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1.
J Nanosci Nanotechnol ; 20(2): 789-801, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31383074

RESUMO

Magnetic Ni0.5Cu0.5Fe2O4/SiO2 nanocomposites were prepared via a solution combustion process, and were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM), Energy dispersive X-ray Spectroscopy (EDX) and vibrating sample magnetometer (VSM). The magnetic Ni0.5Cu0.5Fe2O4/SiO2 nanocomposites were employed to remove Congo red (CR) from aqueous solution, and the adsorption process was optimized by response surface methodology (RSM). The optimum conditions were the silica content of 12.6 wt%, the calcination temperature of 501 °C and the pH value of 7.13. The adsorption kinetics and the adsorption isotherm of CR onto magnetic Ni0.5Cu0.5Fe2O4/SiO2 nanocomposites at room temperature were investigated, and the intraparticle diffusion kinetics model and Redlich-Peterson isotherm model fitted well the respective process.

2.
J Nanosci Nanotechnol ; 20(1): 1-14, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31383134

RESUMO

In this study, a novel antitumor system was designed on the basis of photodynamic therapy and photothermal therapy using gold nanoshells coated 5-aminolevulinic acid (5-ALA) liposomes (GNALs). As a widely used photosensitizer prodrug, 5-aminolevulinic acid (5-ALA)-derived protoporphyrin IX (PpIX) can accumulate to a higher level in tumors than in normal tissues. Protoporphyrin IX (PpIX) initiates a series of cytotoxic reactions after irradiation of target tissue with a measured dose of light with appropriate wavelength, which may be dependent on the generation of reactive oxygen species. Gold nanoshells can strongly absorb NIR lasers at the same time, and can generate hyperthermia to provide photothermic effects. Gold nanoshells coated 5-ALA-Liposomes (GNALs) exhibit a uniform-sized spherical shape of 185.8±0.91 nm, with a zeta potential of 33±1.6 mV. Liposomes with specific sizes ranging from 100 to 200 nm can escape into the tumor interstitial tissue and accumulate preferentially in tumor tissue owing to the EPR effect. In addition, NIR light-excited nanosystems significantly promoted antitumor effects in this study compared to single photodynamic therapy. It was also found that the increased temperature promoted inhibition rate of SKOV3 cells. The novel drug delivery system shows great potential in photothermal-photodynamic antitumor therapy.

3.
J Nanosci Nanotechnol ; 20(4): 2223-2230, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31492231

RESUMO

Tight oil is widely distributed around the world, and industrialized exploitation has been developed and applied in North America, greatly alleviating the contradiction between supply and demand of energy. The main storage space of tight oil reservoirs is micro-nano pores, and a reliable method for studying the occurrence of tight oil in micro-nano pores has not been studied. In this paper, the microscopic occurrence of tight oils in the Songliao Basin, Ordos Basin, and Tarim Basin in China are studied in combination with nuclear magnetic resonance (NMR) and field emission scanning electron microscopy (FE-SEM) scanning techniques. A method for characterizing the storage space, occurrence state, and influencing factors of tight oil based on SEM and NMR was proposed. The results show that the storage space of tight oil reservoirs is nanoscale cracks and pores. Mainly, these are distributed on the scale of less than 1 µm and more than 10 µm, the volume of porecracks is less than 1 µm, which account for more than 80% of the total volume. This indicates that the tight oil mainly exists in the nanoscale pore throat. The scattered distribution of crude oil in the black shape of oil spot is mainly in the micro-nano pores, and the crude oil content in the micro-cracks is small, indicating that nanoscale cracks are the main space for the occurrence of tight oil. However, some micro-cracks can penetrate oil spots or oil stains, and can connect the oil spots with scattered distribution, which will greatly improve the mobility of crude oil. In addition, oil spot accumulation areas often develop illite and illite/smectite mixed-layer, and clay minerals have developed nanoscale pores. The crude oil and clay minerals have certain associated characteristics. This study is of great significance for understanding the law of the occurrence and migration of tight oil and the basic theoretical research and technological innovation of the development of tight oil reservoir.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31565917

RESUMO

Two red fluorophores (TPABTPA and TPABCHO) with hybridized local and charge-transfer (HLCT) properties were systematically studied. TPABTPA and TPABCHO enabled non-doped organic light-emitting diodes (OLEDs) with excellent external quantum efficiency (EQE) of 11.1% and 5.0% respectively, attributing to high exciton utilization efficiency of 82% and 46% respectively. Furthermore, TPABTPA and TPABCHO were utilized as complementary emitters for a sky-blue thermally activated delayed fluorescence material to fabricate two-color fluorescent white OLEDs (WOLEDs) in a fully non-doped emissive-layer configuration. Furthermore, device performance was optimized through a simple device engineering strategy by sandwiching a suitable interlayer between the emitting layers. As a result, the optimized TPABTPA and TPABCHO-based WOLEDs successfully achieved high EQEs of 23.0% and 8.6% respectively, along with low efficiency roll-off and good spectral stability, due to high exciton utilization efficiency of the emitters and importantly efficient suppression of non-radiative energy transfer process.

5.
Int J Environ Health Res ; : 1-12, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31565963

RESUMO

To evaluate the association between ALOX15 gene polymorphism and skeletal fluorosis (SF), a case-control study was conducted. A total of 1023 individuals, including 308 Tibetans, 290 Kazaks and 425 Han, were enrolled in this study, in which cases and controls were 278 and 745, respectively. SF was diagnosed by X-ray absorptiometry. SNPs were genotyped using the Sequenom Mass ARRAY system. The genotypes of ALOX15 rs7220870, rs2664593 and rs1107852 were not associated with the risk of SF. After reconstructing the haplotype of rs7220870 and rs11078528, the risk effect of haplotype CA was found in Han participants aged ≤45 years or with moderate fluoride intake. Diplotype of CC/CC had a protective effect on SF risk in Han participants; whereas, CA/CC diplotype showed a risk effect on SF risk in participants aged ≥65; Our results provide the first evidence of an association between ALOX15 gene polymorphism and SF risk in Han participants. Abbreviation: SF: Skeletal fluorosis; SNP: Single Nucleotide polymorphism.

6.
Adv Mater ; : e1904836, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31566280

RESUMO

Photothermal therapy triggered by near-infrared light in the second biowindow (NIR-II) has attracted extensive interest owing to its deeper penetration depth of biological tissue, lower photon scattering, and higher maximum permissible exposure. In spite of noble metals showing great potential as the photothermal agents due to the tunable localized surface plasmon resonance, the biological applications of platinum are rarely explored. Herein, a monocomponent hollow Pt nanoframe ("Pt Spirals"), whose superstructure is assembled with three levels (3D frame, 2D layered shells, and 1D nanowires), is reported. Pt Spirals exhibit outstanding photothermal conversion efficiency (52.5%) and molar extinction coefficients (228.7 m2 mol-1 ) in NIR-II, which are much higher than those of solid Pt cubes. Simulations indicate that the unique superstructure can be a significant cause for improving both adsorption and the photothermal effect simultaneously in NIR-II. The excellent photothermal effect is achieved and subsequently verified in in vitro and in vivo experiments, along with superb heat-resistance properties, excellent photostability, and a prominent effect on computed tomography (CT) imaging, demonstrating that Pt Spirals are promising as effective theranostic platforms for CT imaging-guided photothermal therapy.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31577406

RESUMO

Defect-engineering of semiconductors has been identified as an effective route towards enhancing the photoelectrochemical performances. There is a security threat in the traditional hydrogen-annealing process. In this work, oxygen defective nanofibers WO3-x/WO3 homojunction photoanode was in-situ synthesized via a novel metal self-reducing method. The as-prepared photoanode exhibits a 1.8-time higher solar water oxidation photocurrent density than that of bare WO3 film at 1.2 V vs. Ag/AgCl. The enhanced photoelectrochemical properties originate from the effective charge separation and injection, attributed to the stronger built-in electric field created by the oxygen-deficient homojunction. Importantly, this novel method is universal applicable to synthesize oxygen-deficient semiconductors materials, including films and powders.

8.
Hepatology ; 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31578733

RESUMO

Liver cancer stem cells (CSCs) exist in the tumor environment and are critically involved in the initiation and progression of hepatocellular carcinoma (HCC). However, the underlying molecular mechanisms of self-renewal and maintenance of liver CSCs remain poorly understood. Herein, we identified that xanthine oxidoreductase (XOR), which was expressed at low levels in human HCC samples and liver CSCs, restrained HCC formation and chemoresistance by attenuating liver CSCs propagation. Mechanistically, XOR physically interacts with USP15, thereby promoting deubiquitination of Kelch Like ECH Associated Protein 1 (KEAP1) to stabilize its expression, which leads to degradation of Nrf2 via ubiquitination and subsequently reactive oxygen species (ROS) accumulation in liver CSCs. Finally, our data reveal that XOR promotes USP15 mediated Nrf2-KEAP1 signaling to block liver CSCs and tumor propagation. CONCLUSION: we have identified that XOR may represent a potential novel therapeutic target for clinical intervention in HCC driven by liver CSCs.

10.
Medicine (Baltimore) ; 98(38): e17284, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31568012

RESUMO

BACKGROUND: This study will assess the efficacy and safety of blood purification (BP) for severe pancreatitis (SP) and acute respiratory distress syndrome (ARDS). METHODS: We will search the following electronic databases of Ovid MEDLINE, EMBASE, Web of Science, Cochrane Library, Scopus, Cumulative Index to Nursing and Allied Health Literature, the Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, and WANGFANG from inception to the present without language restriction. A systematic review and data synthesis will be carried out of randomized controlled trials of BP for the treatment of patients with SP and ARDS. RevMan 5.3 software will be used for statistical analysis. RESULTS: This systematic review will evaluate the efficacy and safety of BP for the treatment of patients with SP and ARDS. The primary outcome includes respiratory indexes, blood biochemical and inflammatory factors. The secondary outcomes consist of complications, sepsis, abdominal hemorrhage, renal failure, length of hospital stay, and mortality. CONCLUSION: This study will provide up-to-date evidence of BP for the treatment of patients with SP and ARDS. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42019139467.

11.
Cancer ; 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31568564

RESUMO

BACKGROUND: Salvage immunochemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation is the standard-of-care second-line treatment for patients with relapsed/refractory diffuse large B-cell lymphoma after first-line R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Outcomes after receipt of second-line immunochemotherapy in patients with aggressive B-cell lymphomas who relapse or are refractory to intensive first-line immunochemotherapy regimens (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab [R-EPOCH], rituximab, hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with methotrexate and cytarabine [R-HyperCVAD], rituximab, cyclophosphamide, vincristine, doxorubicin, and high-dose methotrexate alternating with ifosfamide, etoposide, and cytarabine [R-CODOX-M/IVAC]) remain unknown. METHODS: Outcomes of patients with non-Burkitt, aggressive B-cell lymphomas and relapsed/refractory disease after first-line treatment with intensive immunochemotherapy regimens who received platinum-based second-line immunochemotherapy were reviewed retrospectively. Analyses were performed to determine progression-free survival (PFS) and overall survival (OS) from the time of receipt of second-line immunochemotherapy. RESULTS: In total, 195 patients from 19 academic centers were included in the study. The overall response rate to second-line immunochemotherapy was 44%, with a median PFS of 3 months and a median OS of 8 months. Patients with early treatment failure (primary refractory or relapse <12 months from completion of first-line therapy) experienced inferior median PFS (2.8 vs 23 months; P < .001) and OS (6 months vs not reached; P < .001) compared with patients with late treatment failure. Although the 17% of patients with early failure who achieved a complete response to second-line immunochemotherapy experienced prolonged survival, this outcome could not be predicted by clinicopathologic features at the start of second-line immunochemotherapy. CONCLUSIONS: Patients with early treatment failure after intensive first-line immunochemotherapy experience poor outcomes after receiving standard second-line immunochemotherapy. The use of standard-of-care or experimental therapies currently available in the third-line setting and beyond should be investigated in the second-line setting for these patients.

12.
Phys Rev Lett ; 123(10): 100505, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31573314

RESUMO

Channel loss seems to be the most severe limitation on the practical application of long distance quantum key distribution. The idea of twin-field quantum key distribution can improve the key rate from the linear scale of channel loss in the traditional decoy-state method to the square root scale of the channel transmittance. However, the technical demands are rather tough because they require single photon level interference of two remote independent lasers. Here, we adopt the technology developed in the frequency and time transfer to lock two independent laser wavelengths and utilize additional phase reference light to estimate and compensate the fiber fluctuation. Further, with a single photon detector with a high detection rate, we demonstrate twin field quantum key distribution through the sending-or-not-sending protocol with a realistic phase drift over 300 km optical fiber spools. We calculate the secure key rates with the finite size effect. The secure key rate at 300 km (1.96×10^{-6}) is higher than that of the repeaterless secret key capacity (8.64×10^{-7}).

13.
Ann Am Thorac Soc ; 16(10): 1207-1214, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31573344

RESUMO

Air quality data from satellites and low-cost sensor systems, together with output from air quality models, have the potential to augment high-quality, regulatory-grade data in countries with in situ monitoring networks and provide much-needed air quality information in countries without them. Each of these technologies has strengths and limitations that need to be considered when integrating them to develop a robust and diverse global air quality monitoring network. To address these issues, the American Thoracic Society, the U.S. Environmental Protection Agency, the National Aeronautics and Space Administration, and the National Institute of Environmental Health Sciences convened a workshop in May 2017 to bring together global experts from across multiple disciplines and agencies to discuss current and near-term capabilities to monitor global air pollution. The participants focused on four topics: 1) current and near-term capabilities in air pollution monitoring, 2) data assimilation from multiple technology platforms, 3) critical issues for air pollution monitoring in regions without a regulatory-quality stationary monitoring network, and 4) risk communication and health messaging. Recommendations for research and improved use were identified during the workshop, including a recognition that the integration of data across monitoring technology groups is critical to maximizing the effectiveness (e.g., data accuracy, as well as spatial and temporal coverage) of these monitoring technologies. Taken together, these recommendations will advance the development of a global air quality monitoring network that takes advantage of emerging technologies to ensure the availability of free, accessible, and reliable air pollution data and forecasts to health professionals, as well as to all global citizens.

14.
Nanoscale ; 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31573595

RESUMO

The therapeutic efficacy of anti-cancer nanomedicines is generally constrained due to limited accumulation in the solid tumors. In this study, we developed a biomimetic nano-carrier to enhance the chemo-therapeutic efficacy of doxorubicin and icotinib in a chemo-resistant non-small cell lung cancer (NSCLC) cell line harboring a mutation in the epidermal growth factor receptor (EGFR). The unique nanomedicine was prepared by coating with targeting cancer cell membrane proteins as highly specific ligands. The resulting biomimetic nanoparticles were highly stable and exhibited superior homologous targeting ability in vitro compared with control groups. In a mouse EGFR-mutated NSCLC xenograft model, intravenous injection of the biomimetic nanomedicine led to a high tumour inhibition rate (87.56%). Histopathological analysis demonstrated that the biomimetic nanomedicine had minimal side effects. Taken together, a cancer cell membrane-based biomimetic drug carrier can significantly enhance drug accumulation and improve therapeutic efficacy in cancers.

15.
J Periodontol ; 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31573683

RESUMO

BACKGROUND: Periodontal ligament stem cells (PDLSCs) play an essential role in periodontal tissue repair. Basic fibroblast growth factor (bFGF) has been used in the clinical treatment of periodontal disease. However, studies have shown that bFGF inhibits the osteogenic differentiation of PDLSCs, which is not conducive to alveolar bone repair. Sulfonated chitosan oligosaccharide (SCOS), a heparan-like compound, can maintain the conformation of bFGF and promote its proliferation activity. This study investigated the effects of bFGF in combination with SCOS on the osteogenic differentiation of hPDLSCs. METHODS: hPDLSCs were isolated from healthy human periodontal ligament and identified by flow cytometry and immunofluorescence. The affinity between SCOS and bFGF was analyzed by surface plasmon resonance. Changes in osteogenic differentiation by combination of bFGF with SCOS were analyzed by alkaline phosphatase activity assay, Sirius Red staining, and Alizarin Red staining. Expression of genes and proteins was investigated by western blotting and reverse transcription-quantitative PCR. RESULTS: Extracted hPDLSCs were mesenchymal stem cells with pluripotent differentiation potential. SCOS exhibited an affinity for bFGF. bFGF (20 ng/mL) promoted the proliferation of hPDLSCs, but inhibited their osteogenic differentiation. SCOS alleviated the inhibitory effect of bFGF on the osteogenic differentiation of hPDLSCs. CONCLUSIONS: SCOS can reduce the inhibitory effect of bFGF on the osteogenic differentiation of hPDLSCs. This study may provide evidence for the clinical use of bFGF to repair periodontal tissue. This article is protected by copyright. All rights reserved.

16.
Rev Sci Instrum ; 90(9): 094705, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31575265

RESUMO

Superconducting shim coils are frequently used in high-field magnetic resonance imaging or nuclear magnetic resonance system for their high sensitivity and shimming strength. The design of superconducting shim coils is based on the spherical harmonic decomposition, and each shim coil is normally dedicated for correcting one specific harmonic component. Conventional superconducting shim coil with a saddle loop has observable winding error near the corner, which gives rise to arc transformation when winding layer by layer. Simulation analysis shows that the arc corner transformation will induce the magnetic field deviation by more than double of the theoretical design ±1%, which may be up to ±3% after real winding. An improved shim coil design method with a quasisaddle geometry was proposed to correct the winding error. With the consideration of both the rounded corner of the saddle loop and the arc side, the new design offers the magnetic field deviation within ±1%. In addition to reducing the winding error, the proposed design also facilitates the winding process.

17.
World J Gastroenterol ; 25(36): 5469-5482, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31576093

RESUMO

BACKGROUND: Irritable bowel syndrome (IBS) is one of the most common functional gas-troenterological diseases characterized by abnormal visceral sensitivity and low-grade inflammation. The role of Clostridium butyricum (C. butyricum) in reducing intestinal low-grade inflammation via immune pathways has been well defined. However, the detailed mechanisms of the effects of C. butyricum on intestinal mucosal immunity, especially on immune cells of the lamina propria, remain unclear. Dendritic cells (DCs), which are important immune cells, secrete proinflammatory cytokines (IL-1ß, IL-6, and others) and express T cell immuno-globulin and mucin domain-3 (TIM3), promoting proliferation and activation of DCs, and mediating Th1 and Th17 inflammatory responses. AIM: To investigate the role of DCs in the development of IBS in a rat model and to understand the regulation of DCs after C. butyricum intervention. METHODS: An IBS animal model was established using C57BL/6 mice, and C. butyricum was continuously administered via the intragastric route to simulate different intestinal immune states. Intestinal visceral hypersensitivity and histopathology were assessed using the abdominal withdrawal reflex (AWR) test and hematoxylin & eosin (H&E) staining, respectively. The expression of proinflammatory cytokines (IL-1ß and IL-6) and TIM3 was analyzed by Western blot analysis and real-time PCR. Flow cytometry was applied to analyze the quantity, function, and membrane molecule TIM3 of the lamina propria dendritic cells (LPDCs). The regulatory effect of C. butyricum was verified in bone marrow-derived dendritic cells by in vitro experiments. RESULTS: The secretion of proinflammatory cytokines (IL-1ß and IL-6) in mice with IBS was significantly increased compared with that of the control group, which suggested that the intestinal mucosa in mice with IBS was in a low-grade inflammatory state. The expression of CD11C+CD80+ and CD11c+TIM3+ in intestinal LPDCs in mice with IBS increased significantly. Meanwhile, the cytokines (IL-1ß and IL-6) were significantly reduced after the intervention with probiotic C. butyricum. The amount and function of LPDCs and the TIM3 on the surface of the LPDCs were decreased with the alleviation of the intestinal inflammatory response. CONCLUSION: The results suggest that C. butyricum regulates the amount and functional status of LPDCs in the intestinal mucosa of mice with IBS, and therefore modulates the local immune response in the intestine.

18.
Eur J Pharmacol ; 863: 172708, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31568785

RESUMO

Obesity is a serious public health problem characterized by abnormal or excessive fat accumulation, which is caused by an energy imbalance between calories consumed and calories expended. MiRNAs have been involved in the regulation of occurrence and progression of obesity. This study aims to investigate the role of miR-324-5p in regulating the adipose tissue mass and preliminarily probe into its effect on progression of obesity. MiR-324-5p was upregulated in the epididymal white adipose tissues (eWAT), inguinal white adipose tissues (iWAT) and brown adipose tissues (BAT) of the mice fed with high fat diet (HFD). Under room temperature (RT) or thermoneutrality (TN) condition, when tail intravenously injected with miR-324-5p antagomir (anta-miR-324-5p), the fat mass and total weight of mice were both significantly suppressed. The suppressive effect was more distinct under TN than RT. The weight of iWAT and BAT were both inhibited by anta-miR-324-5p under TN. Moreover, PM20D1 was a direct target gene of miR-324-5p. In primary iWAT cells, the expression of PM20D1 was significantly increased by anta-miR-324-5p, whereas decreased by the miR-324-5p mimic. Furthermore, anta-miR-324-5p noticeably increased the cellular oxygen consumption in primary BAT and iWAT cells. Our findings indicated that inhibition of miR-324-5p increased PM20D1-mediated fat consumption and reduced body weight in mice, suggesting that miR-324-5p may be a novel therapeutic target against obesity.

19.
Glob Chang Biol ; 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31581368

RESUMO

Climate warming has been shown to affect the timing of the onset of breeding of many bird species across the world. However, for multi-brooded species, climate may also affect the timing of the end of the breeding season, and hence also its duration, and these effects may have consequences for fitness. We used 28 years of field data to investigate the links between climate, timing of breeding, and breeding success in a cooperatively breeding passerine, the superb fairy-wren (Malurus cyaneus). This multi-brooded species from southeastern Australia has a long breeding season and high variation in phenology between individuals. By applying a "sliding window" approach, we found that higher minimum temperatures in early spring resulted in an earlier start and a longer duration of breeding, whereas less rainfall and more heatwaves (days > 29°C) in late summer resulted in an earlier end and a shorter duration of breeding. Using a hurdle model analysis, we found that earlier start dates did not predict whether or not females produced any young in a season. However, for successful females who produced at least one young, earlier start dates were associated with higher numbers of young produced in a season. Earlier end dates were associated with a higher probability of producing at least one young, presumably because unsuccessful females kept trying when others had ceased. Despite larger scale trends in climate, climate variables in the windows relevant to this species' phenology did not change across years, and there were no temporal trends in phenology during our study period. Our results illustrate a scenario in which higher temperatures advanced both start and end dates of individuals' breeding seasons, but did not generate an overall temporal shift in breeding times. They also suggest that the complexity of selection pressures on breeding phenology in multi-brooded species may have been underestimated.

20.
Aging (Albany NY) ; 112019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31582588

RESUMO

Endogenous hydrogen sulfide mediates anti-aging benefits of dietary restriction (DR). However, it is unclear how H2S production is regulated by pathways related to DR. Due to the importance of mTORC1 pathway in DR, we investigated the effects of Sch9, a yeast homolog of mammalian S6K1 and a major substrate of mTORC1 on H2S production in yeast Saccharomyces cerevisiae. We found that inhibition of the mTORC1-Sch9 pathway by SCH9 deletion, rapamycin or myriocin treatment resulted in a dramatic decrease in H2S production. Although deficiency of SCH9 did not alter the intracellular level of methionine, the intracellular level of cysteine increased in Δsch9 cells. The expression of CYS3 and CYS4, two transsulfuration pathway genes encoding cystathionine gamma-lyase (CGL) and cystathionine beta-synthase (CBS), were also decreased under mTORC1-Sch9 inhibition. Overexpression of CYS3 or CYS4 in Δsch9 cells or WT cells treated with rapamycin rescued the deficiency of H2S production. Finally, we also observed a reduction in H2S production and lowering of both mRNA and protein levels of CGL and CBS in cultured human cells treated with rapamycin to reduce mTORC1 pathway activity. Thus, our findings reveal a probably conserved mechanism in which H2S production by the transsulfuration pathway is regulated by mTORC1-Sch9 signaling.

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