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1.
J Gynecol Oncol ; 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-32026657

RESUMO

OBJECTIVE: To assess the outcomes and toxic effects of 5-day actinomycin D (Act-D) salvage therapy and to explore the predictors of Act-D resistance in patients with low-risk gestational trophoblastic neoplasia (GTN)who failed 5-day methotrexate (MTX) chemotherapy. METHODS: This retrospective study analyzed patients with low-risk GTN administered Act-D salvage therapy after failing MTX chemotherapy at Women's Hospital, Zhejiang University School of Medicine between January 2000 and December 2015. The clinical parameters of these patients were collected and analyzed. RESULTS: The final analysis included 89 cases. Of these, 73 cases (82.02%) responded to salvage Act-D. The remaining 16 resistant cases were switched to etoposide, MTX, Act-D/cyclophosphamide, and vincristine chemotherapy and achieved complete remission. Serum human chorionic gonadotrophin levels before Act-D salvage therapy (hCGAct-D)in the Act-D-resistant cases were significantly higher than those in the Act-D responders (median 605 vs. 103 IU/L, p=0.009). However, the range of hCGAct-D values in Act-D responders was wider than that in Act-D-resistant cases (5.76-16,664 IU/L vs. 11.43-6,732 IU/L). Thus, assigning a general cut-off value was difficult considering the individual setting. Except for 2 cases requiring other salvage regimens due to Act-D toxicity, 97.80% of cases (89/91) tolerated the toxicity. During at least 1-year follow-up, the survival rate was 100.00% and no case developed recurrence. CONCLUSION: Based on the good therapeutic effect and tolerable toxicity, we recommend Act-D salvage therapy for all patients with low-risk GTN who fail primary MTX chemotherapy. The higher serum hCG levels before Act-D salvage therapy may be associated with resistance to this treatment.

2.
Fitoterapia ; 142: 104498, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32058053

RESUMO

Three new triterpenoids, mallomacrostins A-C (1-3), and 11 known ones (4-14) were obtained from the twigs and leaves of Mallotus macrostachyus. Mallomacrostin A possessed a new trinor-D:B-friedobaccharane skeleton. The structures of the new compounds were elucidated on the basis of extensive spectroscopic techniques including HR-ESIMS and NMR and the structure of 1 was confirmed by single crystal X-ray diffraction analysis. Spectroscopic data of the known compound 4 were provided for the first time. Compounds 2 and 10 exhibited significant anti-inflammatory activity by inhibiting LPS-induced release of nitric oxide with IC50 of 70.0 µM and 14.0 µM, respectively.

3.
J Immunother Cancer ; 8(1)2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32051287

RESUMO

BACKGROUND: Pancreatic cancer (PC) is a common malignancy of the digestive system and is characterized by poor prognosis and early metastasis. Tumor immune escape plays an important role in PC progression. Programmed death 1 (PD1) blockade therapy is a promising treatment for patients with PC, but is yet to achieve significant clinical effects so far. Interferon gamma (IFN-γ) is a soluble dimeric cytokine that is closely associated with tumor immune surveillance and cytotoxicity. IFN-γ suppresses a variety of tumor-derived cytokines in PC, such as CXCL8. In the present study, we investigated the therapeutic efficacy of combined anti-PD1 and IFN-γ treatment in PC. METHODS: BxPC-3 and Panc-1 human PC cell lines were used to construct a murine PC model. Blood samples (n=44) and surgical resection specimens (n=36) from human patients with PC were also collected. χ2 test, two-tailed unpaired t-test or Kaplan-Meier survival analysis was used to calculate p values. RESULTS: PD1/PD-L1 signaling was overexpressed in PC tumor-bearing mice. Anti-PD1 prevented tumor growth if initiated early after tumor inoculation; however, delayed anti-PD1 treatment showed limited benefit. Murine PC model had a preferential expansion of CXCR2+CD68+ macrophages, and these cells showed an immunosuppressive nature (M2 polarization). PC tumors overexpressed CXCL8 and tumor-derived CXCL8 deficiency prohibited the trafficking of CXCR2+CD68+ macrophages. IFN-γ suppressed the expression of tumor-derived CXCL8, and combined with IFN-γ treatment, delayed anti-PD1 treatment showed significant antitumor effects. Thus, we conclude that murine CXCR2+CD68+ macrophages traffic to PC tumors by tumor-derived CXCL8 and mediate local immunosuppression, which limits the efficacy of PD1 blockade therapy. IFN-γ suppresses tumor-derived CXCL8 and inhibits the tumor trafficking of CXCR2+CD68+ macrophages by blocking the CXCL8-CXCR2 axis to enhance anti-PD1 efficacy. Human PC also produces high levels of CXCL8. Patients with PC present elevated CXCR2 expression on peripheral and tumor-infiltrating CD68+ macrophages, which are associated with advanced tumor stage and poor prognosis. CONCLUSION: Our findings suggest that IFN-γ is a translatable, therapeutic option to improve the efficacy of PD1 blockade therapy by preventing trafficking of CXCR2+CD68+ macrophages via blocking the CXCL8-CXCR2 axis.

4.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(1): 40-50, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32027251

RESUMO

OBJECTIVE: To investigate the correlation of single nucleotide polymorphisms (SNP) in arachidonate 5-lipoxygenase gene (ALOX5) rs2029253, rs2228064 and rs2228065 sites, 5-lipoxygenase activating protein gene (ALOX5AP) rs10507391, rs4769874 sites with the risk for genesis of adult myeloid leukemia. METHODS: By the approval from the hospital ethics committee and the informed consent of participants. 150 patients with myeloid leukemia (ML) as ML group and 134 healthy people as the control group were selected. The genomic DNA was extracted from the samples. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) combined with directly sequencing, PCR-amplified products were applied to test the polymorphism of 5 sites in ALOX5 and ALOX5AP gene. RESULTS: A allele frequencies of ALOX5 gene rs2029253 site in the ML group and the control group were 43.0% and 34.3%, respectively. And the G allele frequencies in the ML group and the control group were 57.0% and 65.7%, respectively. The genotype distributions of AA, AG and GG in ALOX5 gene rs2029253 site in the ML group were 32.2%, 21.5% and 46.3% respectively. That in the control group were 15.7%, 37.3% and 47.0% respectively. The genotype AA and A allele frequency of ALOX5 gene rs2029253 site were linked with the increased risk of myeloid leukemia (OR=2.26, 95% CI: 1.43-4.56, P<0.05; OR=1.44, 95% CI: 1.02-2.03, P<0.05). And the genotype AG and allele G reduced the susceptibility to myeloid leukemia (OR=0.46, 95% CI: 0.27-0.78, P<0.01; OR=0.69, 95% CI: 0.50-0.98, P<0.05), however, the polymorphisms of ALOX5 gene rs2228064 and rs2228065 site not correlated with the risk of myeloid leukemia (P>0.05). The A allele frequency of ALOX5AP gene rs10507391 site in the ML group and the control group were 30.7% and 36.2% respectirely. The genotype distribution rates of AA, AT and TT in ALOX5AP gene rs10507391 site in the ML group was 1.3%, 58.7% and 40.0% respectively, that in the control group were 9.7%, 53.0% and 37.3% respectively. The genotype AA of ALOX5AP gene rs10507391 site correlated with the decreased risk of myeloid leukemia (OR=0.13, 95% CI: 0.03-0.57, P<0.05), but the polymorphism of ALOX5AP gene rs4769874 site not correlated with the risk of myeloid leukemia (P>0.05). CONCLUSION: The genotype AA, AG and allele A, G of ALOX5 rs2029253, as well as ALOX5AP rs10507391 may be correlate with the susceptibility to myeloid leukemia.


Assuntos
Proteínas Ativadoras de 5-Lipoxigenase/genética , Araquidonato 5-Lipoxigenase/genética , Leucemia Mieloide , Adulto , Estudos de Casos e Controles , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Leucemia Mieloide/genética , Polimorfismo de Nucleotídeo Único , Fatores de Risco
5.
Nat Prod Res ; : 1-8, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31999210

RESUMO

Two new compounds including a new 3-arylcoumarin liquiritcoumarin (1), and a new flavonoid glycoside crotoliquiritin (2), together with twelve known compounds (3-14) were isolated from the radix and rhizome of Glycyrrhiza uralensis. Their structures were elucidated on the basis of extensive spectroscopic data analyses. All of the compounds were evaluated for the cytotoxic activities. Only compound 5 showed moderate effects with IC50 of 11.46 µM for A549 cells and IC50 of 7.38 µM for NCI-H292 cells. Compounds 1 and 2 were demonstrated to be Nrf2 pathway activators by using a stable antioxidant response element (ARE)-dependent reporter gene assay together with immunoblot and immunofluorescence analysis.

6.
Biochim Biophys Acta Gene Regul Mech ; 1863(2): 194488, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31926341

RESUMO

Polo-like kinase 4 (PLK4) is a member of the serine/threonine protein kinase family involved in cell-cycle regulation and cellular response to stresses. However, the alteration of PLK4 in response to endoplasmic reticulum (ER) stress has not been well described. In the present study, we focused on the regulation of PLK4 regulation in response to ER stress. PLK4 expression was dramatically reduced under ER stress induced by brefeldin A (BFA), tunicamycin (TM), or thapsigargin (TG) and down regulation of PLK4 expression was dependent on activating transcription factor 6 (ATF6) and CCAAT/enhancer-binding protein ß (C/EBPß). Luciferase activity analysis of the truncated PLK4 promoter indicated that region from -1343 to -1250 of the PLK4 promoter was sensitive to BFA or TG. Additionally, ChIP and ChIP Re-IP assays showed that ATF6 and C/EBPß were assembled on the same region of Plk4 promoter. Notably, we identified one C/EBPß responsive element at position -1284, to which ATF6 or C/EBPß binding was enhanced by BFA or TG under in vitro and in vivo conditions. Finally, overexpression of PLK4 inhibits apoptosis and promotes cell proliferation in response to ER stress. In summary, these results demonstrated that ER stress plays a crucial role in PLK4 expression. ATF6 may upregulate DNA-binding affinities after BFA treatment, via recruiting C/EBPß to the upstream promoter of PLK4. These findings may contribute to the understanding of the molecular mechanism of PLK4 regulation.

7.
ACS Appl Mater Interfaces ; 12(4): 4797-4803, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31909585

RESUMO

Cu2+ ions play essential roles in various biological events that occur in the human body. It is important to establish an efficient and reliable detection of Cu2+ ions for people's health. The solution-gated graphene transistors (SGGTs) have been extensively investigated as a promising platform for chemical and biological sensing applications. Herein, highly sensitive and highly selective sensor for Cu2+ ion detection is successfully constructed based on SGGTs with gate electrodes modified by functional carbon quantum dots (CQDs). The sensing mechanism of the sensor is that the coordination of CQDs and Cu2+ ions induces the capacitance change of the electrical double layer (EDL) near the gate electrode and then results in the change of channel current. Compared to other metal ions, Cu2+ ions have an excellent binding nature with CQDs that make it an ultrahigh selective sensor. The CQD-modified sensor achieves excellent Cu2+ ion detection with a minimal level of concentration (1 × 10-14 M), which is several orders of magnitude lower than the values obtained from other conventional detection methods. Interestingly, the device also displays a quick response time on the order of seconds. Due to the functionalized nature of CQDs, SGGTs with CQD-modified gate show good prospects to achieve multifunctional sensing platform in biochemical detections.

8.
Sci Total Environ ; 713: 136417, 2020 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-31955077

RESUMO

Perfluoroalkyl carboxylates (PFCAs) and perfluoroalkyl sulfonates are widespread in human breast milk. However, the occurrence of chlorinated polyfluorinated ether sulfonates (Cl-PFESAs) and fluorotelomer alcohols (FTOHs) in breast milk and their effects on postnatal growth of infants through breast milk consumption are still not well known. This study characterized the occurrence of 16 poly- and perfluoroalkyl substances (PFASs) in breast milk from 174 women in Hangzhou, China and investigated the association between lactation exposure to these PFASs through breast milk consumption and the postnatal growth of infants. Our results showed that perfluorooctanoate (mean 87 pg/mL) was the predominant PFAS in breast milk, followed by perfluorohexanoate (41 pg/mL), 6:2 Cl-PFESA (28 pg/mL), and perfluorooctane sulfonate (25 pg/mL). The occurrence and levels of Cl-PFESAs in Chinese breast milk were firstly reported in the current study. The 8:2 and 10:2 FTOH were detected in half of breast milk samples, with the mean concentration of 9.0 pg/mL and 10 pg/mL, respectively. Breast milk concentrations of C8-C10 PFCAs and 6:2 Cl-PFESA were negatively correlated with infant's length gain rate. Exposed to higher levels of 8:2 FTOH were correlated with decreased infant's weight gain rate. Daily intakes of PFASs via the consumption of breast milk were calculated for infants. Overall, this study firstly demonstrated that lactation exposure to C8-C10 PFCAs, 8:2 FTOH, and 6:2 Cl-PFESA through breast milk consumption may affect the postnatal growth of infants.

9.
Mol Med Rep ; 21(2): 631-640, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31974607

RESUMO

Cardiac shock wave therapy (SWT) has been described as a novel therapeutic strategy that is able to alleviate myocardial ischemic injury. microRNA (miRNA/miR)­210 plays a cytoprotective role in cardiomyocytes in response to hypoxia by regulating cell apoptosis. The aim of the present study was to investigate whether cardiac SWT could protect cardiomyocytes from hypoxia­induced injury by regulating miR­210 expression. The murine adult cardiomyocyte cell line HL­1 was incubated for 5 h in hypoxic conditions, followed by reoxygenation for 12 h and treatment with SWT immediately following hypoxia in the present study. The cell viability was determined using an MTS assay. Western blot analyses were performed in order to detect cell signaling changes. Reactive oxygen species production was detected using dihydroethidium staining, and malondialdehyde levels were measured using the thiobarbituric acid method. miRNA and mRNA expression levels were confirmed via reverse transcription­quantitative PCR. Apoptosis was evaluated by means of flow cytometry. HL­1 cells were then transfected with miR­210 mimics or inhibitors in order to alter miR­210 expression levels, and the effects on HL­1 cells were determined. Hypoxia led to elevated oxidative stress, enhanced cell apoptosis and upregulated miR­210 expression levels in HL­1 cells, while SWT could alleviate hypoxia­induced cell injury and further promote miR­210 expression. miR­210 overexpression decreased apoptosis and oxidative stress during hypoxic stress in HL­1 cells, whereas inhibition of miR­210 increased cell apoptosis and promoted oxidative stress. Furthermore, miR­210 inhibition could reverse the effects of SWT on HL­1 cells. Finally, the mRNA analysis revealed that SWT significantly attenuated apoptosis­inducing factor mitochondrion­associated 3 and caspase 8 associated protein 2 mRNA expression levels in cardiomyocytes exposed to hypoxia, which were two targets of miR­210. SWT could exert cardioprotective effects against hypoxia­induced cardiac injury by modulating miR­210.

10.
J Mater Chem B ; 8(3): 391-405, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31599917

RESUMO

The regeneration of osteochondral defects faces great challenges because of the limited self-regenerative capabilities of cartilage tissues. In situ inductive regeneration can be realized using bioactive scaffolds combined with endogenous reparative cells. Cell migration could be significantly facilitated by scaffolds with oriented channels. For this purpose, silk fibroin (SF) was composited with collagen (Col) to fabricate extracellular matrix (ECM)-mimetic SF/Col composite scaffolds with random pores, radially aligned pores or axially aligned pores by ice-templated assembly and temperature gradient-guided thermally-induced phase separation. Scanning electron microscopy (SEM) observation confirmed the random and aligned architectures in the respective scaffolds. The three kinds of SF/Col composite scaffolds exhibited a porous structure with a porosity of ∼85%, an appropriate elastic modulus with mechanical anisotropy in the aligned scaffolds, and good biocompatibility. The oriented channels could improve in vivo cell migration and infiltration. During the tissue remodeling processes, the regeneration of osteochondral tissues particularly cartilage was obviously faster in the radially aligned scaffold group than in the other two groups. Nevertheless, satisfactory regeneration was achieved in the two aligned scaffold groups with hyaline cartilage formation at 18 weeks post-surgery, while a hybrid of hyaline cartilage and fibrocartilage was formed in the random scaffold group.

11.
Phytochemistry ; 170: 112191, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31731236

RESUMO

Seven undescribed polyketides javanicols A-E, 5-epi-citreoviridin and 5-epi-isocitreoviridin, together with five known compounds, were isolated from the endolichenic fungus Eupenicillium javanicum. The structures of these polyketides were determined by means of extensive spectroscopic analyses, electronic circular dichroism (ECD) calculations and gauge-independent atomic orbital (GIAO) NMR shift calculations. These compounds were evaluated for potential anti-inflammatory activity against LPS-activated RAW 264.7 cells. Javanicol E and (+)-terrein displayed moderate inhibitory effects on NO production, with IC50 values of 17.00 and 13.46 µM, respectively.

12.
Biomed Pharmacother ; 121: 109669, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31766100

RESUMO

Oxidative stress is closely associated to the onset and progression of many human diseases. Activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway using naturally-derived molecules is an efficient strategy for alleviating the intracellular oxidative insults, and thus blocking the pathogenesis of oxidative stress-induced diseases. In the present study, a naturally-derived isopimarane-type diterpenoid sphaeropsidin C (SC) was identified to be an activator of Nrf2/ARE signaling pathway. Our data indicated that SC was able to stimulate Nrf2-mediated defensive system through promoting Nrf2 translocation, inhibiting Nrf2 ubiquitination, and enhancing Nrf2 stability in normal human lung epithelial Beas-2B cells. Furthermore, SC-induced Nrf2 activation required the involvement of protein kinases, exemplified by protein kinase C (PKC), protein kinase R-like endoplasmic reticulum kinase (PERK), and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K). It alleviated sodium arsenite [As(III)]-induced intracellular oxidative stress in an Nrf2-dependent manner. These results suggested that SC displayed potential application for the prevention and therapy against oxidative stress-induced diseases. Moreover, isopimarane-type diterpenoid represents a promising skeleton for developing Nrf2 activators.

13.
J Pharm Pharmacol ; 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31826333

RESUMO

OBJECTIVES: Withanolides are a group of modified C28 ergostane-type steroids with a C-22, C-26 δ-lactone side chain or a C-23, C-26 γ-lactone side chain. They enjoy a limited distribution in the plant kingdom and predominantly occur in several genera of Solanaceae. Of which, the genus Physalis is an important resource for this type of natural molecules. The present review aims to comprehensively illustrate the structural characteristics and classification of withanolides, and particularly focus on the progression on phytochemical and pharmacological aspects of withanolides from Physalis ranging from January 2015 to June 2019. KEY FINDINGS: Approximately 351 natural withanolides with novel and unique structures have so far been identified from genus Physalis, mainly isolated from the species of P. angulata and P. peruviana. Withanolides demonstrated diverse biological activity, such as anticancer, anti-inflammatory, antimicrobial, immunoregulatory, trypanocidal and leishmanicidal activity. Their observed pharmacological functions supported the uses of Physalis species in traditional or folk medicines. SUMMARY: Due to their unique structure skeleton and potent bioactivities, withanolides are regarded to be promising drug candidates, particularly for developing anticancer and anti-inflammatory agents. Further investigations for discovering novel withanolides of genus Physalis, exploiting their pharmacological values and evaluating their potency as therapeutic agents are significant work.

14.
Artigo em Inglês | MEDLINE | ID: mdl-31837803

RESUMO

Doxorubicin, as a first line chemotherapeutic agent, its usage is limited owing to cardiotoxicity. Necroptosis is a new form of programmed cell death, and recent investigations indicated that necroptosis is vitally involved in serious cardiac pathological conditions. Dexrazoxane is the only cardiac protective drug approved by FDA for anthracycline. We aimed to explore whether and how dexrazoxane regulates doxorubicin-induced cardiomyocyte necroptosis. First, doxorubicin could cause heart failure and reduce cardiomyocyte viability by promoting cell apoptosis and necroptosis in vivo and in vitro. Second, necroptosis plays an important role in doxorubicin induced cardiomyocyte injury, which could be inhibited by Nec-1. Third, dexrazoxane increased cell viability and protect heart function by decreasing both cardiomyocyte apoptosis and necroptosis after doxorubicin treatment. Forth, dexrazoxane attenuated doxorubicin-induced inflammation and necroptosis by the inhibition of p38MAPK/NF-κB pathways. These results indicated that dexrazoxane ameliorates cardiotoxicity and protects heart function by attenuating both apoptosis and necroptosis in doxorubicin induced cardiomyocyte injury.

15.
Environ Pollut ; 259: 113779, 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31887597

RESUMO

Many studies show that bisphenol A (BPA) is widespread in human breast milk. However, the occurrence of other bisphenol analogues (BPs), including bisphenol S (BPS), bisphenol F (BPF), and bisphenol AF (BPAF), in breast milk is still not well known. In this study, breast milk samples were collected from 190 women in Hangzhou, China, with the aims to characterize the occurrence of BPA, BPS, BPF, and BPAF in these samples and to investigate their effects on postnatal growth of infants through breast milk consumption. BPA (mean 2.5 ng/mL, range < LOD-15 ng/mL) was the most abundant BP in breast milk, followed by BPS (0.19 ng/mL,

16.
PLoS One ; 14(11): e0225569, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31774839

RESUMO

BACKGROUND: Enterovirus 71 (EV71) vaccine, which was put into market in China in 2016, has been viewed as a promising prevention measure against severe and fatal hand, foot and mouth disease (HFMD). This study aimed to investigate the knowledge of HFMD and acceptability of EV71 vaccine among parents of under-five in Chongqing, China. METHODOLOGY /PRINCIPAL FINDINGS: A cross-sectional survey was conducted in 2017. A validated questionnaire consisting of three sections including demographic information, knowledge of HFMD, acceptability and reasons for declining vaccination was developed based on literature review. Factors associated with unwillingness to receive EV71 vaccine were explored using multivariate logistic regression. A total of 992 parents finished the questionnaire with a response rate of 91.9%. Awareness of HFMD and EV71 vaccine were reported by 823 (83.0%) parents and 386 (38.9%) parents respectively. Knowledge about HFMD was with a mean score of 5.0 (standard deviation = 3.5) out of a total score of 12. Only 369 (37.2%) participants were classified as with good knowledge level about HFMD. 279 (28.1%) participants had their children received EV71 vaccine and 271 (27.3%) expressed willingness to vaccinate their children after a short-time education about EV71 vaccine. Acceptability of EV71 vaccine increased along with parents' education level (p = 0.008) and HFMD knowledge level (p<0.001). Parents of scattered children had higher acceptability than those of preschool children (p = 0.002). 442 (44.6%) of participants were unwilling to have their children vaccinated with EV71 vaccine. The most common reasons for declining EV71 vaccine were doubts about its safety (56.6%) and efficacy (48.3%), and the necessity of vaccination (38.3%). Physicians and vaccination certificate were the parents' most trusted sources of vaccine information. CONCLUSIONS: Parents' knowledge about HFMD was not sufficient, and nearly half of the parents expressed unwillingness to vaccinate their children with EV71 vaccine. Our findings stress that more efforts by health authorities in Chongqing are needed to increase the acceptability of EV71 vaccine, especially among parents of preschool children with lower education level.

17.
J Phys Chem Lett ; 10(24): 7712-7718, 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31769691

RESUMO

Two-dimensional InSe possesses good electrical conductivity, intrinsic and structural flexibility, high chemical stability, and a tunable band gap, enabling it to be a promising candidate for flexible and wearable solar cells. Here we construct a lateral p-n junction by partially doping molybdenum trioxide (MoO3) at the surface of the InSe monolayer. Our density functional theory calculations reveal that the strong hybridization between MoO3 and InSe induces a lateral built-in electric field in the partially doped substrate and promotes the effective separation of carriers. Under a large range of external stains, the doped InSe can maintain the direct band gap, and the lateral structure device exhibits power conversion efficiencies over 5% and high carrier mobility around 1000 cm2 V-1 s-1. In particular, a power conversion efficiency of 20.7% can be achieved with 10% compressive strain. The partially doped InSe monolayer is expected to be used as an ultrathin flexible solar cell.

18.
Free Radic Biol Med ; 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31760092

RESUMO

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease resulted from airflow obstructions, and there is a driving requirement for novel and effective preventive and therapeutic agents of COPD. Nuclear factor-erythroid 2-related factor 2 (Nrf2) has been regarded to be a promising therapeutic target for COPD. Resveratrol is a natural Nrf2 activator with antioxidant and anti-inflammatory properties, however, its application is limited by its relative low efficiency and poor bioavailability. Herein, based on the skeleton of resveratrol, trans-4,4'-dihydroxystilbene (DHS) has been firstly identified to be an Nrf2 activator, which is more potent than the well-known sulforaphane (SF) and resveratrol. Our results indicate that DHS blocks Nrf2 ubiquitylation through specifically reacting with Cys151 cysteine in Keap1 protein to activate Nrf2-regulated defensive response, and thus enhances intracellular antioxidant capability. Furthermore, DHS relieves lipopolysaccharide (LPS)-stimulated inflammatory response via inhibition of NF-κB. Importantly, DHS significantly ameliorates pathological alterations (e.g. infiltration of leukocytes and fibrosis), downregulates the levels of oxidant biomarkers malondialdehyde (MDA) and 8-oxo-7,8-dihydro-2'-deoxyguanosin (8-oxo-dG), and inhibits the overproductions of inflammatory mediators [e.g. tumor necrosis factor α (TNF-α), cyclooxygenase-2 (COX-2), and matrix metalloproteinase-9 (MMP-9)] in a cigarette smoke (CS)-induced pulmonary impairment mice model. Taken together, this study demonstrates that DHS attenuates the CS-induced pulmonary impairments through inhibitions of oxidative stress and inflammatory response targeting Nrf2 and NF-κB in vitro and in vivo, and could be developed into a preventive agent against pulmonary impairments induced by CS.

19.
Cancer Biol Ther ; : 1-10, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31718519

RESUMO

Despite improvements in surgical resection and adjuvant chemotherapy, the prognosis and outcomes of patients with osteosarcoma remains poor due to the occurrence of metastasis or relapse. Monocyte chemoattractant protein-1-induced protein-1 (MCPIP1), a zinc-finger RNA-binding protein, is known to regulate inflammatory responses and repress breast cancer growth. However, the regulation of MCPIP1 by microRNAs has not been clearly elucidated in osteosarcoma. In this study, we found that miR-421 expression was upregulated and MCPIP1 expression was downregulated in the osteosarcoma specimens from patients. Moreover, MCPIP1 expression was inversely correlated with miR-421 expression in the clinical samples. Furthermore, the upregulation of miR-421 and downregulation of MCPIP1 resulted in poor overall survival and severe disease progression, respectively, in the patients with osteosarcoma. Bioinformatics analysis and luciferase reporter gene assays confirmed that miR-421 specifically targets and binds to the 3'-UTR of MCPIP1. The overexpression of miR-421 induced cell proliferation, invasion, and migration, and the release of pro-inflammatory IL-6 in cultured human osteosarcoma cells. Additionally, the administration of miR-421 to tumor-bearing mice facilitated osteosarcoma growth by downregulating MCPIP1 expression. Taken together, these findings indicate that miR-421 is able to promote the development of osteosarcoma by regulating MCPIP1 expression, and can be a potential therapeutic target for osteosarcoma.

20.
Int J Biol Macromol ; 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31734367

RESUMO

High-value utilization of hemicellulose is critical to improve the append value of integrated biorefineries. In this research, the alkali-soluble sugarcane bagasse hemicellulose was sulfated using chlorosulfonic acid and N,N-dimethylformamide/LiCl under homogeneous conditions. With the aid of flow technique, a rapid, mild, and efficient method for the synthesis of xylan sulfate with high molecular weight and controllable degree of substitution was achieved. The results showed that the reaction time and the degradation of xylan chain were drastically reduced compared to the "in flask" batch conditions. High molecular weight of the product (Mw = 148,217) with a reasonable degree of substitution (DS = 1.49) could be obtained even at room temperature in 10 min under the present flow system. Anticoagulant experiments showed good anticoagulant activity of the resultant xylan sulfate, which could significantly prolong the activated partial thromboplastin time and thrombin time. This work not only provides a novel method for the synthesis of xylan sulfate, but also offers new opportunities for the production of other functional polysaccharide derivatives under the flow reaction conditions.

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