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1.
Sci Total Environ ; 912: 169497, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38142995

RESUMO

Henan Province's plain area is the granary of China, yet its regional aquifer is being polluted by industrial wastewater, agricultural pesticide, fertilizer and domestic wastewater. In order to safeguard the security of food and drinking water, and in response to the problem of low prediction accuracy caused by the lack of samples and unevenly distributed groundwater monitoring data, we propose a new way to predict the aquifer vulnerability in large areas by rich small-scale data, so as to identify the pollution risks and to address the issue of sample shortage. In small regions with abundant nitrate data, we employed a Random Forest model to screen key impact indicators, using them as features and nitrate-N concentration as the target variable. Consequently, we established six machine learning prediction models, and then selected the best bagging model (R2 = 0.86) to predict the vulnerability of aquifers in larger regions lacking nitrate data. The predicted results showed that highly vulnerable areas accounted for 20 %, which were mainly affected by aquifer thickness (65.91 %). High nitrate-N concentration implies serious aquifer contamination. Therefore, a long series of groundwater nitrate-N concentration monitoring data in a large scale, the trend and slope of nitrate-N concentration showed a significant correlation with the model prediction results (Spearman's correlation coefficients are 0.75 and 0.58). This study can help identify the risk of aquifer contamination, solve the problem of sample shortage in large areas, thus contributing to the security of food and drinking water.

2.
Sensors (Basel) ; 23(3)2023 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-36772544

RESUMO

Monocular camera and Lidar are the two most commonly used sensors in unmanned vehicles. Combining the advantages of the two is the current research focus of SLAM and semantic analysis. In this paper, we propose an improved SLAM and semantic reconstruction method based on the fusion of Lidar and monocular vision. We fuse the semantic image with the low-resolution 3D Lidar point clouds and generate dense semantic depth maps. Through visual odometry, ORB feature points with depth information are selected to improve positioning accuracy. Our method uses parallel threads to aggregate 3D semantic point clouds while positioning the unmanned vehicle. Experiments are conducted on the public CityScapes and KITTI Visual Odometry datasets, and the results show that compared with the ORB-SLAM2 and DynaSLAM, our positioning error is approximately reduced by 87%; compared with the DEMO and DVL-SLAM, our positioning accuracy improves in most sequences. Our 3D reconstruction quality is better than DynSLAM and contains semantic information. The proposed method has engineering application value in the unmanned vehicles field.

3.
J Hazard Mater ; 447: 130754, 2023 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-36638675

RESUMO

The extracellular electron transfer capability of some anaerobic ammonium oxidation (anammox) bacteria was confirmed in recent years. However, the effect of conductive carriers on the synchronous formation of anammox biofilm and granules is rarely reported. Anammox biofilm and granules with compact and stable structures accelerate the initiation and enhance the stability of the anammox process. In this study, we found that the conductive carbon fiber brush (CB) carrier promoted synchronous biofilm formation and granulation of anammox bacteria in the internal circulation immobilized blanket (ICIB) reactor. Compared with polyurethane sponge and zeolite carrier, the ICIB reactor packed with CB carrier can be operated under the highest total nitrogen loading rate of 6.53 kg-N/(m3·d) and maintain the effluents NH4+-N and NO2--N at less than 1 mM. The volatile suspended solids concentration in the ICIB reactor packed with conductive carrier increased from 5.17 ± 0.40 g/L of inoculum sludge to 24.24 ± 1.20 g/L of biofilm, and the average particle size of granules increased from 222.09 µm to 879.80 µm in 150 days. Fluorescence in situ hybridization analysis showed that anammox bacteria prevailed in the biofilm and granules. The analysis of extracellular polymeric substances indicated that protein and humic acid-like substances played an important role in the formation of anammox biofilm and granules. Microbiome analysis showed that the relative abundance of Candidatus Jettenia was increased from 0.18% to 38.15% in the biofilm from CB carrier during start-up stage. This study provides a strategy for rapid anammox biofilm and granules enrichment and carrier selection of anammox process.


Assuntos
Compostos de Amônio , Compostos de Amônio/metabolismo , Hibridização in Situ Fluorescente , Oxidação Anaeróbia da Amônia , Oxirredução , Anaerobiose , Esgotos/microbiologia , Bactérias/genética , Bactérias/metabolismo , Biofilmes , Reatores Biológicos/microbiologia , Nitrogênio/metabolismo
4.
Sci Total Environ ; 859(Pt 1): 160264, 2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36402336

RESUMO

The operation of the Three Gorges Dam (TGD) modifies downstream flow and sediment regimes, triggering disproportional fluvial responses at different distances downstream. However, our understanding of the downstream geomorphic changes in the middle-lower Yangtze River remains incomplete due to the complexity of the river responses across temporal and spatial scales. Here, we leverage data on discharge, suspended sediment concentration (SSC), riverbed grain size, cross-sectional profiles and high-resolution channel bathymetric maps at different locations downstream of the TGD to investigate geomorphic responses. The results show that the magnitude of fluvial erosion decreases downstream, with the Yichang-Luoshan Reach (the first ~500 km downstream) experiencing the most severe erosion in 2003-2020 (~9.05 × 104 t/km/yr). Local changes in riverbed morphology include channel bar erosion, channel incision (~0.43 m/yr in CS1 near the dam site over 2002-2019), riverbank retreat and bed material coarsening (an increase in D50 from 0.175 to 43.1 mm at Yichang station from 2002 to 2017). Such marked erosion is caused by the sharply reduced SSC in the dominant discharge range (10,000-30,000 m3/s) and the extended duration of this dominant discharge range. The sediment erosive magnitude in the Luoshan-Datong Reach is relatively small (3.85 × 104 t/km/yr) in 2002-2020. The Luoshan-Hukou Reach (~500-1000 km downstream) exhibits moderate channel incision, minor bed material coarsening and moderate mid-channel bar lateral erosion. The Hukou-Datong Reach (below 1000 km downstream) experienced minor geomorphic change without significant evidence of bed material coarsening. The relatively small impact of the TGD on the lower reach from Luoshan to Datong can be mainly attributed to the progressive SSC recovery along the river induced by upstream channel erosion providing sediment replenishment. These findings have significant implications for estimating geomorphic changes in response to upstream damming and thus could inform better river management and ecological assessment in other similar alluvial rivers.


Assuntos
Monitoramento Ambiental , Rios , Estudos Transversais
5.
Pharmacol Res ; 187: 106577, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36435270

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a fatal disease with high mortality and limited effective therapy. Herein, we reported that fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), used in depression and anxiety treatment, also exhibited therapeutic activities in IPF. Fluvoxamine inhibited cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING), restrained the activation of their downstream targets, including PERK/ eIF2α/ c-Myc/ miR-9-5p/ TBPL1 and TBK1/ YAP/ JNK1/2/ Bnip3/ CaMKII/ cofilin signaling, thus attenuated the activation and migration of fibroblasts upon TGF-ß1 challenge. Fluvoxamine dose-dependently improved pulmonary function, decreased the expression of inflammatory factors, reduced excessive production of extracellular matrix, and thus alleviated bleomycin (BLM)-induced lung fibrosis in mice. Moreover, fluvoxamine at a dose of 10 mg/ kg showed similar efficacy as pirfenidone (PFD) at a dose of 30 mg/kg in a mice model of lung fibrosis. In summary, our results suggest that fluvoxamine is an effective anti-fibrotic agent for IPF.


Assuntos
Antifibróticos , Fluvoxamina , Fibrose Pulmonar Idiopática , Animais , Camundongos , Bleomicina , Fibroblastos/metabolismo , Fluvoxamina/uso terapêutico , Fibrose Pulmonar Idiopática/tratamento farmacológico , Pulmão/efeitos dos fármacos , Nucleotidiltransferases , Fator de Crescimento Transformador beta1/metabolismo , Antifibróticos/uso terapêutico
7.
Pharmacol Res ; 185: 106491, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36244543

RESUMO

Psoriasis is an incurable autoimmune disease that affects 2-3% of the world's population. Limited understanding of its pathogenesis hinders the development of therapies for the disease. Herein, we reported that N-acylethanolamine acid amidase (NAAA), a cysteine enzyme that catalyzes the hydrolysis of fatty acid ethanolamides (FAEs), was upregulated in psoriasis patients and imiquimod (IMQ)-induced mouse model of psoriasis. The upregulated NAAA contributes to the progression of psoriasis via enhancing dendritic cell (DCs) maturation. Transgenic expression of NAAA in mice accelerated the development of psoriasis, whereas genetic ablation of NAAA or local administration of NAAA inhibitor F96 ameliorated psoriasis. NAAA expressed in dendritic cells (DCs), but not in macrophages, T cells, or keratinocytes plays a critical role in psoriasis development. In addition, the results showed that NAAA degrades palmitoylethanolamide (PEA) and reduces PEA-PPARα-mediated dissociation of NF-κB p65 from Sirtuin 1 (SIRT1), subsequently, repressing the acetylation of p65 and down-regulating IL10 production. The decreased IL10 then leads to the maturation of DCs, thus promoting the development of psoriasis. These results provide new insights into the pathophysiological mechanism of psoriasis and identify NAAA as a novel target for the treatment of psoriasis.


Assuntos
Interleucina-10 , Psoríase , Camundongos , Animais , Inibidores Enzimáticos/farmacologia , Amidoidrolases , Inflamação , Psoríase/tratamento farmacológico , Células Dendríticas/metabolismo
8.
Oncol Rep ; 48(3)2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35856443

RESUMO

Anaplastic thyroid cancer (ATC) is an aggressive and lethal malignancy having a dismal prognosis. Phytochemicals are bioactive components obtained from plants that have been proven useful to treat numerous diseases. Phytochemicals are also an important source of novel anticancer drugs and an important area of research due to the numerous available candidates that can potentially treat cancers. This review discusses naturally occurring phytochemicals and their derivatives that show promising anticancer effects in anaplastic thyroid cancer. Anticancer effects include cell growth inhibition, induction of apoptosis, promoting cell cycle arrest, suppressing angiogenesis, modulating autophagy, and increasing the production of reactive oxygen species. Phytochemicals are not only prospective candidates in the therapy of anaplastic thyroid cancer but also exhibit potential as adjuvants to improve the anticancer effects of other drugs. Although some phytochemicals have excellent anticancer properties, drug resistance observed during the use of resveratrol and artemisinin in different anaplastic thyroid cancer cell lines is still a problem. Anaplastic thyroid cancer cells have several biological, clinical, and drug­resistance features that differ from differentiated thyroid cancer cells. Phytochemicals such as resveratrol and quercetin exhibit different biological effects in anaplastic thyroid cancer and differentiated thyroid cancer. Tumor cells depend on increased aerobic glycolysis by mitochondrial oxidative phosphorylation to provide energy for their rapid growth, invasiveness, and drug resistance. Phytochemicals can alter signaling cascades, modulate the metabolic properties of cancer cells, and influence the mitochondrial membrane potential of anaplastic thyroid cancer cells. These findings enrich our knowledge of the anticancer effects of phytochemicals and highlight alternative therapies to prevent drug resistance in anaplastic thyroid cancer.


Assuntos
Carcinoma Anaplásico da Tireoide , Neoplasias da Glândula Tireoide , Linhagem Celular Tumoral , Humanos , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Resveratrol/farmacologia , Carcinoma Anaplásico da Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologia
9.
Materials (Basel) ; 15(9)2022 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-35591404

RESUMO

Fibrous porous materials are one of the most commonly used high-temperature insulation materials because of their high porosity and low thermal conductivity. Due to their wide applications in the aerospace and energy industries, the investigation of high-elastic thermally insulating porous materials has attracted increasing attention. In order to improve the elasticity of fibrous porous materials, quartz fibers with high aspect ratio were used as matrix, sodium hexametaphosphate (SHMP) was selected as dispersant. We innovatively reported that a unique three-dimensional skeleton structure was constructed by adjusting the dispersion of fibers in the slurry, and the lightweight, thermal insulating and elastic SiO2 fibrous porous material was then prepared by the compression molding method. The characterization results of zeta potential and absorbance showed that the addition of SHMP was an effective method to enhance the dispersibility of quartz fibers in the slurry. SiO2 fibrous porous materials with 0.4 wt% SHMP content exhibited an ideal three-dimensional skeleton structure, which endowed the porous material with high porosity (89.39%), low density (0.04751 g/cm3), and low thermal conductivity (0.0356 W·m-1·K-1). The three-dimensional skeleton structure formed by overlapping fibers with high aspect ratios endowed the porous material with excellent elasticity. SiO2 fibrous porous materials with 0.4 wt% SHMP content could undergo large strains of 30% and achieved a resilience ratio of 81.69% under the 30th compression cycle. Moreover, after heat treatment at 800 °C, SiO2 fibrous porous materials also maintained good elasticity with a resilience ratio of more than 80%.

10.
Anticancer Agents Med Chem ; 22(9): 1753-1760, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34515013

RESUMO

BACKGROUND: Anaplastic Thyroid Cancer (ATC) is a rare subtype of thyroid tumors with a high mortality rate. Targeted therapies against ATC are ineffective and mostly transient. Artemisinin has shown excellent anti-tumor activity in several cancers, but its effects on ATC are still unknown. OBJECTIVE: To evaluate the effects of artemisinin on ATC cells and assess the mechanism underlying drug resistance. METHODS: The viability and proliferation rates of the artemisinin-treated CAL-62 and BHT-101 cells were analyzed by MTT and EdU incorporation assays. The protein expression levels were determined by Tandem Mass Tag (TMT) labeling quantitative proteomics and western blotting. RESULTS: Artemisinin treatment significantly decreased the expression levels of COX2 and COX7A2 and increased that of COX14, YEM1l1, ALAS1, and OAT after 48h. In addition, FTL was upregulated in the CAL-62 cells and downregulated in BHT-101 cells. The CAL-62 cells showed transient and reversible resistance to artemisinin, which was correlated to time-dependent changes in HIF1α, PDK1, and PDHA levels. CONCLUSION: Artemisinin targets the mitochondrial respiratory chain proteins in ATC cells. CAL-62 cells show transient resistance to artemisinin via PDH downregulation, indicating that PDH activation may enhance the cytotoxic effects of artemisinin on ATC cells.


Assuntos
Artemisininas , Carcinoma Anaplásico da Tireoide , Neoplasias da Glândula Tireoide , Humanos , Apoptose , Artemisininas/farmacologia , Linhagem Celular Tumoral , Carcinoma Anaplásico da Tireoide/tratamento farmacológico , Carcinoma Anaplásico da Tireoide/metabolismo , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/metabolismo
11.
Eur J Pharmacol ; 912: 174561, 2021 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-34655598

RESUMO

Traumatic brain injury (TBI) is a leading cause of death worldwide, for which there is currently no comprehensive treatment available. Preventing blood-brain barrier (BBB) disruption is crucial for TBI treatment. N-acylethanolamine acid amidase (NAAA)-regulated palmitoylethanolamide (PEA) signaling play an important role in the control of inflammation. However, the role of NAAA in BBB dysfunction following TBI remains unclear. In the present study, we found that TBI induces the increase of PEA levels in the injured cortex, which prevent the disruption of BBB after TBI. TBI also induces the infiltration of NAAA-contained neutrophils, increasing the contribution of NAAA to the PEA degradation. Neutrophil-derived NAAA weakens PEA/PPARα-mediated BBB protective effects after TBI, facilitates the accumulation of immune cells, leading to secondary expansion of tissue injury. Inactivation of NAAA increased PEA levels in injured site, prevents early BBB damage and improves secondary injury, thereby eliciting long-term functional improvements after TBI. This study identified a new role of NAAA in TBI, suggesting that NAAA is a new important target for BBB dysfunction related CNS diseases.


Assuntos
Amidoidrolases/metabolismo , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Lesões Encefálicas Traumáticas/metabolismo , Inibidores Enzimáticos/farmacologia , Fármacos Neuroprotetores/farmacologia , Oxazolidinonas/farmacologia , Amidas/metabolismo , Amidoidrolases/antagonistas & inibidores , Animais , Lesões Encefálicas Traumáticas/sangue , Lesões Encefálicas Traumáticas/patologia , Linhagem Celular , Modelos Animais de Doenças , Células Endoteliais/efeitos dos fármacos , Inibidores Enzimáticos/uso terapêutico , Etanolaminas/metabolismo , Feminino , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Neutrófilos/metabolismo , Oxazolidinonas/uso terapêutico , PPAR alfa/deficiência , PPAR alfa/genética , Ácidos Palmíticos/metabolismo
12.
BMC Complement Med Ther ; 21(1): 156, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34049534

RESUMO

BACKGROUND: Anaplastic thyroid carcinoma is a highly lethal subtype of thyroid cancer without effective therapies. Drug resistance in anaplastic thyroid carcinoma poses a significant problem. Although artemisinin exerts antitumor effects, but its efficacy in anaplastic thyroid carcinoma is unknown. METHODS: We used RNA sequencing to identify differentially expressed genes. Next, we determined the cause of ART resistance by testing the expression and activity of ß-catenin, and enhanced ART activity with a WNT signaling inhibitor. RESULTS: Artemisinin suppressed the growth of BHT-101 but not human thyroid anaplastic carcinoma (CAL-62) cells. The mechanism of artemisinin resistance in CAL-62 was associated with the aberrant activation of WNT signaling. Pyrvinium pamoate, an inhibitor of WNT signaling, was used to overcome ART resistance in CAL-62 cells. The combination of artemisinin and pyrvinium pamoate suppressed the growth of CAL-62 cells and induced the apoptosis. CONCLUSIONS: Our study is the first to prove the efficacy of ART as monotherapy or in combination with PP in the management of anaplastic thyroid cancer, and that the inhibition of WNT signaling may overcome ART resistance.


Assuntos
Antineoplásicos/farmacologia , Artemisininas/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Compostos de Pirvínio/farmacologia , Carcinoma Anaplásico da Tireoide/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Neoplasias da Glândula Tireoide
13.
PLoS One ; 16(5): e0251015, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33961662

RESUMO

This work explores the changes in vegetation coverage and submergence time of floodplains along the middle and lower reaches of the Yangtze River (i.e., the Jingjiang River) and the relations between them. As the Three Gorges Dam has been operating for more than 10 years, the original vegetative environment has been greatly altered in this region. The two main aspects of these changes were discovered by analyzing year-end image data from remote sensing satellites using a dimidiate pixel model, based on the normalized difference vegetation index, and by calculating water level and topographic data over a distance of 360 km from 2003-2015. Given that the channels had adjusted laterally, thus exhibiting deeper and broader geometries due to the Three Gorges Dam, 11 floodplains were classified into three groups with distinctive features. The evidence shows that, the floodplains with high elevation have formed steady vegetation areas and could hardly be affected by runoff and usually occupied by humans. The low elevation group has not met the minimal threshold of submerging time for vegetation growth, and no plants were observed so far. Based on the facts summed up from the floodplains with variable elevation, days needed to spot vegetation ranges from 70 to 120 days which happened typically near 2006 and between 2008 and 2010, respectively, and a negative correlation was detected between submergence time and vegetation coverage within a certain range. Thus, floods optimized by the Three Gorges Dam have directly influenced plant growth in the floodplains and may also affect our ability to manage certain types of large floods. Our conclusions may provide a basis for establishing flood criteria to manage the floodplain vegetation and evaluating possible increases in resistance caused by high-flow flooding when these floodplains are submerged.


Assuntos
Ecossistema , Inundações , Desenvolvimento Vegetal/fisiologia , Rios , China
14.
Pharmacol Res ; 170: 105516, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33636350

RESUMO

Amid the globalization of traditional Chinese medicine (TCM), the English translation of related texts is in full swing. Several representative international organizations in fields regarding standardization and healthcare, one after another, have published a series of international standards for TCM nomenclature. With these efforts, the internationalization of TCM has been dramatically advanced. When selecting parallel texts for reference, translators need to be aware of key factors influencing the English translation of TCM terms in international standards, including the distinctive characteristics of this discipline and relevant influences of international standard makers. In this way, proper standards and reasonable English expression can be chosen for specific terms, thus stimulating the effective use of TCM nomenclature with consensus.


Assuntos
Medicina Tradicional Chinesa/normas , Terminologia como Assunto , Tradução , Vocabulário Controlado , Consenso , Humanos , Cooperação Internacional
15.
Biochem Pharmacol ; 184: 114398, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33385371

RESUMO

Postoperative adhesions and scarring are the particular complication after strabismus surgery, for which there is currently no comprehensive treatment available. Preventing inflammation and fibrosis in the extraocular muscle are crucial for treatment of postoperative adhesions. In the present study, we found that administration of palmitoylethanolamide (PEA) attenuated postoperative inflammation and fibroproliferation through activating peroxisome proliferator-activated receptor α (PPARα), thus prevented scar formation. Inhibition of PEA degradation by N-Acylethanolamine acid amidase (NAAA) inhibitor F96 led to the same pharmacological results. PPARα activation suppressed both canonical and non-canonical TGFß signaling. Mechanistically, we found that PPARα directly bound to TGFß-activated kinase 1 (TAK1), thus preventing its hyperphosphorylation and the activation of downstream p38 and JNK1/2 signaling. Taken together, current study suggested that PEA could be a novel therapeutic approach for postoperative adhesions after strabismus surgery.


Assuntos
Amidas/farmacologia , Etanolaminas/farmacologia , Ácidos Palmíticos/farmacologia , Complicações Pós-Operatórias/tratamento farmacológico , Estrabismo/cirurgia , Amidoidrolases/antagonistas & inibidores , Amidoidrolases/metabolismo , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Fibrose , Células HEK293 , Humanos , MAP Quinase Quinase Quinases/antagonistas & inibidores , Masculino , Camundongos , Células NIH 3T3 , Oxazolidinonas/farmacologia , PPAR alfa/metabolismo , Complicações Pós-Operatórias/etiologia , Coelhos , Aderências Teciduais/tratamento farmacológico
16.
Mol Phylogenet Evol ; 157: 107065, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33387649

RESUMO

Resolving the interordinal relationships in the mammalian superorder Laurasiatheria has been among the most intractable problems in higher-level mammalian systematics, with many conflicting hypotheses having been proposed. The present study collected three different sources of genome-scale data with comprehensive taxon sampling of laurasiatherian species, including two protein-coding datasets (4,186 protein-coding genes for an amino acid dataset comprising 2,761,247 amino acid residues and a nucleotide dataset comprising 5,516,340 nucleotides from 1st and 2nd codon positions), an intronic dataset (1,210 introns comprising 1,162,723 nucleotides) and an ultraconserved elements (UCEs) dataset (1,246 UCEs comprising 1,946,472 nucleotides) from 40 species representing all six laurasiatherian orders and 7 non-laurasiatherian outgroups. Remarkably, phylogenetic trees reconstructed with the four datasets using different tree-building methods (RAxML, FastTree, ASTRAL and MP-EST) all supported the relationship (Eulipotyphla, (Chiroptera, ((Carnivora, Pholidota), (Cetartiodactyla, Perissodactyla)))). We find a resolution of interordinal relationships of Laurasiatheria among all types of markers used in the present study, and the likelihood ratio tests for tree comparisons confirmed that the present tree topology is the optimal hypothesis compared to other examined hypotheses. Jackknifing subsampling analyses demonstrate that the results of laurasiatherian tree reconstruction varied with the number of loci and ordinal representatives used, which are likely the two main contributors to phylogenetic disagreements of Laurasiatheria seen in previous studies. Our study provides significant insight into laurasiatherian evolution, and moreover, an important methodological strategy and reference for resolving phylogenies of adaptive radiation, which have been a long-standing challenge in the field of phylogenetics.


Assuntos
Eutérios/classificação , Eutérios/genética , Genoma , Filogenia , Animais , Loci Gênicos , Marcadores Genéticos , Íntrons/genética , Funções Verossimilhança
17.
Front Pharmacol ; 12: 817603, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35069223

RESUMO

N-Acylethanolamine acid amidase (NAAA) is a lysosomal enzyme responsible for the hydrolysis of fatty acid ethanolamides (FAEs). However, the role of NAAA in FAEs metabolism and regulation of pain and inflammation remains mostly unknown. Here, we generated NAAA-deficient (NAAA-/-) mice using CRISPR-Cas9 technique, and found that deletion of NAAA increased PEA and AEA levels in bone marrow (BM) and macrophages, and elevated AEA levels in lungs. Unexpectedly, genetic blockade of NAAA caused moderately effective anti-inflammatory effects in lipopolysaccharides (LPS)-induced acute lung injury (ALI), and poor analgesic effects in carrageenan-induced hyperalgesia and sciatic nerve injury (SNI)-induced mechanical allodynia. These data contrasted with acute (single dose) or chronic NAAA inhibition by F96, which produced marked anti-inflammation and analgesia in these models. BM chimera experiments indicated that these phenotypes were associated with the absence of NAAA in non-BM cells, whereas deletion of NAAA in BM or BM-derived cells in rodent models resulted in potent analgesic and anti-inflammatory phenotypes. When combined, current study suggested that genetic blockade of NAAA regulated FAEs metabolism and inflammatory responses in a cell-specifical manner.

18.
Front Pharmacol ; 11: 577319, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33117168

RESUMO

N-acylethanolamine-hydrolyzing acid amidase (NAAA) is a lysosomal enzyme that inhibits the degradation of palmitoylethanolamide (PEA), an endogenous lipid that induces analgesic, anti-inflammation, and anti-multiple sclerosis through PPARα activation. Only a few potent NAAA inhibitors have been reported to date, which is mainly due to the restricted substrate-binding site of NAAA. Here, we established a high-throughput fluorescence-based assay for NAAA inhibitor screening. Several new classes of NAAA inhibitors were discovered from a small library of natural products. One of these is atractylodin, a polyethylene alkyne compound from the root of Atractylodes lancea (Thunb) DC., which significantly inhibits NAAA activity and has an IC50 of 2.81 µM. Kinetic analyses and dialysis assays suggested that atractylodin engages in competitive inhibition via reversible reaction to the enzyme. Docking assays revealed that atractylodin occupies the catalytic cavity of NAAA, where the atractylodin furan head group has a hydrophobic-related interaction with the backbone of the Trp181 and Leu152 residues of human NAAA. Further investigation indicated that atractylodin significantly increases PEA and OEA levels and dose-dependently inhibits LPS-induced nitrate, TNF-α, IL-1ß, and IL-6 pro-inflammatory cytokine release in BV-2 microglia. Our results show that atractylodin elevates cellular PEA levels and inhibits microglial activation by inhibiting NAAA activity, which in turn could contribute to NAAA functional research.

19.
In Vitro Cell Dev Biol Anim ; 56(8): 622-634, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32901429

RESUMO

The pathogenesis of diabetes is associated with dysfunction of pancreatic ß-cells. To ameliorate the ß-cell dysfunction, it has propelled great interest to search pharmacological agents from natural plants. This study explored the protective effect of apigetrin, a flavonoid present in natural plants, against streptozotocin (STZ)-induced cell damages in RINm5F cells and the potential mechanisms. Apigetrin was found to inhibit the elevation of intracellular reactive oxygen species levels, restore the impairment of antioxidant enzymes, and recover the disruption of redox homeostasis in the STZ-treated pancreatic ß-cells. Moreover, treatment of apigetrin significantly suppressed the STZ-induced apoptosis in the analysis of apoptotic sub-G1 population and the protein expressions of cleaved poly(ADP-ribose) polymerase and caspase-3. Furthermore, apigetrin attenuated STZ-induced endoplasmic reticulum (ER) stress, indicated by the reduction of ER stress biomarkers, including overloading of mitochondrial calcium, increase in glucose-regulated protein 78, phosphorylation of protein kinase RNA-like ER kinase and its downstream eukaryotic initiation factor 2α, cleavage of activating transcription factor 6 and caspase-12, up-regulation of CCAAT/enhancer binding protein homologous protein, and induction of spliced X-box binding protein 1. Additionally, pretreatment with 4-phenylbutyric acid, a classic ER stress inhibitor, augmented these beneficial effects of apigetrin. In conclusion, these results demonstrated that apigetrin could improve the STZ-induced pancreatic ß-cell damages via mitigation of oxidative stress and ER stress and supported the application of apigetrin to developing the novel therapeutics of diabetes.


Assuntos
Apigenina/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Células Secretoras de Insulina/patologia , Estreptozocina/toxicidade , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Cálcio/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Citoproteção/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/enzimologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Modelos Biológicos , Oxirredução , Substâncias Protetoras/farmacologia , Ratos , Espécies Reativas de Oxigênio/metabolismo
20.
Bioresour Technol ; 317: 123979, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32799080

RESUMO

To reduce start-up time and enhance hydrogen production efficiency, a sequential immobilization and deoxygenization (SIDO) strategy for hydrogen production was investigated in continuous-flow moving bed biofilm reactors (MBBRs). The pre-immobilization process accelerated the initial enrichment of hydrogen-producing bacteria (HPB) and promoted the biofilm formation, which contribute to higher hydrogen production efficiency in SIDO-MBBRs compared to a non-immobilized reactor. A similar deoxygenization effect was achieved by inoculation with Pseudomonas aeruginosa compared with N2 sparging, and the P. aeruginosa pre-immobilized MBBR (Pse-MBBR) showed a higher H2 yield in the initial stage of operation. Microbial community analysis found a higher abundance of putative HPB in the range of 82.82-96.56%, with the predominant populations in the SIDO-MBBR assigned to genera Clostridium and Enterobacter. The results suggest that the SIDO-MBBR is an effective approach for rapid recruitment of HPB and start-up of fermentative hydrogen production.


Assuntos
Biofilmes , Reatores Biológicos , Bactérias , Fermentação , Hidrogênio , Eliminação de Resíduos Líquidos
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