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The sliding ferroelectrics formed by rhombohedral-stacked transition metal dichalcogenides (R-TMDs) greatly broaden the ferroelectric candidate materials. However, the weak ferroelectricity and many failure behaviors (such as irreversible lattice strains or defects) regulated by applied stimuli hinder their application. Here we systematically explore the interface electronic and transport properties of R-MoS2-based van der Waals heterojunctions (vdWHJs) by first-principles calculations. We find that the polarization and the band non-degeneracy of 2R-MoS2 increase with decreasing interlayer distance (d1). Moreover, the polarization direction of graphene (Gra)/2R-MoS2 P↑ state can be switched with a small increase in d1 (about 0.124 Å) due to the weakening of the polarization field (Ep) by a built-in electric field (Ei). The equilibrium state of superposition (|Ep + Ei|) or weakening (|Ep - Ei|) can be modulated by interface distances, which prompts vertical strain-regulated polarization or Schottky barriers. Furthermore, Gra/2R-MoS2 and Gra/R-MoS2/WS2 vdW ferroelectric tunneling junctions (FTJs) demonstrate ultra-high tunneling electroresistance (TER) ratios of 1.55 × 105 and 2.61 × 106, respectively, as the polarization direction switches. Our results provide an avenue for the design of future R-TMD vdW FTJs.
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Objective.In recent years, the robot assisted (RA) rehabilitation training has been widely used to counteract defects of the manual one provided by physiotherapists. However, since the proprioception feedback provided by the robotic assistance or the manual methods is relatively weak for the paralyzed patients, their rehabilitation efficiency is still limited. In this study, a dynamic electrical stimulation (DES) based proprioception enhancement and the associated quantitative analysis methods have been proposed to overcome the limitation mentioned above.Approach.Firstly, the DES based proprioception enhancement method was proposed for the RA neural rehabilitation. In the method, the relationship between the surface electromyogram (sEMG) envelope of the specified muscle and the associated joint angles was constructed, and the electrical stimulation (ES) pulses for the certain joint angles were designed by consideration of the corresponding sEMG envelope, based on which the ES can be dynamically regulated during the rehabilitation training. Secondly, power spectral density, source estimation, and event-related desynchronization of electroencephalogram, were combinedly used to quantitatively analyze the proprioception from multiple perspectives, based on which more comprehensive and reliable analysis results can be obtained. Thirdly, four modes of rehabilitation training tasks, namely active, RA, DES-RA, and ES-only training, were designed for the comparison experiment and validation of the proposed DES based proprioception enhancement method.Main results.The results indicated that the activation of the sensorimotor cortex was significantly enhanced when the DES was added, and the cortex activation for the DES-RA training was similar to that for the active training. Meanwhile, relatively consistent results from the multiple perspectives were obtained, which validates the effectiveness and robustness of the proposed proprioception analysis method.Significance.The proposed methods have the potential to be applied in the practical rehabilitation training to improve the rehabilitation efficiency.
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Electroencefalografía , Rehabilitación Neurológica , Propiocepción , Robótica , Humanos , Propiocepción/fisiología , Robótica/métodos , Electroencefalografía/métodos , Masculino , Rehabilitación Neurológica/métodos , Rehabilitación Neurológica/instrumentación , Adulto , Femenino , Estimulación Eléctrica/métodos , Electromiografía/métodos , Adulto JovenRESUMEN
BACKGROUND: Cardiovascular disease has been the leading cause of morbidity and mortality for type 2 diabetes mellitus (T2DM) patients over the last decade. AIM: To determine whether layer-specific global longitudinal strain (GLS) combined with peak strain dispersion (PSD) can be used to assess left ventricle (LV) myocardium systolic dysfunction in T2DM patients or without hypertension (HP). METHODS: We enrolled 97 T2DM patients, 70 T2DM + HP patients and 101 healthy subjects. Layer-specific GLS and PSD were calculated by EchoPAC software in apical three-, four- and two-chamber views. GLS of the epimyocardial, middle-layer and endomyocardial (GLSepi, GLSmid, and GLSendo) were measured and recorded. Receiver operating characteristic analysis was performed to detect LV myocardium systolic dysfunction in T2DM patients. RESULTS: There were significant differences in GLSepi, GLSmid, GLSendo, and PSD between healthy subjects, T2DM patients and T2DM patients with HP (P < 0.001). Trend tests yielded the ranking of healthy subjects > T2DM patients > T2DM with HP patients in the absolute values of GLSepi, GLSmid and GLSendo (P < 0.001), while PSD was ranked healthy subjects < T2DM < T2DM with HP (P < 0.001). Layer-specific GLS and PSD had high diagnostic efficiency for detecting LV myocardium systolic dysfunction in T2DM patients, however, the area under the curve (AUC) for layer-specific GLS and PSD combined was significantly higher than the AUCs for the individual indices (P < 0.05). CONCLUSION: Layer-specific GLS and PSD were associated with LV myocardium systolic dysfunction in T2DM patients, T2DM patients with HP. T2DM patients with HP have more severe LV myocardium systolic dysfunction than T2DM patients without HP and normal control patients. The combination of layer-specific GLS and PSD may provide additional prognostic information for T2DM patients with or without HP.
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Motor imagery (MI) based brain computer interface (BCI) has been extensively studied to improve motor recovery for stroke patients by inducing neuroplasticity. However, due to the lower spatial resolution and signal-to-noise ratio (SNR) of electroencephalograph (EEG), MI based BCI system that involves decoding hand movements within the same limb remains lower classification accuracy and poorer practicality. To overcome the limitations, an adaptive hybrid BCI system combining MI and steady-state visually evoked potential (SSVEP) is developed to improve decoding accuracy while enhancing neural engagement. On the one hand, the SSVEP evoked by visual stimuli based on action-state flickering coding approach significantly improves the recognition accuracy compared to the pure MI based BCI. On the other hand, to reduce the impact of SSVEP on MI due to the dual-task interference effect, the event-related desynchronization (ERD) based neural engagement is monitored and employed for feedback in real-time to ensure the effective execution of MI tasks. Eight healthy subjects and six post-stroke patients were recruited to verify the effectiveness of the system. The results showed that the four-class gesture recognition accuracies of healthy individuals and patients could be improved to 94.37 ± 4.77 % and 79.38 ± 6.26 %, respectively. Moreover, the designed hybrid BCI could maintain the same degree of neural engagement as observed when subjects solely performed MI tasks. These phenomena demonstrated the interactivity and clinical utility of the developed system for the rehabilitation of hand function in stroke patients.
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Interfaces Cerebro-Computador , Electroencefalografía , Potenciales Evocados Visuales , Mano , Rehabilitación de Accidente Cerebrovascular , Humanos , Rehabilitación de Accidente Cerebrovascular/métodos , Masculino , Electroencefalografía/métodos , Femenino , Potenciales Evocados Visuales/fisiología , Persona de Mediana Edad , Adulto , Algoritmos , Imaginación/fisiología , Accidente Cerebrovascular/fisiopatología , Gestos , Anciano , Voluntarios Sanos , Adulto Joven , Estimulación Luminosa , Relación Señal-Ruido , Reproducibilidad de los ResultadosRESUMEN
Improving tactile sensation by vibrating insoles was recommended to prevent foot ulcers in diabetic peripheral neuropathy (DPN). Lack of an insole design for diabetics was a challenge. Clinical trials on applying vibrating insoles with noise and stochastic resonance (SR) stimulating tactile were also required. In this study, vibrating foot orthoses (VFO) with a total contact design based on orthotics were proposed to provide proper insoles for diabetes. This study aimed to determine if VFO were beneficial at enhancing tactile in DPN. VFO were developed in combination with individual's custom-made foot orthoses and stimulation signals-integrating random 0-100 Hz square wave pulse signals with pseudorandom white noise by a SR approach. Sixty patients with mild-to-severe DPN were randomized to conduct crossover experiments: using and without VFO for 60 minutes stimulation at 90% of individuals' vibration perception threshold (VPT) level. VPT values when using VFO at the 1st and 5th metatarsophalangeal joints of the left foot decreased by 9.35% ( [Formula: see text].001); 9.04% ( [Formula: see text].001), and of the right foot decreased by 7.63% ( [Formula: see text].001); 7.24% ( [Formula: see text].001), respectively. Without VFO, there was no significant difference. Subgroups of mild and moderate DPN tended to benefit greatly from utilizing VFO. VFO can improve tactile in DPN. VFO may contribute to restoring/prolonging tactile and protective sensations, also decreasing peripheral nervous system deterioration. VFO might be useful for neurorehabilitation, and help prevent foot ulcers and disabilities.
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Estudios Cruzados , Diabetes Mellitus Tipo 2 , Neuropatías Diabéticas , Ortesis del Pié , Tacto , Vibración , Humanos , Vibración/uso terapéutico , Masculino , Femenino , Neuropatías Diabéticas/rehabilitación , Persona de Mediana Edad , Anciano , Diabetes Mellitus Tipo 2/complicaciones , Diseño de Equipo , Pie Diabético/rehabilitación , Percepción del Tacto/fisiología , Adulto , Pie , Procesos Estocásticos , Umbral SensorialRESUMEN
Objective: To analyze the clinical characteristics and prognostic impacts of SARS-CoV-2 Omicron infection among cancer inpatients during the December 2022 - February 2023 surge, in order to provide scientific evidence for clinical treatment and prevention and control measures. Methods: A retrospective analysis was conducted on the clinical features, prognosis, and vaccination status of cancer in-patients infected with the Omicron variant during the COVID-19 pandemic of December 2022 - February 2023. Results: A total of 137 cancer inpatients were included in the study, with a median age of 61 years, and 75 patients (54.74%) were male. The main symptoms were cough (69 cases, 50.36%), expectoration (60 cases, 43.80%), and fever (53 cases, 39.69%). Chest CT examination revealed bilateral pneumonia in 47 cases (34.31%, 47/137) and pleural effusion in 24 cases (17.52%, 24/137). Among the cancer patients, 116 cases (84.67%, 116/137) had solid tumors, and 21 cases (15.33%, 21/137) had hematologic malignancies, with the main types being breast cancer (25 cases, 18.25%) and lung cancer (24 cases, 17.52%). Among the cancer patients, 46 cases (33.58%) were asymptomatic, 81 cases (59.12%) had mild disease, 10 cases (7.30%) had severe infection, and 8 cases (5.84%) died. A total of 91 patients (66.42%) had been vaccinated, with 58 patients (42.34%) receiving three doses. Multivariate analysis showed that cerebral infarction and hypoproteinemia were risk factors for death from COVID-19 infection. Conclusion: Cancer patients infected with SARS-CoV-2 Omicron typically exhibit mild disease manifestations, but some cancer patients infected with the Omicron variant might progress to severe illness, and even death, necessitating close monitoring and attention during the early stages of infection. Additionally, the presence of cerebral infarction and hypoproteinemia significantly increases the risk of death.
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Objective: To investigate the clinical characteristics and risk factors of patients with SARS-CoV-2 Omicron variant infection complicated with cardiovascular diseases. Methods: A retrospective analysis of general clinical data was conducted on patients with SARS-CoV-2 omicron infection complicated with hypertension, coronary heart disease, and heart failure admitted to one hospital in Guangdong Province from December 1, 2022, to February 28, 2023. Clinical symptoms, laboratory tests, imaging examinations, treatment, and clinical outcomes were collected. Multivariate logistic regression analysis was used to analyze the risk factors for mortality in patients with SARS-CoV-2 Omicron variant infection complicated with cardiovascular diseases. ROC curves were drawn to evaluate the predictive value of CRP, D-dimer, and CK-MB in predicting the risk of death. Results: A total of 364 confirmed cases were included, divided into the asymptomatic group, mild to moderate group, and severe to critically ill group based on the symptoms of COVID-19. There were 216 males (59.34%) and 148 females (40.66%), with a median age of 75 years. The differences between the three groups in terms of sex and age were statistically significant (p < 0.05). The top three underlying diseases were hypertension (288 cases, 79.12%), coronary heart disease (100 cases, 27.47%), and diabetes (84 cases, 23.08%). The differences in unvaccinated and triple-vaccinated patients among the three groups were statistically significant (p < 0.05). The common respiratory symptoms were cough in 237 cases (65.11%) and sputum production in 199 cases (54.67%). In terms of laboratory tests, there were statistically significant differences in neutrophils, lymphocytes, red blood cells, C-reactive protein, D-dimer, aspartate aminotransferase, and creatinine among the three groups (p < 0.05). In imaging examinations, there were statistically significant differences among the three groups in terms of unilateral pulmonary inflammation, bilateral pulmonary inflammation, and bilateral pleural effusion (p < 0.05). There were statistically significant differences among the three groups in terms of antibiotic treatment, steroid treatment, oxygen therapy, nasal cannula oxygen inhalation therapy, non-invasive ventilation, and tracheal intubation ventilation (p < 0.05). Regarding clinical outcomes, there were statistically significant differences among the three groups in terms of mortality (p < 0.05). Multivariate logistic regression analysis showed that CRP (OR = 1.012, 95% CI = 1.004-1.019) and D-dimer (OR = 1.117, 95% CI = 1.021-1.224) were independent risk factors for patient mortality. The predictive value of CRP, D-dimer, and CK-MB for the risk of death was assessed. D-dimer had the highest sensitivity (95.8%) in predicting patient mortality risk, while CRP had the highest specificity (84.4%). Conclusion: For patients with COVID-19 and concomitant cardiovascular diseases without contraindications, early administration of COVID-19 vaccines and booster shots can effectively reduce the mortality rate of severe cases. Monitoring biomarkers such as CRP, D-dimer, and CK-MB and promptly providing appropriate care can help mitigate the risk of mortality in patients.
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Freezing of gait (FOG) leads to an increased risk of falls and limited mobility in individuals with Parkinson's disease (PD). However, existing research ignores the fine-grained quantitative assessment of FOG severity. This paper provides a double-hurdle model that uses typical spatiotemporal gait features to quantify the FOG severity in patients with PD. Moreover, a novel multi-output random forest algorithm is used as one hurdle of the double-hurdle model, further enhancing the model's performance. We conduct six experiments on a public PD gait database. Results demonstrate that the designed random forest algorithm in the double-hurdle model-hyperparameter independence framework achieves outstanding performances with the highest correlation coefficient (CC) of 0.972 and the lowest root mean square error (RMSE) of 2.488. Furthermore, we study the effect of drug state on the gait patterns of PD patients with or without FOG. Results show that "OFF" state amplifies the visibility of FOG symptoms in PD patients. Therefore, this study holds significant implications for the management and treatment of PD.
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BACKGROUND: Surgery for obese patients carries a higher risk of anesthesia complications compared with surgery for nonobese patients. Thus, a safe and effective anesthesia strategy is necessary to improve the medical experience of such patients and ensure their safety. AIM: To compared the effectiveness and safety of remimazolam besylate versus dexmedetomidine (DEX) in gastrointestinal surgery in obese patients. METHODS: The study cohort included 60 obese patients undergoing gastrointestinal surgery between July 2021 and April 2023, comprising 30 patients who received DEX intervention (control group) and 30 patients who received remimazolam besylate intervention (research group). Heart rate (HR), respiratory rate (RR), mean arterial pressure (MAP), blood oxygen saturation (SpO2), safety (nausea and vomiting, bradycardia, hypotension, and apnea), anesthesia and examination indices [induction time, anesthesia recovery time, and postanesthesia care unit (PACU) discharge time], sedation effect (Ramsay Sedation Scale), and postoperative pain visual analog scale were comparatively analyzed before anesthesia (T0), during anesthesia (T1), and after anesthesia (T2). RESULTS: At T1, the research group showed significantly smaller changes in HR, RR, MAP, and SpO2 than the control group, with a significantly lower adverse reaction rate and shorter induction, anesthesia recovery, and PACU discharge times. Additionally, the intra- and postoperative Ramsay Sedation Scale scores were statistically higher in the research group than in the control group. CONCLUSION: Remimazolam besylate was significantly more effective than DEX in gastrointestinal surgery in obese patients and had a higher safety profile and value in clinical promotion.
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BACKGROUND: Intervertebral disc degeneration (IVDD) is a multifaceted condition characterized by heterogeneity, wherein the balance between catabolism and anabolism in the extracellular matrix of nucleus pulposus (NP) cells plays a central role. Presently, the available treatments primarily focus on relieving symptoms associated with IVDD without offering an effective cure targeting its underlying pathophysiological processes. D-mannose (referred to as mannose) has demonstrated anti-catabolic properties in various diseases. Nevertheless, its therapeutic potential in IVDD has yet to be explored. METHODS: The study began with optimizing the mannose concentration for restoring NP cells. Transcriptomic analyses were employed to identify the mediators influenced by mannose, with the thioredoxin-interacting protein (Txnip) gene showing the most significant differences. Subsequently, small interfering RNA (siRNA) technology was used to demonstrate that Txnip is the key gene through which mannose exerts its effects. Techniques such as colocalization analysis, molecular docking, and overexpression assays further confirmed the direct regulatory relationship between mannose and TXNIP. To elucidate the mechanism of action of mannose, metabolomics techniques were employed to pinpoint glutamine as a core metabolite affected by mannose. Next, various methods, including integrated omics data and the Gene Expression Omnibus (GEO) database, were used to validate the one-way pathway through which TXNIP regulates glutamine. Finally, the therapeutic effect of mannose on IVDD was validated, elucidating the mechanistic role of TXNIP in glutamine metabolism in both intradiscal and orally treated rats. RESULTS: In both in vivo and in vitro experiments, it was discovered that mannose has potent efficacy in alleviating IVDD by inhibiting catabolism. From a mechanistic standpoint, it was shown that mannose exerts its anti-catabolic effects by directly targeting the transcription factor max-like protein X-interacting protein (MondoA), resulting in the upregulation of TXNIP. This upregulation, in turn, inhibits glutamine metabolism, ultimately accomplishing its anti-catabolic effects by suppressing the mitogen-activated protein kinase (MAPK) pathway. More importantly, in vivo experiments have further demonstrated that compared with intradiscal injections, oral administration of mannose at safe concentrations can achieve effective therapeutic outcomes. CONCLUSIONS: In summary, through integrated multiomics analysis, including both in vivo and in vitro experiments, this study demonstrated that mannose primarily exerts its anti-catabolic effects on IVDD through the TXNIP-glutamine axis. These findings provide strong evidence supporting the potential of the use of mannose in clinical applications for alleviating IVDD. Compared to existing clinically invasive or pain-relieving therapies for IVDD, the oral administration of mannose has characteristics that are more advantageous for clinical IVDD treatment.
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Proteínas de Ciclo Celular , Glutamina , Degeneración del Disco Intervertebral , Manosa , Degeneración del Disco Intervertebral/tratamiento farmacológico , Manosa/farmacología , Manosa/uso terapéutico , Animales , Ratas , Glutamina/farmacología , Glutamina/metabolismo , Masculino , Ratas Sprague-Dawley , Humanos , Núcleo Pulposo/efectos de los fármacos , Núcleo Pulposo/metabolismoRESUMEN
Alzheimer's Disease (AD) accounts for the majority of dementia, and Mild Cognitive Impairment (MCI) is the early stage of AD. Early and accurate diagnosis of dementia plays a vital role in more targeted treatments and effectively halting disease progression. However, the clinical diagnosis of dementia requires various examinations, which are expensive and require a high level of expertise from the doctor. In this paper, we proposed a classification method based on multi-modal data including Electroencephalogram (EEG), eye tracking and behavioral data for early diagnosis of AD and MCI. Paradigms with various task difficulties were used to identify different severity of dementia: eye movement task and resting-state EEG tasks were used to detect AD, while eye movement task and delayed match-to-sample task were used to detect MCI. Besides, the effects of different features were compared and suitable EEG channels were selected for the detection. Furthermore, we proposed a data augmentation method to enlarge the dataset, designed an extra ERPNet feature extract layer to extract multi-modal features and used domain-adversarial neural network to improve the performance of MCI diagnosis. We achieved an average accuracy of 88.81% for MCI diagnosis and 100% for AD diagnosis. The results of this paper suggest that our classification method can provide a feasible and affordable way to diagnose dementia.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Humanos , Enfermedad de Alzheimer/diagnóstico , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/psicología , Redes Neurales de la Computación , Diagnóstico PrecozRESUMEN
High-boiling-point nonhalogenated solvents are superior solvents to produce large-area organic solar cells (OSCs) in industry because of their wide processing window and low toxicity; while, these solvents with slow evaporation kinetics will lead excessive aggregation of state-of-the-art small molecule acceptors (e.g. L8-BO), delivering serious efficiency losses. Here, a heterogeneous nucleating agent strategy is developed by grafting oligo (ethylene glycol) side-chains on L8-BO (BTO-BO). The formation energy of the obtained BTO-BO; while, changing from liquid in a solvent to a crystalline phase, is lower than that of L8-BO irrespective of the solvent type. When BTO-BO is added as the third component into the active layer (e.g. PM6:L8-BO), it easily assembles to form numerous seed crystals, which serve as nucleation sites to trigger heterogeneous nucleation and increase nucleation density of L8-BO through strong hydrogen bonding interactions even in high-boiling-point nonhalogenated solvents. Therefore, it can effectively suppress excessive aggregation during growth, achieving ideal phase-separation active layer with small domain sizes and high crystallinity. The resultant toluene-processed OSCs exhibit a record power conversion efficiency (PCE) of 19.42% (certificated 19.12%) with excellent operational stability. The strategy also has superior advantages in large-scale devices, showing a 15.03-cm2 module with a record PCE of 16.35% (certificated 15.97%).
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In recent years, a few asparaginyl endopeptidases (AEPs) from certain higher plants have been identified as efficient peptide ligases with wide applications in protein labeling and cyclic peptide synthesis. Recently, we developed a NanoLuc Binary Technology (NanoBiT)-based peptide ligase activity assay to identify more AEP-type peptide ligases. Herein, we screened 61 bamboo species from 16 genera using this assay and detected AEP-type peptide ligase activity in the crude extract of all tested bamboo leaves. From a popular bamboo species, Bambusa multiplex, we identified a full-length AEP-type peptide ligase candidate (BmAEP1) via transcriptomic sequencing. After its zymogen was overexpressed in Escherichia coli and self-activated in vitro, BmAEP1 displayed high peptide ligase activity, but with considerable hydrolytic activity. After site-directed mutagenesis of its ligase activity determinants, the mutant zymogen of [G238V]BmAEP1 was normally overexpressed in E. coli, but failed to activate itself. To resolve this problem, we developed a novel protease-assisted activation approach in which trypsin was used to cleave the mutant zymogen and was then conveniently removed via ion-exchange chromatography. After the noncovalently bound cap domain was dissociated from the catalytic core domain under acidic conditions, the recombinant [G238V]BmAEP1 displayed high peptide ligase activity with much lower hydrolytic activity and could efficiently catalyze inter-molecular protein ligation and intramolecular peptide cyclization. Thus, the engineered bamboo-derived peptide ligase represents a novel tool for protein labeling and cyclic peptide synthesis.
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Cisteína Endopeptidasas , Cisteína Endopeptidasas/genética , Cisteína Endopeptidasas/metabolismo , Cisteína Endopeptidasas/química , Ingeniería de Proteínas/métodos , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/química , Ligasas/genética , Ligasas/metabolismo , Ligasas/química , Bambusa/genética , Bambusa/enzimología , Mutagénesis Sitio-Dirigida , Hojas de la Planta/enzimología , Hojas de la Planta/genética , Secuencia de AminoácidosRESUMEN
Photocatalysis has the advantages of practical, sustainable and environmental protection, so it plays a significant role in energy transformation and environmental utilization. CeO2 has attracted widespread attention for its unique 4 f electrons, rich defect structures, high oxygen storage capacity and great chemical stability. In this paper, we review the structure of CeO2 and the common methods for the preparation of CeO2-based composites in the first part. In particular, we highlight the co-precipitation method, template method, and sol-gel method methods. Then, in the second part, we introduce the application of CeO2-based composites in photocatalysis, including photocatalytic CO2 reduction, hydrogen production, degradation, selective organic reaction, and photocatalytic nitrogen fixation. In addition, we discuss several modification techniques to improve the photocatalytic performance of CeO2-based composites, such as elemental doping, defect engineering, constructing heterojunction and morphology regulation. Finally, the challenges faced by CeO2-based composites are analyzed and their development prospects are prospected. This review provides a systematic summary of the recent advance of CeO2-based composites in the field of photocatalysis, which can provide useful references for the rational design of efficient CeO2-based composite photocatalysts for sustainable development.
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Secretory myeloid-derived growth factor (MYDGF) exerts beneficial effects on organ repair, probably via a plasma membrane receptor; however, the identity of the expected receptor has remained elusive. In a recent study, MYDGF was reported as an agonist of the sphingosine-1-phosphate receptor 2 (S1PR2), an A-class G protein-coupled receptor that mediates the functions of the signaling lipid, sphingosine-1-phosphate (S1P). In the present study, we conducted living cell-based functional assays to test whether S1PR2 is a receptor for MYDGF. In the NanoLuc Binary Technology (NanoBiT)-based ß-arrestin recruitment assay and the cAMP-response element (CRE)-controlled NanoLuc reporter assay, S1P could efficiently activate human S1PR2 overexpressed in human embryonic kidney (HEK) 293T cells; however, recombinant human MYDGF, overexpressed either from Escherichia coli or HEK293 cells, had no detectable effect. Thus, the results demonstrated that human MYDGF is not a ligand of human S1PR2. Considering the high conservation of MYDGF and S1PR2 in evolution, MYDGF is also probably not a ligand of S1PR2 in other vertebrates.
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Factor Estimulante de Colonias de Granulocitos , Receptores de Lisoesfingolípidos , Esfingosina/análogos & derivados , Animales , Humanos , Receptores de Esfingosina-1-Fosfato , Receptores de Lisoesfingolípidos/genética , Receptores de Lisoesfingolípidos/metabolismo , Ligandos , Células HEK293 , Lisofosfolípidos/farmacologíaRESUMEN
Chronic total occlusion (CTO) is one of the most severe and sophisticated vascular stenosis because of complete blockage, greater operation difficulty, and lower procedural success rate. This study proposes a hydraulic-driven soft robot imitating the earthworm's locomotion to assist doctors or operators in actively opening thrombi in coronary or peripheral artery vessels. Firstly, a three-actuator bionic soft robot is developed based on earthworms' physiological structure. The soft robot's locomotion gait inspired by the earthworm's mechanism is designed. Secondly, the influence of structure parameters on actuator deformation, stress, and strain is explored, which can help us determine the soft actuators' optimal structure parameters. Thirdly, the relationship between hydraulic pressure and actuator deformation is investigated by performing finite element analysis using the bidirectional fluid-structure interaction (FSI) method. The kinematic models of the soft actuators are established to provide a valuable reference for the soft actuators' motion control.
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Background: The pathological damage mechanism of type 2 diabetes (T2D) and macroangiopathy is extremely complex, and T2D and arteriosclerosis obliterans have different biological behaviors and clinical features. To explore the mechanism of lower extremity arteriosclerosis occlusion (LEAOD) in T2D patients, we utilized RNA-seq to identify unique gene expression signatures of T2D and LEAOD through transcriptomic analysis. Methods: We obtained blood samples and performed RNA sequencing from four patients with T2D, five of whom had LEAOD. Another six age- and gender-matched blood samples from healthy volunteers were used for control. By exploring the general and specific differential expression analysis after transcriptome sequencing, specific gene expression patterns of T2D and LEAOD were verified. Results: Transcriptome analysis found differentially expressed genes in T2D, and T2D + LEAOD (vs normal) separately, of which 35/486 (T2D/T2D + LEAOD) were up-regulated and 1290/2970 (T2D/T2D + LEAOD) were down-regulated. A strong overlap of 571 genes across T2D, LEAOD, and coexisting conditions was mainly involved in extracellular exosomes and the transcription process. By exploring the sex difference gene expression features between T2D, T2D + LEAOD, and healthy controls, we noticed that sex chromosome-associated genes do not participate in the sexual dimorphism gene expression profiles of T2D and LEAOD. Protein-Protein Interaction Network analysis and drug target prediction provided the drug candidates to treat T2D and LEAOD. Conclusion: This study provides some evidence at the transcript level to uncover the association of T2D with LEAOD. The screened hub genes and predicted target drugs may be therapeutic targets.
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Background: Diabetic foot ulcers (DFUs) are a severe complication of diabetes. Persistent inflammation and impaired vascularization present considerable challenges in tissue wound healing. The aim of this study was to identify the crucial regulators of DFU wound healing and investigate their specific mechanisms in DFU. Methods: DFU RNA sequencing data were obtained to identify crucial feature genes. The expression levels of the feature genes and their corresponding microRNAs (miRNAs) were verified in clinical samples. Subsequently, the expression of CD68 was determined in DFU and non-diabetic foot skin samples. RAW 264.7 cells were treated with advanced glycation end products (AGEs) to determine their viability and apoptosis. Finally, the roles of the selected crucial genes and their corresponding miRNAs were investigated using in vitro experiments and a mouse model of diabetes. Results: Bioinformatic analysis showed that five crucial feature genes (CORO1A, CSF1R, CTSH, NFE2L3, and SLC16A10) were associated with DFU wound healing. The expression validation showed that miR-361-3p-CSF1R had a significant negative correlation and was thus selected for further experiments. AGEs significantly inhibited the viability of RAW 264.7 cells and enhanced their apoptosis; furthermore, the AGEs significantly downregulated CSF1R and increased miR-361-3p levels compared with the control cells. Additionally, inhibition of miR-361-3p decreased the cell apoptosis caused by AGEs and increased the levels of p-AKT/AKT and p-PI3K/PI3K, whereas CSF1R knockdown reversed the effects of miR-361-3p. In vivo experiments showed that miR-361-3p inhibition promoted wound healing in diabetic mice and regulated PI3K/AKT levels. Conclusions: AGEs may regulate macrophage apoptosis via the miR-361-3p/CSF1R axis and PI3K/AKT pathway, thereby influencing DFU wound healing.
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Clamping bushing structure is an internode connection mechanism designed for the standard section of tubular truss tower. In this paper, the clamping bushing structure of the connecting mechanism of super-large tower crane is taken as the research object, a three-dimensional model of clamping bushing structure is established and imported into ABAQUS, and its multi-body contact model is further constructed to study the contact and bearing relationship of the structure under multiple working conditions, and the accuracy of the calculation results of the model is verified by the experimental stress test under tensile working conditions. In addition, this study is based on the control variable method, and through the design of orthogonal test table, the influence degree of five variable parameters of clamping bushing on the bearing capacity of the structure is investigated. Finally, through the range analysis, the optimal horizontal combination of variables and parameters of clamping bushing structure is obtained, and the optimal matching relationship between the shape of the tower connecting mechanism and the bearing capacity is obtained. The results show that, compared with the original model, the stress concentration at the most dangerous section of the optimized joint and the bushing is obviously alleviated, in which the stress peaks of the upper and lower joints are kept below 500 MPa, and the stress peaks of the bushing groove are also reduced to between 573 and 722 MPa. Moreover, the designed and optimized lower joint can reduce the maximum equivalent plastic strain of the joint root circumference by 56.05% under the original maximum tensile condition, and the overall distribution trend of equivalent plastic strain is more uniform, and a more reliable structural design is obtained, which plays an important guiding role in the design, optimization and analysis of the connecting mechanism of the tower body of large tower crane.
RESUMEN
Photodetectors integrating substrates and semiconductor materials are increasingly attractive for applications in optical communication, optical sensing, optical computing, and military owing to the unique optoelectronic properties of semiconductor materials. However, it is still a challenge to realize high-performance photodetectors by only integrating substrates and semiconductor materials because of the limitation of incident light in contact with sensitive materials. In recent years, waveguides such as silicon (Si) and silicon nitride (Si3N4) have attracted extensive attention owing to their unique optical properties. Waveguides can be easily hetero-integrated with semiconductor materials, thus providing a promising approach for realizing high-performance photodetectors. Herein, we review recent advances in photodetectors integrating waveguides in two parts. The first involves the waveguide types and semiconductor materials commonly used to fabricate photodetectors, including Si, Si3N4, gallium nitride, organic waveguides, graphene, and MoTe2. The second involves the photodetectors of different wavelengths that integrate waveguides, ranging from ultraviolet to infrared. These hybrid photodetectors integrating waveguides and semiconductor materials provide an alternative way to realize multifunctional and high-performance photonic integrated chips and circuits.