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The emergence of generative artificial intelligence (AI) has revolutionized various fields. In ophthalmology, generative AI has the potential to enhance efficiency, accuracy, personalization and innovation in clinical practice and medical research, through processing data, streamlining medical documentation, facilitating patient-doctor communication, aiding in clinical decision-making, and simulating clinical trials. This review focuses on the development and integration of generative AI models into clinical workflows and scientific research of ophthalmology. It outlines the need for development of a standard framework for comprehensive assessments, robust evidence, and exploration of the potential of multimodal capabilities and intelligent agents. Additionally, the review addresses the risks in AI model development and application in clinical service and research of ophthalmology, including data privacy, data bias, adaptation friction, over interdependence, and job replacement, based on which we summarized a risk management framework to mitigate these concerns. This review highlights the transformative potential of generative AI in enhancing patient care, improving operational efficiency in the clinical service and research in ophthalmology. It also advocates for a balanced approach to its adoption.
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AIMS: Microglial cells are integral to the pathogenesis of Alzheimer's disease (AD). The observed sex disparity in AD prevalence, with a notable predominance in women, implies a potential influence of sex hormones, such as androgens, on disease mechanisms. Despite this, the specific effects of androgens on microglia remain unclear. This study is designed to delineate the interplay between androgens and the survival and inflammatory profile of microglial cells, as well as to explore their contribution to the progression of AD. METHODS AND KEY FINDINGS: To create a chronic androgen deficiency model, 3-month-old wild-type (WT) mice and APP/PS1 mice underwent bilateral orchiectomy (ORX), with age-matched sham-operated controls. Cognitive and memory were evaluated at 5 and 12 months, paralleled by assessments of amyloid-beta (Aß) and microglial morphology in hippocampal and cortical areas. The ORX treatment in mice resulted in diminished microglial populations and morphological alterations, alongside an increase in Aß plaques and a concomitant decline in cognitive performance that exacerbated over time. In vitro, dihydrotestosterone (DHT) was found to stimulate microglial proliferation and ameliorate Aß1-42-induced apoptosis. SIGNIFICANCE: These findings suggested that androgens may exert a protective role, maintaining the normal proliferation and functionality of microglial cells. This preservation could potentially slow the progression of AD. As a result, our study provided a conceptual framework for the development of novel therapeutic strategies for AD.
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Atherosclerosis (AS) is one of the most common causes of death from cardiovascular disease, and low folic acid (FA) levels have been reported to be strongly associated with an increased risk of AS. We aimed to obtain causal estimates of the association between FA and AS and to quantify the mediating role of known modifiable risk factors. Based on the largest genome-wide association study (GWAS) from the IEU Open GWAS Project for all human studies, we conducted a two-sample Mendelian randomization (MR) study of genetically predicted FA and AS. A two-step MR design was then used to assess the causal mediating effect of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) on the relationship between FA and AS. This MR analysis showed that genetically determined FA levels [IVW: Odds Ratio (OR) = 0.623, 95% CI 0.421-0.924, P = 0.018] were associated with a reduced risk of AS. Inverse variance weighted (IVW) MR analysis also showed that genetically predicted FA was positively correlated with HDL-C levels (OR = 1.358, 95% CI 1.029-1.792, P = 0.031) and negatively correlated with LDL-C (OR = 0.956, 95% CI 0.920-0.994, P = 0.023) and TG levels (OR = 0.929, 95% CI 0.886-0.974, P = 0.003). LDL-C, HDL-C, and TG mediate 3.00%, 6.80%, and 4.40%, respectively, of the total impact of FA on AS. The combined effect of these three factors accounts for 13.04% of the total effect. Sensitivity analysis verifies the stability and reliability of the results. These results support a potential causal protective effect of FA on AS, with considerable mediation through many modifiable risk factors. Thus, interventions on levels of LDL-C, HDL-C, and TG have the potential to substantially reduce the burden of AS caused by low FA.
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Aterosclerosis , HDL-Colesterol , LDL-Colesterol , Ácido Fólico , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Triglicéridos , Humanos , Ácido Fólico/sangre , Aterosclerosis/genética , Aterosclerosis/sangre , Triglicéridos/sangre , LDL-Colesterol/sangre , HDL-Colesterol/sangre , Factores de Riesgo , Predisposición Genética a la Enfermedad , Lípidos/sangreRESUMEN
Background: The noninvasive computed tomography angiography-derived fractional flow reserve (CT-FFR) can be used to diagnose coronary ischemia. With advancements in associated software, the diagnostic capability of CT-FFR may have evolved. This study evaluates the effectiveness of a novel deep learning-based software in predicting coronary ischemia through CT-FFR. Methods: In this prospective study, 138 subjects with suspected or confirmed coronary artery disease were assessed. Following indication of 30%-90% stenosis on coronary computed tomography (CT) angiography, participants underwent invasive coronary angiography and fractional flow reserve (FFR) measurement. The diagnostic performance of the CT-FFR was determined using the FFR as the reference standard. Results: With a threshold of 0.80, the CT-FFR displayed an impressive diagnostic accuracy, sensitivity, specificity, area under the receiver operating characteristic curve (AUC), positive predictive value (PPV), and negative predictive value (NPV) of 97.1%, 96.2%, 97.7%, 0.98, 96.2%, and 97.7%, respectively. At a 0.75 threshold, the CT-FFR showed a diagnostic accuracy, sensitivity, specificity, AUC, PPV, and NPV of 84.1%, 78.8%, 85.7%, 0.95, 63.4%, and 92.8%, respectively. The Bland-Altman analysis revealed a direct correlation between the CT-FFR and FFR (p < 0.001), without systematic differences (p = 0.085). Conclusions: The CT-FFR, empowered by novel deep learning software, demonstrates a strong correlation with the FFR, offering high clinical diagnostic accuracy for coronary ischemia. The results underline the potential of modern computational approaches in enhancing noninvasive coronary assessment.
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ABSTRACT: Angiomotin-like 2 (AMOTL2) is related to numerous physiological and pathological conditions by affecting signal transduction. However, whether AMOTL2 is linked to pulmonary arterial hypertension (PAH) has not been addressed. This work aimed to investigate the potential role of AMOTL2 in PAH. A decrease in AMOTL2 abundance was observed in the lungs of PAH rats. The upregulation of AMOTL2 significantly decreased right ventricle systolic pressure and right ventricular hypertrophy in PAH rats. Overexpression of AMOTL2 also led to a noteworthy decrease in vascular wall thickness, pulmonary artery area, and collagen deposition in rats with PAH. AMOTL2 was downregulated in hypoxia-stimulated pulmonary arterial smooth muscle cells (PASMCs). Moreover, AMOTL2 overexpression impeded hypoxia-evoked proliferation, migration and phenotypic transformation in rat PASMCs. Mechanistic investigation revealed that Yes-associated protein 1 (YAP1) activation in PAH rats or hypoxia-stimulated PASMCs was markedly inhibited by AMOTL2 overexpression, which was associated with increased large tumor suppressor 1/2 (LATS1/2) phosphorylation. The inhibition of LATS1/2 reversed the AMOTL2-mediated inactivation of YAP1. Restoring the activity of YAP1 reversed the inhibitory effect of AMOTL2 on hypoxia-evoked proliferation, migration and phenotypic transformation of PASMCs. Collectively, these results suggest that AMOTL2 can ameliorate PAH in a rat model by interfering with pulmonary arterial remodeling via the inactivation of YAP1 signaling. Our work indicates that AMOTL2 may be a candidate target for novel drug development for the treatment of PAH.
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BACKGROUND: Specific alterations in gut microbiota and metabolites have been linked to AMI, with CBLB potentially playing an essential role. However, the precise interactions remain understudied, creating a significant gap in our understanding. This study aims to address this by exploring these interactions in CBLB-intervened AMI mice using transcriptome sequencing, 16 S rDNA, and non-targeted metabolite analysis. METHODS: To probe the therapeutic potential and mechanistic underpinnings of CBLB overexpression in AMI, we utilized an integrative multi-omics strategy encompassing transcriptomics, metabolomics, and 16s rDNA sequencing. We selected these particular methods as they facilitate a holistic comprehension of the intricate interplay between the host and its microbiota, and the potential effects on the host's metabolic and gene expression profiles. The uniqueness of our investigation stems from utilizing a multi-omics approach to illuminate the role of CBLB in AMI, an approach yet unreported to the best of our knowledge. Our experimental protocol encompassed transfection of CBLB lentivirus-packaged vectors into 293T cells, followed by subsequent intervention in AMI mice. Subsequently, we conducted pathological staining, fecal 16s rDNA sequencing, and serum non-targeted metabolome sequencing. We applied differential expression analysis to discern differentially expressed genes (DEGs), differential metabolites, and differential microbiota. We performed protein-protein interaction analysis to identify core genes, and conducted correlation studies to clarify the relationships amongst these core genes, paramount metabolites, and key microbiota. RESULTS: Following the intervention of CBLB in AMI, we observed a significant decrease in inflammatory cell infiltration and collagen fiber formation in the infarcted region of mice hearts. We identified key changes in microbiota, metabolites, and DEGs that were associated with this intervention. The findings revealed that CBLB has a significant correlation with DEGs, differential metabolites and microbiota, respectively. This suggests it could play a pivotal role in the regulation of AMI. CONCLUSION: This study confirmed the potential of differentially expressed genes, metabolites, and microbiota in AMI regulation post-CBLB intervention. Our findings lay groundwork for future exploration of CBLB's role in AMI, suggesting potential therapeutic applications and novel research directions in AMI treatment strategies.
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Metabolómica , Ratones Endogámicos C57BL , Infarto del Miocardio , Proteínas Proto-Oncogénicas c-cbl , Transcriptoma , Animales , Infarto del Miocardio/microbiología , Infarto del Miocardio/metabolismo , Infarto del Miocardio/genética , Proteínas Proto-Oncogénicas c-cbl/metabolismo , Proteínas Proto-Oncogénicas c-cbl/genética , Transcriptoma/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Masculino , Microbioma Gastrointestinal , Perfilación de la Expresión Génica , ARN Ribosómico 16S/genética , ADN Ribosómico/genética , Ratones , Metaboloma , HumanosRESUMEN
The gut microbiota and neurological development of neonatal mice are susceptible to environmental factors that may lead to altered behavior into adulthood. However, the role that changed gut microbiota and neurodevelopment early in life play in this needs to be clarified. In this study, by modeling early-life environmental changes by cross-fostering BALB/c mice, we revealed the effects of the environment during the critical period of postnatal development on adult social behavior and their relationship with the gut microbiota and the nervous system. The neural projections exist between the ascending colon and oxytocin neurons in the paraventricular nuclei (PVN), peripheral oxytocin levels and PVN neuron numbers decreased after cross-fostering, and sex-specific alteration in gut microbiota and its metabolites may be involved in social impairments and immune imbalances brought by cross-fostering via the gut-brain axis. Our findings also suggest that social cognitive impairment may result from a combination of PVN oxytocinergic neurons, gut microbiota, and metabolites.
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Eje Cerebro-Intestino , Microbioma Gastrointestinal , Ratones Endogámicos BALB C , Neuronas , Oxitocina , Núcleo Hipotalámico Paraventricular , Conducta Social , Animales , Microbioma Gastrointestinal/fisiología , Ratones , Oxitocina/metabolismo , Masculino , Femenino , Núcleo Hipotalámico Paraventricular/metabolismo , Eje Cerebro-Intestino/fisiología , Neuronas/metabolismo , Encéfalo/metabolismo , Conducta Animal/fisiología , Colon/metabolismo , Colon/microbiología , Animales Recién NacidosRESUMEN
Aqueous zinc ion batteries (AZIBs) are attracting increasing research interest due to their intrinsic safety, low cost, and scalability. However, the issues including hydrogen evolution, interface corrosion, and zinc dendrites at anodes have seriously limited the development of aqueous zinc ion batteries. Here, N,N-methylenebis(acrylamide) (MBA) additives with -CONH- groups are introduced to form hydrogen bonds with water and suppress H2O activity, inhibiting the occurrence of hydrogen evolution and corrosion reactions at the interface. In situ optical microscopy demonstrates that the MBA additive promotes the uniform deposition of Zn2+ and then suppresses the dendrite growth on the zinc anode. Therefore, Zn//Ti asymmetric batteries demonstrate a high plating/stripping efficiency of 99.5%, while Zn//Zn symmetric batteries display an excellent cycle stability for more than 1000 h. The Zn//MnO2 full cells exhibit remarkable cycling stability for 700 cycles in aqueous electrolytes with MBA additives. The additive engineering via MBA achieved the dendrite-free Zn anodes and stable full batteries, which is favorable for advanced AZIBs in practical applications.
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Manganese-based materials are considered as one of the most promising cathodes in zinc-ion batteries (ZIBs) for large-scale energy storage applications owing to their cost-effectiveness, natural availability, low toxicity, multivalent states, high operation voltage, and satisfactory capacity. However, their intricate energy storage mechanisms coupled with unsatisfactory cycling stability hinder their commercial applications. Previous reviews have primarily focused on optimization strategies for achieving high capacity and fast reaction kinetics, while overlooking capacity fluctuation and lacking a systematic discussion on strategies to enhance the cycling stability of these materials. Thus, in this review, the energy storage mechanisms of manganese-based ZIBs with different structures are systematically elucidated and summarized. Next, the capacity fluctuation in manganese-based ZIBs, including capacity activation, degradation, and dynamic evolution in the whole cycle calendar are comprehensively analyzed. Finally, the constructive optimization strategies based on the reaction chemistry of one-electron and two-electron transfers for achieving durable cycling performance in manganese-based ZIBs are proposed.
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Cross-modal analysis of the same whole brain is an ideal strategy to uncover brain function and dysfunction. However, it remains challenging due to the slow speed and destructiveness of traditional whole-brain optical imaging techniques. Here we develop a new platform, termed Photoacoustic Tomography with Temporal Encoding Reconstruction (PATTERN), for non-destructive, high-speed, 3D imaging of ex vivo rodent, ferret, and non-human primate brains. Using an optimally designed image acquisition scheme and an accompanying machine-learning algorithm, PATTERN extracts signals of genetically-encoded probes from photobleaching-based temporal modulation and enables reliable visualization of neural projection in the whole central nervous system with 3D isotropic resolution. Without structural and biological perturbation to the sample, PATTERN can be combined with other whole-brain imaging modalities to acquire the whole-brain image with both high resolution and morphological fidelity. Furthermore, cross-modal transcriptome analysis of an individual brain is achieved by PATTERN imaging. Together, PATTERN provides a compatible and versatile strategy for brain-wide cross-modal analysis at the individual level.
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Encéfalo , Hurones , Imagenología Tridimensional , Técnicas Fotoacústicas , Animales , Encéfalo/diagnóstico por imagen , Técnicas Fotoacústicas/métodos , Imagenología Tridimensional/métodos , Ratones , Algoritmos , Aprendizaje Automático , Tomografía/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Ratas , MasculinoRESUMEN
Abnormal neuronal polarity leads to early deficits in Alzheimer's disease (AD) by affecting the function of axons. Precise and rapid evaluation of polarity changes is very important for the early prevention and diagnosis of AD. However, due to the limitations of existing detection methods, the mechanism related to how neuronal polarity changes in AD is unclear. Herein, we reported a ratiometric fluorescent probe characterized by neutral molecule to disclose the polarity changes in nerve cells and the brain of APP/PS1 mice. Cy7-K showed a sensitive and selective ratiometric fluorescence response to polarity. Remarkably, unlike conventional intramolecular charge transfer fluorescent probes, the fluorescence quantum yield of Cy7-K in highly polar solvents is higher than that in low polar solvents due to the transition of neutral quinones to aromatic zwitterions. Using the ratiometric fluorescence imaging, we found that beta-amyloid protein (Aß) inhibits the expression of histone deacetylase 6, thereby increasing the amount of acetylated Tau protein (AC-Tau) and ultimately enhancing cell polarity. There was a high correlation between polarity and AC-Tau. Furthermore, Cy7-K penetrated the blood-brain barrier to image the polarity of different brain regions and confirmed that APP/PS1 mice had higher polarity than Wild-type mice. The probe Cy7-K will be a promising tool for assessing the progression of AD development by monitoring polarity.
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Enfermedad de Alzheimer , Colorantes Fluorescentes , Proteínas tau , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/diagnóstico , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Animales , Proteínas tau/metabolismo , Proteínas tau/análisis , Ratones , Acetilación , Imagen Óptica , Humanos , Ratones Transgénicos , Estructura MolecularRESUMEN
BACKGROUND: Recent studies have identified empathy deficit as a core impairment and diagnostic criterion for people with autism spectrum disorders; however, the improvement of empathy focuses primarily on behavioural interventions without the target regulation. We sought to compare brain regions associated with empathy-like behaviours of fear and pain, and to explore the role of the oxytocin-oxytocin receptor system in fear empathy. METHODS: We used C57BL mice to establish 2 models of fear empathy and pain empathy. We employed immunofluorescence histochemical techniques to observe the expression of c-Fos throughout the entire brain and subsequently quantified the number of c-Fos-positive cells in different brain regions. Furthermore, we employed chemogenetic technology to selectively manipulate these neurons in Oxt-Cre-/+ mice to identify the role of oxytocin in this process. RESULTS: The regions activated by fear empathy were the anterior cingulate cortex, basolateral amygdala, nucleus accumbens, paraventricular nucleus (PVN), lateral habenula, and ventral and dorsal hippocampus. The regions activated by pain empathy were the anterior cingulate cortex, basolateral amygdala, nucleus accumbens, and lateral habenula. We found that increasing the activity of oxytocin neurons in the PVN region enhanced the response to fear empathy. This enhancement may be mediated through oxytocin receptors. LIMITATIONS: This study included only male animals, which restricts the broader interpretation of the findings. Further investigations on circuit function need to be conducted. CONCLUSION: The brain regions implicated in the regulation of fear and pain empathy exhibit distinctions; the activity of PVN neurons was positively correlated with empathic behaviour in mice. These findings highlight the role of the PVN oxytocin pathway in regulating fear empathy and suggest the importance of oxytocin signalling in mediating empathetic responses.
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Empatía , Miedo , Ratones Endogámicos C57BL , Neuronas , Oxitocina , Núcleo Hipotalámico Paraventricular , Animales , Oxitocina/metabolismo , Masculino , Núcleo Hipotalámico Paraventricular/metabolismo , Miedo/fisiología , Empatía/fisiología , Neuronas/metabolismo , Ratones , Receptores de Oxitocina/metabolismo , Proteínas Proto-Oncogénicas c-fos/metabolismo , Dolor/fisiopatología , Dolor/psicología , Ratones TransgénicosRESUMEN
INTRODUCTION: Transcription factor EB (TFEB), a key regulator of autophagy and lysosomal biogenesis, has diverse roles in various physiological processes. Enhancing lysosomal function by TFEB activation has recently been implicated in restoring neural stem cells (NSCs) function. Overexpression of TFEB can inhibit the cell cycle of newborn cortical NSCs. It has also been found that TFEB regulates the pluripotency transcriptional network in mouse embryonic stem cells independent of autophagy lysosomal biogenesis. This study aims to explore the effects of TFEB activation on neurogenesis in vivo through transgenic mice. METHODS: We developed a GFAP-driven TFEB overexpression mouse model (TFEB GoE) by crossing the floxed TFEB overexpression mice and hGFAP-cre mice. We performed immunohistochemical and fluorescence staining on brain tissue from newborn mice to assess neurogenesis changes, employing markers such as GFAP, Nestin, Ki67, DCX, Tbr1 and Neun to trace different stages of neural development and cell proliferation. RESULTS: TFEB GoE mice exhibited premature mortality, dying at 10-20 days after birth. Immunohistochemical analysis revealed significant abnormalities, including disrupted hippocampal structure and cortical layering. Compared to control mice, TFEB GoE mice showed a marked increase in radial glial cells (RGCs) in the hippocampus and cortex, with Ki67 staining indicating these cells were predominantly in a quiescent state. This suggests that TFEB overexpression suppresses RGCs proliferation. Additionally, abnormal distributions of migrating neurons and mature neurons were observed, highlighted by DCX, Tbr1 and Neun staining, indicating a disruption in normal neurogenesis. CONCLUSION: This study, using transgenic animals in vivo, revealed that GFAP-driven TFEB overexpression leads to abnormal neural layering in the hippocampus and cortex by dysregulating neurogenesis. Our study is the first to discover the detrimental impact of TFEB overexpression on neurogenesis during embryonic development, which has important reference significance in future TFEB overexpression interventions in NSCs for treatment.
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The nature of spinal output pathways that convey nociceptive information to the brain has been the subject of controversy. Here, we provide anatomical, molecular, and functional characterizations of two distinct anterolateral pathways: one, ascending in the lateral spinal cord, triggers nociceptive behaviors, and the other one, ascending in the ventral spinal cord, when inhibited, leads to sensorimotor deficits. Moreover, the lateral pathway consists of at least two subtypes. The first is a contralateral pathway that extends to the periaqueductal gray (PAG) and thalamus; the second is a bilateral pathway that projects to the bilateral parabrachial nucleus (PBN). Finally, we present evidence showing that activation of the contralateral pathway is sufficient for defensive behaviors such as running and freezing, whereas the bilateral pathway is sufficient for attending behaviors such as licking and guarding. This work offers insight into the complex organizational logic of the anterolateral system in the mouse.
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Núcleos Parabraquiales , Médula Espinal , Ratones , Animales , Médula Espinal/fisiología , Tálamo/fisiología , Sustancia Gris Periacueductal/fisiología , Vías Nerviosas/fisiologíaRESUMEN
The advent of generative artificial intelligence and large language models has ushered in transformative applications within medicine. Specifically in ophthalmology, large language models offer unique opportunities to revolutionise digital eye care, address clinical workflow inefficiencies, and enhance patient experiences across diverse global eye care landscapes. Yet alongside these prospects lie tangible and ethical challenges, encompassing data privacy, security, and the intricacies of embedding large language models into clinical routines. This Viewpoint highlights the promising applications of large language models in ophthalmology, while weighing up the practical and ethical barriers towards their real-world implementation. This Viewpoint seeks to stimulate broader discourse on the potential of large language models in ophthalmology and to galvanise both clinicians and researchers into tackling the prevailing challenges and optimising the benefits of large language models while curtailing the associated risks.
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Medicina , Oftalmología , Humanos , Inteligencia Artificial , Lenguaje , PrivacidadRESUMEN
The challenge with aqueous zinc-ion batteries (ZIBs) lies in finding suitable cathode materials that can provide high capacity and fast kinetics. Herein, two-dimensional topological Bi2 Se3 with acceptable Bi-vacancies for ZIBs cathode (Cu-Bi2-x Se3 ) is constructed through one-step hydrothermal process accompanied by Cu heteroatom introduction. The cation-deficient Cu-Bi2-x Se3 nanosheets (≈4 nm) bring improved conductivity from large surface topological metal states contribution and enhanced bulk conductivity. Besides, the increased adsorption energy and reduced Zn2+ migration barrier demonstrated by density-functional theory (DFT) calculations illustrate the decreased Coulombic ion-lattice repulsion of Cu-Bi2-x Se3 . Therefore, Cu-Bi2-x Se3 exhibits both enhanced ion and electron transport capability, leading to more carrier reversible insertion proved by in situ synchrotron X-ray diffraction (SXRD). These features endow Cu-Bi2-x Se3 with sufficient specific capacity (320 mA h g-1 at 0.1 A g-1 ), high-rate performance (97 mA h g-1 at 10 A g-1 ), and reliable cycling stability (70 mA h g-1 at 10 A g-1 after 4000 cycles). Furthermore, quasi-solid-state fiber-shaped ZIBs employing the Cu-Bi2-x Se3 cathode demonstrate respectable performance and superior flexibility even under high mass loading. This work implements a conceptually innovative strategy represented by cation defect design in topological insulator cathode for achieving high-performance battery electrochemistry.
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Objective: Hyperglycemia and insulin resistance or deficiency are characteristic features of diabetes. Diabetes is accompanied by cardiomyocyte hypertrophy, fibrosis and ventricular remodeling, and eventually heart failure. In this study, we established a diabetic cardiomyopathy (DCM) mouse model to explore the role and mechanism of miR-200a-3p in DCM. Methods: We used db/db mice to simulate the animal model of DCM and the expression of miR-200a-3p was then examined by RT-qPCR. Tail vein injection of mice was done with rAAV-miR-200a-3p for 8 weeks, and cardiac function was assessed by cardiac ultrasound. The levels of myocardial tissue injury, fibrosis, inflammation, apoptosis and autophagy in mice were detected by histological staining, TUNEL and other molecular biological experiments. Results: miR-200a-3p expression levels were significantly decreased in the myocardium of DCM mice. Diabetic mice developed cardiac dysfunction and presented pathological changes such as myocardial injury, myocardial interstitial fibrosis, cardiomyocyte apoptosis, autophagy, and inflammation. Overexpression of miR-200a-3p expression significantly ameliorated diabetes induced-cardiac dysfunction and myocardial injury, myocardial interstitial fibrosis, cardiomyocyte apoptosis, and inflammation, and enhanced autophagy. Mechanistically, miR-200a-3p interacted with FOXO3 to promote Mst1 expression and reduce Sirt3 and p-AMPK expression. Conclusion: In type 2 diabetes, increased miR-200a-3p expression enhanced autophagy and participated in the pathogenic process of cardiomyopathy throug7 Mst1/Sirt3/AMPK axis regulation by its target gene FOXO3. This conclusion provides clues for the search of new gene targeted therapeutic approaches for diabetic cardiomyopathy.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Cardiomiopatías Diabéticas , Lesiones Cardíacas , MicroARNs , Sirtuina 3 , Animales , Ratones , Proteínas Quinasas Activadas por AMP/genética , Autofagia/genética , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Cardiomiopatías Diabéticas/genética , Inflamación , MicroARNs/genéticaRESUMEN
BACKGROUND: Non-ST-segment elevation myocardial infarction (NSTEMI) is a common form of acute myocardial infarction and rapid and accurate diagnosis is crucial for timely treatment. Current guidelines recommend using high-sensitivity cardiac troponin (hs-cTn) assays to determine circulating cTnI or cTnT levels. While the accuracy of the 0 h/1 h algorithm for diagnosing NSTEMI in different regions and patient populations remains controversial. Additionally, point-of-care testing (POCT) cTn assays have the potential to provide troponin readings to physicians within 15 min, but their accuracy in diagnosing NSTEMI in the emergency department (ED) requires further investigation. METHODS: A single-center prospective observational cohort study was conducted at Shaanxi Provincial People's Hospital to assess the analytical and diagnostic performance of the laboratory-based Roche Modular E170 hs-cTnT using the 0 h/1 h algorithm with Radiometer AQT90-flex POCT cTnT assay in undifferentiated chest pain patients presenting to the ED. Whole-blood samples were collected and hs-cTnT and POCT cTnI were measured simultaneously at baseline and after 1 h. RESULTS: The study results showed that the POCT cTnT assay using the 0 h/1 h algorithm had comparable diagnostic accuracy to the laboratory-based Roche Modular E170 hs-cTnT assay in diagnosing NSTEMI in patients with chest pain. CONCLUSION: The laboratory-based Roche Modular E170 hs-cTnT using the 0 h/1 h algorithm is reliable and accurate method for diagnosing NSTEMI in undifferentiated chest pain patients presenting to the ED. POCT cTnT assay has comparable diagnostic accuracy to the hs-cTnT assay and its rapid turnaround time makes it a valuable tool in expediting the diagnostic workup of chest pain patients.
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Infarto del Miocardio sin Elevación del ST , Infarto del Miocardio con Elevación del ST , Humanos , Infarto del Miocardio sin Elevación del ST/diagnóstico , Estudios Prospectivos , Dolor en el Pecho/diagnóstico , Dolor en el Pecho/etiología , Troponina T , Troponina I , Algoritmos , Servicio de Urgencia en Hospital , BiomarcadoresRESUMEN
Constructing well-defined nanostructures consisting of the multiple components with distinctive features are a promising but challenging strategy to develop advanced electroactive materials for energy storage applications. Herein, heterogeneous Ni-Co phosphide/phosphate with a specific hollow sea-urchin-like structure has been synthesized as advanced electroactive materials for both hybrid supercapacitor (HSC) and alkaline zinc-metal battery (AZB) applications. The heterogeneous Ni-Co phosphide/phosphate combines the merits of improved electrolyte interfacial property from the specific hollow sea-urchin-like structure, high electron-conductivity of phosphide, and better ion adsorption and solid diffusion property of phosphate. As a result, the Ni-Co phosphide/phosphate achieves a high capacity to 180.7 mA h g-1 at 1 A g-1, excellent rate capability of 51% capacity retention when the specific current increases by 50 times, and stable cycling stability of 85% capacity retention when cycled for 1000 cycles. Ex situ test was conducted to investigate the formation mechanism for the hollow and sea-urchin-like structure, which can be ascribed to the anion exchange reaction between pre-formed hydroxide and CO32- ions. When used to assemble HSCs with reduced graphene oxide (RGO), the HSCs exhibit a high specific energy of 49.4 W h kg-1, an ultrahigh specific power to 11.7 kW kg-1, and an eminent cycling stability over 10,000 cycles. Meanwhile, Ni2Co-P/POx-based AZB also achieves both high-energy and high-power performance with the specific energy of 308.0 W h kg-1 at 828.4 W kg-1 and 117.4 W h kg-1 at 30.8 kW kg-1. These results above suggest that heterogeneous Ni-Co phosphide/phosphate has great potential to be used as a candidate for both HSC and AZB applications.
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Background: Coronary bifurcation lesions are common of percutaneous coronary intervention (PCI), and the optimal interventional therapy strategy is still a matter of debate and remains a challenge for interventional cardiologists. The provisional stenting technique is still a preferred method for most bifurcation lesions, but restenosis of the side branch (SB) occurs in approximately 17-19% of cases. Therefore, the dilemma of reducing SB restenosis still exists, and further research on strategies to reduce restenosis for SB is necessary. Drug-coated balloon (DCB) can reduce clinical events in small vessel disease and in-stent restenosis. The efficacy and safety of DCB for SB of true coronary bifurcation lesions have not been fully investigated. A randomized comparison of DCB combined with cutting balloon angioplasty vs. cutting balloon angioplasty for SB has never been published. Methods and design: The purpose of this study is to explore the superiority of DCB combined with cutting balloon vs. cutting balloon angioplasty for SB after main vessel (MV) drug-eluting stent implantation of true coronary bifurcation lesions. This study is a multicenter, prospective, randomized controlled trial including 140 patients with true coronary bifurcation lesions. Patients will be randomized in a 1:1 manner to receive either DCB combined with cutting balloon or cutting balloon angioplasty for SB after MV drug-eluting stent implantation. The primary endpoint is the evaluation of late lumen loss (LLL) of SB at the 9-month follow-up. The secondary endpoints include procedural success during initial hospitalization, LLL of MV at the 9-month follow-up, binary angiographic restenosis in MV and SB at the 9-month follow-up, the proportion of patients with a final post-PCI quantitative flow ratio result ≤ 0.80 for SB at the 9-month follow-up, and major adverse cardiac events during the 24-month follow-up. Conclusions: This clinical trial will provide evidence as to whether DCB combined with cutting balloon for SB of true coronary bifurcation lesions is a superior treatment approach. Trial Registration Number: ChiCTR2000040475. Dissemination: The results of this clinical trial will be published in a peer-reviewed journal.