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OBJECTIVE: To analyze cerebellar atrophy in genetic epileptic encephalopathies (EEs). METHODS: This research included a retrospective cohort study conducted from January 2016 to December 2023 and a systematic review on cerebellar atrophy in genetic EEs. Pediatric individuals who were diagnosed with EEs based on electroclinical features, carried causative gene variants, and exhibited cerebellar atrophy were recruited. Electroclinical features, neuroimaging findings, and causative variants of eligible individuals were analyzed. RESULTS: The cohort study showed 10 of 67 pediatric individuals (10/67; 15 %) who were diagnosed with genetic EEs had cerebellar atrophy; and 6 of the 10 individuals (6/10; 60 %) exhibited cerebellar signs. Diagnostic delay between the detection of cerebellar atrophy and the identification of genetic diagnosis existed in 6 individuals (6/10; 60 %) and the median duration was 4.4 years. A total of 32 genes, including 31 genes from the literature review and a newly identified SCN2A gene in this cohort, were reported associated with cerebellar atrophy in genetic EEs. Twenty-six genes (26/32; 81 %) accounted for cerebellar atrophy associated with other brain anomalies and 6 genes (6/32; 19 %) caused isolated cerebellar atrophy. Twenty-five genes (25/32; 78 %) showed late-onset cerebellar atrophy identified after the age of 1 year old. CONCLUSION: Cerebellar atrophy is not uncommon in genetic EEs and may serve as an indicator for molecular diagnosis in clinical practice. To shorten the diagnostic delay, follow-up neuroimaging study is crucial because of high rate of clinico-radiological dissociation and late-onset cerebellar atrophy in this patient group.
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Atrofia , Cerebelo , Humanos , Atrofia/patologia , Cerebelo/patologia , Cerebelo/diagnóstico por imagem , Feminino , Masculino , Pré-Escolar , Criança , Lactente , Estudos Retrospectivos , Doenças Cerebelares/genética , Doenças Cerebelares/diagnóstico , Doenças Cerebelares/patologia , Doenças Cerebelares/diagnóstico por imagem , Estudos de Coortes , Epilepsia/genética , Epilepsia/diagnóstico , AdolescenteRESUMO
Adipocytes are the primary sites for fatty acid storage, but the synthesis rate of fatty acids is very low. The physiological significance of this phenomenon remains unclear. Here, we show that surplus fatty acid synthesis in adipocytes induces necroptosis and lipodystrophy. Transcriptional activation of FASN elevates fatty acid synthesis, but decreases NADPH level and increases ROS production, which ultimately leads to adipocyte necroptosis. We identify MED20, a subunit of the Mediator complex, as a negative regulator of FASN transcription. Adipocyte-specific male Med20 knockout mice progressively develop lipodystrophy, which is reversed by scavenging ROS. Further, in a murine model of HIV-associated lipodystrophy and a human patient with acquired lipodystrophy, ROS neutralization significantly improves metabolic disorders, indicating a causal role of ROS in disease onset. Our study well explains the low fatty acid synthesis rate in adipocytes, and sheds light on the management of acquired lipodystrophy.
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Adipócitos , Lipodistrofia , Masculino , Camundongos , Humanos , Animais , Espécies Reativas de Oxigênio/metabolismo , Adipócitos/metabolismo , Lipodistrofia/genética , Lipodistrofia/metabolismo , Ácidos Graxos/metabolismo , Estresse Oxidativo , Camundongos KnockoutRESUMO
To resolve the issue of scientific planning and rational layout of different vegetable greenhouses in Inner Mongolia Autonomous Region, we selected the days of low temperature in winter, sunshine hours, overcast days, extreme minimum temperature, days of monsoon disaster, days of snow cover in production season of greenhouse as the climate zoning indicators, based on ground-based observation data from 119 meteorological stations (1991 to 2020) and the growing demand of leafy and fruity vegetables in greenhouse, combined with the analysis of key meteorological factors in production season and the study of meteorological disaster indicators such as low temperature and cold damage, wind disaster, snow disaster. We analyzed the indices, classification and division of comprehensive climate suitability zoning of leafy and fruity vegetables at various slopes (35°, 40°) of solar greenhouse by the weighted sum method. The results showed that the climatic suitability zoning grades of leafy and fruity vegetables at 35° and 40° slope of greenhouse was highly consistent, and that the greenhouse climate suitability of leafy vegetables was higher than that of fruity vegetables in the same region. As the slope increased, wind disaster index decreased and snow disaster index increased. Climate suitability was different in areas affected by wind and snow disasters. The northeast of the study area was mainly affected by snow disasters, and the climate suitability of 40° slope was higher than 35°. The southeast of the study area was mainly affected by wind disasters, and the climate suitability of 35° slope was higher than 40°. Alxa League, Hetao Irrigation District, Tumochuan Plain, most parts of Ordos, southeast of Yanshan foothills and the south of West Liaohe Plain were the most suitable area for the solar greenhouse, because they had the suitable solar and hot resources and the low risks of wind and snow damage, which were also the key development areas of current and future facility agriculture. Due to the deficiency of solar and hot resources, high energy consumption in greenhouse production and frequent snow storms, the area around Khingan range in the northeast of Inner Mongolia was unsuitable for greenhouse.
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Neve , Verduras , Estações do Ano , China , Agricultura , Mudança ClimáticaRESUMO
BACKGROUND: Nelumbo nucifera Gaertn stem (Hegeng [HG]) is a traditional Chinese medicine that is used to treat mental symptoms in East Asia. However, scientific evidence is generally lacking to support this traditional claim. Aim of the Study. This study's aim is to investigate the antidepression effect of HG and to further explore the possible molecular mechanisms that are involved in its actions. Materials and Methods. HG aqueous extract was administered intragastrically for 21 days after the chronic unpredictable mild stress (CUMS) procedure, and its effect on memory, learning, and emotion was assessed using animal behavioral tests. HG aqueous extract was characterized using HPLC. Immunofluorescence was used to measure the neural cell-adhesion molecule (NCAM) and growth-associated protein-43 (GAP-43) expression. RESULTS: Depression-like behaviors increased in the CUMS group compared with the control (CON) group, while they were reduced in the high-dose HG (H-HG) and fluoxetine (FLU) groups (p < 0.05). Additionally, NCAM and GAP-43 expression was reduced in the CUMS group compared with the CON group, but it increased in the H-HG and FLU groups (p < 0.05). CONCLUSIONS: These findings show the potential antidepressant effects of HG through mechanisms involving regulation of NCAM and GAP-43. This provides a new theoretical basis for its potential application as an antidepressant-like agent.
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BACKGROUND: Huazhuo Jiedu Shugan decoction (HJSD), a traditional Chinese medicine (TCM), has been used to treat epileptic seizures for many years. Some ingredients in these herbs have been demonstrated to be effective for the treatment of brain damage caused by epilepsy. AIM OF THE STUDY: The object of the study is to determine the effects of HJSD on cognitive and emotional disorders in a rat model of epilepsy. MATERIALS AND METHODS: After a predetermined time period, rats were intraperitoneally injected with pentylenetetrazol and observed in different phases of convulsions. The cognitive and emotional changes in the epileptic rats were assessed using behavioral and immunohistochemical tests. RESULTS: Compared with the epilepsy group, the seizure grade was reduced and seizure latency was prolonged following HJSD-H treatment (P < 0.01). Compared with the control group, the epilepsy group displayed marked worse performance on the animal behavior tests (P < 0.05) and the HJSD-H group displayed improved behavioral performance (P < 0.05). After HJSD-H treatment, the expression of adenylate cyclase (AC), cyclic adenosine monophosphate (cAMP), cAMP-response element binding protein (CREB), and neuropeptide Y (NPY) immunoreactive cells markedly increased in the hippocampus, compared with that of the epilepsy group (P < 0.05). CONCLUSIONS: The current results demonstrate that HJSD treatment in epileptic rats markedly inhibits epileptic seizures and improves cognitive and emotional disorders, which may be related to the regulation of AC-cAMP-CREB signaling and NPY expression in the hippocampus. The effects of the HJSD treatment may provide a foundation for the use of HJSD as a prescription medicinal herb in the TCM for the treatment of epilepsy.