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1.
Neuroscience ; 2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-32890665

RESUMO

Our aim was to identify the longitudinal changes in gray matter volume (GMV) and secondary alterations of structural covariance after pontine stroke (PS). Structural MRI and behavioral scores were obtained at 1 week, 1 month, 3 months, 6 months in 11 patients with PS. Twenty healthy subjects underwent the same examination only once. We used voxel-based morphometry and seed-based structural covariance to investigate the altered GMV and structural covariance patterns. Furthermore, the associations between the GMV changes and behavioral scores were assessed. With the progression of the disease, GMV decreased significantly in the bilateral cerebellar posterior lobe (ipsilateral Crus II (CBE Crus II_IL) and contralateral Crus I (CBE Crus I_CL)), which were initially detected at the first month and then continued to decrease during the following 6 months. Based on the CBE Crus II_IL and CBE Crus I_CL as seed regions, structural covariance analysis revealed that there were more positively and negatively correlated brain regions in PS group, mainly distributed in the bilateral prefrontal lobe, parietal lobe, temporal lobe, paralimbic system and cerebellum. In addition, PS group showed more additional correlations between these covariant brain regions, and the changes of GMV in these regions were correlated with behavioral scores related to motor and cognitive functions. These findings indicate that PS could lead to significant GMV atrophy in the bilateral cerebellar posterior lobe at the early stage, accompanied by anomalous structural covariance patterns with more covariant brain regions and additional structural connectivity, which may provide useful information for understanding the neurobiological mechanisms of behavioral recovery after PS.

2.
Food Funct ; 2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-32955075

RESUMO

This study assessed the melanogenesis effects of rice protein hydrolysate (RPH) and explored the underlying molecular mechanism of its characteristic peptides. In this investigation, human epidermal melanocyte (PIG1) cells were used to establish a UVB-induced model to evaluate the effect of RPH on melanin content, tyrosinase activity, and reactive oxygen species (ROS) levels. High performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was employed to identify the peptide composition (2-4 amino acids) in RPH. Enzymatic hydrolysis was employed to screen the characteristic peptides Leu-Leu-Lys (LLK), Leu-Pro-Lys (LPK), and pyroGlu-Lys (pEK), while their effect on the molecular mechanism involved in the melanin synthesis process was further explored using quantitative real-time polymerase chain reaction (PCR) and western blotting. The results indicated that RPH reduced the melanin content, tyrosinase activity, and ROS production in PIG1 cells. The selected peptides LLK, LPK, and pEK from RPH reduced the expression of tyrosinase-related protein 1 (TRP-1) and tyrosinase-related protein 2 (TRP-2) and affected melanin synthesis by regulating the JNK/ß-Trcp/NFκB-p65/MITF signaling pathway at the mRNA and protein levels. This study shows that RPH plays a vital role in the melanogenesis process, therefore, providing a theoretical basis for the use of RPH as a novel additive product.

3.
Microb Pathog ; : 104502, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32947016

RESUMO

AIMS: The aims of this study were to compare the antimicrobial efficacy of Eravacycline (Erava)versus tigecycline (Tig) in vitro against clinical isolates of S. agalactiae from China and further to evaluate the heteroresistance risk and resistance mechanisms of Erava. METHODS: 162 clinical isolates of S. agalactiae were collected retrospectively and the minimal inhibitory concentrations (MICs) of Erava and Tig were determined by agar dilution. Moreover, Tetracycline (Tet) specific resistance genes, genetic mutations in Tet target sites, and sequence types (ST) profiles of clinical isolates of S. agalactiae were investigated with polymerase chain reaction (PCR) experiments. The heteroresistance frequency of Erava and Tig in S. agalactiae was analyzed by population analysis profiling. Furthermore, the resistance mechanisms of both Erava and Tig were investigated in antibiotic-induced resistant S. agalactiae isolates in vitro. RESULTS: The MIC values of Erava and Tig were shown with ≤0.25 mg/L and ≤0.5 mg/L, respectively, against clinical S. agalactiae isolates, including that harboring the Tet-specific resistance genes tet(K), tet(M), or tet(O). The heteroresistance frequency of Tig among the clinical isolates of S. agalactiae was 1.84% (3/162), whereas no positive Erava heteroresistance was found. The enhanced MIC values of both Erava and Tig in the heteroresistance-derivative S. agalactiae clones could be reversed by the efflux pump inhibition experiments. Genetic mutations affecting 30S ribosome units (16SrRNA copies or 30S ribosome protein S10) could result in the cross resistance toward Erava and Tig in the antibiotic-induced resistant S. agalactiae isolates in vitro. CONCLUSIONS: Erava MIC values were nearly half of that of Tig against the clinical isolates of S. agalactiae from China and genetic mutations in the 30S ribosome units of Tet target sites (16SrRNA copies or 30S ribosome protein S10) participated in the resistance evolution of both Erava and Tig under the antibiotic pressure.

4.
Langmuir ; 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32893635

RESUMO

The determination of nitrofurazone (NFZ) has received substantial attention because it is a kind of antibiotic drug. Herein, a rapid and low-cost electrochemical sensor for the analysis of NFZ is reported. The method uses Ag-modified electrodes in which different surfactants, hexadecyltrimethylammonium bromide and sodium dodecyl sulfate, in a ternary choline chloride-urea-glycerol deep eutectic solvent were deposited. The physical properties of the solutions with various surfactants are investigated by a conductivity meter, viscometer, and tensiometer. The morphologies and crystallinity of the Ag-modified electrodes were characterized by using scanning electron microscopy, transmission electron microscopy, and powder X-ray diffraction. Electrochemical impedance spectroscopy and CV analyses indicate that the as-prepared Ag-SDS electrode exhibited better performance as a NFZ sensor. The dynamic linear range of NFZ is 0.66-930 µM with a corresponding detection limit of 0.37 µM. The proposed electrochemical sensor was applied to detect NFZ in the aquaculture water sample, and the results showed good recovery in the range from 100.28 to 102.65%.

5.
Mediators Inflamm ; 2020: 7835284, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32922208

RESUMO

Asthma is associated with innate and adaptive immunity mediated by immune cells. T cell or macrophage dysfunction plays a particularly significant role in asthma pathogenesis. Furthermore, crosstalk between them continuously transmits proinflammatory or anti-inflammatory signals, causing the immune cell activation or repression in the immune response. Consequently, the imbalanced immune microenvironment is the major cause of the exacerbation of asthma. Here, we discuss the role of T cells, macrophages, and their interactions in asthma pathogenesis.

6.
J Food Biochem ; : e13468, 2020 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-32935351

RESUMO

This study aimed to evaluate the effect of oyster peptides and oyster powder on the procreative capacity of rats displaying reproductive dysfunction induced by cyclophosphamide (CTX). The amino acid composition and relative molecular mass of the oyster peptides and oyster powder were detected using an automatic amino acid analyzer and high-performance liquid chromatography (HPLC). After 5 d of exposure to CTX and six weeks of oyster peptide and oyster powder treatment, the biochemical serum indexes of the rats, the expression of related genes and proteins in the testes, as well as the antioxidant status and pathological state of the testes and kidneys were examined. The results showed that oyster peptides could effectively improve the biochemical blood indexes of rats, and increase the level of androgen in the blood, while improving the pathological state and oxidative stress state of the kidneys and testes, therefore, exhibiting a beneficial effect on reproductive injury. PRACTICAL APPLICATIONS: This study examined the activity of oyster peptides and their ability to enhance the procreative capacity of rats with reproductive dysfunction induced by CTX while analyzing the amino acid composition and relative molecular mass of the oyster peptides. The results of this experiment provided a preliminary theoretical basis for the development of new functional foods using oyster peptides.

7.
J Food Biochem ; : e13454, 2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32875583

RESUMO

This study evaluated the effect of four peptides, VLP, LLP, LL, and LL from pea on regulating glucose metabolism and antioxidant through IRS-1/PI3K/AKT and p38MAPK signal pathway in IR-HepG2 cell induced by 10-6 M insulin. The genes expression of PEPCK, G6Pase, GLUT2, and IRS-1 and proteins of IRS-1, p(Ser307)-IRS-1, AKT, p(Ser473)-AKT, p38MAPK, and p-p38MAPK were determined by RT-PCR and western blotting, respectively. Results show that they displayed highly potent on stimulation glucose metabolism and relief oxidative stress in IR-HepG2 cells. VLP, LLP, VA, and LL reduced Ser307 phosphorylation of IRS-1 and promoted Ser473 phosphorylation of AKT. Among them, LLP, VA, and LL increased the expression both gene and protein of GLUT2, and VLP and LL reduced p38MAPK phosphorylation showing strong antioxidant capacity. Therefore, pea oligopeptides have considerable potential for reversing the metabolic abnormalities associated with type 2 diabetes. PRACTICAL APPLICATIONS: This paper examined the intervention effect of VLP, LLP, VA, and LL that from pea on insulin resistance, and the mechanisms were detected by western blotting. The results provide a theoretical knowledge for the prevention of insulin resistance in T2D of pea-derived peptides and lay the foundation for the development of functional products and drugs in the future.

8.
Breast Cancer Res ; 22(1): 99, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32933550

RESUMO

BACKGROUND: Well-tolerated and commonly used medications are increasingly assessed for reducing breast cancer risk. These include metformin and statins, both linked to reduced hormone availability and cell proliferation or growth and sometimes prescribed concurrently. We investigated independent and joint associations of these medications with mammographic breast density (MBD), a useful biomarker for the effect of chemopreventive agents on breast cancer risk. METHODS: Using data from a cross-sectional study of 770 women (78% Hispanic, aged 40-61 years, in a mammography cohort with high cardiometabolic burden), we examined the association of self-reported "ever" use of statins and metformin with MBD measured via clinical Breast Imaging Reporting and Data System (BI-RADS) density classifications (relative risk regression) and continuous semi-automated percent and size of dense area (Cumulus) (linear regression), adjusted for age, body mass index, education, race, menopausal status, age at first birth, and insulin use. RESULTS: We observed high statin (27%), metformin (13%), and combination (9%) use, and most participants were overweight/obese (83%) and parous (87%). Statin use was associated with a lower likelihood of high density BI-RADS (RR = 0.60, 95% CI = 0.45 to 0.80), percent dense area (PD) (ß = - 6.56, 95% CI = - 9.05 to - 4.06), and dense area (DA) (ß = - 9.05, 95% CI = - 14.89 to - 3.22). Metformin use was associated with lower PD and higher non-dense area (NDA), but associations were attenuated by co-medication with statins. Compared to non-use of either medication, statin use alone or with metformin were associated with lower PD and DA (e.g., ß = - 6.86, 95% CI: - 9.67, - 4.05 and ß = - 7.07, 95% CI: - 10.97, - 3.17, respectively, for PD) and higher NDA (ß = 25.05, 95% CI: 14.06, 36.03; ß = 29.76, 95% CI: 14.55, 44.96, respectively). CONCLUSIONS: Statin use was consistently associated with lower MBD, measured both through clinical radiologist assessment and continuous relative and absolute measures, including dense area. Metformin use was associated with lower PD and higher NDA, but this may be driven by co-medication with statins. These results support that statins may lower MBD but need confirmation with prospective and clinical data to distinguish the results of medication use from that of disease.

9.
Nat Commun ; 11(1): 4548, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32917901

RESUMO

Understanding defect evolution and structural transformations constitutes a prominent research frontier for ultimately controlling the electrochemical properties of advanced battery materials. Herein, for the first time, we utilize in situ high-energy Kr ion irradiation with transmission electron microscopy to monitor how defects and microstructures evolve in Na- and Li-layered cathodes with 3d transition metals. Our experimental and theoretical analyses reveal that Li-layered cathodes are more resistant to radiation-induced structural transformations, such as amorphization than Na-layered cathodes. The underlying mechanism is the facile formation of Li-transition metal antisite defects in Li-layered cathodes. The quantitative mathematical analysis of the dynamic bright-field imaging shows that defect clusters preferentially align along the Na/Li ion diffusion channels (a-b planes), which is likely governed by the formation of dislocation loops. Our study provides critical insights into designing battery materials for extreme irradiation environments and understanding fundamental defect dynamics in layered oxides.

10.
Trials ; 21(1): 760, 2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-32883322

RESUMO

BACKGROUND: Systemic glucocorticoids are effective for the management of chronic obstructive pulmonary disease (COPD) exacerbation but have serious adverse effects. Traditional Chinese medicine (TCM) can bring additional benefits to these patients but has few adverse effects. The present study aims to evaluate the efficacy and safety of Jia Wei Bushen Yiqi (JWBY) formulas in patients who suffer from COPD exacerbations and to investigate whether the short-term (5-days) systemic glucocorticoid therapy is non-inferior to the long-term (9-day) regime. METHODS: In this multi-center, randomized, double-blinded trial, eligible inpatients with COPD exacerbation are randomly assigned to four groups (A, B, C, and D). Group A will receive placebo plus 5-day prednisone, group B will receive placebo plus 9-day prednisone, group C will receive JWBY formulas plus 5-day prednisone, and group D will receive JWBY formulas plus 9-day prednisone. The primary outcomes are the time interval to the patient's next exacerbation during a 180-day following up and the COPD assessment test (CAT) during treatment. Secondary outcomes include lung function, TCM syndrome assessment, laboratory tests, and safety. The changes of the hypothalamic pituitary adrenaline axis (HPA axis) and inflammatory cytokine will be measured as well. DISCUSSION: By demonstrating the advantages of utilizing TCM and an appropriate duration of systemic glucocorticoids, this effectiveness comparison trial will provide new references to physicians on how to improve the management of COPD exacerbation. The results of HPA axis and inflammation cytokine measurements will shed light on the molecular mechanisms and entail further mechanism studies. TRIAL REGISTRATION: www.chictr.org.cn ChiCTR1900023364. Registered on 24 May 2019.

11.
Mediators Inflamm ; 2020: 8360936, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32904560

RESUMO

The mechanisms underlying the recurrence of atrial fibrillation (AF) after radiofrequency catheter ablation (RFCA) are not well concerned. The study sought to explore the association between growth differentiation factor-15 (GDF-15) and the incidence of recurrent events among AF patients after the ablation procedure. We prospectively included 150 consecutive AF patients who underwent RFCA. Clinical information about the patients was collected. Blood samples on the second morning of hospital admission and three months after RFCA were collected, and enzyme-linked immunosorbent assay (ELISA) was used to measure the concentration of GDF-15. All participants were followed up at specific times (1st/3rd/6th/12th/18th/24th months) after RFCA to record recurrences events. During a median follow-up of 14.0 months, AF recurrence occurred in 37(24.7%) patients. Baseline serum GDF-15 level in the persistent AF group was significantly higher than the paroxysmal AF group [1140(854~1701)ng/L vs. 1062(651~1374)ng/L, P = 0.039]. Baseline serum GDF-15 level in the recurrence group was significantly higher than the nonrecurrence group [1287(889~1768) ng/L vs. 1062(694~1373)ng/L, P = 0.022]. Serum GDF-15 level at three months after RFCA was significantly lower than the baseline [870 (579~1270) ng/L vs. 1155 (735~1632)ng/L, P < 0.001]. The baseline GDF-15 correlated significantly with LAP (r = 0.296, P < 0.001) and LAAV(r = -0.235, P = 0.003). Kaplan-Meier analysis showed a significantly lower event-free survival time in the high baseline GDF-15 (≥1287.3 ng/L) group than the low baseline GDF-15 (<1287.3 ng/L) group (17.1 months vs. 20.4 months, Log Rank P = 0.017). In the multivariate Cox regression, baseline GDF-15(HR 1.053, 95% CI 1.007-1.100, P = 0.022) and LAD (HR 1.124, 95% CI 1.011-1.250, P = 0.030) were independent predictors of AF recurrence after RFCA. Our study indicated increased preprocedural GDF-15 is associated with left atrial remodeling and acts as a predictor of AF recurrence after ablation.

12.
J Lipid Res ; 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32907989

RESUMO

Mendelian randomization (MR) of lipid traits in coronary artery disease (CAD) has provided evidence for causal associations of low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) in CAD, but many lipid trait genetic variants have pleiotropic effects on other cardiovascular risk factors that may bias MR associations. The goal of this study was to evaluate pleiotropic effects of lipid trait genetic variants and to account for these effects in MR of lipid traits in CAD. We performed multivariable MR using inverse variance-weighted (IVW) and MR-Egger methods in large (n ≥ 300,000) GWAS datasets. We found that 30% of lipid trait genetic variants have effects on metabolic syndrome traits, including body mass index (BMI), type 2 diabetes (T2D), and systolic blood pressure (SBP). Nonetheless, in multivariable MR analysis, LDL-C, high-density lipoprotein cholesterol (HDL-C), TG, BMI, T2D, and SBP are independently associated with CAD, and each of these associations is robust to adjustment for directional pleiotropy. MR at loci linked to direct effects on HDL-C and TG suggests locus- and mechanism-specific causal effects of these factors on CAD.

13.
Nat Commun ; 11(1): 4520, 2020 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-32908154

RESUMO

Tumor extracellular matrix has been associated with drug resistance and immune suppression. Here, proteomic and RNA profiling reveal increased collagen levels in lung tumors resistant to PD-1/PD-L1 blockade. Additionally, elevated collagen correlates with decreased total CD8+ T cells and increased exhausted CD8+ T cell subpopulations in murine and human lung tumors. Collagen-induced T cell exhaustion occurs through the receptor LAIR1, which is upregulated following CD18 interaction with collagen, and induces T cell exhaustion through SHP-1. Reduction in tumor collagen deposition through LOXL2 suppression increases T cell infiltration, diminishes exhausted T cells, and abrogates resistance to anti-PD-L1. Abrogating LAIR1 immunosuppression through LAIR2 overexpression or SHP-1 inhibition sensitizes resistant lung tumors to anti-PD-1. Clinically, increased collagen, LAIR1, and TIM-3 expression in melanoma patients treated with PD-1 blockade predict poorer survival and response. Our study identifies collagen and LAIR1 as potential markers for immunotherapy resistance and validates multiple promising therapeutic combinations.

14.
Ecotoxicol Environ Saf ; 204: 111034, 2020 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-32758695

RESUMO

Trehalose is the major blood sugar in insects; it not only serves as an energy source but also plays important roles in physiological responses to adverse conditions. However, only a few studies have explored the effects of heavy metal exposure stress on trehalose metabolism in insects. Therefore, in this study, we examined the effects of cadmium stress on changes in trehalose metabolism in Aedes albopictus. Three concentrations of cadmium (0.005, 0.01, and 0.1 mg/L) were selected for evaluation of long-term stress in Ae. albopictus (from eggs to adults); Ae. albopictus in double-distilled water was used as the control group. The trehalose and glucose contents, trehalase activity, and trehalose metabolism-related gene expression were determined. The effects of long-term cadmium exposure on growth, development, and reproduction were also assessed. Trehalose contents were increased, whereas glucose contents and trehalase activity were decreased in Ae. albopictus following long-term exposure to low concentrations of cadmium compared with those in untreated individuals. Moreover, the expression of trehalose-6-phosphate synthase was upregulated, and that of trehalase was downregulated, indicating that Ae. albopictus may enhance trehalose synthesis to resist cadmium stress. Cadmium exposure also caused Ae. albopictus individuals to become smaller with a longer developmental duration, whereas both reproduction and hatching rates of the offspring were decreased compared with those in the control group. Our findings demonstrated that cadmium exposure affected the morphology, physiology, and biochemistry of Ae. albopictus. These findings also confirmed the role of trehalose in the response of Ae. albopictus to cadmium stress, providing insights into the effects of heavy metal stress on trehalose metabolism in an insect model.

15.
Artigo em Inglês | MEDLINE | ID: mdl-32845849

RESUMO

Chest computed tomography (CT) becomes an effective tool to assist the diagnosis of coronavirus disease-19 (COVID-19). Due to the outbreak of COVID-19 worldwide, using the computed-aided diagnosis technique for COVID-19 classification based on CT images could largely alleviate the burden of clinicians. In this paper, we propose an Adaptive Feature Selection guided Deep Forest (AFS-DF) for COVID-19 classification based on chest CT images. Specifically, we first extract location-specific features from CT images. Then, in order to capture the high-level representation of these features with the relatively small-scale data, we leverage a deep forest model to learn high-level representation of the features. Moreover, we propose a feature selection method based on the trained deep forest model to reduce the redundancy of features, where the feature selection could be adaptively incorporated with the COVID-19 classification model. We evaluated our proposed AFS-DF on COVID-19 dataset with 1495 patients of COVID-19 and 1027 patients of community acquired pneumonia (CAP). The accuracy (ACC), sensitivity (SEN), specificity (SPE) and AUC achieved by our method are 91.79%, 93.05%, 89.95% and 96.35%, respectively. Experimental results on the COVID-19 dataset suggest that the proposed AFS-DF achieves superior performance in COVID-19 vs. CAP classification, compared with 4 widely used machine learning methods.

16.
Neonatology ; : 1-7, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32799197

RESUMO

BACKGROUND: COVID-19 has spread rapidly over the world. Little is known about the outcomes of infections in pregnant women. The management and characteristics of preterm infants born to COVID-19 mothers need to be clarified. METHODS: In this retrospective, single-center cohort study, we describe the clinical courses of 6 preterm infants born to COVID-19 mothers, the management protocol, and related outcomes. RESULTS: Six preterm infants were admitted to Tongji Hospital between January 23 and March 19, 2020. Gestational age ranged from 28+5 to 36+3 weeks. One late preterm infant was delivered early due to maternal dyspnea from COVID-19. Five infants were delivered by Caesarean section. None had perinatal asphyxia. Two infants required respiratory support due to respiratory distress syndrome and apnea of prematurity. All infants did not develop severe complications of prematurity and are negative for severe acute respiratory syndrome (SARS)-CoV-2 nucleic acid testing. CONCLUSION: With an expedited and adequate delivery protocol, less invasive treatment principle, and active infection precautious, we found a limited impact of COVID-19 mothers on preterm delivery and neonatal short-term outcomes. The risk of vertical transmission of SARS-CoV-2 is low in preterm infants born to COVID-19 mothers if appropriate management is implemented.

17.
Wound Repair Regen ; 2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32856346

RESUMO

Impaired wound healing is a common complication of diabetes. In diabetic wounds, macrophages present dysfunctional efferocytosis and abnormal phenotypes, which could result in excessive neutrophil accumulation and prolonged inflammation, thereby eventually hindering wound repair. ANXA1 N-terminal peptide Ac2-26 exhibits a high potential in mitigating inflammation and improving repair; however, its efficacy in diabetic wound repair remains unclear. In this study, a cutaneous excisional wound model was built in genetically diabetic mice. Ac2-26 or a vehicle solution was employed locally in wound sites. Subsequently, wound zones were measured and sampled at different time intervals post-wounding. Using hematoxylin-eosin and Masson's trichrome staining, we observed the histopathological variations and collagen deposition in wound samples. Based on immunohistochemistry and immunofluorescence, the numbers of neutrophils, macrophages, and CD206-positive macrophages in the wound samples were determined. Cytokine expression in wound samples was studied by immunoblot assay. Results showed that Ac2-26 treatment could facilitate diabetic wound closure, down-regulate the number of neutrophils, and improve angiogenesis and collagen deposition. In addition, Ac2-26 application expedited macrophage recruitment and up-regulated the percentage of macrophages expressing CD206, which is a marker for M2 macrophages. Moreover, Ac2-26 inhibited the expressions of TNF-α and IL-6 and up-regulated the expressions of IL-10, TGF-ß, and VEGFA during diabetic wound healing. Hence, based on the aforementioned findings, Ac2-26 application in diabetic wounds could exert anti-inflammatory and pro-repair effects by reducing neutrophil accumulation and facilitating M2 macrophage development.

18.
Eur J Med Chem ; 205: 112661, 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32827851

RESUMO

Based on the structural modification of molecular-targeted agent sorafenib, a series of quinazolinyl-arylurea derivatives were synthesized and evaluated for their anti-proliferative activities against six human cancer cell lines. Compared with other cell lines tested, T24 was more sensitive to most compounds. Compound 7j exhibited the best profile with lower IC50 value and favorable selectivity. In this study, we focused on 7j-induced death forms of T24 cells and tried to elucidate the reason for its potent proliferative inhibitory activity. Compound 7j treatment could trigger three different cell death forms including apoptosis, ferroptosis, and autophagy; which form would occur depended on the concentrations and incubation time of 7j: (1) Lower concentrations within the initial 8 h of 7j treatment led to apoptosis-dependent death. (2) Ferroptosis and autophagy occurred in the case of higher concentrations combining with extended incubation time through effectively regulating the Sxc-/GPx4/ROS and PI3K/Akt/mTOR/ULK1 pathways, respectively. (3) The above death forms were closely associated with intracellular ROS generation and decreased mitochondrial membrane potential induced by 7j. In molecular docking and structure-activity relationship analyses, 7j could bind well to the active site of the corresponding receptor glutathione peroxidase 4 (GPx4). Compound 7j could be a promising lead for molecular-targeted anti-bladder cancer agents' discovery.

19.
Small ; : e2003678, 2020 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-32830425

RESUMO

Dynamic assembly and cooperation represent future frontiers for next generations of advanced micro/nano robots, but the required local interaction and communication cannot be directly translated from macroscale robots through the minimization because of tremendous technological challenges. Here, an ultrafast growth and locomotion methodology is presented for dandelion-like microswarms assembled from catalytic tubular micromotors. With ultrasound oscillation of self-generated bubbles, such microswarms could overcome the tremendous and chaotic drag force from extensive and disordered bubble generation in single units. Tubular MnO2 micromotor individuals headed by self-generated oxygen bubbles are ultrasonically driven to swim rapidly in surfactant-free H2 O2 solutions. A large bubble core fused from multiple microbubbles is excited to oscillate and the resultant local intensified acoustic field attracts the individual micromotors to school around it, leading to a simultaneous growth of dandelion-like microswarms. The bubble-carried micromotor groups driven by ultrasound could swarm at a zigzag pattern with an average speed of up to 50 mm s-1 , which is validated in low H2 O2 concentrations. Additionally, such superfast locomotion could be ultrasonically modulated on demand. The ultrafast microswarm growth and locomotion strategy offers a new paradigm for constructing distinct dynamic assemblies and rapid transmission of artificial microrobots, paving the way to a myriad of promising applications.

20.
Artigo em Inglês | MEDLINE | ID: mdl-32786252

RESUMO

Replacing organic porous separators with an inorganic solid-state electrolyte (SSE) is a promising strategy to suppress lithium dendrite and inhibit polysulfide dissolution in lithium-sulfur (Li-S) batteries. However, the realization of such a concept is still limited by the large interfacial resistance between SSE and lithium anode. Herein, a new electrolyte additive, copper fluoride (CuF2), is used in liquid electrolytes to construct a stable interphase between Li1.5Al0.5Ge1.5(PO4)3 (LAGP) SSE and Li metal for a quasi-solid-state Li-S battery. A Li||Li symmetric cell with ultralong life over 1500 h (at 0.1 mA cm-2) proves the excellent stability of the as-formed interphase. As a result, the assembled Li-S full cell presents high coulombic efficiency and stable cycling (750 mA h g-1 after 50 cycles) at room temperature with lean liquid electrolytes. This strategy provides an effective method for improving the electrochemical performance of Li-S batteries.

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