermittent and continuous tFUS on motor cortical plasticity before and after tFUS application. Three groups of rats were exposed to either intermittent, continuous, or sham tFUS. We analyzed the neuromodulatory effects on motor cortical excitability by examining changes in motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS). We also investigated the effects of different stimulation patterns on excitatory and inhibitory neural biomarkers, examining c-Fos and glutamic acid decarboxylase (GAD-65) expression using immunohistochemistry staining. Additionally, we evaluated the safety of tFUS by analyzing glial fibrillary acidic protein (GFAP) expression. The current results indicated that intermittent tFUS produced a facilitation effect on motor excitability, while continuous tFUS significantly inhibited motor excitability. Furthermore, neither tFUS approach caused injury to the stimulation sites in rats. Immunohistochemistry staining revealed increased c-Fos and decreased GAD-65 expression following intermittent tFUS. Conversely, continuous tFUS downregulated c-Fos and upregulated GAD-65 expression. In conclusion, our findings demonstrate that both intermittent and continuous tFUS effectively modulate cortical excitability. The neuromodulatory effects may result from the activation or deactivation of cortical neurons following tFUS intervention. These effects are considered safe and well-tolerated, highlighting the potential for using different patterns of tFUS in future clinical neuromodulatory applications. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) is a neurogenerative disorder implicated in dysfunctions of motor functions, particularly gait and balance. Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation offered as a potential adjuvant therapy for PD. This systematic review and meta-analysis were conducted to identify whether tDCS alone and combined with additional rehabilitation therapies improve gait and balance among individuals with PD. Methods: We searched PubMed, Embase, Web of Science, and relevant databases for eligible studies from inception to December 2022. Studies with a comparative design investigating the effects of tDCS on motor functions, including gait and balance among individuals with PD, were included. A meta-analysis was performed for each outcome using a random effects model for subgroup analysis and pooling of overall effect sizes. Results: A total of 23 studies were included in the meta-analysis. The pooled results revealed that tDCS has moderate overall effects on gait, measured by gait speed (standardized mean deviation [SMD] = 0.238; 95% confidence interval [CI] − 0.026 to 0.502); stride length (SMD = 0.318; 95% CI − 0.015 to 0.652); cadence (SMD = − 0.632; 95% CI − 0.932 to − 0.333); freezing of gait questionnaire scores (SMD = − 0.360; 95% CI − 0.692 to − 0.027); step length (SMD = 0.459; 95% CI − 0.031 to 0.949); walking time (SMD = − 0.253; 95% CI − 0.758 to 0.252); stride time (SMD = − 0.785; 95% CI: − 1.680 to 0.111); double support time (SMD = 1.139; 95% CI − 0.244 to 0.523); and balance, measured by timed up and go (TUG) test (SMD = − 0.294; 95% CI − 0.516 to − 0.073), Berg balance scale (BBS) scores (SMD = 0.406; 95% CI − 0.059 to 0.87), and dynamic gait index (SMD = 0.275; 95% CI − 0.349 to 0.898). For the subgroup analysis, gait and balance demonstrated moderate effect sizes. However, only cadence, stride time, and TUG indicated a significant difference between real and sham tDCS (P = 0.027, P = 0.002, and P = 0.023, respectively), whereas cadence and BBS (P < 0.01 and P = 0.045, respectively) significantly differed after real tDCS plus other therapies rather than after sham tDCS plus other therapies. Conclusions: Our results indicated that tDCS is significantly associated with gait and balance improvements among individuals with PD. The findings of this study provide more proof supporting the effectiveness of tDCS, encouraging tDCS to be utilized alone or in combination with other therapies in clinical practice for PD rehabilitation. [ABSTRACT FROM AUTHOR]

Abstract Plants offer a cost-effective and scalable pharmaceutical platform devoid of host-derived contamination risks. However, their medical application is complicated by the potential for acute allergic reactions to external proteins. Developing plant-based protein therapeutics for localized diseases with non-invasive treatment modalities may capitalize on the benefits of plant proteins while avoiding their inherent risks. Dupilumab, which is effective against a variety of allergic and autoimmune diseases but has systemic responses and injection-related side effects, may be more beneficial if delivered locally using a small biological form. In this study, we engineered a single-chain variable fragment (scFv) of dupilumab, termed Dup-scFv produced by Nicotiana benthamiana, and evaluated its tissue permeability and anti-inflammatory efficacy in air–liquid interface cultured human nasal epithelial cells (HNECs). Despite showing 3.67- and 17-fold lower binding affinity for IL-4Ra in surface plasmon resonance assays and cell binding assays, respectively, Dup-scFv retained most of the affinity of dupilumab, which was originally high, with a dissociation constant (KD) of 4.76 pM. In HNECs cultured at the air–liquid interface, Dup-scFv administered on the air side inhibited the inflammatory marker CCL26 in hard-to-reach basal cells more effectively than dupilumab. In addition, Dup-scFv had an overall permeability of 0.8% across cell layers compared to undetectable levels of dupilumab. These findings suggest that plant-produced Dup-scFv can be delivered non-invasively to cultured HNESc to alleviate inflammatory signaling, providing a practical approach to utilize plant-based proteins for topical therapeutic applications.

Objective: Cortical electrical stimulation (CES) can modulate cortical excitability through a plasticity-like mechanism and is considered to have therapeutic potentials in Parkinson's disease (PD). However, the precise therapeutic value of such approach for PD remains unclear. Accordingly, we adopted a PD rat model to determine the therapeutic effects of CES. The current study was thus designed to identify the therapeutic potential of CES in PD rats. Methods: A hemiparkinsonian rat model, in which lesions were induced using unilateral injection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle, was applied to identify the therapeutic effects of long-term (4-week) CES with intermittent theta-burst stimulation (iTBS) protocol (starting 24 h after PD lesion observation, 1 session/day, 5 days/week) on motor function and neuroprotection. After the CES intervention, detailed functional behavioral tests including gait analysis, akinesia, open-field locomotor activity, apomorphine-induced rotation as well as degeneration level of dopaminergic neurons were performed weekly up to postlesion week 4. Results: After the CES treatment, we found that the 4-week CES intervention ameliorated the motor deficits in gait pattern, akinesia, locomotor activity, and apomorphine-induced rotation. Immunohistochemistry and tyrosine hydroxylase staining analysis demonstrated that the number of dopamine neurons was significantly greater in the CES intervention group than in the sham treatment group. Conclusion: This study suggests that early and long-term CES intervention could reduce the aggravation of motor dysfunction and exert neuroprotective effects in a rat model of PD. Further, this preclinical model of CES may increase the scope for the potential use of CES and serve as a link between animal and PD human studies to further identify the therapeutic mechanism of CES for PD or other neurological disorders. [ABSTRACT FROM AUTHOR]

Tin dioxide (SnO 2 ) nanosheets/graphitic carbon nitride (g-C 3 N 4 ) composite was prepared by a hydrothermal method using mercapto acetic acid as the morphology directing agent in an acidic medium. The as-obtained composite was characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscope, and X-ray photoelectron spectroscopy; the results of this study show that in the composite, SnO 2 nanosheets with a thickness in the range ∼20–25 nm dispersed well on the g-C 3 N 4 . The lithium storage capability of the composite was investigated. The cycling performance of the composite was improved and is believed to be attributed by the presence of g-C 3 N 4 support. [ABSTRACT FROM AUTHOR]

The demand for well-designed nanostructured composites with enhanced electrochemical performance for lithium-ion batteries electrode materials has been emerging. In order to improve the electrochemical performance of MoS2-based anode materials, MoS2 nanosheets integrated with g-C3N4 (MoS2/g-C3N4 composite) was synthesized by a facile heating treatment from the precursors of thiourea and sodium molybdate at 550 °C under N2 gas flow. The structure and composition of MoS2/g-C3N4 were confirmed by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, infrared spectroscopy, X-ray photoelectron spectroscopy, thermogravimetric analysis and elemental analysis. The lithium storage capability of the MoS2/g-C3N4 composite was evaluated, indicating high capacity and stable cycling performance at 1 C (A·g−1) with a reversible capacity of 1204 mA·h·g−1 for 200 cycles. This result is believed the role of g-C3N4 as a supporting material to accommodate the volume change and improve charge transport for nanostructured MoS2. Additionally, the contribution of the pseudocapacitive effect was also calculated to further clarify the enhancement in Li-ion storage performance of the composite. [ABSTRACT FROM AUTHOR]