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Throughout human life, the brain undergoes intricate structural changes that support cognition. A study in PLOS Biology introduces new avenues for depicting the trajectory of the brain morphometric connectome and its underlying genetic and molecular mechanisms.
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Encéfalo , Conectoma , Encéfalo/crecimiento & desarrollo , Encéfalo/anatomía & histología , Encéfalo/fisiología , Humanos , Longevidad/fisiología , Imagen por Resonancia Magnética/métodosRESUMEN
Parkinson's disease (PD) is a motor disorder resulting from dopaminergic neuron degeneration in the substantia nigra caused by age, genetics, and environment. The disease severely impacts a patient's quality of life and can even be life-threatening. The hyperpolarization-activated cyclic nucleotide-gated (HCN) channel is a member of the HCN1-4 gene family and is widely expressed in basal ganglia nuclei. The hyperpolarization-activated current mediated by the HCN channel has a distinct impact on neuronal excitability and rhythmic activity associated with PD pathogenesis, as it affects the firing activity, including both firing rate and firing pattern, of neurons in the basal ganglia nuclei. This review aims to comprehensively understand the characteristics of HCN channels by summarizing their regulatory role in neuronal firing activity of the basal ganglia nuclei. Furthermore, the distribution and characteristics of HCN channels in each nucleus of the basal ganglia group and their effect on PD symptoms through modulating neuronal electrical activity are discussed. Since the roles of the substantia nigra pars compacta and reticulata, as well as globus pallidus externus and internus, are distinct in the basal ganglia circuit, they are individually described. Lastly, this investigation briefly highlights that the HCN channel expressed on microglia plays a role in the pathological process of PD by affecting the neuroinflammatory response.
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Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/genética , Canales Regulados por Nucleótidos Cíclicos Activados por Hiperpolarización/genética , Calidad de Vida , Ganglios Basales/fisiología , Sustancia NegraRESUMEN
Transition metal oxides with the merits of high theoretical capacities, natural abundance, low cost, and environmental benignity have been regarded as a promising anodic material for lithium ion batteries (LIBs). However, the severe volume expansion upon cycling and poor conductivity limit their cycling stability and rate capability. To address this issue, NiO embedded and N-doped porous carbon nanorods (NiO@NCNR) and nanotubes (NiO@NCNT) are synthesized by the metal-catalyzed graphitization and nitridization of monocrystalline Ni(II)-triazole coordinated framework and Ni(II)/melamine mixture, respectively, and the following oxidation in air. When applied as an anodic material for LIBs, the NiO@NCNR and NiO@NCNT hybrids exhibit a decent capacity of 895/832 mA h g-1 at 100 mA g-1, high rate capability of 484/467 mA h g-1 at 5.0 A g-1, and good long-term cycling stability of 663/634 mA h g-1 at 600th cycle at 1 A g-1, which are much better than those of NiO@carbon black (CB) control sample (701, 214, and 223 mA h g-1). The remarkable electrochemical properties benefit from the advanced nanoarchitecture of NiO@NCNR and NiO@NCNT, which offers a length-controlled one-dimensional porous carbon nanoarchitecture for effective e-/Li+ transport, affords a flexible carbon skeleton for spatial confinement, and forms abundant nanocavities for stress buffering and structure reinforcement during discharge/charging processes. The rational structural design and synthesis may pave a way for exploring advanced metal oxide based anodic materials for next-generation LIBs.
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Carboxylesterase 1 (CES1), a member of the serine hydrolase superfamily, is involved in a wide range of xenobiotic and endogenous substances metabolic reactions in mammals. The inhibition of CES1 could not only alter the metabolism and disposition of related drugs, but also be benefit for treatment of metabolic disorders, such as obesity and fatty liver disease. In the present study, we aim to develop potential inhibitors of CES1 and reveal the preferred inhibitor structure from a series of synthetic pyrazolones (compounds 1-27). By in vitro high-throughput screening method, we found compounds 25 and 27 had non-competitive inhibition on CES1-mediated N-alkylated d-luciferin methyl ester (NLMe) hydrolysis, while compound 26 competitively inhibited CES1-mediated NLMe hydrolysis. Additionally, Compounds 25, 26 and 27 can inhibit CES1-mediated fluorescent probe hydrolysis in live HepG2 cells with effect. Besides, compounds 25, 26 and 27 could effectively inhibit the accumulation of lipid droplets in mouse adipocytes cells. These data not only provided study basis for the design of newly CES1 inhibitors. The present study not only provided the basis for the development of lead compounds for novel CES1 inhibitors with better performance, but also offered a new direction for the explore of candidate compounds for the treatment of hyperlipidemia and related diseases.
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Adipocitos , Hidrolasas de Éster Carboxílico , Inhibidores Enzimáticos , Pirazolonas , Humanos , Hidrolasas de Éster Carboxílico/metabolismo , Hidrolasas de Éster Carboxílico/antagonistas & inhibidores , Adipocitos/efectos de los fármacos , Adipocitos/metabolismo , Adipocitos/citología , Animales , Ratones , Pirazolonas/farmacología , Pirazolonas/química , Pirazolonas/síntesis química , Relación Estructura-Actividad , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/síntesis química , Estructura Molecular , Células Hep G2 , Diferenciación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Células 3T3-L1RESUMEN
Among the various non-precious metal catalysts that drive hydrogen evolution reactions (HERs) and dye-sensitized solar cells (DSSCs), transition metal selenides (TMSs) stand out due to their unique electronic properties and tunable morphology. Herein, the multicomponent selenide CuSe-Co3Se4@VSe2 was successfully synthesized by doping with metal element vanadium and selenization on the copper-cobalt carbonate hydroxide (CuCo-CH) template. CuSe-Co3Se4@VSe2 exhibited the dandelion-like cluster structure composed of hollow nanotubes doped with VSe2 nanoparticles. Due to the unique structure and the synergistic effect of various elements, CuSe-Co3Se4@VSe2 showed excellent alkaline HER and DSSC performances. The DSSC based on CuSe-Co3Se4@VSe2 exhibited an impressive power conversion efficiency (PCE) of 9.64 %, which was much higher than that of Pt (8.39 %). Besides, it possessed a low HER overpotential of 76 mV@10 mA cm-2 and a small Tafel slope of 88.9 mV dec-1 in 1.0 M KOH.
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Ultrawide-spectra-compatible camouflage materials are imperative for military science and national security due to the continuous advancement of various sophisticated multispectral detectors. However, ultrawide spectra camouflage still has challenges, as the spectral requirements for different bands are disparate and even conflicting. This work demonstrates an ultrawide spectra camouflage material compatible with visible (VIS, 400-800 nm), infrared (IR, 3-5 and 8-14 µm), and microwave (S-Ku bands, 2-12 GHz). The carbon nanotubes adsorbed on porous anodic alumina/aluminum flake powder (CNTs@PAA/AFP) material for ultrawide spectra camouflage is composed of bioinspired porous alumina surface layers for low visible reflection and aluminum flake powder substrate for low infrared emissivity, while the surface of the porous alumina layers is loaded with carbon nanotubes for microwave absorption. Compared with previous low-emissivity materials, CNTs@PAA/AFP has omnidirectional low reflectance (Ravg = 0.29) and high gray scale (72%) in the visible band. Further, it exhibits low emissivity (ε3-5µm = 0.15 and ε8-14µm = 0.18) in the dual infrared atmospheric window, which reduces the infrared lock-on range by 59.6%/49.8% in the mid/far-infrared band at high temperatures (573 K). The infrared camouflage performance calculated from the radiation temperature of CNTs@PAA/AFP coatings is enhanced to over 65%, which is at least 4 times greater than that of its substrate. In addition, the CNTs@PAA/AFP coating achieves high microwave absorption (RLmin = -42.46 dB) and an effective absorption bandwidth (EAB = 7.43 GHz) in the microwave band (S-Ku bands) due to the enhancement of interfacial polarization and conductive losses. This study may introduce new insight and feasible methods for multispectral manipulation, electromagnetic signal processing, and thermal management via bioinspired structural design and fabrication.
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BACKGROUND: The dural puncture epidural technique has been shown in some studies to improve the onset and quality of the initiation of labor analgesia compared with the standard epidural technique. However, few studies have investigated whether this technique confers advantages during the maintenance of analgesia. This randomized double-blinded controlled study compared dural puncture epidural analgesia with standard epidural analgesia when analgesia was maintained using programmed intermittent epidural boluses. METHODS: 400 parturients requesting epidural labor analgesia were randomized to have analgesia initiated with a test dose of 3 mL lidocaine 1.5% with epinephrine 15 µg, followed by 12 mL ropivacaine 0.15% mixed with sufentanil 0.5 µg/mL using the dural puncture epidural or the standard epidural technique. After confirming satisfactory analgesia, analgesia was maintained with ropivacaine 0.1% and sufentanil 0.5 µg/mL via programmed intermittent epidural boluses (fixed volume 8 mL, intervals 40 min). We compared local anesthetic consumption, pain scores, obstetric and neonatal outcomes and patient satisfaction. RESULTS: A total of 339 patients completed the study and had data analyzed. There were no differences between the dural puncture epidural and standard epidural groups in ropivacaine consumption (mean difference -0.724 mg, 95% CI of difference -1.450 to 0.001 mg, p=0.051), pain scores, time to first programmed intermittent epidural bolus, the number of programmed intermittent epidural boluses, the number of manual epidural boluses, obstetric outcome or neonatal outcome. Patient satisfaction scores were statistically higher in the dural puncture epidural group but the absolute difference in scores was small. CONCLUSION: Our findings suggest that when labor analgesia is maintained using the programmed intermittent epidural bolus method, there is no significant advantage to initiating analgesia using the dural puncture epidural compared with the standard epidural technique. TRIAL REGISTRATION NUMBER: ChiCTR2200062349.
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Background: Chinese nurses working with immense stress may have issues with burnout during COVID-19 regular prevention and control. There were a few studies investigating status of burnout and associated factors among Chinese nurses. However, the relationships remained unclear. Objectives: To investigate status and associated factors of nurses' burnout during COVID-19 regular prevention and control. Methods: 784 nurses completed questionnaires including demographics, Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, Insomnia Severity Index, Impact of Event Scale-revised, Perceived Social Support Scale, Connor-Davidson Resilience Scale, General Self-efficacy Scale and Maslach Burnout Inventory. Results: 310 (39.5%), 393 (50.1%) and 576 (73.5%) of respondents were at high risk of emotional exhaustion (EE), depersonalization (DP) and reduced personal accomplishment (PA). The risk of EE, DP and reduced PA were moderate, high and high. Nurses with intermediate and senior professional rank and title and worked >40 h every week had lower scores in EE. Those worked in low-risk department reported lower scores in PA. Anxiety, post-traumatic stress disorder (PTSD), self-efficacy and social support were influencing factors of EE and DP, while social support and resilience were associated factors of PA. Conclusion: Chinese nurses' burnout during COVID-19 regular prevention and control was serious. Professional rank and title, working unit, weekly working hours, anxiety, PTSD, self-efficacy, social support and resilience were associated factors of burnout.
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General anesthetic agents can impact brain function through interactions with neurons and their effects on glial cells. Oligodendrocytes perform essential roles in the central nervous system, including myelin sheath formation, axonal metabolism, and neuroplasticity regulation. They are particularly vulnerable to the effects of general anesthetic agents resulting in impaired proliferation, differentiation, and apoptosis. Neurologists are increasingly interested in the effects of general anesthetic agents on oligodendrocytes. These agents not only act on the surface receptors of oligodendrocytes to elicit neuroinflammation through modulation of signaling pathways, but also disrupt metabolic processes and alter the expression of genes involved in oligodendrocyte development and function. In this review, we summarize the effects of general anesthetic agents on oligodendrocytes. We anticipate that future research will continue to explore these effects and develop strategies to decrease the incidence of adverse reactions associated with the use of general anesthetic agents.
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Anestésicos Generales , Encéfalo , Oligodendroglía , Oligodendroglía/efectos de los fármacos , Animales , Encéfalo/efectos de los fármacos , Anestésicos Generales/efectos adversos , Anestésicos Generales/toxicidad , Síndromes de Neurotoxicidad/etiología , HumanosRESUMEN
DPP-IV inhibitors, which are close to the natural hypoglycemic pathway of human physiology and have few side effects, have been extensively employed in the management of type 2 diabetes mellitus (T2DM). However, there are currently no specific blood indicators that can indicate or predict a patient's suitability for DPP-IV inhibitors. In this study, based on the self-developed high-specificity fluorescent substrate glycyl-prolyl-N-butyl-4-amino-1, 8-naphthimide (GP-BAN), a detection method of human serum DPP-IV activity was established and optimized. The method demonstrates a favorable lower limit of detection (LOD) at 0.32â¯ng/mL and a satisfactory lower limit of quantification (LOQ) of 1.12â¯ng/mL, and can be used for the detection of DPP-IV activity in trace serum (2⯵L). In addition, Vitalliptin and Sitagliptin showed similar IC50 values when human recombinant DPP-IV and human serum were used as enzyme sources, and the intra-day and inter-day precision obtained by the microplate analyzer were less than 15â¯%. These results indicate that the microplate reader based detection technique has good accuracy, repeatability and reproducibility. A total of 700 volunteers were recruited, and 646 serum samples were tested for DPP-IV activity. The results showed that serum DPP-IV activity was higher in patients with T2DM than in controls (P < 0.01). However, the statistical data of family history of diabetes, gender and age of diabetic patients showed no statistical significance, and there was no contrast difference. The DPP-IV activity of serum in T2DM patients ranged from 2.4 µmol/min/L to 78.6 µmol/min/L, with a huge difference of up to 32-fold. These results suggest that it is necessary to test DPP-IV activity in patients with T2DM when taking DPP-IV inhibitors to determine the applicability of DPP-IV inhibitors in T2DM patients. These results suggest that it is necessary to detect the activity of DPP-IV in blood before taking DPP-IV inhibitors in patients with T2DM to judge the applicability of DPP-IV inhibitors in patients with T2DM.
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Diabetes Mellitus Tipo 2 , Dipeptidil Peptidasa 4 , Inhibidores de la Dipeptidil-Peptidasa IV , Límite de Detección , Fosfato de Sitagliptina , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/sangre , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Dipeptidil Peptidasa 4/sangre , Reproducibilidad de los Resultados , Masculino , Persona de Mediana Edad , Femenino , Espectrometría de Fluorescencia/métodos , Fluorescencia , Anciano , Adulto , Hipoglucemiantes/sangre , Hipoglucemiantes/uso terapéuticoRESUMEN
Functional brain networks have preserved architectures in rest and task; nevertheless, previous work consistently demonstrated task-related brain functional reorganization. Efficient rest-to-task functional network reconfiguration is associated with better cognition in young adults. However, aging and cognitive load effects, as well as contributions of intra- and internetwork reconfiguration, remain unclear. We assessed age-related and load-dependent effects on global and network-specific functional reconfiguration between rest and a spatial working memory (SWM) task in young and older adults, then investigated associations between functional reconfiguration and SWM across loads and age groups. Overall, global and network-level functional reconfiguration between rest and task increased with age and load. Importantly, more efficient functional reconfiguration associated with better performance across age groups. However, older adults relied more on internetwork reconfiguration of higher cognitive and task-relevant networks. These reflect the consistent importance of efficient network updating despite recruitment of additional functional networks to offset reduction in neural resources and a change in brain functional topology in older adults. Our findings generalize the association between efficient functional reconfiguration and cognition to aging and demonstrate distinct brain functional reconfiguration patterns associated with SWM in aging, highlighting the importance of combining rest and task measures to study aging cognition.
Brain networks identified by functional connectivity (FC) have preserved architectures from rest to task and across task demands. Higher similarity, implying more efficient network reconfiguration, was associated with better cognition and task performance in young adults. To examine how it may be influenced by aging, we compared whole-brain and network-level FC similarities between resting-state and spatial working memory fMRI in young and older adults. At whole-brain level and higher order cognitive networks, older adults evidenced less efficient network reconfiguration from rest to task than young adults. Importantly, more efficient reconfiguration was associated with better accuracy. This relationship relied more on internetwork connections in older adults. Despite reduced neural resources compared to young, maintaining efficient network updating still contributes to better cognition at older age.
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Aged patients often suffer poorer neurological recovery than younger patients after traumatic brain injury (TBI), but the mechanisms underlying this difference remain unclear. Here, we demonstrate abnormal myelopoiesis characterized by increased neutrophil and classical monocyte output but impaired nonclassical patrolling monocyte population in aged patients with TBI as well as in an aged murine TBI model. Retrograde and anterograde nerve tracing indicated that increased adrenergic input through the central amygdaloid nucleus-bone marrow axis drives abnormal myelopoiesis after TBI in a ß2-adrenergic receptor-dependent manner, which is notably enhanced in aged mice after injury. Selective blockade of ß2-adrenergic receptors rebalances abnormal myelopoiesis and improves the outcomes of aged mice after TBI. We therefore demonstrate that increased ß2-adrenergic input-driven abnormal myelopoiesis exacerbates post-TBI neuroinflammation in the aged, representing a mechanism underlying the poorer recovery of aged patients and that blockade of ß2-adrenergic receptor is a potential approach to promote neurological recovery after TBI.
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Lesiones Traumáticas del Encéfalo , Mielopoyesis , Enfermedades Neuroinflamatorias , Receptores Adrenérgicos beta 2 , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Femenino , Humanos , Masculino , Ratones , Persona de Mediana Edad , Adulto Joven , Lesiones Traumáticas del Encéfalo/metabolismo , Lesiones Traumáticas del Encéfalo/patología , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Enfermedades Neuroinflamatorias/metabolismo , Enfermedades Neuroinflamatorias/etiología , Enfermedades Neuroinflamatorias/patología , Neutrófilos/metabolismo , Receptores Adrenérgicos beta 2/metabolismoRESUMEN
Background: The infusion of phenylephrine to prevent spinal-induced hypotension (SIH) in cesarean delivery may decrease the rostral spread of a spinal local anesthetic. We hypothesized that infusion of norepinephrine may decrease the rostral spread of spinal anesthesia, similar to that caused by phenylephrine. The aim of this study was to compare the block height of spinal anesthesia in the presence or absence of norepinephrine infusion administered to prevent SIH during cesarean delivery. Methods: Eighty patients were enrolled and allocated into groups receiving a norepinephrine infusion (group N) or saline infusion (group C). After intrathecal injection of hyperbaric bupivacaine 10 mg, the block height for cold and pinprick sensation was checked 10 and 20 min after the injection. The demographic characteristics, spinal anesthesia, side effects, and neonatal outcomes were also recorded. Results: The block height for cold and pinprick sensation was similar between the two groups, although the incidence of hypotension was significantly lower (p < 0.00) in group N than in group C. Systolic blood pressure was also more stable in group N than in group C, with the incidence of interventions being significantly lower in group N. There was no significant difference in patient satisfaction between the two groups. Conclusion: Evidence from this study suggested that prophylactic norepinephrine infusion does not reduce the rostral spread of spinal anesthesia in pregnancy. We suggest that it is not necessary to increase the dose of an intrathecal local anesthetic for cesarean delivery when prophylactic norepinephrine is administered. Clinical Trial Registration: https://www.chictr.org.cn/bin/project/edit?pid=152899, identifier [ChiCTR2200057439].