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1.
Chemosphere ; 255: 126955, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32416390

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) can induce skin toxicity. Although some investigations have been conducted to assess the skin toxicity of different PAHs, few comparisons using a series of PAHs with different ring numbers and arrangements have been done. We aimed to explore the skin absorption of 6 PAH compounds and their effect on cutaneous inflammation. In vitro skin permeation was rated by Franz cell with pig skin. Molecular docking was employed to compute the PAH interaction with stratum corneum (SC) lipids. Cultured keratinocytes were exposed to PAHs for analyzing cytotoxicity, cyclooxygenase (COX)-2, prostaglandin E2 (PGE2), chemokines, and differentiation proteins. The in vivo topical PAH exposure in mice was characterized by skin absorption, transepidermal water loss (TEWL), PGE2 level, and histology. The skin deposition from the aqueous vehicle increased following the increase of PAH lipophilicity and molecular size, with benzo[a]pyrene (5-ring PAH) showing the greatest absorption. Pyrene was the compound showing the highest penetration across the skin (flux). Although the PAHs fluoranthene, pyrene, chrysene, and 1,2-benzanthracene all had 4 rings, the skin permeation was quite different. 1,2-Benzanthracene showed the greatest absorption among the 4-ring compounds. The PAHs with higher absorption exhibited stronger interaction with SC lipids according to the in silico modeling. Chrysene and 1,2-benzanthracene generally showed the highest COX-2 and PGE2 expression, followed by benzo[a]pyrene. The lowest COX-2 and PGE2 upregulation was observed for naphthalene (2-ring PAH). A contrary tendency was detected for the upregulation of chemokines. Filaggrin and integrin ß1 in keratinocytes were suppressed at a comparable level by all PAHs. The skin's absorption of PAHs showed strong in vivo-in vitro correlation. 1,2-Benzanthracene and benzo[a]pyrene highly disrupted the skin barrier and elevated the inflammation in vivo. The tendency toward in vivo inflammation caused by various PAHs could be well predicted by the combined estimation using in vitro skin absorption and a keratinocyte bioassay. This study also established the structure-permeation relationship (SPR) of PAHs.

2.
Curr Probl Cancer ; : 100577, 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32418615

RESUMO

Adjuvant chemotherapy following the curative resection could improve the survival outcome of advanced gastric cancer (GC) patients. However, it is unclear whether delayed initiation of adjuvant chemotherapy had a negative impact on survival outcome in GC patients. The purpose of this study was to review current published literature about the impact of delaying adjuvant chemotherapy on survival outcome and summarize risk factors for delaying adjuvant chemotherapy. Delayed initiation of adjuvant chemotherapy was quite frequent in GC patients who underwent gastrectomy due to postoperative complications, poor nutritional status, comorbid diseases and socioeconomic status. Therefore, it is important for these patients to have a sufficient and smooth transition from surgery to initiation of adjuvant chemotherapy. Based on current available evidence, there is no specific timing interval for the initiation of adjuvant chemotherapy in GC patients. Earlier initiation of adjuvant chemotherapy (<4 weeks) may not be mandatory for GC patients who underwent curative resection. However, the patients should be recommended to receive adjuvant chemotherapy within 6-8 weeks if their performance status and nutritional status were deemed to be appropriate. Minimizing postoperative complications and providing requisite nutritional advice may be helpful for timely initiation of adjuvant chemotherapy.

3.
Genetics ; 2020 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-32366512

RESUMO

Selection of mutants in a microbial population depends on multiple cellular traits. In serial-dilution evolution experiments, three key traits are the lag time when transitioning from starvation to growth, the exponential growth rate, and the yield (number of cells per unit resource). Here we investigate how these traits evolve in laboratory evolution experiments using a minimal model of population dynamics, where the only interaction between cells is competition for a single limiting resource. We find that the fixation probability of a beneficial mutation depends on a linear combination of its growth rate and lag time relative to its immediate ancestor, even under clonal interference. The relative selective pressure on growth rate and lag time is set by the dilution factor; a larger dilution factor favors the adaptation of growth rate over the adaptation of lag time. The model shows that yield, however, is under no direct selection. We also show how the adaptation speeds of growth and lag depend on experimental parameters and the underlying supply of mutations. Finally, we investigate the evolution of covariation between these traits across populations, which reveals that the population growth rate and lag time can evolve a nonzero correlation even if mutations have uncorrelated effects on the two traits. Altogether these results provide useful guidance to future experiments on microbial evolution.

4.
Exp Neurol ; : 113324, 2020 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-32320698

RESUMO

Neonatal hypoxic-ischemic encephalopathy remains the most important neurological problem of the newborn. Delays in diagnosing perinatal brain injuries are common, preventing access to acute therapies. Therefore, there is a critical need for therapeutic strategies that are beneficial when delivered beyond 24 h after birth. Here we show that Leukemia Inhibitory Factor (LIF) functions as an essential injury-induced neurotrophic cytokine in the CNS and that non-invasively administering LIF as late as 3 days after a hypoxic-ischemic insult improves neurological function. Using a mouse model of late preterm brain injury we show that astroglial and reactivity to hypoxia-ischemia was diminished at 3 days of recovery, but then exacerbated at 2 weeks of recovery in LIF haplodeficient mice. There also were significantly more CD68+/Iba-1+ cells in the ipsilateral striatum in LIF-Het mice compared to WT mice at 2 weeks of recovery. This desynchronized glial response was accompanied by increased neuronal cell death in the striatum and neocortex (Fluorojade C), hypomyelination (reduced MBP staining and thinner external capsule), increased extent of brain damage (Nissl) and diminished neurological function on sensorimotor tests. To our surprise, injured LIF-Het mice had ~7-fold higher IGF-1 levels than injured WT mice at 3 days after HI injury. Intranasally administered LIF activated the Jak-Stat-3 pathway both within the subventricular zone and the neocortex at 30 min after administration. When delivered with a delay of 3 days after the insult, intranasal LIF reduced the extent of brain injury by ~60%, attenuated astrogliosis and microgliosis in striatum, improved subcortical white matter thickness, increased numbers of Olig2+ cells in corpus callosum and improved performance on sensorimotor tests at 2 weeks of recovery. These studies provide key pre-clinical data recommending LIF administration as a neuroprotectant and regenerative cytokine and they highlight the feasibility of pursuing new therapeutics targeting the tertiary phase of neurodegeneration for hypoxic-ischemic encephalopathies.

5.
Neurol Sci ; 2020 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-32328833

RESUMO

BACKGROUND AND OBJECTIVE: Autoimmune longitudinal extensive transverse myelitis (LETM) is often combined with connective tissue disorders (CTD). The purpose of this study was to compare the clinical characteristics of autoimmune LETM with and without CTD. METHODS: Ninety-two patients diagnosed with autoimmune LETM were enrolled from our clinical database and divided into two groups depending on whether they had a concomitant diagnosis of CTD. Differences in clinical, serological, and imaging characteristics between the two groups were evaluated and compared. RESULTS: Fifty-nine LETM patients without CTD and 33 LETM patients with CTD were included. LETM patients with CTD had higher Kurtzke Expanded Disability Status Scale at nadir and more severe sensory dysfunction (p < 0.05) than those without CTD. It was also found that LETM patients with CTD, compared with those without CTD, had elevated levels of immune inflammation markers such as IgG, IgA, and globulins (p < 0.05). These abovementioned characteristics were more prominent in patients with aquaporin-4 antibodies (AQP4-ab) than in those without them. In addition, the most common type of CTD in LETM was Sjögren syndrome (SS), which was usually diagnosed at the time of LETM or later. CONCLUSION: LETM patients with CTD, especially those with AQP4-ab, had greater sensory dysfunction and higher levels of inflammatory markers than did LETM patients without CTD. Multicenter cooperation and long-term follow-up are necessary to further study the inherent implications and prognosis of the disease.

6.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(2): 622-628, 2020 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-32319406

RESUMO

OBJECTIVE: To investigate the factors affecting counting and collection efficiency of the final product- mononuclear cells (MNCs) in the collection of mononuclear cells for tumor cell biotherapy. METHODS: The collected data of 142 tumor patients and healthy donors were analyzed, including age, sex, height, weight, BMI, the total blood volume, diagnostic category, vascular access, operator, final product volume, ACD anticoagulant usage, flow rate and circulation times, pre-apheresis Hb, RBC, Plt, WBC, lymphocyte count, monocyte count, neutrophil count, circulating blood volume without anticoagulant, final product MNC and collection efficiency of MNC. CE(collection efficiency)%= final product MNC×100/(pre-apheresis MNC×circulating blood volume without anticoagulant). The factors affecting final products MNC and CE of MNC were detected by T test and multiple linear regression analysis. RESULTS: The CE of tumor patients was higher than that of healthy donors (24.41±1.91,vs 20.01±0.99),(P=0.043), and CE of MNC was different among different operators (P=0.01, H=18.59). There was a positive correlation of the final MNC with the volume of final product, ACD anticoagulant usage and pre-apheresis lymphocyte count (P= 0.00, P= 0.01, P= 0.00, r=0.811); CE of MNC negatively correlated with flow rate and pre-apheresis RBC, but positively correlated with operator's working age and ACD anticoagulant usage (P=0.01, P=0.04, P=0.03, P= 0.00, r=0.495). CONCLUSION: more higher pre-apheresis lymphocyte , more amount of the final product and ACD anticoagulant usage, and more high the final MNC. During the collecting process, more ACD anticoagulant usage and more high operator's seniority, lead to the higher MNC'S CE; while more high pre-apheresis RBC and more fast flow rate, cause the lower the CE of MNC.

7.
BMC Cancer ; 20(1): 266, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32228488

RESUMO

BACKGROUND: Lymphovascular invasion (LOI), a key pathological feature of head and neck squamous cell carcinoma (HNSCC), is predictive of poor survival; however, the associated clinical characteristics and underlying molecular mechanisms remain largely unknown. METHODS: We performed weighted gene co-expression network analysis to construct gene co-expression networks and investigate the relationship between key modules and the LOI clinical phenotype. Functional enrichment and KEGG pathway analyses were performed with differentially expressed genes. A protein-protein interaction network was constructed using Cytoscape, and module analysis was performed using MCODE. Prognostic value, expression analysis, and survival analysis were conducted using hub genes; GEPIA and the Human Protein Atlas database were used to determine the mRNA and protein expression levels of hub genes, respectively. Multivariable Cox regression analysis was used to establish a prognostic risk formula and the areas under the receiver operating characteristic curve (AUCs) were used to evaluate prediction efficiency. Finally, potential small molecular agents that could target LOI were identified with DrugBank. RESULTS: Ten co-expression modules in two key modules (turquoise and pink) associated with LOI were identified. Functional enrichment and KEGG pathway analysis revealed that turquoise and pink modules played significant roles in HNSCC progression. Seven hub genes (CNFN, KIF18B, KIF23, PRC1, CCNA2, DEPDC1, and TTK) in the two modules were identified and validated by survival and expression analyses, and the following prognostic risk formula was established: [risk score = EXPDEPDC1 * 0.32636 + EXPCNFN * (- 0.07544)]. The low-risk group showed better overall survival than the high-risk group (P < 0.0001), and the AUCs for 1-, 3-, and 5-year overall survival were 0.582, 0.634, and 0.636, respectively. Eight small molecular agents, namely XL844, AT7519, AT9283, alvocidib, nelarabine, benzamidine, L-glutamine, and zinc, were identified as novel candidates for controlling LOI in HNSCC (P < 0.05). CONCLUSIONS: The two-mRNA signature (CNFN and DEPDC1) could serve as an independent biomarker to predict LOI risk and provide new insights into the mechanisms underlying LOI in HNSCC. In addition, the small molecular agents appear promising for LOI treatment.

8.
Artigo em Inglês | MEDLINE | ID: mdl-32223176

RESUMO

Silicon (Si) films are promising anode materials in thin-film lithium batteries due to their high capacity of 3578 mAh g-1, but the huge volume expansion of lithiated Li15Si4 and the unstable solid electrolyte interphase (SEI) preclude their practical application. Here lithium fluoride (LiF) coated Si nanocolumns are fabricated by glancing angle evaporation to address the obstacle. The LiF coating can elevate the lithium ion diffusion coefficient (LDC) of Si electrodes upon the alloying reaction and reduce the LDC upon the SEI formation. The composition evolution of the outer SEI layer in the LiF/Si electrodes is studied by ex situ X-ray photoelectron spectroscopy. The modified surface and mitigated volume expansion enable the LiF/Si nanocolumns to exhibit superior rate capability and higher cycling stability compared with the pristine Si nanocolumns. This work demonstrates the positive effect of LiF coating for reducing the polarization and forming a robust SEI film on Si anodes.

9.
Ann Surg Oncol ; 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32239339

RESUMO

BACKGROUND: This study aimed to evaluate the feasibility of a wait-and-see strategy for non-small cell lung cancer (NSCLC) patients with special pleural dissemination lesions (r-pM1a and s-pM1a). Furthermore, the study characterized genomic alternations about disease progression. METHODS: For this study, 131 NSCLC patients with a diagnosis of pM1a were retrospectively selected. Survival differences were evaluated among patients treated with three different initial postoperative treatments: chemotherapy, targeted therapy, and wait-and-see strategy. Whole-exome sequencing (WES) was performed on primary and metastatic tumors of 10 patients with dramatic progression and 13 patients with gradual progression. RESULTS: The wait-and-see group showed better progression-free survival (PFS) than the chemotherapy group (p < 0.001) but PFS similar to that of targeted group (p = 0.984). This pattern persisted in epidermal growth factor receptor (EGFR)-positive patients. For patients with EGFR-negative/unknown status, PFS was longer in the wait-and-see group than in the two treatment groups. Furthermore, better overall survival (OS) was observed for the patients who received chemotherapy or targeted therapy after the wait-and-see strategy than for those who received chemotherapy or targeted therapy immediately. Lymph node status was an independent prognostic factor for PFS and OS. Finally, WES analysis showed that a high genomic instability index (GIS) and chromosome 18q loss were more common in metastatic tumors, and low GIS was significantly associated with better PFS (p = 0.016). CONCLUSIONS: The wait-and-see strategy could be considered for special pM1a patients without lymph nodes metastasis, and patients with a low GIS may be suitable for this strategy.

10.
J Prosthodont ; 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32237001

RESUMO

PURPOSE: Image registration of the optical intraoral scan to computed tomography image is essential for computer-guided implant surgery. The remaining teeth, which are considered to be congruent structures observed in the scan and radiographic images, are used to perform the image registration. The purpose of this study was to evaluate the effects of the distribution of matching fiducial points on the accuracy of the image registration. MATERIALS AND METHODS: A partially edentulous model with three anterior remaining teeth was prepared. Two mini dental implants were inserted in the posterior edentulous areas on both sides, and computed tomography and surface scan data were obtained. Three groups were set according to the distribution of the image matching points used: localized distribution, unilateral distribution, and bilateral distribution. Fifteen graduate students performed the registration process in each group using the same image matching method. The accuracy of image registration was evaluated by measuring the geometric discrepancies between the radiographic and registered scan images in the anterior, middle, and posterior regions. One-way and two-way analysis of variance with the Tukey HSD post hoc test were used for statistical analysis (α = 0.05) RESULTS: In general, the registration discrepancy was lowest in the bilateral distribution group, followed by the unilateral distribution and localized distribution groups (p< 0.001). In the regional analysis, the registration error tended to increase as the measurement region moved farther from the matching points. The distribution of the matching points and measurement regions had a statistical interaction in the accuracy of image registration. CONCLUSION: The accuracy of image registration of the surface scan to the computed tomography is affected by the matching point distribution that can be improved by placing artificial markers in the edentulous areas.

11.
Drug Des Devel Ther ; 14: 1257-1262, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32280197

RESUMO

Introduction: The purpose of this study was to analyze the safety and feasibility of low-dose apatinib combined with S-1 as a second-line therapy or beyond in Chinese patients with pulmonary and/or hepatic metastases of nasopharyngeal carcinoma (NPC). Methods: Forty-one Chinese NPC patients with pulmonary and hepatic metastases were treated with low-dose apatinib plus S-1. The S-1 dose was determined according to each patient's body surface area (BSA): 40 mg twice a day for BSA <1.25 m2; 50 mg twice a day for 1.25 m2≤BSA <1.5 m2; and 60 mg twice a day for BSA ≥1.5 m2. S-1 was received for 14 days, after stopping for 7 days, given 3 weeks apart. Apatinib, 125 mg was orally administered daily on days 1 through 28 of each 4-week cycle. If the toxicity was not tolerable, the dose of apatinib was reduced to 125 mg every other day. Results: Treatment efficacy was evaluated in all 41 patients after four courses of chemotherapy. The objective response rate was 34.1%, and the disease control rate was 80.4%. The median progression-free survival was 9.7 months (95% confidence interval, 6.2-13.8 months), and the median overall survival was 22.1 months (95% confidence interval, 15.1-28.9 months). The 2-year survival rate was 41.5%. The most common toxicities included loss of appetite in 39.0% of patients, dyslipidemia in 34.1%, hypertension in 31.7%, myelosuppression in 24.4%, fatigue in 21.9%, and hand-foot syndrome in 17.1%. Seven patients received dose adjustment of apatinib due to side effects. Conclusion: In patients with pulmonary and/or hepatic metastases of NPC, low-dose apatinib plus S-1 yielded an excellent survival benefit, and the toxicities were mild and tolerable.

12.
Cancer ; 2020 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-32286688

RESUMO

BACKGROUND: Glioma is the most common malignant brain cancer. Accessibility to health care is an important factor affecting cancer outcomes in the US general population. The US Military Health System (MHS) provides universal health care to its beneficiaries. It is unknown whether this universal health care has translated into improved survival outcomes among MHS beneficiaries with glioma. This study compared the overall survival of patients with glioma in the MHS with the overall survival of patients with glioma in the general population. METHODS: The MHS cases were identified from the Department of Defense's Automated Central Tumor Registry (ACTUR). Glioma cases from the general population were identified from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program. SEER cases were matched 2:1 to ACTUR cases by age, sex, race, histology, and diagnosis year. All cases had histologically confirmed glioma diagnosed between January 1, 1987, and December 31, 2013. A Kaplan-Meier analysis was conducted to compare survival between the ACTUR and SEER cases. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: The study included 2231 glioma cases from ACTUR and 4462 cases from SEER. ACTUR cases exhibited significantly better overall survival than SEER cases (HR, 0.74; 95% CI, 0.67-0.83). The survival advantage of the ACTUR patients was observed in most subgroups stratified by age, sex, race, diagnosis year, and histology. For glioblastoma, the survival advantage was observed in both the pre- and post-temozolomide periods. CONCLUSIONS: Universal MHS health care may have translated into improved survival outcomes in glioma. Future studies are warranted to identify factors contributing to the improved survival.

13.
Carcinogenesis ; 2020 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-32338281

RESUMO

Tumor suppressor candidate 3 (TUSC3) is a coding gene responsible for N-glycosylation of many critical proteins. TUSC3 gene plays an oncogenic role in colorectal cancer (CRC), however, the role of TUSC3 in drug resistance of CRC is still unclear. The aim of this study is to investigate the biological function and molecular mechanism of TUSC3 in CRC drug resistance. The expression of TUSC3 in CRC is positively correlated to tumor stage in 90 paired clinical samples, and negatively associated with overall survival and disease-free survival of CRC patients. In vitro, TUSC3 promotes the formation of stemness and induces the drug resistance to 5-fluorouracil (5-FU) and cis-Dichlorodiammineplatinum(II) (DDP) in CRC cells. The tissue microarray assay and bioinformatic analysis indicates that TUSC3 may promote the expression of CD133 and ABCC1 via hedgehog signaling pathway. Treatment of Hedgehog signaling pathway agonist or inhibitor in TUSC3-silenced or TUSC3-overexpressed cells reverse the effects of TUSC3 in cellular stemness phenotype and drug resistance. Meanwhile, co-immunoprecipitation and immunofluorescence assays indicate a tight relationship between TUSC3 and SMO protein. Our data suggests that TUSC3 promotes the formation of cellular stemness and induces drug resistance via Hedgehog signaling pathway in CRC.

14.
Biochim Biophys Acta Mol Basis Dis ; 1866(8): 165806, 2020 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-32320827

RESUMO

Diabetic cardiomyopathy (DCM) accounts for increasing deaths of diabetic patients, and effective therapeutic targets are urgently needed. Myocardial lipotoxicity, which is caused by cardiac non-oxidative metabolic fatty acids and cardiotoxic fatty acid metabolites accumulation, has gained more attention to explain the increasing prevalence of DCM. However, whether mammalian Ste20-like kinase 1 (Mst1) plays a role in lipotoxicity in type 2 diabetes-induced cardiomyopathy has not yet been illustrated. Here, we found that Mst1 expression was elevated transcriptionally in the hearts of type 2 diabetes mellitus mice and palmitic acid-treated neonatal rat ventricular myocytes. Adeno-associated virus 9 (AAV9)-mediated Mst1 silencing in db/db mouse hearts significantly alleviated cardiac dysfunction and fibrosis. Notably, Mst1 knockdown in db/db mouse hearts decreased lipotoxic apoptosis and inflammatory response. Mst1 knockdown exerted protective effects through inactivation of MAPK/ERK kinase kinase 1 (MEKK1)/c-Jun N-terminal kinase (JNK) signaling pathway. Moreover, lipotoxicity induced Mst1 expression through promoting the binding of forkhead box O3 (FoxO3) and Mst1 promoter. Conclusively, we elucidated for the first time that Mst1 expression is regulated by FOXO3 under lipotoxicity stimulation and downregulation of Mst1 protects db/db mice from lipotoxic cardiac injury through MEKK1/JNK signaling inhibition, indicating that Mst1 abrogation may be a potential treatment strategy for DCM in type 2 diabetic patients.

15.
Oncol Rep ; 43(6): 1995-2003, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32236602

RESUMO

Hispidulin is a medicinal natural compound isolated from S. involucrata, which exhibits potent anticancer properties. However, there are few reports on its effects on lung cancer cells. Therefore, the current study investigated the effects of hispidulin on cell viability and apoptosis in human non­small­cell lung cancer (NSCLC) cell lines NCI­H460 and A549 in vitro and in vivo. Methyl thiazolyl tetrazolium, colony formation assay, Hoechst 33342 staining, flow cytometry and western blotting were performed on Human NCI­H460 and A549 cells. A mouse xenograft model was also established using NCI­H460 cells. The results showed that the growth of NCI­H460 and A549 cells was inhibited, while apoptosis was promoted by hispidulin via increased generation of reactive oxygen species (ROS) in a dose­dependent manner. Furthermore, hispidulin triggered apoptosis in NSCLC cells through upregulating the expression of cleaved caspase­3 and cleaved poly [ADP­ribose] polymerase. All these effects were reversed upon pretreatment with glutathione, a selective ROS inhibitor. In addition, endoplasmic reticulum stress (ER stress) in NCI­H460 cells was activated by hispidulin. Pretreatment with tauroursodeoxycholic acid, a specific ER stress inhibitor, effectively reduced the cell apoptosis induced by hispidulin. In conclusion, hispidulin induces ROS­mediated apoptosis via activating the ER stress pathway. The current study provides theoretical basis for the antitumor effect of hispidulin in NSCLC.

16.
Cell Death Dis ; 11(4): 269, 2020 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-32327666

RESUMO

Glioma has been a major healthcare burden; however, the specific molecular regulatory mechanism underlying its initiation and progression remains to be elucidated. Although it is known that many miRNAs are involved in the regulation of malignant phenotypes of glioma, the role of miR-4476 has not been reported yet. In the present study, we identify miR-4476 as an upregulated microRNA, which promotes cell proliferation, migration, and invasion in glioma. Further mechanistic analyses indicate that the adenomatous polyposis coli (APC), a negative regulator of the Wnt/ß-catenin signaling pathway, is a direct target of miR-4476 and mediates the oncogenic effects of miR-4476 in glioma. C-Jun, a downstream effector of the Wnt/ß-catenin signaling, is upregulated by miR-4476 overexpression. In turn, c-Jun could positively regulate miR-4476 expression by binding to the upstream of its transcription start site (TSS). Furthermore, in our clinical samples, increased miR-4476 is an unfavorable prognostic factor, and its expression positively correlates with c-Jun expression but negatively correlates with that of APC. In conclusion, our study demonstrates that miR-4476 acts as a tumor enhancer, directly targeting APC to stimulate its own expression and promoting the malignant phenotypes of glioma.

17.
Artigo em Inglês | MEDLINE | ID: mdl-32149494

RESUMO

Solid oxide fuel cells (SOFCs) can directly operate on hydrocarbon fuels such as natural gas; however, the widely used nickel-based anodes face grand challenges such as coking, sulfur poisoning, and redox instability. We report a novel double perovskite oxide Sr2Co0.4Fe1.2Mo0.4O6-δ (SCFM) that possesses excellent redox reversibility and can be used as both the cathode and the anode. When heat-treated at 900 °C in a reducing environment, double perovskite phase SCFM transforms into a composite of the Ruddlesden-Popper structured oxide Sr3Co0.1Fe1.3Mo0.6O7-δ (RP-SCFM) with the Co-Fe alloy nanoparticles homogeneously distributed on the surface of RP-SCFM. At 900 °C in an oxidizing atmosphere, the composite transforms back into the double perovskite phase SCFM. The excellent oxygen reduction reaction catalytic activity and mixed ionic-electronic conductivity make SCFM an excellent cathode material for SOFCs. When SCFM is used as the anode, excellent performance and stability are achieved upon either direct oxidation of methane as a fuel or operation with sulfur-containing fuels. The excellent redox reversibility coupled with outstanding electrical and catalytic properties manifested by SCFM will enable a broad application in energy conversion applications.

18.
Int J Infect Dis ; 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32200109

RESUMO

An outbreak of COVID-19 in Wuhan, China caused by SARS-CoV-2 has led to a serious epidemic in China and other countries, resulting in worldwide concern. With the active efforts from prevention and control, the quantity of discharged patients is escalating. How to manage these patients normatively is still challenging. We hereby reported an asymptomatic discharged patient with COVID-19 who was retested positive for SARS-CoV-2, which arouses concern regarding the present discharge standard of COVID-19.

19.
J Nutr ; 2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32167145

RESUMO

BACKGROUND: The total and specific types of polyunsaturated fatty acids (PUFAs) related to metabolic syndrome (MetS) remain inconsistent. OBJECTIVE: We assessed the association of erythrocyte n-3 and n-6 PUFAs with MetS and the components of MetS in a cohort population. METHODS: This prospective analysis included 2754 participants (aged 40-75 y) from the Guangzhou Nutrition and Health Study (2008-2019) in China. Erythrocyte PUFAs at baseline were measured using gas chromatography. MetS was assessed every 3 y according to the updated National Cholesterol Education Program Adult Treatment Panel III criteria. Multivariable Cox proportional hazard models were used to evaluate HRs and 95% CIs. RESULTS: We identified 716 incident cases of MetS. The primary analyses showed that the HRs (95% CIs) of MetS (tertile 3 versus 1) were 0.67 (0.56, 0.80) for n-3 PUFAs and 0.70 (0.58, 0.85) for n-6 PUFAs (all Ps trend <0.001). The secondary outcomes showed that, higher erythrocyte very-long-chain (VLC) PUFAs [20:3n-3, docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), arachidonic acid (ARA), and 22:4n-6], but lower α-linolenic acid (ALA) and γ-linolenic acid (GLA), tended to be associated with lower incidences of MetS and its components; among individual MetS components, the associations of PUFAs were more pronounced for hypertriglyceridemia (HTG) and hypertension, followed by low high-density lipoproten (HDL) cholesterol. Significantly higher concentrations of n-3 PUFAs (total, DPA, and DHA) and n-6 PUFAs (total, ARA, and 22:4) were observed in participants with improved (versus progressed) status of MetS (all Ps trend ≤0.003). CONCLUSION: This study reveals that higher erythrocyte VLC n-3 and n-6 PUFAs, but lower 18-carbon PUFAs (ALA and GLA), are associated with lower risks of MetS components (HTG, hypertension, and low HDL cholesterol) and thereby lower MetS incidence in Chinese adults.

20.
Theranostics ; 10(8): 3767-3778, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32206121

RESUMO

Purpose: Lung cancer is the leading cause of cancer related deaths worldwide. We have previously identified many differentially expressed genes (DEGs) from large scale pan-cancer dataset using the Cross-Value Association Analysis (CVAA) method. Here we focus on Progestin and AdipoQ Receptor 4 (PAQR4), a member of the progestin and adipoQ receptor (PAQR) family localized in the Golgi apparatus, to determine their clinical role and mechanism in the development of non-small cell lung cancer (NSCLC). Methods: The protein expression profile of PAQR4 was examined by IHC using tissue microarrays, and the effects of PAQR4 on cell proliferation, colony formation and xenograft tumor formation were tested in NSCLC cells. Real-time RT-PCR, co-immunoprecipitation (co-IP) and GST-pulldown assays were used to explore the mechanism of action of PAQR4. Results: We provided evidence showing that PAQR4 is increased in NSCLC cancer cell lines (A549, H1299, H1650, H1975, H358, GLC-82 and SPC-A1), and identified many mutations in PAQR4 in non-small cell lung cancer (NSCLC) tissues. We demonstrated that PAQR4 high expression correlates with a worse clinical outcome, and that its knockdown suppresses cell proliferation by inducing apoptosis. Importantly, overexpressed PAQR4 physically interacts with Nrf2 in NSCLC cells, blocking the interaction between Nrf2 and Keap1. Conclusion: Our results suggest that PAQR4 depletion enhances the sensitivity of cancerous cell to chemotherapy both in vitro and xenograft tumor formation in vivo, by promoting Nrf2 protein degradation through a Keap1-mediated ubiquitination process.

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