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Chiral superconductors, a unique class of unconventional superconductors in which the complex superconducting order parameter winds clockwise or anticlockwise in the momentum space1, represent a topologically non-trivial system with intrinsic time-reversal symmetry breaking (TRSB) and direct implications for topological quantum computing2,3. Intrinsic chiral superconductors are extremely rare, with only a few arguable examples, including UTe2, UPt3 and Sr2RuO4 (refs. 4-7). It has been suggested that chiral superconductivity may exist in non-centrosymmetric superconductors8,9, although such non-centrosymmetry is uncommon in typical solid-state superconductors. Alternatively, chiral molecules with neither mirror nor inversion symmetry have been widely investigated. We suggest that an incorporation of chiral molecules into conventional superconductor lattices could introduce non-centrosymmetry and help realize chiral superconductivity10. Here we explore unconventional superconductivity in chiral molecule intercalated TaS2 hybrid superlattices. Our studies reveal an exceptionally large in-plane upper critical field Bc2,|| well beyond the Pauli paramagnetic limit, a robust π-phase shift in Little-Parks measurements and a field-free superconducting diode effect (SDE). These experimental signatures of unconventional superconductivity suggest that the intriguing interplay between crystalline atomic layers and the self-assembled chiral molecular layers may lead to exotic topological materials. Our study highlights that the hybrid superlattices could lay a versatile path to artificial quantum materials by combining a vast library of layered crystals of rich physical properties with the nearly infinite variations of molecules of designable structural motifs and functional groups11.
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BACKGROUND Cervical cancer is one of the most common malignances among women globally. This study aimed to construct a novel immune-related signature to predict the prognosis and immune infiltration of cervical cancer. MATERIAL AND METHODS Transcriptomic profiles and corresponding clinical information of cervical cancer patients were obtained from The Cancer Genome Atlas (TCGA) database and GEO database. The hub immune-related genes were screened and selected using Cox regression analysis and LASSO regression analysis. A novel signature was established based on the expression levels and corresponding coefficients of the selected hub immune-related genes. Kaplan-Meier survival curve and ROC curve illustrated the prognostic value of this novel signature in cervical cancer. The predictive accuracy and stability of this novel signature were confirmed in the validation cohort, internal testing set and external testing set. Then, a nomogram was constructed to predict individual survival probability of cervical cancer patient. The association between the risk scores of novel signature and immune infiltration was investigated through single-sample gene set enrichment analysis (ssGSEA). RESULTS Ten hub immune-related genes (TFRC, SPP1, CAMP, CSF2, TUBB3, ZAP70, CHIT1, LEPR, DLL4, and DES) were selected to construct a novel signature. The risk score of this novel signature could be an independent prognostic factor in cervical cancer, which divided patients into high-risk and low-risk groups. The patients in high-risk groups showed significantly worse overall survival rates than those in low-risk groups in all training and validation cohorts (all P<0.05). A nomogram model was constructed based on the risk score of the novel signature and other clinical characteristics, which achieved the highest clinical net benefit across the entire range of reasonable threshold probabilities (concordance index=0.813). Furthermore, gene enrichment analysis revealed that the novel signature was closely related with immunology. The novel signature was negatively correlated with the infiltration of most immune cell types, especially T cell subsets (P<0.001). CONCLUSIONS The novel signature could comprehensively predict the prognosis and immune infiltration of cervical cancer. It may provide new insights for the precise treatment in cervical cancer.
Subject(s)
Uterine Cervical Neoplasms , Humans , Female , Uterine Cervical Neoplasms/genetics , Prognosis , Nomograms , Risk Factors , Databases, FactualABSTRACT
Notch3 can act as a tumor suppressor in the breast cancer epithelial cells. Unfortunately, Notch3 expression is decreased or lost, especially in triple-negative breast cancer (TNBC) cells, and the reasons remain unclear. Here, we found Notch3 was upregulated in MDA-MB-231 cells with 5-Aza treatment. Two CpG islands were observed in notch3 promoter. Interestingly, bisulfite sequencing exhibited that large amounts of unconverted cytosines were not only followed by guanine, but also adenine, cytosine and thymine, which implied that there simultaneously existed CpG and non-CpG methylation in notch3 promoter. To better analyze the methylation frequency of non-CpG locus, we designed CpG/non-CpG methylation analysis software. The results showed that the methylation frequency of notch3 gene in different breast cancer cell lines was in order T47D, MCF-7, SKBR3, BT-549 and MDA-MB-231. Furthermore, we identified that DNMT3b, DNMT1, DNMT3L, Mecp2 and EZH2 were important regulators of non-CpG locus of notch3 gene. Immunohistochemistry staining revealed a negative correlation between EZH2 and Notch3 from 22 luminal and 26 TNBC cases. In vitro methylation combined luciferase activity assays showed that non-CpG methylation was still crucial cause leading to notch3 transcriptional repression in TNBC. Our findings provide possible explanation for the downregulation or loss of Notch3 expression in TNBC.
Subject(s)
Epigenesis, Genetic , Gene Expression Regulation, Neoplastic , Promoter Regions, Genetic , Receptor, Notch3/genetics , Antimetabolites, Antineoplastic/pharmacology , Base Sequence , Cell Line, Tumor , CpG Islands , DNA (Cytosine-5-)-Methyltransferase 1/genetics , DNA (Cytosine-5-)-Methyltransferase 1/metabolism , DNA (Cytosine-5-)-Methyltransferases/genetics , DNA (Cytosine-5-)-Methyltransferases/metabolism , DNA Methylation/drug effects , Decitabine/pharmacology , Enhancer of Zeste Homolog 2 Protein/genetics , Enhancer of Zeste Homolog 2 Protein/metabolism , Female , Genes, Reporter , Humans , Luciferases/genetics , Luciferases/metabolism , MCF-7 Cells , Methyl-CpG-Binding Protein 2/genetics , Methyl-CpG-Binding Protein 2/metabolism , Receptor, Notch3/deficiency , Signal Transduction , Triple Negative Breast Neoplasms/genetics , Triple Negative Breast Neoplasms/metabolism , Triple Negative Breast Neoplasms/pathology , DNA Methyltransferase 3BABSTRACT
Adipocytes constitute a major component of the tumour microenvironment. Numerous studies have shown that adipocytes promote aggressiveness and invasion by stimulating cancer cells proliferation and modulating their metabolism. Herein, we reported that Notch3 promotes mouse 3T3-L1 pre-adipocytes differentiation by performing the integrative transcriptome and TMT-based proteomic analyses. The results revealed that aminoacyl-tRNA_biosynthesis pathway was significantly influenced with Nocth3 change during 3T3-L1 pre-adipocytes differentiation, and the expression of LARS in this pathway was positively correlated with Notch3. Published studies have shown that LARS is a sensor of leucine that regulates the mTOR pathway activity, and the latter involves in adipogenesis. We therefore supposed that Notch3 might promote 3T3-L1 pre-adipocytes differentiation by up-regulating LARS expression and activating mTOR pathway. CHIP and luciferase activity assay uncovered that Notch3 could transcriptionally regulate the expression of LARS gene. Oil Red staining identified a positive correlation between Notch3 expression and adipocytic differentiation. The activation of mTOR pathway caused by Notch3 overexpression could be attenuated by knocking down LARS expression. Altogether, our study revealed that Notch3 promotes adipocytic differentiation of 3T3-L1 pre-adipocytes cells by up-regulating LARS expression and activating the mTOR pathway, which might be an emerging target for obesity treatment.
Subject(s)
Adipocytes/cytology , Adipogenesis , Cell Differentiation , Gene Expression Regulation , Leucine-tRNA Ligase/metabolism , Receptor, Notch3/metabolism , TOR Serine-Threonine Kinases/metabolism , 3T3-L1 Cells , Adipocytes/metabolism , Animals , Biomarkers/analysis , Leucine-tRNA Ligase/genetics , Mice , Proteome/analysis , Receptor, Notch3/genetics , TOR Serine-Threonine Kinases/genetics , TranscriptomeABSTRACT
Driving behavior is the main basis for evaluating the performance of an unmanned vehicle. In simulation tests of unmanned vehicles, in order for simulation results to be approximated to the actual results as much as possible, model of driving behaviors must be able to exhibit actual motion of unmanned vehicles. We propose an automatic approach of simulating dynamic driving behaviors of vehicles in traffic scene represented by image sequences. The spatial topological attributes and appearance attributes of virtual vehicles are computed separately according to the constraint of geometric consistency of sparse 3D space organized by image sequence. To achieve this goal, we need to solve three main problems: Registration of vehicle in a 3D space of road environment, vehicle's image observed from corresponding viewpoint in the road scene, and consistency of the vehicle and the road environment. After the proposed method was embedded in a scene browser, a typical traffic scene including the intersections was chosen for a virtual vehicle to execute the driving tasks of lane change, overtaking, slowing down and stop, right turn, and U-turn. The experimental results show that different driving behaviors of vehicles in typical traffic scene can be exhibited smoothly and realistically. Our method can also be used for generating simulation data of traffic scenes that are difficult to collect.
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Road scene model construction is an important aspect of intelligent transportation system research. This paper proposes an intelligent framework that can automatically construct road scene models from image sequences. The road and foreground regions are detected at superpixel level via a new kind of random walk algorithm. The seeds for different regions are initialized by trapezoids that are propagated from adjacent frames using optical flow information. The superpixel level region detection is implemented by the random walk algorithm, which is then refined by a fast two-cycle level set method. After this, scene stages can be specified according to a graph model of traffic elements. These then form the basis of 3D road scene models. Each technical component of the framework was evaluated and the results confirmed the effectiveness of the proposed approach.
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As a special biofilm structure, microbial attachment is believed to play an important role in the granulation of aerobic granular activated sludge (AGAS). This experiment was to investigate the biological effect of Ca(2+), Mg(2+), Cu(2+), Fe(2+), Zn(2+), and K(+) which are the most common ions present in biological wastewater treatment systems, on the microbial attachment of AGAS and flocculent activated sludge (FAS), from which AGAS is always derived, in order to provide a new strategy for the rapid cultivation and stability control of AGAS. The result showed that attachment biomass of AGAS was about 300% higher than that of FAS without the addition of metal ions. Different metal ions had different effects on the process of microbial attachment. FAS and AGAS reacted differently to the metal ions as well, and in fact, AGAS was more sensitive to the metal ions. Specifically, Ca(2+), Mg(2+), and K(+) could increase the microbial attachment ability of both AGAS and FAS under appropriate concentrations, Cu(2+), Fe(2+), and Zn(2+) were also beneficial to the microbial attachment of FAS at low concentrations, but Cu(2+), Fe(2+), and Zn(2+) greatly inhibited the attachment process of AGAS even at extremely low concentrations. In addition, the acylated homoserine lactone (AHL)-based quorum sensing system, the content of extracellular polymeric substances and the relative hydrophobicity of the sludges were greatly influenced by metal ions. As all these parameters had close relationships with the microbial attachment process, the microbial attachment may be affected by changes of these parameters.
Subject(s)
Metals/toxicity , Waste Disposal, Fluid/methods , Water Pollutants, Chemical/toxicity , Acyl-Butyrolactones , Aerobiosis/drug effects , Flocculation , Ions , Quorum Sensing , Sewage/chemistry , WastewaterABSTRACT
Müller cells can completely repair retinal injury by acting as endogenous stem/progenitor cells in lower-order vertebrates. However, a safe and effective approach to activate progenitor potential of retinal Müller cells in higher-order vertebrates, which rarely re-enter the cell cycle, is a bottleneck problem. In the present study, Royal College of Surgeon's (RCS) rats were subjected to rat bone marrow mesenchymal stem cells (rBMSCs) subretinal space transplantation. Electroretinography (ERG) recordings showed that the b-wave amplitudes and ONL thicknesses statistically increased after transplantation. The number of Müller cells expressing proliferative, stem/progenitor and neuronal markers significantly increased after rBMSCs transplantation in vivo or after co-culturing with rBMSCs in vitro. The cultured rBMSCs could secrete nerve growth factor (NGF). In addition, we confirmed that NGF or NGF-neutralizing antibody could activate or depress Müller cells dedifferentiation, both in vivo and in vitro. Furthermore, Müller cells expressing high levels of the NGF receptor neurotrophic tyrosine kinase receptor type 1 (TrkA) were observed in the retinas of rats transplanted with rBMSCs. Moreover, the protein expression of downstream elements of NGF/TrkA signaling, such as p-PI3K, p-Akt and p-CREB, increased in Müller cells in the retinas of rBMSCs-treated rats in vivo or in Müller cells co-cultured with rBMSCs in vitro. Blocking TrkA with K-252a reduced the number of dedifferentiated Müller cells and the expression of NGF/TrkA signaling in vitro. Thus, rBMSCs might initiate endogenous regenerative mechanisms, which may constitute a new therapeutic strategy for retinal dystrophic diseases.
Subject(s)
Bone Marrow Cells/cytology , Ependymoglial Cells/physiology , Mesenchymal Stem Cell Transplantation , Nerve Growth Factor/physiology , Receptor, trkA/physiology , Retinitis Pigmentosa/surgery , Signal Transduction/physiology , Analysis of Variance , Animals , Blotting, Western , Cell Differentiation/physiology , Disease Models, Animal , Electroretinography , Enzyme-Linked Immunosorbent Assay , Rats , Real-Time Polymerase Chain Reaction , Retinitis Pigmentosa/pathology , Retinitis Pigmentosa/physiopathology , Visual Perception/physiologyABSTRACT
N-acyl homoserine lactone (AHL)-based quorum sensing (QS) has been recognized to play an important role in the formation of biofilm. However, aerobic granular sludge is considered as a special biofilm, and its biological implication and role of AHL-based QS still remain unclear. This study investigated the role of AHL-based QS in aerobic granulation. Results showed that AHLs were necessary to the typical aerobic granulation, and AHL-associated coordination of bacteria in sludge aggregation was sludge density dependent only when it reached a threshold of 1.010 g/mL; AHL-based QS was activated to regulate aerobic granulation. Furthermore, a quorum quenching method was firstly adopted to investigate the role of AHLs in aerobic granules. Results showed inhibition of AHL by acylase that reduced the AHL content in aerobic granules and further weakened its attachment potential, which proved that AHLs play an important role in the formation of aerobic granules. Additionally, the assay of quorum quenching not only proved that AHL-based QS could regulate EPS production but also provided additional evidence for the role of AHLs in aerobic granulation by regulating EPS content and its component proportion.
Subject(s)
Acyl-Butyrolactones/metabolism , Bacteria/drug effects , Bacteria/growth & development , Bacterial Physiological Phenomena , Quorum Sensing , Sewage/microbiology , Aerobiosis , Bacteria/metabolism , Biofilms/drug effects , Biofilms/growth & developmentABSTRACT
The present study investigated the relationship between N-acyl-homoserine lactone (AHL)-based quorum sensing (QS) and the physico-chemical properties of aerobic granules. Stable mature granules were observed in SBR2 and SBR3 with average diameters of 0.96, and 1.49 mm, respectively. The sludge densities of aerobic granules in SBR2 and SBR3 were 1.0246, and 1.0201 g/mL, respectively, which were higher than that of flocculent sludge in SBR1 (1.0065 g/mL). The results showed that the activity of AHL-based QS in SBR2 and SBR3 amounted to 2.4- and 2.1-fold induction, however, that in SBR1 with flocculent sludge was 1.6-fold induction. In addition, the results also showed that the activity of AHL-based QS in the three reactors rose in the feast condition, and then dropped with the consumption of substrate. However, the activity of AHL-based QS in these three reactors recovered again in prolonged starvation. Furthermore, the results showed that the enhancement of AHL-based QS favored the extracellular polymeric substance production of microorganisms in activated sludge. Thus, it could be concluded that aerobic granules showed higher AHL-based QS than flocculent sludge, which resulted from the higher sludge density of aerobic granules than flocculent sludge. AHL-based QS was related to the metabolism energy in the feast condition; however, in prolonged starvation, microorganisms would emit more AHL-like molecules to protect themselves to resist starvation. Moreover, the enhancement of AHL-based QS favored the EPS component productivity of the microorganisms in activated sludge, which contributed to maintain the aerobic granular structure.
Subject(s)
Acyl-Butyrolactones/chemistry , Bacteria/isolation & purification , Quorum Sensing/physiology , Aerobiosis , SewageABSTRACT
While breast cancer treatments have advanced significantly nowadays, yet metastatic, especially triple-negative breast cancer (TNBC), remains challenging with low survival. Cancer immunotherapy, a promising approach for HER2-positive and TNBC, still faces resistance hurdles. Recently, numerous studies have set their sights on the resistance of immunotherapy for breast cancer. Our study provides a thorough comprehension of the current research landscape, hotspots, and emerging breakthroughs in this critical area through a meticulous bibliometric analysis. As of March 26, 2024, a total of 1341 articles on immunology resistance in breast cancer have been gathered from Web of Science Core Collection, including 765 articles and 576 reviews. Bibliometrix, CiteSpace and VOSviewer software were utilized to examine publications and citations per year, prolific countries, contributive institutions, high-level journals and scholars, as well as highly cited articles, references and keywords. The research of immunotherapy resistance in breast cancer has witnessed a remarkable surge over the past seven years. The United States and China have made significant contributions, with Harvard Medical School being the most prolific institution and actively engaging in collaborations. The most contributive author is Curigliano, G from the European Institute of Oncology in Italy, while Wucherpfennig, K. W. from the Dana-Farber Cancer Institute in the USA, had the highest citations. Journals highly productive primarily focus on clinical, immunology and oncology research. Common keywords include "resistance", "expression", "tumor microenvironment", "cancer", "T cell", "therapy", "chemotherapy" and "cell". Current research endeavors to unravel the mechanisms of immune resistance in breast cancer through the integration of bioinformatics, basic experiments, and clinical trials. Efforts are underway to develop strategies that improve the effectiveness of immunotherapy, including the exploration of combination therapies and advancements in drug delivery systems. Additionally, there is a strong focus on identifying novel biomarkers that can predict patient response to immunology. This study will provide researchers with an up-to-date overview of the present knowledge in drug resistance of immunology for breast cancer, serving as a valuable resource for informed decision-making and further research on innovative approaches to address immunotherapy resistance.
Subject(s)
Bibliometrics , Breast Neoplasms , Drug Resistance, Neoplasm , Immunotherapy , Female , Humans , Breast Neoplasms/immunology , Breast Neoplasms/therapy , Breast Neoplasms/drug therapy , Immunotherapy/methodsABSTRACT
Melanoma is a highly malignant form of skin cancer that typically originates from abnormal melanocytes. Despite significant advances in treating metastatic melanoma with immune checkpoint blockade (ICB) therapy, a substantial number of patients do not respond to this treatment and face risks of recurrence and metastasis. This study collected data from multiple datasets, including cohorts from Riaz et al., Gide et al., MGH, and Abril-Rodriguez et al., focusing on on-treatment samples during ICB therapy. We used the single-sample gene set enrichment analysis (ssGSEA) method to calculate immunogenic cell death scores (ICDS) and employed an elastic network algorithm to construct a model predicting ICB efficacy. By analyzing 18 ICD gene signatures, we identified 9 key ICD gene signatures that effectively predict ICB treatment response for on-treatment metastatic melanoma specimens. Results showed that patients with high ICD scores had significantly higher response rates to ICB therapy compared to those with low ICD scores. ROC analysis demonstrated that the AUC values for both the training and validation sets were around 0.8, indicating good predictive performance. Additionally, survival analysis revealed that patients with high ICD scores had longer progression-free survival (PFS). This study used an elastic network algorithm to identify 9 ICD gene signatures related to the immune response in metastatic melanoma. These gene features can not only predict the efficacy of ICB therapy but also provide references for clinical decision-making. The results indicate that ICD plays an important role in metastatic melanoma immunotherapy and that expressing ICD signatures can more accurately predict ICB treatment response and prognosis for on-treatment metastatic melanoma specimens, thus providing a basis for personalized treatment.
Subject(s)
Immune Checkpoint Inhibitors , Immunogenic Cell Death , Melanoma , Humans , Melanoma/drug therapy , Melanoma/mortality , Melanoma/pathology , Melanoma/immunology , Melanoma/genetics , Immune Checkpoint Inhibitors/therapeutic use , Immune Checkpoint Inhibitors/pharmacology , Immunogenic Cell Death/drug effects , Skin Neoplasms/drug therapy , Skin Neoplasms/pathology , Skin Neoplasms/mortality , Skin Neoplasms/immunology , Skin Neoplasms/genetics , Neoplasm Metastasis , Gene Expression Profiling , Biomarkers, Tumor/genetics , Gene Expression Regulation, Neoplastic , Transcriptome , PrognosisABSTRACT
Background: Insulin-like growth factor binding protein 5 (IGFBP5) is highly expressed in multiple human cancers, including glioma. Despite this, it remains unclear what role it plays in glioma. The aim of the present study was to analyze whether IGFBP5 could be used as a predictor of prognosis and immune infiltration in glioma. Methods: Glioma patients' clinical information was collected from the Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA), Rembrandt, and Gravendeel databases. The diagnostic and prognostic roles of IGFBP5 were assessed by the Kaplan-Meier survival curves, diagnostic receiver operating characteristic (ROC) curves, nomogram model, Cox regression analysis and Enrichment analysis by R software. Moreover, the correlation between IGFBP5 expression and immune cell infiltration, and immune checkpoint genes was conducted. Immunohistochemistry staining, CCK8, colony formation, scratch and transwell assays and western blot were used to interrogate the expression and function of IGFBP5 in glioma. Results: IGFBP5 levels were obviously increased in glioma with higher malignancy and predicted poor outcomes by Univariate and multivariate Cox analysis. The biological function analysis revealed that IGFBP5 correlated closely with immune signatures. Moreover, IGFBP5 expression was associated with tumor infiltration of B cells, T cells, macrophages, and NK cells. IGFBP5 affected glioma cell proliferation, migration, and invasion probably involved in the epithelial-to-mesenchymal transition (EMT) and Hippo-YAP signaling pathway. Further study showed that IGFBP5 induced the expression of PD-L1 and CXCR4. Conclusions: IGFBP5 as an oncogene is a useful biomarker of prognosis and correlates with progression and immune infiltration in glioma.
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Topological insulators (TI) and magnetic topological insulators (MTI) can apply highly efficient spin-orbit torque (SOT) and manipulate the magnetization with their unique topological surface states (TSS) with ultrahigh efficiency. Here, efficient SOT switching of a hard MTI, V-doped (Bi,Sb)2Te3 (VBST), with a large coercive field that can prevent the influence of an external magnetic field, is demonstrated. A giant switched anomalous Hall resistance of 9.2 kΩ is realized, among the largest of all SOT systems, which makes the Hall channel a good readout and eliminates the need to fabricate complicated magnetic tunnel junction (MTJ) structures. The SOT switching current density can be reduced to 2.8 × 105 A cm-2, indicating its high efficiency. Moreover, as the Fermi level is moved away from the Dirac point by both gate and composition tuning, VBST exhibits a transition from edge-state-mediated to surface-state-mediated transport, thus enhancing the SOT effective field to (1.56 ± 0.12) × 10-6 T A-1 cm2 and the interfacial charge-to-spin conversion efficiency to 3.9 ± 0.3 nm-1. The findings establish VBST as an extraordinary candidate for energy-efficient magnetic memory devices.
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The Notch pathway plays a pivotal role in regulating cell fate decisions in many stem cell systems. However, the full repertoire of Notch target genes in vivo and the mechanisms through which this pathway activity is integrated with other signaling pathways are largely unknown. Here, we report a transgenic mouse in which the activation of the Notch pathway massively expands the neural stem cell (NSC) pool in a cell context-dependent manner. Using this in vivo system, we identify direct targets of RBPJ/N1ICD in cortical NSCs at a genome-wide level through combined ChIP-Seq and transcriptome analyses. Through a highly conservative analysis of these datasets, we identified 98 genes that are directly regulated by N1ICD/RPBJ in vivo. These include many transcription factors that are known to be critical for NSC self-renewal (Sox2, Pax6, Tlx, and Id4) and the transcriptional effectors of the Wnt, SHH, and Hippo pathways, TCF4, Gli2, Gli3, Yap1, and Tead2. Since little is known about the function of the Hippo-Yap pathway in NSCs, we analyzed Yap1 expression and function in NSCs. We show that Yap1 expression is restricted to the stem cell compartment in the developing forebrain and that its expression is sufficient to rescue Notch pathway inhibition in NSC self-renewal assays. Together, results of this study reveal a previously underappreciated complexity and breadth of Notch1 targets in vivo and show direct interaction between Notch and Hippo-Yap pathways in NSCs.
Subject(s)
Gene Expression Regulation , Genome/genetics , Hedgehog Proteins/genetics , Immunoglobulin J Recombination Signal Sequence-Binding Protein/metabolism , Protein Serine-Threonine Kinases/metabolism , Receptor, Notch1/metabolism , Wnt Proteins/genetics , Adaptor Proteins, Signal Transducing/metabolism , Animals , Cell Cycle Proteins , Cell Division , Cell Proliferation , Chromatin Immunoprecipitation , Hedgehog Proteins/metabolism , Mice , Neural Stem Cells , Phenotype , Phosphoproteins/metabolism , Protein Structure, Tertiary , Receptor, Notch1/chemistry , Signal Transduction , Stem Cells/cytology , Transcription, Genetic , Transcriptome/genetics , Wnt Proteins/metabolism , YAP-Signaling ProteinsABSTRACT
Wild, edible plants have received increasing attention as an important complement to cultivate vegetables, as they represent an easily accessible source of nutrients, mineral elements, and antioxidants. In this study, the tender stems and leaves of Gonostegia hirta, an edible species for which only scarce data are available in the literature, are thoroughly evaluated for their nutritional profile, chemical characterization, and antioxidant activity. Being considered as an underexploited, potentially edible plant, the nutritional composition of Gonostegia hirta was identified, and several beneficial compounds were highlighted: sugars, potassium, calcium, organic acids, fatty acids, phenolics, and flavonoids. A total of 418 compounds were identified by metabolomic analysis, including phenolic acids, flavonoids, amino acids, lipids, organic acids, terpenoids, alkaloids, nucleotides, tannins, lignans, and coumarin. The plant sample was found to have good antioxidant capacities, presented by DPPH, FRAP, ABTS+, hydroxyl radical scavenging capacity, and its resistance to the superoxide anion radical test. In general, Gonostegia hirta has a good nutritional and phytochemical composition. The health benefits of Gonostegia hirta as a vegetable and herbal medicine is important for both a modern diet and use in medication.
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Turnip (Brassica rapa subsp. rapa) is a cruciferous plant cultivated worldwide that serves as a source of nutrients and bioactive compounds. Most turnip studies have focused on a few compounds or on part of the plant. The establishment of a complete chemical profile of different plant parts would facilitate its use for nutritional and medicinal purposes. In the current study, mineral elements, soluble sugars, free amino acids (FAA), total phenols (TP), total flavonoids (TF), and glucosinolates (GS) were quantified in the leaves, stems, and roots. Results were compared for 20 strains of turnip. The outcomes showed significant differences between parts of the plant and strains. The leaves exhibited the highest TF, TP, indispensable FAA, and microelement levels, and they showed a higher GS. Moreover, the stems had a high content of GS and macroelements. Furthermore, the roots showed high levels of free sugars and total FAA. The findings of this work provide the basis for utilizing each part of the turnip plant based on its chemical composition.
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Compositional, functional, and nutritional properties are important for the use-value assessments of wild and cultivated edible plants. The aim of this study was to compare the nutritional composition, bioactive compounds, volatile compounds, and potential biological activities of cultivated and wild Zingiber striolatum. Various substances, such as soluble sugars, mineral elements, vitamins, total phenolics, total flavonoids, and volatiles, were measured and analyzed using UV spectrophotometry, ICP-OES, HPLC, and GC-MS methods. The antioxidant capacity of a methanol extract of Z. striolatum, as well as the hypoglycemic abilities of its ethanol and water extracts, were tested. The results showed that the contents of soluble sugar, soluble protein, and total saponin in the cultivated samples were higher, while the wild samples contained higher amounts of K, Na, Se, vitamin C, and total amino acids. The cultivated Z. striolatum also showed a higher antioxidant potential, while the wild Z. striolatum exhibited a better hypoglycemic activity. Thirty-three volatile compounds were identified using GC-MS in two plants, with esters and hydrocarbons being the main volatile compounds. This study demonstrated that both cultivated and wild Z. striolatum have a good nutritional value and biological activity, and can be used as a source of nutritional supplementation or even in medication.
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Breast cancer (BC) and Alzheimer's disease (AD) have pronounced female-to-male disparities and both are the major causes of death in elderly women. Intriguingly, there is an inverse incidence between BC and AD. In our previous study, we found that the expression of ARSD, a female-biased gene on chromosome Xp22.3 that encodes arylsulfatase D, is significantly downregulated in triple-negative breast cancer (TNBC) cells and tissue samples, and that ectopic ARSD overexpression could inhibit proliferation and migration of BC cells. However, the exact mechanism remains unclear. In this study, ARSD-overexpressing MDA-MB-231 cell strains were established. RNA-Seq and qRT-PCR validation were performed followed by GO and KEGG analyses. Transcriptome sequencing unveiled that Alzheimer's/Parkinson's/prion diseases were enriched in ARSD overexpressing BC cells. Besides, the top enriched pathways included lipoprotein/cholesterol metabolism, molecular chaperone and misfolding protein binding, mitochondrial respiration, dysfunction of lysosomes, etc. In which, a battery of genes, e.g., SERF1A, APOE, CD36 etc., were upregulated, while a series of genes, e.g., NDUFA11, NDUFS3, NDUFV1, etc. were downregulated, which were closely related to amyloidosis. The amyloidosis of BC cells and nerval cells caused by ARSD overexpression was verified with western blotting, immunohistochemical and Congo red staining. Collectively, downregulated ARSD may be closely associated with BC, and upregulated ARSD may cause amyloidosis of BC cells. Our findings suggest that ARSD deserves to be considered a new promising target for treating TNBC or for AD.
Subject(s)
Amyloidosis , Breast Neoplasms , Carcinoma , Triple Negative Breast Neoplasms , Aged , Breast Neoplasms/genetics , Cell Line, Tumor , Cell Proliferation , Epithelial Cells/pathology , Female , Humans , Male , Nerve Tissue Proteins , Transcription Factors , Triple Negative Breast Neoplasms/genetics , Triple Negative Breast Neoplasms/pathologyABSTRACT
Okra is a kind of flavonoid-rich food which was reported to have a variety of health functions. Flavonoids are the major polyphenolic compounds in okra and are thought to play a role in reducing the risk of disease. The aim of this study was to isolate and identify the flavonoids composition in okra pods and explore the activity of the main flavonoids components identified on inhibiting tumor cell proliferation in vitro. Six individual flavonoids were identified by HPLC-MS/MS: quercetin-3-gentiobioside (Q3G), quercetin-3-sambubioside (Q3S), rutin, quercetin-7-glucoside (Q7G), isoquercitrin (ISO) and quercetin-3-malonylglucoside (Q3M), which were all separated well within 30 min. The analytical method was validated by the recovery of spiked samples and so on. Moreover, four main flavonoids components, namely Q3G, Q3S, ISO and Q3M, exhibited significant (p < 0.05) inhibition of NCI-N87, A375, A549 cells proliferation (25−100 µmol/L) and of HFLS-RA (200−300 µmol/L) in different levels, according to MTT method, respectively. It is demonstrated that the flavonoids components of okra exhibited a noteworthy development prospect as a possible nutraceutical dietary supplement.