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1.
Medicine (Baltimore) ; 102(37): e35171, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37713830

RESUMO

The psychological condition of community-dwelling older adults is a global concern under coronavirus disease 2019. Loneliness is the key risk factor for depression among community-dwelling older adults. This study aims to explore the role of social support as a mediating factor in the relationship between depression and loneliness among community-dwelling older adults. We conducted a cross-sectional study in Chenzhou, Hunan Province, China, from June to December 2021. The sample consisted of 570 community-dwelling adults aged over 60 years. Data were collected through a general information questionnaire, the Social Support Rating Scale, the University of California at Los Angeles Loneliness Scale, and the Center for Epidemiological Survey, Depression Scale. Statistical Package for the Social Sciences PROCESS macro was used to examine the mediating effect of social support between loneliness and depression. This study found that depression was negatively associated with social support (r = -0.381, P < .001), but it was positively correlated with loneliness (r = 0.403, P < .001); loneliness was a predictor of depression (B = 0.333, P < .001). In addition, social support significantly mediated the relationship between loneliness and depression, with an indirect effect of 0.239 (95% Bootstrap CI -0.264 to -0.510), the overall effect value for depression was 0.572, accounting for 56.3% of the total variance in depression within this model. In conclusion, the findings suggest that social support plays a mediating role between depression and loneliness in older adults. This implies that interventions aimed at reducing loneliness and enhancing social support have the potential to alleviate depressive symptoms among this population. By addressing these factors, healthcare professionals and caregivers can promote the mental well-being of older adults and contribute to improved overall quality of life.


Assuntos
COVID-19 , Humanos , Idoso , Pessoa de Meia-Idade , COVID-19/epidemiologia , Estudos Transversais , Depressão/epidemiologia , Vida Independente , Solidão , Qualidade de Vida , China/epidemiologia , Apoio Social
2.
Int J Ophthalmol ; 16(9): 1456-1464, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37724274

RESUMO

AIM: To investigate the role of autophagy inhibitor 3-methyladenine (3-MA) on a diabetic mice model (DM) and the potential mechanism. METHODS: Male C57BL/6J mice were randomly divided into a normal control group (NC group) and an DM group. DM were induced by multiple low-dose intraperitoneal injection of streptozotocin (STZ) 60 mg/kg·d for 5 consecutive days. DM mice were randomly subdivided into untreated group (DM group), 3-MA (10 mg/kg·d by gavage) treated group (DM+3-MA group) and chloroquine (CQ; 50 mg/kg by intraperitoneal injection) treated group (DM+CQ group). The fasting blood glucose (FBG) levels were recorded every week. At the end of experiment, retinal samples were collected. The expression levels of pro-apoptotic proteins cleaved caspase-3, cleaved poly ADP-ribose polymerase 1 (PARP1) and Bax, anti-apoptotic protein Bcl-2, fibrosis-associated proteins Fibronectin and type 1 collagen α1 chain (COL1A1), vascular endothelial growth factor (VEGF), inflammatory factors interleukin (IL)-1ß and tumor necrosis factor (TNF)-α, as well as autophagy related proteins LC3, Beclin-1 and P62 were determined by Western blotting. The oxidative stress indicators 8-hydroxydeoxyguanosine (8-OHdG) and malondialdehyde (MDA) were detected by commercial kits. RESULTS: Both 3-MA and CQ had short-term hypoglycemic effect on FBG and reduced the expression of VEGF and inflammatory factors IL-1ß and TNF-α in DM mice. 3-MA also significantly alleviated oxidative stress indicators 8-OHdG and MDA, decreased the expression of fibrosis-related proteins Fibronectin and COL1A1, pro-apoptotic proteins cleaved caspase-3, cleaved PARP1, as well as the ratio of Bax/Bcl-2. CQ had no significant impact on the oxidative stress indicators, fibrosis, and apoptosis related proteins. The results of Western blotting for autophagy related proteins showed that the ratio of LC3 II/LC3 I and the expression of Beclin-1 in the retina of DM mice were decreased by 3-MA treatment, and the expression of P62 was further increased by CQ treatment. CONCLUSION: 3-MA has anti-apoptotic and anti-fibrotic effects on the retina of DM mice, and can attenuate retinal oxidative stress, VEGF expression and the production of inflammatory factors in the retina of DM mice. The underlying mechanism of the above effects of 3-MA may be related to its inhibition of early autophagy and hypoglycemic effect.

3.
Chem Rev ; 123(16): 10206-10257, 2023 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-37523660

RESUMO

Using compressive mechanical forces, such as pressure, to induce crystallographic phase transitions and mesostructural changes while modulating material properties in nanoparticles (NPs) is a unique way to discover new phase behaviors, create novel nanostructures, and study emerging properties that are difficult to achieve under conventional conditions. In recent decades, NPs of a plethora of chemical compositions, sizes, shapes, surface ligands, and self-assembled mesostructures have been studied under pressure by in-situ scattering and/or spectroscopy techniques. As a result, the fundamental knowledge of pressure-structure-property relationships has been significantly improved, leading to a better understanding of the design guidelines for nanomaterial synthesis. In the present review, we discuss experimental progress in NP high-pressure research conducted primarily over roughly the past four years on semiconductor NPs, metal and metal oxide NPs, and perovskite NPs. We focus on the pressure-induced behaviors of NPs at both the atomic- and mesoscales, inorganic NP property changes upon compression, and the structural and property transitions of perovskite NPs under pressure. We further discuss in depth progress on molecular modeling, including simulations of ligand behavior, phase-change chalcogenides, layered transition metal dichalcogenides, boron nitride, and inorganic and hybrid organic-inorganic perovskites NPs. These models now provide both mechanistic explanations of experimental observations and predictive guidelines for future experimental design. We conclude with a summary and our insights on future directions for exploration of nanomaterial phase transition, coupling, growth, and nanoelectronic and photonic properties.

4.
Risk Manag Healthc Policy ; 15: 2187-2195, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36447840

RESUMO

Purpose: COVID-19 posed a threat to the public's physical and mental health, and under outbreak control, the opportunities to go outside of the elderly have been reduced and making it more difficult to access health information and detrimental to their health management. This study aims to assess the current status of health information literacy (HIL) among older adults in the community in the context of COVID-19 and to identify its associated factors. Methods: A cross-sectional survey was conducted from April to July, 2021, for which 617 community elderly members were recruited in Chenzhou, China. Data were collected through a general information questionnaire, The Chinese residents' HIL self-rated scale and a reliability evaluation form. Results: The average score of HIL was 75.87 ± 9.85, and after processed by the 100-point system, we found 84.12% (519/617) of the participants scored less than 60 points, which indicates that the overall level of HIL among the community elderly is low. Multiple linear regression showed that age, gender, education, annual family Income, living arrangement, and chronic disease status (ß = -0.341, -0.296, 0.384, 0.327, 0.296, 0.356, respectively; all P < 0.001) were significantly associated with the level of HIL found among the community elderly, out of which education was the most important associated factor. Conclusion: The overall HIL level among the community elderly was low in Central China during the COVID-19 pandemic. Our results further prove the need for tailor-made health education programs for this group, with particular attention paid to the low-educated and low-income among them. Those measures must highlight on three aspects of health information search, evaluation, and application skills to offer useful experiences that improve the HIL level of the elderly and strengthen their ability to cope with emerging public health events.

5.
Opt Express ; 30(12): 20250-20260, 2022 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-36224775

RESUMO

The two-dimensional/three-dimensional van der Waals heterostructures provide novel optoelectronic properties for the next-generation of information devices. Herein, MoS2/Ge heterojunction avalanche photodetectors are readily obtained. The device with an Ag electrode at MoS2 side exhibits more stable rectification characteristics than that with an Au electrode. The rectification radio greater than 103 and a significant avalanche breakdown are observed in the device. The responsivity of 170 and 4 A/W and the maximum gain of 320 and 13 are obtained under 532 and 1550 nm illumination, respectively. Such photoelectric properties are attributed to the carrier multiplication at a Ge/MoS2 junction due to an avalanche breakdown. The mechanism is confirmed by the Sentaurus TCAD-simulated I-V characteristics.

6.
Anal Chem ; 94(37): 12927-12933, 2022 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-36083155

RESUMO

KRAS is one of the most frequently mutated oncogenes, with KRAS G12C recently becoming an actionable target for small molecule intervention. GDC-6036 is an investigational KRAS G12C inhibitor that acts by irreversibly binding to the switch II pocket of KRAS G12C when in the inactive GDP-bound state, thereby blocking GTP binding and activation. Assessing target engagement is an essential component of clinical drug development, helping to demonstrate mechanistic activity, guide dose selection, understand pharmacodynamics as it relates to clinical response, and explore resistance. Here, we report the development of an ultra-sensitive approach for assessing KRAS G12C engagement. Immunoaffinity enrichment with a commercially available anti-RAS antibody was combined with a targeted 2D-LC-MS/MS technique to quantify both free and GDC-6036-bound KRAS G12C proteins. A KRAS G12C-positive non-small cell lung cancer xenograft model was dosed with GDC-6036 to assess the feasibility of this assay for analyzing small core needle biopsies. As predicted, dose-dependent KRAS G12C engagement was observed. To date, a sensitivity of 0.08 fmol/µg of total protein has been achieved for both free and GDC-6036-bound KRAS G12C with as little as 4 µg of total protein extracted from human tumor samples. This sub-fmol/µg level of sensitivity provides a powerful potential approach to assess covalent inhibitor target engagement at the site of action using core needle tumor biopsies from clinical studies.


Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Animais , Antineoplásicos/química , Biópsia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cromatografia Líquida , Guanosina Trifosfato , Humanos , Neoplasias Pulmonares/patologia , Mutação , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Espectrometria de Massas em Tandem
7.
Disaster Med Public Health Prep ; 17: e171, 2022 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-35673807

RESUMO

OBJECTIVE: According to a WHO report, the number of patients with coronavirus disease 2019 (COVID-19) has reached 456,797,217 worldwide as of 15 March, 2022. In Wuhan, China, large teams of health-care personnel were dispatched to respond to the COVID-19 emergency. This study aimed to determine the sociodemographic and psychological predictors of resilience among frontline nurses fighting the current pandemic. METHODS: A total of 143 nurses were recruited from February 15 to February 20, 2020, to participate in this study. The 10-item Connor-Davidson Resilience Scale and the 21-item Depression Anxiety Stress Scale were used to estimate the participants' resilience and mental wellbeing. RESULTS: Results showed that the nurses displayed a moderate resilience level. Their median depression, anxiety, and stress scores were 1, 2, and 3, respectively, which were negatively correlated with resilience. Female gender, being dispatched to Wuhan, and depression levels were the significant predictors of resilience. CONCLUSIONS: The results suggest that particular attention should be given to nurses who were dispatched to Wuhan and who exhibited depression symptoms, and appropriate measures should be taken to boost their resilience.


Assuntos
COVID-19 , Enfermeiras e Enfermeiros , Resiliência Psicológica , Humanos , Feminino , COVID-19/epidemiologia , Pandemias , SARS-CoV-2 , Depressão/epidemiologia , Depressão/etiologia , Depressão/psicologia , Estudos Transversais , Ansiedade/epidemiologia , Ansiedade/etiologia , Ansiedade/psicologia
8.
Opt Express ; 29(9): 12941-12949, 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33985039

RESUMO

A broadband, high-performance infrared Ge photodetector decorated with Au nanoparticles (NPs) is proposed. Photoelectronic characterization demonstrated that the responsivity of devices decorated with Au NPs is as high as 3.95 A/W at a wavelength of 1550 nm. Compared with a Ge photodetector without Au NPs, the responsivity of a device decorated with Au NPs is significantly increased, i.e., by more than 10 times in the entire range of infrared communication wavelengths, including the O, E, S, C, L, and U bands. The increase is ascribed to type-II energy-band alignment between Ge covered with Au NPs and bare Ge, instead of the localized surface-plasmon-resonance effect. The type-II energy-band alignment enhances the spatial electron-hole separation and restrains the electron-hole recombination, thus a larger photocurrent is observed. These results reflect the potential of this approach for achieving broadband, high-performance Ge photodetectors operating in the near-infrared communication band.

9.
Med Sci Monit ; 27: e929168, 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33649288

RESUMO

BACKGROUND There have been few studies to evaluate early warning score (EWS) systems, or track and trigger systems (TTS), to identify early clinical deterioration in patients following brain tumor surgery who are admitted to the Intensive Care Unit (ICU). The National Early Warning Score (NEWS2) is an established method used in the U.K. National Health Service to improve care for in-hospital patients. This retrospective study from a single center aimed to compare the performance of NEWS2 with 24 other types of EWS to evaluate unplanned ICU admissions within 72 h after brain tumor surgery. MATERIAL AND METHODS A total of 326 patients with brain tumors were included in the study. Patients who experienced unplanned ICU transfer after surgery (69 cases) were diagnostically matched with patients who did not require intensive care (257 controls). We collected the physiological variables to calculate the area under the receiver operator characteristic curve (AUROC), sensitivity, specificity, Youden index values, cutoff values, positive predictive values, and negative predictive values. RESULTS The NEWS2 identified postoperative brain tumor patients with AUROC (0.860, p=0.000). The Patient-At-Risk (PAR) score was higher than NEWS2 in terms of AUROC value (0.870, P=0.000), Youden index (0.589 vs 0.542). CONCLUSIONS The findings showed that although the NEWS 2 performed well when used to evaluate unplanned ICU admissions within 72 h of postoperative brain tumor patients, the PAR score was also an accurate EWS.


Assuntos
Previsões/métodos , Complicações Pós-Operatórias/classificação , Medição de Risco/métodos , Adulto , Idoso , Área Sob a Curva , Neoplasias Encefálicas/cirurgia , Estudos de Casos e Controles , Cuidados Críticos , Escore de Alerta Precoce , Feminino , Mortalidade Hospitalar , Hospitalização , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Admissão do Paciente/estatística & dados numéricos , Complicações Pós-Operatórias/mortalidade , Valor Preditivo dos Testes , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença
10.
J Am Chem Soc ; 143(7): 2688-2693, 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33577287

RESUMO

We report here pressure induced nanocrystal coalescence of ordered lead chalcogenide nanocrystal arrays into one-dimensional (1D) and 2D nanostructures. In particular, atomic crystal phase transitions and mesoscale coalescence of PbS and PbSe nanocrystals have been observed and monitored in situ respectively by wide- and small-angle synchrotron X-ray scattering techniques. At the atomic scale, both nanocrystals underwent reversible structural transformations from cubic to orthorhombic at significantly higher pressures than those for the corresponding bulk materials. At the mesoscale, PbS nanocrystal arrays displayed a superlattice transformation from face-centered cubic to lamellar structures, while no clear mesoscale lattice transformation was observed for PbSe nanocrystal arrays. Intriguingly, transmission electron microscopy showed that the applied pressure forced both spherical nanocrystals to coalesce into single crystalline 2D nanosheets and 1D nanorods. Our results confirm that pressure can be used as a straightforward approach to manipulate the interparticle spacing and engineer nanostructures with specific morphologies and, therefore, provide insights into the design and functioning of new semiconductor nanocrystal structures under high-pressure conditions.

11.
Commun Chem ; 4(1): 82, 2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-36697527

RESUMO

Metal-organic frameworks (MOF) are an emerging class of microporous materials with promising applications. MOF nanocrystals, and their assembled super-structures, can display unique properties and reactivities when compared with their bulk analogues. MOF nanostructures of 0-D, 2-D, and 3-D dimensions can be routinely obtained by controlling reaction conditions and ligand additives, while formation of 1-D MOF nanocrystals (nanowires and nanorods) and super-structures has been relatively rare. We report here a facile templated interfacial synthesis methodology for the preparation of a series of 1-D MOF nano- and micro-structures with precisely controlled shapes and sizes. Specifically, by applying track-etched polycarbonate (PCTE) membranes as the templates and at the oil/water interface, we rapidly and reproducibly synthesize zeolitic imidazolate framework-8 (ZIF-8) and ZIF-67 nano- and micro structures of sizes ranging from 10 nm to 20 µm. We also identify a size confinement effect on MOF crystal growth, which leads to single crystals under the most restricted conditions and inter-grown polycrystals at larger template pore sizes, as well as surface directing effects that influence the crystallographic preferred orientation. Our findings provide a potentially generalizable method for controlling the size, morphology, and crystal orientations of MOF nanomaterials, as well as offering fundamental understanding into MOF crystal growth mechanisms.

12.
Chemistry ; 26(61): 13788-13791, 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-32619313

RESUMO

Charge-separated metal-organic frameworks (MOFs) are a unique class of MOFs that can possess added properties originating from the exposed ionic species. A new charge-separated MOF, namely, UNM-6 synthesized from a tetrahedral borate ligand and Co2+ cation is reported herein. UNM-6 crystalizes into the highly symmetric P43n space group with fourfold interpenetration, despite the stoichiometric imbalance between the B and Co atoms, which also leads to loosely bound NO3 - anions within the crystal structure. These NO3 - ions can be quantitatively exchanged with various other anions, leading to Lewis acid (Co2+ ) and Lewis base (anions) pairs within the pores and potentially cooperative catalytic activities. For example, UNM-6-Br, the MOF after anion exchange with Br- anions, displays high catalytic activity and stability in reactions of CO2 chemical fixation into cyclic carbonates.

13.
Anal Chem ; 92(13): 9412-9420, 2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32510921

RESUMO

Mass spectrometry has recently emerged as a powerful analytical tool for the assessment of pharmacokinetics and biomarkers in drug development. Compared with ligand binding assays, a major advantage of mass spectrometry-based assays is that they are less dependent on high quality binding reagents, while a key limitation is the relatively lower sensitivity. To address the sensitivity issue, we have developed a generic reagent, ultratargeted two-dimensional liquid chromatography-tandem mass spectrometry (2D-LC-MS/MS) method which combines commercially available protein A affinity capture, targeted analyte isolation by 2D-LC, and targeted detection by multiple reaction monitoring (MRM). A targeted-2D-with-dilution configuration was designed to automate 2D-LC-MS/MS. This method was systematically evaluated using an anti-CD22 monoclonal antibody spiked into monkey and human serum, where lower limits of quantification (LLOQ) of 0.78 and 1.56 ng/mL were achieved, respectively. This represents an over 100-fold improvement in assay sensitivity compared to the conventional LC-MS/MS method. The performance of the method was further confirmed by analyzing another monoclonal antibody, bevacizumab, as well as a soluble antigen, circulating PD-L1. The results indicate that our method enables quantification of antibody therapeutics and antigen biomarkers in both clinical and nonclinical samples in the pg/mL to low ng/mL range. Protein A affinity capture was employed as a universal sample preparation procedure applicable to both full-length antibody therapeutics and antibody-antigen complexes. This novel method is also fully automated and proven to be highly robust for routine bioanalysis in drug development.


Assuntos
Anticorpos Monoclonais/sangue , Espectrometria de Massas em Tandem/métodos , Animais , Complexo Antígeno-Anticorpo/sangue , Automação , Antígeno B7-H1/sangue , Bevacizumab/sangue , Cromatografia Líquida de Alta Pressão , Haplorrinos , Humanos , Concentração de Íons de Hidrogênio , Limite de Detecção , Lectina 2 Semelhante a Ig de Ligação ao Ácido Siálico/imunologia
14.
J Am Chem Soc ; 142(14): 6505-6510, 2020 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-32202423

RESUMO

Understanding structural stability and phase transformation of nanoparticles under high pressure is of great scientific interest, as it is one of the crucial factors for design, synthesis, and application of materials. Even though high-pressure research on nanomaterials has been widely conducted, their shape-dependent phase transition behavior still remains unclear. Examples of phase transitions of CdS nanoparticles are very limited, despite the fact that it is one of the most studied wide band gap semiconductors. Here we have employed in situ synchrotron wide-angle X-ray scattering and transmission electron microscopy (TEM) to investigate the high-pressure behaviors of CdS nanoparticles as a function of particle shapes. We observed that CdS nanoparticles transform from wurtzite to rocksalt phase at elevated pressure in comparison to their bulk counterpart. Phase transitions also vary with particle shape: rod-shaped particles show a partially reversible phase transition and the onset of the structural phase transition pressure decreases with decreasing surface-to-volume ratios, while spherical particles undergo irreversible phase transition with relatively low phase transition pressure. Additionally, TEM images of spherical particles exhibited sintering-induced morphology change after high-pressure compression. Calculations of the bulk modulus reveal that spheres are more compressible than rods in the wurtzite phase. These results indicate that the shape of the particle plays an important role in determining their high-pressure properties. Our study provides important insights into understanding the phase-structure-property relationship, guiding future design and synthesis of nanoparticles for promising applications.

15.
Bioorg Med Chem Lett ; 30(4): 126907, 2020 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-31902710

RESUMO

Chimeric molecules which effect intracellular degradation of target proteins via E3 ligase-mediated ubiquitination (e.g., PROTACs) are currently of high interest in medicinal chemistry. However, these entities are relatively large compounds that often possess molecular characteristics which may compromise oral bioavailability, solubility, and/or in vivo pharmacokinetic properties. Accordingly, we explored whether conjugation of chimeric degraders to monoclonal antibodies using technologies originally developed for cytotoxic payloads might provide alternate delivery options for these novel agents. In this report we describe the construction of several degrader-antibody conjugates comprised of two distinct ERα-targeting degrader entities and three independent ADC linker modalities. We subsequently demonstrate the antigen-dependent delivery to MCF7-neo/HER2 cells of the degrader payloads that are incorporated into these conjugates. We also provide evidence for efficient intracellular degrader release from one of the employed linkers. In addition, preliminary data are described which suggest that reasonably favorable in vivo stability properties are associated with the linkers utilized to construct the degrader conjugates.


Assuntos
Anticorpos Monoclonais/imunologia , Portadores de Fármacos/química , Receptor alfa de Estrogênio/imunologia , Anticorpos Monoclonais/química , Antineoplásicos/química , Antineoplásicos/imunologia , Antineoplásicos/farmacologia , Desenho de Fármacos , Receptor alfa de Estrogênio/metabolismo , Humanos , Imunoconjugados/química , Imunoconjugados/imunologia , Imunoconjugados/farmacologia , Células MCF-7 , Proteólise/efeitos dos fármacos , Receptor ErbB-2/metabolismo
16.
Nanoscale Adv ; 2(6): 2462-2470, 2020 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-36133384

RESUMO

Hybrid organic-inorganic composites possessing both electronic and magnetic properties are promising materials for a wide range of applications. Controlled and ordered arrangement of the organic and inorganic components is key for synergistic cooperation toward desired functions. In this work, we report the self-assemblies of core-shell composite nanofibers from conjugated block copolymers and magnetic nanoparticles through the cooperation of orthogonal non-covalent interactions. We show that well-defined core-shell conjugated polymer nanofibers can be obtained through solvent induced self-assembly and polymer crystallization, while hydroxy and pyridine functional groups located at the shell of nanofibers can immobilize magnetic nanoparticles via hydrogen bonding and coordination interactions. These precisely arranged nanostructures possess electronic properties intrinsic to the polymers and are simultaneously responsive to external magnetic fields. We applied these composite nanofibers in organic solar cells and found that these non-covalent interactions led to controlled thin film morphologies containing uniformly dispersed nanoparticles, although high loadings of these inorganic components negatively impact device performance. Our methodology is general and can be utilized to control the spatial distribution of functionalized organic/inorganic building blocks, and the magnetic responsiveness and optoelectronic activities of these nanostructures may lead to new opportunities in energy and electronic applications.

17.
Chemistry ; 24(19): 4830-4834, 2018 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-29493023

RESUMO

A novel strategy to attach indole-containing payloads to antibodies through a carbamate moiety and a self-immolating, disulfide-based linker is described. This new strategy was employed to connect a selective estrogen receptor down-regulator (SERD) to various antibodies in a site-selective manner. The resulting conjugates displayed potent, antigen-dependent down-regulation of estrogen receptor levels in MCF7-neo/HER2 and MCF7-hB7H4 cells. They also exhibited similar antigen-dependent modulation of the estrogen receptor in tumors when administered intravenously to mice bearing MCF7-neo/HER2 tumor xenografts. The indole-carbamate moiety present in the new linker was stable in whole blood from various species and also exhibited good in vivo stability properties in mice.


Assuntos
Indóis/química , Animais , Anticorpos Monoclonais/química , Linhagem Celular Tumoral , Humanos , Imunoconjugados/administração & dosagem , Células MCF-7 , Camundongos
18.
Polymers (Basel) ; 8(12)2016 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-30974686

RESUMO

Nanostructuring organic polymers and organic/inorganic hybrid materials and controlling blend morphologies at the molecular level are the prerequisites for modern electronic devices including biological sensors, light emitting diodes, memory devices and solar cells. To achieve all-around high performance, multiple organic and inorganic entities, each designed for specific functions, are commonly incorporated into a single device. Accurate arrangement of these components is a crucial goal in order to achieve the overall synergistic effects. We describe here a facile methodology of nanostructuring conjugated polymers and inorganic quantum dots into well-ordered core/shell composite nanofibers through cooperation of several orthogonal non-covalent interactions including conjugated polymer crystallization, block copolymer self-assembly and coordination interactions. Our methods provide precise control on the spatial arrangements among the various building blocks that are otherwise incompatible with one another, and should find applications in modern organic electronic devices such as solar cells.

19.
Biomed Res Int ; 2014: 273180, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25313354

RESUMO

BACKGROUND: Nek2 is a serine/threonine kinase localized to the centrosome. It promotes cell cycle progression from G2 to M by inducing centrosome separation. Recent studies have shown that high Nek2 expression is correlated with drug resistance in multiple myeloma patients. MATERIALS AND METHODS: To investigate the role of Nek2 in bortezomib resistance, we ectopically overexpressed Nek2 in several cancer cell lines, including multiple myeloma lines. Small-molecule inhibitors of Nek2 were discovered using an in-house library of compounds. We tested the inhibitors on proteasome and cell cycle activity in several cell lines. RESULTS: Proteasome activity was elevated in Nek2-overexpressing cell lines. The Nek2 inhibitors inhibited proteasome activity in these cancer cell lines. Treatment with these inhibitors resulted in inhibition of proteasome-mediated degradation of several cell cycle regulators in HeLa cells, leaving them arrested in G2/M. Combining these Nek2 inhibitors with bortezomib increased the efficacy of bortezomib in decreasing proteasome activity in vitro. Treatment with these novel Nek2 inhibitors successfully mitigated drug resistance in bortezomib-resistant multiple myeloma. CONCLUSION: Nek2 plays a central role in proteasome-mediated cell cycle regulation and in conferring resistance to bortezomib in cancer cells. Taken together, our results introduce Nek2 as a therapeutic target in bortezomib-resistant multiple myeloma.


Assuntos
Complexo de Endopeptidases do Proteassoma/metabolismo , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Bibliotecas de Moléculas Pequenas/farmacologia , Ácidos Borônicos/farmacologia , Bortezomib , Proteína Quinase CDC2/metabolismo , Linhagem Celular Tumoral , Ciclina B/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Sinergismo Farmacológico , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Humanos , Mitose/efeitos dos fármacos , Quinases Relacionadas a NIMA , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Proteínas Serina-Treonina Quinases/metabolismo , Proteólise/efeitos dos fármacos , Pirazinas/farmacologia , Bibliotecas de Moléculas Pequenas/química
20.
J Proteome Res ; 9(1): 22-9, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19354234

RESUMO

Membrane skeletons, which are defined for their resistance to Triton extraction of cell membrane, play a pivotal role in cell shape and signal transduction. In the present work, we applied a complementary proteomics strategy: 2-DE combined with MALDI-TOF MS and 1D-PAGE coupled with LC-ESI-FTICR MS to analyze a membrane skeleton fraction isolated from Sprague-Dawley (SD) rat livers. We report confident identification of 104 proteins (39 membrane skeleton proteins) using 2-DE and MALDI-TOF MS approach and 402 proteins (87 membrane skeleton proteins) using 1D-PAGE LC-MS/MS analysis. In total, 100 membrane skeleton proteins were identified using the two complementary proteomics means. To the best of our knowledge, this is the largest data set of membrane skeleton proteins to date. Noteworthily, almost all of these membrane skeleton proteins were associated with actin or cytokeratin, and more than half of them were involved in various cell junctions. Our results offer insights into the protein components of the actin- and cytokeratin-based membrane skeletons in rat livers, which would improve our understanding of their biological roles.


Assuntos
Actinas/análise , Queratinas/análise , Fígado/química , Proteoma/análise , Proteômica/métodos , Animais , Western Blotting , Membrana Celular/química , Membrana Celular/ultraestrutura , Eletroforese em Gel Bidimensional , Junções Intercelulares/química , Junções Intercelulares/metabolismo , Fígado/citologia , Fígado/metabolismo , Ratos , Reprodutibilidade dos Testes , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
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