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1.
FASEB J ; 38(7): e23598, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38581244

RESUMEN

The precise molecular mechanism behind fetal growth restriction (FGR) is still unclear, although there is a strong connection between placental dysfunction, inadequate trophoblast invasion, and its etiology and pathogenesis. As a new type of non-coding RNA, circRNA has been shown to play a crucial role in the development of FGR. This investigation identified the downregulation of hsa_circ_0034533 (circTHBS1) in FGR placentas through high-sequencing analysis and confirmed this finding in 25 clinical placenta samples using qRT-PCR. Subsequent in vitro functional assays demonstrated that silencing circTHBS1 inhibited trophoblast proliferation, migration, invasion, and epithelial mesenchymal transition (EMT) progression and promoted apoptosis. Furthermore, when circTHBS1 was overexpressed, cell function experiments showed the opposite result. Analysis using fluorescence in situ hybridization revealed that circTHBS1 was primarily found in the cytoplasmic region. Through bioinformatics analysis, we anticipated the involvement of miR-136-3p and IGF2R in downstream processes, which was subsequently validated through qRT-PCR and dual-luciferase assays. Moreover, the inhibition of miR-136-3p or the overexpression of IGF2R partially reinstated proliferation, migration, and invasion abilities following the silencing of circTHBS1. In summary, the circTHBS1/miR-136-3p/IGF2R axis plays a crucial role in the progression and development of FGR, offering potential avenues for the exploration of biological indicators and treatment targets.


Asunto(s)
MicroARNs , Femenino , Humanos , Embarazo , Apoptosis/genética , Movimiento Celular/genética , Proliferación Celular/genética , Retardo del Crecimiento Fetal/metabolismo , Hibridación Fluorescente in Situ , MicroARNs/genética , MicroARNs/metabolismo , Placenta/metabolismo , Trofoblastos/metabolismo
2.
Opt Lett ; 49(11): 2942-2945, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38824298

RESUMEN

In this Letter, an optically transparent and broadband absorber designed using a multi-objective genetic algorithm (MOGA) is proposed. The absorption of the multilayer lossy frequency selective surface-based absorber is calculated by multilayer absorption equations and equivalent circuit models. To solve the problem of the unbalanced structure absorption bandwidth and thickness, an algorithm is used for optimizing the geometric and sheet resistance parameters of the structure. A multilayer and optically transparent absorber with 90% absorption bandwidth covering a frequency range of 2-18 GHz (S-band to Ku-band) is developed based on the MOGA design method with optical transmittance of 60%. Its total thickness consists of a wavelength of only 0.095, and it has high oblique incidence stability, which makes it useful in the stealth technology and transparent electromagnetic shielding applications.

3.
J Magn Reson Imaging ; 57(1): 45-56, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-35993550

RESUMEN

Rectal cancer (RC) accounts for approximately one-third of colorectal cancer (CRC), with death rates increasing in patients younger than 50 years old. Magnetic resonance imaging (MRI) is routinely performed for tumor evaluation. However, the semantic features from images alone remain insufficient to guide treatment decisions. Functional MRIs are useful for revealing microstructural and functional abnormalities and nevertheless have low or modest repeatability and reproducibility. Therefore, during the preoperative evaluation and follow-up treatment of patients with RC, novel noninvasive imaging markers are needed to describe tumor characteristics to guide treatment strategies and achieve individualized diagnosis and treatment. In recent years, the development of artificial intelligence (AI) has created new tools for RC evaluation based on MRI. In this review, we summarize the research progress of AI in the evaluation of staging, prediction of high-risk factors, genotyping, response to therapy, recurrence, metastasis, prognosis, and segmentation with RC. We further discuss the challenges of clinical application, including improvement in imaging, model performance, and the biological meaning of features, which may also be major development directions in the future. EVIDENCE LEVEL: 5 TECHNICAL EFFICACY: Stage 2.


Asunto(s)
Inteligencia Artificial , Neoplasias del Recto , Humanos , Persona de Mediana Edad , Reproducibilidad de los Resultados , Neoplasias del Recto/patología , Imagen por Resonancia Magnética/métodos , Pronóstico
4.
Appl Opt ; 62(13): 3502-3511, 2023 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-37132852

RESUMEN

This paper proposes a deep-learning-assisted design method for 2-bit coding metasurfaces. This method uses a skip connection module and the idea of an attention mechanism in squeeze-and-excitation networks based on a fully connected network and a convolutional neural network. The accuracy limit of the basic model is further improved. The convergence ability of the model increased nearly 10 times, and the mean-square error loss function converges to 0.000168. The forward prediction accuracy of the deep-learning-assisted model is 98%, and the accuracy of inverse design results is 97%. This approach offers the advantages of an automatic design process, high efficiency, and low computational cost. It can serve users who lack metasurface design experience.

5.
Sensors (Basel) ; 23(12)2023 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-37420814

RESUMEN

A low-profile broadband dual-polarized antenna is investigated for base station applications. It consists of two orthogonal dipoles, fork-shaped feeding lines, an artificial magnetic conductor (AMC), and parasitic strips. By utilizing the Brillouin dispersion diagram, the AMC is designed as the antenna reflector. It has a wide in-phase reflection bandwidth of 54.7% (1.54-2.70 GHz) and a surface-wave bound range of 0-2.65 GHz. This design effectively reduces the antenna profile by over 50% compared to traditional antennas without an AMC. For demonstration, a prototype is fabricated for 2G/3G/LTE base station applications. Good agreement between the simulations and measurements is observed. The measured -10-dB impedance bandwidth of our antenna is 55.4% (1.58-2.79 GHz), with a stable gain of 9.5 dBi and a high isolation of more than 30 dB across the impedance passband. As a result, this antenna is an excellent candidate for miniaturized base station antenna applications.


Asunto(s)
Artículos Domésticos , Impedancia Eléctrica
6.
Int J Mol Sci ; 24(23)2023 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-38068884

RESUMEN

Monovalent cation proton antiporters (CPAs) play crucial roles in ion and pH homeostasis, which is essential for plant development and environmental adaptation, including salt tolerance. Here, 68 CPA genes were identified in soybean, phylogenetically dividing into 11 Na+/H+ exchangers (NHXs), 12 K+ efflux antiporters (KEAs), and 45 cation/H+ exchangers (CHXs). The GmCPA genes are unevenly distributed across the 20 chromosomes and might expand largely due to segmental duplication in soybean. The GmCPA family underwent purifying selection rather than neutral or positive selections. The cis-element analysis and the publicly available transcriptome data indicated that GmCPAs are involved in development and various environmental adaptations, especially for salt tolerance. Based on the RNA-seq data, twelve of the chosen GmCPA genes were confirmed for their differentially expression under salt or osmotic stresses using qRT-PCR. Among them, GmCHX20a was selected due to its high induction under salt stress for the exploration of its biological function on salt responses by ectopic expressing in Arabidopsis. The results suggest that the overexpression of GmCHX20a increases the sensitivity to salt stress by altering the redox system. Overall, this study provides comprehensive insights into the CPA family in soybean and has the potential to supply new candidate genes to develop salt-tolerant soybean varieties.


Asunto(s)
Antiportadores , Arabidopsis , Antiportadores/genética , Antiportadores/metabolismo , Protones , Glycine max/genética , Intercambiadores de Sodio-Hidrógeno/genética , Intercambiadores de Sodio-Hidrógeno/metabolismo , Cationes Monovalentes/metabolismo , Arabidopsis/genética , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
7.
Biochem Genet ; 60(1): 286-302, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34195933

RESUMEN

It has been recognized that wall shear stress plays an important role in the development of Bicuspid Aortopathy (BA), but the intrinsic mechanism is not well elucidated. This study aims to explore the underlying relationship between hemodynamical forces and pathological phenomenon. Total RNA was prepared from aortic wall tissues collected from 20 BA patients. RNA sequencing, bioinformatic analysis and quantitative reverse-transcription PCR validation identified nine miRNAs that were up-regulated in the aortic part exposed to high wall shear stress compared to the low wall shear stress control, and six miRNAs that were down-regulated. Among these candidates, miR-34a and miR-125a, both down-regulated in the high wall shear stress parts, were shown to be potential inhibitors of the metalloproteinase 2 gene. Luciferase reporter assays confirmed that both miRNAs could inhibit the expression of metalloproteinase 2 mRNA in CRL1999 by complementing with its 3' untranslated region. Conversely, immunofluorescence assays showed that inhibition of miR-34a or miR-125a could lead to increased metalloproteinase 2 protein level. On the other hand, both miR-34a and miR-125a were shown to alleviate stretch-induced stimulation of metalloproteinase 2 expression in CRL1999 cells. The results suggested that miR-34a and miR-125a might be implicated in wall shear stress induced aortic pathogenesis due to their apparent regulatory roles in metalloproteinase 2 expression and extracellular matrix remodeling, which are key events in the weakening of aortic walls among BA patients.


Asunto(s)
Enfermedades de las Válvulas Cardíacas , MicroARNs , Regiones no Traducidas 3' , Válvula Aórtica , Proliferación Celular , Humanos , Metaloproteinasa 2 de la Matriz/genética , MicroARNs/genética
8.
Opt Lett ; 46(20): 5220-5223, 2021 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-34653157

RESUMEN

Self-accelerating optical Airy beams present attractive characteristics such as self-bending and non-diffraction, which have rendered this field a research hotspot in recent years. In this paper, the desired phase changes of the unit cell structure for the transmitted cross-polarized wave can be realized by modifying the rotation angle of the unit cell, while the amplitude can be modulated by changing the inner diameter R of the double layer split-ring resonator (SRR). As such, the amplitude and phase modulations can be performed simultaneously and independently to achieve the desired transmitted wave envelope. Furthermore, a novel, to the best of our knowledge, strategy of 2D Airy beam deflection control is also presented by simultaneously modifying the phase and amplitude of the envelope of the transmitted beam, and its feasibility is theoretically and experimentally demonstrated. Our proposed designs suggest high application potentials in the fields of optical particle manipulation, controllable wireless energy transmission, and complex terrain exploration.

9.
Ecotoxicol Environ Saf ; 214: 112095, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33667735

RESUMEN

In this study, urban stream sediment samples were collected in the Suzhou Industrial Park (SIP), one of the earliest national demonstration eco-industrial parks of China. PAHs were analyzed in these sediments, and concentrations of total PAHs were 180-81,000 ng g-1 (5700 ± 14,000 ng g-1). Medium molecular weight (4- ring) PAHs were predominant (42 ± 12%), followed by high molecular weight (5- and 6- ring) PAHs (31 ± 10%). No correlation was found between concentrations of PAHs and land uses of SIP in this study. Diagnostic ratios and a positive matrix factorization (PMF) model indicated that coal/biomass combustion might be the primary PAH source (61%), followed by non-combustion sources (21%) and vehicular emission (18%). According to the spatial analysis, PAHs in the sediments of SIP might be mainly associated with the coal/biomass combustion in the northeast industrial zone. Residential & commercial activities seem not to be the major causes of PAH contamination. Total PAH toxic equivalent concentrations, effect range low/effect range median values, and mean effects range-median quotient all showed that PAHs were present at a low toxicity risk level in most regions of the SIP. However, vigilance is required at some sampling sites with extremely high PAH concentrations or high mean effects range-median quotient.


Asunto(s)
Hidrocarburos Policíclicos Aromáticos/análisis , Contaminantes Químicos del Agua/análisis , China , Carbón Mineral/análisis , Monitoreo del Ambiente , Sedimentos Geológicos , Industrias , Medición de Riesgo , Ríos , Emisiones de Vehículos/análisis
10.
Periodontol 2000 ; 84(1): 145-160, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32844418

RESUMEN

Peri-implant diseases are prevalent with a weighted mean prevalence rate of 43% across Europe and 22% across South and North America. Although the main etiologic agent is bacterial biofilm, a myriad of factors influence the initiation and progression of the disease. Unfortunately, the treatment of peri-implant diseases is at best favorable in the short term with a high rate of persistent inflammation and recurrence. Therefore, it is sensible to consider and control all potential factors that may predispose an implant to peri-implant tissue inflammation in an attempt to avoid the disease. This paper reviews recent evidence on factors that may predispose implants to peri-implantitis and measures that can be taken to prevent it.


Asunto(s)
Implantes Dentales , Periimplantitis/epidemiología , Periimplantitis/etiología , Humanos , Inflamación
11.
Appl Opt ; 59(27): 8302-8309, 2020 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-32976416

RESUMEN

An easy-fabricating superdirective antenna with needlelike radiation in the microwave band is proposed for the first time to the best of our knowledge. The electromagnetic field of the superdirective antenna excited by an electric line source is calculated. The parameters of the superdirective antenna are obtained by optimization algorithms. A two-step optimization method is carried out to reduce the difficulty of fabrication. The mechanism of superdirectivity in the microwave band is explained briefly by traditional multilayered dielectric resonances. A machinable 10-layered superdirective antenna, using this method, is proposed. Unlike traditional superdirective antennas, the proposed antenna, after two-step optimization in this paper, has all-positive integral permittivities, which reduce the fabrication difficulty significantly.

12.
Int J Mol Sci ; 22(1)2020 Dec 26.
Artículo en Inglés | MEDLINE | ID: mdl-33375389

RESUMEN

High-molecular-weight glutenin subunits (HMW-GSs) are storage proteins present in the starchy endosperm cells of wheat grain. Encoding the synthesis of HMW-GS, the Glu-1 loci located on the long arms of group 1 chromosomes of the hexaploid wheat (1A, 1B, and 1D) present multiple allelism. In hexaploid wheat cultivars, almost all of them express 3 to 5 HMW-GSs and the 1Ay gene is always silent. Though HMW-GSs are the minor components in gluten, they are crucial for dough properties, and certain HMW-GSs make more positive contributions than others. The HMW-GS acts as a "chain extender" and provides a disulfide-bonded backbone in gluten network. Hydrogen bonds mediated by glutamine side chains are also crucial for stabilizing the gluten structure. In most cases, HMW-GSs with additional or less cysteines are related to the formation of relatively more or less interchain disulfide bonds and HMW-GSs also affect the gluten secondary structures, which in turn impact the end use qualities of dough.


Asunto(s)
Endospermo/metabolismo , Glútenes/genética , Glútenes/metabolismo , Triticum/metabolismo , Endospermo/genética , Glútenes/química , Peso Molecular , Triticum/genética
13.
Molecules ; 26(1)2020 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-33396541

RESUMEN

Disulfide bonds play a pivotal role in maintaining the natural structures of proteins to ensure their performance of normal biological functions. Moreover, biological molecular assembly, such as the gluten network, is also largely dependent on the intermolecular crosslinking via disulfide bonds. In eukaryotes, the formation and rearrangement of most intra- and intermolecular disulfide bonds in the endoplasmic reticulum (ER) are mediated by protein disulfide isomerases (PDIs), which consist of multiple thioredoxin-like domains. These domains assist correct folding of proteins, as well as effectively prevent the aggregation of misfolded ones. Protein misfolding often leads to the formation of pathological protein aggregations that cause many diseases. On the other hand, glutenin aggregation and subsequent crosslinking are required for the formation of a rheologically dominating gluten network. Herein, the mechanism of PDI-regulated disulfide bond formation is important for understanding not only protein folding and associated diseases, but also the formation of functional biomolecular assembly. This review systematically illustrated the process of human protein disulfide isomerase (hPDI) mediated disulfide bond formation and complemented this with the current mechanism of wheat protein disulfide isomerase (wPDI) catalyzed formation of gluten networks.


Asunto(s)
Disulfuros/química , Retículo Endoplásmico/metabolismo , Glútenes/metabolismo , Proteína Disulfuro Isomerasas/metabolismo , Pliegue de Proteína , Animales , Glútenes/química , Humanos , Oxidación-Reducción , Proteína Disulfuro Isomerasas/química
14.
Molecules ; 25(19)2020 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-32987954

RESUMEN

The repetitive sequence of glutenin plays an important role in dough rheology; however, its interaction with wheat protein disulfide isomerase (wPDI) remains unclear. In this study, the conformations of wild type glutenin repetitive sequence (WRS) from the high molecular weight glutenin subunit (HMW-GS) 1Dx5, an artificially designed glutenin repetitive sequence (DRS) of which the amino acid composition is the same but the primary structure is different, and wPDI under different redox states were simulated. The molecular interactions between the aforementioned repetitive sequences with wPDI under different redox states were further investigated. The results indicated that the repetitive sequences bind to the b and b' domains of an "open", oxidized wPDI (wPDIO) which serves as the acceptor state of substrate. The repetitive sequence is partially folded (compressed) in wPDIO, and is further folded in the thermodynamically favored, subsequent conformational transition of wPDIO to reduced wPDI (wPDIR). Compared with the artificially designed one, the naturally designed repetitive sequence is better recognized and more intensively folded by wPDI for its later unfold as the molecular basis of dough extension.


Asunto(s)
Glútenes/química , Pliegue de Proteína , Triticum/química , Oxidación-Reducción , Dominios Proteicos
15.
Clin Oral Implants Res ; 26(10): 1150-7, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25220909

RESUMEN

OBJECTIVES: This study aimed to evaluate the biologic and structural phenotypes of the bone regenerated via the sandwich bone augmentation (SBA) technique, on buccal implant dehiscence defects. MATERIAL AND METHODS: Twenty-six patients with one buccal implant dehiscence defect each were randomly assigned to two groups. Both groups received a standardized amount of mineralized cancellous and cortical allogenic bone graft. In the test group, a bovine pericardium membrane was placed over the graft, while no membrane was placed in the control group. After 6 months of healing, a bone core biopsy of the regenerated bone was harvested and processed for histologic, immunohistochemical, mRNA, and micro-computed tomography (µCT) analyses. Of the 26 bone core biopsies, only six cores from the test group and six cores from the control group were suitable for the analysis. RESULTS: Bone volume (BV) in the test group was maintained, but tissue maturation appeared to be delayed. In contrast, tissue maturation appeared to be completed in the control group, but BV was compromised. Micro-CT analysis showed that specimens from the control group were more structured and mineralized compared with those from the test group. Histologic analysis showed more residual graft particles scattered in a loose fibrous connective tissue matrix with sparse bone formation in the test group, while the control group showed obvious vital bone formation surrounding the residual graft particles. Positive periostin (POSTN), sclerostin, and runt-related transcription factor-2 (RUNX2) immunoreactivities were detected in both the control and test groups. However, tartrate-resistant acid phosphatase (TRAP) positive was mostly noted in the control group. There were significant differences in POSTN, RUNX2 and VEGF expressions between the test and control groups. CONCLUSION: These findings indicated that the SBA technique was an effective method in preserving adequate structural volume while promoting new vital bone formation. Use of the collagen barrier membrane has successfully maintained the volumetric dimensions of the ridge but might have slowed down the complete maturation of the outermost layer of the grafted site.


Asunto(s)
Aumento de la Cresta Alveolar/métodos , Implantación Dental Endoósea/métodos , Histocitoquímica , Inmunohistoquímica , Maxilar/anatomía & histología , ARN/análisis , Tomografía Computarizada por Rayos X , Humanos , Maxilar/química , Maxilar/citología , Maxilar/diagnóstico por imagen , Resultado del Tratamiento
16.
Clin Oral Implants Res ; 25(4): 458-67, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23594026

RESUMEN

OBJECTIVES: Sandwich bone augmentation (SBA) has been proposed to augment the width of edentulous ridges for implant placement. This study aimed to investigate the effect of a membrane on SBA for the regeneration of buccal implant dehiscence defects. MATERIAL AND METHODS: Twenty-six healthy patients, each with a single defect, were randomly assigned into two groups. Both groups received an inner and outer layer of mineralized human cancellous and cortical particulate allograft. In the test group, a bovine pericardium membrane covered the bone grafts, while no membrane was placed in the control group. Cone beam computed tomography (CBCT) scans were taken before and immediately after implant placement and at 6 months post-surgery. RESULTS: All implants placed were successfully osseointegrated at 6 months. Clinical re-entry measurements showed significant buccal bone gain in the test group compared with the control group (P < 0.05). The test group had 1.12, 2.21 and 2.44 mm more buccal bone thickness at 2, 4 and 6 mm below the bone crest. There were no significant differences in the mid-buccal vertical bone height, defect height and width reductions and bone fill between the two groups (P > 0.05). Cone beam computed tomography analysis demonstrated significant buccal bone gain of 1.22 mm in the test group. Radiographic vertical bone loss at 1-year post-surgery showed no significant differences between the groups. CONCLUSION: Sandwich bone augmentation is a predictable technique for regenerating buccal bone on implant dehiscence defects. Addition of a barrier membrane prevented significant horizontal buccal bone resorption as space was maintained more effectively when compared with sites treated without a membrane.


Asunto(s)
Proceso Alveolar/diagnóstico por imagen , Aumento de la Cresta Alveolar/métodos , Trasplante Óseo/métodos , Implantación Dental Endoósea , Implantes Dentales de Diente Único , Maxilar/diagnóstico por imagen , Osteogénesis , Adulto , Proceso Alveolar/cirugía , Resorción Ósea/prevención & control , Tomografía Computarizada de Haz Cónico , Femenino , Humanos , Masculino , Maxilar/cirugía , Membranas Artificiales , Persona de Mediana Edad , Oseointegración , Resultado del Tratamiento
17.
Clin Oral Implants Res ; 25(10): 1119-24, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23937287

RESUMEN

PURPOSE: This systematic review aimed to evaluate the effect of implant length on peri-implant marginal bone loss (MBL) and its associated influencing factors. MATERIAL AND METHODS: An electronic search of the PubMed and MEDLINE databases for relevant studies published in English from November 2006 to July 2012 was performed by one examiner (AM). Selected studies were randomized clinical trials, human experimental clinical trials or prospective studies (e.g., cohort as well as case series) with a clear aim of investigating marginal bone loss of short dental implants (<10 mm) supporting fixed prostheses. A random-effect meta-regression model was used to determine the relationship between the effect size mean MBL and the covariate "implant length." Additionally, a subgroup analysis, by means of a random-effect one-way ANOVA model, comparing mean MBL values at different levels of each factor ("type of connection" and "type of prostheses") was also performed. RESULTS: The meta-regression of mean MBL on the moderator "implant length" was found to be insignificant (P = 0.633). Therefore, it could not be concluded that implant length had an effect on peri-implant MBL. In addition, standardized differences in mean MBL on the subgroups short (<10 mm) and standard (≥ 10 mm) implants, as determined by the meta-analysis (random-effect model), were found to be statistically insignificant (P = 0.222). CONCLUSIONS: Within limitations of the present systematic review, it could be concluded that short dental implants (<10 mm) had similar peri-implant MBL as standard implants (≥ 10 mm) for implant-supported fixed prostheses.


Asunto(s)
Pérdida de Hueso Alveolar/etiología , Implantes Dentales , Prótesis Dental de Soporte Implantado , Implantes Dentales/efectos adversos , Diseño de Prótesis Dental , Prótesis Dental de Soporte Implantado/efectos adversos , Humanos , Factores de Riesgo
18.
Gene ; 909: 148312, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38412945

RESUMEN

BACKGROUND/AIM: Tuberous sclerosis complex (TSC) is a multi-system syndrome caused by loss-of-function mutation in TSC1 or TSC2. Most TSC patients present with cardiac rhabdomyoma or cortical tubers during fetal life, and the symptoms are not uniform as their age. The gene products of TSC1/2 are components of the TSC protein complex and are important role in the PI3K/AKT/mTOR (PAM) signaling pathway. Based on three members of a family with variable expressivity, the purpose of this study was to clarify the clinical features of TSC in different age groups and to analyze the genetic characteristics of TSC2 gene. METHODS: Clinical exome sequencing and co-segregation were used to identify a three-generation family with four affected individuals. HEK-293T cell model was constructed for subsequent experiments. Quantitative RT-PCR, western blotting, and subcellular localization were used to analyze the expression effect of TSC2 mutation. CCK-8 assay, wound healing assay, and cell cycle analysis were used to analyze the function effect of TSC2 mutation. RESULT: We identified a TSC family with heterozygous deletion of exon 4 in TSC2 by clinical exon sequencing. Sanger sequencing indicated that the affected individuals have 2541-bp deletion that encompassed exon 4 and adjacent introns. Deletion of exon 4 decreased the TSC2 mRNA and protein levels in HEK-293T cells, and activated the PI3K/AKT/mTOR pathway, thereby altering the cell cycle and promoting cell proliferation and migration. CONCLUSION: We confirmed the pathogenicity of the large deletion in TSC2 in a three- generations family.. Deletion of exon 4 of TSC2 affected cell proliferation, migration, and cell cycle via abnormal activation of the PAM pathway. This study evaluated the pathogenic effect of deletion of exon 4 of TSC2 and investigated the underlying mechanism.


Asunto(s)
Esclerosis Tuberosa , Proteínas Supresoras de Tumor , Humanos , Mutación , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-akt/genética , Transducción de Señal/genética , Serina-Treonina Quinasas TOR/genética , Esclerosis Tuberosa/genética , Esclerosis Tuberosa/patología , Proteína 1 del Complejo de la Esclerosis Tuberosa/genética , Proteína 2 del Complejo de la Esclerosis Tuberosa/genética , Proteínas Supresoras de Tumor/genética
19.
Genes (Basel) ; 15(4)2024 03 26.
Artículo en Inglés | MEDLINE | ID: mdl-38674339

RESUMEN

The precise identification of splice sites is essential for unraveling the structure and function of genes, constituting a pivotal step in the gene annotation process. In this study, we developed a novel deep learning model, DRANetSplicer, that integrates residual learning and attention mechanisms for enhanced accuracy in capturing the intricate features of splice sites. We constructed multiple datasets using the most recent versions of genomic data from three different organisms, Oryza sativa japonica, Arabidopsis thaliana and Homo sapiens. This approach allows us to train models with a richer set of high-quality data. DRANetSplicer outperformed benchmark methods on donor and acceptor splice site datasets, achieving an average accuracy of (96.57%, 95.82%) across the three organisms. Comparative analyses with benchmark methods, including SpliceFinder, Splice2Deep, Deep Splicer, EnsembleSplice, and DNABERT, revealed DRANetSplicer's superior predictive performance, resulting in at least a (4.2%, 11.6%) relative reduction in average error rate. We utilized the DRANetSplicer model trained on O. sativa japonica data to predict splice sites in A. thaliana, achieving accuracies for donor and acceptor sites of (94.89%, 94.25%). These results indicate that DRANetSplicer possesses excellent cross-organism predictive capabilities, with its performance in cross-organism predictions even surpassing that of benchmark methods in non-cross-organism predictions. Cross-organism validation showcased DRANetSplicer's excellence in predicting splice sites across similar organisms, supporting its applicability in gene annotation for understudied organisms. We employed multiple methods to visualize the decision-making process of the model. The visualization results indicate that DRANetSplicer can learn and interpret well-known biological features, further validating its overall performance. Our study systematically examined and confirmed the predictive ability of DRANetSplicer from various levels and perspectives, indicating that its practical application in gene annotation is justified.


Asunto(s)
Arabidopsis , Oryza , Sitios de Empalme de ARN , Arabidopsis/genética , Sitios de Empalme de ARN/genética , Humanos , Oryza/genética , Aprendizaje Profundo , Programas Informáticos , Empalme del ARN , Biología Computacional/métodos
20.
J Agric Food Chem ; 72(21): 12100-12118, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38748649

RESUMEN

This study aimed to investigate the chemical components and potential health benefits of the fruits of Cannabis sativa L. Fourteen new phenylpropanamides designated as cannabisin I-XIV (1-14) and 40 known analogs were isolated and characterized via nuclear magnetic resonance spectroscopy, high-resolution electrospray ionization mass spectrometry, and electronic circular dichroism. In vitro bioassay using H2O2-induced PC12 cell damage models demonstrated that hempseeds extract and compounds 1, 3, 15, 26, 30, 36, 41, and 48 exhibited neuroprotective properties. 3,3'-Demethylgrossamide (30) displayed encouraging protection activity, which was further investigated to relieve the oxidative stress and apoptosis of PC12 cells treated with H2O2. The isolation and characterization of these neuroprotective phenylpropanamides from the fruits of C. sativa provide insights into its health-promoting properties as a healthy food and herbal medicine for preventing and treating neurodegenerative diseases, especially Alzheimer's disease.


Asunto(s)
Cannabis , Frutas , Fármacos Neuroprotectores , Extractos Vegetales , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/química , Ratas , Células PC12 , Animales , Frutas/química , Cannabis/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Estructura Molecular , Estrés Oxidativo/efectos de los fármacos , Apoptosis/efectos de los fármacos , Amidas/química , Amidas/farmacología , Peróxido de Hidrógeno , Humanos
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