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1.
Vet Med (Praha) ; 69(4): 123-129, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38751989

RESUMO

An 8-year-old, 6.5 kg, neutered female Shih-Tzu dog was presented for surgical resection of a mediastinal mass. A median sternotomy and left cranial lung lobectomy were performed. Intraoperatively, with the patient under general anaesthesia, a bilateral transversus thoracis plane (TTP) block was performed by injecting 0.5% bupivacaine (0.2 ml/kg) per side using real-time ultrasound guidance. After surgery, indwelling catheters for repeated bolus injections of bupivacaine in TTP were placed as follows: the fifth sternebra was palpated in dorsal recumbency, and the transducer was placed in the longitudinal plane lateral to the sternal border. A 16 gauge over-the-needle catheter was inserted caudo-cranially using an in-plane technique and located in the TTP. An intermittent bolus of bupivacaine (0.1 ml/kg) per side was injected via the indwelling catheter every 8 h for 3 days, with a constant rate infusion of an intravenous fentanyl (1 µg/kg/h) and ketamine (0.12 mg/kg/h) combination. Post-operative pain was evaluated using the Glasgow composite measure pain scale and the score was 4-5/24 on the day of surgery and gradually decreased over time. Additional rescue analgesia was not required. Repeated boluses of bupivacaine for a continuous bilateral TTP block may be a useful adjuvant for perioperative pain management strategies, including median sternotomy, in dogs.

2.
Glia ; 71(12): 2735-2752, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37655904

RESUMO

The forkhead box transcription factor O1 (FoxO1) is expressed ubiquitously throughout the central nervous system, including in astrocytes, the most prevalent glial cell type in the brain. While the role of FoxO1 in hypothalamic neurons in controlling food intake and energy balance is well-established, the contribution of astrocytic FoxO1 in regulating energy homeostasis has not yet been determined. In the current study, we demonstrate the essential role of hypothalamic astrocytic FoxO1 in maintaining normal neuronal activity in the hypothalamus and whole-body glucose metabolism. Inhibition of FoxO1 function in hypothalamic astrocytes shifts the cellular metabolism from glycolysis to oxidative phosphorylation, enhancing astrocyte ATP production and release meanwhile decreasing astrocytic export of lactate. As a result, specific deletion of astrocytic FoxO1, particularly in the hypothalamus, causes a hyperactivation of hypothalamic neuropeptide Y neurons, which leads to an increase in acute feeding and impaired glucose regulation and ultimately results in diet-induced obesity and systemic glucose dyshomeostasis.

3.
Nat Immunol ; 12(8): 742-51, 2011 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-21725320

RESUMO

The orphan nuclear receptor SHP (small heterodimer partner) is a transcriptional corepressor that regulates hepatic metabolic pathways. Here we identified a role for SHP as an intrinsic negative regulator of Toll-like receptor (TLR)-triggered inflammatory responses. SHP-deficient mice were more susceptible to endotoxin-induced sepsis. SHP had dual regulatory functions in a canonical transcription factor NF-κB signaling pathway, acting as both a repressor of transactivation of the NF-κB subunit p65 and an inhibitor of polyubiquitination of the adaptor TRAF6. SHP-mediated inhibition of signaling via the TLR was mimicked by macrophage-stimulating protein (MSP), a strong inducer of SHP expression, via an AMP-activated protein kinase-dependent signaling pathway. Our data identify a previously unrecognized role for SHP in the regulation of TLR signaling.


Assuntos
NF-kappa B/imunologia , Receptores Citoplasmáticos e Nucleares/imunologia , Sepse/imunologia , Receptores Toll-Like/imunologia , Proteínas Quinases Ativadas por AMP/imunologia , Animais , Imunoprecipitação da Cromatina , Feminino , Immunoblotting , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Transdução de Sinais , Fator 6 Associado a Receptor de TNF/imunologia , Ubiquitinação/imunologia
4.
Plant Physiol ; 189(3): 1774-1793, 2022 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-35417014

RESUMO

Leaf senescence is the final stage of leaf development and can be triggered by various external factors, such as hormones and light deprivation. In this study, we demonstrate that the overexpression of the GTP-bound form of Arabidopsis (Arabidopsis thaliana) Ran1 (a Ras-related nuclear small G-protein, AtRan1) efficiently promotes age-dependent and dark-triggered leaf senescence, while Ran-GDP has the opposite effect. Transcriptome analysis comparing AtRan1-GDP- and AtRan1-GTP-overexpressing transgenic plants (Ran1T27Nox and Ran1G22Vox, respectively) revealed that differentially expressed genes (DEGs) related to the senescence-promoting hormones salicylic acid (SA), jasmonic acid, abscisic acid, and ethylene (ET) were significantly upregulated in dark-triggered senescing leaves of Ran1G22Vox, indicating that these hormones are actively involved in Ran-GTP/-GDP-dependent, dark-triggered leaf senescence. Bioinformatic analysis of the promoter regions of DEGs identified diverse consensus motifs, including the bZIP motif, a common binding site for TGACG-BINDING FACTOR (TGA) transcription factors. Interestingly, TGA2 and its interactor, NONEXPRESSOR OF PATHOGENESIS-RELATED GENES1 (NPR1), which are two positive transcriptional regulators of SA signaling, differed in their extent of accumulation in the nucleus versus cytoplasm of Ran1T27Nox and Ran1G22Vox plants. Moreover, SA-induced, Ran-GTP-/-GDP-dependent functions of NPR1 included genome-wide global transcriptional reprogramming of genes involved in cell death, aging, and chloroplast organization. Furthermore, the expression of AtRan1-GTP in SA signaling-defective npr1 and SA biosynthesis-deficient SA-induction deficient2 genetic backgrounds abolished the effects of AtRan1-GTP, thus retarding age-promoted leaf senescence. However, ET-induced leaf senescence was not mediated by Ran machinery-dependent nuclear shuttling of ETHYLENE-INSENSITIVE3 and ETHYLENE-INSENSITIVE3-LIKE1 proteins. We conclude that Ran-GTP/-GDP-dependent nuclear accumulation of NPR1 and TGA2 represents another regulatory node for SA-induced leaf senescence.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis , Núcleo Celular/metabolismo , Proteínas de Ligação a RNA/metabolismo , Proteína ran de Ligação ao GTP/metabolismo , Arabidopsis/metabolismo , Etilenos/metabolismo , Regulação da Expressão Gênica de Plantas , Guanosina Difosfato/metabolismo , Guanosina Trifosfato/metabolismo , Hormônios/metabolismo , Hormônios/farmacologia , Senescência Vegetal , Ácido Salicílico/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
5.
Ann Surg Oncol ; 30(12): 7281-7290, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37587360

RESUMO

BACKGROUND: This study used a single-institution cohort, the Severance dataset, validated the results by using the surveillance, epidemiology, and end results (SEER) database, adjusted with propensity-score matching (PSM), and analyzed by using a machine learning method. To determine whether the 5-year, disease-free survival (DFS) and overall survival (OS) of patients undergoing nipple-sparing mastectomy (NSM) with immediate breast reconstruction (IBR) are not inferior to those of women treated with total mastectomy/skin-sparing mastectomy (TM/SSM). METHODS: The Severance dataset enrolled 611 patients with early, invasive breast cancer from 2010 to 2017. The SEER dataset contained data for 485,245 patients undergoing TM and 14,770 patients undergoing NSM between 2000 and 2018. All patients underwent mastectomy and IBR. Intraoperative, frozen-section biopsy for the retro-areolar tissue was performed in the NSM group. The SEER dataset was extracted by using operation types, including TM/SSM and NSM. The primary outcome was DFS for the Severance dataset and OS for the SEER dataset. PSM analysis was applied. Survival outcomes were analyzed by using the Kaplan-Meier method and Cox proportional hazard (Cox PH) regression model. We implemented XGBSE to predict mortality with high accuracy and evaluated model prediction performance using a concordance index. The final model inspected the impact of relevant predictors on the model output using shapley additive explanation (SHAP) values. RESULTS: In the Severance dataset, 151 patients underwent NSM with IBR and 460 patients underwent TM/SSM with IBR. No significant differences were found between the groups. In multivariate analysis, NSM was not associated with reduced oncologic outcomes. The same results were observed in PSM analysis. In the SEER dataset, according to the SHAP values, the individual feature contribution suggested that AJCC stage ranks first. Analyses from the two datasets confirmed no impact on survival outcomes from the two surgical methods. CONCLUSIONS: NSM with IBR is a safe and feasible procedure in terms of oncologic outcomes. Analysis using machine learning methods can be successfully applied to identify significant risk factors for oncologic outcomes.


Assuntos
Neoplasias da Mama , Mamoplastia , Mastectomia Subcutânea , Humanos , Feminino , Neoplasias da Mama/patologia , Mastectomia/métodos , Mastectomia Simples , Mamilos/cirurgia , Mamilos/patologia , Mamoplastia/métodos , Estudos Retrospectivos
6.
Sensors (Basel) ; 21(7)2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33918116

RESUMO

As unmanned aerial vehicles have become popular, the number of accidents caused by an operator's inattention have increased. To prevent such accidents, the operator should maintain an attention status. However, limited research has been conducted on the brain-computer interface (BCI)-based system with an alerting module for the operator's attention recovery of unmanned aerial vehicles. Therefore, we introduce a detection and alerting system that prevents an unmanned aerial vehicle operator from falling into inattention status by using the operator's electroencephalogram signal. The proposed system consists of the following three components: a signal processing module, which collects and preprocesses an electroencephalogram signal of an operator, an inattention detection module, which determines whether an inattention status occurred based on the preprocessed signal, and, lastly, an alert providing module that presents stimulus to an operator when inattention is detected. As a result of evaluating the performance with a real-world dataset, it was shown that the proposed system successfully contributed to the recovery of operator attention in the evaluating dataset, although statistical significance could not be established due to the small number of subjects.


Assuntos
Eletroencefalografia , Processamento de Sinais Assistido por Computador , Cognição , Humanos
7.
J Exp Bot ; 71(4): 1475-1490, 2020 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-31783407

RESUMO

ATBS1-INTERACTING FACTOR 2 (AIF2) is a non-DNA-binding basic helix-loop-helix (bHLH) transcription factor. We demonstrated that AIF2 retards dark-triggered and brassinosteroid (BR)-induced leaf senescence in Arabidopsis thaliana. Dark-triggered BR synthesis and the subsequent activation of BRASSINAZOLE RESISTANT 1 (BZR1), a BR signaling positive regulator, result in BZR1 binding to the AIF2 promoter in a dark-dependent manner, reducing AIF2 transcript levels and accelerating senescence. BR-induced down-regulation of AIF2 protein stability partly contributes to the progression of dark-induced leaf senescence. Furthermore, AIF2 interacts with INDUCER OF CBF EXPRESSION 1 (ICE1) via their C-termini. Formation of the AIF2-ICE1 complex and subsequent up-regulation of C-REPEAT BINDING FACTORs (CBFs) negatively regulates dark-triggered, BR-induced leaf senescence. This involves antagonistic down-regulation of PHYTOCHROME INTERACTING FACTOR 4 (PIF4), modulated through AIF2-dependent inhibition of ICE1's binding to the promoter. PIF4-dependent activities respond to dark-induced early senescence and may promote BR synthesis and BZR1 activation to suppress AIF2 and accelerate dark-induced senescence. Taken together, these findings suggest a coordination of AIF2 and ICE1 functions in maintaining stay-green traits.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Brassinosteroides , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Regulação da Expressão Gênica de Plantas , Fatores de Transcrição
8.
Int J Med Sci ; 17(18): 3082-3090, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33173429

RESUMO

Background: Considering the increasing possibility of emergency situations in dental clinics over time, we conducted this study to evaluate the changes in the knowledge and practical skills of students of dental school before and after retraining for 2 years after the initial education on basic life support (BLS) of the American Heart Association (AHA). Methods: All third-year students of dental school who had received the same education on BLS provider training of the AHA 2 years earlier were included in this study. Among them, 98 students were asked to answer a questionnaire about BLS knowledge and conduct a practical skills assessment of high-quality cardiopulmonary resuscitation using Little Anne QCPR before and after retraining. Results: After retraining, the level of BLS knowledge increased in all 7 categories, and BLS performance increased in all 19 subcategories. Comparison of the QCPR numerical data items before and after retraining showed that all items after retraining met the criteria recommended by the AHA. Conclusion: Students of dental school had low levels of knowledge and practical skills of BLS before retraining after 2 years from the initial education and had high levels after retraining. Therefore, BLS training must be updated periodically, and more effective education methods are required to maintain BLS knowledge and practical skills.


Assuntos
Reanimação Cardiopulmonar/educação , Educação em Odontologia/métodos , Avaliação Educacional/estatística & dados numéricos , Faculdades de Odontologia/estatística & dados numéricos , Estudantes de Odontologia/estatística & dados numéricos , Adulto , American Heart Association , Reanimação Cardiopulmonar/normas , Educação em Odontologia/normas , Educação em Odontologia/estatística & dados numéricos , Avaliação Educacional/normas , Feminino , Humanos , Masculino , Ensaios Clínicos Controlados não Aleatórios como Assunto , Faculdades de Odontologia/normas , Inquéritos e Questionários/estatística & dados numéricos , Estados Unidos , Adulto Jovem
9.
Asian-Australas J Anim Sci ; 33(3): 501-505, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31480178

RESUMO

OBJECTIVE: The purpose of this study was to investigate the effects of aging methods (AM) i.e. dry-aging (DA) and wet-aging (WA) on the physicochemical properties and in vitro digestibility of proteins in beef short loin. METHODS: Short loins (M. longissmus lumborum), were trimmed and boned-out on the fifth day postmortem, from a total of 18 Hanwoo, which were purchased from a commercial slaughterhouse. Short loins were separated randomly grouped into one of the three treatments: control, WA (1°C, 7 days), and DA (1°C, 0.5 m/s, 85% relative humidity [RH], 30 days). RESULTS: Dry-aged beef (DAB) exhibited higher pH, water holding capacity (WHC), myofibrillar fragmentation index (MFI), and digestibility, however lower lightness, redness, and yellowness values, cooking loss, and shear force (SF), than those of wet-aged beef (WAB) (p<0.05). The myosin light chain band intensity of DAB was higher than that of control and WAB in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The in vitro digestibility of aged beef was highly (p<0.001) correlated to physicochemical properties except WHC. The correlation coefficient between AMs and WHC was higher than that between AM and SF (p<0.05) or MFI (p<0.001). A high correlation was observed between SF and MFI (p<0.001). CONCLUSION: Thus, we believe that DAB is more advantageous than WAB owing to its high digestibility and WHC and low SF.

11.
Food Chem X ; 23: 101570, 2024 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-39022786

RESUMO

In this study, the distinctive chemical fingerprints that contribute to the flavor characteristics of various protein materials, such as insects, plant-based protein, and livestock, were investigated. In edible-insects (Tenebrio molitor and Protaetia brevitarsis), aldehydes and cyclic volatile compounds were the predominant volatile components and had distinct flavor characteristics such as cheesy, sharp, green, floral, and sweet. In contrast, the relatively high levels of pyrazines and furans in plant-based protein materials, such as textured vegetable and pea protein. They included unique flavor properties characterized by sweet, fatty, grassy, creamy, and roasted. The primary volatile chemical group detected in livestock protein materials, such as a pork and a beef, was ketones. The pork sample showed specific flavors, such as alcoholic, green, and fruity, while a beef presented distinctive flavor, including creamy, fruity, and alcoholic. Based on the results, this research provided the understanding of the flavor aspects of diverse protein materials.

12.
Adv Food Nutr Res ; 108: 223-264, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38461000

RESUMO

Edible insects, with their high protein and lipid content, offer a safe and cost-effective alternative to traditional protein sources. They are environmentally friendly, emitting fewer greenhouse gases and requiring less water than livestock farming. Their rapid reproduction, efficiency, and labor-saving qualities make them attractive for industry. However, the unappealing appearance of edible insects hinders consumer acceptance. To overcome this, materialization technologies should be developed, and negative perceptions addressed with objective data. Promoting the nutritional value, safe rearing, disease prevention, and cost-efficiency of edible insects can boost consumer interest. Commercializing various insect products is crucial to revitalize their integration into the food industry.


Assuntos
Insetos Comestíveis , Animais , Alimentos , Insetos , Alérgenos , Agricultura
13.
Yonsei Med J ; 65(9): 511-518, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39193759

RESUMO

PURPOSE: The use of advanced energy devices for mastectomy and axillary lymph node dissection can reduce perioperative blood loss, seroma formation, and drainage duration/volume. Retraction using fiberoptic retractors can help visualize deep and narrow surgical fields. We aimed to compare the postoperative outcomes between single-incision breast-conserving surgery (SIBCS) and conventional breast-conserving surgery (CBCS) with axillary staging using advanced energy devices and conventional equipment, respectively. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 244 patients who underwent BCS with axillary surgery between March 2018 and September 2019 at Severance Hospital. The patients were grouped based on the device used to aid in axillary staging: CBCS group (n=117) used conventional electrocautery; and SIBCS group (n=127) used advanced energy devices and fiberoptic retractors. The two groups were compared for postoperative outcomes. RESULTS: The mean patient age was 55.9 and 53.1 years in the CBCS and SIBCS groups, respectively. Incision size was significantly smaller in the SIBCS group than in the CBCS group (6.3±2.1 cm vs. 7.5±2.5 cm, p=0.044). There were no significant differences between the two groups in terms of operating time (126.0±40.0 min vs. 127.0±63.0 min, p=0.828), operative blood loss (11.0±31.0 mL vs. 7.0±18.0 mL, p=0.100), drainage duration (7.0±3.0 d vs. 8.0±4.0 d, p=0.288), and complications (1.70% vs. 2.36%, p=0.523). CONCLUSION: Using advanced energy devices for SIBCS with axillary staging reduced incision size and provided better cosmetic outcomes compared to those using the conventional method. Advanced energy devices may offer better surgical outcomes in patients who undergo BCS with axillary staging.


Assuntos
Neoplasias da Mama , Excisão de Linfonodo , Mastectomia Segmentar , Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Mastectomia Segmentar/métodos , Mastectomia Segmentar/instrumentação , Estudos Retrospectivos , Excisão de Linfonodo/métodos , Excisão de Linfonodo/instrumentação , Adulto , Axila/cirurgia , Idoso , Duração da Cirurgia , Eletrocoagulação/métodos , Eletrocoagulação/instrumentação , Resultado do Tratamento
14.
J Food Sci ; 89(1): 450-459, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38051012

RESUMO

During freeze-drying, the degradation or eutectic melting of duck blood proteins can reduce the quality of duck blood gels. However, the interaction between proteins and polysaccharides during drying can improve protein-based gel quality. Therefore, here, we investigated the physicochemical properties of heat-induced gels of freeze-dried duck blood (FDB) and FDB with different proportions of the polysaccharide konjac glucomannan (KG), which serves as a freeze-denaturation inhibitor agent (FDA) or binder (BG). The pH and water-holding capacity (WHC) of FDB + KG gels were higher than those of FDB gel without KG (control). Especially, the WHC increased from 11.00% for control to 55.65% for FDB gel with 1% KG as a BG. Consequently, cooking loss and texture parameters of FDB + KG gels decreased. The hardness of control was 2.14 kg, which significantly reduced to 0.12-0.87 kg with KG addition. The highest carbonyl content was observed in control gel, and the thiobarbituric acid reactive substance content was reduced by the addition of 1% KG as an FDA (T1) or 0.8% KG as an FDA with 0.2% KG as a BG (T2) (p < 0.05). These changes might be induced by the alteration of tertiary structure and thermodynamic stability of gels. In conclusion, 1% KG can be used as an FDA to improve the quality and physicochemical properties of heat-induced gels of FDB. Optimized FDB gels with KG can be used as an innovative food ingredient to fortify nutrition and develop special dietary purposes.


Assuntos
Patos , Temperatura Alta , Animais , Géis/química , Mananas/química
15.
Food Chem ; 456: 140024, 2024 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-38870818

RESUMO

This study aimed to explore how pulsed electric field (PEF) treatment affects the structural, physicochemical, and emulsification properties of porcine-derived myofibrillar proteins (MPs). Increasing PEF treatment induced partial polarization and protein unfolding, resulting in notable denaturation that affected both the secondary and tertiary structures. PEF treatment also improved the solubility and emulsification ability of MPs by reducing their pH and surface hydrophobicity. Confocal laser scanning microscopy confirmed the effective adsorption of MPs and PEF-treated MPs at the oil/water interface, resulting in well-fabricated Pickering emulsions. A weak particle network increased the apparent viscosity in short-term PEF-treated Pickering emulsions. Conversely, in emulsions with long-term PEF-treated MP, rheological variables decreased, and dispersion stability increased. These results endorse the potential application of PEF-treated porcine-derived MPs as efficient Pickering stabilizers, offering valuable insights into the creative use of PEF for enhancing high-quality meat products, meeting the increasing demand for clean-label choices.


Assuntos
Emulsões , Proteínas Musculares , Solubilidade , Animais , Emulsões/química , Suínos , Proteínas Musculares/química , Viscosidade , Interações Hidrofóbicas e Hidrofílicas , Eletricidade , Miofibrilas/química , Reologia , Manipulação de Alimentos , Concentração de Íons de Hidrogênio , Produtos da Carne/análise
16.
Foods ; 13(14)2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39063331

RESUMO

Scaffolds play a key role in cultured meat production by providing an optimal environment for efficient cell attachment, growth, and development. This study investigated the effects of gelatin coating on the adhesion, proliferation, and adipogenic differentiation of adipose tissue-derived stem cells (ADSCs) cultured on soy protein-agarose scaffolds. Gelatin-coated scaffolds were prepared using 0.5% and 1.0% (w/v) gelatin solutions. The microstructure, water absorption rate, mechanical strength, cytotoxicity, cell adhesion, proliferation, and differentiation capabilities of the scaffolds were analyzed. Field emission scanning electron microscopy revealed the porous microstructure of the scaffolds, which was suitable for cell growth. Gelatin-coated scaffolds exhibited a significantly higher water absorption rate than that of non-coated scaffolds, indicating increased hydrophilicity. In addition, gelatin coating increased the mechanical strength of the scaffolds. Gelatin coating did not show cytotoxicity but significantly enhanced cell adhesion and proliferation. The gene expression levels of peroxisome proliferator-activated receptor gamma, CCAT/enhancer-binding protein alpha, and fatty acid-binding protein 4 were upregulated, and lipid accumulation was increased by gelatin coating. These findings suggest that gelatin-coated scaffolds provide a supportive microenvironment for ADSC growth and differentiation, highlighting their potential as a strategy for the improvement of cultured meat production and adipose tissue engineering.

17.
J Med Chem ; 67(17): 15148-15167, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39207209

RESUMO

Antimicrobial peptides (AMPs) represent promising therapeutic modalities against multidrug-resistant bacterial infections. As a mimic of natural AMPs, peptidomimetic oligomers like peptoids (i.e., oligo-N-substituted glycines) have been utilized for antimicrobials with resistance against proteolytic degradation. Here, we explore the conjugation of catalytic metal-binding motifs─the amino terminal Cu(II) and Ni(II) binding (ATCUN) motif─with cationic amphipathic antimicrobial peptoids to enhance their efficacy. Upon complexation with Cu(II) or Ni(II), the conjugates catalyzed hydroxyl radical generation, and 22 and 22-Cu exhibited over 10-fold improved selectivity compared to the parent peptoid, likely due to reduced hydrophobicity. Cu-ATCUN-peptoids caused bacterial membrane disruption, aggregation of intracellular biomolecules, DNA oxidation, and lipid peroxidation, promoting multiple killing mechanisms. In a mouse sepsis model, 22 demonstrated antimicrobial and anti-inflammatory efficacy with low toxicity. This study suggests a strategy to improve the potency of membrane-acting antimicrobial peptoids by incorporating ROS-generating motifs, thereby adding oxidative damage as a killing mechanism.


Assuntos
Cobre , Peptoides , Espécies Reativas de Oxigênio , Animais , Peptoides/química , Peptoides/farmacologia , Peptoides/síntese química , Espécies Reativas de Oxigênio/metabolismo , Camundongos , Cobre/química , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Catálise , Níquel/química , Níquel/farmacologia , Testes de Sensibilidade Microbiana , Peptídeos Antimicrobianos/farmacologia , Peptídeos Antimicrobianos/química , Peptídeos Antimicrobianos/síntese química , Sepse/tratamento farmacológico , Membrana Celular/metabolismo , Membrana Celular/efeitos dos fármacos , Humanos
18.
Artigo em Inglês | MEDLINE | ID: mdl-39445472

RESUMO

As electronic circuit integration intensifies, there is a rising demand for dielectric insulators that provide both superior insulation and high dielectric constants. This study focuses on developing high-k dielectric insulators by controlling the phase of the Hf0.5Zr0.5O2 (HZO) film with additional doping, utilizing yttrium (Y), tantalum (Ta), gallium (Ga), silicon (Si), and aluminum (Al) as dopants. Doping changes the ratio of tetragonal to monoclinic phases in doped HZO films, and Y-doped HZO (Y:HZO) films specifically exhibit a high tetragonal phase ratio and a dielectric constant of 40.9, indicating superior insulating properties compared to undoped HZO films. To clarify the fundamental mechanism driving the enhancement in dielectric properties, we have carried out various analyses combined with density functional theory (DFT) calculations. Through the optimization of the post-deposition annealing (PDA) process and the heterojunction structure with Al2O3, an Al2O3/Y:HZO heterojunction with a high dielectric constant and even lower leakage current compared to a single layer was developed. The thin-film transistor (TFT) with the Au/Ti/amorphous InGaZnO4 (a-IGZO)/Al2O3/YHZO/TiN heterojunction structure exhibits low subthreshold swing (SS) values within a narrow gate-source voltage (Vsg) range. This study advances knowledge on how the controlled-phase doped HZO films affect the dielectric constant and leakage current and will contribute to semiconductor technology advancements by overcoming the limitations of conventional high-k dielectric insulators.

19.
Food Sci Anim Resour ; 44(1): 146-164, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38229863

RESUMO

Owing to the residual toxicity and adverse health effects of chemical preservatives, there is an increasing demand for using natural preservatives in food. Although many natural extracts have been evaluated, research on their antibacterial effects remains insufficient. Therefore, this study aimed to explore the possibility of developing Psidium guajava, Ecklonia cava, and Paeonia japonica (Makino) Miyabe & Takeda extracts as natural food preservatives. Further, the effect of mixing these extracts on microbial growth and quality was evaluated during the refrigeration of sausages. Optimal mixing ratios were determined based on the minimum inhibitory and bactericidal concentrations of each mixed extract against the Listeria monocytogenes, Salmonella spp. and Escherichia coli. D-optimal mixing design optimization tool was further used to obtain an optimum mixing ratio of Formulation 1 (F1). The antibacterial activity of F1 increased with increasing concentration, with similar activities at 0.5% and 1%. The sausages with synthetic or natural preservatives showed significantly lower lipid oxidation than those of the control and grapefruit extract-treated sausages after 4 wk of refrigeration. Total plate counts were observed only in the control and treatment groups stored for 3 wk, and no significant effect of ascorbic acid was observed. Compared to the other samples, sausages with added natural extracts showed the highest overall acceptability scores initially and after 4 wk. Therefore, similar amounts of grapefruit seed and natural extracts had the same effect on microbiological analysis and lipid rancidity during sausage storage. Hence, this mixture can serve as a potential natural preservative in meat products.

20.
World J Gastroenterol ; 30(26): 3221-3228, 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39086638

RESUMO

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are effective in diabetes and obesity, reducing hyperglycemia by increasing insulin release and delaying gastric emptying. However, they can cause gastroparesis, raising concerns about aspiration during procedures. Recent guidelines advise discontinuing GLP-1 RA before surgery to reduce the risk of pulmonary aspiration. AIM: To evaluate the effect of GLP-1 RAs on gastric residual contents during endoscopic procedures. METHODS: A retrospective chart review at BronxCare Health System, New York, from January 2019 to October 2023, assessed gastric residue and aspiration in GLP-1 RA patients undergoing endoscopic procedures. Two groups were compared based on dietary status before the procedure. Data included demographics, symptoms of gastroparesis, opiate use, hemoglobin A1c, GLP-1 agonist indication, endoscopic details, and aspiration occurrence. IBM SPSS was used for analysis, calculating means, standard deviations, and applying Pearson's chi-square and t-tests for associations, with P < 0.05 as being significant. RESULTS: During the study, 306 patients were included, with 41.2% on a clear liquid/low residue diet and 58.8% on a regular diet before endoscopy. Most patients (63.1%) were male, with a mean age of 60 ± 12 years. The majority (85.6%) were on GLP-1 RAs for diabetes, and 10.1% reported digestive symptoms before endoscopy. Among those on a clear liquid diet, 1.5% had residual food at endoscopy compared to 10% on a regular diet, which was statistically significant (P = 0.03). Out of 31 patients with digestive symptoms, 13% had residual food, all from the regular diet group (P = 0.130). No complications were reported during or after the procedures. CONCLUSION: The study reflects a significant rise in GLP-1 RA use for diabetes and obesity. A 24-hour liquid diet seems safe for endoscopic procedures without aspiration. Patients with upper gastrointestinal symptoms might have a higher residual food risk, though not statistically significant. Further research is needed to assess risks based on diabetes duration, gastroparesis, and GLP-1 RA dosing, aiming to minimize interruptions in therapy during procedures.


Assuntos
Gastroparesia , Agonistas do Receptor do Peptídeo 1 Semelhante ao Glucagon , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Diabetes Mellitus Tipo 2/tratamento farmacológico , Endoscopia Gastrointestinal/efeitos adversos , Endoscopia Gastrointestinal/métodos , Esvaziamento Gástrico/efeitos dos fármacos , Gastroparesia/epidemiologia , Gastroparesia/etiologia , Gastroparesia/prevenção & controle , Agonistas do Receptor do Peptídeo 1 Semelhante ao Glucagon/administração & dosagem , Agonistas do Receptor do Peptídeo 1 Semelhante ao Glucagon/efeitos adversos , Estudos Retrospectivos
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