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1.
Sci Rep ; 10(1): 5157, 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32198373

RESUMO

The gold standard for prostate cancer (PCa) diagnosis is prostate biopsy. However, it remines controversial as an invasive mean for patients with PSA levels in the gray zone (4-10 ng/mL). This study aimed to develop strategy to reduce the unnecessary prostate biopsy. We retrospectively identified 235 patients with serum total PSA testing in the gray zone before prostate biopsy between 2014 and 2018. Age, PSA derivates, prostate volume and multiparametric magnetic imaging (mpMRI) examination were assessed as predictors for PCa and clinically significant PCa with Gleason score ≥ 7 (CSPCa). Univariate analysis showed that prostate volume, PSAD, and mpMRI examination were significant predictors of PCa and CSPCa (P < 0.05). The differences of diagnostic accuracy between mpMRI examination (AUC = 0.69) and other clinical parameters in diagnostic accuracy for PCa were not statistically significant. However, mpMRI examination (AUC = 0.79) outperformed prostate volume and PSAD in diagnosis of CSPCa. The multivariate models (AUC = 0.79 and 0.84 for PCa and CSPCa) performed significantly better than mpMRI examination for detection of PCa (P = 0.003) and CSPCa (P = 0.036) among patients with PSA level in the gray zone. At the same level of sensitivity as the mpMRI examination to diagnose PCa, applying the multivariate models could reduce the number of biopsies by 5% compared with mpMRI examination. Overall, our results supported the view that the multivariate model could reduce unnecessary biopsies without compromising the ability to diagnose PCa and CSPCa. Further prospective validation is required.

2.
J Colloid Interface Sci ; 569: 358-365, 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32126348

RESUMO

Metal-organic frameworks (MOFs) with porous structures, high surface areas, diverse compositions, and functional linkers are promising materials and good carriers for building high-performance devices. In this work, uniform cobalt-doped ZnO nanoparticles (Co-doped ZnO NPs) derived from a MOF mold were synthesized, demonstrating the first example of synthesizing doped semiconductor metal oxide nanostructures using such strategy. The synthesis method produced Co-doped ZnO NPs that had a controllable doping mode, adjustable surface status, good dispensability, ferromagnetism and catalytic activity. The Co-doped ZnO NPs were evaluated as a sensing material for diabetes biomarker detection; the obtained sensors showed a high response to trace acetone (18.2 at 5 ppm), fast response/recovery times, a low detection limit (170 ppb), and long-term stability for 4 months. The enhanced sensing performance can be attributed to the increased number of active sites, additional impurity energy levels, and the catalytic ability of elemental Co. Moreover, the optimized sensor could distinguish between simulated diabetic breath and healthy human breath samples. The MOF-derived Co-doped ZnO NPs are a good candidate for the low-cost and noninvasive diagnosis of diabetes, and the proposed synthesis strategy can be extended to other types of extrinsically doped oxide materials.

3.
Future Med Chem ; 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32125179

RESUMO

Aim: HIV-1 protease inhibitors regimens suffered from a number of drawbacks, among which, the most egregious issue was the growing emergence of drug-resistant strains. Materials & methods: The design strategy of maximizing the protease active site interactions with the inhibitor, especially promoting extensive hydrogen bonding with the protein backbone atoms, might be in favor of combating drug resistance. A series of HIV-1 protease inhibitors that incorporated enantiomeric isopropanols as the P1' ligands in combination with phenols as the P2 ligands were reported herein. Results: A number of inhibitors displayed potent protease enzyme inhibition activity. In particular, inhibitor 14c showed comparable potency as darunavir with IC50 value of 1.91 nM and activity against darunavir-resistant HIV-1 variants. Conclusion: The new kind of HIV-1 protease inhibitors deserves further study.

4.
Bioorg Med Chem Lett ; 30(7): 127019, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32057582

RESUMO

A series of novel HIV-1 protease inhibitors has been designed and synthesized, which contained morpholine derivatives as the P2 ligands and hydrophobic cyclopropyl as the P1' ligand at the meantime in this study, with the aim of improving the interactions between the active sites of HIV-1 protease and the inhibitors. Twenty-eight compounds were synthesized and assessed, among which inhibitors m18 and m1 exhibited excellent inhibitory effect on the activity of HIV-1 protease with IC50 value of 47 nM and 53 nM, respectively. The molecular modeling of m1 revealed possible hydrogen bondings or van der Waals between the inhibitor and the protease, worthy of in-depth study.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32093480

RESUMO

In recent years, significant advances have been achieved in the red and green perovskite quantum dot (PQD)-based light-emitting diodes (LEDs). However, the performances of the blue perovskite LEDs are still seriously lagging behind that of the green and red counterparts. Herein, we successfully developed Ni2+ ion-doped CsPbClxBr3-x PQDs through the room-temperature supersaturated recrystallization synthetic approach. We simultaneously realized the doping of various concentrations of Ni2+ cations and modulated the Cl/Br element ratios by introducing different amounts of NiCl2 solution in the reaction medium. Using the synthetic method, not only the emission wavelength from 508 to 432 nm of Ni2+ ion-doped CsPbClxBr3-x QDs was facially adjusted, but also the photoluminescence quantum yield (PLQY) of PQDs was greatly improved due to efficient removal of the defects of the PQDs. Thus, the blue emission at 470 nm with PLQY of 89% was achieved in 2.5% Ni2+ ion-doped CsPbCl0.99Br2.01 QDs, which increased nearly three times over that of undoped CsPbClBr2 QDs and was the highest for the CsPbX3 PQDs with blue emission, fulfilling the National Television System Committee standards. Benefiting from the highly luminous Ni2+ ion-doped PQDs, the blue-emitting LED at 470 nm was obtained, exhibiting an external quantum efficiency of 2.4% and a maximum luminance of 612 cd/m2, which surpassed the best performance reported previously for the corresponding blue-emitting PQD-based LED.

7.
Eur J Med Chem ; 186: 111900, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31771827

RESUMO

Since dual inhibitors may yield lower toxicity and reduce the likelihood of drug resistance, as well as inhibitors of HIV-1 PR and RT constitute the core of chemotherapy for AIDS treatment, we herein designed and synthesized new coumarin derivatives characterized by various linkers that exhibited excellent potency against PR and a weak inhibition of RT. Among which, compounds 6f and 7c inhibited PR with IC50 values of 15.5 and 62.1 nM, respectively, and weakly affected also RT with IC50 values of 241.8 and 188.7 µM, respectively, showing the possibility in the future of developing dual HIV-1 PR/RT inhibitors. Creative stimulation for further research of more potent dual HIV-1 inhibitors was got according to the molecular docking studies.


Assuntos
Fármacos Anti-HIV/farmacologia , Cumarínicos/farmacologia , Inibidores da Protease de HIV/farmacologia , Protease de HIV/metabolismo , Transcriptase Reversa do HIV/antagonistas & inibidores , Inibidores da Transcriptase Reversa/farmacologia , Fármacos Anti-HIV/síntese química , Fármacos Anti-HIV/química , Linhagem Celular , Cumarínicos/síntese química , Cumarínicos/química , Relação Dose-Resposta a Droga , Desenho de Drogas , Infecções por HIV/tratamento farmacológico , Infecções por HIV/metabolismo , Inibidores da Protease de HIV/síntese química , Inibidores da Protease de HIV/química , Transcriptase Reversa do HIV/metabolismo , HIV-1/efeitos dos fármacos , HIV-1/enzimologia , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Inibidores da Transcriptase Reversa/síntese química , Inibidores da Transcriptase Reversa/química , Relação Estrutura-Atividade
8.
Eur J Med Chem ; 185: 111866, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31734023

RESUMO

Introducing pyrimidine bases, the basic components of nucleic acid, to P2 ligands might enhance the potency of Human Immunodeficiency Virus-1 (HIV-1) protease inhibitors because of the carbonyl and amino groups promoting the formation of extensive hydrogen bonding interactions. In this work, we provide evidence that inhibitor 10e, with N-2-(2,4-Dioxo-3,4-dihydropyrimidin-1(2H)-yl) acetamide as the P2 ligand and a 4-methoxylphenylsulfonamide as the P2' ligand, displayed remarkable enzyme inhibitory and antiviral activity, with the IC50 2.53 nM in vitro and a promising inhibition ratio with 68% against wild-type HIV-1 in vivo, with low cytotoxicity. This inhibitor also exhibited appreciable antiviral activity against DRV-resistant HIV-1 variants, which was of great value for further study.


Assuntos
Acetamidas/farmacologia , Aminas/farmacologia , Fármacos Anti-HIV/farmacologia , Protease de HIV/metabolismo , HIV-1/efeitos dos fármacos , Inibidores de Proteases/farmacologia , Pirimidinas/farmacologia , Acetamidas/síntese química , Acetamidas/química , Aminas/síntese química , Aminas/química , Fármacos Anti-HIV/síntese química , Fármacos Anti-HIV/química , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Células HEK293 , HIV-1/enzimologia , Humanos , Ligantes , Testes de Sensibilidade Microbiana , Estrutura Molecular , Inibidores de Proteases/síntese química , Inibidores de Proteases/química , Pirimidinas/síntese química , Pirimidinas/química , Relação Estrutura-Atividade
9.
Hum Gene Ther ; 30(12): 1494-1504, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31668086

RESUMO

Wilson's disease (WD) is an autosomal recessive disorder of copper metabolism caused by mutations in the ATP7B gene encoding a liver active copper transport enzyme. Gene therapy with adeno-associated virus (AAV) carrying full-length ATP7B, which is about 4.4 kb, was shown to rescue copper metabolism disorder in WD mouse model. However, due to its relatively large size, the AAV vector containing full-length ATP7B could be oversized for its packaging capacity, which could lead to inefficient packaging. To this purpose, we engineered a truncated ATP7B mutant (tATP7B) that is about 3.3 kb in length and used for AAV gene therapy for WD mice. In vitro test showed that the excretion of copper outside the cells could be achieved with tATP7B as efficient as the full-length ATP7B. In vivo delivery of tATP7B to WD mice by AAV8 vectors corrected their copper metabolisms and significantly rescued copper accumulation-related syndromes, including reduced urinary copper excretion, increased serum ceruloplasmin, and improved liver damages. Thus, our study demonstrated that AAV gene therapy based on truncated ATP7B is a promising strategy in the treatment of WD.

10.
J Mater Chem B ; 7(44): 6955-6971, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31617555

RESUMO

Periodontitis is a common bacteria-borne inflammatory disease that can damage the supporting structures of teeth, eventually leading to tooth loss and systemic inflammations. The present study developed novel nanoparticles (ZIF-8:Ce) by doping cerium (Ce) into zeolitic imidazolate framework-8 (ZIF-8) to simultaneously obtain antibacterial and anti-inflammatory capabilities. The objectives of this study were to: (1) develop novel ZIF-8 nanoparticles doped with different Ce/(Ce + Zn) molar ratios of 1%, 5% and 10% to combat periodontitis; (2) investigate the inhibition efficacy of different nanoparticles against biofilms of periodontal pathogens; and (3) evaluate the effects of different ZIF-8:Ce on inflammatory secretion and macrophage polarization in vitro. The results showed that Ce doping at a ratio from 1% to 10% did not compromise the regular and uniform structure of ZIF-8. ZIF-8:Ce possessed a sustained Zn2+ and Ce3+/Ce4+ release and favorable superoxide dismutase/catalase activities without cytotoxicity at a concentration below 30 µg mL-1. ZIF-8 exhibited an excellent anti-biofilm function against periodontal pathogens. Although 10% Ce doping into ZIF-8 slightly reduced the antibacterial effects, the CFU reduction still remained at approximately 2 orders of magnitude. More importantly, ZIF-8:Ce exhibited increasing anti-inflammatory effects with increasing amounts of Ce doping. In addition, ZIF-8:Ce10% exerted much better anti-inflammatory effects by inhibiting pro-inflammatory factor expression via restraining the NF-kB/p65 subunit translocation (p < 0.05). Meanwhile, ZIF-8:Ce10% elevated the polarization of the M2 phenotype of macrophages and promoted anti-inflammatory cytokine secretion. Therefore, the novel ZIF-8:Ce nanoparticles provided a unique insight into the development of effective anti-inflammatory and antibacterial platforms for treating periodontitis.

11.
Dent Mater ; 35(11): 1665-1681, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31551152

RESUMO

OBJECTIVE: Periodontal tissue destruction and tooth loss are increasingly a worldwide problem as the population ages. Periodontitis is caused by bacterial infection and biofilm plaque buildup. Therefore, the objectives of this study were to: (1) develop a near-infrared light (NIR)-triggered core-shell nanostructure of upconversion nanoparticles and TiO2 (UCNPs@TiO2), and (2) investigate its inhibitory effects via antibacterial photodynamic therapy (aPDT) against periodontitis-related pathogens. METHODS: The core ß-NaYF4:Yb3+,Tm3+ were synthesized via thermal decomposition and further modified with the TiO2 shell via a hydrothermal method. The core-shell structure and the upconversion fluorescence-induced aPDT treatment via 980nm laser were studied. Three periodontitis-related pathogens Streptococcus sanguinis (S. sanguinis), Porphyromonas gingivalis (P. gingivalis) and Fusobacterium nucleatum (F. nucleatum) were investigated. The killing activity against planktonic bacteria was detected by a time-kill assay. Single species 4-day biofilms on dentin were tested by live/dead staining, colony-forming units (CFU), and metabolic activity. RESULTS: The hexagonal shaped UCNPs@TiO2 had an average diameter of 39.7nm. UCNPs@TiO2 nanoparticles had positively charged (+12.4mV) surface and were biocompatible and non-cytotoxic. Under the excitation of NIR light (980nm), the core NaYF4:Yb3+,Tm3+ UCNPs could emit intense ultraviolet (UV) light, which further triggered the aPDT function of the shell TiO2 via energy transfer, thereby realizing the remarkable antibacterial effects against planktons and biofilms of periodontitis-associated pathogens. NIR-triggered UCNPs@TiO2 achieved much greater reduction in biofilms than control (p<0.05). Biofilm CFU was reduced by 3-4 orders of magnitude via NIR-triggered aPDT, which is significantly greater than that of negative control and commercial aPDT control groups. The killing efficacy of UCNPs@TiO2-based aPDT against the three species was ranked to be: S. sanguinis

Assuntos
Periodontite , Fotoquimioterapia , Biofilmes , Humanos , Nanotecnologia , Periodonto
12.
ACS Appl Mater Interfaces ; 11(40): 37130-37138, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31500405

RESUMO

Bimorph actuators hold great promise for developing soft robots. However, poor interlayer adhesion between different materials always threatens their stability for long-term usage. In this paper, instead of using a bilayer structure, we reported the gradient assembly of graphene oxide (GO) sheets and polymer nanospheres for developing robust moisture and light dual-responsive actuators. The distribution gradient of poly(methyl methacrylate) (PMMA) nanospheres along the normal direction of a GO paper leads to an asymmetric structure. The front side that mainly consists of GO is quite sensitive to water molecules, which swells upon exposure to moisture, whereas the back side that is rich in PMMA nanospheres expands obviously due to the photothermal effect. The distinct properties of the two sides endow the composite paper with moisture and light dual-responsiveness. Moreover, since GO has been used as a host material, the composite paper shows a moisture-triggered self-healing property, which permits front-to-front and front-to-back healing. The self-healed paper can maintain similar responsive property and reasonable mechanical strength to the pristine one. As a proof of concept, a dual-responsive gripper actuator and a scorpion robot have been fabricated for light and moisture cooperative manipulation. The gradient assembly strategy may open up a new way for developing robust multiresponsive actuators beyond bilayer structures.

13.
J Mater Chem B ; 7(38): 5797-5807, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31483422

RESUMO

Photodynamic therapy (PDT), as an essential tumor treatment method, has received great attention; however, there are still some challenges such as hydrophobicity of most of the photosensitizers, safety of in vivo transport, and characteristics of oxygen consumption. Herein, we used albumin as the nanocarrier for the loading of Chlorin e6 (Ce6) photosensitizer. In the meantime, tirapazaming (TPZ) was co-loaded onto the nanocomposite, which could be activated by hypoxia caused by PDT for enhanced therapy. Considering the over irradiation problem, a strategy for measuring PDT degree by ratio fluorescence was utilized. The PDT monitoring design relies on ratio emissions of C6 (Coumarin 6) and Ce6 molecules since the red emission of Ce6 is dependent on the PDT capability. Based on the characterization of the albumin nanocomposites, we further explored the combined therapy effect at both the in vitro and in vivo levels and attained the corresponding results.

14.
ACS Omega ; 4(5): 8506-8511, 2019 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-31459940

RESUMO

The modulation of threshold voltage (V TH) of organic thin-film transistors (OTFTs) was investigated by embedding a thin CuO layer between the two semiconductor layers. The results showed that the V TH of OTFTs with a CuO layer can be effectively tuned by controlling the positive gate-to-source voltage (V GS0) under stress of gate-to-source voltages. The V TH shifts from -3.67 to -0.82 V when the positive V GS0 varies from 30 to 50 V. This can be explained by the mechanism of trapping electrons at the interface between the CuO charge-separation layer and the active layer. To confirm the role of the CuO layer acting as the charge-separation source, two organic thin-film diodes, indium-tin oxide(ITO)/tris (8-quinolinolato) aluminum(III) (Alq3)/pentacene/Al (inverted-stack diode) and ITO/Alq3/CuO/pentacene/Al (inverted-stack diode with a CuO layer), were fabricated and their diode current characteristics were measured. For the second device, a large current flow was observed at positive bias on the ITO electrodes, which is ascribed to the internal bipolar charge separation within the added CuO zone.

15.
Acta Biomater ; 94: 627-643, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31212111

RESUMO

Peri-implantitis is the most common risk factor for dental implant failure. Nanostructured ceria (nano-CeO2) has anti-inflammatory and antibacterial functions, and different shapes of ceria enclosed by specific crystal planes could be an effective approach to enhance intrinsic catalysis. In the present study, the authors developed a novel implant surface-modification strategy by coating different shapes of nano-CeO2 onto titanium (Ti) surfaces to enhance their antibacterial and anti-inflammatory properties. The objectives of the study were to: (1) develop novel Ti surfaces modified with different shapes of nano-CeO2 (nanorod, nanocube and nano-octahedron) for peri-implantitis prevention; (2) investigate and compare the inhibition efficacy of different shapes of CeO2-modified surfaces against biofilms of peri-implantitis-related pathogens; and (3) evaluate the different CeO2-modified surfaces on cell inflammatory response in vitro and in vivo. The results showed that nanorod CeO2-modified Ti had more bacteria attachment of Streptococcus sanguinis in the early stage, compared with other CeO2-modified Ti (p < 0.05). They all exhibited similarly substantial CFU reductions against peri-implantitis-related biofilms (p > 0.1). Nanocube and nano-octahedron CeO2-modified Ti exerted much better anti-inflammatory effects and ROS-scavenging ability than nanorod CeO2in vitro (p < 0.05). In vivo, the mean mRNA expression of TNF-α, IL-6 and IL-1ß in the tissues around Ti was decreased by the three shapes of nano-CeO2; nano-octahedron CeO2 showed the strongest anti-inflammatory effect among all groups (p < 0.05). In conclusion, all three types of CeO2-modified Ti exerted equally strong antibacterial properties; nano-octahedron CeO2-modified Ti had the best anti-inflammatory effect. Therefore, CeO2-modified Ti surfaces are highly promising for enhancing antimicrobial functions for dental implants. Novel nano-octahedron CeO2 coating on Ti had great therapeutic potential for alleviating and eliminating peri-implantitis. STATEMENT OF SIGNIFICANCE: Peri-implantitis is the most common risk factor for dental implant failure. Nanostructured ceria (nano-CeO2) has anti-inflammatory and antibacterial functions, and different shapes of ceria enclosed by specific crystal planes could be an effective approach to enhance intrinsic catalysis. In the present study, we developed a novel implant surface-modification strategy by coating different shapes of nano-CeO2 onto titanium surfaces to enhance their antibacterial and anti-inflammatory properties for dental implants. In addition, we found that the nano-octahedron CeO2 coating on titanium would have great therapeutic potential for alleviating and eliminating peri-implantitis.

16.
Biomed Pharmacother ; 116: 108976, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31103827

RESUMO

With the development of more effective direct-acting antivirals (DAAs), dual- or triple-therapy regimens represent the major strategy used to cure chronic hepatitis C virus (HCV) infection. Thus, shorter treatment duration regimens with low burden, few adverse effects and good patient adherence are urgently needed. This study theoretically demonstrates a proof-of-concept approach for shortening therapy duration by examining HCV-infected Huh7.5 cells after treatment with a high or low fixed dose of three DAAs (simeprevir + daclatasvir + sofosbuvir) for 6-15 days. The results demonstrated that HCV-infected Huh7.5 cells achieved an ultrarapid virologic response with undetectable HCV RNA and protein and were cured after treatment with the triple-therapy regimen for 15 days. When the treatment duration was shortened, virologic relapse might occur after treatment with a low fixed dose of the three DAAs for 9 days and did occur after treatment with a low fixed dose for 6 days, although HCV was below detectable levels at the end of treatment. However, virologic relapse could be avoided with treatment of a high fixed dose of the three DAAs for 9 or 6 days. Although a virologic breakthrough occurred after an intermittent treatment regimen at the low fixed dose, the high fixed dose cured HCV-positive Huh7.5 cells with intermittent treatment. In conclusion, HCV is persistently present below detectable levels in HCV-infected Huh7.5 cells for a long time after treatment, and a shortened therapy duration is associated with an increased risk of virologic relapse, but virologic relapse or breakthrough might be avoided by treatment with a combination of more highly effective DAAs.


Assuntos
Antivirais/uso terapêutico , Hepacivirus/fisiologia , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Antivirais/farmacologia , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sinergismo Farmacológico , Quimioterapia Combinada , Hepacivirus/efeitos dos fármacos , Humanos , Imidazóis/farmacologia , Imidazóis/uso terapêutico , Espaço Intracelular/virologia , Recidiva , Simeprevir/farmacologia , Simeprevir/uso terapêutico , Sofosbuvir/farmacologia , Sofosbuvir/uso terapêutico , Replicação Viral/efeitos dos fármacos
17.
Nanoscale ; 11(24): 11496-11504, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31112195

RESUMO

The development of a high-performance semiconductor oxide sensor for the accurate detection of trace disease biomarkers in exhaled breath is still a challenge that urgently needs to be addressed. Here, we proposed a self-assembly strategy and spin-coating process to create a graphene quantum dot (GQD)-functionalized three-dimensional ordered macroporous (3DOM) ZnO structure. The strong synergistic effect and the p-n heterojunction between the p-type GQDs and n-type ZnO effectively enlarged the resistance variation due to the change in oxygen adsorption. The specific 3DOM structure induced a hierarchical pore size (286 nm in macroscale and 26 nm in mesoscale) and 3D interconnection, which guaranteed high gas accessibility and fast carrier transportation. As a result, the GQD-modified 3DOM ZnO sensor exhibited a remarkably high response (Rair/Rgas = 15.2 for 1 ppm acetone), rapid response/recovery time (9/16 s), extremely low theoretical detection limit (8.7 ppb), and good selectivity towards acetone against other interfering gases. In particular, the proposed sensor could accurately distinguish trace acetone in the simulated breath of diabetic patients. These results demonstrate a high potential for the feasibility of the GQD-modified 3DOM SMO structure as a new sensing material for the possibility of noninvasive real-time diagnosis of diabetes.


Assuntos
Diabetes Mellitus/diagnóstico , Grafite/química , Pontos Quânticos/química , Óxido de Zinco/química , Humanos
18.
Bioorg Med Chem Lett ; 29(12): 1541-1545, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-31014912

RESUMO

Introducing purine bases to P2-ligands might enhance the potency of Human Immunodeficiency Virus-1 (HIV-1) protease inhibitory because of the carbonyl and NH groups promoting the formation of extensive H-bonding interactions. In this work, thirty-three compounds are synthesized and evaluated, among which inhibitors 16a, 16f and 16j containing N-2-(6-substituted-9H-purin-9-yl)acetamide as the P2-ligands along with 4-methoxylphenylsulfonamide as the P2'-ligand, display potent inhibitory effect on the activity of HIV-1 protease with IC50 43 nM, 42 nM and 68 nM in vitro, respectively.

19.
Chem Sci ; 10(13): 3715-3722, 2019 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-31015915

RESUMO

Hypochlorous acid (HOCl), a reactive oxygen species (ROS), plays a crucial role in the process of pathogenic oxidative stress. Some powerful anticancer agents, such as elesclomol, specifically induce cancer cell apoptosis by increasing HOCl levels. However, sensitive tools to monitor subtle changes of biological HOCl in vivo are limited. To achieve this, we herein present rationally designed probes C1-C7 through introducing a bioorthogonal dimethylthiocarbamate receptor. All the probes were shown to sensitively and rapidly detect HOCl in the nanomolar/biologically relevant concentration range with fluorescence turn-on observed in their respective optical regions, resulting in a blue-to-red "fluorescence rainbow" and providing a broad selection of colors for imaging HOCl in vivo. Remarkably, probe C7 exhibited both a turn-on signal at biologically relevant concentrations (LOD1 = 18 nM) and a ratiometric response at the high risk pathogenic concentrations (LOD2 = 0.47 µM), which gives a higher reliability compared to a single signal and avoids cross-talk caused by the combined use of several probes. C7 was used to monitor the oxidative stress process induced by elesclomol in live cancer cells, and using this probe it was further discovered that an evodiamine derivative was capable of generating cancer-cell HOCl.

20.
Sci Rep ; 9(1): 1207, 2019 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-30718784

RESUMO

Few studies have focused on frailty as a predictor of mortality and readmission among inpatients in the acute care setting, especially over long follow-up periods. We conducted this study to determine the impact of the frailty on subsequent mortality and readmission in this setting. This study was a prospective observational study conducted in the acute geriatric wards, with a three-year follow-up duration. We assessed frailty via the 36-item Frailty Index (FI), and a cut-off value of 0.25 was used to identify the presence or absence of frailty. We collected survival and readmission information through telephone interviews at 12, 24, and 36 months. We used the Cox regression model to examine the association between frailty and outcomes interested (death and readmission). The present study included 271 patients (mean age: 81.1 years old; 20.3% females), of whom 21.4% died during the 3-year follow-up period. One hundred and thirty-three patients (49.1%) were identified as being frail. The prevalence of frailty was similar in men and women (46.8% vs.58.2%, P = 0.130). Compared with non-frail patients, death and hospital readmission rates of frail patients were increased. Frailty was an independent predictor of 3-year death (adjusted hazard ratio (HR): 2.09; 95% confidence interval (CI): 1.20 to 3.63) and readmission (adjusted HR: 1.40; 95% CI: 1.04 to 1.88) after adjusting for several potential confounders. Frailty is prevalent among older inpatients and is a valuable predictor of 3-year mortality and hospital readmission in an acute care setting.

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