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1.
Materials (Basel) ; 14(7)2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33807483

RESUMO

Three novel organic dyes (D6, D7 and D8), based on indolo[3,2-b]carbazole as the donor and different types of electron-withdrawing groups as the acceptors, were synthesized and successfully applied in dye-sensitized solar cells (DSSCs). Their molecular structures were fully characterized by 1H NMR, 13C NMR and mass spectroscopy. The density functional theory (DFT) calculations, electrochemical impedance spectroscopy analysis, UV-Vis absorption characterization and tests of the solar cells were used to investigate the photophysical/electrochemical properties as well as DSSCs' performances based on the dyes. Dye D8 showed the broadest light-response range (300-770 nm) in the incident monochromatic photo-to-electron conversion efficiency (IPCE) curve, due to its narrow bandgap (1.95 eV). However, dye D6 exhibited the best device performance among the three dyes, with power conversion efficiency of 5.41%, Jsc of 12.55 mA cm-2, Voc of 745 mV and fill factor (FF) of 0.59. We also found that dye aggregation was efficiently suppressed by the introduction of alkylated indolo[3,2-b]carbazole, and, hence, better power conversion efficiencies were observed for all the three dyes, compared to the devices of co-sensitization with chenodeoxycholic acid (CDCA). It was unnecessary to add adsorbents to suppress the dye aggregation.

2.
Molecules ; 26(7)2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33807380

RESUMO

Preparation and characterization of microemulsions consisting of a plant-derived alkyl polyglycoside (APG) surfactant and the essential oil of Melaleuca alternifolia (tea tree) was studied. This nonionic APG surfactant used was Triton CG-110 with a CMC at 1748 ppm at 25 °C. Tea tree oil (TTO) was extracted from tea tree leaves by Triton CG-110-assisted hydrodistillation method. The preparation of the microemulsion was aided by the construction of pseudo-ternary phase diagrams, which were investigated at the different weight ratios of surfactant mixtures (Smix = Triton CG-110/PPG) as 0.6:1, 1.8:1, 1:0 with hydrodistilled and commercial TTO by water titration method at room temperature. Particularly, structure of microemulsion was identified by electrical conductivity and viscosity. Moreover, shelf stability of some microemulsion made of 1% TTO with various concentration of Triton CG-110/PPG (1.8:1 w/w) were monitored for over a two-month period with dynamic light scattering. These results showed that microemulsion made of 1% TTO, 9% Triton CG-110/PPG (1.8:1 w/w) was insensitive with time and temperature of storage.

3.
Environ Sci Technol ; 2021 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-33818073

RESUMO

Coal and coal gangue spontaneous combustion (CGSC) occurs globally, causing significant environmental pollution. However, its emissions are poorly quantified and are overlooked in global or regional air pollutant emission inventories in previous studies, resulting in the underestimation of its impacts on climate, environment, and public health. This study quantified the emissions of various air pollutants originating from CGSC in Wuhai, a city in China, investigated emission characteristics, and estimated the contribution of CGSC emissions to fine particulate matter (PM2.5) air pollution and related health impacts on a regional scale. The results revealed that the CGSC-related PM2.5 emissions were approximately 4643 t a-1 (95% confidence interval (95% CI): 721; 10447), accounting for 26.3% of the total PM2.5 emissions. Alkanes, alkenes, and aromatics accounted for 69.4, 17.9, and 2.9%, respectively, of the total emissions of volatile organic compounds (VOCs). Due to CGSC emissions, the ambient PM2.5 concentration in Wuhai increased by 5.7 µg m-3 on average, while the nitrate concentration decreased. The number of premature deaths caused by exposure to ambient PM2.5 associated with CGSC reached 381 (95% CI: 290; 452) in Wuhai and surrounding cities in 2017. Urgent control strategies and engineering techniques are needed to mitigate CGSC to protect public health.

4.
BMJ Open Gastroenterol ; 8(1)2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33648983

RESUMO

OBJECTIVES: The primary aim is to provide a summary of evidence for the diagnostic accuracies of multiplex PCR gastrointestinal (GI) panels-BioFire FilmArray and Luminex xTAG on the detection of gastroenteritis pathogens. The secondary aim is to compare the performance of these GI panels head to head. METHODS: A comprehensive search up to 1 December 2019 was conducted on PubMed, Embase, Ovid Medline and Web of Science for studies that used FilmArray or Luminex xTAG Gastrointestinal Pathogen Panel (GPP) for diagnosis of acute gastroenteritis. A summary of diagnostic accuracies for the 16 pathogens were calculated by comparing the GI panels to the current gold standards (conventional standard microbiology techniques such as culture or PCR for bacteria, PCR or enzyme immunoassay (EIA) for viruses, microscopy or EIA for parasite). Hierarchical summary receiver operating characteristic (HSROC) curve analysis, pretest and post-test probabilities were used for estimating the pathogen detection performance. RESULTS: A total of 11 studies with 7085 stool samples were eligible for analysis. Multiplex PCRs demonstrated high diagnostic accuracy, with specificity ≧0.98 and area under the ROC curve (AUROC) ≧0.97 for all the pathogens except for Yersinia enterocolitica (AUROC 0.91). The FilmArray panel demonstrated a higher sensitivity than xTAG GPP for most of the pathogens with the exception of Rotavirus A (xTAG GPP and FilmArray were both 0.93). CONCLUSIONS: This is the first meta-analysis that is a head-to-head comparison examining the performance of the novel multiplex PCR-based tests Luminex xTAG GPP and FilmArray GI panel in detecting each pathogen. Point estimates calculated from eligible studies showed that both GI panels are highly accurate and may provide important diagnostic information for early identification of gastroenteritis. In addition, although FilmArray has higher sensitivity and post-test probability than xTAG GPP for most of the pathogens, how this will translate to a clinical setting remains unclear.

5.
Front Med ; 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33754282

RESUMO

t(8;21)(q22;q22) acute myeloid leukemia (AML) is a highly heterogeneous hematological malignancy with a high relapse rate in China. Two leukemic myeloblast populations (CD34+CD117dim and CD34+CD117bri) were previously identified in t(8;21) AML, and CD34+CD117dim cell proportion was determined as an independent factor for this disease outcome. Here, we examined the impact of CD34+CD117dim/CD34+CD117bri myeloblast-associated gene expression on t(8;21) AML clinical prognosis. In this study, 85 patients with t(8;21) AML were enrolled. The mRNA expression levels of CD34+CD117dim-associated genes (LGALS1, EMP3, and CRIP1) and CD34+CD117bri-associated genes (TRH, PLAC8, and IGLL1) were measured using quantitative reverse transcription PCR. Associations between gene expression and clinical outcomes were determined using Cox regression models. Results showed that patients with high LGALS1, EMP3, or CRIP1 expression had significantly inferior overall survival (OS), whereas those with high TRH or PLAC8 expression showed relatively favorable prognosis. Univariate analysis revealed that CD19, CD34+CD117dim proportion, KIT mutation, minimal residual disease (MRD), and expression levels of LGALS1, EMP3, CRIP1, TRH and PLAC8 were associated with OS. Multivariate analysis indicated that KIT mutation, MRD and CRIP1 and TRH expression levels were independent prognostic variables for OS. Identifying the clinical relevance of CD34+CD117dim/CD34+CD117bri myeloblast-associated gene expression may provide new clinically prognostic markers for t(8;21) AML.

6.
Oncogene ; 2021 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-33714984

RESUMO

Emerging evidence has demonstrated that circular RNAs (circRNAs) play critical roles in the development and progression of human cancer. However, the biological functions and underlying mechanisms of circRNAs in triple-negative breast cancer (TNBC) remain to be investigated. In our present study, we found that the novel circRNA circHIF1A was significantly overexpressed in breast cancer tissues and that it was associated with metastasis, poor prognosis, and the TNBC subtype. Gain- and loss-of-function experiments were conducted to investigate the biological roles of circHIF1A in TNBC. Overexpression of circHIF1A significantly promoted TNBC growth and metastasis in vitro and in vivo, while knockdown of circHIF1A exerted the opposite effects. Mechanistically, circHIF1A modulated the expression and translocation of NFIB through posttranscriptional and posttranslational modifications, resulting in the activation of the AKT/STAT3 signaling pathway and inhibition of P21. The RNA binding protein FUS could regulate the biogenesis of circHIF1A by interacting with the flanking intron, and FUS was transcriptionally regulated by NFIB, thus forming the circHIF1A/NFIB/FUS positive feedback loop. Moreover, circHIF1A could be packaged into exosomes and was upregulated in the plasma of breast cancer patients. Our findings indicated that circHIF1A played a critical role in the growth and metastasis of TNBC via a positive feedback loop and that circHIF1A could be a promising biomarker for breast cancer diagnosis and a potential therapeutic target for TNBC treatment.

7.
Apoptosis ; 2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33779882

RESUMO

Accumulated evidence has demonstrated that miRNAs are closely implicated in lung carcinogenesis. Herein, we explored the expression pattern of miR-30b-5p in lung cancer, and aimed to uncover miR-30b-5p roles in lung cancer progression and drug resistance. miR-30b-5p expression profiles in lung cancer tissues and the matched non-tumor tissues were determined by using qPCR. Cell viability, migration, invasion and in vivo tumorigenesis were determined by using the CCK-8, colony formation, wound healing, transwell chambers experiments and tumor xenograft models. RNA immunoprecipitation (RIP) and dual luciferase reporter experiments were applied to evaluate the relationship between miR-30b-5p and LRP8. The results demonstrated that miR-30b-5p showed a low expression profile in lung cancer tissues and cells, and closely linked to poor prognosis and malignant clinical process. Cell viability, migration, invasiveness and tumorigenesis were significantly weakened following miR-30b-5p overexpression in A549 and NCI-H1299 cells, while cell apoptosis rates were increased. In addition, miR-30b-5p was lowly expressed in A549/DDP (a cisplatin drug resistant cell line) as compared with A549 cells, and miR-30b-5p increased A549/DDP cell sensitivity to DDP. However, these above roles of miR-30b-5p were all significantly impaired following the overexpression of LRP8 which was overexpressed in lung cancer tissues. Collectively, this study demonstrated that miR-30b-5p functions as a tumor suppressor in lung cancer, and re-sensitizes lung cancer cells to DDP by targeting LRP8.

8.
Commun Biol ; 4(1): 280, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33664385

RESUMO

Irinotecan inhibits cell proliferation and thus is used for the primary treatment of colorectal cancer. Metabolism of irinotecan involves incorporation of ß-glucuronic acid to facilitate excretion. During transit of the glucuronidated product through the gastrointestinal tract, an induced upregulation of gut microbial ß-glucuronidase (GUS) activity may cause severe diarrhea and thus force many patients to stop treatment. We herein report the development of uronic isofagomine (UIFG) derivatives that act as general, potent inhibitors of bacterial GUSs, especially those of Escherichia coli and Clostridium perfringens. The best inhibitor, C6-nonyl UIFG, is 23,300-fold more selective for E. coli GUS than for human GUS (Ki = 0.0045 and 105 µM, respectively). Structural evidence indicated that the loss of coordinated water molecules, with the consequent increase in entropy, contributes to the high affinity and selectivity for bacterial GUSs. The inhibitors also effectively reduced irinotecan-induced diarrhea in mice without damaging intestinal epithelial cells.

9.
BMC Neurol ; 21(1): 109, 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33750325

RESUMO

BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD), a group of autoimmune neurological diseases, involve the optic nerve, spinal cord, and brain. Meningitis is rarely reported as the primary clinical manifestation of both anti-aquaporin-4 (AQP4)/ anti-myelin oligodendrocyte glycoprotein (MOG) antibody-negative NMOSD (NMOSDneg). CASE PRESENTATION: A 30-year-old man initially presented with fever, headache, and neck stiffness. Lumbar puncture revealed mixed cell reaction and decreased glucose levels. As a result, tuberculous meningitis was suspected. After 1 month, the patient developed longitudinally extensive transverse myelitis and area postrema syndrome. This was followed by the presentation of meningitis-like symptoms once again in the third attack, but his condition eventually improved after corticosteroid treatment without relapse for 2 years. However, he was readmitted to our hospital owing to symptoms of diplopia, hiccup, and numbness in the right hand. Brain magnetic resonance imaging (MRI) revealed that the area postrema still contained lesions. Spinal MRI revealed several segmental enhancements at the C4-C5, T1, and T5 levels. Anti-AQP4 and anti-MOG antibodies were persistently absent in the serum and cerebrospinal fluid (CSF). The patient was finally diagnosed with NMOSDneg. CONCLUSIONS: Meningitis could be a recurrent manifestation of NMOSDneg and requires more careful evaluation.

10.
Sci China Life Sci ; 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33772745

RESUMO

Nestin is expressed extensively in neural stem/progenitor cells during neural development, but its expression is mainly restricted to the ependymal cells in the adult spinal cord. After spinal cord injury (SCI), Nestin expression is reactivated and Nestin-positive (Nestin+) cells aggregate at the injury site. However, the derivation of Nestin+ cells is not clearly defined. Here, we found that Nestin expression was substantially increased in the lesion edge and lesion core after SCI. Using a tamoxifen inducible CreER(T2)-loxP system, we verified that ependymal cells contribute few Nestin+ cells either to the lesion core or the lesion edge after SCI. In the lesion edge, GFAP+ astrocytes were the main cell type that expressed Nestin; they then formed an astrocyte scar. In the lesion core, Nestin+ cells expressed αSMA or Desmin, indicating that they might be derived from pericytes. Our results reveal that Nestin+ cells in the lesion core and edge came from various cell types and rarely from ependymal cells after complete transected SCI, which may provide new insights into SCI repair.

12.
Stem Cells ; 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33657255

RESUMO

Spinal cord injury (SCI) typically results in long-lasting functional deficits, largely due to primary and secondary white matter damage at the site of injury. The transplantation of neural stem cells (NSCs) has shown promise for re-establishing communications between separated regions of the spinal cord through the insertion of new neurons between the injured axons and target neurons. However, the inhibitory microenvironment that develops after SCI often causes endogenous and transplanted NSCs to differentiate into glial cells rather than neurons. Functional biomaterials have been shown to mitigate the effects of the adverse SCI microenvironment and promote the neuronal differentiation of NSCs. A clear understanding of the mechanisms of neuronal differentiation within the injury-induced microenvironment would likely allow for the development of treatment strategies designed to promote the innate ability of NSCs to differentiate into neurons. The increased differentiation of neurons may contribute to relay formation, facilitating functional recovery after SCI. In this review, we summarize current strategies used to enhance the neuronal differentiation of NSCs through the reconstruction of the SCI microenvironment and to improve the intrinsic neuronal differentiation abilities of NSCs, which is significant for SCI repair.

13.
Food Chem ; 353: 129474, 2021 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-33740509

RESUMO

This study aims to determine toxic compounds polycyclic aromatic hydrocarbons (PAHs) and cholesterol oxidation products (COPs) in thin slices of dried pork as affected by different flavorings and roasting temperature treatments through employing a QuEChERS method coupled with gas chromatograph-tandem mass spectrometer (GC-MS/MS) and gas chromatograph-mass spectrometer (GC-MS), respectively. By employing this method, high accuracy and precision was attained for freeze-dried pork hind leg sample. Following addition of 8 different flavorings with roasting temperature at 120, 160, and 200 °C, the levels of total COPs and PAHs in thin slices of dried pork followed a temperature-dependent increase during roasting, which was further confirmed by principle component analysis. High level of soy sauce or sugar inhibited COP formation, while the low-level minimized PAH formation in thin slices of dried pork during roasting. Sugar was more effective in inhibiting COP formation while soy sauce was more efficient in reducing PAH formation.

14.
Theranostics ; 11(8): 3932-3947, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33664871

RESUMO

The tumor microenvironment contributes to tumor progression and metastasis. Cancer-associated fibroblasts (CAFs) form a major cellular component of the tumor microenvironment. In this study, we further explored the mechanisms underlying the tumor-promoting roles of CAFs. Methods: Patient-derived CAFs and normal fibroblasts (NFs) were isolated from breast carcinomas and adjacent normal breast tissue. Exosomes were isolated by ultracentrifugation and CAF-derived exosomal microRNAs were screened using next-generation sequencing technology. MiR-500a-5p expression was assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and in situ hybridization; Tumor cell proliferation was determined by MTT assays and three-dimensioned (3D) cultures, and tumor metastasis was determined by Transwell assays in vitro. In vivo assays were performed in a nude mouse subcutaneous xenograft model. Results: We confirmed that CAF-derived exosomes significantly promoted the proliferation and metastasis of breast cancer cells. MiR-500a-5p was highly expressed in MDA-MB-231 and MCF7 cells treated with CAF-derived exosomes. The upregulation of miR-500a-5p was also confirmed in CAFs and CAF-derived exosomes. MiR-500a-5p was transferred from CAFs to the cancer cells, and subsequently promoted proliferation and metastasis by binding to ubiquitin-specific peptidase 28 (USP28). Conclusions: The present study demonstrates that CAFs promote breast cancer progression and metastasis via exosomal miR-500a-5p and indicate that inhibiting CAF-derived miR-500a-5p is an alternative modality for the treatment of breast cancer.

15.
Artigo em Inglês | MEDLINE | ID: mdl-33686389

RESUMO

AIMS: In order to determine acute cardiac involvement in patients with COVID-19, we quantitatively evaluated tissue characteristics and mechanics by non-invasive cardiac magnetic resonance (CMR) in a cohort of patients within the first 10 days of the onset of COVID symptoms. METHODS AND RESULTS: Twenty-five patients with reverse transcription polymerase chain reaction confirmed COVID-19 and at least one marker of cardiac involvement [cardiac symptoms, abnormal electrocardiograph (ECG), or abnormal cardiac biomarkers] and 25 healthy age- and gender-matched control subjects were recruited to the study. Patients were divided into those with elevated (n = 8) or normal TnI (n = 17). There were significant differences in global longitudinal strain among patients who were positive and negative for hs-TnI, and controls [-12.3 (-13.3, -11.5)%, -13.1 (-14.2, -9.8)%, and -15.7 (-18.3, -12.7)%, P = 0.004]. Native myocardial T1 relaxation times in patients with positive and negative hs-TnI manifestation (1169.8 ± 12.9 and 1113.2 ± 31.2 ms) were significantly higher than the normal (1065 ± 57 ms) subjects, respectively (P < 0.001). The extracellular volume (ECV) of patients who were positive and negative for hs-TnI was higher than that of the normal controls [32 (31, 33)%, 29 (27, 30)%, and 26 (24, 27.5)%, P < 0.001]. In our study, quantitative T2 mapping in patients who were positive and negative for hs-TnI [51 (47.9, 52.8) and 48 (47, 49.4) ms] was significantly higher than the normal [42 (41, 45.2) ms] subjects (P < 0.001). CONCLUSION: In patients with early-stage COVID-19, myocardial oedema, and functional abnormalities are a frequent finding, while irreversible regional injury such as necrosis may be infrequent.

16.
Medicine (Baltimore) ; 100(10): e24824, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33725836

RESUMO

INTRODUCTION: There is currently no optimal treatment modality for refractory or relapsed Extranodal NK/T-cell lymphoma, nasal type (ENKTL). In recent years, programmed cell death protein 1 (PD-1)/programmed cell - ligand 1 pathway blockade and histone deacetylase inhibitors have emerged as promising strategies for refractory or relapsed ENKTL. Accumulating evidence has shown that therapeutic effects of anti-PD-1 antibody could be enhanced by histone deacetylase inhibitors. PATIENT CONCERNS: A 52-year-old male patient was diagnosed with stage I ENKTL by biopsy on February 2010. DIAGNOSIS: positron emission tomography-computed tomography (PET-CT) and biopsy were used to diagnose relapsed ENKTL in 2014. INTERVENTIONS: The patient was treated with radiotherapy and six cycles of etoposide, prednisone, vincristine (Oncovin), cyclophosphamide and doxorubicin hydrochloride and achieved complete remission (CR) by PET-CT in August 2010. In November 2014, the patient was diagnosed with relapsed stage IV ENKTL and was treated with six cycles of alternative chemotherapy with the regimen of steroid (dexamethasone), methotrexate, ifosfamide, L-asparaginase, and etoposide and pegaspargase plus Gemcitabine, Oxaliplatin along with radiotherapy. The patient achieved remission and was placed on thalidomide maintenance treatment. Upon suspicion of relapse suggested by PET-CT, Autologous stem cell transplant was performed after BCNU, etoposide, Ara-C, and melphalan preconditioning on February 2016. Following relapse again in December 2016, the lesions of left femur were treated with radiotherapy and he received anti-PD-1 antibody. He was treated with 4 cycles of pegaspargase plus Gemcitabine, Oxaliplatin on August 2017. The patient's condition improved. He received maintenance and consolidation therapy including lenalidomide, radiotherapy of the right nasal cavity and paranasal sinuses and antigen-specific reactive T cell infusions. PET-CT imaging showed there was high metabolic activity signal in the distal end of right femoral on August 2018 and the treatment regimen was adjusted to radiotherapy of the distal end of right femoral and systemic treatment of PD-1 antibody Sintilimab and chidamide 30 mg. After 5 months post-treatment, biopsy of nasopharynx showed no lymphoma cells. The patient continued the treatment of Sintilimab and chidamide 20 mg. OUTCOMES: PET-CT imaging showed his lesions obtained remission after 8 months post-treatment. CONCLUSION: Thus, combination of sintilimab and chidamide can be used to treat relapsed ENKTL following treatment failure from chemo-, radio-, and immuno-therapy. A clinical trial has been launched.


Assuntos
Aminopiridinas/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Benzamidas/uso terapêutico , Inibidores de Histona Desacetilases/uso terapêutico , Linfoma Extranodal de Células T-NK/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Nasais/tratamento farmacológico , Terapia Combinada , Humanos , Masculino , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/imunologia , Indução de Remissão , Resultado do Tratamento
17.
Science ; 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33727252

RESUMO

Substitution for aspartic acid by glycine at position 614 in the spike (S) protein of severe acute respiratory syndrome coronavirus 2 appears to facilitate rapid viral spread. The G614 strain and its recent variants are now the dominant circulating forms. We report here cryo-EM structures of a full-length G614 S trimer, which adopts three distinct prefusion conformations differing primarily by the position of one receptor-binding domain. A loop disordered in the D614 S trimer wedges between domains within a protomer in the G614 spike. This added interaction appears to prevent premature dissociation of the G614 trimer, effectively increasing the number of functional spikes and enhancing infectivity, and to modulate structural rearrangements for membrane fusion. These findings extend our understanding of viral entry and suggest an improved immunogen for vaccine development.

18.
Huan Jing Ke Xue ; 42(2): 634-642, 2021 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-33742857

RESUMO

City-scale high-resolution anthropogenic emission inventories are an important tool for ambient air quality forecasting and early warning, the analysis of underlying causes, and policy making. At present, city-scale anthropogenic emissions inventories for use in air quality models are scarce for West China. By studying the literature on emission inventories, this paper establishes a city-scale anthropogenic emission inventory for Lanzhou (HEI-LZ16) as the basis for an air quality model. The weather research and forecasting with chemistry (WRF-Chem) model was used to evaluate the applicability of the emission inventory at different resolutions in Lanzhou. The results showed that the emission amounts of SO2, NOx, CO, NH3, VOCs, PM10, PM2.5, BC, and OC in Lanzhou were 25642, 53998, 319003, 10475, 35289, 49250, 19822, 2476, and 1482 t·a-1 in 2016,respectively. Compared with the simulation scenario of multi-resolution emission inventory for China (MEIC), normalized mean error (NME) of O3 and PM2.5 under the HEI-LZ16 scenario decreased by 140.2% and 28.8%, respectively. The HEI-LZ16 inventory is more suitable for application in air pollution research in Lanzhou, which was verified by the WRF-Chem model and the observational data. The spatiotemporal distributions of PM2.5 and O3 were also analyzed using the HEI-LZ16 scenario. The ozone concentration of the maximum daily 8-h average (MDA8) in Lanzhou was low in urban areas and high in the suburbs during winter and spring, and high in the west of the urban valley and its downwind areas during summer and autumn. MDA8 in summer and autumn was influenced by easterly winds and photochemical reactions. In winter, ozone concentrations in urban areas are suppressed by NOx emissions but the concentration decreases. High PM2.5 concentrations are mainly concentrated within the Yellow River Valley. This study shows that there is a pollutant transmission channel along the western side of the Baiyin-Lanzhou Yellow River Valley, which has a greater impact on the ambient air quality in Lanzhou.

19.
Cell Death Dis ; 12(2): 208, 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33627636

RESUMO

Chronic myeloid leukemia (CML) is characterized by the accumulation of malignant and immature white blood cells which spread to the peripheral blood and other tissues/organs. Despite the fact that current tyrosine kinase inhibitors (TKIs) are capable of achieving the complete remission by reducing the tumor burden, severe adverse effects often occur in CML patients treated with TKIs. The differentiation therapy exhibits therapeutic potential to improve cure rates in leukemia, as evidenced by the striking success of all-trans-retinoic acid in acute promyelocytic leukemia treatment. However, there is still a lack of efficient differentiation therapy strategy in CML. Here we showed that MPL, which encodes the thrombopoietin receptor driving the development of hematopoietic stem/progenitor cells, decreased along with the progression of CML. We first elucidated that MPL signaling blockade impeded the megakaryocytic differentiation and contributed to the progression of CML. While allogeneic human umbilical cord-derived mesenchymal stem cells (UC-MSCs) treatment efficiently promoted megakaryocytic lineage differentiation of CML cells through restoring the MPL expression and activating MPL signaling. UC-MSCs in combination with eltrombopag, a non-peptide MPL agonist, further activated JAK/STAT and MAPK signaling pathways through MPL and exerted a synergetic effect on enhancing CML cell differentiation. The established combinational treatment not only markedly reduced the CML burden but also significantly eliminated CML cells in a xenograft CML model. We provided a new molecular insight of thrombopoietin (TPO) and MPL signaling in MSCs-mediated megakaryocytic differentiation of CML cells. Furthermore, a novel anti-CML treatment regimen that uses the combination of UC-MSCs and eltrombopag shows therapeutic potential to overcome the differentiation blockade in CML.

20.
Technol Cancer Res Treat ; 20: 1533033821989711, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33596784

RESUMO

Cervical cancer is one of the most malignant tumors in women, particularly those in rural and remote areas. Its underlying molecular mechanisms, including the functions of non-coding RNA (ncRNAs), require more extensive investigation. In this study, high throughput transcriptome sequencing (RNA-seq) was used to identify differentially expressed lncRNAs and mRNAs in normal, cervical intraepithelial neoplasia and cervical cancer tissues from Uyghur women in western China. Dysregulated lncRNAs were found to extensively participate in cervical cancer development, including viral carcinogenesis, cell cycle and cytokine-cytokine receptor signaling. Two miRNA-host lncRNAs, LINC00925 and MIR155HG, showed elevated expression in cervical cancer samples, but prolonged the survival time of cervical cancer patients. The 2 mature miRNAs of the above 2 lncRNAs, miR-9 and miR-155, also showed similar features in cervical cancer. In addition, we identified 545 lncRNAs with potential functions in regulating these 2 miRNAs as competing endogenous RNAs (ceRNAs). In summary, our study demonstrated the dysregulated lncRNAs/miRNAs, particularly LINC00925/miR-9 and MIR155HG/miR-155, regulate the development of cervical cancer by forming a interaction network with mRNAs, highlighting the importance of elucidating the underlying mechanisms of ncRNAs in cervical cancer development.

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