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1.
Microbiome ; 8(1): 69, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32434586

RESUMO

BACKGROUND: We have proved fecal microbiota transplantation (FMT) is an efficacious remedy to mitigate acute radiation syndrome (ARS); however, the mechanisms remain incompletely characterized. Here, we aimed to tease apart the gut microbiota-produced metabolites, underpin the therapeutic effects of FMT to radiation injuries, and elucidate the underlying molecular mechanisms. RESULTS: FMT elevated the level of microbial-derived indole 3-propionic acid (IPA) in fecal pellets from irradiated mice. IPA replenishment via oral route attenuated hematopoietic system and gastrointestinal (GI) tract injuries intertwined with radiation exposure without precipitating tumor growth in male and female mice. Specifically, IPA-treated mice represented a lower system inflammatory level, recuperative hematogenic organs, catabatic myelosuppression, improved GI function, and epithelial integrity following irradiation. 16S rRNA gene sequencing and subsequent analyses showed that irradiated mice harbored a disordered enteric bacterial pattern, which was preserved after IPA administration. Notably, iTRAQ analysis presented that IPA replenishment retained radiation-reprogrammed protein expression profile in the small intestine. Importantly, shRNA interference and hydrodynamic-based gene delivery assays further validated that pregnane X receptor (PXR)/acyl-CoA-binding protein (ACBP) signaling played pivotal roles in IPA-favored radioprotection in vitro and in vivo. CONCLUSIONS: These evidences highlight that IPA is a key intestinal microbiota metabolite corroborating the therapeutic effects of FMT to radiation toxicity. Owing to the potential pitfalls of FMT, IPA might be employed as a safe and effective succedaneum to fight against accidental or iatrogenic ionizing ARS in clinical settings. Our findings also provide a novel insight into microbiome-based remedies toward radioactive diseases. Video abstract.

2.
J Am Chem Soc ; 2020 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-32453557

RESUMO

The high rate of the 'click-to-release' reaction between allylic substituted trans-cyclooctene linker and a tetrazine activator has enabled exceptional control over chemical and biological processes. Here we report the development of a new bioorthogonal cleavage reaction based on trans-cyclooctene and tetrazine, which allows the use of highly reactive trans-cyclooctenes, leading to 3 orders of magnitude higher click rates compared to the parent reaction, and 4 to 6 orders higher than other cleavage reactions. In this new pyridazine elimination mechanism, wherein the roles a reversed, a trans-cyclooctene activator reacts with a tetrazine linker that is substituted with a methylene-linked carbamate, leading to an 1,4-elimination of the carbamate and liberation of a secondary amine. Through a series of mechanistic studies, we identified the 2,5-dihydropyridazine tautomer as the releasing species and found factors that govern its formation and subsequent fragmentation. The bioorthogonal utility was demonstrated by the selective cleavage of a tetrazine-linked antibody-drug conjugate by trans-cyclooctenes, affording efficient drug liberation in plasma and cell culture. Finally, the parent and the new reaction were compared at low concentration, showing that the use of a highly reactive trans-cyclooctene as activator leads to a complete cycloaddition reaction with antibody-drug conjugate in seconds vs. hours for the parent system. Although the subsequent release from the IEDDA adduct is slower, we believe that this new reaction may allow markedly reduced click-to-release reagent doses in vitro and in vivo and could expand the application scope to conditions wherein the trans-cyclooctene has limited stability.

3.
Int J Biol Macromol ; 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32387598

RESUMO

The manufacture of biofuels from cellulose is regarded as one of practicable strategies to meet increasing energy demand and alleviate environmental issues. Cellulases, which play an important role in the production of second-generation biofuels, are expected to be highly thermostable, halostable and organic solvent-stable to adapt to the harsh conditions in practical application. Here we cloned and characterized a novel cellulase (MaCel) from Mahella australiensis 50-1 BON, an anaerobic thermophile isolated from an oil reservoir. MaCel exhibited excellent thermostability, halostability as well as organic solvent stability, and could be efficiently produced in a yield of 1.7 × 106 U/L in 15 h with inexpensive culture medium. These results indicate that MaCel may be a suitable candidate for industrial applications, illustrating the potential benefits of enzymes from oil reservoir extremophiles in the manufacture of biofuels.

4.
Water Res ; 180: 115813, 2020 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-32438139

RESUMO

In this study, a novel coupling process with partial nitritation-anaerobic ammonium oxidation (anammox) (PNA) and sulfur autotrophic denitrification (SAD) was studied using an upflow biofilm reactor with mechanical vibration. At a lower dissolved oxygen (DO) concentration (0.40 ±â€¯0.20 mg L-1), ammonia could be efficiently removed from synthetic wastewater by the coupling system with a total nitrogen removal efficiency (NRE) of 98% and an influent NH4+-N concentration of 600 mg L-1. In this system, the nitrate, which was produced during the anammox reaction, could be timely reduced by the SAD reaction. Compared with the conventional PNA and SAD processes, coupling the PNA and SAD processes in a single reactor prevented nitrite accumulation in the SAD reaction and reduced the total sulfate production by 59%. The high-throughput sequencing analysis supported that the SAD bacteria (Thiobacillus) and anammox bacteria (Candidatus Kuenenia) could coexist on the elemental sulfur stone. Additionally, sulfur consumption and sulfate production were increased under a high DO concentration. The sulfate production/nitrate reduction ratio and changing profile of the substrate suggested that the short-cut SAD process mainly occurred in this coupling system. Otherwise, batch experiments also suggested that the nitrite removal rate in the anammox process was 34.5 times higher than that in the SAD process. The outcomes of these experiments revealed that most of the nitrite, as an intermediate product in the SAD reaction, served as an electron acceptor for the anammox reaction. A stoichiometric calculation of this coupling process indicated that the novel reaction scheme with a high NRE was successfully achieved. Under an ideal short-cut SAD process, almost 55% of the sulfur consumption could be reduced in this coupling system. The coupling system provides a new perspective for nitrogen removal in a single reactor and further promotes anammox and SAD performance in wastewater treatment processes.

5.
J Agric Food Chem ; 68(21): 5900-5909, 2020 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-32348140

RESUMO

In this study, the effects of white light-emitting diode (LED) and UV-C radiation (with the same intensity) on stilbene biosynthesis and phytochemicals accumulation of peanut sprouts were investigated. Results showed that white light radiation promoted the growth of peanut sprouts while UV-C radiation had the opposite effect. Contents of total phenolics, total flavonoids, and phytochemicals significantly increased in peanut sprouts treated by white light or UV-C radiation. Besides, light radiation significantly induced stilbene accumulation by upregulating the expression of genes and enzymes in stilbene biosynthesis-related pathway, and UV-C was more effective to promote stilbene accumulation. Compared with piceid and piceatannol, resveratrol showed the highest accumulation in peanut sprouts treated by light radiation. In summary, white light or UV-C radiation could be used as a method to promote stilbene biosynthesis and phytochemicals accumulation in peanut sprouts and UV-C was more effective.

6.
J Affect Disord ; 270: 118-123, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32339101

RESUMO

BACKGROUND: It has been demonstrated that a reduction in the amount of high-frequency cardiopulmonary coupling (CPC) is indicative of unstable sleep in unmedicated patients with major depressive disorder (MDD). Considering the close relationship between sleep quality and memory consolidation, this study sought to investigate the potential of high-frequency CPC as a novel biomarker for objective evaluation of memory impairment in MDD. METHODS: A total of 64 depressed patients and 35 healthy controls were included in this cross-sectional study. High-frequency coupling (HFC) was assessed by electrocardiogram-based CPC analysis using a portable sleep-respiration monitor during sleep for one night. The next day, subjects completed the cognition assessment with the Assessment of Neuropsychological Status (RBANS). The 17-Item Hamilton Depression Rating Scale (HAMD17) and the Hamilton Rating Scales for Anxiety (HAMA) were used to evaluate the severity of depression and anxiety in each patient, respectively. RESULTS: There was no significant difference in the proportion of HFC between depressed patients and healthy controls. In patients with low HFC proportion (<35%), severe anxiety could significantly decrease HFC proportion. The HFC proportion positively correlated with immediate and delayed memory in depressed patients. Further analysis showed that patients with low HFC proportion may have worse delayed memory. LIMITATIONS: The lack of prior exposure to the monitoring equipment and procedure could have generated artefacts that would have disappeared after habituation. CONCLUSIONS: These results support a positive correlation between the HFC proportion and memory in depressed patients. Further research is required to explore the clinical implications of these findings.

7.
Molecules ; 25(5)2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32155919

RESUMO

Quantitative analysis of formaldehyde (HCHO, FA), especially at low levels, in various environmental media is of great importance for assessing related environmental and human health risks. A highly efficient and convenient FA detection method based on surface-enhanced Raman spectroscopy (SERS) technology has been developed. This SERS-based method employs a reusable and soft silver-coated TiO2 nanotube array (TNA) material, such as an SERS substrate, which can be used as both a sensing platform and a degradation platform. The Ag-coated TNA exhibits superior detection sensitivity with high reproducibility and stability compared with other SERS substrates. The detection of FA is achieved using the well-known redox reaction of FA with 4-amino-3-hydrazino-5-mercapto-1,2,4-triazole (AHMT) at room temperature. The limit of detection (LOD) for FA is 1.21 × 10-7 M. In addition, the stable catalytic performance of the array allows the degradation and cleaning of the AHMT-FA products adsorbed on the array surface under ultraviolet irradiation, making this material recyclable. This SERS platform displays a real-time monitoring platform that combines the detection and degradation of FA.

8.
J Med Chem ; 63(6): 3028-3046, 2020 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-32069401

RESUMO

PI3K-Akt-mTOR signaling pathway has been validated as an effective targeting pathway for cancer therapy. However, no PI3K/mTOR dual inhibitor has been approved by the FDA yet. Therefore, it is still essential to discover a candidate with good efficacy and low toxicity. In our design, a series of imidazo[1,2-a]pyridine derivatives had been synthesized and subjected to activity assessment in vitro and in vivo. 15a was proved to be a potent PI3K/mTOR dual inhibitor with excellent kinase selectivity, modest plasma clearance, and acceptable oral bioavailability. Besides, 15a displayed significant inhibition of tumor growth in HCT116 and HT-29 xenografts without obvious effect on body weight.

9.
Environ Sci Technol ; 54(6): 3129-3137, 2020 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-32092257

RESUMO

Aerosol liquid water content (ALWC) plays fundamental roles in atmospheric radiation and chemical processes. However, there is little information about ALWC vertical distribution due to the lack of sufficient measurement. In this study, a novel method to retrieve ALWC using a polarization lidar is proposed. By analyzing lidar measurement combined with in situ chemical composition measurements at the surface, the particle linear depolarization ratio δp is found to be well correlated with the liquid water mass fraction. The method is built upon a valid relationship between δp and the ratio of ALWC to the particle backscatter coefficient. ALWC can be retrieved with a relative error of 30% with this method. A case study shows that the ALWC in upper levels of the boundary layer may be different from that at the ground, suggesting the importance of measuring ALWC vertical profiles during haze episodes. The study proves that polarization lidars have the potential to retrieve vertical distributions of ALWC which will benefit studies on haze formation.


Assuntos
Monitoramento Ambiental , Água , Aerossóis
10.
Pain Physician ; 23(1): E31-E40, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-32013286

RESUMO

BACKGROUND: Although percutaneous vertebroplasty (PVP) can effectively relieve the pain for patients with acute osteoporotic vertebral compression fractures (OVCFs), many patients still complain of mild back pain in the early postoperative period. OBJECTIVES: The aim of this study was to assess the effect of early limited activity (LA) on prognosis after bipedicular small-cement-volume (i.e., PVP) to treat single-segment acute OVCFs. STUDY DESIGN: A prospective study and retrospective observations were performed on 125 patients with a minimum of 1 year of follow-up. SETTING: A university hospital orthopedics and pathology departments. METHODS: All patients were allocated into an LA group (n = 64) and an unlimited activity group (ULA group, n = 61). Patients in the LA group were suggested to keep time of off-bed activity < 4 hours per day in the first 3 weeks postoperatively. Patients in the ULA group did not limit activity. The demographic, clinical, and radiologic outcomes were assessed, such as pain intensity Numeric Rating Scale (NRS-11) and vertebral height ratio (i.e., fractured vertebral height/adjacent nonfractured vertebral height). Based on outcomes following surgery, all patients were classified as responders (NRS-11 score 1-day postoperation < 50% of preoperative NRS-11 score) or low responders (NRS-11 score 1-day postoperation >= 50% of preoperative NRS-11 score). RESULTS: The demographic results and complications were similar. In the LA group, NRS-11 scores at 1 and 3 months postoperation respectively were 2.23 ± 0.42 and 1.46 ± 0.40, and corresponding scores respectively were 2.85 ± 0.80 and 1.73 ± 0.77 in the ULA group, and there was a difference in the 2 groups in both time points (P < 0.05). At 12 months postoperation, anterior and middle vertebral height ratio respectively were 78.42% ± 3.52% and 82.37% ± 3.49% in the LA group, which were higher than 76.87% ± 3.68% and 81.10% ± 3.31% in the ULA group (P < 0.05). Thirty-two cases were low responders. Among those, NRS-11 scores at 1 and 3 months postoperation respectively were 2.29 ± 0.45 and 1.53 ± 0.46 in the LA group, which were lower than 3.67 ± 0.80 and 2.56 ± 0.79 in the ULA group (P < 0.05), and at 12 months postoperation, anterior vertebral height ratio was 79.81% ± 3.25% in the LA group and 75.60% ± 3.50% in the ULA group (P < 0.05). LIMITATIONS: First, some patients lacked the results of bone mineral density during follow-up; second, the limited time in our study was chosen from our previous working experience, which may lack an objective basis; third, NRS-11 is solely used as an indicator of clinical outcomes in our study; finally, our next studies can increase the sample size to improve the clinically difference. CONCLUSIONS: LA in the early period after PVP can help patients achieve more pain relief postoperatively and maintain better vertebral shape, especially for low responders. KEY WORDS: Osteoporotic vertebral compression fractures, percutaneous vertebroplasty, Numeric Rating Scale, vertebral height, responders, low responders, limited activity, complications.

11.
Sci Total Environ ; 717: 137285, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32092811

RESUMO

Exposure to air pollution is one of the major risk factors contributing to the occurrence and development of chronic obstructive pulmonary disease (COPD). However, few studies have investigated the susceptibility of patients with COPD to air pollution. Here, we provided a study protocol. A panel study of a total of 480 samples to compare the response to air pollution exposure between 60 patients with COPD and 60 healthy control subjects has been performed in Beijing (the COPDB study) since May 2016. The health assessment and exposure evaluation methods used in this COPDB study are summarized here. Throat, exhaled breath and condensate, urine, serum, plasma, and blood samples, as well as cardiopulmonary function indexes were repeatedly collected over four visits. Indicators of inflammation, oxidative stress, infection, metabolic changes, and genetic differences were then analyzed. Personal and ambient levels of fine particles and their components, as well as gaseous pollutants were monitored during the follow-up period. Linear mixed-effects models were used to evaluate the associations between changes in biomarkers and exposure to air pollution in both patients with COPD and healthy control subjects. Based on the COPDB study, the susceptibility of COPD patients and underlying mechanisms, involving difference in inflammatory, infection, metabolic, and genetic response to different air pollutants, were investigated. Our preliminary result shows that air pollution-associated changes in heart rate were higher in COPD patients than the healthy controls. More investigations of the underlying mechanisms of the susceptibility are ongoing. This study has been registered in ChiCTR with the number of ChiCTR1900023692.


Assuntos
Poluição do Ar , Doença Pulmonar Obstrutiva Crônica , Poluentes Atmosféricos , Pequim , Estudos de Casos e Controles , China , Humanos , Material Particulado
13.
J Cell Physiol ; 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32067230

RESUMO

Numerous studies have suggested that urothelial cancer-associated 1 (UCA1) acts as a suppressor gene affecting cell proliferation and migration. However, the biological role and the potential mechanism of UCA1 in the progression of pre-eclampsia (PE) remains unclear. The UCA1 level was markedly upregulated in PE pregnancies relative to non-PE ones in GSE75010 and tissues. A higher body mass index (BMI), maximum systolic blood pressure (BP), and maximum diastolic BP were observed in PE pregnancies, whereas the newborn weight z-score was lower compared with those of non-PE pregnancies. Knockdown of UCA1 accelerated the proliferative migratory abilities and cell cycle progression, but inhibited apoptosis of HTR-8/SVneo and JAR cells. Then, we found that Janus kinases 2 (JAK2) was negatively correlated with UCA1. In addition, JAK2 was downregulated in the placenta of PE pregnancies and was negatively regulated by UCA1. UCA1 was mainly enriched in the nucleus. Knockdown of UCA1 reduced the occupancies of the enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) and H3K27me3 on the Janus kinase 2 (JAK2) promoter regions. Finally, rescue experiments found that transfection of short-hairpin JAK2 attenuated proliferative and migratory abilities of trophoblasts, which were partially reversed after UCA1 knockdown. In short, UCA1 is upregulated in the trophocytes of PE pregnancies and accelerates trophoblast cell invasion and proliferation by downregulating JAK2.

14.
Environ Int ; 136: 105475, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32007923

RESUMO

Fine particulate matter (PM2.5) poses a significant risk to human health worldwide, by promoting oxidative stress and inflammation; however, the components responsible for these effects have not been fully evaluated. In this study, we investigated the cellular response of a macrophage cell line exposed to PM2.5 extracts in vitro. We obtained a dataset of chemical components of PM2.5 and determined those associated with the generation of reactive oxygen species (ROS) and secretion of inflammatory cytokines through an orthogonal partial least-squares (OPLS) regression. The results indicated that after water extracts exposure, both ROS and interleukin (IL)-1ß levels were positively correlated with transition metals. In cells exposed to dichloromethane extracts, IL-1ß secretion was significantly correlated with polycyclic aromatic hydrocarbons (PAHs); meanwhile, tumor necrosis factor (TNF)-α secretion was negatively associated with secondary nitrated PAHs, suggesting that atmospheric nitration process might modify the biological effects of PM2.5 components. We also performed source apportionment using a positive matrix factorization (PMF) model to explore the relative influence of different sources of components on cells. It was found that components from vehicle emissions promoted both ROS and TNF-α, while IL-1ß secretion was induced mainly by those from coal combustion. This study provides information regarding PM2.5 components having biological effects, and the sources thereof, which could inform effective measures for controlling this type of air pollution.

15.
Elife ; 92020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31913118

RESUMO

Inner ear cochlear spiral ganglion neurons (SGNs) transmit sound information to the brainstem. Recent single cell RNA-Seq studies have revealed heterogeneities within SGNs. Nonetheless, much remains unknown about the transcriptome of SGNs, especially which genes are specifically expressed in SGNs. To address these questions, we needed a deeper and broader gene coverage than that in previous studies. We performed bulk RNA-Seq on mouse SGNs at five ages, and on two reference cell types (hair cells and glia). Their transcriptome comparison identified genes previously unknown to be specifically expressed in SGNs. To validate our dataset and provide useful genetic tools for this research field, we generated two knockin mouse strains: Scrt2-P2A-tdTomato and Celf4-3xHA-P2A-iCreER-T2A-EGFP. Our comprehensive analysis confirmed the SGN-selective expression of the candidate genes, testifying to the quality of our transcriptome data. These two mouse strains can be used to temporally label SGNs or to sort them.

16.
Acta Diabetol ; 57(6): 673-679, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31938886

RESUMO

AIMS: To investigate the correlation of impairment in skeletal muscle and heart in spontaneous type 2 diabetes mellitus (T2DM) rhesus monkeys using magnetic resonance image (MRI). METHODS: Fifteen T2DM monkeys and fourteen healthy control (HC) monkeys were included. The microcirculation of skeletal muscle [skeletal muscle blood flow (SMBF), skeletal muscle oxygen extraction fraction (SMOEF)] and the function and strain of heart were evaluated by MRI. Three regions of interests were chosen on the soleus muscle (SOL), gastrocnemius muscle (GAS) and tibialis anterior muscle (TA) for image analysis. RESULTS: Eight T2DM monkeys and eight HC monkeys were obtained the full data. The SMBF reserves and SMOEF reserves were found significantly decreased in T2DM during inflation in SOL, GAS and TA muscles (all p < 0.05), and the SMBF reserves decreased during hyperemia in GAS and TA muscles (all p < 0.05). In these monkeys, the global peak longitudinal strain (longitudinal PS), peak systolic longitudinal strain rate (longitudinal PSSR) and peak diastolic longitudinal strain rate (longitudinal PDSR) were seen significantly different in T2DM compared to HC monkeys (all p < 0.05). The longitudinal PSSR was found negatively correlated with SMBF reserves in SOL, GAS and TA during inflation in all monkeys. CONCLUSIONS: The impaired microcirculation of skeletal muscle and the myocardial deformation were found in T2DM monkeys with normal ejection fraction. And a negative correlation was existed in the longitudinal PSSR and the SMBF reserves.

17.
ACS Appl Mater Interfaces ; 12(3): 3580-3591, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31889436

RESUMO

Graphene oxide (GO) is commonly used in photocatalytic reactions but mainly as a cocatalyst. Limited information is available on the intrinsic ability of GO to photocatalytically reduce CO2 as a sole photocatalyst and the activation of light irradiation. In this study, simulated sunlight (SS) and UV-irradiated GO (GOSS and GOUV, respectively) showed enhanced efficiency of photocatalytic reduction of CO2 compared to pristine GO, with a CO yield (4 h) ratio of GOSS/GOUV/GO of 2.7:2.1:1. Here, irradiation plays two important roles: (1) irradiating GO to eliminate CO released under photolysis from photocatalytic reactions and (2) activating GO to create defects and restore the large π-conjugated network, obtaining photolysis-saturated and photoactivated GO for photocatalytic reduction of CO2. The increasing defect density and π conjugation of irradiated GO, as supported by X-ray photoelectron and Raman spectroscopy, improve the yield of photoelectrons and prolong the lifetime of photogenerated charge carriers, as supported by electron spin resonance and transient absorption spectroscopy. This results in an enhanced photocatalytic efficiency of irradiated GO. The higher CO yield of GOSS compared to GOUV indicates that simulated sunlight irradiation is more favorable for GO activation. Our results show that activating GO under irradiation enhances the photocatalytic reduction of CO2.

18.
J Biomol Struct Dyn ; 38(4): 985-996, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30843759

RESUMO

CDK2 can be used as an attractive target for development of efficient inhibitors curing multiple disease relating with CDK2. In this work, molecular dynamics (MD) simulations and binding free energy calculations were coupled to probe conformational changes of CDK2 due to inhibitor associations and binding mechanisms of inhibitors PM1, FMD and X64 to CDK2. The results suggest that the binding strength of FMD and X64 to CDK2 is stronger than that of PM1. Principal component (PC) analysis and cross-correlation map calculations based on the equilibrated MD trajectories demonstrate that the structural difference in inhibitors exerts important impact on motion modes and dynamics behavior of CDK2. Residue-based free energy decomposition method was adopted to estimate the inhibitor-residue spectrum. The results not only efficiently identify the hot interaction spot of inhibitors with CDK2 but also show that the hydrophobic rings R1, R2 and R3 as well as polar groups of three inhibitors play key roles in favorably binding of inhibitors to CDK2. This work is expected to contribute energetic basis and dynamics information to development of promising inhibitors toward CDK2.Communicated by Ramaswamy H. Sarma.

19.
J Cell Physiol ; 235(4): 3939-3949, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31595977

RESUMO

Ovarian cancer (OC) is a highly prevalent gynecologic malignancy and its mortality is extremely high. Therefore, the development of novel therapeutic approaches for OC is of great significance. In this study, LINC01342 was upregulated in OC tissue in the GSE38666 microarray and in tumor tissue samples collected in our center. The silencing of LINC01342 suppressed the proliferative and metastatic capacities of A2780 and HO8910 cells. Subcellular distribution assays showed that LINC01342 was mainly enriched in the cytoplasm. Subsequently, the downregulation of microRNA-30c-2-3p was proven to be the target of LINC01342. The silencing of microRNA-30c-2-3p enhanced the clonality and migratory capacity of OC cells. Moreover, the silencing of microRNA-30c-2-3p could reverse the inhibited migration and clonality in OC cells caused by LINC01342 knockdown. In addition, hypoxia-inducible factor 3 subunit α (HIF3A) was proven to be the target gene of microRNA-30c-2-3p, which was upregulated. HIF3A was negatively regulated by microRNA-30c-2-3p but positively regulated by LINC01342 in OC cells. An RNA binding protein immunoprecipitation assay showed that microRNA-30c-2-3p, LINC01342, and HIF3A could bind to argonaute RISC catalytic component 2. The overexpression of HIF3A reversed the inhibited migration and clonality in OC cells with LINC01342 knockdown. By analyzing the follow-up data from the enrolled OC patients, the LINC01342 and HIF3A levels were negatively correlated with prognosis, while the microRNA-30c-2-3p level was positively correlated with the same. In short, the upregulated LINC01342 in OC absorbs microRNA-30c-2-3p to release HIF3A. Thus, upregulated HIF3A expression accelerates the progression of OC.

20.
Environ Pollut ; 256: 113401, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31753639

RESUMO

This study reveals the impact of biomass burning (BB) on secondary organic aerosols (SOA) formation in the North China Plain (NCP). Filter samples were analyzed for secondary inorganic aerosols (SIA), oxalic acid (C2) and related aqueous-phase SOA compounds (aqSOA), stable carbon isotope composition of C2 (δ13C(C2)) and aerosol liquid water content (ALWC). Based on the PM2.5 loadings, BB tracer concentrations, wildfire spots and air-mass back trajectories, we distinguished two episodes from the whole campaign, Episode I and Episode II, which were characteristic of regional and local BB, respectively. The abundances of PM2.5 and organic matter in the two events were comparable, but concentrations and fractions of SIA, aqSOA during Episode I were much higher than those during Episode II, along with heavier δ13C(C2), suggesting an enhanced aqSOA formation in the earlier period. We found that the enhancement of aqSOA formation during Episode I was caused by an increased ALWC, which was mainly driven by SIA during the regional BB event. Our work showed that intensive burning of crop residue in East Asia can sharply enhance aqSOA production on a large scale, which may have a significant impact on the regional climate and human health.


Assuntos
Aerossóis/análise , Poluentes Atmosféricos/análise , Monitoramento Ambiental , Biomassa , Carbono/análise , Isótopos de Carbono/análise , China , Clima , Extremo Oriente , Compostos Orgânicos/análise , Material Particulado/análise , Estações do Ano , Água , Incêndios Florestais
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