RESUMEN
PURPOSE: CSF plays important roles in clearing brain waste and homeostasis. However, mapping whole-brain CSF flow in the rodents is difficult, primarily due to its assumed very low velocity. Therefore, we aimed to develop a novel phase-contrast MRI method to map whole-brain CSF flow in the mouse brain. METHODS: A novel generalized Hadamard encoding-based multi-band scheme (dubbed HEAP-METRIC, Hadamard Encoding APproach of Multi-band Excitation for short TR Imaging aCcelerating) using complex Hadamard matrix was developed and incorporated into conventional phase contrast (PC)-MRI to significantly increase SNR. RESULTS: Slow flow phantom imaging validated HEAP-METRIC PC-MRI's ability to achieve fast and accurate mapping of slow flow velocities (~102 µm/s). With the SNR gain afforded by HEAP-METRIC scheme, high-resolution (0.08 × 0.08 mm in-plane resolution and 36 0.4 mm slices) PC-MRI was completed in 21 min for whole-brain CSF flow mapping in the mouse. Using this novel method, we provide the first report of whole-brain CSF flow in the awake mouse brain with an average flow velocity of ~200 µm/s. Furthermore, HEAP-METRIC PC-MRI revealed CSF flow was reduced by isoflurane anesthesia, accompanied by reduction of glymphatic function as measured by dynamic contrast-enhanced MRI. CONCLUSION: We developed and validated a generalized HEAP-METRIC PC-MRI for mapping low velocity flow. With this method, we have achieved the first whole-brain mapping of awake mouse CSF flow and have further revealed that anesthesia reduces CSF flow velocity.
Asunto(s)
Isoflurano , Imagen por Resonancia Magnética , Animales , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Líquido Cefalorraquídeo/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Ratones , Fantasmas de ImagenRESUMEN
Current problems of existing heavy metal-removing technologies, especially for nanomaterials-based ones, are typically single metal ion-specific, high-cost and collected difficult. Herein, facile modification of commercial sulfur creates a versatile adsorbent platform to address challenges. The versatile adsorbent can be easily prepared through solvothermal treatment of a saturated commercial sulfur solution, followed by water precipitation on a commercial foam that eliminates the need for separation. Interestingly, the solvothermal treatment endows the resulting nanosulfur with sulfate acid groups (hard Lewis base), sulfur anions (soft base), and sulfite groups (borderline base), promising the coordination of all types of heavy metal ions (Lewis acids). As such, this versatile adsorbent with well-distributed adsorption sites exhibits highly effective heavy metal adsorption capacity towards diverse heavy metal ions for both single-component and multi-component adsorption, including soft, hard, borderline Lewis metal ions, with ultra-high adsorption ability (e.g., 903.79 mg g-1 for Cu2+). These findings highlighted the potential of this low-cost sulfur-based adsorbent to address the arising challenges in ensuring clean water.
RESUMEN
Developing advanced electrocatalysts toward the oxygen evolution reaction (OER) has always been recognized as the key challenge for green hydrogen production via water electrolysis due to the commonly required high OER overpotential. In this work, we report a branched FeCo-based hydroxide nanotube array (Fe-CoCH NT) synthesized by an ambient Fe-modification strategy, which could be used as a monolithic electrode for efficient OER catalysis. Its OER performance was even comparable to that of RuO2 with a low overpotential of 290 mV to attain a current density of 10 mA cm-2 due to its unique branched nanotube array structure and intrinsic high catalytic activity. Moreover, an acid-base hybrid electrolysis system was built based on this catalyst and an FeCo-based phosphide nanotube array electrode. By collecting electrochemical neutralization energy, this system just needs an ultralow cell voltage of 0.97 V to attain a current density of 10 mA cm-2 with a large decrease in energy consumption of 41.9% compared to traditional alkaline water splitting systems.
RESUMEN
STUDY OBJECTIVE: The incidence of pruritus from neuraxial opioids is about 60%. Pruritus causes discomfort and decreases the quality of recovery. This randomized double-blinded clinical trial was aimed to evaluate the prophylactic effects of a single dose IV nalmefene on the incidence and severity of epidural opioid-induced pruritus within 24 h after surgeries. DESIGN: A two-center, randomized, double blinded, controlled clinical trial. SETTING: The study was conducted from March 2022 to February 2023 at two tertiary care hospitals in China. PATIENTS: Patients aged between 18 and 80 years-old who underwent elective surgeries and received epidural analgesia intra- and post-operatively were screened for study enrollment. A total of 306 patients were enrolled, 302 patients underwent randomization and 296 patients were included in the final analysis. INTERVENTIONS: The nalmefene group was prophylactically given 0.5 µg/kg nalmefene intravenously while the control group was given the same volume of saline. MEASUREMENTS: The primary endpoint was the incidence of pruritus within 24 h after surgeries. The secondary endpoints included time of the first patient-reported pruritus, severity of pruritus after surgeries, severity of acute pain scores after surgeries and other anesthesia/analgesia related side effects. MAIN RESULTS: Pruritus occurred in 51 of the 147 (34.69%) patients in the control group and 35 of the 149 (23.49%) patients in the nalmefene group (odds ratio, 0.58; 95% CI, 0.35 to 0.96; P = 0.034) within 24 h postoperatively. Nalmefene group demonstrated delayed onset of pruritus, reduced severity of pruritus and decreased vomiting within 24 h after surgery. There were no significant differences in postoperative analgesia and the incidence of other anesthesia/analgesia associated side effects. CONCLUSIONS: A single dose of 0.5 µg/kg nalmefene intravenously significantly reduced the incidence and severity of epidural-opioid induced pruritus within 24 h after surgery without affecting the efficacy of epidural analgesia. TRIAL REGISTRATION: Chinese Clinical Trial Registry (www.chictr.org.cn) and the registration number is ChiCTR2100050463. Registered on August 27th, 2021.
Asunto(s)
Analgesia Epidural , Analgésicos Opioides , Humanos , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Morfina , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/prevención & control , Prurito/inducido químicamente , Prurito/epidemiología , Prurito/prevención & control , Analgesia Epidural/efectos adversos , Método Doble CiegoRESUMEN
OBJECTIVES: The effects of general anaesthetics on fetal brain development remain elusive. Radial glial progenitors (RGPs) generate the majority of neurons in developing brains. Here, we evaluated the acute alterations in RGPs after maternal sevoflurane exposure. METHODS: Pregnant mice were exposed to 2.5% sevoflurane for 6 hours on gestational day 14.5. Interkinetic nuclear migration (INM) of RGPs in the ventricular zone (VZ) of the fetal brain was evaluated by thymidine analogues labelling. Cell fate of RGP progeny was determined by immunostaining using various neural markers. The Morris water maze (MWM) was used to assess the neurocognitive behaviours of the offspring. RNA sequencing (RNA-Seq) was performed for the potential mechanism, and the potential mechanism validated by quantitative real-time PCR (qPCR), Western blot and rescue experiments. Furthermore, INM was examined in human embryonic stem cell (hESC)-derived 3D cerebral organoids. RESULTS: Maternal sevoflurane exposure induced temporary abnormities in INM, and disturbed the cell cycle progression of RGPs in both rodents and cerebral organoids without cell fate alternation. RNA-Seq analysis, qPCR and Western blot showed that the Notch signalling pathway was a potential downstream target. Reactivation of Notch by Jag1 and NICD overexpression rescued the defects in INM. Young adult offspring showed no obvious cognitive impairments in MWM. CONCLUSIONS: Maternal sevoflurane exposure during neurogenic period temporarily induced abnormal INM of RGPs by targeting the Notch signalling pathway without inducing long-term effects on RGP progeny cell fate or offspring cognitive behaviours. More importantly, the defects of INM in hESC-derived cerebral organoids provide a novel insight into the effects of general anaesthesia on human brain development.
Asunto(s)
Anestésicos por Inhalación/efectos adversos , Corteza Cerebral/efectos de los fármacos , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Receptores Notch/metabolismo , Sevoflurano/efectos adversos , Animales , Línea Celular , Movimiento Celular/efectos de los fármacos , Corteza Cerebral/patología , Femenino , Feto/efectos de los fármacos , Feto/metabolismo , Feto/patología , Humanos , Ratones Endogámicos C57BL , Células-Madre Neurales/citología , Células-Madre Neurales/efectos de los fármacos , Células-Madre Neurales/patología , Neurogénesis/efectos de los fármacos , Neuroglía/citología , Neuroglía/efectos de los fármacos , Neuroglía/patología , Embarazo , Efectos Tardíos de la Exposición Prenatal/metabolismo , Efectos Tardíos de la Exposición Prenatal/patología , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND: The association between intraoperative hypotension (IOH) and postoperative outcomes is not fully understood. We performed a meta-analysis to determine whether IOH is associated with increased risk of 30-day mortality, major adverse cardiac events (MACEs) and acute kidney injury (AKI) after non-cardiac surgery. METHODS: We searched PubMed and Embase through May 2016 to identify cohort studies that investigated the association between IOH and risk of 30-day mortality, MACEs, or AKI in adult patients after non-cardiac surgery. Ascertainment of IOH and assessment of outcomes were defined by the individual study. Considering the level of clinical heterogeneity, adjusted odds ratios (ORs) with 95% confidence interval (CIs) were pooled using a random-effects model. This meta-analysis is registered on PROSPERO (CRD42016049405). RESULTS: We included 14 cohort studies that were heterogeneous in terms of definition of IOH. IOH alone was associated with increased risk of 30-day mortality (OR 1.29 [95% CI, 1.19-1.41]), MACEs (OR 1.59 [95% CI, 1.23-2.05]), especially myocardial injury (OR 1.67 [95% CI, 1.31-2.13]), and AKI (OR 1.39 [95% CI, 1.09-1.77]). Triple low (IOH coincident with low bispectral index and low minimum alveolar concentration) also predicts increased risk of 30-day mortality (OR 1.32 [95% CI, 1.03-1.68]). CONCLUSIONS: IOH alone significantly increases the risk of postoperative 30-day mortality, MACEs, especially myocardial injury, and AKI in adult patients after non-cardiac surgery. Triple low also predicts increased risk of 30-day mortality after non-cardiac surgery. These findings provide evidence that IOH should be recognized as an independent risk factor for postoperative adverse outcomes after non-cardiac surgery.
Asunto(s)
Lesión Renal Aguda/mortalidad , Cardiopatías/mortalidad , Hipotensión/mortalidad , Complicaciones Intraoperatorias/mortalidad , Complicaciones Posoperatorias/mortalidad , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/etiología , Estudios de Cohortes , Cardiopatías/diagnóstico , Cardiopatías/etiología , Humanos , Hipotensión/complicaciones , Hipotensión/diagnóstico , Complicaciones Intraoperatorias/diagnóstico , Mortalidad/tendencias , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Factores de RiesgoRESUMEN
BACKGROUND: The expression of the let-7 family microRNAs in the myocardium of streptozotocin-induced diabetic rats was measured, and the cardioprotection of inhibition of let-7 microRNAs against ischemia-reperfusion injury was investigated. METHODS: The diabetic rats and nondiabetic rats were subjected to 30 minutes of coronary artery occlusion followed by 120 minutes of reperfusion. The infarct size was determined by triphenyltetrazolium chloride staining. The expression of let-7 was measured by quantitative real-time polymerase chain reaction, and expressions of insulin receptor (InsR), insulin-like growth factor-1 receptor (IGF-1R), glucose transporter type 4 (GLUT4), and the phosphorylation states of Akt and the mammalian target of rapamycin (mTOR) were analyzed using Western blot. Inhibition of let-7 was performed by local transfection of lentivirus gene transfer vectors containing let-7 antimiR. RESULTS: Compared with nondiabetic rats, the expression of let-7 was enhanced in the myocardium of diabetic rats (p = 0.029), whereas expressions of InsR, IGF-1R, and GLUT4 were decreased after ischemia-reperfusion (p < 0.01). Local transfection of the let-7 antimiR markedly inhibited the expression of let-7 (p = 0.038) and improved expressions of InsR, IGF-1R, and GLUT4 in the myocardium of diabetic rats (p < 0.01). The infarct size of diabetic rats was much higher than that of nondiabetic rats (p < 0.0001). Transfection of the let-7 antimiR significantly reduced the infarct size of diabetic rats (p < 0.0001), and such an antiinfarct effect was abolished completely by pretreatment of Akt inhibitor LY294002 or mTOR inhibitor rapamycin. CONCLUSIONS: Inhibition of the let-7 family microRNAs improves glucose uptake and insulin resistance in the diabetic myocardium and induces cardioprotection against ischemia-reperfusion injury through Akt and mTOR pathways.
Asunto(s)
Diabetes Mellitus Experimental/terapia , MicroARNs/fisiología , Daño por Reperfusión Miocárdica/prevención & control , Animales , Diabetes Mellitus Experimental/metabolismo , Transportador de Glucosa de Tipo 4/análisis , Masculino , MicroARNs/análisis , MicroARNs/antagonistas & inhibidores , Miocardio/metabolismo , Fosfatidilinositol 3-Quinasas/fisiología , Proteínas Proto-Oncogénicas c-akt/fisiología , Ratas , Ratas Sprague-Dawley , Receptor IGF Tipo 1/análisis , Transducción de Señal , Estreptozocina , Serina-Treonina Quinasas TOR/fisiologíaRESUMEN
OBJECTIVE: Micro ribonucleic acids (miRNAs) are involved in a wide range of biological functions, in multiple tissues, including the central nervous system. We investigated a novel neuroprotective strategy of down-regulation of miR-320 in the spinal cord under the condition of transient ischemia. METHODS: Spinal cord ischemia was induced in rats by cross-clamping the descending aorta for 14 minutes. Lentivirus vectors containing antisense oligonucleotides of rat miR-320 (antagomiR-320) were transfected into the experimental rats by means of intrathecal injection, 5 days before spinal cord ischemia. Control lentivirus vectors, or the vehicle, were given to the control animals. Hind-limb motor function was assessed during 48 hours after ischemia, using the Motor Deficit Index (MDI), and histologic examination was performed. In parallel experiments, expressions of miR-320, and the phosphorylation state of heat-shock protein 20 (phospho-Hsp20) in the spinal cord were evaluated by quantitative real-time polymerase chain reaction and western blot analysis. RESULTS: The time courses of expressions of miR-320 and phospho-Hsp20 in the spinal cord, after the transient ischemia, indicated that expression of phospho-Hsp20 was negatively correlated with expression of miR-320. Transfection of antagomiR-320 significantly reduced expression of miR-320 in the spinal cord and dramatically up-regulated expression of phospho-Hsp20. Compared with controls, inhibition of miR-320 markedly improved hind-limb motor function, as evidenced by lower MDI scores, at 6, 12, 24, and 48 hours after reperfusion, and increased the number of intact motor neurons in the lumbar spinal cord. CONCLUSIONS: Inhibition of miR-320 induces neuroprotection in the spinal cord, against ischemia-reperfusion injury, possibly via up-regulation of phospho-Hsp20.