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1.
Opt Express ; 29(17): 27481-27492, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34615163

RESUMO

We propose a novel coherent analog radio over fiber (A-RoF) scheme to realize the generation, separation, and detection of four-independent mm-wave signals with the same carrier frequency on a single-wavelength for 5th generation (5G) mobile communication, and no digital signal processing (DSP) algorithms are required in remote antenna unit (RAU). In baseband unit (BBU), four-independent mm-wave signals are modulated on the two orthogonal polarization states of a single wavelength based on a dual-polarization IQ modulator using the dual single-sideband (SSB) modulation and polarization division multiplexing (PDM) technique. In RAU, a novel carrier polarization rotation module based on the self-polarization stabilization technique is proposed, and thus the four-independent mm-wave signals can be detected by self-coherent detection. Besides, the power fading effect induced by the chromatic dispersion could be overcome thanks to the optical SSB modulation, contributing to the increased coverage. By these means, no DSP algorithms are required in RAU, and the latency of signal processing could be significantly reduced. The experimental results show our proposed scheme could support 38.4 Gbps 16-ary quadrature amplitude modulation (16QAM) signals at 14 GHz over 30 km standard single-mode fiber (SSMF) transmission without DSP, satisfying 3rd Generation Partnership Project (3GPP) requirements. Besides, the measured error vector magnitude (EVM) value of 800 MBaud 16QAM signals at 28 GHz over 50 km SSMF transmission is 12.99%. This research provides a potential solution for the 5G mobile fronthaul.

2.
Plant Physiol Biochem ; 167: 771-784, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34530322

RESUMO

Bud endodormancy is accompanied by transport channel apertures blockage through callose deposition, and its resume to growth requires evoking ß-1,3-glucanases (BGs) to unchoke the conduit. To understand out its working manner, the statuses of the transport channels were evaluated and candidate BGs were identified during chilling and gibberellin acids (GA) induced dormancy release in tree peony. Calcein reflects plasmodesmata permeability, and no calcein was observed in the bud together with density aniline blue fluorescent around the stem phloem at 0 d chilling. With the increase of chilling accumulation, the contents of glucan declined and the activities of gulcanase increased gradually in buds, and the calcein reached the top of flower primordia at 21 d chilled bud. Both GA3 and GA4 feedings promoted bud sprouting and growth along with rapidly unchoking the transport channels, and GA3 was more effective. Several candidate ß-1,3-glucanase genes were detected, combining transcriptional profiling and quantitative PCR analysis. PsBG1, PsBG3, PsBG6, PsBG8 and PsBG9 were inducible by chilling accumulation and presented laminarin hydrolyzing activities after prokaryotically expression, while PsBG1, PsBG3, PsBG8 and PsBG9 responded to GAs application. Subcellular localizations revealed that PsBG6 and PsBG9 were plasmodesmata residents. It was concluded that PsBG6 played a vital role in chilling accumulation response and PsBG9 was central in GAs-induced dormancy release, and they could be used as marker genes for dormancy release in tree peony. These results were of great value to understand the mechanism of dormancy regulation and as an important fundamental for forcing culture technology in tree peony.


Assuntos
Giberelinas , Paeonia , Flores , Regulação da Expressão Gênica de Plantas , Árvores
3.
J Pharm Pharmacol ; 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34559879

RESUMO

OBJECTIVES: Nowadays, one of the most common gastrointestinal cancers is colorectal cancer (CRC). Chemotherapy is still one of the main methods to treat cancer. However, the currently available synthetic chemotherapy drugs often cause serious adverse reactions. Apoptosis is generally considered as an ideal way for induction the death of tumour cells without the body's inflammatory response, and it is reported that lots of natural agents could trigger various cancer cells to apoptosis. The overarching aim of this project was to elucidate the specific mechanisms by which natural substances induce apoptosis in CRC cells and to be used as an alternative therapeutic option in the future. KEY FINDINGS: The mechanisms for the pro-apoptotic effects of natural substances derived from herbs or plants include death receptor pathway, mitochondrial pathway, endoplasmic reticulum stress pathway, related signal transduction pathways (PI3K/Akt, MAPK, p53 signalling), and so on. SUMMARY: This paper updated this information regarding the anti-tumour effects of natural agents via induction of apoptosis against CRC, which would be beneficial for future new drug research regarding natural products from herbs or plants.

4.
Cancer Med ; 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34562306

RESUMO

The role of B7-H3 in acute myeloid leukemia (AML) is not fully understood. Two previous studies investigating its expression and significances in AML are partially different. In this study, we aimed to systematically characterize the genomic and immune landscape in AML patients with altered B7-H3 expression using multi-omics data in the public domain. We found significantly increased B7-H3 expression in AML compared to either other hematological malignancies or healthy controls. Clinically, high B7-H3 expression was associated with old age, TP53 mutations, wild-type WT1 and CEBPA, and the M3 and M5 FAB subtypes. Moreover, we observed that increased B7-H3 expression correlated significantly with a poor outcome of AML patients in four independent datasets. Gene set enrichment analysis (GSEA) revealed the enrichment of the "EMT" oncogenic gene signatures in high B7-H3 expressers. Further investigation suggested that B7-H3 was more likely to be associated with immune-suppressive cells (macrophages, neutrophils, dendritic cells, and Th17 cells). B7-H3 was also positively associated with a number of checkpoint genes, such as VISTA (B7-H5), CD80 (B7-1), CD86 (B7-2), and CD70. In summary, we uncovered distinct genomic and immunologic features associated with B7-H3 expression in AML. This may lead to a better understanding of the molecular mechanisms underlying B7-H3 dysregulation in AML and to the development of novel therapeutic strategies.

5.
BMC Neurol ; 21(1): 350, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34517833

RESUMO

BACKGROUND: Asymptomatic carotid artery stenosis (aCAS) impairs haemodynamic and cognitive functions; however, the relationship between these changes and brain network connectivity remains largely unknown. This study aimed to determine the relationship between functional connectivity and neurocognition in patients with aCAS. METHODS: We compared functional status in 14 patients with aCAS and 15 healthy controls using resting state functional magnetic resonance imaging sequences. The subjects underwent a full range of neuropsychological tests and a graphical theoretical analysis of their brain networks. RESULTS: Compared with controls, patients with aCAS showed significant decline in neuropsychological functions, particularly short-term memory (word-memory, p = .046 and picture-memory, p = .014). Brain network connectivity was lower in patients with aCAS than in the controls, and the decline of functional connectivity in aCAS patients was mainly concentrated in the left and right inferior frontal gyri, temporal lobe, left cingulate gyrus, and hippocampus. Decreased connectivity between various brain regions was significantly correlated with impaired short-term memory. Patients with aCAS showed cognitive impairment independent of known vascular risk factors for vascular cognitive impairment. The cognitive defects were mainly manifested in the short-term memory of words and pictures. CONCLUSIONS: This study is the first of its kind to identify an association between disruption of functional connections in left carotid stenosis and impairment of short-term memory. The findings suggest that alterations in network connectivity may be an essential mechanism underlying cognitive decline in aCAS patients. CLINICAL TRIAL REGISTRATION-URL: Unique identifier: 04/06/2019, ChiCTR1900023610 .


Assuntos
Estenose das Carótidas , Disfunção Cognitiva , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Estenose das Carótidas/complicações , Estenose das Carótidas/diagnóstico por imagem , Estudos de Casos e Controles , Cognição , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Humanos , Imageamento por Ressonância Magnética , Memória de Curto Prazo , Testes Neuropsicológicos
6.
Brief Bioinform ; 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34477201

RESUMO

Combination therapy has shown an obvious efficacy on complex diseases and can greatly reduce the development of drug resistance. However, even with high-throughput screens, experimental methods are insufficient to explore novel drug combinations. In order to reduce the search space of drug combinations, there is an urgent need to develop more efficient computational methods to predict novel drug combinations. In recent decades, more and more machine learning (ML) algorithms have been applied to improve the predictive performance. The object of this study is to introduce and discuss the recent applications of ML methods and the widely used databases in drug combination prediction. In this study, we first describe the concept and controversy of synergism between drug combinations. Then, we investigate various publicly available data resources and tools for prediction tasks. Next, ML methods including classic ML and deep learning methods applied in drug combination prediction are introduced. Finally, we summarize the challenges to ML methods in prediction tasks and provide a discussion on future work.

7.
Opt Lett ; 46(17): 4366-4369, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34470016

RESUMO

An asymmetric dual-single-sideband (SSB) modulation scheme for photonic co-frequency millimeter (mm)-wave signals generation and digital signal processing (DSP)-free receiver is experimentally demonstrated for the first time, to the best of our knowledge. To effectively avoid the sideband crosstalk in the traditional symmetric dual-SSB modulation scheme, not only two vector-modulated signals but also two unmodulated sidebands are modulated on the two asymmetric sides of an optical carrier in this scheme. An optical delay line interferometer could easily separate these two asymmetric dual-SSB signals simultaneously in the receiver, and thus the photonic frequency up-conversion is realized. Besides, this scheme is free of dispersion-induced RF power fading thanks to the SSB modulation. By this means, no digital compensation algorithms such as carrier phase recovery, fiber dispersion compensation, and channel equalization are required, contributing to the DSP-free receiver. In our experiment, two 32 GHz 3.2 Gb/s 16-ary quadrature amplitude modulation mm-wave signals are produced using two RF signals with the carrier frequencies of 12 GHz and 20 GHz. The error vector magnitude (EVM) performances of these two mm-wave signals after 25.5 km standard single-mode fiber transmission are better than 3rd Generation Partnership Project requirements without using any digital compensation algorithms.

8.
Front Microbiol ; 12: 712886, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34497594

RESUMO

Minimal inhibitory concentration (MIC) is defined as the lowest concentration of an antimicrobial agent that can inhibit the visible growth of a particular microorganism after overnight incubation. Clinically, antibiotic doses for specific infections are determined according to the fraction of MIC. Therefore, credible assessment of MICs will provide a physician valuable information on the choice of therapeutic strategy. Early and precise usage of antibiotics is the key to an infection therapy. Compared with the traditional culture-based method, the approach of whole genome sequencing to identify MICs can shorten the experimental time, thereby improving clinical efficacy. Klebsiella pneumoniae is one of the most significant members of the genus Klebsiella in the Enterobacteriaceae family and also a common non-social pathogen. Meropenem is a broad-spectrum antibacterial agent of the carbapenem family, which can produce antibacterial effects of most Gram-positive and -negative bacteria. In this study, we used single-nucleotide polymorphism (SNP) information and nucleotide k-mers count based on metagenomic data to predict MICs of meropenem against K. pneumoniae. Then, features of 110 sequenced K. pneumoniae genome data were combined and modeled with XGBoost algorithm and deep neural network (DNN) algorithm to predict MICs. We first use the XGBoost classification model and the XGBoost regression model. After five runs, the average accuracy of the test set was calculated. The accuracy of using nucleotide k-mers to predict MICs of the XGBoost classification model and XGBoost regression model was 84.5 and 89.1%. The accuracy of SNP in predicting MIC was 80 and 81.8%, respectively. The results show that XGBoost regression is better than XGBoost classification in both nucleotide k-mers and SNPs to predict MICs. We further selected 40 nucleotide k-mers and 40 SNPs with the highest correlation with MIC values as features to retrain the XGBoost regression model and DNN regression model. After 100 and 1,000 runs, the results show that the accuracy of the two models was improved. The accuracy of the XGBoost regression model for k-mers, SNPs, and k-mers & SNPs was 91.1, 85.2, and 91.3%, respectively. The accuracy of the DNN regression model was 91.9, 87.1, and 91.8%, respectively. Through external verification, some of the selected features were found to be related to drug resistance.

9.
Front Genet ; 12: 696892, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34367254

RESUMO

Although it is recognized that cadmium (Cd) causes renal tubular dysfunction, the mechanism of Cd-induced nephrotoxicity is not yet fully understood. Mode of action (MOA) is a developing tool for chemical risk assessment. To establish the mechanistic MOA of Cd-induced renal tubular dysfunction, the Comparative Toxicogenomics Database (CTD) was used to obtain genomics data of Cd-induced nephrotoxicity, and Ingenuity® Pathway Analysis (IPA) software was applied for bioinformatics analysis. Based on the perturbed toxicity pathways during the process of Cd-induced nephrotoxicity, we established the MOA of Cd-induced renal tubular dysfunction and assessed its confidence with the tailored Bradford Hill criteria. Bioinformatics analysis showed that oxidative stress, DNA damage, cell cycle arrest, and cell death were the probable key events (KEs). Assessment of the overall MOA of Cd-induced renal tubular dysfunction indicated a moderate confidence, and there are still some evidence gaps to be filled by rational experimental designs.

10.
BMC Cancer ; 21(1): 918, 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34388989

RESUMO

BACKGROUND: Breast cancer (BC) is a complex disease with high heterogeneity, which often leads to great differences in treatment results. Current common molecular typing method is PAM50, which shows positive results for precision medicine; however, room for improvement still remains because of the different prognoses of subtypes. Therefore, in this article, we used lncRNAs, which are more tissue-specific and developmental stage-specific than other RNAs, as typing markers and combined single-cell expression profiles to retype BC, to provide a new method for BC classification and explore new precise therapeutic strategies based on this method. METHODS: Based on lncRNA expression profiles of 317 single cells from 11 BC patients, SC3 was used to retype BC, and differential expression analysis and enrichment analysis were performed to identify biological characteristics of new subtypes. The results were validated for survival analysis using data from TCGA. Then, the downstream regulatory genes of lncRNA markers of each subtype were searched by expression correlation analysis, and these genes were used as targets to screen therapeutic drugs, thus proposing new precision treatment strategies according to the different subtype compositions of patients. RESULTS: Seven lncRNA subtypes and their specific biological characteristics are obtained. Then, 57 targets and 210 drugs of 7 subtypes were acquired. New precision medicine strategies were proposed according to the different compositions of patient subtypes. CONCLUSIONS: For patients with different subtype compositions, we propose a strategy to select different drugs for different patients, which means using drugs targeting multi subtype or combinations of drugs targeting a single subtype to simultaneously kill different cancer cells by personalized treatment, thus reducing the possibility of drug resistance and even recurrence.


Assuntos
Biomarcadores Tumorais , Neoplasias da Mama/genética , Heterogeneidade Genética , RNA Longo não Codificante/genética , Análise de Célula Única , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Tomada de Decisão Clínica , Biologia Computacional/métodos , Gerenciamento Clínico , Feminino , Perfilação da Expressão Gênica/métodos , Predisposição Genética para Doença , Humanos , Medicina de Precisão/métodos , Prognóstico , Análise de Célula Única/métodos
11.
Biosensors (Basel) ; 11(7)2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34356713

RESUMO

Uric acid, as the terminal product of purine metabolism in the body, is an important marker of many diseases. Uric acid is abundant in saliva, offering the possibility of its non-invasive detection. However, it is sensitive to interference in saliva by a variety of factors. A reliable method of processing saliva is centrifugation (CF), but the cost and size of equipment limit its use in everyday life. In this study, a novel portable salivary-sensing system (PSSS) with integrated suction filtration (SF) and temperature insulation was proposed to obtain more accurate salivary uric acid levels through a simple procedure. The PSSS includes a saliva container, a high-sensitive uric acid sensor (UAS), an accompanying printed circuit board (PCB), and a mobile application. The responses produced by the UAS presents excellent linearity (4.6 µA/mM with R2 = 0.9964), selectivity, reproducibility, and stability for the detection of low levels of uric acid. The difference in detection values between the UAS and the commercial sensor is only ~4%. The primary feature of the saliva container is the processing of saliva by SF instead of CF. Samples from CF and SF showed no significant differences regarding uric acid levels, and both exhibited approximately 50% deviation from the untreated samples, while the difference in uric acid levels between the samples after SF and after applying both treatments was ~10%. Besides, insulation of the saliva container can partially eliminate sources of error induced by the environment during uric acid level testing. The PSSS provides a novel strategy for the immediate detection of specific markers in saliva. We believe that the PSSS has promising potential for future application in the rapid saliva testing.


Assuntos
Técnicas Biossensoriais , Saliva/química , Ácido Úrico , Biomarcadores , Humanos , Reprodutibilidade dos Testes
12.
Nutrients ; 13(8)2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34444902

RESUMO

BACKGROUND AND AIMS: Muscle mass reduction (MMR) is one of the three etiologic criteria in the Global Leadership Initiative on Malnutrition (GLIM) framework. This study aimed to evaluate the value of MMR in GLIM criteria among ambulatory cancer patients. METHODS: A single-center prospective cross-sectional study was conducted. All participants underwent calf circumference (CC) measurement and body composition measurement by bioelectrical impedance analysis (BIA). MMR was identified by CC, fat-free mass index (FFMI), appendicular skeletal muscle index (ASMI), or combinations of the above three indicators. Patients-generated Subjective Global Assessment (PG-SGA) was used as the comparator. RESULTS: A total of 562 cancer patients receiving intravenous treatment were evaluated. Of the participants, 62.8% (355/562) were male. The median age of the patients was 59.0 years (range, 21-82 y). The median BMI was 22.8 kg/m2 (range, 14.6-34.5 kg/m2). A total of 41.8% of patients were evaluated as malnutrition (PG-SGA ≥ 4), and 11.9% were diagnosed with severe malnutrition (PG-SGA ≥ 9). For the GLIM criteria, the prevalence of malnutrition was 26.9%, and severe malnutrition was 12.3%. For all criteria combinations of GLIM together versus PG-SGA, sensitivity was 60.4% (53.8-66.7), specificity was 97.9% (95.4-99.1), while the accordance between GLIM and PG-SGA was moderate (κ = 0.614). The performance of the GLIM worsened when MMR was excluded (κ = 0.515), with reduced sensitivity (50.2% (43.7-56.8)) and the same specificity (97.9% (95.4-99.1)). Including FFMI and ASMI by BIA can further improve the performance of GLIM than using CC alone (κ = 0.614 vs. κ = 0.565). CONCLUSIONS: It is important to include MMR in the GLIM framework. Using body composition measurement further improves the performance of the GLIM criteria than using anthropometric measurement alone.


Assuntos
Antropometria , Composição Corporal , Desnutrição/diagnóstico , Neoplasias/fisiopatologia , Avaliação Nutricional , Adulto , Idoso , Assistência Ambulatorial/estatística & dados numéricos , Estudos Transversais , Impedância Elétrica , Feminino , Humanos , Masculino , Desnutrição/etiologia , Pessoa de Meia-Idade , Músculo Esquelético/fisiopatologia , Neoplasias/complicações , Estado Nutricional , Estudos Prospectivos , Reprodutibilidade dos Testes , Adulto Jovem
13.
ACS Sens ; 6(8): 3112-3124, 2021 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-34347450

RESUMO

Infection, the most common complication of chronic wounds, has placed tremendous burden on patients and society. Existing care strategies could hardly reflect in situ wound status, resulting in overly aggressive or conservative therapeutic options. Multiplexed tracking of wound markers to obtain diagnostic information in a more accurate way is highly promising and in great demand for the emerging development of personalized medicine. Here, an integrated multiplex sensing bandage (MSB) system, including a multiplex sensor array (MSA), a corresponding flexible circuit, and a mobile application, was developed for real-time monitoring of sodium, potassium, calcium, pH, uric acid, and temperature indicators in the wound site to provide a quantitative diagnostic basis. The MSB was optimized for wound-oriented management applications, which exhibits a broad linear response, excellent selectivity, temporal stability, mechanical stability, reproducibility, and reliable signal transmission performance on the aforementioned physiological indicators. The results of in vivo experiments demonstrate that the MSA is capable of real-time monitoring of actual wounds as well as early prediction of infection. The results ultimately point to the potential clinical applicability of the MSB, which might benefit the quantifications of the complexity and diversity of the wound healing process. This work provides a unique strategy that holds promise for broad application in optimizing wound management and even coping with other diseases.


Assuntos
Bandagens , Ácido Úrico , Humanos , Reprodutibilidade dos Testes
14.
Sheng Wu Gong Cheng Xue Bao ; 37(7): 2232-2239, 2021 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-34327891

RESUMO

The development and progression of most cancers have been well recognized as the result of highly activated cell cycle. Cyclin dependent kinase 4/6 plays important roles not only in mitosis, but also in multiple biological processes that contribute to cancer development, such as aging, apoptosis and histone modification. Three FDA approved CDK4/6 inhibitors, Palbociclib, Ribociclib and Abemaciclib, have been used as targeted cancer therapeutic agents to benefit patients with endocrine therapy-resistant breast cancer and other types of cancer, prolonging their survival. However, the clinical application of these inhibitors also leads to acquired drug resistance and other problems. This paper reviews the regulatory roles of CDK4/6, the application of CDK4/6 inhibitors in cancer and the challenge of drug resistance.


Assuntos
Neoplasias da Mama , Quinase 6 Dependente de Ciclina , Quinase 4 Dependente de Ciclina/uso terapêutico , Quinase 6 Dependente de Ciclina/uso terapêutico , Feminino , Humanos , Terapia de Alvo Molecular , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Transdução de Sinais
15.
J Dent Sci ; 16(3): 937-947, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34141108

RESUMO

Background/purpose: Relieving immuno-inflammatory responses is the prerequisite step for treating periodontitis. The angiogenic small molecule, dimethyloxalylglycine (DMOG), and osteoinductive inorganic nanomaterial, nanosilicate (nSi) have a powerful effect on bone regeneration, whereas the roles in osteoimmunomodulation have not been totally uncovered. Our study aimed to explore the immunomodulatory effect of DMOG/nSi-loaded fibrous membranes on periodontal bone remodeling. Materials and methods: The fibrous membranes were prepared by incorporating DMOG and nSi into poly (lactic-co-glycolic acid) (PLGA) with electrospinning. The morphology features, surface chemical property and biocompatibility of DMOG/nSi-PLGA fibrous membranes were characterized. Thereafter, the fibrous membranes were implanted into rat periodontal defects, bone remodeling potential and immunomodulatory effect were evaluated by micro-computed tomography (micro-CT), histological evaluation and immunohistochemical analysis. Results: DMOG/nSi-PLGA membranes possessed favorable physicochemical properties and biocompatibility. After the fibrous membranes implanted into periodontal defects, DMOG/nSi-PLGA membranes could relieve immuno-inflammatory responses of the defects (reduction of inflammatory cell infiltration, CD40L and CD11b-positive cells), increased CD206-positive M2 macrophages, and eventually facilitated periodontal bone regeneration. Conclusion: DMOG/nSi-PLGA fibrous membranes exert protective effects during periodontal bone defect repairing, and steer immune response towards bone regeneration. Consequently, DMOG/nSi-PLGA fibrous membranes may serve as a promising scaffold in periodontal tissue engineering.

16.
Toxicology ; 458: 152838, 2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34153373

RESUMO

N,N-dimethylformamide (DMF) is an organic compound widely used in industrial production processes as a solvent with a low evaporation rate. Excessive exposure to DMF may lead to liver damage. Oxidative stress has been reported as one of the main causes of DMF-induced hepatotoxicity. Several doses of DMF (0, 1, 5, and 10 mM) were used to treat HL-7702 cells for a relatively long period to simulate the actual exposure pattern in occupational settings, and oxidative stress was induced. Previous studies illustrated that circular RNA (circRNA) plays a vital role in sustaining hepatocyte physiological function. To explore whether aberrant circRNA expression is involved in DMF-induced excessive ROS generation and hepatotoxicity, high-throughput transcriptional sequencing was performed to identify the altered circRNA expression profiles in HL-7702 liver cells after treatment with 0, 75, or 150 mM DMF for 48 h. We found that levels of induced oxidative stress were similar to those in the long-term exposure model. Among the altered circRNAs, one circRNA (hsa_circ_0005915) was significantly upregulated after DMF exposure, and it affected DMF-mediated oxidative stress in HL-7702 cells. Further experiments revealed that hsa_circ_0005915 downregulated the expression of nuclear factor erythoid-2-related factor 2 (NRF2) at the post-transcriptional level via promoting the ubiquitination and degradation of NRF2, which led to the increase of ROS accumulation. Further investigation demonstrated that the expression levels of NRF2-regulated antioxidative genes-heme oxygenase 1 (HO1) and NAD(P)H quinone dehydrogenase 1 (NQO1)-indeed declined after the overexpression of hsa_circ_0005915. In vivo study also indicated that DMF exposure can upregulate the expression of mmu_circ_0007941 (homologous circRNA of hsa_circ_0005915) and downregulated Nrf2 and Ho1 proteins. In summary, our results revealed that hsa_circ_0005915 plays an important role in promoting DMF-induced oxidative stress by inhibiting the transcriptional activity of the NRF2/ARE axis, which provides a potential molecular mechanism of DMF-mediated hepatotoxicity.


Assuntos
Dimetilformamida/toxicidade , Fator 2 Relacionado a NF-E2/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , RNA Circular/genética , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Heme Oxigenase-1/metabolismo , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , MicroRNAs , NAD(P)H Desidrogenase (Quinona)/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima
17.
BMC Neurosci ; 22(1): 35, 2021 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-33980154

RESUMO

BACKGROUND: Asymptomatic Moyamoya disease (MMD) impairs hemodynamic and cognitive function. The relationship between these changes, cerebral blood flow (CBF), and network connectivity remains largely unknown. The aim of this study was to increase understanding of the relationship between CBF, functional networks, and neurocognition in adults with asymptomatic MMD. We compared CBF and functional status in 26 patients with MMD and 20 healthy controls using arterial spin labeling and resting state functional magnetic resonance imaging sequences. At the same time, a detailed cognitive test was performed in 15 patients with no cerebral or lumen infarction who were selected by magnetic resonance imaging-T2 FLAIR screening. RESULTS: Compared to the controls, the patients showed varying degrees of decline in their computational ability (simple subtraction, p = 0.009; complex subtraction, p = 0.006) and short-term memory (p = 0.042). The asymptomatic MMD group also showed decreased CBF in the left anterior central and left inferior frontal gyri of the island flap with multiple node abnormalities in the brain network and reduced network connectivity. There was a significant association of these changes with cognitive decline in the MMD group. CONCLUSIONS: In patients with asymptomatic MMD, disturbance of CBF and impaired brain network connections may be important causes of cognitive decline and appear before clinical symptoms. Clinical trial registration-URL: http://www.chictr.org.cn Unique identifier: ChiCTR1900023610.

18.
J Hazard Mater ; 417: 125985, 2021 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-33984784

RESUMO

Elucidating the enantiomeric chemistry and enantioselective fate of the novel chiral triazole fungicide mefentrifluconazole is of vital importance for agroecosystem safety and human health. The absolute configuration of mefentrifluconazole was identified firstly as S-(+)-mefentrifluconazole and R-(-)-mefentrifluconazole on a cellulose tris(3-chloro-4-methylphenylcarbamate) chiral phase. A baseline resolution (Rs, 2.51), favorable retention (RT ≤ 2.24 min), and high sensitivity (LOQ, 0.5 µg/kg) of enantiomer pair were achieved by reversed-phase liquid chromatography tandem mass spectrometry combined with a 3D response surface strategy. Nationwide field trials were undertaken to clarify the enantiomer occurrence, enantioselective dissipation, terminal concentrations, and storage stability of S-mefentrifluconazole and R-mefentrifluconazole in watermelon across China. The original deposition of the sum of enantiomer pair was estimated to be 14.4-163.7 µg/kg, and terminally decreased to < LOQ-59.3 µg/kg 10 days after foliage application. S-mefentrifluconazole preferentially degraded (T1/2, 3.3-6.0 days), resulting in the relative enrichment of R-mefentrifluconazole (T1/2, 3.9-6.6 days) in watermelon. A probabilistic model is recommended for the dietary risk assessment, although both acute (%ARfD, 0.435-22.188%) and chronic (%ADI, 1.697-9.658%) risks are acceptable for associated population. The long-term exposures should be continuously emphasized given the increasing applications and persistent fate of mefentrifluconazole, especially for urban children.


Assuntos
Citrullus , Fungicidas Industriais , Criança , China , Cromatografia Líquida de Alta Pressão , Fluconazol/análogos & derivados , Fungicidas Industriais/análise , Fungicidas Industriais/toxicidade , Humanos , Medição de Risco , Estereoisomerismo
19.
Dalton Trans ; 50(16): 5473-5482, 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33908948

RESUMO

In this report, we demonstrate a bimetallic Co/Cu-embedded N-doped carbon structure for trifunctional catalysis of oxygen reduction, oxygen evolution and hydrogen evolution reactions in alkaline media. A hybrid catalyst synthesized through a metal-organic framework-based process (M-NC-CoCu) enables an active trifunctional catalysis due to its multi-faceted favorable characteristics. It is believed that a range of catalytically active sites are formed through the approach including well-dispersed tiny CuCo2O4 phases, a high concentration of pyridinic and graphitic N, and Cu-Ox, Cu-Nx and Co-Nx moieties. In addition, a high-surface-area morphology with a high concentration of sp2 bonding, which is beneficial for facilitated electron conduction, further contributes to the performance as an electrocatalyst.

20.
Food Microbiol ; 98: 103785, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33875213

RESUMO

Cronobacter sakazakii is an emerging opportunistic foodborne pathogen causing rare but severe infections in neonates. Furthermore, the formation of biofilm allows C. sakazakii to persist in different environments. We have demonstrated that the mutator phenotype ascribed to deficiency of the pmrA gene results in more biomass in the first 24 h but less during the post maturation stage (7-14 d) compared with BAA 894. The present study aimed to investigate the regulatory mechanism modulating biofilm formation due to pmrA mutation. The transcriptomic analyses of BAA 894 and s-3 were performed by RNA-sequencing on planktonic and biofilm cells collected at different time points. According to the results, when comparing biofilm to planktonic cells, expression of genes encoding outer membrane proteins, lysozyme, etc. were up-regulated, with LysR family transcriptional regulators, periplasmic proteins, etc. down-regulated. During biofilm formation, cellulose synthase operon genes, flagella-related genes, etc. played essential roles in different stages. Remarkably, pmrA varies the expression of a number of genes related to motility, biofilm formation, and antimicrobial resistance, including srfB, virK, mviM encoding virulence factor, flgF, fliN, etc. encoding flagellar assembly, and marA, ramA, etc. encoding AraC family transcriptional regulators in C. sakazakii. This study provides valuable insights into transcriptional regulation of C. sakazakii pmrA mutant during biofilm formation.


Assuntos
Proteínas de Bactérias/metabolismo , Biofilmes , Cronobacter sakazakii/genética , Plâncton/genética , Transcriptoma , Proteínas de Bactérias/genética , Cronobacter sakazakii/crescimento & desenvolvimento , Cronobacter sakazakii/fisiologia , Regulação Bacteriana da Expressão Gênica , Plâncton/crescimento & desenvolvimento , Plâncton/fisiologia , Transcrição Genética , Fatores de Virulência/genética , Fatores de Virulência/metabolismo
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