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1.
Int J Biol Macromol ; 180: 203-211, 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33737177

RESUMO

African swine fever virus (ASFV), a re-emerging DNA virus, causes a highly contagious disease for domestic pigs. It is running rife worldwide and threatening the global swine industry. Protein p54 is an attractive candidate for ASFV diagnostic and vaccine design. In this work, we designed a peptide to mimic the N-terminal domain (NTD) of ASFV p54 and pretested it with sera from ASFV-infected pigs. The peptide could be well recognized by the sera, implying that the NTD of p54 contained some potential linear B cell epitopes. Then, the conjugates of the peptide with bovine serum albumin were used as the immunogen to generate monoclonal antibodies (mAbs). A total of six mAbs specific to the NTD of ASFV p54 protein were developed. Five of them well reacted with ASFV HLJ/18 strain and recognized a same linear B cell epitope 5FFQPV9. Furthermore, epitope 5FFQPV9 could be well recognized by ASFV-positive sera from natural infected pigs, suggesting that it was a natural linear B-cell epitope. Conservation analysis indicated that epitope 5FFQPV9 were highly conserved among ASFV epidemic isolates belonging to genotype I and II. Alanine-scanning mutagenesis further revealed that the residues (6F to 9V) of epitope 5FFQPV9 were the core binding sites for antibody recognition. This is the first research to characterize specific mAbs against NTD of p54 protein. These findings may help further understand the function of p54 protein and the improvement of ASFV diagnosis.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33784216

RESUMO

Arsanilic acid (ASA) residue, which is the most common contaminant in edible animal tissues such as pork and liver, has caused environmental and food-safety concerns. In this study, direct and indirect competitive fluorescence-linked immunosorbent assays (dc-FLISA and ic-FLISA) incorporating quantum dots (QDs) as the fluorescent label were developed for the first time to detect ASA residues in edible pork and animal liver. Monoclonal antibodies against ASA and rabbit anti-mouse antibody were conjugated to orange QDs with excitation wavelengths at 450 nm, and the QD-Abs served as detection probes. The limits of detection for dc-FLISA and ic-FLISA were 0.11 ng/mL and 0.001 ng/mL, respectively. QD-FLISA was used to analyse spiked samples; recoveries ranged from 80.2%-91.2% in dc-FLISA and 82.5%-91.2% in ic-FLISA, and the coefficients of variations (CV) were less than 12%. Compared with conventional indirect competitive enzyme-linked immunosorbent assay (ic-ELISA), the QD-FLISA described here was more sensitive and accurate in the analysis of ASA residues in animal tissues. Moreover, the results of QD-FLISA correlated well with HPLC. These results indicate that dc-FLISA and ic-FLISA are sensitive and reliable for detection of ASA residues in edible animal tissues.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33651148

RESUMO

BACKGROUND: Cellular immunity against tumor cells is highly dependent on antigen presentation by major histocompatibility complex class I (MHC-I) molecules. However, few published studies have investigated associations between functional variants of MHC-I-related genes and clinical outcomes of lung cancer patients. METHODS: We performed a two-phase Cox proportional hazards regression analysis by using two previously published genome-wide association studies to evaluate associations between genetic variants in the MHC-I-related gene set and the survival of non-small cell lung cancer (NSCLC) patients, followed by expression quantitative trait loci analysis. RESULTS: Of the 7811 single-nucleotide polymorphisms (SNPs) in 89 genes of 1185 NSCLC patients in the discovery dataset of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, 24 SNPs remained statistically significant after validation in additional 984 NSCLC patients from the Harvard Lung Cancer Susceptibility Study. In a multivariate stepwise Cox model, three independent functional SNPs (ERAP1 rs469783 T > C, PSMF1 rs13040574 C > A and NCF2 rs36071574 G > A) remained significant with an adjusted hazards ratio (HR) of 0.83 [95% confidence interval (CI) = 0.77-0.89, P = 8.0 × 10-7], 0.86 (0.80-0.93, P = 9.4 × 10-5) and 1.31 (1.11-1.54, P = 0.001) for overall survival (OS), respectively. Further combined genotypes revealed a poor survival in a dose-response manner in association with the number of unfavorable genotypes (Ptrend < 0.0001 and 0.0002 for OS and disease-specific survival, respectively). Also, ERAP1 rs469783C and PSMF1 rs13040574A alleles were associated with higher mRNA expression levels of their genes. CONCLUSION: These potentially functional SNPs of the MHC-I-related genes may be biomarkers for NSCLC survival, possibly through modulating the expression of corresponding genes.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33667148

RESUMO

The direct and indirect competitive fluorescence-linked immunosorbent assay (FLISA and icFLISA) incorporating quantum dots (QDs) for the detection of fleroxacin (FLE) was established for the first time in this study. The monoclonal antibody specific for FLE was successfully conjugated with QDs after purification by the caprylic acid-ammonium sulphate method. The limits of detection of FLISA and icFLISA were 0.012 ng/mL and 0.006 ng/mL, respectively; IC50 were 0.32 ng/mL and 0.19 ng/mL; and the detection ranges were 0.012-24.490 ng/mL and 0.006-16.210 ng/mL. The recovery was 93.8%-112.4% and the coefficient of variation was below 11.75%. The fabricated FLISA and icFLISA are cost-effective, high sensitive and can be an alternative method in the detection of FLE residues.

5.
BMC Infect Dis ; 21(1): 146, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33546618

RESUMO

BACKGROUND: In December 2019, a pneumonia caused by SARS-CoV-2 emerged in Wuhan, China and has rapidly spread around the world since then. This study is to explore the patient characteristics and transmission chains of COVID-19 in the population of Gansu province, and support decision-making. METHODS: We collected data from Gansu Province National Health Information Platform. A cross-sectional study was conducted, including patients with COVID-19 confirmed between January 23 and February 6, 2020, and analyzed the gender and age of the patients. We also described the incubation period, consultation time and sources of infection in the cases, and calculated the secondary cases that occurred within Gansu for each imported case. RESULTS: We found thirty-six (53.7%) of the patients were women and thirty-one (46.3%) men, and the median ages were 40 (IQR 31-53) years. Twenty-eight (41.8%) of the 67 cases had a history of direct exposure in Wuhan. Twenty-five (52.2%) cases came from ten families, and we found no clear reports of modes of transmission other than family clusters. The largest number of secondary cases linked to a single source was nine. CONCLUSION: More women than men were diagnosed with COVID-19 in Gansu Province. Although the age range of confirmed cases of COVID-19 in Gansu Province covered almost all age groups, most patients with confirmed COVID-19 tend to be middle aged persons. The most common suspected mode of transmission was through family cluster. Gansu and other settings worldwide should continue to strengthen the utilization of big data in epidemic control.


Assuntos
Big Data , /epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores Sexuais , Adulto Jovem
6.
Transl Res ; 2021 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-33400994

RESUMO

The gonadotropin-releasing hormone (GnRH) signaling pathway controls reproductive functions and cancer growth and progression. However, few studies investigated roles of genetic variants of GnRH pathway genes in survival of patients with non-small cell lung cancer (NSCLC). Therefore, we first evaluated associations between 22,528 single-nucleotide polymorphisms (SNPs) in 101 GnRH pathway genes and survival of 1185 NSCLC patients using a dataset from Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. We found 572 SNPs to be significantly associated with overall survival (OS) of NSCLC (P ≤ 0.05, Bayesian false discovery probability ≤0.80). We then validated these SNPs in another dataset with 984 NSCLC patients from the Harvard Lung Cancer Susceptibility Study. Finally, two independent SNPs (HBEGF rs4150236G>A and ITPR3 rs116454384C>T) remained significantly associated with NSCLC OS in the combined analysis with hazards ratios of 0.84 (95% confidence interval = 0.76-0.92, P = 0.0003) and 0.85 (0.78-0.94, 0.0012), respectively; their genetic score (the number of protective genotypes) was associated with a better OS and disease-specific survival (Ptrend = 0.0002 and 0.0001, respectively). Further expression quantitative trail loci analysis showed a significant correlation between ITPR3 rs116454384 T allele and an increased mRNA expression level in both whole blood and normal lung tissue, and high ITPR3 mRNA expression levels in tumors were associated with a better survival of NSCLC patients. Because ITPR3 mutations were rare in tumors, ITPR3 rs116454384C>T likely had an effect on cancer progression by regulating the gene expression. Therefore, genetic variants of HBEGF rs4150236G>A and ITPR3 rs116454384C>T may be predictors for NSCLC survival, but HBEGF rs4150236G>A functional relevance remains to be determined.

7.
Int J Biol Macromol ; 174: 587-595, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33493568

RESUMO

Persistent infection with high-risk mucosal human papillomavirus (HPV) types has much association with the development of cervical cancer. The major capsid protein L1 has been confirmed to be a major candidate antigen for the development of vaccines. Here, the HPV18 L1 protein was successfully expressed and purified, then nine anti-HPV18 L1 monoclonal antibodies were prepared. Four neutralizing monoclonal antibodies (NmAbs) were identified by using hemagglutination inhibition assay and pseudovirus based neutralization assay. The results of Dot-ELISA, Western blot and indirect immunofluorescence assay showed that the neutralizing antibodies could cross-react with HPV16/18/45/31/33/58/35/39 L1. The mimotopes on HPV18/45 L1 proteins were identified and analyzed by using both phage display and Bioinformatics tool. The B cell epitopes 43-54 aa and 116-126 aa of HPV18 L1 protein, the B cell epitope 381-389 aa of HPV45 L1 protein, and the mimotopes epitope of HPV45 L1 protein were identified by peptide-ELISA and competitive ELISA. The results of PyMOL and Pepitope server analysis indicated that epitopes recognized by NmAbs 7F4, 5A6, 3G11, and 2F5 are located on the surface of L1 VLPs. The results of this study enriched the library of HPV neutralizing antibodies, revealed the mechanism of antibody neutralization, might open new perspectives on the antibody-antigen reaction and have important implications for the development of novel HPV vaccines.

8.
Int J Biol Macromol ; 173: 244-250, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33485888

RESUMO

Influenza A virus (IAV) occasionally cross-species transmission among humans, swine and avian. The ectodomain of matrix protein 2 (M2e) is highly conserved in IAV, and multi-copy M2e from different species are usually displayed on the surface of nanoparticles to improve immunogenicity and constitute universal IAV nanovaccines. In our previous study, three M2e were inserted into the C-terminal of Cap protein of porcine circovirus type 2 (PCV2) to form a universal nanovaccine that provides protection against PCV2 and different subtypes of IAV. However, M2e adopts at least two converted conformations, and the intermolecular linker of M2e enhances the conformational instability, which limits the recognition by B cell receptors and production of high-level antibodies. Here, we report that the permutation of M2e affects effectiveness of nanovaccines. Three M2e derived from humans, swine and avian IAV were inserted into the C-terminal of Cap protein to form nanovaccines. Immunoprotective effects of different M2e arrangements were explored in mice. Results showed that the M2e closest to the surface of nanoparticle induced the most efficient protection against IAV derived from corresponding species. The results will contribute to develop more effective PCV2 and universal IAV bivalent nanovaccines for pigs, as well as species-specific universal IAV vaccines.

9.
Ecotoxicol Environ Saf ; 209: 111826, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33360592

RESUMO

BACKGROUND: Excessive fluoride exposure is related to adverse health outcomes, but whether dopamine (DA) relative genes are involved in the health effect of low-moderate fluoride exposure on children's intelligence remain unclear. OBJECTIVES: We conducted a cross-sectional study to explore the role of DA relative genes in the health effect of low-moderate fluoride exposure in drinking water. METHODS: We recruited 567 resident children, aged 6-11 years old, randomly from endemic and non-endemic fluorosis areas in Tianjin, China. Spot urine samples were tested for urinary fluoride concentration, combined Raven`s test was used for intelligence quotient test. Fasting venous blood were collected to analyze ANKK1 Taq1A (rs1800497), COMT Val158Met (rs4680), DAT1 40 bp VNTR and MAOA uVNTR. Multivariable linear regression models were used to assess associations between fluoride exposure and IQ scores. We applied multiplicative and additive models to appraise single gene-environment interaction. Generalized multifactor dimensionality reduction (GMDR) was used to evaluate high-dimensional interactions of gene-gene and gene-environment. RESULTS: In adjusted model, fluoride exposure was inversely associated with IQ scores (ß = -5.957, 95% CI: -9.712, -2.202). The mean IQ scores of children with high-activity MAOA genotype was significantly lower than IQ scores of those with low-activity (P = 0.006) or female heterozygote (P = 0.016) genotype. We detected effect modification by four DA relative genes (ANKK1, COMT, DAT1 and MAOA) on the association between UF and IQ scores. We also found a high-dimensional gene-environment interaction among UF, ANKK1, COMT and MAOA on the effect of IQ (testing balanced accuracy = 0.5302, CV consistency: 10/10, P = 0.0107). CONCLUSIONS: Our study suggests DA relative genes may modify the association between fluoride and intelligence, and a potential interaction among fluoride exposure and DA relative genes on IQ.


Assuntos
Dopamina/genética , Exposição Ambiental/estatística & dados numéricos , Fluoretos/toxicidade , Inteligência/efeitos dos fármacos , Criança , China/epidemiologia , Estudos Transversais , Água Potável , Feminino , Fluoretos/análise , Genótipo , Humanos , Testes de Inteligência , Masculino , Polimorfismo Genético
10.
Artigo em Inglês | MEDLINE | ID: mdl-33293994

RESUMO

Background: Fuzheng Huayu recipe (FZHY) is an original Chinese patent medicine which was developed and marketed by our institute. It could markedly improve liver tissue inflammation and ameliorate hepatic fibrosis in the clinical study. The intrahepatic macrophages recruitment and polarization play an important role in the progress of liver inflammation and fibrosis. Whether FZHY exerted its antiliver fibrosis effects through regulating intrahepatic macrophages phenotypic ratios is still unknown. This study aims to explore the antifibrosis mechanism of FZHY on regulating the recruitment and polarization of intrahepatic macrophages. Methods: C57/B6 mice were used for the establishment of the CCl4-induced mice liver fibrosis model. Liver inflammation and fibrosis were evaluated by HE and Sirius red staining, hydroxyproline assays, and biochemical tests. The levels of chemokines and inflammatory cytokines in liver tissue were measured by RNA-Seq transcriptome analysis, western blot assay, RT-qPCR, and immunofluorescence assay. The macrophages recruitment and phenotypic polarization were observed by flow cytometry. Results: FZHY significantly improved liver inflammation and reduced liver fibrosis degree. TNF signaling pathway, involved in macrophages recruitment and phenotypic polarization, was discovered by RNA-Seq transcriptome analysis. In TNF signaling pathway, CCL2 expression was significantly decreased and CX3CL1 expression was significantly upregulated by FZHY in liver tissue and primary intrahepatic macrophages. The ratio of proinflammatory hepatic resident macrophage-Kupffer cells (F4/80+CD11b-CD86+) was downregulated by FZHY, while the proportion of anti-inflammatory Kupffer cells (F4/80+CD11b-CD206+) was upregulated. Meanwhile, the ratio of proinflammatory Ly6Chigh macrophages (F4/80+CD11b+Ly6Chigh) which were recruited from blood circulation by CCL2 was reduced by FZHY, while the ratio of restorative Ly6Clow macrophages (F4/80+CD11b+Ly6Clow) which were recruited from blood circulation or induced from Ly6Chigh macrophages polarization by CX3CL1 was significantly increased. Conclusions: FZHY could regulate the recruitment and polarization of intrahepatic macrophages via CCL2 and CX3CL1, so as to play its anti-inflammation and antifibrosis pharmacological effects in the liver.

11.
World J Clin Cases ; 8(21): 5409-5414, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33269277

RESUMO

BACKGROUND: Esophageal cancer is a common malignant tumor of the digestive system. At present, surgery is the most important treatment strategy. After esophagectomy and gastric esophagoplasty, the patients are prone to regurgitation. However, these patients currently do not receive much attention, especially from anesthesiologists. CASE SUMMARY: A 55-year-old woman was scheduled for right lower lung lobectomy. The patient had undergone radical surgery for esophageal cancer under general anesthesia 6 mo prior. Although the patient had fasted for > 17 h, unexpected aspiration still occurred during induction of general anesthesia. Throughout the operation, oxygen saturation was 98%-100%, but the airway pressure was high (35 cmH2O at double lung ventilation). The patient was sent to the intensive care unit after surgery. Bedside chest radiography was performed, which showed exudative lesions in both lungs compared with the preoperative image. After surgery, antibiotics were given to prevent lung infection. On day 2 in the intensive care unit, the patient was extubated and discharged on postoperative day 7 without complications related to aspiration pneumonia. CONCLUSION: After esophagectomy, patients are prone to regurgitation. We recommend nasogastric tube placement followed by rapid sequence induction or conscious intubation.

12.
Artigo em Inglês | MEDLINE | ID: mdl-33275090

RESUMO

A Gram-stain-negative, rod-shaped, mesophilic, milky white-pigmented, aerobic, non-spore-forming and non-flagellated bacterium, designated strain X16T, was isolated from urban soil of Zibo, Shandong, China. According to 16S rRNA gene sequence analysis, the isolate showed highest similarities with Paraflavitalea soli 5GH32-13T (97.6 %), Pseudoflavitalea soli KIS20-3T (96.2 %), Pseudobacter ginsenosidimutans Gsoil 221T (96.0 %) and Pseudoflavitalea rhizosphaerae T16R-265T (95.8 %). The neighbour-joining tree based on 16S rRNA gene sequences showed that strain X16T formed a subcluster with Paraflavitalea soli 5GH32-13T, and the subcluster was closely related to Pseudoflavitalea soli KIS20-3T, Pseudobacter ginsenosidimutans Gsoil 221T and Pseudoflavitalea rhizosphaerae T16R-265T. Strain X16T also formed a subcluster with Paraflavitalea soli 5GH32-13T in phylogenetic tree based on genomic sequences. The polar lipids are phosphatidylethanolamine, two unknown aminolipids, two unknown aminophospholipids, two unknown lipids and two unknown phospholipids. The major quinone of strain X16T is menaquinone-7 and the main fatty acids (>10 % of total fatty acids) of strain X16T are iso-C15 : 0, iso-C17 : 0 3-OH and iso-C15 : 1 G. The genome length of strain X16T is 8.7 Mb with a DNA G+C content of 47.4 %. ANI values among strain X16T and strain Paraflavitalea soli 5GH32-13T, Pseudobacter ginsenosidimutans Gsoil 221T, and Pseudoflavitalea rhizosphaerae T16R-265T are 78.1, 70.7, 70.6 %, respectively. On the basis of the results of the polyphasic characterization presented in this study, it is concluded that strain X16T represents a novel species. Besides, strain X16T can detoxify high toxicity selenite [Se(IV)] to low toxicity elemental selenium [Se(0)], for which the name Paraflavitale devenefica sp. nov. is proposed. The type strain is X16T (=KACC 21698T=GDMCC1.1757T).

13.
Front Microbiol ; 11: 581856, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33281776

RESUMO

Porcine reproductive and respiratory syndrome (PRRS), caused by PRRS virus (PRRSV), is a widespread viral disease that has led to huge economic losses for the global swine industry. Non-structural protein 9 (Nsp9) of PRRSV possesses essential RNA-dependent RNA polymerase (RdRp) activity for viral RNA replication. Our previous report showed that Nsp9-specific nanobody, Nb6, was able to inhibit PRRSV replication. In this study, recombinant Nsp9 and Nsp9-Nb6 complex were prepared then characterized using bio-layer interferometry (BLI) and dynamic light scattering (DLS) analyses that demonstrated high-affinity binding of Nb6 to Nsp9 to form a homogeneous complex. Small-angle X-ray scattering (SAXS) characterization analyses revealed that spatial interactions differed between Nsp9 and Nsp9-Nb6 complex molecular envelopes. Enzyme-linked immunosorbent assays (ELISAs) revealed key involvement of Nsp9 residues Ile588, Asp590, and Leu643 and Nb6 residues Tyr62, Trp105, and Pro107 in the Nsp9-Nb6 interaction. After reverse genetics-based techniques were employed to generate recombinant Nsp9 mutant viruses, virus replication efficiencies were assessed in MARC-145 cells. The results revealed impaired viral replication of recombinant viruses bearing I588A and L643A mutations as compared with replication of wild type virus, as evidenced by reduced negative-strand genomic RNA [(-) gRNA] synthesis and attenuated viral infection. Moreover, the isoleucine at position 588 of Nsp9 was conserved across PRRSV genotypes. In conclusion, structural analysis of the Nsp9-Nb6 complex revealed novel amino acid interactions involved in viral RNA replication that will be useful for guiding development of structure-based anti-PRRSV agents.

14.
Sensors (Basel) ; 20(22)2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33228106

RESUMO

Nighttime light (NTL) remote sensing data have been widely used to derive socioeconomic indicators at the national and regional scales to study regional economic development. However, most previous studies only chose a single measurement indicator (such as GDP) and adopted simple regression methods to investigate the economic development of a certain area based on DMSP-OLS or NPP-VIIRS stable NTL data. The status quo shows the problems of using a single evaluation index-it has a low evaluation precision. The LJ1-01 satellite is the first dedicated NTL remote sensing satellite in the world, launched in July 2018. The data provided by LJ1-01 have a higher spatial resolution and fewer blooming phenomena. In this paper, we compared the accuracy of the LJ1-01 data and NPP-VIIRS data in detecting county-level multidimensional economic development. In three provinces in China, namely, Hubei, Hunan and Jiangxi, 20 socioeconomic parameters were selected from the following five perspectives: economic conditions, people's livelihood, social development, public resources and natural vulnerability. Then, a County-level Economic Index (CEI) was constructed to evaluate the level of multidimensional economic development, with the spatial pattern of the multidimensional economic development also identified across the study area. The present study adopted the random forest (RF) and linear regression (LR) algorithms to establish the regression model individually, and the results were evaluated by cross-validation. The results show that the RF algorithm greatly improves the accuracy of the model compared with the LR algorithm, and thus is suitable for the study of NTL data. In addition, a better determinate coefficient (R2) based on the LJ1-01 data (0.8168) was obtained than that from the NPP-VIIRS data (0.7245) in the RF model, which reflects that the LJ1-01 data offer better potential in the evaluation of socioeconomic parameters and can be used to identify, both accurately and efficiently, multidimensional economic development at the county level.

15.
Cancer Med ; 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33200553

RESUMO

Because the cadherin-mediated signaling pathway promotes cancer progression, we assessed associations between genetic variants in 109 cadherin-related genes and risk of pancreatic cancer (PanC) by using genotyping data from publically available genome-wide association studies (GWAS) datasets comprising 15,423 individuals of European ancestry. After initial single-locus analyses and subsequent meta-analysis with multiple testing correction for 29,963 single-nucleotide polymorphisms (SNPs), 11 SNPs remained statistically significant (p < 0.05). In the stepwise logistic regression analysis, three independent PanC risk-associated SNPs (KIF5B rs211304 C > G, FMN1 rs117648907 C > T, and MGAT3 rs34943118 T > C) remained statistically significant (p < 0.05), with odds ratios of 0.89 (95% confidence interval = 0.82-0.95 and p = 6.93 × 10-4 ), 1.33 (1.13-1.56 and 2.11 × 10-4 ), and 1.11 (1.05-1.17 and 8.10 × 10-5 ), respectively. Combined analysis of unfavorable genotypes of these three independent SNPs showed an upward trend in the genotype-risk association (ptrend  < 0.001). Expression quantitative trait loci analyses indicated that the rs211304 G and rs34943118 C alleles were associated with increased mRNA expression levels of KIF5B and MGAT3, respectively (all p < 0.05). Additional bioinformatics prediction suggested that these three SNPs may affect enhancer histone marks that likely have an epigenetic effect on the genes. Our findings provide biological clues for these PanC risk-associated SNPs in cadherin-related genes in European ancestry populations, possibly by regulating the expression of the affected genes. However, our findings need to be validated in additional population, molecular and mechanistic investigations.

16.
Am J Cancer Res ; 10(10): 3382-3394, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33163277

RESUMO

Endosomes regulate cell polarity, adhesion, signaling, immunity, and tumor progression, which may influence cancer outcomes. Here we evaluated associations between 36,068 genetic variants of 228 endosome-related pathway genes and cutaneous melanoma disease-specific survival (CMSS) using genotyping data from two previously published genome-wide association studies. The discovery dataset included 858 CM patients with 95 deaths from The University of Texas MD Anderson Cancer Center, and the replication dataset included 409 CM patients with 48 deaths from the Nurses' Health Study (NHS) and the Health Professionals Follow-up Study (HPFS). In multivariate Cox proportional hazards regression analysis, we found that two novel SNPs (PIP5K1C rs11666894 A>C and MVB12B rs12376285 C>T) predicted CMSS, with adjusted hazards ratios of 1.47 (95% confidence interval = 1.15-1.89 and P = 0.002) and 1.73 (1.30-2.31 and 0.0002), respectively. Combined analysis of risk genotypes of these two SNPs revealed a dose-dependent decrease in CMSS associated with an increased number of risk genotypes (P trend = 0.0002). Subsequent expression quantitative trait loci (eQTL) analysis revealed that PIP5K1C rs11666894 was associated with mRNA expression levels in lymphoblastoid cell lines from 373 European descendants (P<0.0001) and that MVB12B rs12376285 was associated with mRNA expression levels in cultured fibroblasts from 605 European-Americans (P<0.0001). Our findings suggest that novel genetic variants of PIP5K1C and MVB12B in the endosome-related pathway genes may be promising prognostic biomarkers for CMSS, but these results need to be validated in future larger studies.

17.
Nanoscale ; 12(44): 22787-22797, 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33174578

RESUMO

Owing to its rapid response and broad detection range, a phenylboronic acid (PBA)-functionalized hydrogel film-coated quartz crystal microbalance (QCM) sensor is used to non-invasively monitor salivary glucose in diabetic patients. However, nonspecific protein adsorption on the PBA-functionalized hydrogel film can cause dramatic loss of sensitivity and accuracy of the sensor. A traditional zwitterionic polymer surface with ultra-low protein fouling can hinder the interaction of PBA in the hydrogel matrix with glucose molecules owing to its steric hindrance, resulting in poor glucose sensitivity of the sensor. Herein, we developed a novel hydrogel film that enhanced the antifouling properties and sensitivity of the QCM sensor by infiltrating a glucose-sensitive monomer (i.e., PBA) into a zwitterionic polymer brush matrix to form an interpenetrating polymer network (IPN). The IPN hydrogel film could minimize the glucose sensitivity loss since the antifouling polymer distributed in its matrix. Moreover, a stable hydration layer was formed in this film that could prevent water from transporting out of the matrix, thus further improving its antifouling properties and glucose sensitivity. The experimental results confirmed that the IPN hydrogel film possessed excellent resistance to protein fouling by mucin from whole saliva with reductions in adsorption of nearly 88% and could also enhance the glucose sensitivity by nearly 2 fold, compared to the PBA-functionalized hydrogel film. Therefore, the IPN hydrogel film provides improved antifouling properties and sensitivity of the QCM sensor, which paves the way for non-invasive monitoring of low concentrations of glucose in saliva.

18.
ACS Appl Mater Interfaces ; 12(49): 55372-55381, 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33236880

RESUMO

Graphene has attracted extensive attention for the supply of electrically conductive, optically transparent, and mechanical robust electrodes for flexible optoelectrical devices, as an alternative to commercial indium tin oxide, due to its superior mechanical, electrical, and optical properties. However, conventional chemical vapor deposition is impeded by harsh conditions and complicated processes, and it is still a challenge to fabricate high-performance graphene transparent electrode in a facile and scalable solution-processable route. Herein, a wetting-induced scalable solution-processable approach to fabricate graphene hybrid with conductive ionogel and poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS), i.e., graphene/ionogel@PEDOT:PSS (G/Ionogel@PEDOT:PSS), for high-performance flexible transparent electrode (FTE) is reported, achieving a low sheet resistance of 30 Ω sq-1 and a high transmittance of 88% at 550 nm. The as-fabricated trinary hybrid FTE as both transparent electrode and electrochromic layer is applied to a compact indium tin oxide (ITO)-free three-layered flexible electrochromic device, showing fast switching response, good electrochromic contrast, and reliable stability. Our work enables a scalable solution-processable approach for the generation of graphene-based FTE and functional devices.

19.
Int J Syst Evol Microbiol ; 70(11): 5937-5942, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33034554

RESUMO

An aerobic, non-motile, Gram-stain-negative, pink, convex, coccobacilli-shaped, mesophilic bacterium, designated strain BU-1T, was isolated from an urban soil sample from Zibo city, Shandong province, PR China. The strain grew at 20-37 °C (optimum, 30 °C), pH 5-10 (optimum, pH 7) and growth occurred with 0-2 % (w/v) NaCl (optimally with 0.5 %). The results of phylogenetic analysis based on 16S rRNA gene sequences indicated that BU-1T was closely related to members of the genus Roseomonas and had highest 16S rRNA gene sequence similarities with Roseomonas frigidaquae JCM 15073T (97.8 %), Roseomonas tokyonensis JCM 14634T (96.9 %), Roseomonas stagni JCM 15034T (96.5 %), and Roseomonas riguiloci JCM 17520T (95.9 %). BU-1T also formed a subcluster with R. frigidaquae JCM 15073T and R. stagni JCM 15034T in phylogenetic trees based on genomic sequences. The genome size of BU-1T was 5.79 Mb and the DNA G+C content was 71.7 %. ANI, dDDH and AAI values between BU-1T and R. frigidaquae JCM 15073T were 84.0, 27.2 and 86.7 %, respectively. Furthermore, the genome of BU-1T contained 5446 predicted protein coding genes and 4945 (90.8%) of them had classifiable functions. BU-1T contained Q-10 as the main ubiquinone. The predominant fatty acids (>10 %) were summed feature 3, summed feature 8 and C16:0. The polar lipid profile contained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine and five unidentified aminolipids. Combined data from phenotypic, phylogenetic and chemotaxonomic studies indicated that strain BU-1T is a representative of a novel species of the genus Roseomonas. Since strain BU-1T can reduce highly toxic selenite [Se(IV)] to low toxicity elemental selenium [Se(0)], the name Roseomonas selenitidurans sp. nov. is proposed. The type strain is BU-1T (=KACC 21750T =GDMCC 1.1776T).

20.
Am J Cancer Res ; 10(8): 2603-2616, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32905494

RESUMO

Although lymphangiogenesis is a vital step in lung cancer metastasis, the association between lymphangiogenesis and non-small cell lung cancer (NSCLC) survival remains unclear. Since single-nucleotide polymorphisms (SNPs) have been reported to predict NSCLC survival, we investigated associations between SNPs in lymphangiogenesis-related pathway genes and NSCLC survival in a discovery genotyping dataset of 1,185 patients from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial and validated the findings in another genotyping dataset of 984 patients from the Harvard Lung Cancer Susceptibility Study. We evaluated associations between 34,509 genetic variants (3252 genotyped and 31,257 imputed) in 247 genes involved in lymphangiogenesis-related pathway and NSCLC survival. After validation, we finally identified two independent SNPs (SYK rs11787670 A>G and ITGA1 rs67715745 T>C) to be significantly associated with NSCLC overall survival (OS), with adjusted hazards ratios of 0.77 and 0.83 (95% confidence interval =0.66-0.90, P=7.20×10-4) and 0.84 (95% confidence interval =0.75-0.92, P=3.50×10-4), respectively. Moreover, an increasing number of combined protective alleles of these two SNPs was significantly associated with an improved NSCLC OS and disease-specific survival (DSS) in the PLCO dataset (P trend=0.011 and 0.006, respectively). Furthermore, the addition of these protective alleles to the prediction model for the 5-year survival increased the time-dependent area under the curve both from 87% to 87.67% for OS (P=0.029) and from 88.54% to 89.06% for DSS (P=0.022). Subsequent expression quantitative trait loci (eQTL) functional analysis revealed that the rs11787670 G allele was significantly associated with an elevated SYK mRNA expression in normal tissues. Additional analyses suggested a suppressor role for both SYK and ITGA1 in NSCLC survival. Collectively, these findings indicated that SYK rs11787670 A>G and ITGA1 rs67715745 T>C may be independent prognostic factors for NSCLC survival once further validated.

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