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1.
Int J Mol Med ; 47(3): 1, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33537831

RESUMO

Diabetic nephropathy (DN) is the primary cause of end­stage renal disease, which is closely associated with dysfunction of the podocytes, the main component of the glomerular filtration membrane; however, the exact underlying mechanism is unknown. Polyamines, including spermine, spermidine and putrescine, have antioxidant and anti­aging properties that are involved in the progression of numerous diseases, but their role in DN has not yet been reported. The present study aimed to explore the role of polyamines in DN, particularly in podocyte injury, and to reveal the molecular mechanism underlying the protective effect of exogenous spermine. Streptozotocin intraperitoneal injection­induced type 1 diabetic (T1D) rat models and high glucose (HG)­stimulated podocyte injury models were established. It was found that in T1D rat kidneys and HG­induced podocytes, ornithine decarboxylase (a key enzyme for polyamine synthesis) was downregulated, while spermidine/spermine N1­acetyltransferase (a key enzyme for polyamines degradation) was upregulated, which suggested that reduction of the polyamine metabolic pool particularly decreased spermine content, is a major factor in DN progression. In addition, hyperglycemia can induce an increased rat kidney weight ratio, serum creatinine, urea, urinary albumin excretion and glomerular cell matrix levels, and promote mesangial thickening and loss or fusion of podocytes. The expression levels of podocyte marker proteins (nephrin, CD2­associated protein and podocin) and autophagy­related proteins [autophagy protein 5, microtube­associated proteins 1A/1B light chain 3 (LC3)II/LC3I, Beclin 1 and phosphorylated (p)­AMPK] were downregulated, while cleaved caspase­3, P62 and p­mTOR were increased. These changes could be improved by pretreatment with exogenous spermine or rapamycin (autophagic agonist). In conclusion, spermine may have the potential to prevent diabetic kidney injury in rats by promoting autophagy via regulating the AMPK/mTOR signaling pathway.

2.
Drug Discov Today ; 2021 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-33561465

RESUMO

Testosterone replacement therapy (TRT) is the primary treatment for male testosterone deficiency. This therapy raises concerns over the risk of prostate cancer (PC), because testosterone has historically been considered the fuel for PC. We discuss the re-evaluation of the relationship between androgen and PC, and highlight the safety of TRT in the treatment of symptomatic men with testosterone deficiency who have low-risk disease after treatment for localized PC with surgery or radiation. Furthermore, we review the clinical application and potential mechanisms of bipolar androgen therapy (BAT) in the treatment of castration-resistant PC, emphasizing that much remains to be done before BAT can be broadly applied.

3.
Medicine (Baltimore) ; 100(5): e23971, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33592851

RESUMO

BACKGROUND: The purpose of this study is to explore the association between extravascular lung water (EVLW) and prognosis of sepsis (PS). METHODS: We will carry out comprehensive literature search in electronic databases (PUBMED/MEDLINE, EMBASE, CENTRAL, WorldSciNet, PsycINFO, Allied and Complementary Medicine Database, CBM, and CNKI) and additional sources. All electronic databases will be searched from their initial to the present without language restrictions. Case-controlled studies reporting the association between EVLW and PS will be evaluated for inclusion. Outcomes of interest will include mortality rate, extravascular lung water index, pulmonary vascular permeability index, blood lactate clearance, oxygenation index, blood gas analysis, PaO2/FiO2, cardiac output index, global end diastolic volume index, intrathoracic blood volume index, systemic resistance index, acute physiology and chronic health scoring system II, and infection-related organ failure scoring system. Study quality will be evaluated using Newcastle-Ottawa Tool, and statistical analysis will be performed utilizing RevMan 5.4 software. RESULTS: This study will summarize the most recent evidence to investigate the association between EVLW and PS. CONCLUSIONS: The results of this study will provide an exhaustive view of the association between EVLW and PS. STUDY REGISTRATION OSF: osf.io/vhnxw.

4.
Biomed Pharmacother ; 136: 111223, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33450491

RESUMO

The emergence of multidrug resistance (MDR) is one of the main factors that impair therapeutic outcome in cancer therapy. Among all the factors that contribute to MDR, overexpression of ABCG2 transporter has been described as a key factor. GSK1070916 is a potent Aurora kinase inhibitor with broad anticancer effects. The robust efficacy shown in preclinical studies allowed the drug progress to clinical investigation. However, the potential mechanisms of acquired resistance to GSK1070916 remain inconclusive. Since several Aurora kinase inhibitors were reported to be transported substrates of ABCG2, we aimed to identify the potential interaction of GSK1070916 with ABCG2. Our data showed that ABCG2-overexpressing cells demonstrated high resistance-fold to GSK1070916 compared to the parental cells. In addition, combination of GSK1070916 with an ABCG2 inhibitor was able to restore its sensitivity. The multicellular tumor spheroid assay supported this finding by demonstrating attenuated growth inhibition in ABCG2-overexpressing tumor spheroids. In addition, the ABCG2 ATPase assay and computational modeling suggested that GSK1070916 could bind to ABCG2 substrate-binding site. The HPLC assay provided another direct evidence that ABCG2-overexpressing cells showed attenuated intracellular accumulation of GSK1070916, and such phenomenon was abolished by Ko143, a known ABCG2 inhibitor. Furthermore, GSK1070916 was able to hinder the efflux activity of ABCG2, indicating possible drug-drug interactions with other ABCG2 substrate drugs. In summary, we revealed that overexpression of ABCG2 can cause GSK1070916 resistance in cancer cells. The combination of an ABCG2 inhibitor with GSK1070916 may be a rational strategy to overcome the drug resistance and should be considered for clinical investigation.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33392977

RESUMO

Four experiments explore the generalizability of two different types of bias in visual comparison. The first type is a spatial congruency bias, in which two target stimuli are more likely to be classified as matching ('same') if they appear successively at the same location. The second type is an analytic bias, which varies depending on the overall similarity of the displays and the need to select specific parts from each object. Both types of bias had previously been demonstrated in comparisons based on shape and other visual features. The current tasks move beyond feature comparisons, requiring the comparison of the local positions of visual elements (dots or letters) that appear within each pattern. Given the privileged role of location in visual representations and attentional selection, it is important to test how visual comparisons of location differ from comparisons of shape and other features. The spatial congruency bias is replicated in the comparison of local positions and, as in previous experiments, its strength diminishes when the displays being compared are less similar to one another. Also, as demonstrated previously with letter comparisons, there is an analytic bias shifting responses toward 'different' when the displays being compared are less similar to one another. Responses are also shifted more toward 'same' in location comparisons relative to feature comparisons. The general pattern of results suggests that as more attentional selection is required in a comparison task, there is a stronger overall bias to respond 'different'.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33405151

RESUMO

Based on the comprehensive evaluation system of agricultural green development index (AGDI), this paper uses entropy weight method and linear weighted sum method to measure the agricultural green development level of 31 provinces in China from 2013 to 2018. We then incorporate spatial correlation into the traditional convergence test model, study the spatial convergence of AGDI, and explore the reasons for regional differences in AGDI. The results show that the level of AGDI in China showed an overall growth trend during the sample survey period, but there were significant differences in the rate of AGDI among different regions, mainly manifested as "eastern > western > central." The AGDI shows a significant positive spatial correlation on the whole, and its overall spatial distribution is characterized by high-high agglomeration and low-low agglomeration. The provinces with higher and lower level of AGDI still maintain the original relatively concentrated distribution in geographical space. On this basis, the study examines the regional differences of AGDI and its evolution by Dagum Gini coefficient decomposition and spatial convergence. The results showed that the overall difference of AGDI showed a fluctuating downward trend. The intra-regional difference of AGDI in the western region was the largest, and that in the eastern region was the smallest. The contribution rate of intensity of transvariation among regions was the main source of the relative difference of AGDI. Meanwhile, the AGDI of the overall, eastern, central, and western regions present significant σ convergence and conditional ß convergence. Except for the central region, the overall, eastern, and western regions present significant absolute ß convergence. The low-level areas of AGDI have significant "catch-up effect" on the areas with high-level AGDI. Based on the above results, this paper also puts forward some policy suggestions from the perspective of cross-regional collaborative governance to improve China's agricultural green development mode and narrow the regional differences of China's agricultural green development.

7.
FEBS Open Bio ; 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33386701

RESUMO

Abnormal lipid metabolism is closely related to the malignant biological behavior of tumor cells. Such abnormal lipid metabolism provides energy for rapid proliferation, and certain genes related to lipid metabolism encode important components of tumor signaling pathways. In this study, we analyzed pancreatic cancer datasets from The Cancer Genome Atlas (TCGA) and searched for prognostic genes related to lipid metabolism in the Molecular Signature Database. A risk score model was built and verified using the GSE57495 dataset and International Cancer Genome Consortium (ICGC) dataset. Four molecular subtypes and 4,249 differentially expressed genes were identified. The differentially expressed genes obtained by Weighted Gene Co-expression Network Construction (WGCNA) analysis were intersected with 4249 differentially expressed genes to obtain a total of 1340 differentially expressed genes. The final prognosis model included CA8, CEP55, GNB3 and SGSM2, and these had a significant effect on overall survival (OS). The area under the curve (AUC) at 1 years, 3 years and 5 years was 0.72, 0.79 and 0.87, respectively. These same results were obtained using the validation cohort. Survival analysis data showed that the model could stratify the prognosis of patients with different clinical characteristics and the model has clinical independence. Functional analysis indicated that the model is associated with multiple cancer-related pathways. Compared with published models, our model has a higher C-index and greater risk value. In summary, this 4-gene signature is an independent risk factor of pancreatic cancer survival, and may be an effective prognostic indicator.

8.
BMC Musculoskelet Disord ; 22(1): 72, 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33435951

RESUMO

BACKGROUND: There is no recommended standard for positioning of a mouse for radiographic assessment of the spine. This is necessary to have reproducible radiographic data and avoid false positive results. The objective of this study was to investigate the impact of various postures on Cobb angle measurements and to set up a positioning standard for imaging mouse spines. METHODS: This study was conducted in three parts. Firstly, we identified the problem of lack of posture standardization for radiographs. We collected 77 C57BL/6 J mice for spine radiographs and found a scoliosis prevalence of 28.6% with large variations in curve magnitude. Secondly, 24 C57BL/6 J mice underwent 4 consecutive weekly radiographs and observed high variations (relative standard deviation: 125.3%) between radiographs. Thirdly, we collected another 82 C57BL/6 J mice and designed 14 different postures that could take place during imaging. These postures were related to curling of the limbs, and head, pelvic and tail tilting. RESULTS: The results showed that head and pelvic tilting significantly affects the curve magnitude with effect size (Glass's delta) over 1.50. Avoiding these incorrect positions during radiographs is warranted. The standard recommended posture for mouse imaging entails positioning the snout, interorbital space, neck and whole spine in one line, and with the limbs placed symmetrical to the trunk, whilst avoiding stretching the body of the mouse. CONCLUSIONS: Our work exemplified the importance of standard protocol during imaging when using an animal model in the scoliosis study. We recommend utilizing this standard in studying various disorders of the spine to avoid technical causes for the appearance of a curve.

9.
BMC Public Health ; 20(1): 1828, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33256679

RESUMO

BACKGROUND: The prevalence of metabolic syndrome continues to rise sharply worldwide, seriously threatening people's health. The optimal model can be used to identify people at high risk of metabolic syndrome as early as possible, to predict their risk, and to persuade them to change their adverse lifestyle so as to slow down and reduce the incidence of metabolic syndrome. METHODS: Design existing circumstances research. A total of 1468 workers from an oil company who participated in occupational health physical examination from April 2017 to October 2018 were included in this study. We established the Logistic regression model, the random forest model and the convolutional neural network model, and compared the prediction performance of the models according to the F1 score, sensitivity, accuracy and other indicators of the three models. RESULTS: The results showed that the accuracy of the three models was 82.49,95.98 and 92.03%, the sensitivity was 87.94,95.52 and 90.59%, the specificity was 74.54, 96.65 and 94.14%, the F1 score was 0.86,0.97 and 0.93, and the area under ROC curve was 0.88,0.96 and 0.92, respectively. The Brier score of the three models was 0.15, 0.08 and 0.12, Observed-expected ratio was 0.83, 0.97 and 1.13, and the Integrated Calibration Index was 0.075,0.073 and 0.074, respectively, and explained how the random forest model was used for individual disease risk score. CONCLUSIONS: The study showed that the prediction performance of random forest model is better than other models, and the model has higher application value, which can better predict the risk of metabolic syndrome in oil workers, and provide corresponding theoretical basis for the health management of oil workers.

10.
Materials (Basel) ; 13(23)2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33255365

RESUMO

Isothermal compression tests of in situ TiB2/7050Al composites fabricated by powder metallurgy were performed at 300-460 °C with the strain rate varying from 0.001 s-1 to 1 s-1. The Arrhenius constitutive equation and hot processing map of composites were established, presenting excellent hot workability with low activation energies and broad processing windows. Dramatic discontinuous/continuous dynamic recrystallization (DDRX/CDRX) and grain boundary sliding (GBS) take place in composites during deformation, depending on the Zener-Hollomon parameter (Z) values. It was found that initially uniform TiB2 particles and fine grain structures are beneficial to the DDRX, which is the major softening mechanism in composites at high Z values. With the Z value decreasing, dynamic recovery and CDRX around particles are enhanced, preventing the occurrence of DDRX. In addition, fine grain structures in composites are stable at elevated temperature thanks to the pinning of dense nanoparticles, which triggers the occurrence of GBS and ensures good workability at low Z values.

11.
Phys Rev Lett ; 125(21): 215502, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33274988

RESUMO

Friction between two solid surfaces often exhibits strong rate and slip-history dependence, which critically determines the dynamic stability of frictional sliding. Empirically, such an evolutional effect has been captured by the rate-and-state friction (RSF) law based on laboratory-scale experiments; but its applicability for generic sliding interfaces under different length scales remains unclear. In this Letter, frictional aging, the key manifestation of the evolutional behavior, of silica-silica contacts is studied via slide-hold-slide tests with apparent contact size spanning across 3 orders of magnitude. The experimental results demonstrate a clear and strong length scale dependency in frictional aging characteristics. Assisted by a multiasperity RSF model, we attribute the length scale effect to roughness-dependent true contact area evolution as well as scale-dependent friction stress due to nonconcurrent slip.

12.
J Med Chem ; 2020 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-33280384

RESUMO

ABCB1 is a promising therapeutic target for overcoming multidrug resistance (MDR). In this work, we reported the structure-based design of triazolo[1,5-a]pyrimidines as new ABCB1 modulators, of which WS-691 significantly increased sensitization of ABCB1-overexpressed SW620/Ad300 cells to paclitaxel (PTX) (IC50 = 22.02 nM). Mechanistic studies indicated that WS-691 significantly increased the intracellular concentration of PTX and [3H]-PTX while decreasing the efflux of [3H]-PTX in SW620/Ad300 cells by inhibiting the efflux function of ABCB1. The cellular thermal shift assay suggested that WS-691 could stabilize ABCB1 by directly binding to ABCB1. WS-691 could stimulate the activity of ABCB1 ATPase but had almost no inhibitory activity against CYP3A4. Importantly, WS-691 increased the sensitivity of SW620/Ad300 cells to PTX in vivo without observed toxicity. Collectively, WS-691 is a highly potent and orally active ABCB1 modulator capable of overcoming MDR. The triazolo[1,5-a]pyrimidine may be a promising scaffold for developing more potent ABCB1 modulators.

13.
Brachytherapy ; 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33288488

RESUMO

PURPOSE: Multiple dwell positions ("multidwell") within a Leipzig-style applicator can be used to increase dose uniformity and treatment area. Model-based dose calculation algorithms (MBDCAs) are necessary for accurate calculations involving these applicators because of their nonwater equivalency and complex geometry. The purpose of this work was to create template plans from MBDCA calculations and present their dwell times and positions for users of these applicators without access to MBDCAs. METHODS AND MATERIALS: The Leipzig-style solid applicator model within our treatment planning system was used to design template plans. Five template plans, normalized to 0.3 cm depth within a water phantom, were optimized using the treatment planning system MBDCA. Each template plan contained unique dwell positions, times, and active lengths (0.5-1.5 cm). A single-dwell distribution was optimized for comparison. The stem of this applicator stops within the shell; therefore, one template plan contained an intrafraction rotation to determine the largest dose distribution achievable. Effects of imperfect applicator rotation were quantified by inserting rotational offsets and comparing the V100%, D95%, and minimum dose coverage for planning target volumes created from 80%/90% isodose lines. RESULTS: The 90% (80%) isodose line dimensions at 0.3 cm depth for single-dwell increased from 0.94 × 0.97 (1.53 × 1.57) cm2 to 2.09 × 1.24 (2.75 × 1.88) cm2 in the largest template plan. Manually inserted angular offsets up to ±10° for the template plan requiring rotation preserved V100%, D95%, and minimum dose within 2.0%, 1.9%, and 8.0%, respectively. CONCLUSION: A set of template plans was created to provide accessibility to the multidwell methodology, even for users without access to MBDCAs. Each template plan should be reviewed before clinical implementation.

14.
Drug Des Devel Ther ; 14: 5129-5141, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33262574

RESUMO

Aim: We aimed to systematically examine the effects of enzymatic activity of 38 human CYP2C9 alleles and 21 human CYP3A4 alleles, including wild-type CYP2C9.1 and CYP3A4.1, which contain the 24 CYP2C9 novel alleles (*36-*60) and 6 CYP3A4 novel alleles (*28-*34) newly found in the Chinese population, on sildenafil metabolism through in vitro experiment. Methods: The recombinant cytochrome P450 alleles protein of CYP2C9 and CYP3A4 expressed in insect baculovirus expression system were reacted with 10-500 µM sildenafil for 30 minutes at 37°C, and the reaction was terminated by cooling to -80°C immediately. Next, we used ultra-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) detection system to detect sildenafil and its active metabolite N-desmethyl sildenafil. Results: The intrinsic clearance (Vmax/Km) values of most CYP2C9 variants were significantly altered when compared with the wild-type CYP2C9*1, with most of these variants exhibiting either reduced Vmax and/or increased Km values. Four alleles (CYP2C9*11, *14, *31, *49) exhibited no markedly decreased relative clearance (1-fold). The relative clearance of the remaining thirty-three variants exhibited decrease in different levels, ranging from 1.81% to 88.42%. For the CYP3A4 metabolic pathway, when compared with the wild-type CYP3A4*1, the relative clearance values of four variants (CYP3A4*3, *10, *14 and *I335T) showed significantly higher relative clearance (130.7-134.9%), while five variants (CYP3A4*2, *5, *24, *L22V and *F113I) exhibited sharply reduced relative clearance values (1.80-74.25%), and the remaining nine allelic variants showed no statistical difference. In addition, the kinetic parameters of two CYP3A4 variants (CYP3A4*17 and CYP3A4*30) could not be detected, due to the defect of the CYP3A4 gene. Conclusion: These findings were the first evaluation of all these infrequent CYP2C9 and CYP3A4 alleles for sildenafil metabolism; when treating people who carry these CYP2C9 and CYP3A4 variants, there should be more focus on the relation of dose intensity, side effects and therapeutic efficacy when administering sildenafil. The study will provide fundamental data on effect of CYP2C9 and CYP3A4 allelic variation on sildenafil metabolism for further clinical research.

15.
ACS Nano ; 2020 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-33373181

RESUMO

Second-harmonic generation (SHG) in plasmonic nanostructures has been investigated for decades due to their wide applications in photonic circuit, quantum optics and biosensing. Development of large-scale, uniform, and efficient plasmonic nanostructure system with tunable modes is desirable for their feasible utilizations. Herein, we design an efficient inch-scale SHG source by a solution-processed method instead of traditional high-cost processes. By assembling the gold nanoparticles with the porous anodic alumina templates, multiresonance in both visible and near-infrared regions can be achieved in hexagonal plasmonic nanostructure arrays, which provide strong electric field enhancement at the gap region. Polarization-independence SHG radiation has been realized owing to the in-plane isotropic characteristic of assembled unit. The tilt-angle dependent and angle-resolved measurement showed that wide-angle nonlinear response is achieved in our device because of the gap geometry of ball-in-bowl nanostructure with nonlinear emission electric dipoles distributed on the concave surface, which makes it competitive in practical applications. Our progress not only makes it possible to produce uniform inch-scale nonlinear arrays through low-cost solution process; and also advances the understanding of the SHG radiation in plasmonic nanostructures.

16.
Opt Lett ; 45(24): 6740-6743, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33325885

RESUMO

We demonstrate theoretically and experimentally a novel photonic spin Hall effect (PSHE), to the best of our knowledge, at an interface between air and uniaxial crystal, whose optical axis is within the interface plane. Owing to the anisotropy of the crystal, partial cross polarization conversion occurs. For a horizontally polarized paraxial Gaussian beam incidence, a linear polarization gradient forms along the in-plane wavevector in the reflected beam, allowing us to achieve spin separation in real space. The spin separation of the reflected beam can be tuned by rotating the optical axis of the crystal. A maximum spin-dependent displacement up to 0.45 times the incident beam waist is obtained at Brewster incidence. This novel anisotropy-induced PSHE deepens the understanding of spin-orbit interaction and provides a new way for control of spin photons.

17.
Br Poult Sci ; 2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33336589

RESUMO

1. Stocking density is an issue for poultry production. High stocking density can impact biochemical parameters, production, and reproductive performance; however, information regarding the effects of stocking density on serum metabolites in geese is limited. 2. Twenty-day-old, Sanhua male geese (n=240) were allocated to one of two experimental groups for 50 days. One group was housed under a low stocking density (LSD; two birds per m2) and one under a high stocking density (HSD; five birds per m2). Body weight and feed intake were recorded every 10 d. Eight serum samples per group were used for metabonomic analysis by liquid chromatography-mass spectrometry. 3. Stocking density did not affect the spleen, liver, thymus, or bursa of Fabricius weights after 50 d. Feed intake and body weight was significantly lower in geese from the HSD group versus the LSD group (P<0.05). Thirty-six differential serum metabolites were identified (P<0.05), indicating altered amino acid, carbohydrate, lipid and vitamin cofactor metabolism. 4. The results demonstrated that high-density stocking impacts geese, and provides insights into the mechanisms underlying the adverse health effects associated with HSD.

18.
Artigo em Inglês | MEDLINE | ID: mdl-33347272

RESUMO

On graphite, friction is known to be more than an order of magnitude larger at step edge defects as compared to on the basal plane, especially when the counter surface slides from the lower terrace of the step to the upper terrace. Very different mechanisms have been proposed to explain this phenomenon, including atomic interactions between the counter surface and step edge (without physical deformation) and buckling or peeling deformation of the upper graphene terrace. Here, we use atomic force microscopy (AFM) and reactive molecular dynamic (MD) simulations to capture and differentiate the mechanisms proposed to cause high friction at step edges. AFM experiments reveal the difference between cases of no deformation and buckling deformation, and the latter case is attributed to the physical stress exerted by the sliding tip. Reactive MD simulations explore the process of peeling deformation due to tribochemical bond formation between the tip and the step edge. Combining the results of AFM experiments and MD simulations, it is found that each mechanism has identifiable and characteristic features in the lateral force and vertical height profiles recorded during the step-up process. The results demonstrate that buckling and peeling deformation of the graphene edge rarely occur under typical AFM experimental conditions and thus are unlikely to be the origin of high friction at step edges in most measurements. Instead, the high step-up friction is due to stick-slip behavior facilitated by the topographical change and atomic interactions between the tip and step edge without deformation of the graphene itself.

19.
Artigo em Inglês | MEDLINE | ID: mdl-33226694

RESUMO

All-DNA nanomedicines have emerged as potential anti-tumor drugs. DNA nanotechnology provides all-DNA nanomedicines unlimited possibilities in controlling the diversification of size, shape, and loads of the therapeutic motifs. What's more, as DNA is a biological polymer, it is possible to genetically encode and produce the all-DNA nanomedicines in living bacteria. Herein, DNA-dendrimer-based nanomedicines are designed to adapt to the biological production, which is constructed by the flexible 3-arm building blocks to enable a highly efficient "one-pot" DNA assembly. For the first time, a DNA nanomedicine, D4-3-As-DzSur, is successfully genetically encoded, biotechnological produced, and directly self-assembled. By the following in vitro and in vivo studies, the performance of the biologically produced D4-3-As-DzSur in targeted gene regulation has been confirmed. We conclude that, as an advantageous superiority, the biological production capability will fulfill the low-cost and large-scale production of all-DNA nanomedicines and promote their clinical applications in the future.

20.
ACS Appl Mater Interfaces ; 12(49): 54517-54523, 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33226761

RESUMO

The transition metal-based nitride (TMN) holds great promise as catalysts with high efficiency for energy-related technologies. Herein, on the basis of global structure search and density functional theory calculations, a novel two-dimensional (2D) TMN was identified: RuN2 monolayer with tetracoordinated Ru atoms and isolated N═N dimers, which is revealed to possess high thermal, dynamic, and chemical stabilities as well as metallic nature, thus providing great feasibility for its practical application in electrochemical reactions. Remarkably, we found that the predicted RuN2 monolayer exhibits superior catalytic performance for the oxygen reduction reaction (ORR) with a rather high limiting potential (0.99 V) and an overwhelming four-electron reduction pathway selectivity. Thus, our results suggested the robust applicability of RuN2 monolayer as a novel non-Pt catalyst due to its excellent catalytic efficiency and outstanding selectivity for ORR, which not only proposes a new member to the hypercoordinate 2D TMN with novel properties, but also provides a feasible strategy to further develop novel TMN-based nanomaterials for electrocatalytic energy conversion.

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