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Hippocampus is a critical component of the central nervous system. SRSF10 is expressed in central nervous system and plays important roles in maintaining normal brain functions. However, its role in hippocampus development is unknown. In this study, using SRSF10 conditional knock-out mice in neural progenitor cells (NPCs), we found that dysfunction of SRSF10 leads to developmental defects in the dentate gyrus of hippocampus, which manifests as the reduced length and wider suprapyramidal blade and infrapyramidal blade.Furthermore, we proved that loss of SRSF10 in NPCs caused inhibition of the differentiation activity and the abnormal migration of NPCs and granule cells, resulting in reduced granule cells and more ectopic granule cells dispersed in the molecular layer and hilus. Finally, we found that the abnormal migration may be caused by the radial glia scaffold and the reduced DISC1 expression in NPCs. Together, our results indicate that SRSF10 is required for the cell migration and formation of dentate gyrus during the development of hippocampus.
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Movimiento Celular , Giro Dentado , Ratones Noqueados , Células-Madre Neurales , Factores de Empalme Serina-Arginina , Animales , Células-Madre Neurales/metabolismo , Giro Dentado/metabolismo , Movimiento Celular/fisiología , Factores de Empalme Serina-Arginina/metabolismo , Factores de Empalme Serina-Arginina/genética , Neuronas/metabolismo , Hipocampo/metabolismo , Ratones , Neurogénesis/fisiología , Diferenciación Celular/fisiología , Proteínas del Tejido Nervioso/metabolismo , Proteínas del Tejido Nervioso/genética , Ratones Endogámicos C57BLRESUMEN
Sepsis is a lifethreatening multiple organ failure disease caused by an uncontrolled inflammatory response and can progress to acute lung injury (ALI). Heatshock protein B8 (HSPB8) serves a cytoprotective role in multiple types of diseases; however, to the best of our knowledge, the regulatory role of HSPB8 in sepsisinduced ALI remains unclear. A549 human alveolar type II epithelial cells were treated with lipopolysaccharide (LPS) for 24 h to simulate a sepsisinduced ALI model. Cell transfection was performed to overexpress HSPB8, and cells were treated with mitochondrial division inhibitor1 (Mdivi1) for 2 h before LPS induction to assess the underlying mechanism. Protein expression was evaluated using western blotting and an immunofluorescence assay. Cytokines were examined using ELISA assay kits and antioxidant enzymes were examined using their detection kits. Cell apoptosis was detected using flow cytometry. The mitochondrial membrane potential was detected by JC1 staining. HSPB8 was upregulated in A549 cells treated with LPS and HSPB8 overexpression attenuated LPSinduced inflammatory cytokine levels, oxidative stress and apoptosis in A549 cells. LPS inhibited mitophagy and reduced the mitochondrial membrane potential in A549 cells, which was partly inhibited by HSPB8 overexpression. Furthermore, Mdivi1 decreased the inhibitory effect of HSPB8 on the inflammatory response, oxidative stress and apoptosis in LPStreated A549 cells. In conclusion, HSPB8 overexpression attenuated the LPSmediated inflammatory response, oxidative stress and apoptosis in A549 cells by promoting mitophagy, indicating HSPB8 as a potential therapeutic target in sepsisinduced ALI.
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Lesión Pulmonar Aguda , Apoptosis , Citocinas , Proteínas de Choque Térmico , Lipopolisacáridos , Potencial de la Membrana Mitocondrial , Mitofagia , Chaperonas Moleculares , Estrés Oxidativo , Humanos , Mitofagia/efectos de los fármacos , Lesión Pulmonar Aguda/metabolismo , Lesión Pulmonar Aguda/patología , Lesión Pulmonar Aguda/inducido químicamente , Lipopolisacáridos/efectos adversos , Células A549 , Proteínas de Choque Térmico/metabolismo , Proteínas de Choque Térmico/genética , Apoptosis/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Citocinas/metabolismo , Chaperonas Moleculares/metabolismo , Chaperonas Moleculares/genéticaRESUMEN
AIMS/HYPOTHESIS: Continuous glucose monitoring (CGM) provides comprehensive information on the exposure to dysglycaemia. This study aimed to investigate the threshold of hyperglycaemia related to mortality risk in critically ill patients using CGM technology. METHODS: A total of 293 adult critically ill patients admitted to intensive care units of five medical centres were prospectively included between May 2020 and November 2021. Participants wore intermittently scanned CGM for a median of 12.0 days. The relationships between different predefined time above ranges (TARs), with the thresholds of hyperglycaemia ranging from 7.8 to 13.9 mmol/l (140-250 mg/dl), and in-hospital mortality risk were assessed by multivariate Cox proportional regression analysis. Time in ranges (TIRs) of 3.9 mmol/l (70 mg/dl) to the predefined hyperglycaemic thresholds were also assessed. RESULTS: Overall, 66 (22.5%) in-hospital deaths were identified. Only TARs with a threshold of 10.5 mmol/l (190 mg/dl) or above were significantly associated with the risk of in-hospital mortality, after adjustment for covariates. Furthermore, as the thresholds for TAR increased from 10.5 mmol/l to 13.9 mmol/l (190 mg/dl to 250 mg/dl), the hazards of in-hospital mortality increased incrementally with every 10% increase in TARs. Similar results were observed concerning the associations between TIRs with various upper thresholds and in-hospital mortality risk. For per absolute 10% decrease in TIR 3.9-10.5 mmol/l (70-190 mg/dl), the risk of in-hospital mortality was increased by 12.1% (HR 1.121 [95% CI 1.003, 1.253]). CONCLUSIONS/INTERPRETATION: A glucose level exceeding 10.5 mmol/l (190 mg/dl) was significantly associated with higher risk of in-hospital mortality in critically ill patients.
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Glucemia , Enfermedad Crítica , Mortalidad Hospitalaria , Hiperglucemia , Humanos , Enfermedad Crítica/mortalidad , Hiperglucemia/mortalidad , Hiperglucemia/sangre , Masculino , Estudios Prospectivos , Femenino , Glucemia/análisis , Glucemia/metabolismo , Persona de Mediana Edad , Anciano , Unidades de Cuidados Intensivos , Monitoreo Fisiológico/métodos , Monitoreo Continuo de GlucosaRESUMEN
INTRODUCTION: Developmental changes due to early life variations in the serotonin system affect stress-related behavior and neuroplasticity in adulthood. These outcomes can be caused both by offspring's own and maternal serotonergic genotype. We aimed to dissociate the contribution of the own genotype from the influences of mother genotype. METHODS: Sixty-six male homozygous (5-HTT-/-) and heterozygous (5-HTT+/-) serotonin transporter knockout and wild-type rats from constant 5-HTT genotype mothers crossed with varying 5-HTT genotype fathers were subjected to tests assessing anxiety- and depression-like behaviors. Additionally, we measured plasma corticosterone levels and mRNA levels of BDNF, GABA system and HPA-axis components in the prelimbic and infralimbic cortex. Finally, we assessed the effect of paternal 5-HTT genotype on these measurements in 5-HTT+/- offspring receiving their knockout allele from their mother or father. RESULTS: 5-HTT-/- offspring exhibited increased anxiety- and depression-like behavior in the elevated plus maze and sucrose preference test. Furthermore, Bdnf isoform VI expression was reduced in the prelimbic cortex. Bdnf isoform IV and GABA related gene expression was also altered but did not survive false discovery rate (FDR) correction. Finally, 5-HTT+/- offspring from 5-HTT-/- fathers displayed higher levels of anxiety- and depression-like behavior and changes in GABA, BDNF and HPA-axis related gene expression not surviving FDR correction. LIMITATIONS: Only male offspring was tested. CONCLUSIONS: Offspring's own 5-HTT genotype influences stress-related behaviors and Bdnf isoform VI expression, independently of maternal 5-HTT genotype. Paternal 5-HTT genotype separately influenced these outcomes. These findings advance our understanding of the 5-HTT genotype dependent susceptibility to stress-related disorders.
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Ansiedad , Depresión , Proteínas de Transporte de Serotonina en la Membrana Plasmática , Animales , Masculino , Ratas , Ansiedad/genética , Factor Neurotrófico Derivado del Encéfalo/genética , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Depresión/genética , Ácido gamma-Aminobutírico , Genotipo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Proteínas de Transporte de Serotonina en la Membrana Plasmática/genéticaRESUMEN
INTRODUCTION: In this study, JJH201501 was examined for reproductive toxicity during the perinatal period to support its safety as a novel serotonergic agent (5-HT) antidepressant. Pregnant Sprague-Dawley rats (F0, n = 24/group) were continuously exposed to 0 (control), 6, 18, and 60 mg/kg body weight/day of JJH201501 by intragastric administration from gestation day 15 to lactation day 21. METHODS: During this period, maternal toxicity was evaluated based on clinical signs, body weight, feed intake, delivery condition, litter parameters, and necropsy, with body weight, sex ratios, malformation incidence, physical, and neurodevelopmental assessments conducted on all offspring rats. Ten pups (male:female 1:1) from each dam within each dose group on postnatal day 4 (PND4) were randomly selected. One pair was evaluated for behavior evaluations (F1a) after PND35, one for reproduction performance (F1b) after 10 weeks, and three for organ weight and deformities (F1c) on PND35. After successful mating, F1b male rats were weighed and dissected to assess reproductive organ weight and sperm motility. Pregnant F1b rats were weighed and monitored for food intake twice weekly until laparotomy on GD14, which recorded live/dead fetuses, resorptions, implantations, corpora lutea, and uterine weight. Some statistical differences were found between the JJH-treated and control groups in maternal weight, food consumption, and F1 body weight and water maze performance. RESULTS: Autopsy results showed that JJH201501 had a low cardiac index effect in F0, with no significant histopathological changes detected. Only one F1 offspring died in the high-dose group throughout the experiment. Due to the lack of dose-dependent effects and the consistent growth pattern of these alterations, the study findings do not suggest any toxicological significance for the observed results. CONCLUSION: In conclusion, the no-observed-adverse-effect level of JJH201501 for perinatal rats is about 60 mg/kg b.w./day.
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Reproducción , Motilidad Espermática , Embarazo , Ratas , Masculino , Animales , Femenino , Ratas Sprague-Dawley , Parto , Peso CorporalRESUMEN
Background and Aims: Intestinal ultrasound (IUS) is considered a nonirradiating, noninvasive, well-tolerated, and valuable tool for objectively assessing Crohn's disease (CD) activity. However, there is no widely accepted intestinal ultrasound scoring system. This study is aimed at evaluating the efficacy of IUS key parameters, the International Bowel Ultrasound Activity Score (IBUS-SAS), and IBUS-SAS combined with blood inflammatory markers in assessing CD activity. Methods: 40 CD patients were reviewed in this retrospective study and were divided into the moderate-severe group (n = 25) and nonmoderate-severe group (n = 15) based on a simplified endoscopic score of Crohn's disease (SES-CD). Double-balloon enteroscopy/colonoscopy were reviewed by three gastroenterologists. A transabdominal ultrasound was performed by two ultrasound specialists. Blood inflammatory markers were measured from morning samples. Results: In evaluating moderate to severe CD patients, (1) IBUS-SAS had a good predictive effect with an area-under-the-curve (AUC) of 0.855 (P < 0.001); (2) IUS key parameters (including BWT, CDS, BWS, and I-fat) yielded good predictive effects with AUC of 0.811, 0.731, 0.724, and 0.747, respectively (P < 0.001); (3) blood inflammatory markers (including ESR, CRP, PLR, MLR, and NLR) also had good predictive effects with AUC of 0.771, 0.837, 0.728, 0.743, and 0.775, respectively (P < 0.001); (4) IBUS-SAS combined with ESR and CRP exerted the best predictive effect with the highest AUC of 0.912 (95% CI: 0.823-1.000), and the sensitivity and specificity were 88.0% and 80.0%, respectively (P < 0.001). Conclusion: IBUS-SAS combined with ESR and CRP is a more efficient tool than IBUS-SAS alone or inflammatory markers alone in evaluating CD patients with moderate to severe disease activity.
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BACKGROUND: This article aims to analyze the relationship between user characteristics on social networks and influenza. METHODS: Three specific research questions are investigated: (1) we classify Weibo updates to recognize influenza-related information based on machine learning algorithms and propose a quantitative model for influenza susceptibility in social networks; (2) we adopt in-degree indicator from complex networks theory as social media status to verify its coefficient correlation with influenza susceptibility; (3) we also apply the LDA topic model to explore users' physical condition from Weibo to further calculate its coefficient correlation with influenza susceptibility. From the perspective of social networking status, we analyze and extract influenza-related information from social media, with many advantages including efficiency, low cost, and real time. RESULTS: We find a moderate negative correlation between the susceptibility of users to influenza and social network status, while there is a significant positive correlation between physical condition and susceptibility to influenza. CONCLUSIONS: Our findings reveal the laws behind the phenomenon of online disease transmission, and providing important evidence for analyzing, predicting, and preventing disease transmission. Also, this study provides theoretical and methodological underpinnings for further exploration and measurement of more factors associated with infection control and public health from social networks.
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Gripe Humana , Medios de Comunicación Sociales , Humanos , Gripe Humana/epidemiología , Algoritmos , Control de Infecciones , Red SocialRESUMEN
Alternative pre-mRNA splicing plays critical roles in brain development. SRSF10 is a splicing factor highly expressed in central nervous system and plays important roles in maintaining normal brain functions. However, its role in neural development is unclear. In this study, by conditional depleting SRSF10 in neural progenitor cells (NPCs) in vivo and in vitro, we found that dysfunction of SRSF10 leads to developmental defects of the brain, which manifest as abnormal ventricle enlargement and cortical thinning anatomically, as well as decreased NPCs proliferation and weakened cortical neurogenesis histologically. Furthermore, we proved that the function of SRSF10 on NPCs proliferation involved the regulation of PI3K-AKT-mTOR-CCND2 pathway and the alternative splicing of Nasp, a gene encoding isoforms of cell cycle regulators. These findings highlight the necessity of SRSF10 in the formation of a structurally and functionally normal brain.
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Tetrodotoxin (TTX) could result in serious diseases due to its extremely high neurotoxicity. Thus, it is of great importance to measure TTX for food safety. In this study, an anti-TTX monoclonal antibody with good specificity and high affinity was used to develop the immunochromatographic test strips (ICTS). Gold nanoflower (AuNF) with multiple branches and latex microsphere (LM) with large particle size as signal reporters were employed for improving the sensitivity of test strips. Both AuNF and LM probes are stable, and the developed ICTS were specific to TTX, demonstrating no cross-reactivity with other marine toxins. The linear range of AuNF- and LM-based strips for TTX was 9.49-330.98 ng/mL and 5.40-443.19 ng/mL, respectively. The limit of detection (LOD) of AuNF- and LM-based strips was determined to be 9.49 ng/mL and 5.40 ng/mL, respectively. In summary, the developed ICTS based on AuNF and LM signal probes displayed enhancement of sensitivity and provided rapid and specific detection of TTX.
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Purpose: To investigate the relationship between intraoperative anesthesia-related factors and postoperative complications in patients undergoing emergency abdominal surgery, and to identify risk factors for these postoperative complications. Methods: We retrospectively analyzed 942 emergency surgery patients who underwent general anesthesia and emergency abdominal operations at Jiangsu Province Hospital during the period September 2015 to December 2016. Logistic regression analysis was performed to analyze the association between preoperative or intraoperative parameters and postoperative complications. Results: Among the 942 patients whose data were analyzed, 226 (24.0%) had major postoperative complications within 30 days after surgery. The most common postoperative complications were respiratory complications (31.8% of those experiencing complications). After adjusting for the role of multiple confounding factors, multivariable analysis showed that the independent risk factors for postoperative complications were patient age (OR 1.648; 95% CI 1.352-2.008), the ASA classification (OR 3.220; 95% CI 2.492-4.162), intraoperative hypotension lasting more than 20 min (OR 2.031; 95% CI 1.256-3.285), intraoperative tachyarrhythmias (OR 2.205; 95% CI 1.114-4.365), and the surgical level (i.e. type and difficulty level) [OR 1.895; 95% CI 1.306-2.750]. Conclusion: Prolonged intraoperative hypotension (>20 min) and the occurrence of tachyarrhythmias are independent risk factors for postoperative complications in patients who undergo emergency abdominal surgery. During hemodynamic management of these patients, systolic blood pressure should be controlled to within 20% of the baseline value to reduce the risk of postoperative complications. In addition, a higher patient age, higher ASA grade, and a higher surgical classification level also significantly increase the risk of postoperative complications.
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BACKGROUND: Elderly patients after surgery are prone to cognitive decline known as postoperative cognitive dysfunction (POCD). Several studies have shown that the microglial activation and the increase of complement protein expression in hippocampus induced by surgery may be related to the pathogenesis of POCD. The purpose of this study was to determine whether microglia and complement system were involved in cognitive dysfunction in aged mice. METHODS: The POCD model was established by exploratory laparotomy in 15-month-old male C57BL/6J mice and animal behavioral tests were performed to test hippocampal-dependent memory capacity. Minocycline was used to suppress the activation of microglia, and complement 3 receptor inhibitor was used to suppress the association between microglia and complement 3. Western blot and immunofluorescence were used to detect the microglial activation, complement protein, and synaptic protein expressions. RESULTS: Operation induced hippocampal-dependent memory impairment (P < 0.01), which was accompanied by microglial activation (P < 0.01). There was also a significant reduction in inhibitory synaptic protein expression in the hippocampus of mice in the surgery group (P < 0.01). However, minocycline, a microglia inhibitor, rescued all the above changes. In addition, C3RI intervention inhibited the phagocytosis of inhibitory synapses by microglia (P < 0.05) and improved the cognitive function of mice (P < 0.01). CONCLUSION: Microglia participate in postoperative cognitive dysfunction by mediating inhibitory synaptic loss through the complement pathway.
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Disfunción Cognitiva , Complicaciones Cognitivas Postoperatorias , Masculino , Ratones , Animales , Complicaciones Cognitivas Postoperatorias/metabolismo , Microglía/metabolismo , Minociclina/farmacología , Ratones Endogámicos C57BL , Hipocampo/metabolismo , SinapsisRESUMEN
Nonpharmaceutical policies for epidemic prevention and control have been extensively used since the outbreak of COVID-19. Policies ultimately work by limiting individual behavior. The aim of this paper is to evaluate the effectiveness of policies by combining macro nonpharmaceutical policies with micro-individual going-out behavior. For different going out scenarios triggered by individual physiological safety needs, friendship needs, and family needs, this paper categorizes policies with significant differences in intensity, parameterizes the key contents of the policies, and simulates and analyzes the effectiveness of the policies in different going-out scenarios with simulation methods. The empirical results show that enhancing policy intensity can effectively improve policy effectiveness. Among different types of policies, restricting the times of going out is more effective. Further, the effect of controlling going out based on physiological safety needs is better than other needs. We also evaluate the policy effectiveness of 26 global countries or regions. The results show that the policy effectiveness varies among 26 countries or regions. The quantifiable reference provided by this study facilitates decision makers to establish policy and practices for epidemic prevention and control.
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COVID-19 , Epidemias , Humanos , COVID-19/prevención & control , Política de Salud , Formulación de Políticas , Brotes de EnfermedadesRESUMEN
Background: Assays of transposase accessible chromatin sequencing (ATAC-seq) is an efficient assay to investigate chromatin accessibility, which depends on the activity of a robust Tn5 transposase to fragment the genome while cutting in the sequencing adapters. Methods: We propose reliable approaches for purifying hyperactive Tn5 transposase by chitin magnetic bead sorting. Double-stranded DNA of J76 cells and 293T cells were digested and subjected to tagmentation as test samples with Tn5 transposase, and libraries were established and sequenced. Sequencing data was then analyzed for peak calling, GO enrichment, and motif analysis. Results: We report a set of rapid, efficient, and low-cost methods for ATAC-seq library construction and data analysis, through large-scale and rapid sequencing. These methods can provide a reference for the study of epigenetic regulation of gene expression.
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Secuenciación de Inmunoprecipitación de Cromatina , Secuenciación de Nucleótidos de Alto Rendimiento , Cromatina/genética , Epigénesis Genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Análisis de Secuencia de ADN/métodos , Tecnología , Transposasas/genética , Transposasas/metabolismoRESUMEN
Recently, with the development of geophysical exploration technology, geophysical engineering instruments and methods have also improved. The multi-electrode resistivity method is widely used in engineering exploration. In this paper, multi-electrode resistivity tests were carried out in a seasonal frozen soil area in Heilongjiang Province, to provide an optimized multi-electrode resistivity method under the conditions of frozen soil. Combined with shear wave velocity tests and standard penetration tests, multi-electrode resistivity tests were used to comprehensively analyze and evaluate the physical and mechanical properties of Tertiary semi-diagenesis rocks. The results show that the high resistivity due to the frozen surface layer acting as a shield can be eliminated by technical means. It is feasible to test the resistivity through the frozen surface layer. The multi-electrode resistivity method can visually reflect the interface between saturated sand and semi-diagenetic rocks. Dividing the interface between saturated sand and semi-diagenetic rocks is advantageous as the morphology of the resistivity curve has a significant curvature change. There is a strong correlation between the resistance and shear wave velocity of a strata in which the Pearson correlation coefficient is as high as 0.99. The multi-electrode resistivity method test used in combination with the shear wave velocity test and the standard penetration test could give the bearing capacity and frictional resistance of semi-diagenetic rocks, which saves a lot of time and material costs in engineering exploration.
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Accurately predicting the number of severe and critical COVID-19 patients is critical for the treatment and control of the epidemic. Social media data have gained great popularity and widespread application in various research domains. The viral-related infodemic outbreaks have occurred alongside the COVID-19 outbreak. This paper aims to discover trustworthy sources of social media data to improve the prediction performance of severe and critical COVID-19 patients. The innovation of this paper lies in three aspects. First, it builds an improved prediction model based on machine learning. This model helps predict the number of severe and critical COVID-19 patients on a specific urban or regional scale. The effectiveness of the prediction model, shown as accuracy and satisfactory robustness, is verified by a case study of the lockdown in Hubei Province. Second, it finds the transition path of the impact of social media data for predicting the number of severe and critical COVID-19 patients. Third, this paper provides a promising and powerful model for COVID-19 prevention and control. The prediction model can help medical organizations to realize a prediction of COVID-19 severe and critical patients in multi-stage with lead time in specific areas. This model can guide the Centers for Disease Control and Prevention and other clinic institutions to expand the monitoring channels and research methods concerning COVID-19 by using web-based social media data. The model can also facilitate optimal scheduling of medical resources as well as prevention and control policy formulation.
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COVID-19 , Medios de Comunicación Sociales , COVID-19/epidemiología , Control de Enfermedades Transmisibles , Humanos , Infodemia , SARS-CoV-2 , Estados UnidosRESUMEN
Anxiety disorders are a series of mental disorders characterized by anxiety and fear, but the molecular basis of these disorders remains unclear. In the present study, we find that the global Slack KO male mice exhibit anxious behaviors, whereas the Slack Y777H male mice manifest anxiolytic behaviors. The expression of Slack channels is rich in basolateral amygdala (BLA) glutamatergic neurons and downregulated in chronic corticosterone-treated mice. In addition, electrophysiological data show enhanced excitability of BLA glutamatergic neurons in the Slack KO mice and decreased excitability of these neurons in the Slack Y777H mice. Furthermore, the Slack channel deletion in BLA glutamatergic neurons is sufficient to result in enhanced avoidance behaviors, whereas Kcnt1 gene expression in the BLA or BLA-ventral hippocampus (vHPC) glutamatergic projections reverses anxious behaviors of the Slack KO mice. Our study identifies the role of the Slack channel in controlling anxious behaviors by decreasing the excitability of BLA-vHPC glutamatergic projections, providing a potential target for anxiolytic therapies.SIGNIFICANCE STATEMENT Anxiety disorders are a series of mental disorders characterized by anxiety and fear, but the molecular basis of these disorders remains unclear. Here, we examined the behaviors of loss- and gain-of-function of Slack channel mice in elevated plus maze and open field tests and found the anxiolytic role of the Slack channel. By altering the Slack channel expression in the specific neuronal circuit, we demonstrated that the Slack channel played its anxiolytic role by decreasing the excitability of BLA-vHPC glutamatergic projections. Our data reveal the role of the Slack channel in the regulation of anxiety, which may provide a potential molecular target for anxiolytic therapies.
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Ansiedad , Complejo Nuclear Basolateral , Proteínas del Tejido Nervioso , Canales de potasio activados por Sodio , Animales , Ansiedad/metabolismo , Complejo Nuclear Basolateral/metabolismo , Hipocampo/metabolismo , Masculino , Ratones , Ratones Noqueados , Proteínas del Tejido Nervioso/metabolismo , Canales de potasio activados por Sodio/metabolismoRESUMEN
Acidic organic wastewater with toxic and carcinogenic properties has long been a tough problem for industrial treatment. To break down the barrier of poor acidic stability as well as the high cost of materials and reactors, a novel strategy of utilizing a high-performance and acid-tolerant TiO2/carbon electrocatalytic membrane (TiO2/CEM) for acidic organic wastewater treatment was proposed. Study results showed that high concentrations of organic pollutants were separated and degraded by the synergistic effects of membrane separation and electrocatalytic oxidation simultaneously on the TiO2/CEM. The great treatment performance with membrane removal efficiency of >97.4% was obtained by treating acidic rhodamine B (RhB) dye wastewater under optimized applied voltage. Treatment experiments under various pH and electrochemical tests demonstrated the outstanding acid-tolerant property and long service life of TiO2/CEM. Furthermore, the feasibility of TiO2/CEM for industrial application and various acidic organic wastewater treatment was proved by treating typical organic pollutants (phenol, tetracycline and oil) under high acidic circumstances.
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Contaminantes Ambientales , Contaminantes Químicos del Agua , Purificación del Agua , Carbono , Titanio/química , Aguas Residuales , Contaminantes Químicos del Agua/química , Purificación del Agua/métodosRESUMEN
BACKGROUND: The current process used to diagnose cognitive impairment in patients with Parkinson's disease (PD) is unsatisfactory. More and more researchers had introduced machine learning into this field in recent years. This study explored the application of machine learning and its diagnostic performance in this field. METHODS: Since Parkinson's concurrent cognitive impairment is currently divided into different periods, most studies focus on the prodromal or early stages of Parkinson's cognitive impairment, and a few focuses on the dementia stage of Parkinson's. To ensure comprehensiveness, and model stability, we included patients with Parkinson's concurrent cognitive impairment in different periods who met the nadir criteria. A comprehensive literature search was carried out of the PubMed, Cochrane, Embase, and Web of Science databases. We used Prediction Model Risk of Bias Assessment Tool (PROBAST) to assess the risk of bias for the machine learning models covered by the included original studies. The outcome indicators included the concordance-index (C-index), sensitivity, and specificity. A meta-analysis using the random-effects model was conducted to determine the C-index, and a double variable mixed-effects model was used to determine the sensitivity and specificity. The meta-analysis in this article was completed in STATA. RESULTS: A total of 32 articles, comprising 10,778 patients and 51 prognostic models [summary c-statistic: 0.857, 95% confidence interval (CI) (0.842-0.873)], met the selection criteria and were included in this analysis. The total sensitivity and specificity of all models were 0.77 (95% CI: 0.72-0.81) and 0.83 (95% CI: 0.80-0.85), respectively, and those of the testing test were 0.85 (95% CI: 0.79-0.89), and 0.74 (95% CI: 0.70-0.78), respectively. A large part of the model showed a high risk of bias mainly because the study design was almost retrospective investigation. CONCLUSIONS: This study constitutes a detailed mapping and assessment of the machine learning for prediction in PD patients with cognitive decline, which may provide stronger discriminative performance and can be used as a potential tool for early diagnosis.
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Disfunción Cognitiva , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico , Estudios Retrospectivos , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/etiología , Sensibilidad y Especificidad , PronósticoRESUMEN
BACKGROUND: Postoperative nausea and vomiting (PONV) as a clinically most common postoperative complication requires multimodal antiemetic medications targeting at a wide range of neurotransmitter pathways. Lacking of neurobiological mechanism makes this 'big little problem' still unresolved. We aim to investigate whether gut-vagus-brain reflex generally considered as one of four typical emetic neuronal pathways might be the primary mediator of PONV. METHODS: Three thousand two hundred twenty-three patients who underwent vagus nerve trunk resection (esophagectomy and gastrectomy) and non-vagotomy surgery (hepatectomy, pulmonary lobectomy and colorectomy) from December 2016 to January 2019 were enrolled. Thirty cases of gastrectomy with selective resection on the gastric branch of vagus nerve were also recruited. Nausea and intensity of vomiting was recorded within 24 h after the operation. RESULTS: PONV occurred in 11.9% of 1187 patients who underwent vagus nerve trunk resection and 28.7% of 2036 non-vagotomy patients respectively. Propensity score matching showed that vagotomy surgeries accounted for 19.9% of the whole PONV incidence, much less than that observed in the non-PONV group (35.1%, P < 0.01). Multivariate logistic regression result revealed that vagotomy was one of underlying factor that significantly involved in PONV (OR = 0.302, 95% CI, 0.237-0.386). Nausea was reported in 5.9% ~ 8.6% vagotomy and 12 ~ 17% non-vagotomy patients. Most vomiting were mild, being approximately 3% in vagotomy and 8 ~ 13% in non-vagotomy patients, while sever vomiting was much less experienced. Furthermore, lower PONV occurrence (10%) was also observed in gastrectomy undergoing selective vagotomy. CONCLUSION: Patients undergoing surgeries with vagotomy developed less PONV, suggesting that vagus nerve dependent gut-brain signaling might mainly contribute to PONV.
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Analgesia/métodos , Eje Cerebro-Intestino/efectos de los fármacos , Encéfalo/efectos de los fármacos , Náusea y Vómito Posoperatorios/epidemiología , Nervio Vago/efectos de los fármacos , Nervio Vago/cirugía , Encéfalo/fisiopatología , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Vías Nerviosas/efectos de los fármacos , Reflejo/efectos de los fármacosRESUMEN
BACKGROUND: The mechanisms underlying cognitive impairments induced by systemic inflammation remain unclear. Increasing evidence has suggested that parvalbumin (PV) interneurons play an important role in regulating cognitive behaviors and its dysfunction is implicated in many neurological disorders. Thus, the present study was aimed to detect whether the destruction of PV interneurons mediates cognitive impairment associated with systemic inflammation. METHODS: Male wild-type C57BL/6J mice (12-14 weeks old) received lipopolysaccharide (LPS 2 mg/kg i.p.) injection to establish the systemic inflammation model. For the suppression of microglial activation, minocycline (50 mg/kg i.p.) was applied. Animal behavior tests were conducted on day 3 post-LPS injection including the open field test, fear conditioning test and Y maze test. The PV expression in hippocampus was detected by Western blot and immunofluorescence. The number of perisomatic boutons around the NeuN-positive cells and microglia in hippocampus was detected by immunofluorescence. RESULTS: LPS induced hippocampus-dependent memory and working memory impairment, coinciding with decreased PV expression, reduced perisomatic boutons around the NeuN-positive cells and activated microglia in the hippocampus. Notably, the treatment of minocycline suppressed the microglial activation and rescued the PV expression as well as the perisomatic boutons around the NeuN-positive cells in the hippocampus, contributing to improved cognitive function. CONCLUSION: Our study suggests that the dysfunction of parvalbumin interneurons mediated by microglia plays a key role in LPS-induced cognitive impairments, which may serve a therapeutic strategy for cognitive disorders associated with systemic inflammation.