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1.
Biochim Biophys Acta Mol Basis Dis ; : 165989, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33065235

RESUMO

We previously showed that increased epithelial sodium channel (ENaC) activity in endothelial cells induced by oxidized low-density lipoprotein (ox-LDL) contributes to vasculature dysfunction. Here, we investigated whether ENaC participates in the pathological process of atherosclerosis using LDL receptor-deficient (LDLr-/-) mice. Male C57BL/6 and LDLr-/- mice were fed a normal diet (ND) or high fat diet (HFD) for 10 weeks. Our data show that treatment of LDLr-/- mice with a specific ENaC blocker, benzamil, significantly decreased atherosclerotic lesion formation and expression of matrix metalloproteinase 2 (MMP2) and metalloproteinase 9 (MMP9) in aortic arteries. Furthermore, benzamil ameliorated HFD-induced impairment of aortic endothelium-dependent dilation by reducing expression of proinflammatory cytokines, including TNF-α, IL-1ß, and IL-6 and production of adhesion molecules including VCAM-1 and ICAM-1 in both C57BL/6 and LDLr-/- mice fed with HFD. In addition, HFD significantly increased ENaC activity and the levels of serum lipids, including ox-LDL. Our in vitro data further demonstrated that exogenous ox-LDL significantly increased the production of TNF-α, IL-1ß, IL-6, VCAM-1 and ICAM-1. This ox-LDL-induced increase in inflammatory cytokines and adhesion molecules was reversed by γ-ENaC silencing or by treatment with the cyclooxygenase-2 (COX-2) antagonist celecoxib. Benzamil inhibited HFD-induced increase in COX-2 expression in aortic tissue in both C57BL/6 and LDLr-/- mice, and γ-ENaC gene silencing attenuated ox-LDL-induced COX-2 expression in HUVECs. These data together suggest that HFD-induced activation of ENaC stimulates inflammatory signaling, thereby contributes to HFD-induced endothelial dysfunction and atherosclerotic lesion formation. Thus, targeting endothelial ENaC may be a promising strategy to halt atherogenesis.

2.
Curr Psychol ; : 1-9, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33046955

RESUMO

To assess the psychological effects of the novel coronavirus disease (COVID-19) on medical staff and the general public. During the outbreak of COVID-19, an internet-based questionnaire included The Self-rating Depression Scale (SDS), Perceived Stress Scale (PSS-10), and Impact of Event Scale-Revised (IES-R) was used to assess the impact of the pandemic situation on the mental health of medical staff and general population in Wuhan and its surrounding areas. Among the 1493 questionnaires completed, 827 (55.39%) of these were men, and 422 (28.27%) of these were medical personnel. The results suggest that the outbreak of COVID-19 has affected individuals significantly, the degree of which is related to age, sex, occupation and mental illness. There was a significant difference in PSS-10 and IES-R scores between the medical staff and the general population. The medical staff showed higher PSS-10 scores (16.813 ± 4.87) and IES-R scores (22.40 ± 12.12) compared to members of the general population PSS-10 (14.80 ± 5.60) and IES-R scores (17.89 ± 13.08). However, there was no statistically significant difference between the SDS scores of medical staff (44.52 ± 12.36) and the general public (43.08 ± 11.42). In terms of the need for psychological assistance, 50.97% of interviewees responded that they needed psychological counseling, of which medical staff accounted for 65.87% and non-medical staff accounted for 45.10%. During the ongoing COVID-19 outbreak, great attention should be paid to the mental health of the population, especially medical staff, and measures such as psychological intervention should be actively carried out for reducing the psychosocial effects.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33015852

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common lethal human malignancies worldwide. Sorafenib is the first-line drug approved by the United States Food and Drug Administration for HCC. However, the acquired resistance to sorafenib reduces its beneficial effects and limits clinical use. In this study, we established a sorafenib-resistant HCC cell line HepG2-SR by low concentration gradient induction. Compared with the parental cell HepG2, the proliferation and anti-apoptosis were increased in drug-resistant cell HepG2-SR. Thorough comparisons of the molecular changes between parental HepG2 and sorafenib-resistant HepG2-SR cells indicated that the Notch signaling pathway and PI3K/Akt signaling pathway were associated with sorafenib resistance mechanisms. Notch1 and Akt were up-regulated in sorafenib-resistant cells. However, we surprisingly found that VPA combined with sorafenib could enhance the sensitivity of drug-resistant cells and reverse the increased levels of Notch1 and Akt in sorafenib-resistant HCC cells. Moreover, Akt inhibitor could suppress Notch1 expression, whereas the level of Akt phosphorylation decreased along with increasing dose of Notch inhibitor. Besides, we found that knockdown of Akt resulted in Notch 1 reduction, whereas Notch1 reduction also led to a significant reduction in the phosphorylation of Akt. Collectively, our results indicated that Notch1 and Akt might play vital roles in sorafenib resistance in HCC cells and VPA might overcome the drug resistance to enhance the sensitivity of HCC cells to sorafenib through suppressing Notch/Akt signaling pathway. VPA combined with sorafenib may provide a potential targeting therapeutic regimen for clinically to solve the problem of sorafenib resistance.

4.
J Prosthet Dent ; 2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33023743

RESUMO

STATEMENT OF PROBLEM: Synchronous online prosthodontic courses became a popular learning mode during the 2020 COVID-19 pandemic crisis. Nonetheless, the extent of learner participation and completion of these courses remains unknown. PURPOSE: The purpose of this study was to assess learner behaviors in synchronous online prosthodontic continuing education lectures in China during the 2020 COVID-19 pandemic. MATERIAL AND METHODS: All live online prosthodontic courses held by an online dental school in China from February to May 2020 were retrieved. The no-cost lectures could be accessed anonymously and viewed repeatedly on the day of broadcast. Learning behavior data (teacher speaking time, audience total, timing of first visit to the online classroom, viewing time, and completion rate) were obtained. Learning progress was calculated by dividing viewing time by teacher speaking time. When a learner progressed through 95% of a lecture, the lecture was considered completed. RESULTS: A total of 41 781 learners participated in 18 online prosthodontic courses, which had a mean duration of 77.2 ±15.8 minutes. For each lecture, 2321 ±1454 participants attended, with 510 ±404 participants completing each session. There were 13 098 participants (31.35%) who viewed the lectures for less than 1 minute. Approximately half of the participants viewed the lectures for less than 10 minutes, with their learning progress failing to pass 10%. The average completion rate was 21.97%, with variation in completion rate dependent on when a learner first visited the online classroom. Significant differences were found among the lecture completion rates and the timing of the first visit to the online classroom (P<.001). CONCLUSIONS: Synchronous online prosthodontic education courses in China had a high number of participants but low learning progress and completion rates during the 2020 COVID-19 pandemic.

5.
Brief Bioinform ; 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33051665

RESUMO

Cholangiocarcinoma (CCA) is a type of cancer with limited treatment options and a poor prognosis. Although some important genes and pathways associated with CCA have been identified, the relationship between coexpression and phenotype in CCA at the systems level remains unclear. In this study, the relationships underlying the molecular and clinical characteristics of CCA were investigated by employing weighted gene coexpression network analysis (WGCNA). The gene expression profiles and clinical features of 36 patients with CCA were analyzed to identify differentially expressed genes (DEGs). Subsequently, the coexpression of DEGs was determined by using the WGCNA method to investigate the correlations between pairs of genes. Network modules that were significantly correlated with clinical traits were identified. In total, 1478 mRNAs were found to be aberrantly expressed in CCA. Seven coexpression modules that significantly correlated with clinical characteristics were identified and assigned representative colors. Among the 7 modules, the green and blue modules were significantly related to tumor differentiation. Seventy-eight hub genes that were correlated with tumor differentiation were found in the green and blue modules. Survival analysis showed that 17 hub genes were prognostic biomarkers for CCA patients. In addition, we found five new targets (ISM1, SULT1B1, KIFC1, AURKB and CCNB1) that have not been studied in the context of CCA and verified their differential expression in CCA through experiments. Our results not only promote our understanding of the relationship between the transcriptome and clinical data in CCA but will also guide the development of targeted molecular therapy for CCA.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32965100

RESUMO

We characterize the magnetic interfacial coupling of the Fe/FeGe heterostructure and its influence on the magnetic damping via ferromagnetic resonance in the temperature range of 200-300 K. When the temperature is below the critical temperature of FeGe, the interfacial coupling rises. The strength of the magnetic interfacial coupling is determined as a function of the temperature and reaches up to 0.194 erg/cm2 at 200 K. Meanwhile, the Gilbert damping of the Fe layer is enhanced from 0.035 at 300 K to 0.050 at 200 K. The enhancement is linearly proportional to the strength of magnetic interfacial coupling. We attribute the enhancement to the interfacial coupling that transfers spin angular momentum from Fe to FeGe via the exchange interaction. Our results reveal that the interfacial coupling is an effective approach to inject spin current into the chiral spin texture.

7.
Ann Palliat Med ; 9(5): 3366-3372, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32921126

RESUMO

BACKGROUND: To analyze the relationship of serum ATPase activity and the levels of neuron-specific enolase (NSE), S100B protein and B-cell lymphoma/leukemia (Bcl)-2 with cognitive function in patients after epileptic seizure. METHODS: A total of 65 epilepsy patients were enrolled as the epilepsy group from the hospital between May 2017 and February 2019. A control group was formed by 30 healthy volunteers at the same period and in the same area whose basic data matched with those of the epileptic patients. Cognitive function was evaluated using the Montreal Cognitive Assessment Form (MoCA). Time and frequency of epileptic seizures were recorded in epileptic group. Within 6 hours following the attack, blood tests were carried out to measure the hydrolysis rates of serum adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), phosphodiesterase (PDE) activity, and levels of serum NSE, S100B and Bcl-2. The relationship of these indexes with the time of epileptic seizure and MoCA total score was analyzed. RESULTS: The epilepsy group included 18 cases (27.69%) with cognitive dysfunction. The time and frequency of epileptic seizure in the patients with cognitive dysfunction was significantly higher than that of patients without cognitive dysfunction, while the total MoCA score was significantly lower with cognitive dysfunction than that without (P<0.05). The total MoCA score of epileptic patients with and without cognitive dysfunction was significantly lower than that of the control group (P<0.05). The hydrolysis rates of ATP, ADP and AMP, PDE activity, and serum NES, S100B and Bcl-2 levels in patients with cognitive dysfunction were significantly higher than those without cognitive dysfunction (P<0.05). The above serum indexes of the patients were significantly higher than those of people in the control group (P<0.05). Spearman's correlation analysis showed that hydrolysis rates of serum ATP, ADP and AMP, PDE activity, and serum NES, S100B and Bcl-2 levels were positively correlated with time and frequency of epileptic seizure (P<0.05), and negatively correlated with total MoCA score (P<0.05). CONCLUSIONS: The cognitive function of epilepsy patients is significantly decreased compared with that of healthy individuals. Serum ATPase activity, along with serum NES, S100B and Bcl-2 levels, is associated with time and frequency of epileptic seizure and cognitive function after attack.

8.
Sensors (Basel) ; 20(18)2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32916857

RESUMO

Wireless sensor networks (WSNs) have been used in many fields due to its wide applicability. In this kind of network, each node is independent of each other and has its own local clock and communicates wirelessly. Time synchronization plays a vital role in WSNs and it can ensure accuracy requirements for coordination and data reliability. However, two key challenges exist in large-scale WSNs that are severe resource constraints overhead and multihop time synchronization errors. To address these issues, this paper proposes a novel unmanned aerial vehicle (UAV)-assisted low-consumption time synchronization algorithm based on cross-technology communication (CTC) for a large-scale WSN. This algorithm uses a UAV to send time synchronization data packets for calibration. Moreover, to ensure coverage and a high success rate for UAV data transmission, we use CTC for time synchronization. Without any relays, a high-power time synchronization packet can be sent by a UAV to achieve the time synchronization of low-power sensors. This algorithm can achieve accurate time synchronization with almost zero energy consumption for the sensor nodes. Finally, we implemented our algorithm with 30 low-power RF-CC2430 ZigBee nodes and a Da Jiang Innovations (DJI) M100 UAV on a 1 km highway and an indoor site. The results show that time synchronization can be achieved accurately with almost zero energy consumption for the sensor nodes, and the time synchronization error is less than 30 µs in 99% of cases.

9.
Clin Nucl Med ; 2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-32969907

RESUMO

A patient with multiple episodes of gastrointestinal bleeding underwent Tc-labeled red blood cell scintigraphy to detect the source of bleeding, which showed a focally increased activity in the upper midabdomen. SPECT/CT demonstrated that the activity was located in the pancreatic head. Angiography confirmed the diagnosis of pancreatic arteriovenous malformation. After transarterial embolization therapy, the patient no longer had bleeding episode. Based on the present case, pancreatic arteriovenous malformation should be included as differential diagnosis during Tc-red blood cell scintigraphy.

10.
Artigo em Inglês | MEDLINE | ID: mdl-32940029

RESUMO

Hexagonal boron nitride (hBN) and diamond are promising materials for next-generation electronics and optoelectronics. However, their combination is rarely reported. In this study, we for the first time demonstrate the success to direct growth of two-dimensional (2D) hBN crystal layers on diamond substrates by metalorganic vapor phase epitaxy. Compared with the disordered growth we found on diamond (100), atomic force microscopy, X-ray diffraction, and transmission electron microscopy results all support 2D hBN with highly oriented lattice formation on diamond (111). Also, the epitaxial relationship between hBN and diamond (111) substrate is revealed to be [0 0 0 1]hBN // [1 1 1]diamond and [1 0 1̅ 0]hBN // [1 1 2̅]diamond. The valence band offset at hBN/diamond (111) heterointerface determined by X-ray photoelectron spectroscopy is 1.4 ± 0.2 eV, thus yielding a conduction band offset of 1.0 ± 0.2 eV and type II staggered band alignment with a bandgap of 5.9 eV assumed for hBN. Furthermore, prior thermal cleaning of diamond in a pure H2 atmosphere smoothens the surface for well-ordered layered hBN epitaxy, while thermal cleaning in a mixed H2 and NH3 atmosphere etches the diamond surface, creating many small faceted pits that destroy the following epitaxy of hBN.

11.
Ecotoxicol Environ Saf ; 205: 111321, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32979800

RESUMO

Soil pollution with cadmium (Cd) has posed a threat to our food safety. And rice consumption is the main source of Cd intake in China. Rice intercropping with water spinach is an efficient way for crop production and phytoremediation in Cd-contaminated soil. However, few people work on the Cd remediation by a combination of the passivation and intercropping. In this study, two passivators (the Si-Ca-Mg ameliorant and the Fe-modified biochar with microbial inoculants) were used in the monoculture and intercropping systems to evaluate the potential of co-effect of passivators and cropping systems on the plant growth and Cd phytoremediation. Results showed that the highest rice biomass and rice yield were presented in the intercropping system with the passivator additions, however, relatively lower biomass was showed in water spinach due to the competition with rice. And more Cd accumulated in water spinach while lower Cd in that of different rice parts. The intercropping system with the addition of the Si-Ca-Mg ameliorant and the microbial Fe-modified biochar significantly reduced the Cd contents in brown rice by 58.86% and 63.83%, while notably enhanced the Cd accumulation of water spinach by 32.0% and 22.0%, compared with the monoculture without passivation, respectively. This probably due to the increased pH, the lowered Cd availability in soil, and the reduced TF and BCF values in rice plants with passivator applications. Collectively, this study indicated that rice-water spinach intercropping, especially with the passivator additions, may function as an effective way for Cd remediation and guarantee rice grain safety.

12.
Mol Genet Genomic Med ; : e1482, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32875744

RESUMO

BACKGROUND: Hemophilia B (HB) is an X-linked recessive inherited bleeding disorder caused by mutations in the F9 gene that lead to plasma factor IX deficiency. To identify the causative mutations in HB, a molecular analysis of HB pedigrees in China was performed. METHODS: Using next-generation sequencing (NGS) and an in-house bioinformatics pipeline, 76 unrelated HB pedigrees were analyzed. The mutations identified were validated by comparison with the results of Sanger sequencing or Multiplex Ligation-dependent Probe Amplification assays. The pathogenicity of the causative mutations was classified following the American College of Medical Genetics and Genomics guidelines. RESULTS: The mutation detection rate was 94.74% (72/76) using NGS. Of the 76 HB pedigrees analyzed, 59 causative variants were found in 72 pedigrees, with 38 (64.41%) missense mutations, 9 (15.25%) nonsense mutations, 2 (3.39%) splicing mutations, 5 (8.47%) small deletions, 4 (6.78%) large deletions, and 1 intronic mutation (1.69%). Of the 59 different F9 mutations, 10 were novel: c.190T>G, c.199G>T, c.290G>C, c.322T>A, c.350_351insACAATAATTCCTA, c.391+5delG, c.416G>T, c.618_627delAGCTGAAACC, c.863delA, and c.1024_1027delACGA. Of these 10 novel mutations, a mosaic mutation, c.199G>T(p.Glu67Ter), was identified in a sporadic HB pedigree. Using in-silico analysis, these novel variants were predicted to be disease-causing. However, no potentially causative mutations were found in the F9 coding sequences of the four remaining HB pedigrees. In addition, two HB pedigrees carrying additional F8/F9 mutations were discovered. CONCLUSION: The identification of these mutations enriches the spectrum of F9 mutations and provides further insights into the pathogenesis of HB in the Chinese population.

13.
Artigo em Inglês | MEDLINE | ID: mdl-32966212

RESUMO

Domain adaptation, which transfers the knowledge from label-rich source domain to unlabeled target domains, is a challenging task in machine learning. The prior domain adaptation methods focus on pairwise adaptation assumption with a single source and a single target domain, while little work concerns the scenario of one source domain and multiple target domains. Applying pairwise adaptation methods to this setting may be suboptimal, as they fail to consider the semantic association among multiple target domains. In this work we propose a deep semantic information propagation approach in the novel context of multiple unlabeled target domains and one labeled source domain. Our model aims to learn a unified subspace common for all domains with a heterogeneous graph attention network, where the transductive ability of the graph attention network can conduct semantic propagation of the related samples among multiple domains. In particular, the attention mechanism is applied to optimize the relationships of multiple domain samples for better semantic transfer. Then, the pseudo labels of the target domains predicted by the graph attention network are utilized to learn domain-invariant representations by aligning labeled source centroid and pseudo-labeled target centroid. We test our approach on four challenging public datasets, and it outperforms several popular domain adaptation methods.

14.
Clin Nucl Med ; 2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32910056

RESUMO

A 51-year-old woman with a history of sarcomatoid hepatocellular carcinoma, status post resection, underwent FDG PET/CT. In addition to abnormal activity elsewhere, the images showed focal activity in the isthmus of the thyroid, suggestive of malignant involvement, and diffuse mild activity in the left lobe of the thyroid, suggestive of thyroiditis. After a 10-week anti-PD-1 pembrolizumab therapy, the follow-up FDG PET/CT scan demonstrated much more intense activity in both the isthmus and the left lobe of the thyroid. Pathological examination revealed papillary thyroid cancer in the isthmus and thyroiditis in the left lobe of the thyroid.

15.
Sci Total Environ ; 751: 141734, 2020 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-32882555

RESUMO

We estimated associations between ambient air pollution, home environment and asthma as well as rhinitis among adults across China. A total of 40,279 young adults from eight Chinese cities participated in a questionnaire survey (participation rate 75%). There were questions on health and home environment. Information on city level gross domestic product (GDP) per capita, ambient temperature and PM10 and NO2 were collected from registers. Two-level logistic regression models were used to study health associations. Totally 1.6% reported asthma and 6.6% reported allergic rhinitis (AR). Higher temperature was associated with more asthma but less AR. Higher GDP was associated with less asthma but more AR. Higher degree of urbanization, higher level of NO2 and living near heavily trafficked road were risk factors for asthma and AR. Participants in older buildings reported more asthma. Redecoration and buying new furniture were related to more asthma and AR (OR = 1.15-1.91). Using natural gas (OR = 1.34) and biomass (OR = 1.35) for cooking were risk factors for AR. Burning mosquito coils and incense increased the risk of asthma and AR. Cat keeping (OR = 2.88), dog keeping (OR = 2.04), cockroaches (OR = 1.54) and rats or mice (OR = 1.46) were associated with asthma. Cockroaches increased the risk of AR (OR = 1.22). Air humidifier and air cleaner were linked to asthma and AR. Frequent cleaning and exposing bedding to sunshine were protective. In conclusion, urbanization, NO2 and traffic exhaust can increase the risk of adult asthma and AR. Higher ambient temperature was related to more asthma but less AR. Indoor animals such as cats, dogs, rats/mice and presence of cockroaches were associated with asthma or AR. Indoor chemical sources such as redecoration and new furniture were other risk factors. Cooking with natural gas or biomass and burning mosquito coils and incense were associated with asthma or AR. Frequent cleaning and exposing bedding to sunshine were protective.

16.
Artigo em Inglês | MEDLINE | ID: mdl-32924914

RESUMO

Two Gram-stain-negative, aerobic, non-motile bacterial strains, 36D10-4-7T and 30C10-4-7T, were isolated from bark canker tissue of Populus × euramericana, respectively. 16S rRNA gene sequence analysis revealed that strain 36D10-4-7T shows 98.0 % sequence similarity to Sphingomonas adhaesiva DSM 7418T, and strain 30C10-4-7T shows highest sequence similarity to Sphingobacterium arenae H-12T (95.6 %). Average nucleotide identity analysis indicates that strain 36D10-4-7T is a novel member different from recognized species in the genus Sphingomonas. The main fatty acids and respiratory quinone detected in strain 36D10-4-7T are C18 : 1 ω7c and/or C18 : 1 ω6c and Q-10, respectively. The polar lipids are diphosphatidylglycerol, phosphatidylcholine, phosphatidylglycerol, aminolipid, phosphatidylethanolamine, sphingoglycolipid, two uncharacterized phospholipids and two uncharacterized lipids. For strain 30C10-4-7T, the major fatty acids and menaquinone are iso-C15 : 0, C16 : 1 ω7c and/or C16 : 1 ω6c and iso-C17 : 0 3-OH and MK-7, respectively. The polar lipid profile includes phosphatidylethanolamine, phospholipids, two aminophospholipids and six unidentified lipids. Based on phenotypic and genotypic characteristics, these two strains represent two novel species within the genera Sphingomonas and Sphingobacterium. The name Sphingomonas corticis sp. nov. (type strain 36D10-4-7T=CFCC 13112T=KCTC 52799T) and Sphingobacterium corticibacterium sp. nov. (type strain 30C10-4-7T=CFCC 13069T=KCTC 52797T) are proposed.

17.
World J Gastroenterol ; 26(30): 4465-4478, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32874058

RESUMO

BACKGROUND: Lenvatinib has become an indispensable part of treatment regimens for patients with advanced hepatocellular carcinoma (aHCC). Several recent real-world studies appear to have confirmed this; however, there are etiological differences. This necessitates further real-world studies of lenvatinib across diverse populations, such as in China. AIM: To investigate the efficacy and safety of lenvatinib in a Chinese HCC patient population under real-world conditions. METHODS: This is a retrospective and multiregional study involving patients with aHCC receiving lenvatinib monotherapy. Efficacy was assessed using the Response Evaluation Criteria in Solid Tumors version 1.1. Baseline characteristics and adverse events (AEs) were recorded throughout the entire study. RESULTS: In total, 54 HCC patients treated with lenvatinib monotherapy were included for final analysis. The objective response rate was 22% (n = 12) with a progression-free survival (PFS) of 168 d; however, AEs occurred in 92.8% of patients. Multivariate analysis showed that the Barcelona Clinic Liver Cancer stage [hazard ratio (HR) 0.465; 95%CI: 0.23-0.93; P = 0.031], portal vein tumor thrombus (HR 0.38; 95%CI: 0.15-0.94; P = 0.037) and Child-Pugh classifications (HR 0.468; 95%CI: 0.22-0.97; P = 0.042) were significant factors affecting PFS. The sensitivity (56.7%) and specificity (83.3%) of decreasing serum biomarkers including alpha-fetoprotein were calculated in order to predict tumor size reduction. Gene sequencing also provided insights into potential gene mutation signatures related to the effect of lenvatinib. CONCLUSION: Our findings confirm previous evidence from the phase III REFLECT study. The majority of patients in this Chinese sample were suffering from concomitant hepatitis B virus-related HCC. However, further analysis suggested that baseline characteristics, changes in serum biomarkers and gene sequencing may hold the key for predicting lenvatinib responses. Further large-scale prospective studies that incorporate more basic medical science measures should be conducted.

18.
BMC Genomics ; 21(1): 643, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32948145

RESUMO

BACKGROUND: Histone deacetylases (HDACs) catalyze histone deacetylation and suppress gene transcription during various cellular processes. Within the superfamily of HDACs, RPD3/HDA1-type HDACs are the most studied, and it is reported that RPD3 genes play crucial roles in plant growth and physiological processes. However, there is a lack of systematic research on the RPD3/HDA1 gene family in cotton. RESULTS: In this study, genome-wide analysis identified 9, 9, 18, and 18 RPD3 genes in Gossypium raimondii, G. arboreum, G. hirsutum, and G. barbadense, respectively. This gene family was divided into 4 subfamilies through phylogenetic analysis. The exon-intron structure and conserved motif analysis revealed high conservation in each branch of the cotton RPD3 genes. Collinearity analysis indicated that segmental duplication was the primary driving force during the expansion of the RPD3 gene family in cotton. There was at least one presumed cis-element related to plant hormones in the promoter regions of all GhRPD3 genes, especially MeJA- and ABA-responsive elements, which have more members than other hormone-relevant elements. The expression patterns showed that most GhRPD3 genes had relatively high expression levels in floral organs and performed higher expression in early-maturity cotton compared with late-maturity cotton during flower bud differentiation. In addition, the expression of GhRPD3 genes could be significantly induced by one or more abiotic stresses as well as exogenous application of MeJA or ABA. CONCLUSIONS: Our findings reveal that GhRPD3 genes may be involved in flower bud differentiation and resistance to abiotic stresses, which provides a basis for further functional verification of GhRPD3 genes in cotton development and a foundation for breeding better early-maturity cotton cultivars in the future.

19.
Mol Ther Nucleic Acids ; 22: 153-165, 2020 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-32927364

RESUMO

Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated cancer characterized by a high degree of recurrence, angiogenesis, and metastasis. The importance of alternative pro-angiogenesis pathways including viral factors has emerged after decades of directly targeting various signaling components. Using NPC as a model, we identified an essential oncogenic pathway underlying angiogenesis regulation that involves the inhibition of a tumor suppressor, Spry3, and its downstream targets by EBV-miR-BART10-5p (BART10-5p) and hsa-miR-18a (miR-18a). Overexpression of EBV-miR-BART10-5p and hsa-miR-18a strongly promotes angiogenesis in vitro and in vivo by regulating the expression of VEGF and HIF1-α in a Spry3-dependent manner. In vitro or in vivo treatment with iRGD-tagged exosomes containing antagomiR-BART10-5p and antagomiR-18a preferentially suppressed the angiogenesis and growth of NPC. Our findings first highlight the role of EBV-miR-BART10-5p and oncogenic hsa-miR-18a in NPC angiogenesis and also shed new insights into the clinical intervention and therapeutic strategies for nasopharyngeal carcinoma and other virus-associated tumors.

20.
Mater Sci Eng C Mater Biol Appl ; 114: 111027, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32994012

RESUMO

BACKGROUND AND PURPOSE: New capillaries are essential for deep tissue pressure injury wound healing. Tazarotene is a recently discovered small molecule drug and functions to promote neovascularization and tissue repair. At present, the application of tazarotene in the repair of pressure injuries has not previously been investigated. This study used poly (lactic-co-glycolic acid) (PLGA) as nanoparticle carriers loaded with tazarotene (Ta/PLGA NPs) for drug delivery and to overcome shortcomings associated with the low water solubility, short half-life, easy photolysis and low bioavailability of tazarotene itself. METHODS: The physicochemical properties, drug release and bioactivity of Ta/PLGA NPs were examined in vitro by transmission electron microscope, spectrophotometry and cell assays. Mouse models of deep tissue pressure injuries (DTPI) were established and the therapeutic effects and mechanisms of Ta/PLGA NPs in local wound repair were studied. RESULTS: The results showed that Ta/PLGA NPs were of uniform size and distribution and were non-toxic both in vitro and in vivo. In vivo experiments suggested that Ta/PLGA NPs significantly promoted DTPI wound repair through activation of the VEGF/VEGFR-Notch1/DLL4 signaling pathway. CONCLUSION: This study highlights the potential clinical significance of implementation of tazarotene small molecule drugs in combination with effective biomaterial carriers for the treatment of chronic refractory wounds, such as DTPI.

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