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1.
JAMA Netw Open ; 4(4): e215302, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33835173

RESUMO

Importance: The World Health Organization End TB (Tuberculosis) Strategy aims to decrease the global incidence and mortality of TB by 90% and 95%, respectively, as of 2035. Objective: To characterize the recent epidemiological trend of pulmonary TB (PTB) in mainland China based on the national surveillance data. Design, Setting, and Participants: This cross-sectional study collected demographic and clinical data of all patients reported in the national Tuberculosis Information Management System of China from January 1, 2005, to November 21, 2016. Data were analyzed from December 1, 2019, to July 31, 2020. Exposures: Pulmonary TB was defined as bacteriologically confirmed or clinically diagnosed TB in the lung parenchyma or the tracheobronchial tree. Main Outcomes and Measures: Temporal and spatial variation of annual incidence and demographic features of PTB in mainland China. Results: In total, 10 582 903 patients with PTB were reported in mainland China from 2005 to 2016. The median age of patients with PTB was 46 (interquartile range [IQR], 30-61) years, and 28.53% were 60 years or older. Most patients with PTB were male (69.8%) and farmers or herders (70.0%). The mean (SD) incidence of PTB was 66.61 (8.09) per 100 000 population. The annual incidence decreased from 72.95 per 100 000 population in 2005 to 52.18 per 100 000 population in 2016, and the reduction was greater in the eastern and central regions (31.6%; from 69.43 to 47.48 per 100 000 population) than in the western region (21.0%; from 82.06 to 64.82 per 100 000 population). Xinjiang Uygur Autonomous Region (135.03 per 100 000 population), Guizhou Province (115.98 per 100 000 population), and the Tibet Autonomous Region (101.98 per 100 000 population) had the highest mean annual incidences. The median time from onset of illness to diagnosis decreased from 36 (IQR, 16-92) days from 2005 to 2007 to 31 (IQR, 15-63) days in 2008 and later (P < .001) and was longer in the western region than in the eastern and central regions (41 [IQR, 20-91] vs 30 [IQR, 13-61] days; P < .001). Conclusions and Relevance: Although this study found that the incidence of PTB in mainland China showed a downward trend from 2005 to 2016, to achieve the World Health Organization 2035 goal, innovative and more efficient prevention and control strategies are needed, particularly among the most susceptible population, that is, farmers and herders in western China.

2.
Ann Palliat Med ; 10(3): 3086-3096, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33752434

RESUMO

BACKGROUND: Canagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, is widely used for the treatment of type 2 diabetes mellitus. However, drug interactions with canagliflozin can affect its glucoselowering therapeutic effects or exacerbate its adverse effects. Telmisartan, an angiotensin receptor blocker (ARB), has been approved for the treatment of diabetic kidney disease. This study aimed to investigate the effects of telmisartan on the pharmacokinetics and tissue distribution of canagliflozin. METHODS: An ultra-performance liquid chromatography-tandem mass spectrometry method was successfully validated to determine the levels of canagliflozin in the plasma and tissues. The main pharmacokinetic parameters were calculated using the non-compartmental model. RESULTS: Compared with animals administered canagliflozin alone, the area under the receiver operating characteristic curve of animals co-administered telmisartan and canagliflozin was significantly increased after a single-day administration, but significantly decreased after a seven-day treatment regimen (both P<0.05). The highest concentrations of canagliflozin were detected in the kidneys, followed by the intestine, liver, heart, lung, spleen, and brain tissues. Furthermore, the concentration of canagliflozin in the heart, liver, lung, and kidney tissues at 2 hours post-administration was significantly higher in the telmisartan and canagliflozin group compared to the group treated with canagliflozin alone (P<0.05). CONCLUSIONS: A pharmacokinetic drug-drug interaction between telmisartan and canagliflozin might occur during drug co-administration.

3.
Huan Jing Ke Xue ; 42(3): 1354-1360, 2021 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-33742932

RESUMO

Phenol is widely used in the production of insulation and thermal insulation materials, adhesives, perfumes, coatings for food containers, paints, and pharmaceutical production, and is also widely detected in the aquatic environment. Long-term exposure to phenol can elicit adverse effects, such as skin burn, liver and central system damage. Here, phenol concentrations in the water and aquatic products of Poyang Lake were investigated. Human health risks from phenol to adults and adolescents were also assessed based on local population exposure parameters. The exposure concentration range of phenol in the studied water and aquatic products was not detected (ND)-556.26 ng·L-1 and 11.98-255.51 µg·kg-1, respectively. Human health risk based on drinking water in different areas ranged from 3.80×10-7-8.46×10-5. Higher human health risks from drinking water was detected in the southern area of Poyang Lake and at the confluence of the Yangtze River to the north. Health risks caused by different types of aquatic products ranges 2.65×10-5-1.47×10-4. In particular, human health risks from the consumption of yellow catfish and catfish are an order of magnitude higher than for other aquatic products. Probabilistic risk assessment was also conducted through Monte Carlo simulation to analyze the health risk to the population in the Poyang Lake Basin and assess its sensitivity of different exposure parameters. The 95th percentile health risk of drinking water and aquatic product consumption in the Poyang Lake Basin was calculated as being acceptable. Overall, the concentrations of phenol had the greatest impact on the calculated health risk values. This study provides valuable information for phenol risk management in the Poyang Lake basin.


Assuntos
Lagos , Fenol , Adolescente , China , Monitoramento Ambiental , Humanos , Lagos/análise , Medição de Risco , Rios , Água
4.
J Gene Med ; : e3333, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33789360

RESUMO

BACKGROUND: A growing body of studies have suggested that LINC00460 is instrumental in tumorigenesis and tumour progression. Nonetheless, the biological function and mechanisms of LINC00460 in pancreatic ductal adenocarcinoma (PDAC) remains vague. METHODS: Analysis based on public databases and qRT-PCR were performed to screen for differentially expressed lncRNAs in PDAC and to detect LINC00460 expression in PDAC cell lines and clinical samples. The survival of patients in the upregulated and downregulated LINC00460 expression groups was compared by using the Kaplan-Meier method. In addition, the potential biological functions of LINC00460 in PDAC were explored by cell counting kit-8 (CCK-8), colony formation, flow cytometry, and transwell assays. Furthermore, bioinformatics analysis, luciferase reporter assays and rescue experiments were applied to demonstrate the mechanism by which LINC00460 could directly bind to and inhibit miR-491-5p. RESULTS: LINC00460 is upregulated in PDAC and correlates with adverse survival outcomes. The results of functional tests verified that LINC00460 knockdown inhibited cell proliferation as well as cell migration. Additionally, knockdown led to G0/G1 cell cycle blockage and enhanced cell apoptosis. Mechanistic investigation revealed that LINC00460 directly binds to and attenuates the tumour suppressor miR-491-5p, thus accelerating PDAC progression. CONCLUSION: This research showed that LINC00460 is overexpressed in PDAC and correlates with adverse clinical outcomes. Additionally, LINC00460 promotes the aggressiveness of PDAC by targeting miR-491-5p. Thus, LINC00460 may serve as diagnostic biomarker of PDAC and a new target for PDAC therapy.

5.
J Biol Chem ; : 100483, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33647318

RESUMO

Vascular calcification is the ectopic deposition of calcium hydroxyapatite minerals in arterial wall which involves the transdifferentiation of vascular smooth muscle cells (VSMCs) toward an osteogenic phenotype. However, the underlying molecular mechanisms regulating the VSMC osteogenic switch remain incompletely understood. In this study, we examined the roles of microRNAs (miRNAs) in vascular calcification. miRNA-seq transcriptome analysis identified miR-223-3p as a candidate miRNA in calcified mouse aortas. MiR-223-3p knockout aggravated calcification in both medial and atherosclerotic vascular calcification models. Further, RNA-seq transcriptome analysis verified JAK-STAT and PPAR signaling pathways were upregulated in both medial and atherosclerotic calcified aortas. Overlapping genes in these signaling pathways with predicted target genes of miR-223-3p derived from miRNA databases, we identified signal transducer and activator of transcription 3 (STAT3) as a potential target gene of miR-223-3p in vascular calcification. In vitro experiments showed that miR-223-3p blocked interleukin-6 (IL-6)/STAT3 signaling, thereby preventing the osteogenic switch and calcification of VSMCs. In contrast, overexpression of STAT3 diminished the effect of miR-223-3p. Taken together, the results indicate a protective role of miR-223-3p that inhibits both medial and atherosclerotic vascular calcification by regulating IL-6/STAT3 signaling mediated VSMC transdifferentiation.

6.
Cancer Biol Med ; 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33710807

RESUMO

OBJECTIVE: Dysfunction in fibroblast growth factor receptor (FGFR) signaling has been reported in diverse cancer types, including non-small cell lung cancer (NSCLC). The frequency of FGFR aberrations in Chinese NSCLC patients is therefore of great clinical significance. METHODS: A total of 10,966 NSCLC patients whose tumor specimen and/or circulating cell-free DNA (cfDNA) underwent hybridization capture-based next-generation sequencing were reviewed. Patients' clinical characteristics and treatment histories were also evaluated. RESULTS: FGFR aberrations, including mutations, fusions, and gene amplifications, were detected in 1.9% (210/10,966) of the population. FGFR abnormalities were more frequently observed in lung squamous cell carcinomas (6.8%, 65/954) than lung adenocarcinomas (1.3%, 128/9,596). FGFR oncogenic mutations were identified in 19 patients (~0.17%), of which, 68% were male lung squamous cell carcinoma patients. Eleven out of the 19 patients (58%) had concurrent altered PI3K signaling, thus highlighting a potential combination therapeutic strategy of dual-targeting FGFR and PI3K signaling in such patients. Furthermore, FGFR fusions retaining the intact kinase domain were identified in 12 patients (0.11%), including 9 FGFR3-TACC3, 1 FGFR2-INA, 1 novel FGFR4-RAPGEFL1, and 1 novel fusion between the FGFR1 and SLC20A2 5'-untranslated regions, which may have caused FGFR1 overexpressions. Concomitant EGFR mutations or amplifications were observed in 6 patients, and 4 patients received anti-EGFR inhibitors, in whom FGFR fusions may have mediated resistance to anti-EGFR therapies. FGFR amplification was detected in 24 patients, with the majority being FGFR1 amplifications. Importantly, FGFR oncogenic mutations, fusions, and gene amplifications were almost always mutually exclusive events. CONCLUSIONS: We report the prevalence of FGFR anomalies in a large NSCLC population, including mutations, gene amplifications, and novel FGFR fusions.

7.
Environ Pollut ; 276: 116628, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33601198

RESUMO

In the absence of water quality criteria (WQC) support for the current water quality standard (WQS), systematic WQC studies have been carried out in recent years in China. WQC for the protection of human health is established to reflect long-term consumption safety of aquatic products and water. Human health WQC for 15 toxic metals and metalloids based on exposure factors of the Chinese population and 40 field bioaccumulation factors (BAFs) were developed and analyzed in this study. Moreover, age-specific (age 2-5, 6-8, 9-11, 12-14, 15-17, and adult) and region-specific (east, central and west China) WQC were analyzed to better understanding of the impact of specific parameter values on WQC. Human health WQC with consumption of fishes and water, consumption of fishes only, and consumption of water only were derived separately. WQC with consumption of water and organism for Hg, Cd, As, Sb, Se, Zn, Co, Cu, Ni, Pb, Mn, Sn, Ba, and Sr were 0.0264, 0.710, 0.827, 3.48, 22.1, 25.7, 32.2, 32.9, 35.5, 41.8, 72.1, 97.1, 206 and 2.20 × 103 µg/L, and were 13.3 and 6.67 × 103 µg/L for Cr(VI) and Cr(III) with consumption of water only. Comparison of age-specific and region-specific WQC showed that the protection for a specific population should be considered in the development of WQC and WQS, as well as cancer effect for carcinogenic metals. Health risk analysis showed that Cd, Cu, Zn, As, Hg and Mn average concentrations in 7, 5, 9, 22, 11 and 5 provinces exceeded the WQC values with consumption of water and aquatic product, showing potential long-term health risk (HQ ≥ 1) to the local population. Therefore, health risks posed by these metals from dietary intake related to surface water should be paying more attention.


Assuntos
Metais Pesados , Poluentes Químicos da Água , Adulto , Animais , Pré-Escolar , China , Monitoramento Ambiental , Humanos , Metais Pesados/análise , Medição de Risco , Água , Poluentes Químicos da Água/análise , Qualidade da Água
8.
Plant Physiol Biochem ; 161: 86-97, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33581622

RESUMO

In this study, winter wheat G6PDH (TaG6PDH) and 6PGDH (Ta6PGDH) were investigated. Both their expression and their activity were upregulated under cold stress, suggesting that TaG6PDH and Ta6PGDH positively respond to cold stress in winter wheat. Exogenous abscisic acid (ABA) treatment markedly increased the expression and activity levels of TaG6PDH and Ta6PGDH in winter wheat under cold stress. Subsequently, TaG6PDH-and Ta6PGDH were overexpressed in Arabidopsis, and showed stronger reactive oxygen species (ROS)-scavenging ability and higher survival rate compared with wild-type (WT) plants under cold stress. In addition, we found that TaG6PDH and Ta6PGDH overexpression can promote the oxidative pentose phosphate pathway (OPPP) in the cytoplasm and peroxisomes of Arabidopsis. In summary, Arabidopsis overexpressing TaG6PDH and Ta6PGDH showed improved cold tolerance.

9.
Chemosphere ; 274: 129784, 2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33548643

RESUMO

The benzenes have attracted worldwide attention due to their high biological toxicity in the environment. In this study, using species sensitivity distribution method to derive the aquatic life criteria of 7 benzenes (carbazole, 1,3-Dichlorobenzene, 1,4-Dichlorobenzene, 1,2,4-Trichlorobenzene, phenol, 2,4-Dichlorophenol and nitrobenzene), then risk quotient method (RQ), potentially affected fraction (PAF) method and joint probability curve (JPC) method were applied for multilevel ecological risk assessment for 7 benzenes in Tai Lake Basin. In addition, the human health ambient water quality criteria (AWQC) of 7 benzenes were derived according to USEPA guidelines, and the probability distributions of human health AWQC for 7 benzenes in China were simulated by Monte Carlo simulation combined with crystal ball software. Finally, the health risks of 7 benzenes in Tai Lake were assessed by RQ method assisted by Monte Carlo simulation. The results showed that nitrobenzene had the maximum aquatic life criteria value, followed by phenol, chlorobenzenes, 2,4-Dichlorophenol and carbazole. All recommended human health AWQC values of 7 benzenes were found at a position of 27th-55th percentiles in the output criteria distributions, indicating that recommended national human health AWQC values could provide effective protection for most of the population in China. Furthermore, the consumption of aquatic products was found to be the most influential parameter of human health AWQC for benzenes with higher Kow values. The risk assessments showed that noncarcinogenic 2,4-Dichlorophenol had potential ecological risk, carcinogenic carbazole and 1,2,4-Trichlorobenzene had significant human health risk in Tai Lake.

10.
J Pharm Biomed Anal ; 195: 113887, 2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33418444

RESUMO

Combination therapies of compound danshen dripping pill (CDDP) and Azilsartan (AZ) represent a promising treatment option in clinical practice in China, but there are no reports on drug-drug interactions between CDDP and AZ. This study investigated the effects of CDDP on the pharmacokinetics of AZ and clarified its potential mechanism. The pharmacokinetic profiles of oral administration of AZ (2 mg/kg) in Sprague-Dawley rats, with or without pre-treatment of CDDP (81, 405, 810 mg/kg/d for 7 d) were investigated using UPLC-MS/MS. The main pharmacokinetic parameters were calculated and compared. The MS analysis was performed in positive ionization mode. The purpose of chromatographic separation of AZ and the internal standard (IS, Valsartan) was finished on a Waters XBridge BEH C18 column (2.1 × 100 mm, 2.5 µm). The mobile phase was acetonitrile and 0.1 % formic acid-water with gradient elution at a flow rate of 0.4 mL/min. The mRNA and protein levels of CYP2B1, CYP2C6, and CYP2C11 in the rat liver were detected by qRT-PCR and western blot, respectively. The results indicated that low, medium and high doses of CDDP significantly increased the Cmax (6.47 ± 2.28, 6.51 ± 1.99, 7.04 ± 1.31 vs. 3.30 ± 1.87) of AZ, compared with that in the AZ single-drug group (p<0.05). The AUC0-t of AZ (47.77 ± 23.41, 50.69 ± 25.46, 54.50 ± 11.57 vs. 26.85 ± 16.79) tended to increase in combination with CDDP. The gene and protein expression levels of CYP2B1, CYP2C6, and CYP2C11 were significantly reduced in the rat liver by CDDP. CDDP may diminish the AZ metabolism in vivo by suppressing the expression of the CYP2B1, CYP2C6, and CYP2C11 enzymes. This observation suggested the occurrence of potential interactions between CDDP and AZ when clinically administered as combination therapy, which may require adjustment of the clinical dose of AZ.

11.
J Diabetes ; 2021 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-33491329

RESUMO

BACKGROUND: The relationship of immunoglobulin G (IgG) glycosylation with diabetes and diabetic nephropathy has been reported, but its role in diabetic retinopathy (DR) remains unclear. We aimed to investigate and validate the association of IgG glycosylation with DR. METHODS: We analyzed the IgG N-linked glycosylation profile and primarily selected candidate glycans by lasso (least absolute shrinkage and selection operator) regression analysis in the discovery population. The findings were validated in the replication population using a binary logistics model. The association between the significant glycosylation panel and clinical features was illustrated with Spearman's coefficient. The results were confirmed by sensitivity analyses. RESULTS: Among 16 selected glycan candidates using lasso, two IgG glycans (GP15, GP20) and two derived traits (IGP32, IGP54) were identified and validated to be significantly associated with DR (P < .05), and the combined adjusted odds ratios (ORs) were 0.587, 0.613, 1.970, and 0.593, respectively. The glycosylation panel showed a weak correlation with clinical features, except for age. In addition, the results remained consistent when the subjects with prediabetes were excluded from the controls, and the adjusted ORs were 0.677, 0.738, 1.597, and 0.678 in the whole population. Furthermore, in the 1:3 rematched population, a significant association was observed, apart from GP20. CONCLUSIONS: The IgG glycosylation profile, reflecting an aging and pro-inflammatory status, was significantly associated with DR. The variation in the IgG glycome deserves more attention in diabetic complications.

12.
Oncoimmunology ; 10(1): 1866287, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33489472

RESUMO

Chimeric antigen receptor (CAR) T-cell adoptive therapy is set to transform the treatment of a rapidly expanding range of malignancies. Although the activation process of normal T cells is well characterized, comparatively little is known about the activation of cells via the CAR. Here we have used flow cytometry together with single-cell transcriptome profiling to characterize the starting material (peripheral blood mononuclear cells) and CAR therapeutic products of 3 healthy donors in the presence and absence of antigen-specific stimulation. Analysis of 53,191 single-cell transcriptomes showed APRIL-based CAR products to contain several subpopulations of cells, with cellular composition reproducible from donor to donor, and all major cellular subsets compatible with CAR expression. Only 50% of CAR-expressing cells displayed transcriptional changes upon CAR-specific antigen exposure. The resulting molecular signature for CAR T-cell activation provides a rich resource for future dissection of underlying mechanisms. Targeted data interrogation also revealed that a small proportion of antigen-responding CAR-expressing cells displayed an exhaustion signature, with both known markers and genes not previously associated with T-cell exhaustion. Comprehensive single-cell transcriptomic analysis thus represents a powerful way to guide the assessment and optimization of clinical-grade CAR-T-cells, and inform future research into the underlying molecular processes.

13.
Technol Cancer Res Treat ; 20: 1533033820979702, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33455540

RESUMO

BACKGROUND: Testicular cancer represents the most common malignancy in young adult men. In the current study, we sought to analyze and compare the prognostic value of lymph node ratio (LNR) as well as positive lymph node counts (LNC) to understand its clinical significance in testicular germ cell tumors. METHODS: We employed eligibility criteria to recruit a total of 931 patients, with testicular cancer, from 2010 to 2015 from The Surveillance, Epidemiology, and End Results (SEER) database. We then used the X-Tile program to calculate LNR and LNC cutoff values and discriminate survival. We then calculated the overall and cancer specific survival rates and analyzed the association between LNR/LNC and clinical pathological characteristics using the χ2 test. Finally, we assessed the relationships between clinical pathological factors and patient survival using univariate Cox proportional hazard analysis. RESULTS: Univariate analysis revealed a significant association between prognosis with age (HR, 5.169; 95% CI, 1.758-15.200; P = 0.003), AJCC stage (III vs I: HR, 9.298; 95% CI, 2.691-32.131; P < 0.001), M stage (HR, 7.897; 95% CI, 3.417-18.251; P < 0.001) and LNR (HR, 3.009; 95% CI, 1.275-7.098; P = 0.012). On the other hand, LNC (HR, 1.743; 95% CI, 0.687-4.420; P = 0.242) was not significantly associated with prognosis. Analysis of the association between LNR/LNC and clinical pathological characteristics showed that high LNR patients tended to have significantly larger tumor sizes (χ2 = 7.877, P = 0.005), as well as advanced T (χ2 = 13.195, P = 0.004), N ( χ2 = 86.775, P < 0.001), M (χ2 = 19.948, P < 0.001) and 7th AJCC (χ2 = 103.074, P < 0.001) stages. In addition, high LNC patients were significantly associated with T (χ2 = 8.799, P = 0.032), N (χ2 = 74.390, P < 0.001) and 7th AJCC (χ2 = 111.759, P < 0.001) stages. CONCLUSION: LNR was a better predictor for long-term prognosis and was closely associated with clinical pathological characteristics than LNC in patients with testicular germ cell tumors.

14.
Chemosphere ; 262: 127864, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32768751

RESUMO

Phthalate esters (PAEs) are a class of endocrine disruptors that are produced and used extensively in China. Given its presence in various products, a great quantity of PAEs flows into different aquatic systems each year. Hence, it is important to study the pollution levels and ecological risk of PAEs. This study investigated the distribution and seasonal variation of six priority PAEs in the surface water of Poyang Lake, the largest freshwater lake in China. In the wet season, the mean concentration of the total PAEs was 0.544 ± 0.173 µg/L, while the dry season concentration (1.003 ± 0.451 µg/L) nearly doubled. The most abundant PAE congeners were di-n-butyl phthalate (DBP), followed by bis (2-ethylhexyl) phthalate (DEHP). To evaluate the ecological risks in Poyang Lake, the predicted no-effect concentrations (PNECs) of four PAEs based on non-lethal effects were derived. For diethyl phthalate (DEP), butyl benzyl phthalate (BBP), DBP, and DEHP, the PNECs were 31.6, 3.30, 2.31, and 0.0210 µg/L, respectively. The tiered ecological risk assessment showed that DEP and BBP posed no risk in Poyang Lake. Meanwhile, DBP posed a potential risk in Poyang Lake, but the risk of DEHP was unacceptable and requires more actions. Specifically, the probabilities of exceeding the threshold for the protection of 95% of the aquatic organisms (HC5) were 3.30% and 4.43% for DEHP in the wet and dry season, respectively. This study provides an appropriate reference for the surface water management of PAE pollution in China.


Assuntos
Exposição Ambiental/análise , Ésteres/análise , Ácidos Ftálicos/análise , Poluentes Químicos da Água/análise , Organismos Aquáticos , China , Dibutilftalato , Disruptores Endócrinos , Lagos , Medição de Risco , Rios , Estações do Ano , Água
15.
Ecotoxicol Environ Saf ; 207: 111541, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33254401

RESUMO

Ammonia has been of concern for its high toxicity to aquatic species and frequent detection in waters worldwide. This study calculated the national aquatic life criteria for ammonia in China. The temporal and spatial distributions were investigated and the multi-tier ecological risks were assessed for ammonia and un-ionized ammonia (NH3) during 2014-2018 based on a total of 18989 ammonia monitoring data from 110 monitoring sites in seven river basins. The sensitivity comparison of different species taxa to ammonia showed that Perciformes fish should be listed as a priority protected species in the derivation of ammonia criteria. The participation of introduced aquaculture species have no significant impact on the final criteria values (t-test, p > 0.05). The final criterion maximum concentration (CMC) and criterion continuous concentration (CCC) were 10.24 and 3.31 mg/L for ammonia (pH 7.0 and 20 °C). The interannual variation showed that decreasing trends were observed for ammonia and NH3 pollutions in the past five years. However, the increasing trends were observed for ammonia in Liao River basin, for NH3 in Yangtze River and Pearl River basins (2014-2018). The significant seasonal and geographical differences of ammonia and NH3 pollution were found. Moreover, the pollutions of ammonia and NH3 in some monitoring points of Huai River, Yellow River and Songhua River basins at the provincial borders were significant. The result of ecological risk assessment showed that the average exceedance probability for 5% affected species by NH3 in long-term exposure was 28.96% in the past five years.


Assuntos
Amônia/análise , Monitoramento Ambiental , Poluentes Químicos da Água/análise , Amônia/toxicidade , Animais , China , Ecossistema , Peixes , Água Doce , Medição de Risco , Rios , Poluentes Químicos da Água/toxicidade
16.
Artigo em Inglês | MEDLINE | ID: mdl-33303693

RESUMO

This study aimed to investigate the association of IgG glycosylation and esophageal precancerosis for squamous cell carcinoma and determine its role in inflammation. Primary glycans selected by the LASSO algorithm were validated using univariate and multivariate logistics models plus restricted cubic spline functions. In total, 24 direct glycans and 27 derived traits were detected, among which 4 glycans and 3 derived traits were primarily selected. Then, GP5 (adjusted OR: 0.805), GP17 (adjusted OR: 1.305), G12n (adjusted OR: 1.271), Gal_1 (adjusted OR: 0.776) and Fuc (adjusted OR: 0.737) were validated and significantly associated with esophageal precancerosis. Additionally, there was a consistent positive association in GP17 and G12n and a negative association in GP5, Gal_1, and Fuc by restricted cubic spline function. Compared with esophageal inflammation, GP17, G12n, and Fuc were still independently associated with precancerosis. In brief, the IgG glycosylation profile was independently associated with esophageal precancerosis beyond inflammation, which could be an early biomarker for esophageal cancer.

17.
Nat Commun ; 11(1): 6083, 2020 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-33247113

RESUMO

The evolutionary trajectories of early lung adenocarcinoma (LUAD) have not been fully elucidated. We hypothesize that genomic analysis between pre-invasive and invasive components will facilitate the description of LUAD evolutionary patterns. We micro-dissect malignant pulmonary nodules (MPNs) into paired pre-invasive and invasive components for panel-genomic sequencing and recognize three evolutionary trajectories. Evolutionary mode 1 (EM1) demonstrates none of the common driver events between paired components, but another two modes, EM2A and EM2B, exhibit critical private alterations restricted to pre-invasive and invasive components, respectively. When ancestral clones harbor EGFR mutations, truncal mutation abundance significantly decrease after the acquisition of invasiveness, which may be associated with the intratumoral accumulation of infiltrated B cells. Harboring EGFR mutations is critical to the selective pressure and further impacts the prognosis. Our findings extend the understanding of evolutionary trajectories during invasiveness acquisition in early LUAD.

18.
Exp Dermatol ; 2020 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-33247967

RESUMO

BACKGROUND: Melanoma is an aggressive malignant skin tumor endangering the health of patients. Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) have been increasingly reported to be implicated in the carcinogenesis of melanoma. Long intergenic non-coding RNA 00665 (LINC00665) has been found to exert important regulatory roles in some cancers, yet its function in melanoma remains to be investigated. METHODS: QRT-PCR analysis was conducted to evaluate the relative expression of RNAs. Functional experiments in vitro including colony formation, EdU, wound-healing and transwell assays, as well as in vivo xenograft assays, were utilized to study the role of LINC00665 in melanoma. Mechanical experiments were implemented to probe into the molecular linkage of LINC00665, miR-224-5p and VMA21. RESULTS: LINC00665 was abnormally highly expressed in melanoma cells. Silencing LINC00665 could inhibit the proliferation and migration of melanoma cells. LINC00665 sponged miR-224-5p to up-regulate VMA21. VMA21 knockdown exerted similarly interfering effects on above biological processes in melanoma cells. However, VMA21 overexpression abolished the in vitro and in vivo outcomes of LINC00665 silencing. CONCLUSION: LINC00665 promotes proliferative and migrating abilities of melanoma cells via targeting miR-224-5p/VMA21 axis.

19.
Cancer Lett ; 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33249197

RESUMO

The gut microbiota is closely associated with colorectal neoplasia. While most metagenomics studies utilized fecal samples, circulating bacterial DNA in colorectal neoplasia patients remained unexplored. This proof-of-concept study aims to characterize alterations of circulating bacterial DNA in colorectal neoplasia patients. We performed WGS of plasma samples from 25 colorectal cancer (CRC) patients, 10 colorectal adenoma (CRA) patients and 22 healthy controls (HC). Bacterial relative abundance was measured by removing the host genome and mapping reads into bacterial genomes. By diversity analysis, we found plasma samples required less sample size to approach saturation than fecal samples, and species diversity in HC was slightly higher compared with CRC/CRA patients. The majority of circulating bacterial DNA came from bacterial genera which commonly associated with gastrointestine and oral tract. By differential analysis, a total of 127 significant species between CRC patients and HC were identified, on which basis 28 species with top predictive ability were selected and showed promise in preliminary discrimination between CRC/CRA and HC. In CRA patients, relative abundance of the selected 28 species more closely resembled those in CRC patients than HC. By comparing with fecal metagenomics studies, we found there was moderate positive correlation between fold changes of the overlapped fecal and circulating bacterial DNA. Finally, species correlation analysis revealed that CRC and HC displayed distinct patterns of species association. In conclusion, this study demonstrated alterations of circulating bacterial DNA in colorectal neoplasia patients, which had the potential to become non-invasive biomarkers for colorectal neoplasia screening and early diagnosis.

20.
Molecules ; 25(22)2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33218025

RESUMO

Proteases catalyse irreversible posttranslational modifications that often alter a biological function of the substrate. The protease dipeptidyl peptidase 4 (DPP4) is a pharmacological target in type 2 diabetes therapy primarily because it inactivates glucagon-like protein-1. DPP4 also has roles in steatosis, insulin resistance, cancers and inflammatory and fibrotic diseases. In addition, DPP4 binds to the spike protein of the MERS virus, causing it to be the human cell surface receptor for that virus. DPP4 has been identified as a potential binding target of SARS-CoV-2 spike protein, so this question requires experimental investigation. Understanding protein structure and function requires reliable protocols for production and purification. We developed such strategies for baculovirus generated soluble recombinant human DPP4 (residues 29-766) produced in insect cells. Purification used differential ammonium sulphate precipitation, hydrophobic interaction chromatography, dye affinity chromatography in series with immobilised metal affinity chromatography, and ion-exchange chromatography. The binding affinities of DPP4 to the SARS-CoV-2 full-length spike protein and its receptor-binding domain (RBD) were measured using surface plasmon resonance and ELISA. This optimised DPP4 purification procedure yielded 1 to 1.8 mg of pure fully active soluble DPP4 protein per litre of insect cell culture with specific activity >30 U/mg, indicative of high purity. No specific binding between DPP4 and CoV-2 spike protein was detected by surface plasmon resonance or ELISA. In summary, a procedure for high purity high yield soluble human DPP4 was achieved and used to show that, unlike MERS, SARS-CoV-2 does not bind human DPP4.

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