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BACKGROUND: Colorectal cancer (CRC) is a serious global health burden because of its high morbidity and mortality rates. Hypoxia and massive lactate production are hallmarks of the CRC microenvironment. However, the effects of hypoxia and lactate metabolism on CRC have not been fully elucidated. This study aimed to develop a novel molecular subtyping based on hypoxia-related genes (HRGs) and lactate metabolism-related genes (LMRGs) and construct a signature to predict the prognosis of patients with CRC and treatment efficacy. METHODS: Bulk and single-cell RNA-sequencing and clinical data of CRC were downloaded from the TCGA and GEO databases. HRGs and LMRGs were obtained from the Molecular Signatures Database. The R software package DESeq2 was used to perform differential expression analysis. Molecular subtyping was performed using unsupervised clustering. A predictive signature was developed using univariate Cox regression, random forest model, LASSO, and multivariate Cox regression analyses. Finally, the sensitivity of tumor cells to chemotherapeutic agents before and after hypoxia was verified using in vitro experiments. RESULTS: We classified 575 patients with CRC into three molecular subtypes and were able to distinguish their prognoses clearly. The C1 subtype, which exhibits high levels of hypoxia, has a low proportion of CD8 + T cells and a high proportion of macrophages. The expression of immune checkpoint genes is generally elevated in C1 patients with severe immune dysfunction. Subsequently, we constructed a predictive model, the HLM score, which effectively predicts the prognosis of patients with CRC and the efficacy of immunotherapy. The HLM score was validated in GSE39582, GSE106584, GSE17536, and IMvigor210 datasets. Patients with high HLM scores exhibit high infiltration of CD8 + exhausted T cells (Tex), especially terminal Tex, and oxidative phosphorylation (OXPHOS)-Tex in the immune microenvironment. Finally, in vitro experiments confirmed that CRC cell lines were less sensitive to 5-fluorouracil, oxaliplatin, and irinotecan under hypoxic conditions. CONCLUSION: We constructed novel hypoxia- and lactate metabolism-related molecular subtypes and revealed their immunological and genetic characteristics. We also developed an HLM scoring system that could be used to predict the prognosis and efficacy of immunotherapy in patients with CRC.
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Neoplasias Colorrectales , Ácido Láctico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Humanos , Pronóstico , Ácido Láctico/metabolismo , Regulación Neoplásica de la Expresión Génica , Masculino , Hipoxia/genética , Hipoxia/metabolismo , Microambiente Tumoral/genética , Femenino , Línea Celular Tumoral , Persona de Mediana Edad , Hipoxia de la Célula/genética , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacologíaRESUMEN
Recent advancements in polymer-assisted layer-by-layer (LbL) fabrication have revolutionized the development of wearable sensors for health monitoring. LbL self-assembly has emerged as a powerful and versatile technique for creating conformal, flexible, and multi-functional films on various substrates, making it particularly suitable for fabricating wearable sensors. The incorporation of polymers, both natural and synthetic, has played a crucial role in enhancing the performance, stability, and biocompatibility of these sensors. This review provides a comprehensive overview of the principles of LbL self-assembly, the role of polymers in sensor fabrication, and the various types of LbL-fabricated wearable sensors for physical, chemical, and biological sensing. The applications of these sensors in continuous health monitoring, disease diagnosis, and management are discussed in detail, highlighting their potential to revolutionize personalized healthcare. Despite significant progress, challenges related to long-term stability, biocompatibility, data acquisition, and large-scale manufacturing are still to be addressed, providing insights into future research directions. With continued advancements in polymer-assisted LbL fabrication and related fields, wearable sensors are poised to improve the quality of life for individuals worldwide.
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Técnicas Biosensibles , Polímeros , Dispositivos Electrónicos Vestibles , Polímeros/química , Humanos , Monitoreo Fisiológico/instrumentación , Monitoreo Fisiológico/métodos , Técnicas Biosensibles/instrumentación , Técnicas Biosensibles/métodosRESUMEN
Application of silicon-based anodes is significantly challenged by low initial Coulombic efficiency (ICE) and poor cyclability. Traditional pre-lithiation reagents often pose safety concerns due to their unstable chemical nature. Achieving a balance between water-stability and high ICE in prelithiated silicon is a critical issue. Here, we present a lithium-enriched silicon/graphite material with an ultra-high ICE of ≥110 % through a high-stable lithium pre-storage methodology. Lithium pre-storage prepared a nano-drilled graphite material with surficial lithium functional groups, which can form chemical bonds with adjacent silicon during high-temperature sintering. This results in an unexpected O-Li-Si interaction, leading to in situ pre-lithiation of silicon nanoparticles and providing high stability in air and water. Additionally, the lithium-enriched silicon/graphite materials impart a combination of high ICE, high specific capacity (620â mAh g-1), and long cycling stability (>400 cycles). This study opens up a promising avenue for highly air- and water-stable silicon anode prelithiation methods.
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Current fiber chromatic confocal probes suffer from a low axial resolution. This study proposes a fiber chromatic confocal method with a tilt-coupling source module for axial super-resolution. An annular intensity distribution is generated at the fiber port of the probe by adjusting the tilt-coupling angle between the fiber and source module to reduce the width of the confocal axial response characteristic curve at each wavelength and to enhance the intensity contrast of the spectral signal. Compared with the coaxial coupling state, the developed 21° tilt-coupling state can reduce the FWHM by approximately 17%, and the axial resolution increases by 1.7 times.
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China ranks the first worldwide in the number of new colorectal cancer (CRC) cases and CRC-related deaths. The increasing incidence of early-onset CRC in recent years highlights the challenges related to CRC screening and prevention. High-quality colonoscopy is the universally used gold standard for CRC screening. Risk assessment combined with a two-step screening strategy based on colonoscopy and non-invasive examinations was proven to be highly effective. However, systematic use of well-established risk factors associated with CRC, beyond age, could better identify those who might harbor advanced colorectal neoplasia, improve the diagnostic yield of current screening modalities, and optimize the selection of individuals who might benefit most from preventive strategies. "Personalization" and "Standardization" are the future development directions of CRC screening, from the initiation of screening in those at high risk for CRC to follow-up after treatment, which are the key to ensure the screening efficiency.
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Circular RNAs (circRNAs) are key regulatory factors in the development of multiple cancers. This study is targeted at exploring the effect of circ_0002623 on bladder cancer (BCa) progression and its mechanism. Circ_0002623 was screened out by analyzing the expression profile of circRNAs in BCa tissues. Circ_0002623, miR-1276, and SMAD2 mRNA expression levels in clinical sample tissues and cell lines were detected through quantitative real-time polymerase chain reaction (qRT-PCR). After circ_0002623 had been overexpressed or silenced in BCa cells, the cell proliferation, migration, and cell cycle were evaluated by CCK-8, BrdU, Transwell assay, and flow cytometry. Tumor xenograft model was used to validate the biological function of circ_0002623 in vivo. Bioinformatics analysis and dual-luciferase reporter gene assay were conducted for analyzing and confirming, respectively, the targeted relationship between circ_0002623 and miR-1276, as well as between miR-1276 and SMAD2. The regulatory effects of circ_0002623 and miR-1276 on the expression levels of TGF-ß, WNT1, and SMAD2 in BCa cells were detected by Western blot. We reported that, in BCa tissues and cell lines, circ_0002623 was upregulated, whereas miR-1276 was downregulated. Circ_0002623 positively regulated BCa cell proliferation, migration, and cell cycle progression. Additionally, circ_0002623 could competitively bind with miR-1276 to increase the expression of SMAD2, the target gene of miR-1276. Furthermore, circ_0002623 could regulate the expression of TGF-ß and WNT1 via modulating miR-1276 and SMAD2. This study helps to better understand the molecular mechanism underlying BCa progression.
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MicroARNs , Neoplasias de la Vejiga Urinaria , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Humanos , MicroARNs/genética , MicroARNs/metabolismo , ARN Circular/genética , Proteína Smad2/genética , Proteína Smad2/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
In the method of surface reconstruction from polarization, the reconstructed area is generally non-rectangular and contains a large number of sampling points. There is a difficulty that the coefficient matrix in front of the height vector changes with the shape of the measured data when using the zonal estimation. The traditional iterative approaches consume more time for the reconstruction of this type of data. This paper presents a non-iterative zonal estimation to reduce the computing time and to accurately reconstruct the surface. The index vector is created according to the positions of both the valid and invalid elements in the difference and gradient matrices. It is used to obtain the coefficient matrix corresponding to the general data. The heights in the non-rectangular area are calculated non-iteratively by the least squares method. At the same time, the sparse matrix is applied for handling the large-scale data quickly. The simulation and the experiment are designed to verify the feasibility of the proposed method. The results show that the proposed method is highly efficient and accurate in the reconstruction of the non-rectangular data.
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The two-dimensional Fourier-transform-based integration algorithm is widely used in shape or wavefront reconstruction from gradients. However, its reconstruction accuracy is limited by the truncation error of the difference model. The truncation error is affected by the distribution of the sampling points. It increases when the sampling points are unevenly distributed and arranged irregularly. For improving, a novel way to calculate the difference is proposed based on Taylor expansion theory of binary functions. The first-order partial derivative terms are used to estimate the second- and third-order partial derivative terms for reducing the truncation error. The proposed difference model is applied to Fourier-transform-based integration. The reconstruction results show that it can get better results when the sampling points are irregularly distributed.
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The present study aimed to give a short report on a possible mechanism of glycyrrhizin to acetaminophen-induced liver toxicity. Seven-day intraperitoneal administration of glycyrrhizin (400 mg/kg/day) to 2- to 3-month-old male C57BL/6N mice (mean weight 27 g) significantly prevents acetaminophen-induced liver damage, as indicated by the activity of alanine transaminase and aspartate aminotransferase. Metabolomics analysis and principal component analysis (PCA) using ultra-fast liquid chromatography coupled to triple time-of-flight mass spectrometer were performed. PCA separated well the control, glycyrrhizin-treated, acetaminophen-treated, and glycyrrhizin+acetaminophen-treated groups. Long-chain acylcarnitines were listed as the top ions that contribute to this good separation, which include oleoylcarnitine, palmitoylcarnitine, palmitoleoylcarnitine, and myristoylcarnitine. The treatment of glycyrrhizin significantly reversed the increased levels of long-chain acylcarnitines induced by acetaminophen administration. In conclusion, this metabolomic study indicates a significant glycyrrhizin protection effect against acetaminophen-induced liver damage through reversing fatty acid metabolism.
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Acetaminofén/toxicidad , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Ácido Glicirrínico/farmacología , Metabolismo de los Lípidos/efectos de los fármacos , Metaboloma , Alanina Transaminasa/metabolismo , Animales , Aspartato Aminotransferasas/metabolismo , Carnitina/análogos & derivados , Carnitina/química , Cromatografía Liquida , Masculino , Espectrometría de Masas , Ratones , Ratones Endogámicos C57BLRESUMEN
Inferior air stability is a primary barrier for large-scale applications of garnet electrolytes in energy storage systems. Herein, a deeply hydrated hydrogarnet electrolyte generated by a simple ion-exchange-induced phase transition from conventional garnet, realizing a record-long air stability of more than two years when exposed to ambient air is proposed. Benefited from the elimination of air-sensitive lithium ions at 96 h/48e sites and unobstructed lithium conduction path along tetragonal sites (12a) and vacancies (12b), the hydrogarnet electrolyte exhibits intrinsic air stability and comparable ion conductivity to that of traditional garnet. Moreover, the unique properties of hydrogarnet pave the way for a brand-new aqueous route to prepare lithium metal stable composite electrolyte on a large-scale, with high ionic conductivity (8.04 × 10-4 S cm-1), wide electrochemical windows (4.95 V), and a high lithium transference number (0.43). When applied in solid-state lithium batteries (SSLBs), the batteries present impressive capacity and cycle life (164 mAh g-1 with capacity retention of 89.6% after 180 cycles at 1.0C under 50 °C). This work not only designs a new sort of hydrogarnet electrolyte, which is stable to both air and lithium metal but also provides an eco-friendly and large-scale fabrication route for SSLBs.
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Background: Mucinous adenocarcinoma (MAC) is a unique subtype of colorectal cancer and its prognostic value remains controversial. This study aimed to compare the clinicopathological characteristics and prognostic differences between patients with MAC and non-mucinous adenocarcinoma (NMAC). Methods: 674 patients with NMAC, 110 patients with adenocarcinoma with mucinous component (ACWM) and 77 patients with MAC between 2016-2019 were enrolled in the study. Univariate and multivariate Cox regression were performed to analyze the factors associated with prognosis. Predictive nomograms of overall survival (OS) and cancer-specific survival (CSS) for patients with colorectal adenocarcinoma were constructed. Confounding factors were eliminated by propensity score matching (PSM). Results: Compared with patients with NMAC, patients with MAC were more likely to have a tumor located at the proximal colon, present with a larger tumor diameter, more advanced T stage, higher frequency of metastasis, deficiency of mismatch repair, and elevated preoperative carcinoembryonic antigen. Patients with MAC were related to worse OS (HR=2.53, 95%CI 1.73-3.68, p<0.01) and CSS (HR=3.09, 95%CI 2.10-4.57, p<0.01), which persisted after PSM. Subgroup analysis demonstrated that patients with left-sided or stage III/IV MAC exhibited a comparatively worse OS and CSS than those with NMAC. Furthermore, in patients with stage II with a high-risk factor and stage III MAC, adjuvant chemotherapy was associated with an improved OS, CSS, and RFS. Conclusion: Compared with the NMAC phenotype, the MAC phenotype was an independent risk factor for poor prognosis in colorectal adenocarcinoma with worse OS and CSS, particularly patients with left-sided colorectal cancer and stage III/IV. However, patients with MAC can still benefit from adjuvant chemotherapy.
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Background: Insulin resistance has been proven to be associated with renal cell carcinoma (RCC). However, the prognostic value of the triglyceride-glucose (TyG) index, as a marker for insulin resistance (IR), is still unclear. Therefore, we conducted research to explore the prognostic value and the predictive performance of the TyG index in postoperative RCC patients. Methods: A total of 651 postoperative RCC patients from January 2016 to June 2018 were enrolled in the final study. Their clinical and laboratory parameters were collected from medical records and through follow-up by phone. The triglyceride-glucose (TyG) index was calculated as follows: TyG = Ln[TG (mg/dl) × FBG (mg/dL)/2]. The overall survival (OS) and disease-free survival (DFS) were identified as the main outcomes. Results: The TyG index is an independent prognostic factor for OS (HR = 2.340, 95% CI = 1.506 to 3.64, P < 0.001) and DFS (HR = 2.027, 95% CI = 1.347 to 3.051, P < 0.001) in postoperative RCC patients. Kaplan-Meier survival curves of the different TyG index levels showed statistically significant differences in terms of OS and DFS (log-rank test, P < 0.0001). Furthermore, the TyG index was significantly associated with RCC risk factors. Conclusion: The TyG index is significantly associated with RCC survival. The mechanisms responsible for these results may contribute toward the improvement of RCC prognosis and immunotherapy efficacy and the development of new immunotherapeutic targets.
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Carcinoma de Células Renales , Resistencia a la Insulina , Neoplasias Renales , Humanos , Estudios Retrospectivos , Pronóstico , Glucosa , TriglicéridosRESUMEN
BACKGROUND AND PURPOSE: The delineation of clinical target volume (CTV) for primary nasopharyngeal carcinoma (NPC) is currently controversial and the international guideline still recommend a uniform border for CTV regardless of the tumor extent. We conducted this prospective, real-world study to evaluate the clinical outcomes of our individualized CTV delineation method based on distance plus substructures. MATERIALS AND METHODS: We preliminarily investigated the local extension patterns of NPC on 354 newly diagnosed patients and defined the structures surrounding the nasopharynx as Level-1 to Level-4 substructures stratified by the risk of invasion. We then enrolled patients with newly diagnosed NPC without distant metastasis to investigate our individualized CTV delineation protocol. All patients received intensity modulated radiotherapy. CTV1 and CTV2 were prescribed doses of 60 Gy and 54 Gy in 30 â¼ 33 fractions. The primary endpoint was local recurrence-free survival (LRFS); secondary endpoints included regional control and survival, estimated using the Kaplan-Meier method. The local failure patterns were also analyzed. RESULTS: From January 2008 to December 2012 and from January 2013 to September 2019, 356 and 648 patients were enrolled, named as training set and validation set, respectively. With a median follow-up of 104.6 (interquartile, 73.1-126.9) and 51.4 (39.5-78.5) months, 31 (8.7 %) and 38 (5.9 %) patients in training and validation sets experienced local recurrence, and the 5-year LRFS was 93.0 % and 93.2 %, respectively; 63 (17.7 %) and 39 (6 %) patients died in training and validation sets, and the 5-year overall survival (OS) was 88.5 % and 93.4 %, respectively. For the whole study cohort (N = 1004) with a median follow-up of 66.6 (41.5-98.0) months, the 5-year LRFS and OS was 93.2 % and 91.5 %. The grade 3 late toxicities included xerostomia, subcutaneous fibrosis, hearing impairment, trismus, visuality impairment and skin atrophy, with a total incidence of 1.5 %. Sixty-seven of 69 (97.1 %) local recurrence was in high-dose area. CONCLUSION: Our individualized CTV delineation method can achieve favorable local tumor control and long-term survival outcomes with acceptable late toxicities.
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Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Invasividad Neoplásica , Radioterapia de Intensidad Modulada , Humanos , Masculino , Femenino , Estudios Prospectivos , Persona de Mediana Edad , Carcinoma Nasofaríngeo/radioterapia , Carcinoma Nasofaríngeo/patología , Carcinoma Nasofaríngeo/mortalidad , Radioterapia de Intensidad Modulada/métodos , Radioterapia de Intensidad Modulada/efectos adversos , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/patología , Neoplasias Nasofaríngeas/mortalidad , Adulto , Anciano , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador/métodos , Adulto JovenRESUMEN
Lithium-oxygen batteries have attracted widespread attention owing to their superior theoretical energy density. However, they are obstructed by sluggish oxygen reduction (ORR) and evolution reaction (OER) kinetics at air cathodes. Herein, different from using single solid or soluble catalysts, solid-soluble synergistic catalysis is proposed to conjointly enhance ORR/OER performances. During discharge, single-atomic zinc/cobalt embedded in nitrogen-doped carbon (Zn, Co-N/C) is judiciously engineered as a solid catalyst to regulate the growth pathway of Li2O2 and promote ORR kinetics. During charge, a typical redox mediator (RM, LiI) is added as a soluble catalyst to permit efficient oxidation of Li2O2. Of note is that the atomic Zn/Co-Nx sites can chemically adsorb oxidized iodine (I2) and accelerate OER kinetics, which plays a decisive role in eliminating the shuttle effect of I3-/I2 to the Li anode. Coupling a single-atomic catalyst with restricted oxidized iodine offers an exceptional discharge capacity, remarkably low polarization, and superior long-term cycling stability.
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Developing an efficient and environment-friendly route for waste valorization is extremely significant in accelerating the transition toward a circular economy. A novel waste-to-synthetic natural gas (SNG) conversion process comprising hybrid renewable energy systems is proposed for this purpose. This includes thermochemical waste conversion and power-to-gas technologies for simultaneous waste utilization and renewable energy storage applications. The energy and environmental performances of the proposed waste-to-SNG plant are assessed and optimized. Results indicated that the implementation of a thermal pretreatment unit prior to the plasma gasification (two-step) is beneficial to improve the yield of hydrogen in the syngas, thereby leading to less renewable energy requirement for green hydrogen production used in the methanation process. This also enhances SNG yield by a factor of 30% as compared to the case without thermal pretreatment (one-step). The overall energy efficiency (OE) of the proposed waste-to-SNG plant is in the range of 61.36-77.73%, while the energy return on investment (EROI) ranges between 2.66 and 6.11. Most environmental impacts are mainly contributed by the indirect carbon emissions as a consequence of the power requirement for thermal pretreatment, plasma gasifier, and auxiliary equipment. The value of specific electricity consumption for SNG production of the treated RDF exhibits 1.70-9.25 % less than that of raw RDF when the pretreatment temperature is less than 300 °C. The OE of the system declines by 4.52% when 50 wt% of biomass is mixed in the fuel, whereas an enhancement of 18.33% in EROI and a reduction of 16.19% in specific CO2 emissions are obtained.
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Gas Natural , Eliminación de Residuos , Eliminación de Residuos/métodos , Energía Renovable , Temperatura , HidrógenoRESUMEN
Background: Mucinous adenocarcinoma (MAC) is a unique clinicopathological colorectal cancer (CRC) type that has been recognized as a separate entity from non-mucinous adenocarcinoma (NMAC), with distinct clinical, pathologic, and molecular characteristics. We aimed to construct prognostic signatures and identifying candidate biomarkers for patients with MAC. Methods: Differential expression analysis, weighted correlation network analysis (WGCNA), and least absolute shrinkage and selection operator (LASSO)-Cox regression model were used to identify hub genes and construct a prognostic signature based on RNA sequencing data from TCGA datasets. The Kaplan-Meier survival curve, gene set enrichment analysis (GSEA), cell stemness, and immune infiltration were analyzed. Biomarker expression in MAC and corresponding normal tissues from patients operated in 2020 was validated using immunohistochemistry. Results: We constructed a prognostic signature based on ten hub genes. Patients in the high-risk group had significantly worse overall survival (OS) than patients in the low-risk group (p < 0.0001). We also found that ENTR1 was closely associated with OS (p = 0.016). ENTR1 expression was significantly positively correlated with cell stemness of MAC (p < 0.0001) and CD8+ T cell infiltration (p = 0.01), whereas it was negatively associated with stromal scores (p = 0.03). Finally, the higher expression of ENTR1 in MAC tissues than in normal tissues was validated. Conclusion: We established the first MAC prognostic signature, and determined that ENTR1 could serve as a prognostic marker for MAC.
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N6-Methyladenosine (m6A) plays a key role in the occurrence and development of various cancers. Fat mass and obesity-associated protein (FTO) was is involved in multiple cancers owing to its demethylase activity, and the molecular mechanism underlying FTO-promoted bladder cancer proliferation and migration via the regulation of RNA stability requires further investigation. In the present study, FTO was upregulated in bladder cancer and related to poor prognosis. Gain- and loss-of-function experiments showed that the upregulation of FTO promoted bladder cancer proliferation and migration. Mechanistic studies showed that FTO enhanced the stability of signal transducer and activator of transcription 3 (STAT3) mRNA in an m6A-dependent manner, thereby increasing STAT3 expression, which subsequently promoted P-STAT3 expression and activated STAT3 signalling pathway. Overall, this study revealed that the critical role of FTO in the progression of bladder cancer and could provide a novel avenue to regulate oncogene STAT3.
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Factor de Transcripción STAT3 , Neoplasias de la Vejiga Urinaria , Humanos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo , Metilación de ADN , Neoplasias de la Vejiga Urinaria/genética , Proliferación Celular , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/genética , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/metabolismoRESUMEN
Colorectal cancer (CRC) is a deadly form of cancer worldwide. Patients with locally advanced rectal cancer and metastatic CRC have a poor long-term prognosis, and rational and effective treatment remains a major challenge. Common treatments include multi-modal combinations of surgery, radiotherapy, and chemotherapy; however, recurrence and metastasis rates remain high. The combination of radiotherapy and immunotherapy (radioimmunotherapy [RIT]) may offer new solutions to this problem, but its prospects remain uncertain. This review aimed to summarize the current applications of radiotherapy and immunotherapy, elaborate on the underlying mechanisms, and systematically review the preliminary results of RIT-related clinical trials for CRC. Studies have identified several key predictors of RIT efficacy. Summarily, rational RIT regimens can improve the outcomes of some patients with CRC, but current study designs have limitations. Further studies on RIT should focus on including larger sample sizes and optimizing the combination therapy regimen based on underlying influencing factors.
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Neoplasias Colorrectales , Radioinmunoterapia , Humanos , Radioinmunoterapia/métodos , Terapia Combinada , Inmunoterapia , Resultado del Tratamiento , Neoplasias Colorrectales/terapia , Neoplasias Colorrectales/patologíaRESUMEN
The aprotic Li-O2 battery (LOB) has the highest theoretical energy density of any rechargeable batteries. However, such system is largely restricted by the electrochemically formed lithium peroxide (Li2 O2 ) on the cathode surface, leading ultimately to low actual capacities and early cell death. In contrast to the surface-mediated growth of thin film with a thickness <50 nm, a non-crystalline Li2 O2 film with a thickness of >400 nm can be formed via an optimal OCe hybridized electronic structure. Specially, oxygen can react with dissolved cerium cations in the electrolyte via a cerium-oxygen reaction to form a high-energy faceted cerium oxide catalyst, which not only generates a great number of non-saturable active sites, but also erects electron transport bridges between the lattice O and adjacent Ce atoms. Such CeO orbital hybridization also forms a direct charge transfer channel from Ce-4f of CeO2 to O 2 2 - ${\rm{O}}_2^{2 - }$ -π* of Li2 O2 , eventually leading to submicron-thick Li2 O2 shells via a subsequent lithium-oxygen reaction. Relying on the above merits, this work unlocks the rechargeable capacities of LOB from restricted 1000 to unprecedented 10 000 mAh g-1 with good cyclabilities and reduced charge-discharge overpotentials.
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Studies have shown that tripartite motif-containing (TRIM) family proteins function as E3 ubiquitin ligases and play essential roles in cancer biology. In the present study, we validated a contribution of TRIM9 to bladder cancer progression. 296 patients derived from The Cancer Genome Atlas (TCGA) database and 22 clinical specimens were included, in which accumulated TRIM9 correlated with the poor prognosis and higher relapse in bladder patients. In vitro, TRIM9 promoted bladder cancer cells Biu-87 and T24 cell proliferation and migration. Meanwhile, overexpression of TRIM9 reduced the chemosensitivity in Biu-87 and T24 to mitomycin C (MMC) and gemcitabine (GEM). As an underlying mechanism, we found that TRIM9 stimulated carcinoembryonic antigen 6 (CEACAM6) upregulation, which further facilitated Smad2/3-matrix metalloproteinase 2 (MMP2) signaling activation both in vitro and in vivo. Those results indicated that TRIM9 facilitated bladder cancer development and chemoresistance by CEACAM6-Smad2/3 axis. TRIM9 and its associated molecules could be a potential diagnostic indicator and therapeutic target in bladder cancer.