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1.
Chem Sci ; 13(23): 6899-6919, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35774173

RESUMO

In vivo data are rare but essential for establishing the clinical potential of ruthenium-based photoactivated chemotherapy (PACT) compounds, a new family of phototherapeutic drugs that are activated via ligand photosubstitution. Here a novel trisheteroleptic ruthenium complex [Ru(dpp)(bpy)(mtmp)](PF6)2 ([2](PF6)2, dpp = 4,7-diphenyl-1,10-phenanthroline, bpy = 2,2'-bipyridine, mtmp = 2-methylthiomethylpyridine) was synthesized and its light-activated anticancer properties were validated in cancer cell monolayers, 3D tumor spheroids, and in embryonic zebrafish cancer models. Upon green light irradiation, the non-toxic mtmp ligand is selectively cleaved off, thereby releasing a phototoxic ruthenium-based photoproduct capable notably of binding to nuclear DNA and triggering DNA damage and apoptosis within 24-48 h. In vitro, fifteen minutes of green light irradiation (21 mW cm-2, 19 J cm-2, 520 nm) were sufficient to generate high phototherapeutic indexes (PI) for this compound in a range of cancer cell lines including lung (A549), prostate (PC3Pro4), conjunctival melanoma (CRMM1, CRMM2, CM2005.1) and uveal melanoma (OMM1, OMM2.5, Mel270) cancer cell lines. The therapeutic potential of [2](PF6)2 was further evaluated in zebrafish embryo ectopic (PC3Pro4) or orthotopic (CRMM1, CRMM2) tumour models. The ectopic model consisted of red fluorescent PC3Pro4-mCherry cells injected intravenously (IV) into zebrafish, that formed perivascular metastatic lesions at the posterior ventral end of caudal hematopoietic tissue (CHT). By contrast, in the orthotopic model, CRMM1- and CRMM2-mCherry cells were injected behind the eye where they developed primary lesions. The maximally-tolerated dose (MTD) of [2](PF6)2 was first determined for three different modes of compound administration: (i) incubating the fish in prodrug-containing water (WA); (ii) injecting the prodrug intravenously (IV) into the fish; or (iii) injecting the prodrug retro-orbitally (RO) into the fish. To test the anticancer efficiency of [2](PF6)2, the embryos were treated 24 h after engraftment at the MTD. Optimally, four consecutive PACT treatments were performed on engrafted embryos using 60 min drug-to-light intervals and 90 min green light irradiation (21 mW cm-2, 114 J cm-2, 520 nm). Most importantly, this PACT protocol was not toxic to the zebrafish. In the ectopic prostate tumour models, where [2](PF6)2 showed the highest photoindex in vitro (PI > 31), the PACT treatment did not significantly diminish the growth of primary lesions, while in both conjunctival melanoma orthotopic tumour models, where [2](PF6)2 showed more modest photoindexes (PI ∼ 9), retro-orbitally administered PACT treatment significantly inhibited growth of the engrafted tumors. Overall, this study represents the first demonstration in zebrafish cancer models of the clinical potential of ruthenium-based PACT, here against conjunctival melanoma.

2.
Sci Total Environ ; 835: 155568, 2022 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-35490817

RESUMO

Human activities severely affect the global nitrogen (N) cycle. Croplands receive intensive N fertilization; consequently, cropland and natural ecosystem differentiation often results in community and functional variation in N-transforming microbes, including nitrifiers, which perform nitrification central to N cycle. However, evidence of such variation is mostly limited to ammonia oxidizers (AO) in local fields, excluding soil heterogeneity and nitrite-oxidizing bacteria (NOB); the variation under diverse climatic and soil conditions is not comprehensively understood. We conducted a large-scale survey of 131 cropland and natural sites in China. The community patterns of ammonia-oxidizing bacteria (AOB) and NOB differed significantly between croplands and some natural ecosystems, whereas ammonia-oxidizing archaea (AOA) were not affected by ecosystem type. The AOB population and nitrification potential (NP) were significantly higher in agroecosystems than in natural systems except wetlands. Fewer co-occurrence interactions involving nitrifiers were observed in croplands than in natural ecosystems except forests, systematically indicating the ecological diversification of nitrifiers in potential microbial associations among these habitats. Ecosystem type, pH, organic matter (OM), total phosphorus (TP), mean annual temperature (MAT) and mean annual precipitation (MAP) were primary drivers of nitrifier community and functional shifts. This study provides the first large-scale evidence of overall nitrifier community (i.e., AOA, AOB and NOB) and potential functional shifts between agroecosystems and natural environments, enabling predictions of terrestrial N cycle under foreseeable natural land use conversions and global climate change.


Assuntos
Betaproteobacteria , Ecossistema , Amônia , Archaea , Bactérias , Humanos , Nitrificação , Nitritos , Oxirredução , Filogenia , Solo , Microbiologia do Solo
3.
Asia Pac J Oncol Nurs ; 9(2): 125-129, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35529418

RESUMO

Objective: Regofinib is a novel, oral, anticancer target which greatly improves survival of patients with colorectal cancer. However, it causes 47%-71% patients occur hand-foot skin reaction (HFSR), which affects the quality of life (QOL) or prognosis of patients. However targeted and effective methods are rare. The study attempted to test the efficacy of the compound traditional Chinese medicine (CTCM) oil in relieving HFSR and improving the QOL. Methods: The present study was conducted in 85 patients with metastatic colorectal cancer presenting with HFSR from July 2019 to June 2020. These patients were divided into the control group (n = 42) and the intervention group (n = 43). The HFSR in the control group was managed using traditional methods, whereas that in the intervention group was treated with a CTCM oil comprising five selected herbs. This oil functions by regulating the vascular endothelial growth factor receptor, inflammatory factors, and immune status, and it was provided to the patients to apply externally twice a day. HFSR remission and QOL were evaluated in both groups after 2 weeks of intervention. Results: The post-intervention HFSR remission rate was significantly higher in the intervention group than in the control group (65.1% vs. 16.7%) (P < 0.01). The overall QOL, physical function, social function, and emotional function of the patients in the intervention group were significantly improved (P < 0.05), whereas the pain symptoms were more significantly improved (P < 0.01). Conclusions: The CTCM oil can effectively alleviate HFSR and improve the QOL of patients using regorafenib.

4.
Analyst ; 147(9): 1968-1975, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35416808

RESUMO

Acquiring information on telomerase activity at multiple levels contributes to a better understanding of its role in various physiological and pathological processes. Herein, a primer extension activating 3D DNAzyme walker is developed for in situ imaging and sensitive detection of telomerase activity. This walker is constructed via co-modifying specially designed hairpin structured walking strands and track strands on a gold nanoparticle (AuNP). The walking strand contains a pre-blocked DNAzyme sequence and a telomerase primer hybridized to its root. The track strand embeds at an RNA cleavage site and is labeled with the FAM group. After this walker is taken up by cells, the telomerase primer is extended under the action of endogenous telomerase to liberate DNAzyme. The liberated DNAzyme cuts track strands in the presence of the cofactor Mn2+ to drive the walker's processive operation, resulting in an enhanced fluorescence recovery of the AuNP-quenched FAM fluorophore. In situ imaging of telomerase activity in three different cell lines (MCF-7 cells, HeLa cells and HL-7702 cells) was well implemented. The discrimination of cancer cells from normal cells and the screening of telomerase inhibitors have been achieved. The sensitive detection of telomerase activity in HeLa cell lysate has also been realized with a detection limit of 10 cells. This walker performed a new approach for monitoring telomerase activity from different levels, providing a potential tool for clinical diagnosis, prognostic evaluation and drug screening.


Assuntos
Técnicas Biossensoriais , DNA Catalítico , Nanopartículas Metálicas , Telomerase , Técnicas Biossensoriais/métodos , DNA Catalítico/genética , Ouro/metabolismo , Células HeLa , Humanos , Telomerase/metabolismo
5.
Artigo em Inglês | MEDLINE | ID: mdl-35399628

RESUMO

To explore the potential biomarkers and metabolic pathways underlying the anti-asthma effects of Belamcanda chinensis extract, this study established an ovalbumin-induced allergic bronchial asthma model in guinea pigs. Sixty guinea pigs were randomly divided into the blank control group, model control group, Belamcanda chinensis extract groups (0.8 g/kg, 1.2 g/kg, 1.6 g/kg, respectively), and dexamethasone acetate tablet group (0.5 mg/kg). Starting on the 22nd day, the drugs were administered by gavage for seven consecutive days. Serum and bronchoalveolar lavage fluid (BALF) were collected. The levels of IL-4 and IgE in the serum and IFN-γ and TNF-α in the BALF were detected by ELISA. UPLC-MS was combined with multivariate statistical analyses, including partial least squares discriminant analysis (PLS-DA), and differential metabolites between groups were identified. Metabolic pathway analysis was performed by querying the KEGG (Kyoto Encyclopedia of Genes and Genomes) online database. Female and male guinea pigs were analyzed. The results showed that compared with the model group, the IgE and IL-4 serum levels were significantly decreased in the 1.6 g/kg group, and the IFN-γ level in the BALF was significantly increased. The TNF-α level was significantly decreased in the 1.2 g/kg and 1.6 g/kg groups. There were 39 common differential metabolites among females and males, and 37 differential metabolites showed opposite regulatory trends in the serum of guinea pigs with asthma and after treatment, mainly involving 17 metabolic pathways, such as pantothenate and CoA biosynthesis, the arachidonic acid mechanism, and glycerophospholipid metabolism. Belamcanda chinensis extract improved OVA-induced asthma, as determined based on immune mechanisms, inflammation, nerve metabolism, and energy metabolism. The serum levels of metabolites produced by the model animals exhibited distinct sex-specific differences, and the treatment effect of Belamcanda chinensis extract also showed sex-specific differences and bidirectional regulation.

6.
Mol Biol Evol ; 39(5)2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35485492

RESUMO

The antibiotic resistance crisis continues to threaten human health. Better predictions of the evolution of antibiotic resistance genes could contribute to the design of more sustainable treatment strategies. However, comprehensive prediction of antibiotic resistance gene evolution via laboratory approaches remains challenging. By combining site-specific integration and high-throughput sequencing, we quantified relative growth under the respective selection of cefotaxime or ceftazidime selection in ∼23,000 Escherichia coli MG1655 strains that each carried a unique, single-copy variant of the extended-spectrum ß-lactamase gene blaCTX-M-14 at the chromosomal att HK022 site. Significant synergistic pleiotropy was observed within four subgenic regions, suggesting key regions for the evolution of resistance to both antibiotics. Moreover, we propose PEARP and PEARR, two deep-learning models with strong clinical correlations, for the prospective and retrospective prediction of blaCTX-M-14 evolution, respectively. Single to quintuple mutations of blaCTX-M-14 predicted to confer resistance by PEARP were significantly enriched among the clinical isolates harboring blaCTX-M-14 variants, and the PEARR scores matched the minimal inhibitory concentrations obtained for the 31 intermediates in all hypothetical trajectories. Altogether, we conclude that the measurement of local fitness landscape enables prediction of the evolutionary trajectories of antibiotic resistance genes, which could be useful for a broad range of clinical applications, from resistance prediction to designing novel treatment strategies.


Assuntos
Infecções por Escherichia coli , beta-Lactamases , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Resistência Microbiana a Medicamentos , Escherichia coli/genética , Infecções por Escherichia coli/tratamento farmacológico , Humanos , Estudos Prospectivos , Estudos Retrospectivos , beta-Lactamases/genética
7.
JAMA Netw Open ; 5(3): e224427, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35357459

RESUMO

Importance: Cancer immunotherapy causes a wide range of immune-related adverse events (irAEs) that require close and timely follow-up. Objectives: To compare the efficiency between electronic patient-reported outcomes (ePRO) and traditional follow-up models in cancer immunotherapy. Design, Setting, and Participants: This open-label randomized clinical trial was performed from September 1, 2019, to March 31, 2021. Patients were randomized to the ePRO model intervention or a control group by a computer system. A total of 28 Chinese tertiary care hospitals participated. Patients who were receiving cancer immunotherapy and could use smartphones or computers were eligible. A total of 300 patients were screened and 278 (92.7%) were enrolled. Interventions: The control group was followed up using traditional methods, including clinic visits every 21 days and telephone follow-up every 3 months. In the intervention group, the ePRO follow-up model included a questionnaire of common symptoms and an image recognition function to evaluate grades of typical irAEs. Patients completed questionnaires weekly and uploaded pictures of results between visits. When grade 1 or 2 irAEs occurred, standardized advice was sent automatically. If grade 3 or 4 irAEs were reported, the model alerted the health care team for assessment and intervention immediately. All patients were followed up for 6 months or until treatment completion. Main Outcomes and Measures: Incidence of serious (grades 3 to 4) irAEs, emergency department (ED) visits, quality of life (QOL), time spent implementing the ePRO model, rate of treatment discontinuation, and death were compared between groups post intervention. Results: A total of 278 patients (mean [SD] age, 58.8 [12.7 (range, 27-78)] years; 206 men [74.1%]) were included in the analysis, consisting of 141 in the intervention group and 137 in the control group. At the postintervention evaluation, the intervention group showed a reduced incidence of serious irAEs (29 of 141 [20.6%] vs 46 of 137 [33.6%]; hazard ratio [HR], 0.51 [95% CI, 0.30-0.88]; P = .01), fewer ED visits (23 of 141 [16.3%] vs 41 of 137 [29.9%]; HR, 0.46 [95% CI, 0.26-0.81]; P = .01), a lower rate of treatment discontinuation (5 of 141 [3.6%] vs 15 of 137 [11.0%]; HR, 0.30 [95% CI, 0.11-0.85]; P = .02), a higher QOL level (mean [SD] score, 74.2 [15.1; 95% CI, 71.7-76.9] vs 64.7 [28.5; 95% CI, 61.0-68.4]; P = .001), and less time implementing follow-up (mean [SD], 8.2 [3.9; 95% CI, 5.0-10.6] minutes vs 36.1 [15.3; 95% CI, 33.6-38.8] minutes; P < .001). However, there were no significant differences between groups in death rates (2 of 141 [1.4%] vs 5 of 137 [3.6%]; HR, 0.38 [95% CI, 0.07-1.99]; P = .28). Conclusions and Relevance: This randomized clinical trial found that the ePRO follow-up model can improve safety and QOL of patients receiving cancer immunotherapy as well as reduce time spent monitoring. This model may provide reliable information and management recommendations. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2100052819.


Assuntos
Neoplasias , Qualidade de Vida , Registros Eletrônicos de Saúde , Humanos , Imunoterapia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Neoplasias/terapia , Medidas de Resultados Relatados pelo Paciente
8.
Comput Intell Neurosci ; 2022: 5259305, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35300392

RESUMO

With the amount of online information continuously growing, it becomes more and more important for online stores to recommend corresponding products precisely based on users' preferences. Reviews for various products can be of great help for the recommendation task. However, most recommendation platforms only classify positive and negative reviews based on sentiment analysis, without considering the actual demands of users, and it will reduce the effectiveness on classification task. To count this issue, we propose a new model, which integrates heterogeneous neural network and text pretraining model into this task, and compare this model with others on a travel type classification task. The model combines a pretrained text model named Bidirectional Encoder Representation from Transformers (BERT) and heterogeneous graph attention network (HGAN). Firstly, we do a fine-tuning task on BERT by a dataset consisting of 1.4 million hotel reviews from the Ctrip website to obtain fine representations of trip-related words. Then, we proposed the similarity fussy-matching method to get the main topic of each review. Then, we construct a heterogeneous neural network and apply the attention mechanism to it to mine the preference of users for traveling. Finally, the classification task is done based on each user's preference. In Section 5 of this study, we do an experiment, which compares our model with five others. The results show that the accuracy of ours is 70%, which is higher than the other five models.


Assuntos
Algoritmos , Redes Neurais de Computação
9.
Front Microbiol ; 13: 809074, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35154054

RESUMO

Studies of methane-oxidizing bacteria are updating our views of their composition and function in paddy and natural wetlands. However, few studies have characterized differences in the methane-oxidizing bacterial communities between paddy and natural wetlands. Here, we conducted a 13C stable isotope-probing experiment and high-throughput sequencing to determine the structure profiling, co-occurrence relationships, and assembly processes of methanotrophic communities in four wetlands of Northeast China. There was a clear difference in community structure between paddy and natural wetlands. LEfSe analyses revealed that Methylobacter, FWs, and Methylosinus were enriched in natural wetlands, while Methylosarcina were prevailing in paddy, all identified as indicative methanotrophs. We observed distinct co-occurrence relationships between paddy and natural wetlands: more robust and complex connections in natural wetlands than paddy wetlands. Furthermore, the relative importance of stochastic processes was greater than that of deterministic processes, as stochastic processes explained >50% of the variation in communities. These results demonstrated that the co-occurrence relationships and assembly processes of active methanotrophic communities in paddy and natural wetlands were distinct. Overall, the results of this study enhance our understanding of the communities of methane-oxidizing bacteria in paddy and natural wetlands of Northeast China.

10.
Environ Res ; 208: 112778, 2022 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-35065067

RESUMO

Diverging area is widespread in river networks, and understanding its biogeochemical process characteristics is of great significance to river ecological restoration and environmental quality improvement. Microbial communities affected by hydrodynamics play an important role in biogeochemical processes, but their relationship in diverging area is little known. Here, the composition of microbial community and its feedback to hydrodynamics and nitrogen conversion in the diverging area of river networks were first studied by coupling ecological theory, biogeochemical theory, microbial DNA sequencing and mathematical model of water environment. The results showed that there were five hydrodynamic zones with significant velocity differences in the diverging area, namely low velocity zone, maximum velocity zone, stagnant zone, separation zone, and deflection zone. According to the flow velocity grouping, there were significant differences in the microbial diversity and abundance among low velocity group, maximum velocity group and stagnant group had significant differences (p < 0.05, stress = 0.1207). In the low velocity group, Firmicutes was the dominant phylum which had a highest abundance and may promot the conversion of organic nitrogen into ammonia nitrogen. In the maximum velocity group, Bdellovibrionota was the dominant phylum which had a highest abundance and may promot the conversion of nitrate and nitric oxide to nitrogen. In the stagnant zone, Methylomirabilota was the dominant phylum which had a highest abundance and may promot the conversion of nitrogen into nitrate and ammonium. In addition, dissolved oxygen was the most sensitive environmental factor for shaping microorganisms and nitrogen conversion in the diverging area of the river networks by canonical correlation analysis. The denitrifying bacteria Rhodocyclaceae, was shown to negatively correlated with the flow velocity. This research improves the scientific basis for the study of the ecosystem in river networks, which will guide the construction of river ecological projects.


Assuntos
Microbiota , Rios , China , Hidrodinâmica , Nitratos/análise , Nitrogênio/análise , Rios/química
11.
Microbiol Spectr ; 10(1): e0132221, 2022 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-35019676

RESUMO

Clostridioides difficile, which causes life-threatening diarrheal disease, presents an urgent threat to health care systems. In this study, we present a retrospective genomic and epidemiological analysis of C. difficile in a large teaching hospital. First, we collected 894 nonduplicate fecal samples from patients during a whole year to elucidate the C. difficile molecular epidemiology. We then presented a detailed description of the population structure of C. difficile based on 270 isolates separated between 2015 and 2020 and clarified the genetic and phenotypic features by MIC and whole-genome sequencing. We observed a high carriage rate (19.4%, 173/894) of C. difficile among patients in this hospital. The population structure of C. difficile was diverse with a total of 36 distinct STs assigned. In total, 64.8% (175/270) of the isolates were toxigenic, including four CDT-positive (C. difficile transferase) isolates, and 50.4% (135/268) of the isolates were multidrug-resistant. Statistically, the rates of resistance to erythromycin, moxifloxacin, and rifaximin were higher for nontoxigenic isolates. Although no vancomycin-resistant isolates were detected, the MIC for vancomycin was higher for toxigenic isolates (P < 0.01). The in-hospital transmission was observed, with 43.8% (110/251) of isolates being genetically linked to a prior case. However, no strong correlation was detected between the genetic linkage and epidemiological linkage. Asymptomatic colonized patients play the same role in nosocomial transmission as infected patients, raising the issue of routine screening of C. difficile on admission. This work provides an in-depth description of C. difficile in a hospital setting and paves the way for better surveillance and effective prevention of related diseases in China. IMPORTANCE Clostridioides difficile infections (CDI) are the leading cause of healthcare-associated diarrhea and are known to be resistant to multiple antibiotics. In the past decade, C. difficile has emerged rapidly and has spread globally, causing great concern among American and European countries. However, research on CDI remains limited in China. Here, we characterized the comprehensive spectrum of C. difficile by whole-genome sequencing (WGS) in a Chinese hospital, showing a high detection rate among patients, diverse genome characteristics, a high level of antibiotic resistance, and an unknown nosocomial transmission risk of C. difficile. During the study period, two C. difficile transferase (CDT)-positive isolates belonging to a new multilocus sequence type (ST820) were detected, which have caused serious clinical symptoms. This work describes C. difficile integrally and provides new insight into C. difficile surveillance based on WGS in China.


Assuntos
Antibacterianos/farmacologia , Clostridioides difficile/efeitos dos fármacos , Clostridioides difficile/genética , Infecções por Clostridium/microbiologia , Infecção Hospitalar/microbiologia , Farmacorresistência Bacteriana , Adolescente , Adulto , Idoso , Proteínas de Bactérias/genética , Criança , Pré-Escolar , China/epidemiologia , Clostridioides difficile/classificação , Clostridioides difficile/isolamento & purificação , Infecções por Clostridium/tratamento farmacológico , Infecções por Clostridium/epidemiologia , Infecções por Clostridium/transmissão , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/transmissão , Eritromicina/farmacologia , Feminino , Genoma Bacteriano , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Moxifloxacina/farmacologia , Filogenia , Estudos Retrospectivos , Rifaximina/farmacologia , Vancomicina/farmacologia , Sequenciamento Completo do Genoma , Adulto Jovem
12.
FEBS Open Bio ; 12(1): 258-269, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34800087

RESUMO

Dermatomyositis and rheumatoid arthritis are inflammatory diseases that affect the skeletal muscles and joints, respectively. A common systemic complication of these diseases is interstitial lung disease (ILD), which leads to a poor prognosis and increased mortality. However, the mechanism for the initiation and development of ILD in patients with dermatomyositis is currently unknown. In the present study, we used 16S rRNA high-throughput sequencing to profile the bacterial community composition of bronchoalveolar lavage fluid of patients with dermatomyositis associated with ILD (DM-ILD; shortened to DM below), rheumatoid arthritis associated with ILD (RA-ILD; shortened to RA below) and healthy controls (N) aiming to understand the differences in their lung microbiota and to predict gene function. We found that there were more operational taxonomic units (OTUs) in the lung microbiota of both RA and DM compared to N, although there was no significant difference in the number of OTUs between RA and DM. Similarly, the diversity in alphaproteobacteria differed between RA and DM compared to N, but not between RA and DM. The lung microbiota of RA, DM and N was mainly comprised of five phyla: Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria and Fusobacteria, with 10 dominant genera. Despite the similarity in microbiota composition, we also identified 41 OTUs of lung microbiota that differed among RA, DM and N. Additionally, linear discriminant analysis effect size and linear discriminant analysis genus scores confirmed that 31 microbial biomarkers were clearly distinguished among RA, DM and N. The functional and metabolic alterations of the lung microbiota among RA, DM and N were predicted using picrust, and differentially abundant KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways were identified. Research on the lung microbiota of patients with DM and RA may open new opportunities for developing biomarkers to identify high-risk patients.


Assuntos
Artrite Reumatoide , Dermatomiosite , Doenças Pulmonares Intersticiais , Microbiota , Dermatomiosite/complicações , Humanos , Pulmão , Doenças Pulmonares Intersticiais/complicações , Microbiota/genética , RNA Ribossômico 16S/genética
13.
Integr Environ Assess Manag ; 18(3): 770-783, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34329535

RESUMO

The sustainable development of resource-based cities is vital to China's high-quality development. Based on the support-pressure framework, this study simplifies the city system into an economy-society subsystem (ESS) and a resource-environment subsystem (RES), and measures the economy social developmental level (ESDL) and resource environmental carrying capacity (RECC) of China's 116 resource-based cities using the improved entropy-TOPSIS model. Then, it applies the coupling coordination degree (CCD) and relative development models to explore their coupling coordination relationships and relative developmental types. The results are as follows. (1) The ESDL and RECC of China's resource-based cities have improved significantly, and there is a large divergence between cities in different regions, development stages, and dominant resource types. (2) The CCD between the ESDL and RECC of China's resource-based cities is still not ideal, and no city qualifies for the high coordination category. (3) Overall, the RECC lags behind the ESDL, and the cities with a lagging ESDL are concentrated in the western and northeastern regions. Based on these conclusions, three specific suggestions are put forth. This study may provide a scientific reference for the Chinese government to formulate a sustainable development plan for resource-based cities. Integr Environ Assess Manag 2022;18:770-783. © 2021 SETAC.


Assuntos
Conservação dos Recursos Naturais , Desenvolvimento Sustentável , China , Cidades , Desenvolvimento Econômico
14.
J Ethnopharmacol ; 291: 115007, 2022 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-35150815

RESUMO

ETHNOPHARMACOLOGY RELEVANCE: Polygonum capitatum Buch-Ham. ex D. Don (CNPC2009), a traditional Miao-national herbal medicine, has been widely used with considerable therapeutic efficacy in the treatment of various urologic disorders including prostatitis. However, the molecular mechanism of action (MOA) remains unclear. AIM OF THE STUDY: In this study, UPLC-Q-Exactive-MS and Network pharmacological methods were used to explore the underlying molecular MOA of Polygonum capitatum Buch-Ham. Ex D. Don (P.capitatum) for the treatment bacterial prostatitis (BP). MATERIALS AND METHODS: The UPLC-Q-Exactive-MS technique was used to identify the chemical components of P. capitatum. Databases such as SwissTargetPrediction, Gene Cards, and OMIM were used to predict the targets of P. capitatum for the treatment of BP. The Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) was used to analyze the protein-protein interaction (PPI) and construct a PPI network, and the Metascape was used for Gene Ontology (GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. In addition, experimental treatment of Escherichia coli (E.coli)-induced BP was verified. RESULTS: A total of 31 molecular components were identified by UPLC-Q-Exactive-MS. Network pharmacology revealed that P. capitatum may act on the AKT1, PI3K, MTO, EGFR and other targets through active components such as Gallic acid, Quercetin, Luteolin, Protocatechuic Acid, Kaempferol and thereby regulate PI3K-AKT, ErbB, AMPK, HIF-1, and other signaling pathways to intervene in the pathological mechanism of BP. Verification through experimental results showed that compared with the model group, treatment with P. capitatum could significantly inhibit bacterial growth in prostate tissues, lowered the prostate index, down-regulated the levels of inflammatory mediators(IL-1ß, IL-6, and TNF-α) in prostate tissues, and down-regulate the protein expression and mRNA expression levels of AKT and PI3K. CONCLUSION: This study preliminarily revealed the MOA of P. capitatum for treating BP with multiple components, multiple targets, and multiple pathways, especially affecting the PI3K-AKT signaling pathways.


Assuntos
Medicamentos de Ervas Chinesas , Polygonum , Prostatite , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Simulação de Acoplamento Molecular , Fosfatidilinositol 3-Quinases/metabolismo , Polygonum/química , Prostatite/tratamento farmacológico
15.
Asia Pac J Oncol Nurs ; 9(3): 167-173, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35494091

RESUMO

Objective: The aim of the study was to evaluate the effectiveness of palliative care simulations with standardized patients in improving the knowledge, skill performance, and critical thinking of newly hired oncology nurses. Methods: By convenience sampling, 59 newly hired oncology nurses in 2019 were enrolled as control group and 50 in 2020 as simulation group at a grade-A tertiary cancer hospital. Simulation group accepted theory (3 sessions) and simulation teaching includes three representative scenarios (6 sessions) in palliative care: pain management, special scenario communication, and turn over. Control group accepted traditional theory and skill teaching (9 sessions). Then both groups underwent four weeks clinical practice. The knowledge score was assessed by knowledge questionnaires, skill performance by standardized clinical evaluations, and critical thinking by the California Critical Thinking Disposition Inventory in both groups before and after intervention. The satisfaction of two groups was assessed by the learning satisfaction scale. Analysis of variance was conducted among the two groups by SPSS20.0. A difference was considered significant when P â€‹< â€‹0.05. Results: After intervention, the simulation group was significantly greater in knowledge of pain management (t â€‹= â€‹-7.560, P â€‹< â€‹0.001), and knowledge of special scenario communication (Z â€‹= â€‹5.031, P â€‹< â€‹0.001), as well as the skill score of turnover (Z â€‹= â€‹2.808, P â€‹= â€‹0.005) than the control group. The critical-thinking score was also significantly greater in the simulation group (Z â€‹= â€‹6.229, P â€‹< â€‹0.001). The simulation group had higher satisfaction (Z â€‹= â€‹5.144,P â€‹< â€‹0.001). Conclusions: Palliative care simulation with standardized patients can improve newly hired oncology nurses' knowledge, skill performance, and critical thinking and satisfaction of teaching. It would be an effective strategy to train newly hired oncology nurses.

16.
Bioengineered ; 13(1): 71-82, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34898361

RESUMO

The present study aimed to investigate the protective effects and molecular mechanisms of Dendrobium officinale polysaccharides on gastric mucosal injuries. Following one week of continuous intragastric administration, a gastric mucosal injury model was established using intragastric administration of anhydrous ethanol. The area of gastric ulcer was measured, the contents of interleukin- 6 (IL-6), epidermal growth factor receptor (EGFR), and thyroid transcription factor 1 (TFF-1) in serum were detected by enzyme linked immunosorbent assay (ELISA), and the expressions of EGFR, TFF-1, IL-6, Raf-2, MAP kinase kinase 1 (MEK1), MEK2, and ERK1 in the gastric tissue were determined utilizing qPCR, Western blotting and immunohistochemistry. Simultaneously, Dendrobium officinale polysaccharides and anhydrous ethanol were added to the gastric mucosal cells (GES1) cultured in vitro, and the protective effects of Dendrobium officinale polysaccharides on cell viability was detected using Cell Counting Kit (CCK)-8. The addition of Dendrobium officinale polysaccharides markedly improved the gastric epithelial defect, inflammatory cell infiltration, and redness and swelling stemmed from gastric mucosal injuries and greatly reduced the area of gastric ulcer. The inhibition rates of gastric ulcer were 48.12 ± 2.98, 42.95 ± 1.52, and 27.96 ± 2.05% in the high, medium, and low concentration Dendrobium officinale polysaccharide groups, respectively. Dendrobium officinale polysaccharides could increase the expressions of EGFR and TFF-1 and decrease the expressions of IL-6, Raf-2, MEK1, MEK2, and ERK1. Dendrobium officinale polysaccharides could reduce the level of inflammatory factors and protect gastric mucosa by inhibiting the expression of MAPK pathway genes and proteins.


Assuntos
Anti-Inflamatórios/administração & dosagem , Dendrobium/química , Etanol/efeitos adversos , Mucosa Gástrica/citologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Polissacarídeos/administração & dosagem , Úlcera Gástrica/tratamento farmacológico , Animais , Anti-Inflamatórios/farmacologia , Linhagem Celular , Sobrevivência Celular , Modelos Animais de Doenças , Mucosa Gástrica/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Genes erbB-1/efeitos dos fármacos , Humanos , Interleucina-6/metabolismo , Masculino , Extratos Vegetais , Polissacarídeos/farmacologia , Ratos , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patologia , Fator Trefoil-1/efeitos dos fármacos , Fator Trefoil-1/metabolismo
17.
Artigo em Inglês | MEDLINE | ID: mdl-34855586

RESUMO

Contextual information has been shown to be powerful for semantic segmentation. This work proposes a novel Context-based Tandem Network (CTNet) by interactively exploring the spatial contextual information and the channel contextual information, which can discover the semantic context for semantic segmentation. Specifically, the Spatial Contextual Module (SCM) is leveraged to uncover the spatial contextual dependency between pixels by exploring the correlation between pixels and categories. Meanwhile, the Channel Contextual Module (CCM) is introduced to learn the semantic features including the semantic feature maps and class-specific features by modeling the long-term semantic dependence between channels. The learned semantic features are utilized as the prior knowledge to guide the learning of SCM, which can make SCM obtain more accurate long-range spatial dependency. Finally, to further improve the performance of the learned representations for semantic segmentation, the results of the two context modules are adaptively integrated to achieve better results. Extensive experiments are conducted on four widely-used datasets, i.e., PASCAL-Context, Cityscapes, ADE20K and PASCAL VOC2012. The results demonstrate the superior performance of the proposed CTNet by comparison with several state-of-the-art methods. The source code and models are available at https://github.com/syp2ysy/CTNet.

18.
Molecules ; 26(24)2021 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-34946539

RESUMO

The well-known toxic medicine Gelsemium elegans is widely and historically used to treat bone fracture and skin ulcers by the folk people of China. Two new monoterpenoid indole alkaloids, gelselegandines D and E, together with the known analogue gelegamine A were isolated from G. elegans. Their structures were elucidated by means of spectroscopic techniques and quantum chemical calculations. All isolated compounds were tested for the effects on RANKL-induced osteoclast formation. Interestingly, gelselegandine E and gelegamine A, respectively, showed significant promoting and inhibitory activities on osteoclastogenesis, while gelselegandine D had no activity under the same concentration. This work suggested the different configurations for the carbons near the C-19/20 oxygen rings of the isolated compounds may be the key active groups on osteoclast formation and provided the evidence for the rationality as the traditional treatment for bone-related diseases of G. elegans.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Gelsemium/química , Osteoclastos/metabolismo , Alcaloides de Triptamina e Secologanina , Animais , Camundongos , Células RAW 264.7 , Alcaloides de Triptamina e Secologanina/química , Alcaloides de Triptamina e Secologanina/isolamento & purificação , Alcaloides de Triptamina e Secologanina/farmacologia
19.
Sensors (Basel) ; 21(21)2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34770487

RESUMO

This study presents a 2-D lidar odometry based on an ICP (iterative closest point) variant used in a simple and straightforward platform that achieves real-time and low-drift performance. With a designated multi-scale feature extraction procedure, the lidar cloud information can be utilized at multiple levels and the speed of data association can be accelerated according to the multi-scale data structure, thereby achieving robust feature extraction and fast scan-matching algorithms. First, on a large scale, the lidar point cloud data are classified according to the curvature into two parts: smooth collection and rough collection. Then, on a small scale, noise and unstable points in the smooth or rough collection are filtered, and edge points and corner points are extracted. Then, the proposed tangent-vector-pairs based on edge and corner points are applied to evaluate the rotation term, which is significant for producing a stable solution in motion estimation. We compare our performance with two excellent open-source SLAM algorithms, Cartographer and Hector SLAM, using collected and open-access datasets in structured indoor environments. The results indicate that our method can achieve better accuracy.

20.
Comput Intell Neurosci ; 2021: 6540972, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34824580

RESUMO

Expressway, as the main artery of urban traffic, realizes the smooth operation of the whole urban road network through reasonably balancing the traffic flow. However, due to the lack of reasonable and effective traffic control, the safety and congestion of expressways are becoming more and more serious. The development of intelligent network technology provides a new idea to solve the control problem of expressways. In this paper, a data-driven ramp control model of urban expressway is constructed. The interaction of traffic information is realized through intelligent network connection technology. The cooperative control strategy of VSL and RM is adopted. The mutual feedback of VSL and RM is realized based on the improved METANET model. The simulation experiment based on VISSIM secondary development shows that the collaborative control strategy under the intelligent network environment could make the vehicle travel time reduced by 20.59% and the speed difference between adjacent sections of the expressway mainline by 34.07%, which realized the coordinated control of the mainline and the on-ramp under the intelligent network environment, alleviate the expressway traffic congestion, reduce the traffic pressure, and improve the efficiency of the road network.


Assuntos
Acidentes de Trânsito , Condução de Veículo , Simulação por Computador
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