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Grafted biopolymer binders are demonstrated to improve the processability and cycling stability of the silicon (Si) nanoparticle anodes. However, there is little systematical exploration regarding the relationship between grafting density and performance of grafted binder for Si anodes, especially when Si particles exceed the critical breaking size. Herein, a series of guar gum grafted polyacrylamide (GP) binders with different grafting densities are designed and prepared to determine the optimal grafting density for maximizing the electrochemical performance of Si submicroparticle (SiSMP) anodes. Among various GP binders, GP5 with recommended grafting density demonstrates the strongest adhesion strength, best mechanical properties, and highest intrinsic ionic conductivity. These characteristics enable the SiSMP electrodes to sustain the electrode integrity and accelerate lithium-ion transport kinetics during cycling, resulting in high capacity and stable cyclability. The superior role of GP5 binder in enabling robust structure and stable interface of SiSMP electrodes is revealed through the PeakForce atomic force microscopy and in situ differential electrochemical mass spectrometry. Furthermore, the stable cyclabilities of high-loading SiSMP@GP5 electrode with ultralow GP5 content (1 wt%) at high areal capacity as well as the good cyclability of Ah-level LiNi0.8Co0.1Mn0.1O2/SiSMP@GP5 pouch cell strongly confirms the practical viability of the GP5 binder.
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PURPOSE: This study aimed to comprehensively explore the different metabolic connectivity topological changes in MTLE and NTLE, as well as their association with surgical outcomes. METHODS: This study enrolled a cohort of patients with intractable MTLE and NTLE. Each individual's metabolic connectome, as determined by Kullback-Leibler divergence similarity estimation for the [18F]FDG PET image, was employed to conduct a comprehensive analysis of the cerebral metabolic network. Alterations in network connectivity were assessed by extracting and evaluating the strength of edge and weighted connectivity. By utilizing these two connectivity strength metrics with the cerebellum, we explored the network properties of connectivity and its association with prognosis in surgical patients. RESULTS: Both MTLE and NTLE patients exhibited substantial alterations in the connectivity of the metabolic network at the edge and nodal levels (p < 0.01, FDR corrected). The key disparity between MTLE and NTLE was observed in the cerebellum. In MTLE, there was a predominance of increased connectivity strength in the cerebellum. Whereas, a decrease in cerebellar connectivity was identified in NTLE. It was found that in MTLE, higher edge connectivity and weighted connectivity strength in the contralateral cerebellar hemisphere correlated with improved surgical outcomes. Conversely, in NTLE, a higher edge metabolic connectivity strength in the ipsilateral cerebellar hemisphere suggested a worse surgical prognosis. CONCLUSION: The cerebellum exhibits distinct topological characteristics in the metabolic networks between MTLE and NTLE. The hyper- or hypo-metabolic connectivity in the cerebellum may be a prognostic biomarker of surgical prognosis, which might aid in therapeutic decision-making for TLE individuals.
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Cerebelo , Conectoma , Humanos , Femenino , Masculino , Cerebelo/diagnóstico por imagen , Cerebelo/metabolismo , Cerebelo/cirugía , Pronóstico , Adulto , Persona de Mediana Edad , Tomografía de Emisión de Positrones , Fluorodesoxiglucosa F18RESUMEN
N-methyl-D-aspartate receptors (NMDARs) play vital roles in normal brain functions (i.e., learning, memory, and neuronal development) and various neuropathological conditions, such as epilepsy, autism, Parkinson's disease, Alzheimer's disease, and traumatic brain injury. Endogenous neuroactive steroids such as 24(S)-hydroxycholesterol (24(S)-HC) have been shown to influence NMDAR activity, and positive allosteric modulators (PAMs) derived from 24(S)-hydroxycholesterol scaffold can also enhance NMDAR function. This study describes the structural determinants and mechanism of action for 24(S)-hydroxycholesterol and two novel synthetic analogs (SGE-550 and SGE-301) on NMDAR function. We also show that these agents can mitigate the altered function caused by a set of loss-of-function missense variants in NMDAR GluN subunit-encoding GRIN genes associated with neurological and neuropsychiatric disorders. We anticipate that the evaluation of novel neuroactive steroid NMDAR PAMs may catalyze the development of new treatment strategies for GRIN-related neuropsychiatric conditions.
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Enfermedad de Alzheimer , Enfermedades del Sistema Nervioso , Neuroesteroides , Humanos , Receptores de N-Metil-D-Aspartato/metabolismo , Neuroesteroides/farmacología , Neuroesteroides/uso terapéutico , Hidroxicolesteroles/farmacología , Hidroxicolesteroles/uso terapéutico , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Enfermedades del Sistema Nervioso/genética , Enfermedad de Alzheimer/tratamiento farmacológico , Esteroides/farmacología , Regulación Alostérica/fisiologíaRESUMEN
Objective To investigate the relationship between cerebrovascular reactivity (CVR) and emotional disorders in the patients undergoing continuous hemodialysis for end-stage renal disease (ESRD).Methods The clinical data of the ESRD patients undergoing continuous hemodialysis were collected.Anxiety and depression of the patients were assessed by the Hamilton anxiety scale (HAMA) and Beck depression inventory,respectively.The cerebral hemodynamic changes during the breath holding test were monitored by transcranial Doppler sonography,and the breath-holding index (BHI) was calculated.The BHI≥0.69 and BHI<0.69 indicate normal CVR and abnormal CVR,respectively.Binary Logistic regression was employed to analyze the factors affecting the depressive state of ESRD patients.Results The group with abnormal CVR exhibited higher total cholesterol level (P=0.010),low density lipoprotein level (P=0.006),and incidence of depression (P=0.012) than the group with normal CVR.Compared with the non-depression group,the depression group displayed prolonged disease course (P=0.039),reduced body mass index (P=0.048),elevated HAMA score (P=0.001),increased incidence of anxiety (P<0.001),decreased BHI (P=0.015),and increased incidence of abnormal CVR (P=0.012).Binary Logistic regression analysis indicated anxiety as a contributing factor (OR=22.915,95%CI=2.653-197.956,P=0.004) and abnormal CVR as a risk factor (OR=0.074,95%CI=0.008-0.730,P=0.026) for depression.Conclusion Impaired CVR could pose a risk for depression in the patients with ESRD.
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Depresión , Fallo Renal Crónico , Humanos , Masculino , Femenino , Persona de Mediana Edad , Fallo Renal Crónico/fisiopatología , Fallo Renal Crónico/complicaciones , Depresión/fisiopatología , Adulto , Diálisis Renal , Circulación Cerebrovascular/fisiología , AncianoRESUMEN
N-methyl-D-aspartate receptors (NMDAR), ionotropic glutamate receptors, mediate a slow component of excitatory synaptic transmission in the central nervous system and play a key role in normal brain function and development. Genetic variations in GRIN genes encoding NMDAR subunits that alter the receptor's functional characteristics are associated with a wide range of neurological and neuropsychiatric conditions. Pathological GRIN variants located in the M2 re-entrant loop lining the channel pore cause significant functional changes, the most consequential alteration being a reduction in voltage-dependent Mg2+ inhibition. Voltage-dependent Mg2+ block is a unique feature of NMDAR biology whereby channel activation requires both ligand binding and postsynaptic membrane depolarization. Thus, loss of NMDAR Mg2+ block will have a profound impact on synaptic function and plasticity. Here, we choose 11 missense variants within the GRIN1, GRIN2A, and GRIN2B genes that alter residues located in the M2 loop and significantly reduce Mg2+ inhibition. Each variant was evaluated for tolerance to genetic variation using the 3-dimensional structure and assessed for functional rescue pharmacology via electrophysiological recordings. Three FDA-approved NMDAR drugs-memantine, dextromethorphan, and ketamine-were chosen based on their ability to bind near the M2 re-entrant loop, potentially rectifying dysregulated NMDAR function by supplementing the reduced voltage-dependent Mg2+ block. These results provide insight of structural determinants of FDA-approved NMDAR drugs at their binding sites in the channel pore and may further define conditions necessary for the use of such agents as potential rescue pharmacology.
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BACKGROUND: POLR3-related leukodystrophy is a group of rare neurodegenerative disorders characterized by degeneration of the white matter with different combinations of major clinical features. CASE: An 18-year-old lady was admitted for no menstruation since childhood. She gradually developed slight symptoms, such as choking after drinking water and unsteady walking in the last 2 years. Furthermore, her test scores and response capability were far lower than that of her peers. Physical examination revealed her to be of a slightly short stature, with stiff expressions and bilateral breast enlargement. She revealed clumsy movements when examined for ataxia, with an SARA score of 9. FINDINGS: The laboratory data revealed a decreased level of estradiol, FSH, and LH, with a MoCA score of 7. Conventional karyotype analysis revealed a 46 XX 9qh + karyotype. Ultrasound indicated primordial uterus (19 × 11 × 10 mm). Brain MRI showed bilateral cerebral hemisphere myelin dysplasia, brain atrophy, thin corpus callosum, and small pituitary gland with uneven reinforcement and enlarged ventricles. Exome sequencing exhibited two missense mutations in the POLR3A gene (c.3013C > T and c.1757C > T), which were inherited from her mother and father, respectively. CONCLUSION: Collectively, we identified novel compound heterozygous mutations of the POLR3A gene that caused POLR3A-related hypomyelinating leukodystrophy with hypogonadism in the patient combined with the clinical presentation, MRI brain pattern, and medical exome sequencing. TEACHING POINTS: The complexity of clinical phenotypes and heterogeneity of genotypes raise new challenges in genetic diagnoses. This study will further aid our understanding of POLR3A-related leukodystrophy and promote further analysis of phenotype-genotype correlations of related diseases.
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Enfermedades Desmielinizantes , Enfermedades Desmielinizantes del Sistema Nervioso Central Hereditarias , Humanos , Femenino , Enfermedades Desmielinizantes del Sistema Nervioso Central Hereditarias/diagnóstico por imagen , Enfermedades Desmielinizantes del Sistema Nervioso Central Hereditarias/genética , Mutación , Pueblos del Este de Asia , Mutación Missense , ARN Polimerasa III/genéticaRESUMEN
OBJECTIVES: To investigate the influencing factors for the quality of bowel preparation before colonoscopy in children and the association of the interval from the last administration of laxative to the start of colonoscopy (shortly referred to as waiting time) with the quality of bowel preparation. METHODS: A retrospective analysis was performed for the children who were admitted to the Department of Gastroenterology, Children's Hospital of Nanjing Medical University, from January to November 2020, and received bowel preparation with polyethylene glycol electrolyte powder combined with diet control before colonoscopy. According to the score of Boston bowel preparation scale, they were divided into two groups: adequate bowel preparation group (n=337) and inadequate bowel preparation group (n=30). Related data were collected from the children in both groups, including general information, possible influencing factors for the quality of bowel preparation, adverse reactions associated with bowel preparation, duration of colonoscopy, and postoperative diagnosis. Univariate and multivariate analyses were used to explore the influencing factors for the quality of bowel preparation. RESULTS: The univariate analysis showed that age, body weight, and waiting time were associated with inadequate bowel preparation (P<0.05). The multivariate analysis showed that older age (OR=2.155, 95%CI: 1.087-4.273, P=0.028) and longer waiting time (OR=1.559, 95% CI: 1.191-2.041, P=0.001) were independent risk factors for inadequate bowel preparation. The receiver operating characteristic (ROC) curve analysis showed that the cut-off value of waiting time was 5.5 hours in determining whether bowel preparation was adequate or not, with a sensitivity of 90.0%, a specificity of 50.7%, and an area under the ROC curve of 0.708. After grouping based on waiting time, it was found that the incidence rate of inadequate bowel preparation in the ≥5.5 hours group was significantly higher than that in the <5.5 hours group [14.0% (27/193) vs 1.7% (3/174), P<0.001]. CONCLUSIONS: For children who use polyethylene glycol electrolyte powder combined with diet control for bowel preparation, older age is an independent risk factor for inadequate bowel preparation before colonoscopy, which may be associated with an insufficient dose of polyethylene glycol in older children. Longer waiting time is also an independent risk factor for inadequate bowel preparation, and it is recommended that the waiting time should not exceed 5.5 hours.
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Catárticos , Colonoscopía , Niño , Dieta , Electrólitos , Humanos , Polietilenglicoles/efectos adversos , Polvos , Estudios RetrospectivosRESUMEN
NMDA receptors play crucial roles in excitatory synaptic transmission. Rare variants in GRIN2A encoding the GluN2A subunit are associated with a spectrum of disorders, ranging from mild speech and language delay to intractable neurodevelopmental disorders, including but not limited to developmental and epileptic encephalopathy. A de novo missense variant, p.Ser644Gly, was identified in a child with this disorder, and Grin2a knock-in mice were generated to model and extend understanding of this intractable childhood disease. Homozygous and heterozygous mutant mice exhibited altered hippocampal morphology at 2 weeks of age, and all homozygotes exhibited lethal tonic-clonic seizures by mid-third week. Heterozygous adults displayed susceptibility to induced generalized seizures, hyperactivity, repetitive and reduced anxiety behaviours, plus several unexpected features, including significant resistance to electrically-induced limbic seizures and to pentylenetetrazole induced tonic-clonic seizures. Multielectrode recordings of neuronal networks revealed hyperexcitability and altered bursting and synchronicity. In heterologous cells, mutant receptors had enhanced NMDA receptor agonist potency and slow deactivation following rapid removal of glutamate, as occurs at synapses. NMDA receptor-mediated synaptic currents in heterozygous hippocampal slices also showed a prolonged deactivation time course. Standard anti-epileptic drug monotherapy was ineffective in the patient. Introduction of NMDA receptor antagonists was correlated with a decrease in seizure burden. Chronic treatment of homozygous mouse pups with NMDA receptor antagonists significantly delayed the onset of lethal seizures but did not prevent them. These studies illustrate the power of using multiple experimental modalities to model and test therapies for severe neurodevelopmental disorders, while revealing significant biological complexities associated with GRIN2A developmental and epileptic encephalopathy.
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Modelos Animales de Enfermedad , Epilepsia Generalizada/tratamiento farmacológico , Epilepsia Generalizada/genética , Antagonistas de Aminoácidos Excitadores/uso terapéutico , Receptores de N-Metil-D-Aspartato/genética , Animales , Dextrometorfano/uso terapéutico , Epilepsia Generalizada/patología , Técnicas de Sustitución del Gen , Humanos , Lactante , Masculino , Memantina/uso terapéutico , Ratones , Trastornos del Neurodesarrollo/genética , Trastornos del Neurodesarrollo/patologíaRESUMEN
PURPOSE: Abnormal neurogenesis in the hippocampus after status epilepticus (SE) has been suggested as a key pathogeny of temporal lobe epilepsy. This study aimed to investigate the effect of deep brain stimulation of the anterior thalamic nucleus (ANT-DBS) on hippocampal neurogenesis in LiCl-pilocarpine-induced epileptic rats and to analyze its relationship with postoperative spontaneous recurrent seizures (SRS) and anxiety. METHOD: SE was induced by a systemic LiCl-pilocarpine injection in adult male rats. Rats in the DBS group underwent ANT-DBS immediately after successful SE induction. SRS was only recorded during the chronic stage. An elevated plus maze was used to evaluate the level of anxiety in rats 7, 28, and 60 days after SE onset. After the elevated plus-maze experiment, rats were sacrificed under anesthesia in order to evaluate hippocampal neurogenesis. Doublecortin (DCX) was used as a marker for neurogenesis. RESULTS: During the chronic stage, SRS in rats in the DBS group were significantly decreased. The level of anxiety was increased significantly in rats in the DBS group 28 days after SE, while no significant differences in anxiety levels were found 7 and 60 days after SE. The number of DCX-positive cells in the hippocampus was significantly increased 7 days after SE and was significantly decreased 60 days after SE in all rats in which SE was induced. However, the number of DCX-positive cells in the DBS group was significantly lower than that in the other groups 28 days after SE. CONCLUSIONS: ANT-DBS may suppress SRS and increase the postoperative anxiety of epileptic rats by influencing hippocampal neurogenesis.
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Estimulación Encefálica Profunda/métodos , Epilepsia/fisiopatología , Hipocampo/fisiología , Cloruro de Litio/toxicidad , Neurogénesis/fisiología , Pilocarpina/toxicidad , Animales , Núcleos Talámicos Anteriores/efectos de los fármacos , Núcleos Talámicos Anteriores/fisiología , Estimulación Encefálica Profunda/efectos adversos , Proteína Doblecortina , Epilepsia/inducido químicamente , Epilepsia/terapia , Hipocampo/citología , Masculino , Neurogénesis/efectos de los fármacos , Ratas , Ratas Sprague-DawleyRESUMEN
N-methyl-D-aspartate receptors (NMDARs) mediate slow excitatory postsynaptic transmission in the central nervous system, thereby exerting a critical role in neuronal development and brain function. Rare genetic variants in the GRIN genes encoding NMDAR subunits segregated with neurological disorders. Here, we summarize the clinical presentations for 18 patients harboring 12 de novo missense variants in GRIN1, GRIN2A, and GRIN2B that alter residues in the M2 re-entrant loop, a region that lines the pore and is intolerant to missense variation. These de novo variants were identified in children with a set of neurological and neuropsychiatric conditions. Evaluation of the receptor cell surface expression, pharmacological properties, and biophysical characteristics show that these variants can have modest changes in agonist potency, proton inhibition, and surface expression. However, voltage-dependent magnesium inhibition is significantly reduced in all variants. The NMDARs hosting a single copy of a mutant subunit showed a dominant reduction in magnesium inhibition for some variants. These variant NMDARs also show reduced calcium permeability and single-channel conductance, as well as altered open probability. The data suggest that M2 missense variants increase NMDAR charge transfer in addition to varied and complex influences on NMDAR functional properties, which may underlie the patients' phenotypes.
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Mutación Missense , Proteínas del Tejido Nervioso/genética , Enfermedades del Sistema Nervioso/genética , Receptores de N-Metil-D-Aspartato/genética , Animales , Niño , Modelos Animales de Enfermedad , Femenino , Células HEK293 , Humanos , Masculino , Modelos Moleculares , Proteínas del Tejido Nervioso/química , Fenotipo , Conformación Proteica , Receptores de N-Metil-D-Aspartato/química , Xenopus laevisRESUMEN
BACKGROUND: Prior studies have shown an association between high blood urea nitrogen (BUN) and an elevated risk of mortality in heart failure patients, but data on the prognostic significance of BUN and other markers of kidney function in acute ischemic stroke (AIS) patients are sparse.MethodsâandâResults:A total of 3,355 AIS patients were enrolled from December 2013 to May 2014, across 22 hospitals. Admission BUN was divided into quartiles (Q1, <4.39 mmol/L; Q2, ≥4.39 and <5.40 mmol/L; Q3, ≥5.40 and <6.70 mmol/L and Q4, ≥6.70 mmol/L) and estimated glomerular filtration rate (eGFR), creatinine (Cr) and BUN/Cr were also categorized. Cox proportional hazard and logistic regression models were used to estimate the effect of BUN, eGFR, Cr and BUN/Cr on all-cause in-hospital mortality and poor outcome on discharge (modified Rankin Scale score ≥3) in AIS patients. During hospitalization, 120 patients (3.6%) died from all causes and 1,287 (38.4%) had poor outcome at discharge. BUN was independently associated with all-cause in-hospital mortality (adjusted HR for Q4 vs. Q1, 3.75; 95% CI: 1.53-9.21; P-trend=0.003) but not poor outcome at discharge (P-trend=0.229). No significant association was found, however, between reduced eGFR, increased Cr and BUN/Cr and all-cause in-hospital mortality and poor outcome at discharge (all P-trend ≥0.169). CONCLUSIONS: Increased BUN at admission is a significant prognostic factor associated with in-hospital mortality in AIS patients, but not with poor discharge outcome.
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Nitrógeno de la Urea Sanguínea , Accidente Cerebrovascular/sangre , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Isquemia Encefálica/sangre , Isquemia Encefálica/diagnóstico , Creatinina/sangre , Femenino , Tasa de Filtración Glomerular , Mortalidad Hospitalaria , Humanos , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/mortalidadRESUMEN
Malformations of cortical development (MCD) are critical brain development disorders associated with varied abnormalities in both anatomic structures and neural functioning. It is also a very common etiology to the epilepsy, in which the alteration on excitability of cortical neurons is hypothesized as one of important causes to the epileptic seizures. Due to the key role in regulating neuron firing properties, the plasticity of axon initial segment (AIS) was investigated in present study to further determine the relation between MCD and epilepsy. Our results showed a prolonged decrease in the length of AIS occurred in MCD animal models. Besides, the AIS was also found greatly shortened in MCD models during the acute, but not chronic phase of status epileptics compared with intact controls. Our findings of identification of AIS plasticity in MCD animal models and its hypersensitivity to status epilepsy are significant in furthering our understanding of the pathophysiological mechanisms involved in this disorder.
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Segmento Inicial del Axón/efectos de los fármacos , Hipersensibilidad/etiología , Malformaciones del Desarrollo Cortical/complicaciones , Neuronas/efectos de los fármacos , Estado Epiléptico/complicaciones , Animales , Modelos Animales de Enfermedad , Femenino , Plasticidad Neuronal/efectos de los fármacos , Plasticidad Neuronal/fisiología , Neuronas/fisiología , Pilocarpina/farmacología , Ratas Sprague-Dawley , Estado Epiléptico/inducido químicamenteRESUMEN
Background: Orthostatic intolerance (OI) is the inability to tolerate orthostatic stress during any postural change. The etiology of OI varies, and methods to obtain a specific diagnosis and plan appropriate treatment are important. The tools available within the Chinese context to swiftly identify orthostatic intolerance syndrome (OIS) are currently limited. Methods: Patients with OI symptoms were included in this study and categorized into two groups based on the results of the supine-to-stand test. Those with abnormal test results were assigned to the OIS group, while those with normal test results were placed in the non-OIS group. We evaluated the internal consistency and predictive value of the Chinese Orthostatic Discriminant and Severity Scale (ODSS) by comparing patients' scores with their physiological measurements collected during orthostatic stress tests and the results of other available questionnaires, including the orthostatic Symptom Questionnaire and Orthostatic Grading Scale (OGS). Results: Patients with OIS scored significantly higher on all three questionnaires and showed significant differences in autonomic responses during orthostatic stress tests compared with non-OIS patients. Receiver operating characteristic curve analysis showed that the orthostatic score from the ODSS had moderate predictive value for the supine test (area under the curve [AUC] = 0.754). Further subgroup analysis revealed that the orthostatic score from the ODSS had uniquely high specificity and sensitivity for identifying patients with orthostatic hypotension with abnormal cerebral blood flow (OH-U, AUC = 0.919). Conclusions: We conclude that the Chinese version of the ODSS has sufficient reliability and validity to distinguish patients with OIS and could possibly be used as a diagnostic tool for OH-U patients. Thus, the Chinese ODSS offers a beneficial screening tool for quickly assessing whether patients have OIS that requires further clinical assessment.
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Metal exposure is associated with vascular endothelial inflammation, an early pathological phenotype of atherosclerotic cardiovascular events. However, the underlying mechanism linking exposure, metabolic changes, and outcomes remains unclear. We aimed to investigate the metabolic changes underlying the associations of chronic exposure to metal mixtures with vascular endothelial inflammation. We recruited 960 adults aged 20-75 years from residential areas surrounding rivers near abandoned lead-zinc mine and classified them into river area and non-river area exposure groups. Urine levels of 25 metals, Framingham risk score (FRS), and serum concentrations of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), as biomarkers of vascular endothelial inflammation, were assessed. A "meet-in-the-middle" approach was applied to identify causal intermediate metabolites and metabolic pathways linking metal exposure to vascular endothelial inflammation in representative metabolic samples from 64 participants. Compared to the non-river area exposure group, the river area exposure group had significantly greater urine concentrations of chromium, copper, cadmium, and lead; lower urine concentrations of selenium; elevated FRS; and increased concentrations of ICAM-1 and VCAM-1. In total, 38 differentially abundant metabolites were identified between the river area and non-river area exposure groups. Among them, 25 metabolites were significantly associated with FRS, 8 metabolites with ICAM-1 expression, and 10 metabolites with VCAM-1 expression. Furthermore, fructose, ornithine, alpha-ketoglutaric acid, urea, and cytidine monophosphate, are potential mediators of the relationship between metal exposure and vascular endothelial inflammation. Additionally, the metabolic changes underlying these effects included changes in arginine and proline metabolism, pyrimidine metabolism, starch and sucrose metabolism, galactose metabolism, arginine biosynthesis, and alanine, aspartate, and glutamate metabolism, suggesting the disturbance of amino acid metabolism, the tricarboxylic acid cycle, nucleotide metabolism, and glycolysis. Overall, our results reveal biomechanisms that may link chronic exposure to multiple metals with vascular endothelial inflammation and elevated cardiovascular risk.
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Exposición a Riesgos Ambientales , Inflamación , Molécula 1 de Adhesión Intercelular , Plomo , Minería , Ríos , Molécula 1 de Adhesión Celular Vascular , Zinc , Humanos , Persona de Mediana Edad , Adulto , Masculino , Femenino , Anciano , Plomo/sangre , Zinc/sangre , Exposición a Riesgos Ambientales/estadística & datos numéricos , Molécula 1 de Adhesión Intercelular/sangre , Molécula 1 de Adhesión Intercelular/metabolismo , Molécula 1 de Adhesión Celular Vascular/sangre , Adulto Joven , Biomarcadores/sangre , Biomarcadores/orina , Endotelio Vascular/metabolismo , Metales/orina , Metales/sangreRESUMEN
OBJECTIVES: To investigate the facial scan patterns during emotion recognition (ER) through the dynamic facial expression task and the awareness of social interference test (TASIT) using eye tracking (ET) technology, and to find some ET indicators that can accurately depict the ER process, which is a beneficial supplement to existing ER assessment tools. METHOD: Ninety-six patients with TLE and 88 healthy controls (HCs) were recruited. All participants watched the dynamic facial expression task and TASIT including a synchronized eye movement recording and recognized the emotion (anger, disgust, happiness, or sadness). The accuracy of ER was recorded. The first fixation time, first fixation duration, dwell time, and fixation count were selected and analyzed. RESULTS: TLE patients exhibited ER impairment especially for disgust (Z = - 3.391; p = 0.001) and sadness (Z = - 3.145; p = 0.002). TLE patients fixated less on the face, as evidenced by the reduced fixation count (Z = - 2.549; p = 0.011) of the face and a significant decrease in the fixation count rate (Z = - 1.993; p = 0.046). During the dynamic facial expression task, TLE patients focused less on the eyes, as evidenced by the decreased first fixation duration (Z = - 4.322; p = 0.000), dwell time (Z = - 4.083; p = 0.000), and fixation count (Z = - 3.699; p = 0.000) of the eyes. CONCLUSION: TLE patients had ER impairment, especially regarding negative emotions, which may be attributable to their reduced fixation on the eyes during ER, and the increased fixation on the mouth could be a compensatory effect to improve ER performance. Eye-tracking technology could provide the process indicators of ER, and is a valuable supplement to traditional ER assessment tasks.
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Emociones , Epilepsia del Lóbulo Temporal , Tecnología de Seguimiento Ocular , Expresión Facial , Fijación Ocular , Humanos , Masculino , Femenino , Adulto , Fijación Ocular/fisiología , Emociones/fisiología , Epilepsia del Lóbulo Temporal/fisiopatología , Epilepsia del Lóbulo Temporal/psicología , Persona de Mediana Edad , Reconocimiento Facial/fisiología , Adulto JovenRESUMEN
Micron-sized silicon oxide (SiOx) has been regarded as a promising anode material for new-generation lithium-ion batteries due to its high capacity and low cost. However, the distinct volume expansion during the repeated (de)lithiation process and poor conductivity can lead to structural collapse of the electrode and capacity fading. In this study, SiOx anode materials coated with TiO0.6N0.4 layers are fabricated by a facile solvothermal and thermal reduction technique. The TiO0.6N0.4 layers are homogeneously dispersed on SiOx particles and form an intimate contact. The TiO0.6N0.4 layers can enhance the conductivity and suppress volume expansion of the SiOx anode, which facilitate ion/electron transport and maintain the integrity of the overall electrode structure. The as-prepared SiOx-TiON-200 composites demonstrate a high reversible capacity of 854 mAh g-1 at 0.5 A g-1 with a mass loading of 2.0 mg cm-2 after 250 cycles. This surface modification technique could be extended to other anodes with low conductivity and large volume expansion for lithium-ion batteries.
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The large volume expansion hinders the commercial application of silicon oxide (SiOx) anodes in lithium-ion batteries. Recent studies show that binders play a vital role in mitigating the volume change of SiOx electrodes. Herein, we introduce the small molecule tannic acid (TA) with high branching into the linear poly(acrylic acid) (PAA) binder for SiOx anodes. The three-dimensional (3D) crosslinked network with multiple hydrogen bonds is formed by the incorporation of abundant hydroxyl groups with unique carboxyl groups, which increases the interfacial adhesive strength with SiOx particles. As a consequence, SiOx electrodes based on the PAA-TA binder show an excellent cycling performance with a high specific capacity of 1025 mA h g-1 at 500 mA g-1 after 250 cycles. Moreover, the SiOx||NCM811 full cell exhibits a reversible capacity of 143 mA h g-1 corresponding to 87.4% capacity retention after 100 cycles.
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The neuromuscular adverse events of immune checkpoint inhibitor (ICI) treatment include myositis, polymyalgia rheumatica, myocarditis, and myasthenia syndrome. We report a 47-year old female presenting with external ophthalmoplegia, generalized muscle weakness, and third-degree atrioventricular block 4 weeks after toripalimab treatment for metastatic thymoma. Creatine kinase was elevated to 25,200 U/l and cardiac troponin I to 2.796 ng/ml. Autoantibody profiling shows positive anti-ryanodine receptor and anti-acetylcholine receptor antibodies and negative myositis specific antibodies. Repetitive nerve stimulation did not reveal decrement of compound muscle action potentials. Pulse methylprednisolone and immunoglobulin infusion, together with temporary pacemaker insertion normalized her muscle enzyme levels and cardiac rhythm. This is the first report of overlaping neuromuscular adverse event of toripalimab.
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We report a case of genetic Creutzfeldt-Jakob disease (gCJD), which has a clinical phenotype that is highly similar to Fatal Family Insomnia (FFI) and has a triad of Wernicke-Korsakoff syndrome (WKs) at the developmental stage of the disease. The 51-year-old male complained of sleep disorder and imbalance who had visited five different hospitals before diagnosed. A neurological examination revealed a triad of symptoms characteristic for WKs such as gaze paresis, ataxia of limbs and trunk, and memory disturbances. The disturbances increased during the course of the disease, which led to the death of the patient 18 months after the appearance of the signs. Although the patient show negative in brain magnetic resonance imaging (MRI) and 14-3-3 protein of cerebrospinal fluid (CSF), he was finally diagnosed with gCJD disease by the human prion protein (PRNP) gene mutations.
Asunto(s)
Síndrome de Creutzfeldt-Jakob , Insomnio Familiar Fatal , Priones , Trastornos del Inicio y del Mantenimiento del Sueño , Síndrome de Creutzfeldt-Jakob/genética , Humanos , Insomnio Familiar Fatal/genética , Masculino , Persona de Mediana Edad , Fenotipo , Priones/genéticaRESUMEN
BACKGROUND: Remnant cholesterol makes great contribution to residual risk of cardiovascular disease, but population-based evidence on the relationship between remnant cholesterol and atherosclerosis is rare. Common carotid artery intima-media thickness (cIMT) is an imaging marker of subclinical atherosclerosis. We aimed to explore the association between remnant cholesterol levels and cIMT in patients with ischemic stroke. METHODS: One thousand four hundred ninety-six ischemic stroke patients with baseline serum lipids and carotid artery imaging data were included in this analysis. Fasting remnant cholesterol was calculated as total cholesterol minus HDL (high-density lipoprotein) cholesterol minus LDL (low-density lipoprotein) cholesterol. Abnormal cIMT was defined as mean cIMT and maximum cIMT value ≥1 mm. Logistic regression and restricted cubic spline models were used to assess the relationships between remnant cholesterol levels and abnormal cIMT. RESULTS: The multivariable-adjusted odds ratios (95% CIs) for the highest versus lowest quartile of remnant cholesterol were 2.06 (1.46-2.91) for abnormal mean cIMT and 1.70 (1.23-2.35) for abnormal maximum cIMT. There were linear associations between remnant cholesterol levels and both abnormal mean cIMT (P for linearity, <0.001) and abnormal maximum cIMT (P for linearity, 0.003). Moreover, the remnant cholesterol-cIMT association remained significant in the subsample of patients with optimal LDL cholesterol levels (n=179). CONCLUSIONS: Elevated fasting remnant cholesterol levels were positively associated with mean cIMT and maximum cIMT in patients with ischemic stroke, even in patients with optimal LDL cholesterol levels. Future prospective studies are needed to verify our findings and to assess the effect of remnant cholesterol-lowering interventions in patients with ischemic stroke.