Acupuncture combined with mirror therapy for post-stroke dyskinesia: A meta-analysis and systematic review.

BACKGROUND: Dyskinesia is one of the most common complications of stroke. Acupuncture therapy (AT) and mirror therapy (MT) are promising rehabilitation measures for the treatment of post-stroke dyskinesia. Although some studies suggested that AT and MT are effective and safe for dyskinesia, the effects, and safety remain uncertain due to lacking strong evidence. The purpose of this study is to investigate the efficacy and safety of AT combined with MT in the treatment of post-stroke dyskinesia. METHODS: We searched the following databases: PubMed, Web of Science, Cochrane Library, EMBASE, Medline, China Knowledge Network, WANFANG, and China Biomedical Literature Database, from inception to 1 January 2023 to identify eligible studies. Total effective rate, the Fugl-Meyer assessment scale (FMA) upper and lower limb scores, modified Barthel index scores, Berg balance scale, modified Ashworth scale, and adverse reactions were adopted as outcome indicators. The Grading of Recommendations Assessment Development and Evaluation system was used by 2 independent reviewers to assess the quality of evidence for the outcome indicators included in the study. The statistical analysis was conducted by RevMan V.5.4 software. RESULTS: A total of 24 randomized controlled studies included 2133 patients with post-stroke dyskinesia were included. The total effective rate of AT combined with MT was more advantageous in the treatment of post-stroke dyskinesia (relative risk = 1.31, 95% confidence interval [CI] [1.22-1.42], Z = 6.96, P < .0001). AT combined with MT was more advantageous for FMA upper limb score (mean difference [MD] = 6.67, 95% CI [5.21-8.13], Z = 8.97, P < .00001) and FMA lower limb score (MD = 3.72, 95% CI [2.81-4.63], Z = 7.98, P < .00001). Meta-analysis showed that AT combined with MT for post-stroke dyskinesia had a more advantageous modified Barthel index score (MD = 9.51, 95% CI [7.44-11.58], Z = 9.01, P < .00001). CONCLUSION: AT combined with MT is effective in improving motor function and daily living ability of patients, especially in improving muscle spasms. However, these results should be regarded with caution given the low quality of evidence for the evaluation results.

Peripheral gating of mechanosensation by glial diazepam binding inhibitor.

We report that diazepam binding inhibitor (DBI) is a glial messenger mediating satellite glia-sensory neuron crosstalk in the dorsal root ganglion (DRG). DBI is highly expressed in satellite glia cells (SGCs) of mice, rat and human, but not in sensory neurons or most other DRG-resident cells. Knockdown of DBI results in a robust mechanical hypersensitivity without major effects on other sensory modalities. In vivo overexpression of DBI in SGCs reduces sensitivity to mechanical stimulation and alleviates mechanical allodynia in neuropathic and inflammatory pain models. We further show that DBI acts as an unconventional agonist and positive allosteric modulator at the neuronal GABAA receptors, particularly strongly effecting those with a high-affinity benzodiazepine binding site. Such receptors are selectively expressed by a subpopulation of mechanosensitive DRG neurons and these are also more enwrapped with DBI-expressing glia, as compared to other DRG neurons, suggesting a mechanism for specific effect of DBI on mechanosensation. These findings identified a new, peripheral neuron-glia communication mechanism modulating pain signalling, which can be targeted therapeutically.

Textured Perovskite/Silicon Tandem Solar Cells Achieving Over 30% Efficiency Promoted by 4-Fluorobenzylamine Hydroiodide.

Monolithic textured perovskite/silicon tandem solar cells (TSCs) are expected to achieve maximum light capture at the lowest cost, potentially exhibiting the best power conversion efficiency. However, it is challenging to fabricate high-quality perovskite films and preferred crystal orientation on commercially textured silicon substrates with micrometer-size pyramids. Here, we introduced a bulky organic molecule (4-fluorobenzylamine hydroiodide (F-PMAI)) as a perovskite additive. It is found that F-PMAI can retard the crystallization process of perovskite film through hydrogen bond interaction between F- and FA+ and reduce (111) facet surface energy due to enhanced adsorption energy of F-PMAI on the (111) facet. Besides, the bulky molecular is extruded to the bottom and top of perovskite film after crystal growth, which can passivate interface defects through strong interaction between F-PMA+ and undercoordinated Pb2+/I-. As a result, the additive facilitates the formation of large perovskite grains and (111) preferred orientation with a reduced trap-state density, thereby promoting charge carrier transportation, and enhancing device performance and stability. The perovskite/silicon TSCs achieved a champion efficiency of 30.05% based on a silicon thin film tunneling junction. In addition, the devices exhibit excellent long-term thermal and light stability without encapsulation. This work provides an effective strategy for achieving efficient and stable TSCs.

TMC7 functions as a suppressor of Piezo2 in primary sensory neurons blunting peripheral mechanotransduction.

The transmembrane channel-like (TMC) protein family comprises eight members, with TMC1 and TMC2 being extensively studied. This study demonstrates substantial co-expression of TMC7 with the mechanosensitive channel Piezo2 in somatosensory neurons. Genetic deletion of TMC7 in primary sensory ganglia neurons in vivo enhances sensitivity in both physiological and pathological mechanosensory transduction. This deletion leads to an increase in proportion of rapidly adapting (RA) currents conducted by Piezo2 in dorsal root ganglion (DRG) neurons and accelerates RA deactivation kinetics. In HEK293 cells expressing both proteins, TMC7 significantly suppresses the current amplitudes of co-expressed Piezo2. Our findings reveal that TMC7 and Piezo2 exhibit physical interactions, and both proteins also physically interact with cytoskeletal ß-actin. We hypothesize that TMC7 functions as an inhibitory modulator of Piezo2 in DRG neurons, either through direct inhibition or by disrupting the transmission of mechanical forces from the cytoskeleton to the channel.

The transmembrane channel-like 6 (TMC6) in primary sensory neurons involving thermal sensation via modulating M channels.

Introduction: The transmembrane channel-like (TMC) protein family contains eight members, TMC1-TMC8. Among these members, only TMC1 and TMC2 have been intensively studied. They are expressed in cochlear hair cells and are crucial for auditory sensations. TMC6 and TMC8 contribute to epidermodysplasia verruciformis, and predispose individuals to human papilloma virus. However, the impact of TMC on peripheral sensation pain has not been previously investigated. Methods: RNAscope was employed to detect the distribution of TMC6 mRNA in DRG neurons. Electrophysiological recordings were conducted to investigate the effects of TMC6 on neuronal characteristics and M channel activity. Zn2+ indicators were utilized to detect the zinc concentration in DRG tissues and dissociated neurons. A series of behavioural tests were performed to assess thermal and mechanical sensation in mice under both physiological and pathological conditions. Results and Discussion: We demonstrated that TMC6 is mainly expressed in small and medium dorsal root ganglion (DRG) neurons and is involved in peripheral heat nociception. Deletion of TMC6 in DRG neurons hyperpolarizes the resting membrane potential and inhibits neuronal excitability. Additionally, the function of the M channel is enhanced in TMC6 deletion DRG neurons owing to the increased quantity of free zinc in neurons. Indeed, heat and mechanical hyperalgesia in chronic pain are alleviated in TMC6 knockout mice, particularly in the case of heat hyperalgesia. This suggests that TMC6 in the small and medium DRG neurons may be a potential target for chronic pain treatment.

PI4KIIIß-Mediated Phosphoinositides Metabolism Regulates Function of the VTA Dopaminergic Neurons and Depression-Like Behavior.

Phosphoinositides, including phosphatidylinositol-4,5-bisphosphate (PIP2), play a crucial role in controlling key cellular functions such as membrane and vesicle trafficking, ion channel, and transporter activity. Phosphatidylinositol 4-kinases (PI4K) are essential enzymes in regulating the turnover of phosphoinositides. However, the functional role of PI4Ks and mediated phosphoinositide metabolism in the central nervous system has not been fully revealed. In this study, we demonstrated that PI4KIIIß, one of the four members of PI4Ks, is an important regulator of VTA dopaminergic neuronal activity and related depression-like behavior of mice by controlling phosphoinositide turnover. Our findings provide new insights into possible mechanisms and potential drug targets for neuropsychiatric diseases, including depression. Both sexes were studied in basic behavior tests, but only male mice could be used in the social defeat depression model.

Diffusible Capping Layer Enabled Homogeneous Crystallization and Component Distribution of Hybrid Sequential Deposited Perovskite.

Nowadays, the development of wide-bandgap perovskite by thermal evaporation and spin-coating hybrid sequential deposition (HSD) method has special meaning on textured perovskite/silicon tandem solar cells. However, the common issues of insufficient reaction caused by blocking of perovskite capping layer are exacerbated in HSD, because evaporated precursors are usually denser with higher crystallinity and the widely used additive-assisted microstructure is also difficult to access. Here, a facile "diffusible perovskite capping layer" (DPCL) strategy to solve this dilemma is presented. With DPCL, crystallization alleviation of perovskite and more diffusion channels of organic salts can be realized simultaneously, contributing to a homogenization process. The resultant perovskite films exhibit complete conversion, uniform crystallization, enhanced quality, and reduced defect, leading to obvious improvements in device efficiency, repeatability, and stability. This work offers a way to promote the development of textured tandems a step further.

Peripheral gating of pain by glial endozepine.

We report that diazepam binding inhibitor (DBI) is a glial messenger mediating satellite glia-sensory neuron crosstalk in the dorsal root ganglion (DRG). DBI is highly and specifically expressed in satellite glia cells (SGCs) of mice, rat and human, but not in sensory neurons or other DRG-resident cells. Knockdown of DBI results in a robust mechanical hypersensitivity without significant effects on other sensory modalities. In vivo overexpression of DBI in SGCs reduces sensitivity to mechanical stimulation and alleviates mechanical allodynia in neuropathic and inflammatory pain models. We further show that DBI acts as a partial agonist and positive allosteric modulator at the neuronal GABAA receptors, particularly strongly effecting those with a high-affinity benzodiazepine binding site. Such receptors are selectively expressed by a subpopulation of mechanosensitive DRG neurons and these are also more enwrapped with DBI-expressing glia, as compared to other DRG neurons, suggesting a mechanism for specific effect of DBI on mechanosensation. These findings identified a new, peripheral neuron-glia communication mechanism modulating pain signalling, which can be targeted therapeutically.

Impact of Maternal Preoperative Hemoglobin Levels on Intraoperative Hemorrhage Risk in Placenta Accrete Spectrum Disorders: A Retrospective Cross-Sectional Study.

BACKGROUND Placenta accreta spectrum (PAS) disorders involve abnormal adhesion or invasion of chorionic villi through the myometrium and uterine serosa. Maternal anemia during pregnancy is common and may contribute to complications during delivery, particularly with abnormal placentation. This study examines the association between preoperative maternal hemoglobin levels and the risk of intraoperative massive hemorrhage in pregnant women with PAS disorders. MATERIAL AND METHODS A retrospective study included 538 consecutive participants (mean age=31.12±4.68 years) who underwent cesarean sections and met the diagnostic criteria for PAS disorders. Logistic regression analysis was performed to investigate the relationship between maternal preoperative hemoglobin levels and the risk of massive intraoperative hemorrhage (blood loss ≥1500 mL). RESULTS The incidence of intraoperative massive hemorrhage among patients with PAS disorders was 38.66%. The mean preoperative maternal hemoglobin level was 10.99±1.39 g/dL, and overall anemia incidence (<11 g/dL) was 48.88% in our study. After adjusting for potential confounders, a non-linear relationship was observed between preoperative maternal hemoglobin levels and the risk of intraoperative massive hemorrhage. When the preoperative hemoglobin level of pregnant women was below 11.5 g/dL (OR=0.52, 95% CI 0.39-0.70), the lower hemoglobin level significantly increased the risk of intraoperative hemorrhage. CONCLUSIONS Maternal preoperative hemoglobin levels were inversely associated with the risk of massive intraoperative hemorrhage in PAS disorders. A non-linear relationship was identified, with a turning point at 11.5 g/dL. These findings emphasize the importance of monitoring and managing maternal hemoglobin levels to mitigate the risk of intraoperative hemorrhage in pregnant women with PAS disorders.

Si-integrated lanthanide-doped ferroelectrics for a photomemory based on a photochromic reaction.

We describe a Si-integrated photochromic photomemory based on lanthanide-doped ferroelectric Na0.5Bi2.5Nb2O9:Er3+ (NBN:Er) thin films. We show that upconversion emission can be effectively modulated by up to 78% through the photochromic reaction. The coupling between lanthanide upconversion emission and the photochromic effect ensures rewritable and nondestructive readout characteristics. Moreover, integrating photochromic thin films with Si would benefit from its compatibility with the mature complementary metal-oxide semiconductor (CMOS) technique. These results demonstrate the opportunity to develop more compact photochromic photomemories and related photonic devices.

Impact of environmental factors on diversity of fungi in sediments from the Shenzhen River Estuary.

In this study, to explore the relationship between environmental factors and fungal diversity in the Shenzhen River ecosystem, multiple methods including chemical analysis, culture isolation, qPCR analysis of fungal ITS region and ITS-based Illumina next-generation-sequencing were integrated. A total of 115 isolates were finally isolated and could be classified into 23 genera. Top three abundant genera isolated were Meyerozyma (18 strains), Aspergillus (17 strains) and Penicillium (14 strains). Based on the Illumina sequencing approach, 829 OTUs were affiliated to seven phyla, 17 known classes, and 162 genera, indicating the Shenzhen estuary sediments are rich in fungal diversity. The major fungal genera were Meyerozyma, Trichoderma and Talaromyces. Environmental factors showed a gradient change in Shenzhen estuary, and fungal abundance was only significantly correlated with NH4+. Shannon index was significantly correlated with pH and IC (P < 0.05). Principal coordinate analysis based on OTU level grouped into three clusters among sampling sites along with the IC and pH gradient. Functional guilds analysis suggests most of the fungi in this studying area were almost all saprotrophs, suggesting a large number of saprophytic fungi may play a significant role in the organic matter decomposition and nutrient cycling process. In summary, this study will deepen our understanding of fungi community in Shenzhen River ecosystem and their distribution and potential function shaped by environmental factors.

Dorsal root ganglia control nociceptive input to the central nervous system.

Accumulating observations suggest that peripheral somatosensory ganglia may regulate nociceptive transmission, yet direct evidence is sparse. Here, in experiments on rats and mice, we show that the peripheral afferent nociceptive information undergoes dynamic filtering within the dorsal root ganglion (DRG) and suggest that this filtering occurs at the axonal bifurcations (t-junctions). Using synchronous in vivo electrophysiological recordings from the peripheral and central processes of sensory neurons (in the spinal nerve and dorsal root), ganglionic transplantation of GABAergic progenitor cells, and optogenetics, we demonstrate existence of tonic and dynamic filtering of action potentials traveling through the DRG. Filtering induced by focal application of GABA or optogenetic GABA release from the DRG-transplanted GABAergic progenitor cells was specific to nociceptive fibers. Light-sheet imaging and computer modeling demonstrated that, compared to other somatosensory fiber types, nociceptors have shorter stem axons, making somatic control over t-junctional filtering more efficient. Optogenetically induced GABA release within DRG from the transplanted GABAergic cells enhanced filtering and alleviated hypersensitivity to noxious stimulation produced by chronic inflammation and neuropathic injury in vivo. These findings support "gating" of pain information by DRGs and suggest new therapeutic approaches for pain relief.

Unrevealing Temporal Mechanoluminescence Behaviors at High Frequency via Piezoelectric Actuation.

Mechanoluminescence (ML) materials present widespread applications. Empirically, modulation for a given ML material is achieved by application of programmed mechanical actuation with different amplitude, repetition velocity and frequency. However, to date modulation on the ML is very limited within several to a few hundred hertz low-frequency actuation range, due to the paucity of high-frequency mechanical excitation apparatus. The universality of temporal behavior and frequency response is an important aspect of ML phenomena, and serves as the impetus for much of its applications. Here, we push the study on ML into high-frequency range (∼250 kHz) by combining with piezoelectric actuators. Two representative ML ZnS:Mn and ZnS:Cu, Al phosphors were chosen as the research objects. Time-resolved ML of ZnS:Mn and ZnS:Cu, Al shows unrevealed frequency-dependent saturation and quenching, which is associated with the dynamic processes of traps. From the point of applications, this study sets the cut-off frequency for ML sensing. Moreover, by in-situ tuning the strain frequency, ZnS:Mn exhibits reversible frequency-induced broad red-shift into near-infrared range. These findings offer keen insight into the photophysics nature of ML and also broaden the physical modulation of ML by locally adjusting the excitation frequency.

Potassium Channel Conductance Is Involved in Phenylephrine-Induced Spontaneous Firing of Serotonergic Neurons in the Dorsal Raphe Nucleus.

The serotonergic (5-HT) network from the dorsal raphe nucleus (DRN) of the brain has been demonstrated to regulate cognition, emotion, and behaviors, including learning and the sleep-wake cycle. Dysregulation of the activity of 5-HT neurons in the DRN is thought to play an important role in emotional disorders. The activity of 5-HT neurons is regulated by norepinephrine (NE) released from the projection terminals of noradrenergic input from the locus coeruleus (LC) via activation of the α1-adrenoceptor. However, insight into the molecular mechanism underlying this NE-induced regulation of 5-HT neuron activity is not clear. In this study, using the agonist of α1-adrenoceptor phenylephrine (PE), brain slices, and patch clamp, we found that A-type, Kv7/KCNQ, and calcium-activated low-conductance K+ channels (SK) underlie PE-induced spontaneous firing in DRN 5-HT neurons. Using single-cell PCR and immunofluorescence, we also identified the isoforms of these K+ channel families that might contribute to the NE/PE-induced spontaneous firing of DRN 5-HT neurons.

Protein disulfide isomerase modulation of TRPV1 controls heat hyperalgesia in chronic pain.

Protein disulfide isomerase (PDI) plays a key role in maintaining cellular homeostasis by mediating protein folding via catalyzing disulfide bond formation, breakage, and rearrangement in the endoplasmic reticulum. Increasing evidence suggests that PDI can be a potential treatment target for several diseases. However, the function of PDI in the peripheral sensory nervous system is unclear. Here we report the expression and secretion of PDI from primary sensory neurons is upregulated in inflammatory and neuropathic pain models. Deletion of PDI in nociceptive DRG neurons results in a reduction in inflammatory and neuropathic heat hyperalgesia. We demonstrate that secreted PDI activates TRPV1 channels through oxidative modification of extracellular cysteines of the channel, indicating that PDI acts as an unconventional positive modulator of TRPV1. These findings suggest that PDI in primary sensory neurons plays an important role in development of heat hyperalgesia and can be a potential therapeutic target for chronic pain.

Control of upconversion luminescence by tailoring energy migration in doped perovskite superlattices.

We describe an experimental investigation of photon upconversion (UC) in a series of perovskite BaTiO3/SrTiO3 superlattices doped with different lanthanide compositions. We show that UC emission can be effectively enhanced by precisely incorporating a set of lanthanide ions into separated layers rather than homogeneously distributing the dopant ions in the host lattice. The use of an inert layer in the superlattice can suppress deleterious energy cross-relaxation. Furthermore, UC emission can be rendered by controlling the energy migration mediated by the Yb-doped sublattice. These results demonstrate the opportunity to modulate energy migration and transfer processes through the rational design of superlattice structures.

Mechanically induced enhancement and modulation of upconversion photoluminescence by bending lanthanide-doped perovskite oxides.

We report experimental studies of the bending strain impact on the upconversion processes in Yb3+, Er3+, and Mn2+ co-doped BaTiO3 (BTO) thin films with mica as the flexible substrate. Bending strain induces strong enhancement and modulation of the upconversion emission in doped BTO thin films. Because the unshielded 3d5 configuration of Mn2+ is more susceptible to crystal field changes, the introduction of an Mn2+ ion further promotes the strain-induced modulation effect. The upconversion intensity is amplified by six times at bending strain ε = 1.83% in BTO:Yb3+/Er3+/Mn2+ thin films. These results demonstrate the opportunity of rendering an upconversion emission through integrating lanthanide-doped ferroelectric films with flexible mica, especially by incorporating an Mn2+ ion.

Activation of parabrachial nucleus - ventral tegmental area pathway underlies the comorbid depression in chronic neuropathic pain in mice.

Depression symptoms are often found in patients suffering from chronic pain, a phenomenon that is yet to be understood mechanistically. Here, we systematically investigate the cellular mechanisms and circuits underlying the chronic-pain-induced depression behavior. We show that the development of chronic pain is accompanied by depressive-like behaviors in a mouse model of trigeminal neuralgia. In parallel, we observe increased activity of the dopaminergic (DA) neuron in the midbrain ventral tegmental area (VTA), and inhibition of this elevated VTA DA neuron activity reverses the behavioral manifestations of depression. Further studies establish a pathway of glutamatergic projections from the spinal trigeminal subnucleus caudalis (Sp5C) to the lateral parabrachial nucleus (LPBN) and then to the VTA. These glutamatergic projections form a direct circuit that controls the development of the depression-like behavior under the state of the chronic neuropathic pain.

Neuropathic Injury-Induced Plasticity of GABAergic System in Peripheral Sensory Ganglia.

GABA is a major inhibitory neurotransmitter in the mammalian central nervous system (CNS). Inhibitory GABAA channel circuits in the dorsal spinal cord are the gatekeepers of the nociceptive input from the periphery to the CNS. Weakening of these spinal inhibitory mechanisms is a hallmark of chronic pain. Yet, recent studies have suggested the existence of an earlier GABAergic "gate" within the peripheral sensory ganglia. In this study, we performed systematic investigation of plastic changes of the GABA-related proteins in the dorsal root ganglion (DRG) in the process of neuropathic pain development. We found that chronic constriction injury (CCI) induced general downregulation of most GABAA channel subunits and the GABA-producing enzyme, glutamate decarboxylase, consistent with the weakening of the GABAergic inhibition at the periphery. Strikingly, the α5 GABAA subunit was consistently upregulated. Knock-down of the α5 subunit in vivo moderately alleviated neuropathic hyperalgesia. Our findings suggest that while the development of neuropathic pain is generally accompanied by weakening of the peripheral GABAergic system, the α5 GABAA subunit may have a unique pro-algesic role and, hence, might represent a new therapeutic target.