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1.
Proc Natl Acad Sci U S A ; 121(8): e2311326121, 2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38349884

RESUMEN

Photoelectrochemical (PEC) coupling of CO2 and nitrate can provide a useful and green source of urea, but the process is affected by the photocathodes with poor charge-carrier dynamics and low conversion efficiency. Here, a NiFe diatomic catalysts/TiO2 layer/nanostructured n+p-Si photocathode is rationally designed, achieving a good charge-separation efficiency of 78.8% and charge-injection efficiency of 56.9% in the process of PEC urea synthesis. Compared with the electrocatalytic urea synthesis by using the same catalysts, the Si-based photocathode shows a similar urea yield rate (81.1 mg·h-1·cm-2) with a higher faradic efficiency (24.2%, almost twice than the electrocatalysis) at a lower applied potential under 1 sun illumination, meaning that a lower energy-consumption method acquires more aimed productions. Integrating the PEC measurements and characterization results, the synergistic effect of hierarchical structure is the dominating factor for enhancing the charge-carrier separation, transfer, and injection by the matched band structure and favorable electron-migration channels. This work provides a direct and efficient route of solar-to-urea conversion.

2.
Mol Cell Proteomics ; 23(9): 100825, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39111711

RESUMEN

Personalized cancer immunotherapies such as therapeutic vaccines and adoptive transfer of T cell receptor-transgenic T cells rely on the presentation of tumor-specific peptides by human leukocyte antigen class I molecules to cytotoxic T cells. Such neoepitopes can for example arise from somatic mutations and their identification is crucial for the rational design of new therapeutic interventions. Liquid chromatography mass spectrometry (LC-MS)-based immunopeptidomics is the only method to directly prove actual peptide presentation and we have developed a parameter optimization workflow to tune targeted assays for maximum detection sensitivity on a per peptide basis, termed optiPRM. Optimization of collision energy using optiPRM allows for the improved detection of low abundant peptides that are very hard to detect using standard parameters. Applying this to immunopeptidomics, we detected a neoepitope in a patient-derived xenograft from as little as 2.5 × 106 cells input. Application of the workflow on small patient tumor samples allowed for the detection of five mutation-derived neoepitopes in three patients. One neoepitope was confirmed to be recognized by patient T cells. In conclusion, optiPRM, a targeted MS workflow reaching ultra-high sensitivity by per peptide parameter optimization, makes the identification of actionable neoepitopes possible from sample sizes usually available in the clinic.


Asunto(s)
Mutación , Proteómica , Flujo de Trabajo , Humanos , Cromatografía Liquida , Proteómica/métodos , Espectrometría de Masas/métodos , Epítopos/inmunología , Neoplasias/inmunología , Péptidos , Animales , Antígenos de Neoplasias/inmunología , Ratones , Cromatografía Líquida con Espectrometría de Masas
3.
Angew Chem Int Ed Engl ; 62(24): e202304079, 2023 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-37084003

RESUMEN

Photoelectrochemical lithium (Li) extraction can be expected to provide a useful recycle of Li+ from waste Li-containing battery, but the process is limited by the photocathodes with poor Li+ absorption and low yield rate. Here, we have designed a hierarchical silicon (Si)-based photocathode with mixed-phase tungsten oxide (WO3 ) cocatalysts for photoelectrochemical Li extraction under 1 sun illumination, achieving a high Li yield rate of ≈223.0 µg cm-2 h-1 and an excellent faradaic efficiency of 91.9 % at 0.0817 V versus Li0/+ redox couple. The WO3 cocatalysts with the mixture of amorphous and crystalline phase accelerates the Li+ insertion and precipitation and enriches the concentration of Li+ at the photocathode surface. This robust photoelectrochemical Li extraction system provides a new insight on designing green and efficient route for cyclic utilization of Li resources in the sustainable energy field.

4.
Clin Immunol ; 232: 108868, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34587513

RESUMEN

Receptor-interacting protein 2 (RIP2) is a key mediator implicated in multiple cellular processes, and its dysregulation has been recently reported in colitis, asthma and other inflammatory diseases. However, the effects of RIP2 on osteoarthritis (OA) and the underlying mechanisms remain unclear. In this study, we found that RIP2 expression was upregulated in human articular cartilage tissues with OA and interleukin-1ß (IL-1ß)-treated chondrocytes. Knockdown of RIP2 inhibited IL-1ß-induced extracellular matrix (ECM) and oxidative stress. Moreover, knockdown of TRAF3 reversed the effects of RIP2 silencing on cartilage degradation and oxidative stress in IL-1ß-induced chondrocytes. In addition, p38 mitogen-activated protein kinase (MAPK) activator dehydrocorydalmine chloride (Dc) also reversed the effects of RIP2 silencing on IL-1ß-induced chondrocytes. Taken together, our data reveal that RIP2 knockdown inhibits cartilage degradation and oxidative stress in IL-1ß-treated chondrocytes by regulating TRAF3 expression and p38 MAPK pathway activation.


Asunto(s)
Cartílago Articular/metabolismo , Regulación de la Expresión Génica/fisiología , Sistema de Señalización de MAP Quinasas/fisiología , Osteoartritis de la Rodilla/metabolismo , Proteína Serina-Treonina Quinasa 2 de Interacción con Receptor/metabolismo , Factor 3 Asociado a Receptor de TNF/metabolismo , Anciano , Cartílago Articular/patología , Células Cultivadas , Condrocitos/metabolismo , Condrocitos/patología , Femenino , Técnicas de Silenciamiento del Gen , Humanos , Interleucina-1beta/metabolismo , Interleucina-1beta/farmacología , Masculino , Persona de Mediana Edad , Osteoartritis de la Rodilla/patología , Estrés Oxidativo
5.
Small ; 16(14): e1906867, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32162756

RESUMEN

Cobalt pnictides show good catalytic activity and stability on oxygen evolution reaction (OER) behaviors in a strong alkaline solution. Identifying the intrinsic composition/structure-property relationship of the oxide layer on the cobalt pnictides is critical to design better and cheaper electrocatalysts for the commercial viability of OER technologies. In this work, the restructured oxide layer on the cobalt pnictides and its effect on the activity and mechanism for OER is systematically analyzed. In-situ electrochemical impedance spectroscopy (EIS) and near edge x-ray absorption fine structure (NEXAFS) spectra indicate that a higher OER performance of cobalt pnictides than Co3 O4 is attributed to the more structural disorder and oxygen defect sites in the cobalt oxide layer evolved from cobalt pnictides. Using angle resolved x-ray photoelectron spectroscopy (AR-XPS) further demonstrates that the oxygen defect sites mainly concentrate on the subsurface of cobalt oxide layer. The current study demonstrated promising opportunities for further enhancing the OER performance of cobalt-based electrocatalysts by controlling the subsurface defects of the restructured active layer.

6.
Angew Chem Int Ed Engl ; 58(51): 18604-18609, 2019 Dec 16.
Artículo en Inglés | MEDLINE | ID: mdl-31535425

RESUMEN

The (photo)electrochemical N2 reduction reaction (NRR) provides a favorable avenue for the production of NH3 using renewable energy in mild operating conditions. Understanding and building an efficient catalyst with high NH3 selectivity represents an area of intense interest for the early stages of development for NRR. Herein, we introduce a CoOx layer to tune the local electronic structure of Au nanoparticles with positive valence sites for boosting conversion of N2 to NH3 . The catalysts, possessing high average oxidation states (ca. 40 %), achieve a high NH3 yield rate of 15.1 µg cm-2 h-1 and a good faradic efficiency of 19 % at -0.5 V versus reversible hydrogen electrode. Experimental results and simulations reveal that the ability to tune the oxidation state of Au enables the control of N2 adsorption and the concomitant energy barrier of NRR. Altering the Au oxidation state provides a unique strategy for control of NRR in the production of valuable NH3 .

7.
ChemSusChem ; 17(17): e202301526, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-38538545

RESUMEN

The amount of global hybrid-electric and all electric vehicle has increased dramatically in just five years and reached an all-time high of over 10 million units in 2022. A good deal of waste lithium (Li)-containing batteries from dead vehicles are invaluable unconventional resources with high usage of Li. However, the recycle of Li by green approaches is extremely inefficient and rare from waste batteries, giving rise to severe environmental pollutions and huge squandering of resources. Thus, in this mini review, we briefly summarized a green and promising route-photoelectrochemical (PEC) technology for extracting the Li from the waste lithium-containing batteries. This review first focuses on the critical factors of PEC performance, including light harvesting, charge-carrier dynamics, and surface chemical reactions. Subsequently, the conventional and PEC technologies applying in the area of Li recovery processes are analyzed and discussed in depth, and the potential challenges and future perspective for rational and healthy development of PEC Li extraction are provided positively.

8.
Psychol Res Behav Manag ; 17: 1115-1128, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38505350

RESUMEN

Background: Improving academic engagement of medical postgraduates is crucial for enhancing the quality of learning and the development of medical education. Due to medical postgraduates face high levels of stress and rigorous demands, yet the mechanisms linking challenge-hindrance stressors to academic engagement in this context remain largely unexplored. This study aims to explore the comprehensive relationship between challenge-hindrance stressors and academic engagement among medical postgraduates in China. Methods: Data were collected from 437 medical postgraduates in China, to investigate their challenge-hindrance stressors, emotional exhaustion, learning, relaxation and academic engagement. Among these postgraduates, 40.3% were male and 59.7% were female, with the mean age of the participants being 25.71 years. Statistical procedures were conducted using Mplus 8.3, ensuring a robust analysis of the data collected. Results: Our study showed that both challenge and hindrance stressors are significantly positively correlated with emotional exhaustion among Chinese medical postgraduates, and emotional exhaustion is negatively associated with academic engagement. Emotional exhaustion mediates the relationship between challenge-hindrance stressors and academic engagement. Learning plays a protective role, moderating the challenge stressors and emotional exhaustion relationship and its indirect effect on academic engagement. However, relaxation was not identified as a significant moderating factor in this context. Conclusion: Our findings not only revealed emotional exhaustion as a potential mechanism underlying the relationship between challenge-hindrance stressors and academic engagement but also validated the moderating role of learning in mitigating the adverse effects of challenge stressors on emotional exhaustion and academic engagement among Chinese medical postgraduates. This comprehensive insight into the complex dynamics between different stressors and academic engagement provides both theoretical and empirical evidence for medical universities. It underscores the importance of interventions to enhance academic engagement in stressful environments and serves as a valuable reference for the development of reasonable assessment systems. These contributions are crucial for fostering a supportive educational atmosphere and promoting the well-being of medical postgraduates.

9.
Med Educ Online ; 29(1): 2379110, 2024 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-39016967

RESUMEN

This study investigated the relationship between challenge-hindrance stressors and innovative behavior of medical postgraduates in China, examining the mediating role of academic engagement and the moderating effect of relaxation. Drawing from a sample of 437 medical postgraduates from three Chinese universities, our findings revealed that challenge stressors positively correlated with innovative behavior, while the direct relationship between hindrance stressors and innovative behavior was not statistically significant. Furthermore, academic engagement mediated the relationship between two types of stressors and innovative behavior. Challenge stressors enhanced academic engagement, which in turn fostered innovative behavior. Conversely, hindrance stressors were found to diminish academic engagement, which in turn indirectly limited innovative behavior. Additionally, relaxation was identified as a moderating factor that helped mitigate the negative effects of hindrance stressors on academic engagement and indirectly on innovative behavior. These results suggested that academic engagement as a mechanism played a pivotal role in determining how different stressors influenced innovative behavior, underscoring the need for stress management, particularly through relaxation techniques, to maintain high levels of academic engagement and innovative behavior. This study offers practical insights for medical education policymakers and educators in China, emphasizing the importance of balancing stressors and incorporating relaxation practices to enhance the innovative capabilities of medical postgraduates in demanding academic environments.


Asunto(s)
Relajación , Estrés Psicológico , Humanos , China/epidemiología , Estrés Psicológico/epidemiología , Estrés Psicológico/psicología , Masculino , Femenino , Relajación/psicología , Creatividad , Adulto , Educación de Postgrado en Medicina
10.
Artículo en Inglés | MEDLINE | ID: mdl-39031110

RESUMEN

OBJECTIVE: To evaluate the prognostic factors and survival outcomes of patients with surgically treated high-grade neuroendocrine carcinoma of the cervix (NECC). METHODS: This multicenter, retrospective study involved 98 cervical cancer patients with stage IA2-IIA2 and IIIC1/2p high-grade NECC. We divided the patients into two groups based on histology: the pure and mixed groups. All clinicopathologic variables were retrospectively evaluated. Cox regression and Kaplan-Meier methods were used for analysis. RESULTS: In our study, 60 patients were in the pure group and 38 patients were in the mixed group. Cox multivariate analysis showed that mixed histology was a protective factor impacting overall survival (OS) (P = 0.026) and progression free survival (PFS) (P = 0.018) in surgically treated high-grade NECC. Conversely, survival outcomes were negatively impacted by ovarian preservation (OS: HR, 20.84; 95% CI: 5.02-86.57, P < 0.001), age >45 years (OS: HR, 4.50; 95% CI: 1.0-18.83, P = 0.039), tumor size >4 cm (OS: HR, 6.23; 95% CI: 2.34-16.61, P < 0.001), parity >3 (OS: HR, 4.50; 95% CI: 1.02-19.91, P = 0.048), and perineural invasion (OS: HR, 5.21; 95% CI: 1.20-22.53, P = 0.027). Kaplan-Meier survival curves revealed notable differences in histologic type (OS: P = 0.045; PFS: P = 0.024), chemotherapy (OS: P = 0.0056; PFS: P = 0.0041), ovarian preservation (OS: P = 0.00031; PFS: P = 0.0023), uterine invasion (OS: P < 0.0001; PFS: P < 0.0001), and depth of stromal invasion (OS: P = 0.043; PFS: P = 0.022). CONCLUSION: Patients with mixed histologic types who undergo surgery for high-grade NECC have a better prognosis. Meanwhile, ovarian preservation, tumor size >4 cm, parity >3, age >45 years and perineural invasion were poor prognostic predictors. Therefore, patients with high-risk factors should be considered in clinical practice.

11.
Cell Mol Immunol ; 2024 Oct 29.
Artículo en Inglés | MEDLINE | ID: mdl-39472748

RESUMEN

Although major progress has been made in the use of chimeric antigen receptor (CAR)-T-cell therapy for hematological malignancies, this method is ineffective against solid tumors largely because of the limited infiltration, activation and proliferation of CAR-T cells. To overcome this issue, we engineered CAR-T cells with synthetic Notch (synNotch) receptors, which induce local tumor-specific secretion of extracellular matrix (ECM)-degrading enzymes at the tumor site. SynNotch CAR-T cells achieve precise ECM recognition and robustly kill targeted tumors, with synNotch-induced enzyme production enabling the degradation of components of the tumor ECM. In addition, this regulation strongly increased the infiltration of CAR-T cells and the clearance of solid tumors, resulting in tumor regression without toxicity in vivo. Notably, synNotch CAR-T cells also promoted the persistent activation of CAR-T cells in patient-derived tumor organoids. Thus, we constructed a synthetic T-cell system that increases the infiltration and antitumor function of CAR-T cells, providing a strategy for targeting ECM-rich solid tumors.

12.
Adv Mater ; 35(21): e2211894, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36905214

RESUMEN

As a widely used commodity chemical, ammonia is critical for producing nitrogen-containing fertilizers and serving as the promising zero-carbon energy carrier. Photoelectrochemical nitrogen reduction reaction (PEC NRR) can provide a solar-powered green and sustainable route for synthesis of ammonia (NH3 ). Herein, an optimum PEC system is reported with an Si-based hierarchically-structured PdCu/TiO2 /Si photocathode and well-thought-out trifluoroethanol as the proton source for lithium-mediated PEC NRR, achieving a record high NH3 yield of 43.09 µg cm-2 h-1 and an excellent faradaic efficiency of 46.15% under 0.12 MPa O2 and 3.88 MPa N2 at 0.07 V versus lithium(0/+) redox couple (vs Li0/+ ). PEC measurements coupled with operando characterization reveal that the PdCu/TiO2 /Si photocathode under N2 pressures facilitate the reduction of N2 to form lithium nitride (Li3 N), which reacts with active protons to produce NH3 while releasing the Li+ to reinitiate the cycle of the PEC NRR. The Li-mediated PEC NRR process is further enhanced by introducing small amount of O2 or CO2 under pressure by accelerating the decomposition of Li3 N. For the first time, this work provides mechanistic understanding of the lithium-mediated PEC NRR process and opens new avenues for efficient solar-powered green conversion of N2 -to-NH3 .

13.
JACS Au ; 3(2): 592-602, 2023 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-36873698

RESUMEN

Enhancing charge-carrier dynamics is imperative to achieve efficient photoelectrodes for practical photoelectrochemical devices. However, a convincing explanation and answer for the important question which has thus far been absent relates to the precise mechanism of charge-carrier generation by solar light in photoelectrodes. Herein, to exclude the interference of complex multi-components and nanostructuring, we fabricate bulky TiO2 photoanodes through physical vapor deposition. Integrating photoelectrochemical measurements and in situ characterizations, the photoinduced holes and electrons are transiently stored and promptly transported around the oxygen-bridge bonds and 5-coordinated Ti atoms to form polarons on the boundaries of TiO2 grains, respectively. Most importantly, we also find that compressive stress-induced internal magnetic field can drastically enhance the charge-carrier dynamics for the TiO2 photoanode, including directional separation and transport of charge carriers and an increase of surface polarons. As a result, bulky TiO2 photoanode with high compressive stress displays a high charge-separation efficiency and an excellent charge-injection efficiency, leading to 2 orders of magnitude higher photocurrent than that produced by a classic TiO2 photoanode. This work not only provides a fundamental understanding of the charge-carrier dynamics of the photoelectrodes but also provides a new paradigm for designing efficient photoelectrodes and controlling the dynamics of charge carriers.

14.
Redox Biol ; 62: 102639, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36958250

RESUMEN

Despite a strong rationale for why cancer cells are susceptible to redox-targeting drugs, such drugs often face tumor resistance or dose-limiting toxicity in preclinical and clinical studies. An important reason is the lack of specific biomarkers to better select susceptible cancer entities and stratify patients. Using a large panel of lung cancer cell lines, we identified a set of "antioxidant-capacity" biomarkers (ACB), which were tightly repressed, partly by STAT3 and STAT5A/B in sensitive cells, rendering them susceptible to multiple redox-targeting and ferroptosis-inducing drugs. Contrary to expectation, constitutively low ACB expression was not associated with an increased steady state level of reactive oxygen species (ROS) but a high level of nitric oxide, which is required to sustain high replication rates. Using ACBs, we identified cancer entities with a high percentage of patients with favorable ACB expression pattern, making it likely that more responders to ROS-inducing drugs could be stratified for clinical trials.


Asunto(s)
Antioxidantes , Neoplasias Pulmonares , Humanos , Especies Reactivas de Oxígeno/metabolismo , Antioxidantes/metabolismo , Neoplasias Pulmonares/metabolismo , Oxidación-Reducción , Biomarcadores/metabolismo
15.
Front Immunol ; 14: 1294565, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38239352

RESUMEN

Peptide-loaded MHC class I (pMHC-I) multimers have revolutionized our capabilities to monitor disease-associated T cell responses with high sensitivity and specificity. To improve the discovery of T cell receptors (TCR) targeting neoantigens of individual tumor patients with recombinant MHC molecules, we developed a peptide-loadable MHC class I platform termed MediMer. MediMers are based on soluble disulfide-stabilized ß2-microglobulin/heavy chain ectodomain single-chain dimers (dsSCD) that can be easily produced in large quantities in eukaryotic cells and tailored to individual patients' HLA allotypes with only little hands-on time. Upon transient expression in CHO-S cells together with ER-targeted BirA biotin ligase, biotinylated dsSCD are purified from the cell supernatant and are ready to use. We show that CHO-produced dsSCD are free of endogenous peptide ligands. Empty dsSCD from more than 30 different HLA-A,B,C allotypes, that were produced and validated so far, can be loaded with synthetic peptides matching the known binding criteria of the respective allotypes, and stored at low temperature without loss of binding activity. We demonstrate the usability of peptide-loaded dsSCD multimers for the detection of human antigen-specific T cells with comparable sensitivities as multimers generated with peptide-tethered ß2m-HLA heavy chain single-chain trimers (SCT) and wild-type peptide-MHC-I complexes prior formed in small-scale refolding reactions. Using allotype-specific, fluorophore-labeled competitor peptides, we present a novel dsSCD-based peptide binding assay capable of interrogating large libraries of in silico predicted neoepitope peptides by flow cytometry in a high-throughput and rapid format. We discovered rare T cell populations with specificity for tumor neoepitopes and epitopes from shared tumor-associated antigens in peripheral blood of a melanoma patient including a so far unreported HLA-C*08:02-restricted NY-ESO-1-specific CD8+ T cell population. Two representative TCR of this T cell population, which could be of potential value for a broader spectrum of patients, were identified by dsSCD-guided single-cell sequencing and were validated by cognate pMHC-I multimer staining and functional responses to autologous peptide-pulsed antigen presenting cells. By deploying the technically accessible dsSCD MHC-I MediMer platform, we hope to significantly improve success rates for the discovery of personalized neoepitope-specific TCR in the future by being able to also cover rare HLA allotypes.


Asunto(s)
Linfocitos T CD8-positivos , Péptidos , Humanos , Receptores de Antígenos de Linfocitos T , Antígenos HLA/metabolismo , Antígenos de Neoplasias
16.
ACS Appl Mater Interfaces ; 14(7): 8955-8962, 2022 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-35147408

RESUMEN

The rechargeable zinc-iodine (Zn-I2) battery is a promising energy-storage system due to its low cost and good security, but the practical use of the battery is largely constrained by the shuttle effect and high dissolvability of iodides. Here a multifunctional iodine host, constructed with nitrogen-doped porous carbon nanocages (NCCs) by the polymerization carbonization activation method, is exploited to improve the electrochemical performance and lifespan of the Zn-I2 battery, achieving a high specific capacity of 259 mAh g-1, a good rate performance (maintaining 50.6% expanding 50 times), and a high cycle stability (retention of 100% after 1000 cycles). On the basis of the experimental results and theoretical calculations, NCCs via the introduction of N doping and nanosized porous structure can simultaneously provide rich and robust anchoring and catalytic sites to carry out the electrostatic adsorption of iodides and facilitate the reversible conversion between iodine and iodides. This work shows a novel and efficient strategy to develop high-performance and long-life Zn-I2 batteries.

17.
ACS Appl Mater Interfaces ; 13(51): 60995-61003, 2021 Dec 29.
Artículo en Inglés | MEDLINE | ID: mdl-34914880

RESUMEN

Environmentally friendly lead-free piezoelectric materials have been attracting significant attention in recent years. Na1/2Bi1/2TiO3-based relaxor ferroelectrics have found acceptance for application in promising lead-free transducers in high-power ultrasonic devices. However, their low thermal stability, i.e., their relatively low ferroelectric-relaxor transition temperature (TF-R), hinders their practical application. Herein, a thermal-quenching approach is applied on a Na1/2Bi1/2TiO3 (NBT)-based single crystal, which yields a large increase in TF-R and dramatic enhancement of its ferroelectric ordering, leading to excellent thermal stability of its dielectric, ferroelectric, and piezoelectric properties. This behavior is mainly attributed to quenching-induced domain evolution as well as its octahedral tilt, which is linked to the increased oxygen vacancies. The substitution of long-range ordered ferroelectric domains for short-range polar nanodomains contributes to its increased coherence length and, consequently, enhancement of TF-R. This work provides an approach to the optimization of the ferroelectric ordering and thermal stability of NBT as well as an in-depth understanding of the quenching effect on the local structure, which could be applied to other relaxor-based ferroelectrics for optimization of their macroscopic properties.

18.
Cancers (Basel) ; 12(10)2020 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-33066523

RESUMEN

Circular RNAs (circRNAs) play critical roles in a broad spectrum of physiological and pathological processes, including cancer. Here, we provide a comprehensive database-circ2GO-systematically linking circRNAs to the functions and processes of their linear counterparts. circ2GO contains 148,811 circular human RNAs originating from 12,251 genes, which we derived from deep transcriptomics after rRNA depletion in a panel of 60 lung cancer and non-transformed cell lines. The broad circRNA expression dataset is mapped to all isoforms of the respective gene. The data are visualized in transcript maps and in heatmaps, to intuitively display a comprehensive portrait for the abundance of circRNAs across transcripts and cell lines. By integrating gene ontology (GO) information for all genes in our dataset, circ2GO builds a connection between circRNAs and their host genes' biological functions and molecular mechanisms. Additionally, circ2GO offers target predictions for circRNA-microRNA (miRNA) pairs for 25,166 highly abundant circRNAs from 6578 genes and 897 high-confidence human miRNAs. Visualization, user-friendliness, intuitive and advanced forward and reverse search options, batch processing and download options make circ2GO a comprehensive source for circRNA information to build hypotheses on their function, processes, and miRNA targets.

19.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 36(8): 699-703, 2020 Aug.
Artículo en Zh | MEDLINE | ID: mdl-32958126

RESUMEN

Objective To detect the expression of chemokine and adhesion molecules related to leukocytes' transendothelial migration, meanwhile, to investigate changes of reticular fibers and the expression of vimentin and matrix metalloproteinase-9 (MMP9) in lung tissues after surgical removal of mouse tumor-bearing lymph node, revealing their changes and roles in the formation of pre-metastatic microenvironment in the lung. Methods B16F10 melanoma cells were inoculated into mouse subiliac lymph node (SiLN). Twenty mice were equally divided into groups with or without (as a control group) tumor-bearing SiLN removal. Fifteen days later, tumor-bearing lymph node was surgically removed; 3 days after resection, mouse lung tissues were collected. The change of reticular fibers in lung tissues was observed by silver impregnation staining. The expression of C-C motif chemokine ligand 4 (CCL4), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), vimentin and MMP9 in lung tissues was detected by Western blotting. Results Compared with control group, expression of MMP9 and vimentin increased significantly in the lung tissues of SiLN removal group; reticular fibers were obviously fractured and its per area was reduced. Moreover, expression of CCL4, ICAM-1 and VCAM-1 also significantly increased. Conclusion Expression of CCL4, ICAM-1, VCAM-1, MMP9 and vimentin in mouse lung tissues is promoted after surgical removal of tumor-bearing lymph node, contributing to inflammatory cells' adhesion to and extravasation across vascular endothelium and further resulting in the formation of inflammatory microenvironment.


Asunto(s)
Quimiocina CCL4 , Regulación de la Expresión Génica , Molécula 1 de Adhesión Intercelular , Ganglios Linfáticos , Neoplasias , Molécula 1 de Adhesión Celular Vascular , Animales , Quimiocina CCL4/genética , Regulación de la Expresión Génica/inmunología , Molécula 1 de Adhesión Intercelular/genética , Ganglios Linfáticos/inmunología , Ganglios Linfáticos/cirugía , Ratones , Neoplasias/inmunología , Neoplasias/cirugía , Migración Transendotelial y Transepitelial/inmunología , Molécula 1 de Adhesión Celular Vascular/genética
20.
Cancers (Basel) ; 12(5)2020 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-32353949

RESUMEN

The class of circular RNA (circRNA) is characterized by head-to-tail bonds between exons formed by backsplicing. Here, we provide a resource of circRNA expression in a comprehensive panel of 60 lung cancer and non-transformed cell lines (FL3C dataset). RNA sequencing after depletion of ribosomal RNA quantified the expression of circRNA and linear RNA. We detected 148,811 circular RNAs quantified by 2.8 million backsplicing reads originating from 12,251 genes. The number of identified circRNAs was markedly higher using rRNA depletion compared to public polyA-enriched RNA-seq datasets. CircRNAs almost never started in the first exon nor ended in the last exon and started more frequently in earlier exons. Most circRNAs showed high cell line specificity and correlated positively with their linear RNA counterpart. Known cancer genes produced more circRNAs than non-cancer genes. Subsets of circRNAs correlated with cell proliferation, histological subtype or genotype. CircTNFRSF21 was translated crossing the backsplice site in two different reading frames. Overexpression of circPVT1, circERBB2, circHIPK3, circCCNB1, circSMAD2, circTNFRSF21 and circKIF5B significantly increased colony formation. In conclusion, our data provide a comprehensive map of circRNA expression in lung cancer cells and global patterns of circRNA production as a useful resource for future research into lung cancer circRNAs.

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