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1.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 32(1): 50-55, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-32148231

RESUMO

OBJECTIVE: To estimate the predictive performance of the population pharmacokinetics software JPKD-vancomycin on predicting the vancomycin steady-state trough concentration, and to analyze the related factors affecting the predictive performance. METHODS: The clinical data of patients who were treated with vancomycin and received therapeutic drug monitoring (TDM) admitted to Suzhou Hospital Affiliated to Nanjing Medical University from July 2013 to December 2018 were enrolled. All patients were designed an empirical vancomycin regimen (initial regimen) according to vancomycin medication guidelines. Steady-state trough concentrations of vancomycin were determined at 48 hours after the first dose and 0.5 hour before the next dose. Dosage regimen was adjusted when steady-state trough concentration was not in 10-20 mg/L (adjustment regimen), and then the steady-state trough concentration was determined again 48 hours after adjustment. First, the JPKD-vancomycin software was used to calculate the initial regimen and predict the steady-state trough concentration according to the results calculated by classic pharmacokinetic software Vancomycin Calculator. Second, the JPKD-vancomycin software was used to adjust the vancomycin dosage regime and predict the steady-state trough concentration of adjustment regimen. The weight residual (WRES) between the predicted steady-state trough concentration (Cpre) and the measured steady-state trough concentration (Creal) was used to evaluate the ability of the JPKD-vancomycin software for predicting the vancomycin steady-state trough concentration. The TDM results of initial regimen were divided into accurate prediction group (WRES < 30%) and the inaccurate prediction group (WRES ≥ 30%) according to the WRES value. Patient and disease characteristics including gender, age, weight, height, the length of hospital stay, comorbidities, vasoactive agent, mechanical ventilation, smoking history, postoperative, obstetric patients, trauma, laboratory indicators, vancomycin therapy and TDM results were collected from electronic medical records. Univariate and multivariate Logistic regression analysis was used to screen the related factors that influence the predictive performance of JPKD-vancomycin software, and the receiver operating characteristic (ROC) curve was drawn to evaluate its predictive value. RESULTS: A total of 310 patients were enrolled, and 467 steady-state trough concentrations of vancomycin were collected, including 310 concentrations of initial regimen and 157 concentrations of adjustment regimen. Compared with the initial regimen, the WRES of adjusted regimen was significantly reduced [14.84 (6.05,22.89)% vs. 20.41 (11.06,45.76)%, P < 0.01], and the proportion of WRES < 30% increased significantly [82.80% (130/157) vs. 63.87% (198/310), P < 0.01]. These results indicated that JPKD-vancomycin software had a better accuracy prediction for steady-state trough concentration of the adjusted regimen than the initial regimen. There were 198 concentrations in the accurate prediction group and 112 in the inaccurate prediction group. Univariate Logistic regression analysis showed that women [odds ratio (OR) = 0.466, 95% confidence interval (95%CI) was 0.290-0.746, P = 0.002], low body weight (OR = 0.974, 95%CI was 0.953-0.996, P = 0.022), short height (OR = 0.963, 95%CI was 0.935-0.992, P = 0.014), low vancomycin clearance (CLVan; OR < 0.001, 95%CI was 0.000-0.231, P = 0.023) and postoperative patients (OR = 1.695, 95%CI was 1.063-2.702, P = 0.027) were related factors affecting the predictive performance of JPKD-vancomycin software. Multivariate Logistic regression analysis indicated that women (OR = 0.449, 95%CI was 0.205-0.986, P = 0.046), low CLVan (OR < 0.001, 95%CI was 0.000-0.081, P = 0.015) and postoperative patients (OR = 2.493, 95%CI was 1.455-4.272, P = 0.001) were independent risk factors for inaccurate prediction of JPKD-vancomycin software. The ROC analysis indicated that the area under ROC curve (AUC) of the CLVan for evaluating the accuracy of JPKD-vancomycin software in predicting vancomycin steady-state trough concentration was 0.571, the sensitivity was 56.3%, and the specificity was 57.1%. The predictive performance of JPKD-vancomycin software was decreased when CLVan was lower than 0.065 L×h-1×kg-1. CONCLUSIONS: JPKD-vancomycin software had a better predictive performance for the vancomycin steady-state trough concentrations of adjustment regimen than initial regimen. JPKD-vancomycin software had a poor predictive performance when the patient was female, having low CLVan, and was postoperative. The predictive performance of JPKD-vancomycin software was decreased when CLVan was lower than 0.065 L×h-1×kg-1.

2.
Int J Mol Sci ; 21(5)2020 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-32156004

RESUMO

High-dose dexamethasone (DEX) is used to treat chemotherapy-induced nausea and vomiting or to control immunotherapy-related autoimmune diseases in clinical practice. However, the underlying mechanisms of high-dose DEX in tumor progression remain unaddressed. Therefore, we explored the effects of high-dose DEX on tumor progression and the potential mechanisms of its anti-tumor function using immunohistochemistry, histological examination, real-time quantitative PCR (qPCR), and Western blotting. Tumor volume, blood vessel invasion, and levels of the cell proliferation markers Ki67 and c-Myc and the anti-apoptotic marker Bcl2 decreased in response to high-dose DEX. However, the cell apoptosis marker cleaved caspase 3 increased significantly in mice treated with 50 mg/kg DEX compared with controls. Some genes associated with immune responses were significantly downregulated following treatment with 50 mg/kg DEX e.g., Cxcl9, Cxcl10, Cd3e, Gzmb, Ifng, Foxp3, S100a9, Arg1, and Mrc1. In contrast, the M1-like tumor-associated macrophages (TAMs) activation marker Nos2 was shown to be increased. Moreover, the expression of peroxisome proliferator-activated receptors α and γ (Pparα and Pparg, respectively) was shown to be significantly upregulated in livers or tumors treated with DEX. However, high-dose DEX treatment decreased the expression of glucose and lipid metabolic pathway-related genes such as glycolysis-associated genes (Glut1, Hk2, Pgk1, Idh3a), triglyceride (TG) synthesis genes (Gpam, Agpat2, Dgat1), exogenous free fatty acid (FFA) uptake-related genes (Fabp1, Slc27a4, and CD36), and fatty acid oxidation (FAO) genes (Acadm, Acaa1, Cpt1a, Pnpla2). In addition, increased serum glucose and decreased serum TG and non-esterified fatty acid (NEFA) were observed in DEX treated-xenografted tumor mice. These findings indicate that high-dose DEX-inhibited tumor progression is a complicated process, not only activated by M1-like TAMs, but also decreased by the uptake and consumption of glucose and lipids that block the raw material and energy supply of cancer cells. Activated M1-like TAMs and inefficient glucose and lipid metabolism delayed tumor cell growth and promoted apoptosis. These findings have important implications for the application of DEX combined with drugs that target key metabolism pathways for tumor therapy in clinical practice.

3.
Brain Behav Immun ; 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32169498

RESUMO

Since December 2019, more than 79,000 people have been diagnosed with infection of the Corona Virus Disease 2019 (COVID-19). A large number of medical staff was sent to Wuhan city and Hubei province to aid COVID-19 control. Psychological stress, especially vicarious traumatization caused by the COVID-19 pandemic, should not be ignored. To address this concern, the study employed a total of 214 general public and 526 nurses (i.e., 234 front-line nurses and 292 non-front-line nurses) to evaluate vicarious traumatization scores via a mobile app-based questionnaire. Front-line nurses are engaged in the process of providing care for patients with COVID-19. The results showed that the vicarious traumatization scores for front-line nurses including scores for physiological and psychological responses, were significantly lower than those of non-front-line nurses (P < 0.001). Interestingly, the vicarious traumatization scores of the general public were significantly higher than those of the front-line nurses (P < 0.001); however, no statistical difference was observed compared to the scores of non-front-line nurses (P > 0.05). Therefore, increased attention should be paid to the psychological problems of the medical staff, especially non-front-line nurses, and general public under the situation of the spread and control of COVID-19. Early strategies that aim to prevent and treat vicarious traumatization in medical staff and general public are extremely necessary.

4.
Sci Total Environ ; 722: 137428, 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32197168

RESUMO

Soda saline-alkali soils are characterized by high concentration of sodium cations on the exchange complex or in soil-water resulting in soils which are physically as well as nutritionally challenging for crop production. Biochar application has received growing interest as a sustainable technology to improve physicochemical properties in non-saline and non-alkali soils. However, information is inadequate regarding potential of using corn straw derived biochar as an organic material to reduce soda saline-alkali stress. Based on the established model of corn straw biochar-soda saline alkali soil-corn system, soil and plant samples were collected from long-term field experiment in soda saline-alkali land with different addition rates of corn straw biochar (CK: control, T5: 5 ton ha-1, T10: 10 ton ha-1, T15: 15 ton ha-1, T20: 20 ton ha-1, T25: 25 ton ha-1, T30: 30 ton ha-1). In the seedling and harvest period, addition of corn straw biochar enhanced the contents of cation exchange capacity (CEC), organic matter, and nutrients of 0-20 cm and 20-40 cm saline-alkali soil layers and the above ground and underground parts of corn. However, the results were contrary as far as pH, salt, and Na+ were concerned, and the effect of T20 was the most significant. Principal component analysis showed that CEC, pH, salinity, and organic matter could be used as indicators to evaluate the improvement effect of biochar on soda saline-alkali soil. Irrespective of the application of biochar, pH, salt content, Na+, and nutrients concentrations at seedling stage were higher than those at harvest stage, indicating that planting corn could improve soda saline-alkali soil. It may be concluded that corn straw biochar can be used as an organic amendment for reducing adverse effects of salinity and alkalinity on soil functions governed by their rates of addition.

5.
Mediators Inflamm ; 2020: 8098439, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32184702

RESUMO

Neuroinflammation contributes to or even causes central nervous system (CNS) diseases, and its regulation is thus crucial for brain disorders. Mast cells (MCs) and microglia, two resident immune cells in the brain, together with astrocytes, play critical roles in the progression of neuroinflammation-related diseases. MCs have been demonstrated as one of the fastest responders, and they release prestored and newly synthesized mediators including histamine, ß-tryptase, and heparin. However, temporal changes in MC activation in this inflammation process remain unclear. This study demonstrated that MC activation began at 2 h and peaked at 4 h after lipopolysaccharide (LPS) administration. The number of activated MCs remained elevated until 24 h after LPS administration. In addition, the levels of histamine and ß-tryptase in the hippocampus markedly and rapidly increased within 6 h and remained higher than the baseline level within 24 h after LPS challenge. Furthermore, mast cell-deficient KitW-sh/W-sh mice were used to investigate the effects of MCs on microglial and astrocytic activation and blood-brain barrier (BBB) permeability at 4 h after LPS stimulation. Notably, LPS-induced proinflammatory cytokine secretion, microglial activation, and BBB damage were inhibited in KitW-sh/W-sh mice. However, no detectable astrocytic changes were found in WT and KitW-sh/W-sh mice at 4 h after LPS stimulation. Our findings indicate that MC activation precedes CNS inflammation and suggest that MCs are among the earliest participants in the neuroinflammation-initiating events.

6.
Sci Rep ; 10(1): 1817, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32019948

RESUMO

Mesenchymal stem cells (MSCs) specifically differentiate into cardiomyocytes as a potential way to reverse myocardial injury diseases, and uncovering this differentiation mechanism is immensely important. We have previously shown that histone acetylation/methylation and DNA methylation are involved in MSC differentiation into cardiomyocytes induced by islet-1. These modifications regulate cardiac-specific genes by interacting with each other in the promoter regions of these genes, but the molecular mechanism of these interactions remains unknown. In this study, we found that the key enzymes that regulate GATA4/Nkx2.5 expression are Gcn5/HDAC1, G9A, and DNMT-1. When α-methylene-γ-butyrolactone 3 (MB-3) was used to inhibit Gcn5 expression, we observed that the interactions among these key enzymes in the GATA4/Nkx2.5 promoters were blocked, and MSCs could not be induced into cardiomyocytes. Our results indicated that islet-1 could induce Gcn5 binding to GATA4/Nkx2.5 promoter regions and induce the interactions among Gcn5, HDAC1, G9A and DNMT-1, which upregulated GATA4/Nkx2.5 expression and promoted MSC differentiation into cardiomyocytes.

7.
Mol Plant ; 13(3): 483-498, 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32017999

RESUMO

In response to competition for light from their neighbors, shade-intolerant plants flower precociously to ensure reproductive success and survival. However, the molecular mechanisms underlying this key developmental switch are not well understood. Here, we show that a pair of Arabidopsis transcription factors essential for phytochrome A signaling, FAR-RED ELONGATED HYPOCOTYL3 (FHY3) and FAR-RED IMPAIRED RESPONSE1 (FAR1), regulate flowering time by integrating environmental light signals with the miR156-SPL module-mediated aging pathway. We found that FHY3 and FAR1 directly interact with three flowering-promoting SQUAMOSA-PROMOTER BINDING PROTEIN-LIKE (SPL) transcription factors, SPL3, SPL4, and SPL5, and inhibit their binding to the promoters of several key flowering regulatory genes, including FRUITFUL (FUL), LEAFY (LFY), APETALA1 (AP1), and MIR172C, thus downregulating their transcript levels and delaying flowering. Under simulated shade conditions, levels of SPL3/4/5 proteins increase, whereas levels of FHY3 and FAR1 proteins decline, thus releasing SPL3/4/5 from FHY3/FAR1 inhibition to allow activation of FUL, LFY, AP1, and MIR172C and, consequently, early flowering. Taken together, these results unravel a novel mechanism whereby plants regulate flowering time by integrating environmental cues (such as light conditions) and an internal developmental program (the miR156-SPL module-mediated aging pathway).

8.
Environ Pollut ; 259: 113901, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32023788

RESUMO

Soil antibiotic resistome and the nitrogen cycle are affected by florfenicol addition to manured soils but their interactions have not been fully described. In the present study, antibiotic resistance genes (ARGs) and nitrogen cycle genes possessed by soil bacteria were characterized using real-time fluorescence quantification PCR (qPCR) and metagenomic sequencing in a short-term (30 d) soil model experiment. Florfenicol significantly changed in the abundance of genes conferring resistance to aminoglycosides, ß-lactams, tetracyclines and macrolides. And the abundance of Sphingomonadaceae, the protein metabolic and nitrogen metabolic functions, as well as NO reductase, nitrate reductase, nitrite reductase and N2O reductase can also be affected by florfenicol. In this way, ARG types of genes conferring resistance to aminoglycosides, ß-lactamases, tetracyclines, colistin, fosfomycin, phenicols and trimethoprim were closely associated with multiple nitrogen cycle genes. Actinobacteria, Chlorobi, Firmicutes, Gemmatimonadetes, Nitrospirae, Proteobacteria and Verrucomicrobia played an important role in spreading of ARGs. Moreover, soil physicochemical properties were important factors affecting the distribution of soil flora. This study provides a theoretical basis for further exploration of the transmission regularity and interference mechanism of ARGs in soil bacteria responsible for nitrogen cycle.

9.
Food Funct ; 11(2): 1869-1880, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32068229

RESUMO

This study aimed to quantify the short-chain fatty acids (SCFAs) and medium-chain fatty acids (MCFAs) in human milk triacylglycerols (TAGs) and investigate their concentrations in human milk consumed during lactation by infants born at different gestational ages. One hundred and eighty milk samples from the mothers of 30 full-term, 10 early-preterm (≤32 weeks), 10 mild-preterm (32-34 weeks), and 10 near-term (34-37 weeks) infants were collected from the colostrum, transitional, and mature milk. The human milk TAGs were transferred into fatty-acid methyl esters via potassium methoxide in methanol and determined using gas chromatography (GC). The total SCFA (4:0) and MCFA concentrations (6:0 and 8:0) were highest in the mature milk (1.47 ± 0.66 mg g-1 fat from full-term infant milk), approximately 42.18% higher than those in transitional milk. Significantly higher SCFA and MCFA concentrations were found in full-term milk than in preterm milk (p = 0.001). The milk TAGs were analyzed using ultra-high-performance supercritical fluid chromatography with quadrupole-time-of-flight mass spectrometry (UHPSFC-Q-TOF-MS), which showed that the SCFAs and MCFAs were mainly esterified with long-chain fatty-acid groups (16:0, 18:1 n-9, and 18:2 n-6) at the glycerol backbone. The infants' daily SCFA intake from human milk was estimated; this was highest from mature milk for full-term infants (∼14 mg d-1) which was significantly different from that of preterm infants from colostrum and transitional milk (p < 0.001). The correlation between dietary SCFAs and MCFAs in human milk and nutrition in newborns, especially in the gut microbiotas of preterm infants, requires further study.

10.
J Agric Food Chem ; 2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32073852

RESUMO

Interactions between gluten proteins and water-extractable arabinoxylan (WEAX) during the heating stage are crucial for the organoleptic quality of high-fiber cereal products. To reveal the molecular mechanism of WEAX on gluten characteristic upon heating, the current study comparatively investigated the effects of WEAX with different molecular weights (Mw) on the heat-evoked conformational variation and polymerization behavior of gluten. Results showed that WEAX, especially low Mw WEAX (L-WEAX), facilitated the polymerization ability of α-/γ-gliadins into glutenins, whereas high Mw WEAX (H-WEAX) reduced the polymerizing temperature of glutenin and gliadin. L-WEAX could develop more hydrogen bonds with tyrosine of gluten and stabilize the secondary structure more evidently than H-WEAX upon heating. Compared with disulfide bridge formation, hydrophobic interactions were not the driving force involved in the heat-induced polymerization behavior affected by WEAX. WEAX evoked the reinforced glutenin network and heterogeneous distribution of gliadin, with a more uniform molecular surface developed for gluten.

11.
Cancer Discov ; 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31924700

RESUMO

AKT inhibitors have promising activity in AKT1 E17K-mutant estrogen receptor (ER)-positive metastatic breast cancer, but the natural history of this rare genomic subtype remains unknown. Utilizing AACR Project GENIE, an international clinicogenomic data-sharing consortium, we conducted a comparative analysis of clinical outcomes of patients with matched AKT1 E17K-mutant (n = 153) and AKT1-wild-type (n = 302) metastatic breast cancer. AKT1-mutant cases had similar adjusted overall survival (OS) compared with AKT1-wild-type controls (median OS, 24.1 vs. 29.9, respectively; P = 0.98). AKT1-mutant cases enjoyed longer durations on mTOR inhibitor therapy, an observation previously unrecognized in pivotal clinical trials due to the rarity of this alteration. Other baseline clinicopathologic features, as well as durations on other classes of therapy, were broadly similar. In summary, we demonstrate the feasibility of using a novel and publicly accessible clincogenomic registry to define outcomes in a rare genomically defined cancer subtype, an approach with broad applicability to precision oncology. SIGNIFICANCE: We delineate the natural history of a rare genomically distinct cancer, AKT1 E17K-mutant ER-positive breast cancer, using a publicly accessible registry of real-world patient data, thereby illustrating the potential to inform drug registration through synthetic control data.See related commentary by Castellanos and Baxi, p. 490.

12.
Gynecol Oncol ; 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31959492

RESUMO

OBJECTIVE: We assessed the safety and maximum tolerated dose (MTD) of the poly ADP-ribose polymerase (PARP) inhibitor olaparib with intravenous (IV)/intraperitoneal (IP) cisplatin/paclitaxel and IV bevacizumab, followed by olaparib and bevacizumab maintenance, in patients with newly diagnosed ovarian cancer who had undergone primary debulking surgery. METHODS: Treatment included: (Cycles 1-6) Day 1, IV paclitaxel 135 mg/m2/3 h + (from Cycle 2 onward) bevacizumab 15 mg/kg; Day 2, IP cisplatin 75 mg/m2; Days 2-8, olaparib (50/100/200 mg BID); Day 8, IP paclitaxel 60 mg/m2 of a 21-day cycle. Maintenance (Cycles 7-22) included: olaparib 300 mg BID and bevacizumab 15 mg/kg Day 1. The primary endpoint was MTD of olaparib, chemotherapy, and bevacizumab. RESULTS: Seventeen women were treated (Cohort 1 [50 mg olaparib], 8 patients; Cohort 2 [100 mg], 3 patients; and Cohort 3 [200 mg], 6 patients). Median age was 57 years (47-73); 94% had stage III disease; 29% had a germline BRCA mutation. Two of 6 patients in Cohort 3 experienced a dose-limiting toxicity (DLT). Grade 3/4 toxicities included: neutropenia (56%), lymphopenia (31%), anemia (25%), and fatigue (19%). Most patients started (88%, 81%) and completed (75%, 50%) maintenance olaparib and bevacizumab, respectively; 36% of patients on olaparib maintenance required a dose reduction. Median PFS was 33 months (26.2-NA). CONCLUSIONS: The MTD of intermittently dosed olaparib with concurrent IV/IP cisplatin/paclitaxel and bevacizumab is 100 mg BID. Non-hematologic toxicities were predominantly low grade. One-third of patients on olaparib maintenance required dose reduction.

13.
Cancer Sci ; 111(3): 857-868, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31930596

RESUMO

Increasing evidence indicates that extracellular vesicles (EVs) play an important role in cancer cell-to-cell communication. The Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1), which is closely associated with nasopharyngeal carcinoma (NPC) pathogenesis, can trigger multiple cell signaling pathways that affect cell progression. Several reports have shown that LMP1 promotes EV secretion, and LMP1 trafficking by EVs can enhances cancer progression and metastasis. However, the molecular mechanism by which LMP1 promotes EV secretion is not well understood. In the present study, we found that LMP1 promotes EV secretion by upregulated syndecan-2 (SDC2) and synaptotagmin-like-4 (SYTL4) through nuclear factor (NF)-κB signaling in NPC cells. Further study indicated that SDC2 interacted with syntenin, which promoted the formation of the EVs, and SYTL4 is associated with the release of EVs. Moreover, we found that stimulation of EV secretion by LMP1 can enhance the proliferation and invasion ability of recipient NPC cells and tumor growth in vivo. In summary, we found a new mechanism by which LMP1 upregulates SDC2 and SYTL4 through NF-κB signaling to promote EV secretion, and further enhance cancer progression of NPC.


Assuntos
Vesículas Extracelulares/metabolismo , Herpesvirus Humano 4/metabolismo , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Sindecana-2/metabolismo , Proteínas de Transporte Vesicular/metabolismo , Proteínas da Matriz Viral/metabolismo , Animais , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Feminino , Regulação Neoplásica da Expressão Gênica/fisiologia , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , NF-kappa B/metabolismo , Transdução de Sinais/fisiologia , Regulação para Cima/fisiologia
14.
J Prosthet Dent ; 123(2): 290.e1-290.e8, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31902534

RESUMO

STATEMENT OF PROBLEM: The adhesion properties of modified cement-retained implant prostheses have not been elucidated. PURPOSE: The purpose of this in vitro study was to compare the adhesion strength and the flow conditions of the adhesives of 3 common modified cement-retained methods (MCRMs). MATERIAL AND METHODS: Four cement-retained methods were used: an occlusal hole for screw access (OH), a lingual hole for releasing the excess adhesive (LH), a resin replica for the titanium abutment (RR), and a control group (no holes and no resin trial abutments). Eight zirconia prostheses in each group were processed and cemented. The adhesion strength was examined by mechanical tensile experiments (MTE) in vitro. One-way ANOVA and the LSD post hoc tests were used to compare the results of the MTE (α=.05). The flow conditions of adhesives in the adhesion process were analyzed by computational fluid dynamics (CFD). CFD-Post 16.0 (ANSYS, Inc) was used to analyze the results of the CFD analyses. RESULTS: The adhesion strength of each group was 289.3 ±37.7 N in the LH group, 281.3 ±50.1 N in the OH group, 263.3 ±49.3 N in the RR group, and 239.2 ±29.4 N in the control group. A statistically significant difference is seen in the adhesion strength between the LH group and the control group (P=.025). The internal filling ratio of adhesives between the groups ranges from high to low in the order the LH group, the OH group, the RR group, and the control group. The amount of cervical overflow of adhesives between the groups ranges from less to more in the order the RR group, the OH group, the LH group, and the control group. CONCLUSIONS: MCRMs can effectively reduce the amount of cervical overflow of adhesives and improve the filling condition of the adhesive and its clearance to ensure the adhesion strength of the prostheses.


Assuntos
Dente Suporte , Implantes Dentários , Cimentos Dentários , Prótese Dentária Fixada por Implante , Análise do Estresse Dentário , Hidrodinâmica , Teste de Materiais , Resistência à Tração
15.
Sci Adv ; 6(1): eaax5819, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31911943

RESUMO

Autophagy is an evolutionarily conserved catabolic process, which plays a vital role in removing misfolded proteins and clearing damaged organelles to maintain internal environment homeostasis. Here, we uncovered the checkpoint kinase 2 (CHK2)-FOXK (FOXK1 and FOXK2) axis playing an important role in DNA damage-mediated autophagy at the transcriptional regulation layer. Mechanistically, following DNA damage, CHK2 phosphorylates FOXK and creates a 14-3-3γ binding site, which, in turn, traps FOXK proteins in the cytoplasm. Because FOXK functions as the transcription suppressor of ATGs, DNA damage-mediated FOXKs' cytoplasmic trapping induces autophagy. In addition, we found that a cancer-derived FOXK mutation induces FOXK hyperphosphorylation and enhances autophagy, resulting in chemoresistance. Cotreatment with cisplatin and chloroquine overcomes the chemoresistance caused by FOXK mutation. Overall, our study highlights a mechanism whereby DNA damage triggers autophagy by increasing autophagy genes via CHK2-FOXK-mediated transcriptional control, and misregulation of this pathway contributes to chemoresistance.

16.
Cancer Lett ; 473: 62-73, 2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-31904479

RESUMO

Several studies have indicated that cancer-associated fibroblasts (CAFs) could promote cancer progression in many malignancies. However, the mechanism by which CAFs promote the growth and metastasis of lung cancer remains poorly defined. In the present study, CAFs and normal fibroblasts (NFs) were isolated from human lung cancer and adjacent tissue. The data showed that the conditional medium (CM) of CAFs could increase the proliferation, migration and invasion of lung cancer cells. Vascular cell adhesion molecule-1 (VCAM-1) showed a higher expression in CAF-CM than NF-CM, and blocking VCAM-1 in CAF-CM attenuated the proliferation and invasion of cancer cells. Further, the results showed that VCAM-1 secreted from CAFs activated AKT and MAPK signaling via receptor α4ß1 integrin (very-late antigen (VLA)-4) in lung cancer cells. Moreover, CAFs promoted VCAM-1 expression and tumor growth in vivo. Additionally, bioinformatics analysis indicated a positive correlation on the CAF marker protein alpha-smooth muscle actin (α-SMA) and VCAM-1 expression, which was associated with a poor prognosis in lung cancer patients. These findings demonstrate that the VCAM-1 secreted from CAFs enhances growth and invasion by activating the AKT and MAPK signaling of lung cancer cells.

17.
Int Immunopharmacol ; 80: 106208, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31955065

RESUMO

As a natural flavonoid compound, baicalin(BA)has been reported to exhibit hepatoprotective and anti-inflammatory properties. However, the characteristic of poor solubility and low bioavailability greatly limits its application. In addition, the effects and underlying mechanisms of BA in nonalcoholic fatty liver disease (NAFLD) remain elusive. In this study, Methionine and choline deficient diet (MCD)-induced NAFLD mice were treated with baicalin or baicalin-loaded nanoliposomes (BA-NL), then hepatic histopathological changes, biochemical parameters and inflammatory molecules were observed. We found that mice in MCD group showed significant increases in plasma transaminase, hepatocyte apoptosis, hepatic lipid accumulation, liver fibrosis, and infiltration of neutrophils and macrophages compared with control group, however, BA and BA-NL markedly attenuated MCD-induced the above changes. Besides, further analysis indicated that BA and BA-NL also inhibited the up-regulation of toll-like receptor 4 (TLR4) signal and the production of inflammatory mediators in MCD mice. Importantly, BA-NL was found to be more effective than baicalin on MCD-induced NAFLD in mice. These data suggested that BA and its nanoliposomes BA-NL could effectively protect mice against MCD-induced NAFLD, which might be mediated through inhibiting TLR4 signaling cascade.

18.
Nanotechnology ; 31(12): 125704, 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-31775124

RESUMO

Molecular dynamics simulations are used to study the formation and development of interlayer dislocations in bilayer graphene (BLG) subjected to uniaxial tension. Two different BLGs are employed for the simulation: armchair (AC-BLG) and zigzag (ZZ-BLG). The atomic-level strains are calculated and the parameter 'dislocation intensity' is introduced to identify the dislocations. The interlayer dislocation is found to start at the edge and propagate to the center. For AC-BLG, the dislocations arise successively with the increase of applied strain, and all dislocations have the same width. For ZZ-BLG, the first dislocation arises alone. After that, two dislocations with different widths appear together every time. The simulated dislocation widths are in good agreement with existing experimental results. Across every dislocation, there is a transition from AB stacking to AC stacking, or vice versa. When temperature is taken into account, the dislocation boundaries become indistinct and the formation of dislocations is postponed due to the existence of dispersive small slippages. Due to the disturbance of temperature, dislocations present reciprocating movement. These findings contribute to the understanding of interlayer dislocations in two-dimensional materials, and will enable the exploration of many more strain related fundamental science problems and application challenges.

19.
J Clin Lab Anal ; 34(2): e23035, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31568605

RESUMO

BACKGROUND: Non-invasive prenatal testing (NIPT) is routinely used in clinical practice for fetal trisomy screening, but low total cfDNA content and low fetal fraction (LFF) are two factors that affect the detection rate. Samples with low total cfDNA or LFF usually end up with "no-call" results, followed by the blood redraw and re-testing, which is inconvenient for pregnant women and clinicians. METHODS: We created mock trisomy 21 (T21) samples to investigate the effects of low total cfDNA with low LFF and possible solutions to increase their detection rate. RESULTS: Samples with low total cfDNA resulted in the decreased unique reads number and increased duplication rate. Abnormal correlations between library concentration and raw reads number and the coverage fluctuation value, ZsdNorm, were also discovered, suggesting that low total cfDNA could lead to the overestimation of the library concentration. Additionally, a non-reference-based derivative value method (DV method) was evaluated and the data demonstrated that the detection sensitivity of trisomy 21 was increased from 33.33% (6/18) to 94.44% (17/18) in samples with 5% fetal fraction comparing with the z-score approach, whereas for LFF (3.5%) group, the performance was raised from 0% to 35.29% (6/17). CONCLUSION: Low total cfDNA has significant impacts on NIPT performance by altering sequencing quality. The non-reference-based DV method could increase the T21 detection rate in samples with limited cfDNA content and 5% fetal fraction, but it was not as effective for those with LFF.

20.
Clin Drug Investig ; 40(1): 41-53, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31586305

RESUMO

BACKGROUND AND OBJECTIVE: Because of the narrow therapeutic window and huge inter-individual variation, the individual precision on anticoagulant therapy of warfarin is challenging. In our study, we aimed to construct a Back Propagation Neural Network (BPNN) model to predict the individual warfarin maintenance dose among Chinese patients who have undergone heart valve replacement, and validate its prediction accuracy. METHODS: In this study, we analyzed 13,639 eligible patients extracted from the Chinese Low Intensity Anticoagulant Therapy after Heart Valve Replacement database, which collected data on patients using warfarin after heart valve replacement from 15 centers all over China. Ten percent of patients who were finally enrolled in the database were used as the external validation, while the remaining were randomly divided into the training and internal validation groups at a ratio of 3:1. Input variables were selected by univariate analysis of the general linear model; 2.0, the mean value of the international normalized ratio (INR) range 1.5-2.5, was used as the mandatory variable. The BPNN model and the multiple linear regression (MLR) model were constructed by the training group and validated through comparisons of the mean absolute error (MAE), mean squared error (MSE), root mean squared error (RMSE), and ideal predicted percentage. RESULTS: Finally, 10 input variables were selected and a three-layer BPNN model was constructed. In the BPNN model, the value of MAE (0.688 mg/day and 0.740 mg/day in internal and external validation, respectively), MSE (0.580 mg/day and 0.599 mg/day in internal and external validation, respectively), and RMSE (0.761 mg/day and 0.774 mg/day in internal and external validation, respectively) were achieved. Ideal predicted percentages were high in both internal (63.0%) and external validation (59.7%), respectively. Compared with the MLR model, the BPNN model showed a higher ideal prediction percentage in the external validation group (59.7% vs. 56.6%), and showed the best prediction accuracy in the intermediate-dose subgroup (internal validation group: 85.2%; external validation group: 84.7%) and a high predicted percentage in the high-dose subgroup (internal validation group: 36.2%; external validation group: 39.8%), but poor performance in the low-dose subgroup (internal validation group: 0%; external validation group: 0.3%). Meanwhile, the BPNN model showed better ideal prediction percentage in the high-dose group than the MLR model (internal validation: 36.2% vs. 31.6%; external validation: 42.8% vs. 37.8%). CONCLUSION: The BPNN model shows promise for predicting the warfarin maintenance dose after heart valve replacement.

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