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1.
Bioact Mater ; 19: 139-154, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35475028

RESUMO

Ligamentum flavum (LF) hypertrophy (LFH) has been recognised as one of the key contributors to lumbar spinal stenosis. Currently, no effective methods are available to ameliorate this hypertrophy. In this study, human umbilical cord mesenchymal stromal cell-derived extracellular vesicles (hUCMSC-EVs) were introduced for the first time as promising vehicles for drug delivery to treat LFH. The downregulation of miR-146a-5p and miR-221-3p expressions in human LF tissues negatively correlated with increased LF thickness. The hUCMSC-EVs enriched with these two miRNAs significantly suppressed LFH in vivo and notably ameliorated the progression of transforming growth factor ß1(TGF-ß1)-induced fibrosis in vitro after delivering these two miRNAs to mouse LF cells. The results further demonstrated that miR-146a-5p and miR-221-3p directly bonded to the 3'-UTR regions of SMAD4 mRNA, thereby inhibiting the TGF-ß/SMAD4 signalling pathway. Therefore, this translational study determined the effectiveness of a hUCMSC-EVs-based approach for the treatment of LFH and revealed the critical target of miR-146a-5p and miR-221-3p. Our findings provide new insights into promising therapeutics using a hUCMSC-EVs-based delivery system for patients with lumbar spinal stenosis.

2.
Neural Regen Res ; 18(1): 170-175, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35799538

RESUMO

According to clinical statistics, the mortality of patients with early brainstem hemorrhage is high. In this study, we established rat models of brainstem hemorrhage by injecting type VII collagenase into the right basotegmental pontine and investigated the pathological changes of early brainstem hemorrhage using multi-sequence magnetic resonance imaging and histopathological methods. We found that brainstem hematoma gradually formed in the injured rats over the first 3 days and then reduced after 7 days. The edema that occurred was mainly of the vasogenic type. No complete myelin sheath structure was found around the focus of the brainstem hemorrhage. The integrity and continuity of nerve fibers gradually deteriorated over the first 7 days. Neuronal degeneration was mild in the first 3 days and then obviously aggravated on the 7th day. Inflammatory cytokines, interleukin-1ß, and tumor necrosis factor α appeared on the 1st day after intracerebral hemorrhage, reached peak levels on the 3rd day, and decreased from the 7th day. Our findings show the characteristics of the progression of early brainstem hemorrhage.

3.
J Hazard Mater ; 443(Pt A): 130167, 2023 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-36270188

RESUMO

Due to the coexistence of various heavy metals in the contaminated environment, it is essential to comprehensively study the multicomponent adsorption of heavy metals in order to tackle these combined pollutants. Herein, the adsorption processes of Pb(Ⅱ), Cu(Ⅱ) and Cd(Ⅱ) by biogenic hydroxyapatite (BHAp) were investigated in single and multicomponent systems. The maximum adsorption capacity for Pb(Ⅱ), Cu(Ⅱ) and Cd(Ⅱ) by BHAp in single system reached 311.16, 82.05 and 92.54 mg g-1, respectively, while adsorption capacity for Cu(Ⅱ) and Cd(Ⅱ) in multicomponent system decreased more obviously than that of Pb(Ⅱ). Furthermore, the stability of Cu(Ⅱ) and Cd(Ⅱ) adsorbed on BHAp was indeed influenced in multicomponent system. By means of the characterization analysis, it was found that ion exchange was more instrumental in the adsorption processes of Cu(Ⅱ) and Cd(Ⅱ) in single system than in multicomponent system. Significantly, it was observed that the proportion of generally stable Pb(II) adsorbed on BHAp exceeded 95% in both single and multicomponent systems. This result might be due to the in-site growth of stable crystals of PbxCa10-x(PO4)6(OH)2, which was synergistically induced by surface functional groups and inorganic mineral of BHAp, and was unaffected by the coexistence of Cu(Ⅱ) and Cd(Ⅱ).


Assuntos
Metais Pesados , Poluentes Químicos da Água , Adsorção , Chumbo , Cádmio/análise , Durapatita , Metais Pesados/química , Poluentes Químicos da Água/análise , Concentração de Íons de Hidrogênio
4.
Bioact Mater ; 21: 69-85, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36017070

RESUMO

Stem cell-based transplantation is a promising therapeutic approach for intervertebral disc degeneration (IDD). Current limitations of stem cells include with their insufficient cell source, poor proliferation capacity, low nucleus pulposus (NP)-specific differentiation potential, and inability to avoid pyroptosis caused by the acidic IDD microenvironment after transplantation. To address these challenges, embryo-derived long-term expandable nucleus pulposus progenitor cells (NPPCs) and esterase-responsive ibuprofen nano-micelles (PEG-PIB) were prepared for synergistic transplantation. In this study, we propose a biomaterial pre-modification cell strategy; the PEG-PIB were endocytosed to pre-modify the NPPCs with adaptability in harsh IDD microenvironment through inhibiting pyroptosis. The results indicated that the PEG-PIB pre-modified NPPCs exhibited inhibition of pyroptosis in vitro; their further synergistic transplantation yielded effective functional recovery, histological regeneration, and inhibition of pyroptosis during IDD regeneration. Herein, we offer a novel biomaterial pre-modification cell strategy for synergistic transplantation with promising therapeutic effects in IDD regeneration.

5.
Environ Res ; 216(Pt 2): 114593, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36252838

RESUMO

Aquaculture can substantially alter the accumulation and cycling of nutrients in sediments. However, the microbial mechanisms mediating sediment dissimilatory nitrate (NO3-) reduction in freshwater aquaculture ponds are still unclear, which rule the removal and retention of N element. In the present study, three microbial NO3- reduction processes in riparian aquaculture pond sediments (i.e., crab, shrimp and fish ponds) and natural freshwater sediments (i.e., lakes and rivers) were investigated via isotopic tracing and molecular analyses. The potential rates of denitrification, anaerobic ammonium oxidation (anammox) and dissimilatory nitrate reduction to ammonium (DNRA) significantly increased in the aquaculture ponds compared with the natural freshwaters. Denitrification contributed 90.40-94.22% to the total NO3- reduction (product as N2), followed by 2.49-5.82% of anammox (product as N2) and 2.09-5.18% of DRNA (product as NH4+). The availability of C and N substrates, rather than functional gene abundance, regulated the activities of NO3- reductions and microbiome composition. Microbial mechanism based on network analysis indicated that heterotrophic denitrifiers and DNRA bacteria (e.g., Bacillus, Micromonospora, Mycobacterium and Brachybacterium) determined the community structure and function for N conversions in aquaculture ponds, whereas the such microbial network in natural freshwater sediments was manipulated by autotrophic denitrifiers (e.g., Desulfuromonas, Polaromonas, Solitalea). Collectively, this study provides an in-depth exploration of microbial nitrogen removal in freshwater aquaculture areas and supports management strategies for N pollution caused by reclamation for aquaculture in riparian zones.


Assuntos
Compostos de Amônio , Nitratos , Animais , Nitratos/análise , Desnitrificação , Nitrogênio , Óxidos de Nitrogênio , Aquicultura , Lagos , Oxirredução
6.
Food Chem ; 405(Pt B): 134895, 2023 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-36435100

RESUMO

Establishing an effective and sustainable strategy for zearalenone (ZEN) degradation is of great significance to agricultural development and food safety. Herein, more than 98 % of ZEN (2 ppm) was photocatalytic degraded within 90 min over the oxygen-deficient Bi2WO6 ultrathin layers (BWO-U), along with the sharp elimination of biotoxicity to GES-1 cells. Theoretical calculations and characterizations revealed the ultrathin structure and oxygen vacancies endowed BWO-U with strengthened photoelectrochemical activity and O2-adsorption capacity, facilitating the generation of •O2- and 1O2 which play decisive roles in ZEN degradation. Furthermore, a possible mechanism was proposed based on nine intermediates identified via LC-MS, including the steps of cis-trans isomerization, oxidation and cleavage. Eventually, the method also exhibited immense potential in reducing ZEN-contamination in corn oil, and made no significant impact on the quality of corn oil. This work might provide a feasible strategy to mitigate ZEN-contamination and cast a new light on the ROS-mediated mechanism.


Assuntos
Óleo de Milho , Zearalenona , Espécies Reativas de Oxigênio , Adsorção , Oxigênio
8.
IUCrdata ; 7(Pt 4): x220377, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36337687

RESUMO

In the title compound, [NiCl2(C20H18N4)2] n , the Ni2+ cation is situated on an inversion center and is coordinated by two chloride ions and four imidazole N atoms of four different 4,4'-bis-[(1H-imidazol-1-yl)meth-yl]-1,1'-biphenyl (BIMB), forming a slightly distorted octa-hedral geometry. Each BIMB ligand adopts a linear linker to connect Ni2+ ions, forming a two-dimensional layer with an sql network. In the crystal, neighboring layers repeat in an ABAB stacking mode, and weak inter-molecular C-H⋯Cl hydrogen bonds between alternate layers lead to a three-dimensional, twofold inter-penetrated, supra-molecular framework with a pcu topology net.

9.
Nat Prod Res ; : 1-7, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36318871

RESUMO

The chemical investigation of the EtOAc extract from the solid rice medium cultured with a sponge-associated fungus Penicillium sp. SCSIO41033 led to the isolation of two quinolones including a new one, penicinolone (1), three xanthone derivatives (3-5), and four anthraquinones (6-9). Their structures were determined by comprehensive analysis of 1H and 13C NMR, COSY, HSQC, and HMBC spectroscopic, and HRESIMS mass spectrometric data. The bioactive assays revealed that compounds 1 and 2 showed no antimicrobial activities against five bacteria and eight fungi, and compounds 5, 8 and 9 exhibited inhibition against AChE with IC50 values of 45.9, 42.5 and 40.5 µg/mL. Molecular docking analysis was performed to explore the interactions between active molecules and AChE protein, which indicated that xanthone and anthraquinone derivatives had the potential for developing AChE inhibitors.

10.
Anesth Analg ; 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36322461

RESUMO

BACKGROUND: The aim of this study was to explore whether ice slush (IS) causing local hypothermia can effectively inhibit the oculocardiac reflex (OCR) during strabismus surgery. METHODS: This prospective, randomized, double-blind study included 58 patients with concomitant strabismus scheduled for lateral rectus (LR) recession under general anesthesia. Patients were randomly allocated to receive IS (IS group) or standard treatment (control group) with sterile saline at room temperature before surgery. OCR was defined as a sudden decrease in heart rate (HR) of >15% from baseline. If one incidence of the OCR was found in 1 patient in any stage (0/I/II/III), the patient was defined as an OCR responder, and the incidence of overall OCR was the incidence of OCR responders. The primary outcome was the incidence of overall OCR during all stages of the surgery, which was analyzed by the Z test and computed based on the absolute risk difference with 2-sided 95% confidence intervals (CIs) using the Newcombe method. RESULTS: The overall OCR occurred in 19 of 29 patients (62.5% [95% CI, 45.7-82.1]) in the IS group and 28 of 29 patients (96.6% [95% CI, 82.2-99.9]) in the control group (absolute risk difference, -31.0% [95% CI, -49.4 to -11.0]; Z test, P < .001), which demonstrated that the incidence of overall OCR in IS group was significantly lower than that in the control group. CONCLUSIONS: IS on the ocular surface causing local hypothermia is a promising and easily accessible method to reduce the overall OCR, which can improve the safety of strabismus surgery.

11.
Transl Stroke Res ; 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36324028

RESUMO

Early brain injury (EBI) following subarachnoid hemorrhage (SAH) is characterized by rapid development of neuron apoptosis and dysregulated inflammatory response. Microglia efferocytosis plays a critical role in the clearance of apoptotic cells, attenuation of inflammation, and minimizing brain injury in various pathological conditions. Here, using a mouse SAH model, we aim to investigate whether microglia efferocytosis is involved in post-SAH inflammation and to determine the underlying signaling pathway. We hypothesized that TAM receptors and their ligands regulate this process. To prove our hypothesis, the expression and cellular location of TAM (Tyro3, Axl, and Mertk) receptors and their ligands growth arrest-specific 6 (Gas6) and Protein S (ProS1) were examined by PCR, western blots, and fluorescence immunostaining. Thirty minutes after SAH, mice received an intraventricular injection of recombinant Gas6 (rGas6) or recombinant ProS1 (rPros1) and underwent evaluations of inflammatory mediator expression, neurological deficits, and blood-brain barrier integrity at 24 h. Microglia efferocytosis of apoptotic neurons was analyzed in vivo and in vitro. The potential mechanism was determined by inhibiting or knocking down TAM receptors and Rac1 by specific inhibitors or siRNA. SAH induced upregulation of Axl and its ligand Gas6. The administration of rGas6 but not rPros1 promoted microglia efferocytosis, alleviated inflammation, and ameliorated SAH-induced BBB breakdown and neurological deficits. The beneficial effects of rGas6 were arrogated by inhibiting or knocking down Axl and Rac1. We concluded that rGas6 attenuated the development of early brain injury in mice after SAH by facilitating microglia efferocytosis and preventing inflammatory response, which is partly dependent on activation of Axl and Rac1.

12.
Ann Surg Oncol ; 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36322275

RESUMO

BACKGROUND: The optimal interval between neoadjuvant therapy and oesophagectomy for oesophageal cancer remains controversial. METHODS: Patients with locally advanced oesophageal squamous cell carcinoma (ESCC) who received neoadjuvant chemoradiotherapy followed by oesophagectomy between June 2017 and December 2020 were prospectively enrolled and retrospectively analysed. Patients were divided into two groups: timely (group A; < 10 weeks) and delayed (group B; ≥ 10 weeks) surgery groups. Survival was the primary outcome, and tumour response and post-operative complications were the secondary outcomes. RESULTS: Overall, 224 patients were recruited; 116 patients (51.8%) underwent timely surgery within 10 weeks (group A), and 108 patients (49.2%) underwent delayed surgery over 10 weeks (group B) after chemoradiotherapy. In patients with clinical complete response (cCR), two groups had no significant difference of survival benefit (P = 0.618). However, in patients without cCR, delayed surgery was associated with poor survival (P = 0.035) and cancer progression (P = 0.036). A total of 40 patients (34.5%) in group A and 54 patients (50.0%) in group B achieved pCR (P = 0.019). pCR rates were significantly different across the four groups and increased over time (P = 0.006). CONCLUSIONS: Patients with a prolonged time interval from neoadjuvant chemoradiation to surgery had higher pCR rates. For patients with cCR to neoadjuvant chemoradiation, the time interval to surgery can be safely prolonged for at least 10 weeks. However, for patients with non-cCR to neoadjuvant chemoradiation, delayed surgery is associated with poor survival, and surgery should be performed within 10 weeks of neoadjuvant chemoradiation.

13.
Front Oncol ; 12: 818953, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36439428

RESUMO

Purpose: It is difficult to contour nerve structures with the naked eye due to poor differentiation between the nerve structures with other soft tissues on CT images. Magnetic resonance neurography (MRN) has the advantage in nerve visualization. The purpose of this study is to identify one MRN sequence to better assist the delineation of the lumbosacral plexus (LSP) nerves to assess the radiation dose to the LSP using the magnetic resonance (MR)/CT deformable coregistration technique. Methods: A total of 18 cases of patients with prostate cancer and one volunteer with radiation-induced lumbosacral plexopathy (RILSP) were enrolled. The data of simulation CT images and original treatment plans were collected. Two MRN sequences (Lr_NerveVIEW sequence and Cs_NerveVIEW sequence) were optimized from a published MRN sequence (3D NerveVIEW sequence). The nerve visualization ability of the Lr_NerveVIEW sequence and the Cs_NerveVIEW sequence was evaluated via a four-point nerve visualization score (NVS) scale in the first 10 patients enrolled to determine the better MRN sequence for assisting nerve contouring. Deformable registration was applied to the selected MRN sequence and simulation CT images to get fused MR/CT images, on which the LSP was delineated. The contouring of the LSP did not alter treatment planning. The dosimetric data of the LSP nerve were collected from the dose-volume histogram in the original treatment plans. The data of the maximal dose (Dmax) and the location of the maximal radiation point received by the LSP structures were collected. Results: The Cs_NerveVIEW sequence gained lower NVS scores than the Lr_NerveVIEW sequence (Z=-2.887, p=0.004). The LSP structures were successfully created in 18 patients and one volunteer with MRN (Lr_NerveVIEW)/CT deformable registration techniques, and the LSP structures conformed with the anatomic distribution. In the patient cohort, the percentage of the LSP receiving doses exceeding 50, 55, and 60 Gy was 68% (12/18), 33% (6/18), and 17% (3/18), respectively. For the volunteer with RILSP, the maximum irradiation dose to his LSP nerves was 69 Gy. Conclusion: The Lr_NerveVIEW MRN sequence performed better than the Cs_NerveVIEW sequence in nerve visualization. The dose in the LSP needs to be measured to understand the potential impact on treatment-induced neuropathy.

14.
J Alzheimers Dis ; 2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36442191

RESUMO

BACKGROUND: Accumulation of hyperphosphorylated Tau (pTau) contributes to the formation of neurofibrillary tangles in Alzheimer's disease (AD), and targeting Tau/pTau metabolism has emerged as a therapeutic approach. We have previously reported that mitochondrial 3-hydroxy-3-methylglutaryl-COA synthase 2 (HMGCS2) is involved in AD by promoting autophagic clearance of amyloid-ß protein precursor via ketone body-associated mechanism, whether HMGCS2 may also regulate Tau metabolism remains elusive. OBJECTIVE: The present study was to investigate the role of HMGCS2 in Tau/p degradation. METHODS: The protein levels of Tau and pTau including pT217 and pT181, as well as autophagic markers LAMP1 and LC3-II were assessed by western blotting. The differentially regulated genes by HMGCS2 were analyzed by RNA sequencing. Autophagosomes were assessed by transmission electron microscopy. RESULTS: HMGCS2 significantly decreased Tau/pTau levels, which was paralleled by enhanced formation of autophagic vacuoles and prevented by autophagic regulators chloroquine, bafilomycin A1, 3-methyladenine, and rapamycin. Moreover, HMGCS2-induced alterations of LAMP1/LC3-II and Tau/pTau levels were mimicked by ketone body acetoacetate or ß-hydroxybutyrate. Further RNA-sequencing identified ankyrin repeat domain 24 (ANKRD24) as a target gene of HMGCS2, and silencing of ANKRD24 reduced LAMP1/LC3-II levels, which was accompanied by the altered formation of autophagic vacuoles, and diminished the effect of HMGCS2 on Tau/pTau. CONCLUSION: HMGCS2 promoted autophagic clearance of Tau/pTau, in which ketone body and ANKRD24 played an important role.

16.
Traffic ; 2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36412210

RESUMO

AP2S1 is the sigma 2 subunit of adaptor protein 2 (AP2) that is essential for endocytosis. In this study, we investigated the potential role of AP2S1 in intracellular processing of amyloid precursor protein (APP), which contributes to the pathogenesis of Alzheimer's disease (AD) by generating the toxic ß-amyloid peptide (Aß). We found that knockdown or overexpression of AP2S1 decreased or increased the protein levels of APP and Aß in cells stably expressing human full-length APP695, respectively. This effect was unrelated to endocytosis but involved lysosomal degradation. Morphological studies revealed that silencing of AP2S1 promoted the translocalization of APP from RAB9-positive late endosomes (LE) to LAMP1-positive lysosomes, which was paralleled by the enhanced LE-lysosome fusion. In support, silencing of vacuolar protein sorting-associated protein 41 (VPS41) that is implicated in LE-lyso fusion prevented AP2S1-mediated regulation of APP degradation and translocalization. In APP/PS1 mice, an animal model of AD, AAV-mediated delivery of AP2S1 shRNA in the hippocampus significantly reduced the protein levels of APP and Aß, with the concomitant APP translocalization, LE-lyso fusion and the improved cognitive functions. Taken together, these data uncover a LE-lyso fusion mechanism in APP degradation and suggest a novel role for AP2S1 in the pathophysiology of AD.

17.
Artigo em Inglês | MEDLINE | ID: mdl-36361443

RESUMO

Background: Study results regarding attentional bias in depressed individuals are inconsistent. Recent studies have found that attention is a discrete process, alternating between periods of either enhanced or diminished attention sensitivity. Whether a visual target can be detected depends on when it occurs relative to these oscillation rhythms. We infer that the inconsistency of attentional bias may be related to the abnormality of attentional oscillations in depressed individuals. Methods: A pre-cueing attentional task was used. We set 48 levels of stimulus onset asynchrony (SOA) between cues and targets and measured the response time (RT) of participants, as well as their EEG signals. Results: The RTs showed patterns of behavioral oscillations. Repeated-measure ANOVA indicated that subthreshold depressed participants had significantly higher RTs for negative expressions than for neutral but significantly lower RTs for positive than for neutral. The frequency analysis indicated that the RT oscillational frequency of subthreshold depressed participants to negative/positive expressions was different from that to neutral. The EEG time-frequency analysis showed that when faced with negative expressions, the intensity of the neural alpha oscillatory power of subthreshold depressed participants was significantly lower than that of normal controls. When faced with positive expressions, the intensity of neural alpha oscillatory power was significantly higher than that of normal controls. Conclusion: Compared to normal persons, subthreshold depressed individuals may have biases in both the amplitude and frequency of attentional oscillations. These attentional biases correspond to the intensity of their neural alpha wave rhythms.


Assuntos
Sinais (Psicologia) , Expressão Facial , Humanos , Julgamento , Depressão , Atenção/fisiologia , Viés
18.
Food Funct ; 13(23): 12246-12257, 2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36342407

RESUMO

Vitamin B2 is essential for DNA methylation, stability and repair, which may influence the development and pathogenesis of several cancers. However, data regarding the associations of circulating vitamin B2 with colorectal cancer risk are limited. The purpose of this study was to investigate the associations between serum vitamin B2 and colorectal cancer risk, particularly among participants with different serum levels of vitamin B6 or folate. A hospital-based case-control study, including 1009 colorectal cancer cases and 1182 controls matched by age and sex, was conducted in Guangdong Province, China. Vitamin B2 including riboflavin and flavin mononucleotide (FMN), the vitamin B6 indicator pyridoxal-5'-phosphate (PLP) and folate in serum samples were measured by ultra-high-performance liquid chromatography-tandem mass spectrometry. Vitamin B2 sum was calculated as the sum of riboflavin plus FMN. A significant inverse association was observed between serum FMN, but not serum riboflavin or vitamin B2 sum, and colorectal cancer risk. The adjusted odds ratio (OR) and 95% confidence interval (95% CI) of serum FMN, by comparing the highest with the lowest quartile, was 0.63 (0.46-0.85, Ptrend = 0.001). Stratified analysis by serum PLP and folate levels indicated that serum FMN was inversely associated with colorectal cancer risk among participants with lower serum PLP or higher folate levels. This study added supporting data to the limited evidence that vitamin B2 could play a preventive role in colorectal carcinogenesis among the Chinese population, primarily by FMN. Individuals with a lower PLP level or an adequate folate level could be more sensitive to the protective role of vitamin B2.


Assuntos
Neoplasias Colorretais , Mononucleotídeo de Flavina , Humanos , Estudos de Casos e Controles , Vitamina B 6 , Riboflavina , Ácido Fólico , Neoplasias Colorretais/genética , Vitaminas
19.
Dev Sci ; : e13346, 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36419407

RESUMO

Music and language are two fundamental forms of human communication. Many studies examine the development of music- and language-specific knowledge, but few studies compare how listeners know they are listening to music or language. Although we readily differentiate these domains, how we distinguish music and language-and especially speech and song- is not obvious. In two studies, we asked how listeners categorize speech and song. Study 1 used online survey data to illustrate that 4- to 17-year-olds and adults have verbalizable distinctions for speech and song. At all ages, listeners described speech and song differences based on acoustic features, but compared with older children, 4- to 7-year-olds more often used volume to describe differences, suggesting that they are still learning to identify the features most useful for differentiating speech from song. Study 2 used a perceptual categorization task to demonstrate that 4-8-year-olds and adults readily categorize speech and song, but this ability improves with age especially for identifying song. Despite generally rating song as more speech-like, 4- and 6-year-olds rated ambiguous speech-song stimuli as more song-like than 8-year-olds and adults. Four acoustic features predicted song ratings: F0 instability, utterance duration, harmonicity, and spectral flux. However, 4- and 6-year-olds' song ratings were better predicted by F0 instability than by harmonicity and utterance duration. These studies characterize how children develop conceptual and perceptual understandings of speech and song and suggest that children under age 8 are still learning what features are important for categorizing utterances as speech or song. RESEARCH HIGHLIGHTS: Children and adults conceptually and perceptually categorize speech and song from age 4. Listeners use F0 instability, harmonicity, spectral flux, and utterance duration to determine whether vocal stimuli sound like song. Acoustic cue weighting changes with age, becoming adult-like at age 8 for perceptual categorization and at age 12 for conceptual differentiation. Young children are still learning to categorize speech and song, which leaves open the possibility that music- and language-specific skills are not so domain-specific.

20.
J Vasc Interv Neurol ; 13(1): 35-41, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36447624

RESUMO

Introduction: Sympathetic activity from the superior cervical ganglion (SCG) has been shown to cause cerebral hypoperfusion in swine, similar to that seen with clinical cerebral vasospasm. Although the mechanism of such perfusion deficit has been speculated to be from pathologic cerebral vasoconstriction, the extent of sympathetic contribution to vasoconstriction has not been wellestablished. Objective: We aimed to demonstrate that SCG stimulation in swine leads to significant cerebral vasoconstriction on digital subtraction angiography (DSA). Additionally, we aimed to show that inhibition of SCG can mitigate the effects of sympathetic-mediated cerebral vasoconstriction. Methods: Five SCGs were surgically identified in Yorkshire swine and were electrically stimulated to achieve sympathetic activation. DSA was performed to measure and compare changes in cerebral vessel diameter. Syngo iFlow was also used to quantify changes in contrast flow through the cerebral and neck vessels. Results: SCG stimulation resulted in 35-45% narrowing of the ipsilateral ascending pharyngeal, anterior middle cerebral and anterior cerebral arteries. SCG stimulation also decreased contrast flow through ipsilateral ascending pharyngeal, internal carotid and anterior cerebral arteries as seen on iFLow. These effects were prevented with prior SCG blockade. Minimal vessel caliber changes were seen in the posterior cerebral, posterior middle cerebral and internal carotid arteries with SCG stimulation. Conclusion: SCG stimulation results in significant luminal narrowing and reduction in flow through various intracranial arteries in swine. The results of sympathetic hyperactivity from the SCG closely models cerebral vasoconstriction seen in human cerebral vasospasm. SCG inhibition is a potential promising therapeutic approach to treating cerebral vasospasm.

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