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Glioblastoma (GBM) is a highly aggressive, infiltrative malignancy that cannot be completely cured by current treatment modalities, and therefore requires more precise molecular subtype signatures to predict treatment response for personalized precision therapy. Expression subtypes of GBM samples from the Cancer Genome Atlas (TCGA) were identified using BayesNM and compared with existing molecular subtypes of GBM. Biological features of the subtypes were determined by single-sample gene set enrichment analysis. Genomic and proteomic data from GBM samples were combined and Genomic Identification of Significant Targets in Cancer analysis was used to screen genes with recurrent somatic copy-number alterations phenomenon. The immune environment among subtypes was compared by assessing the expression of immune molecules and the infiltration of immune cells. Molecular subtypes adapted to immunotherapy were identified based on Tumor Immune Dysfunction and Exclusion (TIDE) score. Finally, least absolute shrinkage and selection operator (LASSO) logistic regression was performed on the expression profiles of S2, S3 and S4 in TCGA-GBM and RPPA to determine the respective corresponding best predictive model. Four novel molecular subtypes were classified. Specifically, S1 exhibited a low proliferative profile; S2 exhibited the profile of high proliferation, IDH1 mutation, TP53 mutation and deletion; S3 was characterized by high immune scores, innate immunity and adaptive immune infiltration scores, with the lowest TIDE score and was most likely to benefit from immunotherapy; S4 was characterized by high proliferation, EGFR amplification, and high protein abundance, and was the most suitable subtype for bevacizumab. LASSO analysis constructed the best prediction model composed of 13 genes in S2 with an accuracy of 96.7%, and the prediction model consisting of 17 genes in S3 with an accuracy of 86.7%, and screened 14 genes as components of the best prediction model in S4 with an accuracy of 93%. To conclude, our study classified reproducible and robust molecular subtypes of GBM, and these findings might contribute to the identification of patients responding to immunotherapy, thereby improving GBM prognosis.
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Bevacizumab , Neoplasias Encefálicas , Genómica , Glioblastoma , Inmunoterapia , Proteómica , Glioblastoma/genética , Glioblastoma/tratamiento farmacológico , Glioblastoma/terapia , Glioblastoma/inmunología , Glioblastoma/patología , Humanos , Bevacizumab/uso terapéutico , Inmunoterapia/métodos , Proteómica/métodos , Genómica/métodos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/inmunología , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/patología , Regulación Neoplásica de la Expresión Génica , Biomarcadores de Tumor/genética , Antineoplásicos Inmunológicos/uso terapéutico , MutaciónRESUMEN
Despite the superior efficacy of radiotherapy in esophageal squamous cell carcinoma (ESCC), radioresistance by cancer stem cells (CSCs) leads to recurrence, metastasis, and treatment failure. Therefore, it is necessary to develop CSC-based therapies to enhance radiotherapy. miR-339-5p (miR339) is involved in stem cell division and DNA damage checkpoint signaling pathways based on ESCC cohort. miR339 inhibited ESCC cell stemness and enhanced radiation-induced DNA damage by targeting USP8, suggesting that it acts as a potential CSC regulator and radiosensitizer. Considering the limited circulating periods and poor tumor-targeting ability of miRNA, a multifunctional nanoplatform based on bismuth sulfide nanoflower (Bi@PP) is developed to efficiently deliver miR339 and improve radioresistance. Intriguingly, Bi@PP encapsulates more miR339 owing to their flower-shaped structure, delivering more than 1000-fold miR339 into cells, superior to free miR339 alone. Besides being used as a carrier, Bi@PP is advantageous for dynamically monitoring the distribution of delivered miR339 in vivo while simultaneously inhibiting tumor growth. Additionally, Bi@PP/miR339 can significantly enhance radiotherapy efficacy in patient-derived xenograft models. This multifunctional platform, incorporating higher miRNA loading capacity, pH responsiveness, hypoxia relief, and CT imaging, provides another method to promote radiosensitivity and optimize ESCC treatment.
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Bismuto , Neoplasias Esofágicas , MicroARNs , Células Madre Neoplásicas , Sulfuros , Bismuto/química , Bismuto/farmacología , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/tratamiento farmacológico , Sulfuros/química , Sulfuros/farmacología , Animales , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/patología , Ratones , Tolerancia a Radiación/efectos de los fármacos , Ubiquitina Tiolesterasa/metabolismo , Ubiquitina Tiolesterasa/antagonistas & inhibidores , Ratones Desnudos , Ratones Endogámicos BALB C , Proliferación Celular/efectos de los fármacos , Línea Celular Tumoral , Carcinoma de Células Escamosas de Esófago/patología , Carcinoma de Células Escamosas de Esófago/metabolismo , Carcinoma de Células Escamosas de Esófago/genéticaRESUMEN
Controlling the coherence of chaotic soliton bunch holds the promise to explore novel light-matter interactions and manipulate dynamic events such as rogue waves. However, the coherence control of chaotic soliton bunch remains challenging, as there is a lack of dynamic equilibrium mechanism for stochastic soliton interactions. Here, we develop a strategy to effectively control the coherence of chaotic soliton bunch in a laser. We show that by introducing a lumped fourth-order-dispersion (FOD), the soliton oscillating tails can be formed and generate the potential barriers among the chaotic solitons. The repulsive force between neighboring solitons enabled by the potential barriers gives rise to an alleviation of the soliton fusion/annihilation from stochastic interactions, endowing the capability to control the coherence in chaotic soliton bunch. We envision that this result provides a promising test-bed for a variety of dynamical complexity science and brings new insights into the nonlinear behavior of chaotic laser sources.
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BACKGROUND: The 5-year survival rate of oesophageal squamous cell carcinoma (ESCC) is approximately 20%. The prognosis and drug response exhibit substantial heterogeneity in ESCC, impeding progress in survival outcomes. Our goal is to identify a signature for tumour subtype classification, enabling precise clinical treatments. METHODS: Utilising pre-treatment multi-omics data from an ESCC dataset (n = 310), an enhancer methylation-eRNA-target gene regulation network was constructed and validated by in vitro experiments. Four machine learning methods collectively identified core target genes, establishing an Enhancer Demethylation-Regulated Gene Score (EDRGS) model for classification. The molecular function of EDRGS subtyping was explored in scRNA-seq (n = 60) and bulk-seq (n = 310), and the EDRGS's potential to predict treatment response was assessed in datasets of various cancer types. FINDINGS: EDRGS stratified ESCCs into EDRGS-high/low subtypes, with EDRGS-high signifying a less favourable prognosis in ESCC and nine additional cancer types. EDRGS-high exhibited an immune-hot but immune-suppressive phenotype with elevated immune checkpoint expression, increased T cell infiltration, and IFNγ signalling in ESCC, suggesting a better response to immunotherapy. Notably, EDRGS outperformed PD-L1 in predicting anti-PD-1/L1 therapy effectiveness in ESCC (n = 42), kidney renal clear cell carcinoma (KIRC, n = 181), and bladder urothelial carcinoma (BLCA, n = 348) cohorts. EDRGS-low showed a cell cycle-activated phenotype with higher CDK4 and/or CDK6 expression, demonstrating a superior response to the CDK4/6 inhibitor palbociclib, validated in ESCC (n = 26), melanoma (n = 18), prostate cancer (n = 15) cells, and PDX models derived from patients with pancreatic cancer (n = 30). INTERPRETATION: Identification of EDRGS subtypes enlightens ESCC categorisation, offering clinical insights for patient management in immunotherapy (anti-PD-1/L1) and CDK4/6 inhibitor therapy across cancer types. FUNDING: This study was supported by funding from the National Key R&D Program of China (2021YFC2501000, 2020YFA0803300), the National Natural Science Foundation of China (82030089, 82188102), the CAMS Innovation Fund for Medical Sciences (2021-I2M-1-018, 2022-I2M-2-001, 2021-I2M-1-067), the Fundamental Research Funds for the Central Universities (3332021091).
Asunto(s)
Biomarcadores de Tumor , Quinasa 4 Dependiente de la Ciclina , Quinasa 6 Dependiente de la Ciclina , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Regulación Neoplásica de la Expresión Génica , Inmunoterapia , Humanos , Quinasa 6 Dependiente de la Ciclina/antagonistas & inhibidores , Quinasa 6 Dependiente de la Ciclina/genética , Quinasa 4 Dependiente de la Ciclina/antagonistas & inhibidores , Quinasa 4 Dependiente de la Ciclina/genética , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/mortalidad , Carcinoma de Células Escamosas de Esófago/terapia , Carcinoma de Células Escamosas de Esófago/inmunología , Carcinoma de Células Escamosas de Esófago/metabolismo , Carcinoma de Células Escamosas de Esófago/patología , Inmunoterapia/métodos , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/metabolismo , Pronóstico , Metilación de ADN , Elementos de Facilitación Genéticos , Perfilación de la Expresión Génica , Biología Computacional/métodos , Línea Celular Tumoral , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/farmacología , Redes Reguladoras de Genes , AnimalesRESUMEN
[This corrects the article DOI: 10.1016/j.heliyon.2023.e14515.].
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Dissipative solitons (DSs), due to the complex interplay among dispersion, nonlinear, gain and loss, illustrate abundant nonlinear dynamics behaviors. Especially, dispersion plays an important role in the research of DS dynamics in ultrafast fiber lasers. Previous studies have mainly focused on the effect of even-order dispersion, i.e., group velocity dispersion (GVD) and fourth-order dispersion. In fact, odd-order dispersions, such as third-order dispersion (TOD), also significantly influences the dynamics of DSs. However, due to the lack of dispersion engineering tools, few experimental researches in this domain have been reported. In this work, by employing a pulse shaper in ultrafast fiber laser, an in-depth exploration of the DS dynamics influenced by TOD was conducted. With the increase of TOD value, the stable single DS undergoes a splitting into two solitons and then enters explosion state, and ultimately evolves into a chaotic state. The laser operation state is correlated to dispersion profile, which could be controlled by TOD. Here, the positive dispersion at long-wavelength side will be gradually shifted to negative dispersion by increasing the TOD, where soliton effect will drive the transitions. These findings offer valuable insights into the nonlinear dynamics of ultrafast lasers and may also foster applications involving higher-order dispersion.
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Cancer stem cells (CSCs) are essential for tumor initiation, recurrence, metastasis, and resistance. However, targeting CSCs as a therapeutic approach remains challenging. Here, a stemness signature based on 22-gene is developed to predict prognosis in esophageal squamous cell carcinoma (ESCC). Staurosporine (STS) is identified as a radioresistance suppressor by high-throughput screening of a library of 2131 natural compounds, leading to dramatically improved radiotherapy efficacy in subcutaneous tumor models. Mechanistically, STS inhibits cell proliferation through the mTOR/AKT signaling pathway and suppressed stemness by targeting ATP-binding cassette A1 (ABCA1), which is transcriptionally regulated by liver X receptor alpha (LXRα). STS can selectively bind to the nucleotide-binding domain (NBD) of ABCA1 and compete for ATP, blocking ABCA1-mediated drug efflux and facilitating intracellular accumulation of STS. Considering the cytotoxicity of STS, an extracellular vesicle-encapsulated STS system (EV-STS) is established for effective STS delivery. EV-STS shows remarkable tumor growth inhibition, even at half the dose of STS, with superior safety and efficacy. These findings indicate that ABCA1 may serve as a predictor of response to neoadjuvant chemotherapy and/or radiotherapy in ESCC patients. EV-STS has shown improved antitumor efficacy and low systemic toxicity, offering a promising therapeutic approach for ESCC.
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Transportador 1 de Casete de Unión a ATP , Vesículas Extracelulares , Tolerancia a Radiación , Estaurosporina , Humanos , Transportador 1 de Casete de Unión a ATP/metabolismo , Transportador 1 de Casete de Unión a ATP/genética , Estaurosporina/farmacología , Estaurosporina/análogos & derivados , Animales , Vesículas Extracelulares/metabolismo , Tolerancia a Radiación/efectos de los fármacos , Línea Celular Tumoral , Ratones , Proliferación Celular/efectos de los fármacos , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/metabolismo , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/terapia , Ratones Desnudos , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/patología , Carcinoma de Células Escamosas de Esófago/metabolismo , Ratones Endogámicos BALB CRESUMEN
Spatiotemporal mode-locked (STML) fiber lasers have become a new platform for investigating nonlinear phenomena. In this work, spatiotemporal dual-periodic soliton pulsation (SDSP) is firstly observed in an STML fiber laser. It is found that in the SDSP, the long-period pulsations (LPPs) of different transverse modes are synchronous, while the short-period pulsations (SPPs) exhibit asynchronous modulations. The numerical simulation confirms the experimental results and further reveals that the proportion of transverse mode components can manipulate the periods of the LPP and SPP but does not affect the synchronous and asynchronous pulsations of different transverse modes. The obtained results bring the study of spatiotemporal dissipative soliton pulsation into the multi-period modulation stage, which helps to understand the complex spatiotemporal dynamics in STML fiber lasers and discover new dynamics in high-dimensional nonlinear systems.
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Therapy resistance and metastatic progression jointly determine the fatal outcome of cancer, therefore, elucidating their crosstalk may provide new opportunities to improve therapeutic efficacy and prevent recurrence and metastasis in esophageal squamous cell carcinoma (ESCC). Here, we have established radioresistant ESCC cells with the remarkable metastatic capacity, and identified miR-494-3p (miR494) as a radioresistant activator. Mechanistically, we demonstrated that cullin 3 (CUL3) is a direct target of miR494, which is transcriptionally regulated by JunD, and highlighted that JunD-miR494-CUL3 axis promotes radioresistance and metastasis by facilitating epithelial-mesenchymal transition (EMT) and restraining programmed cell death 1 ligand 1 (PD-L1) degradation. In clinical specimens, miR494 is significantly up-regulated and positively associated with T stage and lymph node metastasis in ESCC tissues and serum. Notably, patients with higher serum miR494 expression have poor prognosis, and patients with higher CUL3 expression have more conventional dendritic cells (cDCs) and plasmacytoid DCs (pDCs), less cancer-associated fibroblasts (CAF2/4), and tumor endothelial cells (TEC2/3) infiltration than patients with lower CUL3 expression, suggesting that CUL3 may be involved in tumor microenvironment (TME). Overall, miR494 may serve as a potential prognostic predictor and therapeutic target, providing a promising strategy for ESCC treatment.
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Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , MicroARNs , Humanos , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas de Esófago/radioterapia , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/metabolismo , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/radioterapia , Neoplasias Esofágicas/metabolismo , Células Endoteliales/metabolismo , Pronóstico , Transición Epitelial-Mesenquimal , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Movimiento Celular , Microambiente Tumoral , Proteínas Proto-Oncogénicas c-jun/metabolismo , Proteínas Cullin/genéticaRESUMEN
Multimode fiber lasers have become a new platform for investigating nonlinear phenomena since the report on spatiotemporal mode-locking. In this work, the multimode soliton pulsation with a tunable period is achieved in a spatiotemporal mode-locked fiber laser. It demonstrates that the pulsation period drops while increasing the pump power. Moreover, it is found that different transverse modes have the same pulsation period, asynchronous pulsation evolution and different dynamical characteristics through the spatial sampling technique and the dispersive Fourier transform technique. To further verify the experimental results, we numerically investigate the influences of the gain and the loss on the pulsation properties. It is found that within a certain parameter range, the pulsation period drops and rises linearly with the increase of the gain and the loss, respectively. The obtained results contribute to understanding the formation and regulating of soliton pulsations in fiber lasers.
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Radiotherapy, a widely used therapeutic strategy for esophageal squamous cell carcinoma (ESCC), is always limited by radioresistance of tumor tissues and side-effects on normal tissues. Herein, a signature based on four core genes of cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, is developed to predict prognosis and assess immune cell infiltration, indicating that the cGAS-STING pathway and radiotherapy efficacy are closely intertwined in ESCC. A novel lipid-modified manganese diselenide nanoparticle (MnSe2-lipid) with extraordinarily uniform sphere morphology and tumor microenvironment (TME) responsiveness is developed to simultaneously overcome radioresistance and reduce side-effects of radiation. The uniform MnSe2 encapsulated lipid effectively achieves tumor accumulation. Octadecyl gallate on surface of MnSe2 forming pH-responsive metal-phenolic covalent realizes rapid degradation in TME. The released Mn2+ promotes radiosensitivity by generating reactive oxygen species induced by Fenton-like reaction and activating cGAS-STING pathway. Spontaneously, selenium strengthens immune response by promoting secretion of cytokines and increasing white blood cells, and performs antioxidant activity to reduce side-effects of radiotherapy. Overall, this multifunctional remedy which is responsive to TME is capable of providing radiosensitivity by cGAS-STING pathway-mediated immunostimulation and chemodynamic therapy, and radioprotection of normal tissues, is highlighted here to optimize ESCC treatment.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Nanopartículas , Tolerancia a Radiación , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/patología , Humanos , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/metabolismo , Tolerancia a Radiación/efectos de los fármacos , Animales , Nanopartículas/química , Línea Celular Tumoral , Ratones , Ácido Gálico/química , Ácido Gálico/farmacología , Ácido Gálico/análogos & derivados , Lípidos/química , Selenio/química , Selenio/farmacología , Microambiente Tumoral/efectos de los fármacos , Protectores contra Radiación/farmacología , Protectores contra Radiación/química , Manganeso/química , Fármacos Sensibilizantes a Radiaciones/química , Fármacos Sensibilizantes a Radiaciones/farmacologíaRESUMEN
We develop an all polarization-maintaining (PM) 920â nm Nd-doped fiber amplifier delivering a train of pulses with â¼0.53â W average power and sub-50â fs duration. The sub-50â fs pulse benefits from the pre-chirping management method that allows for over 60â nm broadening spectrum without pulse breaking in the amplification stage. By virtue of the short pulse duration, the pulse peak power can reach to â¼0.31â MW in spite of the moderate average power. These results represent a key step in developing high-peak-power pulse Nd-doped fiber laser systems at 920â nm, which will find important applications in fields such as biomedical imaging, ultrafast optical spectroscopy, and excitation of quantum-dot single photon sources.
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Soliton self-mode conversion is a versatile technique that allows for both wavelength changes and mode transformations. This process can be controlled by adjusting the input power, with higher power resulting in a stronger nonlinear effect that facilitates soliton self-mode conversion. Our research has demonstrated that soliton self-mode conversion is a viable method for achieving spatiotemporal coupling. This technique can be applied in optical fibers to link two pulses, resulting in distinct spatial distributions that can be controlled by adjusting the initial time intervals.
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Due to its unique geometric structure, the bidirectional ultrafast fiber laser is an excellent light source for dual-comb applications. However, sharing the same gain between the counter-propagating solitons also gives rise to complex dynamics. Herein, we report the anti-phase pulsation of counter-propagating dissipative solitons in a bidirectional fiber laser. The in-phase and anti-phase soliton pulsation can be manipulated by adjusting the intracavity birefringence. The periodic modulation of polarization-dependent gain (PDG) caused by polarization hole burning (PHB) in the gain fiber can be responsible for anti-phase pulsation of bidirectional dissipative solitons. These findings offer new, to the best of our knowledge, insights into the complex dynamics of solitons in dissipative optical systems and performance improvement of bidirectional ultrafast fiber lasers.
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The Mamyshev oscillator (MO) is a promising platform to generate high-peak-power pulse with environmentally stable operation. However, rare efforts have been dedicated to unveil the dynamics from seed signal to oscillator pulse, particularly for the multi-pulse operation. Herein, we investigate the buildup dynamics of the oscillator pulse from the seed signal in a fiber MO. It is revealed that the gain competition among the successively injected seed pulses leads to higher pump power that is required to ignite the MO, hence resulting in the higher optical gain that supports buildup of multiple oscillator pulses. The multiple oscillator pulses are identified to be evolved from the multiple seed pulses. Moreover, the dispersive Fourier transform (DFT) technique is used to reveals the real-time spectral dynamics during the starting process. As a proof-of-concept demonstration, a highly intensity-modulated pulse bunch was employed as the seed signal to reduce the gain competition effect and avoid the multi-pulse starting operation. The experimental results are verified by numerical simulations. These findings would give new insights into the pulse dynamics in MO, which will be meaningful to the communities interested in ultrafast laser technologies and nonlinear optics.
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Real-time monitoring of volatile organic compounds (VOCs) is crucial for both industrial production and daily life. However, the non-reactive nature of VOCs and their low concentrations pose a significant challenge for developing sensors. In this study, we investigated the adsorption behaviors of typical VOCs (C2H4, C2H6, and C6H6), on pristine and Pt-decorated SnS monolayers using density functional theory (DFT) calculations. Pristine SnS monolayers have limited charge transfer and long adsorption distances to VOC molecules, resulting in VOC insensitivity. The introduction of Pt atoms promotes charge transfer, creates new energy levels, and increases the overlap of the density of states, thereby enhancing electron excitation and improving gas sensitivity. Pt-decorated SnS monolayers exhibited high sensitivities of 241,921.7%, 35.7%, and 74.3% towards C2H4, C2H6, and C6H6, respectively. These values are 142,306.9, 23.8, and 82.6 times higher than those of pristine SnS monolayers, respectively. Moreover, the moderate adsorption energies of adsorbing C2H6 and C6H6 molecules ensure that Pt-decorated SnS monolayers possess good reversibility with a short recovery time at 298 K. When heated to 498 K, C2H4 molecules desorbs from the surface of Pt-decorated SnS monolayer in 162.33 s. Our results indicate that Pt-decorated SnS monolayers could be superior candidates for sensing VOCs with high selectivity, sensitivity, and reversibility.
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Cancer stem cells (CSCs) are crucial for tumorigenesis, metastasis, and therapy resistance in esophageal squamous cell carcinoma (ESCC). To further elucidate the mechanism underlying characteristics of CSCs and develop CSCs-targeted therapy, an efficient culture system that could expand and maintain CSCs is needed. CSCs reside in a complex tumor microenvironment, and three-dimensional (3D) culture systems of biomimetic scaffolds are expected to better support the growth of CSCs by recapitulating the biophysical properties of the extracellular matrix (ECM). Here, we established gelatin-based 3D biomimetic scaffolds mimicking the stiffness and collagen content of ESCC, which could enrich ESCC CSCs efficiently. Biological changes of ESCC cells laden in scaffolds with three different viscoelasticity emulating physiological stiffness of esophageal tissues were thoroughly investigated in varied aspects such as cell morphology, viability, cell phenotype markers, and transcriptomic profiling. The results demonstrated the priming effects of viscoelasticity on the stemness of ESCC. The highly viscous scaffolds (G': 6-403 Pa; G'': 2-75 Pa) better supported the enrichment of ESCC CSCs, and the TGF-beta signaling pathway might be involved in regulating the stemness of ESCC cells. Compared to two-dimensional (2D) cultures, highly viscous scaffolds significantly promoted the clonal expansion of ESCC cells in vitro and tumor formation ability in vivo. Our findings highlight the crucial role of biomaterials' viscoelasticity for the 3D culture of ESCC CSCs in vitro, and this newly-established culture system represents a valuable platform to support their growth, which could facilitate the CSCs-targeted therapy in the future.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Carcinoma de Células Escamosas de Esófago/metabolismo , Carcinoma de Células Escamosas de Esófago/patología , Carcinoma de Células Escamosas de Esófago/terapia , Gelatina/farmacología , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patología , Biomimética , Línea Celular Tumoral , Células Madre Neoplásicas/patología , Microambiente TumoralRESUMEN
We report, for the first time to the best of our knowledge, a spatiotemporal mode-locked (STML) multimode fiber laser based on nonlinear amplifying loop mirror (NALM), generating dissipative soliton resonance (DSR) pulses. Due to the complex filtering characteristics caused by the inherent multimode interference filtering structure and NALM in the cavity, the STML DSR pulse has wavelength tunable function. What's more, kinds of DSR pulses are also achieved, including multiple DSR pulses, and the period doubling bifurcations of single DSR pulse and multiple DSR pulses. These results contribute to further understand the nonlinear properties of STML lasers and may shed some light on improving the performance of the multimode fiber lasers.
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Circulating miRNA expression is most commonly measured by qRT-PCR, however, the lack of a suitable endogenous control hinders people from evaluating the accurate changes in miRNA expression levels and developing the non-invasive biomarkers. In this study, we aimed to screen the specific, highly stable endogenous control in esophageal squamous cell carcinoma (ESCC) to overcome the obstacle. We selected "housekeeping" miRNAs according to the published database and initially acquired 21 miRNAs. Subsequently, we screened these miRNAs using GSE106817 and TCGA datasets according to specific inclusion criteria and evaluated the suitability of "candidate" miRNAs. Among these miRNAs, the average abundance of miR-423-5p was relatively high in serum. Notably, miR-423-5p expression in serum showed no significant difference between ESCC patients and healthy controls (n = 188, P = 0.29). Moreover, among these miRNAs, miR-423-5p was the most stable miRNA using the NormFinder algorithms. Overall, these results indicate that miR-423-5p, as a novel and optimal endogenous control, could be used to quantify circulating miRNAs in ESCC.
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Due to the fascinating features, pulsating solitons attract much attention in the field of nonlinear soliton dynamics and ultrafast lasers. So far, most of the investigations on pulsating soliton are conducted in Er-doped fiber lasers. In this work, we reported the periodic transition between two evolving pulsating soliton states in an Yb-doped fiber laser. By using the real-time measurement techniques, the spectral and temporal characteristics of this transition state were investigated. Two evolving soliton pulsation states have similar evolution process, i.e., from pulsating towards quasi-stable mode-locked states. However, the details of the two processes are different, such as the pulse energy levels, pulsating modulation depths, duration of quasi-stable mode-locked states. The transition between two evolving soliton pulsation states could be attributed to the interaction of the polarizer and the varying polarization states of the pulse inside the laser cavity. The experimental results will contribute to the further understanding of soliton pulsating dynamics in dissipative optical systems.