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We present deterministic barcoding in tissue for spatial omics sequencing (DBiT-seq) for co-mapping of mRNAs and proteins in a formaldehyde-fixed tissue slide via next-generation sequencing (NGS). Parallel microfluidic channels were used to deliver DNA barcodes to the surface of a tissue slide, and crossflow of two sets of barcodes, A1-50 and B1-50, followed by ligation in situ, yielded a 2D mosaic of tissue pixels, each containing a unique full barcode AB. Application to mouse embryos revealed major tissue types in early organogenesis as well as fine features like microvasculature in a brain and pigmented epithelium in an eye field. Gene expression profiles in 10-µm pixels conformed into the clusters of single-cell transcriptomes, allowing for rapid identification of cell types and spatial distributions. DBiT-seq can be adopted by researchers with no experience in microfluidics and may find applications in a range of fields including developmental biology, cancer biology, neuroscience, and clinical pathology.
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Código de Barras de DNA Taxonômico , Genômica , Especificidade de Órgãos/genética , Animais , Automação , Encéfalo/embriologia , Análise por Conglomerados , DNA Complementar/genética , Embrião de Mamíferos/metabolismo , Olho/embriologia , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Camundongos Endogâmicos C57BL , Microfluídica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reprodutibilidade dos Testes , Análise de Célula Única , Transcriptoma/genéticaRESUMO
Transcriptional divergence of duplicated genes after whole genome duplication (WGD) has been described in many plant lineages and is often associated with subgenome dominance, a genome-wide mechanism. However, it is unknown what underlies the transcriptional divergence of duplicated genes in polyploid species that lack subgenome dominance. Soybean is a paleotetraploid with a WGD that occurred 5 to 13 Mya. Approximately 50% of the duplicated genes retained from this WGD exhibit transcriptional divergence. We developed accessible chromatin region (ACR) datasets from leaf, flower, and seed tissues using MNase-hypersensitivity sequencing. We validated enhancer function of several ACRs associated with known genes using CRISPR/Cas9-mediated genome editing. The ACR datasets were used to examine and correlate the transcriptional patterns of 17,111 pairs of duplicated genes in different tissues. We demonstrate that ACR dynamics are correlated with divergence of both expression level and tissue specificity of individual gene pairs. Gain or loss of flanking ACRs and mutation of cis-regulatory elements (CREs) within the ACRs can change the balance of the expression level and/or tissue specificity of the duplicated genes. Analysis of DNA sequences associated with ACRs revealed that the extensive sequence rearrangement after the WGD reshaped the CRE landscape, which appears to play a key role in the transcriptional divergence of duplicated genes in soybean. This may represent a general mechanism for transcriptional divergence of duplicated genes in polyploids that lack subgenome dominance.
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Evolução Molecular , Glycine max , Glycine max/genética , Glycine max/metabolismo , Genoma , Genes Duplicados/genética , Sequência de Bases , Duplicação Gênica , Genoma de Planta/genéticaRESUMO
Super-enhancers (SEs) are exceptionally large enhancers and are recognized to play prominent roles in cell identity in mammalian species. We surveyed the genomic regions containing large clusters of accessible chromatin regions (ACRs) marked by deoxyribonuclease (DNase) I hypersensitivity in Arabidopsis thaliana. We identified a set of 749 putative SEs, which have a minimum length of 1.5 kilobases and represent the top 2.5% of the largest ACR clusters. We demonstrate that the genomic regions associating with these SEs were more sensitive to DNase I than other nonpromoter ACRs. The SEs were preferentially associated with topologically associating domains. Furthermore, the SEs and their predicted cognate genes were frequently associated with organ development and tissue identity in A. thaliana. Therefore, the A. thaliana SEs and their cognate genes mirror the functional characteristics of those reported in mammalian species. We developed CRISPR/Cas-mediated deletion lines of a 3,578-bp SE associated with the thalianol biosynthetic gene cluster (BGC). Small deletions (131-157 bp) within the SE resulted in distinct phenotypic changes and transcriptional repression of all five thalianol genes. In addition, T-DNA insertions in the SE region resulted in transcriptional alteration of all five thalianol genes. Thus, this SE appears to play a central role in coordinating the operon-like expression pattern of the thalianol BGC.
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Arabidopsis , Triterpenos , Animais , Arabidopsis/genética , Sequências Reguladoras de Ácido Nucleico , Cromatina/genética , Mamíferos/genéticaRESUMO
Maleic acid (MA) induces renal tubular cell dysfunction directed to acute kidney injury (AKI). AKI is an increasing global health burden due to its association with mortality and morbidity. However, targeted therapy for AKI is lacking. Previously, we determined mitochondrial-associated proteins are MA-induced AKI affinity proteins. We hypothesized that mitochondrial dysfunction in tubular epithelial cells plays a critical role in AKI. In vivo and in vitro systems have been used to test this hypothesis. For the in vivo model, C57BL/6 mice were intraperitoneally injected with 400 mg/kg body weight MA. For the in vitro model, HK-2 human proximal tubular epithelial cells were treated with 2 mM or 5 mM MA for 24 h. AKI can be induced by administration of MA. In the mice injected with MA, the levels of blood urea nitrogen (BUN) and creatinine in the sera were significantly increased (p < 0.005). From the pathological analysis, MA-induced AKI aggravated renal tubular injuries, increased kidney injury molecule-1 (KIM-1) expression and caused renal tubular cell apoptosis. At the cellular level, mitochondrial dysfunction was found with increasing mitochondrial reactive oxygen species (ROS) (p < 0.001), uncoupled mitochondrial respiration with decreasing electron transfer system activity (p < 0.001), and decreasing ATP production (p < 0.05). Under transmission electron microscope (TEM) examination, the cristae formation of mitochondria was defective in MA-induced AKI. To unveil the potential target in mitochondria, gene expression analysis revealed a significantly lower level of ATPase6 (p < 0.001). Renal mitochondrial protein levels of ATP subunits 5A1 and 5C1 (p < 0.05) were significantly decreased, as confirmed by protein analysis. Our study demonstrated that dysfunction of mitochondria resulting from altered expression of ATP synthase in renal tubular cells is associated with MA-induced AKI. This finding provides a potential novel target to develop new strategies for better prevention and treatment of MA-induced AKI.
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Injúria Renal Aguda , Apoptose , Maleatos , Camundongos Endogâmicos C57BL , Mitocôndrias , ATPases Mitocondriais Próton-Translocadoras , Animais , Humanos , Masculino , Camundongos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/genética , Injúria Renal Aguda/patologia , Apoptose/efeitos dos fármacos , Linhagem Celular , Células Epiteliais/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Túbulos Renais Proximais/patologia , Túbulos Renais Proximais/efeitos dos fármacos , Túbulos Renais Proximais/metabolismo , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , ATPases Mitocondriais Próton-Translocadoras/metabolismo , ATPases Mitocondriais Próton-Translocadoras/genética , Espécies Reativas de Oxigênio/metabolismoRESUMO
Enhancers located in introns are abundant and play a major role in the regulation of gene expression in mammalian species. By contrast, the functions of intronic enhancers in plants have largely been unexplored and only a handful of plant intronic enhancers have been reported. We performed a genome-wide prediction of intronic enhancers in Arabidopsis thaliana using open chromatin signatures based on DNase I sequencing. We identified 941 candidate intronic enhancers associated with 806 genes in seedling tissue and 1,271 intronic enhancers associated with 1,069 genes in floral tissue. We validated the function of 15 of 21 (71%) of the predicted intronic enhancers in transgenic assays using a reporter gene. We also created deletion lines of three intronic enhancers associated with two different genes using CRISPR/Cas. Deletion of these enhancers, which span key transcription factor binding sites, did not abolish gene expression but caused varying levels of transcriptional repression of their cognate genes. Remarkably, the transcriptional repression of the deletion lines occurred at specific developmental stages and resulted in distinct phenotypic effects on plant morphology and development. Clearly, these three intronic enhancers are important in fine-tuning tissue- and development-specific expression of their cognate genes.
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Arabidopsis/genética , Elementos Facilitadores Genéticos , Edição de Genes/métodos , Regulação da Expressão Gênica de Plantas , Íntrons , Arabidopsis/crescimento & desenvolvimento , Proteínas de Arabidopsis/genética , Cromatina/genética , Flores/genética , Genes Reporter , Glucuronidase/genética , Plantas Geneticamente Modificadas , Regiões Promotoras Genéticas , Fatores de Transcrição/genéticaRESUMO
Ferroelectricity in two-dimensional (2D) systems generally arises from phonons and has been widely investigated. On the contrary, electronic ferroelectricity in 2D systems has been rarely studied. Using first-principles calculations, the ferroelectric behavior of the buckled blue SiSe monolayer under strain are explored. It is found that the direction of the out-of-plane ferroelectric polarization can be reversed by applying an in-plane strain. And such polarization switching is realized without undergoing geometric inversion. Besides, the strain-triggered polarization reversal emerges in both biaxial and uniaxial strain cases, indicating it is an intrinsic feature of such a system. Further analysis shows that the polarization switching is the result of the reversal of the magnitudes of the positive and negative charge center vectors. And the variation of buckling is found to play an important role, which results in the switch. Moreover, a non-monotonic variation of band gap with strain is revealed. Our findings throws light on the investigation of novel electronic ferroelectric systems.
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Cell therapies have gained prominence as a promising therapeutic modality for treating a range of diseases. Despite the recent clinical successes of cell therapy products, very few formal training programs exist for cell therapy manufacturing. To meet the demand for a well-trained workforce, we assembled a team of university researchers and industry professionals to develop an online course on the principles and practice of cell therapy manufacturing. The course covers the basic cell and systems physiology underlying cell therapy products, in addition to explaining end-to-end manufacturing from cell acquisition through to patient treatment, industrialization, and regulatory processes. So far, over 10,000 learners have enrolled in the course, and over 90% of respondents to the course exit survey indicated that they were 'very likely' or 'likely' to recommend the course to a peer. In this paper, we discuss our experience in the collaborative design and implementation of the online course, as well as lessons learned from quantitative and qualitative student feedback. We believe that this course can serve as a model for how academia and industry can collaborate to create innovative, scalable training programs to meet the demands of the modern biotechnology workforce.
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Micro-expressions, which are spontaneous and difficult to suppress, reveal a person's true emotions. They are characterized by short duration and low intensity, making the task of micro-expression recognition challenging in the field of emotion computing. In recent years, deep learning-based feature extraction and fusion techniques have been widely used for micro-expression recognition, particularly methods based on Vision Transformer that have gained popularity. However, the Vision Transformer-based architecture used in micro-expression recognition involves a significant amount of invalid computation. Additionally, in the traditional two-stream architecture, although separate streams are combined through late fusion, only the output features from the deepest level of the network are utilized for classification, thus limiting the network's ability to capture subtle details due to the lack of fine-grained information. To address these issues, we propose a new two-level spatio-temporal feature fused with a two-stream architecture. This architecture includes a spatial encoder (modified ResNet) for learning texture features of the face, a temporal encoder (Swin Transformer) for learning facial muscle motor features, a feature fusion algorithm for integrating multi-level spatio-temporal features, a classification head, and a weighted average operator for temporal aggregation. The two-stream architecture has the advantage of extracting richer features compared to the single-stream architecture, leading to improved performance. The shifted window scheme of Swin Transformer restricts self-attention computation to non-overlapping local windows and allows cross-window connections, significantly improving the performance and reducing the computation compared to Vision Transformer. Moreover, the modified ResNet is computationally less intensive. Our proposed feature fusion algorithm leverages the similarity in output feature shapes at each stage of the two streams, enabling the effective fusion of multi-level spatio-temporal features. This algorithm results in an improvement of approximately 4% in both the F1 score and the UAR. Comprehensive evaluations conducted on three widely used spontaneous micro-expression datasets (SMIC-HS, CASME II, and SAMM) consistently demonstrate the superiority of our approach over comparative methods. Notably, our approach achieves a UAR exceeding 0.905 on CASME II, making it one of the few frameworks in the published micro-expression recognition literature to achieve such high performance.
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Algoritmos , Fontes de Energia Elétrica , Humanos , Emoções , Luz , MúsculosRESUMO
The numerical aperture of the spectrometer is crucial for weak signal detection. The transmission lens-based configuration has more optimization variations, and the grating can work approximately in the Littrow condition; thus, it is easier to acquire high numerical aperture (NA). However, designing a large aperture focusing lens remains challenging, and thus, ultra-high NA spectrometers are still difficult to acquire. In this paper, we propose a method of setting image plane tilt ahead directly when designing the large aperture focusing lens to simplify the high NA spectrometer design. By analyzing the accurate demands of the focusing lens, it can be concluded that a focusing lens with image plane tilt has much weaker demand for achromatism, and other monochromatic aberration can also be reduced, which is helpful to increase the NA. An NA0.5 fiber optic spectrometer design is given to demonstrate the proposed method. The design results show that the NA can achieve 0.5 using four lenses of two materials, and the MTF is higher than 0.5 when the spectral dispersion length is 12.5 mm and the pixel size is 25 µm, and thus, the spectral resolution can achieve 6.5 nm when the spectral sampling ratio is 2:1. The proposed method can provide reference for applications when appropriate materials are limited and high sensitivity is necessary.
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Ovarian clear cell carcinoma (OCCC) is often considered a relatively platinum-resistant malignancy. The aim of this study was to explore the influence of progesterone receptor (PR) expression levels on platinum sensitivity and survival outcomes in people with OCCC. A retrospective analysis was conducted with 80 people with OCCC who underwent surgery followed by adjuvant chemotherapy. PR expression was assessed via immunohistochemical (IHC) staining and quantified using the H score. The platinum sensitivity and survival outcomes of patients with weak and strong PR expression were compared. Additionally, cisplatin viability and migration experiments were conducted with OCCC cell lines (ES-2 and TOV-21G) with varying PR isoform expressions. Among the 80 patients, 62 were classified as having platinum-sensitive disease, while 18 had platinum-resistant disease. The mean total PR H- score of platinum-sensitive tumors was significantly higher than that of platinum-resistant tumors (p = 0.002). Although no significant differences in progression-free and overall survival were observed between patients with high and low PR expression, those with high PR expression tended to have longer survival. While PR protein was only weakly detectable in ES-2 and TOV-21G cells, a transfection of the PR-A or PR-B gene resulted in a strong expression of PR-A or PR-B, which led to significantly reduced proliferation and migration in ES-2 and TOV-21G cells. Furthermore, overexpression of PR-A or PR-B enhanced cisplatin cytotoxicity in these cell lines. In conclusion, strong PR expression was associated with improved platinum sensitivity and survival outcomes, consistent with our experimental findings. The potential of PR as a tumor sensitizer to cisplatin in OCCC warrants further investigation.
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Adenocarcinoma de Células Claras , Cisplatino , Resistencia a Medicamentos Antineoplásicos , Neoplasias Ovarianas , Receptores de Progesterona , Humanos , Feminino , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Receptores de Progesterona/metabolismo , Receptores de Progesterona/genética , Pessoa de Meia-Idade , Adenocarcinoma de Células Claras/metabolismo , Adenocarcinoma de Células Claras/tratamento farmacológico , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma de Células Claras/genética , Resistencia a Medicamentos Antineoplásicos/genética , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Linhagem Celular Tumoral , Idoso , Adulto , Estudos Retrospectivos , Movimento Celular/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Platina/farmacologia , Platina/uso terapêutico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacosRESUMO
The bioretention system is one of the most widely used low impact development (LID) facilities with efficient purification capacity for stormwater, and its planting design has been a hot spot for research at home and abroad. In this paper, ryegrass (Lolium perenne L.), bermuda (Cynodon dactylon Linn.), bahiagrass (Paspalum notatum Flugge), and green grass (Cynodon dactylon × C .transadlensis 'Tifdwarf') were chosen as plant species to construct a shallow bioretention system. The growth traits and nutrient absorption ability of four gramineous plants were analyzed. Their tolerance, enrichment, and transportation capacity were also evaluated to compare plant species and their absorptive capacity of heavy metals (Cu, Pb, and Zn). Results showed that the maximum absorption rate (Imax) ranged from 22.1 to 42.4 µg/(g·h) for P and ranged from 65.4 to 104.8 µg/(g·h) for NH4+-N; ryegrass had the strongest absorption capacity for heavy metals and the maximum removal rates of Cu, Pb, and Zn by four grasses were 78.4, 59.4, and 51.3%, respectively; the bioretention cell with ryegrass (3#) was significantly more effective in purifying than the unplanted bioretention cell (1#) during the simulated rainfall test. Overall, the system parameters were optimized to improve the technical application of gramineous plants in the bioretention system.
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Chuva , Poluentes Químicos da Água , Metais Pesados , Biodegradação Ambiental , Poaceae , Lolium/metabolismo , Purificação da Água/métodosRESUMO
Electrically conducting two-dimensional (2D) metal-organic frameworks (MOFs) have garnered significant interest due to their remarkable structural tunability and outstanding electrical properties. However, the design and synthesis of high-performance materials face challenges due to the limited availability of specific ligands and pore structures. In this study, we have employed a novel highly branched D3h symmetrical planar conjugated ligand, dodechydroxylhexabenzotrinaphthylene (DHHBTN) to fabricate a series of 2D conductive MOFs, named M-DHHBTN (M=Co, Ni, and Cu). This new family of MOFs offers two distinct types of pores, elevating the structural complexity of 2D conductive MOFs to a more advanced level. The intricate tessellation patterns of the M-DHHBTN are elucidated through comprehensive analyses involving powder X-ray diffraction, theoretical simulations, and high-resolution transmission electron microscope. Optical-pump terahertz-probe spectroscopic measurements unveiled carrier mobility in DHHBTN-based 2D MOFs spanning from 0.69 to 3.10â cm2 V-1 s-1. Among M-DHHBTN famility, Cu-DHHBTN displayed high electrical conductivity reaching 0.21â S cm-1 at 298â K with thermal activation behavior. This work leverages the "branched conjugation" of the ligand to encode heteroporosity into highly conductive 2D MOFs, underscoring the significant potential of heterogeneous double-pore structures for future applications.
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Perylene diimides (PDIs) have garnered considerable attention due to its immense potential in photocatalysis. However, manipulating the molecular packing within their aggregates and enhancing the efficiency of photogenerated carrier recombination remain significant challenges. In this study, we demonstrate the incorporation of a PDI unit into a covalent organic framework (COF), named PDI-PDA, by linking an ortho-substituted PDI with p-phenylenediamine (PDA) to control its intermolecular aggregation. The incorporation enables precise modulation of electron transfer dynamics, leading to a ten-fold increase in the efficiency of photocatalytic oxidation of thioether to sulfoxide with PDI-PDA compared to the PDI molecular counterpart, achieving yields exceeding 90%. Electron property studies and density functional theory calculations show that the PDI-PDA with its well-defined crystal structure, enhances π-π stacking and lowers the electron transition barrier. Moreover, the strong electron-withdrawing ability of the PDI unit promotes the spatial separation of the valency band maximum and conduction band minimum of PDI-PDA suppressing the rapid recombination of photogenerated electron-hole pairs and improving charge separation efficiency to give high photocatalytic efficiency. This study provides a brief yet effective way for the improvement of the photocatalytic efficiency of commonly used PDI-based dyes by integrating them into a framework skeleton.
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Cascade hydroxyl radical generating hydrogel reactor structures including a chemotherapeutic agent are invented for multiple treatment of breast cancer. Glucose oxidase (GOx) and cupric sulfate (Cu) are introduced for transforming accumulated glucose (in cancer cells) to hydroxyl radicals for starvation/chemodynamic therapy. Cu may also suppress cancer cell growth via cuproptosis-mediated cell death. Berberine hydrochloride (BER) is engaged as a chemotherapeutic agent in the hydrogel reactor for combining with starvation/chemodynamic/cuproptosis therapeutic modalities. Moreover, Cu is participated as a gel crosslinker by coordinating with catechol groups in hyaluronic acid-dopamine (HD) polymer. Controlling viscoelasticity of hydrogel reactor can extend the retention time following local injection and provide sustained drug release patterns. Low biodegradation rate of designed HD/BER/GOx/Cu hydrogel can reduce dosing frequency in local cancer therapy and avoid invasiveness-related inconveniences. Especially, it is anticipated that HD/BER/GOx/Cu hydrogel system can be applied for reducing size of breast cancer prior to surgery as well as tumor growth suppression in clinical application.
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Apoptose , Neoplasias da Mama , Neoplasias , Feminino , Humanos , Neoplasias da Mama/tratamento farmacológico , Catálise , Linhagem Celular Tumoral , Glucose Oxidase/metabolismo , Hidrogéis , Peróxido de Hidrogênio/química , Radical Hidroxila/química , Neoplasias/terapia , CobreRESUMO
MOTIVATION: The emergence of next-generation sequencing techniques opens up tremendous opportunities for researchers to uncover the basic mechanisms of disease at the molecular level. Recently, automatic machine learning (AutoML) frameworks have been employed for genomic and epigenomic data analysis. However, to analyze those high-dimensional data, existing AutoML frameworks suffer from the following issues: (i) they could not effectively filter out the redundant features from the original data, and (ii) they usually obey the rule of feature engineering first and algorithm hyper-parameter tuning later to build the machine learning pipeline, which could lead to sub-optimal outcomes. Thus, it is an urgent need to design a new AutoML framework for high-dimensional omics data analysis. RESULTS: We introduce a new method: AutoDC, a tailored AutoML framework, for different disease classification based on gene expression data. AutoDC designs two novel optimization strategies to improve the performance. One is that AutoDC designs a novel two-stage feature selection method to select the features with high gene contribution scores. The other is that AutoDC proposes a novel optimization method, based on a two-layer Multi-Armed Bandit framework, to jointly optimize the feature engineering, algorithm selection and algorithm hyper-parameter tuning. We apply our framework to two public gene expression datasets. Compared with three state-of-the-art AutoML frameworks, AutoDC could effectively classify diseases with higher predictive accuracy. AVAILABILITY AND IMPLEMENTATION: The data and codes of AutoDC are available at https://github.com/dingdian110/AutoDC. The data underlying this article are available in the article and in its online supplementary material. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Algoritmos , Aprendizado de Máquina , Genômica/métodos , Análise de Dados , GenomaRESUMO
Objective: Natural products in diet have shown a potential role in the prevention and treatment of cancer. Ginger (Zingiber officinale Roscoe) is a great candidate because of its properties of anti-inflammatory, antioxidant, and anti-cancer, but little is known about its effect on head and neck cancer. 6-Shogaol is an active compound derived from Ginger. Thus, this study aimed to investigate the possible anticancer effects of 6-shogaol, a major ginger derivate, on head and neck squamous cell carcinomas (HNSCCs) and the underlying mechanisms. Material and Methods: Two HNSCC cell lines, SCC4 and SCC25, were used in this study. Both SCC4 and SCC25 cells were kept as control or treated with 6-shogaol for 8 and 24 hours and then the cell apoptosis and cell cycle progression of treated cells were examined by PI and Annexin V-FITC double stain and flow cytometry analysis. The Cleaved caspase 3, phosphorylations of ERK1/2 and p38 kinases were examined by Western blot analysis. Results: The results showed that 6-shogaol significantly initiated the G2/M phase arrest of the cell cycle and apoptosis to inhibit the survival of both cell lines. Moreover, these responses could be regulated by ERK1/2 and p38 signaling. And, finally, we also demonstrated that 6-shogaol could enhance the cytotoxicity of cisplatin in HNSCC cells. Conclusion: Our data provided new insights to understand the potential pharmaceutical efficacy of a ginger derivate, 6-shogaol, in antagonizing HNSCC survival. The present study suggests that 6-shogaol is a potential novel candidate for anti-HNSCCs therapy.
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Catecóis , Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Catecóis/farmacologia , Catecóis/uso terapêutico , Apoptose , Neoplasias de Cabeça e Pescoço/tratamento farmacológicoRESUMO
To address the shortcomings in many traditional spectral feature extraction algorithms in practical application of low modeling accuracy and poor stability, this paper introduces the "Boruta algorithm-based local optimization process" based on the traditional simulated annealing algorithm and proposes the "two-step simulated annealing algorithm (TSSA)". This algorithm combines global optimization and local optimization. The Boruta algorithm ensures that the feature extraction results are all strongly correlated with the dependent variable, reducing data redundancy. The accuracy and stability of the algorithm model are significantly improved. The experimental results show that compared with the traditional feature extraction method, the accuracy indexes of the inversion model established by using the TSSA algorithm for feature extraction were significantly improved, with the determination coefficient R2 of 0.9654, the root mean square error (RMSE) of 3.6723 µg/L, and the mean absolute error (MAE) of 3.1461 µg/L.
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AlgoritmosRESUMO
Meniere's disease (MD) is one of the most complicated diseases in the otologic clinic. The complexity of MD is partially due to the multifactorial etiological mechanisms and the heterogenous symptoms, including episodic vertigo, hearing loss, aural fullness and tinnitus. As a result, the diagnosis of MD and differentiating MD from other diseases with similar symptoms, such as vestibular migraine (VM), is challenging. In addition, it is difficult to predict the progression of hearing loss and the frequency of vertigo attacks. Detailed studies have revealed that functional markers, such as pure tone audiometry (PTA), electrocochleography (ECochG), vestibular evoked myogenic potential (VEMP), caloric test, video head impulse test (vHIT) and magnetic resonance imaging (MRI) could help to evaluate MD with different hearing levels and frequency of vertigo attacks. Investigations of molecular markers such as autoimmunity, inflammation, protein signatures, vasopressin and circadian clock genes in MD are still underway. This review will summarize these functional and molecular markers, address how these markers are associated with hearing loss and vertigo attacks in MD, and analyze the results of the markers between MD and VM.
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Surdez , Perda Auditiva , Doença de Meniere , Zumbido , Humanos , Doença de Meniere/diagnóstico , Vertigem/etiologia , Vertigem/complicações , Perda Auditiva/etiologia , Surdez/complicaçõesRESUMO
Danshen has been widely used for the treatment of central nervous system diseases. We investigated the effect of dihydroisotanshinone I (DT), a compound extracted from Danshen, as well as the corresponding mechanisms in an in vitro-based 6-OHDA-induced Parkinson's disease (PD) model. SH-SY5Y human neuroblastoma cell lines were pretreated with 6-hydroxydopamine (6-OHDA) and challenged with DT. Subsequently, the cell viability and levels of reactive oxygen species (ROS) and caspase-3 were analyzed. The effect of DT on the 6-OHDA-treated SH-SY5Y cells and the expression of the core circadian clock genes were measured using a real-time quantitative polymerase chain reaction. Our results indicated that DT attenuated the 6-OHDA-induced cell death in the SH-SY5Y cells and suppressed ROS and caspase-3. Moreover, DT reversed both the RNA and protein levels of BMAL1 and SIRT1 in the 6-OHDA-treated SH-SY5Y cells. Additionally, the SIRT1 inhibitor attenuated the effect of DT on BMAL1 and reduced the cell viability. The DT and SIRT1 activators activated SIRT1 and BMAL1, and then reduced the death of the SH-SY5Y cells damaged by 6-OHDA. SIRT1 silencing was enhanced by DT and resulted in a BMAL1 downregulation and a reduction in cell viability. In conclusion, our investigation suggested that DT reduces cell apoptosis, including an antioxidative effect due to a reduction in ROS, and regulates the circadian genes by enhancing SIRT1 and suppressing BMAL1. DT may possess novel therapeutic potential for PD in the future, but further in vivo studies are still needed.
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Neuroblastoma , Fármacos Neuroprotetores , Doença de Parkinson , Humanos , Doença de Parkinson/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Oxidopamina/farmacologia , Caspase 3/genética , Sirtuína 1/genética , Sirtuína 1/metabolismo , Fatores de Transcrição ARNTL/genética , Linhagem Celular Tumoral , Neuroblastoma/metabolismo , Apoptose , Fármacos Neuroprotetores/farmacologiaRESUMO
Metasurface based on independent and simultaneous control of near field and far field has significant potential for use in multichannel optics platform devices. However, the previous studies cannot satisfy independent and simultaneous control of near field and far field under a single line source, which made a significant challenge to multichannel optical platforms working in a compact environment. To manipulate effectively and freely the amplitude and phase of transmission under line source, Marius' law and Propagation phase was introduced on all-dielectric encoding metasurfaces meta-atoms. The Marius' law and Propagation phase can control the size and rotation angle of meta-atoms to encode grayscale amplitude images and holographic phase images. Finite-difference time-domain simulation results reveal that dual channel metasurface under a single line source achieves the same display effect as the dual channel metasurface under multiple light sources, which proves the feasibility of our studies. Moreover, under different angles of the line source, we encode the near-field binary image by using the degeneracy rotation angle of meta-atoms. Finally, a three-channel metasurface was obtained without affecting the display of the previous two-channel metasurface. As a result, the independent control amplitude, phase, and polarization of the incident light wave were achieved. The proposed metasurface could be applied in creating a multi-channel metasurface optical platform in a compact environment, which has application potential in image displays, optical storage, optical anti-counterfeiting, and information encryption technology.