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1.
Small ; 18(5): e2106108, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34984817

RESUMO

Using a simple, rapid solvent evaporation process, the authors produced 3D carbon nanotube (CNT)/polydimethylsiloxane (PDMS) foams with both high thermoelectric (TE) and good mechanical performance and used them to fabricate highly flexible and durable TE generators. The numerous pores and interfaces in the CNT/PDMS foams, which have porosities exceeding 87%, afford very low thermal conductivity of 0.13 W m-1 K-1 . The foam has a zT value of 6.6 × 10-3 , which is twice as high as that of pristine CNT foam. Importantly, the CNT/PDMS foam exhibits good tensile strength of 0.78 MPa, elongation greater than 20%, and excellent resilience even at compressive strain of 80%. This foam is used to fabricate a highly flexible TE foam generator that exhibits a moderate output power of 1.9 µW generated from the large temperature gradient of 18.1 K produced by applied heat. The authors also demonstrate a practical TE foam generator that produces sustainable output power of 3.1 µW under a compressive strain of 80% and 38.2 nW under the continuous vibrational stress produced by a car engine. The TE foam generator also exhibits excellent stability and durability under cyclic bending and harsh vibrational stress.

2.
Transgenic Res ; 26(6): 791-798, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28819706

RESUMO

Humanized mouse models are important tools in many areas of biological drug development including, within oncology research, the development of antagonistic antibodies that have the potential to block tumor growth by controlling vascularization and are key to the generation of in vivo proof-of-concept efficacy data. However, due to cross reactivity between human antibodies and mouse target such studies regularly require mouse models expressing only the human version of the target molecule. Such humanized knock-in/knock-out, KIKO, models are dependent upon the generation of homozygous mice expressing only the human molecule, compensating for loss of the mouse form. However, KIKO strategies can fail to generate homozygous mice, even though the human form is expressed and the endogenous mouse locus is correctly targeted. A typical strategy for generating KIKO mice is by ATG fusion where the human cDNA is inserted downstream of the endogenous mouse promoter elements. However, when adopting this strategy it is possible that the mouse promoter fails to express the human form in a manner compensating for loss of the mouse form or alternatively the human protein is incompatible in the context of the mouse pathway being investigated. So to understand more around the biology of KIKO models, and to overcome our failure with a number of ATG fusion strategies, we developed a range of humanized models focused on Delta-like 4 (Dll4), a target where we initially failed to generate a humanized model. By adopting a broader biologic strategy, we successfully generated a humanized DLL4 KIKO which led to a greater understanding of critical biological aspects for consideration when developing humanized models.


Assuntos
Antineoplásicos/farmacologia , Peptídeos e Proteínas de Sinalização Intercelular/genética , Camundongos Transgênicos/genética , Proteínas Adaptadoras de Transdução de Sinal , Animais , Anticorpos Monoclonais/farmacologia , Proteínas de Ligação ao Cálcio , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/imunologia , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Proteínas de Membrana/genética , Camundongos Knockout , Camundongos SCID , Ensaios Antitumorais Modelo de Xenoenxerto
3.
Bioconjug Chem ; 26(10): 2085-96, 2015 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-26340339

RESUMO

Antibody-drug conjugates (ADCs) have emerged as an important class of therapeutics for cancer treatment that combine the target specificity of antibodies with the killing activity of anticancer chemotherapeutics. Early conjugation technologies relied upon random conjugation to either lysine or cysteine residues, resulting in heterogeneous ADCs. Recent technology advancements have resulted in the preparation of homogeneous ADCs through the site-specific conjugation at engineered cysteines, glycosylated amino acids, and bioorthogonal unnatural amino acids. Here we describe for the first time the conjugation of an anti-mitotic drug to an antibody following the mild and selective oxidation of a serine residue engineered at the N-terminus of the light chain. Using an alkoxyamine-derivatized monomethyl auristatine E payload, we have prepared a hydrolytically stable ADC that retains binding to its antigen and displays potent in vitro cytotoxicity and in vivo tumor growth inhibition.


Assuntos
Anticorpos/química , Anticorpos/farmacologia , Engenharia de Proteínas/métodos , Animais , Anticorpos/metabolismo , Antineoplásicos/química , Antineoplásicos/farmacologia , Humanos , Hidrólise , Camundongos Nus , Oximas/química , Estabilidade Proteica , Ratos , Receptor EphA2/imunologia , Receptor EphA2/metabolismo , Serina/química , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Sci Total Environ ; 873: 162331, 2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-36805061

RESUMO

Biochar being made up of recalcitrant carbon (C) compounds is considered a negative emission technology (NET) due to its indirect removal of atmospheric carbon dioxide (CO2). However, there is no clear report about how biochar remains a NET when organic amendment application in rice paddy results in a huge emission of greenhouse gases (GHG) particularly, methane (CH4). To evaluate the net impact of biochar application on the net global warming potential (GWP) in rice paddy, no organic amendment (control), fresh manure, compost, and biochar treatments were selected during the whole investigation period. Compared to compost, biochar application decreased annual CH4 and N2O emissions by 55 and 31 %, respectively. In comparison to the control, biochar application increased CH4 emission by 163 % but decreased N2O emission by 19 %. Soil organic carbon (SOC) stock would annually deplete by 2.2 Mg C ha-1 under control; however, biochar application could increase the SOC stock by 18.1 Mg C ha-1 which was 63 and 33 % higher than fresh and compost treatments, respectively. As a result, the control had a net GWP of 10 Mg CO2-eq ha-1 however, this impact was increased with fresh manure and compost application by around 319 and 159 %, respectively. Interestingly, biochar application converted rice paddy into a C sink having a net GWP of -0.104 to -0.191 Mg CO2-eq ha-1. Since there was a comparable difference in grain yield among organic amendments, greenhouse gas intensity (GHGI) which is the net GWP per grain yield was significantly high in compost application of approximately 3.1 Mg CO2-eq Mg-1 grain being 127 % higher than control. However, the biochar application had a -0.02 Mg CO2-eq Mg-1 grain which was 1.4 Mg CO2-eq Mg-1 grain lower than the control. Conclusively, biochar application could be a considerable option in maintaining soil quality and productivity without contributing any GHG emissions and their associated impacts.


Assuntos
Gases de Efeito Estufa , Oryza , Solo , Agricultura/métodos , Dióxido de Carbono/análise , Esterco , Carbono , Gases de Efeito Estufa/análise , Aquecimento Global , Carvão Vegetal , Metano/análise , Óxido Nitroso/análise
5.
J Org Chem ; 77(18): 8329-31, 2012 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-22900882

RESUMO

We developed a new synthetic method for bicyclo[2.2.2]octadiene (BCOD)-fused porphyrin (1), a tetrabenzoporphyrin (TBP, 2) precursor that is well-known as a good material for use in organic electronic devices. The newly developed method synthesizes the BCOD-fused pyrrole intermediate (which is the most important intermediate in synthesizing BCOD-fused porphyrin) in a simpler and easier manner than other existing methods, and thus, the new method can efficiently synthesize the TBP precursor.

6.
Sci Total Environ ; 807(Pt 2): 151015, 2022 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-34666093

RESUMO

Plastic film mulching (FM) became a general practice to enhance crop productivity and its net primary production (NPP), but it can increase greenhouse gas (GHG) emissions. The proper addition of organic amendments might effectively decrease the impact of FM on global warming. To evaluate the feasibility of biomass addition on decreasing this negative influence, cover crop biomass as a green manure was incorporated with different recycling levels (0-100% of aboveground biomass) under FM and no-mulching. The net global warming potential (GWP) which integrated with soil C stock change and GHG (N2O and CH4) fluxes with CO2-equivalent was evaluated during maize cultivation. Under the same biomass incorporation, FM significantly enhanced the grain productivity and NPP of maize by 22-61 and 18-58% over no-mulching, respectively. In contrast, FM also highly increased the respired C loss, which was 11-95% higher than NPP increase, over no-mulching. Irrespective with biomass recycling ratio and mulching system, negative NECB which indicates the decrease of soil C stock was observed, mainly due to big harvest removal. FM decreased more soil C stock by 57-158% over no-mulching, but its C stock was clearly increased with increasing biomass addition. FM significantly increased total N2O and CH4 fluxes by 4-61 and 140-600% over no-mulching, respectively. Soil C stock changes mainly decided net GWP scale, but N2O and CH4 fluxes negligibly influenced. As a result, FM highly increased net GWP over no-mulching, while this net GWP was clearly decreased with increasing biomass application. However, cover cropping, and its biomass recycling was not enough to compensate the negative impact of FM on global warming. Therefore, more biomass incorporation might be essential to compensate this negative effect of FM.


Assuntos
Aquecimento Global , Plásticos , Biomassa
7.
Sci Total Environ ; 809: 151140, 2022 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-34695470

RESUMO

Biochar utilization is accepted as the most cost-effective practice to mitigate global warming via increase in soil C stock. However, its utilization effect on greenhouse gas (GHG) fluxes was evaluated only within land application without considering industrial processes. To evaluate the net effect of biochar utilization on global warming within whole system boundary, swine manure-saw dust mixture was pyrolyzed under four different temperatures, and GHG fluxes were characterized under with/without syngas recycling systems. To determine GHG fluxes from biochar amended soil, 40 Mg ha-1 of biochar was mixed with soil and incubated under flooded and dried soil conditions. Finally, the effect of biochar utilization was generalized using net global warming potential (GWP) from industrial process to land application. Under without syngas recycling system, huge amounts of GHGs were emitted during pyrolysis, and GHG fluxes highly increased with increasing pyrolysis temperature, due to direct and indirect GHG emissions from feedstock combustion and electricity, respectively. However, syngas recycling system removed most of GHGs, except for direct N2O and indirect GHG emissions from electricity. Biochar application was very effective to mitigate GHG emissions within soil system boundary, and biochar produced at higher pyrolysis temperature showed higher effectivity in decreasing GHG fluxes. Within the whole system boundary from pyrolysis to soil application, without the installation of syngas recycling system, fresh manure application was more effective than biochar to reduce GHG emissions, regardless of soil water conditions. However, with the installation of syngas recycling system, biochar application was much more effective than fresh manure to decrease GHG fluxes. Biochar produced at higher temperature had higher effectivity to mitigate global warming impacts. In conclusion, to functionally mitigate global warming in soils, biochar should be produced in pyrolysis reactors equipped with syngas recycling system under higher temperature.


Assuntos
Carbono , Solo , Agricultura , Animais , Carvão Vegetal , Óxido Nitroso/análise , Suínos
8.
Sci Total Environ ; 827: 154344, 2022 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-35257754

RESUMO

Biochar and compost were accepted as a stable organic amendment to increase soil C stock as well as to decrease greenhouse gas (GHG) emissions in rice paddy soils. However, in most studies, their effect on GHG flux was evaluated only within the cropping boundary without considering industrial processes. To compare the net effect of these organic amendment utilizations on global warming within the whole rice cropping system boundary from industrial process to cropping, fresh, compost, and biochar manures were applied at a rate of 12 Mg ha-1 (dry weight) in a rice paddy, and total GHG fluxes were evaluated. Compared with fresh manure, compost utilization decreased net global warming potential (GWP) which summated GHG fluxes and soil C stock change with CO2 equivalent by 43% within rice cropping boundary, via a 25% decrease of CH4 flux and 39% increase of soil C stock. However, 34 Mg CO2-eq. of GHGs were additionally emitted during composting to make 12 Mg of compost and then increased the net GWP by 34% within the whole system boundary. In comparison, biochar changed paddy soil into a GHG sink, via 56% decrease of CH4 flux and 13% increase of soil C stock. However, pyrolysis emitted a total of 0.08 and 19 Mg CO2-eq. of GHGs under with and without syngas recycling system, respectively, to make 12 Mg of biochar. As a result, biochar utilization decreased net GWP by approximately 28-70% over fresh manure within the whole system boundary. Rice grain productivity was not discriminated between biochar and compost manures, but compost considerably increased grain yield over fresh manure. Consequently, biochar utilization significantly decreased GHG intensity which indicates net GWP per grain by 33-72% over fresh manure, but compost increased by 22%. In conclusion, biochar could be a sustainable organic amendment to mitigate GHG emission impact in the rice paddy, but compost should be carefully selected.


Assuntos
Gases de Efeito Estufa , Oryza , Agricultura , Dióxido de Carbono/análise , Carvão Vegetal , Aquecimento Global , Esterco , Metano/análise , Óxido Nitroso/análise , Solo
9.
Sci Total Environ ; 804: 150159, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34509846

RESUMO

Rice is the main staple food for more than half of the world's population. Yet, rice cultivation is subjected to criticism because of its important role in methane (CH4) emissions. Although several agronomic practices such as controlled irrigation and conservation tillage have been widely adopted to mitigate CH4 emissions from rice cultivation, the benefits gained by these practices are highly dependent on site-specific soil and climate conditions, and often offset by yield reduction. The use of plant growth regulating compounds having the potential to increase the crop yield and mitigate CH4 emissions may be an innovative approach to sustainable agriculture. Ethylene (C2H4), a plant growth regulator is known to have a strong inhibitory effect on methanogenesis. However, due to gaseous form and low water solubility, C2H4 has not been used to suppress methanogenesis in paddy fields. To develop C2H4 as a prospective soil amendment for reducing methane (CH4) emissions, ethephon (2-Chloroethylphosphonic acid), a precursor of C2H4 was tested. We found that ethephon reduced CH4 formation by 43%, similar to other well known methanogenic inhibitors (2-Bromoethanesulfonate, 2-Chlomoethanesulfonate, 2-Mercaptoethanesulfonate). However, ethephon rapidly hydrolyzed to C2H4 and methanogenic activity recuperated completely after C2H4 removal. To slow down the release of C2H4, ethephon was mixed with bio-degradable polymers such as cellulose acetate and applied to paddy soils. We found that compared with the control, the C2H4 release of ethephon slowed down to 90 days, and the CH4 emissions were reduced by 90%. The application of ethephon at lower concentrations did not significantly alter bacterial communities, their relative abundance, and the abundance of methanotrophs, but it significantly reduced archaeal communities and the relative abundance and expression level of methanogens in paddy soils. Results suggest that cellulose acetate-mixed ethephon has great promise to suppress CH4 emissions in rice paddies while ensuring sustainable yields.


Assuntos
Metano , Oryza , Agricultura , Óxido Nitroso/análise , Compostos Organofosforados , Estudos Prospectivos , Solo
10.
J Psychiatr Res ; 151: 113-121, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35477075

RESUMO

Work-family conflict (WFC), an inter-role conflict between work and family, negatively affects mental health. Using a nationally representative systematic sample, this study aimed to investigate the association between WFC, depressive symptoms, and potential moderators in the association of adult female workers. Data of 4714 female workers (aged ≥19 years) were obtained cross-sectionally from the 2018 nationwide Korean Longitudinal Survey of Women and Families (KLoWF). WFC was assessed using a 7-item questionnaire, based on which scores were classified into high (>75th percentile score) and low (≤75th percentile score) levels of WFC. Significant depressive symptoms were defined as a score of ≥10 on the 10-item version of the Center for Epidemiologic Studies for Depression Scale. Female workers with high WFC levels were more likely to have depressive symptoms than those with low WFC levels (odds ratio = 2.29, 95% confidence interval = 1.91-2.74). In stratified analyses, high WFC levels were associated with the highest odds of depressive symptoms in the following groups: young adults (19-39 years), those with a college degree or above or with high income, never-married individuals, those with a family size of three or a single child, nonstandard workers, and pink-collar workers. This study replicated and extended previous findings on the association between WFC and depressive symptoms. The association was moderated by age, education and income levels, marital status, family size, number of children, and job conditions.


Assuntos
Depressão , Conflito Familiar , Criança , Estudos Transversais , Depressão/epidemiologia , Depressão/psicologia , Conflito Familiar/psicologia , Feminino , Humanos , Estresse Psicológico/psicologia , Inquéritos e Questionários , Adulto Jovem
11.
Sci Total Environ ; 787: 147503, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-33992938

RESUMO

Winter cover crop cultivation and its biomass recycling as green manure (GM) were accepted as an ideal nutrient management practice in temperate organic farming fields. Since its biomass growth was boosted with air temperature rising from late Spring to early Summer, this stage overlapped with cash crops' seeding or transplanting. Thus, organic farmers were suffering from low crop productivity, due to delayed mineralization of incorporated biomass. To accelerate the mineralization of biomass nutrients and control weeds, plastic film mulching (PM) was broadly utilized in organic farming fields of temperate-monsoon climate region. However, the effect of PM on increasing nutrient use efficiency was not properly quantified in GM amended soil. To determine the effect of PM on crop productivity and nutrient use efficiency in GM amended soils, PM and no-mulching treatments were installed under different levels of GM biomass amended soils (0, 25, 50 and 100% of harvested aboveground biomass). The biomass productivity of barley and hairy vetch mixture as cover crop and biomass nitrogen productivity were dramatically increased from the mid May to the early June. PM significantly improved soil temperature and moisture regimes during maize cropping seasons, and then increased inorganic N (NH4+ and NO3-) contents in soils. These improved soil properties under PM highly increased maize productivity and nitrogen use efficiency (NUE). Comparing with no-mulching, as GM application level was increased, the effect of PM on increasing maize productivity became greater, but its effect on increasing NUE became smaller. In conclusion, PM could be very useful tool to improve productivity and NUE of cash crop maize in organic cropping fields, in which the harvesting time of GM biomass might be sustained to increase GM biomass productivity.


Assuntos
Nitrogênio , Zea mays , Agricultura , Fertilizantes , Nitrogênio/análise , Agricultura Orgânica , Plásticos , República da Coreia , Solo
12.
PLoS One ; 16(9): e0256796, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34543286

RESUMO

In rice paddy, the closed chamber method is broadly used to estimate methane (CH4) emission rate. Since rice plants can significantly affect CH4 production, oxidation and emission, rice plantation inside the chamber is standardized in IPCC guidelines. Methane emission rate is calculated using the increased concentration inside the headspace. Biomass growth might decrease the headspace volume, and thus CH4 emission rates might be overestimated. To evaluate the influence of chamber headspace decreased by rice plant development on CH4 emission rates, five Korean rice cultivars were cultivated in a typical rice paddy, and physical volume changes in rice biomass were assayed using water displacement method. The recommended acrylic closed chambers (H. 1.2 m x W. 0.6 m x L. 0.6 m) were installed, and eight rice plants were transplanted inside the chamber with the same space interval with the outside. Biomass growth significantly decreased the headspace volume of the chamber. However, this volume covered only 0.48-0.55% of the closed chamber volume at the maximum growth stage. During the whole cropping period, mean 0.24-0.28% of chamber headspace was allocated by plant biomass, and thus this level of total CH4 emissions was overestimated. However, this overestimation was much smaller than the errors coming from other investigation processes (i.e., chamber closing hour, temperature recording, inconstant flooding level, different soil environments, etc.) and rice physiological changes. In conclusion, the influence of physical biomass volume inside the closed chamber was negligible to make the error in total CH4 emission assessment in rice paddies.


Assuntos
Gases de Efeito Estufa/análise , Metano/análise , Oryza/fisiologia , Agricultura , Biomassa , República da Coreia , Solo , Incerteza , Água/química
13.
Biomed Pharmacother ; 137: 111415, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33761619

RESUMO

Aging alters body composition to induce sarcopenia, particularly in women, but the mechanism remains unclear. We hypothesized that silk peptide(SP) intake could prevent an age-related decrease in muscle mass and strength in middle-aged female rats and explored the action mechanism. After the acute intake of SP and defatted soybean peptides, serum concentrations of amino acids were measured in ten middle-aged rats in each group. Forty 12-month-old female Sprague-Dawley rats were fed a high-fat and high-carbohydrate diet for 12 weeks including 0.5 g casein/kg body weight(BW)/day(Aged), 0.15 g SP plus 0.35 g casein/kg BW/day(Low-SP), 0.5 g SP/kg BW/day(High-SP), or 40 mg metformin plus 0.5 g casein/kg BW/day(Metformin). Ten rats aged 7-week old(Young) had the same treatment as the Aged-group. The body composition, grip strength, glucose metabolism, intestinal tissue morphology, and gut microbiota were also determined. After an acute consumption, total amino acids were more quickly absorbed and maintained at higher levels in SP than soybean peptides. Lean body mass(LBM) and grip strength were lower in the Aged-group than the Young and Low-SP groups, and the High-SP regimen increased these parameters as much as the Young-group. Serum concentrations and mRNA expression of TNF-α in the gastrocnemius and quadriceps muscles were higher in the Aged-group than the Young-group, whereas SP intake reduced their serum levels and skeletal muscles. Glucose and insulin tolerance indicated that insulin resistance was elevated in the Aged-group compared to the Young-group, while Low-SP and High-SP alleviated them as much as the Young-group. High-SP increased serum propionate and butyrate concentrations compared to the Aged-group. SP intake increased the relative abundance of Bacteroides and Prevotella and decreased Blautia and Clostridium in the feces. In conclusion, SP intake protects against a decrease in lean body mass and grip strength in middle-aged female rats. The protection was partly related to maintaining higher serum concentrations of total amino acids after SP consumption and decreasing inflammation and insulin resistance through gut microbiota modulation.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Inflamação/prevenção & controle , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/crescimento & desenvolvimento , Peptídeos/farmacologia , Seda/química , Envelhecimento , Aminoácidos/análise , Animais , Composição Corporal/efeitos dos fármacos , Butiratos/metabolismo , Dieta Hiperlipídica , Carboidratos da Dieta , Feminino , Glucose/metabolismo , Força da Mão , Intestinos/anatomia & histologia , Intestinos/efeitos dos fármacos , Peptídeos/análise , Ratos , Ratos Sprague-Dawley , Glycine max/química , Fator de Necrose Tumoral alfa/metabolismo
14.
J Affect Disord ; 291: 375-383, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34091325

RESUMO

BACKGROUND: Low-grade systemic inflammation evidenced by elevated serum high-sensitivity C-reactive protein (hsCRP) levels can be a biomarker for depression. This study aimed to investigate the association between serum hsCRP levels and depressive symptoms and to explore the potential moderating effects of age, sex, body mass index (BMI), and aerobic physical activity on the association. METHODS: Data of 10,702 adults (≥ 19 years) were obtained from the nationwide cross-sectional Korea National Health and Nutrition Examination Surveys of 2016 and 2018. Significant depressive symptoms were defined as ≥ 10 on the Patient Health Questionnaire-9, and high hsCRP level was defined as > 3.0 mg/L. RESULTS: Adults with high hsCRP levels were more likely to have depressive symptoms (odds ratio [OR]: 1.41, 95% confidence interval [CI]: 1.07-1.84) and suicidal ideation (OR: 1.39, 95% CI: 1.07-1.80) than those with low hsCRP levels. In the age- and sex-stratified analysis, high hsCRP levels were associated with depressive symptoms in the non-geriatric population (age ≤ 64 years) alone, with a higher OR in males than females. In subgroup analyses, the association between them was observed only among obese adults and adults without aerobic physical activity. LIMITATIONS: Causal interpretation is limited due to the cross-sectional design. CONCLUSIONS: Our results replicate previous findings of an association between high hsCRP levels and depressive symptoms in adults using a large nationally representative sample. The association between them was more prominent in the non-geriatric population, males, obese adults, and those without aerobic physical activity.


Assuntos
Proteína C-Reativa , Depressão , Adulto , Idoso , Proteína C-Reativa/análise , Estudos Transversais , Depressão/epidemiologia , Exercício Físico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , República da Coreia/epidemiologia , Fatores de Risco
15.
Clin Cancer Res ; 27(13): 3602-3609, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33795255

RESUMO

PURPOSE: MEDI3726 is an antibody-drug conjugate targeting the prostate-specific membrane antigen and carrying a pyrrolobenzodiazepine warhead. This phase I study evaluated MEDI3726 monotherapy in patients with metastatic castration-resistant prostate cancer after disease progression on abiraterone and/or enzalutamide and taxane-based chemotherapy. PATIENTS AND METHODS: MEDI3726 was administered at 0.015-0.3 mg/kg intravenously every 3 weeks until disease progression/unacceptable toxicity. The primary objective was to assess safety, dose-limiting toxicities (DLT), and MTD/maximum administered dose (MAD). Secondary objectives included assessment of antitumor activity, pharmacokinetics, and immunogenicity. The main efficacy endpoint was composite response, defined as confirmed response by RECIST v1.1, and/or PSA decrease of ≥50% after ≥12 weeks, and/or decrease from ≥5 to <5 circulating tumor cells/7.5 mL blood. RESULTS: Between February 1, 2017 and November 13, 2019, 33 patients received MEDI3726. By the data cutoff (January 17, 2020), treatment-related adverse events (TRAE) occurred in 30 patients (90.9%), primarily skin toxicities and effusions. Grade 3/4 TRAEs occurred in 15 patients (45.5%). Eleven patients (33.3%) discontinued because of TRAEs. There were no treatment-related deaths. One patient receiving 0.3 mg/kg had a DLT of grade 3 thrombocytopenia. The MTD was not identified; the MAD was 0.3 mg/kg. The composite response rate was 4/33 (12.1%). MEDI3726 had nonlinear pharmacokinetics with a short half-life (0.3-1.8 days). The prevalence of antidrug antibodies was 3/32 (9.4%), and the incidence was 13/32 (40.6%). CONCLUSIONS: Following dose escalation, no MTD was identified. Clinical responses occurred at higher doses, but were not durable as patients had to discontinue treatment due to TRAEs.


Assuntos
Imunoconjugados , Neoplasias de Próstata Resistentes à Castração , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Androstenos/uso terapêutico , Antígenos de Superfície , Benzamidas/uso terapêutico , Glutamato Carboxipeptidase II/antagonistas & inibidores , Imunoconjugados/farmacologia , Imunoconjugados/uso terapêutico , Metástase Neoplásica , Nitrilas/uso terapêutico , Feniltioidantoína/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Falha de Tratamento
16.
Korean J Intern Med ; 36(5): 1115-1125, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34289586

RESUMO

BACKGROUND/AIMS: Hypertension (HT) has a significant impact on public health and medical expenses. However, HT is a chronic disease that requires the long-term follow-up of a large number of patients. METHODS: The Korean Hypertension Cohort (KHC) study aimed to develop a model for calculating cardiovascular risk in HT patients by linking and utilizing the detailed clinical and longitudinal data from hospitals and the national health insurance claim database, respectively. This cohort had a planned sample size of over 11,000 HT patients and 100,000 non-HT controls. Eligible patients were hypertensive patients, who were presenting for the first time and were diagnosed with HT as a main disease from 2006 to 2011. Long-term survival data over a period of approximately 9 years were obtained from the national health insurance claim and national health examination data. RESULTS: This cohort enrolled 11,083 patients with HT. The mean age was 58.87 ± 11.5 years, 50.5% were male, and 31.4% were never-treated HT. Of the enrolled patients, 32.9% and 37.7% belonged to the high and moderate cardiovascular risk groups, respectively. Initial blood pressures were 149.4 ± 18.5/88.5 ± 12.5 mmHg. During the 2 years hospital data follow-up period, blood pressures lowered to 130.8 ± 14.1/78.0 ± 9.7 mmHg with 1.9 ± 1.0 tablet doses of antihypertensive medication. Cardiovascular events occurred in 7.5% of the overall patients; 8.5%, 8.8%, and 4.7% in the high, moderate, and low risk patients, respectively. CONCLUSION: The KHC study has provided important information on the long-term outcomes of HT patients according to the blood pressure, comorbid diseases, medication, and adherence, as well as health behaviors and health resource use.


Assuntos
Hipertensão , Idoso , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Estudos de Coortes , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia
17.
Int J Syst Evol Microbiol ; 60(Pt 12): 2979-2983, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20118286

RESUMO

A bacterial strain designated TNR-18(T) was isolated from stream water in southern Taiwan and characterized using a polyphasic taxonomic approach. Cells of strain TNR-18(T) were Gram-stain-negative, strictly aerobic, non-motile and vibrioid, and the strain formed orange colonies. Growth occurred at 10-30°C, with 0-0.2 % NaCl and at pH6.0-10.0. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain TNR-18(T) belonged to the genus Arcicella; its closest neighbours were Arcicella rosea TW5(T) and Arcicella aquatica NO-502(T), with respective sequence similarities of 97.9 and 97.8 %. Predominant cellular fatty acids (>10 %) were summed feature 3 (C(16 : 1)ω7c/C(16 : 1)ω6c; 37.7 %), C(16 : 1)ω5c (13.0 %) and iso-C(15 : 0) (11.1 %). The major respiratory quinone was MK-7. The polar lipid profile contained phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and several uncharacterized polar lipids. The DNA G+C content was 39.9 mol%. On the basis of the phylogenetic and phenotypic data, strain TNR-18(T) should be classified as representing a novel species, for which the name Arcicella aurantiaca sp. nov. is proposed. The type strain is TNR-18(T) (=LMG 25207(T) =BCRC 17969(T)).


Assuntos
Cytophagaceae/classificação , Filogenia , Rios/microbiologia , Técnicas de Tipagem Bacteriana , Composição de Bases , Cytophagaceae/genética , Cytophagaceae/isolamento & purificação , DNA Bacteriano/genética , Ácidos Graxos/química , Dados de Sequência Molecular , Hibridização de Ácido Nucleico , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Taiwan , Vitamina K 2/análogos & derivados , Vitamina K 2/química , Microbiologia da Água
18.
ACS Appl Mater Interfaces ; 12(13): 15396-15405, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32148019

RESUMO

Perhydropolysilazane (PHPS), an inorganic polymer composed of Si-N and Si-H, has attracted much attention as a precursor for gate dielectrics of thin-film transistors (TFTs) due to its facile processing even at a relatively low temperature. However, an in-depth understanding of the tunable dielectric behavior of PHPS-derived dielectrics and their effects on TFT device performance is still lacking. In this study, the PHPS-derived dielectric films formed at different annealing temperatures have been used as the gate dielectric layer for solution-processed indium zinc oxide (IZO) TFTs. Notably, the IZO TFTs fabricated on PHPS annealed at 350 °C exhibit mobility as high as 118 cm2 V-1 s-1, which is about 50 times the IZO TFTs made on typical SiO2 dielectrics. The outstanding electrical performance is possible because of the exceptional capacitance of PHPS-derived dielectric caused by the limited hydrolysis reaction of PHPS at a low processing temperature (<400 °C). According to our analysis, the exceptional dielectric behavior is originated from the electric double layer formed by mobile of protons in the low temperature-annealed PHPS dielectrics. Furthermore, proton conduction through the PHPS dielectric occurs through a three-dimensional pathway by a hopping mechanism, which allows uniform polarization of the dielectric even at room temperature, leading to amplified performance of the IZO TFTs.

19.
Sci Rep ; 10(1): 9633, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32541794

RESUMO

We report the microstructure and thermoelectric properties of composite nanofiber webs, which were fabricated by dual-electrospinning of polyacrylonitrile (PAN) and sodium cobalt oxide (NaCo2O4) precursor solutions with different input compositions and following heat-treatment at 600-900 °C for simultaneous carbonation and calcination. The SEM and EDS mapping images revealed that PAN-derived carbon nanofibers (CNFs) and NaCo2O4-based ceramic nanofibers coexisted in the composite nanofiber webs and that their relative contents could be controlled by the input compositions. The Seebeck coefficient increased from ~26.77 to ~73.28 µV/K and from ~14.83 to ~40.56 µV/K with increasing the relative content of NaCo2O4 nanofibers in the composite nanofiber webs fabricated at 700 and 800 °C, respectively. On the other hand, the electrical conductivity of the composite nanofiber webs increased with the decrement of the relative content of NaCo2O4 nanofibers as well as the increment of the heat-treatment temperature. Owing to the opposite contributions of NaCo2O4 nanofibers and CNFs to the Seebeck coefficient, electrical conductivity and thermal conductivity, a maximum power factor of ~5.79 µW/mK2 and a figure of merit of ~0.01 were attained for CNF/NaCo2O4-based composite nanofiber webs fabricated at 45 wt% input composition of NaCo2O4 and at heat-treatment of 700 °C.

20.
Toxicol Res ; 36(2): 99-108, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32257921

RESUMO

The risk of atopic dermatitis (AD)-like skin lesions has increased due to the elevated levels of allergens worldwide. Natural-origin agents, which are effective and safe, show promise for the prevention and treatment of inflammatory conditions. Orostachys japonicus (OJ) A. Berger is an ingredient of traditional herbal medicines for fever, gingivitis, and cancer in Korea, China, and Japan. However, the effect of OJ on AD-like skin lesions is unknown. Therefore, we investigated the effect of OJ ethanol extract (OJEE) on AD-like skin symptoms in mice and cells. OJEE reduced the 2,4-dinitrochlorobenzene-induced AD severity, serum levels of IgE and TARC, and mRNA levels of TARC, TNF-α, and IL-4 in NC/Nga mice. Histopathological analysis showed that OJEE reduced the thickness of the epidermis/dermis and dermal infiltration of inflammatory cells in ear tissue. Furthermore, OJEE suppressed the TNF-α/IFN-γ-increased TARC mRNA level by inhibiting NF-κB and STAT1 activation in HaCaT cells. Taken together, our findings show that OJEE reduced the risk of AD-like skin symptoms by decreasing TARC expression via inhibiting NF-κB and STAT1 activation in skin keratinocytes and thus shows promise as an alternative therapy for AD-like skin lesions.

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