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1.
Toxicol In Vitro ; 65: 104795, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32061800

RESUMO

Hexavalent chromium (Cr(VI)), a well-known toxic industrial and environmental pollutant, has been shown to cause serious toxic and health effects. However, limited information is available on Cr(VI)-induced neurotoxic potential, with the underlying toxicological mechanisms remain mostly unclear. The present study demonstrated that the mitochondria-dependent apoptosis pathway was involved in Cr(VI)-induced SH-SY5Y cell (the human neuroblastoma cell line) death, which was accompanied by the appearance of cell shrinkage, increased mitochondrial membrane potential (MMP) depolarization and cytochrome c release, and the activation of caspase cascades and poly (ADP-ribose) polymerase (PARP). Cr(VI) treatment also increased the generation of intracellular reactive oxygen species (ROS). Pretreatment of SH-SY5Y cells with antioxidant N-acetylcysteine (NAC) effectively attenuated ROS production and reversed these Cr(VI)-induced cytotoxicity and apoptotic responses. Furthermore, exposure to Cr(VI) significantly increased the phosphorylation levels of Akt, extracellular regulated kinase (ERK)1/2, and AMP-activated protein kinase (AMPK)α. NAC and the pharmacological inhibitor of Akt (LY294002), ERK1/2 (PD980590), and AMPKα (Compound C) markedly abrogated the Cr(VI)-induced activation of Akt, ERK1/2, and AMPKα signal, respectively, with the concomitant inhibition of mitochondrial dysfunction and caspase activation. Additionally, all these inhibitors suppressed Cr(VI)-induced phosphorylation of Akt, ERK1/2, and AMPKα and of each other. Collectively, these results suggest that Cr(VI) exerts its cytotoxicity on neuronal cells by inducing mitochondria-dependent apoptosis through the interdependent activation of Akt, ERK1/2, and AMPKα, which are mainly mediated by ROS generation.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32078018

RESUMO

Plants associate with numerous microbes, but little is known about how microbiome components, especially fungi, adapt to specific plant compartments. The adaptability of microbial function to the plant compartment is also not clear especially for woody species. Here, we characterized the bacterial and fungal communities in root endosphere, stems, and rhizospheres of 33 Broussonetia papyrifera seedlings, based on amplification of 16S and ITS rRNA. Results showed that the α-diversity indexes of the bacterial community were significantly different in different plant compartments and they significantly increased from stem to root endosphere to the rhizosphere, whereas those of the fungal community were similar (p > 0.05). However, the result of constrained PCoA (CPCoA) and analysis of similarity (ANOSIM) showed that both bacterial and fungal compositions were significantly affected by plant compartments (p < 0.01). In detail, the operational taxonomic units (OTUs) distribution of the bacterial community was significantly different, but 249 of 252 fungal OTUs were shared in different plant compartments. Both the bacterial and fungal compositions were significantly influenced by plant compartments, based on the result on phyla, core OTUs, and indicator OTUs level. Further, 40 of 42 enriched KEGG pathways involving the bacteria also differed significantly among plant compartments (p < 0.01). This study provides an understanding of the influence of plant compartments on the microbiome and confirms that the disperse limitation of fungal OTUs across different plant compartments is smaller. This study sheds light on how the microbial community adapts to and thrives in different plant compartments.

3.
Int J Mol Sci ; 21(3)2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32041250

RESUMO

The present study aimed to explore the possible radioprotective effects of celastrol and relevant molecular mechanisms in an in vitro cell and in vivo mouse models exposed to gamma radiation. Human keratinocytes (HaCaT) and foreskin fibroblast (BJ) cells were exposed to gamma radiation of 20Gy, followed by treatment with celastrol for 24 h. Cell viability, reactive oxygen species (ROS), nitric oxide (NO) and glutathione (GSH) production, lipid peroxidation, DNA damage, inflammatory cytokine levels, and NF-κB pathway activation were examined. The survival rate, levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in blood, and p65 and phospho-p65 expression were also evaluated in mice after exposure to gamma radiation and celastrol treatment. The gamma irradiation of HaCaT cells induced decreased cell viability, but treatment with celastrol significantly blocked this cytotoxicity. Gamma irradiation also increased free radical production (e.g., ROS and NO), decreased the level of GSH, and enhanced oxidative DNA damage and lipid peroxidation in cells, which were effectively reversed by celastrol treatment. Moreover, inflammatory responses induced by gamma irradiation, as demonstrated by increased levels of IL-6, TNF-α, and IL-1ß, were also blocked by celastrol. The increased activity of NF-κB DNA binding following gamma radiation was significantly attenuated after celastrol treatment. In the irradiated mice, treatment with celastrol significantly improved overall survival rate, reduced the excessive inflammatory responses, and decreased NF-κB activity. As a NF-κB pathway blocker and antioxidant, celastrol may represent a promising pharmacological agent with protective effects against gamma irradiation-induced injury.

4.
Curr Med Chem ; 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31965936

RESUMO

Radiation exposure may induce Alzheimer disease (AD), depression or schizophrenia. A number of experimental and clinical studies suggest the involvement of miRNA in the development of these diseases, and also in the neuropathological changes after brain radiation exposure. Current literature review indicated the involvement of 65 miRNAs in neuronal development in the brain. In the brain tissue, blood, or cerebral spinal fluid (CSF), 11, 55, or 28 miRNAs are involved in the development of AD respectively, 89, 50, 19 miRNAs in depression, and 102, 35, 8 miRNAs in schizophrenia. We compared miRNAs regulating neuronal development to those involved in genesis of AD, depression and schizophrenia and also those driving radiation-induced brain neuropathological changes by reviewing the available data. We found that 3, 11, or 8 neuronal development related miRNAs from the brain tissue, 13, 16 or 14 miRNAs from the blood of patient with AD, depression and schizophrenia respectively were also involved in radiation-induced brain pathological changes, suggesting a possibly specific involvement of these miRNAs in radiation-induced development of AD, depression and schizophrenia respectively. On the other hand, we noted that radiation-induced changes of two miRNAs, i.e., miR-132, miR-29 in the brain tissue, three miRNAs, i.e., miR-29c-5p, miR-106b-5p, miR-34a-5p in the blood were also involved in the development of AD, depression and schizophrenia, thereby suggesting that these miRNAs may be involved in the common brain neuropathological changes, such as impairment of neurogenesis and reduced learning memory ability observed in these three diseases and also after radiation exposure.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31963563

RESUMO

The present study explores the relations between work hours and the difficulty in leaving work on time to both work-to-family conflict (WFC) and burnout among female workers in Taiwan. A cross-sectional research design and questionnaire were employed to obtain the research data. In total, 738 full-time female workers took part in the study. The results of regression analyses showed that when age, marital status, economic status, occupation, parental status, and housework responsibilities were controlled, more work hours were positively associated with WFC and burnout. When the difficulty in leaving work on time was also considered in the analysis, long working hours were still significantly associated with burnout; however, the significant relation with WFC disappeared. It is surmised that if female employees work overtime voluntarily, the perception of WFC diminishes; nevertheless, the adverse effect of long working hours on health remains unabated. This study concludes that female employees who work overtime on a voluntary basis are at risk of health problems, which should be a focus of concern.

6.
Mol Biol Rep ; 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31925644

RESUMO

Recent decades, there is significant progress in understanding the mechanisms of tumor progression and immune evasion. The newly discovered protein NLRC5 is demonstrated to participate in regulating cancer immune escape through enhancing MHC class I genes expression in certain tumors. Nevertheless, increasing evidence has revealed that NLRC5 is up-regulated in some other tumors and promote tumor development and progression. The purpose of this review is to describe the role of NLRC5 in tumors and discuss whether NLRC5 can be a potential target in cancer treatment.

7.
Med Eng Phys ; 77: 80-87, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31937437

RESUMO

Endovascular aneurysm repair (EVAR) is a popular and effective treatment for descending aortic disease. However, the majority of existing coating stents used in EVAR are of a standard design which may not meet the size or structural requirements of different patients. Therefore, in this paper, we propose using 3D printing and controlled deposition as a patient-specific aortic stent graft manufacturing technique. The methodology involves the use of a rapid prototyping study sacrificial core-coating forming (RPSC-CF) technique to develop an aortic stent graft that consists of a film and metallic stent. Polyether polyurethane and nickel-titanium alloys were chosen due to their shape memory properties and good biocompatibility. The resulting customized stent grafts meet the demands of personalized therapy and invasive surgery, and perform well as demonstrated from burst pressure testing and the degree of radial support provided and radial support force tests, laying the foundation for precise aortic dissection treatment.

8.
Sci Total Environ ; 706: 135741, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31791790

RESUMO

Invasive non-native species (INNS) with marine or brackish origins have become increasingly common occupying freshwater habitats. The transition of INNS from marine or brackish water into physiologically stressful freshwater environments may be facilitated by compensatory growth and elevated feeding rates. In this study, we investigate the capacity of the Gulf wedge clam (Rangia cuneata), a brackish NNS that is spreading quickly across European waterways, to survive in freshwater conditions and consider its resultant impacts as an ecosystem engineer. To investigate the performance of R. cuneata under freshwater conditions, we compared the population structure, the physiological condition, and the growth of R. cuneata collected from its distributional limits in Great Britain. Feeding rate of R. cuneata was quantified by conducting a reciprocal transfer experiment with a two-way factorial design on individuals obtained from the freshwater and saline extremes. R. cuneata density was almost 10-fold higher at its most saline distributional limit (213 individual m-2, 3.1‰) compared to its most freshwater limit (22 individuals m-2, 1.2‰). The impaired physiological condition (18.7% lower relative soft tissue mass and 26.4% lower shell mass) and the lack of juvenile individuals also suggests that the R. cuneata inhabiting the freshwater extreme may not be able to maintain a persistent population over the long term. Although R. cuneata at its freshwater extreme were under stress, the per capita impacts caused by these individuals were not weakened at the suboptimal conditions, evidenced by their elevated growth and over four times as high relative clearance rate (0.28 L-1 g-1 h-1) compared to those from the saline limit (0.06 L-1 g-1 h-1). This study demonstrates that under suboptimal conditions, the physiological responses of INNS may result in elevated per capita effects which may lead to unexpected or under-estimated impacts on recipient ecosystems.

9.
Bioorg Chem ; 94: 103391, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31761409

RESUMO

Thermostability of monoclonal antibodies (mAbs) and antibody-drug conjugates (ADCs), as a critical property of biotherapeutics, is important for their physicochemical processes, pharmacodynamics, and pharmacokinetics. Fc glycosylation of mAbs plays a crucial role in antibody functions including thermostability, however, due to the lack of homogeneous glycosylation for comparison, the precise impact of glycoforms on thermostability of mAbs and ADCs remains challenging to elucidate. In this paper, we employed the technique of differential scanning fluorimetry (DSF) to investigate the thermostability of Fc domains, glycoengineered mAbs, and ADCs, carrying well-defined N-glycan structures for comparison. The results revealed that high-mannose-type N-glycans dramatically reduce the Tm value of Fc, compared to complex-type N-glycans. We also found that core-fucose contributes to the thermostability of mAbs, and the unnatural modification on non-reducing end of biantennary N-glycan can compensate the reduced stability of afucosylated mAbs and maintain the advantage of enhanced antibody-dependent cell-mediated cytotoxicity (ADCC). DSF analysis of lysine-linked and glycosite-specific ADCs indicated that thermostability of glycan-linked ADCs is reduced, but it could be improved by using an optimized linkage. This work provides an in-depth analysis on thermostability of mAbs and ADCs with homogeneous glycoforms, and also proposes new strategies for optimizing glycoengineered mAbs and glycosite-specific ADCs using unnatural glycan and stabilized linkage.

10.
Cell Cycle ; 19(1): 1-14, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31809227

RESUMO

Tumorigenic cancer stem cells (CSCs) exist in various tumors including the cutaneous squamous cell carcinoma (cSCC) as a minor subpopulation and are tightly associated with metastasis and therapeutic resistance. Better understanding of CSCs properties is essential for the novel therapeutic strategy targeted toward these cancers. The cSCC stem cells (cSCCSCs) were enriched from a cSCC cell line A431 by repeated sphere culture, and identified via the expression analysis of stemness marker genes and CD44 proteolysis. MiR-199a-5p was previously reported to be related with the proteolysis modulation of CD44, so the specific regulation mechanisms were verified by overexpression in vitro and in vivo. MiR-199a-5p is under-expressed in cSCCSCs and functions as a tumor suppressive molecule. Overexpression of miR-199a-5p reduced the stemness of cSCCSCs and inhibited cell proliferation. By targeting the deacetylase Sirt1, miR-199a-5p inhibited cellular proteolysis of CD44 and reduced the CD44 intracellular domain (CD44ICD) release and nuclear translocation. Overexpression of CD44ICD reversed the effects of miR-199a-5p overexpression or Sirt1 silencing, and increased the transcriptional expression of stemness genes. Our results revealed that the miR-199a-5p/Sirt1/CD44ICD signaling pathway regulates cSCCSCs progression by affecting its migration ability and tumorigenicity, therefore can be utilized to develop a curative approach for cSCC.Abbreviations: CSCs: cancer stem cells; cSCC cutaneous squamous cell carcinoma; cSCCSCs: cSCC stem cells; CD44ICD: CD44 intracellular domain; HA: hyaluronic acid; HNSCC: hand and neck squamous cell carcinoma; ESCC: esophageal squamous cell carcinoma;MMPs: matrix metalloproteinases; SFM: sphere formation medium; EGF: epidermal growth factor; bFGF: basic fibroblast growth factor; BSA: bovine serum albumin; CCK-8: cell counting kit-8.

11.
Mol Biol Rep ; 47(1): 433-441, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31637620

RESUMO

Glioma is the most aggressive primary brain tumor. We have previously provided evidence that IFITM3 promoted glioma cells migration. However, the mechanism of how IFITM3 regulates glioma cells invasion and whether IFITM3 participates in TGF-ß-mediated glioma invasion are still unknown. In this paper, we proved that IFITM3 was notably up-regulated in glioma tissues. Knockdown of IFITM3 suppressed STAT3 phosphorylation in vitro, and a specific STAT3 inhibitor AG490 reversed IFITM3-induced invasion of glioma cells. Furthermore, IFITM3 expression was induced by TGF-ß in glioma and IFITM3 knockdown abolished TGF-ß-mediated glioma cells invasion. Collectively, the results indicate that IFITM3/STAT3 axis may promote TGF-ß-induced glioma cells invasion. This study provided some suggestions for the clinical treatment of the brain tumor.

12.
Cancer Med ; 9(1): 12-18, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31692291

RESUMO

The response to icotinib in advanced non-small cell lung cancers (NSCLC) with EGFR uncommon mutation (EGFRum) is unclear. Here we reported the efficacy and potential resistance mechanism of icotinib in Chinese EGFRum NSCLC patients. Between July 2013 and November 2016, 3117 NSCLC patients were screened for EGFRum in a multi-center study in China. Circulating tumor DNA (ctDNA) was detected and analyzed using next-generation sequencing (NGS) after progression from icotinib. The efficacy, safety and the potential resistance mechanism of icotinib were explored. After a median follow-up of 6.2 months, 69 patients (70.41%) developed disease progression, the objective rate (ORR) and disease control rate (DCR) were 13.27% and 29.59% respectively, and the median progression-free survival (PFS) was 5.5 months (95% CI: 1.2-13.0 months). Both complex-pattern with EGFR classical mutations (EGFRcm) and single-pattern have better PFS than complex-pattern without EGFRcm (median PFS was 7.2 (95% CI: 4.65-9.75), 5.2 (95% CI: 3.24-7.16) and 3.2 (95% CI: 2.97-3.44) months, respectively, P < .05); patients harboring S768I mutation had the worst PFS than others (2.0 months, P < .05). Diarrhea was the most frequent side effect (42.9%). Forty-eight (69.6%) patients developed drug resistance after 3.0 months and 81.2% of them acquired T790M mutation. Better response was observed in complex-pattern with the EGFRcm group. S768I mutation carriers may not benefit from icotinib. Acquired T790M mutation was common in icotinib-resistant EGFRum NSCLC patients.

13.
Appl Biochem Biotechnol ; 190(2): 601-615, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31399929

RESUMO

Isoorientin and isovitexin, kinds of flavone C-glycosides, exhibit a number of biological properties. In this work, The C-glucosyltransferase (Gt6CGT) gene from Gentiana triflora was cloned and expressed in Escherichia coli BL21(DE3). The optimal activity of Gt6CGT was at pH 7.5 and 50° C. The enzyme was stable over pH range of 6.5-9.0, and had a 1-h half-life at 50° C. The Vmax for luteolin and apigenin was 21.1 nmol/min/mg and 31.7 nmol/min/mg, while the Km was 0.21 mM and 0.22 mM, respectively. Then, we developed an environmentally safe and efficient method for isoorientin and isovitexin production using the coupled catalysis of Gt6CGT and Glycine max sucrose synthase (GmSUS). By optimizing coupled reaction conditions, the titer of isoorientin and isovitexin reached 3820 mg/L with a corresponding molar conversion of 94.7% and 3772 mg/L with a corresponding molar conversion of 97.1%, respectively. The maximum number of UDP-glucose regeneration cycles (RCmax) reached 28.4 for isoorientin and 29.1 for isovitexin. The coupled catalysis reported herein represents a promising method to meet industrial requirements for large-scale isoorientin and isovitexin production in the future. Graphical Abstract.

14.
J Membr Biol ; 253(1): 43-55, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31820013

RESUMO

Lysophosphatidylcholine (LPC) is a major atherogenic lipid that stimulates an increase in mitochondrial reactive oxygen species (mtROS) and the release of cytokines under inflammasome activation. However, the potential receptors of LPC in macrophages are poorly understood. Members of the transient receptor potential (TRP) channel superfamily, which is crucially involved in transducing environmental irritant stimuli into nociceptor activity, are potential receptors of LPC. In this study, we investigated whether LPC can induce the activation of transient receptor potential ankyrin 1 (TRPA1), a member of the TRP superfamily. The functional expression of TRPA1 was first detected by quantitative real-time polymerase chain reaction (qRT-PCR), western blotting and calcium imaging in human acute monocytic leukemia cell line (THP-1)-derived macrophages. The mechanism by which LPC induces the activation of macrophages through TRPA1 was verified by cytoplasmic and mitochondrial calcium imaging, mtROS detection, a JC-1 assay, enzyme-linked immunosorbent assay, the CCK-8 assay and the lactate dehydrogenase (LDH) cytotoxic assay. LPC induced the activation of THP-1-derived macrophages via calcium influx, and this activation was suppressed by potent and selective inhibitors of TRPA1. These results indicated that TRPA1 can mediate mtROS generation, mitochondrial membrane depolarization, the secretion of IL-1ß and cytotoxicity through cellular and mitochondrial Ca2+ influx in LPC-treated THP-1-derived macrophages. Therefore, the inhibition of TRPA1 may protect THP-1-derived macrophages against LPC-induced injury.

15.
Free Radic Biol Med ; 147: 159-166, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31874250

RESUMO

OBJECTIVE: To investigate the role of geranylgeranyl diphosphate synthase 1 (GGPPS1) in ventilator-induced lung injury along with the underlying mechanism. METHODS: A murine VILI model was induced by high-tidal volume ventilation in both wild-type and GGPPS1 knockout mice. GGPPS1 expression was detected in the bronchoalveolar lavage fluid (BALF) supernatants of acute respiratory distress syndrome (ARDS) patients and healthy volunteers, as well as in lung tissues and BALF supernatants of the VILI mice using enzyme-linked immunosorbent assay (ELISA), quantitative reverse transcription polymerase chain reaction (qRT-PCR), western bolt and immunohistochemical (IHC). The wet/dry ratio, total BALF proteins, and lung injury score were analyzed. The percentage of neutrophils was detected by flow cytometry and IHC. Inflammatory cytokine levels were measured by ELISA and qRT-PCR. The related expression of Toll-like receptor (TLR)2/4 and its downstream proteins was evaluated by western blot. RESULTS: GGPPS1 in BALF supernatants was upregulated in ARDS patients and the VILI mice. Depletion of GGPPS1 significantly alleviated the severity of ventilator induced lung injury in mice. Total cell count, neutrophils and inflammatory cytokines (interleukin [IL]-6, IL-1ß, IL-18 and tumor necrosis factor-α) levels in BALF were reduced after GGPPS1 depletion. Moreover, addition of exogenous GGPP in GGPPS-deficient mice significantly exacerbated the severity of ventilator induced lung injury as compared to the PBS treated controls. Mechanistically, the expression of TLR2/4, as well as downstream proteins including activator protein-1 (AP-1) was suppressed in lung tissues of GGPPS1-deficient mice. CONCLUSION: GGPPS1 promoted the pathogenesis of VILI by modulating the TLR2/4-AP-1 signaling pathway, and GGPPS1 knockout significantly alleviated the lung injury and inflammation in the VILI mice.

16.
Brain Res ; 1726: 146474, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31557476

RESUMO

Intranasal insulin exerts neuroprotective effects in a variety of neurological diseases. Whether intranasal insulin affects epileptic activity and whether it has neuroprotective effects in epileptic diseases is however still unknown. In this study we show that low-dose intranasal insulin inhibited kainic acid (KA)- or pentylenetetrazole (PTZ)-induced acute seizures and reduced epileptic discharge activities in mice, potentially by alleviating the increase in seizure-induced glutamate in the hippocampus. Meanwhile, intranasal insulin increased GABA levels and the activities of hippocampal theta, which may affect the excitability of the hippocampus. In chronic KA-induced epilepsy, low-dose intranasal insulin reduces the frequency of spontaneous recurrent seizures and epileptic discharges, while it increases theta energy and thereby improves spatial memory. Larger doses of intranasal insulin increased the frequency of seizures but did not aggravate cognitive impairment, suggesting that the frequency of seizures may not be related to impaired cognitive function. Overall, our findings show that low-dose intranasal insulin inhibits epileptic events and improves cognitive impairment in epileptic mice, suggesting that learning and memory can be improved by intranasal insulin. However, larger doses might increase the risk of epileptic seizures.

17.
Methods Mol Biol ; 2103: 189-198, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31879926

RESUMO

Branched peptide as an attractive mimic of natural peptide is widely used in structural design of functional or therapeutic peptides, to improve their biological activity, stability, and pharmacokinetic properties. In this protocol, we employ a function group of side-chain benzyl ester as the precursor of hydrazide, which could be conveniently used to assemble a branch peptide by native chemical ligation or direct amidation. This method is convergent and efficient, and facilitates the synthesis and application of branched peptides.

18.
Bioresour Technol ; 296: 122347, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31704602

RESUMO

In this study, hyper-butanol producing Clostridium tyrobutyricum Δcat1::adhE2 was used for butanol production from paper mill sludge (PMS) and corn steep liquor (CSL). Our results demonstrated that CSL can not only serve as a cheap nitrogen source, but also provide lactic acid that can be assimilated by C. tyrobutyricum for enhanced butanol production. Through a separate hydrolysis and fermentation, 16.5 g/L butanol with a yield of 0.26 g/g was obtained from PMS hydrolysates supplemented with 5% CSL. Further, a separate repeated hydrolysis was conducted to improve PMS hydrolysis rate and enhance sugar yield. Fermentation using hydrolysates from such process also generated high-level butanol with high yield. Our results suggested an innovative bioprocess for efficient biobutanol production from low-value waste streams.


Assuntos
Clostridium tyrobutyricum , 1-Butanol , Butanóis , Clostridium , Fermentação , Esgotos , Zea mays
19.
Cancer Med ; 9(3): 1196-1208, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31860169

RESUMO

According to the global cancer statistic, lung cancer is one of the most dangerous tumors, which poses a serious threat to human health. Exploration the mechanism of lung cancer and new targeted therapeutic measures is always the hot topic. Long noncoding RNA (lncRNA) is an important factor affecting the development of tumors. However, the research on the mechanism of lncRNA in the progress of lung cancer needs to be further expanded. In this study, we found that the expression of lncRNA GMDS-AS1 was significantly reduced in lung adenocarcinoma (LUAD) tissues and cells. Upregulated GMDS-AS1 can significantly inhibit the proliferation of LUAD cells and promote cell apoptosis in vitro and in vivo. The results indicate that GMDS-AS1 acts as a tumor suppressor gene to affect the development of LUAD. Further studies revealed that GMDS-AS1 is a target gene of miR-96-5p, and GMDS-AS1 regulates proliferation and apoptosis of LUAD cells in association with miR-96-5p. In addition, we also confirmed that CYLD lysine 63 deubiquitinase (CYLD) is also a target gene of miR-96-5p. Through various validations, we confirmed that GMDS-AS1 can act as a ceRNA to upregulate the expression of CYLD by sponging miR-96-5p. Moreover, the intervention of GMDS-AS1/miR-96-5p/CYLD network can regulate the proliferation and apoptosis of LUAD cells. In this study, we revealed that the GMDS-AS1/miR-96-5p/CYLD network based on ceRNA mechanism plays an important role in the development of LUAD and provides a new direction and theoretical basis for targeted therapy of LUAD.

20.
Sci Rep ; 9(1): 18787, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31827212

RESUMO

Invasive alien species (IAS) are one of the greatest drivers of ecological change. Typically, control uses chemical agents that often are ineffective, harmful to non-target organisms, and environmentally persistent. Bivalves are frequently high impact IAS, but have proven particularly hard to control due to their valve-closing response when exposed to conventional control agents. Microencapsulation of biocides with edible coatings represents a highly targeted delivery route, bypassing avoidance responses and accumulating in bivalves through their prodigious filter feeding. Uneaten microcapsules degrade and become biologically inactive within hours thus reducing potential impacts on non-target biota. We manufactured two new formulations of microcapsules (BioBullets). Particles were designed to mimic natural food particles (algae) in terms of size (9.5 ± 0.5 to 19.4 ± 1.3 SE µm diameter), buoyancy (near neutral) and shape (spherical). Laboratory exposures demonstrated that two formulations effectively controlled the Gulf wedge clam Rangia cuneata, an IAS currently spreading rapidly through Europe. A single dose of 2-6 mg L-1 of the active ingredient in a static system achieved 90% mortality after 30 days of exposure. Microencapsulation offers an effective and targeted management tool for rapid responses following the early detection of both Gulf wedge clams and many other filter-feeding IAS, and may be especially effective in closed systems or where populations remain very localised.

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