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1.
Biomacromolecules ; 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32119533

RESUMO

The hydrolysis of a newly synthesized polyether urethane (PEU) that uses polydimethylsiloxane (PDMS) as a second macrodiol and fluorinated diol (FDO) as another chain extender has been studied via immersion in buffer solutions at 70 °C. The hydrolysis process was monitored using scanning electron microscopy (SEM), gel permeation chromatography (GPC), and tensile testing. After aging for 32 weeks, no surface defect was observed on the fluorinated silicon-containing PEUs (FSPEU). Meanwhile, the addition of FDO did not alter the other issues of bulk hydrolysis, such as the changes in molecular weight and mechanical strength. Moreover, microphase separation of FSPEU was suppressed during temperature-accelerated hydrolysis, whereas aging induced a more noticeable phase of morphological change in silicon-modified PEUs (SPEU) due to the hindrance effect of the fluorinated side chains. The formation of hydrolysis-prone allophanate is also reduced in the presence of FDO. FSPEU with enhanced antihydrolysis performance can potentially be applied to biostable medical devices.

2.
Inorg Chem ; 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32163270

RESUMO

Because of the permission of the manipulations of modular construction on the atomic level, covalent organic frameworks (COFs) have attracted extensive attention in the electrocatalytic field. Owing to the lack of metal sites in pristine COFs constructed only by metal-free organic building units, it generally exhibits extremely low electrocatalytic activity. Thereby, linking metal sites on the backbone of pyrolysis-free COFs but not loading them on the surface to enhance the electrocatalytic activity is highly desirable but still remains a huge challenge. To this end, herein, we report an efficient and general cation-exchange strategy to synthesize Ni/Fe metal-ion-incorporated COFs (NixFe1-x@COF-SO3) for the oxygen evolution reaction (OER) based on the fundamental structure design of COFs. Impressively, the turnover frequency (TOF) value in Ni0.5Fe0.5@COF-SO3 reaches 0.14 s-1 at the overpotential of 300 mV, which outperforms most recently reported OER electrocatalysts, indicative of ultrahigh metal-atom utilization efficiency.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32187577

RESUMO

Negative differential resistance (NDR) effect and magnetoresistance (MR) effect attract a lot of attention since they have been widely applied in fields such as circuit amplifiers and information storage, respectively. In general, the NDR and MR effects derive from different physical mechanisms, which makes it difficult to obtain both NDR effect and large unsaturated MR effect in a device based on the same physical mechanism. In this paper, the NDR and unsaturated MR effect were observed simultaneously in In/SiO2/p-Si/SiO2/In heterojunction devices, and their physical mechanisms were investigated. It is found that under zero magnetic field conditions, the NDR effect can be observed up to 25 K which is much higher than the temperature of NDR obtaining in intrinsic silicon. The NDR effect is significantly enhanced by applying a small magnetic field of 0.1 T. Meanwhile, the unsaturated positive MR effect is obtained when an external magnetic field is applied. Our analysis shows that the NDR effect and the unsaturated MR effect can be explained on the basis of the same physical mechanism of the avalanche breakdown in the In/SiO2/p-Si heterojunction. The NDR effect is mainly resulted from complex effects containing the carrier injection after avalanche breakdown in the heterojunction, the reduction of the Schottky barrier height and the Joule heating effect. The large unsaturated MR effect derives from the suppression of the plasma due to avalanche breakdown by the applied magnetic field. The largest value of MR based on avalanche breakdown can reach about 530%@1 T at 10 K, and MR sensitivity can be as high as about 29.4 T-1 under 0.05 T.

4.
Inorg Chem ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32045221

RESUMO

Due to the intrinsic coordination preference of the linear uranyl unit, uranyl-organic frameworks (UOFs) are generally prone to exhibiting low-dimensional structures. Reactions of uranyl nitrate with biphenyl-3,3'-disulfonyl-4,4'-dicarboxylic acid dipotassium salt (K2H2BPDSDC) under different conditions led to three UOFs, namely, {(Me2NH2)[K2(UO2)3(µ3-O)(µ3-OH)2(µ2-OH)(BPDSDC)(H2O)3]·4DMF}n (1), {[K2(UO2)(µ3-O)(BPDSDC)0.5(H2O)2]}n (2), and {(Me2NH2)2.5[K1.5(UO2)(BPDSDC)1.5(H2O)3]}n (3). Compounds 1 and 2 contain one-dimensional (1D) ribbon structures formed from UO22+ units bridged by µ3-O atoms and carboxylate groups. The 1D ribbons in 1 are linked by K+ atoms to form a two-dimensional (2D) layer, which is further pillared by the biphenyl units to give a three-dimensional (3D) framework. For 2, the oxygen atoms of UO22+ units in each 1D ribbon bridge the K+ atoms to form four -[K-O-K]n- infinite chains located above and below the ribbon. The 1D ribbons in 2 are bridged by sulfonate groups to generate a 3D substructure featuring 1D channels occupied by biphenyl moieties. In 3, each mononuclear [(UO2)(COO)3] unit is bridged by three K+ atoms to form a 3D substructure featuring 1D small left-handed and large righted helical channels occluded by biphenyl moieties. Compound 2 exhibits an excellent proton conductivity with the highest conductivity of 1.07 × 10-3 S cm-1. The inner walls of 1D channels of 2 are full of the hydrophilic sulfonate groups, which boost enrichment of the guest water molecules, thus resulting in a high proton conductivity. Finally, temperature dependence of fluorescent studies showed that compounds 1 and 2 display the characteristic uranyl emissions. This work presents the elegant examples of the rarely explored 3D UOFs and expands the potentials of UOFs.

5.
Biochem Biophys Res Commun ; 523(4): 880-886, 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-31955886

RESUMO

Metal homeostasis is essential cellular progress for cell growth. Metal ion transporters play important roles in the first line of defense to cellular metal homeostasis perturbations. NRAMP transporter family was one of the most important classes in plant cells. However, functions and substrate specificities of the NRAMP family remain unknown in Chlamydomonas reinhardtii, a model unicellular plant. In this study, we identified CrNRAMP1 as an important transporter involved in zinc and cobalt transport. Heterologous and homologous functional analyses of CrNRAMP1 showed that CrNRAMP1 plays important roles in zinc and cobalt homeostasis. The expression of CrNRAMP1 correlated with zinc or cobalt concentrations, but excluding cadmium. These results help to understand the functions and specificities of NRAMP family members in C. reinhardtii.

6.
Chem Soc Rev ; 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31939973

RESUMO

As star material, perovskites have been widely used in the fields of optics, photovoltaics, electronics, magnetics, catalysis, sensing, etc. However, some inherent shortcomings, such as low efficiency (power conversion efficiency, external quantum efficiency, etc.) and poor stability (against water, oxygen, ultraviolet light, etc.), limit their practical applications. Downsizing the materials into nanostructures and incorporating rare earth (RE) ions are effective means to improve their properties and broaden their applications. This review will systematically summarize the key points in the design, synthesis, property improvements and application expansion of RE-containing (including both RE-based and RE-doped) halide and oxide perovskite nanomaterials (PNMs). The critical factors of incorporating RE elements into different perovskite structures and the rational design of functional materials will be discussed in detail. The advantages and disadvantages of different synthesis methods for PNMs will be reviewed. This paper will also summarize some practical experiences in selecting suitable RE elements and designing multi-functional materials according to the mechanisms and principles of REs promoting the properties of perovskites. At the end of this review, we will provide an outlook on the opportunities and challenges of RE-containing PNMs in various fields.

7.
Cancer Biol Ther ; 21(2): 189-196, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31684807

RESUMO

The combination of some parameters, including the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR) and neutrophil to monocyte ratio (NMR), which are associated with patient prognosis, our goal is to find the best indicator to predict the efficacy of neoadjuvant chemotherapy(NAC)in breast cancer patients. A cohort of 808 breast cancer patients treated with NAC and subsequent surgery was analyzed retrospectively. In addition, 2424 people without breast cancer served as the normal group, which included three-fold more individuals compared with the breast cancer group. Receiver operating characteristics (ROC) curves were used to determine the optimal cutoff values of inflammatory markers and compare their predictive capacity. No significant differences in age, PLR, LMR and NMR were noted between the normal group and the patient group. However, the mean value of the NLR was significantly increased in breast cancer patients (2.28) compared with the normal population (2.04) (P < .05). The LMR was significantly associated with age (P = .003), menopausal status (P = .004), cT category (P = .017), cN category (P = .024) and response to NAC (P = .001). The multivariate analysis indicated that among these inflammatory markers, the LMR (6.1 < vs ≥ 6.1) was the only independent predictive factor for the efficacy of NAC (OR = 1.771, 95% CI = 1.273-2.464, P = .001). A low LMR is considered a favorable predicative factor of the efficacy of NAC in breast cancer patients.

8.
Bioinformatics ; 36(3): 920-921, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31386102

RESUMO

SUMMARY: The recent advance in genome engineering technologies based on CRISPR/Cas9 system is enabling people to systematically understand genomic functions. A short RNA string (the CRISPR guide RNA) can guide the Cas9 endonuclease to specific locations in complex genomes to cut DNA double-strands. The CRISPR guide RNA is essential for gene editing systems. Recently, the GuideScan software is developed to design CRISPR guide RNA libraries, which can be used for genome editing of coding and non-coding genomic regions effectively. However, GuideScan is a serial program and computationally expensive for designing CRISPR guide RNA libraries from large genomes. Here, we present an efficient guide RNA library designing tool (MultiGuideScan) by implementing multiple processes of GuideScan. MultiGuideScan speeds up the guide RNA library designing about 9-12 times on a 32-process mode comparing to GuideScan. MultiGuideScan makes it possible to design guide RNA libraries from large genomes. AVAILABILITY AND IMPLEMENTATION: MULTIGUIDESCAN IS AVAILABLE AT GITHUB: https://github.com/bioinfomaticsCSU/MultiGuideScan. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

9.
Genomics ; 112(2): 1233-1244, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31323298

RESUMO

AT-hook motif nuclear localized (AHL) genes have diverse but poorly understood biological functions. We identified and analyzed 37 AHL genes in maize. We also discovered four and one additional AHLs in rice and sorghum, respectively, besides those reported earlier. The maize AHLs were classified into two clades (A and B) and three distinct types (I, II, and III) as also reported in Arabidopsis. Phylogenetic and ortholog analyses showed that, while the evolutionary classification was conserved in plants, expansion of the AHL gene family in maize was accompanied with new biological functions. Gene structure analysis showed that, while all but one Type-I AHLs lacked an intron, origin of Type-II and Type-III AHLs was associated with the gain of introns suggesting evolutionarily distinct temporal and spatial expression patterns and, likely, neofunctionalization. Gene duplication analysis revealed that AHLs in maize expanded via dispersive duplication further supporting their functional diversity. To discern these functions, we analyzed 71 transcriptomes from diverse tissues and developmental stages of maize and classified AHLs into eight groups with distinct temporal/spatial expression profiles. Coexpression analysis implicated 5 AHLs and 33 novel genes in networks specific to endosperm, seed, root, leaf, and reproductive tissues indicating their role in the development of these organs. Major processes coregulated by AHLs include pollen development, drought response, senescence, and wound response. We also identified interactions of AHL proteins in coregulating important processes including stress response. These novel insights into the role of AHLs in plant development provide a platform for functional analyses in maize and related grasses.

10.
Cancer Chemother Pharmacol ; 85(1): 61-67, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31745592

RESUMO

PURPOSE: Chemotherapy-related cognitive impairments in breast cancer patients were usually reported through cognitive questionnaires or scales which may be subjective and insensitive. This study is to assess the effect of chemotherapy on cognitive function in breast cancer patients stratified by age using objective electrophysiological measure, the P300 component of event-related potentials (ERPs) with a large sample size. METHODS: Totally, 529 primary breast cancer patients, including 178 cases at initial diagnosis stage and before chemotherapy (Group1), 167 cases during chemotherapy (Group2), and 184 cases post chemotherapy and during follow-up period (Group3), were examined with ERPs (P300 component) to assess the effect of chemotherapy on their cognitive function. RESULTS: There were significant differences of P300 latency in Group2 (364.74 ± 15.73 ms) and Group3 (364.02 ± 17.12 ms, mean follow-up period of 2.42 years) compared with Group1 (355.13 ± 19.47 ms, P < 0.001), respectively. With further age stratification: in patients of < 50 years, P300 latency was significantly prolonged in Group2 and Group3 compared with Group1 (P < 0.001), respectively; in patients of 50-59 years, P300 latency was significantly prolonged in Group2 compared with Group1 (P < 0.05), but without difference in Group1 and Group3 (P>0.05); In patients of ≥ 60 years, there were no differences of P300 latency among three the groups (P>0.05). CONCLUSIONS: It is first suggested by our objective detection data that the side effect of chemotherapy on cognitive functions in breast cancer patients may decrease with age. Electrophysiological cognitive impairments mainly occur in younger breast cancer patients undergoing chemotherapy and would last for years after chemotherapy, which highlights the importance of early intervention for those patients, especially in younger patients.

11.
Life Sci ; 242: 117167, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31838134

RESUMO

Recent studies suggested that prolyl hydroxylase 2 (PHD2) functions as an important regulator in vascular inflammation and Streptococcus pneumonia infection. However, whether PHD2 contributed to tumor progression prompted by intratumoral inflammation remains elusive. In this study, the effects of PHD2 in colon cancer were evaluated, and the underlying molecular mechanisms were investigated. The results showed that overexpressing PHD2 exerted proliferative and migratory inhibition in colon cancer cells. The expression of cell cycle and epithelial-mesenchymal transition (EMT)-associated proteins were changed: CyclinD1, CDK4, N-cadherin, and Vimentin were down-regulated, while E-cadherin was up-regulated in PHD2-overexpressing colon cancer cells. Moreover, in colon cancer xenograft mice, PHD2 overexpression suppressed tumor growth accompanied by decreased Ki67 expression. Importantly, we further demonstrated that overexpressing PHD2 attenuated inflammation in colon cancer xenograft mice through weakening accumulation of myeloid-derived suppressor cells (MDSCs) and M2-like tumor-associated macrophages (TAMs), as well as secretions of pro-inflammatory cytokines including G-CSF, TNF-α, IL-6, IL-8, IL-1ß, and IL-4. Mechanistically, PHD2 overexpression obviously suppressed NF-κB activity through decreasing phosphorylated IκB-α while increasing cytoplasmic NF-κB p65 levels in colon cancer. Our findings support the anti-cancer and anti-inflammatory roles of PHD2 and offer a preclinical proof of tumor progression regulated by cancer cells and inflammation.


Assuntos
Neoplasias do Colo/metabolismo , Prolina Dioxigenases do Fator Induzível por Hipóxia/fisiologia , Inflamação/fisiopatologia , NF-kappa B/metabolismo , Animais , Western Blotting , Linhagem Celular Tumoral , Neoplasias do Colo/fisiopatologia , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Imunofluorescência , Humanos , Prolina Dioxigenases do Fator Induzível por Hipóxia/metabolismo , Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Transplante de Neoplasias
12.
Artigo em Inglês | MEDLINE | ID: mdl-30059317

RESUMO

Due to sequencing bias, sequencing error, and repeat problems, the genome assemblies usually contain misarrangements and gaps. When tackling these problems, current assemblers commonly consider the read libraries as a whole and adopt the same strategy to deal with them. However, if we can divide reads into different categories and take different assembly strategies for different read categories, we expect to reduce the mutual effects on problems in genome assembly and facilitate to produce satisfactory assemblies. In this paper, we present a new pipeline for genome assembly based on read classification (ARC). ARC classifies reads into three categories according to the frequencies of k-mers they contain. The three categories refer to (1) low depth reads, which contain a certain low frequency k-mers and are often caused by sequencing errors or bias; (2) high depth reads, which contain a certain high frequency k-mers and usually come from repetitive regions; and (3) normal depth reads, which are the rest of reads. After read classification, an existing assembler is used to assemble different read categories separately, which is beneficial to resolve problems in the genome assembly. ARC adopts loose assembly parameters for low depth reads, and strict assembly parameters for normal depth and high depth reads. We test ARC using five datasets. The experimental results show that, assemblers combining with ARC can generate better assemblies in terms of NA50, NGA50, and genome fraction.

13.
Artigo em Inglês | MEDLINE | ID: mdl-30059318

RESUMO

The methylation of DNA is an important mechanism to control biological processes. Recently, the Pacbio SMRT technology provides a new way to identify base methylation in the genome. MotifMaker is a tool developed by Pacbio for discovering DNA methylation motifs from methylated DNA sequences. However, MotifMaker is single-threaded and computational expensive for identifying methylation motifs from large genomes. Here, we present an efficient motif finding algorithm (MultiMotifMaker) by implementing multi threads of the MotifMaker. The MultiMotifMaker speeds up the motif search about 8-9 times on a 32 core computer comparing to MotifMaker. MultiMotifMaker makes it possible to identify methylation motifs from Pacbio reads for large genomes.

14.
Food Chem ; 309: 125737, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-31780227

RESUMO

Chlorophyll degradation is the main reason for postharvest yellowing of broccoli. To uncover the role of jasmonic acid (JA) on the degradation of chlorophyll, broccoli flowers were treated with exogenous methyl jasmonate (MeJA) and diethyldithiocarbamic acid (DIECA). We found a surge of endogenous JA content with the yellowing process, and a significant correlation between JA and chlorophyll content. MeJA treatments led to increased endogenous JA, increased allene oxide cyclase (AOC) activity, and enhanced expression of JA synthesis genes. MeJA caused a stronger reduction in the maximum quantum yield (Fv/Fm), fluorescence decline ratio (Rfd), and total chlorophyll content, advanced the peak of pheide a oxygenase (PAO) activity, and up-regulated the expression of chlorophyll degradation genes. The DIECA treatment resulted in lower endogenous levels of JA, and AOC and 12-oxo-phytodienoic acid reductase (OPR) activity. This study revealed that the potential role of JA on broccoli yellowing is to promote the chlorophyll degradation.


Assuntos
Brassica/metabolismo , Clorofila/metabolismo , Ciclopentanos/metabolismo , Oxilipinas/metabolismo , Acetatos/farmacologia , Brassica/efeitos dos fármacos , Clorofila/química , Ciclopentanos/química , Ciclopentanos/farmacologia , Ditiocarb/farmacologia , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Oxirredutases Intramoleculares/metabolismo , Oxigenases/metabolismo , Oxilipinas/química , Oxilipinas/farmacologia
15.
Medicine (Baltimore) ; 98(49): e18282, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31804370

RESUMO

RATIONALE: Fetal adenocarcinoma of the lung (FLAC) with fetal lung-like morphology is a rare entity of pulmonary adenocarcinoma. Well-differentiated fetal adenocarcinoma (WDFA) belongs to its the low-grade form, which possesses a relatively favorable prognosis. Tuberculosis (TB) is an aggressive infectious disease that has been ranked as one of the top 10 causes of death worldwide. There may be a connection between the 2 and attention should be paid to the differential diagnosis. PATIENT CONCERNS: A 28-year-old non-smoking female was admitted with signs of hemoptysis, and she had been coughing up phlegm for 5 years. The patient was previously diagnosed with TB in another hospital, and underwent an anti-TB regimen. DIAGNOSIS: The co-existence of WDFA and TB was confirmed via histopathological evaluation of postoperative samples. INTERVENTIONS: The patient was subjected to a right lower lobectomy together with a wedge resection of the right upper lobe using video-assisted thoracoscopic surgery, with systemic lymphadenectomy. OUTCOMES: The patient tolerated the surgical procedure well and underwent an uneventful postoperative course. LESSONS: To our knowledge, no previous reports exist of cases with WDFA accompanied by TB. The present case indicated that a prior diagnosis of TB might predispose to lung cancer regardless of smoking history. It is also essential to distinguish WDFA from TB because of the similarity in clinical features and sites of pathological changes. Patients with WDFA usually have a better prognosis and surgery is the preferred treatment.


Assuntos
Adenocarcinoma de Pulmão/complicações , Tuberculose Pulmonar/complicações , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/cirurgia , Adulto , Antituberculosos/uso terapêutico , Feminino , Humanos , Biópsia Guiada por Imagem , Excisão de Linfonodo , Pneumonectomia , Cirurgia Torácica Vídeoassistida , Tomografia Computadorizada por Raios X , Tuberculose Pulmonar/diagnóstico por imagem , Tuberculose Pulmonar/tratamento farmacológico
16.
Oncol Lett ; 18(6): 5699-5708, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31788042

RESUMO

Breast cancer is the most common malignant neoplasm in women worldwide, and the treatment regimens currently available are far from optimal. Targeted therapy, based on molecular typing of breast cancer, is the most precise form of treatment, and CXC chemokine receptor 2 (CXCR2) is one of the molecular markers used in targeted therapies. As a member of the seven transmembrane G-protein-coupled receptor family, CXCR2 and its associated ligands have been increasingly implicated in tumor-associated processes. These processes include proliferation, angiogenesis, invasion, metastasis, chemoresistance, and stemness and phenotypic maintenance of cancer stem cells. Thus, the inhibition of CXCR2 or its downstream signaling pathways could significantly attenuate tumor progression. Therefore, studies on the biological functions of CXCR2 and its association with neoplasia may help improve the prognosis of breast cancer. Furthermore, the targeting of CXCR2 could supplement the present clinical approaches of breast cancer treatment strategies. The present review discusses the structures and mechanisms of CXCR2 and its ligands. Additionally, the contribution of CXCR2 to the development of breast cancer and its potential therapeutic benefits are also discussed.

17.
Future Oncol ; 15(32): 3711-3721, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31664862

RESUMO

Aim: Circulation miRNAs have become increasingly appreciated in the diagnosis and prognosis of lung cancer. This study aims to identify and evaluate plasma miRNA-30a-5p as an early noninvasive biomarker for the diagnosis and prognosis of lung cancer. Pateints & methods: Expression levels of plasma miRNA 30a-5p were measured by quantitative real-time PCR. Receiver operating characteristic analysis and area under the curve were used to differentiate malignant from benign tumors and from healthy controls. Kaplan-Meier curves and Cox regression were used to determine survival and prognosis. Results: Our results suggest that the level of miRNA-30a-5p in plasma might be a considerable early novel noninvasive diagnostic and prognostic biomarker for lung cancer. Conclusion: Prospective studies must be performed to confirm this new early novel noninvasive diagnostic and prognostic biomarker for lung cancer.

18.
Nat Commun ; 10(1): 4664, 2019 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-31604935

RESUMO

Signal transduction systems enable organisms to monitor their external environments and accordingly adjust the cellular processes. In mast cells, the second messenger Ap4A binds to the histidine triad nucleotide-binding protein 1 (HINT1), disrupts its interaction with the microphthalmia-associated transcription factor (MITF), and eventually activates the transcription of genes downstream of MITF in response to immunostimulation. How the HINT1 protein recognizes and is regulated by Ap4A remain unclear. Here, using eight crystal structures, biochemical experiments, negative stain electron microscopy, and cellular experiments, we report that Ap4A specifically polymerizes HINT1 in solution and in activated rat basophilic leukemia cells. The polymerization interface overlaps with the area on HINT1 for MITF interaction, suggesting a possible competitive mechanism to release MITF for transcriptional activation. The mechanism depends precisely on the length of the phosphodiester linkage of Ap4A. These results highlight a direct polymerization signaling mechanism by the second messenger.


Assuntos
Fosfatos de Dinucleosídeos/metabolismo , Mastócitos/metabolismo , Proteínas do Tecido Nervoso/fisiologia , Linhagem Celular , Cristalografia por Raios X , Técnicas de Silenciamento de Genes , Fator de Transcrição Associado à Microftalmia/genética , Fator de Transcrição Associado à Microftalmia/metabolismo , Fator de Transcrição Associado à Microftalmia/fisiologia , Proteínas do Tecido Nervoso/química , Proteínas do Tecido Nervoso/metabolismo , Polimerização , Estrutura Terciária de Proteína , Transdução de Sinais
19.
ACS Omega ; 4(15): 16551-16563, 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31616835

RESUMO

Polymeric nanocarriers have been extensively used in medicinal applications for drug delivery. However, intravenous nanocarriers circulating in the blood will be rapidly cleared from the mononuclear macrophage system. The surface physicochemical characterizations of nanocarriers are the primary factors to determine their fate in vivo, such as evading the reticuloendothelial system, exhibiting long blood circulation times, and accumulating in the targeted site. In this work, we develop a series of polyurethane micelles containing segments of an anionic tripeptide, hydrophilic mPEG, and disulfide bonds. It is found that the long hydrophilic mPEG can shield the micellar surface and have a synergistic effect with the negatively charged tripeptide to minimize macrophage phagocytosis. Meanwhile, the disulfide bond can rapidly respond to the intracellular reduction environment, leading to the acceleration of drug release and improvement of the therapeutic effect. Our results verify that these anionic polyurethane micelles hold great potential in the development of the stealth immune system and controllable intracellular drug transporters.

20.
Biomater Sci ; 7(12): 5369-5382, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31621697

RESUMO

Infections resulting from the attachment of bacteria and biofilm formation on the surface of medical implants give rise to a severe problem for medical device safety. Thus, the development of antibacterial materials that integrate bactericidal and antifouling properties is a promising approach to prevent biomaterial-associated infections. In this study, two types of dopamine-modified polymers, dopamine-terminated quaternary ammonium salt polymer (D-PQAs) with various lengths of N-alkyl chain (D-PQA4C, D-PQA8C, and D-PQA12C) and dopamine-terminated poly(sulfobetaine methacrylate) (D-PSBMA), were synthesized via atom transfer radical polymerization (ATRP). Mixed polymer brushes of D-PQAs and D-PSBMA with various ratios were well-integrated onto the surface of a silicon wafer via a facile mussel-inspired adhesion. We demonstrate that the synergistic antibacterial effect depends on both the ratio of the two components and the surface structures of the mixed polymer brushes, originating from the interactions between D-PQAs and D-PSBMA. The N-alkyl chain length of D-PQAs influenced the distribution and orientation of the alkyl chain on the mixed polymer brushes. A chart of the antibacterial efficiency of the mixed polymer brushes was obtained to reveal the synergistic role of their cationic and zwitterionic chains to resist S. aureus. The dominant amount of antifouling D-PSBMA with a minor amount of bactericidal D-PQAs with a short N-alkyl chain length facilitated the synergistic antibacterial effect. The selected polymer brushes (PSBMA/PQA4C-10%, PSBMA/PQA4C-30%, and PSBMA/PQA8C-10%) could effectively prevent biofilm formation by S. aureus for a long time, while having good biocompatibility. This work may provide a universal design strategy for the preparation of anti-biofilm and biocompatible surfaces for biomedical applications.

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