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1.
Mol Cell Proteomics ; 23(5): 100762, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38608839

RESUMO

Protein post-translational modifications (PTMs) are crucial in plant cellular processes, particularly in protein folding and signal transduction. N-glycosylation and phosphorylation are notably significant PTMs, playing essential roles in regulating plant responses to environmental stimuli. However, current sequential enrichment methods for simultaneous analysis of phosphoproteome and N-glycoproteome are labor-intensive and time-consuming, limiting their throughput. Addressing this challenge, this study introduces a novel tandem S-Trap-IMAC-HILIC (S-Trap: suspension trapping; IMAC: immobilized metal ion affinity chromatography; HILIC: hydrophilic interaction chromatography) strategy, termed TIMAHAC, for simultaneous analysis of plant phosphoproteomics and N-glycoproteomics. This approach integrates IMAC and HILIC into a tandem tip format, streamlining the enrichment process of phosphopeptides and N-glycopeptides. The key innovation lies in the use of a unified buffer system and an optimized enrichment sequence to enhance efficiency and reproducibility. The applicability of TIMAHAC was demonstrated by analyzing the Arabidopsis phosphoproteome and N-glycoproteome in response to abscisic acid (ABA) treatment. Up to 1954 N-glycopeptides and 11,255 phosphopeptides were identified from Arabidopsis, indicating its scalability for plant tissues. Notably, distinct perturbation patterns were observed in the phosphoproteome and N-glycoproteome, suggesting their unique contributions to ABA response. Our results reveal that TIMAHAC offers a comprehensive approach to studying complex regulatory mechanisms and PTM interplay in plant biology, paving the way for in-depth investigations into plant signaling networks.

2.
BMC Med Inform Decis Mak ; 24(1): 77, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38500135

RESUMO

OBJECTIVE: To address the challenge of assessing sedation status in critically ill patients in the intensive care unit (ICU), we aimed to develop a non-contact automatic classifier of agitation using artificial intelligence and deep learning. METHODS: We collected the video recordings of ICU patients and cut them into 30-second (30-s) and 2-second (2-s) segments. All of the segments were annotated with the status of agitation as "Attention" and "Non-attention". After transforming the video segments into movement quantification, we constructed the models of agitation classifiers with Threshold, Random Forest, and LSTM and evaluated their performances. RESULTS: The video recording segmentation yielded 427 30-s and 6405 2-s segments from 61 patients for model construction. The LSTM model achieved remarkable accuracy (ACC 0.92, AUC 0.91), outperforming other methods. CONCLUSION: Our study proposes an advanced monitoring system combining LSTM and image processing to ensure mild patient sedation in ICU care. LSTM proves to be the optimal choice for accurate monitoring. Future efforts should prioritize expanding data collection and enhancing system integration for practical application.


Assuntos
Aprendizado Profundo , Agitação Psicomotora , Humanos , Agitação Psicomotora/diagnóstico , Inteligência Artificial , Unidades de Terapia Intensiva , Cuidados Críticos
3.
Heliyon ; 9(9): e19736, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37809370

RESUMO

Previous research has presented conflicting evidence regarding whether Chinese characters are processed holistically. In past work, we applied Systems Factorial Technology (SFT) and discovered that native Chinese speakers exhibited limited capacity when processing characters and words. To pinpoint the source of this limitation, our current research delved further into the mental architecture involved in processing Chinese characters and English words, taking into consideration information from each component. In our current study, participants were directed to make the same/different judgments on characters/words presented sequentially. Our results indicated that participants utilized a parallel self-terminating strategy when both or neither of the left/right components differed (Experiment 1). Faced with the decisional uncertainty that either the left/right component would also differ, most participants processed with a parallel exhaustive architecture, while a few exhibited the coactive architecture (Experiment 2). Taken together, our work provides evidence that in word/character perception, there is weak holistic processing (parallel self-terminating processing) when partial information is sufficient for the decision; robust holistic processing (coactive or parallel exhaustive processing) occurs under decisional uncertainty. Our findings underscore the significant role that the task and presentation context play in visual word processing.

4.
Phytomedicine ; 121: 155119, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37801894

RESUMO

BACKGROUND: Previous studies have reported that puerarin possesses cardioprotective, vasodilatory, anti-inflammatory, anti-apoptotic, and hypoglycemic properties. However, the impact of puerarin on sepsis-associated encephalopathy (SAE) remains unexplored. In this study, we explored whether puerarin can modulate microglia-mediated neuroinflammation for the treatment of SAE and delved into the underlying mechanisms. METHODS: We established a murine model of SAE through intraperitoneal injection of lipopolysaccharide (LPS). The puerarin treatment group received pretreatment with puerarin. For in vitro experiments, BV2 cells were pre-incubated with puerarin for 2 h before LPS exposure. We employed network pharmacology, the Morris Water Maze (MWM) test, Novel Object Recognition (NOR) test, immunofluorescence staining, enzyme-linked immunosorbent assay (ELISA), Western blotting, and quantitative real-time PCR (qRT-PCR) to elucidate the molecular mechanism of underlying puerarin's effects in SAE treatment. RESULTS: Our findings demonstrate that puerarin significantly reduced the production of inflammatory cytokines (TNF-α and IL-6) in the peripheral blood of LPS-treated mice. Moreover, puerarin treatment markedly ameliorated sepsis-associated cognitive impairment. Puerarin also exhibited inhibitory effects on the release of TNF-α and IL-6 from microglia, thereby preventing hippocampal neuronal cell death. Network pharmacology analysis identified AKT1 as a potential therapeutic target for puerarin in SAE treatment. Subsequently, we validated these results in both in vitro and in vitro experiments. Our study conclusively demonstrated that puerarin reduced LPS-induced phosphorylation of AKT1, with the AKT activator SC79 reversing puerarin's anti-inflammatory effects through the activation of the AKT1 signaling pathway. CONCLUSION: Puerarin exerts an anti-neuroinflammatory effect against SAE by modulating the AKT1 pathway in microglia.


Assuntos
Encefalopatia Associada a Sepse , Camundongos , Animais , Encefalopatia Associada a Sepse/tratamento farmacológico , Encefalopatia Associada a Sepse/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Microglia , Lipopolissacarídeos/farmacologia , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/metabolismo
5.
EBioMedicine ; 94: 104673, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37392599

RESUMO

BACKGROUND: Therapeutic hypothermia (TH) is standard of care for moderate to severe neonatal hypoxic ischemic encephalopathy (HIE) but many survivors still suffer lifelong disabilities and benefits of TH for mild HIE are under active debate. Development of objective diagnostics, with sensitivity to mild HIE, are needed to select, guide, and assess response to treatment. The objective of this study was to determine if cerebral oxygen metabolism (CMRO2) in the days after TH is associated with 18-month neurodevelopmental outcomes as the first step in evaluating CMRO2's potential as a diagnostic for HIE. Secondary objectives were to compare associations with clinical exams and characterise the relationship between CMRO2 and temperature during TH. METHODS: This was a prospective, multicentre, observational, cohort study of neonates clinically diagnosed with HIE and treated with TH recruited from the tertiary neonatal intensive care units (NICUs) of Boston Children's Hospital, Brigham and Women's Hospital, and Beth Israel Deaconess Medical Center between December 2015 and October 2019 with follow-up to 18 months. In total, 329 neonates ≥34 weeks gestational age admitted with perinatal asphyxia and suspected HIE were identified. 179 were approached, 103 enrolled, 73 received TH, and 64 were included. CMRO2 was measured at the NICU bedside by frequency-domain near-infrared and diffuse correlation spectroscopies (FDNIRS-DCS) during the late phases of hypothermia (C), rewarming (RW) and after return to normothermia (NT). Additional variables were body temperature and clinical neonatal encephalopathy (NE) scores, as well as findings from magnetic resonance imaging (MRI) and spectroscopy (MRS). Primary outcome was the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) at 18 months, normed (SD) to 100 (15). FINDINGS: Data quality for 58 neonates was sufficient for analysis. CMRO2 changed by 14.4% per °C (95% CI, 14.2-14.6) relative to its baseline at NT while cerebral tissue oxygen extraction fraction (cFTOE) changed by only 2.2% per °C (95% CI, 2.1-2.4) for net changes from C to NT of 91% and 8%, respectively. Follow-up data for 2 were incomplete, 33 declined and 1 died, leaving 22 participants (mean [SD] postnatal age, 19.1 [1.2] month; 11 female) with mild to moderate HIE (median [IQR] NE score, 4 [3-6]) and 21 (95%) with BSID-III scores >85 at 18 months. CMRO2 at NT was positively associated with cognitive and motor composite scores (ß (SE) = 4.49 (1.55) and 2.77 (1.00) BSID-III points per 10-10 moL/dl × mm2/s, P = 0.009 and P = 0.01 respectively; linear regression); none of the other measures were associated with the neurodevelopmental outcomes. INTERPRETATION: Point of care measures of CMRO2 in the NICU during C and RW showed dramatic changes and potential to assess individual response to TH. CMRO2 following TH outperformed conventional clinical evaluations (NE score, cFTOE, and MRI/MRS) at predicting cognitive and motor outcomes at 18 months for mild to moderate HIE, providing a promising objective, physiologically-based diagnostic for HIE. FUNDING: This clinical study was funded by an NIH grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, United States (R01HD076258).


Assuntos
Hipotermia Induzida , Hipóxia-Isquemia Encefálica , Doenças do Recém-Nascido , Recém-Nascido , Lactente , Gravidez , Humanos , Feminino , Adulto Jovem , Adulto , Estudos de Coortes , Estudos Prospectivos , Hipóxia-Isquemia Encefálica/diagnóstico , Hipóxia-Isquemia Encefálica/etiologia , Hipóxia-Isquemia Encefálica/terapia , Oxigênio/metabolismo , Hipotermia Induzida/métodos
6.
Mol Cell Proteomics ; 22(9): 100624, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37495186

RESUMO

Secondary mutation, T790M, conferring tyrosine kinase inhibitors (TKIs) resistance beyond oncogenic epidermal growth factor receptor (EGFR) mutations presents a challenging unmet need. Although TKI-resistant mechanisms are intensively investigated, the underlying responses of cancer cells adapting drug perturbation are largely unknown. To illuminate the molecular basis linking acquired mutation to TKI resistance, affinity purification coupled mass spectrometry was adopted to dissect EGFR interactome in TKI-sensitive and TKI-resistant non-small cell lung cancer cells. The analysis revealed TKI-resistant EGFR-mutant interactome allocated in diverse subcellular distribution and enriched in endocytic trafficking, in which gefitinib intervention activated autophagy-mediated EGFR degradation and thus autophagy inhibition elevated gefitinib susceptibility. Alternatively, gefitinib prompted TKI-sensitive EGFR translocating toward cell periphery through Rab7 ubiquitination which may favor efficacy to TKIs suppression. This study revealed that T790M mutation rewired EGFR interactome that guided EGFR to autophagy-mediated degradation to escape treatment, suggesting that combination therapy with TKI and autophagy inhibitor may overcome acquired resistance in non-small cell lung cancer.


Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Gefitinibe/farmacologia , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Mutação/genética , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral
7.
Acta Psychol (Amst) ; 238: 103986, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37454588

RESUMO

The Word Superiority Effect (WSE) refers to the phenomenon where a single letter is recognized more accurately when presented within a word, compared to when it is presented alone or in a random string. However, previous research has produced conflicting findings regarding whether this effect also occurs in the processing of Chinese characters. The current study employed the capacity coefficient, a measure derived from the Systems Factorial Technology framework, to investigate processing efficiency and test for the superiority effect in Chinese characters and English words. We hypothesized that WSE would result in more efficient processing of characters/words compared to their individual components, as reflected by super capacity processing. However, contrary to our predictions, results from both the "same" (Experiment 1) and "different" (Experiment 2) judgment tasks revealed that native Chinese speakers exhibited limited processing capacity (inefficiency) for both English words and Chinese characters. In addition, results supported an English WSE with participants integrating English words and pseudowords more efficiently than nonwords, and decomposing nonwords more efficiently than words and pseudowords. In contrast, no superiority effect was observed for Chinese characters. To conclude, the current work suggests that the superiority effect only applies to English processing efficiency with specific context rules and does not extend to Chinese characters.


Assuntos
Reconhecimento Visual de Modelos , Processamento de Texto , Humanos , Leitura , Percepção Visual
8.
J Surg Case Rep ; 2023(6): rjad298, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37293329

RESUMO

Portal vein cannulation is a very rare complication of endoscopic retrograde cholangiopancreatography (ERCP). In most reported cases, the event was managed safely with immediate catheter, guidewire withdrawn and procedure termination. Here, we report an unusual case of portobiliary fistula created during ERCP. To our knowledge, this is the first report of such case managed with immediate surgical biliary exposure.

9.
Front Public Health ; 11: 1080525, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37333540

RESUMO

Introduction: Literature is limited on quantified acute stress reaction, the impact of event scale on medical staff when facing medical malpractice (MMP), and how to individually care for staff. Methods: We analyzed data in the Taichung Veterans General Hospital from October 2015 to December 2017, using the Stanford Acute Stress Reaction Questionnaire (SASRQ), the Impact of Event Scale-Revised (IES-R), and the medical malpractice stress syndrome (MMSS). Results and Discussion: Of all 98 participants, most (78.8%) were women. Most MMPs (74.5%) did not involve injury to patients, and most staff (85.7%) indicated receiving help from the hospital. The internal-consistency evaluations of the three questionnaires showed good validity and reliability. The highest score of IES-R was the construct of intrusion (30.1); the most severe construct of SASRQ was "Marked symptoms of anxiety or increased arousal," and the most were having mental and mild physical symptoms for MMES. A higher total IES-R was associated with younger age (<40 y/o), and more severe injury on patients (mortality). Those who indicated receiving very much help from the hospital were those having significantly lower SASRQ sores. Our study highlighted that hospital authorities should regularly follow up on staff's response to MMP. With timely interventions, vicious cycles of bad feelings can be avoided, especially in young, non-doctor, and non-administrative staff.


Assuntos
Imperícia , Transtornos de Estresse Pós-Traumáticos , Humanos , Feminino , Masculino , Reprodutibilidade dos Testes , Ansiedade , Hospitais
10.
Zhongguo Zhen Jiu ; 43(5): 545-51, 2023 May 12.
Artigo em Chinês | MEDLINE | ID: mdl-37161808

RESUMO

OBJECTIVE: To observe the effects of electroacupuncture at "Siguan" points on behavior, colonic 5-hydroxytryptamine (5-HT) and fecal short-chain fatty acids (SCFAs) in rats with post-stroke depression (PSD), and explore the effect mechanism of electroacupuncture at Siguan points on PSD. METHODS: Fifty SD rats were randomly divided into a sham-operation group, a stroke group, a PSD group, a drug group and an electroacupuncture group, with 10 rats in each one. The stroke model was established by middle cerebral artery occlusion (MCAO) method in the stroke group; except for the sham-operation group, the rats in the other groups were intervened with MCAO combined with solitary and chronic unpredictable mild stress (CUMS) to establish PSD model. In the electroacupuncture group, electroacupuncture was delivered at "Hegu" (LI 4) and "Taichong" (LR 3), with disperse-dense wave, 2 Hz/10 Hz in frequency, for 30 min in each intervention, once daily, for consecutive 21 days. Simultaneously, distilled water (0.01 L•kg-1•d-1) was administrated intragastrically. Fluoxetine solution (2.33 mg•kg-1•d-1) was given by gavage , once a day and for 21 days in the drug group. The same procedure of fixation and gavage with distilled water were adopted in the sham-operation group, the stroke group and the PSD group. Separately, before stroke modeling, after PSD modeling and after 21-day intervention, the consumption of sugar water and the scores of horizontal movement and vertical movement in open-field test were observed. After 21-day intervention, the content of colonic 5-HT was detected by immunohistochemical method, and that of fecal SCFAs was determined by gas chromatography mass spectrometry. RESULTS: After PSD modeling, compared with the stroke group, the sugar water consumption, the horizontal movement scores and vertical movement scores of the open-field test were all reduced in the PSD group, the drug group and the electroacupuncture group (P<0.05). After 21-day intervention, the sugar water consumption and the scores of horizontal movement and vertical movement of the open-field test were increased in the drug group and the electroacupuncture group (P<0.05) when compared with the PSD group; and the horizontal movement score in the electroacupuncture group was lower than that of the drug group (P<0.05). Compared with the sham-operation group, the contents of total fecal SCFAs and acetic acid were lower in the stroke group (P<0.05), and the contents of colonic 5-HT and total fecal SCFAs, acetic acid, propionic acid and butyric acid were reduced in the PSD group (P<0.05). In comparison with the PSD group, the contents of colonic 5-HT and total fecal SCFAs, acetic acid and propionic acid were increased in the drug group and the electroacupuncture group (P<0.05); and the content of colonic 5-HT in the electroacupuncture group was lower than that of the drug group (P<0.05). The level of colonic 5-HT was positively correlated with the contents of total fecal SCFAs and propionic acid (r=0.424, P=0.005; r=0.427, P=0.004). CONCLUSION: Electroacupuncture at "Siguan" points can relieve the depression-like behavior of PSD rats, and its underlying mechanism may be related to the regulation of fecal SCFAs, which affects the release of colonic 5-HT.


Assuntos
Eletroacupuntura , Acidente Vascular Cerebral , Animais , Ratos , Ratos Sprague-Dawley , Propionatos , Serotonina , Depressão/etiologia , Depressão/terapia , Ácidos Graxos Voláteis , Acidente Vascular Cerebral/complicações , Ácido Acético , Ácido Butírico , Água
12.
Neuron ; 111(10): 1591-1608.e4, 2023 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-36893755

RESUMO

Post-hemorrhagic hydrocephalus (PHH) refers to a life-threatening accumulation of cerebrospinal fluid (CSF) that occurs following intraventricular hemorrhage (IVH). An incomplete understanding of this variably progressive condition has hampered the development of new therapies beyond serial neurosurgical interventions. Here, we show a key role for the bidirectional Na-K-Cl cotransporter, NKCC1, in the choroid plexus (ChP) to mitigate PHH. Mimicking IVH with intraventricular blood led to increased CSF [K+] and triggered cytosolic calcium activity in ChP epithelial cells, which was followed by NKCC1 activation. ChP-targeted adeno-associated viral (AAV)-NKCC1 prevented blood-induced ventriculomegaly and led to persistently increased CSF clearance capacity. These data demonstrate that intraventricular blood triggered a trans-choroidal, NKCC1-dependent CSF clearance mechanism. Inactive, phosphodeficient AAV-NKCC1-NT51 failed to mitigate ventriculomegaly. Excessive CSF [K+] fluctuations correlated with permanent shunting outcome in humans following hemorrhagic stroke, suggesting targeted gene therapy as a potential treatment to mitigate intracranial fluid accumulation following hemorrhage.


Assuntos
Plexo Corióideo , Hidrocefalia , Humanos , Hidrocefalia/terapia , Hemorragia Cerebral/complicações , Hemorragia Cerebral/terapia
13.
Proc Natl Acad Sci U S A ; 120(13): e2300363120, 2023 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-36961922

RESUMO

α- and ß-neurexins are extensively alternatively spliced, presynaptic cell-adhesion molecules that are thought to organize synapse assembly. However, recent data revealed that, in the hippocampus in vivo, the deletion of one neurexin isoform, Nrxn2, surprisingly increased excitatory synapse numbers and enhanced their presynaptic release probability, suggesting that Nrxn2 restricts, instead of enabling, synapse assembly. To delineate the synaptic function and mechanism of action of Nrxn2, we examined cultured hippocampal neurons as a reduced system. In heterologous synapse formation assays, different alternatively spliced Nrxn2ß isoforms robustly promoted synapse assembly similar to Nrxn1ß and Nrxn3ß, consistent with a general synaptogenic function of neurexins. Deletion of Nrxn2 from cultured hippocampal neurons, however, caused a significant increase in synapse density and release probability, replicating the in vivo data that suggested a synapse-restricting function. Rescue experiments revealed that two of the four Nrxn2ß splice variants (Nrxn2ß-SS4+/SS5- and Nrxn2ß-SS4+/SS5+) reversed the increase in synapse density in Nrxn2-deficient neurons, whereas only one of the four Nrxn2ß splice variants (Nrxn2ß-SS4+/SS5+) normalized the increase in release probability in Nrxn2-deficient neurons. Thus, a subset of Nrxn2 splice variants restricts synapse numbers and restrains their release probability in cultured neurons.


Assuntos
Processamento Alternativo , Sinapses , Sinapses/metabolismo , Hipocampo/metabolismo , Moléculas de Adesão Celular/metabolismo , Neurônios/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Moléculas de Adesão de Célula Nervosa/genética , Moléculas de Adesão de Célula Nervosa/metabolismo
14.
Tissue Cell ; 81: 102039, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36805774

RESUMO

BACKGROUND: Accumulation of glutamate damages neurons via the reactive oxygen species (ROS) injury, which was involved in the development of neurodegenerative diseases. However, the mechanism of neuronal oxidative stress damage caused by glutamate and the intervention targets still needs to be further studied. This study explored whether 5' adenosine monophosphate-activated protein kinase (AMPK)-induced glucose metabolic and mitochondrial dysfunction were related to glutamate-dependent ROS injury of the neuron. METHODS: Neuronal oxidative stress injury was induced by glutamate treatment in HT-22 cells. Western blotting was used to evaluate the phosphorylation of the AMPK. The XF24 Flux Analyzer was used to measure the effect of glutamate and Compound C (a well-known pharmacological inhibitor of AMPK phosphorylation) on the cellular oxygen consumption rate (OCR) of HT-22 cells. Glucose uptake, intracellular ROS, mitochondrial potential, apoptosis and cell viability were quantified using biochemical assays. RESULTS: Glutamate caused the phosphorylation of AMPK and subsequently promoted the glucose uptake. Furthermore, AMPK-mediated glucose uptake enhanced OCR and increased the intracellular ROS levels in neurons. The pharmacological inhibition of AMPK phosphorylation by Compound C attenuated glutamate-induced toxicity in HT22 cells by regulating the glucose uptake/mitochondrial respiration/ROS pathway. CONCLUSIONS: The AMPK phosphorylation/glucose uptake/mitochondrial respiration/ROS pathway was involved in glutamate-induced excitotoxic injury in HT22 cells. The inhibition of AMPK phosphorylation may be a potential target for the development of therapeutic agents for treating the glutamate-induced neurotoxicity.


Assuntos
Ácido Glutâmico , Fármacos Neuroprotetores , Espécies Reativas de Oxigênio/metabolismo , Ácido Glutâmico/metabolismo , Ácido Glutâmico/farmacologia , Proteínas Quinases Ativadas por AMP/metabolismo , Linhagem Celular , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo , Apoptose , Mitocôndrias/metabolismo , Glucose/metabolismo
15.
Sci Adv ; 9(1): eadd8856, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36608123

RESUMO

Neurexins are widely thought to promote synapse formation and to organize synapse properties. Here we found that in contrast to neurexin-1 and neurexin-3, neurexin-2 unexpectedly restricts synapse formation. In the hippocampus, constitutive or neuron-specific deletions of neurexin-2 nearly doubled the strength of excitatory CA3➔CA1 region synaptic connections and markedly increased their release probability. No effect on inhibitory synapses was detected. Stochastic optical reconstruction microscopy (STORM) superresolution microscopy revealed that the neuron-specific neurexin-2 deletion elevated the density of excitatory CA1 region synapses nearly twofold. Moreover, hippocampal neurexin-2 deletions also increased synaptic connectivity in the CA1 region when induced in mature mice and impaired the cognitive flexibility of spatial memory. Thus, neurexin-2 controls the dynamics of hippocampal synaptic circuits by repressing synapse assembly throughout life, a restrictive function that markedly differs from that of neurexin-1 and neurexin-3 and of other synaptic adhesion molecules, suggesting that neurexins evolutionarily diverged into opposing pro- and antisynaptogenic organizers.

16.
Scand J Occup Ther ; 30(3): 322-333, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35701083

RESUMO

BACKGROUND: Picture My Participation (PmP) is a picture-supported child-report instrument of participation of children with disabilities. AIMS: This study described the development of a mobile application of the PmP Traditional Chinese version (PmP-C) and evaluated its usability. METHODS: The PmP-C App includes features that allow the input of a child's demographics, identification of frequency and involvement of 22 culturally appropriate activities, selection of the three most important activities and the specification of the environmental facilitators and barriers. The usability test was conducted with 10 healthcare workers, who interviewed 10 children with disabilities aged 6-12 years. The healthcare workers completed a usability questionnaire and were asked to provide feedback on the ease of use, learning, satisfaction and perceived usefulness. RESULTS: The mean score for the usability questionnaire ranged from 2.7 to 4.6 out of 5.0. The feedback indicated that the interface was simple to operate by the healthcare workers and was attractive and motivating to children. Improvements of layout design, operation instructions and technical problems were recommended, which contributed to the app program optimization. CONCLUSIONS: The PmP-C App provides a practical tool with initial support for usability to enable active engagement and communication of children with disabilities with healthcare providers.


Assuntos
Crianças com Deficiência , Aplicativos Móveis , Humanos , Inquéritos e Questionários , Aprendizagem , Pessoal de Saúde
17.
Cereb Cortex ; 33(4): 1130-1139, 2023 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-35349640

RESUMO

Mild isolated fetal ventriculomegaly (iFVM) is the most common abnormality of the fetal central nervous system. It is characterized by enlargement of one or both of the lateral ventricles (defined as ventricular width greater than 10 mm, but less than 12 mm). Despite its high prevalence, the pathophysiology of iFVM during fetal brain development and the neurobiological substrate beyond ventricular enlargement remain unexplored. In this work, we aimed to establish the relationships between the structural development of transient fetal brain zones/compartments and increased cerebrospinal fluid volume. For this purpose, we used in vivo structural T2-weighted magnetic resonance imaging of 89 fetuses (48 controls and 41 cases with iFVM). Our results indicate abnormal development of transient zones/compartments belonging to both hemispheres (i.e. on the side with and also on the contralateral side without a dilated ventricle) in fetuses with iFVM. Specifically, compared to controls, we observed enlargement of proliferative zones and overgrowth of the cortical plate in iFVM with associated reduction of volumes of central structures, subplate, and fetal white matter. These results indicate that enlarged lateral ventricles might be linked to the development of transient fetal zones and that global brain development should be taken into consideration when evaluating iFVM.


Assuntos
Hidrocefalia , Imageamento por Ressonância Magnética , Gravidez , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Ultrassonografia Pré-Natal/métodos , Hidrocefalia/diagnóstico por imagem , Hidrocefalia/complicações , Hidrocefalia/patologia , Encéfalo/patologia , Feto
18.
Int J Mol Sci ; 25(1)2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38203247

RESUMO

MicroRNAs (miRNAs) can regulate the expression of genes involved in the establishment of the window of implantation (WOI) in the endometrium. Recent studies indicated that cell-free miRNAs in uterine fluid and blood samples could act as alternative and non-invasive sample types for endometrial receptivity analysis. In this study, we attempt to systematically evaluate whether the expression levels of cell-free microRNAs in blood samples could be used as non-invasive biomarkers for assessing endometrial receptivity status. We profiled the miRNA expression levels of 111 blood samples using next-generation sequencing to establish a predictive model for the assessment of endometrial receptivity status. This model was validated with an independent dataset (n = 73). The overall accuracy is 95.9%. Specifically, we achieved accuracies of 95.9%, 95.9%, and 100.0% for the pre-receptive group, the receptive group, and the post-respective group, respectively. Additionally, we identified a set of differentially expressed miRNAs between different endometrial receptivity statuses using the following criteria: p-value < 0.05 and fold change greater than 1.5 or less than -1.5. In conclusion, the expression levels of cell-free miRNAs in blood samples can be utilized in a non-invasive manner to distinguish different endometrial receptivity statuses.


Assuntos
MicroRNA Circulante , MicroRNAs , Feminino , Humanos , Implantação do Embrião/genética , Transferência Embrionária , Endométrio , MicroRNAs/genética
19.
Front Psychol ; 13: 908421, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35719514

RESUMO

Engineering design is a core activity in integrated science, technology, engineering, and mathematics (STEM) education. During the design process, teachers should possess interdisciplinary communication capacities to collaborate with their peers who are teaching different subjects and have epistemic fluency to comprehend multiple ways of subject matter knowing for the collective design of high-quality integrated STEM (iSTEM) lessons. This is especially so for the online mode of instruction during and after the pandemic. Teachers' efficacies for interdisciplinary communication and epistemic fluency have rarely been explored. In this study, we aimed to examine primary school, junior high school, and high school STEM teachers' (N = 483) efficacies for daily instruction, student engagement, interdisciplinary communication, epistemic fluency, and technological pedagogical engineering knowledge (TPEK) and designing integrated STEM instruction. An exploratory factor analysis (EFA) (n = 155) and a subsequent confirmatory factor analysis (CFA) (n = 328) were used to validate the measurement and structural model. Next, a structural equation model (SEM) was employed to examine whether these variables were reliable predictors of teachers' integrated STEM instruction. The survey was validated with good reliabilities and the structural equation modeling supported most of the hypotheses. Statistically, the results also showed that teachers' general efficacies for daily teaching and students' engagement predicted their interdisciplinary communication, epistemic fluency, and TPEK. Teachers' interdisciplinary communication predicted their epistemic fluency, TPEK, and iSTEM. Teachers' epistemic fluency also predicted their TPEK and iSTEM. In addition, multi-group analyses were used to test the measurement invariance of the scale and to compare the latent means between the genders and subject matters. The results of the various analyses confirmed that the measurement model appeared to be equivalent across the genders and subject matters examined. Genders and subject matters did not significantly differ in any of the measured variables. The results from this study indicate that teachers' epistemic fluency and interdisciplinary communication play essential roles in advancing their TPEK and iSTEM. Hence, this study suggests that teacher professional development should focus on enhancing teacher epistemic fluency through interdisciplinary collaboration to support the development of TPEK and iSTEM instruction.

20.
J Neural Eng ; 19(3)2022 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-35617937

RESUMO

Objective.An understanding of functional interhemispheric asymmetry in ischemic stroke patients is a crucial factor in the designs of efficient programs for post-stroke rehabilitation. This study evaluates interhemispheric synchronization and cortical activities in acute stroke patients with various degrees of severity and at different post-stroke stages.Approach.Twenty-three patients were recruited to participate in the experiments, including resting-state and speed finger-tapping tasks at week-1 and week-3 post-stroke. Multichannel near-infrared spectroscopy (NIRS) was used to measure the changes in hemodynamics in the bilateral prefrontal cortex (PFC), the supplementary motor area (SMA), and the sensorimotor cortex (SMC). The interhemispheric correlation coefficient (IHCC) measuring the synchronized activities in time and the wavelet phase coherence (WPCO) measuring the phasic activity in time-frequency were used to reflect the symmetry between the two hemispheres within a region. The changes in oxyhemoglobin during the finger-tapping tasks were used to present cortical activation.Main results.IHCC and WPCO values in the severe-stroke were significantly lower than those in the minor-stroke at low frequency bands during week-3 post-stroke. Cortical activation in all regions in the affected hemisphere was significantly lower than that in the unaffected hemisphere in the moderate-severe stroke measured in week-1, however, the SMC activation on the affected hemisphere was significantly enhanced in week-3 post-stroke.Significance.In this study, non-invasive NIRS was used to observe dynamic synchronization in the resting-state based on the IHCC and WPCO results as well as hemodynamic changes in a motor task in acute stroke patients. The findings suggest that NIRS could be used as a tool for early stroke assessment and evaluation of the efficacy of post-stroke rehabilitation.


Assuntos
Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Hemodinâmica , Humanos , Oxiemoglobinas , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Acidente Vascular Cerebral/diagnóstico , Reabilitação do Acidente Vascular Cerebral/métodos
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