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1.
Environ Int ; 138: 105648, 2020 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-32187572

RESUMO

Microcystins (MCs) produced by cyanobacteria pose serious threats to human health. However, the contribution of long-term exposure to MCs to the development of nonalcoholic fatty liver disease (NAFLD) remains poorly documented. In this study, we estimated the environmental uptake of MCs by a small population of fishers who have lived for many years on Meiliang Bay of Lake Taihu, where cyanobacterial blooms occur frequently. Serum biochemical indices of liver function and their relationships with MC contamination in these people were also investigated. Moreover, to mimic the long-term effects of MC on the livers of fishers, an animal model was established in which mice were exposed to MC-LR at an environmentally relevant level, a reference level (the no-observed adverse effect level, NOAEL), and three times the NOAEL through drinking water for 12 months. We estimated the total daily intake of MCs by fishers through contaminated lake water and food to be 5.95 µg MC-LReq, far exceeding the tolerable daily intake (2.40 µg MC-LReq) proposed by the World Health Organization (WHO). More than 80% of participants had at least one abnormal serum marker. The indices of aspartate aminotransferase (AST)/alanine aminotransferase (ALT), triglyceride (TG), globulin (GLB), and lactate dehydrogenase (LDH) had close positive associations with MC contamination, indicating that both liver damage and lipid metabolism dysfunction were induced by chronic MC exposure. Furthermore, the animal experimental results showed that long-term exposure to MC-LR at the environmentally relevant level led to hepatic steatosis with molecular alterations in circadian rhythm regulation, lipid metabolic processes, and the cell cycle pathway. Exposure to MC-LR at or above the NOAEL worsened the pathological phenotype towards nonalcoholic steatohepatitis disease (NASH) or fibrosis. These results suggest that prolonged exposure to the reference level (NOAEL) of MC-LR could cause severe liver injury to mammals. People with long-term environmental exposure to MCs might be at high risk for developing NAFLD.

2.
Biol Reprod ; 2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32167535

RESUMO

Formin-like 3 (FMNL3) is a member of the formin-likes (FMNLs), which belong to the formin family. As an F-actin nucleator, FMNL3 is essential for several cellular functions, such as polarity control, invasion, and migration. However, the roles of FMNL3 during oocytes meiosis remain unclear. In this study, we investigated the functions of FMNL3 during mouse oocyte maturation. Our results showed that FMNL3 mainly concentrated in the oocyte cortex and spindle periphery. Depleting FMNL3 led to the failure of polar body extrusion, and we also found large polar bodies in the FMNL3-deleted oocytes, indicating the occurrence of symmetric meiotic division. There was no effect of FMNL3 on spindle organization; however, we observed spindle migration defects at late metaphase I, which might be due to the decreased cytoplasmic actin. Microinjecting Fmnl3-EGFP mRNA into Fmnl3-depleted oocytes significantly rescued these defects. In addition, the results of co-immunoprecipitation and the perturbation of protein expression experiments suggested that FMNL3 interacted with the actin-binding protein FASCIN for the regulation of actin filaments in oocytes. Thus, our results provide the evidence that FMNL3 regulates FASCIN for actin-mediated spindle migration and cytokinesis during mouse oocyte meiosis.

3.
Pathol Res Pract ; : 152883, 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32088087

RESUMO

OBJECTIVE: To investigate the role and mechanisms of HAUSP (Herpesvirus Associated Ubiquitin Specific Protease) and NANOG in pathogenesis of malignant human gliomas progression. METHODS: Lentivirus-mediated HAUSP over-expression and RNAiHAUSP mediated HAUSP down-regulation were established in the glioma cells (U87 and U251 cell lines). Firstly, Real-time qPCR, western-blot (WB) and immunofluorescence staining were performed to detect mRNA levels, protein expressions and deposition of HAUSP and NANOG in the glioma cells, respectively. Then cell proliferation, invasion, apoptosis and xenograft tumor growth in nude mice were assessed by using cell counting kit-8 (CCK-8) assay, transwell assay, flow cytometry (FCM) and Hematoxylin-Eosin (HE) staining. RESULTS: We first demonstrated HAUSP was significantly increased in lentivirus- mediated HAUSP over-expression cells compared to the Control group. HAUSP over-expression could upregulate genes involved in proliferation and invasion such as NANOG. However, the mRNA of NANOG had no significant changes. Similarly, in RNAiHAUSP mediated HAUSP down-regulation group, HAUSP were significantly decreased compared to the Control group. Simultaneously, NANOG protein were decreased significantly, which decreased the proliferation and invasion, increased the apoptosis rate of glioma cells. Finally, low expression of HAUSP could suppress xenograft tumors growth in nude mice in different periods. CONCLUSION: This study revealed that HAUSP-NANOG pathway is a key target to inhibit glioma cells proliferation, and NANOG play important role in the formation and evolution of glioma cells. The regulation of HAUSP could change the biological activity of glioma cells through regulate NANOG expression.

4.
Steroids ; 157: 108598, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32068075

RESUMO

Three new oxygenated steroids, sinulasterols A-C (1-3), along with seven known related steroids 4-10, were isolated from the Chinese soft coral Sinularia depressa. The structures of the new compounds were established from extensive spectroscopic data analyses and by comparison of their spectral data with those reported in the literature. Among the new compounds, metabolites 1 and 2 featured on unusual C-18 oxygenated pattern. In the TNF-α bioassay, compound 4 exhibited a potent inhibitory activity (IC50 = 12.1 µM), which was analogous to the positive control dexamethasone (IC50 = 8.7 µM), metabolites 1 and 2 displayed a moderate inhibitory activity (IC50 51.1 µM and 22.7 µM respectively).

5.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1865(5): 158633, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31988050

RESUMO

BACKGROUND AND AIMS: Fargesin mainly functions in the improvement of lipid metabolism and the inhibition of inflammation, but the role of fargesin in atherogenesis and the molecular mechanisms have not been defined. We aimed to explore if and how fargesin affects atherosclerosis by regulating lipid metabolism and inflammatory response. METHODS AND RESULTS: ApoE-/- mice were fed a high-fat diet to form atherosclerotic plaques and then administrated with fargesin or saline via gavage. Oil Red O, HE and Masson staining were performed to assess atherosclerostic plaques in apoE-/- mice. [3H] labeled cholesterol was used to detect cholesterol efflux and reverse cholesterol transport (RCT) efficiency. Enzymatic methods were performed to analyze plasma lipid profile in apoE-/- mice. Immunohistochemistry was used to analyze macrophage infiltration. THP-1-derived macrophages were incubated with fargesin or not. Both Western blot and qRT-PCR were applied to detect target gene expression. Oil Red O staining was applied to examine lipid accumulation in THP-1-derived macrophages. ELISA and qRT-PCR were used to examine the levels of inflammatory mediotors. We found that fargesin reduced atherosclerotic lesions by elevating efficiency of RCT and decreasing inflammatory response via upregulation of ABCA1 and ABCG1 expression in apoE-/- mice. Further, fargesin reduced lipid accumulation in THP-1-derived macrophages. Besides, fargesin increased phosphorylation of CEBPα in Ser21 and then upregulated LXRα, ABCA1 and ABCG1 expression in THP-1-derived macrophages. In addition, fargesin could reduce ox-LDL-induced inflammatory response by inactivation of the TLR4/NF-κB pathway. CONCLUSION: These results suggest that fargesin inhibits atherosclerosis by promoting RCT process and reducing inflammatory response via CEBPαS21/LXRα and TLR4/NF-κB pathways, respectively.

6.
Theriogenology ; 144: 132-138, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31940504

RESUMO

N-WASP is the mammalian ortholog of WASP which is an actin nucleation promoting factor and has been reported to regulate actin nucleation and polymerization for multiple cell activities. However, the expression and functions of N-WASP in porcine oocytes are still unclear. In this study, we showed that N-WASP expressed at all stages during porcine oocyte maturation, and immunofluorescence staining indicated that N-WASP mainly accumulated at the cortex in different stages of meiosis. Inhibition of N-WASP activity by Wiskostatin significantly decreased the rate of first polar body extrusion and disturbed the cell cycle progression of porcine oocytes. Further analysis indicated that cortical actin distribution was interfered by N-WASP inhibition, and this might be through its regulatory roles on the expression and localization of ARP2, a key component of actin nucleator Arp2/3 complex. Moreover, the expression of N-WASP decreased after ROCK activity inhibition, indicating a ROCK-N-WASP-ARP2/3 pathway for actin assembly in porcine oocytes. Taken together, these results suggest that N-WASP is critical for the regulation of actin filaments for cytokinesis during porcine oocyte maturation.

7.
Pediatr Transplant ; 24(2): e13618, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31944495

RESUMO

This is a retrospective study to evaluate the efficacy and safety of umbilical cord blood-derived mesenchymal stromal cells (MSCs) for the treatment of pediatric patients with severe BK virus-associated late-onset hemorrhagic cystitis (BKV-HC) after unrelated cord blood transplantation (UCBT). Thirteen pediatric patients with severe BKV-HC from December 2013 to December 2015 were treated with MSCs. The number of MSCs transfused in each session was 1 × 106 /kg once a week until the symptoms improved. The median follow-up time was 1432 (89-2080) days. The median frequency of MSC infusion was 2 (1-3), with eight cured cases and five effective cases; the total efficacy rate was 100%. The copy number of urine BKV DNA was 4.43 (0.36-56.9) ×108 /mL before MSC infusion and 2.67 (0-56.3) ×108 /mL after MSC infusion; the difference was not significant (P = .219). There were no significant differences in the overall survival, disease-free survival, and the incidence of relapse and acute and chronic graft-versus-host disease between the MSC infusion group and non-MSC infusion group. There was also no significant difference in the cytomegalovirus, Epstein-Barr virus (EBV), and fungal and bacterial infection rates between the two groups. Although umbilical cord blood-derived MSCs do not reduce the number of BKV DNA copies in the urine, the cells have a high efficacy rate and minimal side effects in treating severe BKV-HC after UCBT among pediatric patients. MSCs do not affect the rates of relapse, long-term infection, or survival of patients with leukemia.

8.
Nat Commun ; 11(1): 518, 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31980616

RESUMO

Ethylene plays essential roles during adaptive responses to water-saturating environments in rice, but knowledge of its signaling mechanism remains limited. Here, through an analysis of a rice ethylene-response mutant mhz1, we show that MHZ1 positively modulates root ethylene responses. MHZ1 encodes the rice histidine kinase OsHK1. MHZ1/OsHK1 is autophosphorylated at a conserved histidine residue and can transfer the phosphoryl signal to the response regulator OsRR21 via the phosphotransfer proteins OsAHP1/2. This phosphorelay pathway is required for root ethylene responses. Ethylene receptor OsERS2, via its GAF domain, physically interacts with MHZ1/OsHK1 and inhibits its kinase activity. Genetic analyses suggest that MHZ1/OsHK1 acts at the level of ethylene perception and works together with the OsEIN2-mediated pathway to regulate root growth. Our results suggest that MHZ1/OsHK1 mediates the ethylene response partially independently of OsEIN2, and is directly inhibited by ethylene receptors, thus revealing mechanistic details of ethylene signaling for root growth regulation.

9.
Bioorg Chem ; 94: 103350, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31640933

RESUMO

One new polycyclic furanobutenolide-derived norcembranoid, xiguscabrolide H (1), together with eleven known related norditerpenoids 2-12 were isolated from South China Sea soft corals Sinularia scabra and S. polydactyla, respectively. Among them, compounds 1, 6, 8, and 12 were discovered from the former species, while compounds 2-5, 7, and 9-11 were obtained from the latter species. The structure of new compound 1 was elucidated by extensive spectroscopic analysis and by the comparison with the reported data. With the assistance of time-dependent density functional theory electronic circular dichroism (TDDFT-ECD) calculations, its absolute configuration was determined. Moreover, the absolute stereostructures of the known compounds 3, 4, and 9-12, of which only relative configurations were assigned, were established for the first time by X-Ray diffraction analysis and TDDFT-ECD calculations, respectively. In bioassay, several isolates exhibited potent inhibitory effects on the ConA-induced T lymphocytes and/or LPS-induced B lymphocytes proliferation.

10.
Environ Pollut ; 256: 113374, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31672358

RESUMO

Melatonin is a hormone which is generated from pineal gland, and it is responsible for the regulation of wake-sleep cycle. Melatonin is a well-known antioxidant and free radical scavenger to protect against multiple type of tissue damage. While ochratoxin A (OTA) is a mycotoxin found widely in contaminated food and foodstuffs, which causes nephrotoxicity, hepatotoxicity, immunotoxicity, and reproductive damage in humans and animals. In present study we report the toxicity of OTA on porcine oocyte quality and the protective effects of melatonin on OTA-exposed oocytes. Using transcriptome analysis our results show that OTA exposure alters the expression of multiple genes in oocytes, indicating its effect on oocyte maturation. The cellular changes following OTA treatment are examined, and the results show that OTA adversely affects oocyte polar body extrusion, which is confirmed by the delay of Cdc2-mediated cell cycle progression. OTA exposure also disrupts meiotic spindle formation, which is confirmed by altered phosphorylated MAPK expression. RNA-seq screening and further fluorescence staining results show that OTA induces aberrant mitochondria distribution and oxidative phosphorylation defects, which then causes oxidative stress, followed by early apoptosis and autophagy. Treatment with melatonin significantly ameliorates oxidative stress and apoptosis, which further protects cell cycle and spindle formation in OTA-exposed oocytes. Collectively, these results show the protective effects of melatonin against defects induced by OTA during porcine meiotic oocyte maturation.


Assuntos
Apoptose/efeitos dos fármacos , Melatonina/farmacologia , Ocratoxinas/toxicidade , Oócitos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Suínos , Animais , Antioxidantes/metabolismo , Autofagia/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/genética , Feminino , Humanos , Oócitos/metabolismo , Oócitos/patologia
11.
Sci Total Environ ; 706: 135955, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31855648

RESUMO

Constructed wetlands (CWs) have been used to remove organic pollutants including antibiotics based on the roles of plants and microbial communities, but how rhizosphere and bulk substrate-associated microbiomes respond to antibiotics during biodegradation have seldom been researched. The effects of sulfonamides (SAs) on the microbiome composition in different compartments, namely rhizosphere, near rhizosphere and bulk substrate, in CWs planted with either Cyperus alternifolius, Cyperus papyrus or Juncus effuses were evaluated using specially designed rhizoboxes and 16S rRNA gene high-throughput sequencing. Results revealed that wastewater-borne SAs significantly reduced the microbial biodiversity in CWs, and inhibited the functional bacterial groups related to sulphur and nitrogen cycles. On the contrary, SAs significantly enriched methylotrophs with potential to initially biodegrade SAs, such as Methylosinus, Methylotenera, Methylocaldum and Methylomonas, and such enrichment was more significant in rhizosphere than in bulk substrate. The network analysis indicated that a more complex network in bulk substrate was more fragile to SA stress. The presence of wetland plants significantly influenced the bacterial community structure in CWs, but in the same compartment, the difference among the three plants species was not obvious. Wetland plants ensured the stability of rhizosphere microorganisms and increased their ability to tolerate SA stress. The present study enhances our understanding of the importance of plant-bacteria interactions in CWs and responses of substrate microbiome to antibiotics.


Assuntos
Microbiota , Rizosfera , Áreas Alagadas , Biodegradação Ambiental , RNA Ribossômico 16S , Sulfonamidas , Eliminação de Resíduos Líquidos , Águas Residuárias
12.
Sci Rep ; 9(1): 17528, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31772202

RESUMO

The passive sampling method of diffusive gradients in thin-films (DGT) was developed to provide a quantitative and time-integrated measurement of microcystin-LR (MC-LR) in waters. The DGT method in this study used HLB (hydrophilic-lipophilic-balanced) material as a binding agent, and methanol as an eluent. The diffusion coefficient of MC-LR was 5.01 × 10-6 cm2 s-1 at 25 °C in 0.45 mm thick diffusion layer. This DGT method had a binding capacity of 4.24 µg per binding gel disk (3.14 cm2), ensuring sufficient capacity to measure MC-LR in most water matrices. The detection limit of HLB DGT was 0.48 ng L-1. DGT coupled to analysis by HPLC appears to be an accurate method for MC-LR monitoring. Comparison of DGT measurements for MC-LR in water and a conventional active sampling method showed little difference. This study demonstrates that HLB-based DGT is a useful tool for in situ monitoring of MC-LR in fresh waters.

13.
J Lipid Res ; 60(12): 2020-2033, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31662443

RESUMO

CXC chemokine ligand 12 (CXCL12) is a member of the CXC chemokine family and mainly acts on cell chemotaxis. CXCL12 also elicits a proatherogenic role, but the molecular mechanisms have not been fully defined yet. We aimed to reveal if and how CXCL12 promoted atherosclerosis via regulating lipid metabolism. In vitro, our data showed that CXCL12 could reduce ABCA1 expression, and it mediated cholesterol efflux from THP-1-derived macrophages to apoA-I. Data from the luciferase reporter gene and chromatin immunoprecipitation assays revealed that transcription factor 21 (TCF21) stimulated the transcription of ABCA1 via binding to its promoter region, which was repressed by CXCL12. We found that CXCL12 increased the levels of phosphorylated glycogen synthase kinase 3ß (GSK3ß) and the phosphorylation of ß-catenin at the Thr120 position. Inactivation of GSK3ß or ß-catenin increased the expression of TCF21 and ABCA1. Further, knockdown or inhibition of CXC chemokine receptor 4 (CXCR4) blocked the effects of CXCL12 on TCF21 and ABCA1 expression and the phosphorylation of GSK3ß and ß-catenin. In vivo, the overexpression of CXCL12 in Apoe-/- mice via lentivirus enlarged the atherosclerotic lesion area and increased macrophage infiltration in atherosclerotic plaques. We further found that the overexpression of CXCL12 reduced the efficiency of reverse cholesterol transport and plasma HDL-C levels, decreased ABCA1 expression in the aorta and mouse peritoneal macrophages (MPMs), and suppressed cholesterol efflux from MPMs to apoA-I in Apoe-/- mice. Collectively, these findings suggest that CXCL12 interacts with CXCR4 and then activates the GSK-3ß/ß-cateninT120/TCF21 signaling pathway to inhibit ABCA1-dependent cholesterol efflux from macrophages and aggravate atherosclerosis. Targeting CXCL12 may be a novel and promising strategy for the prevention and treatment of atherosclerotic cardiovascular diseases.

14.
J Cancer ; 10(20): 4978-4988, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31598170

RESUMO

Tissue-derived RNA, DNA and protein samples become more and more crucial for molecular detection in clinical research, personalized and targeted cancer therapy. This study evaluated how to biobanking colorectal tissues through examining the influences of cold ischemic time and freeze-thaw cycles on RNA, DNA and protein integrity. Here, 144 pairs of tumor and normal colorectal tissues were used to investigate the impact of cold ischemic times (0-48h) on RNA, DNA and protein integrity at on ice or room temperature conditions. Additionally, 45 pairs of tissues experienced 0-9 freeze-thaw cycles, and then the RNA, DNA and protein quality were analyzed. On ice, RNA, DNA and protein from colorectal tumor and normal tissues were all stable up to 48h after surgery. At room temperature, RNA in colorectal tumor and normal tissues began to degrade at 8h and 24h, respectively. Meanwhile, the tumor tissues DNA degradation occurred at 24h after surgery at room temperature. Similarly, the protein expression level of tumor and normal tissues began to change at 24h after the surgery at room temperature. Interestingly, tissue RNA and DNA remained stable even after 9 freeze-thaw cycles, whereas the proteins levels were remarkably changed after 7 freeze-thaw cycles. This study provided a useful evidence on how to store human colorectal tissues for biobanking. Preserving the surgical colorectal tissue on ice was an effective way to prevent RNA, DNA and protein degradation. Importantly, more than 7 repeated freeze-thaw cycles were not recommended for colorectal tissues.

15.
PLoS One ; 14(10): e0223978, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31618247

RESUMO

Guertu virus (GTV) is a tick-borne phleboviruses (TBPVs) which belongs to the genus Banyangvirus in the family of Phenuiviridae. In vitro and in vivo studies of GTV demonstrated that it was able to infect animal and human cell lines and could cause pathological lesions in mice. Glycoproteins (GP, including Gn and Gc) on the surface of Guertu virus (GTV) could bind to receptors on host cells and induce protective immunity in the host, but knowledge is now lacking on the information of B cell epitopes (BCEs) present on GTV-GP protein. The aim of this study was to identify all BCEs on Gn of the GTV DXM strain using rabbit pAbs against GTV-Gn. Seven fine BCEs and two antigenic peptides (APs) from nine reactive 16mer-peptides were identified, which are EGn1 (2PIICEGLTHS11), EGn2 (135CSQDSGT141), EGn3 (165IP EDVF170), EGn4 (169VFQEL K174), EGn5 (187IDGILFN193), EGn6 (223QTKWIQ228), EGn7 (237CHKDGIGPC245), AP-8 (299GVRVRPKCYGFSRMMA314) and AP-9 (355CASH FCSSAESGKKNT370), of which six of mapped BCEs were recognized by the IgG-positive sheep serum obtained from sheep GTV-infected naturally. Multiple sequence alignments (MSA) based on each mapped BCE motif identified that the most of identified BCEs and APs are highly conserved among 10 SFTSV strains from different countries and lineages that share relatively close evolutionary relationships with GTV. The fine epitope mapping of the GTV-Gn would provide basic data with which to explore the GTV-Gn antigen structure and pathogenic mechanisms, and it could lay the foundation for the design and development of a GTV multi-epitope peptide vaccine and detection antigen.

16.
Light Sci Appl ; 8: 60, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31645910

RESUMO

A digital-coding programmable metasurface (DCPM) is a type of functional system that is composed of subwavelength-scale digital coding elements with opposite phase responses. By configuring the digital coding elements, a DCPM can construct dynamic near-field image patterns in which the intensity of each pixel of the image can be dynamically and independently modulated. Thus, a DCPM can perform both spatial and temporal modulations. Here, this advantage is used to realize multichannel direct transmissions of near-field information. Three points are selected in the near-field region to form three independent channels. By applying various digital phase codes on the DCPM, independent binary digital symbols defined by amplitude codes (namely, weak and strong amplitudes) are transmitted through the three channels. The measured near-field distributions and temporal transmissions of the system agree with numerical calculations. Compared with the conventional multichannel transmission, the proposed mechanism achieves simultaneous spatial and temporal modulations by treating DCPM as an energy radiator and information modulator, thereby enduing DCPM with high potential in near-field information processing and communications.

17.
Sensors (Basel) ; 19(20)2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31652626

RESUMO

In the indoor location field, the quality of received-signal-strength-indicator (RSSI) fingerprints plays a key role in the performance of indoor location services. However, changes in an indoor environment may lead to the decline of location accuracy. This paper presents a localization method employing a Hybrid Wireless fingerprint (HW-fingerprint) based on a convolutional neural network (CNN). In the proposed scheme, the Ratio fingerprint was constructed by calculating the ratio of different RSSIs from important contribution access points (APs). The HW-fingerprint combined the Ratio fingerprint and the RSSI to enhance the expression of indoor environment characteristics. Moreover, a CNN architecture was constructed to learn important features from the complex HW-fingerprint for indoor locations. In the experiment, the HW-fingerprint was tested in an actual indoor scene for 15 days. Results showed that the average daily location accuracy of the K-Nearest Neighbor (KNN), Support Vector Machines (SVMs), and CNN was improved by 3.39%, 8.03% and 9.03%, respectively, when using the HW-fingerprint. In addition, the deep-learning method was 4.19% and 16.37% higher than SVM and KNN in average daily location accuracy, respectively.

18.
Ecotoxicol Environ Saf ; 185: 109668, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31574372

RESUMO

Microcystins and polycyclic aromatic hydrocarbons commonly co-exist in eutrophic freshwater environments. However, their combined toxicity remains unknown. The aim of this study was to evaluate the combined toxic effects of microcystin-LR (MC-LR) and phenanthrene (Phe) on duckweed (Lemna gibba L.) during a short-term exposure (7 d). L. gibba was exposed to a range of environmentally relevant concentrations of MC-LR (5, 50, 250, 500 µg/L) and Phe (0.1, 1, 5, 10 µg/L), both individually and in MC-LR + Phe mixtures (5 + 0.1, 50 + 1, 250 + 5, 500 + 10 µg/L). Subsequently, biomarkers of toxicity such as growth, chlorophyll-a, and antioxidant enzyme activity (catalase, superoxide dismutase, and peroxidase) were analyzed in L. gibba. Growth and the antioxidant system of L. gibba were not significantly inhibited by Phe alone, whereas higher concentrations of individual MC-LR (≥50 µg/L) significantly inhibited growth and induced oxidative stress. Based on Abott's formula, their interaction effects were concentration dependent. Antagonistic effects were observed when exposed to combinations of lower concentrations of MC-LR and Phe (≤50 + 1 µg/L), while additive or synergistic effects were induced at higher concentrations of both compounds (≥250 + 5 µg/L). Moreover, higher concentrations of Phe (≥5 µg/L) increased the accumulation of MC-LR in L. gibba. Our results suggested that the toxic effects of MC-LR and phenanthrene were exacerbated only when they co-exist in water bodies at relatively high concentrations. Consequently, co-existence of MC-LR and Phe at low levels are unlikely to exacerbate ecological hazards to L. gibba in most aquatic environments, at least based on responses of this plant.


Assuntos
Antioxidantes/metabolismo , Araceae/efeitos dos fármacos , Microcistinas/toxicidade , Fenantrenos/toxicidade , Araceae/enzimologia , Catalase/metabolismo , Clorofila/análogos & derivados , Clorofila/metabolismo , Sinergismo Farmacológico , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/metabolismo , Superóxido Dismutase/metabolismo
19.
EMBO Mol Med ; 11(10): e10168, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31475771

RESUMO

Accurate risk stratification for patients with stage II/III colon cancer is pivotal for postoperative treatment decisions. Here, we aimed to identify and validate a circRNA-based signature that could improve postoperative prognostic stratification for these patients. In current retrospective analysis, we included 667 patients with R0 resected stage II/III colon cancer. Using RNA-seq analysis of 20 paired frozen tissues collected postoperation, we profiled differential circRNA expression between patients with and without recurrence, followed by quantitative validation. With clinical information, we generated a four-circRNA-based cirScore to classify patients into high-risk and low-risk groups in the training cohort. The patients with high cirScores in the training cohort had a shorter disease-free survival (DFS) and overall survival (OS) than patients with low cirScores. The prognostic capacity of the classifier was validated in the internal and external cohorts. Loss-of-function assays indicated that the selected circRNAs played functional roles in colon cancer progression. Overall, our four-circRNA-based classifier is a reliable prognostic tool for postoperative disease recurrence in patients with stage II/III colon cancer.

20.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(4): 1246-1252, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31418388

RESUMO

OBJECTIVE: To analyze the clinical outcomes of engraftment, graft-versus-host disease (GVHD) and survival in the patients with AML1-ETO positive acute myeloid leukemia (AML) treated with unrelated umbilical cord blood transplantation (UCBT). METHODS: Forty-Five patients with high-risk refractory AML1-ETO positive AML were treated with a single UCBT in a single center from July 2010 to April 2018. All the patients underwent a myeloablative preconditioning regimen,and cyclosporine A (CSA) combined with mycophenolate mofetil (MMF) was used to prevent GVHD. RESULTS: The median value of total nucleated cells (TNC) in cord blood was 5.21 (1.96-12.68)×107/kg recipient body weight, and that of CD34+ cells was 5.61 (0.56-15.4)×105/kg recipient weight. The implantation rate of neutrophil at 42 d and that of platelet at 120 d were 95.6% and 86.7%, respectively. The median time of absolute neutrophil count (ANC)>0.5×109/L and platelet 20×109/L were 16 (12-18) d and 37 (17-140) d after transplantation, respectively. The cumulative incidence of Ⅰ -Ⅳ grade acute GVHD (aGVHD) at 100 d after transplantation was 48.9% (95% CI 33.5%-62.6%), Ⅱ-Ⅳ grade aGVHD occurred in 12 cases (33.3%) (95% CI 20%-47.2%) , and Ⅲ-Ⅳ grade a GVHD in 8 cases (20%) (95% CI 9.8% -32.8%). In 5 cases of 40 patients survived over 100 days, the chronic GVHD (cGVHD) occurred after transplantation, among which 4 were localized, and 1 was extensive. 3 patients relapsed, and the 2-year cumulative relapse rate was 9.5% (95% CI 2.4%-22.8%). The median follow-up time was 23.5 (0.9-89.67) months, 10 patients died, 2-year disease-free survival rate (DFS) was 72.7%, and overall survival rate (OS) was 75.5%. Multivariate analysis showed that Ⅲ-Ⅳ. acute GVHD (aGVHD) affected overall survival. CONCLUSION: UCBT is an effective rescue treatment for patients with high-risk refractory AML1-ETO positive AML.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença Enxerto-Hospedeiro , Leucemia Mieloide Aguda , Transplante de Células-Tronco de Sangue Periférico , Subunidade alfa 2 de Fator de Ligação ao Core , Humanos , Ácido Micofenólico , Proteínas de Fusão Oncogênica , Proteína 1 Parceira de Translocação de RUNX1 , Condicionamento Pré-Transplante
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