Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 317
Filtrar
1.
PeerJ ; 10: e13473, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35602894

RESUMO

Background: The genome map of hepatocellular carcinoma (HCC) is complex. In order to explore whether circulating tumor cell DNA (ctDNA) can be used as the basis for sequencing and use ctDNA to find tumor related biomarkers, we analyzed the mutant genes of ctDNA in patients with liver cancer by sequencing. Methods: We used next-generation targeted sequencing technology to identify mutations in patients with liver cancer. The ctDNA from 10 patients with hepatocellular carcinoma (including eight cases of primary hepatocellular carcinoma and two cases of secondary hepatocellular carcinoma) was sequenced. We used SAMtools to detect and screen single nucleotide polymorphisms (SNPs) and insertion deletion mutations (INDELs) and ANNOVAR to annotate the structure and function of the detected mutations. Screening of pathogenic and possible pathogenic genes was performed using American College of Medical Genetics and Genomics (ACMG) guidelines. GO analysis and KEGG analysis of pathogenic and possible pathogenic genes were performed using the DAVID database, and protein-protein interaction network analysis of pathogenic and possible pathogenic genes was performed using the STRING database. Then, the Kaplan-Meier plotter database, GEPIA database and HPA database were used to analyse the relationship between pathogenic and possible pathogenic genes and patients with liver cancer. Results: Targeted capture and deep sequencing of 560 cancer-related genes in 10 liver cancer ctDNA samples revealed 8,950 single nucleotide variation (SNV) mutations and 70 INDELS. The most commonly mutated gene was PDE4DIP, followed by SYNE1, KMT2C, PKHD1 and FN1. We compared these results to the COSMIC database and determined that ctDNA could be used for sequencing. According to the ACMG guidelines, we identified 54 pathogenic and possible pathogenic mutations in 39 genes in exons and splice regions of 10 HCC patients and performed GO analysis, KEGG analysis, and PPI network analysis. Through further analysis, four genes significantly related to the prognosis of liver cancer were identified. Conclusion: In this study, our findings indicate that ctDNA can be used for sequencing. Our results provide some molecular data for the mapping of genetic variation in Chinese patients with liver cancer, which enriches the understanding of HCC pathogenesis and provides new ideas for the diagnosis and prognosis of HCC patients.

2.
Materials (Basel) ; 15(7)2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-35407888

RESUMO

In this work, hydrogen-terminated diamond (H-diamond) metal-oxide-semiconductor field-effect-transistors (MOSFETs) on a heteroepitaxial diamond substrate with an Al2O3 dielectric and a passivation layer were characterized. The full-width at half maximum value of the diamond (004) X-ray rocking curve was 205.9 arcsec. The maximum output current density and transconductance of the MOSFET were 172 mA/mm and 10.4 mS/mm, respectively. The effect of a low-temperature annealing process on electrical properties was also investigated. After the annealing process in N2 atmosphere, the threshold voltage (Vth) and flat-band voltage (VFB) shifts to negative direction due to loss of negative charges. After annealing at 423 K for 3 min, the maximum value of hole field effective mobility (µeff) increases by 27% at Vth - VGS = 2 V. The results, which are not inferior to those based on homoepitaxial diamond, promote the application of heteroepitaxial diamond in the field of electronic devices.

3.
J Immunother Cancer ; 10(3)2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35347072

RESUMO

BACKGROUND: Immune checkpoint blockade (ICB) targeting programmed death ligand-1 (PD-L1)/programmed cell death protein-1 (PD-1) pathway has become an attractive strategy for cancer treatment; however, unsatisfactory efficacy has limited its clinical benefits. Therefore, a more comprehensive understanding of the regulation of PD-L1 expression is essential for developing more effective cancer immunotherapy. Recent studies have revealed the important roles of eukaryotic elongation factor 2 kinase (eEF2K) in promoting epithelial-mesenchymal transition (EMT), angiogenesis, tumor cell migration and invasion; nevertheless, the exact role of eEF2K in the regulation of tumor immune microenvironment (TIME) remains largely unknown. METHODS: In this study, we used a cohort of 38 patients with melanoma who received anti-PD-1 treatment to explore the association between eEF2K expression and immunotherapy efficacy against melanoma. Immunoprecipitation-mass spectrometry analysis and in vitro assays were used to examine the role and molecular mechanism of eEF2K in regulating PD-L1 expression. We also determined the effects of eEF2K on tumor growth and cytotoxicity of CD8+ T cells in TIME in a mouse melanoma model. We further investigated the efficacy of the eEF2K inhibition in combination with anti-PD-1 treatment in vivo. RESULTS: High eEF2K expression is correlated with better therapeutic response and longer survival in patients with melanoma treated with PD-1 monoclonal antibody (mAb). Moreover, eEF2K protein expression is positively correlated with PD-L1 protein expression. Mechanistically, eEF2K directly bound to and inactivated glycogen synthase kinase 3 beta (GSK3ß) by phosphorylating it at serine 9 (S9), leading to PD-L1 protein stabilization and upregulation, and subsequently tumor immune evasion. Knockdown of eEF2K decreased PD-L1 expression and enhanced CD8+ T cell activity, thus dramatically attenuating murine B16F10 melanoma growth in vivo. Clinically, p-GSK3ß/S9 expression is positively correlated with the expressions of eEF2K and PD-L1, and the response to anti-PD-1 immunotherapy. Furthermore, eEF2K inhibitor, NH125 treatment or eEF2K knockdown enhanced the efficacy of PD-1 mAb therapy in a melanoma mouse model. CONCLUSIONS: Our results suggest that eEF2K may serve as a biomarker for predicting therapeutic response and prognosis in patients receiving anti-PD-1 therapy, reveal a vital role of eEF2K in regulating TIME by controlling PD-L1 expression and provide a potential combination therapeutic strategy of eEF2K inhibition with ICB therapy.


Assuntos
Antígeno B7-H1 , Melanoma , Animais , Anticorpos Monoclonais/uso terapêutico , Linfócitos T CD8-Positivos/metabolismo , Quinase do Fator 2 de Elongação , Glicogênio Sintase Quinase 3 beta , Humanos , Melanoma/patologia , Camundongos , Receptor de Morte Celular Programada 1/uso terapêutico , Microambiente Tumoral
4.
Front Cardiovasc Med ; 9: 778027, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35252381

RESUMO

BACKGROUNDS: The presence of impaired global longitudinal strain (GLS) may be a valuable bio-marker in the early diagnosis for left ventricle (LV) impairment, which would help scrutinize asymptomatic aortic stenosis (AS) patients with high risk of adverse outcomes, such as major adverse cardiovascular events (MACE). METHODS: The study was prospectively registered in PROPSERO (CRD 42021223472). Databases, such as Pubmed, Embase, Cochrane Library, Web of science, and Scopus were searched for studies evaluating the impact of impaired GLS on MACE, all-cause mortality, and aortic valve replacement (AVR) in asymptomatic AS. Hazard ratios (HRs) with 95% CIs were calculated with meta-analysis for binary variants. Meta-regression, subgroup analysis, and sensitivity analyses were applied as needed to explore the heterogeneity. RESULTS: Eventually, a total of nine studies reporting 1,512 patients were enrolled. Compared with the normal GLS group, impaired GLS significantly increased MACE (HR = 1.20, 95% CI: 1.10-1.30, I 2 = 79%) with evident heterogeneity, all-cause mortality (HR = 1.42, 95% CI: 1.24-1.63), and AVR (HR = 1.17, 95% CI: 1.07-1.28). Subgroup analyses stratified by left ventricular ejection fraction (LVEF) > 50% or LVEF without precise cut-off point found that compared with the normal GLS group, impaired GLS remarkably increased MACE both in two subgroups (LVEF > 50%: HR: 1.22, 95% CI: 1.05-1.50; LVEF without cutpoint: HR: 1.25, 95% CI: 1.05-1.50). The results stratified by AS severity (mild/moderate and severe) or follow-up time resembled those stratified by LVEF. In addition, when subgroup analysis was stratified by mean aortic valve pressure gradient (MG ≥ 40 mm Hg and MG <40 mm Hg), compared with normal GLS, impaired GLS significantly increased MACE both in two subgroups (MG ≥ 40 mm Hg: HR: 3.41, 95% CI: 1.64-7.09; MG below 40 mm Hg: HR: 3.17, 95% CI: 1.87-5.38). Moreover, the effect sizes here were substantially higher than those in the former two stratified factors. CONCLUSIONS: The presence of impaired GLS substantially worsens the outcomes for adverse cardiovascular events in asymptomatic patients with AS regardless of LVEF or AS severity or follow-up time or mean aortic valve pressure gradient, which highlights the importance of incorporating impaired GLS into risk algorithms in asymptomatic AS. SYSTEMATIC REVIEW REGISTRATION: PROSPERO (registration number: CRD42021223472).

5.
Int J Comput Assist Radiol Surg ; 17(5): 857-865, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35294715

RESUMO

PURPOSE: Bronchoscopic intervention is a widely used clinical technique for pulmonary diseases, which requires an accurate and topological complete airway map for its localization and guidance. The airway map could be extracted from chest computed tomography (CT) scans automatically by airway segmentation methods. Due to the complex tree-like structure of the airway, preserving its topology completeness while maintaining the segmentation accuracy is a challenging task. METHODS: In this paper, a long-term slice propagation (LTSP) method is proposed for accurate airway segmentation from pathological CT scans. We also design a two-stage end-to-end segmentation framework utilizing the LTSP method in the decoding process. Stage 1 is used to generate a coarse feature map by an encoder-decoder architecture. Stage 2 is to adopt the proposed LTSP method for exploiting the continuity information and enhancing the weak airway features in the coarse feature map. The final segmentation result is predicted from the refined feature map. RESULTS: Extensive experiments were conducted to evaluate the performance of the proposed method on 70 clinical CT scans. The results demonstrate the considerable improvements of the proposed method compared to some state-of-the-art methods as most breakages are eliminated and more tiny bronchi are detected. The ablation studies further confirm the effectiveness of the constituents of the proposed method and the efficacy of the framework design. CONCLUSION: Slice continuity information is beneficial to accurate airway segmentation. Furthermore, by propagating the long-term slice feature, the airway topology connectivity is preserved with overall segmentation accuracy maintained.

6.
Am J Nephrol ; 53(2-3): 129-138, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35272286

RESUMO

INTRODUCTION: Anti-phospholipase A2 receptor antibody (PLA2R-Ab) is highly specific for primary membranous nephropathy (PMN). Here, we compare the diagnostic value of different circulating PLA2R-Ab cutoff titers in multicenter cohorts, with particular focus on determining the optimal cutoff value for Chinese patients. METHODS: In total, 288 patients with PMN and 301 with other nephropathies were recruited retrospectively from five hospitals in China between September 2011 and October 2018. PLA2R-Ab in serum obtained at renal biopsy was determined by enzyme-linked immunosorbent assay. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and receiver operating characteristic (ROC) curve of PLA2R-Ab in diagnosing PMN were assessed. Diagnostic efficiency was evaluated by internal validation. RESULTS: The sensitivity, specificity, PPV, NPV, and Youden index for PMN diagnosis were 71%, 90%, 88%, 75%, and 0.61 at the cutoff of 3.8 RU/mL; 74%, 86%, 84%, 76%, and 0.60 at 2.7 RU/mL; 68%, 92%, 90%, 73%, and 0.60 at 5.2 RU/mL; 64%, 95%, 93%, 72%, and 0.59 at 9.0 RU/mL; 57%, 96%, 94%, 68%, and 0.54 at 14.0 RU/mL; 51%, 97%, 95%, 66%, and 0.49 at 20.0 RU/mL; 47%, 98%, 96%, 64%, and 0.45 at 40.0 RU/mL, respectively. The area under the ROC curve was 0.83. CONCLUSION: By comprehensively considering specificity and sensitivity, we show that 3.8 RU/mL is the optimal cutoff of PLA2R-Ab in Chinese PMN patients, with a sensitivity of 71% and a specificity of 90%. The cutoff values were 5.2 RU/mL and 9.0 RU/mL when the diagnostic specificity was increased to 92% and 95%, respectively.


Assuntos
Glomerulonefrite Membranosa , Autoanticorpos , Ensaio de Imunoadsorção Enzimática , Humanos , Curva ROC , Receptores da Fosfolipase A2 , Estudos Retrospectivos
7.
Structure ; 30(5): 685-696.e5, 2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35247327

RESUMO

Serine beta-lactamase-like protein (LACTB) is a mammalian mitochondrial serine protease that can specifically hydrolyze peptide bonds adjacent to aspartic acid residues and is structurally related to prokaryotic penicillin-binding proteins. Here, we determined the cryoelectron microscopy structures of human LACTB (hLACTB) filaments from wild-type protein, a middle region deletion mutant, and in complex with the inhibitor Z-AAD-CMK at 3.0-, 3.1-, and 2.8-Å resolution, respectively. Structural analysis and activity assays revealed that three interfaces are required for the assembly of hLACTB filaments and that the formation of higher order helical structures facilitates its cleavage activity. Further structural and enzymatic analyses of middle region deletion constructs indicated that, while this region is necessary for substrate hydrolysis, it is not required for filament formation. Moreover, the inhibitor-bound structure showed that hLACTB may cleave peptide bonds adjacent to aspartic acid residues. These findings provide the structural basis underlying hLACTB catalytic activity.


Assuntos
Serina , beta-Lactamases , Animais , Ácido Aspártico/metabolismo , Microscopia Crioeletrônica , Humanos , Mamíferos/metabolismo , Proteínas de Membrana/metabolismo , Proteínas Mitocondriais/metabolismo , Peptídeos , Serina/química , beta-Lactamases/genética , beta-Lactamases/metabolismo
8.
Front Immunol ; 13: 806877, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35273597

RESUMO

The presence of infiltrating CD8+ T lymphocytes in the tumor microenvironment of lung adenocarcinoma (LUAD) is correlated with improved patient prognosis, but underlying regulatory mechanisms remain unknown. To identify biomarkers to improve early diagnosis and treatment of LUAD, we downloaded 13 immune cell line-associated datasets from the GEO database. We identified CD8+ T cell-associated genes via weighted correlation network analysis. We constructed molecular subtypes based on CD8+ T cell-associated genes and constructed a multi-gene signature. We identified 252 CD8+ T cell-associated genes significantly enriched in immune function-related pathways and two molecular subtypes of LUAD (immune cluster 1 [IC1] and IC2) using our CD8+ T cell-associated gene signature. Patients with the IC2 subtype had a higher tumor mutation burden and lower immune infiltration scores, whereas those with the IC1 subtype were more sensitive to immune checkpoint inhibitors. Prioritizing the top candidate genes to construct a 10-gene signature, we validated our model using independent GSE and TCGA datasets to confirm its robustness and stable prognostic ability. Our risk model demonstrated good predictive efficacy using the Imvigor210 immunotherapy dataset. Thus, we established a novel and robust CD8+ T cell-associated gene signature, which could help assess prognostic risk and immunotherapy response in LUAD patients.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/terapia , Biomarcadores Tumorais/genética , Linfócitos T CD8-Positivos/patologia , Humanos , Imunoterapia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Prognóstico , Microambiente Tumoral/genética
9.
Artigo em Inglês | MEDLINE | ID: mdl-35274203

RESUMO

Runoff forecasting is essential for the reasonable use of regional water resources, flood prevention, and mitigation, as well as the development of ecological civilization. Runoff is influenced by the intersection of many factors, and the change process is extremely complex, showing significant stochasticity, nonlinearity, and heterogeneity, making traditional prediction models less adaptable. The Hodrick-Prescott filter (HP filter) is a well-established signal separation method. The traditional GM(1,1) model is capable of portraying the growth trend of the time series but cannot capture the periodic characteristics of the time series. Therefore, a novel coupled prediction model-HPF-GM(1,1) model is proposed in this study and applied to the runoff prediction of the Zhuzhou section of Xiangjiang River in Hunan Province. This model enables to separate seasonal factors from non-seasonal factors in the runoff time series, and introduce seasonal factors based on the traditional GM(1,1) model, which solves the challenge that the traditional GM(1,1) model is unable to predict seasonal time series. The results show that the HPF-GM(1,1) model has a mean relative error of 4.82%, a root mean square error of 7.44, and a Nash efficiency coefficient of 0.93, which is better than the traditional GM(1,1) model, the DGGM(1,1) model and the SGM(1,1) model of prediction accuracy. Obviously, the HP filter provides a new approach to data pre-processing of runoff series and the proposed HPF-GM(1,1)-coupled model extends new ideas for nonlinear runoff prediction.

10.
Vaccines (Basel) ; 10(3)2022 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-35335037

RESUMO

COVID-19 is still prevalent around the globe. Although some SARS-CoV-2 vaccines have been distributed to the population, the shortcomings of vaccines and the continuous emergence of SARS-CoV-2 mutant virus strains are a cause for concern. Thus, it is vital to continue to improve vaccines and vaccine delivery methods. One option is nasal vaccination, which is more convenient than injections and does not require a syringe. Additionally, stronger mucosal immunity is produced under nasal vaccination. The easy accessibility of the intranasal route is more advantageous than injection in the context of the COVID-19 pandemic. Nanoparticles have been proven to be suitable delivery vehicles and adjuvants, and different NPs have different advantages. The shortcomings of the SARS-CoV-2 vaccine may be compensated by selecting or modifying different nanoparticles. It travels along the digestive tract to the intestine, where it is presented by GALT, tissue-resident immune cells, and gastrointestinal lymph nodes. Nasal nanovaccines are easy to use, safe, multifunctional, and can be distributed quickly, demonstrating strong prospects as a vaccination method for SARS-CoV-2, SARS-CoV-2 variants, or SARS-CoV-n.

11.
Magn Reson Imaging ; 89: 12-23, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35124179

RESUMO

Dynamic cardiac magnetic resonance imaging (CMRI) is an important tool for the non-invasive assessment of cardiovascular disease. However, dynamic CMRI suffers from long acquisition times due to the need of obtaining images with high temporal and spatial resolution, whole-heart coverage. Conventionally, a multidimensional dataset in dynamic CMRI is treated as a series of two-dimensional matrices, and then various matrix/vector transforms are used to explore the sparsity of MR images. In this paper, we propose a low-rank tensor coding (LRTC) model with tensor sparsity for the application of compressive sensing (CS) in dynamic CMRI. In this framework, each group of 3D similar patches extracted from high-dimensional images is considered to be a low-rank tensor. LRTC can better capture the sparse part of dynamic CMRI and make full use of the redundancy between the feature vectors of adjacent positions. ADMM technique is introduced to tackle the proposed model, where soft threshold operator is used to solving the l1 norm relaxation. Higher-order singular value decomposition (HOSVD) is exploited to process high-dimensional tensors and mine correlations in space-time dimensions. Validations based on cardiac cine and myocardial perfusion datasets indicate that the proposed method achieved comparable reconstruction accuracy with the low-rank matrix recovery methods, and outperformed the conventional sparse recovery methods.


Assuntos
Algoritmos , Compressão de Dados , Coração/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Radiografia
12.
J Hematol Oncol ; 15(1): 16, 2022 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-35135567

RESUMO

The neoadjuvant and adjuvant anti-PD-1/PD-L1 treatment has been increasingly noticed. To summarize the global landscape of these clinical trials will provide essential data for all the stakeholders of drug development. Based on the Trialtrove database, a total of 668 clinical trials initiated by the end of 2020 were retrospectively analyzed. We found that a rising capability of global neoadjuvant and adjuvant anti-PD-1/PD-L1 clinical development has been achieved. High prevalent cancer types were extensively studied though the priorities in China and the United States were different. However, a lack of phase III trials and industry-sponsored trials was addressed. The confirmatory neoadjuvant trials were particularly insufficient, and the combination strategy mainly focused on chemotherapy. Thus, more public funding and accelerated regulatory strategies are needed in this field. Efforts should be made to confirm the benefit of neoadjuvant treatment and explore novel combination strategies.


Assuntos
Terapia Neoadjuvante , Neoplasias , Antígeno B7-H1 , Quimioterapia Adjuvante , China , Humanos , Neoplasias/tratamento farmacológico , Estudos Retrospectivos , Estados Unidos
13.
J Exp Clin Cancer Res ; 41(1): 67, 2022 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-35180863

RESUMO

BACKGROUND: Epidemiological studies have confirmed that abnormal circadian rhythms are associated with tumorigenesis in breast cancer. However, few studies have investigated the pathological roles of rhythm genes in breast cancer progression. In this study, we aimed to evaluate the aberrant expression of 32 rhythm genes in breast cancer and detect the pathological roles and molecular mechanisms of the altered rhythm gene in regulating the progression of triple negative breast cancer (TNBC). METHODS: The aberrant expression of rhythm genes in breast cancer was screened by searching the GEPIA database and validated by using qRT-PCR and immunohistochemistry staining. Bioinformatics analysis combined with luciferase reporter experiment and chromatinimmunopercitation (ChIP) were used to investigate the molecular mechanism about aberrant expression of identified rhythm gene in breast cancer. The pathological roles of identified rhythm gene in TNBC progression was evaluated by colony formation assay, wound healing experiment, transwell assay, subcutaneous tumor formation and the mouse tail vein injection model through gain-of-function and loss-of-function strategies respectively. mRNA array, bioinformatics analysis, luciferase reporter experiment, ChIP and immunoflurescence assay were employed to investigate the key molecules and signaling pathways by which the identified rhythm gene regulating TNBC progression. RESULTS: We identified that nuclear factor interleukin 3 regulated (NFIL3) expression is significantly altered in TNBC compared with both normal breast tissues and other subtypes of breast cancer. We found that NFIL3 inhibits its own transcription, and thus, downregulated NFIL3 mRNA indicates high expression of NFIL3 protein in breast cancer. We demonstrated that NFIL3 promotes the proliferation and metastasis of TNBC cells in vitro and in vivo, and higher expression of NFIL3 is associated with poor prognosis of patients with TNBC. We further demonstrated that NFIL3 enhances the activity of NF-κB signaling. Mechanistically, we revealed that NFIL3 directly suppresses the transcription of NFKBIA, which blocks the activation of NF-κB and inhibits the progression of TNBC cells in vitro and in vivo. Moreover, we showed that enhancing NF-κB activity by repressing NFKBIA largely mimics the oncogenic effect of NFIL3 in TNBC, and anti-inflammatory strategies targeting NF-κB activity block the oncogenic roles of NFIL3 in TNBC. CONCLUSION: NFIL3 promotes the progression of TNBC by suppressing NFKBIA transcription and then enhancing NF-κB signaling-mediated cancer-associated inflammation. This study may provide a new target for TNBC prevention and therapy.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Inibidor de NF-kappaB alfa/metabolismo , Neoplasias de Mama Triplo Negativas/genética , Animais , Linhagem Celular Tumoral , Proliferação de Células , Progressão da Doença , Regulação para Baixo , Feminino , Humanos , Imuno-Histoquímica , Camundongos , Camundongos Nus , Transdução de Sinais
14.
Sci Rep ; 12(1): 2779, 2022 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-35177763

RESUMO

Urbanization and human activities have exerted a tremendous adverse influence on the water quality of the Licun River, Qingdao, China. In order to restore the water quality, a succession of measures have been carried out since 1996, mainly encompassing flood controlling, sewage intercepting and watercourse greening (before 2007), watercourse and point source control based on administrative region (2008-2017), as well as the comprehensive governance based on river basin (after 2018). In 2019, the amount of discharged industrial wastewater, chemical oxygen demand, and ammonia nitrogen decreased by 53.91%, 87.75% and 89.88%, respectively, compared with 2000. Such results indicate that continuous governance has achieved a quantitative effect, and that industrial discharge is not the main pollution source. In the present work, the Spearman rank correlation coefficient and river comprehensive pollution index methods were used to analyze the change trend of main pollutants. The water quality was improved continuously, and the reduction of total phosphorus and ammonia nitrogen was the key to upgrading water quality. Afterward, the emission of pollution sources was accounted for from viewpoints of the point source, non-point source and sludge. Finally, suggestions were put forward to improve the water quality of the Licun River and provide some reference for the urban river management in northern China.

15.
J Hazard Mater ; 430: 128416, 2022 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-35149503

RESUMO

In this work, activated carbon treated in N2 atmosphere, as a non-metallic catalyst, exhibits excellent catalytic performance in reduction of Cr (VI) to Cr (III) using HCOOH as the reducing agent at room temperature. A series of characterizations and control experiments were carried out to deduce the possible reaction mechanism. The results showed that the improved catalytic performance can be attributed to the enhanced graphitization degree and basic sites such as pyrone-like, which favor electron transferring and activation of reactant. The reaction rate constant observed herein for the C-800 was 22 and 6 times more than that for C-0 and Pd/C catalyst, respectively. In addition, C-800 showed good recycle performance, and no loss of activity was observed after 5 cycles. This study broadens the application of nonmetallic catalyst and provides an easy-available and cost-effective catalytic material for removing toxic Cr (VI).

16.
J Alzheimers Dis ; 86(1): 297-313, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35068466

RESUMO

BACKGROUND: Dendrobium nobile Lindl. alkaloids (DNLA) are effective in ameliorating cognitive deficit in SAMP8, AßPP/PS1, and LPS-induced AD animal models, and prevented Aß-induced synaptic degeneration in cultured hippocampal neurons. However, the underlying mechanisms remain unexplored. OBJECTIVE: This study investigated the protective effects of DNLA on synaptic damage in an Aß25-35-induced rat AD model, in primary cortical neuron cultures, and in PC12 cells transfected with human AßPP695, focusing on the Wnt/ß-catenin pathway. METHODS: Sprague-Dawley rats received a single Aß25-35 injection (10µg) into the bilateral hippocampi. DNLA (40 and 80 mg/kg/d) was intragastrically administrated 7 days prior to Aß injection and continued for 28 days. The spatial learning and memory, synaptic morphology, synapse-related proteins, and Wnt signaling components GSK3ß and ß-catenin phosphorylation were evaluated. Rat primary cortical neuron cultures and AßPP695-PC12 cells were used to evaluate axonal mitochondria distribution, reactive oxygen species production, amyloidogenesis, and Wnt pathway in the protection. RESULTS: DNLA ameliorated Aß-induced cognitive impairment, increased the number of synapses, elevated the postsynaptic density thickness and expression of synapsin and PSD95 in the hippocampus, and suppressed Aß-mediated GSK3ß activity and the ß-catenin phosphorylation. In primary neurons and AßPP695-PC12 cells, DNLA restored Aß25-35 induced mitochondrial dysfunction and inhibited reactive oxygen species production and amyloidogenesis. Furthermore, the Wnt/ß-catenin pathway inhibitor Dkk-1 blocked the effect of DNLA on the expression of Aß1-42 and PSD95. CONCLUSION: DNLA rescued Aß-mediated synaptic and mitochondrial injury and inhibited amyloidogenesis in vivo and in vitro, probably through the activation of Wnt/ß-catenin signaling pathway to protect synaptic integrity.


Assuntos
Alcaloides , Doença de Alzheimer , Dendrobium , Alcaloides/farmacologia , Alcaloides/uso terapêutico , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/toxicidade , Animais , Modelos Animais de Doenças , Glicogênio Sintase Quinase 3 beta , Hipocampo , Humanos , Fragmentos de Peptídeos , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio , Via de Sinalização Wnt , beta Catenina
17.
Molecules ; 27(1)2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-35011537

RESUMO

Angelica sinensis is a traditional Chinese medicinal plant that has been primarily used as a blood tonic. It largely relies on its bioactive metabolites, which include ferulic acid, volatile oils, polysaccharides and flavonoids. In order to improve the yield and quality of A. sinensis, the two cultivars Mingui 1 (M1), with a purple stem, and Mingui 2 (M2), with a green stem, have been selected in the field. Although a higher root yield and ferulic acid content in M1 than M2 has been observed, the differences of flavonoid biosynthesis and stem-color formation are still limited. In this study, the contents of flavonoids and anthocyanins were determined by spectrophotometer, the differences of flavonoids and transcripts in M1 and M2 were conducted by metabolomic and transcriptomic analysis, and the expression level of candidate genes was validated by qRT-PCR. The results showed that the contents of flavonoids and anthocyanins were 1.5- and 2.6-fold greater in M1 than M2, respectively. A total of 26 differentially accumulated flavonoids (DAFs) with 19 up-regulated (UR) and seven down-regulated (DR) were obtained from the 131 identified flavonoids (e.g., flavonols, flavonoid, isoflavones, and anthocyanins) in M1 vs. M2. A total 2210 differentially expressed genes (DEGs) were obtained from the 34,528 full-length isoforms in M1 vs. M2, and 29 DEGs with 24 UR and 5 DR were identified to be involved in flavonoid biosynthesis, with 25 genes (e.g., CHS1, CHI3, F3H, DFR, ANS, CYPs and UGTs) mapped on the flavonoid biosynthetic pathway and four genes (e.g., RL1, RL6, MYB90 and MYB114) belonging to transcription factors. The differential accumulation level of flavonoids is coherent with the expression level of candidate genes. Finally, the network of DAFs regulated by DEGs was proposed. These findings will provide references for flavonoid production and cultivars selection of A. sinensis.


Assuntos
Angelica sinensis/genética , Angelica sinensis/metabolismo , Flavonoides/biossíntese , Regulação da Expressão Gênica de Plantas , Metaboloma , Transcriptoma , Antocianinas/metabolismo , Vias Biossintéticas , Biologia Computacional/métodos , Perfilação da Expressão Gênica , Metabolômica/métodos , Anotação de Sequência Molecular
18.
Magn Reson Chem ; 60(4): 427-433, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34993993

RESUMO

In this study, the transverse relaxation time (T2 ) of activated carbon (AC) in different relative environment humidity was detected firstly by low-field nuclear magnetic resonance (LFNMR). The pore size (diameter) of AC distributions was calculated by the relationship between T2 and surface relaxation rate (ρ), where ρ was obtained by the detection of nine porous materials with known pore size. The results showed that the pore size distributions of AC calculated by ρ < 0.19 nm/ms were in good agreement with that obtained by nitrogen adsorption method and proved that LFNMR as a new detection method was feasible for characterizing AC pore size distribution.


Assuntos
Carvão Vegetal , Imageamento por Ressonância Magnética , Adsorção , Espectroscopia de Ressonância Magnética/métodos , Porosidade
19.
Materials (Basel) ; 15(2)2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-35057163

RESUMO

In this work, a hydrogen-terminated (H-terminated) diamond field effect transistor (FET) with HfAlOx/Al2O3 bilayer dielectrics is fabricated and characterized. The HfAlOx/Al2O3 bilayer dielectrics are deposited by the atomic layer deposition (ALD) technique, which can protect the H-terminated diamond two-dimensional hole gas (2DHG) channel. The device demonstrates normally-on characteristics, whose threshold voltage (VTH) is 8.3 V. The maximum drain source current density (IDSmax), transconductance (Gm), capacitance (COX) and carrier density (ρ) are -6.3 mA/mm, 0.73 mS/mm, 0.22 µF/cm2 and 1.53 × 1013 cm-2, respectively.

20.
J Nutr Biochem ; 101: 108924, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34843932

RESUMO

Amino acids can activate mTOR to promote milk synthesis in mammary epithelial cells (MECs), but the underlying molecular mechanism is still largely unknown. The objective is to investigate the regulatory mechanism of amino acids (Met and Leu) in stimulating mRNA expression of mTOR in MECs. We found that the protein abundance of AT-rich interaction domain 1A (ARID1A) was poorly expressed in mouse mammary gland tissues of lactating period. ARID1A knockdown and gene activation experiments detected whether ARID1A negatively regulated milk protein and fat synthesis in bovine MECs, cell proliferation and the expression and activation of mTOR. ChIP-PCR detected that ARID1A, H3K27ac, H3K27me3 and H3K4me3 all bound to the mTOR promoter at -548∼-793 nt. Knockdown or gene activation of ARID1A enhanced or weakened the binding of H3K27ac on the mTOR promoter, respectively. The stimulation of Met and Leu on mTOR expression and phosphorylation were eliminated by ARID1A gene activation. Furthermore, Met and Leu decreased the protein level of ARID1A through ubiquitination and proteasomal degradation. TRIM21 bound to ARID1A, and TRIM21 knockdown blocked the stimulation of Met and Leu on ARID1A degradation. In summary, these data reveal that ARID1A blocks Met and Leu signaling to mTOR gene transcription through inhibiting H3K27ac deposition on its promoter, and Met and Leu decrease ARID1A protein level through TRIM21-mediated ubiquitination and proteasomal degradation. Our findings uncover that Met and Leu promote mTOR expression for milk synthesis through the TRIM21-ARID1A signaling pathway, providing a novel theoretical basis for the application of amino acids in milk production.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Lactação , Leucina/metabolismo , Glândulas Mamárias Animais/metabolismo , Metionina/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Fatores de Transcrição/metabolismo , Animais , Bovinos , Proliferação de Células , Células Cultivadas , Proteínas de Ligação a DNA/genética , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Feminino , Histonas/metabolismo , Glândulas Mamárias Animais/citologia , Camundongos , Camundongos Endogâmicos ICR , Leite/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Transdução de Sinais , Fatores de Transcrição/genética , Ubiquitina/metabolismo , Ubiquitina-Proteína Ligases/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...