RESUMO
In archaea and eukaryotes, the evolutionarily conserved KEOPS is composed of four core subunits-Kae1, Bud32, Cgi121 and Pcc1, and a fifth Gon7/Pcc2 that is found in fungi and metazoa. KEOPS cooperates with Sua5/YRDC to catalyze the biosynthesis of tRNA N6-threonylcarbamoyladenosine (t6A), an essential modification needed for fitness of cellular organisms. Biochemical and structural characterizations of KEOPSs from archaea, yeast and humans have determined a t6A-catalytic role for Kae1 and auxiliary roles for other subunits. However, the precise molecular workings of KEOPSs still remain poorly understood. Here, we investigated the biochemical functions of A. thaliana KEOPS and determined a cryo-EM structure of A. thaliana KEOPS dimer. We show that A. thaliana KEOPS is composed of KAE1, BUD32, CGI121 and PCC1, which adopts a conserved overall arrangement. PCC1 dimerization leads to a KEOPS dimer that is needed for an active t6A-catalytic KEOPS-tRNA assembly. BUD32 participates in direct binding of tRNA to KEOPS and modulates the t6A-catalytic activity of KEOPS via its C-terminal tail and ATP to ADP hydrolysis. CGI121 promotes the binding of tRNA to KEOPS and potentiates the t6A-catalytic activity of KEOPS. These data and findings provide insights into mechanistic understanding of KEOPS machineries.
Assuntos
Proteínas de Arabidopsis , Complexos Multiproteicos , RNA de Plantas , RNA de Transferência , Adenosina/análogos & derivados , Adenosina/metabolismo , Adenosina/química , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/química , Microscopia Crioeletrônica , Modelos Moleculares , Ligação Proteica , Multimerização Proteica , RNA de Transferência/metabolismo , RNA de Transferência/química , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/química , Proteínas de Ligação a RNA/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/genética , Complexos Multiproteicos/metabolismo , RNA de Plantas/química , RNA de Plantas/metabolismoRESUMO
The burgeoning crisis of antibiotic resistance has directed attention to bacteriophages as natural antibacterial agents capable of circumventing bacterial defenses. Central to this are the bacterial defense mechanisms, such as the BREX system, which utilizes the methyltransferase BrxX to protect against phage infection. This study presents the first in vitro characterization of BrxX from Escherichia coli, revealing its substrate-specific recognition and catalytic activity. We demonstrate that BrxX exhibits nonspecific DNA binding but selectively methylates adenine within specific motifs. Kinetic analysis indicates a potential regulation of BrxX by the concentration of its co-substrate, S-adenosylmethionine, and suggests a role for other BREX components in modulating BrxX activity. Furthermore, we elucidate the molecular mechanism by which the T7 phage protein Ocr (Overcoming classical restriction) inhibits BrxX. Despite low sequence homology between BrxX from different bacterial species, Ocr effectively suppresses BrxX's enzymatic activity through high-affinity binding. Cryo-electron microscopy and biophysical analyses reveal that Ocr, a DNA mimic, forms a stable complex with BrxX, highlighting a conserved interaction interface across diverse BrxX variants. Our findings provide insights into the strategic counteraction by phages against bacterial defense systems and offer a foundational understanding of the complex interplay between phages and their bacterial hosts, with implications for the development of phage therapy to combat antibiotic resistance.
Assuntos
Proteínas de Escherichia coli , Escherichia coli , Proteínas Virais , Escherichia coli/virologia , Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas Virais/metabolismo , S-Adenosilmetionina/metabolismo , Ligação Proteica , Bacteriófago T7/genética , Metiltransferases/metabolismo , CinéticaRESUMO
Triple-negative breast cancer (TNBC) is an aggressive breast cancer sub-type with limited treatment options and poor prognosis. Currently, standard treatments for TNBC include surgery, chemotherapy, and anti-PDL1 therapy. These therapies have limited efficacy in advanced stages. Myeloid-cell leukemia 1 (MCL1) is an anti-apoptotic BCL2 family protein. High expression of MCL1 contributes to chemotherapy resistance and is associated with a worse prognosis in TNBC. MCL1 inhibitors are in clinical trials for TNBC, but response rates to these inhibitors can vary and predictive markers are lacking. Currently, we identified a 4-member (AXL, ETS1, IL6, EFEMP1) gene signature (GS) that predicts MCL1 inhibitor sensitivity in TNBC cells. Factors encoded by these genes regulate signaling pathways to promote MCL1 inhibitor resistance. Small molecule inhibitors of the GS factors can overcome resistance and sensitize otherwise resistant TNBC cells to MCL1 inhibitor treatment. These findings offer insights into potential therapeutic strategies and tumor stratification for MCL1 inhibitor use in TNBC.
Assuntos
Resistencia a Medicamentos Antineoplásicos , Proteína de Sequência 1 de Leucemia de Células Mieloides , Neoplasias de Mama Triplo Negativas , Humanos , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Proteína de Sequência 1 de Leucemia de Células Mieloides/genética , Proteína de Sequência 1 de Leucemia de Células Mieloides/antagonistas & inibidores , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Feminino , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Antineoplásicos/farmacologia , Interleucina-6/metabolismo , Interleucina-6/genética , Proteína Proto-Oncogênica c-ets-1RESUMO
Underlying medical conditions, such as cancer, kidney disease and heart failure, are associated with a higher risk for severe COVID-19. Accurate classification of COVID-19 patients with underlying medical conditions is critical for personalized treatment decision and prognosis estimation. In this study, we propose an interpretable artificial intelligence model termed VDJMiner to mine the underlying medical conditions and predict the prognosis of COVID-19 patients according to their immune repertoires. In a cohort of more than 1400 COVID-19 patients, VDJMiner accurately identifies multiple underlying medical conditions, including cancers, chronic kidney disease, autoimmune disease, diabetes, congestive heart failure, coronary artery disease, asthma and chronic obstructive pulmonary disease, with an average area under the receiver operating characteristic curve (AUC) of 0.961. Meanwhile, in this same cohort, VDJMiner achieves an AUC of 0.922 in predicting severe COVID-19. Moreover, VDJMiner achieves an accuracy of 0.857 in predicting the response of COVID-19 patients to tocilizumab treatment on the leave-one-out test. Additionally, VDJMiner interpretively mines and scores V(D)J gene segments of the T-cell receptors that are associated with the disease. The identified associations between single-cell V(D)J gene segments and COVID-19 are highly consistent with previous studies. The source code of VDJMiner is publicly accessible at https://github.com/TencentAILabHealthcare/VDJMiner. The web server of VDJMiner is available at https://gene.ai.tencent.com/VDJMiner/.
Assuntos
Asma , COVID-19 , Humanos , Inteligência Artificial , Curva ROC , SoftwareRESUMO
Trastuzumab is the first-line therapy for human epidermal growth factor receptor 2-positive (HER2+) breast cancer, but often patients develop acquired resistance. Although other agents are in clinical use to treat trastuzumab-resistant (TR) breast cancer; still, the patients develop recurrent metastatic disease. One of the primary mechanisms of acquired resistance is the shedding/loss of the HER2 extracellular domain, where trastuzumab binds. We envisioned any new agent acting downstream of the HER2 should overcome trastuzumab resistance. The mixed lineage kinase 3 (MLK3) activation by trastuzumab is necessary for promoting cell death in HER2+ breast cancer. We designed nanoparticles loaded with MLK3 agonist ceramide (PPP-CNP) and tested their efficacy in sensitizing TR cell lines, patient-derived organoids, and patient-derived xenograft (PDX). The PPP-CNP activated MLK3, its downstream JNK kinase activity, and down-regulated AKT pathway signaling in TR cell lines and PDX. The activation of MLK3 and down-regulation of AKT signaling by PPP-CNP induced cell death and inhibited cellular proliferation in TR cells and PDX. The apoptosis in TR cells was dependent on increased CD70 protein expression and caspase-9 and caspase-3 activities by PPP-CNP. The PPP-CNP treatment alike increased the expression of CD70, CD27, cleaved caspase-9, and caspase-3 with a concurrent tumor burden reduction of TR PDX. Moreover, the expressions of CD70 and ceramide levels were lower in TR than sensitive HER2+ human breast tumors. Our in vitro and preclinical animal models suggest that activating the MLK3-CD70 axis by the PPP-CNP could sensitize/overcome trastuzumab resistance in HER2+ breast cancer.
Assuntos
Antineoplásicos Imunológicos , Neoplasias da Mama , Ligante CD27 , Resistencia a Medicamentos Antineoplásicos , MAP Quinase Quinase Quinases , Nanopartículas , Trastuzumab , Animais , Antineoplásicos Imunológicos/farmacologia , Antineoplásicos Imunológicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Ligante CD27/metabolismo , Caspase 3/metabolismo , Caspase 9/metabolismo , Linhagem Celular Tumoral , Ceramidas/química , Feminino , Humanos , MAP Quinase Quinase Quinases/metabolismo , Camundongos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor ErbB-2/análise , Trastuzumab/farmacologia , Trastuzumab/uso terapêutico , Ensaios Antitumorais Modelo de Xenoenxerto , MAP Quinase Quinase Quinase 11 Ativada por MitógenoRESUMO
BACKGROUND: Firmiana danxiaensis is a critically endangered and ecologically important tree currently only found in four locations in Danxia or Karst habitats in northern Guangdong Province, China. The specialized habitat preference makes it an ideal model species for study of adaptive evolution. Meanwhile, the phylogenetic relationships of F. danxiaensis in four locations under two landforms are unclear. Therefore, we sequenced its complete chloroplast (cp.) genomes and conducted comprehensive interspecific and intrageneric plastome studies. RESULTS: The F. danxiaensis plastomes in four locations showed a typical quadripartite and circular structure that ranged from 160,832 to 161,206 bp in size, with 112 unique genes encoded. Comparative genomics showed that the plastomes of F. danxiaensis were relatively conserved with high similarity of genome organization, gene number, GC content and SSRs. While the genomes revealed higher biased codon preferences in Karst habitat than those in Danxia habitats. Eighteen and 11 divergent hotpots were identified at interspecific and intrageneric levels for species identification and further phylogenetic studies. Seven genes (clpP, accD, ccsA, ndhH, rpl20, rpoC2, and rps4) were under positive selection and may be related to adaptation. Phylogenetic analysis revealed that F. danxiaensis is sister to F. major and F. simplex. However, the interspecific relationships are not consistent with the habitat types. CONCLUSIONS: The characteristics and interspecific relationship of F. danxiaensis plastomes provide new insights into further integration of geographical factors, environmental factors, and genetic variations on the genomic study of F. danxiaensis. Together, our study will contribute to the study of species identification, population genetics, and conservation biology of F. danxiaensis.
Assuntos
Genoma de Cloroplastos , Filogenia , Genoma de Cloroplastos/genética , Genômica , Sequência de Bases , Genética PopulacionalRESUMO
In this paper, we report on the discovery of a spinel compound, Co0.7Al2S4, which was synthesized at high-pressure. The systematic characterizations were carried out by structural, magnetic, and heat capacity measurements. The compound crystallizes into a cubic structure with the space group Fd3Ì m (no. 227) and the lattice constant a = 9.9580(1) Å. Magnetic susceptibility measurements suggest that Co0.7Al2S4 exhibits a spin glass ground state, freezing at Tf â¼ 7.2 K with a Weiss temperature Tθ â¼ -115.9 K, which is verified by ac magnetic susceptibility and heat capacity measurements. The frustration parameter f for Co0.7Al2S4 is calculated to be about 16.6, based on the formula f = | Tθ/Tf |, indicating that Co0.7Al2S4 is a high-frustration magnet. Specific heat data displays a T2 dependence below the freezing temperature, which is different from the linear dependence observed in a common spin glass system. Compared with the similar compound CoAl2O4, it is suggested that the vacancies in the Co sites should be responsible for the occurrence of the spin glass behavior of Co0.7Al2S4.
RESUMO
Direct nitrous oxide (N2O) emissions from fertilizer application are the largest anthropogenic source of global N2O, but the factors influencing these emissions remain debated. Here, we compile 1134 observations of fertilizer-induced N2O emission factor (EF) from 229 publications, covering various regions and crops globally. We then employ an interpretable machine learning model to investigate the driving factors of fertilizer-induced N2O emissions. Our results reveal that pH, soil organic carbon, precipitation, and temperature are the most influential factors, overweighing the impacts of management practices. Nitrogen application rate has a positive impact on the EF, but the effect diminishes as nitrogen application rate increases, which has been overestimated in previous studies. Soil pH has three-stage influence on EF: positive when 7.3 ≤ pH ≤ 8.7, significantly negative between 6.8 and 7.3, and insignificant at lower pH levels (4.7 ≤ pH ≤ 6.8). Moreover, we confirm the nonlinear contributions of temperature and precipitation to EF, which may cause an unexpected increase in N2O emission under climate change. Our research provides crucial insights for global N2O modeling and mitigation strategies.
Assuntos
Fertilizantes , Aprendizado de Máquina , Óxido Nitroso , Óxido Nitroso/análise , Solo/química , Mudança ClimáticaRESUMO
Dissolved organic carbon (DOC) dynamics are critical to carbon cycling in forest ecosystems and sensitive to global change. Our study, spanning from 2001 to 2020 in a headwater catchment in subtropical China, analyzed DOC and water chemistry of throughfall, litter leachate, soil waters at various depths, and streamwater. We focused on DOC transport through hydrological pathways and assessed the long-term trends in DOC dynamics amidst environmental and climatic changes. Our results showed that the annual DOC deposition via throughfall and stream outflow was 14.2 ± 2.2 and 1.87 ± 0.83 g C m-2 year-1, respectively. Notably, there was a long-term declining trend in DOC deposition via throughfall (-0.195 mg C L-1 year-1), attributed to reduced organic carbon emissions from clean air actions. Conversely, DOC concentrations in soil waters and stream waters showed increasing trends, primarily due to mitigated acid deposition. Moreover, elevated temperature and precipitation could partly explain the long-term rise in DOC leaching. These trends in DOC dynamics have significant implications for the stability of carbon sink in terrestrial, aquatic, and even oceanic ecosystems at regional scales.
Assuntos
Carbono , Florestas , Ecossistema , China , Solo/química , Ciclo do CarbonoRESUMO
Drug-target interaction (DTI) prediction serves as the foundation of new drug findings and drug repositioning. For drugs/targets, the sequence data contains the biological structural information, while the heterogeneous network contains the biochemical functional information. These two types of information describe different aspects of drugs and targets. Due to the complexity of DTI machinery, it is necessary to learn the representation from multiple perspectives. We hereby try to design a way to leverage information from multi-source data to the maximum extent and find a strategy to fuse them. To address the above challenges, we propose a model, named MOVE (short for integrating multi-source information for predicting DTI via cross-view contrastive learning), for learning comprehensive representations of each drug and target from multi-source data. MOVE extracts information from the sequence view and the network view, then utilizes a fusion module with auxiliary contrastive learning to facilitate the fusion of representations. Experimental results on the benchmark dataset demonstrate that MOVE is effective in DTI prediction.
Assuntos
Desenvolvimento de Medicamentos , Reposicionamento de Medicamentos , Simulação por Computador , Desenvolvimento de Medicamentos/métodosRESUMO
Mobocertinib, as a structural analog of the third generation TKI Osimertinib, can selectively act on the EGFRex20 mutation. We have structurally modified Mobocertinib to obtain new EGFR inhibitors. In this paper, we chose Mobocertinib as a lead compound for structural modification to investigate the effect of Mobocertinib derivatives on EGFRT790M mutation. We designed and synthesized 63 Mobocertinib derivatives by structural modification using the structural similarity strategy and the bioelectronic isoarrangement principle. Then, we evaluated the in vitro antitumor activity of the 63 Mobocertinib derivatives and found that the IC50 of compound H-13 against EGFRL858R/T790M mutated H1975 cells was 3.91 µM, and in further kinase activity evaluation, the IC50 of H-13 against EGFRL858R/T790M kinase was 395.2 nM. In addition, the preferred compound H-13 was able to promote apoptosis of H1975 tumor cells and block the proliferation of H1975 cells in the G0/G1 phase; meanwhile, it was able to significantly inhibit the migratory ability of H1975 tumor cells and inhibit the growth of H1975 cells in a time-concentration-dependent manner. In the in vivo anti-tumor activity study, the preferred compound H-13 had no obvious toxicity to normal mice, and the tumor inhibition effect on H1975 cell-loaded nude mice was close to that of Mobocertinib. Finally, molecular dynamics simulations showed that the binding energy between compound H-13 and 3IKA protein was calculated to be -162.417 ± 14.559 kJ/mol. In summary, the preferred compound H-13 can be a potential third-generation EGFR inhibitor.
Assuntos
Antineoplásicos , Apoptose , Proliferação de Células , Relação Dose-Resposta a Droga , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB , Inibidores de Proteínas Quinases , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Proliferação de Células/efeitos dos fármacos , Relação Estrutura-Atividade , Estrutura Molecular , Animais , Apoptose/efeitos dos fármacos , Camundongos , Camundongos Nus , Linhagem Celular Tumoral , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Neoplasias Experimentais/metabolismoRESUMO
Objective: The present study was performed to evaluate the effect of ultrasound-guided erector spinae plane block (ESPB) on pain after laparoscopic transabdominal preperitoneal (TAPP) repair. Therefore, improved postoperative pain management is crucial for enhancing the overall patient experience and recovery. Methods: This prospective, double-blind, randomized controlled trial enrolled 40 male patients with a unilateral inguinal hernia at Xi'an Aerospace General Hospital from November 1, 2020, to February 1, 2021. Participants were assigned through a random number table at a 1:1 ratio to receive either ESPB with 20 ml 0.5% ropivacaine in the experimental group (Group E) or ESPB with 20 ml normal saline in the control group (Group C), with 20 cases in each group. The primary outcome was assessed using visual analogue scale (VAS) scores for exercise pain at 2h, 6h, 12h, 18h, and 24h postoperatively. Secondary outcomes included time lapses before patient-controlled intravenous analgesia (PCIA) use, intraoperative remifentanil usage, additional sufentanil, postoperative nalbuphine consumption, analgesic remedies at 24h postoperatively, and incidence of postoperative adverse events. Results: Group E provided more pain mitigation for patients than Group C, as evidenced by the significantly lower VAS scores during exercise pain at 2h (Group C: 1.95±1.19; Group E:4.00±1.38), 6h (Group C: 2.00±1.12; Group E:3.90±1.37), and 12h (Group C: 2.05±1.05; Group E:3.55±1.36) postoperatively (P < .05), and the pain mitigation for Group C was significant only at 18h and 24h postoperatively compared to at 2h postoperatively (P < .05). Group E resulted in significantly reduced intraoperative use of remifentanil and, additional sufentanil and postoperative nalbuphine consumption versus Group C (P < .05). Group E exhibited a better pain tolerance than Group C, as demonstrated by the longer time lapse before the use of PCIA (RR value=5.709, t=8.446, P < .05). Group C required more analgesic remedies within 24 h after surgery than Group E (P < .05). Group E did not increase the risk of postoperative adverse events, given the absence of statistical significance in the intergroup comparison (P > .05). Conclusion: Ultrasound-guided ESPB demonstrates notable benefits by decreasing intraoperative and postoperative anesthetic drug requirements, enhancing pain management, and elevating postoperative comfort and quality of life for patients. While acknowledging the study's limitations, it is crucial to highlight the potential clinical implications of these findings. The incorporation of ESPB with ropivacaine into postoperative pain management protocols could represent a significant advancement in clinical practice. The observed improvements in pain management and reduced reliance on anesthetic drugs may lead to more tailored and efficient postoperative care, potentially enhancing patient recovery experiences. Further research and practical implementation studies are warranted to fully elucidate the specific impact and optimal integration of ESPB with ropivacaine within broader clinical settings.
RESUMO
Many patients with non-small cell lung cancer (NSCLC) initially benefit from epidermal growth factor receptor (EGFR) targeted therapy. Unfortunately, varying degrees of resistance or side effects eventually develop. Overcoming and preventing the resistance and side effects of EGFR inhibitors has become a hot topic of research today. Based on the previous studies on AZD-9291, we designed and synthesized two series of 2,4-dichloro-6-methylpyrimidine derivatives, 19 compounds in total, as potential inhibitors of the EGFR kinase. The most promising compound, L-18, showed better inhibitory activity (81.9%) and selectivity against EGFRT790M/L858R kinase. In addition, L-18 showed strong antiproliferative activity against H1975 cells with an IC50 value of 0.65 ± 0.06 µM and no toxicity to normal cells (LO-2). L-18 was able to dose-dependently induce the apoptosis of H1975 cells and produced a cell-cycle-blocking effect, and it can also dose-dependently inhibit the migration and invasion of H1975 cells. L-18 also showed in vivo anticancer efficacy in H1975 cells xenograft mice. We also performed a series of in vivo and in vitro toxicological evaluations of compound L-18, which did not cause obvious injury in mice during administration. These results suggest that L-18 may be a promising drug candidate that warrants further investigation.
Assuntos
Antineoplásicos , Apoptose , Carcinoma Pulmonar de Células não Pequenas , Proliferação de Células , Relação Dose-Resposta a Droga , Desenho de Fármacos , Receptores ErbB , Neoplasias Pulmonares , Inibidores de Proteínas Quinases , Pirimidinas , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Pirimidinas/farmacologia , Pirimidinas/síntese química , Pirimidinas/química , Animais , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Relação Estrutura-Atividade , Apoptose/efeitos dos fármacos , Camundongos , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Estrutura Molecular , Camundongos Nus , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos Endogâmicos BALB CRESUMO
Background: Clinical studies have shown that the onset and exacerbation of chronic obstructive pulmonary disease (COPD) are related to obesity and dietary behaviours, but the genetic relationship between them is not clear.Aims: To investigate the relationship between the genetic determinants of obesity, dietary habits (alcohol consumption, intake of sweets, salt intake) and COPD.Methods: Exposure and outcome datasets were obtained from the IEU Open GWAS project. The exposure dataset includes dietary habits (Salt added to food, Sweets intake, Alcohol consumption), obesity level (represented by body mass index (BMI) and body fat percentage (BFP) data sets.). The outcome dataset includes COPD and acute COPD admissions. The collected data were imported into the RStudio software and conducted Mendelian randomisation analysis. Additionally, heterogeneity and horizontal pleiotropy tests were conducted on the data to ensure the veracity of the results.Results: The results showed that BMI was positively correlated with the risk of acute COPD admission (OR = 1.74, 95% CI 1.39-2.18) and COPD (OR = 1.81, 95%CI 1.41-2.33). In addition, BFP was also a risk factor for COPD (OR = 1.98, 95% CI 1.42-2.77) and acute exacerbation of COPD admission (OR = 1.99, 95%CI 1.43-2.77). The increase of salt, sugar and alcohol consumption will not increase the risk of COPD and the risk of hospitalisation due to COPD.Conclusion: Therefore, we should strengthen the guidance of diet and living habits of obese patients. For patients with heavier weight and higher body fat rate, they should be instructed to lose weight and fat to prevent the occurrence of COPD. For obese patients with COPD, more attention should be paid to prevent the occurrence of acute exacerbation of COPD in advance.
Assuntos
Doença Pulmonar Obstrutiva Crônica , Humanos , Índice de Massa Corporal , Comportamento Alimentar , Obesidade/epidemiologia , Obesidade/genética , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/genética , Fatores de Risco , Análise da Randomização MendelianaRESUMO
Metasurfaces have enabled precise electromagnetic (EM) wave manipulation with strong potential to obtain unprecedented functionalities and multifunctional behavior in flat optical devices. One promising aspect to achieve multifunction is polarization-dependent metadevices enabled by simultaneous phase control over orthogonally polarized waves. Among these, metasurfaces with geometric phase shows their natural and robust phase control ability over different circularly polarized waves. However, the phase responses under the circularly polarized incidence are locked to be opposite with each other, resulting in limited multifunctionality. In this study, we propose what we believe to be a novel transmission-type microwave metadevice constructed by linear-to-circular metasurface and spin-decoupled metasurface. By endowing independent phase adjustment capability to each unit structure in a spin-decoupled metasurface, the metadevice can reconfigure arbitrary phase wavefronts under orthogonal polarization state incidence, thereby achieving flexible multifunctionality. As a proof-of-concept, the feasibility and reliability of proposed metasurfaces were verified by simulating multifunctional directional deflection, off-axis focusing, and focused vortex beam generation. Finally, the multifunctional manipulation capability of the metadevice is successfully demonstrated by actually measuring the generation of orbital angular momentum modes. This work is expected to drive the application development of metasurface devices in wireless communication.
RESUMO
BACKGROUND: Enterovirus (EV) infections are being increasingly seen in younger infants, often being more severe than in older children. The risk factors of EV infection in infants have been inadequately investigated till date. METHODS: We conducted a retrospective study on hospitalized children with laboratory-confirmed EV infection (50 infants aged 0-3 months and 65 older than 3 months) at a tertiary care center in China. Prevalence, clinical characteristics, and genetic features of the virus were analyzed, and independent predictors for severe infection were assessed. RESULTS: Clinical findings showed that severe infection was more common in infants aged 0-3 months than in older children (78.0% vs. 35.4%, p < 0.001), with higher morbidity of pneumonia, meningitis, and sepsis (p < 0.01). EV-B types were detected more frequently in infants aged 0-3 months than in older children (88.0% vs. 7.7%, p < 0.001). Echovirus 11 was the most identified EV-B, and it recombined with E6 in P2 and P3 regions. Risk factors for severe EV infection included EV-B types infection, age less than 3 months, elevated alanine aminotransferase level, abnormal platelet count, and abnormal cerebrospinal fluid characteristics. CONCLUSIONS: Our data indicated that EV-B types mainly cause severe infection in infants aged 0-3 months. Therefore, knowledge about EV-B types could have implications in designing effective intervention and prevention strategies for young infants with severe EV infection.
Assuntos
Infecções por Enterovirus , Enterovirus , Parechovirus , Infecções por Picornaviridae , Humanos , Lactente , Enterovirus/genética , Enterovirus Humano B , Infecções por Enterovirus/epidemiologia , Parechovirus/genética , Estudos RetrospectivosRESUMO
BACKGROUND: Patients with cognitive dysfunction may present with significantly prolonged the P2 wave latency of flash visual evoked potential. However, no studies have been reported on whether the P2 wave latency of flash visual evoked potential is prolonged in patients with subcortical arteriosclerotic encephalopathy (SAE). OBJECTIVE: To examine the relationship between flash visual evoked potential P2 wave latency (FVEP-P2 wave latency) and cognitive impairment in patients with SAE. METHODS: Overall, we recruited 38 SAE patients as the observation cohort (OC) and 34 healthy volunteers as the control cohort (CC). We measured the FVEP-P2 wave latency for both groups. The SAE patients' cognitive abilities were evaluated via mini-mental state examination (MMSE) and the association between the latency of FVEP-P2 and MMSE score was explored by Pearsons´s correlation test. RESULTS: There is no significant difference between OC (21 males and 17 females; 68.6 ± 6.7 years of age and 9.6 ± 2.8 years of education) and CC (19 males and 15 females; 65.3 ± 5.9 years of age and 10.1 ± 2.6 years of education) in gender and age composition and education level. The FVEP-P2 wave latency of the CC group was (108.80 ± 16.70) ms and the OC FVEP-P2 wave latency was (152.31 ± 20.70) ms. The OC FVEP-P2 wave latency was significantly longer than the CC (P < 0.05). In terms of MMSE scores, the MMSE scores of CC was (28.41 ± 2.34), and that of OC was (9.08 ± 4.39). Compared to the CC, the OC MMSE score was significantly lower (P < 0.05). In addition, the FVEP-P2 wave latency was inversely related to the MMSE (r = -0.4465, P < 0.05) in SAE patients. CONCLUSION: The FVEP-P2 wave latency wave latency was significantly prolonged in SAE patients and strongly associated with the degree of cognitive dysfunction.
Assuntos
Disfunção Cognitiva , Demência Vascular , Masculino , Feminino , Humanos , Potenciais Evocados Visuais , Disfunção Cognitiva/diagnóstico , Cognição , EscolaridadeRESUMO
In response to climate change, China is making great efforts to increase the green area for carbon sequestration. Road verges, as marginal land with favorable conditions for plant growth and ease of transportation, can be used for biomass production, but the biomass production and carbon sequestration potential have not been assessed. Here, we mapped the biomass production potential of road verges in China by combining a biomass model and Geographic Information System and then evaluated the effect of road runoff and CO2 fertilization on the production according to the runoff coefficient and vehicle emission inventory. Nationwide, road verges can produce 15.86 Mt C yr-1 of biomass. Road runoff contributes to a biomass production of 1.26 Mt C yr-1 through increasing soil water availability, which mainly occurs in arid regions. The CO2 fertilization effect by vehicle emission is considerable in Eastern and Southern China, contributing to a production of 0.09 Mt C yr-1. Life cycle assessment shows that major road verges in China have a carbon sequestration potential of 6.87 Mt C yr-1 currently. Our results revealed that road verges can make a significant contribution to carbon neutrality under proper management.
Assuntos
Dióxido de Carbono , Sequestro de Carbono , Biomassa , Emissões de Veículos , ChinaRESUMO
Non-coding RNAs are gaining prominence in biology and medicine, as they play major roles in cellular homeostasis among which the circRNA-miRNA-mRNA axes are involved in a series of disease-related pathways, such as apoptosis, cell invasion and metastasis. Recently, many computational methods have been developed for the prediction of the relationship between ncRNAs and diseases, which can alleviate the time-consuming and labor-intensive exploration involved with biological experiments. However, these methods handle ncRNAs separately, ignoring the impact of the interactions among ncRNAs on the diseases. In this paper we present a novel approach to discovering disease-related circRNA-miRNA-mRNA axes from the disease-RNA information network. Our method, using graph convolutional network, learns the characteristic representation of each biological entity by propagating and aggregating local neighbor information based on the global structure of the network. The approach is evaluated using the real-world datasets and the results show that it outperforms other state-of-the-art baselines on most of the metrics.
Assuntos
MicroRNAs , Neoplasias , Biologia Computacional/métodos , Humanos , MicroRNAs/genética , RNA Circular/genética , RNA Mensageiro/genéticaRESUMO
Childhood adversities have a well-established dose-response relationship with later mental health. However, less attention has been given to intergenerational influences. Further, it is unknown how intergenerational influences intersect with children's developmental stages and gender. The current study examined whether a developmental inflection point exists when the intergenerational influences of childhood adversities gain salience and explored differences by children's gender. Data were from the Young Women and Child Development Study (n = 361). Time-varying effect models (TVEMs) and moderation TVEMs by child's gender were evaluated. Our findings reveal that ages 5-8, the period of transition into primary schools, may represent a developmental inflection point when the intergenerational influences of maternal childhood adversity start emerging substantially. The results from gender interaction TVEMs reveal that maternal childhood adversity was a statistically significant predictor of internalizing problems until age 11, regardless of child's gender, and remained statistically significant for girls' internalizing problems until age 16.7. For externalizing problems, maternal childhood adversity was a statistically significant predictor until age 13, regardless of gender.