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1.
Nature ; 617(7961): 477-482, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37198310

RESUMO

Type Ia supernovae (SNe Ia) are thermonuclear explosions of degenerate white dwarf stars destabilized by mass accretion from a companion star1, but the nature of their progenitors remains poorly understood. A way to discriminate between progenitor systems is through radio observations; a non-degenerate companion star is expected to lose material through winds2 or binary interaction3 before explosion, and the supernova ejecta crashing into this nearby circumstellar material should result in radio synchrotron emission. However, despite extensive efforts, no type Ia supernova (SN Ia) has ever been detected at radio wavelengths, which suggests a clean environment and a companion star that is itself a degenerate white dwarf star4,5. Here we report on the study of SN 2020eyj, a SN Ia showing helium-rich circumstellar material, as demonstrated by its spectral features, infrared emission and, for the first time in a SN Ia to our knowledge, a radio counterpart. On the basis of our modelling, we conclude that the circumstellar material probably originates from a single-degenerate binary system in which a white dwarf accretes material from a helium donor star, an often proposed formation channel for SNe Ia (refs. 6,7). We describe how comprehensive radio follow-up of SN 2020eyj-like SNe Ia can improve the constraints on their progenitor systems.

2.
Small ; 20(26): e2310201, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38243889

RESUMO

Enhancing the mobility of lithium-ions (Li+) through surface engineering is one of major challenges facing fast-charging lithium-ion batteries (LIBs). In case of demanding charging conditions, the use of a conventional artificial graphite (AG) anode leads to an increase in operating temperature and the formation of lithium dendrites on the anode surface. In this study, a biphasic zeolitic imidazolate framework (ZIF)-AG anode, designed strategically and coated with a mesoporous material, is verified to improve the pathways of Li+ and electrons under a high charging current density. In particular, the graphite surface is treated with a coating of a ZIF-8-derived carbon nanoparticles, which addresses sufficient surface porosity, enabling this material to serve as an electrolyte reservoir and facilitate Li+ intercalation. Moreover, the augmentation in specific surface area proves advantageous in reducing the overpotential for interfacial charge transfer reactions. In practical terms, employing a full-cell with the biphasic ZIF-AG anode results in a shorter charging time and improved cycling performance, demonstrating no evidence of Li plating during 300 cycles under 3.0 C-charging and 1.0 C-discharging. The research endeavors to contribute to the progress of anode materials by enhancing their charging capability, aligning with the increasing requirements of the electric vehicle applications.

3.
Sensors (Basel) ; 24(11)2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38894305

RESUMO

This paper presents a current-mode VCSEL driver (CMVD) implemented using 180 nm CMOS technology for application in short-range LiDAR sensors, in which current-steering logic is suggested to deliver modulation currents from 0.1 to 10 mApp and a bias current of 0.1 mA simultaneously to the VCSEL diode. For the simulations, the VCSEL diode is modeled with a 1.6 V forward-bias voltage and a 50 Ω series resistor. The post-layout simulations of the proposed CMVD clearly demonstrate large output pulses and eye-diagrams. Measurements of the CMVD demonstrate large output pulses, confirming the simulation results. The chip consumes a maximum of 11 mW from a 3.3 V supply, and the core occupies an area of 0.1 mm2.

4.
Int J Mol Sci ; 25(3)2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38338991

RESUMO

Side streams and byproducts of food are established sources of natural ingredients in cosmetics. In the present study, we obtained upcycled low-molecular-weight anionic peptides (LMAPs) using byproducts of the post-yuzu-juicing process by employing an enzyme derived from Bacillus sp. For the first time, we isolated anionic peptides less than 500 Da in molecular weight from Citrus junos TANAKA seeds via hydrolysis using this enzyme. The protective effect of LMAPs against UVR-induced photoaging was evaluated using a reconstructed skin tissue (RST) model and keratinocytes. The LMAPs protected the keratinocytes by scavenging intracellular reactive oxygen species and by reducing the levels of paracrine cytokines (IL-6 and TNF-α) in UVR (UVA 2 J/cm2 and UVB 15 mJ/cm2)-irradiated keratinocytes. Additionally, the increase in melanin synthesis and TRP-2 expression in RST caused by UVR was significantly inhibited by LMAP treatment. This treatment strongly induced the expression of filaggrin and laminin-5 in UVR-irradiated RST. It also increased type I collagen expression in the dermal region and in fibroblasts in vitro. These results suggest that a hydrolytic system using the enzyme derived from Bacillus sp. can be used for the commercial production of LMAPs from food byproducts and that these LMAPs can be effective ingredients for improving photoaging-induced skin diseases.


Assuntos
Citrus , Envelhecimento da Pele , Dermatopatias , Pele/metabolismo , Citocinas/metabolismo , Dermatopatias/metabolismo , Raios Ultravioleta/efeitos adversos , Fibroblastos/metabolismo
5.
Medicina (Kaunas) ; 60(6)2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38929597

RESUMO

Backgound and Objectives: Gastric metastasis from invasive ductal breast cancer (BC) is rare. It mainly occurs in patients with lobular BC. The occurrence of multiple metastases is typically observed several years after the primary diagnosis. Endoscopic findings of gastric metastasis of the BC were usually the linitis plastic type. Case presentation: A 72-year-old women who underwent right modified radical mastectomy (MRM) 10 month ago was referred after being diagnosed with early gastric cancer (EGC) during systemic chemotherapy. EGC type I was found at gastric fundus, and pathologic finding showed poorly differentiated adenocarcinoma. Metachronous double primary tumor EGC was considered. Management and Outcome: A laparoscopic total gastrectomy was performed, and postoperative pathology revealed submucosa invasion and two lymph node metastases. A pathologic review that focused on immunohistochemical studies of selected antibodies such as GATA binding protein 3 (GATA3), gross cystic disease fluid protein-15 (GCDFP-15), cytokeratin 7 (CK7) was performed again, comparing previous results. As a result, gastric metastasis from BC was diagnosed. After totally laparoscopic total gastrectomy, palliative first-line chemotherapy with paclitaxel/CDDP was performed. Two months after gastrectomy, she was diagnosed with para-aortic lymph node metastasis and multiple bone metastases. She expired six months after gastrectomy. Conclusions: Gastric metastasis from invasive ductal carcinoma of the breast, which is clinically manifested as EGC, is a very rare condition. If there is a history of BC, careful pathological review will be required.


Assuntos
Neoplasias da Mama , Carcinoma Ductal de Mama , Gastrectomia , Neoplasias Gástricas , Humanos , Feminino , Neoplasias Gástricas/patologia , Neoplasias Gástricas/diagnóstico , Idoso , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/secundário , Carcinoma Ductal de Mama/diagnóstico , Gastrectomia/métodos , Diagnóstico Diferencial , Metástase Linfática
6.
Curr Issues Mol Biol ; 45(10): 7721-7733, 2023 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-37886931

RESUMO

This study addresses the propagation challenges faced by 'Shine Muscat', a newly introduced premium grapevine cultivar in South Korea, where multiple viral infections pose considerable economic loss. The primary objective was to establish a robust in vitro propagation method for producing disease-free grapes and to identify effective plant growth regulators to facilitate large-scale mass cultivation. After experimentation, 2.0 µM 6-benzyladenine (BA) exhibited superior shoot formation in the Murashige and Skoog medium compared with kinetin and thidiazuron. Conversely, α-naphthaleneacetic acid (NAA) hindered shoot growth and induced callus formation, while indole-3-butyric acid (IBA) and indole-3-acetic acid (IAA) demonstrated favorable root formation, with IBA showing better results overall. Furthermore, inter simple sequence repeat analysis confirmed the genetic stability of in vitro-cultivated seedlings using 2.0 µM BA and 1.0 µM IBA, validating the suitability of the developed propagation method for generating disease-free 'Shine Muscat' grapes. These findings offer promising prospects for commercial grape cultivation, ensuring a consistent supply of healthy grapes in the market.

7.
BMC Cancer ; 23(1): 1215, 2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38066476

RESUMO

BACKGROUND: The objective of this study was to estimate the accuracy of transcriptome-based classifier in differential diagnosis of uterine leiomyoma and leiomyosarcoma. We manually selected 114 normal uterine tissue and 31 leiomyosarcoma samples from publicly available transcriptome data in UCSC Xena as training/validation sets. We developed pre-processing procedure and gene selection method to sensitively find genes of larger variance in leiomyosarcoma than normal uterine tissues. Through our method, 17 genes were selected to build transcriptome-based classifier. The prediction accuracies of deep feedforward neural network (DNN), support vector machine (SVM), random forest (RF), and gradient boosting (GB) models were examined. We interpret the biological functionality of selected genes via network-based analysis using GeneMANIA. To validate the performance of trained model, we additionally collected 35 clinical samples of leiomyosarcoma and leiomyoma as a test set (18 + 17 as 1st and 2nd test sets). RESULTS: We discovered genes expressed in a highly variable way in leiomyosarcoma while these genes are expressed in a conserved way in normal uterine samples. These genes were mainly associated with DNA replication. As gene selection and model training were made in leiomyosarcoma and uterine normal tissue, proving discriminant of ability between leiomyosarcoma and leiomyoma is necessary. Thus, further validation of trained model was conducted in newly collected clinical samples of leiomyosarcoma and leiomyoma. The DNN classifier performed sensitivity 0.88, 0.77 (8/9, 7/9) while the specificity 1.0 (8/8, 8/8) in two test data set supporting that the selected genes in conjunction with DNN classifier are well discriminating the difference between leiomyosarcoma and leiomyoma in clinical sample. CONCLUSION: The transcriptome-based classifier accurately distinguished uterine leiomyosarcoma from leiomyoma. Our method can be helpful in clinical practice through the biopsy of sample in advance of surgery. Identification of leiomyosarcoma let the doctor avoid of laparoscopic surgery, thus it minimizes un-wanted tumor spread.


Assuntos
Leiomioma , Leiomiossarcoma , Neoplasias Uterinas , Feminino , Humanos , Leiomiossarcoma/diagnóstico , Leiomiossarcoma/genética , Leiomiossarcoma/patologia , Diagnóstico Diferencial , Leiomioma/diagnóstico , Leiomioma/genética , Leiomioma/patologia , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/genética , Neoplasias Uterinas/patologia , Perfilação da Expressão Gênica/métodos
8.
Cereb Cortex ; 32(24): 5530-5543, 2022 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-35258078

RESUMO

Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) has been widely used as an effective treatment for refractory temporal lobe epilepsy. Despite its promising clinical outcome, the exact mechanism of how ANT-DBS alleviates seizure severity has not been fully understood, especially at the cellular level. To assess effects of DBS, the present study examined electroencephalography (EEG) signals and locomotor behavior changes and conducted immunohistochemical analyses to examine changes in neuronal activity, number of neurons, and neurogenesis of inhibitory neurons in different hippocampal subregions. ANT-DBS alleviated seizure activity, abnormal locomotor behaviors, reduced theta-band, increased gamma-band EEG power in the interictal state, and increased the number of neurons in the dentate gyrus (DG). The number of parvalbumin- and somatostatin-expressing inhibitory neurons was recovered to the level in DG and CA1 of naïve mice. Notably, BrdU-positive inhibitory neurons were increased. In conclusion, ANT-DBS not only could reduce the number of seizures, but also could induce neuronal changes in the hippocampus, which is a key region involved in chronic epileptogenesis. Importantly, our results suggest that ANT-DBS may lead to hippocampal subregion-specific cellular recovery of GABAergic inhibitory neurons.


Assuntos
Núcleos Anteriores do Tálamo , Estimulação Encefálica Profunda , Epilepsia , Camundongos , Animais , Pilocarpina/toxicidade , Estimulação Encefálica Profunda/métodos , Núcleos Anteriores do Tálamo/fisiologia , Convulsões/induzido quimicamente , Convulsões/terapia , Hipocampo/fisiologia
9.
Sensors (Basel) ; 23(13)2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37447851

RESUMO

This paper presents a test methodology to facilitate the measuring processes of LiDAR receiver ICs by avoiding the inherent walk error issue. In a typical LiDAR system, a costly laser diode driver emits narrow light pulses with fast rising edges, and the reflected pulses from targets enter an optical detector followed by an analog front-end (AFE) circuit. Then, the received signals pass through the cascaded amplifiers down to the time-to-digital converter (TDC) that can estimate the detection range. However, this relatively long signal journey leads to the significant decline of rising-edge slopes and the output pulse spreading, thus producing inherent walk errors in LiDAR receiver ICs. Compensation methods requiring complex algorithms and extra chip area have frequently been exploited to lessen the walk errors. In this paper, however, a simpler and lower-cost methodology is proposed to test LiDAR receiver ICs by employing a high-speed buffer and variable delay cells right before the TDC. With these circuits, both START and STOP pulses show very similar pulse shapes, thus effectively avoiding the walk error issue. Additionally, the time interval between two pulses is easily determined by varying the number of the delay cells. Test chips of the proposed receiver IC implemented in a 180-nm CMOS process successfully demonstrate easier and more accurate measurement results.


Assuntos
Algoritmos , Amplificadores Eletrônicos , Desenho de Equipamento
10.
Nano Lett ; 22(13): 5069-5076, 2022 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-35648998

RESUMO

Structural colors have advantages compared with chemical pigments or dyes, such as iridescence, tunability, and unfading. Many studies have focused on developing the ability to switch ON/OFF the structural color; however, they often suffer from a simple and single stimulus, remaining structural colors, and target selectivity. Herein, we present regionally controlled multistimuli-responsive structural color switching surfaces. The key part is the utilization of a micropatterned DNA-hydrogel assembly on a single substrate. Each hydrogel network contains a unique type of stimuli-responsive DNA motifs as an additional cross-linker to exhibit swelling/deswelling via stimuli-responsive DNA interactions. The approach enables overcoming the existing limitations and selectively programming the DNA-hydrogel to a decrypted state (ON) and an encrypted state (OFF) in response to multiple stimuli. Furthermore, the transitions are reversible, providing cyclability. We envision the potential of our method for diverse applications, such as sensors or anticounterfeiting, requiring multistimuli-responsive structural color switching surfaces.


Assuntos
DNA , Hidrogéis , Corantes , DNA/química , Hidrogéis/química
11.
BMC Womens Health ; 22(1): 237, 2022 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-35715768

RESUMO

BACKGROUND: This cross-sectional study evaluated women's attitudes toward the certification logos, labels, and advertisements for organic disposable sanitary pads (OSPs) and investigated what could be the main reason for them. Additionally, the present study examined whether a relationship could be found between these attitudes and OSPs purchasing behavior. METHODS: This study was conducted using a self-reported online survey of Korean adult women who have purchased OSPs. The study questionnaire had four sections, covering (1) characteristics of OSP purchasing behavior, (2) attitudes toward OSP certification logos, labels, and advertisements, (3) demand on government and companies for proper management, and (4) respondent's sociodemographic information. The Cronbach's alpha value of the questionnaire was 0.857. RESULTS: A total of 500 respondents completed the questionnaire. Overall, high reliability was found for the certification logos (3.73 ± 0.61), labels on the product packaging (3.71 ± 0.63), and advertisements of OSPs (3.41 ± 0.62). Respondents indicated that these had fairly positive effects on their decision-making regarding product reliability, product image, and their own purchasing behavior. The aspects most frequently affected from the informants were safety to human health. All attitudes toward OSP certification logos, labels, and advertisements that were evaluated in this study became more positive in the direction from non-buyers to occasional buyers and to habitual buyers (all P < 0.05). The most significant demand from the respondents for OSP companies and the government was to clearly indicate hazardous ingredients on the OSP packaging (42.0%) and to strengthen the sanctions for false advertising (37.8%), respectively. CONCLUSIONS: The results of this study clearly indicate the importance of using certification logos, labels, and advertisements in the OSP market. These results can be utilized by OSP companies to improve the effectiveness of their marketing strategies or by policy makers and certifying bodies to manage the informants properly in the OSP market.


Assuntos
Publicidade , Atitude , Adulto , Publicidade/métodos , Certificação , Estudos Transversais , Feminino , Humanos , Reprodutibilidade dos Testes
12.
Sensors (Basel) ; 22(14)2022 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-35890781

RESUMO

Heart and respiration rates represent important vital signs for the assessment of a person's health condition. To estimate these vital signs accurately, we propose a multitask Siamese network model (MTS) that combines the advantages of the Siamese network and the multitask learning architecture. The MTS model was trained by the images of the cheek including nose and mouth and forehead areas while sharing the same parameters between the Siamese networks, in order to extract the features about the heart and respiratory information. The proposed model was constructed with a small number of parameters and was able to yield a high vital-sign-prediction accuracy, comparable to that obtained from the single-task learning model; furthermore, the proposed model outperformed the conventional multitask learning model. As a result, we can simultaneously predict the heart and respiratory signals with the MTS model, while the number of parameters was reduced by 16 times with the mean average errors of heart and respiration rates being 2.84 and 4.21. Owing to its light weight, it would be advantageous to implement the vital-sign-monitoring model in an edge device such as a mobile phone or small-sized portable devices.


Assuntos
Fotopletismografia , Taxa Respiratória , Coração , Humanos , Respiração , Sinais Vitais
13.
Sensors (Basel) ; 22(2)2022 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-35062641

RESUMO

Motion classification can be performed using biometric signals recorded by electroencephalography (EEG) or electromyography (EMG) with noninvasive surface electrodes for the control of prosthetic arms. However, current single-modal EEG and EMG based motion classification techniques are limited owing to the complexity and noise of EEG signals, and the electrode placement bias, and low-resolution of EMG signals. We herein propose a novel system of two-dimensional (2D) input image feature multimodal fusion based on an EEG/EMG-signal transfer learning (TL) paradigm for detection of hand movements in transforearm amputees. A feature extraction method in the frequency domain of the EEG and EMG signals was adopted to establish a 2D image. The input images were used for training on a model based on the convolutional neural network algorithm and TL, which requires 2D images as input data. For the purpose of data acquisition, five transforearm amputees and nine healthy controls were recruited. Compared with the conventional single-modal EEG signal trained models, the proposed multimodal fusion method significantly improved classification accuracy in both the control and patient groups. When the two signals were combined and used in the pretrained model for EEG TL, the classification accuracy increased by 4.18-4.35% in the control group, and by 2.51-3.00% in the patient group.


Assuntos
Amputados , Interfaces Cérebro-Computador , Aprendizado Profundo , Algoritmos , Eletroencefalografia , Eletromiografia , Humanos , Punho
14.
Sensors (Basel) ; 22(20)2022 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-36298279

RESUMO

This paper introduces an indoor-monitoring LiDAR sensor for patients with Alzheimer disease residing in long-term care facilities (LTCFs), and this sensor exploits an optoelectronic analog front-end (AFE) to detect light signals from targets by utilizing on-chip avalanche photodiodes (APDs) realized in a 180 nm CMOS process and a neural processing unit (NPU) used for motion detection and decisions, especially for incidents of falls occurring in LTCFs. The AFE consists of an on-chip CMOS P+/N-well APD, a linear-mode transimpedance amplifier, a post-amplifier, and a time-to-digital converter, whereas the NPU exploits network sparsity and approximate processing elements for low-power operation. This work provides a potential solution of low-cost, low-power, indoor-monitoring LiDAR sensors for patients with Alzheimer disease in LTCFs.


Assuntos
Doença de Alzheimer , Humanos , Assistência de Longa Duração , Amplificadores Eletrônicos , Semicondutores
15.
Small ; 17(23): e2100910, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33938152

RESUMO

Liquid crystal elastomers (LCEs) are broadly recognized as programmable actuating materials that are responsive to external stimuli, typically heat or light. Yet, soft LCEs that respond to changes in environmental humidity are not reported, except a few examples based on rigid liquid crystal networks with limited processing. Herein, a new class of highly deformable hygroscopic LCE actuators that can be prepared by versatile processing methods, including surface alignment as well as 3D printing is presented. The dimethylamino-functionalized LCE is prepared by the aza-Michael addition reaction between a reactive LC monomer and N,N'-dimethylethylenediamine as a chain extender, followed by photopolymerization. The humidity-responsive properties are introduced by activating one of the LCE surfaces with an acidic solution, which generates cations on the surface and provides asymmetric hydrophilicity to the LCE. The resulting humidity-responsive LCE undergoes programmed and reversible hygroscopic actuation, and its shape transformation can be directed by the cut angle with respect to a nematic director or by localizing activation regions in the LCE. Most importantly, various hygroscopic LCE actuators, including (porous) bilayers, a flower, a concentric square array, and a soft gripper, are successfully fabricated by using LC inks in UV-assisted direct-ink-writing-based 3D printing.

16.
Sensors (Basel) ; 21(13)2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34202334

RESUMO

This paper presents an optoelectronic receiver (Rx) IC with an on-chip avalanche photodiode (APD) realized in a 0.18-µm CMOS process for the applications of home-monitoring light detection and ranging (LiDAR) sensors, where the on-chip CMOS P+/N-well APD was implemented to avoid the unwanted signal distortion from bondwires and electro-static discharge (ESD) protection diodes. Various circuit techniques are exploited in this work, such as the feedforward transimpedance amplifier for high gain, and a limiting amplifier with negative impedance compensation for wide bandwidth. Measured results demonstrate 93.4-dBΩ transimpedance gain, 790-MHz bandwidth, 12-pA/√Hz noise current spectral density, 6.74-µApp minimum detectable signal that corresponds to the maximum detection range of 10 m, and 56.5-mW power dissipation from a 1.8-V supply. This optoelectronic Rx IC provides a potential for a low-cost low-power solution in the applications of home-monitoring LiDAR sensors.

17.
Sensors (Basel) ; 21(5)2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33668260

RESUMO

We present a back-to-back (BTB) structured, dual-mode ultrasonic device that incorporates a single-element 5.3 MHz transducer for high-intensity focused ultrasound (HIFU) treatment and a single-element 20.0 MHz transducer for high-resolution ultrasound imaging. Ultrasound image-guided surgical systems have been developed for lesion monitoring to ensure that ultrasonic treatment is correctly administered at the right locations. In this study, we developed a dual-element transducer composed of two elements that share the same housing but work independently with a BTB structure, enabling a mode change between therapy and imaging via 180-degree mechanical rotation. The optic fibers were embedded in the HIFU focal region of ex vivo chicken breasts and the temperature change was measured. Images were obtained in vivo mice before and after treatment and compared to identify the treated region. We successfully acquired B-mode and C-scan images that display the hyperechoic region indicating coagulation necrosis in the HIFU-treated volume up to a depth of 10 mm. The compact BTB dual-mode ultrasonic transducer may be used for subcutaneous thermal ablation and monitoring, minimally invasive surgery, and other clinical applications, all with ultrasound only.


Assuntos
Ablação por Ultrassom Focalizado de Alta Intensidade , Ultrassom , Animais , Camundongos , Transdutores , Ultrassonografia
18.
Int J Mol Sci ; 22(6)2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33809961

RESUMO

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative neuromuscular disease. Although genome-wide association studies (GWAS) have successfully identified many variants significantly associated with ALS, it is still difficult to characterize the underlying biological mechanisms inducing ALS. In this study, we performed a transcriptome-wide association study (TWAS) to identify disease-specific genes in ALS. Using the largest ALS GWAS summary statistic (n = 80,610), we identified seven novel genes using 19 tissue reference panels. We conducted a conditional analysis to verify the genes' independence and to confirm that they are driven by genetically regulated expressions. Furthermore, we performed a TWAS-based enrichment analysis to highlight the association of important biological pathways, one in each of the four tissue reference panels. Finally, utilizing a connectivity map, a database of human cell expression profiles cultured with bioactive small molecules, we discovered functional associations between genes and drugs to identify 15 bioactive small molecules as potential drug candidates for ALS. We believe that, by integrating the largest ALS GWAS summary statistic with gene expression to identify new risk loci and causal genes, our study provides strong candidates for molecular basis experiments in ALS.


Assuntos
Esclerose Lateral Amiotrófica/genética , Marcadores Genéticos , Predisposição Genética para Doença , Transcriptoma , Esclerose Lateral Amiotrófica/diagnóstico , Esclerose Lateral Amiotrófica/tratamento farmacológico , Biomarcadores , Biologia Computacional/métodos , Desenvolvimento de Medicamentos , Reposicionamento de Medicamentos , Perfilação da Expressão Gênica , Humanos , Anotação de Sequência Molecular , Terapia de Alvo Molecular , Medição de Risco , Fatores de Risco , Fluxo de Trabalho
19.
Int J Mol Sci ; 22(16)2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34445113

RESUMO

Nuclear factor erythroid 2-related factor (Nrf2) is a transcriptional activator of the cell protection gene that binds to the antioxidant response element (ARE). Therefore, Nrf2 protects cells and tissues from oxidative stress. Normally, Kelch-like ECH-associated protein 1 (Keap1) inhibits the activation of Nrf2 by binding to Nrf2 and contributes to Nrf2 break down by ubiquitin proteasomes. In moderate oxidative stress, Keap1 is inhibited, allowing Nrf2 to be translocated to the nucleus, which acts as an antioxidant. However, under unusually severe oxidative stress, the Keap1-Nrf2 mechanism becomes disrupted and results in cell and tissue damage. Oxide-containing atmospheric environment generally contributes to the development of respiratory diseases, possibly leading to the failure of the Keap1-Nrf2 pathway. Until now, several studies have identified changes in Keap1-Nrf2 signaling in models of respiratory diseases, such as acute respiratory distress syndrome (ARDS)/acute lung injury (ALI), chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and asthma. These studies have confirmed that several Nrf2 activators can alleviate symptoms of respiratory diseases. Thus, this review describes how the expression of Keap1-Nrf2 functions in different respiratory diseases and explains the protective effects of reversing this expression.


Assuntos
Fator 2 Relacionado a NF-E2/metabolismo , Doenças Respiratórias/metabolismo , Animais , Antioxidantes/metabolismo , Humanos , Estresse Oxidativo/fisiologia , Transdução de Sinais/fisiologia
20.
Molecules ; 26(8)2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33917070

RESUMO

Hair loss by excessive stress from work and lifestyle changes has become a growing concern, particularly among young individuals. However, most drugs for alopecia impose a plethora of side effects. We have found the powerful impact of Malva verticillata seed extracts on alleviating hair loss. This study further isolated effective chemicals in M. verticillata seed extracts by liquid silica gel column chromatography. Under the screening for the growth rate (%) of human follicles dermal papilla cells (HFDPCs), we identified linoleic acid (LA) and oleic acid in n-hexane of M. verticillate (MH)2 fraction. LA treatment activated Wnt/ß-catenin signaling and induced HFDPCs growth by increasing the expression of cell cycle proteins such as cyclin D1 and cyclin-dependent kinase 2. LA treatment also increased several growth factors, such as vascular endothelial growth factor, insulin-like growth factor-1, hepatocyte growth factor, and keratinocyte growth factor, in a dose-dependent manner. Besides, LA significantly inhibited Dickkopf-related protein expression (DKK-1), a primary alopecia signaling by dihydrotestosterone. Our findings suggest that LA treatment may alleviate a testosterone-induced signaling molecule and induces HFDPCs growth by activating Wnt/ß-catenin signaling.


Assuntos
Folículo Piloso/citologia , Peptídeos e Proteínas de Sinalização Intercelular/agonistas , Ácido Linoleico/farmacologia , Malva/química , Extratos Vegetais/farmacologia , Sementes/química , Biomarcadores , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Fracionamento Químico , Expressão Gênica , Folículo Piloso/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Ácido Linoleico/química , Ácido Linoleico/isolamento & purificação , Modelos Biológicos , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Via de Sinalização Wnt/efeitos dos fármacos
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