Phenolic Glycoside Monomer from Reed Rhizome Inhibits Melanin Production via PI3K-Akt and Ras-Raf-MEK-ERK Pathways.

INTRODUCTION: Melanogenesis, the process responsible for melanin production, is a critical determinant of skin pigmentation. Dysregulation of this process can lead to hyperpigmentation disorders. METHOD: In this study, we identified a novel Reed Rhizome extract, (1'S, 2'S)-syringyl glycerol 3'-O-ß-D-glucopyranoside (compound 5), and evaluated its anti-melanogenic potential in zebrafish models and in vitro assays. Compound 5 inhibited melanin synthesis by 36.66% ± 14.00% and tyrosinase in vivo by 48.26% ± 6.94%, surpassing the inhibitory effects of arbutin. Network pharmacological analysis revealed key targets, including HSP90AA1, HRAS, and PIK3R1, potentially involved in the anti-melanogenic effects of compound 5. RESULTS: Molecular docking studies supported the interactions between compound 5 and these targets. Further, gene expression analysis in zebrafish indicated that compound 5 up-regulates hsp90aa1.1, hrasa, and pik3r1, and subsequently down-regulating mitfa, tyr, and tyrp1, critical genes in melanogenesis. CONCLUSION: These findings suggest that compound 5 inhibits melanin production via PI3K-Akt and Ras-Raf-MEK-ERK signaling pathways, positioning it as a promising candidate for the treatment of hyperpigmentation.

Insights on pathophysiology of hydrocephalus rats induced by kaolin injection.

Hydrocephalus can affect brain function and motor ability. Current treatments mostly involve invasive surgeries, with a high risk of postoperative infections and failure. A successful animal model plays a significant role in developing new treatments for hydrocephalus. Hydrocephalus was induced in Sprague-Dawley rats by injecting 25% kaolin into the subarachnoid space at the cerebral convexities with different volumes of 30, 60 and 90 µL. Magnetic resonance imaging (MRI) was performed 1 month and 4 months after kaolin injection. The behavioral performance was assessed weekly, lasting for 7 weeks. The histopathological analyses were conducted to the lateral ventricles by hematoxylin-eosin (HE) staining. Transcriptomic analysis was used between Normal Pressure Hydrocephalus (NPH) patients and hydrocephalus rats. MRI showed a progressive enlargement of ventricles in hydrocephalus group. Kaolin-60 µL and kaolin-90 µL groups showed larger ventricular size, higher anxiety level, bigger decline in body weight, motor ability and cognitive competence. These symptoms may be due to higher-grade inflammatory infiltrate and the damage of the structure of ependymal layer of the ventricles, indicated by HE staining. The overlap upregulated genes and pathways mainly involve immunity and inflammation. Transcriptomic revealed shared pathogenic genes CD40, CD44, CXCL10, and ICAM1 playing a dominance role. 60 µL injection might be recommended for the establishment of hydrocephalus animal model, with a high successful rate and high stability. The hydrocephalus model was able to resemble the inflammatory mechanism and behavioral performance observed in human NPH patients, providing insights for identifying therapeutic targets for hydrocephalus.

A Male Patient with Hydrocephalus via Multimodality Diagnostic Approaches: A Case Report.

Introduction: Idiopathic normal pressure hydrocephalus (iNPH) is a kind of hydrocephalus that is easily to be misdiagnosed with brain atrophy due to the similarity of ventricular dilation and cognitive impairment. In this case, we present an old male patient who was diagnosed with iNPH by multimodality approaches. Outcomes: A 68-year-old male patient, with deteriorated gait, declined cognitive function for at least 3 years and urinary incontinence for 3 months. The doctors suspected him a patient with hydrocephalus or Alzheimer's disease based on his symptoms. We used multimodality diagnostic approaches including brain imaging, cerebrospinal fluid tap test, continuous intracranial pressure monitoring, and infusion study to make the final diagnosis of iNPH. He underwent ventriculoperitoneal shunt surgery and was well recovered. Conclusion: This case demonstrates the efficacy of using multimodality approaches for iNPH diagnosis, which saves patient time and clinical cost, worthy of further promotion.

RetSat stabilizes mitotic chromosome segregation in pluripotent stem cells.

BACKGROUND: Chromosome stability is crucial for homeostasis of pluripotent stem cells (PSCs) and early-stage embryonic development. Chromosomal defects may raise carcinogenic risks in regenerative medicine when using PSCs as original materials. However, the detailed mechanism regarding PSCs chromosome stability maintenance is not fully understood. METHODS: Mouse embryonic stem cells (line D3) and human embryonic stem cells (line H9) were cultured under standard conditions. To confirm the loading of RetSat protein on mitotic chromosomes of PSCs, immunostaining was performed in PSCs spontaneous differentiation assay and iPSC reprogramming assay from mouse embryonic fibroblasts (MEFs), respectively. In addition, qPCR, immunoprecipitation, LC-MS/MS and immunoblotting were used to study the expression of RetSat, and interactions of RetSat with cohesin/condensin components. RNA sequencing and teratoma formation assay was conducted to evaluate the carcinogenic risk of mouse embryonic stem cells with RetSat deletion. RESULTS: We reported a PSC high-expressing gene, RetSat, plays key roles in chromosome stabilization. We identified RetSat protein localizing onto mitotic chromosomes specifically in stemness positive cells such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). We found dramatic chromosome instability, e.g. chromosome bridging, lagging and interphase micronuclei in mouse and human ESCs when down regulating RetSat. RetSat knock-out mouse ESCs upregulated cancer associated gene pathways, and displayed higher tumorigenic capacities in teratoma formation assay. Mechanistically, we confirmed that RetSat interacts with cohesin/condensin components Smc1a and Nudcd2. RetSat deletion impaired the chromosome loading dosage of Smc1a, Smc3 and Nudcd2. CONCLUSIONS: In summary, we reported RetSat to be a key stabilizer of chromosome condensation in pluripotent stem cells. This highlights the crucial roles of RetSat in early-stage embryonic development, and potential value of RetSat as an effective biomarker for assessing the quality of pluripotent stem cells.

Congenital hydrocephalus: a review of recent advances in genetic etiology and molecular mechanisms.

The global prevalence rate for congenital hydrocephalus (CH) is approximately one out of every five hundred births with multifaceted predisposing factors at play. Genetic influences stand as a major contributor to CH pathogenesis, and epidemiological evidence suggests their involvement in up to 40% of all cases observed globally. Knowledge about an individual's genetic susceptibility can significantly improve prognostic precision while aiding clinical decision-making processes. However, the precise genetic etiology has only been pinpointed in fewer than 5% of human instances. More occurrences of CH cases are required for comprehensive gene sequencing aimed at uncovering additional potential genetic loci. A deeper comprehension of its underlying genetics may offer invaluable insights into the molecular and cellular basis of this brain disorder. This review provides a summary of pertinent genes identified through gene sequencing technologies in humans, in addition to the 4 genes currently associated with CH (two X-linked genes L1CAM and AP1S2, two autosomal recessive MPDZ and CCDC88C). Others predominantly participate in aqueduct abnormalities, ciliary movement, and nervous system development. The prospective CH-related genes revealed through animal model gene-editing techniques are further outlined, focusing mainly on 4 pathways, namely cilia synthesis and movement, ion channels and transportation, Reissner's fiber (RF) synthesis, cell apoptosis, and neurogenesis. Notably, the proper functioning of motile cilia provides significant impulsion for cerebrospinal fluid (CSF) circulation within the brain ventricles while mutations in cilia-related genes constitute a primary cause underlying this condition. So far, only a limited number of CH-associated genes have been identified in humans. The integration of genotype and phenotype for disease diagnosis represents a new trend in the medical field. Animal models provide insights into the pathogenesis of CH and contribute to our understanding of its association with related complications, such as renal cysts, scoliosis, and cardiomyopathy, as these genes may also play a role in the development of these diseases. Genes discovered in animals present potential targets for new treatments but require further validation through future human studies.

Molecular understanding of the therapeutic potential of melanin inhibiting natural products.

With the development of society and the improvement of people's living standards, there is an increasing demand for melanin-inhibiting products that prioritize health, safety, and efficacy. Therefore, the development of natural products that can safely and efficiently inhibit melanin synthesis is of great social significance and has significant market potential. In this paper, by reviewing the literature reported in recent years, we summarized the natural products with inhibition of melanin synthesis effects that have been put into or not yet put into the market, and classified them according to the chemical groups of their compounds or the extraction methods of the natural products. Through the summary analysis, we found that these compounds mainly include terpenoids, phenylpropanoids, flavonoids and so on, while the natural product extracts mainly include methanol extracts, ethanol extracts, and aqueous extracts. Their main inhibition of melanin synthesis mechanisms include: (1) direct inhibition of tyrosinase activity; (2) down-regulation of the α-MSH-MC1R, Wnt, NO, PI3K/Akt and MAPK pathways through the expression of MITF and its downstream genes TYR, TRP-1, and TRP-2; (3) antioxidant; (4) inhibition of melanocyte growth through cytotoxicity; (5) inhibition of melanosome production and transport. This paper provides an in-depth discussion on the research progress of whitening natural products and their market value. The aim is to offer guidance for future research and development of natural skin whitening products.

Nomo1 deficiency causes autism-like behavior in zebrafish.

Patients with neuropsychiatric disorders often exhibit a combination of clinical symptoms such as autism, epilepsy, or schizophrenia, complicating diagnosis and development of therapeutic strategies. Functional studies of novel genes associated with co-morbidities can provide clues to understand the pathogenic mechanisms and interventions. NOMO1 is one of the candidate genes located at 16p13.11, a hotspot of neuropsychiatric diseases. Here, we generate nomo1-/- zebrafish to get further insight into the function of NOMO1. Nomo1 mutants show abnormal brain and neuronal development and activation of apoptosis and inflammation-related pathways in the brain. Adult Nomo1-deficient zebrafish exhibit multiple neuropsychiatric behaviors such as hyperactive locomotor activity, social deficits, and repetitive stereotypic behaviors. The Habenular nucleus and the pineal gland in the telencephalon are affected, and the melatonin level of nomo1-/- is reduced. Melatonin treatment restores locomotor activity, reduces repetitive stereotypic behaviors, and rescues the noninfectious brain inflammatory responses caused by nomo1 deficiency. These results suggest melatonin supplementation as a potential therapeutic regimen for neuropsychiatric disorders caused by NOMO1 deficiency.

Influence of Transcutaneous Vagus Nerve Stimulation on Motor Planning: A Resting-State and Task-State EEG Study.

Transcutaneous vagus nerve stimulation (tVNS) shows a potential regulatory role for motor planning. Still, existing research mainly focuses on behavioral studies, and the neural modulation mechanism needs to be clarified. Therefore, we designed a multi-condition (active or sham, pre or under, difficult or easy, left-hand or right-hand) motor planning experiment to explore the effect of online tVNS (i.e., tVNS and tasks synchronized). Twenty-eight subjects were recruited and randomly assigned to active and sham groups. Both groups performed the same tasks in the experiment and separately collected task-state EEG and 5-min eye-open resting-state EEG. The results showed that the changes in event-related potential (ERP) and movement-related cortical potential (MRCP) amplitudes were more significant for the left-hand difficult task (LD) under active-tVNS. According to the power spectrum results, active-tVNS significantly modulated the activities of the contralateral motor cortex at beta and gamma bands in the resting state. The functional connectivity based on partial directed coherence (PDC) showed significant changes in the parietal lobe after active-tVNS. These findings suggest that tVNS is a promising way to improve motor planning ability.

Enhancing Motor Sequence Learning via Transcutaneous Auricular Vagus Nerve Stimulation (taVNS): An EEG Study.

Motor learning plays a crucial role in human life, and various neuromodulation methods have been utilized to strengthen or improve it. Transcutaneous auricular vagus nerve stimulation (taVNS) has gained increasing attention due to its non-invasive nature, affordability and ease of implementation. Although the potential of taVNS on regulating motor learning has been suggested, its actual regulatory effect has yet been fully explored. Electroencephalogram (EEG) analysis provides an in-depth understanding of cognitive processes involved in motor learning so as to offer methodological support for regulation of motor learning. To investigate the effect of taVNS on motor learning, this study recruited 22 healthy subjects to participate a single-blind, sham-controlled, and within-subject serial reaction time task (SRTT) experiment. Every subject involved in two sessions at least one week apart and received a 20-minute active/sham taVNS in each session. Behavioral indicators as well as EEG characteristics during the task state, were extracted and analyzed. The results revealed that compared to the sham group, the active group showed higher learning performance. Additionally, the EEG results indicated that after taVNS, the motor-related cortical potential amplitudes and alpha-gamma modulation index decreased significantly and functional connectivity based on partial directed coherence towards frontal lobe was enhanced. These findings suggest that taVNS can improve motor learning, mainly through enhancing cognitive and memory functions rather than simple movement learning. This study confirms the positive regulatory effect of taVNS on motor learning, which is particularly promising as it offers a potential avenue for enhancing motor skills and facilitating rehabilitation.

Acoustoelectric brain imaging with different conductivities and acoustic distributions.

Objective: Acoustoelectric brain imaging (AEBI) is a promising imaging method for mapping brain biological current densities with high spatiotemporal resolution. Currently, it is still challenging to achieve human AEBI with an unclear acoustoelectric (AE) signal response of medium characteristics, particularly in conductivity and acoustic distribution. This study introduces different conductivities and acoustic distributions into the AEBI experiment, and clarifies the response interaction between medium characteristics and AEBI performance to address these key challenges. Approach: AEBI with different conductivities is explored by the imaging experiment, potential measurement, and simulation on a pig's fat, muscle, and brain tissue. AEBI with different acoustic distributions is evaluated on the imaging experiment and acoustic field measurement through a deep and surface transmitting model built on a human skullcap and pig brain tissue. Main results: The results show that conductivity is not only inversely proportional to the AE signal amplitude but also leads to a higher AEBI spatial resolution as it increases. In addition, the current source and sulcus can be located simultaneously with a strong AE signal intensity. The transcranial focal zone enlargement, pressure attenuation in the deep-transmitting model, and ultrasound echo enhancement in the surface-transmitting model cause a reduced spatial resolution, FFT-SNR, and timing correlation of AEBI. Under the comprehensive effect of conductivity and acoustics, AEBI with skull finally shows reduced imaging performance for both models compared with no-skull AEBI. On the contrary, the AE signal amplitude decreases in the deep-transmitting model and increases in the surface-transmitting model. Significance: This study reveals the response interaction between medium characteristics and AEBI performance, and makes an essential step toward developing AEBI as a practical neuroimaging technique.

[Gut microbial dysbiosis under space environment: a review].

Unique factors in the space environment can cause dysbiosis of astronauts' gut microbiota and its metabolites, which may exert systematic physiological effects on human body. Recent progress regarding the effect of space flight/simulated space environment (SF/SPE) on the composition of gut microbiota and its metabolites was reviewed in this paper. SF/SPE may cause the increase of invasive pathogenic bacteria and the decrease of beneficial bacteria, aggravating intestinal inflammation and increasing intestinal permeability. SF/SPE may also cause the decrease of beneficial metabolites or the increase of harmful metabolites of gut microbiota, leading to metabolism disorder in vivo, or inducing damage of other systems, thus not beneficial to the health and working efficiency of astronauts. Summarizing the effects of SF/SPE on gut microbiota may provide scientific basis for further researches in this field and the on-orbit health protection of astronauts.

Hypothermic Protection in Neocortex Is Topographic and Laminar, Seizure Unmitigating, and Partially Rescues Neurons Depleted of RNA Splicing Protein Rbfox3/NeuN in Neonatal Hypoxic-Ischemic Male Piglets.

The effects of hypothermia on neonatal encephalopathy may vary topographically and cytopathologically in the neocortex with manifestations potentially influenced by seizures that alter the severity, distribution, and type of neuropathology. We developed a neonatal piglet survival model of hypoxic-ischemic (HI) encephalopathy and hypothermia (HT) with continuous electroencephalography (cEEG) for seizures. Neonatal male piglets received HI-normothermia (NT), HI-HT, sham-NT, or sham-HT treatments. Randomized unmedicated sham and HI piglets underwent cEEG during recovery. Survival was 2-7 days. Normal and pathological neurons were counted in different neocortical areas, identified by cytoarchitecture and connectomics, using hematoxylin and eosin staining and immunohistochemistry for RNA-binding FOX-1 homolog 3 (Rbfox3/NeuN). Seizure burden was determined. HI-NT piglets had a reduced normal/total neuron ratio and increased ischemic-necrotic/total neuron ratio relative to sham-NT and sham-HT piglets with differing severities in the anterior and posterior motor, somatosensory, and frontal cortices. Neocortical neuropathology was attenuated by HT. HT protection was prominent in layer III of the inferior parietal cortex. Rbfox3 immunoreactivity distinguished cortical neurons as: Rbfox3-positive/normal, Rbfox3-positive/ischemic-necrotic, and Rbfox3-depleted. HI piglets had an increased Rbfox3-depleted/total neuron ratio in layers II and III compared to sham-NT piglets. Neuronal Rbfox3 depletion was partly rescued by HT. Seizure burdens in HI-NT and HI-HT piglets were similar. We conclude that the neonatal HI piglet neocortex has: (1) suprasylvian vulnerability to HI and seizures; (2) a limited neuronal cytopathological repertoire in functionally different regions that engages protective mechanisms with HT; (3) higher seizure burden, insensitive to HT, that is correlated with more panlaminar ischemic-necrotic neurons in the somatosensory cortex; and (4) pathological RNA splicing protein nuclear depletion that is sensitive to HT. This work demonstrates that HT protection of the neocortex in neonatal HI is topographic and laminar, seizure unmitigating, and restores neuronal depletion of RNA splicing factor.

An Atypical Incontinentia Pigmenti Female with Persistent Mucocutaneous Hyperinflammation and Immunodeficiency Caused by a Novel Germline IKBKG Missense Mutation.

While most missense mutations of the IKBKG gene typically result in Ectodermal Dysplasia with Immunodeficiency, there have been rare reported instances of missense mutations of the IKBKG gene causing both Incontinentia Pigmenti (IP) and immunodeficiency in female patients. In this study, we described an atypical IP case in a 19-year-old girl, characterized by hyperpigmented and verrucous skin areas over the entire body. Remarkably, she experienced recurrent red papules whenever she had a feverish upper respiratory tract infection. Immunohistochemical staining unveiled a substantial accumulation of CD68+ macrophages alongside the TNF-α positive cells in the dermis tissue of new pustules, with increased apoptotic basal keratinocytes in the epidermis tissue of these lesions. Starting from the age of 8 years old, the patient suffered from severe and sustained chronic respiratory mucous membrane scar hyperplasia and occluded subglottic lumen. In addition to elevated erythrocyte sedimentation rate values, inflammatory cells were observed in the pathologic lesions of endobronchial biopsies and Bronchoalveolar Lavage Fluid (BALF) smear. Further histological analysis revealed a destructive bronchus epithelium integrity with extensive necrosis. Simultaneously, the patient experienced recurrent incomplete intestinal obstructions and lips contracture. The patient's BALF sample displayed an augmented profile of proinflammatory cytokines and chemokines, suggesting a potential link to systemic hyperinflammation, possibly underlying the pathogenic injuries affecting the subglottic, respiratory, and digestive systems. Furthermore, the patient presented with recurrent pneumonias and multiple warts accompanied by a T+BlowNKlow immunophenotype. Next generation sequencing showed that the patient carried a novel de novo germline heterozygous missense mutation in the IKBKG gene (c. 821T>C, p. L274P), located in the highly conserved CC2 domain. TA-cloning sequencing of patient's cDNA yielded 30 mutant transcripts out of 44 clones. In silico analysis indicated that the hydrogen bond present between Ala270 and Leu274 in the wild-type NEMO was disrupted by the Leu274Pro mutation. However, this mutation did not affect NEMO expression in peripheral blood mononuclear cells (PBMCs). Moreover, patient PBMCs exhibited significantly impaired TNF-α production following Lipopolysaccharide (LPS) stimulation. X-chromosome inactivation in T cells and neutrophils were not severely skewed. Reduced levels of IκBα phosphorylation and degradation in patient's PBMCs were observed. The NF-κB luciferase reporter assay conducted using IKBKG-deficient HEK293T cells revealed a significant reduction in NF-kB activity upon LPS stimulation. These findings adds to the ever-growing knowledge on female IP that might contribute to the better understanding of this challenging disorder.

Mortality prediction using medical time series on TBI patients.

BACKGROUND AND OBJECTIVE: Traumatic Brain Injury (TBI) is one of the leading causes of injury-related mortality in the world, with severe cases reaching mortality rates of 30-40%. It is highly heterogeneous both in causes and consequences making more complex the medical interpretation and prognosis. Gathering clinical, demographic, and laboratory data to perform a prognosis requires time and skill in several clinical specialties. Artificial intelligence (AI) methods can take advantage of existing data by performing helpful predictions and guiding physicians toward a better prognosis and, consequently, better healthcare. The objective of this work was to develop learning models and evaluate their capability of predicting the mortality of TBI. The predictive model would allow the early assessment of the more serious cases and scarce medical resources can be pointed toward the patients who need them most. METHODS: Long Short Term Memory (LSTM) and Transformer architectures were tested and compared in performance, coupled with data imbalance, missing data, and feature selection strategies. From the Medical Information Mart for Intensive Care III (MIMIC-III) dataset, a cohort of TBI patients was selected and an analysis of the first 48 hours of multiple time series sequential variables was done to predict hospital mortality. RESULTS: The best performance was obtained with the Transformer architecture, achieving an AUC of 0.907 with the larger group of features and trained with class proportion class weights and binary cross entropy loss. CONCLUSIONS: Using the time series sequential data, LSTM and Transformers proved to be both viable options for predicting TBI hospital mortality in 48 hours after admission. Overall, using sequential deep learning models with time series data to predict TBI mortality is viable and can be used as a helpful indicator of the well-being of patients.

Calcium Imaging Characterize the Neurobiological Effect of Terahertz Radiation in Zebrafish Larvae.

(1) Objective: To explore the neurobiological effects of terahertz (THz) radiation on zebrafish larvae using calcium (Ca2+) imaging technology. (2) Methods: Zebrafish larvae at 7 days post fertilization (dpf) were exposed to THz radiation for 10 or 20 min; the frequency was 2.52 THz and the amplitude 50 mW/cm2. The behavioral experiments, neural Ca2+ imaging, and quantitative polymerase chain reaction (qPCR) of the dopamine-related genes were conducted following the irradiation. (3) Results: Compared with the control group, the behavioral experiments demonstrated that THz radiation significantly increased the distance travelled and speed of zebrafish larvae. In addition, the maximum acceleration and motion frequency were elevated in the 20 min radiation group. The neural Ca2+ imaging results indicated a substantial increase in zebrafish neuronal activity. qPCR experiments revealed a significant upregulation of dopamine-related genes, such as drd2b, drd4a, slc6a3 and th. (4) Conclusion: THz radiation (2.52 THz, 50 mW/cm2, 20 min) upregulated dopamine-related genes and significantly enhanced neuronal excitability, and the neurobiological effect of THz radiation can be visualized using neural Ca2+ imaging in vivo.

NKG2D-CAR T cells eliminate senescent cells in aged mice and nonhuman primates.

Cellular senescence, characterized by stable cell cycle arrest, plays an important role in aging and age-associated pathologies. Eliminating senescent cells rejuvenates aged tissues and ameliorates age-associated diseases. Here, we identified that natural killer group 2 member D ligands (NKG2DLs) are up-regulated in senescent cells in vitro, regardless of stimuli that induced cellular senescence, and in various tissues of aged mice and nonhuman primates in vivo. Accordingly, we developed and demonstrated that chimeric antigen receptor (CAR) T cells targeting human NKG2DLs selectively and effectively diminish human cells undergoing senescence induced by oncogenic stress, replicative stress, DNA damage, or P16INK4a overexpression in vitro. Targeting senescent cells with mouse NKG2D-CAR T cells alleviated multiple aging-associated pathologies and improved physical performance in both irradiated and aged mice. Autologous T cells armed with the human NKG2D CAR effectively delete naturally occurring senescent cells in aged nonhuman primates without any observed adverse effects. Our findings establish that NKG2D-CAR T cells could serve as potent and selective senolytic agents for aging and age-associated diseases driven by senescence.

EEG dynamics induced by zolpidem forecast consciousness evolution in prolonged disorders of consciousness.

OBJECTIVE: To explore whether the EEG dynamics induced by zolpidem can predict consciousness evolution in patients with prolonged disorders of consciousness (PDOC). METHODS: We conducted a prospective explorative analysis on thirty-six patients with PDOC and eleven healthy controls. The EEG power spectrum was analyzed and categorized into 'ABCD' patterns at baseline and one hour after zolpidem administration at 10 mg. The clinical outcome was defined as consciousness improvement and no improvement six months after enrollment using the Coma Recovery Scale-Revised (CRS-R) score. RESULTS: Zolpidem administration significantly increased the EEG power in the delta & theta bands and decreased EEG power in the beta bands in healthy controls. Further follow-up studies indicated that the increased EEG beta-band power induced by zolpidem can predict an improved consciousness six months after enrollment with an area under the receiver operating characteristic curve (AUC) of 0.829, the sensitivity of 94.38% and an accuracy of 81.48%. CONCLUSIONS: Our work revealed that the specific EEG responses to zolpidem can predict consciousness recovery in PDOC patients. SIGNIFICANCE: The zolpidem-induced specific EEG responses could potentially predict the recovery of PDOC patients, which may help clinicians and patients' families in their decision-making process.

Right versus left eye asymmetry of microvasculature in diabetes revealed by optical coherence tomography angiography.

In this study, we explored inter-ocular asymmetry (between the two eyes of the same patient) using optical coherence tomography angiography (OCTA) in patients with diabetes mellitus (DM) at different retinopathy stages. A total of 258 patients were divided into four groups: no DM, DM without diabetic retinopathy (DR), non-proliferative DR (NPDR), and proliferative DR (PDR). Superficial and deep vessel density (SVD, DVD), superficial and deep perfusion density (SPD, DPD), foveal avascular zone (FAZ) area, perimeter and circularity were calculated, and asymmetry index (AI) was used to evaluate the asymmetry of two eyes of the same subject. AIs of SPD, SVD, FAZ area and FAZ perimeter in the PDR group were larger than all other 3 groups (all p < 0.05). The AIs of DPD, DVD, FAZ area and FAZ perimeter in males were larger than in females (p = 0.015, p = 0.023, p = 0.006 and p = 0.017). Hemoglobin A1c (HbA1c) was positively correlated with AI of FAZ perimeter (p = 0.02) and circularity (p = 0.022). In conclusion, PDR patients' eyes were significantly asymmetric in both vascular density and FAZ metrics. Male sex and HbA1c are risk factors that influenced symmetry. This study highlights that right-left asymmetry should be taken into account in DR-related studies, particularly those analyzing microvascular changes with OCTA.

Enhancing Motor Imagery Performance by Antiphasic 10 Hz Transcranial Alternating Current Stimulation.

Motor imagery (MI), as a cognitive motor process, involves the coordinated activation of frontal and parietal cortices and has been widely studied as an effective way to improve motor functions. However, there are large inter-individual differences in MI performance, with many subjects unable to elicit sufficiently reliable MI brain patterns. It has been shown that dual-site transcranial alternating current stimulation (tACS) applied on two brain sites can modulate functional connectivity between the targeted regions. Here, we investigated whether electrically stimulating frontal and parietal regions using dual-site tACS at mu frequency will modulate motor imagery performance. Thirty-six healthy participants were recruited and randomly divided into in-phase (0° lag), anti-phase (180° lag) and sham stimulation group. All groups performed the simple (grasping movement) and complex (writing movement) motor imagery tasks before and after tACS. Simultaneously collected EEG data showed that the event-related desynchronization (ERD) of mu rhythm and classification accuracy during complex task were significantly improved after anti-phase stimulation. In addition, anti-phase stimulation resulted in decreased event-related functional connectivity between regions within frontoparietal network in the complex task. In contrast, no beneficial after-effects of anti-phase stimulation were found in the simple task. These findings suggest that dual-site tACS effects on MI dependent on the phase lag of the stimulation and the complexity of the task. Anti-phase stimulation applied to the frontoparietal regions is a promising way to foster demanding MI task.