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1.
Carbohydr Polym ; 275: 118611, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34742454

RESUMO

The hypoxia in tumor microenvironment (TME) can upregulate the HIF-1α and PD-L1 expression and cause immunosuppression of tumor. In this study, a carboxymethyl chitosan-based pH/hypoxia-responsive and γ-Fe2O3/isosorbide dinitrate carrying micelle was designed, and it could catalyze endogenous H2O2 to generate oxygen and relieve hypoxia in TME, so as to relieve the overexpression of HIF-1α and PD-L1 in tumor; meanwhile, it could react with H2O2 to release ROS via Fenton reaction and induce cytotoxicity in tumor. Along with these multiple effects, this carboxymethyl chitosan-based micelles could provide a comprehensive strategy for tumor treatment.

2.
Mol Cell Endocrinol ; 539: 111473, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34610358

RESUMO

High concentrations of free fatty acids (FFAs) or lipopolysaccharide (LPS) could lead to ß-cell apoptosis and dysfunction, while low-grade elevation of FFAs or LPS, which are more common in people with type 2 diabetes mellitus (T2DM) or obesity, have no obvious toxic effect on ß-cells. Palmitate is a component closely related to metabolic disorders in FFAs. Recent studies have found that low-grade elevation of palmitate and LPS synergistically affects the sphingolipid signaling pathway by activating Toll-like receptor 4 (TLR4) and further enhances the expression of inflammatory cytokines in immune cells. Previous studies demonstrated that sphingolipids also played an important role in the occurrence and development of T2DM. This study aimed to investigate the synergistic effects of low-grade elevation of palmitate and LPS on viability, apoptosis and insulin secretion in the rat pancreatic ß-cell line INS-1 or islets and the role of sphingolipids in this process. We showed that low-grade elevation of palmitate or LPS alone did not affect the viability, apoptosis, glucose-stimulated insulin secretion (GSIS) or intracellular insulin content of INS-1 cells or islets, while the combination of the two synergistically inhibited cell viability, induced apoptosis and decreased basal insulin secretion in INS-1 cells or islets. Treatment with palmitate and LPS markedly upregulated TLR4 protein expression and downregulated neutral ceramidase (NCDase) activity and protein expression. Additionally, low-grade elevation of palmitate and LPS synergistically induced a significant increase in ceramide and a decrease in sphingosine-1-phosphate. Blocking TLR4 signaling or overexpressing NCDase remarkably attenuated INS-1 cell injury induced by the combination of palmitate and LPS. However, inhibition of ceramide synthase did not ameliorate injury induced by palmitate and LPS. Overall, we show for the first time that low-grade elevation of palmitate and LPS synergistically induced ß-cell damage by activating TLR4 signaling, inhibiting NCDase activity, and further modulating sphingolipid metabolism, which was different from a high concentration of palmitate-induced ß-cell injury by promoting ceramide synthesis.

3.
Food Chem ; 372: 131255, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-34627084

RESUMO

Tibet's native fruit resources have not been explored and remain underutilized due to geographical isolation. "Medog lemon" (ML), an ethno-species of wild citron, is an important functional food and dietary resource for the local people in southeastern Tibet. Herein comprehensive characterization of components of ML were firstly performed with an integrated strategy based on UHPLC-QE Orbitrap MS. A total of 196 components were characterized, among which 33 were detected from Citrus genus for the first time, and 55 were identified as potential new phytochemicals. The chemical comparison of ML with cultivated citron and fingered citron based on partial least squares-discriminant analysis model and univariate analysis revealed the distinct chemical composition of ML and in which more than 30 differentiated components were identified. The distinct morphological and chemical characters, as well as its good antioxidant properties, indicated ML as a potential new food resource that can be beneficial for human health.

4.
J Cosmet Dermatol ; 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34731521

RESUMO

OBJECTIVE: To the knowledge of the authors, no data about the reproducibility and accuracy of 3-dimensional surface imaging of the face using a whole-body scanner are available. Thus, the objective of this investigation was to assess the reproducibility of facial scans acquired using a whole-body imaging device. MATERIAL AND METHODS: This investigation investigated 220 3-D scans of a total of 22 healthy volunteers (with a mean age of 29.36 years). Two consecutive 3-D images using a Vectra WB360 of the volunteers were obtained utilizing a whole-body imaging device. Predefined distances in the face were performed in each scan and compared. Furthermore, surface deviation between two consecutively captured scans was assessed. RESULTS: The distance with the smallest statistical significance was found to be at the nose with p = 0.998, while the biggest statistical significance was found in the midface with p = 0.658. The area with the biggest surface deviation between the superimposed scans was the neck with a root mean square (RMS) of 1.62 ± 1.71, and the area with the smallest surface deviation was the forehead with a RMS of 0.17 ± 0.05. CONCLUSION: The whole-body imaging device investigated in this study can be utilized to capture the face and provides enough accuracy to compare scans. Even though not directly investigated, it can be hypothesized that the error caused by repositioning the patient between a baseline and a follow-up scan will not be too big to consider measurements performed with the whole-body imaging device as impractical.

5.
Transl Oncol ; 15(1): 101259, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34735896

RESUMO

Melanoma is an aggressive skin cancer that metastasizes to other organs. While immune checkpoint blockade with anti-PD-1 has transformed the treatment of advanced melanoma, many melanoma patients fail to respond to anti-PD-1 therapy or develop acquired resistance. Thus, effective treatment of melanoma still represents an unmet clinical need. Our prior studies support the anti-cancer activity of the 17ß-hydroxywithanolide class of natural products, including physachenolide C (PCC). As single agents, PCC and its semi-synthetic analog demonstrated direct cytotoxicity in a panel of murine melanoma cell lines, which share common driver mutations with human melanoma; the IC50 values ranged from 0.19-1.8 µM. PCC treatment induced apoptosis of tumor cells both in vitro and in vivo. In vivo treatment with PCC alone caused the complete regression of established melanoma tumors in all mice, with a durable response in 33% of mice after discontinuation of treatment. T cell-mediated immunity did not contribute to the therapeutic efficacy of PCC or prevent tumor recurrence in YUMM2.1 melanoma model. In addition to apoptosis, PCC treatment induced G0-G1 cell cycle arrest of melanoma cells, which upon removal of PCC, re-entered the cell cycle. PCC-induced cycle cell arrest likely contributed to the in vivo tumor recurrence in a portion of mice after discontinuation of treatment. Thus, 17ß-hydroxywithanolides have the potential to improve the therapeutic outcome for patients with advanced melanoma.

6.
Arch Oral Biol ; 133: 105301, 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34781072

RESUMO

OBJECTIVE: To investigate claudin-17 (CLDN17) expression in oral cancer and its effect on epithelial-mesenchymal transition (EMT), invasion and migration in oral cancer cells. METHODS: The GEO2R tool was used to analyze gene expression in two microarray datasets (GSE74530 and GSE146483) derived from the Gene Expression Omnibus (GEO) database. Gene Expression Profiling Interactive Analysis (GEPIA) verified CLDN17 expression in head and neck squamous cell carcinoma (HNSC) patients. Moreover, oral cancer cells were transfected with CLDN17 overexpression plasmid or CLDN17 shRNA to evaluate cell invasion and migration. Gene and protein expression was detected by qRT-PCR, immunohistochemistry and western blotting. RESULTS: CLDN17 was one of the top 200 differentially expressed genes in the GSE74530 and GSE146483 datasets and was downregulated in oral cancer. CLDN17 expression was higher in HNSC tissues, and it was related to TNM staging. In HNSC tumors, CLDN17 expression was positively correlated with CDH1 but negatively related to VIM, SNAIL1, SNAIL2, and TWIST1. Meanwhile, we found that CLDN17 expression was lower in oral cancer tissues; it declined with higher T status, N status, M status and staging, lower differentiation grade, and a worse prognosis. Upregulation of CLDN17 inhibited the invasion and migration of oral cancer cells, with elevated CDH1 and reduced VIM, SNAIL1, SNAIL2, and TWIST1, while CLDN17 downregulation had the opposite effects. CONCLUSION: CLDN17 may serve as a tumor suppressor in oral cancer since it could reduce the invasion and migration of cells by inhibiting the EMT process, thus becoming a potential therapeutic target in oral cancer.

7.
Sci Total Environ ; : 151814, 2021 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-34813814

RESUMO

While the secondary metabolites of DDT such as 2,2-bis(chlorophenyl)-1-chloroethylene (DDMU) and 2,2-bis(chlorophenyl)methane (DDM) have been detected in the environment for several decades, knowledge is extremely limited on their bioaccumulation characteristics. Here, we reported the bioaccumulation and maternal transfer of p,p'-DDMU and p,p'-DDM in two wild fishes, i.e., the northern snakehead (Channa argus) and crucian carp (Carassius auratus), from a DDT contaminated site in South China. The hepatic concentrations of p,p'-DDMU and p,p'-DDM in the fish were up to 549 and 893 ng/g lipid weight, contributing 5.3% and 3.2% in average to ΣDDXs (the sum concentrations of DDT and its 6 metabolites), respectively. The residues of p,p'-DDMU and p,p'-DDM in the fish exhibited interspecific and intraspecific variations, resulting from the differences in lipid content, sex, and body sizes (length and mass) between or within species. Both p,p'-DDMU and p,p'-DDM were consistently detected in the fish eggs, demonstrating their maternal transfer in female fish. The mean eggs to liver lipid-normalized concentration (E/L) ratios of p,p'-DDMU and p,p'-DDM were 0.98 and 1.77 in the northern snakehead, 0.35 and 0.01 in crucian carp, respectively; which were comparable to or even exceeded those of DDT and its major metabolites calculated in the same individual. Statistical analyses of the data showed that the E/L ratios were positively correlated with body sizes of the fish, but negatively correlated with the hepatic concentrations of p,p'-DDMU and p,p'-DDM in females; suggesting the influences of fish sizes and the mother body residues on their maternal transfer efficiencies.

8.
FEBS Open Bio ; 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34792288

RESUMO

Exposure to extended periods of darkness is a common source of abiotic stress that significantly affects plant growth and development. To understand how Nicotiana benthamiana responds to dark stress, the proteomes and metabolomes of leaves treated with darkness were studied. In total, 5,763 proteins and 165 primary metabolites were identified following dark treatment. Additionally, the expression of autophagy-related gene (ATG) proteins was transiently up-regulated. Weighted gene co-expression network analysis (WGCNA) was utilized to find the protein modules associated with the response to dark stress. A total of four co-expression modules were obtained. The results indicated that heat shock protein (HSP70), SnRK1- interacting protein 1, 2A phosphatase associated protein of 46 kDa (Tap46) and glutamate dehydrogenase (GDH) might play crucial roles in N. benthamiana's response to dark stress. Furthermore, a protein-protein-interaction (PPI) network was constructed and top-degreed proteins were predicted to identify potential key factors in the response to dark stress. These proteins include isopropylmalate isomerase (IPMI), eukaryotic elongation factor 5A (ELF5A) and ribosomal protein 5A (RPS5A). Finally, metabolic analysis suggested that some amino acids and sugars were involved in the dark responsive pathways. Thus, these results provide a new avenue for understanding the defensive mechanism against dark stress at the protein and metabolic levels in N. benthamiana.

9.
Commun Biol ; 4(1): 1307, 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34795381

RESUMO

The domestication and subsequent development of sheep are crucial events in the history of human civilization and the agricultural revolution. However, the impact of interspecific introgression on the genomic regions under domestication and subsequent selection remains unclear. Here, we analyze the whole genomes of domestic sheep and their wild relative species. We found introgression from wild sheep such as the snow sheep and its American relatives (bighorn and thinhorn sheep) into urial, Asiatic and European mouflons. We observed independent events of adaptive introgression from wild sheep into the Asiatic and European mouflons, as well as shared introgressed regions from both snow sheep and argali into Asiatic mouflon before or during the domestication process. We revealed European mouflons might arise through hybridization events between a now extinct sheep in Europe and feral domesticated sheep around 6000-5000 years BP. We also unveiled later introgressions from wild sheep to their sympatric domestic sheep after domestication. Several of the introgression events contain loci with candidate domestication genes (e.g., PAPPA2, NR6A1, SH3GL3, RFX3 and CAMK4), associated with morphological, immune, reproduction or production traits (wool/meat/milk). We also detected introgression events that introduced genes related to nervous response (NEURL1), neurogenesis (PRUNE2), hearing ability (USH2A), and placental viability (PAG11 and PAG3) into domestic sheep and their ancestral wild species from other wild species.

10.
Materials (Basel) ; 14(21)2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34772055

RESUMO

Diatomite-based X zeolite was obtained and its crystallinity, morphology, and interface properties were investigated by XRD, BET, SEM, EDS, and XRF. The obtained X zeolite possessed a unique meso-microporous structure and showed good ion exchange properties for Cu2+ and Zn2+. The pseudo-second-order model and Langmuir isotherm model can best describe the adsorption kinetics and isotherms of Cu2+ and Zn2+, respectively. The maximal adsorption capacities of X zeolite for Cu2+ and Zn2+ were 146 and 195 mg/g at 323 K, respectively. Meanwhile, the adsorption process for Cu2+ and Zn2+ were chemical adsorption and ion exchange, respectively. Furthermore, the adsorption data turned out to be an endothermic and spontaneous process. Compared with other reported materials, the adsorption capacity of X zeolite synthesized from diatomite was among the highest. Therefore, it could be a promising adsorbent for the disposal of wastewater that contains metal ions.

11.
Front Nutr ; 8: 737539, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34604284

RESUMO

Ganpu tea, an emerging pu-erh compound tea, which is cofermented with the peel of Citrus reticulata "Chachi," has been widely favored by Chinese consumers due to its potential health effects and distinct flavor and taste. So far, the influence of this cofermentation procedure on the chemical profile of pu-erh tea has barely been addressed yet. In this work, an ultra-high-performance liquid chromatography-Q Exactive Orbitrap mass spectrometry (UHPLC-QE Orbitrap MS)-based qualitative and quantitative method combined with multivariate analysis was conducted to comprehensively investigate the chemical changes in pu-erh tea after cofermented with Citrus peel. A total of 171 compounds were identified based on a three-level strategy, among which seven phenolic acids, 11 flavan-3-ols, and 27 flavonoids and flavonoid glycosides were identified from pu-erh tea for the first time. Eighty-nine main constituents were selected for further quantitative analysis using a validated method. Both the principal component analysis (PCA) of untargeted metabolomics and orthogonal partial least squares discriminant analysis (OPLS-DA) models of targeted components revealed the significant chemical profile disparity between the raw pu-erh tea and Ganpu tea. It showed that Citrus tea cofermentation process significantly decreased the total contents of phenolic acids, flavan-3-ols, and flavonoid aglycones, while most of the quercetin glycosides and myricetin glycosides as well as the vitexin were significantly increased. In addition, hesperidin, a flavonoid glycoside only existed in Citrus, was first found in pu-erh tea after cofermented with Citrus. This study clearly profiled the chemical composition and content changes of pu-erh tea after cofermented with Citrus peel, which revealed that Citrus tea cofermentation process further accelerated the fermentation of pu-erh tea and improved the unique flavor of tea.

12.
Oncol Lett ; 22(5): 792, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34630703

RESUMO

Previous studies have reported that the aberrant expression of circulating microRNAs (miRNAs/miRs) can be used as diagnostic and prognostic markers in non-small cell lung cancer (NSCLC). The present study aimed to assess the diagnostic and prognostic predictive values of four plasma miRNAs for NSCLC. A total of 12 candidate miRNAs were selected that have previously been reported to be aberrantly expressed in NSCLC, and their plasma levels in the training set were detected via reverse transcription-quantitative PCR analysis. The screened out miRNAs were further validated in the testing set. The area under the curve (AUC) of the receiver operating characteristic curve was constructed to evaluate diagnostic performance. Kaplan-Meier survival analysis was performed to assess the association between the plasma miRNA levels and disease-free survival (DFS) time. The results demonstrated that 4/12 plasma miRNAs (miR-210, miR-1290, miR-150 and miR-21-5p) were highly expressed in patients with NSCLC compared with their expression levels in patients with benign lung disease (BLD) and healthy controls in the training and testing sets, respectively. The AUC values of the four-miRNA panel were 0.96 and 0.93 in the training and testing sets, respectively, for distinguishing patients with NSCLC from healthy controls, which were similar to the AUC values for distinguishing patients with NSCLC from patients with BLD (0.96 and 0.94). The AUC values of the four-miRNA panel in patients with stage I NSCLC were comparable to that of patients with stage II-III NSCLC (0.942 and 0.965). Patients with high plasma levels of miR-210 and miR-150 had worse DFS than those with low plasma levels of these miRNAs. In addition, patients whose plasma levels of the four miRNAs decreased by >50% after surgery exhibited a good DFS. Taken together, the results of the present study suggest that these four miRNAs (miR-210, miR-1290, miR-150 and miR-21-5p) act as useful biomarkers for early diagnosis and prognosis of NSCLC.

13.
Front Neurol ; 12: 713293, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34664012

RESUMO

Objective: We test the hypothesis that lysine acetylation is involved in the metabolic process of glioma-associated seizures (GAS). Methods: We used label-free mass spectrometry-based quantitative proteomics to quantify dynamic changes of protein acetylation between gliomas with seizure (CA1 group) and gliomas without seizure (CA2 group). Furthermore, differences of acetyltransferase and deacetylase expression between CA1 and CA2 groups were performed by a quantitative proteomic study. We further classified acetylated proteins into groups according to cell component, molecular function, and biological process. In addition, metabolic pathways and protein interaction networks were analyzed. Regulated acetyltransferases and acetylated profiles were validated by PRM and Western blot. Results: We detected 169 downregulated lysine acetylation sites of 134 proteins and 39 upregulated lysine acetylation sites of 35 proteins in glioma with seizures based on acetylome. We detected 407 regulated proteins by proteomics, from which ACAT2 and ACAA2 were the differentially regulated enzymes in the acetylation of GAS. According to the KEGG analysis, the upregulated acetylated proteins within the PPIs were mapped to pathways involved in the TCA cycle, oxidative phosphorylation, biosynthesis of amino acids, and carbon metabolism. The downregulated acetylated proteins within the PPIs were mapped to pathways involved in fatty acid metabolism, oxidative phosphorylation, TCA cycle, and necroptosis. Regulated ACAT2 expression and acetylated profiles were validated by PRM and Western blot. Conclusions: The data support the hypothesis that regulated protein acetylation is involved in the metabolic process of GAS, which may be induced by acetyl-CoA acetyltransferases.

14.
Front Endocrinol (Lausanne) ; 12: 740902, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34621244

RESUMO

Fatty acid binding protein 4 (FABP4) has been associated with insulin resistance. Gestational diabetes mellitus (GDM) impairs fetal insulin sensitivity. Female newborns are more insulin resistant than male newborns. We sought to evaluate the association between GDM and cord blood FABP4, and explore potential sex dimorphic associations and the roles of sex hormones. This was a nested case-control study in the Shanghai Birth Cohort, including 153 pairs of newborns in GDM vs. euglycemic pregnancies matched by infant sex and gestational age at delivery. Cord plasma FABP4, leptin, total and high-molecular-weight adiponectin, testosterone and estradiol concentrations were measured. Adjusting for maternal and neonatal characteristics, cord plasma FABP4 (Mean ± SD: 27.0 ± 19.6 vs. 18.8 ± 9.6 ng/mL, P=0.045) and estradiol (52.0 ± 28.6 vs. 44.2 ± 26.6, ng/mL, P=0.005) concentrations were higher comparing GDM vs. euglycemic pregnancies in males, but similar in females (all P>0.5). Mediation analyses showed that the positive association between GDM and cord plasma FABP4 in males could be partly mediated by estradiol (P=0.03), but not by testosterone (P=0.72). Cord plasma FABP4 was positively correlated with total adiponectin in females (r=0.17, P=0.053), but the correlation was in the opposite direction in males (r=-0.11, P=0.16) (test for difference in r, P=0.02). Cord plasma FABP4 was not correlated with leptin in both sexes. The study is the first to demonstrate sex-dimorphic associations between GDM and cord plasma FABP4 or estradiol, and between FABP4 and adiponectin in newborns. GDM may affect fetal circulating FABP4 and estradiol levels in males only.

15.
Front Immunol ; 12: 711980, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34594327

RESUMO

Regulatory B cells (Breg) are considered as immunosuppressive cells. Different subsets of Breg cells have been identified both in human beings and in mice. However, there is a lack of unique markers to identify Breg cells, and the heterogeneity of Breg cells in different organs needs to be further illuminated. In this study, we performed high-throughput single-cell RNA sequencing (scRNA-seq) and single-cell B-cell receptor sequencing (scBCR-seq) of B cells from the murine spleen, liver, mesenteric lymph nodes, bone marrow, and peritoneal cavity to better define the phenotype of these cells. Breg cells were identified based on the expression of immunosuppressive genes and IL-10-producing B (B10) cell-related genes, to define B10 and non-B10 subsets in Breg cells based on the score of the B10 gene signatures. Moreover, we characterized 19 common genes significantly expressed in Breg cells, including Fcrl5, Zbtb20, Ccdc28b, Cd9, and Ptpn22, and further analyzed the transcription factor activity in defined Breg cells. Last, a BCR analysis was used to determine the clonally expanded clusters and the relationship of Breg cells across different organs. We demonstrated that Atf3 may potentially modulate the function of Breg cells as a transcription factor and that seven organ-specific subsets of Breg cells are found. Depending on gene expression and functional modules, non-B10 Breg cells exhibited activated the TGF-ß pathway, thus suggesting that non-B10 Breg cells have specific immunosuppressive properties different from conventional B10 cells. In conclusion, our work provides new insights into Breg cells and illustrates their transcriptional profiles and BCR repertoire in different organs under physiological conditions.

16.
Metab Eng ; 68: 142-151, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34610458

RESUMO

Glycolysis is the primary metabolic pathway in all living organisms. Maintaining the balance of glycolysis flux and biosynthetic pathways is the crucial matter involved in the microbial cell factory. Few regulation systems can address the issue of metabolic flux imbalance in glycolysis. Here, we designed and constructed a bifunctional glycolysis flux biosensor that can dynamically regulate glycolysis flux for overproduction of desired biochemicals. A series of positive-and negative-response biosensors were created and modified for varied thresholds and dynamic ranges. These engineered glycolysis flux biosensors were verified to be able to characterize in vivo fructose-1,6-diphosphate concentration. Subsequently, the biosensors were applied for fine-tuning glycolysis flux to effectively balance the biosynthesis of two chemicals: mevalonate and N-acetylglucosamine. A glycolysis flux-dynamically controlled Escherichia coli strain achieved a 111.3 g/L mevalonate titer in a 1L fermenter.

17.
Environ Pollut ; 291: 118270, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34601034

RESUMO

The crude e-waste recycling has been regulated in China since the late 2000s; however, information on the recent levels and the ecological risks of e-waste derived contaminants such as halogenated flame retardants (HFRs) in the e-waste sites are limited. We therefore examined the concentrations of several HFRs in wild, prey-sized mud carps collected from a typical e-waste site in 2006, 2011 and 2016, to understand the exposure dynamics and ecological risk of these chemicals. Several ecological and biological parameters including δ15N, δ13C, body size and lipid content of the fish were also examined, to ensure an overall uniformity of the sample set among the sampling years. Among the HFRs measured, polybrominated diphenyl ethers (PBDEs) were detected at the highest concentrations (contributing >90% to ∑HFRs), followed by Dechlorane Plus (DPs), polybrominated biphenyls (PBBs), and alternative brominated flame retardants (ABFRs). The fish concentrations of ∑PBDEs, ∑PBBs and ∑DPs significantly dropped by 65%, 57% and 53% from 2006 to 2011, and 12%, 74% and 51% from 2011 to 2016, respectively; likely reflecting the positive impact of the environmental regulations on crude e-waste recycling. The ∑ABFRs concentrations were also decreased by 80% from 2006 to 2011, but increased by 127% from 2011 to 2016; suggesting possible fresh input of these novel HFRs in recent years. In addition to the changes in the HFR concentrations, contaminant profiles in the fish were also changed, possibly due to environmental degradation of the HFRs. Despite our conservative method of risk assessment, we found that PBDEs posed an important risk both for the mud carp and for piscivorous wildlife that inhabit the e-waste site.


Assuntos
Carpas , Resíduo Eletrônico , Retardadores de Chama , Animais , China , Monitoramento Ambiental , Retardadores de Chama/análise , Éteres Difenil Halogenados/análise , Reciclagem , Medição de Risco
18.
Ecotoxicol Environ Saf ; 227: 112898, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34673416

RESUMO

In the hazard assessment of mixtures, the mixture predicted no-effect concentration (mPNEC) is always derived by the concentration addition (CA) model (mPNECCA) to assess the risk of mixtures combined with exposure assessment. However, the independent action (IA) model, which is also widely used as the CA model in the prediction and evaluation of mixture toxicity, is always used to calculate the population fraction showing a predefined effect, not mPNEC, and this limits the application of IA model in the mixture risk assessment. In this study, we explored the process of mPNEC derived by the IA method (mPNECIA) based on the species sensitivity distribution (SSD) and compared mPNECIA with mPNECCA. Taking two common pesticides, dimethoate (DIM) and dichlorvos (DIC), exposed in the actual water environment as an example, their SSD models were constructed separately using nine distribution functions after toxicity data screening and quality testing. For both DIC and DIM, all different nine models had passed the Kolmogorov-Smirnov test. Then, the PNECs of two pesticides were derived based on SSD models. Finally, mPNECIA with different concentration ratios was derived and compared to mPNECCA based on 81 combinations of nine SSD models. Most mPNEC values derived by IA model were more conservative than those by CA. It is worth noting that the mPNECIA is more conservative than mPNECCA for the commonly used log-logit distribution (function 7), log-normal distribution (8), and log-Weibull distribution (9). This study provides a new direction for the application of IA in the risk assessment and enriches the framework of mixture risk assessment.


Assuntos
Praguicidas , Diclorvós , Dimetoato , Praguicidas/toxicidade , Medição de Risco
19.
Asian J Androl ; 23(6): 572-579, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34708719

RESUMO

Programmed DNA double-strand breaks (DSBs) are necessary for meiosis in mammals. A sufficient number of DSBs ensure the normal pairing/synapsis of homologous chromosomes. Abnormal DSB repair undermines meiosis, leading to sterility in mammals. The DSBs that initiate recombination are repaired as crossovers and noncrossovers, and crossovers are required for correct chromosome separation. Thus, the placement, timing, and frequency of crossover formation must be tightly controlled. Importantly, mutations in many genes related to the formation and repair of DSB result in infertility in humans. These mutations cause nonobstructive azoospermia in men, premature ovarian insufficiency and ovarian dysgenesis in women. Here, we have illustrated the formation and repair of DSB in mammals, summarized major factors influencing the formation of DSB and the theories of crossover regulation.

20.
Sci Rep ; 11(1): 18824, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34552120

RESUMO

Akt and nuclear factor kappa B (NF-κB) signaling pathways are involved in germ cell apoptosis and inflammation after testicular heat stress (THS). We observed that after THS induced by the exposure of rat testes to 43 °C for 20 min, their weight decreased, the fraction of apoptotic testicular germ cells significantly increased, and the proliferation of germ cells was inhibited. In addition, THS lowered serum testosterone (T) level, whereas the levels of follicle stimulating hormone and luteinizing hormone were not significantly changed. The ultrastructure of the seminiferous tubules became abnormal after THS, the structure of the blood-testis barrier (BTB) became loose, and the Sertoli cells showed a trend of differentiation. The level of phosphorylated Akt was reduced, whereas the amount of phosphorylated NF-κB p65 was augmented by THS. Wuzi-Yanzong (WZYZ), a classic Chinese medicine prescription for the treatment of male reproductive dysfunctions, alleviated the changes induced by THS. In order to determine the mechanism of action of WZYZ, we investigated how this preparation modulated the levels of T, androgen receptor (AR), erythropoietin (EPO), EPO receptor, and Tyro-3, Axl, and Mer (TAM) family of tyrosine kinase receptors. We found that WZYZ activated the Akt pathway, inhibited the Toll-like receptor/MyD88/NF-κB pathway, and repaired the structure of BTB by regulating the levels of T, AR, TAM receptors, and EPO. In conclusion, these results suggest that WZYZ activates the Akt pathway and inhibits the NF-κB pathway by acting on the upstream regulators, thereby improving spermatogenesis deficit induced by THS.

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