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Gamma-aminobutyric acid (GABA) is an vital neurotransmitter, and the reaction to obtain GABA through biocatalysis requires coenzymes, which are therefore limited in the production of GABA. In this study, polyacrylamide hydrogels doped with chitosan and waste toner were synthesized for glutamate decarboxylase (GAD) and coenzyme co-immobilization to realize the production of GABA and the recovery of coenzymes. Enzymatic properties of immobilized GAD were discussed. The immobilized enzymes have significantly improved pH and temperature tolerance compared to free enzymes. In terms of reusability, after 10 repeated reuses of the immobilized GAD, the residual enzyme activity of immobilized GAD still retains 100% of the initial enzyme activity, and the immobilized coenzyme can also be kept at about 32%, with better stability and reusability. And under the control of no exogenous pH, immobilized GAD showed good performance in producing GABA. Therefore, in many ways, the new composite hydrogel provides another way for the utilization of waste toner and promises the possibility of industrial production of GABA.
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Quitosano , Glutamato Descarboxilasa/química , Ácido gamma-Aminobutírico , Coenzimas , Fenómenos MagnéticosRESUMEN
The unique microbiome found in the lungs has been studied and shown to be associated with both pulmonary homeostasis and lung diseases. The lung microbiome has the potential to produce metabolites that modulate host-microbe interactions. Specifically, short-chain fatty acids (SCFAs) produced by certain strains of the lung microbiota have been shown to regulate immune function and maintain gut mucosal health. In response, this review described the distribution and composition of the microbiota in lung diseases and discussed the impact of the lung microbiota on health and lung disease. In addition, the review further elaborated on the mechanism of microbial metabolites in microbial-host interaction and their application in the treatment of lung diseases. A better understanding of the interaction between the microbiota, metabolites, and host will provide potential strategies for the development of novel methods for the treatment of pulmonary microbial induced lung diseases.
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Enfermedades Pulmonares , Microbiota , Humanos , Pulmón/metabolismo , Enfermedades Pulmonares/terapia , Ácidos Grasos Volátiles/metabolismoRESUMEN
Menopausal women often face long-term estrogen treatment. G protein-coupled estrogen receptor (GPER) expressed in intestinal crypt was activated by estrogen therapy, but it was unclear whether chronic GPER activation during menopause had an effect on intestinal stem cells (ISCs). We tested the effect of chronic GPER activation on ISCs of ovariectomized (OVX) mice by injection of the selective GPER agonist G-1 for 28 days, or G-1 stimulation of organoids derived from crypts of OVX mice. G-1 up-regulated crypt depth, the number of Ki67+, bromodeoxyuridine+ cells and Olfm4+ ISCs, and the expression of ISCs marker genes (Lgr5, Olfm4 and Axin2). G-1 administration promoted organoid growth, increased the number of EdU+ cells per organoid and protein expression of Cyclin D1 and cyclin B1 in organoids. After G-1 treatment in vivo or in vitro, Paneth cell-derived Wnt3, Wnt3 effector ß-catenin and Wnt target genes c-Myc and Cyclin D1 increased in ileum or organoids. Once blocking the secretion of Wnt3 from Paneth cells, the effects of G-1 on organoids growth, ISCs marker genes and Wnt/ß-catenin signaling were abolished. G-1 did not affect the number of Paneth cells in ex vivo organoids, while activated Mmp7/cryptdin program in Paneth cells, promoted their maturation, and increased the expression of lysozyme protein. G-1 pretreatment in OVX mice inhibited radiation-induced ISCs proliferation injury and enhanced the resistance of mice to intestinal injury. In conclusion, chronic GPER activation prompted the Wnt3 synthesis in Paneth cells, thus increased the proliferation of ISCs via activation of Wnt3/ß-catenin signaling in OVX mice.
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Ciclina D1 , Células de Paneth , Ratones , Femenino , Animales , Células de Paneth/metabolismo , Ciclina D1/metabolismo , beta Catenina/metabolismo , Íleon/metabolismo , Células Madre , Vía de Señalización Wnt , Proliferación Celular , Estrógenos/farmacología , Estrógenos/metabolismo , Mucosa Intestinal/metabolismo , Proteína Wnt3/metabolismo , Proteína Wnt3/farmacologíaRESUMEN
BACKGROUND: Predicting the risk of malaria in countries certified malaria-free is crucial for the prevention of re-introduction. This review aimed to identify and describe existing prediction models for malaria re-introduction risk in eliminated settings. METHODS: A systematic literature search following the PRISMA guidelines was carried out. Studies that developed or validated a malaria risk prediction model in eliminated settings were included. At least two authors independently extracted data using a pre-defined checklist developed by experts in the field. The risk of bias was assessed using both the prediction model risk of bias assessment tool (PROBAST) and the adapted Newcastle-Ottawa Scale (aNOS). RESULTS: A total 10,075 references were screened and 10 articles describing 11 malaria re-introduction risk prediction models in 6 countries certified malaria free. Three-fifths of the included prediction models were developed for the European region. Identified parameters predicting malaria re-introduction risk included environmental and meteorological, vectorial, population migration, and surveillance and response related factors. Substantial heterogeneity in predictors was observed among the models. All studies were rated at a high risk of bias by PROBAST, mostly because of a lack of internal and external validation of the models. Some studies were rated at a low risk of bias by the aNOS scale. CONCLUSIONS: Malaria re-introduction risk remains substantial in many countries that have eliminated malaria. Multiple factors were identified which could predict malaria risk in eliminated settings. Although the population movement is well acknowledged as a risk factor associated with the malaria re-introduction risk in eliminated settings, it is not frequently incorporated in the risk prediction models. This review indicated that the proposed models were generally poorly validated. Therefore, future emphasis should be first placed on the validation of existing models.
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Malaria , Humanos , Malaria/epidemiología , Malaria/prevención & control , Factores de Riesgo , Medición de Riesgo , PronósticoRESUMEN
BACKGROUND: Current research related to electroencephalogram (EEG)-based driver's emergency braking intention detection focuses on recognizing emergency braking from normal driving, with little attention to differentiating emergency braking from normal braking. Moreover, the classification algorithms used are mainly traditional machine learning methods, and the inputs to the algorithms are manually extracted features. METHODS: To this end, a novel EEG-based driver's emergency braking intention detection strategy is proposed in this paper. The experiment was conducted on a simulated driving platform with three different scenarios: normal driving, normal braking and emergency braking. We compared and analyzed the EEG feature maps of the two braking modes, and explored the use of traditional methods, Riemannian geometry-based methods, and deep learning-based methods to predict the emergency braking intention, all using the raw EEG signals rather than manually extracted features as input. RESULTS: We recruited 10 subjects for the experiment and used the area under the receiver operating characteristic curve (AUC) and F1 score as evaluation metrics. The results showed that both the Riemannian geometry-based method and the deep learning-based method outperform the traditional method. At 200 ms before the start of real braking, the AUC and F1 score of the deep learning-based EEGNet algorithm were 0.94 and 0.65 for emergency braking vs. normal driving, and 0.91 and 0.85 for emergency braking vs. normal braking, respectively. The EEG feature maps also showed a significant difference between emergency braking and normal braking. Overall, based on EEG signals, it was feasible to detect emergency braking from normal driving and normal braking. CONCLUSIONS: The study provides a user-centered framework for human-vehicle co-driving. If the driver's intention to brake in an emergency can be accurately identified, the vehicle's automatic braking system can be activated hundreds of milliseconds earlier than the driver's real braking action, potentially avoiding some serious collisions.
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Electroencefalografía , Intención , Humanos , Algoritmos , Aprendizaje Automático , Curva ROCRESUMEN
The identification of the growth and development period of rice is of great significance to achieve high-yield and high-quality rice. However, the acquisition of rice growth period information mainly relies on manual observation, which has problems such as low efficiency and strong subjectivity. In order to solve these problems, a lightweight recognition method is proposed to automatically identify the growth period of rice: Small-YOLOv5, which is based on improved YOLOv5s. Firstly, the new backbone feature extraction network MobileNetV3 was used to replace the YOLOv5s backbone network to reduce the model size and the number of model parameters, thus improving the detection speed of the model. Secondly, in the feature fusion stage of YOLOv5s, we introduced a more lightweight convolution method, GsConv, to replace the standard convolution. The computational cost of GsConv is about 60-70% of the standard convolution, but its contribution to the model learning ability is no less than that of the standard convolution. Based on GsConv, we built a lightweight neck network to reduce the complexity of the network model while maintaining accuracy. To verify the performance of Small-YOLOv5s, we tested it on a self-built dataset of rice growth period. The results show that compared with YOLOv5s (5.0) on the self-built dataset, the number of the model parameter was reduced by 82.4%, GFLOPS decreased by 85.9%, and the volume reduced by 86.0%. The mAP (0.5) value of the improved model was 98.7%, only 0.8% lower than that of the original YOLOv5s model. Compared with the mainstream lightweight model YOLOV5s- MobileNetV3-Small, the number of the model parameter was decreased by 10.0%, the volume reduced by 9.6%, and the mAP (0.5:0.95) improved by 5.0%-reaching 94.7%-and the recall rate improved by 1.5%-reaching 98.9%. Based on experimental comparisons, the effectiveness and superiority of the model have been verified.
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The confinement of π-conjugated chromophores on silicon (Si) electrode surfaces is a powerful approach to engineer electroresponsive monolayers relevant to microelectronics, electrocatalysis, and information storage and processing. While common strategies to functionalize Si interfaces exploit molecularly dissolved building blocks, only a handful number of studies have leveraged the structure-function relationships of π-aggregates to tune the electronic structures of hybrid monolayers at Si interfaces. Herein, we show that the semiconducting properties of n-type monolayers constructed on Si electrodes are intimately correlated to the initial aggregation state of π-conjugated chromophore precursors derived from bay-substituted perylene bisimide (PBI) units. Specifically, our study unravels that for n-type monolayers engineered using PBI π-aggregates, the cathodic reduction potentials required to inject negative charge carriers into the conduction bands can be stabilized by 295 mV through reversible switching of the maximum anodic potential (MAP) that is applied during the oxidative cycles (+0.5 or +1.5 V vs Ag/AgCl). This redox-assisted stabilization effect is not observed with n-type monolayers derived from molecularly dissolved PBI cores and monolayers featuring a low surface density of the redox-active probes. These findings unequivocally point to the crucial role played by PBI π-aggregates in modulating the conduction band energies of n-type monolayers where a high MAP of +1.5 V enables the formation of electronic trap states that facilitate electron injection when sweeping back to cathodic potentials. Because the structure-function relationships of PBI π-aggregates are shown to modulate the semiconducting properties of hybrid n-type monolayers constructed at Si interfaces, our results hold promising opportunities to develop redox-switchable monolayers for engineering nonvolatile electronic memory devices.
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BACKGROUND: Brain-controlled wheelchairs (BCWs) are important applications of brain-computer interfaces (BCIs). Currently, most BCWs are semiautomatic. When users want to reach a target of interest in their immediate environment, this semiautomatic interaction strategy is slow. METHODS: To this end, we combined computer vision (CV) and augmented reality (AR) with a BCW and proposed the CVAR-BCW: a BCW with a novel automatic interaction strategy. The proposed CVAR-BCW uses a translucent head-mounted display (HMD) as the user interface, uses CV to automatically detect environments, and shows the detected targets through AR technology. Once a user has chosen a target, the CVAR-BCW can automatically navigate to it. For a few scenarios, the semiautomatic strategy might be useful. We integrated a semiautomatic interaction framework into the CVAR-BCW. The user can switch between the automatic and semiautomatic strategies. RESULTS: We recruited 20 non-disabled subjects for this study and used the accuracy, information transfer rate (ITR), and average time required for the CVAR-BCW to reach each designated target as performance metrics. The experimental results showed that our CVAR-BCW performed well in indoor environments: the average accuracies across all subjects were 83.6% (automatic) and 84.1% (semiautomatic), the average ITRs were 8.2 bits/min (automatic) and 8.3 bits/min (semiautomatic), the average times required to reach a target were 42.4 s (automatic) and 93.4 s (semiautomatic), and the average workloads and degrees of fatigue for the two strategies were both approximately 20. CONCLUSIONS: Our CVAR-BCW provides a user-centric interaction approach and a good framework for integrating more advanced artificial intelligence technologies, which may be useful in the field of disability assistance.
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Realidad Aumentada , Interfaces Cerebro-Computador , Silla de Ruedas , Inteligencia Artificial , Encéfalo , Computadores , Electroencefalografía , HumanosRESUMEN
BACKGROUND: Mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) has been reported worldwidely. However, the data about recurrent cases is limited. We aimed to analyze the clinical and radiographic features of recurrent MERS, and its possible mechanisms. CASE PRESENTATION: Two patients with clinically recurrent MERS were reported here, exhibiting neurological symptoms such as limbs weakness and numbness, stand/walk unsteadily, slurred speech and irritability, and typical lesions in the corpus callosum and white matter. One of them experienced another four episodes with a similar clinical course and magnetic resonance imaging findings over a period of 10 years. The Na levels in the present two patients were normal. DISCUSSION AND CONCLUSION: Combined with the patients reported previously, recurrence could be seen in both MERS type 1 and type 2 patients, from two to multiple times, with the latter possibly more common. It suggested that some genetic factors might be involved in MERS, especially for MERS type 2 or familial MERS.
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Encefalopatías , Encefalitis , Encefalopatías/diagnóstico por imagen , Encefalopatías/etiología , Cuerpo Calloso/diagnóstico por imagen , Cuerpo Calloso/patología , Encefalitis/diagnóstico por imagen , Humanos , Imagen por Resonancia MagnéticaRESUMEN
G protein-coupled estrogen receptor (GPER) might be involved in ulcerative colitis (UC), but the direct effect of GPER on UC is still unclear. We used male C57BL/6 mice to establish the acute colitis model with administration of dextran sulfate sodium and explored the effect of GPER on acute colitis and its possible mechanism. The selective GPER agonist G-1 inhibited weight loss and colon shortening and decreased the disease activity index for colitis and histologic damage in mice with colitis. All of these effects were prevented by a selective GPER blocker. G-1 administration prevented the dysfunction of tight junction protein expression and goblet cells in colitis model and thus inhibited the increase of mucosal permeability in colitis-suffering mice significantly. GPER activation reduced expression of glucose-regulating peptide-78 and anti-CCAAT/enhancer-binding protein homologous protein and attenuated the three arms of the unfolded protein response in colitis. G-1 therapy inhibited the increase of cleavage caspase-3- and TUNEL-positive cells in colonic crypts in the colitis model, increased the number of Ki67- and bromodeoxyuridine-positive cells in crypts, and reversed the decrease of cyclin D1 and cyclin B1 expression in colitis, indicating its protective effect on crypt cells. In cultured CCD841 cells, G-1 treatment fought against cell injury induced by endoplasmic reticulum stress. These findings demonstrate that GPER activation prevents colitis by protecting the colonic crypt cells, which are associated with inhibition of endoplasmic reticulum stress. SIGNIFICANCE STATEMENT: We demonstrate that G protein-coupled estrogen receptor (GPER) activation prevents dextran sulfate sodium-induced acute colitis by protecting the crypt cells, showing that it inhibited the crypt cell apoptosis and protected proliferation of crypt cells, which resulted in protection of the intestinal mucosal barrier. This protective effect was achieved (at least in part) by inhibiting endoplasmic reticulum stress. Mucosal healing is regarded as a key therapeutic target for colitis, and GPER is expected to become a new therapeutic target for colitis.
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Antiinflamatorios/farmacología , Colitis Ulcerosa/metabolismo , Enterocitos/metabolismo , Receptores Acoplados a Proteínas G/agonistas , Células Madre/efectos de los fármacos , Animales , Antiinflamatorios/uso terapéutico , Apoptosis , Proteínas Potenciadoras de Unión a CCAAT/genética , Proteínas Potenciadoras de Unión a CCAAT/metabolismo , Células Cultivadas , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/prevención & control , Chaperón BiP del Retículo Endoplásmico , Estrés del Retículo Endoplásmico , Células Caliciformes/metabolismo , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Receptores de Estrógenos/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Células Madre/metabolismo , Proteínas de Uniones Estrechas/genética , Proteínas de Uniones Estrechas/metabolismo , Respuesta de Proteína DesplegadaRESUMEN
BACKGROUND AND AIM: The role of hypoxia-inducible factor-1α (HIF-1α) and hypoxia-inducible factor-2α (HIF-2α) has been implicated in the clinical prognosis of hepatocellular carcinoma (HCC), but the results remain controversial. We aim to investigate the association of HIF-1α and HIF-2α overexpression with the prognosis and clinicopathological features of HCC. METHODS: A systematic search was conducted in PubMed, Embase, Scopus, Web of Science, and Cochrane Library until June 20, 2020. Meta-analysis was conducted to generate combined HRs with 95% confidence intervals (CI) for overall survival (OS) and disease-free survival (DFS). Odds ratios (ORs) with 95% CI were also derived by fixed or random effect model. RESULTS: Twenty-two studies involving 3238 patients were included. Combined data suggested that overexpression of HIF-1α in HCC was not only correlated with poorer OS [HR = 1.75 (95% CI: 1.53-2.00)] and DFS [HR = 1.64 (95% CI: 1.34-2.00)] but was also positively associated with vascular invasion [OR = 1.83 (95% CI: 1.36-2.48)], tumor size [OR = 1.36 (95% CI: 1.12-1.66)], and tumor number [1.74 (95% CI: 1.34-2.25)]. In contrast, HIF-2α overexpression was not associated with the prognosis and clinicopathological features of HCC. CONCLUSION: Our data provided compelling evidence of a worse prognosis of HCC in HIF-1α overexpression patients but not HIF-2α overexpression ones.
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Carcinoma Hepatocelular/genética , Expresión Génica , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Neoplasias Hepáticas/genética , Carcinoma Hepatocelular/mortalidad , Femenino , Humanos , Neoplasias Hepáticas/mortalidad , Masculino , Pronóstico , Tasa de SupervivenciaRESUMEN
The development of supramolecular tools to modulate the excitonic properties of non-covalent assemblies paves the way to engineer new classes of semicondcuting materials relevant to flexible electronics. While controlling the assembly pathways of organic chromophores enables the formation of J-like and H-like aggregates, strategies to tailor the excitonic properties of pre-assembled aggregates through post-modification are scarce. In the present contribution, we combine supramolecular chemistry with redox chemistry to modulate the excitonic properties and solid-state morphologies of aggregates built from stacks of water-soluble perylene diimide building blocks. The n-doping of initially formed aggregates in an aqueous medium is shown to produce π-anion stacks for which spectroscopic properties unveil a non-negligible degree of electron-electron interactions. Oxidation of the n-doped intermediates produces metastable aggregates where free exciton bandwidths (ExBW) increase as a function of time. Kinetic data analysis reveals that the dynamic increase of free exciton bandwidth is associated with the formation of superstructures constructed by means of a nucleation-growth mechanism. By designing different redox-assisted assembly pathways, we highlight that the sacrificial electron donor plays a non-innocent role in regulating the structure-function properties of the final superstructures. Furthermore, supramolecular architectures formed via a nucleation-growth mechanism evolve into ribbon-like and fiber-like materials in the solid-state, as characterized by SEM and HRTEM. Through a combination of ground-state electronic absorption spectroscopy, electrochemistry, spectroelectrochemistry, microscopy, and modeling, we show that redox-assisted assembly provides a means to reprogram the structure-function properties of pre-assembled aggregates.
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INTRODUCTION: There is a steep learning curve for a successful posterior endoscopic cervical foraminotomy and discectomy (PECFD), an important surgery for cervical foraminal or lateral disc herniation, and cervical radiculopathy due to a small operation field. PECFD becomes even more challenging in patients who have prominent shoulders and/or short necks with C6-7-disc herniation, because of the difficulty to localize C6-7 vertebral structure under fluoroscopy. The study objective is to prove that the PECFD can be performed safely and successfully to C6-7-disc herniation on patients with prominent shoulders and/or short necks following our novel surgical techniques under fluoroscopic guidance. MATERIALS AND METHODS: PECFD was performed on a patient who had an extruded foraminal disc herniation at C6-7 on the left with left arm pain and weakness. Due to his prominent shoulders and a short neck, the C6-7 anatomic site was not visible under traditional anterior-posterior (AP) and lateral fluoroscopic views. The authors inserted a reference needle to C4-5 facets between C4 and C5 pedicles under AP and lateral fluoroscopic views. Following the reference needle, the C6-7 facets were easily located with an oblique fluoroscopic view. A large endoscopic cannula was used initially for adequate resection of C6-7 facets, followed by a small cannula for nerve root handling with minimal pressure and discectomy. RESULTS: The novel surgical techniques resulted in a complete resection of the C6-7-disc herniation and resolution of the patient's radiculopathy with no postoperative complications. CONCLUSION: PECFD can be safely and successfully applied for C6-7-disc herniation in patients with prominent shoulders and/or short necks using our novel surgical techniques.
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Foraminotomía , Desplazamiento del Disco Intervertebral , Vértebras Cervicales/diagnóstico por imagen , Vértebras Cervicales/cirugía , Discectomía , Humanos , Desplazamiento del Disco Intervertebral/diagnóstico por imagen , Desplazamiento del Disco Intervertebral/cirugía , Hombro , Resultado del TratamientoRESUMEN
OBJECTIVES: To describe a transforaminal endoscopic spinal decompression technique for treating adult patients with isthmic spondylolisthesis and report preliminary surgical and radiological results. BACKGROUND: Spondylolisthesis is prevalent in the general population. Surgical approaches for symptomatic spondylolisthesis that is refractory to conservative treatment vary. Direct repair of pars fractures and spinal nerve decompression with or without fusion have been reported with varied clinical results. The de facto gold standard, "fusion," is often associated with high complication rates and costs, and may not be necessary for many patients whose spine is relatively stable. METHODS: Transforaminal endoscopic lumbar decompression (TFELD) was performed to resect fractured bone or bone fragments and inflamed tissue compressing the exiting nerve root in 2 patients with isthmic spondylolisthesis (grade 1 in one patient and grade 2 in another). We describe the technique step-by-step and assess the Oswestry Disability Index and pain scores for back and leg pain before and after surgery. RESULTS: Radiographic images demonstrated spondylolisthesis with L5 pars fracture. The fractured bone and bone fragment were intraoperatively visible in the gap between facets and fractured pars in patients with isthmic spondylolisthesis. The core pathology of the patients was fractured bone and bone fragment coupled with scar or inflamed tissue compressing the exiting L5 nerve roots. After the bone fragments and scar tissue were removed using TFELD, the patients' back and leg pain was significantly reduced, and physical function was restored. CONCLUSION: For patients with spondylolisthesis-associated low back and leg pain without spinal instability, TFELD is a safe and effective surgical treatment option.
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Fusión Vertebral , Espondilolistesis , Descompresión Quirúrgica , Endoscopía , Humanos , Vértebras Lumbares , Resultado del TratamientoRESUMEN
Locking-in the conformation of supramolecular assemblies provides a new avenue to regulate the (opto)electronic properties of robust nanoscale objects. In the present contribution, we show that the covalent tethering of a perylene bisimide (PBI)-derived supramolecular polymer with a molecular locker enables the formation of a locked superstructure equipped with emergent structure-function relationships. Experiments that exploit variable-temperature ground-state electronic absorption spectroscopy unambiguously demonstrate that the excitonic coupling between nearest neighboring units in the tethered superstructure is preserved at a temperature (371â K) where the pristine, non-covalent assembly exists exclusively in a molecularly dissolved state. A close examination of the solid-state morphologies reveals that the locked superstructure engenders the formation of hierarchical 1D materials which are not achievable by unlocked assemblies. To complement these structural attributes, we further demonstrate that covalently tethering a supramolecular polymer built from PBI subunits enables the emergence of electronic properties not evidenced in non-covalent assemblies. Using cyclic voltammetry experiments, the elucidation of the potentiometric properties of the locked superstructure reveals a 100-mV stabilization of the conduction band energy when compared to that recorded for the non-covalent assembly.
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The intestinal ischemia/reperfusion (I/R) injury is a common clinical event related with high mortality in patients undergoing surgery or trauma. Estrogen exerts salutary effect on intestinal I/R injury, but the receptor type is not totally understood. We aimed to identify whether the G protein-coupled estrogen receptor (GPER) could protect the intestine against I/R injury and explored the mechanism. Adult male C57BL/6 mice were subjected to intestinal I/R injury by clamping (45 min) of the superior mesenteric artery followed by 4 h of intestinal reperfusion. Our results revealed that the selective GPER blocker abolished the protective effect of estrogen on intestinal I/R injury. Selective GPER agonist G-1 significantly alleviated I/R-induced intestinal mucosal damage, neutrophil infiltration, up-regulation of TNF-α and cyclooxygenase-2 (Cox-2) expression, and restored impaired intestinal barrier function. G-1 could ameliorate the impaired crypt cell proliferation ability induced by I/R and restore the decrease in villus height and crypt depth. The up-regulation of inducible nitric oxide synthase (iNOS) expression after I/R treatment was attenuated by G-1 administration. Moreover, selective iNOS inhibitor had a similar effect with G-1 on promoting the proliferation of crypt cells in the intestinal I/R model. Both GPER and iNOS were expressed in leucine-rich repeat containing G-protein coupled receptor 5 (Lgr5) positive stem cells in crypt. Together, these findings demonstrate that GPER activation can prompt epithelial cell repair following intestinal injury, which occurred at least in part by inhibiting the iNOS expression in intestinal stem cells (ISCs). GPER may be a novel therapeutic target for intestinal I/R injury.
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Mucosa Intestinal/metabolismo , Receptores de Estrógenos/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Daño por Reperfusión/metabolismo , Animales , Proliferación Celular , Humanos , Intestinos/cirugía , Masculino , Ratones , Ratones Endogámicos C57BL , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Receptores de Estrógenos/genética , Receptores Acoplados a Proteínas G/genética , Daño por Reperfusión/genética , Daño por Reperfusión/fisiopatologíaRESUMEN
A convenient synthesis of novel 3-deoxy-5-hydroxy-1-aminocarbasugars was developed here. The benzyl-protected glucose-derived ketone 12 was selectively converted in high yield to enone 13via retro-Michael elimination of BnOH. The double bond of 13 was regio- and stereo-selectively reduced by the induction of C4-α-OBn to the multi-functionalized 15. 15 contained all the functionalities with similar configurations to carbasugars but with 3-H and 5-OH in the ring, and it would be a very interesting building block for organic synthesis or for bioactive compounds. As one application, 15 was further transformed into 1-amino-carbasugars by the reductive amination and final deprotection of benzyls. The targets were subjected to the in vitro inhibitory activity test against sucrase or maltase. The inhibitory activity of 17b, 17h or 17j against sucrase was nearly similar to that of voglibose. In comparison with voglibose, in vivo results similarly showed that 17b, 17h or 17j could lower the post-prandial blood glucose level after sucrose loading in healthy male ICR mice, while miglitol or acarbose was less effective. The molecular modeling study of some targets or voglibose with human sucrase could explain the inhibiting action.
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Carba-azúcares/farmacología , Inhibidores de Glicósido Hidrolasas/farmacología , Hipoglucemiantes/farmacología , alfa-Glucosidasas/metabolismo , Animales , Carba-azúcares/síntesis química , Carba-azúcares/química , Inhibidores de Glicósido Hidrolasas/síntesis química , Inhibidores de Glicósido Hidrolasas/química , Humanos , Hipoglucemiantes/síntesis química , Hipoglucemiantes/química , Masculino , Ratones , Ratones Endogámicos ICR , Modelos Moleculares , Estructura Molecular , Sacarasa/antagonistas & inhibidores , Sacarasa/metabolismoRESUMEN
BACKGROUND: Paragangliomas, also known as chemodectomas, are rare tumors arise from chemoreceptor tissue, and most commonly locate at the bifurcation of the common carotid, the jugular foramen, aortic arch, and retroperitoneum. Paragangliomas generally are considered to be benign tumors, and rarely produce local or distant metastases. Metastasis to liver is extremely rare. CASE PRESENTATION: We report the case of a 39-year-old woman, who had undergone resection of a retroperitoneal paraganglioma at her local hospital for 12 years. She was referred to our hospital for further evaluation of a hepatic mass, which was misdignosed as hepatocellular carcinoma (HCC) and was treated by transarterial chemoembolization (TACE) in the local hospital 6 years ago. At admission, CT scan revealed a huge hypervascular mass with many feeding arteries, almost the same size as 5 years ago. Ultrasound-guided biopsy of the liver tumor was performed and immunohistochemical examination confirmed the diagnosis of hepatic metastatic paraganglioma. Though liver metastasis failed to achieve complete response or partial response to TACE treatment, it remained stable without progression during the 7-year follow-up. CONCLUSION: Paragangliomas are slow growing tumors and metastasis may develop decades after resection of the primary lesion. Long-term follow-up is necessary, and curative or palliative treatment should be considered to control symptoms, improve life quality, reduce complications and prolong survival.
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Neoplasias Hepáticas/diagnóstico , Paraganglioma/diagnóstico , Neoplasias Retroperitoneales/diagnóstico , Adulto , Femenino , Humanos , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/terapia , Paraganglioma/secundario , Paraganglioma/terapia , Neoplasias Retroperitoneales/patología , Neoplasias Retroperitoneales/terapiaRESUMEN
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RESUMEN
BACKGROUND: The optimal PECD surgical approach for cervical intervertebral disc herniation (CIVDH) remains controversial. The conventional posterior K-hole approach for PECD leads to damage of facet joint. OBJECTIVES: This article is to first describe a novel posterior lamina-hole approach of percutaneous endoscopic cervical discectomy (PECD) for CIVDH. The objective of this study is to evaluate the feasibility and short-term clinical effect of this approach. METHODS: Single-center retrospective observational study of all patients managed with posterior percutaneous endoscopic cervical discectomy (PPECD) using the lamina-hole approach for symptomatic single-level CIVDH between January 2015 and January 2016. The clinical outcomes were evaluated with the visual analog scale, modified MacNab criteria and radiographical results. RESULTS: Twelve patients (seven women, five men) were enrolled in the study. Positive clinical response for pain relief was achieved in these patients receiving PPECD through lamina-hole approach for CIVDH. Postoperative MRI showed complete removal of the disc material in all the patients, no failure due to residual fragment was observed. CONCLUSION: As an alternative surgical approach of PPECD, PPECD through lamina-hole approach is a novel access for CIVDH and may be considered a valid and safe therapeutic option for CIVDH. The advantages of this approach are not only providing a valid and secure access to herniated cervical intervertebral fragment but also avoiding the iatrogenic damage to the facet joint and relevant functional spinal unit (FSU). Theoretically, the potential of secondary degeneration of FSU is low.