RESUMO
The twilight zone (from the base of the euphotic zone to the depth of 1,000 m) is the major area of particulate organic carbon (POC) remineralization in the ocean, and heterotrophic microbes contribute to more than 70% of the estimated remineralization. However, little is known about the microbial community and metabolic activity directly associated with POC remineralization in this chronically understudied realm. Here, we characterized the microbial community proteomes of POC samples collected from the twilight zone of three contrasting sites in the Northwest Pacific Ocean using a metaproteomic approach. The particle-attached bacteria from Alteromonadales, Rhodobacterales, and Enterobacterales were the primary POC remineralizers. Hydrolytic enzymes, including proteases and hydrolases, that degrade proteinaceous components and polysaccharides, the main constituents of POC, were abundant and taxonomically associated with these bacterial groups. Furthermore, identification of diverse species-specific transporters and metabolic enzymes implied niche specialization for nutrient acquisition among these bacterial groups. Temperature was the main environmental factor driving the active bacterial groups and metabolic processes, and Enterobacterales replaced Alteromonadales as the predominant group under low temperature. This study provides insight into the key bacteria and metabolic processes involved in POC remineralization, and niche complementarity and species substitution among bacterial groups are critical for efficient POC remineralization in the twilight zone. IMPORTANCE The ocean's twilight zone is a critical zone where more than 70% of the sinking particulate organic carbon (POC) is remineralized. Therefore, the twilight zone determines the size of biological carbon storage in the ocean and regulates the global climate. Prokaryotes are major players that govern remineralization of POC in this region. However, knowledge of microbial community structure and metabolic activity is still lacking. This study unveiled microbial communities and metabolic activities of POC samples collected from the twilight zone of three contrasting environments in the Northwest Pacific Ocean using a metaproteomic approach. Alteromonadales, Rhodobacterales, and Enterobacterales were the major remineralizers of POC. They excreted diverse species-specific hydrolytic enzymes to split POC into solubilized POC or dissolved organic carbon. Temperature played a crucial role in regulating the community composition and metabolism. Furthermore, niche complementarity or species substitution among bacterial groups guaranteed the efficient remineralization of POC in the twilight zone.
Assuntos
Carbono/metabolismo , Microbiota , Água do Mar/microbiologia , Bactérias/isolamento & purificação , Proteínas de Bactérias/análise , Oceano Pacífico , Material Particulado , ProteomaRESUMO
Cognitive motor dissociation describes a subset of patients with disorders of consciousness who show neuroimaging evidence of consciousness but no detectable command-following behaviours. Although essential for family counselling, decision-making, and the design of rehabilitation programmes, the prognosis for patients with cognitive motor dissociation remains under-investigated. The current study included 78 patients with disorders of consciousness who showed no detectable command-following behaviours. These patients included 45 patients with unresponsive wakefulness syndrome and 33 patients in a minimally conscious state, as diagnosed using the Coma Recovery Scale-Revised. Each patient underwent an EEG-based brain-computer interface experiment, in which he or she was instructed to perform an item-selection task (i.e. select a photograph or a number from two candidates). Patients who achieved statistically significant brain-computer interface accuracies were identified as cognitive motor dissociation. Two evaluations using the Coma Recovery Scale-Revised, one before the experiment and the other 3 months later, were carried out to measure the patients' behavioural improvements. Among the 78 patients with disorders of consciousness, our results showed that within the unresponsive wakefulness syndrome patient group, 15 of 18 patients with cognitive motor dissociation (83.33%) regained consciousness, while only five of the other 27 unresponsive wakefulness syndrome patients without significant brain-computer interface accuracies (18.52%) regained consciousness. Furthermore, within the minimally conscious state patient group, 14 of 16 patients with cognitive motor dissociation (87.5%) showed improvements in their Coma Recovery Scale-Revised scores, whereas only four of the other 17 minimally conscious state patients without significant brain-computer interface accuracies (23.53%) had improved Coma Recovery Scale-Revised scores. Our results suggest that patients with cognitive motor dissociation have a better outcome than other patients. Our findings extend current knowledge of the prognosis for patients with cognitive motor dissociation and have important implications for brain-computer interface-based clinical diagnosis and prognosis for patients with disorders of consciousness.
Assuntos
Interfaces Cérebro-Computador , Transtornos da Consciência/diagnóstico , Eletroencefalografia/métodos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
The majority of the protein structures have been elucidated under equilibrium conditions. The aim herein is to provide a better understanding of the dynamic behavior inherent to proteins by fabricating a label-free nanodevice comprising a single-peptide junction to measure real-time conductance, from which their structural dynamic behavior can be inferred. This device contains an azobenzene photoswitch for interconversion between a well-defined cis, and disordered trans isomer. Real-time conductance measurements revealed three distinct states for each isomer, with molecular dynamics simulations showing each state corresponds to a specific range of hydrogen bond lengths within the cis isomer, and specific dihedral angles in the trans isomer. These insights into the structural dynamic behavior of peptides may rationally extend to proteins. Also demonstrated is the capacity to modulate conductance which advances the design and development of bioinspired electronic nanodevices.
Assuntos
Compostos Azo/química , Simulação de Dinâmica Molecular , Nanopartículas/química , Nanotecnologia , Peptídeos Cíclicos/química , Conformação Molecular , Peptídeos Cíclicos/síntese química , Processos Fotoquímicos , Estereoisomerismo , Fatores de TempoRESUMO
Identifying more missing proteins (MPs) is an important mission of C-HPP. With the number of identified MPs being attenuated year by year (2,949 to 2,129 MPs from 2016 to 2019), we have realized that the difficulty of exploring the remaining MPs is a challenge in technique. Herein, we propose a comprehensive strategy to effectively enrich, separate, and identify proteins with low molecular weights, aiming at the discovery of MPs. Basically, a protein extract from human placenta was passed through a C18 SPE column, and the bound proteins that were eluted were further separated with an SDS-PAGE gel or a 50 kDa cutoff filter. The separated proteins were subjected to trypsin digestion, and the MS/MS signals were searched against data sets with two different digestion modes (full-trypsin and semitrypsin). The strategy was adopted, resulting in the identification of 4 MPs with 8 unique peptides (≥2 non-nested unique peptides with ≥9 amino acids). Importantly, the identification of 6 out of 8 of the unique peptides derived from the MPs was further supported by parallel reaction monitoring, which confirmed the identification of 3 MPs from human placenta tissues (Q6NT89: TMF-regulated nuclear protein 1; A0A183: late cornified envelope protein 6A; and Q6UWQ7: insulin growth factor-like family member 2, mapped to chromosomes 1, 1, and 19, respectively). The three proteins ranged in length from 80 aa to 227 aa. The study not only establishes a feasible strategy for analyzing proteins with low molecular weights but also fills a small part of a large gap in the list of MPs. The data obtained in this study are available via ProteomeXchange (PXD014083) and PeptideAtlas (PASS01389).
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Peptídeos/análise , Placenta/química , Proteômica/métodos , Eletroforese em Gel de Poliacrilamida , Feminino , Humanos , Peso Molecular , Peptídeos/química , Gravidez , Espectrometria de Massas em Tandem/métodos , Tripsina/químicaRESUMO
Phytoplankton blooms are natural phenomena in the ocean, which are the results of rapid cell growth of some phytoplankton species in a unique environment. However, little is known about the molecular events occurring during the bloom. Here, we compared metaproteomes of two phytoplankton Heterosigma akashiwo and Prorocentrum donghaiense in the coastal East China Sea. H. akashiwo and P. donghaiense accounted for 7.82% and 4.74% of the phytoplankton community protein abundances in the nonbloom sample, whereas they contributed to 60.13% and 78.09%, respectively, in their individual blooming samples. Compared with P. donghaiense, H. akashiwo possessed a significantly higher abundance of light-harvesting complex proteins, carbonic anhydrasem and RuBisCO. The blooming H. akashiwo cells expressed more proteins related to external nutrient acquisition, such as bicarbonate transporter SLC4, ammonium transporter, nitrite transporter, and alkaline phosphatase, while the blooming P. donghaiense cells highly expressed proteins related to extra- and intracellular organic nutrient utilization, such as amino acid transporter, 5'-nucleotidase, acid phosphatase, and tripeptidyl-peptidase. The strong capabilities of light harvesting, as well as acquisition and assimilation of inorganic carbon, nitrogen, and phosphorus, facilitated the formation of the H. akashiwo bloom under the high turbidity and inorganic nutrient-sufficient condition, whereas the competitive advantages in organic nutrient acquisition and reallocation guaranteed the occurrence of the P. donghaiense bloom under the inorganic nutrient-insufficient condition. This study highlights the power of metaproteomics for revealing the underlying molecular behaviors of different coexisting phytoplankton species and advances our knowledge on the formation of phytoplankton blooms.IMPORTANCE A deep understanding of the mechanisms driving bloom formation is a prerequisite for effective bloom management. Metaproteomics was applied in this study to reveal the adaptive and responsive strategies of two coexisting phytoplankton species, H. akashiwo and P. donghaiense, during their bloom periods. Metabolic features and niche divergence in light harvesting, as well as carbon, nitrogen, and phosphorus acquisition and assimilation likely promoted the bloom occurrence under different environments. The molecular behaviors of coexisting bloom-causing species will give clues for bloom monitoring and management in the oceans.
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Fitoplâncton/genética , Fitoplâncton/metabolismo , Proteoma/metabolismo , Carbono/metabolismo , China , Proliferação Nociva de Algas , Nitrogênio/metabolismo , Oceano Pacífico , Fósforo/metabolismoRESUMO
Understanding the neural mechanisms of disorders of consciousness (DOC) is essential for estimating the conscious level and diagnosing DOC patients. Although previous studies reported brain functional connectivity (FC) and spontaneous neural activity patterns associated with consciousness, the relationship between them remains unclear. In this study, we identified the abnormal brain regions in DOC patients by performing voxel-wise FC strength (FCS) and fractional amplitude of low-frequency fluctuations (fALFF) analyses on resting-state functional magnetic resonance imaging data of 15 DOC patients and 24 healthy controls. Furthermore, we detected spatial intersections between two measures and estimated the correlations between either the FCS or the fALFF and the subscales of the Coma Recovery Scale-Revised (CRS-R). We found that the right superior frontal gyrus, left thalamus and right precuneus in which the DOC patients had a lower local FCS and fALFF than healthy controls, are coincident with regions of the mesocircuit model. In the right precuneus, the local FCS/fALFF was significantly positively correlated with the oromotor and motor scores/motor score of the CRS-R. Our findings may indicate that the co-occurrent pattern of spontaneous neural activity and functional connectivity in the thalamo-frontal circuit and the precuneus are associated with motor function in DOC patients.
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Lobo Frontal/fisiopatologia , Lobo Parietal/fisiopatologia , Estado Vegetativo Persistente/fisiopatologia , Tálamo/fisiopatologia , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Mapeamento Encefálico , Estudos de Casos e Controles , Estado de Consciência , Transtornos da Consciência/diagnóstico por imagem , Transtornos da Consciência/fisiopatologia , Feminino , Lobo Frontal/diagnóstico por imagem , Neuroimagem Funcional , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiopatologia , Lobo Parietal/diagnóstico por imagem , Estado Vegetativo Persistente/diagnóstico por imagem , Tálamo/diagnóstico por imagemRESUMO
Following an enormous effort by the global scientific community coordinated by HUPO's Human Proteome Project, the number of proteins without high-quality MS or other evidence (colloquially termed missing proteins) has substantially decreased; however, some highly hydrophobic MPs remain on the list. We believe that efficient peptide separation is an approach that can be used to improve the identification of these hydrophobic MPs. We propose that peptides prepared from the membrane fractions of human cell lines and placental tissue can be well separated from hydrophilic peptides in organic solvents at high concentrations due to the precipitation of hydrophilic peptides with lower solubility. Using a combination strategy of peptide separation in 98% acetonitrile prior to traditional 2D reverse-phase liquid chromatography, more hydrophobic peptides were detected in the supernatants of the organic solvent extractions than were found in the pellets. When this strategy was adopted, 30 MPs (≥2 non-nested unique peptides with ≥9 amino acids) with 114 unique peptides were identified at protein false discovery rate (FDR) < 1%, including 7, 12, and 13 MPs obtained from membrane preparations derived from K562, HeLa cells, and human placenta, respectively. Of the 30 MPs identified in this study, 19 were categorized as membrane proteins or extracellular matrix proteins. Furthermore, 20 were verified to possess two non-nested unique peptides through parallel reaction monitoring with the corresponding chemically synthesized peptides. The use of organic solvents at high concentrations was shown to be an efficient way to improve the exploration of hydrophobic MPs. The data obtained in this study are available via ProteomeXchange (PXD010630) and PeptideAtlas (PASS01218).
Assuntos
Interações Hidrofóbicas e Hidrofílicas , Proteínas de Membrana/análise , Peptídeos/análise , Linhagem Celular , Feminino , Células HeLa , Humanos , Células K562 , Peptídeos/isolamento & purificação , Placenta/citologia , Gravidez , Proteômica/métodos , Solventes/químicaRESUMO
Currently, the commercial reagents for isobaric peptides labeling (TMT and iTRAQ) have some drawbacks, such as high cost in experiments, especially in quantitation for the modified peptides, and inconvenient handling for variable sizes of samples. Herein, we developed a set of 10-plex isobaric tags (IBT) with high stability and low cost. The labeled peptides were sensitively detected on Orbitrap Q Exactive MS with an MS2 resolution of 35â¯000 at 30% NCE, while the peptides were efficiently labeled over 97% by IBT at a ratio of 10:1 of reagent/peptide (w/w) in 200 mM TEAB buffer for 2 h. The IBT labeling was demonstrated with a wide dynamic range of 50-fold without obvious matrix effects on quantification. Importantly, there was little quantification bias found among the individual IBT tags, indicating that the peptides labeled by different tags were quantitatively comparable. The IBT 10-plex reagents were applied for dynamically monitoring the quantitative responses of phosphoproteome stimulated by EGF treatment in HeLa cells. In total, 5â¯361 unique phosphopeptides were identified, which reached a similar conclusion as others reported. The IBT reagents were therefore experimentally proven as a new type of reagents for isobaric peptides labeling and useful in a large quantity peptides of quantitative proteomics.
Assuntos
Indicadores e Reagentes/química , Marcação por Isótopo , Peptídeos/análise , Proteômica , Células HeLa , Humanos , Estrutura MolecularRESUMO
BACKGROUND: Currently, it is challenging to detect the awareness of patients who suffer disorders of consciousness (DOC). Brain-computer interfaces (BCIs), which do not depend on the behavioral response of patients, may serve for detecting the awareness in patients with DOC. However, we must develop effective BCIs for these patients because their ability to use BCIs does not as good as healthy users. METHODS: Because patients with DOC generally do not exhibit eye movements, a gaze-independent audiovisual BCI is put forward in the study where semantically congruent and incongruent audiovisual number stimuli were sequentially presented to evoke event-related potentials (ERPs). Subjects were required to pay attention to congruent audiovisual stimuli (target) and ignore the incongruent audiovisual stimuli (non-target). The BCI system was evaluated by analyzing online and offline data from 10 healthy subjects followed by being applied to online awareness detection in 8 patients with DOC. RESULTS: According to the results on healthy subjects, the audiovisual BCI system outperformed the corresponding auditory-only and visual-only systems. Multiple ERP components, including the P300, N400 and late positive complex (LPC), were observed using the audiovisual system, strengthening different brain responses to target stimuli and non-target stimuli. The results revealed the abilities of three of eight patients to follow commands and recognize numbers. CONCLUSIONS: This gaze-independent audiovisual BCI system represents a useful auxiliary bedside tool to detect the awareness of patients with DOC.
Assuntos
Conscientização/fisiologia , Interfaces Cérebro-Computador , Encéfalo/fisiologia , Transtornos da Consciência/fisiopatologia , Estado de Consciência/fisiologia , Adulto , Eletroencefalografia , Potenciais Evocados/fisiologia , Feminino , Humanos , Masculino , Adulto JovemRESUMO
Human Proteome Project (HPP) aims at mapping entire human proteins with a systematic effort upon all the emerging techniques, which would enhance understanding of human biology and lay a foundation for development of medical applications. Until now, 2563 missing proteins (MPs, PE2-4) are still undetected even using the most sensitive approach of protein detection. Herein, we propose that enrichment of low-abundance proteins benefits MPs finding. ProteoMiner is an equalizing technique by reducing high-abundance proteins and enriching low-abundance proteins in biological liquids. With triton X-100/TBS buffer extraction, ProteoMiner enrichment, and peptide fractionation, 20 MPs (at least two non-nested unique peptides with more than eight a.a. length) with 60 unique peptides were identified from four human tissues including eight membrane/secreted proteins and five nucleus proteins. Then 15 of them were confirmed with two non-nested unique peptides (≥9 a.a.) identified by matching well with their chemically synthetic peptides in PRM assay. Hence, these results demonstrated ProteoMiner as a powerful means in discovery of MPs.
Assuntos
Proteoma/análise , Proteômica/métodos , Fracionamento Químico , Humanos , Métodos , OctoxinolRESUMO
BACKGROUND: For patients with disorders of consciousness such as coma, a vegetative state or a minimally conscious state, one challenge is to detect and assess the residual cognitive functions in their brains. Number processing and mental calculation are important brain functions but are difficult to detect in patients with disorders of consciousness using motor response-based clinical assessment scales such as the Coma Recovery Scale-Revised due to the patients' motor impairments and inability to provide sufficient motor responses for number- and calculation-based communication. METHODS: In this study, we presented a hybrid brain-computer interface that combines P300 and steady state visual evoked potentials to detect number processing and mental calculation in Han Chinese patients with disorders of consciousness. Eleven patients with disorders of consciousness who were in a vegetative state (n = 6) or in a minimally conscious state (n = 3) or who emerged from a minimally conscious state (n = 2) participated in the brain-computer interface-based experiment. During the experiment, the patients with disorders of consciousness were instructed to perform three tasks, i.e., number recognition, number comparison, and mental calculation, including addition and subtraction. In each experimental trial, an arithmetic problem was first presented. Next, two number buttons, only one of which was the correct answer to the problem, flickered at different frequencies to evoke steady state visual evoked potentials, while the frames of the two buttons flashed in a random order to evoke P300 potentials. The patients needed to focus on the target number button (the correct answer). Finally, the brain-computer interface system detected P300 and steady state visual evoked potentials to determine the button to which the patients attended, further presenting the results as feedback. RESULTS: Two of the six patients who were in a vegetative state, one of the three patients who were in a minimally conscious state, and the two patients that emerged from a minimally conscious state achieved accuracies significantly greater than the chance level. Furthermore, P300 potentials and steady state visual evoked potentials were observed in the electroencephalography signals from the five patients. CONCLUSIONS: Number processing and arithmetic abilities as well as command following were demonstrated in the five patients. Furthermore, our results suggested that through brain-computer interface systems, many cognitive experiments may be conducted in patients with disorders of consciousness, although they cannot provide sufficient behavioral responses.
Assuntos
Interfaces Cérebro-Computador , Potenciais Evocados P300/fisiologia , Potenciais Evocados Visuais/fisiologia , Conceitos Matemáticos , Estado Vegetativo Persistente/fisiopatologia , Resolução de Problemas/fisiologia , Adulto , Eletroencefalografia , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
There is a growing body of evidence suggesting that Hashimoto's thyroiditis (HT) may contribute to an increased risk of papillary thyroid carcinoma (PTC). However, the exact relationship between HT and PTC is still not fully understood. The objective of this study was to identify potential common biomarkers that may be associated with both PTC and HT. Three microarray datasets from the GEO database and RNA-seq dataset from TCGA database were collected to identify shared differentially expressed genes (DEGs) between HT and PTC. A total of 101 genes was identified as common DEGs, primarily enriched inflammation- and immune-related pathways through GO and KEGG analysis. We performed protein-protein interaction analysis and identified six significant modules comprising a total of 29 genes. Subsequently, tree hub genes (CD53, FCER1G, TYROBP) were selected using random forest (RF) algorithms for the development of three diagnostic models. The artificial neural network (ANN) model demonstrates superior performance. Notably, CD53 exerted the greatest influence on the ANN model output. We analyzed the protein expressions of the three genes using the Human Protein Atlas database. Moreover, we observed various dysregulated immune cells that were significantly associated with the hub genes through immune infiltration analysis. Immunofluorescence staining confirmed the differential expression of CD53, FCER1G, and TYROBP, as well as the results of immune infiltration analysis. Lastly, we hypothesise that benzylpenicilloyl polylysine and aspirinmay be effective in the treatment of HT and PTC and may prevent HT carcinogenesis. This study indicates that CD53, FCER1G, and TYROBP play a role in the development of HT and PTC, and may contribute to the progression of HT to PTC. These hub genes could potentially serve as diagnostic markers and therapeutic targets for PTC and HT.
Assuntos
Biomarcadores Tumorais , Biologia Computacional , Doença de Hashimoto , Aprendizado de Máquina , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide , Humanos , Doença de Hashimoto/genética , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/diagnóstico , Biologia Computacional/métodos , Biomarcadores Tumorais/genética , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/diagnóstico , Mapas de Interação de Proteínas/genética , Regulação Neoplásica da Expressão Gênica , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Redes Neurais de ComputaçãoRESUMO
In this paper, a novel spatio-temporal self-constructing graph neural network (ST-SCGNN) is proposed for cross-subject emotion recognition and consciousness detection. For spatio-temporal feature generation, activation and connection pattern features are first extracted and then combined to leverage their complementary emotion-related information. Next, a self-constructing graph neural network with a spatio-temporal model is presented. Specifically, the graph structure of the neural network is dynamically updated by the self-constructing module of the input signal. Experiments based on the SEED and SEED-IV datasets showed that the model achieved average accuracies of 85.90% and 76.37%, respectively. Both values exceed the state-of-the-art metrics with the same protocol. In clinical besides, patients with disorders of consciousness (DOC) suffer severe brain injuries, and sufficient training data for EEG-based emotion recognition cannot be collected. Our proposed ST-SCGNN method for cross-subject emotion recognition was first attempted in training in ten healthy subjects and testing in eight patients with DOC. We found that two patients obtained accuracies significantly higher than chance level and showed similar neural patterns with healthy subjects. Covert consciousness and emotion-related abilities were thus demonstrated in these two patients. Our proposed ST-SCGNN for cross-subject emotion recognition could be a promising tool for consciousness detection in DOC patients.
Assuntos
Estado de Consciência , Emoções , Humanos , Benchmarking , Redes Neurais de Computação , EletroencefalografiaRESUMO
Out-of-hospital cardiac arrest (OHCA) is a leading cause of global mortality, with numerous factors influencing the patient survival rate and prognosis. This study aimed to evaluate the OHCA epidemiology in China and elaborate on the current Hangzhou emergency system status. This retrospective analysis was based on the medical history system of the Hangzhou Emergency Center registered from 2015-2021. We provided a detailed description of OHCA characteristics and investigated the factors affecting the success rate of emergency treatment in terms of epidemiology, causes of onset, bystander rescue, and outcome factors. We included 9585 out-of-hospital cardiac arrest cases, of which 5442 (56.8%) had evidence of resuscitation. Patients with underlying diseases constituted the vast majority (80.1%); trauma and physicochemical factors accounted for 16.5% and 3.4%, respectively. Only 30.4% of patients (about 80.0% of bystanders witnessed) received bystander first aid. The outcome rate of emergency doctors dispatched by emergency centres was significantly higher than doctors dispatched by hospitals. Additionally, physician's first-aid experience, emergency response time, emergency telephone availability, initial heart rhythm, out-of-hospital defibrillation, out-of-hospital intubation, and using of epinephrine significantly can significantly improve the out-of-hospital return of spontaneous circulation in patients. All steps in pre-hospital care are important for patients, especially for bystander first aid and physician's first-aid experience. The popularity of first-aid training and the public emergency medical system are not potent enough. We should take those key factors into consideration when developing a pre-hospital care system for OHCA.
Assuntos
Reanimação Cardiopulmonar , Serviços Médicos de Emergência , Parada Cardíaca Extra-Hospitalar , Humanos , Estudos Retrospectivos , Parada Cardíaca Extra-Hospitalar/epidemiologia , Parada Cardíaca Extra-Hospitalar/terapia , Hospitais , China/epidemiologiaRESUMO
Disorders of consciousness are impaired states of consciousness caused by severe brain injuries. Previous resting-state functional magnetic resonance imaging studies have reported abnormal brain network properties at different topological scales in patients with disorders of consciousness by using graph theoretical analysis. However, it is still unclear how inter-regional directed propagation activities affect the topological organization of functional brain networks in patients with disorders of consciousness. To reveal the altered topological organization in patients with disorders of consciousness, we constructed whole-brain directed functional networks by combining functional connectivity analysis and time delay estimation. Then we performed graph theoretical analysis based on the directed functional brain networks at three topological scales, from the nodal scale, the resting-state network scale to the global scale. Finally, the canonical correlation analysis was used to determine the correlations between altered topological properties and clinical scores in patients with disorders of consciousness. At the nodal scale, we observed decreased in-degree and increased out-degree in the precuneus in patients with disorders of consciousness. At the resting-state network scale, the patients with disorders of consciousness showed reorganized motif patterns within the default mode network and between the default mode network and other resting-state networks. At the global scale, we found a lower global clustering coefficient in the patients with disorders of consciousness than in the controls. The results of the canonical correlation analysis showed that the abnormal degree and the disrupted motif were significantly correlated with the clinical scores of the patients with disorders of consciousness. Our findings showed that consciousness impairment can be revealed by abnormal directed connection patterns at multiple topological scales in the whole brain, and the disrupted directed connection patterns may serve as clinical biomarkers to assess the dysfunction of patients with disorders of consciousness.
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lncRNA ANRIL is an oncogene, however the role of ANRIL in the regulation of colorectal cancer on human lymphatic endothelial cells (HLECs) is remain elusive. Pien Tze Huang (PZH, PTH) a Tradition Chinese Medicine (TCM) as an adjunctive medication could inhibit the cancer metastasis, however the mechanism still uncovering. We used network pharmacology, subcutaneous and orthotopic transplanted colorectal tumors models to determine the effect of PZH on tumor metastasis. Differential expressions of ANRIL in colorectal cancer cells, and stimulating the regulation of cancer cells on HLECs by culturing HLECs with cancer cells' supernatants. Network pharmacology, transcriptomics, and rescue experiments were carried out to verify key targets of PZH. We found PZH interfered with 32.2% of disease genes and 76.7% of pathways, and inhibited the growth of colorectal tumors, liver metastasis, and the expression of ANRIL. The overexpression of ANRIL promoted the regulation of cancer cells on HLECs, leading to lymphangiogenesis, via upregulated VEGF-C secretion, and alleviated the effect of PZH on inhibiting the regulation of cancer cells on HLECs. Transcriptomic, network pharmacology and rescue experiments show that PI3K/AKT pathway is the most important pathway for PZH to affect tumor metastasis via ANRIL. In conclusion, PZH inhibits the regulation of colorectal cancer on HLECs to alleviate tumor lymphangiogenesis and metastasis by downregulating ANRIL dependent PI3K/AKT/VEGF-C pathway.
Assuntos
Neoplasias Colorretais , Proteínas Proto-Oncogênicas c-akt , Humanos , Apoptose , Linhagem Celular Tumoral , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Células Endoteliais/metabolismo , Fosfatidilinositol 3-Quinases , Fator C de Crescimento do Endotélio Vascular/metabolismoRESUMO
BACKGROUND: It is common to obtain a low detection rate and unsatisfactory detection results in complex infection or rare pathogen detection. This retrospective study aimed to illustrate the application value and prospect of the third-generation sequencing technology in lower respiratory tract infection disease. METHODS: This study recruited 70 patients with lower respiratory tract infection (LRTI). Pathogen detection of bronchoalveolar lavage fluid (BALF) from all patients was performed using nanopore metagenomic sequencing technology and traditional culture. BALF culture combined with quantitiative PCR (qPCR) was used as a reference standard to analyze the sensitivity and specificity of nanopore sequencing technology. The current study also collected the examination results of enrolled samples using technical methods sputum culture, tuberculosis DNA (TB-DNA), and Xpert MTB/RIF and analyzed the detection efficiency of nanopore sequencing for Mycobacterium tuberculosis. RESULTS: The positive rates of pathogens in 70 BALF samples detected by conventional culture and nanopore sequencing were 25.71% and 84.29%, respectively. Among the 59 positive BALF cases using nanopore sequencing, a total of 31 pathogens were identified, of which the proportions of bacteria, fungi, viruses, and other pathogens were 50%, 17%, 32%, and 1%, respectively. Using the results combined with culture and qPCR detection methods as the standard, the pathogen detection of BALF using nanopore sequencing had a sensitivity of 70% and a specificity of 91.7%. Additionally, the positive rate of the detection of M. tuberculosis using nanopore sequencing was 33.3% (6/18). The clinical medication plans of 74.3% (52/70) of the patients were referred to the nanopore sequencing results, of which 31 cases changed their treatment strategy, 21 supported the previous treatment plans, and 90% (47/52) of the patients finally had clinical improvement. CONCLUSIONS: BALF detection using nanopore sequencing technology improves the process of detecting pathogens in patients with LRTI, especially for M. tuberculosis, fungi, and viruses, by reducing the report time from three days to six hours. The clinical application prospect of nanopore sequencing technology is promising in the pathogen diagnosis of LRTI.
Assuntos
Mycobacterium tuberculosis , Infecções Respiratórias , Tuberculose Pulmonar , Tuberculose , Humanos , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/microbiologia , Estudos Retrospectivos , Tuberculose/diagnóstico , Mycobacterium tuberculosis/genética , Infecções Respiratórias/diagnóstico , Sensibilidade e Especificidade , Fungos/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodosRESUMO
Outer membrane protein A (OmpA) is a major structural component of the outer membranes and functions as a multifaceted molecular with many diverse roles in Gram-negative bacteria. In Haemophilus parasuis, OmpA has been recognized and named as OmpP5 in genomic literature. In this study, to determine the precise functions of OmpP5, an ompP5 deficient mutant (ΔompP5) of a H. parasuis serovar 4 filed strain SC096 was constructed using a natural transformation method. Compared to the wild-type SC096 strain, the ΔompP5 mutant displayed a detectable delay in growth. However, the wild-type and mutant strains were indistinguishable with respect to the other phenotypes including resistance to killing by porcine and rabbit sera, adhesion to and invasion of porcine umbilicus veins endothelial cells (PUVEC) and porcine kidney epithelial cells (PK-15). To analyze the differences of proteome expression between wild-type and mutant strains, a 2-dimensional gel electrophoresis (2-DE)-based proteomics comparison was performed. There were 24 differentially expressed proteins which were mainly involved in carbohydrate, lipid, nucleotide and amino acid metabolism, or served as transcription and translation factors and chaperone proteins. Collectively, loss of OmpP5 expression in the H. parasuis SC096 strain resulted in global protein expression changes which might be responsible for novel phenotypes occurred in ΔompP5 mutant.
Assuntos
Proteínas da Membrana Bacteriana Externa/genética , Deleção de Genes , Haemophilus parasuis/química , Proteoma/análise , Animais , Aderência Bacteriana , Atividade Bactericida do Sangue , Células Cultivadas , Eletroforese em Gel Bidimensional , Células Endoteliais/microbiologia , Células Epiteliais/microbiologia , Haemophilus parasuis/crescimento & desenvolvimento , Haemophilus parasuis/patogenicidade , Viabilidade Microbiana , Coelhos , SuínosRESUMO
Convolutional Neural Network (CNN) is commonly used for the Electroencephalogram (EEG) based motor-imagery (MI) decoding. However, its performance is generally limited due to the small size sample problem. An alternative way to address such issue is to segment EEG trials into small slices for data augmentation, but this approach usually inevitably loses the valuable long-range dependencies of temporal information in EEG signals. To this end, we propose a novel self-supervised learning (SSL) based channel attention MLP-Mixer network (S-CAMLP-Net) for MI decoding with EEG. Specifically, a new EEG slice prediction task is designed as the pretext task to capture the long-range information of EEG trials in the time domain. In the downstream task, a newly proposed MLP-Mixer is applied to the classification task for signals rather than for images. Moreover, in order to effectively learn the discriminative spatial representations in EEG slices, an attention mechanism is integrated into MLP-Mixer to adaptively estimate the importance of each EEG channel without any prior information. Thus, the proposed S-CAMLP-Net can effectively learn more long-range temporal information and global spatial features of EEG signals. Extensive experiments are conducted on the public MI-2 dataset and the BCI Competition IV Dataset 2A. The experimental results indicate that our proposed S-CAMLP-Net achieves superior classification performance over all the compared algorithms.
Assuntos
Interfaces Cérebro-Computador , Algoritmos , Eletroencefalografia/métodos , Humanos , Imaginação , Redes Neurais de Computação , Aprendizado de Máquina SupervisionadoRESUMO
In both hydrophobic and hydrophilic nanochannels, confined water clusters spontaneously form dense internal hydrogen bond networks and hence exhibit fast mass-transfer kinetics. Covalent organic frameworks (COFs), a porous polymer, enables one-dimensional open channels to achieve ordered assembly guided by synthetic techniques and allows the accommodation of a large number of water molecules within the nanochannels. In the field of alkaline anion exchange membrane fuel cells, it has been a long-term pursuit of scientists to build abundant hydrogen bonds around hydrogen oxides (OH-) to improve the conduction of OH- by increasing the water content. Here, we designed and synthesized a OH- conductor by assembling benzimidazolium into COFs, and a significantly high conductivity of 10-1 S cm-1 was achieved at 353 K. Theoretical calculations showed that the water clusters confined in the pores of COFs and the regularly arranged hydroxides cooperatively formed a dense hydrogen bond network and OH- conducted diffusive conduction through the Grotthuss hopping of protons in this hydrogen bond network.