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Background: COVID-19-induced pneumonia has become a persistent health concern, with severe cases posing a significant threat to patient lives. However, the potential of artificial intelligence (AI) in assisting physicians in predicting the prognosis of severe COVID-19 patients remains unclear. Methods: To obtain relevant studies, two researchers conducted a comprehensive search of the PubMed, Web of Science, and Embase databases, including all studies published up to October 31, 2023, that utilized AI to predict mortality rates in severe COVID-19 patients. The PROBAST 2019 tool was employed to assess the potential bias in the included studies, and Stata 16 was used for meta-analysis, publication bias assessment, and sensitivity analysis. Results: A total of 19 studies, comprising 26 models, were included in the analysis. Among them, the models that incorporated both clinical and radiological data demonstrated the highest performance. These models achieved an overall sensitivity of 0.81 (0.64-0.91), specificity of 0.77 (0.71-0.82), and an overall area under the curve (AUC) of 0.88 (0.85-0.90). Subgroup analysis revealed notable findings. Studies conducted in developed countries exhibited significantly higher predictive specificity for both radiological and combined models (p < 0.05). Additionally, investigations involving non-intensive care unit patients demonstrated significantly greater predictive specificity (p < 0.001). Conclusion: The current evidence suggests that artificial intelligence prediction models show promising performance in predicting the prognosis of severe COVID-19 patients. However, due to variations in the suitability of different models for specific populations, it is not yet certain whether they can be fully applied in clinical practice. There is still room for improvement in their predictive capabilities, and future research and development efforts are needed. Systematic review registration: https://www.crd.york.ac.uk/prospero/ with the Unique Identifier CRD42023431537.
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Inteligencia Artificial , COVID-19 , Humanos , COVID-19/mortalidad , Pronóstico , SARS-CoV-2 , Índice de Severidad de la EnfermedadRESUMEN
Scanning tunneling microscopy (STM) serves as a critical tool for high-resolution surface imaging, yet deciphering the atomic structures from STM images on multielement surfaces, such as oxides and carbides, remains a challenging task that heavily relies on the expertise and intuition of researchers. In this study, we introduce a data-driven method for rapid structural recognition from STM images. This method involves extracting structural features, filtering through a structural database, and matching with simulated STM images and surface energy analyses, thereby providing researchers with several of the most probable structures. We demonstrate the capabilities of this technique using our previously reported iron carbide grown on an Fe(110) crystal. By proposing a candidate structure set and establishing a comprehensive database linking STM images to corresponding structures and surface energies, we selected 6 out of more than 10â¯000 possible surfaces. On the basis of these 6 recommendations, researchers can conveniently determine the real surface structures. Our work provides an efficient tool for the structure recognition of STM images to construct surface structures, potentially serving as a universal auxiliary tool for STM structural analysis.
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BACKGROUND: Angina with no obstructive coronary disease (ANOCA) and ischemia with no obstructive coronary disease, prevalent yet underrecognized conditions, mostly affect women. Previous studies rarely distinguished between them. We aimed to compare the prevalence of objective ischemia through various examinations in women with ANOCA and assess the impact of objective and subjective ischemia on their mental health. METHODS AND RESULTS: A total of 84 eligible women with ANOCA and 42 controls underwent mental stress, pharmacological stress, exercise stress, and Holter testing. Objective evidence of myocardial ischemia was assessed by positron emission tomography-computed tomography and ECG, and subjective symptoms were graded using the Canadian Cardiovascular Society scale (CCS). Psychological assessments were conducted using 6 scales. Among 84 women with ANOCA, 37 (44%) received a diagnosis of ischemia with no obstructive coronary disease following mental stress testing, 20 (28.6%) through pharmacological stress testing, 14 (21.2%) via exercise stress testing, and 24 (32.9%) from Holter. Mental stress-induced myocardial ischemia was more prevalent (P<0.05). Among 54 patients with ANOCA who completed all tests, 30% showed no ischemia, and only 1 (1.9%) showed ischemia in all tests. In addition, patients with ANOCA had higher psychological scores than controls (P<0.01). No significant differences was observed in psychological scores between ANOCA with positive and negative ischemia test results (P>0.05). However, ANOCA with milder angina (CCS I) exhibited higher scores across the Hospital Anxiety and Depression Scale, State-Trait Anxiety Inventory, Perceived Stress Scale, and Posttraumatic Stress Disorder Checklist-Civilian Version and a higher prevalence of Type D personality traits (P<0.05). CONCLUSIONS: In patients with ANOCA, the positive rate of myocardial ischemia exhibits variability among several noninvasive tests. A worsened psychological state is more closely linked to milder angina symptoms than to ischemia performance, highlighting the importance of focusing on symptom management in their psychological care. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03982901.
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Angina de Pecho , Prueba de Esfuerzo , Isquemia Miocárdica , Humanos , Femenino , Persona de Mediana Edad , Isquemia Miocárdica/psicología , Isquemia Miocárdica/epidemiología , Isquemia Miocárdica/diagnóstico , Angina de Pecho/psicología , Angina de Pecho/epidemiología , Angina de Pecho/diagnóstico , Prevalencia , Anciano , Distrés Psicológico , Electrocardiografía Ambulatoria , Estudios de Casos y Controles , Tomografía Computarizada por Tomografía de Emisión de Positrones , Estrés Psicológico/epidemiologíaRESUMEN
Background: Exercise capacity serves as a direct representation of cardiac function. The Duke Activity Status Index (DASI), a self-administered 12-item questionnaire, covers aspects of daily living, household tasks, sexual function, and physical activity. Although widely used to evaluate exercise capacity, its validation in Chinese cardiovascular disease (CVD) patients has not been thoroughly explored. Considering the significant cultural and lifestyle differences between China and Western countries, which may influence Chinese patients' comprehension and responses to DASI, our objective is to culturally adapt DASI for Chinese patients with CVD to ensure its precision in assessing exercise capacity. Methods: The cultural adaptation of the original DASI questionnaire into Chinese followed a rigorous process to ensure its validity, reliability, and sensitivity to Chinese CVD patients. The study included 107 outpatients diagnosed with CVD who completed the DASI and cardiopulmonary exercise testing (CPET). Cronbach's alpha, Spearman correlation, and factor analysis were utilized to test reliability and validity. Receiver operating characteristic (ROC) curve analysis was employed to assess the prognostic utility of the DASI. Results: Participants had a mean DASI score of 39.40 ± 10.75 and a peak oxygen uptake (Peak VO 2 ) of 19.53 ± 5.89 mL/min/kg. The Chinese version of the DASI exhibited satisfactory reliability and validity in CVD patients, with a Chronbach's alpha coefficient of 0.706. The DASI score demonstrated a moderate correlation with Peak VO 2 measured by CPET (r = 0.67, p < 0.001). Factor analysis yielded three factors, accounting for 56.76% of the total variance, with factor 1 contributing to 26.38% of the variance. ROC curve analysis demonstrated that the DASI exhibited discriminative utility in the identification of patients with improved long-term prognosis (p < 0.001). The ROC curve had an area of 0.788 [95% confidence interval (CI) = 0.704-0.871]. The DASI score ≥ 36.85 served as the optimal threshold for enhanced long-term prognosis, exhibiting a sensitivity of 0.80 and a specificity of 0.69. Conclusions: The culturally adapted DASI questionnaire is a straightforward and efficient tool for reasonably evaluating exercise capacity in Chinese CVD patients.
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OBJECTIVES: To explore the long-term trends in unhealthy lifestyle factors and the risk sociodemographic subgroups among people with dyslipidemia. METHODS: Data extracted from the 1999 to 2018 National Health and Nutrition Examination Survey (NHANES). Lifestyle factors were smoking status, alcohol drinking, obesity, dietary quality, depression, physical activity, and sedentary behavior. A Joinpoint regression model was used to estimate trends in the log-transformed age-standardized prevalence. Multinomial logistic regression models adjusted for age, sex, and race/ethnicity were used to analyze subgroups by sociodemographic factors. RESULTS: Data for 33,680 respondents were extracted between 1999 and 2018. The prevalence of smoking and poor-quality diet decreased from 1999 to 2018 (P<0.001), while obesity significantly increased (P<0.001). The prevalence of depression marginally increased from 2005 to 2018 (P=0.074). We observed that non-Hispanic Black individuals, Hispanics, males, as well as those with lower family income-to-poverty ratios and education levels, unemployed individuals, or those lacking a spouse/live-in partner, were at elevated risk of unhealthy lifestyle factors when compared to the reference groups. CONCLUSIONS: Among NHANES respondents from 1999 to 2018 with dyslipidemia, significant reductions in the prevalence of current smoking and poor diet were observed, while the prevalence of obesity was markedly increased. There were sociodemographic differences in the management of lifestyle factors. Further initiatives to encourage people with dyslipidemia are required to reduce potential adverse outcomes.
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Although randomised controlled trials are considered the gold standard in clinical research, they are not always feasible due to limitations in the study population, challenges in obtaining evidence, high costs and ethical considerations. As a result, single-arm trial designs have emerged as one of the methods to address these issues. Single-arm trials are commonly applied to study advanced-stage cancer, rare diseases, emerging infectious diseases, new treatment methods and medical devices. Single-arm trials have certain ethical advantages over randomised controlled trials, such as providing equitable treatment, respecting patient preferences, addressing rare diseases and timely management of adverse events. While single-arm trials do not adhere to the principles of randomisation and blinding in terms of scientific rigour, they still incorporate principles of control, balance and replication, making the design scientifically reasonable. Compared with randomised controlled trials, single-arm trials require fewer sample sizes and have shorter trial durations, which can help save costs. Compared with cohort studies, single-arm trials involve intervention measures and reduce external interference, resulting in higher levels of evidence. However, single-arm trials also have limitations. Without a parallel control group, there may be biases in interpreting the results. In addition, single-arm trials cannot meet the requirements of randomisation and blinding, thereby limiting their evidence capacity compared with randomised controlled trials. Therefore, researchers consider using single-arm trials as a trial design method only when randomised controlled trials are not feasible.
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Accurate differentiation between angina with no obstructive coronary arteries (ANOCA) and mental stress-induced myocardial ischemia (MSIMI) is crucial for tailored treatment strategies, yet public data scarcity hampers understanding. Given the higher incidence of both conditions in women, this study prospectively enrolled 80 female ANOCA and 39 age-matched female controls, subjecting them to three types of mental stress tasks. ECGs were continuously monitored across Rest, Stress, and Recover stages of the mental stress tasks, with PET/CT imaging during the Stress stage to evaluate myocardial perfusion. With PET/CT serving as the gold standard for MSIMI diagnosis, 35 of the 80 ANOCA patients were diagnosed as MSIMI. Using ECG variables from different stages of mental stress tasks, we developed five machine learning models to diagnose MSIMI. The results showed that ECG data from different stages provide valuable information for MSIMI classification. Additionally, the dataset encompassed demographic details, physiological, and blood sample test results of the patients. We anticipate this new dataset will significantly push further progress in ANOCA and MSIMI research.
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Electrocardiografía , Isquemia Miocárdica , Estrés Psicológico , Humanos , Femenino , Isquemia Miocárdica/diagnóstico por imagen , Isquemia Miocárdica/fisiopatología , Isquemia Miocárdica/psicología , Estrés Psicológico/complicaciones , Aprendizaje Automático , Tomografía Computarizada por Tomografía de Emisión de Positrones , Persona de Mediana Edad , Angina de Pecho/fisiopatología , Estudios ProspectivosRESUMEN
Purpose: Mental stress induced myocardial ischemia (MSIMI) is regarded as the primary cause of the angina with no obstructive coronary artery disease (ANOCA). Obstructive sleep apnea (OSA) is autonomously linked to obstructive coronary heart disease, hypertension, and sudden cardiac death. Similar to the impact of psychological stress on the cardiovascular system, individuals with OSA experience periodic nocturnal hypoxia, resulting in the activation of systemic inflammation, oxidative stress, endothelial dysfunction, and sympathetic hyperactivity. The contribution of OSA to MSIMI in ANOCA patients is unclear. To explore the prevalence of OSA in ANOCA patients and the correlation between OSA and MSIMI, a prospective cohort of female ANOCA patients was recruited. Patients and Methods: We recruited female patients aged 18 to 75 years old with ANOCA and evaluated MSIMI using positron emission tomography-computed tomography. Subsequently, Level III portable monitors was performed to compare the relationship between OSA and MSIMI. Results: There is higher REI (7.8 vs 2.6, P=0.019), ODI (4.7 vs 9.2, P=0.028) and percentage of OSA (67.74% vs 33.33%, P=0.004) in MSIMI patients. The patients diagnosed with OSA demonstrated higher myocardial perfusion imaging scores (SSS: 1.5 vs 3, P = 0.005, SDS: 1 vs 3, P = 0.007). Adjusted covariates, the risk of developing MSIMI remained 3.6 times higher in OSA patients (ß=1.226, OR = 3.408 (1.200-9.681), P = 0.021). Conclusion: Patients with MSIMI exhibit a greater prevalence of OSA. Furthermore, the myocardial blood flow perfusion in patients with OSA is reduced during mental stress.
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BACKGROUND: Despite the fact that red blood cell (RBC) transfusion is commonly applied in surgical intensive care unit (ICU), the effect of RBC transfusion on long-term outcomes remains undetermined. We aimed to explore the association between RBC transfusion and the long-term prognosis of surgical sepsis survivors. METHODS: This retrospective study was conducted on adult sepsis patients admitted to a tertiary surgical ICU center in China. Patients were divided into transfusion and non-transfusion groups based on the presence of RBC transfusion. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW)were performed to balance the potential confounders. RESULTS: A total of 1421 surgical sepsis survivors were enrolled, including 403 transfused patients and 1018 non-transfused patients. There was a significant difference in 1-year mortality between the two groups (23.1 â% vs 12.7 â%, HR: 1.539, 95 â% confidence interval [CI]: 1.030-2.299, P â< â0.001). After PSM and IPTW, transfused patients still showed significantly increased 1-year mortality risks compared to non-transfused individuals (PSM: 23.6 â% vs 15.9 â%, HR 1.606, 95 â% CI 1.036-2.488 âP â= â0.034; IPTW: 20.1 â% vs 12.9 â%, HR 1.600, 95 â% CI 1.040-2.462 âP â= â0.032). Among patients with nadir hemoglobin below 70 âg/L, 1-year mortality risks in both groups were similar (HR 1.461, 95 â% CI 0.909-2.348, P â= â0.118). However, among patients with nadir hemoglobin above 70 âg/L, RBC transfusion was correlated with increased 1-year mortality risk (HR 1.556, 95 â% CI 1.020-2.374, P â= â0.040). CONCLUSION: For surgical sepsis survivors, RBC transfusion during ICU stay was associated with increased 1-year mortality, especially when patients show hemoglobin levels above 70 âg/L.
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High performance computing (HPC) is renowned for its capacity to tackle complex problems. Meanwhile, quantum computing (QC) provides a potential way to accurately and efficiently solve quantum chemistry problems. The emerging field of quantum-centric high performance computing (QCHPC), which merges these two powerful technologies, is anticipated to enhance computational capabilities for solving challenging problems in quantum chemistry. The implementation of QCHPC for quantum chemistry requires interdisciplinary research and collaboration across multiple fields, including quantum chemistry, quantum physics, computer science and so on. This perspective provides an introduction to the quantum algorithms that are suitable for deployment in QCHPC, focusing on conceptual insights rather than technical details. Parallel strategies to implement these algorithms on quantum-centric supercomputers are discussed. We also summarize high performance quantum emulating simulators, which are considered a viable tool to explore QCHPC. We conclude with challenges and outlooks in this field.
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BACKGROUND: The utility of radionuclide myocardial perfusion imaging including positron emission tomography (PET) for diagnosing mental stress-induced myocardial ischemia (MSIMI) is clinically restricted. This study aims to assess the diagnostic performance of novel echocardiographic techniques, including automated strain and quantitative myocardial contrast echocardiography (MCE) with dedicated software and deep neural network model, for MSIMI detection. The secondary objective was to explore the correlation between changes in myocardial blood flow and MSIMI. METHODS: Seventy-two female patients ages 18 to 75 with angina and nonobstructive coronary artery disease (ANOCA) and 23 healthy controls were prospectively recruited. Both echocardiography with contrast agent and PET imaging were performed during structured mental stress testing. Mental stress-induced myocardial ischemia was defined as a summed difference score ≥3 on PET. Echocardiographic parameters including left ventricular global longitudinal strain, ß, and A × ß were obtained, and their trends during mental stress testing were observed. ΔGLS was defined as the ratio of difference between global longitudinal strain values at stress and rest to the rest data. ß reserve and A×ß reserve were respectively calculated. RESULTS: Thirty-two ANOCA patients (44%) and 1 control (4%) were diagnosed with MSIMI (P < .01). For ANOCA patients with MSIMI, left ventricular GLS, ß, and A × ß declined to varied extents during mental stress testing compared with those without MSIMI and the controls (P < .05). Bland-Altman plots demonstrated good consistency between ß reserve and A × ß reserve output by the deep neural network model and iMCE software. Receiver operating characteristic curve analyses showed that ΔGLS, ß reserve, and A × ß reserve demonstrated favorable ability to predict MSIMI, especially the combination of A × ß reserve using iMCE analysis and ΔGLS (area under the curve, 0.94; sensitivity, 83%; specificity, 97%). CONCLUSIONS: Novel technologies in echocardiography exhibit the potential to be a clinical alternative to cardiac PET for effectively detecting MSIMI. Attenuated myocardial blood flow response during structured mental stress testing was correlated with MSIMI, providing a reasonable explanation for the chest discomfort persisting in ANOCA women.
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The design and construction of continuous flow biochemical reactors comprising immobilized biocatalysts have generated great interest in the efficient synthesis of value-added chemicals. Living cells use compartmentalization and reaction-diffusion processes for spatiotemporal regulation of biocatalytic reactions, and implementing these strategies into continuous flow reactors can offer new opportunities in reactor design and application. Herein, the fabrication of protocell-based continuous flow reactors for enzyme and whole-cell mediated biocatalysis is demonstrated. Semipermeable membranized coacervate vesicles are employed as model protocells that spontaneously sequester enzymes or accumulate living bacteria to produce embodied microreactors capable of single- or multiple-step catalytic reactions. By packing millions of the enzyme/bacteria-containing coacervate vesicles in a glass column, a facile, cost-effective, and modular methodology capable of performing oxidoreductase, peroxidase and lipolytic reactions, enzyme-mediated L-DOPA synthesis, and whole-cell glycolysis under continuous flow conditions, is demonstrated. It is shown that the protocell-nested enzymes and bacterial cells exhibit enhanced activities and stability under deleterious operating conditions compared with their non-encapsulated counterparts. These results provide a step toward the engineering of continuous flow reactors based on cell-like microscale agents and offer opportunities in the development of green and sustainable industrial bioprocessing.
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Células Artificiales , Biocatálisis , Reactores Biológicos , Células Artificiales/metabolismo , Células Artificiales/química , Enzimas Inmovilizadas/química , Enzimas Inmovilizadas/metabolismo , Glucólisis , Enzimas/metabolismo , Enzimas/químicaRESUMEN
INTRODUCTION: Excess salt intake is not only an independent risk factor for heart failure, but also one of the most important dietary factors associated with cardiovascular disease worldwide. Metabolic reprogramming in cardiomyocytes is an early event provoking cardiac hypertrophy that leads to subsequent cardiovascular events upon high salt loading. Although SGLT2 inhibitors, such as canagliflozin, displayed impressive cardiovascular health benefits, whether SGLT2 inhibitors protect against cardiac hypertrophy-related metabolic reprogramming upon salt loading remain elusive. OBJECTIVES: To investigate whether canagliflozin can improve salt-induced cardiac hypertrophy and the underlying mechanisms. METHODS: Dahl salt-sensitive rats developed cardiac hypertrophy by feeding them an 8% high-salt diet, and some rats were treated with canagliflozin. Cardiac function and structure as well as mitochondrial function were examined. Cardiac proteomics, targeted metabolomics and SIRT3 cardiac-specific knockout mice were used to uncover the underlying mechanisms. RESULTS: In Dahl salt-sensitive rats, canagliflozin showed a potent therapeutic effect on salt-induced cardiac hypertrophy, accompanied by lowered glucose uptake, reduced accumulation of glycolytic end-products and improved cardiac mitochondrial function, which was associated with the recovery of cardiac expression of SIRT3, a key mitochondrial metabolic regulator. Cardiac-specific knockout of SIRT3 not only exacerbated salt-induced cardiac hypertrophy but also abolished the therapeutic effect of canagliflozin. Mechanistically, high salt intake repressed cardiac SIRT3 expression through a calcium-dependent epigenetic modifications, which could be blocked by canagliflozin by inhibiting SGLT1-mediated calcium uptake. SIRT3 improved myocardial metabolic reprogramming by deacetylating MPC1 in cardiomyocytes exposed to pro-hypertrophic stimuli. Similar to canagliflozin, the SIRT3 activator honokiol also exerted therapeutic effects on cardiac hypertrophy. CONCLUSION: Cardiac mitochondrial dysfunction caused by SIRT3 repression is a critical promotional determinant of metabolic pattern switching underlying salt-induced cardiac hypertrophy. Improving SIRT3-mediated mitochondrial function by SGLT2 inhibitors-mediated calcium handling would represent a therapeutic strategy against salt-related cardiovascular events.
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Distributed energy systems encompass a diverse range of generation and storage solutions on the user side, where decentralized management schemes to maximize the overall social welfare are preferred considering their dispersed ownership. However, either security or privacy problems occur in recently proposed schemes. Here we report a decentralized framework leveraging the strengths of blockchain and parallelizable mathematical algorithms to overcome these potential drawbacks. The system owners bid cost functions and operating constraints through masked but coupled management subproblems, which are redistributed by the blockchain to be verifiably solved by competent peers. Such processes are iteratively executed as decisions and shadow prices are exchanged among participants, until an equilibrium is reached. The interactive framework ensures decentralized, privacy-preserving, and secure management of multiple energy sources, and reduces the total cost by 3.0 ~ 7.5% in the test system. Our results benefit the energy prosumers and promote a more active and competitive power grid.
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Soil microorganisms can be used as one of the important indicators of wetland ecosystem restoration. To study the effects of different restoration stages on soil microbial community composition and diversity in Naolihe Wetland, we employed a "time and space parallel" method. Four restoration stages, namely corn field (Corn), short-term restoration wetland (2 years, ST), long-term restoration wetland (8 years, LT) and natural wetland (>25 years, NW), were selected to represent the restoration time and geographical location in Naolihe Nature Wetland. We investigated the composition and diversity of soil microbial communities in different restoration wetland (from corn fields to natural wetlands) by using 16S rRNA and ITS rRNA gene sequencing. We also performed chemical experiments to measure soil enzyme activity and physicochemical properties at each sampling site. The results showed that soil physicochemical properties and enzyme activities significantly differed with the extension of wetland restoration years (p < 0.05). Proteobacteria, Acidobacteria, and Actinobacteria are the most dominant phyla in bacterial. The alpha diversity of soil bacteria was the highest in the corn field (Corn), and ST-LT-NW first decreased and then increased with the extension of wetland restoration years. There are two most dominant phyla (Ascomycota and Mucoromycota) in fungal. However, the alpha diversity of soil fungi was the lowest in the Corn and LT stage, and ST-LT-NW first decreased and then increased with the extension of wetland restoration years. The research findings indicated that the changes in soil physicochemical properties with the extension of wetland restoration years play a significant role in shaping the structure and diversity changes of soil microbial communities. Through the analyses of bacterial and fungal functions using the FUNGuild and FAPROTAX databases, the results showed that the abundance of aerobic bacteria in the soil increased more than that of anaerobic bacteria as the wetland restoration years prolonged, while the abundance of saprotrophic, symbiotic, and pathogenic fungi in the soil significantly decreased with the prolonged wetland restoration years. This study will help us better understand the process of restoration after farmland abandonment, providing valuable reference information for the implementation of a series of wetland ecological restoration projects in the future.
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Perfluoroalkyl sulfonate (PFOS) is a commonly used chemical compound that often found in materials such as waterproofing agents, food packaging, and fire retardants. Known for its stability and persistence in the environment, PFOS can enter the human body through various pathways, including water and the food chain, raising concerns about its potential harm to human health. Previous studies have suggested a cardiac toxicity of PFOS, but the specific cellular mechanisms remained unclear. Here, by using AC16 cardiomyocyte as a model to investigate the molecular mechanisms potential the cardiac toxicity of PFOS. Our findings revealed that PFOS exposure reduced cell viability and induces apoptosis in human cardiomyocyte. Proteomic analysis and molecular biological techniques showed that the Endoplasmic Reticulum (ER) stress-related pathways were activated, while the cellular autophagy flux was inhibited in PFOS-exposed cells. Subsequently, we employed strategies such as autophagy activation and ER stress inhibition to alleviate the PFOS-induced apoptosis in AC16 cells. These results collectively suggest that PFOS-induced ER stress activation and autophagy flux inhibition contribute to cardiomyocyte apoptosis, providing new insights into the mechanisms of PFOS-induced cardiomyocyte toxicity.
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Ácidos Alcanesulfónicos , Apoptosis , Autofagia , Estrés del Retículo Endoplásmico , Fluorocarburos , Miocitos Cardíacos , Estrés del Retículo Endoplásmico/efectos de los fármacos , Miocitos Cardíacos/efectos de los fármacos , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Fluorocarburos/toxicidad , Ácidos Alcanesulfónicos/toxicidad , Humanos , Línea Celular , Contaminantes Ambientales/toxicidadRESUMEN
In a recent study, Oliveira and colleagues revealed how growth arrest and DNA damage-inducible protein 34 (GADD34), an effector of the integrated stress response, initiates the translation of synaptic plasticity-related mRNAs following brain-derived neurotrophic factor (BDNF) stimulation. This work suggests that GADD34 may link transcriptional products with translation control upon neuronal activation, illuminating how protein synthesis is orchestrated in neuronal plasticity.
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Plasticidad Neuronal , Neuronas , Biosíntesis de Proteínas , Proteína Fosfatasa 1 , Animales , Humanos , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Plasticidad Neuronal/fisiología , Neuronas/metabolismo , Neuronas/fisiología , Biosíntesis de Proteínas/fisiología , Proteína Fosfatasa 1/metabolismo , Estrés Fisiológico/fisiologíaRESUMEN
The development of layered metal sulfides with stable structure and accessible active sites is of great importance for sodium-ion batteries (SIBs). Herein, a simple liquid-mixing method is elaborately designed to immobilize WS2 nanoflakes on N-doped carbon (NC), then further coat carbon to produce WS2/NC@C. In the formation process of this composite, the presence of NC not only avoids the overlap and improves the dispersion of WS2 nanoflakes, but also creates a connection network for charge transfer, where the wrapped carbon provides a stable chemical and electrochemical reaction interface. Thus, the composite of WS2/NC@C exhibits the desired Na+ storage capacity as anticipated. The reversible capacity reaches the high value of 369.8 mA h g-1 at 0.2 A g-1 after 200 cycles, while excellent rate performances and cycle life are also acquired in that capacity values of 256.7 and 219.6 mA h g-1 at 1 and 5 A g-1 are preserved after 1000 cycles, respectively. In addition, the assembled sodium-ion hybrid capacitors (SIHCs, AC//WS2/NC@C) exhibit an energy/power density of 68 W h kg-1 at 64 W kg-1, and capacity retention of 82.9% at 1 A g-1 after 2000 cycles. The study provides insight into developing layered metal sulfides with eminent performance of Na+ storage.
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The immune responses during the initiation and invasion stages of human lung adenocarcinoma (LUAD) development are largely unknown. Here, we generated a single-cell RNA sequencing map to decipher the immune dynamics during human LUAD development. We found that T follicular helper (Tfh)-like cells, germinal center B cells, and dysfunctional CD8+ T cells increase during tumor initiation/invasion and form a tertiary lymphoid structure (TLS) inside the tumor. This TLS starts with an aggregation of CD4+ T cells and the generation of CXCL13-expressing Tfh-like cells, followed by an accumulation of B cells, and then forms a CD4+ T and B cell aggregate. TLS and its associated cells are correlated with better patient survival. Inhibiting TLS formation by Tfh or B cell depletion promotes tumor growth in mouse models. The anti-tumoral effect of the Tfh-dependent TLS is mediated through interleukin-21 (IL-21)-IL-21 receptor signaling. Our study establishes an anti-tumoral role of the Tfh-dependent TLS in the development of LUAD.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Estructuras Linfoides Terciarias , Animales , Ratones , Humanos , Linfocitos T Colaboradores-Inductores , Estructuras Linfoides Terciarias/patología , Linfocitos T CD8-positivos/patologíaRESUMEN
Paternal deprivation (PD) impairs social cognition and sociality and increases levels of anxiety-like behavior. However, whether PD affects the levels of empathy in offspring and its underlying mechanisms remain unknown. The present study found that PD increased anxiety-like behavior in mandarin voles (Microtus mandarinus), impaired sociality, reduced the ability of emotional contagion, and the level of consolation behavior. Meanwhile, PD reduced OT neurons in the paraventricular nucleus (PVN) in both male and female mandarin voles. PD decreased the level of OT receptor (OTR) mRNA in the anterior cingulate cortex (ACC) of male and female mandarin voles. Besides, OTR overexpression in the ACC reversed the PD-induced changes in anxiety-like behavior, social preference, emotional contagion, and consolation behavior. Interference of OTR expression in the ACC increased levels of anxiety-like behaviors, while it reduced levels of sociality, emotional contagion, and consolation. These results revealed that the OTR in the ACC is involved in the effects of PD on empathetic behaviors, and provide mechanistic insight into how social experiences affect empathetic behaviors.