Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 92
Filtrar
1.
Acta Biomater ; 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38719158

RESUMEN

Bacterial infections are among the most critical global health challenges that seriously threaten the security of human. To address this issue, a biocompatible engineered living hydrogel patch was developed by co-embedding engineered photothermal bacteria (EM), photosensitizer (porphyrin) and reactive oxygen species amplifier (laccase) in a protein hydrogel. Remarkably, the genetice engineered bacteria can express melanin granules in vivo and this allows them to exhibit photothermal response upon being exposed to NIR-II laser (1064 nm) irradiation. Besides, electrostatically adhered tetramethylpyridinium porphyrin (TMPyP) on the bacterial surface and encapsulated laccase (Lac) in protein gel can generate highly toxic singlet oxygen (1O2) and hydroxyl radical (·OH) in the presence of visible light and lignin, respectively. Interestingly, the engineered bacteria hydrogel patch (EMTL@Gel) was successfully applied in synergistic photothermal, photodynamic and chemodynamic therapy, in which it was able to efficiently treat bacterial infection in mouse wounds and enhance wound healing. This work demonstrates the concept of "fighting bacteria with bacteria" combining bacterial engineering and material engineering into an engineered living hydrogel path that can synergistically boost the therapeutic outcome. STATEMENT OF SIGNIFICANCE: Genetically engineered bacteria produce melanin granules in vivo, exhibiting remarkable photothermal properties. These bacteria, along with a photosensitizer (TMPyP) and a reactive oxygen species amplifier (laccase), are incorporated into a biocompatible protein hydrogel patch. Under visible light, the patch generates toxic singlet oxygen (1O2) and hydroxyl radical (·OH), demonstrates outstanding synergistic effects in photothermal, photodynamic, and chemodynamic therapy, effectively treating bacterial infections and promoting wound healing in mice.

2.
Sci Total Environ ; 934: 173313, 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38761952

RESUMEN

Taiwan, identified as pivotal in the Asian drug trafficking chain, has been experiencing a surge in illicit drug-related issues. Wastewater-based epidemiology (WBE) has emerged as a promising approach for comprehensive evaluation of actual illicit drug usage. This study presents the first WBE investigation of illicit drug consumption in Taiwan based on the analysis of wastewater from four wastewater treatment plants (WWTPs) in the Taipei metropolitan area. Additionally, it demonstrates a high correlation between the amounts of illicit drugs seized and influent concentrations over an extended period of time. The reliability of solid-phase extraction and analysis via high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was validated for 16 illicit drugs (methamphetamine, ketamine, cocaine, codeine, methadone, morphine, meperidine, fentanyl, sufentanil, para-methoxyamphetamine (PMA), para-methoxymethamphetamine (PMMA), 3,4-methylenedioxymethamphetamine (MDMA), cathinone, methcathinone, mephedrone (MEPH), and 4-methylethcathinone (4-MEC)). Methamphetamine, ketamine, and 4-MEC were consistently detected in all wastewater samples, underscoring their prevalence in the Taipei metropolitan area. Biochemical oxygen demand (BOD) and ammonia nitrogen (ammonia N) were employed to reduce uncertainty in estimations of population size during back-calculation of illicit drug consumption. The results indicate that methamphetamine was the most consumed drug (175-740 mg day-1 1000 people-1), followed by ketamine (22-280 mg day-1 1000 people-1). In addition, urban-related WWTPs exhibited higher consumption of methamphetamine and ketamine than did the suburban-related WWTP, indicating distinct illicit drug usage patterns between suburban and urban regions. Moreover, an examination of temporal trends in wastewater from the Dihua WWTP revealed a persistent predominance of ketamine and methamphetamine, consistent with statistical data pertaining to seizure quantities and urine test results. The study provides encouraging insight into spatial and temporal variations in illicit drug usage in the Taipei metropolitan area, emphasizing the complementary role of WBE in understanding trends in illicit drug abuse.

3.
Front Neurosci ; 18: 1371290, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38550564

RESUMEN

Introduction: Spiking Neural Networks (SNNs), inspired by brain science, offer low energy consumption and high biological plausibility with their event-driven nature. However, the current SNNs are still suffering from insufficient performance. Methods: Recognizing the brain's adeptness at information processing for various scenarios with complex neuronal connections within and across regions, as well as specialized neuronal architectures for specific functions, we propose a Spiking Global-Local-Fusion Transformer (SGLFormer), that significantly improves the performance of SNNs. This novel architecture enables efficient information processing on both global and local scales, by integrating transformer and convolution structures in SNNs. In addition, we uncover the problem of inaccurate gradient backpropagation caused by Maxpooling in SNNs and address it by developing a new Maxpooling module. Furthermore, we adopt spatio-temporal block (STB) in the classification head instead of global average pooling, facilitating the aggregation of spatial and temporal features. Results: SGLFormer demonstrates its superior performance on static datasets such as CIFAR10/CIFAR100, and ImageNet, as well as dynamic vision sensor (DVS) datasets including CIFAR10-DVS and DVS128-Gesture. Notably, on ImageNet, SGLFormer achieves a top-1 accuracy of 83.73% with 64 M parameters, outperforming the current SOTA directly trained SNNs by a margin of 6.66%. Discussion: With its high performance, SGLFormer can support more computer vision tasks in the future. The codes for this study can be found in https://github.com/ZhangHanN1/SGLFormer.

4.
Clin Exp Pharmacol Physiol ; 51(3): e13843, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38302075

RESUMEN

This study explores the potential mechanisms of obstructive sleep apnoea (OSA) complicates type 2 diabetes mellitus (T2DM) by which chronic intermittent hypoxia (CIH) induces insulin resistance and cell apoptosis in the pancreas through oxidative stress. Four- and eight-week CIH rat models were established, and Tempol (100 mg/kg/d), was used as an oxidative stress inhibitor. This study included five groups: 4-week CIH, 4-week CIH-Tempol, 8-week CIH, 8-week CIH-Tempol and normal control (NC) groups. Fasting blood glucose and insulin levels were measured in the serum. The expression levels of 8-hidroxy-2-deoxyguanosine (8-OHdG), tribbles homologue 3 (TRB3), c-Jun N-terminal kinase (JNK), phosphorylated JNK (p-JNK), insulin receptor substrate-1 (IRS-1), phosphorylated IRS-1 (Ser307) (p-IRS-1ser307 ), protein kinase B (AKT), phosphorylated AKT (Ser473) (p-AKTser473 ), B cell lymphoma protein-2 (Bcl-2), cleaved-caspase-3 (Cl-caspase-3), and the islet cell apoptosis were detected in the pancreas. CIH induced oxidative stress in the pancreas. Compared with that in the NC group and CIH-Tempol groups individually, the homeostasis model assessment of insulin resistance (HOMA-IR) and apoptosis of islet cells was increased in the CIH groups. CIH-induced oxidative stress increased the expression of p-IRS-1Ser307 and decreased the expression of p-AKTSer473 . The expression levels of TRB3 and p-JNK were higher in the CIH groups than in both the CIH-Tempol and NC groups. Meanwhile, the expressions of Cl-caspase-3 and Bcl-2 were upregulated and downregulated, respectively, in the CIH groups. Hence, the present study demonstrated that CIH-induced oxidative stress might not only induce insulin resistance but also islet cell apoptosis in the pancreas through TRB3 and p-JNK.


Asunto(s)
Óxidos N-Cíclicos , Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Marcadores de Spin , Animales , Ratas , Apoptosis , Caspasa 3/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Hipoxia/complicaciones , Estrés Oxidativo , Páncreas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteína Quinasa 8 Activada por Mitógenos/metabolismo
5.
Kidney Int Rep ; 8(11): 2284-2293, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38025230

RESUMEN

Introduction: Dysregulated complement activation is likely the primary driver of disease in C3 glomerulopathy (C3G) and contributes to other complement-mediated diseases, including immunoglobulin A nephropathy (IgAN), lupus nephritis (LN), and primary membranous nephropathy (PMN). No complement inhibitors are proven to halt disease progression in these diseases. Pegcetacoplan, a targeted C3 and C3b inhibitor, may mitigate complement-mediated kidney damage in C3G and other glomerular diseases in which complement may have a pathogenic role. Methods: This open-label, phase 2, 48-week study evaluated the preliminary efficacy and safety of subcutaneous pegcetacoplan for patients with complement-mediated glomerular diseases. The primary end point was proteinuria reduction, measured as 24-hour urine protein-to-creatinine ratio. Secondary end points included remission status, changes in estimated glomerular filtration rate (eGFR), and pharmacodynamic biomarkers. Treatment-emergent adverse events (TEAEs) were monitored. Results: Efficacy results for the C3G cohort are reported herein, along with safety results for the study population. In the C3G cohort, mean proteinuria reduction from baseline to week 48 was 50.9% in the intent-to-treat (ITT) population (n = 7) and 65.4% in the per-protocol (PP) population (n = 4). Mean serum albumin normalized and mean eGFR was stable over 48 weeks. Mean serum C3 levels increased 6-fold and mean soluble C5b-9 levels decreased by 57.3% at week 48. The most common adverse events (AEs) were upper respiratory tract infection, injection site erythema, nausea, and headache. No meningitis or sepsis cases were reported, and no serious treatment-related AEs were observed. Conclusion: Pegcetacoplan may provide therapeutic benefit for C3G and has a favorable safety profile across the 4 glomerular diseases studied.

6.
Sci Adv ; 9(40): eadi1480, 2023 10 06.
Artículo en Inglés | MEDLINE | ID: mdl-37801497

RESUMEN

Spiking neural networks (SNNs) aim to realize brain-inspired intelligence on neuromorphic chips with high energy efficiency by introducing neural dynamics and spike properties. As the emerging spiking deep learning paradigm attracts increasing interest, traditional programming frameworks cannot meet the demands of the automatic differentiation, parallel computation acceleration, and high integration of processing neuromorphic datasets and deployment. In this work, we present the SpikingJelly framework to address the aforementioned dilemma. We contribute a full-stack toolkit for preprocessing neuromorphic datasets, building deep SNNs, optimizing their parameters, and deploying SNNs on neuromorphic chips. Compared to existing methods, the training of deep SNNs can be accelerated 11×, and the superior extensibility and flexibility of SpikingJelly enable users to accelerate custom models at low costs through multilevel inheritance and semiautomatic code generation. SpikingJelly paves the way for synthesizing truly energy-efficient SNN-based machine intelligence systems, which will enrich the ecology of neuromorphic computing.


Asunto(s)
Algoritmos , Neuronas , Redes Neurales de la Computación , Aprendizaje Automático , Inteligencia
7.
Nanoscale ; 15(17): 7877-7893, 2023 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-37060124

RESUMEN

Radiation-induced oral mucositis (RIOM) is considered to be one of the most important public health problems today, affecting the overall well-being of millions of patients who have received radiotherapy. Nevertheless, the field of preventing and treating RIOM is still widely unexplored. Curcumin (Cur) with its promising anti-inflammatory and antioxidant properties is accompanied with obstacles in application, including poor dissolubility, instability and low bioavailability. In this study, a tetrahedral framework nucleic acid drug delivery system (TFNAS) was synthesized and established using a novel method to carry Cur (Cur-TFNAS) for efficient drug delivery. The results showed that Cur-TFNAS enhanced the antioxidant capacity of human oral mucosal keratin-forming cells (HOKs) compared to free Cur and TFNAS. Meanwhile, Cur-TFNAS reduced DNA damage and shielded the cells from inflammatory factors. A similar result was also well documented in vivo. Herein, we consider that Cur-TFNAS acts as a nano-shield for preventing radiation oral mucositis and shows important clinical value in the future.


Asunto(s)
Curcumina , Mucositis , Ácidos Nucleicos , Estomatitis , Humanos , Antioxidantes/farmacología , Sistemas de Liberación de Medicamentos , Curcumina/farmacología , Estomatitis/tratamiento farmacológico , Estomatitis/etiología
9.
Open Med (Wars) ; 17(1): 1509-1514, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36237832

RESUMEN

Dexamethasone can be used to prevent nausea and vomiting after surgery, but there is concern that it may induced perineal irritation. The aim of this study was to investigate the attenuation effect of dilution and slow injection on dexamethasone-induced perineal irritation. In this prospective, randomized, double-blind study, a total of 400 patients were enrolled and allocated into four groups: Group I, receiving 2 mL dexamethasone (5 mg/mL), Group II, receiving 5 mL dexamethasone (2 mg/mL), Group III, receiving 10 mL dexamethasone (1 mg/mL), and Group IV receiving 20 mL dexamethasone (0.5 mg/mL). Dexamethasone was diluted with 5% glucose. The injection time of dexamethasone was less than 2 s in Group I, while it was 30 s in Groups II, III, and IV. The incidence, onset, duration, and severity of perineal irritation were recorded. The incidence of dexamethasone-induced perineal irritation was 49, 33, 17, and 15% in Groups I, II, III, and IV, respectively. Group IV had less severity than Group I in mild and moderate perineal irritation (P < 0.008). The onset and duration of perineal irritation of Groups II, III, and IV were significantly improved compared to Group I (P < 0.001). Dexamethasone-induced perineal irritation can be alleviated by dilution of dexamethasone to 0.5 mg/mL with 5% glucose combined with prolonged injection time of 30 s.

10.
Invest Ophthalmol Vis Sci ; 63(11): 2, 2022 10 03.
Artículo en Inglés | MEDLINE | ID: mdl-36194423

RESUMEN

Purpose: The purpose of this study was to elucidate the effect of methyltransferase-like enzyme 3 (METTL3) on inflammation and the NF-κB signaling pathway in fungal keratitis (FK). Methods: We established corneal stromal cell models and FK mouse models by incubation with Fusarium solani. The overall RNA N6-methyladenosine (m6A) level was determined using an m6A RNA methylation assay kit. The expression of METTL3 was quantified via real-time quantitative polymerase chain reaction (RT-PCR), Western blotting, and immunofluorescence. Subsequently, the level of tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) was identified by Western blotting and immunofluorescence. Moreover, we assessed the effect of METTL3 by transfecting cells with siRNA (in vitro) or adeno-associated virus (in vivo). Hematoxylin and eosin (H&E) staining and slit-lamp biomicroscopy were performed to evaluate corneal damage. Furthermore, the state of NF-κB signaling pathway activation was examined by Western blotting. In addition, RT-PCR and enzyme-linked immunosorbent assays (ELISAs) were performed to evaluate levels of the pro-inflammatory factors interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and TNF-ɑ. Results: Our data demonstrated that the levels of the RNA m6A methylation and METTL3 were dramatically increased and that the NF-κB signaling pathway was activated in Fusarium solani-induced keratitis. Inhibition of METTL3 decreased the level of TRAF6, downregulated the phospho-p65(p-p65)/p65 and phospho-IκB(p-IκB)/IκB protein ratios, simultaneously attenuating the inflammatory response and fungal burden in FK. Conclusions: Our research suggests that the m6A methyltransferase METTL3 regulates the inflammatory response in FK by modulating the NF-κB signaling pathway.


Asunto(s)
Queratitis , FN-kappa B , Animales , Eosina Amarillenta-(YS)/farmacología , Fusarium , Hematoxilina/farmacología , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Metiltransferasas/genética , Ratones , FN-kappa B/metabolismo , ARN Interferente Pequeño/farmacología , Transducción de Señal , Factor 6 Asociado a Receptor de TNF/metabolismo , Factor 6 Asociado a Receptor de TNF/farmacología , Factor de Necrosis Tumoral alfa/metabolismo
11.
Chem Pharm Bull (Tokyo) ; 70(9): 637-641, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36047235

RESUMEN

Human epidermal growth factor (EGFR) is an important target for antitumor drug research. A series of novel quinazolinone derivatives were synthesized and developed as potent inhibitors of EGFR. The results showed that most of the aimed compounds had potential anti-tumor cell proliferation activities. Some compounds were tested for their EGFR inhibitory activity. Especially, compound 6d showed the most potent antitumor activity with IC50 values of 1.58 µM against human breast cancer (MCF-7) cell lines and exhibited the most potent EGFR inhibitory activity with IC50 of 0.77 µM. Docking simulation was performed to position compound 6d into the EGFR active site to determine the probable binding conformation.


Asunto(s)
Antineoplásicos , Quinazolinonas , Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular , Diseño de Fármacos , Ensayos de Selección de Medicamentos Antitumorales , Receptores ErbB , Humanos , Simulación del Acoplamiento Molecular , Estructura Molecular , Inhibidores de Proteínas Quinasas/química , Quinazolinonas/química , Quinazolinonas/farmacología , Relación Estructura-Actividad
12.
Artículo en Inglés | MEDLINE | ID: mdl-36121959

RESUMEN

Among various value decomposition-based multiagent reinforcement learning (MARL) algorithms, the overall performance of the multiagent system is represented by a scalar global Q value and optimized by minimizing the temporal difference (TD) error with respect to that global Q value. However, the global Q value cannot accurately model the distributed dynamics of the multiagent system, since it is only a simplified representation for different individual Q values of agents. To explicitly consider the correlations between different cooperative agents, in this article, we propose a distributional framework and construct a practical model called distributional multiagent cooperation (DMAC) from a novel distributional perspective. Specifically, in DMAC, we view the individual Q value for the executed action of a random agent as a value distribution, whose expectation can further represent the overall performance. Then, we employ distributional RL to minimize the difference between the estimated distribution and its target for the optimization. The advantage of DMAC is that the distributed dynamics of agents can be explicitly modeled, and this results in better performance. To verify the effectiveness of DMAC, we conduct extensive experiments under nine different scenarios of the StarCraft Multiagent Challenge (SMAC). Experimental results show that the DMAC can significantly outperform the baselines with respect to the average median test win rate.

13.
Invest Ophthalmol Vis Sci ; 63(10): 20, 2022 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-36169946

RESUMEN

Purpose: Our previous investigations revealed a significant role of methyltransferase-like 3 (METTL3)-mediated N6-methyladenosine (m6A) modification in the development of corneal inflammation in Fusarium infection, but the exact mechanism is unknown. Therefore, this research aimed to explore how METTL3 affects the inflammatory process of fungal keratitis (FK) in mice. Methods: We established in vitro and in vivo models by inoculating mice and primary corneal stromal cells with F. solani. METTL3 expression was confirmed by real-time quantitative polymerase chain reaction, immunofluorescence, and western blotting. After that, siRNAMETTL3 and AAV-sh-METTL3 were transfected into cells and mice to explore the role of METTL3 in the PI3K/AKT signaling pathway and inflammation. PI3K, p-PI3K, AKT, and p-AKT expression was analyzed by western blotting. Viability of corneal stromal cells was measured using a Cell Counting Kit-8 (CCK-8). Additionally, we detected interleukin (IL)-6, IL-1ß, and tumor necrosis factor alpha (TNF-α) levels in corneal tissues and analyzed the role of METTL3 in inflammation in FK using slit-lamp biomicroscopy and hematoxylin and eosin staining. Results: Here, our results show that METTL3 increased in mouse FK, and the expression of p-PI3K and p-AKT decreased when METTL3 was downregulated. We also found that knockdown of METTL3 expression attenuated the inflammatory response and decreased TNF-α, IL-1ß, and IL-6 expression in corneal-infected mice. Furthermore, inhibition of the PI3K/AKT pathway attenuated the inflammatory response of FK, decreased the expression of the above inflammatory factors, and enhanced the viability of corneal stromal cells. Conclusions: Based on the study results, METTL3 downregulation attenuates Fusarium-induced corneal inflammation via the PI3K/AKT signaling pathway.


Asunto(s)
Infecciones Fúngicas del Ojo , Fusarium , Queratitis , Animales , Eosina Amarillenta-(YS) , Infecciones Fúngicas del Ojo/metabolismo , Hematoxilina , Inflamación/metabolismo , Interleucina-6/metabolismo , Queratitis/microbiología , Metiltransferasas/genética , Ratones , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/fisiología , Factor de Necrosis Tumoral alfa/metabolismo
14.
Sci Adv ; 8(20): eabn2030, 2022 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-35594353

RESUMEN

Two-dimensional (2D) oxides have unique electrical, optical, magnetic, and catalytic properties, which are promising for a wide range of applications in different fields. However, it is difficult to fabricate most oxides as 2D materials unless they have a layered structure. Here, we present a facile strategy for the synthesis of ultrathin oxide nanosheets using a self-formed sacrificial template of carbon layers by taking advantage of the Maillard reaction and violent redox reaction between glucose and ammonium nitrate. To date, 36 large-area ultrathin oxides (with thickness ranging from ~1.5 to ~4 nm) have been fabricated using this method, including rare-earth oxides, transition metal oxides, III-main group oxides, II-main group oxides, complex perovskite oxides, and high-entropy oxides. In particular, the as-obtained perovskite oxides exhibit great electrocatalytic activity for oxygen evolution reaction in an alkaline solution. This facile, universal, and scalable strategy provides opportunities to study the properties and applications of atomically thin oxide nanomaterials.

15.
Invest Ophthalmol Vis Sci ; 63(1): 41, 2022 01 03.
Artículo en Inglés | MEDLINE | ID: mdl-35089329

RESUMEN

Purpose: Increasing evidence suggested that microRNAs (miRs) are implicated in the regulation of the inflammatory response and autophagy in multiple diseases. The present study aimed to explore the effect of miR-223-3p on inflammation and autophagy in fungal keratitis (FK). Methods: An FK mouse model was established, and primary corneal stromal cells were isolated by inoculation with Fusarium solani. The expression of miR-223-3p was determined by quantitative RT-PCR. Subsequently, the target gene of miR-223-3p was identified by a dual-luciferase reporter assay. The levels of miR-223-3p were altered by transfecting miR agomir/antagomir to evaluate its effects. Slit-lamp biomicroscopy and hematoxylin and eosin staining were employed to detect corneal damage. The levels of autophagy were assessed by immunofluorescence, Western blotting, mRFP-GFP-LC3 fluorescence microscopy, and electron microscopy. In addition, inflammation was demonstrated by determining the proinflammatory mediators IL-1ß and TNF-ɑ. Results: Our data suggested that miR-223-3p was increased and that autophagic flux was impaired in mouse FK. Then, we confirmed that autophagy-related gene 16L1 (ATG16L1) was a potential target of miR-223-3p and that this miR negatively regulated the expression of ATG16L1. The inhibition of miR-223-3p attenuated inflammation in FK, reduced P62 expression, and increased the ratio of LC3-II/LC3-I, whereas the overexpression of miR-223-3p displayed the opposite results. Conclusions: Taken together, miR-223-3p might regulate autophagy via targeting ATG16L1 in experimental F. solani keratitis and is associated with the inflammatory response. MiR-223-3p might be a potential therapeutic target for FK.


Asunto(s)
Autofagia/genética , Infecciones Fúngicas del Ojo/genética , Fusarium/patogenicidad , Regulación de la Expresión Génica , Queratitis/genética , MicroARNs/genética , Animales , Células Cultivadas , Modelos Animales de Enfermedad , Infecciones Fúngicas del Ojo/metabolismo , Infecciones Fúngicas del Ojo/microbiología , Queratitis/metabolismo , Queratitis/microbiología , Ratones , Ratones Endogámicos BALB C , MicroARNs/biosíntesis , ARN/genética
16.
Fish Shellfish Immunol ; 121: 332-341, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35032679

RESUMEN

The ubiquitin-specific proteases (USPs) have attracted particular attention due to their multiple functions in different biological processes. USP12, a member of the USP family, has been demonstrated to exert critical roles in diverse cellular processes, including cell death, cancer and antiviral immunity. Here, we cloned a USP12 homolog from orange spotted grouper (Epinephelus coioides, E. coioides), and its roles in fish RNA virus replication were investigated. EcUSP12 contained a 1119-bp open reading frame (ORF) encoding a 372-amino acid polypeptide, which shared 100.00% and 91.32% identity with USP12 homolog of Etheostoma cragini and Homo sapiens, respectively. Sequence analysis indicated that EcUSP12 contained a conserved peptidase-C19G domain (aa 40-369). qPCR analysis showed that EcUSP12 transcript was most abundant in head kidney and spleen of grouper E. coioides. The expression of EcUSP12 was significantly upregulated in grouper spleen (GS) cells in response to red-spotted grouper nervous necrosis virus (RGNNV) infection. Subcellular localization analysis showed that EcUSP12 was evenly distributed throughout the cytoplasm, and mainly co-localized with endoplasmic reticulum (ER). Interestingly, during RGNNV infection, the endogenous distribution of EcUSP12 was obviously altered, and mostly overlapped with viral coat protein (CP). Co-Immunoprecipitation (Co-IP) assay indicated that EcUSP12 interacted with viral CP. In addition, overexpression of EcUSP12 significantly inhibited the replication of RGNNV in vitro, as evidenced by the decrease in viral gene transcription and protein synthesis during infection. Consistently, knockdown of EcUSP12 by small interfering RNA (siRNA) promoted the replication of RGNNV. Furthermore, EcUSP12 overexpression also increased the transcription level of inflammatory factors and interferon-related genes, including tumor necrosis factor α (TNF-α), interleukin (IL)-1ß, IL-6, IL-8, interferon regulatory factor 3 (IRF3), and IRF7. Taken together, our results demonstrated that EcUSP12, as a positive regulator of IFN signaling, interacted with viral CP to inhibit virus infection.


Asunto(s)
Lubina , Infecciones por Virus ADN , Enfermedades de los Peces , Proteínas de Peces/inmunología , Inmunidad Innata , Proteasas Ubiquitina-Específicas/inmunología , Secuencia de Aminoácidos , Animales , Lubina/inmunología , Lubina/virología , Infecciones por Virus ADN/inmunología , Infecciones por Virus ADN/veterinaria , Enfermedades de los Peces/virología , Nodaviridae , Filogenia , Alineación de Secuencia
17.
Sci Total Environ ; 806(Pt 3): 151261, 2022 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-34715222

RESUMEN

The Taiwan Maternal and Infant Cohort Study (TMICS) was launched with the aim to assess the effects of prenatal exposure to phthalic acid esters (PAEs) on infant health. A total of 1102 pregnant women were enrolled in this study from 2012 to 2015. All participants completed a structured questionnaire, and provided urine specimens. The urinary concentrations of PAE metabolites in the third trimester were measured using liquid chromatography-electrospray ionization tandem mass spectrometry. Generalized additive model-penalized regression splines and logistic regression models were employed to determine the risk for low birth weight (LBW) or small for gestational age (SGA) among pregnant women exposed to PAEs. After adjustments for other covariates, each incremental unit of ln-transformed mono-n-butyl phthalate (MnBP) for pregnant women increased the odds of SGA in male neonates by 1.44 (95% CI: 0.92-2.23). An inverse association between SGA and maternal MnBP exposure level was observed in female neonates. An increase in one ln-transformed MnBP concentration unit decreased the risk of female SGA to 0.50 (95% CI: 0.24-0.97). In the penalized regression splines, increased risks of LBW/SGA in male neonates were presented while pregnant women exposed to increased MnBP levels. However, an association in the opposite direction was observed between maternal MnBP and LBW or SGA for male and female neonates. This study indicated that high maternal MnBP exposure in the third trimester was associated with LBW or SGA for male infants. Adverse effects on susceptible populations exposed to high levels of PAEs should be of concern.


Asunto(s)
Ácidos Ftálicos , Estudios de Cohortes , Femenino , Edad Gestacional , Humanos , Lactante , Recién Nacido de Bajo Peso , Recién Nacido , Recién Nacido Pequeño para la Edad Gestacional , Masculino , Exposición Materna/efectos adversos , Ácidos Ftálicos/efectos adversos , Embarazo , Encuestas y Cuestionarios , Taiwán/epidemiología
18.
IEEE Trans Cybern ; 52(11): 12028-12041, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34398777

RESUMEN

Deep reinforcement learning (DRL)-based recommender systems have recently come into the limelight due to their ability to optimize long-term user engagement. A significant challenge in DRL-based recommender systems is the large action space required to represent a variety of items. The large action space weakens the sampling efficiency and thereby, affects the recommendation accuracy. In this article, we propose a DRL-based method called deep hierarchical category-based recommender system (DHCRS) to handle the large action space problem. In DHCRS, categories of items are used to reconstruct the original flat action space into a two-level category-item hierarchy. DHCRS uses two deep Q -networks (DQNs): 1) a high-level DQN for selecting a category and 2) a low-level DQN to choose an item in this category for the recommendation. Hence, the action space of each DQN is significantly reduced. Furthermore, the categorization of items helps capture the users' preferences more effectively. We also propose a bidirectional category selection (BCS) technique, which explicitly considers the category-item relationships. The experiments show that DHCRS can significantly outperform state-of-the-art methods in terms of hit rate and normalized discounted cumulative gain for long-term recommendations.


Asunto(s)
Refuerzo en Psicología
19.
Small ; 18(4): e2106441, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34862724

RESUMEN

Rechargeable aqueous zinc ion batteries (ZIBs) represent a promising technology for large-scale energy storage due to their high capacity, intrinsic safety and low cost. However, Zn anodes suffer from poor reversibility and cycling stability caused by the side-reactions and dendrite issues, which limit the Zn utilization in the ZIBs. Herein, to improve the durability of Zn under high utilization, an aluminum-doped zinc oxide (AZO) interphase is presented. The AZO interphase inhibits side reactions by isolating active Zn from the bulk electrolyte, and enables facile and uniform Zn deposition kinetics by accelerating the desolvation of hydrated Zn2+ and homogenizing the electric field distribution. Accordingly, the AZO-coated Zn (AZO@Zn) anode exhibits a long lifespan of 600 h with Zn utilization of 34.1% at the current density of 10 mA cm-2 . Notably, even under ultrahigh Zn utilization of 80%, the AZO@Zn remains stable cycling over 200 h. Meanwhile, the V2 O5 /AZO@Zn full cell with limited Zn excess displays high capacity retention of 86.8% over 500 cycles at 2 A g-1 . This work provides a simple and efficient strategy to ensure the reversibility and durability of Zn anodes under high utilization conditions, holding a great promise for commercially available ZIBs with competitive energy density.

20.
BMC Med Imaging ; 21(1): 148, 2021 10 14.
Artículo en Inglés | MEDLINE | ID: mdl-34649505

RESUMEN

BACKGROUND: Cervical plexus (CP) tumours are difficult to diagnose because of atypical symptoms. This study aimed to summarize the features of a normal CP and CP tumours observed on high-frequency ultrasonography. METHODS: The ultrasound data of 11 CP tumour patients and 22 normal volunteers were collected. All 11 patients underwent magnetic resonance imaging (MRI), and 4 patients also underwent computed tomography (CT). The imaging data were compared with surgery and pathology data. RESULTS: The C7 vertebra and bifurcation of the carotid common artery (CCA) were useful anatomic markers for identifying the CP. In contrast to the C1 nerve (22.7%), the C2-4 nerves were well displayed and thinner than the brachial plexus (P < 0.05). CP tumours were more common in females (72.7%) and generally located at C4 (72.7%) on the right side (81.8%). Additionally, the nerve trunk in tumour patients was obviously wider than that in normal controls (7.49 ± 1.03 mm vs 2.67 ± 0.36 mm, P < 0.01). Compared with pathology, the diagnostic rates of CP tumours by MRI, CT and high-frequency ultrasound were 72.7% (8/11), 25% (1/4) and 90.9% (10/11), respectively. CONCLUSIONS: The diagnosis of CP neuropathy is accurate and reliable by high-frequency ultrasound, and the C7 vertebra and bifurcation of the CCA are useful anatomic markers in CP ultrasonography.


Asunto(s)
Plexo Cervical/diagnóstico por imagen , Neoplasias del Sistema Nervioso Periférico/diagnóstico por imagen , Ultrasonografía/métodos , Adolescente , Adulto , Puntos Anatómicos de Referencia , Estudios de Casos y Controles , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos X
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA