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1.
Small ; 20(19): e2310873, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38279618

RESUMO

Ferroptosis, characterized by the induction of cell death via lipid peroxidation, has been actively studied over the last few years and has shown the potential to improve the efficacy of cancer nanomedicine in an iron-dependent manner. Radiation therapy, a common treatment method, has limitations as a stand-alone treatment due to radiation resistance and safety as it affects even normal tissues. Although ferroptosis-inducing drugs help alleviate radiation resistance, there are no safe ferroptosis-inducing drugs that can be considered for clinical application and are still in the research stage. Here, the effectiveness of combined treatment with radiotherapy with Fe and hyaluronic acid-based nanoparticles (FHA-NPs) to directly induce ferroptosis, considering the clinical applications is reported. Through the induction of ferroptosis by FHA-NPs and apoptosis by X-ray irradiation, the therapeutic efficiency of cancer is greatly improved both in vitro and in vivo. In addition, Monte Carlo simulations are performed to assess the physical interactions of the X-rays with the iron-oxide nanoparticle. The study provides a deeper understanding of the synergistic effect of ferroptosis and X-ray irradiation combination therapy. Furthermore, the study can serve as a valuable reference for elucidating the role and mechanisms of ferroptosis in radiation therapy.


Assuntos
Ferroptose , Nanopartículas , Ferroptose/efeitos dos fármacos , Humanos , Nanopartículas/química , Animais , Raios X , Linhagem Celular Tumoral , Camundongos , Apoptose/efeitos dos fármacos , Ácido Hialurônico/química , Terapia Combinada
2.
Eur J Nucl Med Mol Imaging ; 51(6): 1763-1772, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38200396

RESUMO

PURPOSE: [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) has limitations in prostate cancer (PCa) detection owing to low glycolysis in the primary tumour. Recently, prostate-specific membrane antigen (PSMA) PET/CT has been useful for biochemical failure detection and radioligand therapy (RLT) guidance. However, few studies have evaluated its use in primary prostate tumours using PSMA and [18F]FDG PET/CT. This study aimed to evaluate [18F]PSMA-1007 and [18F]FDG PET/CT for primary tumour detection and understand the association of metabolic heterogeneity with clinicopathological characteristics at staging and postoperatively. METHOD: This prospective study included 42 index tumours (27 acinar and 15 ductal-dominant) in 42 patients who underwent [18F]PSMA-1007 and [18F]FDG PET/CT and subsequent radical prostatectomy. All patients were followed for a median of 26 mo, and serum prostate-specific antigen levels were measured every 3 mo to evaluate biochemical failure. One-way analysis of variance, Tukey's multiple comparison test, and Fisher's exact test were performed. RESULTS: All 42 index tumours were detected on [18F]PSMA-1007 PET/CT, whereas only 15 were detected on [18F]FDG PET/CT (62.3% vs. 37.7%, p < 0.0001). A high SUVmax for [18F]PSMA-1007 was observed in tumours with high Gleason scores (GS 6-7 vs. GS 8-10; 12.1 vs. 20.1, p < 0.05). Tumours with [18F]FDG uptake were mostly ductal dominant (acinar-dominant 4/27; ductal-dominant; 11/15, p < 0.001), with lower [18F]PSMA-1007 uptake than tumours without [18F]FDG uptake (SUVmax 16.58 vs. 11.19, p < 0.001). There were 16.6% (7/42) of patients with pStage IV in whom the primary tumours were [18F]FDG positive. Biochemical failure was observed in 14.8% (4/27) of patients with [18F]FDG negative tumours but in 53.3% (8/15) of patients with [18F]FDG positive tumours (p = 0.013). CONCLUSIONS: [18F]PSMA-1007 PET/CT was superior to [18F]FDG PET/CT in detecting primary PCa. In contrast, tumours with [18F]FDG uptake are associated with larger size, a ductal-dominant type, and likely to undergo metastasis at staging and biochemical failure postoperatively.


Assuntos
Fluordesoxiglucose F18 , Estadiamento de Neoplasias , Niacinamida/análogos & derivados , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/patologia , Idoso , Pessoa de Meia-Idade , Oligopeptídeos/química , Estudos Prospectivos , Compostos Radiofarmacêuticos , Período Pós-Operatório
3.
Biomacromolecules ; 25(7): 4344-4357, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38917335

RESUMO

Wound dressings made from natural-derived polymers are highly valued for their biocompatibility, biodegradability, and biofunctionality. However, natural polymer-based hydrogels can come with their own set of limitations, such as low mechanical strength, limited cell affinity, and the potential cytotoxicity of cross-linkers, which delineate the boundaries of their usage and hamper their practical application. To overcome the limitation of natural-derived polymers, this study utilized a mixture of oxidized alginate and gelatin with 5 mg/mL polycaprolactone (PCL):gelatin nanofiber fragments at a ratio of 7:3 (OGN-7) to develop a hydrogel composite wound dressing that can be injected and has the ability to be remended. The in situ formation of the remendable hydrogel is facilitated by dual cross-linking of oxidized alginate chains with gelatin and PCL/gelatin nanofibers through Schiff-base mechanisms, supported by the physical integration of nanofibers, thereby obviating the need for additional cross-linking agents. Furthermore, OGN-7 exhibits increased stiffness (γ = 79.4-316.3%), reduced gelation time (543 ± 5 to 475 ± 5 s), improved remendability of the hydrogel, and excellent biocompatibility. Notably, OGN-7 achieves full fusion within 1 h of incubation and maintains structural integrity under external stress, effectively overcoming the inherent mechanical weaknesses of natural polymer-based dressings and enhancing biofunctionality. The therapeutic efficacy of OGN-7 was validated through a full-thickness in vivo wound healing analysis, which demonstrated that OGN-7 significantly accelerates wound closure compared to alginate-based dressings and control groups. Histological analysis further revealed that re-epithelialization and collagen deposition were markedly enhanced in the regenerating skin of the OGN-7 group, confirming the superior therapeutic performance of OGN-7. In summary, OGN-7 optimized the synergistic effects of natural polymers, which enhances their collective functionality as a wound dressing and expands their utility across diverse biomedical applications.


Assuntos
Alginatos , Gelatina , Hidrogéis , Nanofibras , Cicatrização , Alginatos/química , Gelatina/química , Nanofibras/química , Cicatrização/efeitos dos fármacos , Hidrogéis/química , Hidrogéis/farmacologia , Animais , Camundongos , Bandagens , Reagentes de Ligações Cruzadas/química , Poliésteres/química , Regeneração/efeitos dos fármacos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Masculino
4.
Bioorg Med Chem ; 100: 117588, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38295487

RESUMO

Microsatellite instability (MSI) is a hypermutable condition caused by DNA mismatch repair system defects, contributing to the development of various cancer types. Recent research has identified Werner syndrome ATP-dependent helicase (WRN) as a promising synthetic lethal target for MSI cancers. Herein, we report the first discovery of thiophen-2-ylmethylene bis-dimedone derivatives as novel WRN inhibitors for MSI cancer therapy. Initial computational analysis and biological evaluation identified a new scaffold for a WRN inhibitor. Subsequent SAR study led to the discovery of a highly potent WRN inhibitor. Furthermore, we demonstrated that the optimal compound induced DNA damage and apoptotic cell death in MSI cancer cells by inhibiting WRN. This study provides a new pharmacophore for WRN inhibitors, emphasizing their therapeutic potential for MSI cancers.


Assuntos
Instabilidade de Microssatélites , Neoplasias , Tiofenos , Humanos , Cicloexanonas , Neoplasias/tratamento farmacológico , Neoplasias/genética , Helicase da Síndrome de Werner/antagonistas & inibidores , Helicase da Síndrome de Werner/metabolismo , Tiofenos/química , Tiofenos/farmacologia
5.
Brain ; 146(7): 2957-2974, 2023 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-37062541

RESUMO

Reactive astrogliosis is a hallmark of Alzheimer's disease (AD). However, a clinically validated neuroimaging probe to visualize the reactive astrogliosis is yet to be discovered. Here, we show that PET imaging with 11C-acetate and 18F-fluorodeoxyglucose (18F-FDG) functionally visualizes the reactive astrocyte-mediated neuronal hypometabolism in the brains with neuroinflammation and AD. To investigate the alterations of acetate and glucose metabolism in the diseased brains and their impact on the AD pathology, we adopted multifaceted approaches including microPET imaging, autoradiography, immunohistochemistry, metabolomics, and electrophysiology. Two AD rodent models, APP/PS1 and 5xFAD transgenic mice, one adenovirus-induced rat model of reactive astrogliosis, and post-mortem human brain tissues were used in this study. We further curated a proof-of-concept human study that included 11C-acetate and 18F-FDG PET imaging analyses along with neuropsychological assessments from 11 AD patients and 10 healthy control subjects. We demonstrate that reactive astrocytes excessively absorb acetate through elevated monocarboxylate transporter-1 (MCT1) in rodent models of both reactive astrogliosis and AD. The elevated acetate uptake is associated with reactive astrogliosis and boosts the aberrant astrocytic GABA synthesis when amyloid-ß is present. The excessive astrocytic GABA subsequently suppresses neuronal activity, which could lead to glucose uptake through decreased glucose transporter-3 in the diseased brains. We further demonstrate that 11C-acetate uptake was significantly increased in the entorhinal cortex, hippocampus and temporo-parietal neocortex of the AD patients compared to the healthy controls, while 18F-FDG uptake was significantly reduced in the same regions. Additionally, we discover a strong correlation between the patients' cognitive function and the PET signals of both 11C-acetate and 18F-FDG. We demonstrate the potential value of PET imaging with 11C-acetate and 18F-FDG by visualizing reactive astrogliosis and the associated neuronal glucose hypometablosim for AD patients. Our findings further suggest that the acetate-boosted reactive astrocyte-neuron interaction could contribute to the cognitive decline in AD.


Assuntos
Doença de Alzheimer , Camundongos , Humanos , Ratos , Animais , Doença de Alzheimer/metabolismo , Fluordesoxiglucose F18/metabolismo , Astrócitos/metabolismo , Radioisótopos de Carbono/metabolismo , Gliose/diagnóstico por imagem , Encéfalo/patologia , Tomografia por Emissão de Pósitrons/métodos , Ácido gama-Aminobutírico/metabolismo
6.
Health Econ ; 33(6): 1123-1132, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38498377

RESUMO

We use a difference-in-differences design to study the effect of opioid use on traffic fatalities. Following Alpert et al., we focus on the 1996 introduction and marketing of OxyContin, and we examine its long-term impacts on traffic fatalities involving Schedule II drugs or heroin. Based on the national fatal vehicle crash database, we find that the states heavily targeted by the initial marketing of OxyContin (i.e., non-triplicate states) experienced 2.4 times more traffic fatalities (1.6 additional deaths per million individuals) involving Schedule II drugs or heroin during 2011-2019, when overdose deaths from heroin and fentanyl became more prominent. We find no difference in traffic fatalities until after the mid-2000s between states with and without a triplicate prescription program. The effect is mainly concentrated in fatal crashes with drug involvement of drivers ages between 25 and 44. Our results highlight additional long-term detrimental consequences of the introduction and marketing of OxyContin.


Assuntos
Acidentes de Trânsito , Transtornos Relacionados ao Uso de Opioides , Humanos , Acidentes de Trânsito/mortalidade , Adulto , Masculino , Transtornos Relacionados ao Uso de Opioides/mortalidade , Feminino , Estados Unidos/epidemiologia , Analgésicos Opioides , Pessoa de Meia-Idade , Oxicodona , Overdose de Drogas/mortalidade , Fentanila/intoxicação , Heroína/intoxicação
7.
Sensors (Basel) ; 24(9)2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38732990

RESUMO

In this paper, a volumetric Rotman lens antenna operating at 28 GHz is proposed. The design formula and procedure were derived for the 3-D Rotman lens antenna. The number of tilted beams is 3 × 3. The six rectangular blocks are assembled using a metallic bolt. The input port consists of a waveguide, and the output port is made of an open-ended waveguide. The input and output waveguides are drilled in a flat conducting plate. The input and output port positions are optimized. Simulated and measured results show that the radiating beam is controlled almost exactly as calculated. Compared with the previous two-stage stacked Rotman lens antenna, the proposed Rotman lens antenna can dramatically decrease the antenna volume by approximately 75%.

8.
BMC Geriatr ; 23(1): 724, 2023 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-37940846

RESUMO

BACKGROUND: Older adults have muscle loss and are at risk of falling. Recently, research in the healthcare field has been actively conducted, and Samsung Electronics has developed EX1, a hip joint assisted robot for exercise. This study aimed to verify the effect of a 4-week combined exercise program applying EX1 on older adults. METHODS: This study design was an evaluator-blinded, pre- and post-test. A total of 21 older adults performed an exercise program consisting of walking and fitness wearing EX1 for 50 min per session, 3 days a week during the 4-week exercise period. For comparison before and after participating in the exercise program, the spatio-temporal parameters, pelvic movement were analyzed by G-Walk, functional outcomes were evaluated by TUG, muscle power were evaluated by RUSI, and waist-hip ratio were analyzed by Inbody. All data were analyzed before and after exercise using paired t-test, and the statistical significance level was set at 0.05. RESULTS: In spatio-temporal parameters, stride length showed statistically significant improvements after exercise with EX1 (P < 0.01). Also, propulsion showed statistically significant improvements after exercise with EX1 (P < 0.01) Regarding changes of the gait posture, there was a statistically significant improvement in pelvic movement (P < 0.05). In the functional evaluation, the time required was statistically significantly reduced in the timed up and go test (P < 0.05). CONCLUSION: These results demonstrate that a 4-week exercise program with EX1 was effective in improving the functional gait of the elderly. However, because the participants were 21, it is difficult to generalize the results. TRIAL REGISTRATION: Clinical Research Information Service, KCT0007367. Registered 08/06/2022.


Assuntos
Robótica , Dispositivos Eletrônicos Vestíveis , Humanos , Idoso , Terapia por Exercício/métodos , Equilíbrio Postural/fisiologia , Estudos de Tempo e Movimento , Marcha/fisiologia
9.
Bioconjug Chem ; 33(12): 2420-2427, 2022 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-36446084

RESUMO

To deliver membrane-impermeable drugs into eukaryotic cells, a lot of cell-penetrating peptides (CPPs) were discovered. Previously we designed an amphipathic α-helical peptide which dimerizes itself via its two C-residues. This bis-disulfide-linked dimeric bundle, LK-3, has remarkable cell-penetrating ability at nanomolar concentration, which is an essential prerequisite for CPP. In an effort to optimize the sequence of LK-3, we adjusted its length and evaluated changes in the dimerization rate. We found that a 10-amino-acid monomer has the fastest dimerization rate and subsequently modified its hydrophobic and hydrophilic residues to construct a small peptide library. The evaluation of cell permeability of these derivatives showed that their cell-penetrating ability is comparable to that of the LK-3, except V- or H-containing ones. In this library, diLR10 was found to display fast nanomolar cell membrane penetration, low toxicity, and ease of production. The methotrexate (MTX) conjugate of diLR10, MTX-diLR10, has a 19-fold increased efficacy over MTX in MDA-MB-231 cells and efficiently deflates lesions in a rheumatoid arthritis (RA) in vivo mouse model.


Assuntos
Peptídeos Penetradores de Células , Animais , Camundongos , Peptídeos Penetradores de Células/química , Sistemas de Liberação de Medicamentos , Aminoácidos , Conformação Proteica em alfa-Hélice
10.
Chem Res Toxicol ; 35(5): 774-781, 2022 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-35317551

RESUMO

The recent terrorist attacks using Novichok agents and subsequent operations have necessitated an understanding of its physicochemical properties, such as vapor pressure and toxicity, as well as unascertained nerve agent structures. To prevent continued threats from new types of nerve agents, the organization for the prohibition of chemical weapons (OPCW) updated the chemical weapons convention (CWC) schedule 1 list. However, this information is vague and may encompass more than 10 000 possible chemical structures, which makes it almost impossible to synthesize and measure their properties and toxicity. To assist this effort, we successfully developed machine learning (ML) models to predict the vapor pressure to help with escape and removal operations. The model shows robust and high-accuracy performance with promising features for predicting vapor pressure when applied to Novichok materials and accurate predictions with reasonable errors. The ML classification model was successfully built for the swallow globally harmonized system class of organophosphorus compounds (OP) for toxicity predictions. The tuned ML model was used to predict the toxicity of Novichok agents, as described in the CWC list. Although its accuracy and linearity can be improved, this ML model is expected to be a firm basis for developing more accurate models for predicting the vapor pressure and toxicity of nerve agents in the future to help handle future terror attacks with unknown nerve agents.


Assuntos
Substâncias para a Guerra Química , Agentes Neurotóxicos , Substâncias para a Guerra Química/análise , Substâncias para a Guerra Química/toxicidade , Aprendizado de Máquina , Agentes Neurotóxicos/química , Agentes Neurotóxicos/toxicidade , Organofosfatos/química , Pressão de Vapor
11.
Eur J Nucl Med Mol Imaging ; 48(11): 3422-3431, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33693968

RESUMO

PURPOSE: White matter hyperintensities (WMH) are typically segmented using MRI because WMH are hardly visible on 18F-FDG PET/CT. This retrospective study was conducted to segment WMH and estimate their volumes from 18F-FDG PET with a generative adversarial network (WhyperGAN). METHODS: We selected patients whose interval between MRI and FDG PET/CT scans was within 3 months, from January 2017 to December 2018, and classified them into mild, moderate, and severe groups by following the semiquantitative rating method of Fazekas. For each group, 50 patients were selected, and of them, we randomly selected 35 patients for training and 15 for testing. WMH were automatically segmented from FLAIR MRI with manual adjustment. Patches of WMH were extracted from 18F-FDG PET and segmented MRI. WhyperGAN was compared with H-DenseUnet, a deep learning method widely used for segmentation tasks, for segmentation performance based on the dice similarity coefficient (DSC), recall, and average volume differences (AVD). For volume estimation, the predicted WMH volumes from PET were compared with ground truth volumes. RESULTS: The DSC values were associated with WMH volumes on MRI. For volumes >60 mL, the DSC values were 0.751 for WhyperGAN and 0.564 for H-DenseUnet. For volumes ≤60 mL, the DSC values rapidly decreased as the volume decreased (0.362 for WhyperGAN vs. 0.237 for H-DenseUnet). For recall, WhyperGAN achieved the highest value in the severe group (0.579 for WhyperGAN vs. 0.509 for H-DenseUnet). For AVD, WhyperGAN achieved the lowest score in the severe group (0.494 for WhyperGAN vs. 0.941 for H-DenseUnet). For the WMH volume estimation, WhyperGAN performed better than H-DenseUnet and yielded excellent correlation coefficients (r = 0.998, 0.983, and 0.908 in the severe, moderate, and mild group). CONCLUSIONS: Although limited by visual analysis, the WhyperGAN based can be used to automatically segment and estimate volumes of WMH from 18F-FDG PET/CT. This would increase the usefulness of 18F-FDG PET/CT for the evaluation of WMH in patients with cognitive impairment.


Assuntos
Fluordesoxiglucose F18 , Substância Branca , Humanos , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudos Retrospectivos , Substância Branca/diagnóstico por imagem
12.
Health Econ ; 30(11): 2943-2951, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34464484

RESUMO

Recent papers have documented positive externalities of Medicaid expansions on several non-health related variables, such as crime, financial stress, child support, and child abuse. In this paper, we investigate the relationship between access to public health insurance and foster care admissions following state decisions to expand Medicaid coverage after the Affordable Care Act. Over 70% of all foster care admissions are related to child abuse incidents, which have been found to decrease following the Medicaid expansions. Our results suggest that the Medicaid expansions are associated with a large decrease in foster care admissions, driven by neglect incidents.


Assuntos
Medicaid , Patient Protection and Affordable Care Act , Criança , Acessibilidade aos Serviços de Saúde , Hospitalização , Humanos , Cobertura do Seguro , Seguro Saúde , Estados Unidos
13.
Am J Emerg Med ; 40: 184-187, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33243534

RESUMO

BACKGROUND: Aconitine is well-known for its potential analgesic, anti-inflammatory, and circulation promoting effects and has been widely used as a folk medicine in South Korea. Owing to its extremely toxic nature and relatively low safety margin, intoxication is sometimes fatal. The toxic compound mainly affects the central nervous system, heart, and muscle, resulting in cardiovascular complications. PURPOSE: To determine the exact relationship between blood concentration of aconitine and clinical manifestation. BASIC PROCEDURES: The National Forensic Service (NFS) was commissioned to assist in a quantitative analysis of highly toxic aconitine and corresponding blood concentrations by analyzing the body fluids of three patients who were suspected of aconitine poisoning. MAIN FINDINGS: Aconitine blood values tested by the NFS showed that patients with a blood concentration below a certain level developed symptoms slowly and showed a high severity of clinical manifestation. There was no correlation between blood concentration and symptoms or ECG results. CONCLUSIONS: In case of suspected aconitine poisoning, an emergency care department should be visited, even with symptomatic improvement, and the patient should be monitored for at least 24 h, depending on the level of recovery and changes in ECG results.


Assuntos
Aconitina/sangue , Aconitina/intoxicação , Idoso , Idoso de 80 Anos ou mais , Eletrocardiografia , Serviço Hospitalar de Emergência , Feminino , Medicina Legal , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia
14.
Energy (Oxf) ; 231: 120915, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34054202

RESUMO

COVID-19 made considerable changes in the lifestyle of people, which have led to a rise in energy use in homes. So, this study investigated the relationship between COVID-19 and domestic hot water demands. For this purpose, a nondimensional and principal component analysis were conducted to find out the influencing factors using demand data before and after COVID-19 from our study site. Analysis showed that the COVID-19 outbreak affected the daily peak time and the amount of domestic hot water usage, the active case number of COVID-19 was a good indicator for correlating the changes in hot water demand and patterns. Based on this, a machine learning model with an artificial neural network was developed to predict hot water demand depending on the severity of COVID-19 and the relevant correlation was also derived. The model analysis showed that the increase in the number of active cases in the region affected the hot water demand increased at a certain rate and the maximum demand peak in morning during weekdays and weekends decreased. Furthermore, if the number of active cases reached more than 4000, the peak in morning moved to afternoon so that the energy use patterns of weekdays and weekends are assimilated.

15.
Int J Mol Sci ; 22(5)2021 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-33673701

RESUMO

Chinese hamster ovary (CHO) cells are the most valuable expression host for the commercial production of biotherapeutics. Recent trends in recombinant CHO cell-line development have focused on the site-specific integration of transgenes encoding recombinant proteins over random integration. However, the low efficiency of homology-directed repair upon transfection of Cas9, single-guide RNA (sgRNA), and the donor template has limited its feasibility. Previously, we demonstrated that a double-cut donor (DCD) system enables highly efficient CRISPR/Cas9-mediated targeted integration (TI) in CHO cells. Here, we describe several CRISPR/Cas9 vector systems based on DCD templates using a promoter trap-based TI monitoring cell line. Among them, a multi-component (MC) system consisting of an sgRNA/DCD vector and Cas9 expression vector showed an approximate 1.5-fold increase in knock-in (KI) efficiency compared to the previous DCD system, when a systematically optimized relative ratio of sgRNA/DCD and Cas9 vector was applied. Our optimization efforts revealed that concurrently increasing sgRNA and DCD components relative to Cas9 correlated positively with KI efficiency at a single KI site. Furthermore, we explored component bottlenecks, such as effects of sgRNA components and applicability of the MC system on simultaneous double KI. Taken together, we improved the DCD vector design by tailoring plasmid constructs and relative component ratios, and this system can be widely used in the TI strategy of transgenes, particularly in CHO cell line development and engineering.


Assuntos
Sistemas CRISPR-Cas , Edição de Genes , Marcação de Genes/métodos , Plasmídeos/genética , Proteínas Recombinantes/genética , Transgenes/fisiologia , Animais , Células CHO , Cricetinae , Cricetulus , Plasmídeos/metabolismo
16.
Nanotechnology ; 31(26): 265302, 2020 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-32131063

RESUMO

The etch characteristics of Si and TiO2 nanostructures for optical devices were investigated using pulse biased inductively coupled plasmas (ICP) with SF6/C4F8/Ar and BCl3/Ar, respectively, and the results were compared with those etched using continuous wave (CW) biased ICP. By using pulse biasing compared to CW biasing in the etching of the line/pillar nanostructures with various aspect ratios, there was a reduction of the aspect ratio dependent etching (ARDE) and therefore, uniform etch depths for nanostructures with different pattern widths, as well as the improvement of the etch profiles without any notching, were obtained not only for silicon nanostructures but also for TiO2 nanostructures. The investigation has determined that the improvement of etch profiles and reduced ARDE effect when using pulse biasing are related to the decreased surface charging caused by neutralization of the surface and the improved radical adsorption (or etch byproduct removal) on the etched surfaces during the pulse-off period for pulse biasing compared to CW biasing.

17.
J Chem Phys ; 152(3): 034704, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31968967

RESUMO

The correlation between the structural phase transition (SPT) and oxygen vacancy in SrRuO3 (SRO) thin films was investigated by in situ X-ray diffraction (XRD) and ambient pressure X-ray photoelectron spectroscopy (AP-XPS). In situ XRD shows that the SPT occurs from a monoclinic SRO phase to a tetragonal SRO phase near ∼200 °C, regardless of the pressure environment. On the other hand, significant core level shifts in both the Ru and Sr photoemission spectra are found under ultrahigh vacuum, but not under the oxygen pressure environment. The directions and behavior of the core level shift of Ru and Sr are attributed to the formation of oxygen vacancy across the SPT temperature of SRO. The analysis of in situ XRD and AP-XPS results provides an evidence for the formation of metastable surface oxide possibly due to the migration of internal oxygen atoms across the SPT temperature, indicating the close relationship between oxygen vacancy and SPT in SRO thin films.

18.
Sensors (Basel) ; 20(4)2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32059413

RESUMO

In this paper, we investigate the so-called noise propagation effect in a mixed radio-frequency/free-space optical (RF/FSO) amplifying-and-forwarding (AF) relaying system that is applied for data transmission in wireless sensor networks. The noise propagation could be essentially severe when battery-charged sensor nodes have very limited transmit power. We provide an exact expression on the cumulative distribution function (CDF) of end-to-end signal-to-noise power ratio (SNR) for a dual-hop mixed RF/FSO AF relaying system. We assume a tightly power-constrained amplifying gain at the relay, which has been usually ignored in existing performance studies for the mixed RF/FSO AF system. It however should be considered to properly evaluate the noise propagation effect especially if the relaying power is not infinite or the sensor has a poor budget in transmit power. We apply the derived exact CDF to evaluate the system performances such as outage probability, average bit-error rate, and ergodic capacity. Numerical investigation is used to justify that the proposed analysis is exactly matched with the simulation and shows that the performance gap caused by the inclusion of the noise propagation effect is significant (about 2-12%) especially when the SNR per hop is in the medium- or the low-SNR ranges (i.e., at 10-20 dB).

19.
Eur J Nucl Med Mol Imaging ; 46(8): 1678-1684, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31102001

RESUMO

PURPOSE: We evaluated the usefulness of 11C-methionine (MET) positron emission tomography/computed tomography (PET/CT) for grading cerebral gliomas according to the 2016 WHO classification with special emphasis on the presence of the isocitrate dehydrogenase 1 (IDH1) gene mutation and 1p/19q codeletion. METHODS: In total, 144 patients underwent MET PET/CT before surgery. The ratios of the maximum standardized uptake value (SUV) of the gliomas to the mean SUV of the contralateral cortex on MET PET/CT (MET TNR) were calculated. RESULTS: The median MET TNRs in IDH1-mutant and IDH1-wildtype tumours were 1.95 and 3.35, respectively. From among 74 IDH1-mutant tumours, the oligodendrogliomas showed a higher median MET TNR than the astrocytic tumours (2.90 vs. 1.40, P < 0.001). In grade II, III and IV IDH1-mutant astrocytic tumours, the median MET TNRs were 1.20, 2.05 and 2.20, respectively (grade II vs. grade III, P < 0.0001; grade II vs. grade IV, P = 0.023). In oligodendrogliomas, the MET TNR was lower fin grade II tumours than in grade III tumours (2.30 vs. 3.30 P = 0.008). In differentiating low-grade (grade II) from high-grade (grade III and IV) gliomas, receiver operating characteristic analysis showed a higher area under the curve for wildtype tumours (0.976) than for all tumours (0.852; P < 0.001) and IDH1-mutant tumours (0.817; P = 0.004). CONCLUSION: IDH1-mutant tumours showed lower MET uptake than IDH1-wildtype tumours. Regardless of IDH1 mutation status, oligodendrogliomas with 1p/19q codeletion showed MET uptake as high as that in high-grade IDH1-wildtype tumours. Therefore, MET uptake for glioma grading was more consistent for IDH1-wildtype tumours than for IDH1-mutant tumours.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Glioma/diagnóstico por imagem , Metionina/análogos & derivados , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/normas , Compostos Radiofarmacêuticos/farmacocinética , Adulto , Idoso , Neoplasias Encefálicas/classificação , Neoplasias Encefálicas/genética , Radioisótopos de Carbono , Feminino , Glioma/classificação , Glioma/genética , Humanos , Isocitrato Desidrogenase/genética , Masculino , Pessoa de Meia-Idade , Mutação , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos
20.
Ecotoxicol Environ Saf ; 169: 361-369, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30458403

RESUMO

A fine particulate matter less than 2.5 µm (PM2.5) in the underground subway system are the cause of many diseases. The iron containing PMs frequently confront in underground stations, which ultimately have an impact on the health of living beings especially in children. Hence, it is necessary to conduct toxicity assessment of chemical species and regularized the indoor air pollutants to ensure the good health of children. Therefore, in this study, a new indoor air quality (IAQ) index is proposed based on toxicity assessment by quantitative structure-activity relationship (QSAR) model. The new indices called comprehensive indoor air toxicity (CIAT) and cumulative comprehensive indoor air toxicity (CCIAT) suggests the new standards based on toxicity assessment of PM2.5. QSAR based deep neural network (DNN) exhibited the best model in predicting the toxicity assessment of chemical species in particulate matters, which yield lowest RMSE and QF32 values of 0.6821 and 0.8346, respectively, in the test phase. After integration with a standard concentration of PM2.5, two health risk indices of CIAT and CCIAT are introduced based on toxicity assessment results, which can be use as the toxicity standard of PM2.5 for detail IAQ management in a subway station. These new health risk indices suggest more sensitive air pollutant level of iron containing fine particulate matters or molecular level contaminants in underground spaces, alerting the health risk of adults and children in "unhealthy for sensitive group".


Assuntos
Poluentes Atmosféricos , Poluição do Ar em Ambientes Fechados/análise , Monitoramento Ambiental/métodos , Ferro/análise , Material Particulado , Ferrovias , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/química , Criança , Humanos , Tamanho da Partícula , Material Particulado/análise , Material Particulado/química , Relação Quantitativa Estrutura-Atividade
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