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Single-cell RNA sequencing (scRNA-seq) has emerged as a powerful tool for investigating cellular heterogeneity through high-throughput analysis of individual cells. Nevertheless, challenges arise from prevalent sequencing dropout events and noise effects, impacting subsequent analyses. Here, we introduce a novel algorithm, Single-cell Gene Importance Ranking (scGIR), which utilizes a single-cell gene correlation network to evaluate gene importance. The algorithm transforms single-cell sequencing data into a robust gene correlation network through statistical independence, with correlation edges weighted by gene expression levels. We then constructed a random walk model on the resulting weighted gene correlation network to rank the importance of genes. Our analysis of gene importance using PageRank algorithm across nine authentic scRNA-seq datasets indicates that scGIR can effectively surmount technical noise, enabling the identification of cell types and inference of developmental trajectories. We demonstrated that the edges of gene correlation, weighted by expression, play a critical role in enhancing the algorithm's performance. Our findings emphasize that scGIR outperforms in enhancing the clustering of cell subtypes, reverse identifying differentially expressed marker genes, and uncovering genes with potential differential importance. Overall, we proposed a promising method capable of extracting more information from single-cell RNA sequencing datasets, potentially shedding new lights on cellular processes and disease mechanisms.
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Redes Reguladoras de Genes , Análisis de la Célula Individual , Análisis de Secuencia de ARN/métodos , Análisis de la Célula Individual/métodos , Algoritmos , Análisis por Conglomerados , Perfilación de la Expresión Génica/métodosRESUMEN
Although tyrosine kinase inhibitor (TKI) therapy has markedly improved the survival of people with chronic-phase chronic myeloid leukemia (CML), 20-30% of people still experienced therapy failure. Data from 1,955 consecutive subjects with chronic-phase CML diagnosed by the European LeukemiaNet (ELN) recommendations from 1 center receiving initial TKI imatinib or a second-generation (2G-) TKI therapy were interrogated to develop a clinical prediction model for TKI therapy failure. This model was subsequently validated in 3,454 subjects from 76 other centers. Using the predictive clinical co-variates associated with TKI therapy failure, we developed a model that stratified subjects into low-, intermediate- and high-risk subgroups with significantly different cumulative incidences of therapy failure (p < 0.001). There was good discrimination and calibration in the external validation dataset, and the performance was consistent with that of the training dataset. Our model had the better prediction discrimination than the Sokal and ELTS scores did, with the greater time-dependent area under the receiver-operator characteristic curve (AUROC) values and a better ability to re-defined the risk of therapy failure. Our model could help physicians estimate the likelihood of initial imatinib or 2G-TKI therapy failure in people with chronic-phase CML.
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Inferring the developmental potential of single cells from scRNA-Seq data and reconstructing the pseudo-temporal path of cell development are fundamental but challenging tasks in single-cell analysis. Although single-cell transcriptional diversity (SCTD) measured by the number of expressed genes per cell has been widely used as a hallmark of developmental potential, it may lead to incorrect estimation of differentiation states in some cases where gene expression does not decrease monotonously during the development process. In this study, we propose a novel metric called single-cell transcriptional complexity (SCTC), which draws on insights from the economic complexity theory and takes into account the sophisticated structure information of scRNA-Seq count matrix. We show that SCTC characterizes developmental potential more accurately than SCTD, especially in the early stages of development where cells typically have lower diversity but higher complexity than those in the later stages. Based on the SCTC, we provide an unsupervised method for accurate, robust, and transferable inference of single-cell pseudotime. Our findings suggest that the complexity emerging from the interplay between cells and genes determines the developmental potential, providing new insights into the understanding of biological development from the perspective of complexity theory.
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Análisis de la Célula Individual , Análisis de la Célula Individual/métodos , Animales , Diferenciación Celular/genética , Ratones , Transcripción Genética , Regulación del Desarrollo de la Expresión Génica , Perfilación de la Expresión Génica/métodos , Algoritmos , Humanos , Análisis de Secuencia de ARN/métodosRESUMEN
Exploration of multifunctional integrated catalysts is of great significance for photocatalysis toward practical application. Herein, a 1D confined nanoreactor with a heterogeneous core-shell structure is designed for synergies of efficient catalysis and temperature monitoring by custom encapsulation of Z-scheme heterojunction CuS quantum dots/BiVO4 (CuS QDs/BiVO4) and Y2O2S-Er, Yb. The dispersed active sites created by the QDs with high surface energy improve the mass transfer efficiency, and the efficient electron transport channels at the heterogeneous interface extend the carrier lifetime, which endows the nanoreactor with excellent catalytic performance. Meanwhile, real-time temperature monitoring is realized based on the thermally coupled levels 2H11/2/4S3/2â4I15/2 of Er3+ using fluorescence intensity ratio, which enables the monitorable photocatalysis. Furthermore, the nanoreactor with a multidimensional structure increases effective intermolecular collisions to facilitate the catalytic process by restricting the reaction within distinct enclosed spaces and circumvents potential unknown interaction effects. The design of multi-space nanoconfined reactors opens up a new avenue to modulate catalyst function, providing a unique perspective for photocatalytic applications in the mineralization of organic pollutants, hydrogen production, and nitrogen fixation.
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Marangoni actuators that are propelled by surface tension gradients hold significant potential in small-scale swimming robots. Nevertheless, the release of "fuel" for conventional chemical Marangoni actuators is not easily controllable, and the single swimming function also limits application areas. Constructing controllable Marangoni robots with multifunctions is still a huge challenge. Herein, inspired by water striders, electricity-driven strategies are proposed for a multifunctional swimming Marangoni robot (MSMR), which is fabricated by super-aligned carbon nanotube (SACNT) and polyimide (PI) composite. The MSMR consists of a Marangoni actuator and air-ambient actuators. Owing to the temperature gradient generated by the electrical stimulation on the water surface, the Marangoni actuators can swim controllably with linear, turning, and rotary motions, mimicking the walking motion of water striders. In addition, the Marangoni actuators can also be driven by light. Importantly, the air-ambient actuators fabricated by SACNT/PI bilayer structures demonstrate the function of grasping objects on the water surface when electrically Joule-heated, mimicking the predation behavior of water striders. With the synergistic effect of the Marangoni actuator and air-ambient actuators, the MSMR can navigate mazes with tunnels and grasp objects. This research will provide a new inspiration for smart actuators and swimming robots.
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BACKGROUND: SERPINB2, a biomarker of Type-2 (T2) inflammatory processes, has been described in the context of asthma. Chronic rhinosinusitis with nasal polyps (CRSwNP) is also correlated with T2 inflammation and elevated 15LO1 induced by IL-4/13 in nasal epithelial cells. The aim of this study was to evaluate the expression and location of SERPINB2 in nasal epithelial cells (NECs) and determine whether SERPINB2 regulates 15LO1 and downstream T2 markers in NECs via STAT6 signalling. METHODS: SERPINB2 gene expression in bulk and single-cell RNAseq database was analysed by bioinformatics analysis. SERPINB2, 15LO1 and other T2 markers were evaluated from CRSwNP and HCs NECs. The colocalization of SERPINB2 and 15LO1 was evaluated by immunofluorescence. Fresh NECs were cultured at an air-liquid interface with or without IL-13, SERPINB2 Dicer-substrate short interfering RNAs (DsiRNAs) transfection, exogenous SERPINB2, 15-HETE recombinant protein and pSTAT6 inhibitors. 15LO1, 15-HETE and downstream T2 markers were analysed by qRT-PCR, western blot and ELISA. RESULTS: SERPINB2 expression was increased in eosinophilic nasal polyps compared with that in noneosinophilic nasal polyps and control tissues and positively correlated with 15LO1 and other downstream T2 markers. SERPINB2 was predominantly expressed by epithelial cells in NP tissue and was colocalized with 15LO1. In primary NECs in vitro, SERPINB2 expression was induced by IL-13. Knockdown or overexpression SERPINB2 decreased or enhanced expression of 15LO1 and 15-HETE in NECs, respectively, in a STAT6-dependent manner. SERPINB2 siRNA also inhibited the expression of the 15LO1 downstream genes, such as CCL26, POSTN and NOS2. STAT6 inhibition similarly decreased SERPINB2-induced 15LO1. CONCLUSIONS: SERPINB2 is increased in NP epithelial cells of eosinophilic CRSwNP (eCRSwNP) and contributes to T2 inflammation via STAT6 signalling. SERPINB2 could be considered a novel therapeutic target for eCRSwNP.
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Células Epiteliales , Pólipos Nasales , Rinitis , Factor de Transcripción STAT6 , Transducción de Señal , Sinusitis , Humanos , Factor de Transcripción STAT6/metabolismo , Factor de Transcripción STAT6/genética , Pólipos Nasales/metabolismo , Pólipos Nasales/patología , Pólipos Nasales/inmunología , Sinusitis/metabolismo , Sinusitis/patología , Sinusitis/inmunología , Rinitis/metabolismo , Rinitis/patología , Enfermedad Crónica , Células Epiteliales/metabolismo , Inhibidor 2 de Activador Plasminogénico/metabolismo , Inhibidor 2 de Activador Plasminogénico/genética , Femenino , Masculino , Quimiocina CCL26/metabolismo , Quimiocina CCL26/genética , Adulto , Persona de Mediana Edad , Eosinofilia/metabolismo , Eosinofilia/patología , Mucosa Nasal/metabolismo , Mucosa Nasal/patología , Mucosa Nasal/inmunología , Regulación de la Expresión Génica , RinosinusitisRESUMEN
To evaluate the efficacy and safety of flumatinib in the later-line treatment of Chinese patients with Philadelphia chromosome-positive chronic-phase chronic myeloid leukemia (CP-CML previously treated with tyrosine kinase inhibitors (TKIs). Patients with CML-CP were evaluated for the probabilities of responses including complete hematologic response (CHR), cytogenetic response, and molecular response (MR) and adverse events (AEs) after the later-line flumatinib therapy. Of 336 enrolled patients with median age 50 years, median duration of treatment with flumatinib was 11.04 (2-25.23) months. Patients who achieved clinical responses at baseline showed maintenance of CHR, complete cytogenetic response (CCyR)/2-log molecular response (MR2), major molecular response (MMR), and 4-log molecular response or deep molecular response (MR4/DMR) in 100%, 98.9%, 98.6%, and 92.9% patients, respectively. CHR, CCyR/MR2, MMR, and MR4/DMR responses were achieved in 86.4%, 52.7%, 49.6%, and 23.5% patients respectively, which showed the lack of respective clinical responses at baseline. The patients without response at baseline, treated with flumatinib as 2L TKI, having no resistance to prior TKI or only resistance to imatinib, with response to last TKI, and with BCR::ABL ≤10% had higher CCyR/MR2, MMR, or MR4/DMR. The AEs observed during the later-line flumatinib treatment were tolerable and consistent with those reported with the first-line therapy. Flumatinib was effective and safe in patients who are resistant or intolerant to other TKIs. In particular, 2L flumatinib treatment induced high response rates and was more beneficial to patients without previous 2G TKI resistance, thus serving as a probable treatment option for these patients.
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Quantum entanglement marks a definitive feature of topological states. However, the entanglement spectrum remains insufficiently explored for topological states without a bulk energy gap. Using a combination of field theory and numerical techniques, we accurately calculate and analyze the entanglement spectrum of gapless symmetry protected topological states in one dimension. We highlight that the universal entanglement spectrum not only encodes the nontrivial edge degeneracy, generalizing the Li-Haldane conjecture to gapless topological states, but also contains the operator content of the underlying boundary conformal field theory. This implies that the bulk wave function can act as a fingerprint of both quantum criticality and topology in gapless symmetry protected topological states. We also identify a symmetry enriched conformal boundary condition that goes beyond the conventional conformal boundary condition.
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BACKGROUND: Inaccurate Forrest classification may significantly affect clinical outcomes, especially in high risk patients. Therefore, this study aimed to develop a real-time deep convolutional neural network (DCNN) system to assess the Forrest classification of peptic ulcer bleeding (PUB). METHODS: A training dataset (3868 endoscopic images) and an internal validation dataset (834 images) were retrospectively collected from the 900th Hospital, Fuzhou, China. In addition, 521 images collected from four other hospitals were used for external validation. Finally, 46 endoscopic videos were prospectively collected to assess the real-time diagnostic performance of the DCNN system, whose diagnostic performance was also prospectively compared with that of three senior and three junior endoscopists. RESULTS: The DCNN system had a satisfactory diagnostic performance in the assessment of Forrest classification, with an accuracy of 91.2% (95%CI 89.5%-92.6%) and a macro-average area under the receiver operating characteristic curve of 0.80 in the validation dataset. Moreover, the DCNN system could judge suspicious regions automatically using Forrest classification in real-time videos, with an accuracy of 92.0% (95%CI 80.8%-97.8%). The DCNN system showed more accurate and stable diagnostic performance than endoscopists in the prospective clinical comparison test. This system helped to slightly improve the diagnostic performance of senior endoscopists and considerably enhance that of junior endoscopists. CONCLUSION: The DCNN system for the assessment of the Forrest classification of PUB showed satisfactory diagnostic performance, which was slightly superior to that of senior endoscopists. It could therefore effectively assist junior endoscopists in making such diagnoses during gastroscopy.
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Úlcera Péptica Hemorrágica , Humanos , Úlcera Péptica Hemorrágica/diagnóstico , Úlcera Péptica Hemorrágica/clasificación , Estudios Retrospectivos , Masculino , Persona de Mediana Edad , Femenino , Inteligencia Artificial , Redes Neurales de la Computación , Curva ROC , Estudios Prospectivos , Anciano , Grabación en Video , Gastroscopía/métodos , Reproducibilidad de los Resultados , AdultoRESUMEN
Developing efficient catalysts to degrade pollutants in water is a very important way to alleviate water pollution. However, it is crucial but challenging to broaden the functions of conventional photocatalysts and improve their environmental adaptability. In this paper, Bi(Er3+/Yb3+)OBr/polyacrylonitrile (BOB-EY/PAN) composite fibers with a swallowed-embedded structure assembled with nanopetal-rich microflowers were designed and fabricated, integrating photocatalytic and temperature-monitoring functions simultaneously. Their unique structure brings a large specific surface area, and the doping of rare earth ions improves the separation efficiency of electron-hole pairs, which enhances the photocatalytic efficiency and endows the fibers with a temperature-monitoring function at the same time. Under simulated sunlight irradiation, the nanofibers show a maximum degradation efficiency of 99.2% for tetracycline hydrochloride (TC) with a degradation constant of K as high as 0.078 min-1. Based on the fluorescence intensity ratio (FIR), the two thermally coupled levels of Er3+ in the nanofibers, 2H11/2 and 4S3/2, provide real-time temperature feedback, displaying a maximum relative sensitivity as high as 0.0215 K-1 at 303 K. Dual-functional BOB-EY/PAN composite nanofibers show great potential for industrial wastewater disposition, providing solutions for wastewater purification in special scenarios.
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An efficient, practical, and metal-free protocol for the synthesis of silicon-containing isoindolin-1-ones and deuterated analogues via the synergistic combination of an organic photoredox and hydrogen atom transfer process is described. This strategy features mild reaction conditions, high atom economy, and excellent functional group compatibility, delivering a myriad of structurally diverse and valuable products with good to excellent yields.
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Cancer treatment has faced severe obstacles due to the smart biological system of cancer cells. Herein, we report a three-in-one agent Ir-CA via attenuation of cancer cell stemness with the down-regulated biomarker CD133 expression from the mitochondria-directed chemotherapy. Over 80% of Ir-CA could accumulate in mitochondria, result in severe mitochondrial dysfunctions, and subsequently initiate mitophagy and cell cycle arrest to kill cisplatin-resistant A549R cells. In vitro and in vivo antimetastatic experiments demonstrated that Ir-CA can effectively inhibit metastasis with down-regulated MMP-2/MMP-9. RNA seq analysis and Western blotting indicated that Ir-CA also suppresses the GSTP1 expression to decrease the intracellular Pt-GS adducts, resulting in the detoxification and resensitization to cisplatin of A549R cells. In vivo evaluation indicated that Ir-CA restrains the tumor growth and has minimal side effects and superior biocompatibility. This work not only provides the first three-in-one agent to attenuate cancer cell stemness and simultaneously realize anticancer, antimetastasis, and conquer metallodrug resistance but also demonstrates the effectiveness of the mitochondria-directed strategy in cancer treatment.
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Antineoplásicos , Neoplasias , Cisplatino/farmacología , Línea Celular Tumoral , Ciclo Celular , Mitocondrias , Apoptosis , Antineoplásicos/farmacología , Antineoplásicos/metabolismo , Neoplasias/metabolismoRESUMEN
A series of Ca3Al2Ge3O12: xDy3+, yEu3+ phosphors were successfully prepared by the high-temperature solid-phase method. The phase and morphology of the phosphors were studied by means of Rietveld refinement and scanning electron microscopy. The results show that the phase is pure, and the crystal structure is the Ia3Ì d space group. In the Ca3Al2Ge3O12: xDy3+ phosphors, using 380 nm excitation, phosphors showed blue (4F9/2 â 6H15/2) and yellow (4F9/2 â 6H13/2) emission peaks at 481 and 581 nm, respectively. In Ca3Al2Ge3O12: xDy3+, yEu3+ phosphors, the energy transfer was inferred by the spectrum overlap of Dy3+ and Eu3+, and the lifetime attenuation was analyzed from the perspective of dynamics; finally, the band gap structure of the phosphors was analyzed by combining diffuse reflection spectra with the first principle, and the energy transfer mechanism and luminescence mechanism were elaborated by combining theory and practice. The transition from blue white light to red light can be achieved by tuning the range of y in Ca3Al2Ge3O12: 0.015Dy3+, yEu3+. Wherein, when y = 0.07, phosphors, the chromaticity coordinate of warm white CIE is (0.3932, 0.3203), the color temperature is 3093 K, and the warm white light is synthesized. The thermal stability of the synthesized warm white phosphors is 90.1% (423 K), the thermal sensing factors are Samax = 5.51 × 10-4 K-1 (303 K) and Srmax = 0.0359% K-1 (303 K), and the actual quantum efficiency is IQE = 52.48%. These results prove that Ca3Al2Ge3O12: Dy3+, Eu3+ have good application prospects as single-component warm w-LED devices.
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A facile synthetic method for direct C(sp2)-H bond trifluoromethylation of 3-methylene-isoindolin-1-ones under visible-light-induced metal-free conditions is presented. This protocol features mild reaction conditions, broad substrate scope and excellent functional group tolerance, resulting in a range of structurally diverse trifluoromethylated products in good to excellent yields.
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The global trade of plastic waste has raised environmental concerns, especially regarding pollution in waste-importing countries. However, the overall environmental contribution remains unclear due to uncertain treatment shares between handling plastic waste abroad and domestically. Here, we conduct a life cycle assessment of global plastic waste trade in 2022 across 18 countries and six plastic waste types, alongside three "nontrade" counterfactual scenarios. By considering the required cycling rate, which balances importers' costs and recycling revenues, we find that the trade resulted in lower environmental impacts than treating domestically with the average treatment mix. The trade scenario alone reduced climate change impact by 2.85 million tonnes of CO2 equivalent and mitigated damages to ecosystem quality, human health, and resource availability by 12 species-years, 6200 disability-adjusted life years (DALYs), and 1.4 billion United States dollars (USD in 2013), respectively. These results underscore the significance of recognizing plastic waste trade as a pivotal factor in regulating global secondary plastic production when formulating a global plastics treaty.
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Plásticos , Reciclaje , Comercio , Humanos , Cambio Climático , AmbienteRESUMEN
LiYGeO4 phosphors doped with Dy3+ and Eu3+ ions were synthesized using the solid phase method, and their color characteristics were adjustable. The bandgap value of LiYGeO4 calculated by diffuse reflection data is very close to the theoretical value of 3.669 eV, indicating that LiYGeO4 is an ideal candidate for doped rare earth activated ions. The analysis of the emission spectra and fluorescence attenuation curves of Dy3+ and Eu3+ co-doped LiYGeO4 phosphors revealed a clear energy transfer process: energy transfer from Dy3+ to Eu3+. Analysis of emission spectra and fluorescence attenuation curves revealed a transfer of energy from Dy3+ to Eu3+. This transfer mechanism is attributed to the dipole-dipole interactions. In addition, by constantly adjusting the doping levels of Dy3+ and Eu3+, a warm white phosphor with a color temperature of 3881 K was obtained. Finally, the emission intensity of the LiYGeO4:0.015Dy3+,0.02Eu3+ phosphor at 423 K was 86%, indicating that the phosphor has excellent thermal stability and 40% internal quantum efficiency, which proves the potential application of the LiYGeO4 phosphor in white light-emitting diodes (w-LEDs).
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A recombinant L-rhamnose isomerase (L-RhI) from probiotic Lactobacillus rhamnosus Probio-M9 (L. rhamnosus Probio-M9) was expressed. L. rhamnosus Probio-M9 was isolated from human colostrum and identified as a probiotic lactic acid bacterium, which can grow using L-rhamnose. L-RhI is one of the enzymes involved in L-rhamnose metabolism and catalyzes the reversible isomerization between L-rhamnose and L-rhamnulose. Some L-RhIs were reported to catalyze isomerization not only between L-rhamnose and L-rhamnulose but also between D-allulose and D-allose, which are known as rare sugars. Those L-RhIs are attractive enzymes for rare sugar production and have the potential to be further improved by enzyme engineering; however, the known crystal structures of L-RhIs recognizing rare sugars are limited. In addition, the optimum pH levels of most reported L-RhIs are basic rather than neutral, and such a basic condition causes non-enzymatic aldose-ketose isomerization, resulting in unexpected by-products. Herein, we report the crystal structures of L. rhamnosus Probio-M9 L-RhI (LrL-RhI) in complexes with L-rhamnose, D-allulose, and D-allose, which show enzyme activity toward L-rhamnose, D-allulose, and D-allose in acidic conditions, though the activity toward D-allose was low. In the complex with L-rhamnose, L-rhamnopyranose was found in the catalytic site, showing favorable recognition for catalysis. In the complex with D-allulose, D-allulofuranose and ring-opened D-allulose were observed in the catalytic site. However, bound D-allose in the pyranose form was found in the catalytic site of the complex with D-allose, which was unfavorable for recognition, like an inhibition mode. The structure of the complex may explain the low activity toward D-allose. KEY POINTS: ⢠Crystal structures of LrL-RhI in complexes with substrates were determined. ⢠LrL-RhI exhibits enzyme activity toward L-rhamnose, D-allulose, and D-allose. ⢠The LrL-RhI is active in acidic conditions.
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Isomerasas Aldosa-Cetosa , Lacticaseibacillus rhamnosus , Humanos , Rayos X , Ramnosa , MonosacáridosRESUMEN
KEY MESSAGE: The silencing of GhGASA14 and the identification of superior allelic variation in its coding region indicate that GhGASA14 may positively regulate flowering and the response to GA3. Gibberellic acid-stimulated Arabidopsis (GASA), a member of the gibberellin-regulated short amino acid family, has been extensively investigated in several plant species and found to be critical for plant growth and development. However, research on this topic in cotton has been limited. In this study, we identified 38 GhGASAs that were dispersed across 18 chromosomes in upland cotton, and all of these genes had a GASA core domain. Transcriptome expression patterns and qRT-PCR results revealed that GhGASA9 and GhGASA14 exhibited upregulated expression not only in the floral organs but also in the leaves of early-maturing cultivars. The two genes were functionally characterized by virus-induced gene silencing (VIGS), and the budding and flowering times after silencing the target genes were later than those of the control (TRV:00). Compared with that in the water-treated group (MOCK), the flowering period of the different fruiting branches in the GA3-treated group was more concentrated. Interestingly, allelic variation was detected in the coding sequence of GhGASA14 between early-maturing and late-maturing accessions, and the frequency of this favorable allele was greater in high-latitude cotton cultivars than in low-latitude ones. Additionally, a significant linear relationship was observed between the expression level of GhGASA14 and flowering time among the 12 upland cotton accessions. Taken together, these results indicated that GhGASA14 may positively regulate flowering time and respond to GA3. These findings could lead to the use of valuable genetic resources for breeding early-maturing cotton cultivars in the future.
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Flores , Regulación de la Expresión Génica de las Plantas , Giberelinas , Gossypium , Proteínas de Plantas , Gossypium/genética , Gossypium/fisiología , Gossypium/efectos de los fármacos , Flores/genética , Flores/efectos de los fármacos , Flores/fisiología , Flores/crecimiento & desarrollo , Giberelinas/farmacología , Giberelinas/metabolismo , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Filogenia , Silenciador del GenRESUMEN
BACKGROUND: Resistance can develop during treatment of advanced endometrial cancer (EC), leading to unsatisfactory results. Fanconi anemia complementation group D2 (Fancd2) has been shown to be closely related to drug resistance in cancer cells. Therefore, this study was designed to explore the correlation of Fancd2 with EC resistance and the mechanism of Fancd2. METHODS: Real-time quantitative PCR (RT-qPCR) was used to detect the expression of Fancd2 in EC tissues and cells. EC cells (Ishikawa) and paclitaxel-resistant EC cells (Ishikawa/TAX) were transfected to knock down Fancd2. In addition, the ferroptosis inhibitor Ferrostatin-1 was adopted to treat Ishikawa/TAX cells. The sensitivity of cancer cells to chemotherapeutic agents was observed via 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, and inhibitory concentration (IC)50 was calculated. Reactive oxygen species (ROS) levels were measured by flow cytometry, the activity of malondialdehyde (MDA) and the levels of glutathione (GSH) and Fe2+ in cells were detected by corresponding kits, and protein expression of solute farrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) was obtained through western blot. RESULTS: Compared with the normal tissues and endometrial epithelial cells, Fancd2 expression was significantly increased in EC tissues and Ishikawa cells, respectively. After knock-down of Fancd2, Ishikawa cells showed significantly increased sensitivity to chemotherapeutic agents. Besides, compared with Ishikawa cells, the levels of ROS, the activity of MDA, and the levels of GSH and Fe2+ were significantly decreased in Ishikawa/TAX cells, while the expression levels of SLC7A11 and GPX4 were significantly increased. Knock-down of Fancd2 significantly increased the ferroptosis levels in Ishikawa/TAX cells, but this effect could be reversed by Ferrostatin-1. CONCLUSION: Fancd2 increases drug resistance in EC cells by inhibiting the cellular ferroptosis pathway.
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Ciclohexilaminas , Neoplasias Endometriales , Anemia de Fanconi , Ferroptosis , Fenilendiaminas , Femenino , Humanos , Especies Reactivas de Oxígeno/uso terapéutico , Neoplasias Endometriales/tratamiento farmacológico , Neoplasias Endometriales/genéticaRESUMEN
BACKGROUND: MULTIPLEX is a single-scan three-dimensional multi-parametric MRI technique that provides 1 mm isotropic T1-, T2*-, proton density- and susceptibility-weighted images and the corresponding quantitative maps. This study aimed to investigate its feasibility of clinical application in Parkinson's disease (PD). METHODS: 27 PD patients and 23 healthy control (HC) were recruited and underwent a MULTIPLEX scanning. All image reconstruction and processing were automatically performed with in-house C + + programs on the Automatic Differentiation using Expression Template platform. According to the HybraPD atlas consisting of 12 human brain subcortical nuclei, the region-of-interest (ROI) based analysis was conducted to extract quantitative parameters, then identify PD-related abnormalities from the T1, T2* and proton density maps and quantitative susceptibility mapping (QSM), by comparing patients and HCs. RESULTS: The ROI-based analysis revealed significantly decreased mean T1 values in substantia nigra pars compacta and habenular nuclei, mean T2* value in subthalamic nucleus and increased mean QSM value in subthalamic nucleus in PD patients, compared to HCs (all p values < 0.05 after FDR correction). The receiver operating characteristic analysis showed all these four quantitative parameters significantly contributed to PD diagnosis (all p values < 0.01 after FDR correction). Furthermore, the two quantitative parameters in subthalamic nucleus showed hemicerebral differences in regard to the clinically dominant side among PD patients. CONCLUSIONS: MULTIPLEX might be feasible for clinical application to assist in PD diagnosis and provide possible pathological information of PD patients' subcortical nucleus and dopaminergic midbrain regions.