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Coronaviruses have threatened humans repeatedly, especially COVID-19 caused by SARS-CoV-2, which has posed a substantial threat to global public health. SARS-CoV-2 continuously evolves through random mutation, resulting in a significant decrease in the efficacy of existing vaccines and neutralizing antibody drugs. It is critical to assess immune escape caused by viral mutations and develop broad-spectrum vaccines and neutralizing antibodies targeting conserved epitopes. Thus, we constructed CovEpiAb, a comprehensive database and analysis resource of human coronavirus (HCoVs) immune epitopes and antibodies. CovEpiAb contains information on over 60 000 experimentally validated epitopes and over 12 000 antibodies for HCoVs and SARS-CoV-2 variants. The database is unique in (1) classifying and annotating cross-reactive epitopes from different viruses and variants; (2) providing molecular and experimental interaction profiles of antibodies, including structure-based binding sites and around 70 000 data on binding affinity and neutralizing activity; (3) providing virological characteristics of current and past circulating SARS-CoV-2 variants and in vitro activity of various therapeutics; and (4) offering site-level annotations of key functional features, including antibody binding, immunological epitopes, SARS-CoV-2 mutations and conservation across HCoVs. In addition, we developed an integrated pipeline for epitope prediction named COVEP, which is available from the webpage of CovEpiAb. CovEpiAb is freely accessible at https://pgx.zju.edu.cn/covepiab/.
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Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19 , Epitopos , SARS-CoV-2 , Humanos , SARS-CoV-2/imunologia , SARS-CoV-2/genética , Anticorpos Antivirais/imunologia , COVID-19/imunologia , COVID-19/virologia , Anticorpos Neutralizantes/imunologia , Epitopos/imunologia , Epitopos/química , Epitopos/genética , Coronavirus/imunologia , Coronavirus/genética , Bases de Dados Factuais , Reações Cruzadas/imunologiaRESUMO
The dehydrogenation reaction of bioderived ethanol is of particular interest for the synthesis of fuels and value-added chemicals. However, this reaction historically suffered from high energy consumption (>260 °C or >0.8 V) and low efficiency. Herein, the efficient conversion of alcohol to hydrogen and aldehyde is achieved by integrating the thermal dehydrogenation reaction with electrochemical hydrogen transfer at low temperature (120 °C) and low voltage (0.06 V), utilizing a bifunctional catalyst (Ru/C) with both thermal-catalytic and electrocatalytic activities. Specifically, the coupled electrochemical hydrogen separation procedure can serve as electrochemical hydrogen pumps, which effectively promote the equilibrium of ethanol dehydrogenation toward hydrogen and acetaldehyde production and simultaneously purifies hydrogen at the cathode. By utilizing this strategy, we achieved boosted hydrogen and acetaldehyde yields of 1,020 mmol g-1 h-1 and 1,185 mmol g-1 h-1, respectively, which are threefold higher than the exclusive ethanol thermal dehydrogenation. This work opens up a prospective route for the high-efficiency production of hydrogen and acetaldehyde via coupled thermal-electrocatalysis.
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Current anesthetic theory is mostly based on neurons and/or neuronal circuits. A role for astrocytes also has been shown in promoting recovery from volatile anesthesia, while the exact modulatory mechanism and/or the molecular target in astrocytes is still unknown. In this study by animal models in male mice and electrophysiological recordings in vivo and in vitro, we found that activating astrocytes of the paraventricular thalamus (PVT) and/or knocking down PVT astrocytic Kir4.1 promoted the consciousness recovery from sevoflurane anesthesia. Single-cell RNA sequencing of the PVT reveals two distinct cellular subtypes of glutamatergic neurons: PVT GRM and PVT ChAT neurons. Patch-clamp recording results proved astrocytic Kir4.1-mediated modulation of sevoflurane on the PVT mainly worked on PVT ChAT neurons, which projected mainly to the mPFC. In summary, our findings support the novel conception that there is a specific PVTâprefrontal cortex projection involved in consciousness recovery from sevoflurane anesthesia, which is mediated by the inhibition of sevoflurane on PVT astrocytic Kir4.1 conductance.
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Astrócitos , Estado de Consciência , Núcleos da Linha Média do Tálamo , Canais de Potássio Corretores do Fluxo de Internalização , Sevoflurano , Animais , Astrócitos/fisiologia , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Masculino , Camundongos , Sevoflurano/farmacologia , Estado de Consciência/fisiologia , Estado de Consciência/efeitos dos fármacos , Núcleos da Linha Média do Tálamo/fisiologia , Núcleos da Linha Média do Tálamo/efeitos dos fármacos , Núcleos da Linha Média do Tálamo/citologia , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo , Camundongos Endogâmicos C57BL , Anestésicos Inalatórios/farmacologia , Vias Neurais/fisiologia , Vias Neurais/efeitos dos fármacos , Neurônios/fisiologia , Neurônios/efeitos dos fármacos , Córtex Pré-Frontal/fisiologia , Córtex Pré-Frontal/efeitos dos fármacos , Lobo Frontal/fisiologia , Lobo Frontal/efeitos dos fármacos , Período de Recuperação da AnestesiaRESUMO
There are two general approaches to developing artificial general intelligence (AGI)1: computer-science-oriented and neuroscience-oriented. Because of the fundamental differences in their formulations and coding schemes, these two approaches rely on distinct and incompatible platforms2-8, retarding the development of AGI. A general platform that could support the prevailing computer-science-based artificial neural networks as well as neuroscience-inspired models and algorithms is highly desirable. Here we present the Tianjic chip, which integrates the two approaches to provide a hybrid, synergistic platform. The Tianjic chip adopts a many-core architecture, reconfigurable building blocks and a streamlined dataflow with hybrid coding schemes, and can not only accommodate computer-science-based machine-learning algorithms, but also easily implement brain-inspired circuits and several coding schemes. Using just one chip, we demonstrate the simultaneous processing of versatile algorithms and models in an unmanned bicycle system, realizing real-time object detection, tracking, voice control, obstacle avoidance and balance control. Our study is expected to stimulate AGI development by paving the way to more generalized hardware platforms.
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Black and white information is asymmetrically distributed in natural scenes, evokes asymmetric neuronal responses, and causes asymmetric perceptions. Recognizing the universality and essentiality of black-white asymmetry in visual information processing, the neural substrates for black-white asymmetry remain unclear. To disentangle the role of the feedforward and recurrent mechanisms in the generation of cortical black-white asymmetry, we recorded the V1 laminar responses and LGN responses of anesthetized cats of both sexes. In a cortical column, we found that black-white asymmetry starts at the input layer and becomes more pronounced in the output layer. We also found distinct dynamics of black-white asymmetry between the output layer and the input layer. Specifically, black responses dominate in all layers after stimulus onset. After stimulus offset, black and white responses are balanced in the input layer, but black responses still dominate in the output layer. Compared with that in the input layer, the rebound response in the output layer is significantly suppressed. The relative suppression strength evoked by white stimuli is notably stronger and depends on the location within the ON-OFF cortical map. A model with delayed and polarity-selective cortical suppression explains black-white asymmetry in the output layer, within which prominent recurrent connections are identified by Granger causality analysis. In addition to black-white asymmetry in response strength, the interlaminar differences in spatial receptive field varied dynamically. Our findings suggest that the feedforward and recurrent mechanisms are dynamically recruited for the generation of black-white asymmetry in V1.SIGNIFICANCE STATEMENT Black-white asymmetry is universal and essential in visual information processing, yet the neural substrates for cortical black-white asymmetry remain unknown. Leveraging V1 laminar recordings, we provided the first laminar pattern of black-white asymmetry in cat V1 and found distinct dynamics of black-white asymmetry between the output layer and the input layer. Comparing black-white asymmetry across three visual hierarchies, the LGN, V1 input layer, and V1 output layer, we demonstrated that the feedforward and recurrent mechanisms are dynamically recruited for the generation of cortical black-white asymmetry. Our findings not only enhance our understanding of laminar processing within a cortical column but also elucidate how feedforward connections and recurrent connections interact to shape neuronal response properties.
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Córtex Visual Primário , Córtex Visual , Masculino , Feminino , Animais , Córtex Visual/fisiologia , Estimulação Luminosa , Percepção Visual/fisiologia , Neurônios/fisiologia , Vias Visuais/fisiologiaRESUMO
Hydrogen production from methanol represents an energy-sustainable way to produce ethanol, but it normally results in heavy CO2 emissions. The selective conversion of methanol into H2 and valuable chemical feedstocks offers a promising strategy; however, it is limited by the harsh operating conditions and low conversion efficiency. Herein, we realize efficient high-purity H2 and CO production from methanol by coupling the thermocatalytic methanol dehydrogenation with electrocatalytic hydrogen oxidation on a bifunctional Ru/C catalyst. Electrocatalysis enables the acceleration of C-H cleavage and reduces the partial pressure of hydrogen at the anode, which drives the chemical equilibrium and significantly enhances methanol dehydrogenation. Furthermore, a bilayer Ru/C + Pd/C electrode is designed to mitigate CO poisoning and facilitate hydrogen oxidation. As a result, a high yield of H2 (558.54 mmol h-1 g-1) with high purity (99.9%) was achieved by integrating an applied cell voltage of 0.4 V at 200 °C, superior to the conventional thermal and electrocatalytic processes, and CO is the main product at the anode. This work presents a new avenue for efficient H2 production together with valuable chemical synthesis from methanol.
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In populations in China, colorectal cancer (CRC) screening can be mainly accessed through organized screening, opportunistic screening, and physical examination. This screening intervention is found to be effective but the exact coverage rate is difficult to measure. Based on data from published articles, official websites, and available program reports, the screening coverage rate and related indicators were quantified. A rapid review was then conducted to estimate the overall and the breakdown coverage rates of the sub-type screening services, by leveraging the numbers of articles and the by-type median sample sizes. Up to 2020, two central government-funded and four provincial/municipal-level organized CRC screening programs have been initiated and included in this analysis. For populations aged 40-74, the estimated coverage rate of organized programs in China was 2.7% in 2020, and the 2-year cumulative coverage rate in 2019-2020 was 5.3% and the 3-year cumulative coverage rate in 2018-2020 was 7.7%. The corresponding coverage rates of 50-74-year-olds were estimated to be 3.4%, 7.1%, and 10.3%, respectively. Based on the rapid review approach, the overall screening coverage rate for 40-74 years, considering organized screening programs, opportunistic screening, and physical examinations, was then estimated to be 3.0% in China in 2020. However, comparing the findings of this study with the number of health check-ups reported in the local national health statistics yearbooks suggests that the number of CRC physical examinations may be underestimated in this study. The findings suggest that further efforts are needed to improve population access to CRC screening in China. Furthermore, evidence for access to opportunistic CRC screening and physical examination is limited, and more quantitative investigation is needed.
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Neoplasias Colorretais , Detecção Precoce de Câncer , Acessibilidade aos Serviços de Saúde , Humanos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Detecção Precoce de Câncer/estatística & dados numéricos , Detecção Precoce de Câncer/métodos , China/epidemiologia , Pessoa de Meia-Idade , Idoso , Adulto , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Feminino , Masculino , Programas de Rastreamento/estatística & dados numéricos , Programas de Rastreamento/métodosRESUMO
MOTIVATION: In the training of predictive models using high-dimensional genomic data, multiple studies' worth of data are often combined to increase sample size and improve generalizability. A drawback of this approach is that there may be different sets of features measured in each study due to variations in expression measurement platform or technology. It is often common practice to work only with the intersection of features measured in common across all studies, which results in the blind discarding of potentially useful feature information that is measured in individual or subsets of studies. RESULTS: We characterize the loss in predictive performance incurred by using only the intersection of feature information available across all studies when training predictors using gene expression data from microarray and sequencing datasets. We study the properties of linear and polynomial regression for imputing discarded features and demonstrate improvements in the external performance of prediction functions through simulation and in gene expression data collected on breast cancer patients. To improve this process, we propose a pairwise strategy that applies any imputation algorithm to two studies at a time and averages imputed features across pairs. We demonstrate that the pairwise strategy is preferable to first merging all datasets together and imputing any resulting missing features. Finally, we provide insights on which subsets of intersected and study-specific features should be used so that missing-feature imputation best promotes cross-study replicability. AVAILABILITY AND IMPLEMENTATION: The code is available at https://github.com/YujieWuu/Pairwise_imputation. SUPPLEMENTARY INFORMATION: Supplementary information is available at Bioinformatics online.
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Algoritmos , Genômica , Humanos , Tamanho da Amostra , Genoma , Simulação por ComputadorRESUMO
BACKGROUND: Exposure to extreme cold or heat temperature is one leading cause of weather-associated mortality and morbidity in animals. Emerging studies demonstrate that the microbiota residing in guts act as an integral factor required to modulate host tolerance to cold or heat exposure, but common and unique patterns of animal-temperature associations between cold and heat have not been simultaneously examined. Therefore, we attempted to investigate the roles of gut microbiota in modulating tolerance to cold or heat exposure in mice. RESULTS: The results showed that both cold and heat acutely change the body temperature of mice, but mice efficiently maintain their body temperature at conditions of chronic extreme temperatures. Mice adapt to extreme temperatures by adjusting body weight gain, food intake and energy harvest. Fascinatingly, 16 S rRNA sequencing shows that extreme temperatures result in a differential shift in the gut microbiota. Moreover, transplantation of the extreme-temperature microbiota is sufficient to enhance host tolerance to cold and heat, respectively. Metagenomic sequencing shows that the microbiota assists their hosts in resisting extreme temperatures through regulating the host insulin pathway. CONCLUSIONS: Our findings highlight that the microbiota is a key factor orchestrating the overall energy homeostasis under extreme temperatures, providing an insight into the interaction and coevolution of hosts and gut microbiota.
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Microbioma Gastrointestinal , Temperatura Alta , Animais , Camundongos , Temperatura , Microbioma Gastrointestinal/fisiologia , Temperatura Baixa , Adaptação Fisiológica/fisiologiaRESUMO
BACKGROUND: Acute myeloid leukemia (AML) patients with various nucleophosmin 1 (NPM1) mutations are controversial in the prognosis. This study aimed to investigate the prognosis of patients according to types of NPM1 mutations (NPM1mut). METHODS: Bone marrow samples of 528 patients newly diagnosed with AML, were collected for morphology, immunology, cytogenetics, and molecular biology examinations. Gene mutations were detected by next-generation sequencing (NGS) technology. RESULTS: About 25.2% of cases exhibited NPM1mut. 83.5% of cases were type A, while type B and D were respectively account for 2.3% and 3.0%. Furthermore, 15 cases of rare types were identified, of which 2 cases have not been reported. Clinical characteristics were similar between patients with A-type NPM1 mutations (NPM1A - type mut) and non-A-type NPM1 mutations (NPM1non - A-type mut). Event-free survival (EFS) was significantly different between patients with low NPM1non - A-type mut variant allele frequency (VAF) and low NPM1A - type mut VAF (median EFS = 3.9 vs. 8.5 months, P = 0.020). The median overall survival (OS) of the NPM1non - A-type mutFLT3-ITDmut group, the NPM1A - type mutFLT3-ITDmut group, the NPM1non - A-type mutFLT3-ITDwt group, and the NPM1A - type mutFLT3-ITDwt group were 3.9, 10.7, 17.3 and 18.8 months, while the median EFS of the corresponding groups was 1.4, 5.0, 7.6 and 9.2 months (P < 0.0001 and P = 0.004, respectively). CONCLUSIONS: No significant difference was observed in OS and EFS between patients with NPM1A - type mut and NPM1non - A-type mut. However, types of NPM1 mutations and the status of FLT3-ITD mutations may jointly have an impact on the prognosis of AML patients.
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Leucemia Mieloide Aguda , Mutação , Proteínas Nucleares , Nucleofosmina , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/diagnóstico , Masculino , Pessoa de Meia-Idade , Feminino , Proteínas Nucleares/genética , Adulto , Idoso , Adolescente , Prognóstico , Idoso de 80 Anos ou mais , Adulto Jovem , Taxa de SobrevidaRESUMO
Gamma rhythms in many brain regions, including the primary visual cortex (V1), are thought to play a role in information processing. Here, we report a surprising finding of 3 narrowband gamma rhythms in V1 that processed distinct spatial frequency (SF) signals and had different neural origins. The low gamma (LG; 25 to 40 Hz) rhythm was generated at the V1 superficial layer and preferred a higher SF compared with spike activity, whereas both the medium gamma (MG; 40 to 65 Hz), generated at the cortical level, and the high gamma HG; (65 to 85 Hz), originated precortically, preferred lower SF information. Furthermore, compared with the rates of spike activity, the powers of the 3 gammas had better performance in discriminating the edge and surface of simple objects. These findings suggest that gamma rhythms reflect the neural dynamics of neural circuitries that process different SF information in the visual system, which may be crucial for multiplexing SF information and synchronizing different features of an object.
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Ritmo Gama/fisiologia , Córtex Visual Primário/fisiologia , Percepção Visual/fisiologia , Animais , Encéfalo/fisiologia , Gatos , Neurônios/fisiologia , Estimulação Luminosa/métodos , Córtex Visual Primário/patologia , Córtex Visual/fisiologiaRESUMO
BACKGROUND: Stimulation of the paraventricular thalamus has been found to enhance anesthesia recovery; however, the underlying molecular mechanism by which general anesthetics modulate paraventricular thalamus is unclear. This study aimed to test the hypothesis that the sodium leak channel (NALCN) maintains neuronal activity in the paraventricular thalamus to resist anesthetic effects of sevoflurane in mice. METHODS: Chemogenetic and optogenetic manipulations, in vivo multiple-channel recordings, and electroencephalogram recordings were used to investigate the role of paraventricular thalamus neuronal activity in sevoflurane anesthesia. Virus-mediated knockdown and/or overexpression was applied to determine how NALCN influenced excitability of paraventricular thalamus glutamatergic neurons under sevoflurane. Viral tracers and local field potentials were used to explore the downstream pathway. RESULTS: Single neuronal spikes in the paraventricular thalamus were suppressed by sevoflurane anesthesia and recovered during emergence. Optogenetic activation of paraventricular thalamus glutamatergic neurons shortened the emergence period from sevoflurane anesthesia, while chemogenetic inhibition had the opposite effect. Knockdown of the NALCN in the paraventricular thalamus delayed the emergence from sevoflurane anesthesia (recovery time: from 24 ± 14 to 64 ± 19 s, P < 0.001; concentration for recovery of the righting reflex: from 1.13% ± 0.10% to 0.97% ± 0.13%, P < 0.01). As expected, the overexpression of the NALCN in the paraventricular thalamus produced the opposite effects. At the circuit level, knockdown of the NALCN in the paraventricular thalamus decreased the neuronal activity of the nucleus accumbens, as indicated by the local field potential and decreased single neuronal spikes in the nucleus accumbens. Additionally, the effects of NALCN knockdown in the paraventricular thalamus on sevoflurane actions were reversed by optical stimulation of the nucleus accumbens. CONCLUSIONS: Activity of the NALCN maintains the excitability of paraventricular thalamus glutamatergic neurons to resist the anesthetic effects of sevoflurane in mice.
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Anestésicos Inalatórios , Núcleos da Linha Média do Tálamo , Neurônios , Sevoflurano , Animais , Sevoflurano/farmacologia , Camundongos , Anestésicos Inalatórios/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Núcleos da Linha Média do Tálamo/efeitos dos fármacos , Núcleos da Linha Média do Tálamo/fisiologia , Masculino , Camundongos Endogâmicos C57BL , Canais de Sódio/efeitos dos fármacos , Canais de Sódio/fisiologia , Ácido Glutâmico/metabolismo , Ácido Glutâmico/farmacologia , Canais Iônicos , Proteínas de MembranaRESUMO
PURPOSE: In the local administration methods for treating eye diseases, the application of microneedles has great potential due to the shortcomings of low efficacy and significant side effects of local administration preparations. This article provides ideas for the research on the application of ophthalmic microneedle in the treatment of eye diseases. RESULTS: This article analyzes the physiological structures of the eyes, ocular diseases and its existing ocular preparations in sequence. Finally, this article reviews the development and trends of ocular microneedles in recent years, and summarizes and discusses the drugs of ocular microneedles as well as the future directions of development. At the same time, according to the inspiration of previous work, the concept of "microneedle with spinule" is proposed for the first time, and its advantages and limitations are discussed in the article. CONCLUSIONS: At present, the application of ocular microneedles still faces multiple challenges. The aspects of auxiliary devices, appearance, the properties of the matrix materials, and preparation technology of ophthalmic microneedle are crucial for their application in the treatment of eye diseases.
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Oftalmopatias , Agulhas , Humanos , Microinjeções , Sistemas de Liberação de Medicamentos , Preparações Farmacêuticas , Oftalmopatias/tratamento farmacológico , Administração CutâneaRESUMO
Bone defects are characterized by a hypoxic environment, which affects bone tissue repair. However, the role of hypoxia in the repair of alveolar bone defects remains unclear. Human periodontal ligament stem cells (hPDLSCs) are high-quality seed cells for repairing alveolar bone defects, whose behavior changes under hypoxia. However, their mechanism of action is not known and needs to be elucidated. We hypothesized that hypoxia might be beneficial to alveolar bone defect repair and the osteogenic differentiation of hPDLSCs. To test this hypothesis, cobalt chloride (CoCl2) was used to create a hypoxic environment, both in vitro and in vivo. In vitro study, the best osteogenic effect was observed after 48 h of hypoxia in hPDLSCs, and the AKT/mammalian target of rapamycin/eukaryotic translation initiation factor 4e-binding protein 1 (AKT/mTOR/4EBP-1) signaling pathway was significantly upregulated. Inhibition of the AKT/mTOR/4EBP-1 signaling pathway decreased the osteogenic ability of hPDLSCs under hypoxia and hypoxia-inducible factor 1 alpha (HIF-1α) expression. The inhibition of HIF-1α also decreased the osteogenic capacity of hPDLSCs under hypoxia without significantly affecting the level of phosphorylation of AKT/mTOR/4EBP-1. In vitro study, Micro-CT and tissue staining results show better bone regeneration in hypoxic group than control group. These results suggested that hypoxia promoted alveolar bone defect repair and osteogenic differentiation of hPDLSCs, probably through AKT/mTOR/4EBP-1/HIF-1α signaling. These findings provided important insights into the regulatory mechanism of hypoxia in hPDLSCs and elucidated the effect of hypoxia on the healing of alveolar bone defects. This study highlighted the importance of physiological oxygen conditions for tissue engineering.
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Perda do Osso Alveolar , Diferenciação Celular , Hipóxia Celular , Cobalto , Subunidade alfa do Fator 1 Induzível por Hipóxia , Osteogênese , Ligamento Periodontal , Humanos , Proteínas Adaptadoras de Transdução de Sinal/efeitos dos fármacos , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Perda do Osso Alveolar/metabolismo , Regeneração Óssea/efeitos dos fármacos , Proteínas de Ciclo Celular/metabolismo , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Cobalto/farmacologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Osteogênese/efeitos dos fármacos , Ligamento Periodontal/metabolismo , Ligamento Periodontal/citologia , Fosfoproteínas/metabolismo , Proteínas Proto-Oncogênicas c-akt/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Células-Tronco/metabolismo , Serina-Treonina Quinases TOR/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismoRESUMO
The Alchemical Transfer Method (ATM) is herein validated against the relative binding-free energies (RBFEs) of a diverse set of protein-ligand complexes. We employed a streamlined setup workflow, a bespoke force field, and AToM-OpenMM software to compute the RBFEs of the benchmark set prepared by Schindler and collaborators at Merck KGaA. This benchmark set includes examples of standard small R-group ligand modifications as well as more challenging scenarios, such as large R-group changes, scaffold hopping, formal charge changes, and charge-shifting transformations. The novel coordinate perturbation scheme and a dual-topology approach of ATM address some of the challenges of single-topology alchemical RBFE methods. Specifically, ATM eliminates the need for splitting electrostatic and Lennard-Jones interactions, atom mapping, defining ligand regions, and postcorrections for charge-changing perturbations. Thus, ATM is simpler and more broadly applicable than conventional alchemical methods, especially for scaffold-hopping and charge-changing transformations. Here, we performed well over 500 RBFE calculations for eight protein targets and found that ATM achieves accuracy comparable to that of existing state-of-the-art methods, albeit with larger statistical fluctuations. We discuss insights into the specific strengths and weaknesses of the ATM method that will inform future deployments. This study confirms that ATM can be applied as a production tool for RBFE predictions across a wide range of perturbation types within a unified, open-source framework.
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Simulação de Dinâmica Molecular , Software , Termodinâmica , Ligantes , Entropia , Ligação ProteicaRESUMO
This study aims to explore the link between Apo-E, brain white matter, and suicide in patients with major depressive disorder (MDD) to investigate the potential neuroimmune mechanisms of Apo-E that may lead to suicide. Thirty-nine patients with MDD (22 patients with suicidality) and 57 age, gender, and education-matched healthy controls participated in this study, provided plasma Apo-E samples, and underwent diffusion tensor imaging scans. Plasma Apo-E levels and white matter microstructure were analyzed among the MDD with suicidality, MDD without suicidality, and HC groups using analysis of variance with post hoc Bonferroni correction and tract-based spatial statistics (TBSS) with threshold-free cluster enhancement correction. Mediation analysis investigated the relationship between Apo-E, brain white matter, and suicidality in MDD. The MDD with suicidality subgroup had higher depressive and suicide scores, longer disease course, and lower plasma Apo-E levels than MDD without suicidality. TBSS revealed that the MDD non-suicide subgroup showed significantly increased mean diffusivity in the left corticospinal tract and body of the left corpus callosum, as well as increased axial diffusivity in the left anterior corona radiata and the right posterior thalamic radiation compared to the suicidal MDD group. The main finding was that the increased MD of the left corticospinal tract contributed to the elevated suicide score, with Apo-E mediating the effect. Preliminary result that Apo-E's mediating role between the left corticospinal tract and the suicide factor suggests the neuroimmune mechanism of suicide in MDD. The study was registered on ClinicalTrials.gov (NCT03790085).
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Apolipoproteínas E , Transtorno Depressivo Maior , Imagem de Tensor de Difusão , Tratos Piramidais , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Apolipoproteínas E/genética , Apolipoproteínas E/sangue , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/patologia , Transtorno Depressivo Maior/fisiopatologia , Tratos Piramidais/diagnóstico por imagem , Tratos Piramidais/patologia , Tratos Piramidais/fisiopatologia , Ideação Suicida , Suicídio , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Estudos de Casos e ControlesRESUMO
BACKGROUND: Universities have widely switched from traditional face-to-face classes to online instruction as a result of the epidemic. Self-directed learning is becoming the new norm for university students' learning styles. The ability of health professions students to learn independently during online study directly impacts the effectiveness of online medical education. The ability to learn on their own initiative may be affected by health professions students' professional identities, defined as their positive perceptions, evaluations, emotional experiences, and identity as professionals related to medicine. This study aimed to look into the current status and the factors that influence health professions students' self-directed learning ability (SDLA) during online study and its relationship with professional identity. METHODS: This study was conducted from September to November 2022 at a medical school in East China. An online questionnaire was used to collect participants' status of online learning, self-directed learning ability (SDLA), and professional identity. RESULTS: One thousand two hundred ninety-eight health professions students demonstrated intermediate self-directed learning ability during online study. In terms of teacher-student interaction (F = 14.778, P < 0.001), student-student interaction (F = 15.713, P < 0.001), and learning concentration (F = 13.424, P < 0.001), there were significant differences in health professions students' self-directed learning ability. Professional identity and self-directed learning ability positively correlated (r = 0.589-0.802, P < 0.01). Academic atmosphere and professional identity were significant predictors. CONCLUSIONS: The self-directed learning ability of health professions students while receiving instruction online is at an intermediate level and is influenced by several factors. Developing health professions students' professional identities can enhance their ability for self-directed learning.
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Educação Médica , Estudantes de Ciências da Saúde , Estudantes de Medicina , Humanos , Estudantes de Medicina/psicologia , Aprendizagem , Ocupações em SaúdeRESUMO
Accurate identification of Seriola dumerili (SD) offers crucial technical support for aquaculture practices and behavioral research of this species. However, the task of discerning S. dumerili from complex underwater settings, fluctuating light conditions, and schools of fish presents a challenge. This paper proposes an intelligent recognition model based on the YOLOv8 network called SD-YOLOv8. By adding a small object detection layer and head, our model has a positive impact on the recognition capabilities for both close and distant instances of S. dumerili, significantly improving them. We construct a convenient S. dumerili dataset and introduce the deformable convolution network v2 (DCNv2) to enhance the information extraction process. Additionally, we employ the bottleneck attention module (BAM) and redesign the spatial pyramid pooling fusion (SPPF) for multidimensional feature extraction and fusion. The Inner-MPDIoU bounding box regression function adjusts the scale factor and evaluates geometric ratios to improve box positioning accuracy. The experimental results show that our SD-YOLOv8 model achieves higher accuracy and average precision, increasing from 89.2% to 93.2% and from 92.2% to 95.7%, respectively. Overall, our model enhances detection accuracy, providing a reliable foundation for the accurate detection of fishes.
Assuntos
Algoritmos , Animais , Peixes , Redes Neurais de Computação , Aquicultura/métodosRESUMO
AIMS AND OBJECTIVES: This study investigated the relationship between clinical nurses' critical thinking ability and medication safety competence, as well as the factors related to medication safety competence. BACKGROUND: Nurses can have an active role in promoting medication safety. However, the main factors associating with nurses' competence in medication safety are uncertain. DESIGN: This was a descriptive, multicenter cross-sectional survey study. METHODS: A total of 1196 nurses from four different tertiary hospital in China were included in this study. A demographic information questionnaire, the Critical Thinking Diagnostic for nurses, and the Medication Safety Competence Scale for nurses were used to survey. Descriptive statistics, comparisons, correlation and regression analysis of the collected data were performed using SPSS 26.00 software. The study was reported using STROBE checklist. RESULTS: Included nurses obtained satisfactory scores on the critical thinking and medication safety scales and subscales. There was a strong statistically significant positive correlation between critical thinking ability and medication safety competence. Multiple linear regression analysis indicated that personal critical thinking scores and working years were positively associated with nurses' medication safety scores, accounting for 62.50% of the variance. CONCLUSION: Clinical nurses' critical thinking ability is positively associated with medication safety competence. RELEVANCE TO CLINICAL PRACTICE: As critical thinking ability positively predicts nurses' medication safety competence, hospitals and nursing administrators should consider continuing nursing education and training to improve critical thinking skills, thereby promoting medication safety competence among clinical nurses.
RESUMO
Wheat is one of the most important food crops globally, and understanding the regulation of grain size is crucial for wheat breeding to achieve a higher grain yield. MicroRNAs (miRNAs) play vital roles in plant growth and development. However, the miRNA-mediated mechanism underlying grain size regulation remains largely elusive in wheat. Here, we report the characterization and functional validation of a miRNA, TamiR397a, associated with grain size regulation in wheat. The function of three TaMIR397 homoeologs was determined through histochemical ß-glucuronidase-dependent assay. MiRNA expression was detected using quantitative reverse transcription polymerase chain reaction (qRT-PCR), and the function of TamiR397a was validated through its transgenic overexpression and repression in wheat. It was found that TaMIR397-6A and TaMIR397-6B encode active TamiR397a. The expression profiling indicated that TamiR397a was differentially expressed in various tissues and gradually up-regulated during grain filling. The inhibition of TamiR397a perturbed grain development, leading to a decrease in grain size and weight. Conversely, the overexpression of TamiR397a resulted in increased grain size and weight by accelerating the grain filling process. Transcriptome analysis revealed that TamiR397a regulates a set of genes involved in hormone response, desiccation tolerance, regulation of cellular senescence, seed dormancy, and seed maturation biological processes, which are important for grain development. Among the down-regulated genes in the grains of the TamiR397a-overexpressing transgenic plants, 11 putative targets of the miRNA were identified. Taken together, our results demonstrate that TamiR397a is a positive regulator of grain size and weight, offering potential targets for breeding wheat with an increased grain yield.