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Micro-sensors, such as pressure and flow sensors, are usually adopted to attain actual fluid information around swimming biomimetic robotic fish for hydrodynamic analysis and control. However, most of the reported micro-sensors are mounted discretely on body surfaces of robotic fish and it is impossible to analyzed the hydrodynamics between the caudal fin and the fluid. In this work, a biomimetic caudal fin integrated with a resistive pressure sensor is designed and fabricated by laser machined conductive carbon fibre composites. To analyze the pressure exerted on the caudal fin during underwater oscillation, the pressure on the caudal fin is measured under different oscillating frequencies and angles. Then a model developed from Bernoulli equation indicates that the maximum pressure difference is linear to the quadratic power of the oscillating frequency and the maximum oscillating angle. The fluid disturbance generated by caudal fin oscillating increases with an increase of oscillating frequency, resulting in the decrease of the efficiency of converting the kinetic energy of the caudal fin oscillation into the pressure difference on both sides of the caudal fin. However, perhaps due to the longer stability time of the disturbed fluid, this conversion efficiency increases with the increase of the maximum oscillating angle. Additionally, the pressure variation of the caudal fin oscillating with continuous different oscillating angles is also demonstrated to be detected effectively. It is suggested that the caudal fin integrated with the pressure sensor could be used for sensing thein situflow field in real time and analyzing the hydrodynamics of biomimetic robotic fish.
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Nadadeiras de Animais , Biomimética , Desenho de Equipamento , Peixes , Robótica , Natação , Animais , Robótica/instrumentação , Nadadeiras de Animais/fisiologia , Biomimética/instrumentação , Biomimética/métodos , Peixes/fisiologia , Natação/fisiologia , Hidrodinâmica , Análise de Falha de Equipamento , Transdutores de Pressão , Pressão , Materiais Biomiméticos , TransdutoresRESUMO
BACKGROUND: Decompressive craniectomy (DC) reduces mortality without increasing the risk of very severe disability among patients with life-threatening massive cerebral infarction. However, its efficacy was demonstrated before the era of endovascular thrombectomy trials. It remains uncertain whether DC improves the prognosis of patients with malignant middle cerebral artery (MCA) infarction receiving endovascular therapy. METHODS: We pooled data from two trials (DEVT and RESCUE BT studies in China) and patients with malignant MCA infarction were included to assess outcomes and heterogeneity of DC therapy effect. Patients with herniation were dichotomized into DC and conservative groups according to their treatment strategy. The primary outcome was the rate of mortality at 90 days. Secondary outcomes included disability level at 90 days as measured by the modified Rankin Scale score (mRS) and quality-of-life score. The associations of DC with clinical outcomes were performed using multivariable logistic regression. RESULTS: Of 98 patients with herniation, 37 received DC surgery and 61 received conservative treatment. The median (interquartile range) was 70 (62-76) years and 40.8% of the patients were women. The mortality rate at 90 days was 59.5% in the DC group compared with 85.2% in the conservative group (adjusted odds ratio, 0.31 [95% confidence interval (CI), 0.10-0.94]; P=0.04). There were 21.6% of patients in the DC group and 6.6% in the conservative group who had a mRS score of 4 (moderately severe disability); and 10.8% and 4.9%, respectively, had a score of 5 (severe disability). The quality-of-life score was higher in the DC group (0.00 [0.00-0.14] vs 0.00 [0.00-0.00], P=0.004), but DC treatment was not associated with better quality-of-life score in multivariable analyses (adjusted ß Coefficient, 0.02 [95% CI, -0.08-0.11]; p=0.75). CONCLUSIONS: DC was associated with decreased mortality among patients with malignant MCA infarction who received endovascular therapy. The majority of survivors remained moderately severe disability and required improvement on quality of life. CLINICAL TRIAL REGISTRATION: The DEVT trial: http://www.chictr.org. Identifier, ChiCTR-IOR-17013568. The RESCUE BT trial: URL: http://www.chictr.org. Identifier, ChiCTR-INR-17014167.
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Craniectomia Descompressiva , Avaliação da Deficiência , Infarto da Artéria Cerebral Média , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , China , Craniectomia Descompressiva/mortalidade , Craniectomia Descompressiva/efeitos adversos , Estado Funcional , Infarto da Artéria Cerebral Média/mortalidade , Infarto da Artéria Cerebral Média/cirurgia , Infarto da Artéria Cerebral Média/terapia , Infarto da Artéria Cerebral Média/diagnóstico , Infarto da Artéria Cerebral Média/fisiopatologia , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Recuperação de Função Fisiológica , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
In this paper, two-dimensional Graphdiyne and Hexakis-[(trimethylsilyl)ethynyl]benzene nanosheets were prepared using the liquid-phase exfoliation method and were then successfully applied to 1.06â µm passively Q-Switched all-solid-state lasers. The Hexakis-[(trimethylsilyl)ethynyl]benzene was applied for the first time in passively Q-Switched all-solid-state lasers, as we know. For Graphdiyne, the Q-Switched pulse achieved a narrowest pulse width of 415â ns, a maximum repetition frequency of 244.2 kHz, a maximum pulse energy of 133.53 nJ, and peak power of 321.77â mW was obtained. While, the narrowest pulse width, maximum repetition frequency, maximum pulse energy, and peak power for Hexakis-[(trimethylsilyl)ethynyl]benzene are approximately 398.4â ns, 297.1 kHz, 89.61 nJ, and 220.39â mW respectively. The findings demonstrate the promising potential of both candidates as saturable absorbers for signal modulation in solid-state lasers.
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Cell imaging technology is undoubtedly a powerful tool for studying single-cell heterogeneity due to its non-invasive and visual advantages. It covers microscope hardware, software, and image analysis techniques, which are hindered by low throughput owing to abundant hands-on time and expertise. Herein, a cellular nucleus image-based smarter microscope system for single-cell analysis is reported to achieve high-throughput analysis and high-content detection of cells. By combining the hardware of an automatic fluorescence microscope and multi-object recognition/acquisition software, we have achieved more advanced process automation with the assistance of Robotic Process Automation (RPA), which realizes a high-throughput collection of single-cell images. Automated acquisition of single-cell images has benefits beyond ease and throughout and can lead to uniform standard and higher quality images. We further constructed a single-cell image database-based convolutional neural network (Efficient Convolutional Neural Network, E-CNN) exceeding 20618 single-cell nucleus images. Computational analysis of large and complex data sets enhances the content and efficiency of single-cell analysis with the assistance of Artificial Intelligence (AI), which breaks through the super-resolution microscope's hardware limitation, such as specialized light sources with specific wavelengths, advanced optical components, and high-performance graphics cards. Our system can identify single-cell nucleus images that cannot be artificially distinguished with an accuracy of 95.3%. Overall, we build an ordinary microscope into a high-throughput analysis and high-content smarter microscope system, making it a candidate tool for Imaging cytology.
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Inteligência Artificial , Técnicas Biossensoriais , Software , Processamento de Imagem Assistida por Computador/métodos , Microscopia de Fluorescência , Análise de Célula ÚnicaRESUMO
In the face of increasing energy demand, the approach of transformation that combines energy restructuring and environmental governance has become a popular research direction. As an important part of electrocatalytic reactions for gas molecules, reduction reactions of oxygen (ORR) and carbon dioxide (CO2RR) are very indispensable in the field of energy conversion and storage. However, the non-interchangeability and irreversibility of electrode materials have always been a challenge in electrocatalysis. Hereon, nickel and nitrogen decorated biomass carbon-based materials (Ni/N-BC) has been prepared by high temperature pyrolysis using agricultural waste straw as raw material. Surprisingly, it possesses abundant active sites and specific surface area as a bifunctional electrocatalyst for ORR and CO2RR. The three-dimensional porous cavity structure for the framework of biomass could not only provide a strong anchoring foundation for the active site, but also facilitate the transport and enrichment of reactants around the site. In addition, temperature modulation during the preparation process also optimizes the composition and structure of biomass carbon and nitrogen. Benefit from above structure and morphology advantages, Ni/N-BC-800 exhibits the superior electrocatalytic activity for both ORR and CO2RR simultaneously. More specifically, Ni/N-BC-800 exhibits satisfactory ORR activity in terms of initial potential and half wave potential, while also enables the production of CO under high selective. The research results provide ideas for the development and design of electrode materials and green electrocatalysts, and also expand new applications of agricultural waste in fields such as energy conversion, environmental protection, and resource utilization.
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OBJECTIVE: To evaluate the non-inferiority of endovascular treatment (EVT) alone versus intravenous thrombolysis (IVT) followed by EVT and to assess its heterogeneity across prespecified subgroups. METHODS: We pooled data from two trials (SKIP in Japan; DEVT in China). Individual patient data were pooled to assess outcomes and heterogeneity of treatment effect. The primary outcome was functional independence (modified Rankin Scale score 0-2) at 90 days. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and 90-day mortality. RESULTS: We included 438 patients (217 EVT alone; 221 combined IVT+EVT). The meta-analysis failed to demonstrate the non-inferiority of EVT alone over combined IVT+EVT in achieving 90-day functional independence (56.7% vs 51.6%; adjusted common odds ratio (cOR)=1.27, 95% CI 0.84 to 1.92, pnon-inferiority=0.06). Effect sizes favoring EVT alone were present with stroke onset to puncture time longer than 180 min (cOR=2.28, 95% CI 1.18 to 4.38, pinteraction ≤180 vs >180 min=0.02) and intracranial internal carotid artery ICA occlusions (for ICA cOR=3.04, 95% CI 1.10 to 8.43, pinteraction ICA vs MCA=0.08). The rates of sICH (6.5% vs 9.0%; cOR=0.77, 95% CI 0.37 to 1.61) and 90-day mortality (12.9% vs 13.6%; cOR=1.05, 95% CI 0.58 to 1.89) were comparable. CONCLUSIONS: The cumulative data of these two recent Asian trials failed to unequivocally demonstrate the non-inferiority of EVT alone over combined IVT+EVT. However, our study suggests a potential role for more individualized decision-making. Specifically, Asian patients with stroke onset to EVT longer than 180 min, as well as those with intracranial ICA occlusions and those with atrial fibrillation might have better outcomes with EVT alone than with combined IVT+EVT.
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Arteriopatias Oclusivas , Isquemia Encefálica , Procedimentos Endovasculares , Acidente Vascular Cerebral , Humanos , Isquemia Encefálica/terapia , Procedimentos Endovasculares/efeitos adversos , Fibrinolíticos/uso terapêutico , Hemorragias Intracranianas , Distribuição Aleatória , Acidente Vascular Cerebral/terapia , Trombectomia , Terapia Trombolítica , Resultado do Tratamento , Ensaios Clínicos como AssuntoRESUMO
Major facilitator superfamily domain-containing 2a (Mfsd2a) is a sodium-dependent lysophosphatidylcholine cotransporter that plays an important role in maintaining the integrity of the blood-brain barrier and neurological function. Abnormal degradation of Mfsd2a often leads to dysfunction of the blood-brain barrier, while upregulation of Mfsd2a can retrieve neurological damage. It has been reported that Mfsd2a can be specifically recognized and ubiquitinated by neural precursor cell-expressed developmentally downregulated gene 4 type 2 (NEDD4-2) ubiquitin ligase and finally degraded through the proteasome pathway. However, the structural basis for the specific binding of Mfsd2a to NEDD4-2 is unclear. In this work, we combined deep learning and molecular dynamics simulations to obtain a Mfsd2a structure with high quality and a stable Mfsd2a/NEDD4-2-WW3 interaction model. Moreover, molecular mechanics generalized Born surface area (MM-GBSA) methods coupled with per-residue energy decomposition studies were carried out to analyze the key residues that dominate the binding interaction. Based on these results, we designed three peptides containing the key residues by truncating the Mfsd2a sequences. One of them was found to significantly inhibit Mfsd2a ubiquitination, which was further validated in an oxygen-glucose deprivation (OGD) model in a human microvascular endothelial cell line. This work provides some new insights into the understanding of Mfsd2a and NEDD4-2 interaction and might promote further development of drugs targeting Mfsd2a ubiquitination.
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Barreira Hematoencefálica , Simulação de Dinâmica Molecular , Humanos , Transporte Biológico , Barreira Hematoencefálica/metabolismo , Linhagem Celular , UbiquitinaçãoRESUMO
Machine learning (ML) models have recently shown important advantages in predicting nanomaterial properties, which avoids many trial-and-error explorations. However, complex variables that control the formation of nanomaterials exhibiting the desired properties still need to be better understood owing to the low interpretability of ML models and the lack of detailed mechanism information on nanomaterial properties. In this study, we developed a methodology for accurately predicting multiple synthesis parameter-property relationships of nanomaterials to improve the interpretability of the nanomaterial property mechanism. As a proof-of-concept, we designed glutathione-gold nanoclusters (GSH-AuNCs) exhibiting an appropriate fluorescence quantum yield (QY). First, we conducted 189 experiments and synthesized different GSH-AuNCs by varying the thiol-to-metal molar ratio and reaction temperature and time in reasonable ranges. The fluorescence QY of GSH-AuNCs could be systematically and independently programmed using different experimental parameters. We used limited GSH-AuNC synthesis parameter data to train an extreme gradient boosting regressor model. Moreover, we improved the interpretability of the ML model by combining individual conditional expectation, double-variable partial dependence, and feature interaction network analyses. The interpretability analyses established the relationship between multiple synthesis parameters and fluorescence QYs of GSH-AuNCs. The results represent an essential step towards revealing the complex fluorescence mechanism of thiolated AuNCs. Finally, we constructed a synthesis phase diagram exceeding 6.0 × 104 prediction variables for accurately predicting the fluorescence QY of GSH-AuNCs. A multidimensional synthesis phase diagram was obtained for the fluorescence QY of GSH-AuNCs by searching the synthesis parameter space in the trained ML model. Our methodology is a general and powerful complementary strategy for application in material informatics.
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The present study focuses on summarizing the recent advancements in the field of fish swimming mode research and bionic robotic fish prototypes based on smart materials. It has been widely acknowledged that fish exhibit exceptional swimming efficiency and manoeuvrability compared to conventional underwater vehicles. In the pursuit of developing autonomous underwater vehicles (AUVs), conventional experimental methods often prove to be complex and expensive. Hence, the utilization of computer simulations for hydrodynamic modelling provides a cost-effective and efficient approach for analysing the swimming behaviour of bionic robotic fish. Additionally, computer simulations can provide data that are difficult to obtain through experimental methods. Smart materials, which integrate perception, drive, and control functions, are increasingly being applied to bionic robotic fish research. However, the utilization of smart materials in this field is still an area of ongoing research and several challenges remain unresolved. This study provides an overview of the current state of research on fish swimming modes and the development of hydrodynamic modelling. The application of four distinct types of smart materials in bionic robotic fish is then reviewed, with a focus on analysing the advantages and disadvantages of each material in driving swimming behaviour. In conclusion, the paper highlights the key technical challenges that must be addressed for the practical implementation of bionic robotic fish and provides insights into the potential future directions of this field.
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DNA self-assembly provides a "bottom-up" route to fabricating complex shapes on the nanometer scale. However, each structure needs to be designed separately and carried out by professionally trained technicians, which seriously restricts its development and application. Herein, a point-and-shoot strategy based on enzyme-assisted DNA "paper-cutting" to construct planar DNA nanostructures using the same DNA origami as the template is reported. Precisely modeling the shapes with high precision in the strategy based on each staple strand of the desired shape structure hybridizes with its nearest neighbor fragments from the long scaffold strand. As a result, some planar DNA nanostructures by one-pot annealing the long scaffold strand and selected staple strands is constructed. The point-and-shoot strategy of avoiding DNA origami staple strands' re-designing based on different shapes breaks through the shape complexity limitation of the planar DNA nanostructures and enhances the simplicity of design and operation. Overall, the strategy's simple operability and great generality enable it to act as a candidate tool for manufacturing DNA nanostructures.
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Nanoestruturas , Nanotecnologia , Conformação de Ácido Nucleico , Nanoestruturas/química , DNA/químicaRESUMO
Cerebral ischemia, resulting from compromised blood flow, is one of the leading causes of death worldwide with limited therapeutic options. Potential deleterious injuries resulting from reperfusion therapies remain a clinical challenge for physicians. This study aimed to explore the metabolomic alterations during ischemia-reperfusion injury by employing metabolomic analysis coupled with gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) and ultraperformance liquid chromatography quadrupole (UPLC/Q)-TOF-MS. Metabolomic data from mice subjected to middle cerebral artery occlusion (MCAO) followed by reperfusion (MCAO/R) were compared to those of the sham and MCAO groups. A total of 82 simultaneously differentially expressed metabolites were identified among each group. The top three major classifications of these differentially expressed metabolites were organic acids, lipids, and organooxygen compounds. Metabolomics pathway analysis was conducted to identify the underlying pathways implicated in MCAO/R. Based on impactor scores, the most significant pathways involved in the response to the reperfusion after cerebral ischemia were glycerophospholipid metabolism, linoleic acid metabolism, pyrimidine metabolism, and galactose metabolism. 17 of those 82 metabolites were greatly elevated in the MCAO/Reperfusion group, when compared to those in the sham and MCAO groups. Among those metabolites, glucose-6-phosphate 1, fructose-6-phosphate, cellobiose 2, o-phosphonothreonine 1, and salicin were the top five elevated metabolites in MCAO/R group, compared with the MCAO group. Glycolysis, the pentose phosphate pathway, starch and sucrose metabolism, and fructose and mannose degradation were the top four ranked pathways according to metabolite set enrichment analysis (MSEA). The present study not only advances our understanding of metabolomic changes among animals in the sham and cerebral ischemia groups with or without reperfusion via metabolomic profiling, but also paves the way to explore potential molecular mechanisms underlying metabolic alteration induced by cerebral ischemia-reperfusion.
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INTRODUCTION: The aim of this study was to test the hypothesis that intravenous tirofiban improves functional outcomes without promoting the risk of intracranial hemorrhage (ICH) in stroke secondary to basilar artery occlusion (BAO) receiving endovascular thrombectomy. METHODS: Patients with acute BAO stroke who were treated with endovascular thrombectomy and had tirofiban treatment information were derived from "BASILAR": a nationwide, prospective registry. All eligible patients were divided into tirofiban and no-tirofiban groups according to whether tirofiban was used intravenously. The primary endpoint was the 90-day severity of disability as assessed by the modified Rankin scale score. Safety outcomes were the frequency of ICH and mortality. RESULTS: Of 645 patients included in this cohort, 363 were in the tirofiban group and 282 were in the no-tirofiban group. Thrombectomy with intravenous tirofiban reduced the 90-day disability level over the range of the modified Rankin scale (adjusted common odds ratio, 2.08; 95% confidence interval (CI), 1.45-2.97; p < 0.001). The 90-day mortality of patients in the tirofiban group was lower than that in the no-tirofiban group (41.6% vs. 52.1%; adjusted hazard ratio, 0.60; 95% CI, 0.47-0.77; p < 0.001). The frequency of any ICH (6.7% vs. 13.7%; p = 0.004) and symptomatic ICH (4.8% vs. 10.1%; p = 0.01) in the tirofiban group was significantly lower than that in the no-tirofiban group. CONCLUSIONS: In patients with acute BAO stroke who underwent endovascular treatment, intravenous tirofiban might be associated with favorable outcome, reduced mortality, and a decreased frequency of ICH.
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AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Tirofibana/efeitos adversos , Artéria Basilar , Resultado do Tratamento , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/terapia , Trombectomia/efeitos adversos , Hemorragias Intracranianas/induzido quimicamenteRESUMO
To carry out effective resource reforming of sustainable electricity, hydrogen production by electrochemical water splitting provides an eco-friendly and economical way. Nevertheless, the oxygen evolution reaction (OER) at the anode is limited by the slow reaction process, which hinders the large-scale development and application of electrolysis technology. In this work, we present an electrocatalyst with superior OER performance, which attributed to the abundant active sites and good electronic conductivity. The two-dimensional CoMo Layered Double Hydroxide nanosheets are synthesized and deposited on conductive carbon nanotubes (CoMo LDH/CNTs), and then hybrid composites show better catalytic performance than their undecorated counterpart under identical conditions. Specifically, CoMo LDH/CNTs exhibit the low overpotential of 268 mV to obtain 10 mA cm-2and satisfactory stability (more than 40 h). We emphasize that this hybridization strategy with a conductive supporting framework could design more abundant and low-cost OER electrocatalysts to minimize electrical energy consumption, thereby achieving efficient conversion between energy sources.
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This manuscript describes the formation of an artifact shoulder peak with a slightly larger retention time than the main peak under the standard non-reduced capillary electrophoresis with sodium dodecyl sulfate (nrCE-SDS) analysis of a therapeutic recombinant protein X, and clarifies the formation mechanism of the artifact caused by N-ethylmaleimide (NEM) during the sample preparation procedure. A design of experiment (DoE) approach was used to investigate the impact of the factors on the formation of the impurity. Additionally, orthogonal analytical experiments were performed to study the root cause of this phenomenon. The results consistently suggested that the Michael addition reaction between NEM and lysine residues in protein X, and decreased electrophoretic mobility due to increased molecular weight, was the root cause for the artifact, which could be partially inhibited by modifications of incubation conditions. Thus, before performing the nrCE-SDS method, the effects of alkylation reagents and sample preparation procedure on analytical results need to be considered seriously.
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Artefatos , Eletroforese Capilar , Alquilação , Eletroforese Capilar/métodos , Eletroforese em Gel de Poliacrilamida , Etilmaleimida , Indicadores e Reagentes , Dodecilsulfato de Sódio/químicaRESUMO
The novel BaFe12O19/Bi3.64Mo0.36O6.55 composite materials were constructed as magnetically recyclable photo-Fenton-like degradation systems. The composite catalyst not only promoted the effective transfer of photo-generated electrons and improved the Mo6+/Mo4+ cycle consequent, but also activated hydrogen peroxide to generate oxidizing free radicals. BaFe12O19/Bi3.64Mo0.36O6.55-0.25 exhibited an outstanding degradation performance for tetracycline hydrochloride it is 1.3 times to Bi3.64Mo0.36O6.55. The thermal catalytic performance of the Bi3.64Mo0.36O6.55 monomer is similar to that of the BaFe12O19/Bi3.64Mo0.36O6.55 material without light. However, the removal rate of BaFe12O19/Bi3.64Mo0.36O6.55 material reaches 84.5% after 60 min with light, far exceeding that of Bi3.64Mo0.36O6.55 material. By way of the contrast experiment with light and without light, it is further demonstrated that interfacial interaction between BaFe12O19 and Bi3.64Mo0.36O6.55 acted a key role in the photocatalytic reaction system. It is also a good advantage that pollutants can be efficiently degraded without adjusting the pH. The characterization of photocurrent and X-ray photoelectron spectroscopy (XPS) also further proved the synergy between the two materials, which is useful to the separation of electrons and holes. The synergy ultimately improves the degradation performance. Besides, BaFe12O19/Bi3.64Mo0.36O6.55 can be easily separated by an external magnetic field after the photocatalytic activity reaction owing to BaFe12O19's magnetic properties. It provides a new research idea for the construction and iron-based heterogeneous Fenton-like system for magnetic degradation of antibiotics.
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Poluentes Ambientais , Peróxido de Hidrogênio , Antibacterianos/química , Catálise , Peróxido de Hidrogênio/química , Ferro/química , Oxirredução , Tetraciclina/químicaRESUMO
Introduction: According to the literature on anterior circulation, comorbid atrial fibrillation (AF) is not associated with a worse functional outcome, lower reperfusion rates, or higher rates of intracranial hemorrhage after mechanical thrombectomy (MT) compared to intravenous thrombolysis (IVT) or treatment with supportive care. However, data are limited for the effect of comorbid AF on procedural and clinical outcomes of acute basilar artery occlusion (ABAO) after MT. This study aimed to investigate the effect of atrial fibrillation on outcomes after MT and long-term ischemic recurrence in patients with ABAO. Methods: We performed a registered study of the Endovascular Treatment for Acute Basilar Artery Occlusion Study (BASILAR, which is registered in the Chinese Clinical Trial Registry, http://www.chictr.org.cn; ChiCTR1800014759) from January 2014 to May 2019, which included 647 patients who underwent MT for ABAO, 136 of whom had comorbid AF. Prospectively defined baseline characteristics, procedural outcomes, and clinical outcomes were reported and compared. Results: On multivariate analysis, AF predicted a shorter puncture-to-recanalization time, higher first-pass effect rate, and lower incidence of angioplasty and/or stenting (p < 0.01). AF had no effect on intracranial hemorrhage incidence [adjusted odds ratio (aOR), 1.093; 95% confidence interval (CI), 0.451-2.652], 90-day functional outcomes (adjusted common odds ratio, 0.915; 95% CI, 0.588-1.424), or mortality (aOR, 0.851; 95% CI, 0.491-1.475) after MT. The main findings were robust in the subgroup and 1-year follow-up analyses. Comorbid AF was the remaining predictor of ischemic recurrence (aOR, 4.076; 95% CI, 1.137-14.612). Conclusions: The study revealed no significant difference in the safety and efficacy of MT for ABAO regardless of whether patients had comorbid AF. However, a higher proportion of patients with AF experienced ischemic recurrence within 1 year after MT.
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GLKs (GOLDEN 2-LIKEs) are a group of plant-specific transcription factors regulating the chloroplast biogenesis, differentiation and function maintains by triggering the expression of the photosynthesis-associated nuclear genes (PhANGs). The GLKs also play important roles in nutrient's accumulation in fruits, leaf senescence, immunity and abiotic stress response. The expression of GLK genes were affected by multiple hormones or environmental factors. Therefore, GLKs were considered as the key nodes of regulatory network in plant cells, and potential candidates to improve the photosynthetic capacity of crops. Since numerous researches of GLKs have been reported in plants, the biological function, molecular mechanism of GLKs genes and its applications in breeding were summarized and a GLK-mediated signaling network model was developed. This review may facilitate future research and application of GLKs.
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Melhoramento Vegetal , Fatores de Transcrição , Cloroplastos/genética , Regulação da Expressão Gênica de Plantas , Fotossíntese/genética , Fatores de Transcrição/metabolismoRESUMO
Importance: Tirofiban is a highly selective nonpeptide antagonist of glycoprotein IIb/IIIa receptor, which reversibly inhibits platelet aggregation. It remains uncertain whether intravenous tirofiban is effective to improve functional outcomes for patients with large vessel occlusion ischemic stroke undergoing endovascular thrombectomy. Objective: To assess the efficacy and adverse events of intravenous tirofiban before endovascular thrombectomy for acute ischemic stroke secondary to large vessel occlusion. Design, Setting, and Participants: This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 55 hospitals in China, enrolling 948 patients with stroke and proximal intracranial large vessel occlusion presenting within 24 hours of time last known well. Recruitment took place between October 10, 2018, and October 31, 2021, with final follow-up on January 15, 2022. Interventions: Participants received intravenous tirofiban (n = 463) or placebo (n = 485) prior to endovascular thrombectomy. Main Outcomes and Measures: The primary outcome was disability level at 90 days as measured by overall distribution of the modified Rankin Scale scores from 0 (no symptoms) to 6 (death). The primary safety outcome was the incidence of symptomatic intracranial hemorrhage within 48 hours. Results: Among 948 patients randomized (mean age, 67 years; 391 [41.2%] women), 948 (100%) completed the trial. The median (IQR) 90-day modified Rankin Scale score in the tirofiban group vs placebo group was 3 (1-4) vs 3 (1-4). The adjusted common odds ratio for a lower level of disability with tirofiban vs placebo was 1.08 (95% CI, 0.86-1.36). Incidence of symptomatic intracranial hemorrhage was 9.7% in the tirofiban group vs 6.4% in the placebo group (difference, 3.3% [95% CI, -0.2% to 6.8%]). Conclusions and Relevance: Among patients with large vessel occlusion acute ischemic stroke undergoing endovascular thrombectomy, treatment with intravenous tirofiban, compared with placebo, before endovascular therapy resulted in no significant difference in disability severity at 90 days. The findings do not support use of intravenous tirofiban before endovascular thrombectomy for acute ischemic stroke. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR-IOR-17014167.
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Procedimentos Endovasculares , AVC Isquêmico , Inibidores da Agregação Plaquetária , Trombectomia , Tirofibana , Administração Intravenosa , Idoso , Arteriopatias Oclusivas/complicações , Arteriopatias Oclusivas/tratamento farmacológico , Arteriopatias Oclusivas/cirurgia , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/etiologia , Isquemia Encefálica/cirurgia , Método Duplo-Cego , Procedimentos Endovasculares/métodos , Feminino , Humanos , Hemorragias Intracranianas/induzido quimicamente , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/etiologia , AVC Isquêmico/cirurgia , Masculino , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/cirurgia , Trombectomia/métodos , Tirofibana/administração & dosagem , Tirofibana/efeitos adversos , Tirofibana/uso terapêutico , Resultado do TratamentoRESUMO
Insulin treatment is currently considered to be the main strategy for controlling diabetes. Although the recombinant insulin formulation is relatively mature, we found that a batch of insulin formulation exhibited an unusual degradation rate in the stability experiment. The main purposes of this article are to identify the root cause for this phenomenon and characterize of chemical and physical degradation products. We compared the chemical and physical stability of two batches of insulin formulations prepared separately with simulated repeated use and freshly opened glycerol. The chemical stability of insulin was identified by liquid chromatography coupled with tandem mass spectrometry (LC- MS/MS). Micro-flow imaging (MFI), far-ultraviolet circular dichroism (Far-UV CD) and Thioflavin T (ThT) fluorescent assays were used to reveal protein aggregation and fibrosis. The chemical and physical stability of the insulin formulation with newly opened glycerol was much better than that with degraded glycerol, and both groups of formulations were extremely sensitive to light. The results indicated that the original batch insulin formulation with abnormal stability was indeed caused by the excipient glycerol after long-term storage and repeated usage. More attention should be paid to the quality changes of excipients during repeated usage and storage of excipients for the practical purpose. Moreover, we have discovered a novel degradation pathway for insulin and peptides in general. In addition, LC-MS/MS results suggested that the N-terminus of insulin B-chain was prone to chemical degradation which enlightens that it could be potentially modified to improve the stability of insulin formulations.