Spatiotemporal coordination of transcription preinitiation complex assembly in live cells.

Transcription initiation by RNA polymerase II (RNA Pol II) requires preinitiation complex (PIC) assembly at gene promoters. In the dynamic nucleus, where thousands of promoters are broadly distributed in chromatin, it is unclear how multiple individual components converge on any target to establish the PIC. Here we use live-cell, single-molecule tracking in S. cerevisiae to visualize constrained exploration of the nucleoplasm by PIC components and Mediator's key role in guiding this process. On chromatin, TFIID/TATA-binding protein (TBP), Mediator, and RNA Pol II instruct assembly of a short-lived PIC, which occurs infrequently but efficiently within a few seconds on average. Moreover, PIC exclusion by nucleosome encroachment underscores regulated promoter accessibility by chromatin remodeling. Thus, coordinated nuclear exploration and recruitment to accessible targets underlies dynamic PIC establishment in yeast. Our study provides a global spatiotemporal model for transcription initiation in live cells.

Neuronal innervation regulates the secretion of neurotrophic myokines and exosomes from skeletal muscle.

Myokines and exosomes, originating from skeletal muscle, are shown to play a significant role in maintaining brain homeostasis. While exercise has been reported to promote muscle secretion, little is known about the effects of neuronal innervation and activity on the yield and molecular composition of biologically active molecules from muscle. As neuromuscular diseases and disabilities associated with denervation impact muscle metabolism, we hypothesize that neuronal innervation and firing may play a pivotal role in regulating secretion activities of skeletal muscles. We examined this hypothesis using an engineered neuromuscular tissue model consisting of skeletal muscles innervated by motor neurons. The innervated muscles displayed elevated expression of mRNAs encoding neurotrophic myokines, such as interleukin-6, brain-derived neurotrophic factor, and FDNC5, as well as the mRNA of peroxisome-proliferator-activated receptor γ coactivator 1α, a key regulator of muscle metabolism. Upon glutamate stimulation, the innervated muscles secreted higher levels of irisin and exosomes containing more diverse neurotrophic microRNAs than neuron-free muscles. Consequently, biological factors secreted by innervated muscles enhanced branching, axonal transport, and, ultimately, spontaneous network activities of primary hippocampal neurons in vitro. Overall, these results reveal the importance of neuronal innervation in modulating muscle-derived factors that promote neuronal function and suggest that the engineered neuromuscular tissue model holds significant promise as a platform for producing neurotrophic molecules.

Medial Prefrontal Cortex stimulation reduces Retrieval Induced Forgetting via fronto-parietal Beta desynchronization.

The act of recalling memories can paradoxically lead to the forgetting of other associated memories, a phenomenon known as retrieval-induced forgetting (RIF). Inhibitory control mechanisms, primarily mediated by the prefrontal cortex, are thought to contribute to RIF. In this study, we examined whether stimulating the medial prefrontal cortex (mPFC) with transcranial direct current stimulation modulates RIF and investigated the associated electrophysiological correlates. In a randomized study, fifty participants (27 males and 23 females) received either real or sham stimulation before performing retrieval practice on target memories. After retrieval practice, a final memory test to assess RIF was administered. We found that stimulation selectively increased the retrieval accuracy of competing memories, thereby decreasing RIF, while the retrieval accuracy of target memories remained unchanged. The reduction in RIF was associated with a more pronounced beta desynchronization within the left dorsolateral prefrontal cortex (left-DLPFC), in an early time window (<500 msec) after cue onset during retrieval practice. This led to a stronger beta desynchronization within the parietal cortex in a later time window, an established marker for successful memory retrieval. Together, our results establish the causal involvement of the mPFC in actively suppressing competing memories and demonstrate that while forgetting arises as a consequence of retrieving specific memories, these two processes are functionally independent. Our findings suggest that stimulation potentially disrupted inhibitory control processes, as evidenced by reduced RIF and stronger beta desynchronization in fronto-parietal brain regions during memory retrieval, although further research is needed to elucidate the specific mechanisms underlying this effect.Significance statement Retrieval can induce forgetting of competing memories, a phenomenon known as Retrieval Induced Forgetting (RIF). Inhibitory control mechanisms, primarily mediated by the frontal cortex, are thought to contribute to RIF. In this study, we modulated a key region (medial prefrontal cortex (mPFC)) involved in this process using brain stimulation to investigate its influence on RIF and its electrophysiological correlates. Stimulation of mPFC lead to an increased retrieval of non-target memories and reduced RIF. The reduction in RIF was accompanied by stronger beta desynchronization in the frontoparietal brain regions, with beta desynchronization in the left-dorsolateral prefrontal cortex predicting the extent of reduction in RIF.

PNBACE: an ensemble algorithm to predict the effects of mutations on protein-nucleic acid binding affinity.

BACKGROUND: Mutations occurring in nucleic acids or proteins may affect the binding affinities of protein-nucleic acid interactions. Although many efforts have been devoted to the impact of protein mutations, few computational studies have addressed the effect of nucleic acid mutations and explored whether the identical methodology could be applied to the prediction of binding affinity changes caused by these two mutation types. RESULTS: Here, we developed a generalized algorithm named PNBACE for both DNA and protein mutations. We first demonstrated that DNA mutations could induce varying degrees of changes in binding affinity from multiple perspectives. We then designed a group of energy-based topological features based on different energy networks, which were combined with our previous partition-based energy features to construct individual prediction models through feature selections. Furthermore, we created an ensemble model by integrating the outputs of individual models using a differential evolution algorithm. In addition to predicting the impact of single-point mutations, PNBACE could predict the influence of multiple-point mutations and identify mutations significantly reducing binding affinities. Extensive comparisons indicated that PNBACE largely performed better than existing methods on both regression and classification tasks. CONCLUSIONS: PNBACE is an effective method for estimating the binding affinity changes of protein-nucleic acid complexes induced by DNA or protein mutations, therefore improving our understanding of the interactions between proteins and DNA/RNA.

Dissociable Neural Mechanisms Underlie the Effects of Attention on Visual Appearance and Response Bias.

A prominent theoretical framework spanning philosophy, psychology, and neuroscience holds that selective attention penetrates early stages of perceptual processing to alter the subjective visual experience of behaviorally relevant stimuli. For example, searching for a red apple at the grocery store might make the relevant color appear brighter and more saturated compared with seeing the exact same red apple while searching for a yellow banana. In contrast, recent proposals argue that data supporting attention-related changes in appearance reflect decision- and motor-level response biases without concurrent changes in perceptual experience. Here, we tested these accounts by evaluating attentional modulations of EEG responses recorded from male and female human subjects while they compared the perceived contrast of attended and unattended visual stimuli rendered at different levels of physical contrast. We found that attention enhanced the amplitude of the P1 component, an early evoked potential measured over visual cortex. A linking model based on signal detection theory suggests that response gain modulations of the P1 component track attention-induced changes in perceived contrast as measured with behavior. In contrast, attentional cues induced changes in the baseline amplitude of posterior alpha band oscillations (∼9-12 Hz), an effect that best accounts for cue-induced response biases, particularly when no stimuli are presented or when competing stimuli are similar and decisional uncertainty is high. The observation of dissociable neural markers that are linked to changes in subjective appearance and response bias supports a more unified theoretical account and demonstrates an approach to isolate subjective aspects of selective information processing.SIGNIFICANCE STATEMENT Does attention alter visual appearance, or does it simply induce response bias? In the present study, we examined these competing accounts using EEG and linking models based on signal detection theory. We found that response gain modulations of the visually evoked P1 component best accounted for attention-induced changes in visual appearance. In contrast, cue-induced baseline shifts in alpha band activity better explained response biases. Together, these results suggest that attention concurrently impacts visual appearance and response bias, and that these processes can be experimentally isolated.

Genome-wide analysis and expression profiling of the HD-ZIP gene family in kiwifruit.

The homeodomain-leucine zipper (HD-Zip) gene family plays a pivotal role in plant development and stress responses. Nevertheless, a comprehensive characterization of the HD-Zip gene family in kiwifruit has been lacking. In this study, we have systematically identified 70 HD-Zip genes in the Actinidia chinensis (Ac) genome and 55 in the Actinidia eriantha (Ae) genome. These genes have been categorized into four subfamilies (HD-Zip I, II, III, and IV) through rigorous phylogenetic analysis. Analysis of synteny patterns and selection pressures has provided insights into how whole-genome duplication (WGD) or segmental may have contributed to the divergence in gene numbers between these two kiwifruit species, with duplicated gene pairs undergoing purifying selection. Furthermore, our study has unveiled tissue-specific expression patterns among kiwifruit HD-Zip genes, with some genes identified as key regulators of kiwifruit responses to bacterial canker disease and postharvest processes. These findings not only offer valuable insights into the evolutionary and functional characteristics of kiwifruit HD-Zips but also shed light on their potential roles in plant growth and development.

ABCC4 suppresses glioblastoma progression and recurrence by restraining cGMP-PKG signalling.

BACKGROUND: Cyclic nucleotides are critical mediators of cellular signalling in glioblastoma. However, the clinical relevance and mechanisms of regulating cyclic nucleotides in glioblastoma progression and recurrence have yet to be thoroughly explored. METHODS: In silico, mRNA, and protein level analyses identified the primary regulator of cyclic nucleotides in recurrent human glioblastoma. Lentiviral and pharmacological manipulations examined the functional impact of cyclic nucleotide signalling in human glioma cell lines and primary glioblastoma cells. An orthotopic xenograft mice model coupled with aspirin hydrogels verified the in vivo outcome of targeting cyclic nucleotide signalling. RESULTS: Elevated intracellular levels of cGMP, instead of cAMP, due to a lower substrate efflux from ATP-binding cassette sub-family C member 4 (ABCC4) is engaged in the recurrence of glioblastoma. ABCC4 gene expression is negatively associated with recurrence and overall survival outcomes in glioblastoma specimens. ABCC4 loss-of-function activates cGMP-PKG signalling, promoting malignancy in glioblastoma cells and xenografts. Hydrogels loaded with aspirin, inhibiting glioblastoma progression partly by upregulating ABCC4 expressions, augment the efficacy of standard-of-care therapies in orthotopic glioblastoma xenografts. CONCLUSION: ABCC4, repressing the cGMP-PKG signalling pathway, is a tumour suppressor in glioblastoma progression and recurrence. Aspirin hydrogels impede glioblastoma progression through ABCC4 restoration and constitute a viable translational approach.

SERPINA12 promotes the tumorigenic capacity of HCC stem cells through hyperactivation of AKT/ß-catenin signaling.

BACKGROUND AND AIMS: HCC is an aggressive disease with poor clinical outcome. Understanding the mechanisms that drive cancer stemness, which we now know is the root cause of therapy failure and tumor recurrence, is fundamental for designing improved therapeutic strategies. This study aims to identify molecular players specific to CD133 + HCC to better design drugs that can precisely interfere with cancer stem cells but not normal stem cell function. APPROACH AND RESULTS: Transcriptome profiling comparison of epithelial-specific "normal" CD133 + cells isolated from fetal and regenerating liver against "HCC" CD133 + cells isolated from proto-oncogene-driven and inflammation-associated HCC revealed preferential overexpression of SERPINA12 in HCC but not fetal and regenerating liver CD133 + cells. SERPINA12 upregulation in HCC is tightly associated with aggressive clinical and stemness features, including survival, tumor stage, cirrhosis, and stemness signatures. Enrichment of SERPINA12 in HCC is mediated by promoter binding of the well-recognized ß-catenin effector TCF7L2 to drive SERPINA12 transcriptional activity. Functional characterization identified a unique and novel role of endogenous SERPINA12 in promoting self-renewal, therapy resistance, and metastatic abilities. Mechanistically, SERPINA12 functioned through binding to GRP78, resulting in a hyperactivated AKT/GSK3ß/ß-catenin signaling cascade, forming a positive feed-forward loop. Intravenous administration of rAAV8-shSERPINA12 sensitized HCC cells to sorafenib and impeded the cancer stem cell subset in an immunocompetent HCC mouse model. CONCLUSIONS: Collectively, our findings revealed that SERPINA12 is preferentially overexpressed in epithelial HCC CD133 + cells and is a key contributor to HCC initiation and progression by driving an AKT/ß-catenin feed-forward loop.

Gated Recurrent Neural Network for Predicting the Plasmonic Colloid Composition from Spectra.

In current research on the synthesis of colloidal nanostructures, the size and morphology of nanoparticles still exhibit certain dispersion and variation from batch to batch. Characterization of size distribution and morphology distribution of nanoparticles often requires techniques such as scanning electron microscopy or transmission electron microscopy, which involve high vacuum environments, are time-consuming, and costly. Experienced researchers can roughly estimate the size and distribution of nanostructure from spectra for a given synthetic route, but the accuracy is often limited. This paper reports the potential of using neural networks to accurately predict the composition of colloidal nanostructures from spectra. We address several fundamental issues in neural network prediction of colloidal composition. We first demonstrate the prediction of the composition of a colloidal binary mixture of gold nanoparticles using a gated recurrent neural network (GRU). The evolution of prediction errors for scattering, absorption, and extinction spectra of nanostructures with sizes ranging from 5 to 120 nm are analyzed. Furthermore, we demonstrate that the neural network model operates robustly under white noise in experimental testing scenarios. Compared to fully connected neural networks, the gated recurrent unit exhibits better testing accuracy in spectral prediction. When confronted with experimental data that deviates from simulation outputs, minor adjustments to the training set can allow the predictions to align closely with the experimental spectra, paving the way for the characterization of complex colloidal compositions with artificial intelligence.

APOE-ε4 Alleles Modify the Decline of MMSE Scores Associated With Time-Dependent PM2.5 Exposure: Findings From a Community-Based Longitudinal Cohort Study.

OBJECTIVE: Limited research has explored the long-term effect of reduced PM2.5 exposure on cognitive function. This study aimed to investigate the effects of time-dependent PM2.5 exposure and the interactions of PM2.5 and aging on declines in Mini-Mental State Examination (MMSE) scores, in carriers and non-carriers of the APOE-ε4 allele. METHODS: Participants aged over 60 were recruited for this cohort study, undergoing MMSE tests twice from the Taiwan Biobank Program from 2008 to 2020. Participants with dementia or baseline MMSE scores <24 were excluded. Annual PM2.5 levels were estimated using a hybrid kriging/land use regression model with extreme gradient boosting, treated as a time-dependent variable. Generalized estimating equations were used to assess the impacts of repeated PM2.5 on MMSE decline, further stratified by the presence of APOE-ε4 alleles. RESULTS: After follow-up, 290 participants out of the overall 7,000 community residents in the Biobank dataset demonstrated incidences of MMSE declines (<24), with an average MMSE score decline of 1.11 per year. Participants with ε4/ε4 alleles in the APOE gene had significantly 3.68-fold risks of MMSE decline. High levels of PM2.5 across all visits were significantly associated with worsening of scores on the overall MMSE. As annual levels of PM2.5 decreased over time, the impact of PM2.5 on MMSE decline also slowly diminished. CONCLUSION: Long-term PM2.5 exposure may be associated with increased risk of MMSE decline, despite improvements in ambient PM2.5 levels over time. Validation of these results necessitates a large-scale prospective cohort study with more concise cognitive screening tools.

Gyrus rectus asymmetry predicts trait alexithymia, cognitive empathy, and social function in neurotypical adults.

Reduced empathy and elevated alexithymia are observed in autism spectrum disorder (ASD), which has been linked to altered asymmetry in brain morphology. Here, we investigated whether trait autism, empathy, and alexithymia in the general population is associated with brain morphological asymmetry. We determined left-right asymmetry indexes for cortical thickness and cortical surface area (CSA) and applied these features to a support-vector regression model that predicted trait autism, empathy, and alexithymia. Results showed that less leftward asymmetry of CSA in the gyrus rectus (a subregion of the orbitofrontal cortex) predicted more difficulties in social functioning, as well as reduced cognitive empathy and elevated trait alexithymia. Meta-analytic decoding of the left gyrus rectus annotated functional items related to social cognition. Furthermore, the link between gyrus rectus asymmetry and social difficulties was accounted by trait alexithymia and cognitive empathy. These results suggest that gyrus rectus asymmetry could be a shared neural correlate among trait alexithymia, cognitive empathy, and social functioning in neurotypical adults. Left-right asymmetry of gyrus rectus influenced social functioning by affecting the cognitive processes of emotions in the self and others. Interventions that increase leftward asymmetry of the gyrus rectus might improve social functioning for individuals with ASD.

Menstrually-related migraine shapes the structural similarity network integration of brain.

Menstrually-related migraine (MM) is a primary migraine in women of reproductive age. The underlying neural mechanism of MM was still unclear. In this study, we aimed to reveal the case-control differences in network integration and segregation for the morphometric similarity network of MM. Thirty-six patients with MM and 29 healthy females were recruited and underwent MRI scanning. The morphometric features were extracted in each region to construct the single-subject interareal cortical connection using morphometric similarity. The network topology characteristics, in terms of integration and segregation, were analyzed. Our results revealed that, in the absence of morphology differences, disrupted cortical network integration was found in MM patients compared to controls. The patients with MM showed a decreased global efficiency and increased characteristic path length compared to healthy controls. Regional efficiency analysis revealed the decreased efficiency in the left precentral gyrus and bilateral superior temporal gyrus contributed to the decreased network integration. The increased nodal degree centrality in the right pars triangularis was positively associated with the attack frequency in MM. Our results suggested MM would reorganize the morphology in the pain-related brain regions and reduce the parallel information processing capacity of the brain.

Intracerebral Nanoparticle Transport Facilitated by Alzheimer Pathology and Age.

Nanoparticles have emerged as potential transporters of drugs targeting Alzheimer's disease (AD), but their design should consider the blood-brain barrier (BBB) integrity and neuroinflammation of the AD brain. This study presents that aging is a significant factor for the brain localization and retention of nanoparticles, which we engineered to bind with reactive astrocytes and activated microglia. We assembled 200 nm-diameter particles using a block copolymer of poly(lactic-co-glycolic acid) (PLGA) and CD44-binding hyaluronic acid (HA). The resulting PLGA-b-HA nanoparticles displayed increased binding to CD44-expressing reactive astrocytes and activated microglia. Upon intravascular injection, nanoparticles were localized to the hippocampi of both APP/PS1 AD model mice and their control littermates at 13-16 months of age due to enhanced transvascular transport through the leaky BBB. No particles were found in the hippocampi of young adult mice. These findings demonstrate the brain localization of nanoparticles due to aging-induced BBB breakdown regardless of AD pathology.

Pedaling Asymmetry Reflected by Bilateral EMG Complexity in Chronic Stroke.

This study examines pedaling asymmetry using the electromyogram (EMG) complexity of six bilateral lower limb muscles for chronic stroke survivors. Fifteen unilateral chronic stroke and twelve healthy participants joined passive and volitional recumbent pedaling tasks using a self-modified stationary bike with a constant speed of 25 revolutions per minute. The fuzzy approximate entropy (fApEn) was adopted in EMG complexity estimation. EMG complexity values of stroke participants during pedaling were smaller than those of healthy participants (p = 0.002). For chronic stroke participants, the complexity of paretic limbs was smaller than that of non-paretic limbs during the passive pedaling task (p = 0.005). Additionally, there was a significant correlation between clinical scores and the paretic EMG complexity during passive pedaling (p = 0.022, p = 0.028), indicating that the paretic EMG complexity during passive movement might serve as an indicator of stroke motor function status. This study suggests that EMG complexity is an appropriate quantitative tool for measuring neuromuscular characteristics in lower limb dynamic movement tasks for chronic stroke survivors.

Colchicine usage for prevention of post atrial fibrillation ablation pericarditis in patients undergoing high-power short-duration ablation.

INTRODUCTION: Radiofrequency ablation (RFA) for atrial fibrillation (AF) has been associated with variable incidence (0.88%-10%) of pericarditis manifested as chest pain, possibly more prevalent with the advent of high-power short-duration (HPSD) ablation. This has led to the widespread use of colchicine in preventative protocols for postablation pericarditis. However, the efficacy of preventative colchicine has not been validated yet. OBJECTIVE: To evaluate the efficacy of a routine postoperative colchicine regimen (0.6 mg twice a day for 14 days post-AF ablation) for prevention of postablation pericarditis in patients undergoing HPSD ablation. METHOD: We retrospectively evaluated consecutive single-operator HPSD AF ablation procedures at our institution from June 2019 to July 2022. A colchicine protocol was introduced in June 2021 for the prevention of postablation pericarditis. All ablations were performed with 50 watts. Patients were divided into colchicine and noncolchicine groups. We recorded incidence of postablation chest pain, emergency room (ER) visit for chest pain, pericardial effusion, pericardiocentesis, any ER visit, hospitalization, AF recurrence, and cardioversion for AF within the first 30 days following ablation. We also recorded colchicine-related side effects and medication compliance. RESULTS: Two hundred and ninety-four consecutive HPSD AF ablation patients were screened for the study. After implementing the prespecified exclusion criteria, a total of 205 patients were included in the final analysis, yielding 101 patients in the colchicine group and 104 patients in the noncolchicine group. Both groups were well-matched for demographic and procedural parameters. There was no significant difference in postablation chest pain (9.9% vs. 8.6%, p = .7), pericardial effusion (2.9% vs. 0.9%, p = .1), ER visits (11.9% vs. 12.5%, p = .2), 30-day hospitalization for AF recurrence (0.9% vs. 0.96%, p = .3), and 30-day need for cardioversion for AF (3.9% vs. 5.7%, p = .2). Fifteen (15) patients had severe colchicine-related diarrhea, out of which 12 discontinued it prematurely. There were no major procedural complications in either group. CONCLUSION: In this single-operator retrospective analysis, prophylactic colchicine was not associated with significant reduction in the incidence of postablation chest pain, pericarditis, 30 day hospitalization, ER visits, or AF recurrence or need of cardioversion within first 30 days after HPSD ablation for AF. However, its usage was associated with significant diarrhea. This study concludes no additional advantage of prophylactic use of colchicine after HPSD AF ablation.

Predicting the outcomes of hepatocellular carcinoma downstaging with the use of clinical and radiomics features.

BACKGROUND: Downstaging of hepatocellular carcinoma (HCC) makes it possible for patients beyond the criteria to have the chance of liver transplantation (LT) and improved outcomes. Thus, a procedure to predict the prognosis of the treatment is an urgent requisite. The present study aimed to construct a comprehensive framework with clinical information and radiomics features to accurately predict the prognosis of downstaging treatment. METHODS: Specifically, three-dimensional (3D) tumor segmentation from contrast-enhanced computed tomography (CT) is employed to extract spatial information of the lesions. Then, the radiomics features within the segmented region are calculated. Combining radiomics features and clinical data prompts the development of feature selection to enhance the robustness and generalizability of the model. Finally, we adopt the support vector machine (SVM) algorithm to establish a classification model for predicting HCC downstaging outcomes. RESULTS: Herein, a comparative study was conducted on three different models: a radiomics features-based model (R model), a clinical features-based model (C model), and a joint radiomics clinical features-based model (R-C model). The average accuracy of the three models was 0.712, 0.792, and 0.844, and the average area under the receiver-operating characteristic (AUROC) of the three models was 0.775, 0.804, and 0.877, respectively. CONCLUSIONS: The novel and practical R-C model accurately predicted the downstaging outcomes, which could be utilized to guide the HCC downstaging toward LT treatment.

Examining Eye Tracking Metrics and Cognitive Function in Post-Stroke Individuals: A Comparison of Visual Searching Tasks Between Those with and without Cognitive Impairment.

INTRODUCTION: After a stroke, individuals commonly experience visual problems and impaired cognitive function, which can significantly impact their daily life. In addition to visual neglect and hemianopia, stroke survivors often have difficulties with visual search tasks. Researchers are increasingly interested in using eye tracking technology to study cognitive processing and determine whether eye tracking metrics can be used to screen and assess cognitive impairment in patients with neurological disorders. As such, assessing these areas and understanding their relationship is crucial for effective stroke rehabilitation. METHODS: We enrolled 60 stroke patients in this study and evaluated their eye tracking performance and cognitive function through a series of tests. Subsequently, we divided the subjects into two groups based on their scores on the HK-MoCA test, with scores below 21 out of 30 indicating cognitive impairment. We then compared the eye tracking metrics between the two groups and identified any significant differences that existed. Spearman correlation analysis was conducted to explore the relationship between clinical test scores and eye tracking metrics. Moreover, we employed a Mann-Whitney U test to compare eye tracking metrics between groups with and without cognitive impairment. RESULTS: Our results revealed significant correlations between various eye tracking metrics and cognitive tests (p=<.001-.041). Furthermore, the group without cognitive impairment demonstrated higher saccade velocity, gaze path velocity, and shorter time to target than the group with cognitive impairment (p=<.001-.040). ROC curve analyses were performed, and the optimal cut-off values for gaze path velocity and saccade velocity were 329.665 (px/s) (sensitivity= 0.80, specificity = 0.533) and 2.150 (px/s) (sensitivity= 0.733, specificity= 0.633), respectively. CONCLUSIONS: Our findings indicate a significant correlation between eye tracking metrics and cognitive test scores. Furthermore, the group with cognitive impairment exhibited a significant difference in these metrics, and a cut-off value was identified to predict whether a client was experiencing cognitive impairment.

The real-time detection of acupuncture-induced extracellular ATP mobilization in acupoints and exploration of its role in acupuncture analgesia.

Our and in vitro studies had confirmed that mechanosensitive ATP release and accumulation in acupoints was elicited by acupuncture (AP), which might be a pivotal step for triggering AP analgesia. But to date, the dynamics of extracellular ATP (eATP) in the interstitial space during AP process was poorly known, mainly due to the low temporal resolution of the current detection approach. This study attempted to capture rapid eATP signals in vivo in the process of needling, and further explored the role of this eATP mobilization in initiating AP analgesic effect. Ipsilateral 20-min needling was applied on Zusanli acupoint (ST36) of complete Freund's adjuvant (CFA)-induced ankle arthritis rats. Pain thresholds were assessed in injured-side hindpaws. eATP in the interstitial space was microdialyzed and real-time quantified by luciferin-luciferase assay at 1-min interval with the aid of the microfluid chip. We revealed in behavioral tests that modulation of eATP levels in ST36 influenced AP analgesic effect on ankle arthritis. A transient eATP accumulation was induced by needling that started to mobilize at 4 min, climbed to the peak of 11.21 nM within 3.25 min and gradually recovered. Such AP-induced eATP mobilization was significantly impacted by ankle inflammation, needling depth, needle manipulation, and the presence of local ecto-nucleotidases. This work reveals that needling elicits a transient eATP mobilization in acupoints, which contributes to initiating AP analgesia. This study will help us better understand the peripheral mechanism of AP analgesia and guide clinicians to optimize the needle manipulations to improve AP efficacy.

Effect of nanoclay supported nanosilver on the growth inhibition of aquatic pathogens and immunomodulatory effect in Penaeusvannamei.

Hybrid of nanosilver and nanoscale silicate platelet (AgNSP) is a safe, non-toxic nanomaterial which has been applied in medical use due to its strong antibacterial activity. The application of AgNSP in aquaculture was first proposed in the present study by evaluating the in vitro antibacterial activities against four aquatic pathogens, in vitro effects toward shrimp haemocytes as well as the immune responses and disease resistance in Penaeus vannamei fed with AgNSP for 7 days. For evaluating the antibacterial activities of AgNSP in culture medium, the minimum bactericidal concentration (MBC) values against Aeromonas hydrophila, Edwardsiella tarda, Vibrio alginolyticus and Vibrio parahaemolyticus were 100, 15, 625 and 625 mg/L, respectively. Moreover, the inhibition of pathogen growth over a period of 48 h could be achieved by the appropriate treatment of AgNSP in culturing water. In freshwater containing bacterial size of 103 and 106 CFU/mL, the effective doses of AgNSP against A. hydrophila were 12.5 and 450 mg/L, respectively while the effective doses against E. tarda were 0.2 and 50 mg/L, respectively. In seawater with same bacterial size, the effective doses against V. alginolyticus were 150 and 2000 mg/L, respectively while the effective doses against V. parahaemolyticus were 40 and 1500 mg/L, respectively. For the in vitro immune tests, the superoxide anion production and phenoloxidase activity in haemocytes were elevated after in vitro incubation with 0.5-10 mg/L of AgNSP. In the assessment of dietary supplemental effects of AgNSP (2 g/kg), no negative effect on the survival was found at the end of 7 day feeding trail. In addition, the gene expression of superoxide dismutase, lysozyme and glutathione peroxidase were up-regulated in haemocytes taken from shrimps received AgNSP. The following challenge test against Vibrio alginolyticus showed that the survival of shrimp fed with AgNSP was higher than that of shrimp fed with control diet (p = 0.083). Dietary AgNSP improved the Vibrio resistance of shrimp by increasing 22.7% of survival rate. Therefore, AgNSP could potentially be used as a feed additive in shrimp culture.

Safety of fluoroless radiofrequency catheter ablation for atrial fibrillation in patients with pre-existing cardiac implantable electronic device: A single-center study.

BACKGROUND: Radiofrequency catheter ablation (RFA) for atrial fibrillation (AF) is being increasingly performed without fluoroscopy. This study aims to determine the safety of fluoroless RFA for patients with pre-existing cardiac implantable electronic devices (CIED). METHODS: This is a single-center, single-operator, retrospective, observational study of 225 consecutive fluoroless RFA procedures for AF from June 1, 2019 to June 1, 2022. All procedures were performed with intracardiac echocardiography (ICE) support. Patients with pre-existing CIED were extracted from the database. Each CIED was interrogated at the start and end of each procedure and at 30-day follow-up. Pre- and post-procedure CIED interrogations were compared for any change in device or lead parameters. Patients were tracked for any subsequent device malfunction. RESULTS: Out of 225 fluoroless AF ablations, 25 (10.2%) had pre-existing CIED (14 dual-chamber pacemakers, three dual-chamber defibrillators, three single-chamber defibrillators, one single chamber pacemaker, and four biventricular devices). Mean patient age was 71 ± 6 years. The mean duration of indwelling CIED was 1804 ± 1645 days (range: 78-6267 days). One (4%) patient had lead-related fibrin on ICE imaging. There was no significant difference in lead(s) threshold, impedance, or sensing post procedure or at 30-day follow-up compared to pre procedure. None of the patients required lead revision. There were no intra- or post-op thromboembolic events or subsequent device infection. One patient underwent CIED extraction after 11 months for an unrelated secondary device infection. CONCLUSIONS: Radiofrequency catheter ablation for AF can be safely performed without fluoroscopy in patients with pre-existing CIED.