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High Ozone Production Rate (OPR) leads to O3 pollution episodes and adverse human health outcomes. OPR observation (Obs-OPR) and OPR modelling (Mod-OPR) have been obtained from observed and modelled peroxy radicals and nitrogen oxides. However, discrepancies between them remind of an imperfect understanding of O3 photochemistry. Direct measurement of OPR (Mea-OPR) by a twin-chamber system emerges. Herein, we optimized Mea-OPR design, i.e., minimizing the chamber surface area to volume ratio (S/V) to 9.8 m-1 from 18 m-1 and the dark uptake coefficient of O3 to 9.9 × 10-9 from 7.1 × 10-8 in the literature. In addition, control experiments further revealed and quantified a photo-enhanced O3 uptake, and therefore recommended an essential correction of Mea-OPR. We finally characterized a measurement uncertainty of ±38% and a detection limit of 3.2 ppbv h-1 (3SD), which suggested that Mea-OPR would be sensitive enough to measure OPR in urban or suburban environments. Further application of this system in urban Beijing during the Beijing 2022 Olympic Winter Games recorded a noontime OPR of 7.3 (±3.3, 1SD) ppbv h-1. These observational results added up to our confidence in future field application of Mea-OPR, to facilitate pollution control policy evaluation and to shed light on O3 photochemistry puzzle.
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Poluentes Atmosféricos , Ozônio , Compostos Orgânicos Voláteis , Humanos , Ozônio/análise , Poluentes Atmosféricos/análise , Monitoramento Ambiental , Poluição Ambiental/análise , Óxidos de Nitrogênio/análise , China , Compostos Orgânicos Voláteis/análiseRESUMO
Nitrated aromatic compounds (NACs) are key components of air pollution; however, due to the presence of complex mixtures of primary and secondary species, especially in urban environments, their atmospheric formation is poorly understood. Here we conducted a field campaign during a winter haze episode in urban Beijing, China to monitor gaseous and particulate NACs at 2-h time resolution. Through a standard-independent non-targeted approach, a total of 238 NACs were screened, of which 127 species were assigned chemical formula and 25 structures were confirmed. Four main classes were identified: nitrated aromatic hydrocarbons, nitrophenols, oxygenated nitrated aromatic compounds, and nitrated heterocyclic aromatic compounds. Hierarchical clustering analysis revealed disparate temporal variances of diurnal or nocturnal elevation, among which different nitration formations were captured, i.e., daytime photochemical oxidation and nighttime heterogeneous reactions. Isomeric information, particularly the substitution position of the nitro group on biphenyl, further demonstrated a potential heterogeneous mechanism of electrophilic nitration by NO2+. Assisted by source apportionment, we found that nighttime heterogeneous reactions significantly contributed to NAC formation, e.g., 31.3 % and 60.8 %, respectively, to 2-nitrofluoranthene and 2-nitropyrene, which were previously considered as classical daytime gas-phase products. This study provides comprehensive information on urban NAC species and highlights the importance of unheeded heterogeneous reactions in the atmosphere.
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BACKGROUND: Circular RNAs (circRNAs) have been reported to play important roles in cancers. Here, we characterized circVMP1 (hsa_circ_0006508), an important circRNA which promoted glycolysis and disease progression in colorectal cancer (CRC). In this study, we aimed to explore the mechanism by which circVMP1 regulated tumor glycolysis and its related pathways in promoting CRC cell proliferation and metastasis. METHODS: The expression level of circVMP1 in CRC tissues and adjacent normal tissues was detected using quantitative PCR. In vitro and in vivo functional experiments were used to evaluate the effects of circVMP1 in the regulation of CRC cell proliferation and migration. Mitochondrial stress tests and glycolysis stress tests were conducted to detect the effect of circVMP1 on oxidative phosphorylation and glycolysis. Dual-luciferase reporter and RNA immunoprecipitation assays were used to evaluate the interaction between circVMP1, miR-3167, and HKDC1. RESULTS: We demonstrated that the level of circVMP1 was significantly upregulated in CRC tissues compared with normal tissues. In HCT116 and SW480 cells, overexpression of circVMP1 promoted proliferation, metastasis, and glycolysis. In vivo analysis indicated that circVMP1 accelerated the proliferation of xenograft tumors. As for the mechanism, overexpression of circVMP1 increased the levels of hexokinase domain component 1 (HKDC1) through competitive binding with miR-3167. CONCLUSION: Our study reported that circVMP1 was one of the tumor driver genes that promoted CRC malignant progression and glycolysis by upregulating HKDC1. CircVMP1/miR-3167/HKDC1 was a signaling axis that might be a target for CRC therapy.
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Neoplasias Colorretais , Hexoquinase , RNA Circular , Humanos , Linhagem Celular Tumoral , Proliferação de Células , Progressão da Doença , Glicólise , Hexoquinase/metabolismo , MicroRNAsRESUMO
External cycling regenerating nitrogen oxides (NOx ≡ NO + NO2) from their oxidative reservoir, NOz, is proposed to reshape the temporal-spatial distribution of NOx and consequently hydroxyl radical (OH), the most important oxidant in the atmosphere. Here we verify the in situ external cycling of NOx in various environments with nitrous acid (HONO) as an intermediate based on synthesized field evidence collected onboard aircraft platform at daytime. External cycling helps to reconcile stubborn underestimation on observed ratios of HONO/NO2 and NO2/NOz by current chemical model schemes and rationalize atypical diurnal concentration profiles of HONO and NO2 lacking noontime valleys specially observed in low-NOx atmospheres. Perturbation on the budget of HONO and NOx by external cycling is also found to increase as NOx concentration decreases. Consequently, model underestimation of OH observations by up to 41% in low NOx atmospheres is attributed to the omission of external cycling in models.
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Incomplete combustion of fossil fuels and biomass burning emit large amounts of soot particles into the troposphere. The condensation process is considered to influence the size (Dp) and mixing state of soot particles, which affects their solar absorption efficiency and lifetimes. However, quantifying aging evolution of soot remains hampered in the real world because of complicated sources and observation technologies. In the Himalayas, we isolated soot sourced from transboundary transport of biomass burning and revealed soot aging mechanisms through microscopic observations. Most of coated soot particles stabilized one soot core under Dp < 400 nm, but 34.8% of them contained multi-soot cores (nsoot ≥ 2) and nsoot increased 3-9 times with increasing Dp. We established the soot mixing models to quantify transformation from condensation- to coagulation-dominant regime at Dp ≈ 400 nm. Studies provide essential references for adopting mixing rules and quantifying the optical absorption of soot in atmospheric models.
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In the urban atmosphere, nitrogen oxide (NOxâNO + NO2)-related reactions dominate the formation of nitrous acid (HONO). Here, we validated an external cycling route of HONO and NOx, i.e., formation of HONO resulting from precursors other than NOx, in the background atmosphere. A chemical budget closure experiment of HONO and NOx was conducted at a background site on the Tibetan Plateau and provided direct evidence of the external cycling. An external daytime HONO source of 100 pptv h-1 was determined. Both soil emissions and photolysis of nitrate on ambient surfaces constituted likely candidate mechanisms characterizing this external source. The external source dominated the chemical production of NOx with HONO as an intermediate tracer. The OH production was doubled as a result of the external cycling. A high HONO/NOx ratio (0.31 ± 0.06) during the daytime was deduced as a sufficient condition for the external cycling. Literature review suggested the prevalence of high HONO/NOx ratios in various background environments, e.g., polar regions, pristine mountains, and forests. Our analysis validates the prevalence of external cycling in general background atmosphere and highlights the promotional role of external cycling regarding the atmospheric oxidative capacity.
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Nitrogênio , Ácido Nitroso , Ácido Nitroso/análise , Ácido Nitroso/química , Óxidos de Nitrogênio/análise , Nitratos , Óxido Nítrico , Atmosfera/químicaRESUMO
Circular RNAs (circRNAs) have been demonstrated to be important regulators in human malignant tumors, including colorectal cancer (CRC). While the role circ-ZEB1 played in CRC remains unclear. In this study, we aim to explore the biological function and the underlying mechanism of circ-ZEB1 in CRC. RNAscope was used to analyze the expression and localization of circ-ZEB1 in CRC tissues. Loss of function experiments were conducted, including CCK-8, transwell assays, flow cytometry analysis, and murine xenograft models, so as to detect the effect of circ-ZEB1 on CRC cells. IC50 assay was used to evaluate the influence of circ-ZEB1 on the chemoresistance of CRC cells. Epithelial-mesenchymal transition (EMT) related markers were detected. The relationship between circ-ZEB1 and miR-200c-5p was investigated by FISH, dual-luciferase reporter assay, and RIP assay. We found in our study that circ-ZEB1 was significantly upregulated in CRC tissues. Downregulation of circ-ZEB1 inhibited cell proliferation, colony formation, as well as cell migration and invasion abilities of CRC cell lines. In vivo experiments indicated that knockdown of circ-ZEB1 suppressed tumorigenesis and distant metastasis of CRC cells in nude mice. What's more, EMT and chemoresistance of CRC cells were also attenuated following circ-ZEB1 knockdown. Mechanistically, we proved that circ-ZEB1 could directly bind with miR-200c and functioned as miR-200c sponge to exert its biological functions in CRC cells. In conclusion, circ-ZEB1 could promote CRC cells progression, EMT, and chemoresistance via acting on miR-200c, elucidating a potential therapeutic target to inhibit CRC progression.
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Background: Alternative splicing (AS) plays a crucial role in regulating the progression of colorectal cancer (CRC), but its distribution remains to be explored. Here, we aim to investigate the genes edited by AS which show differential expression in patients with mismatch repair deficiency (dMMR)/microsatellite instability (MSI). Materials and Methods: We applied long-read nanopore sequencing to determine the mRNA profiles and screen AS genes using Oxford Nanopore Technologies (ONT) method in ten paired CRC tissues. CRC tissue and plasma samples were used to validate the differential genes with AS using real-time fluorescent quantitative PCR, immunohistochemistry, and enzyme-linked immunosorbent assay. Results: ONT sequencing identified 404 genes were downregulated, and 348 genes were upregulated in MSI cancer tissues compared with microsatellite stability (MSS) cancer tissues. In total, 6,200 AS events were identified in 2,728 mRNA transcripts. WGCNA revealed dMMR/MSI-correlated gene modules, including INHBA and RPL22L1, which were upregulated; conversely, HMGCS2 was downregulated in MSI cancer. Overexpression of RPL22L1, INHBA, and CAPZA1 was further confirmed in CRC tissues. INHBA was found to be associated with tumor lymphatic metastasis. Importantly, the levels of INHBA in CRC plasma were significantly increased compared with those in noncancer plasma. INHBA showed a higher level in dMMR/MSI CRC than in MSS CRC, indicating that INHBA is a useful biomarker. Conclusion: Our results showed that ONT-identified genes provide a pool to explore AS-associated markers for dMMR/MSI CRC. We demonstrated INHBA as a promising signature for clinical application in predicting tumor lymphatic metastasis and screening dMMR/MSI candidates.
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Neoplasias do Colo , Neoplasias Colorretais , Sequenciamento por Nanoporos , Processamento Alternativo , Neoplasias Colorretais/patologia , Reparo de Erro de Pareamento de DNA/genética , Humanos , Metástase Linfática , Instabilidade de Microssatélites , RNA Mensageiro/genéticaRESUMO
PURPOSE: Extralevator (ELAPE) and abdominoperineal excision (APE) are two major surgical approaches for low rectal cancer patients. Although excellent short-term efficacy is achieved in patients undergoing ELAPE, the long-term benefits have not been established. In this study we evaluated the safety, pathological and survival outcomes in rectal cancer patients who underwent ELAPE and APE. METHODS: One hundred fourteen patients were enrolled, including 68 in the ELAPE group and 46 in the APE group at the Beijing Chaoyang Hospital, Capital Medical University from January 2011 to November 2020. The baseline characteristics, overall survival (OS), progression-free survival (PFS), and local recurrence-free survival (LRFS) were calculated and compared between the two groups. RESULTS: Demographics and tumor stage were comparable between the two groups. The 5-year PFS (67.2% versus 38.6%, log-rank P = 0.008) were significantly improved in the ELAPE group compared to the APE group, and the survival advantage was especially reflected in patients with pT3 tumors, positive lymph nodes or even those who have not received neoadjuvant chemoradiotherapy. Multivariate analysis showed that APE was an independent risk factor for OS (hazard ratio 3.000, 95% confidence interval 1.171 to 4.970, P = 0.004) and PFS (hazard ratio 2.730, 95% confidence interval 1.506 to 4.984, P = 0.001). CONCLUSION: Compared with APE, ELAPE improved long-term outcomes for low rectal cancer patients, especially among patients with pT3 tumors, positive lymph nodes or those without neoadjuvant chemoradiotherapy.
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Procedimentos Cirúrgicos do Sistema Digestório , Protectomia , Neoplasias Retais , Abdome/patologia , Abdome/cirurgia , Humanos , Períneo/cirurgia , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Resultado do TratamentoRESUMO
Accurate and sensitive measurements of NO2 play an extremely important role in atmospheric studies. Increasingly, studies require NO2 measurements with parts per trillion by volume (pptv-level) detection limits. Other desirable instrument attributes include ease of use, long-term stability, and low maintenance. In this work, we report the development of an amplitude-modulated multimode-diode-laser-based cavity-enhanced absorption spectroscopy (AM-CEAS) system operating at 406 nm that uses phase-sensitive detection for extremely sensitive NO2 detection. The laser was TTL-modulated at 35 kHz. The mirror reflectivity was determined to be 99.985% based on the ring-down time measurement. The cavity base length was 47.5 cm, giving an effective absorption pathlength of â¼3.26 km. AM-CEAS achieved a 1σ detection precision of 35 pptv in a 1 s data acquisition time (4.98 × 10-10 cm-1), over 4 times lower than that attained using a ring-down approach and the same optical system. The AM-CEAS precision improved to 8 pptv over a data acquisition time of 30 s (1.14 × 10-10 cm-1). The AM-CEAS method with the multimode diode laser integrates the advantages of high light injection efficiency like on-axis alignment cavity ring-down spectroscopy, low cavity-mode noise like off-axis alignment CEAS, and narrow-bandwidth high-sensitivity weak signal detection of modulation spectroscopy, providing a powerful, straightforward, and general method for ultrasensitive absorption and extinction measurements.
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Lasers , Dióxido de Nitrogênio , Luz , Análise Espectral/métodosRESUMO
Nitrates formed on mineral dust through heterogeneous reactions in high NOx areas can undergo photolysis to regenerate NOx and potentially interfere in the photochemistry in the downwind low NOx areas. However, little is known about such renoxification processes. In this study, photolysis of various nitrates on different mineral oxides was comprehensively investigated in a flow reactor and in situ diffuse reflectance Fourier-transform infrared spectroscopy (in situ DRIFTS). TiO2 was found much more reactive than Al2O3 and SiO2 with both NO2 and HONO as the two major photolysis products. The yields of NO2 and HONO depend on the cation basicity of the nitrate salts or the acidity of particles. As such, NH4NO3 is much more productive than other nitrates like Fe(NO3)3, Ca(NO3)2, and KNO3. SO2 and water vapor promote the photodegradation by increasing the surface acidity due to the photoinduced formation of H2SO4/sulfate and H+, respectively. O2 enables the photo-oxidation of NOx to regenerate nitrate and thus inhibits the NOx yield. Overall, our results demonstrated that the photolysis of nitrate can be accelerated under complex air pollution conditions, which are helpful for understanding the transformation of nitrate and the nitrogen cycle in the atmosphere.
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Nitratos , Óxidos , Óxidos de Nitrogênio , Fotólise , Dióxido de SilícioRESUMO
Wintertime urban air pollution in many global megacities is characterised by episodic rapid increase in particulate matter concentrations associated with elevated relative humidity - so-called haze episodes, which have become characteristic of cities such as Beijing. Atmospheric chemistry within haze combines gas- and condensed-phase chemical processes, leading to the growth in secondary species such as sulphate aerosols. Here, we integrate observations of reactive gas phase species (HONO, OH, NOx) and time-resolved aerosol composition, to explore observational constraints on the mechanisms responsible for sulphate growth during the onset of haze events. We show that HONO abundance is dominated by established fast gas-phase photochemistry, but the consideration of the additional formation potentially associated with condensed-phase oxidation of S species by aqueous NO2 leading to NO2- production and hence HONO release, improves agreement between observed and calculated gas-phase HONO levels. This conclusion is highly dependent upon aerosol pH, ionic strength and particularly the parameterisation employed for S(iv) oxidation kinetics, for which an upper limit is derived.
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PURPOSE: Pancreatic cancer is associated with a high mortality rate owing to insufficient approaches for early diagnosis and the invasive biological behavior of the cancer. CD26 is a membrane-anchored protein involved in multiple physiological and pathological processes. Here, we investigated correlations between CD26 expression and clinicopathological features in patients with pancreatic tumors. METHODS: We collected 170 tumor tissue specimens and 138 paired paratumoral tissues from patients with pancreatic tumors and evaluated CD26 expression using immunohistochemistry. RESULTS: CD26 was expressed in 79.4% of pancreatic tumors, which was significantly (P < 0.001) higher than that in paratumoral pancreatic tissues (23.2%). High expression of CD26 was correlated with ABO blood type (P = 0.035), malignancy degree (P = 0.001), CA199 (P = 0.01), and CA242 (P = 0.027). In pancreatic malignancies, CD26 expression was observed in 80.7% (130/161) of cases. Lower CD26 expression was correlated with longer disease-free survival (P = 0.048) and overall survival (P = 0.024) and was an independent predictor of overall survival (hazard ratio [HR]: 1.713; P = 0.042). Similar results were observed in pancreatic ductal adenocarcinoma (PDAC) tissues, and CD26 expression level (HR: 2.117; P = 0.008) was an independent predictor of overall survival in patients with PDAC. CD26 expression was significantly increased in pancreatic tumors and gradually increased with increasing malignancy degree, suggesting that CD26 may be involved in the tumorigenic proliferation of pancreatic tumors. CONCLUSION: Therefore, CD26 is a potential marker for early diagnosis and a promising therapeutic target in pancreatic tumors.
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BACKGROUND: Emerging evidence suggests that circular RNAs (circRNAs) are vital regulators in a range of cancers. "miRNA sponge" is the most reported role played by circRNAs in many tumors. The insulin-like growth factor (IGF) 1 pathway plays a key role in the development and progression of many cancers, including colorectal cancer (CRC). The aim of the study is to establish the potential clinical value and driving molecular mechanisms of circRNAs in CRC. MATERIALS AND METHODS: Real-time quantitative RT-PCR (qRT-PCR) was performed to measure the circRUNX1 expression in 52 tissue samples from CRC patients. We verified the tumor promotor role of circRUNX1 in cell-based in vitro and in vivo assays. Human growth factor array was used to identify circRUNX1-regulated signaling pathways. We then used a double luciferase reporter assay and RNA fluorescence in situ hybridization to identify the downstream miR-145-5p of circRUNX1. Furthermore, we performed Western blotting and biological function assays to demonstrate if the circRUNX1/miR-145-5p/IGF1 axis is responsible for the proliferation of CRC cells and promotes CRC development. RESULTS: By performing qRT-PCR from CRC tissues and paired adjacent normal mucosa tissues, we identified that circRUNX1 expression was significantly upregulated in CRC tissues and positively related with lymph node metastasis, distant metastasis and advanced tumor-node-metastasis tumor stage in patients. Functionally, circRUNX1 knockdown inhibited cell proliferation and migration and promoted apoptosis, whereas its overexpression exerted opposite effects. In vivo, circRUNX1 promoted tumor growth and metastasis. Mechanically, circRUNX1 shared miRNA response elements with IGF1. circRUNX1 competitively bound to miR-145-5p and prevented miR-145-5p from decreasing the expression of IGF1, which facilitated tumor growth. CONCLUSION: Our studies verified that circRUNX1 functions as a tumor promotor in CRC cells by targeting the miR-145-5p/IGF1 signaling pathway and may have potential use as a prognostic indicator and therapeutic target in CRC patients.
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The active nitrogen species (HONO, NO, and NO2) have important impacts on the atmospheric oxidative capacity and the transformation of many atmospheric species. In this study, a fast photochemical renoxification rate of adsorbed HNO3/NO3- to active nitrogen species (HONO, NO, and NO2) was detected on real urban PM2.5, and sulfate was found to play a key role in this process. Different from the reported direct photolysis pathway, the photochemical reaction of HNO3/NO3- on PM2.5 is dominated by a photosensitizing mechanism. Acidic protons are proved to be essential for this pathway. The role of sulfate, because of the nonvolatility of its conjugated acid, is to conserve the necessary acidic protons when interacting with HNO3 and thus maintain its photoreactivity. This work implies that sulfate will have important implications in atmospheric nitrogen cycling by accelerating the release of nitrogen oxides from photochemical renoxification of HNO3/NO3- adsorbed on ambient particulates and thus can cause major environmental problems.
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Óxidos de Nitrogênio , Sulfatos , Nitrogênio , Material Particulado , Óxidos de EnxofreRESUMO
BACKGROUND: Emerging studies have revealed that circular RNAs (circRNAs) correlate with diverse diseases including cancers. However, little is known about the functions of circRNAs in colorectal cancer (CRC). In our previous research, downregulation of hsa_circ_0140388 (circHUEW1) has been detected in CRC tissues through high-throughput sequencing. However, the underlying mechanism by which circHUWE1 regulates the proliferation and apoptosis in CRC has not been investigated. MATERIALS AND METHODS: The levels of circHUWE1 in 58 pairs of CRC tissues and corresponding adjacent healthy tissues were detected by RT-qPCR. In addition, the effects of circHUWE1 on cell proliferation, apoptosis migration and invasion were evaluated by cell proliferation assays, flow cytometry, and transwell assays in HCT116 and SW480 cell lines respectively. Meanwhile, the dual-luciferase reporter system assay was used to explore the interaction between circHUWE1 and miR-486 (hsa-miR-486-5p). RESULTS: In this study, we demonstrate that the expression of circHUEW1 is upregulated in CRC tissues. High expression of circHUEW1 was significantly associated with lymphovascular invasion (P =0.036), lymph node metastasis (P =0.017), distant metastasis (P =0.024), and TNM stage (P =0.009). Moreover, the area under the curve (AUC) of the receiver operating characteristic (ROC) curve was 0.732, which indicated that circHUWE1 could serve as a potential biomarker in the detection of CRC. Silencing circHUWE1 significantly inhibited the proliferation, migration and invasion capacity of CRC cells in vitro. Mechanistically, we demonstrated that circHUWE1 could sponge miR-486 and the downregulation of miR-486 could reverse the cancer suppressive effects caused by silencing circHUWE1. CONCLUSION: In this study, our results revealed that circHUWE1 may be a potential therapeutic target and diagnostic biomarker for CRC.
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BACKGROUND: There is growing evidence proving that many human carcinomas, including colon cancer, can overexpress immunoglobulin (Ig); the non B cancer cell-derived Ig usually displayed unique V(D)J rearrangement pattern that are distinct from B cell-derived Ig. Especially, the cancer-derived Ig plays important roles in cancer initiation, progression, and metastasis. However, it still remains unclear if the colon cancer-derived Ig can display unique V(D)J pattern and sequencing, which can be used as novel target for colon cancer therapy. AIM: To investigate the Ig repertoire features expressed in human colon cancer cells. METHODS: Seven cancerous tissue samples of colon adenocarcinoma and corresponding noncancerous tissue samples were sorted by fluorescence-activated cell sorting using epithelial cell adhesion molecule as a marker for epithelial cells. Ig repertoire sequencing was used to analyze the expression profiles of all 5 classes of Ig heavy chains (IgH) and the Ig repertoire in colon cancer cells and corresponding normal epithelial cells. RESULTS: We found that all 5 IgH classes can be expressed in both colon cancer cells and normal epithelial cells. Surprisingly, unlike the normal colonic epithelial cells that expressed 5 Ig classes, our results suggested that cancer cells most prominently express IgG. Next, we found that the usage of Ig in cancer cells caused the expression of some unique Ig repertoires compared to normal cells. Some VH segments, such as VH3-7, have been used in cancer cells, and VH3-74 was frequently present in normal epithelial cells. Moreover, compared to the normal cell-derived Ig, most cancer cell-derived Ig showed unique VHDJH patterns. Importantly, even if the same VHDJH pattern was seen in cancer cells and normal cells, cancer cell-derived IgH always displayed distinct hypermutation hot points. CONCLUSION: We found that colon cancer cells could frequently express IgG and unique IgH repertoires, which may be involved in carcinogenesis of colon cancer. The unique IgH repertoire has the potential to be used as a novel target in immune therapy for colon cancer.
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Photolysis rate constant of HNO3 on the surface (HNO3(s)) has been found to be enhanced by 1-4 orders of magnitude from that of gaseous HNO3, with HONO and NO2 as the main products. Such Re-NOx-ification pathway extends the apparent lifetime of reactive nitrogen species and modifies the atmospheric oxidative capacity along its long-rang transport. Despite of its importance, the detailed kinetics and mechanisms of HNO3(s) photolysis are still not clear. Surface film of HNO3 and organic compounds is ubiquitous in the environment and imposes matrix effect on HNO3(s) photolysis. Here we studied photolysis of HNO3 on Pyrex glass in a photochemical flow reactor over a wide range of HNO3 surface density (DHNO3) with or without the presence of model organic compounds. The photolysis rate constant of HNO3(s) varied with DHNO3 and surface-catalysis mechanism was proposed. Organic compounds further enhance the photolysis rate constant by up to one order of magnitude via both photosensitization and H-donating reaction. The H-donating reaction enhances as well the secondary HONO yield from reaction between the primary product NO2 and adjacent H-donor, and thus increases the HONO/NO2 production ratio. Finally, detailed mechanisms involving surface-catalyisis, photosensitization and H-donating reactions was integrated.
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Circular RNAs (circRNAs) are a novel class of non-coding RNAs with distinct properties and diverse physiological and pathological functions. However, the functions of circRNAs in colorectal cancer (CRC) remain elusive. This study aimed to investigate the functional roles of circVAPA in CRC. High-throughput RNA sequencing was performed in 4 paired CRC tissues, and circVAPA (hsa_circ_0006990), was identified as a potential functional circRNA. Using quantitative real-time polymerase chain reaction (qRT-PCR), circVAPA was found to be up-regulated in CRC patients' tissues and plasma. Furthermore, circVAPA level was associated with unfavorable clinicopathologic features in CRC. The area under curve (AUC) of ROC was 0.724, suggesting that plasma level of circVAPA could serve as a promising biomarker for CRC detection. Sanger sequencing confirmed the back-splice junction sequences of circVAPA. Actinomycin D and RNase R treatments suggested that circVAPA was highly stable compared with its linear counterpart, and qRT-PCR for the circVAPA level in nuclear and cytoplasmic fractions indicated that circVAPA was predominantly localized in the cytoplasm. Gain-of-function and loss-of-function studies in CRC cell lines indicated that circVAPA could promote CRC cell proliferation, migration, invasion, and inhibit apoptosis. miRanda software (v3.3a) was used to predict target miRNAs of circVAPA. Moreover, target miRNAs associated with the KEGG pathway of COLORECTAL CANCER (Entry: map05210; https://www.kegg.jp/) were screened using DIANA-miRPath v.3 platform (Reverse Search module; TarBase v7.0 method). The analyses by miRanda and miRPath suggested that circVAPA could potentially bind to hsa-miR-101-3p (miR-101) associated with the COLORECTAL CANCER pathway. Luciferase reporter assay confirmed a direct interaction between circVAPA and miR-101. Furthermore, circVAPA had no effect on the expression level of miR-101, and miR-101 over-expression had the similar tumor-suppressing effects as circVAPA silencing. The tumor-promoting effect of circVAPA over-expression could be reversed by the up-regulation of miR-101. These data demonstrated that circVAPA promoted CRC progression by sponging miR-101. In conclusion, we have verified that circVAPA is up-regulated in CRC patients' tissues and plasma, and exerts oncogenic properties by sponging miR-101 in CRC. CircVAPA could serve as a promising biomarker and a therapeutic target for CRC.
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Biomarcadores Tumorais/biossíntese , Neoplasias Colorretais/metabolismo , MicroRNAs/biossíntese , RNA/biossíntese , Regulação para Cima/fisiologia , Proteínas de Transporte Vesicular/biossíntese , Idoso , Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Células HCT116 , Células HEK293 , Células HT29 , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , RNA/genética , RNA Circular , Proteínas de Transporte Vesicular/genéticaRESUMO
BACKGROUND: Circular RNA (circRNA) is a novel class of noncoding RNAs with functions in various pathophysiological activities. However, the expression profiles and functions of circRNAs in colorectal cancer (CRC) remain largely unknown. METHODS: High-throughput RNA sequencing (RNA-seq) was performed to assess circRNA expression profiles in 4 paired CRC tissues, and significantly dysregulated circRNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to predict the potential functions of dysregulated circRNAs. Target miRNAs of circRNAs were predicted using miRanda software, and were further analyzed combining DIANA-miRPath v.3 platform (Reverse Search module) with KEGG pathways of COLORECTAL CANCER and MicroRNAs in cancer (Entry: map05210 and map05206). CircRNA-miRNA interaction networks were constructed using Cytoscape software. Expression levels of a significantly down-regulated circRNA, circDDX17 (hsa_circ_0002211), was detected by qRT-PCR in 60 paired CRC tissues. CircDDX17 was knockdown by siRNA, and the biological functions of circDDX17 were examined in CRC cell lines. RESULTS: Totally 448 differentially expressed circRNAs were identified, including 394 up-regulated and 54 down-regulated circRNAs. qRT-PCR validation confirmed the reliability of the RNA-Seq data. GO and KEGG analyses revealed that these dysregulated circRNAs were potentially implicated in CRC pathogenesis. Analyses by combining miRanda and miRPath softwares with KEGG pathways suggested that the miRNAs targeted by the top 10 dysregulated circRNAs were associated with the KEGG pathways of COLORECTAL CANCER and MicroRNAs in cancer, indicating that circRNA-miRNA interactions might play important functional roles in the initiation and progression of CRC. The results of qRT-PCR for circDDX17 in 60 paired CRC tissues showed that circDDX17 was significantly down-regulated in CRC tissues and associated with unfavorable clinicopathological parameters. In vitro experiments showed that silencing of circDDX17 promoted CRC cell proliferation, migration, invasion, and inhibited apoptosis. CONCLUSIONS: In conclusion, we have identified numerous circRNAs that are dysregulated in CRC tissues compared with adjacent normal mucosa tissues. Bioinformatic analyses suggested that these dysregulated circRNAs might play important functional roles in CRC tumorigenesis. CircDDX17 functions as a tumor suppressor and could serve as a potential biomarker and a therapeutic target for CRC.