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Molecular rotations influence numerous condensed matter phenomena but are often difficult to isolate in molecular dynamics (MD) simulations. This work presents a rotational/roto-translational constraint algorithm designed for condensed matter simulations. The method is based on the velocity Verlet scheme, ensuring a direct constraint on velocity and simplifying implementation within material simulation software packages. We implemented the algorithm in a customized version of a CP2K package and validated its effectiveness through MD simulations of molecule and crystal. The results demonstrate successful selective constraint of rotational and roto-translational motions, enabling stable long-term simulations. This capability opens avenues for studying rotation-related phenomena (e.g., paddle-wheel mechanism in solid-state electrolytes) and constrained sampling.
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This work reports on the emergence of quantum Griffiths singularity (QGS) associated with the magnetic field induced superconductor-metal transition (SMT) in unconventional Nd_{0.8}Sr_{0.2}NiO_{2} infinite layer superconducting thin films. The system manifests isotropic SMT features under both in-plane and perpendicular magnetic fields. Importantly, after scaling analysis of the isothermal magnetoresistance curves, the obtained effective dynamic critical exponents demonstrate divergent behavior when approaching the zero-temperature critical point B_{c}^{*}, identifying the QGS characteristics. Moreover, the quantum fluctuation associated with the QGS can quantitatively explain the upturn of the upper critical field around zero temperature for both the in-plane and perpendicular magnetic fields in the phase boundary of SMT. These properties indicate that the QGS in the Nd_{0.8}Sr_{0.2}NiO_{2} superconducting thin film is isotropic. Moreover, a higher magnetic field gives rise to a metallic state with the resistance-temperature relation R(T) exhibiting lnT dependence among the 2-10 K range and T^{2} dependence of resistance below 1.5 K, which is significant evidence of Kondo scattering. The interplay between isotropic QGS and Kondo scattering in the unconventional Nd_{0.8}Sr_{0.2}NiO_{2} superconductor can illustrate the important role of rare region in QGS and help to uncover the exotic superconductivity mechanism in this system.
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A key challenge in aging research is extending lifespan in tandem with slowing down functional decline so that life with good health (healthspan) can be extended. Here, we show that monthly clearance, starting from 20 months, of a small number of cells that highly express p21Cip1 (p21high) improves cardiac and metabolic function and extends both median and maximum lifespans in mice. Importantly, by assessing the health and physical function of these mice monthly until death, we show that clearance of p21high cells improves physical function at all remaining stages of life, suggesting healthspan extension. Mechanistically, p21high cells encompass several cell types with a relatively conserved proinflammatory signature. Clearance of p21high cells reduces inflammation and alleviates age-related transcriptomic signatures of various tissues. These findings demonstrate the feasibility of healthspan extension in mice and indicate p21high cells as a therapeutic target for healthy aging.
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Inibidor de Quinase Dependente de Ciclina p21 , Longevidade , Camundongos Endogâmicos C57BL , Animais , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/genética , Camundongos , Masculino , Envelhecimento/metabolismo , FemininoRESUMO
N-Acyl/sulfonyl-α-functionalized 1,2,3,4-tetrahydroisoquinolines (THIQs) are significant structural motifs in organic synthesis and drug discovery. However, the one-pot approach enabling direct difunctionalization of THIQs remains challenging. Herein we report a photomediated one-pot three-component strategy to access N-acyl/sulfonyl-α-functionalized THIQs. This method features the use of oxygen (from air) as the green oxidant, high atom and step economy, and decent structural diversity. The synthetic applicability of the method was further demonstrated via the facile construction of valuable bioactive molecules. Mechanistic studies indicated that oxidation with singlet oxygen and the acceptor-less dehydrogenation were involved in the photoredox process.
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Once considered a tissue culture-specific phenomenon, cellular senescence has now been linked to various biological processes with both beneficial and detrimental roles in humans, rodents and other species. Much of our understanding of senescent cell biology still originates from tissue culture studies, where each cell in the culture is driven to an irreversible cell cycle arrest. By contrast, in tissues, these cells are relatively rare and difficult to characterize, and it is now established that fully differentiated, postmitotic cells can also acquire a senescence phenotype. The SenNet Biomarkers Working Group was formed to provide recommendations for the use of cellular senescence markers to identify and characterize senescent cells in tissues. Here, we provide recommendations for detecting senescent cells in different tissues based on a comprehensive analysis of existing literature reporting senescence markers in 14 tissues in mice and humans. We discuss some of the recent advances in detecting and characterizing cellular senescence, including molecular senescence signatures and morphological features, and the use of circulating markers. We aim for this work to be a valuable resource for both seasoned investigators in senescence-related studies and newcomers to the field.
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Myocardial infarction refers to the ischemic necrosis of myocardium, characterized by a sharp reduction or interruption of blood flow in the coronary arteries due to the coronary artery occlusion, resulting in severe and prolonged ischemia in the corresponding myocardium and ultimately leading to ischemic necrosis of the myocardium. Given its high risk, it is considered as one of the most serious health threats today. In current clinical practice, multiple approaches have been explored to diminish myocardial oxygen consumption and alleviate symptoms, but notable success remains elusive. Accumulated clinical evidence has showed that the implantation of mesenchymal stem cell for treating myocardial infarction is both effective and safe. Nevertheless, there persists controversy and variability regarding the standardizing MSC transplantation protocols, optimizing dosage, and determining the most effective routes of administration. Addressing these remaining issues will pave the way of integration of MSCs as a feasible mainstream cardiac treatment.
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Transplante de Células-Tronco Mesenquimais , Infarto do Miocárdio , Humanos , Transplante de Células-Tronco Mesenquimais/métodos , Infarto do Miocárdio/terapia , Células-Tronco Mesenquimais , AnimaisRESUMO
Gliomas are the most common tumours in the central nervous system. In the present study, we aimed to find a promising anti-glioma compound and investigate the underlying molecular mechanism. Glioma cells were subjected to the 50 candidate compounds at a final concentration of 10 µM for 72 h, and CCK-8 was used to evaluate their cytotoxicity. NPS-2143, an antagonist of calcium-sensing receptor (CASR), was selected for further study due to its potent cytotoxicity to glioma cells. Our results showed that NPS-2143 could inhibit the proliferation of glioma cells and induce G1 phase cell cycle arrest. Meanwhile, NPS-2143 could induce glioma cell apoptosis by increasing the caspase-3/6/9 activity. NPS-2143 impaired the immigration and invasion ability of glioma cells by regulating the epithelial-mesenchymal transition process. Mechanically, NPS-2143 could inhibit autophagy by mediating the AKT-mTOR pathway. Bioinformatic analysis showed that the prognosis of glioma patients with low expression of CASR mRNA was better than those with high expression of CASR mRNA. Gene set enrichment analysis showed that CASR was associated with cell adhesion molecules and lysosomes in glioma. The nude mice xenograft model showed NPS-2143 could suppress glioma growth in vivo. In conclusion, NPS-2143 can suppress the glioma progression by inhibiting autophagy.
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Glioma , Naftalenos , Proteínas Proto-Oncogênicas c-akt , Animais , Humanos , Camundongos , Apoptose , Autofagia , Linhagem Celular Tumoral , Proliferação de Células , Glioma/tratamento farmacológico , Glioma/genética , Glioma/metabolismo , Camundongos Nus , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/genética , Serina-Treonina Quinases TOR/metabolismo , Naftalenos/farmacologiaRESUMO
BACKGROUND: The prospective cohort study PROTECT is the largest study in pediatric ulcerative colitis (UC) with standardized treatments, providing valuable data for predicting clinical outcomes. PROTECT and previous studies have identified characteristics associated with clinical outcomes. In this study, we aimed to compare predictive modeling between Bayesian analysis including machine learning and frequentist analysis. METHODS: The key outcomes for this analysis were week 4, 12 and 52 corticosteroid (CS)-free remission following standardized treatment from diagnosis. We developed predictive modeling with multivariable Bayesian logistic regression (BLR), Bayesian additive regression trees (BART) and frequentist logistic regression (FLR). The effect estimate of each risk factor was estimated and compared between the BLR and FLR models. The predictive performance of the models was assessed including area under curve (AUC) of the receiver operating characteristic (ROC) curve. Ten-fold cross-validation was performed for internal validation of the models. The estimation contained 95% credible (or confidence) interval (CI). RESULTS: The statistically significant associations between the risk factors and early or late outcomes were consistent between all BLR and FLR models. The model performance was similar while BLR and BART models had narrower credible intervals of AUCs. To predict week 4 CS-free remission, the BLR model had AUC of 0.69 (95% CI 0.67-0.70), the BART model had AUC of 0.70 (0.67-0.72), and the FLR had AUC of 0.70 (0.65-0.76). To predict week 12 CS-free remission, the BLR model had AUC of 0.78 (0.77-0.79), the BART model had AUC of 0.78 (0.77-0.79), and the FLR model had AUC of 0.79 (0.74-0.83). To predict week 52 CS-free remission, the BLR model had AUC of 0.69 (0.68-0.70), the BART model had AUC of 0.69 (0.67-0.70), and the FLR model had AUC of 0.69 (0.64-0.74). The BART model identified nonlinear associations. CONCLUSIONS: BLR and BART models had intuitive interpretation on interval estimation, better precision in estimating the AUC and can be alternatives for predicting clinical outcomes in pediatric patients with UC. BART model can estimate nonlinear nonparametric association.
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Colite Ulcerativa , Colite , Humanos , Criança , Teorema de Bayes , Estudos Prospectivos , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/tratamento farmacológico , Área Sob a CurvaRESUMO
Background: Adolescence is a crucial period for the development of depression, and previous studies have suggested that the Behavioral Activation System (BAS) plays a significant role. However, little is known about the underlying mechanisms. This study aimed to explore the mediating role of anhedonia in the relationship between BAS and depressive symptoms among Chinese adolescents. Method: A total of 1,023 high-school students aged 15-18 years participated in the study, with 916 continuing their participation three months later. All participants completed the Behavioral Inhibition System/Activation System (BIS/BAS) scale, Dimensional Anhedonia Rating Scale (DARS), Children's Depression Inventory (CDI), and the State-Trait Anxiety Inventory (STAI-S/T). Pathway model analysis was performed to examine the concurrent and prospective mediating effects of anhedonia and the potential moderating effect of sex. Result: Anhedonia in the domains of social activities, hobbies and sensory experiences significantly mediated the cross-sectional relationship between BAS and depressive level three months later. Furthermore, the beta-value of the mediating effect of social activities was significantly higher than that of the other domains of hedonic capacity cross-sectionally and longitudinally. However, sex showed no significant moderating effect. Conclusion: Our findings underscore the importance of hedonic capacity, especially within the social domain, in the development of depressive symptoms. These findings contribute to the early diagnosis and prevention of depressive disorders.
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Prostaglandins and their receptors regulate various physiological processes. Carboprost, an analog of prostaglandin F2α and an agonist for the prostaglandin F2-alpha receptor (FP receptor), is clinically used to treat postpartum hemorrhage (PPH). However, off-target activation of closely related receptors such as the prostaglandin E receptor subtype EP3 (EP3 receptor) by carboprost results in side effects and limits the clinical application. Meanwhile, the FP receptor selective agonist latanoprost is not suitable to treat PPH due to its poor solubility and fast clearance. Here, we present two cryo-EM structures of the FP receptor bound to carboprost and latanoprost-FA (the free acid form of latanoprost) at 2.7 Å and 3.2 Å resolution, respectively. The structures reveal the molecular mechanism of FP receptor selectivity for both endogenous prostaglandins and clinical drugs, as well as the molecular mechanism of G protein coupling preference by the prostaglandin receptors. The structural information may guide the development of better prostaglandin drugs.
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Carboprosta , Dinoprosta , Receptores de Prostaglandina , Feminino , Humanos , Carboprosta/farmacologia , Dinoprosta/farmacologia , Latanoprosta , Ligantes , Receptores de Prostaglandina/agonistas , Receptores de Prostaglandina/química , Microscopia CrioeletrônicaRESUMO
OBJECTIVE: To investigate the relationship between dietary carotenoid intake and sleep duration. METHODS: Adults enrolled in the National Health and Nutrition Examination Survey (NHANES) 2007-2018 without missing information on dietary carotenoid intake (α-carotene, ß-carotene, ß-cryptoxanthin, lycopene, and lutein + zeaxanthin), sleep duration, and covariates were included. Participants' carotenoid consumption was divided into three groups by quartiles and sleep duration was grouped as short (< 7 h/night), optimal (7-8 h/night), and long (> 8 h/night). Multinominal logistic regression was constructed to examine the association between dietary carotenoid intake and sleep duration. Restricted cubic spline (RCS) regression was further utilized to explore their dose-response relationship. The weighted quantile sum (WQS) model was adopted to calculate the mixed and individual effect of 5 carotenoid sub-types on sleep duration. RESULTS: Multinominal logistic regression presented that people with higher intakes of α-carotene, ß-carotene, ß-cryptoxanthin, lycopene, and lutein + zeaxanthin were less likely to sleep too short or too long. Consistent with the findings from multinominal logistic regression, the RCS models suggested a reverse U-shaped relationship between sleep duration and carotenoid intakes. The mixed effects were also significant, where ß-cryptoxanthin and lutein + zeaxanthin were the top 2 contributors associated with the decreased risks of short sleep duration, while ß-carotene, α-carotene, and ß-cryptoxanthin were the main factors related to the lower risk of long sleep duration. CONCLUSION: Our study revealed that the American adults with optimal sleep duration were associated with more dietary carotenoid intake, in comparison to short or long sleepers.
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Luteína , beta Caroteno , Adulto , Humanos , Estados Unidos , Licopeno , Inquéritos Nutricionais , Zeaxantinas , beta-Criptoxantina , Duração do Sono , Carotenoides , DietaRESUMO
How CD4+ lineage gene expression is initiated in differentiating thymocytes remains poorly understood. Here, we show that the paralog transcription factors Zfp281 and Zfp148 control both this process and cytokine expression by T helper cell type 2 (TH2) effector cells. Genetic, single-cell, and spatial transcriptomic analyses showed that these factors promote the intrathymic CD4+ T cell differentiation of class II major histocompatibility complex (MHC II)-restricted thymocytes, including expression of the CD4+ lineage-committing factor Thpok. In peripheral T cells, Zfp281 and Zfp148 promoted chromatin opening at and expression of TH2 cytokine genes but not of the TH2 lineage-determining transcription factor Gata3. We found that Zfp281 interacts with Gata3 and is recruited to Gata3 genomic binding sites at loci encoding Thpok and TH2 cytokines. Thus, Zfp148 and Zfp281 collaborate with Gata3 to promote CD4+ T cell development and TH2 cell responses.
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Linfócitos T CD4-Positivos , Fatores de Transcrição , Animais , Camundongos , Linfócitos T CD4-Positivos/metabolismo , Diferenciação Celular/genética , Citocinas/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
Salinity is one of the most severe abiotic stresses that adversely affect plant growth and agricultural productivity. The plant Na+/H+ antiporter Salt Overly Sensitive 1 (SOS1) located in the plasma membrane extrudes excess Na+ out of cells in response to salt stress and confers salt tolerance. However, the molecular mechanism underlying SOS1 activation remains largely elusive. Here we elucidate two cryo-electron microscopy structures of rice (Oryza sativa) SOS1, a full-length protein in an auto-inhibited state and a truncated version in an active state. The SOS1 forms a dimeric architecture, with an NhaA-folded transmembrane domain portion in the membrane and an elongated cytosolic portion of multiple regulatory domains in the cytoplasm. The structural comparison shows that SOS1 adopts an elevator transport mechanism accompanied by a conformational transition of the highly conserved Pro148 in the unwound transmembrane helix 5 (TM5), switching from an occluded conformation in the auto-inhibited state to a conducting conformation in the active state. These findings allow us to propose an inhibition-release mechanism for SOS1 activation and elucidate how SOS1 controls Na+ homeostasis in response to salt stress.
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Proteínas de Arabidopsis , Arabidopsis , Oryza , Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Oryza/metabolismo , Antiporters/metabolismo , Trocadores de Sódio-Hidrogênio/genética , Trocadores de Sódio-Hidrogênio/metabolismo , Microscopia Crioeletrônica , Sódio/metabolismo , Regulação da Expressão Gênica de PlantasRESUMO
The recent discovery of superconductivity in infinite-layer nickelates generates tremendous research endeavors, but the ground state of their parent compounds is still under debate. Here, we report experimental evidence for the dominant role of Kondo scattering in the underdoped Nd1-xSrxNiO2 thin films. A resistivity minimum associated with logarithmic temperature dependence in both longitudinal and Hall resistivities are observed in the underdoped Nd1-xSrxNiO2 samples before the superconducting transition. At lower temperatures down to 0.04 K, the resistivities become saturated, following the prediction of the Kondo model. A linear scaling behavior [Formula: see text] between anomalous Hall conductivity [Formula: see text] and conductivity [Formula: see text]is revealed, verifying the dominant Kondo scattering at low temperature. The effect of weak (anti-)localization is found to be secondary. Our experiments can help in clarifying the basic physics in the underdoped Nd1-xSrxNiO2 infinite-layer thin films.
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Frailty and depression were linked in observational studies, but the causality remains ambiguous. We intended to explore it using Mendelian randomization (MR). We obtained frailty genome-wide association study (GWAS) data from UK Biobank and TwinGen meta-analysis, and depression GWAS data from Psychiatric Genomics Consortium (PGC) and FinnGen (respectively recorded as PD and FD). We performed univariable and multivariable-adjusted MR with adjustments for body mass index (BMI) and physical activity (PA). Frailty was significantly associated with elevated risks of PD (OR, 1.860; 95% CI, 1.439 to 2.405; P < 0.001) and FD (OR, 1.745; 95% CI, 1.193 to 2.552; P = 0.004), and depression was meanwhile a susceptible factor for frailty (PD: ß, 0.146; 95% CI, 0.086 to 0.201; P < 0.001; and FD: ß, 0.112; 95% CI, 0.051 to 0.174; P < 0.001). This association was robust after adjustments for BMI or PA. Our study provides evidence of the bidirectional causal association between frailty and depression from genetic perspectives.
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Depressão , Fragilidade , Humanos , Depressão/genética , Fragilidade/epidemiologia , Fragilidade/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Índice de Massa CorporalRESUMO
BACKGROUND: The association between coffee/caffeine consumption and obstructive sleep apnea (OSA) risk remains unclear. PURPOSE: To determine the relationship between coffee/caffeine consumption and the risk of OSA, using the Mendelian randomization (MR) method in the European population. METHODS: Two sets of coffee consumption-associated genetic variants were, respectively, extracted from the recent genome-wide meta-analysis (GWMA) and genome-wide association study (GWAS) of coffee consumption. Taking other caffeine sources into account, genetic variants associated with caffeine consumption from tea and plasma caffeine (reflecting total caffeine intake) were also obtained. The inverse variance weighted (IVW) technique was utilized as the primary analysis, supplemented by the MR-Egger, weighted-median, and MR-Pleiotropy RESidual Sum and Outlier (PRESSO) techniques. Leave-one-out (LOO) analysis was performed to assess whether the overall casual estimates were driven by a single SNP. Additional sensitivity analyses were performed using similar methods, while the genetic variants associated with confounders, e.g., body mass index and hypertension, were excluded. RESULTS: The IVW method demonstrated that coffee consumption GWMA (OR: 1.065, 95% CI 0.927-1.224, p = 0.376), coffee consumption GWAS (OR: 1.665, 95% CI 0.932-2.977, p = 0.086), caffeine from tea (OR: 1.198, 95% CI 0.936-1.534, p = 0.151), and blood caffeine levels (OR: 1.054, 95% CI 0.902-1.231, p = 0.508) were unlikely to be associated with the risk of OSA. The other three methods presented similar results, where no significant associations were found. No single genetic variant was driving the overall estimates by the LOO analysis. These findings were also supported by the sensitivity analyses with no confounding genetic variants. CONCLUSION: Our study found no association between coffee/caffeine consumption and the risk of OSA.
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Café , Apneia Obstrutiva do Sono , Humanos , Cafeína , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Apneia Obstrutiva do Sono/genética , CháRESUMO
BACKGROUND: Whether there is an association between dietary choline intake and non-alcoholic fatty liver disease (NAFLD) in American adults remains unclear. METHODS: Data came from the National Health and Nutrition Examination Survey 2017-2018. Choline intake was defined by the mean amounts of two 24 h dietary recalls, and choline intake was categorized into three groups according to the quartiles: inadequate (
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Hepatopatia Gordurosa não Alcoólica , Masculino , Adulto , Humanos , Feminino , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/complicações , Inquéritos Nutricionais , Colina , Dieta , Modelos LogísticosRESUMO
BACKGROUND: Ideal sedation and analgesia strategies for fiberoptic bronchoscopy have not been found. At present, propofol based sedation strategy still has some defects, such as respiratory depression and blood pressure drop. It is difficult to meet the requirements of safety and effectiveness at the same time. The aim of this study was to compare the clinical efficacy of propofol/remifentanil with propofol/esketamine for patient sedation during fiberoptic bronchoscopy. METHOD: Patients undergoing fiberoptic bronchoscopy were randomly assigned to propofol/ remifentanil (PR group; n = 42) or propofol/esketamine (PK group; n = 42) for sedation and analgesia. The primary outcome was the rate of transient hypoxia (oxygen saturation (SpO2) < 95%). The secondary outcomes are the intraoperative hemodynamics, including the changes in blood pressure, heart rate, the incidence of adverse reactions, the total amount of propofol usage were recorded, and the satisfaction level of patients and bronchoscopists. RESULTS: After sedation, the arterial pressure and heart rate of patients in the PK group were stable without significant decrease. Decreases in diastolic blood pressure, mean arterial pressure, and heart rate were observed in patients in the PR group (P < 0.05), although it was not of clinical relevance. The dosage of propofol in the PR group was significantly higher than that in the PK group (144 ± 38 mg vs. 125 ± 35 mg, P = 0.012). Patients in the PR group showed more transient hypoxia (SpO2 < 95%) during surgery (7 vs. 0, 0% versus 16.6%, P = 0.018), more intraoperative choking (28 vs. 7, P < 0.01), postoperative vomiting (22 vs. 13, P = 0.076) and vertigo (15 vs. 13, P = 0.003). Bronchoscopists in the PK group showed more satisfaction. CONCLUSION: Compared with remifentanil, the combination of esketamine with propofol in fiberoptic bronchoscopy leaded to more stable intraoperative hemodynamics, lower dosage of propofol, lower transient hypoxia rate, fewer incidence of adverse events, and greater bronchoscopists satisfaction.
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Broncoscopia , Propofol , Humanos , Propofol/efeitos adversos , Remifentanil , Hipóxia/induzido quimicamenteRESUMO
CONTEXT: Long-term health effects after coronavirus disease 2019 (COVID-19) have been increasingly reported but their prevalence and significance in the pediatric population remains uncertain. OBJECTIVE: To present the prevalence and characteristics of the long-term clinical features of COVID-19 (long COVID) in the global pediatric population. DATA SOURCES: PubMed, Embase, Web of Science, Cochrane Library, WHO COVID-19 database, google scholar, medRxiv, bioRxiv, and multiple national public health databases. STUDY SELECTION: Published articles and preprints from December, 2019 to December, 2022 investigating the epidemiology and characteristics of persistent clinical features at least 3 months after COVID-19 in children and adolescents (0-19 years old) were included. DATA EXTRACTION: Study characteristics and detailed description of long COVID were extracted into a predefined form. RESULTS: Twenty seven cohorts and 4 cross-sectional studies met the inclusion criteria and involved over 15 000 pediatric participants. A total of more than 20 persistent symptoms and clinical features were reported among children and adolescents. 16.2% (95% confidence interval 8.5% to 28.6%) of the pediatric participants experienced 1 or more persistent symptom(s) at least 3 months post COVID-19. Female gender might be associated with developing certain long COVID symptoms. LIMITATIONS: Included studies presented with great heterogeneity because of significant variations in the definition of "long COVID," follow up duration, and method. There could be nonresponse and other potential bias. CONCLUSIONS: Persistent clinical features beyond 3 months among children and adolescents with proven COVID-19 are common and the symptom spectrum is wide. High-quality, prospective studies with proper controls are necessary in the future.
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COVID-19 , SARS-CoV-2 , Adolescente , Criança , Feminino , Humanos , Recém-Nascido , Lactente , Pré-Escolar , Adulto Jovem , Adulto , COVID-19/epidemiologia , Síndrome de COVID-19 Pós-Aguda , Estudos Transversais , Estudos ProspectivosRESUMO
For over half a century, by activation of alcohols with activators, deoxygenative substitution of alcohols has been limited to employing nucleophiles with a single nucleophilic site. Herein, we demonstrate a fluoroolefin-mediated deoxygenative substitution of nonactivated and activated alcohols with diverse acidic nucleophiles, with inversion of configuration, to allow chemo- and enantiospecific construction of C-S, C-N, C-O, and C-Se bonds by the distinction of the different nucleophilic sites of the nucleophiles. The formed O-tethered monofluoroalkene was the intermediate.