RESUMO
When exposed to pathogen infection or ultraviolet (UV) radiation, grapevine (Vitis vinifera) plants rapidly accumulate the stilbenoid resveratrol (Res) with concomitant increase of stilbene synthase (STS), the key enzyme in stilbene biosynthesis. Although a few transcription factors have been shown to regulate STSs, the molecular mechanism governing the regulation of STSs is not well elucidated. Our previous work showed that a VvMYB14-VvWRKY8 regulatory loop fine-tunes stilbene biosynthesis in grapevine through protein-protein interaction; overexpression of VvWRKY8 down-regulates VvMYB14 and VvSTS15/21; and application of exogenous Res up-regulates WRKY8 expression. Here, we identified an R2R3-MYB repressor, VvMYB30, which competes with the activator VvMYB14 for binding to the common binding sites in the VvSTS15/21 promoter. Similar to VvMYB14, VvMYB30 physically interacts with VvWRKY8 through their N-termini, forming a complex that does not bind DNA. Exposure to UV-B/C stress induces VvMYB14, VvWRKY8, and VvSTS15/21, but represses VvMYB30 in grapevine leaves. In addition, MYB30 expression is up-regulated by VvWRKY8-overexpression or exogenous Res. These findings suggest that the VvMYB14-VvWRKY8-VvMYB30 regulatory circuit allows grapevine to respond to UV stress by producing Res and prevents over-accumulation of Res to balance metabolic costs. Our work highlights the stress-mediated induction and feedback inhibition of stilbene biosynthesis through a complex regulatory network involving multiple positive and negative transcriptional regulators.
Assuntos
Estilbenos , Vitis , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas , Regiões Promotoras Genéticas/genética , Aciltransferases/genética , Aciltransferases/metabolismo , Vitis/genética , Vitis/metabolismo , Estilbenos/metabolismo , Resveratrol/metabolismoRESUMO
The phosphoinositide 3-kinase (PI3K)-Akt axis is one of the most frequently activated pathways and is demonstrated as a therapeutic target in Kirsten rat sarcoma viral oncogene homolog (KRAS)-mutated colorectal cancer (CRC). Targeting the PI3K-Akt pathway has been a challenging undertaking through the decades. Here we unveiled an essential role of E3 ligase SMAD ubiquitylation regulatory factor 1 (Smurf1)-mediated phosphoinositide-dependent protein kinase 1 (PDK1) neddylation in PI3K-Akt signaling and tumorigenesis. Upon growth factor stimulation, Smurf1 immediately triggers PDK1 neddylation and the poly-neural precursor cell expressed developmentally downregulated protein 8 (poly-Nedd8) chains recruit methyltransferase SET domain bifurcated histone lysine methyltransferase 1 (SETDB1). The cytoplasmic complex of PDK1 assembled with Smurf1 and SETDB1 (cCOMPASS) consisting of PDK1, Smurf1 and SETDB1 directs Akt membrane attachment and T308 phosphorylation. Smurf1 deficiency dramatically reduces CRC tumorigenesis in a genetic mouse model. Furthermore, we developed a highly selective Smurf1 degrader, Smurf1-antagonizing repressor of tumor 1, which exhibits efficient PDK1-Akt blockade and potent tumor suppression alone or combined with PDK1 inhibitor in KRAS-mutated CRC. The findings presented here unveil previously unrecognized roles of PDK1 neddylation and offer a potential strategy for targeting the PI3K-Akt pathway and KRAS mutant cancer therapy.
RESUMO
MOTIVATION: Effective identification of cell types is of critical importance in single-cell RNA-sequencing (scRNA-seq) data analysis. To date, many supervised machine learning-based predictors have been implemented to identify cell types from scRNA-seq datasets. Despite the technical advances of these state-of-the-art tools, most existing predictors were single classifiers, of which the performances can still be significantly improved. It is therefore highly desirable to employ the ensemble learning strategy to develop more accurate computational models for robust and comprehensive identification of cell types on scRNA-seq datasets. RESULTS: We propose a two-layer stacking model, termed CTISL (Cell Type Identification by Stacking ensemble Learning), which integrates multiple classifiers to identify cell types. In the first layer, given a reference scRNA-seq dataset with known cell types, CTISL dynamically combines multiple cell-type-specific classifiers (i.e. support-vector machine and logistic regression) as the base learners to deliver the outcomes for the input of a meta-classifier in the second layer. We conducted a total of 24 benchmarking experiments on 17 human and mouse scRNA-seq datasets to evaluate and compare the prediction performance of CTISL and other state-of-the-art predictors. The experiment results demonstrate that CTISL achieves superior or competitive performance compared to these state-of-the-art approaches. We anticipate that CTISL can serve as a useful and reliable tool for cost-effective identification of cell types from scRNA-seq datasets. AVAILABILITY AND IMPLEMENTATION: The webserver and source code are freely available at http://bigdata.biocie.cn/CTISLweb/home and https://zenodo.org/records/10568906, respectively.
Assuntos
Análise de Célula Única , Análise da Expressão Gênica de Célula Única , Animais , Humanos , Camundongos , Análise de Sequência de RNA/métodos , Análise de Célula Única/métodos , Software , Aprendizado de Máquina Supervisionado , Perfilação da Expressão Gênica/métodos , Análise por ConglomeradosRESUMO
Colorectal cancer (CRC) is the most prevalent malignancy of the digestive system. Glucose metabolism plays a crucial role in CRC development. However, the heterogeneity of glucose metabolic patterns in CRC is not well characterized. Here, we classified CRC into specific glucose metabolic subtypes and identified the key regulators. 2228 carbohydrate metabolism-related genes were screened out from the GeneCards database, 202 of them were identified as prognosis genes in the TCGA database. Based on the expression patterns of the 202 genes, three metabolic subtypes were obtained by the non-negative matrix factorization clustering method. The C1 subtype had the worst survival outcome and was characterized with higher immune cell infiltration and more activation in extracellular matrix pathways than the other two subtypes. The C2 subtype was the most prevalent in CRC and was characterized by low immune cell infiltration. The C3 subtype had the smallest number of individuals and had a better prognosis, with higher levels of NRF2 and TP53 pathway expression. Secreted frizzled-related protein 2 (SFRP2) and thrombospondin-2 (THBS2) were confirmed as biomarkers for the C1 subtype. Their expression levels were elevated in high glucose condition, while their knockdown inhibited migration and invasion of HCT 116 cells. The analysis of therapeutic potential found that the C1 subtype was more sensitive to immune and PI3K-Akt pathway inhibitors than the other subtypes. To sum up, this study revealed a novel glucose-related CRC subtype, characterized by SFRP2 and THBS2, with poor prognosis but possible therapeutic benefits from immune and targeted therapies.
Assuntos
Neoplasias Colorretais , Regulação Neoplásica da Expressão Gênica , Glucose , Transcriptoma , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Glucose/metabolismo , Transcriptoma/genética , Prognóstico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Trombospondinas/genética , Trombospondinas/metabolismo , Movimento Celular/genética , Perfilação da Expressão Gênica , Células HCT116 , Transdução de Sinais , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismoRESUMO
BACKGROUND: The liver function reserve has a significant impact on the therapeutic effects of anti-programmed cell death-1 (PD-1) for hepatocellular carcinoma (HCC). This study aimed to comprehensively evaluate the ability of liver-function-based indicators to predict prognosis and construct a novel prognostic score for HCC patients with anti-PD-1 immunotherapy. METHODS: Between July 2018 and January 2020, patients diagnosed with HCC who received anti-PD-1 treatment were screened for inclusion in the study. The valuable prognostic liver-function-based indicators were selected using Cox proportional hazards regression analysis to build a novel liver-function-indicators-based signature (LFIS). Concordance index (C-index), the area under the receiver operating characteristic (ROC) curve (AUC), and Kaplan-Meier survival curves were utilized to access the predictive performance of LFIS. RESULTS: A total of 434 HCC patients who received anti-PD-1 treatment were included in the study. The LFIS, based on alkaline phosphatase-to-albumin ratio index, Child-Pugh score, platelet-albumin score, aspartate aminotransferase-to-lymphocyte ratio index, and gamma-glutamyl transpeptidase-to-lymphocyte ratio index, was constructed and identified as an independent risk factor for patient survival. The C-index of LFIS for overall survival (OS) was 0.692, which was higher than the other single liver-function-based indicator. The AUC of LFIS at 6-, 12-, 18-, and 24-month were 0.74, 0.714, 0.747, and 0.865 for OS, respectively. Patients in the higher-risk LFIS group were associated with both worse OS and PFS. An online and easy-to-use calculator was further constructed for better application of the LFIS signature. CONCLUSION: The LFIS score had an excellent prognosis prediction ability superior to every single liver-function-based indicator for anti-PD-1 treatment in HCC patients. It is a reliable, easy-to-use tool to stratify risk for OS and PFS in HCC patients who received anti-PD-1 treatment.
Assuntos
Carcinoma Hepatocelular , Inibidores de Checkpoint Imunológico , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/mortalidade , Masculino , Feminino , Prognóstico , Pessoa de Meia-Idade , Inibidores de Checkpoint Imunológico/uso terapêutico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Idoso , Testes de Função Hepática/métodos , Estudos Retrospectivos , Taxa de Sobrevida , Fígado/patologia , Imunoterapia/métodos , Biomarcadores Tumorais , AdultoRESUMO
BACKGROUND: Growing evidence demonstrates that the synergistic interaction of far-red light with shorter wavelength lights could evidently improve the photosynthesis efficiency of multiple species. However, whether/how far-red light affects sink organs and consequently modulates the sourceâsink relationships are largely unknown. RESULTS: Here, equal intensities of white and far-red lights were added to natural light for grape plantlets to investigate the effects of far-red light supplementation on grapevine growth and carbon assimilate allocation, as well as to reveal the underlying mechanisms, through physiological and transcriptomic analysis. The results showed that additional far-red light increased stem length and carbohydrate contents in multiple organs and decreased leaf area, specific leaf weight and dry weight of leaves in comparison with their counterparts grown under white light. Compared to white light, the maximum net photosynthetic rate of the leaves was increased by 31.72% by far-red light supplementation, indicating that far-red light indeed elevated the photosynthesis efficiency of grapes. Transcriptome analysis revealed that leaves were most responsive to far-red light, followed by sink organs, including stems and roots. Genes related to light signaling and carbon metabolites were tightly correlated with variations in the aforementioned physiological traits. In particular, VvLHCB1 is involved in light harvesting and restoring the balance of photosystem I and photosystem II excitation, and VvCOP1 and VvPIF3, which regulate light signal transduction, were upregulated under far-red conditions. In addition, the transcript abundances of the sugar transporter-encoding genes VvSWEET1 and VvSWEET3 and the carbon metabolite-encoding genes VvG6PD, VvSUS7 and VvPGAM varied in line with the change in sugar content. CONCLUSIONS: This study showed that far-red light synergistically functioning with white light has a beneficial effect on grape photosystem activity and is able to differentially affect the growth of sink organs, providing evidence for the possible addition of far-red light to the wavelength range of photosynthetically active radiation (PAR).
Assuntos
Clorofila , Luz Vermelha , Clorofila/metabolismo , Transcriptoma , Fotossíntese , Açúcares , CarbonoRESUMO
Grapevine (Vitis ssp.) is a deciduous perennial fruit crop, and the canes and buds of grapevine should withstand low temperatures (LTs) annually during winter. However, the widely cultivated Vitis vinifera is cold-sensitive and cannot survive the severe winter in regions with extremely LTs, such as viticulture regions in northern China. By contrast, a few wild Vitis species like V. amurensis and V. riparia exhibit excellent freezing tolerance. However, the mechanisms underlying grapevine cold tolerance remain largely unknown. In recent years, much progress has been made in elucidating the mechanisms, owing to the advances in sequencing and molecular biotechnology. Assembly of grapevine genomes together with resequencing and transcriptome data enable researchers to conduct genomic and transcriptomic analyses in various grapevine genotypes and populations to explore genetic variations involved in cold tolerance. In addition, a number of pivotal genes have been identified and functionally characterized. In this review, we summarize recent major advances in physiological and molecular analyses of cold tolerance in grapevine and put forward questions in this field. We also discuss the strategies for improving the tolerance of grapevine to cold stress. Understanding grapevine cold tolerance will facilitate the development of grapevines for adaption to global climate change.
Assuntos
Resposta ao Choque Frio , Vitis , Transcriptoma , Genômica , Perfilação da Expressão Gênica , Análise de Sequência de DNA , Vitis/fisiologia , Temperatura BaixaRESUMO
High-altitude pulmonary hypertension (HAPH) is a severe and progressive disease that can lead to right heart failure. Intermittent short-duration reoxygenation at high altitude is effective in alleviating HAPH; however, the underlying mechanisms are unclear. In the present study, a simulated 5,000-m hypoxia rat model and hypoxic cultured pulmonary artery smooth muscle cells (PASMCs) were used to evaluate the effect and mechanisms of intermittent short-duration reoxygenation. The results showed that intermittent 3-h/per day reoxygenation (I3) effectively attenuated chronic hypoxia-induced pulmonary hypertension and reduced the content of H2O2 and the expression of NADPH oxidase 4 (NOX4) in lung tissues. In combination with I3, while the NOX inhibitor apocynin did not further alleviate HAPH, the mitochondrial antioxidant MitoQ did. Furthermore, in PASMCs, I3 attenuated hypoxia-induced PASMCs proliferation and reversed the activated HIF-1α/NOX4/PPAR-γ axis under hypoxia. Targeting this axis offset the protective effect of I3 on hypoxia-induced PASMCs proliferation. The present study is novel in revealing a new mechanism for preventing HAPH and provides insights into the optimization of intermittent short-duration reoxygenation.
Assuntos
Doença da Altitude , Hipertensão Pulmonar , Animais , Ratos , Altitude , Proliferação de Células , Células Cultivadas , Peróxido de Hidrogênio/metabolismo , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/prevenção & controle , Hipertensão Pulmonar/metabolismo , Hipóxia/metabolismo , Miócitos de Músculo Liso/metabolismo , NADPH Oxidase 4/genética , NADPH Oxidase 4/metabolismo , PPAR gama/metabolismo , Artéria Pulmonar/metabolismo , Transdução de SinaisRESUMO
This study bridges the knowledge gap pertaining to the pathways of heavy metal accumulation and migration within the industrial chain of large-scale cattle farms. Two such farms in Shaanxi serve as a basis for our exploration into Zn, Cu, Cr, Pb, As, and Cd dynamics. Employing material flow analysis complemented by predictive models, we evaluate the potential ecological risks of arable soil from heavy metal influx via manure application. Our findings indicate that Zn and Cu predominate the heavy metal export from these operations, composing up to 60.00%-95.67% of their total content. Predictive models based on 2021 data reveal a potential increase in Cd soil concentration by 0.08 mg/kg by 2035, insinuating a reduced safe usage period for cattle manure at less than 50 years. Conversely, projections from 2022 data point towards a gradual Cu rise in soil, reaching risk threshold levels after 126 years. These outcomes inform limitations in cattle manure utilisation strategies, underscoring Cu and Cd content as key barriers. The study underscores the criticality of continuous heavy metal surveillance within farm by products to ensure environmental protection and sustainable agricultural practices.
Assuntos
Fazendas , Esterco , Metais Pesados , Poluentes do Solo , Metais Pesados/análise , Animais , Esterco/análise , Bovinos , Medição de Risco , Poluentes do Solo/análise , Solo/química , Agricultura , Monitoramento AmbientalRESUMO
The mule is the interspecific hybrid of horse and donkey and has hybrid vigor in muscular endurance, disease resistance, and longevity over its parents. Here, we examined adult fibroblasts of mule (MAFs) compared with the cells from their parents (donkey adult fibroblasts and horse adult fibroblasts) (each species has repeated three independent individuals) in proliferation, apoptosis, and glycolysis and found significant differences. We subsequently derived mule, donkey, and horse doxycycline (Dox)-independent induced pluripotent stem cells (miPSCs, diPSCs, and hiPSCs) from three independent individuals of each species and found that the reprogramming efficiency of MAFs was significantly higher than that of cells of donkey and horse. miPSCs, diPSCs, and hiPSCs all expressed the high levels of crucial endogenous pluripotency genes such as POU class 5 homeobox 1 (POU5F1, OCT4), SRY-box 2 (SOX2), and Nanog homeobox (NANOG) and propagated robustly in single-cell passaging. miPSCs exhibited faster proliferation and higher pluripotency and differentiation than diPSCs and hiPSCs, which were reflected in co-cultures and separate-cultures, teratoma formation, and chimera contribution. The establishment of miPSCs provides a unique research material for the investigation of "heterosis" and perhaps is more significant to study hybrid gamete formation.
Assuntos
Células-Tronco Pluripotentes Induzidas , Cavalos , Animais , Reprogramação Celular , Equidae , Células Cultivadas , Diferenciação Celular/genética , Fibroblastos , Fator 3 de Transcrição de Octâmero/genéticaRESUMO
Studies have shown that the activation of the NOD-like receptor protein 3 (NLRP3) inflammasome is detrimental to the functional recovery of the sciatic nerve, but the regulatory mechanisms of the NLRP3 inflammasome in peripheral nerves are unclear. C-X-C motif chemokine 12 (CXCL12) can bind to C-X-C chemokine receptor type 4 (CXCR4) and participate in a wide range of nerve inflammation by regulating the NLRP3 inflammasome. Based on these, we explore whether CXCL12-CXCR4 axis regulates the NLRP3 inflammasome in the peripheral nerve. We found that CXCR4/CXCL12, NLRP3 inflammasome-related components, pyroptosis-related proteins and inflammatory factors in the sciatic nerve injured rats were markedly increased compared with the sham-operated group. AMD3100, a CXCR4 antagonist, reverses the activation of NLRP3 inflammasome, Schwann cell pyroptosis and sciatic nerve demyelination. We further treated rat Schwann cells with LPS (lipopolysaccharide) and adenosine triphosphate (ATP) to mimic the cellular inflammation model of sciatic nerve injury, and the results were consistent with those in vivo. In addition, both in vivo and in vitro experiments demonstrated that AMD3100 treatment reduced the phosphorylation of nuclear factor κB (NF-κB) and the expression of thioredoxin interacting protein (TXNIP), which contributes to activating NLRP3 inflammasome. Therefore, our findings suggest that, after sciatic nerve injury, CXCL12-CXCR4 axis may promote Schwann cell pyroptosis and sciatic nerve demyelination through activating NLRP3 inflammasome and slow the recovery process of the sciatic nerve.
Assuntos
Doenças Desmielinizantes , Inflamassomos , Ratos , Animais , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Piroptose , Proteínas NLR/metabolismo , Nervo Isquiático , Células de Schwann/metabolismo , Inflamação/metabolismo , Doenças Desmielinizantes/metabolismo , Proteínas de Ciclo Celular/metabolismo , Quimiocina CXCL12/metabolismoRESUMO
CD169, a specific marker for macrophages, is a member of the sialic acid-binding immunoglobulin-like lectin (Siglec) family which acts as an adhesion molecule implicated in cell-cell interaction via sialylated glycoconjugates. Although CD169+ macrophages have been found to participate in erythroblastic island (EBI) formation and support erythropoiesis under homeostasis and stress, the exact role of CD169 and its counter receptor in EBI remains unknown. Herein, we generated CD169-CreERT knock-in mice and investigated the function of CD169 in EBI formation and erythropoiesis using CD169-null mice. EBI formation was impaired in vitro by both blockade of CD169 using anti-CD169 antibody and deletion of CD169 on macrophages. Furthermore, CD43 expressed by early erythroblasts (EB) was identified as the counter receptor for CD169 in mediating the EBI formation via surface plasmon resonance and imaging flow cytometry. Interestingly, CD43 was proven to be a novel indicator of erythroid differentiation due to the progressive decrease of CD43 expression as EB mature. Although CD169-null mice did not display defects in bone marrow (BM) EBI formation in vivo, CD169 deficiency impeded BM erythroid differentiation probably via CD43 under stress erythropoiesis, in concert with the role of CD169 recombinant protein in hemin-induced K562 erythroid differentiation. These findings have shed light on the role of CD169 in EBI under steady and stress erythropoiesis through binding with its counter receptor CD43, suggesting that CD169-CD43 interaction might be a promising therapeutic target for erythroid disorders.
Assuntos
Medula Óssea , Eritroblastos , Animais , Camundongos , Eritroblastos/metabolismo , Medula Óssea/fisiologia , Eritropoese , Macrófagos/metabolismo , Diferenciação Celular , Camundongos KnockoutRESUMO
Objectives: To study trends of utilization, in-hospital outcomes, and short outcomes in patients undergoing transcatheter mitral valve repair (TMVR) vs. surgical mitral valve repair (SMVR) in atrial fibrillation (AF). Background: TMVR is a treatment option in inoperable or high-risk patients with mitral regurgitation (MR). AF is a common comorbidity of MR. Data comparing between TMVR and SMVR in MR patients with AF is lacking. Methods: The National Readmission Database from 2016 to 2019 was utilized to identify hospitalizations undergoing TMVR or SMVR with AF. Outcomes of interest included mortality, postoperative complications, length of stay, and 30-day readmission rate. Results: A total of 9,195 patients underwent TMVR and 16,972 patients underwent SMVR with AF; the number of AF undergoing TMVR was increasing from 1,342 in 2016 to 4,215 in 2019 and SMVR. The incidence of in-hospital mortality decreased from 2.6% in 2016 to 1.8% in 2019. We identified length of stay>5 days, dyslipidemia, cerebrovascular disease, heart failure with reduced ejection fraction, and urgent/emergent admissions as independent risk factors for in-hospital mortality. After matching, we included 4,680 patients in each group; the in-hospital death, transfusion, acute kidney injury, sepsis, stroke, and mechanical ventilation were lower in TMVR compared with SMVR. TMVR was associated with a similar rate of all-cause readmission at 30 days compared with SMVR. Conclusion: Patients with AF receiving TMVR have been increasing along with progressive improvement in in-hospital death and length of stay. Compared to SMVR, AF patients receiving TMVR had a lower rate of in-hospital death and postoperative complications.
Assuntos
Fibrilação Atrial , Implante de Prótese de Valva Cardíaca , Insuficiência da Valva Mitral , Humanos , Valva Mitral/cirurgia , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/cirurgia , Implante de Prótese de Valva Cardíaca/efeitos adversos , Mortalidade Hospitalar , Resultado do Tratamento , Complicações Pós-Operatórias/etiologia , Cateterismo Cardíaco/efeitos adversosRESUMO
Long-term accumulation of toxic heavy metals in the environment was a potential hidden danger. High energy consumption, complicated operation and low adsorption capacity were the disadvantages of most current adsorbents. This study used one-step modification of fly ash (FA) by low-temperature melting method with KOH as the activator to generate modified fly ash (KFA) with high adsorption capacity to remove heavy metals from aqueous solutions. Various characterization results revealed a destruction that occurred on the surface structure of adsorbent, 12 times increase in specific surface area, and metal ions were successfully adsorbed onto KFA surface. Furthermore, adsorption proceeded most favorably at pH of 5, the presence of ionic strength and co-existing cations significantly influenced the adsorption effects. The description of adsorption data was more suitable by pseudo-second-order kinetics and Langmuir isotherm models. And in single system at 25 °C, for Pb(II), Cu(II), and Cd (II), the qm were 337.41, 310.09 and 125.00 mg·g-1. However, in ternary system, the qm decreased for all three ions in the order Pb(II) > Cu(II) > Cd(II), which was different from the law in single system, and the Pb(II) adsorption was found to have a significant inhibited effect on adsorption of Cd(II) and Cu(II). The adsorption mechanisms including ion exchange, electrostatic attraction and complexation were revealed. And by exploring the bioaccessibility of absorbed heavy metals in four simulated digestive fluids, it was found that KFA could load heavy metal ions and enable their release in organisms and other aquatic environments, which provided the possibility for subsequent related studies. Therefore, KFA with low energy consumption and high adsorption capacity is equipped a prospective development space on removing heavy metals from wastewater.
Assuntos
Metais Pesados , Poluentes Químicos da Água , Cinza de Carvão , Cádmio/análise , Chumbo , Estudos Prospectivos , Poluentes Químicos da Água/análise , Metais Pesados/química , Íons , Adsorção , Cinética , Concentração de Íons de HidrogênioRESUMO
Metabolic dysfunction-associated fatty liver disease (MAFLD) is the main cause of chronic liver disease. Baicalin (Bai), a bioactive molecule found in Scutellaria baicalensis Georgi, possesses antioxidant and antiinflammatory properties. These activities suggest Bai could be a promising therapeutic agent against NAFLD; however, its specific effects and underlying mechanism are still not clear. This study aims to explore the effect of Bai to attenuate MAFLD and associated molecular mechanisms. Bai (50, 100 or 200 mg/kg) was orally administered to db/db mice with MAFLD for 4 weeks or db/m mice as the normal control. Bai markedly attenuated lipid accumulation, cirrhosis and hepatocytes apoptosis in the liver tissues of MAFLD mice, suggesting strong ability to attenuate MAFLD. Bai significantly reduced proinflammatory biomarkers and enhanced antioxidant enzymes, which appeared to be modulated by the upregulated p62-Keap1-Nrf2 signalling cascade; furthermore, cotreatment of Bai and all-trans-retinoic acid (Nrf2 inhibitor) demonstrated markedly weakened liver protective effects by Bai and its induced antioxidant and antiinflammatory responses. The present study supported the use of Bai in attenuating MAFLD as a promising therapeutic agent, and its strong mechanism of action in association with the upregulating the p62-keap1-Nrf2 pathway.
RESUMO
PURPOSE: To friendly predict a reference prognostic outcome for idiopathic sudden sensorineural hearing loss (ISSNHL) patients with or without anxiety, we identified independent prognostic factors and developed practical predictive tools without invasive tests. METHODS: Patients with ISSNHL in our center were enrolled from June 2013 to December 2018. Univariate and multivariate logistic regression analyses were performed to identify independent prognostic factors of the complete recovery and the overall recovery for ISSNHL, which were subsequently utilized to develop the web nomograms. The discrimination, calibration, and clinical benefit were used to evaluate the performance of nomograms for ISSNHL. RESULTS: 704 ISSNHL patients were finally enrolled in this study. Multivariate logistic regression analysis showed that age, time of onset, gender, affected ear, degree, and type of hearing loss were independent prognostic factors of complete recovery. Age, time of onset, affected ear, and type of hearing loss were independent prognostic factors of overall recovery. Web predictive nomograms were developed with excellent discrimination, calibration, and clinical value. CONCLUSION: Based on the patients' data with a considerable size, independent noninvasive prognostic factors of complete recovery and overall recovery of ISSNHL were identified. Integrating these prognostic factors without invasive tests, practical web predictive nomograms were developed. Using web nomograms, clinical doctors could provide reference data (the predicted recovery rate) for supporting prognostic consultation of ISSNHL patients, especially those with anxiety.
Assuntos
Surdez , Perda Auditiva Neurossensorial , Perda Auditiva Súbita , Humanos , Prognóstico , Estudos Retrospectivos , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Súbita/diagnósticoRESUMO
OBJECTIVE: Observational studies suggested that peripheral blood eosinophils were associated with the risk of nasal polyps. However, these studies did not confirm the causality. This study aims to apply Mendelian randomization (MR) method to comprehensively assess the potential causal association between peripheral blood eosinophils and nasal polyps. METHODS: Genetic instrumental variables were extracted from the largest available genome-wide association study (GWAS) of European participants, which were used to investigate the relationship between peripheral blood eosinophils and nasal polyps. The inverse variance weighted method, the MR Egger method, and the weighted median method were applied for this analysis. MR-Egger intercept tests, leave-one-out analyses, and funnel plots were performed for the sensitivity analysis. RESULTS: With the inverse variance weighted method, the MR analysis suggested that there was a significant difference between peripheral blood eosinophils and the risk of nasal polyps (ukb-a-97, OR 1.004, 95% CI 1.003-1.005, p < 0.001; ukb-a-541, OR 1.005, 95% CI 1.004-1.006, p < 0.001; ukb-b-7211, OR 1.004, 95% CI 1.003-1.005, p < 0.001; ukb-b-8425, OR 1.004, 95% CI 1.003-1.005, p < 0.001; finn-b-J10_NASALPOLYP, OR 3.089, 95% CI 2.537-3.761, p < 0.001). Consistent results were also proved by using the weighted median method and the MR Egger method. CONCLUSIONS: Our findings reveal the causal effect of peripheral blood eosinophils on the increased risk of nasal polyps.
Assuntos
Eosinófilos , Pólipos Nasais , Humanos , Pólipos Nasais/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Causalidade , Polimorfismo de Nucleotídeo ÚnicoRESUMO
A new damaged cable identification method using the basis vector matrix (BVM) is proposed to identify multiple damaged cables in cable-stayed bridges. The relationships between the cable tension stiffness and the girder bending strain of the cable-stayed bridge are established using a force method. The difference between the maximum bending strains of the bridges with intact and damaged cables is used to obtain the damage index vectors (DIXVs). Then, BVM is obtained by the normalized DIXV. Finally, the damage indicator vector (DIV) is obtained by DIXV and BVM to identify the damaged cables. The damage indicator is substituted into the damage severity function to identify the corresponding damage severity. A field cable-stayed bridge is used to verify the proposed method. The three-dimensional finite element model is established using ANSYS, and the model is validated using the field measurements. The validated model is used to simulate the strain response of the bridge with different damage scenarios subject to a moving vehicle load, including one, two, three, and four damaged cables with damage severity of 10%, 20%, and 30%, respectively. The noise effect is also discussed. The results show that the BVM method has good anti-noise capability and robustness.
RESUMO
In the field of human pose estimation, heatmap-based methods have emerged as the dominant approach, and numerous studies have achieved remarkable performance based on this technique. However, the inherent drawbacks of heatmaps lead to serious performance degradation in methods based on heatmaps for smaller-scale persons. While some researchers have attempted to tackle this issue by improving the performance of small-scale persons, their efforts have been hampered by the continued reliance on heatmap-based methods. To address this issue, this paper proposes the SSA Net, which aims to enhance the detection accuracy of small-scale persons as much as possible while maintaining a balanced perception of persons at other scales. SSA Net utilizes HRNetW48 as a feature extractor and leverages the TDAA module to enhance small-scale perception. Furthermore, it abandons heatmap-based methods and instead adopts coordinate vector regression to represent keypoints. Notably, SSA Net achieved an AP of 77.4% on the COCO Validation dataset, which is superior to other heatmap-based methods. Additionally, it achieved highly competitive results on the Tiny Validation and MPII datasets as well.
Assuntos
Conscientização , Postura , HumanosRESUMO
The challenges of point cloud registration in intelligent vehicle driving lie in the large scale, complex distribution, high noise, and strong sparsity of lidar point cloud data. This paper proposes an efficient registration algorithm for large-scale outdoor road scenes by selecting the continuous distribution of key area laser point clouds as the registration point cloud. The algorithm extracts feature descriptions of the key point cloud and introduces local geometric features of the point cloud to complete rough and fine registration under constraints of key point clouds and point cloud features. The algorithm is verified through extensive experiments under multiple scenarios, with an average registration time of 0.5831 s and an average accuracy of 0.06996 m, showing significant improvement compared to other algorithms. The algorithm is also validated through real-vehicle experiments, demonstrating strong versatility, reliability, and efficiency. This research has the potential to improve environment perception capabilities of autonomous vehicles by solving the point cloud registration problem in large outdoor scenes.