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Background: This study examines whether clot patterns at large artery occlusion sites, as observed using digital subtraction angiography (DSA) and computed tomography angiography (CTA), can reliably indicate intracranial atherosclerotic stenosis (ICAS) in acute ischemic stroke (AIS) patients. Methods: We conducted a retrospective analysis of patients treated with stent retriever thrombectomy for intracranial occlusions at our institute since 2017, with follow-up assessments conducted at 3 months. The patients were grouped based on the initial angiography clot topographies (i.e., cut-off or tapered signs). We assessed the potential of these topographies in predicting ICAS, including a clinical outcome analysis based on clot pattern, age, Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification, and onset-to-door time. Results: Among 131 patients (with a mean age of 66.6 years), the clot pattern emerged as a significant predictor of ICAS. The DSA-based model had a predictive area under the curve (AUC) of 0.745, with 55.1% sensitivity and 94.0% specificity. A multivariate model including age, onset-to-door time, TOAST classification as large artery atherosclerosis (LAA), and the presence of the tapered sign in clot patterns had an AUC of 0.916. In patients over 65 years of age with an onset-to-door time of >5 h and exhibiting a tapered sign in the clot pattern, the AUC reached 0.897. The predictive ability of the tapered sign was similar in DSA and CTA, showing 73.4% agreement between modalities. Conclusion: The clot pattern with the tapered sign as observed using DSA is significantly associated with ICAS. Incorporating this clot pattern with age, TOAST classification as LAA, and onset-to-door time enhances the prediction of ICAS. The clot pattern identified by CTA is also a reliable predictor, highlighting the importance of assessing clot patterns in ICAS identification.
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Forest defoliators are one of the major biological disturbances to forest ecosystems. As one of the abnormal nutrient input paths into forest ecosystems, frass deposition from the pest outbreak plays a critical role in regulating soil organic carbon (SOC) in forest ecosystems. However, how frass deposition affects SOC and its fractions in forests remains unclear. Based on a severe outbreak of defoliator in an oak-sweetgum mixed forest in Jigong Mountain in 2014, we compared the difference in SOC between plots with and without frass deposition for 4 consecutive years. The results showed that frass deposition led to a significant increase of 25.1 % in soil microbial biomass C (MBC) and 32.0 % in dissolved organic C (DOC) in 2014, which further escalated to 50.4 % and 50.6 % in the subsequent year (2015), respectively. The response of SOC to frass deposition lagged behind MBC and DOC. Specifically, there was no change in SOC in 2014, but a significant increase (50.9 %) was observed in the subsequent 2-3 years. The positive dependences of MBC and DOC upon fine root biomass were negated under frass deposition, while the relationship between SOC and fine root biomass remained unaffected. Soil organic carbon and DOC showed non-linear responses to frass amount and the changed soil nitrogen content. Our finding that the response of SOC to frass deposition lagged behind soil labile C indicates that SOC exhibits a certain resilience towards forest disturbance. The findings also imply that investigating the long-term impacts of frass deposition on SOC in forests would contribute to the scientific assessment of forest C cycling under disturbance.
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Carbono , Bosques , Suelo , Suelo/química , Carbono/análisis , Microbiología del Suelo , Monitoreo del Ambiente , China , Árboles , BiomasaRESUMEN
Exposure to light has been demonstrated to stimulate brain regions associated with cognition; however, investigations into its cognitive-enhancing effects have primarily focused on wild-type rodents. This study seeks to elucidate how bright light exposure mitigates cognitive deficits associated with schizophrenia by examining its impact on hippocampal neurogenesis and its potential to alleviate sub-chronic MK-801-induced cognitive impairments in mice. Following three weeks of juvenile bright light exposure (5-8 weeks old), significant increases in proliferating neurons (BrdU+) and immature neurons (DCX+ cells) were observed in the dentate gyrus (DG) and lateral ventricle of MK-801-treated mice. Long-term bright light treatment further promoted the differentiation of BrdU+ cells into immature neurons (BrdU+ DCX+ cells), mature neurons (BrdU+ NeuN+ cells), or astrocytes (BrdU+ GFAP+ cells) in the hippocampal DG. This augmented neurogenesis correlated with the attenuation of sub-chronic MK- 801-induced cognitive deficits, as evidenced by enhancements in Y-maze, novel object recognition (NOR), novel location recognition (NLR), and Morris water maze (MWM) test performances. These findings suggest a promising noninvasive clinical approach for alleviating cognitive impairments associated with neuropsychiatric disorders.
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Disfunción Cognitiva , Modelos Animales de Enfermedad , Proteína Doblecortina , Neurogénesis , Esquizofrenia , Animales , Neurogénesis/fisiología , Esquizofrenia/terapia , Esquizofrenia/fisiopatología , Esquizofrenia/metabolismo , Disfunción Cognitiva/terapia , Disfunción Cognitiva/etiología , Disfunción Cognitiva/fisiopatología , Ratones , Masculino , Hipocampo/metabolismo , Maleato de Dizocilpina/farmacología , Conducta Animal/fisiología , Giro Dentado/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Ratones Endogámicos C57BL , LuzRESUMEN
Hepatic fibrosis (HF) is a pathological process of structural and functional impairment of the liver and is a key component in the progression of chronic liver disease. There are no specific anti-hepatic fibrosis (anti-HF) drugs, and HF can only be improved or prevented by alleviating the cause. Autophagy of hepatic stellate cells (HSCs) is closely related to the development of HF. In recent years, traditional Chinese medicine (TCM) has achieved good therapeutic effects in the prevention and treatment of HF. Several active ingredients from TCM (AITCM) can regulate autophagy in HSCs to exert anti-HF effects through different pathways, but relevant reviews are lacking. This paper reviewed the research progress of AITCM regulating HSCs autophagy against HF, and also discussed the relationship between HSCs autophagy and HF, pointing out the problems and limitations of the current study, in order to provide references for the development of anti-HF drugs targeting HSCs autophagy in TCM. By reviewing the literature in PubMed, Web of Science, Embase, CNKI and other databases, we found that the relationship between autophagy of HSCs and HF is currently controversial. HSCs autophagy may promote HF by consuming lipid droplets (LDs) to provide energy for their activation. However, in contrast, inducing autophagy in HSCs can exert the anti-HF effect by stimulating their apoptosis or senescence, reducing type I collagen accumulation, inhibiting the extracellular vesicles release, degrading pro-fibrotic factors and other mechanisms. Some AITCM inhibit HSCs autophagy to resist HF, with the most promising direction being to target LDs. While, others induce HSCs autophagy to resist HF, with the most promising direction being to target HSCs apoptosis. Future research needs to focus on cell targeting research, autophagy targeting research and in vivo verification research, and to explore the reasons for the contradictory effects of HSCs autophagy on HF.
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Autofagia , Medicamentos Herbarios Chinos , Células Estrelladas Hepáticas , Cirrosis Hepática , Medicina Tradicional China , Células Estrelladas Hepáticas/efectos de los fármacos , Células Estrelladas Hepáticas/metabolismo , Células Estrelladas Hepáticas/patología , Autofagia/efectos de los fármacos , Humanos , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/patología , Cirrosis Hepática/metabolismo , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , AnimalesRESUMEN
BACKGROUND: Chronic enteropathy associated with SLCO2A1 gene (CEAS) results from loss-of-function variants in SLCO2A1, which encodes the prostaglandin transporter (PGT). CEAS follows an autosomal recessive inheritance pattern. To date, approximate 30 pathogenic variants have been reported in CEAS. METHODS: We performed whole exome sequencing (WES) to screen for potential pathogenic variants in a patient suspected of having CEAS, and confirmed a variant in SLCO2A1 using Sanger sequencing. We established an in vitro minigene model to compare splicing between wild type (WT) and mutant transcripts. Quantitative polymerase chain reaction (qPCR) was used to evaluate SLCO2A1 transcription in the stomach and colon tissues from the patient and a healthy control (HC). The transcripts were further cloned and sequenced. RESULTS: The patient had a novel, homozygous, recessive c.929A > G variant in exon 7 of SLCO2A1, which has not been previously reported in CEAS or PHO. This variant altered splicing, resulting in an exon 7-truncated transcript lacking 16 bases. No normal transcript was detected in the patient's stomach or colon tissue. qPCR also showed significantly decreased SLCO2A1 transcription compared to HC. CONCLUSION: A previously unreported variant caused defective SLCO2A1 splicing and reduced mRNA levels in a patient with CEAS and PHO. This research enhances understanding of CEAS and PHO pathophysiology and aids genetic counseling and diagnosis.
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Transportadores de Anión Orgánico , Osteoartropatía Hipertrófica Primaria , Humanos , Osteoartropatía Hipertrófica Primaria/genética , Transportadores de Anión Orgánico/genética , Masculino , Enfermedades Gastrointestinales/genética , Femenino , Secuenciación del Exoma , Mutación/genética , Pueblo Asiatico/genética , Pueblos del Este de AsiaRESUMEN
Cerebral palsy (CP) is the most common motor disability in children. To ascertain the role of major genetic variants in the etiology of CP, we conducted exome sequencing on a large-scale cohort with clinical manifestations of CP. The study cohort comprised 505 girls and 1,073 boys. Utilizing the current gold standard in genetic diagnostics, 387 of these 1,578 children (24.5%) received genetic diagnoses. We identified 412 pathogenic and likely pathogenic (P/LP) variants across 219 genes associated with neurodevelopmental disorders, and 59 P/LP copy number variants. The genetic diagnostic rate of children with CP labeled at birth with perinatal asphyxia was higher than the rate in children without asphyxia (P = 0.0033). Also, 33 children with CP manifestations (8.5%, 33 of 387) had findings that were clinically actionable. These results highlight the need for early genetic testing in children with CP, especially those with risk factors like perinatal asphyxia, to enable evidence-based medical decision-making.
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Parálisis Cerebral , Variaciones en el Número de Copia de ADN , Secuenciación del Exoma , Heterogeneidad Genética , Humanos , Parálisis Cerebral/genética , Femenino , Masculino , Niño , Preescolar , Variaciones en el Número de Copia de ADN/genética , Exoma/genética , Lactante , Pruebas Genéticas , Estudios de Cohortes , Predisposición Genética a la Enfermedad , Recién NacidoRESUMEN
BACKGROUND AND AIMS: Chronic enteropathy associated with SLCO2A1 gene is a rare intestinal disease caused by loss-of-function SLCO2A1 mutations, with clinical and genetic characteristics remaining largely unknown, especially in Chinese patients. This study aims to reveal clinical and genetic features of Chinese CEAS patients, highlighting the previously unreported or unemphasized characteristics. METHODS: We enrolled 12 Chinese patients with chronic enteropathy associated with SLCO2A1 gene admitted to Peking Union Medical College Hospital from January 2018 to December 2022. Clinical and genetic data of these patients were collected and analyzed. RESULTS: 58.3% of patients were male, who also had primary hypertrophic osteoarthropathy, whereas female patients did not have primary hypertrophic osteoarthropathy. Apart from common symptoms associated with anemia and hypoalbuminemia, abdominal pain, ileus, diarrhea, and hematochezia were present. 4 of the 5 female patients had early-onset amenorrhea, though the causal relationship remained to be clarified. Endoscopy and computed tomography enterography revealed that lesions can occur in any part of the digestive tract, most commonly in the ileum. Pathology showed multiple superficial ulcers with adjacent vascular dilatation, and loss of SLCO2A1 expression, particularly in gastrointestinal vascular endothelial cells. Genetic analysis confirmed SLCO2A1 mutations in all patients and identified 11 new SLCO2A1 variants for CEAS. CONCLUSIONS: This study reports new clinical, pathological, and genetic findings in 12 Chinese patients with chronic enteropathy associated with SLCO2A1 gene. This study provides insights into the pathogenesis of this disease. However, studies with larger sample sizes and more in-depth mechanism research are still required.
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Enfermedades Intestinales , Transportadores de Anión Orgánico , Humanos , Femenino , Masculino , Transportadores de Anión Orgánico/genética , Adulto , Enfermedades Intestinales/genética , Enfermedades Intestinales/patología , Mutación/genética , Adulto Joven , Adolescente , Persona de Mediana Edad , China , Pueblo Asiatico/genética , Enfermedad Crónica , Pueblos del Este de AsiaRESUMEN
BACKGROUND: Cornelia de Lange syndrome (CdLS) is a multisystem genetic disorder, and cases caused by variants in the structural maintenance of chromosomes protein 3 (SMC3) gene are uncommon. Here, we report two cases of CdLS associated with novel pathogenic variants in SMC3 from two Chinese families. METHODS: Clinical presentations of two patients with CdLS were evaluated, and specimens from the patients and other family members were collected for Trio-based whole-exome sequencing. Pyrosequencing, chip-based digital PCR, minigene splicing assay, and in silico analysis were carried out to elucidate the impact of novel variants. RESULTS: Novel heterozygous variants in SMC3 were identified in each proband. One harbored a novel splicing and mosaic variant (c.2535+1G>A) in SMC3. The mutated allele G>A conversion was approximately 23.1% by digital PCR, which indicated that 46.2% of peripheral blood cells had this variant. Additionally, in vitro minigene splicing analysis validated that the c.2535+1G>A variant led to an exon skipping in messenger RNA splicing. The other carried a heterozygous variant (c.435C>A), which was predicted to be pathogenic as well as significantly altered in local electrical potential. The former showed multiple abnormalities and marked clinical severity, and the latter mainly exhibited a speech developmental disorder and slightly facial anomalies. CONCLUSION: Both patients were clinically diagnosed with Cornelia de Lange syndrome 3 (CdLS3). The newly identified SMC3 gene variants can expand the understanding of CdLS3 and provide reliable evidence for genetic counseling to the affected family.
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Proteínas de Ciclo Celular , Proteínas Cromosómicas no Histona , Síndrome de Cornelia de Lange , Femenino , Humanos , Masculino , Proteínas de Ciclo Celular/genética , Proteoglicanos Tipo Condroitín Sulfato , Proteínas Cromosómicas no Histona/genética , Síndrome de Cornelia de Lange/genética , Síndrome de Cornelia de Lange/patología , Heterocigoto , Mutación , Linaje , Fenotipo , Empalme del ARNRESUMEN
BACKGROUND: Auxin response factor (ARF), a transcription factors that controls the expression of genes responsive to auxin, plays a key role in the regulation of plant growth and development. Analyses aimed at identifying ARF family genes and characterizing their functions in Juglans sigillata Dode are lacking. METHODS AND RESULTS: We used bioinformatic approaches to identify members of the J. sigillata ARF gene family and analyze their evolutionary relationships, collinearity, cis-acting elements, and tissue-specific expression patterns. The expression patterns of ARF gene family members under natural drought conditions were also analyzed. The J. sigillata ARF gene family contained 31 members, which were unevenly distributed across 16 chromosomes. We constructed a phylogenetic tree of JsARF genes and other plant ARF genes. Cis-acting elements in the promoters of JsARF were predicted. JsARF28 showed higher expressions in both the roots and leaves. A heat map of the transcriptome data of the cluster analysis under drought stress indicated that JsARF3/9/11/17/20/26 are responsive to drought. The expression of the 11 ARF genes varied under PEG treatment and JsARF18 and JsARF20 were significantly up-regulated. CONCLUSIONS: The interactions between abiotic stresses and plant hormones are supported by our cumulative data, which also offers a theoretical groundwork for comprehending the ARF mechanism and drought resistance in J. sigillata.
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Ácidos Indolacéticos , Juglans , Ácidos Indolacéticos/metabolismo , Filogenia , Juglans/genética , Sequías , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estrés Fisiológico/genéticaRESUMEN
Photon blockade (PB) is an important quantum phenomenon in cavity quantum electrodynamics (QED). Here, we investigate the PB effect in the simplest cavity QED systems (one cavity containing first a single atom and then two atoms), where only the atoms are weakly driven. Via the analytical calculation and numerical simulation, we show that the strong PB can be generated even with the weak-coupling regime at the total resonance. This blockade is ascribed to the two-photon absorption, which is fundamentally different from the conventional and unconventional blockade mechanisms. Therefore, our study provides an alternative approach to produce the PB in the atom-driven cavity QED system.
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Corticotropin-releasing hormone (CRH) neurons are densely distributed in the medial prefrontal cortex (mPFC), which plays a crucial role in integrating and processing emotional and cognitive inputs from other brain regions. Therefore, it is important to know the neural afferent patterns of mPFCCRH neurons, which are still unclear. Here, we utilized a rabies virus-based monosynaptic retrograde tracing system to map the presynaptic afferents of the mPFCCRH neurons throughout the entire brain. The results show that the mPFCCRH neurons receive inputs from three main groups of brain regions: (1) the cortex, primarily the orbital cortex, somatomotor areas, and anterior cingulate cortex; (2) the thalamus, primarily the anteromedial nucleus, mediodorsal thalamic nucleus, and central medial thalamic nucleus; and (3) other brain regions, primarily the basolateral amygdala, hippocampus, and dorsal raphe nucleus. Taken together, our results are valuable for further investigations into the roles of the mPFCCRH neurons in normal and neurological disease states. These investigations can shed light on various aspects such as cognitive processing, emotional modulation, motivation, sociability, and pain.
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Encéfalo , Hormona Liberadora de Corticotropina , Ratones , Animales , Neuronas/fisiología , Corteza Prefrontal/fisiología , Mapeo Encefálico , Vías Nerviosas/fisiologíaRESUMEN
BACKGROUND: Gabriele-de Vries syndrome is a rare autosomal dominant genetic disease characterized by global development delay/intellectual disability, delayed language development, feeding difficulties, and distinctive facial dysmorphism. It is caused by pathogenic variants in YY1. METHODS: The current report describes a female patient with motor delay and a facial dysmorphism phenotype. We identified pathogenic mutations in the patient by whole-exome sequencing and confirmed them by Sanger sequencing. RESULTS: A novel heterozygous frameshift mutation NM_003403.5:c.458_476del (p. V153fs*97) in the YY1 gene was detected in the proband. Finally, we provide a case-based review of the clinical features associated with Gabriele-de Vries syndrome. A total of 28 patients with genetic abnormalities and clinical phenotypes have been reported in the literature thus far. CONCLUSIONS: The mutation site is reported for the first time, and its discovery would expand the mutation spectrum of the YY1 gene. The main clinical manifestations of Gabriele-de Vries syndrome are developmental delay/intellectual disability, craniofacial dysplasia, intrauterine growth delay, low birth weight, feeding difficulties, and rare congenital malformations. Genetic tests are crucial techniques for its diagnosis because of its nonspecific clinical manifestations.
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Discapacidad Intelectual , Anomalías Musculoesqueléticas , Humanos , Femenino , Discapacidad Intelectual/genética , Discapacidad Intelectual/diagnóstico , Mutación , Fenotipo , Síndrome , Factor de Transcripción YY1/genéticaRESUMEN
The level of vitamin B group in human serum is an important index of human health. Among B vitamins, cyanocobalamin in serum is unstable and its content is extremely low. Rapid and simultaneous detection of multiple B vitamins including cyanocobalamin is a challenge. Herein, we have developed a rapid and stable method that can realize the determination of thiamine, riboflavin, nicotinamide, pantothenic acid, pyridoxic acid, biotin, 5-methyltetrahydrofolate, and cyanocobalamin simultaneously in 6 min. The method was established based on protein precipitation with methanol and then chromatographic separation was achieved using Waters acquity ultra-high-performance liquid chromatography high strength silica T3 column, which was stable and sensitive especially for cyanocobalamin. Limit of quantification, precision, trueness, and matrix effect were validated according to the European Medicines Agency and United States Food and Drug guidelines and Clinical and Laboratory Standards Institute guidelines on bioanalytical method. The limit of quantification for thiamine, riboflavin, nicotinamide, pantothenic acid, pyridoxic acid, biotin, 5-methyltetrahydrofolate, and cyanocobalamin was 0.4, 0.4, 0.8, 2.0, 0.4, 0.1, 0.4, and 0.04 ng/mL separately, respectively. Intra- and interday precisions were 1.1%-12.4% and 2.0%-13.5%, respectively. The relative errors were between 0.3% and 13.3%, and the matrix effects were between 2.6% and 10.4%.
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Complejo Vitamínico B , Humanos , Ácido Pantoténico/análisis , Biotina/análisis , Espectrometría de Masas en Tándem/métodos , Ácido Piridóxico , Cromatografía Liquida/métodos , Tiamina/análisis , Riboflavina/análisis , Niacinamida/análisis , Vitamina B 12/análisis , Cromatografía Líquida de Alta Presión/métodos , Vitamina A/análisis , Vitamina K/análisisRESUMEN
BACKGROUND: Kinase D-interacting substrate of 220 kDa (KIDINS220) is a multifunctional scaffolding protein essential for neuronal development. It has been implicated in neurological diseases with either autosomal dominant (AD) or autosomal recessive (AR) inheritance patterns. The molecular mechanisms underlying the AR/AD dual nature of KIDINS220 remain elusive, posing challenges to genetic interpretation and clinical interventions. Moreover, increased KIDINS220 exhibited neurotoxicity, but its role in neurodevelopment remains unclear. OBJECTIVE: The aim was to investigate the genotype-phenotype correlations of KIDINS220 and elucidate its pathophysiological role in neuronal development. METHODS: Whole-exome sequencing was performed in a four-generation family with cerebral palsy. CRISPR/Cas9 was used to generate KIDINS220 mutant cell lines. In utero electroporation was employed to investigate the effect of KIDINS220 variants on neurogenesis in vivo. RESULTS: We identified in KIDINS220 a pathogenic nonsense variant (c.4177C > T, p.Q1393*) that associated with AD cerebral palsy. We demonstrated that the nonsense variants located in the terminal exon of KIDINS220 are gain-of-function (GoF) variants, which enable the mRNA to escape nonsense-mediated decay and produce a truncated yet functional KIDINS220 protein. The truncated protein exhibited significant resistance to calpain and consequently accumulated within cells, resulting in the hyperactivation of Rac1 and defects in neuronal development. CONCLUSIONS: Our findings demonstrate that the location of variants within KIDINS220 plays a crucial role in determining inheritance patterns and corresponding clinical outcomes. The proposed interaction between Rac1 and KIDINS220 provides new insights into the pathogenesis of cerebral palsy, implying potential therapeutic perspectives. © 2023 International Parkinson and Movement Disorder Society.
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Parálisis Cerebral , Neuronas , Humanos , Neuronas/metabolismo , Transducción de Señal , Parálisis Cerebral/genética , Mutación con Ganancia de Función , Neurogénesis/genética , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Proteínas del Tejido Nervioso/genéticaRESUMEN
The hypothesis of N-methyl-D-aspartate receptor (NMDAR) dysfunction for cognitive impairment in schizophrenia constitutes the theoretical basis for the translational application of NMDAR co-agonist D-serine or its analogs. However, the cellular mechanism underlying the therapeutic effect of D-serine remains unclear. In this study, we utilize a mouse neurodevelopmental model for schizophrenia that mimics prenatal pathogenesis and exhibits hypoexcitability of parvalbumin-positive (PV) neurons, as well as PV-preferential NMDAR dysfunction. We find that D-serine restores excitation/inhibition balance by reconstituting both synaptic and intrinsic inhibitory control of cingulate pyramidal neurons through facilitating PV excitability and activating small-conductance Ca2+-activated K+ (SK) channels in pyramidal neurons, respectively. Either amplifying inhibitory drive via directly strengthening PV neuron activity or inhibiting pyramidal excitability via activating SK channels is sufficient to improve cognitive function in this model. These findings unveil a dual mechanism for how D-serine improves cognitive function in this model.
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Esquizofrenia , Ratones , Animales , Embarazo , Femenino , Esquizofrenia/tratamiento farmacológico , Serina/farmacología , Células Piramidales/fisiología , Neuronas/metabolismo , Transmisión Sináptica , Receptores de N-Metil-D-Aspartato/metabolismoRESUMEN
Recognition memory is a cognitive process that enables us to distinguish familiar objects and situations from new items, which is essential for mammalian survival and adaptation to a changing environment. Social isolation (SI) has been implicated as a detrimental factor for recognition memory. The medial prefrontal cortex (mPFC) has been shown to carry information concerning the relative familiarity of individual stimuli, and modulating neuronal function in this region may contribute to recognition memory. The present study aimed to investigate the neuronal mechanisms in the mPFC of environmental enrichment (EE) on recognition memory in adult mice following SI. Mice were assigned into three groups: control, SI, and SI + EE groups. Novel location recognition (NLR) and novel object recognition (NOR) tests were performed to evaluate the recognition memory. The levels of Kv4 channels were assessed by qRT-PCR and western blotting. The effects of SI and SI + EE on the excitability of pyramidal neurons in the mPFC were measured using whole-cell recording. We found that SI led to a reduction in the excitability of pyramidal neurons. Specifically, we have identified that the reduction in the firing activity of pyramidal neurons resulted from alterations in the function and expression of Kv4.2 channels. Furthermore, EE regulated Kv4.2 channels, normalized the activity of pyramidal neurons, and restored the behavioral deficits following SI. Thus, the roles of Kv4.2 channels in excitability of pyramidal neurons suggest that the Kv4.2 channels present a promising therapeutic target for recognition memory impairment.
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OBJECTIVE: To explore the clinical characteristics and genetic variants in two children with Tuberous sclerosis complex (TSC). METHODS: Two children who had presented at the Children's Hospital Affiliated to Zhengzhou University respectively in June 2020 and July 2021 were selected as the study subjects. Clinical data of the children were collected, and potential pathogenic variants were screened by whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing of their family members. RESULTS: Child 1 was a 7-month-and-29-day-old male, and child 2 was a 2-year-and-6-month-old male. Both children had shown symptoms of epileptic seizures and multiple hypomelanotic macules. Genetic testing revealed that both children had harbored de novo variants of the TSC2 gene, namely c.3239_3240insA and c.3330delC, which were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were rated as pathogenic (PVS1+PS2+PM2_Supporting). CONCLUSION: This study has uncovered the genetic etiology for two children with TSC. Above findings have also enriched the phenotypic and mutational spectrum of TSC in the Chinese population.
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Esclerosis Tuberosa , Humanos , Lactante , Masculino , Familia , Pruebas Genéticas , Genómica , Mutación , Esclerosis Tuberosa/genética , Preescolar , Pueblos del Este de AsiaRESUMEN
PURPOSE: To compare the effect of different polishing methods and time treatment on the fitness of CAD/CAM zirconia ceramic crowns. METHODS: Sixteen intact maxillary premolars were randomly divided into two groups, group A was treated with silicon carbide burs, while group B was treated with tungsten steel burs. At different polishing time points of the same tooth, digital impressions of each group were obtained, which were used to manufacture CAD/CAM zirconium ceramic crowns. After trial fitting, the gap impressions were obtained by using silicone rubber replication method, and the marginal and internal discrepancies were assessed. The data were statistically analyzed with SPSS 21.0 software package. RESULTS: The difference between the gap values of the marginal and internal markers of group A and group B was not statistically significant(Pï¼0.05). Compared with the no-polishing process, the differences of the marginal gap (39.67±8.35) µm and internal gap (45.18±7.16) µm of group A polished for 4 min, and the marginal gap (51.25±14.73) µm, and internal gap (48.56±6.45) µm of group B polished for 3 min, as well as the marginal gap (48.87±8.90) µm, and internal gap (45.99±7.12) µm of group B polished for 4 min, were all significant(Pï¼0.05). CONCLUSIONS: CAD/CAM zirconia ceramic crowns treated with silicon carbide bur for polishing 4 min and tungsten steel for 3 min has the best fitness.
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Coronas , Circonio , Tungsteno , Diseño de Prótesis Dental/métodos , Adaptación Marginal Dental , Porcelana Dental , Diseño Asistido por Computadora , AceroRESUMEN
BACKGROUND: Simulation is an increasingly used novel method for the education of medical professionals. This study aimed to systematically review the efficacy of high-fidelity (HF) simulation compared with low-fidelity (LF) simulation or no simulation in advanced life support (ALS) training. METHODS: A comprehensive search of the PubMed, Chinese Biomedicine Database, Embase, CENTRAL, ISI, and China Knowledge Resource Integrated Database was performed to identify randomized controlled trials (RCTs) that evaluated the use of HF simulation in ALS training. Quality assessment was based on the Cochrane Handbook for Systematic Reviews of Interventions version 5.0.1. The primary outcome was the improvement of knowledge and skill performance. The secondary outcomes included the participants' confidence and satisfaction at the course conclusion, skill performance at one year, skill performance in actual resuscitation, and patient outcomes. Data were synthesized using the RevMan 5.4 software. RESULTS: Altogether, 25 RCTs with a total of 1,987 trainees were included in the meta-analysis. In the intervention group, 998 participants used HF manikins, whereas 989 participants received LF simulation-based or traditional training (classical training without simulation). Pooled data from the RCTs demonstrated a benefit in improvement of knowledge [standardized mean difference (SMD) = 0.38; 95% confidence interval (CI): 0.18-0.59, P = 0.0003, I2 = 70%] and skill performance (SMD = 0.63; 95% CI: 0.21-1.04, P = 0.003, I2 = 92%) for HF simulation when compared with LF simulation and traditional training. The subgroup analysis revealed a greater benefit in knowledge with HF simulation compared with traditional training at the course conclusion (SMD = 0.51; 95% CI: 0.20-0.83, P = 0.003, I2 = 61%). Studies measuring knowledge at three months, skill performance at one year, teamwork behaviors, participants' satisfaction and confidence demonstrated no significant benefit for HF simulation. CONCLUSIONS: Learners using HF simulation more significantly benefited from the ALS training in terms of knowledge and skill performance at the course conclusion. However, further research is necessary to enhance long-term retention of knowledge and skill in actual resuscitation and patient's outcomes.
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Enseñanza Mediante Simulación de Alta Fidelidad , Humanos , Simulación por Computador , Escolaridad , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Background and aim: Good collateral circulation is recognized to maintain perfusion and contribute to favorable clinical outcomes in acute ischemic stroke. This study aimed to derive and validate an optimal collateral time measurement on perfusion computed tomography imaging for patients with acute ischemic stroke. Methods: This study included 106 acute ischemic stroke patients with complete large vessel occlusions. In deriving cohort of 23 patients, the parasagittal region of the ischemic hemisphere was divided into six pial arterial zones according to pial branches of the middle cerebral artery. Within the 85 arterial zones with collateral vessels, the receiver operating characteristic analysis was performed to derive the optimal collateral time threshold for fast collateral flow on perfusion computed tomography. The reference for fast collateral flow was the peak contrast delay on the collateral vessels within each ischemic arterial zone compared to its contralateral normal arterial zone on dynamic computed tomography angiography. The optimal perfusion collateral time threshold was then tested in predicting poor clinical outcomes (modified Rankin score of 5-6) and final infarct volume in the validation cohort of 83 patients. Results: For the derivation cohort of 85 arterial zones, the optimal collateral time threshold for fast collateral flow on perfusion computed tomography was a delay time of 4.04 s [area under the curve = 0.78 (0.67, 0.89), sensitivity = 73%, and specificity = 77%]. Therefore, the delay time of 4 s was used to define the perfusion collateral time. In the validation cohort, the perfusion collateral time showed a slightly higher predicting power than dynamic computed tomography angiography collateral time in poor clinical outcomes (area under the curve = 0.72 vs. 0.67; P < 0.001). Compared to dynamic computed tomography angiography collateral time, the perfusion collateral time also had better performance in predicting final infarct volume (R-squared values = 0.55 vs. 0.23; P < 0.001). Conclusion: Our results indicate that perfusion computed tomography can accurately quantify the collateral time after acute ischemic stroke.