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1.
Proc Natl Acad Sci U S A ; 121(40): e2403260121, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39298475

RESUMEN

Cellular processes are controlled by the thermodynamics of the underlying biomolecular interactions. Frequently, structural investigations use one monomeric binding partner, while ensemble measurements of binding affinities generally yield one affinity representative of a 1:1 interaction, despite the majority of the proteome consisting of oligomeric proteins. For example, viral entry and inhibition in SARS-CoV-2 involve a trimeric spike surface protein, a dimeric angiotensin-converting enzyme 2 (ACE2) cell-surface receptor and dimeric antibodies. Here, we reveal that cooperativity correlates with infectivity and inhibition as opposed to 1:1 binding strength. We show that ACE2 oligomerizes spike more strongly for more infectious variants, while exhibiting weaker 1:1 affinity. Furthermore, we find that antibodies use induced oligomerization both as a primary inhibition mechanism and to enhance the effects of receptor-site blocking. Our results suggest that naive affinity measurements are poor predictors of potency, and introduce an antibody-based inhibition mechanism for oligomeric targets. More generally, they point toward a much broader role of induced oligomerization in controlling biomolecular interactions.


Asunto(s)
Enzima Convertidora de Angiotensina 2 , COVID-19 , Unión Proteica , Multimerización de Proteína , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , SARS-CoV-2/metabolismo , Enzima Convertidora de Angiotensina 2/metabolismo , Enzima Convertidora de Angiotensina 2/química , Glicoproteína de la Espiga del Coronavirus/metabolismo , Glicoproteína de la Espiga del Coronavirus/química , Humanos , COVID-19/virología , COVID-19/metabolismo , COVID-19/inmunología , Internalización del Virus/efectos de los fármacos , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/metabolismo , Termodinámica
2.
Mol Psychiatry ; 28(9): 3955-3965, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37798418

RESUMEN

Diabetic patients receiving the antidiabetic drug metformin have been observed to exhibit a lower prevalence of anxiety disorders, yet the precise mechanism behind this phenomenon is unclear. In our study, we found that anxiety induces a region-specific reduction in AMPK activity in the medial prefrontal cortex (mPFC). Concurrently, transgenic mice with brain-specific AMPK knockout displayed abnormal anxiety-like behaviors. Treatment with metformin or the overexpression of AMPK restored normal AMPK activity in the mPFC and mitigated social stress-induced anxiety-like behaviors. Furthermore, the specific genetic deletion of AMPK in the mPFC not only instigated anxiety in mice but also nullified the anxiolytic effects of metformin. Brain slice recordings revealed that GABAergic excitation and the resulting inhibitory inputs to mPFC pyramidal neurons were selectively diminished in stressed mice. This reduction led to an excitation-inhibition imbalance, which was effectively reversed by metformin treatment or AMPK overexpression. Moreover, the genetic deletion of AMPK in the mPFC resulted in a similar defect in GABAergic inhibitory transmission and a consequent hypo-inhibition of mPFC pyramidal neurons. We also generated a mouse model with AMPK knockout specific to GABAergic neurons. The anxiety-like behaviors in this transgenic mouse demonstrated the unique role of AMPK in the GABAergic system in relation to anxiety. Therefore, our findings suggest that the activation of AMPK in mPFC inhibitory neurons underlies the anxiolytic effects of metformin, highlighting the potential of this primary antidiabetic drug as a therapeutic option for treating anxiety disorders.


Asunto(s)
Ansiolíticos , Metformina , Humanos , Ratones , Animales , Ansiolíticos/farmacología , Proteínas Quinasas Activadas por AMP/farmacología , Metformina/farmacología , Hipoglucemiantes/farmacología , Corteza Prefrontal , Neuronas GABAérgicas
3.
Environ Sci Technol ; 58(2): 1244-1254, 2024 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-38178789

RESUMEN

Carbonaceous aerosols (CA) from anthropogenic emissions have been significantly reduced in urban China in recent years. However, the relative contributions of fossil and nonfossil sources to CA in rural and background regions of China remain unclear. In this study, the sources of different carbonaceous fractions in fine aerosols (PM2.5) from five background sites of the China Meteorological Administration Atmosphere Watch Network during the winter of 2019 and 2020 were quantified using radiocarbon (14C) and organic markers. The results showed that nonfossil sources contributed 44-69% to total carbon at these five background sites. Fossil fuel combustion was the predominant source of elemental carbon at all sites (73 ± 12%). Nonfossil sources dominated organic carbon (OC) in these background regions (61 ± 13%), with biomass burning or biogenic-derived secondary organic carbon (SOC) as the most important contributors. However, the relative fossil fuel source to OC in China (39 ± 13%) still exceeds those at other regional/background sites in Asia, Europe, and the USA. SOC dominated the fossil fuel-derived OC, highlighting the impact of regional transport from anthropogenic sources on background aerosol levels. It is therefore imperative to develop and implement aerosol reduction policies and technologies tailored to both the anthropogenic and biogenic emissions to mitigate the environmental and health risks of aerosol pollution across China.


Asunto(s)
Contaminantes Atmosféricos , Contaminantes Atmosféricos/análisis , Material Particulado/análisis , Fósiles , Monitoreo del Ambiente/métodos , China , Carbono , Combustibles Fósiles/análisis , Aerosoles/análisis , Estaciones del Año , Atmósfera
4.
BMC Oral Health ; 24(1): 1111, 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39300430

RESUMEN

BACKGROUND: To verify the validity of diagnosing initial caries on occlusal surface of permanent posterior teeth by laser fluorescence instrument DIAGNOdent pen. METHODS: Patients from School of Stomatology in Wuhan University were selected and their posterior teeth were examined using DIAGNOdent pen and the International Caries Detection and Assessment System (ICDAS II) by an experienced dentist. After teeth extraction, histological criteria were used to determine the severity of the lesions. The sensitivity, specificity, accuracy, the area under the curve (AUC), and correlation of DIAGNOdent pen and ICDAS II were analyzed compared with histological criteria. Examiners' agreement was measured. RESULTS: The sensitivity range was 0.440-1 while that of specificity was 0.750-0.994. The accuracy and AUC were above 80% and 0.7 respectively. Consistency of examiners' kappa values of ICDAS II, DIAGNOdent pen, and histological criteria were ranged from 0.629 to 0.840. CONCLUSIONS: ICDAS II and DIAGNOdent pen can be effectively used in tandem or independently for the assessment of initial caries.


Asunto(s)
Caries Dental , Sensibilidad y Especificidad , Humanos , Caries Dental/diagnóstico , Caries Dental/patología , Femenino , Masculino , Dentición Permanente , Rayos Láser , Adulto , Adolescente , Niño , Reproducibilidad de los Resultados
5.
Mol Divers ; 2023 Oct 29.
Artículo en Inglés | MEDLINE | ID: mdl-37898972

RESUMEN

This study was to evaluate the potential mechanism of action of Artemisia annua L. (A. annua) in the treatment of acute myocardial infarction (AMI) using network pharmacology, molecular docking and in vivo experiments. 22 active chemical compounds and 193 drug targets of A. annua were screened using the Traditional Chinese Medicine System Pharmacological (TCMSP) database. 3876 disease targets were also collected. Then 158 intersection targets between AMI and A. annua were obtained using R 4.2.0 software. String database was used to construct the protein-protein interaction (PPI) network and 6 core targets (MAPK1, TP53, HSP90AA1, RELA, AKT1, and MYC) were screened. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed using the R package. GO enrichment results were mainly related to cell responses to chemical stress and cell membrane microregions. KEGG pathways were mainly involved in lipids, atherosclerosis and fluid shear stress. In addition, molecular docking between A. annua active compounds and core targets showed high binding activity. As for in vivo validation, A. annua extract showed significant effects on improving post-infarction ventricular function, delaying ventricular remodeling, and reducing myocardial fibrosis and apoptosis. This study has revealed the potential components and molecular mechanisms of A. annua in the treatment of AMI. Our work also showed that A. annua has great effect on reducing myocardial fibrosis and scar area after infarction.

6.
J Wound Care ; 32(Sup9a): cxcv-cc, 2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-37703218

RESUMEN

OBJECTIVE: The aim of this study was to compare Biatain Ag and Biatain Alginate Ag (both Coloplast, Denmark) as skin graft donor site dressings. METHOD: A single-centre, prospective, randomised clinical study was conducted. In patients who had undergone a skin graft operation, adjacent split-thickness skin graft donor sites were dressed with Biatain Ag and Biatain Alginate Ag, respectively. The primary outcomes were time to re-epithelialisation and pain score after the operation. The secondary outcomes were scar scores of the donor site after the operation, haematoma rates, infection rates, and exudation rates before wound healing. Results were compared using the Wilcoxon test and the Chi-squared test. RESULTS: A total of 16 paired wounds in 16 patients were studied. The donor sites dressed with Biatain Ag needed more time for >90% re-epithelialisation than those dressed with Biatain Alginate Ag. On day 3 postoperatively, the pain scores with Biatain Ag were significantly less severe than those with Biatain Alginate Ag. On days 6, 9 and 12, the pain scores of both dressings did not differ significantly. The scar scores of the donor site dressed with Biatain Ag were significantly worse than those dressed with Biatain Alginate Ag at 6 months. With respect to infection rates, no significant differences were detected between these two groups. However, the exudation rates of the donor site dressed with Biatain Ag were significantly lower than those dressed with Biatain Alginate Ag. CONCLUSION: As skin graft donor site dressings, both Biatain Ag and Biatain Alginate Ag have advantages.


Asunto(s)
Cicatriz , Trasplante de Piel , Humanos , Estudios Prospectivos , Vendajes , Alginatos/uso terapéutico , Dolor
7.
J Clin Lab Anal ; 36(9): e24611, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35837987

RESUMEN

BACKGROUND: N6-methyladenosine (m6A) is the addition of a methyl group on the N6 position of adenosine and is the most prevalent and abundant epigenetic modification in eukaryote mRNA. m6A marks are added to mRNA by the m6A methyltransferase complex ("writers"), removed by m6A demethylases ("erasers"), and recognized by m6A-binding proteins ("readers"). Recent evidence has shown that the m6A modification plays a crucial role in the pathogenic mechanism and malignant progression of pancreatic cancer, with roles in cell survival, proliferation, migration, invasion, tumor metastasis, and drug resistance. METHODS: Literature was searched in Pubmed and Web of Science for the following keywords: "N6-methyladenosine", "pancreatic cancer", "epigenetic modification", "immunotherapy". RESULTS: Among classical m6A regulators, while METTL3, METTL14, WTAP, FTO, YTHDF2, IGF2BP1-3, hnRNPC, and NKAP are upregulated in pancreatic cancer, METTL16 and ALKBH5 are downregulated in pancreatic cancer. m6A modification has been investigated in pancreatic cancer therapy. CONCLUSION: Dysregulated m6A and its related factors in pancreatic cancer cells and patients indicate their potential values as novel biomarkers in pancreatic cancer diagnosis and targeted therapy.


Asunto(s)
Metiltransferasas , Neoplasias Pancreáticas , Adenosina/análogos & derivados , Adenosina/metabolismo , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/genética , Humanos , Metiltransferasas/genética , Metiltransferasas/metabolismo , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/terapia , ARN Mensajero/metabolismo , Proteínas Represoras , Neoplasias Pancreáticas
8.
Org Biomol Chem ; 19(11): 2468-2472, 2021 03 21.
Artículo en Inglés | MEDLINE | ID: mdl-33650628

RESUMEN

Valuable aromatic nitrogen compounds can be synthesized by reduction of nitroarenes. Herein, we report electrochemical reduction of nitroarenes by a protocol that uses inert graphite felt as electrodes and ammonia as a reductant. Depending on the cell voltage and the solvent, the protocol can be used to obtain aromatic azoxy, azo, and hydrazo compounds, as well as aniline derivatives with high chemoselectivities. The protocol can be readily scaled up to >10 g with no decrease in yield, demonstrating its potential synthetic utility. A stepwise cathodic reduction pathway was proposed to account for the generations of products in turn.

9.
Zhongguo Zhong Yao Za Zhi ; 45(20): 4978-4983, 2020 Oct.
Artículo en Zh | MEDLINE | ID: mdl-33350272

RESUMEN

To study the effect of Lonicera fulvotometosa(LFH) on expression of genes related to inflammatory pathways in the lung tissue of rats with acute lung injury(ALI) induced by lipopolysaccharide(LPS), explore the lung-protective effects and inflammatory mechanisms of L. fulvotometosa water extract, and provide experimental and theoretical basis for the clinical application of LFH. Forty SD rats were randomly divided into 4 groups: normal group, model group(LPS, 5 mg·kg~(-1)), LFH group(7.2 g·kg~(-1)) and dexa-methasone group(Dexa, 5 mg·kg~(-1)). The rats in LFH group received intragastric administration of water extract once a day for 5 days; rats in dexamethasone group received intraperitoneal injection for 2 hours before modeling. Except the normal group, the rats in other groups were injected intraperitoneally with LPS(5 mg·kg~(-1)) to induce ALI rats model. Serum, bronchoalveolar lavage fluid(BALF) and lung tissues were collected 6 hours after modeling. The lung tissues were taken for pathological observation; enzyme-linked immunosorbent assay(ELISA) was used to detect changes of inflammatory factors in serum and BALF; Real-time quantitative polymerase chain reaction(RT-qPCR) was applied to detect mRNA expression of tumor necrosis factor alpha inducible protein 3(TNFAIP3), interleukin(IL) 1 R1, interleukin(IL) 6 R and nuclear factor κB inhibitor α(NFKBIA) in the lung tissues. The degree of lung injury was lighter in LFH group than that in the LPS group. As compared with the LPS group, the levels of interleukin-1ß(IL-1ß), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α) in serum and BALF, malondialdehyde(MDA) and myeloperoxidase(MPO) in lung tissues were significantly reduced in LFH group and Dexa group, while glutathione peroxidase(GSH-Px), superoxide dismutase(SOD) in lung tissues were significantly increased; the mRNA expression of TNFAIP3, IL1 R1, IL6 R and NFKBIA in the lung tissues of the LFH group was significantly lower than that of the LPS group. The water extract of LFH can significantly reduce the content of inflammatory factors in rats with ALI, and down-regulate the mRNA expression of TNFAIP3, IL1 R1, IL6 R and NFKBIA in the lung tissues, showing significant anti-inflammatory effect. Its mechanism may be related to the regulation of NF-κB signaling pathway, and the pulmonary inflammation response may be reduced by down-regulating the expression of downstream-related inflammatory factors.


Asunto(s)
Lesión Pulmonar Aguda , Lonicera , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/genética , Animales , Antiinflamatorios/uso terapéutico , Líquido del Lavado Bronquioalveolar , Lipopolisacáridos/toxicidad , Pulmón , FN-kappa B/genética , Ratas , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/genética
10.
Zhongguo Zhong Yao Za Zhi ; 45(18): 4455-4465, 2020 Sep.
Artículo en Zh | MEDLINE | ID: mdl-33164376

RESUMEN

In this paper, the possible molecular mechanism of Forsythia suspensa for the anti-tumor effect was investigated through the network pharmacology and molecular docking. The main components of F. suspensa were obtained by literature mining and TCMSP database. Cancer-related genes were collected with use of GAD and OMIM databases. The interaction network of Compounds-Targets-Pathways was constructed through Cytoscpe software. The targets were analyzed by GO and KEGG means in DAVID database, and the KEGG signal pathways were visualized. Component-Target network analysis results were verified by PyRx molecular docking. The results showed that a total of 26 main components of F. suspensa may act on key targets such as AKT1, IL6, ESR1, EGFR, EGF and CCND1, and were involved in 20 signal pathways. Molecular docking analysis showed that hydrogen bonding, hydrophobic action and Pi-cation bonding maybe the main forms of interaction. In this study, we revealed the anti-tumor effect of F. suspensa through the network of Compounds-Targets-Pathways and molecular docking verification, providing reference and guidance for systematically elucidating the anti-tumor molecular mechanism of the main components of F. suspensa.


Asunto(s)
Medicamentos Herbarios Chinos , Forsythia , Neoplasias , Medicamentos Herbarios Chinos/farmacología , Forsythia/genética , Humanos , Simulación del Acoplamiento Molecular , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Transducción de Señal
11.
J Cell Physiol ; 233(11): 8578-8587, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-29797561

RESUMEN

Increasing evidence has shown that the lncRNA Nuclear Enriched Abundant Transcript 1 (NEAT1) play important roles in cell proliferation, migration, and invasion in various tumors. In our current study, we concentrated on the biological mechanisms of NEAT1 in hepatocellular carcinoma (HCC) development. It was found that NEAT1 was significantly increased in human HCC cell lines including Hep3B, LM3, MHCC97L, SK-hep1, and HepG2 cells compared to the normal human liver cell line LO2. Meanwhile, we observed that hsa-miR-139-5p was greatly decreased in HCC cells, which suggested a negative correlation between NEAT1 and hsa-mir-139-5p. In addition, NEAT1 downregulation can restrain HCC cell growth, migration, and invasion. Consistently, overexpression of hsa-mir-139-5p exerted a similar phenomenon. Dual-luciferase reporter assay, RIP assay, and RNA pull-down assay confirmed that NEAT1 can function as a ceRNA by sponging hsa-mir-139-5p. In addition, TGF-ß1 was identified as a downstream target of hsa-mir-139-5p and hsa-mir-139-5p overexpression was able to suppress TGF-ß1 levels. Furthermore, it was indicated that TGF-ß1 inhibition can inhibit HCC cell growth, migration, and invasion ability. Taken these together, we speculated that NEAT1 can modulate TGF-ß1 expression by sponging hsa-mir-139-5p in HCC. These data indicates that targeting the NEAT1/hsa-mir-139-5p/TGF-ß1 axis could be a new strategy for HCC.


Asunto(s)
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , MicroARNs/genética , ARN Largo no Codificante/genética , Factor de Crecimiento Transformador beta1/genética , Apoptosis/genética , Carcinoma Hepatocelular/patología , Movimiento Celular/genética , Proliferación Celular/genética , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Células Hep G2 , Humanos , Neoplasias Hepáticas/patología , Invasividad Neoplásica/genética , Invasividad Neoplásica/patología
12.
Ear Hear ; 39(1): 85-100, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-28678077

RESUMEN

OBJECTIVES: Distortion-product otoacoustic emissions (DPOAEs) are repeatable over time at lower frequencies (≤8 kHz) and higher frequencies (>8 kHz) in healthy, normal-hearing subjects. The purpose of this study was to examine the repeatability of DPOAEs measured with high-frequency (HF) stimuli in a patient population. It was hypothesized that HF DPOAEs would be repeatable over four trials. DESIGN: DPOAEs were measured in 40 cystic fibrosis (CF) patients (17 females and 23 males) with measurable behavioral thresholds and present DPOAEs for at least 2 of the high frequencies tested (8 to 16 kHz). A depth-compensated simulator sound pressure level (SPL) method of calibration was utilized. Each patient attended four trials, in which a complete set of data were collected. At each trial, three different DPOAE paradigms were completed. First, a discrete frequency sweep was measured between 8 and 16 kHz with a ratio (f2/f1) of 1.2 and levels of 65/50 dB SPL for L1/L2. Next, ratio and level sweeps were obtained at the two highest frequencies with a present DPOAE determined from the discrete frequency sweep, and the results were used to calculate DPOAE group delay and DPOAE detection thresholds, respectively. Ratio sweeps were collected with f2/f1 varied from 1.1 to 1.3 and stimulus levels of 60/45 dB SPL (L1/L2). Level sweeps were collected with an f2/f1 of 1.22 and L2 = 50 and L1 varied between 20 and 70 dB SPL. Differences and correlations between trials, SE of the measurement, and confidence intervals were calculated, as well as a repeated-measures analysis of variance. RESULTS: DPOAE response and behavioral threshold variability in CF patients were not significantly different across four trials. It can be expected in 95% of CF patients that differences between trials of DPOAE levels, group delay, and detection thresholds and behavioral thresholds are less than 6.26 dB, 0.87 msec, 9.34 dB, and 9.60 dB, respectively. CONCLUSIONS: HF DPOAEs were repeatable across four test trials for all three paradigms measured in a group of CF patients. These results are encouraging for the measurement of HF DPOAEs to be monitored in those exposed to ototoxic agents.


Asunto(s)
Fibrosis Quística/fisiopatología , Pérdida Auditiva/diagnóstico , Emisiones Otoacústicas Espontáneas , Estimulación Acústica , Adulto , Umbral Auditivo , Fibrosis Quística/complicaciones , Citotoxinas/efectos adversos , Femenino , Pérdida Auditiva/inducido químicamente , Humanos , Masculino , Persona de Mediana Edad , Distorsión de la Percepción , Reproducibilidad de los Resultados , Adulto Joven
13.
BMC Neurosci ; 15: 50, 2014 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-24755246

RESUMEN

BACKGROUND: How it is possible to "faithfully" represent a three-dimensional stereoscopic scene using Cartesian coordinates on a plane, and how three-dimensional perceptions differ between an actual scene and an image of the same scene are questions that have not yet been explored in depth. They seem like commonplace phenomena, but in fact, they are important and difficult issues for visual information processing, neural computation, physics, psychology, cognitive psychology, and neuroscience. RESULTS: The results of this study show that the use of plenoptic (or all-optical) functions and their dual plane parameterizations can not only explain the nature of information processing from the retina to the primary visual cortex and, in particular, the characteristics of the visual pathway's optical system and its affine transformation, but they can also clarify the reason why the vanishing point and line exist in a visual image. In addition, they can better explain the reasons why a three-dimensional Cartesian coordinate system can be introduced into the two-dimensional plane to express a real three-dimensional scene. CONCLUSIONS: 1. We introduce two different mathematical expressions of the plenoptic functions, Pw and Pv that can describe the objective world. We also analyze the differences between these two functions when describing visual depth perception, that is, the difference between how these two functions obtain the depth information of an external scene.2. The main results include a basic method for introducing a three-dimensional Cartesian coordinate system into a two-dimensional plane to express the depth of a scene, its constraints, and algorithmic implementation. In particular, we include a method to separate the plenoptic function and proceed with the corresponding transformation in the retina and visual cortex.3. We propose that size constancy, the vanishing point, and vanishing line form the basis of visual perception of the outside world, and that the introduction of a three-dimensional Cartesian coordinate system into a two dimensional plane reveals a corresponding mapping between a retinal image and the vanishing point and line.


Asunto(s)
Percepción de Profundidad/fisiología , Modelos Neurológicos , Red Nerviosa/fisiología , Retina/fisiología , Corteza Visual/fisiología , Vías Visuales/fisiología , Simulación por Computador , Humanos
14.
ScientificWorldJournal ; 2014: 608158, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24982970

RESUMEN

In order to overcome the limitation of traditional nonnegative factorization algorithms, the paper presents a generalized discriminant orthogonal non-negative tensor factorization algorithm. At first, the algorithm takes the orthogonal constraint into account to ensure the nonnegativity of the low-dimensional features. Furthermore, the discriminant constraint is imposed on low-dimensional weights to strengthen the discriminant capability of the low-dimensional features. The experiments on facial expression recognition have demonstrated that the algorithm is superior to other non-negative factorization algorithms.


Asunto(s)
Inteligencia Artificial , Expresión Facial , Reconocimiento de Normas Patrones Automatizadas , Algoritmos , Humanos
15.
Int J Rheum Dis ; 27(7): e15256, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38982864

RESUMEN

The cyclic GMP-AMP synthase (cGAS), a prominent intracellular DNA sensor in mammalian cells, controls the innate immune response and the stimulator of interferon genes (STING)-mediated synthesis of pro-inflammatory cytokines, such as type-I interferon (IFN-I). For decades, IFN-I has been hypothesized to be essential in the development of systemic lupus erythematosus (SLE), a chronic multisystem autoimmunity characterized by immune complex (IC) deposition in small vessels. Recent findings revealed that the activation of the cGAS-STING pathway by self-DNA would propagate the autoimmune responses via upregulating IFN-I production in SLE. In this review, we aimed to provide a comprehensive outlook of the role of the cGAS-STING pathway in SLE pathobiology, as well as, a better understanding of current therapeutic opportunities targeting this axis.


Asunto(s)
Lupus Eritematoso Sistémico , Proteínas de la Membrana , Nucleotidiltransferasas , Transducción de Señal , Humanos , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/metabolismo , Lupus Eritematoso Sistémico/tratamiento farmacológico , Nucleotidiltransferasas/metabolismo , Proteínas de la Membrana/metabolismo , Animales , Autoinmunidad , Interferón Tipo I/metabolismo , Interferón Tipo I/inmunología , Terapia Molecular Dirigida , Inmunidad Innata
16.
Eval Rev ; : 193841X241276023, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39151047

RESUMEN

This study focuses on the second round of Taiwanese teacher preparation program (TPP) evaluation (2012-2017) to analyze how evaluation policy shapes TPPs. In-depth interviews were conducted with 13 stakeholders, which included professors, administrators, researchers, and staff involved in TPP evaluation. First, the findings revealed that neoliberalism influences evaluation policy and restricts the diversity of TPP development. Second, different evaluation approaches may be used to bring more inclusiveness and flexibility to evaluation standards. Third, evaluation plays an important role in TPP development, and a professional organization responsible for evaluation should be established in Taiwan in the future. To conclude, it is significant for TPP evaluation policy to consider policy ideology, evaluation standards, and program diversity to aid in improving the quality of teacher education not only in Taiwan but also internationally.

17.
Heliyon ; 10(17): e37383, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39296092

RESUMEN

This research investigates the ecological impacts of heavy metals in downstream river sediments with a focus on carbon emission efficiency in agriculture under the environmental regulation context. In this study, thirty sediment samples have been taken from the downstream region of the Shichuanhe River located in Xi'an, Shaanxi province, China, to analyze the availability of heavy metals. The results show that there are high ecological impacts in relation to the heavy metals and that impacts the carbon emission efficiency in agriculture directly. The analysis has also found the importance of significant environmental regulations in the management of such risks. This research has offered a unique angle on the relationship between heavy metal pollution and agricultural carbon release and has given important information on the improvement of environmental control measures. The implications highlight the need for the implementation of measures to enhance the policies that will help to prevent the ecological threats that are connected with heavy metals in the agricultural areas and, thus, improve the management of the environment.

18.
Sci Rep ; 14(1): 15301, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38961173

RESUMEN

Under the condition that the working face was directly covered with hard roof, the abrupt breaking of hard roof release significant amount of energy, thus prone to triggering dynamic disasters such as roadway instability or rockburst. This paper based on the engineering background of the Xieqiao Coal Mine's 11,618 working face, a numerical simulation method was put forward to study the dynamic response of roadway under the disturbance of hard roof breaking and proposed an evaluation index IC for roadway stability. Research indicates that the elastic energy released during the periodic weighting of the hard roof is higher than that released during the first weighting. Under the dynamic disturbance caused by hard roof breaking, the peak stresses of the roadway was slight decreased, accompanied by a significant increase in the range of stress concentration and plastic zone expansion. Roadway deformation patterns are significantly influenced by hard roof breaking, with noticeable increases in deformation on the roof and right side. During the period of hard roof breaking, the possibility of instability of the roadway increase significantly due to the disturbance caused by the dynamic load. The research results reveal the instability mechanism of roadway under the condition of hard roof, and provide a more reliable basis for evaluating the stability of roadway.

19.
Technol Health Care ; 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39302395

RESUMEN

BACKGROUND: Endoscopic submucosal dissection (ESD) is a well-established treatment for gastrointestinal tumors and enables en bloc resection. Adequate counter traction with good visualization is important for safe and effective dissection. OBJECTIVE: Based on magnetic anchor-guided endoscopic submucosal dissection (MAG-ESD), we would like to explore the feasibility of magnetic hydrogel as an internal magnetic anchor that can be injected into the submucosa through an endoscopic needle to assist colonic endoscopic submucosal dissection. METHODS: This prospective trial was conducted on 20 porcine colons ex vivo. We injected magnetic hydrogel into submucosa of the porcine colons ex vivo for MAG-ESD to evaluate the traction effect and operation satisfaction. RESULTS: Magnetic hydrogel assisted ESD was successfully performed on 20 porcine colons ex vivo. Adequate counter traction with good visualization was successfully obtained during the procedure of dissection. CONCLUSION: Magnetic hydrogel assisted MAG-ESD is feasible and effective.

20.
Front Genet ; 15: 1396375, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39055260

RESUMEN

NHX proteins are transmembrane antiporters belonging to the cation/proton antiporter gene family, with a conserved Na+ (K+)/H+ exchange (PF00999) protein domain. NHXs play a prominent role in plant growth, development, and defense. However, the role of NHX gene family in potato (Solanum tuberosum L.) is yet to be known. In this study, we conducted a genome-wide analysis of the potato NHX gene family. A total of 25 StNHX family members were identified to be unevenly distributed on 10 chromosomes. The proteins ranged in length from 252 to 1,153 amino acids, with molecular masses ranging from 27516.32 to 127860.87 kD, and isoelectric points (pI) ranging from 4.96 to 9.3. Analyses of gene structures and conserved motifs indicated that StNHX genes in the same phylogenetic cluster are conserved. Phylogenetic analysis divided the StNHX genes into three subfamilies (Classes I, II, and III). Synteny analysis indicated that StNHX gene family Class III of NHX and all Arabidopsis thaliana NHXs shared a close evolutionary relationship. Analysis of cis-acting elements in the upstream 1,500 bp promoter region of potato NHX genes showed that these genes could be regulated by light, stress, and hormones such as abscisic acid and gibberellic acid. Protein-protein interaction network analysis indicated that StNHX proteins may participate in the regulation of potato growth and stress response. Besides, To determine a potential role of these genes in tissue development and drought response, we analyzed the RNA-seq data of different DM potato tissues. The results showed that NHX genes exhibited distinct tissue-specific expression patterns. We further examined the expression patterns of StNHX in different tissues (leaves, roots, shoots, tubers, stolons, and flowers) during the flowering stage in 'Jizhangshu NO.8.' potato. The qRT-PCR results further confirmed the importance of StNHX genes in potato plant growth and development. We further analyzed the RNA-seq data (DM potato) under different abiotic stresses (salt, drought, and heat), and found that the expression of StNHX genes was induced under abiotic stress. qRT-PCR analysis of shoots and roots of 'Jizhangshu NO.8.' potato treated for 0, 6, 12, and 24 h with 15% PEG6000 confirmed that the 25 StNHX genes are involved in the response to drought stress in potato. The results of this study may be useful for selecting appropriate candidate genes for the breeding of new drought-tolerant potato varieties. Furthermore, this study lays a foundation for prospective analysis of StNHX gene functions.

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