miR-196b-5p-mediated downregulation of TSPAN12 and GATA6 promotes tumor progression in non-small cell lung cancer.

Lung cancer is the leading cause of cancer-related deaths worldwide and non-small cell lung cancer (NSCLC) accounts for over 80% of lung cancer cases. The RNA binding protein, QKI, belongs to the STAR family and plays tumor-suppressive functions in NSCLC. QKI-5 is a major isoform of QKIs and is predominantly expressed in NSCLC. However, the underlying mechanisms of QKI-5 in NSCLC progression remain unclear. We found that QKI-5 regulated microRNA (miRNA), miR-196b-5p, and its expression was significantly up-regulated in NSCLC tissues. Up-regulated miR-196b-5p promotes lung cancer cell migration, proliferation, and cell cycle through directly targeting the tumor suppressors, GATA6 and TSPAN12. Both GATA6 and TSPAN12 expressions were down-regulated in NSCLC patient tissue samples and were negatively correlated with miR-196b-5p expression. Mouse xenograft models demonstrated that miR-196b-5p functions as a potent onco-miRNA, whereas TSPAN12 functions as a tumor suppressor in NSCLC in vivo. QKI-5 bound to miR-196b-5p and influenced its stability, resulting in up-regulated miR-196b-5p expression in NSCLC. Further analysis showed that hypomethylation in the promoter region enhanced miR-196b-5p expression in NSCLC. Our findings indicate that QKI-5 may exhibit novel anticancer mechanisms by regulating miRNA in NSCLC, and targeting the QKI5∼miR-196b-5p∼GATA6/TSPAN12 pathway may enable effectively treating some NSCLCs.

Down-regulation of MTHFD2 inhibits NSCLC progression by suppressing cycle-related genes.

Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is a bifunctional enzyme located in the mitochondria. It has been reported to be overexpressed in several malignancies. However, the relationship between the expression of MTHFD2 and non-small cell lung cancer (NSCLC) remains largely unknown. In this study, we found that MTHFD2 was significantly overexpressed in NSCLC tissues and cell lines. Knockdown of MTHFD2 resulted in reduced cell growth and tumorigenicity in vitro and in vivo. Besides, the mRNA and protein expression level of cell cycle genes, such as CCNA2, MCM7 and SKP2, was decreased in MTHFD2 knockdown H1299 cells. Our results indicate that the inhibitory effect of MTHFD2 knockdown on NSCLC may be mediated via suppressing cell cycle-related genes. These findings delineate the role of MTHFD2 in the development of NSCLC and may have potential applications in the treatment of NSCLC.

Downregulation of CPA4 inhibits non small-cell lung cancer growth by suppressing the AKT/c-MYC pathway.

Carboxypeptidase A4 (CPA4) is a member of the metallocarboxypeptidase family. A previous study indicated that CPA4 may participate in the modulation of peptide hormone activity and hormone-regulated tissue growth and differentiation. However, the role of CPA4 in lung tumorigenesis remains unclear. Our study revealed that CPA4 expression was higher in both lung cancer cells and tumor tissues. We performed 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assays, colony-formation assays, and Cellomics ArrayScan Infinity analysis to demonstrate that CPA4 knockdown inhibited non small-cell lung cancer (NSCLC) cell proliferation. Conversely, ectopic expression of CPA4 enhanced lung cancer cell proliferation. Consistent with these observations, we generated xenograft tumor models to confirm that CPA4 downregulation suppressed NSCLC cell growth. Mechanistically, we revealed that CPA4 downregulation may induce apoptosis and G1-S arrest by suppressing the protein kinase B/c-MYC pathway. These results suggest that CPA4 has an oncogenic effect on lung cancer growth. Taken together, we identified a novel gene in lung cancer that might provide a basis for new therapeutic targets.

Temporal dynamics of bacterial colonization on five types of microplastics in a freshwater lake.

Microplastics (MPs), as a new substrate, provide a unique niche for microbial colonization in the freshwater ecosystems; however, the impacts of long-term MP exposure on colonized bacteria are still unclear. In this study, five MP types were exposed in a freshwater lake for approximately one year, and the MP particles, together with the surrounding water, were collected on days 60, 150, 250 and 330 during the in situ field experiment. Bacteria on the MP surface, as well as free-living bacteria in the surrounding water, were analyzed to evaluate the temporal dynamics of these bacterial communities. Results show that all five MP types exhibited signs of degradation during the exposure process. Additionally, the alpha diversity, community structure and composition of MP-attached bacteria significantly differed from that of the free-living bacteria in the surrounding water, indicating that the five MP types could provide a preferable niche for bacterial colonization in a freshwater environment. Proteobacteria, Chloroflexi, Verrucomicrobiota, Actinobacteriota and Firmicutes were the top five dominant phyla. Some plastic-degrading bacteria included in these phyla were detected, verifying that MP-attached biofilms had a certain degree of MP degradation potential. Some potentially pathogenic bacteria were also detected, suggesting an ecological threat for spreading disease in the aquatic ecosystem. Furthermore, the bacterial community and some metabolic pathways were significantly affected by the MP type (P < 0.01) and exposure time (P < 0.01), indicating that the presence of MPs not only alters the bacterial community structure and composition, but also influences their potential functional properties in freshwater ecosystems. Multiple factors, including the physicochemical properties related to MPs and the environmental parameters of the surrounding water, affect the community composition and the function of MP-attached bacteria to different degrees. Our findings indicate that the presence of MPs has a potential ecological impact on freshwater ecosystems.

Activated carbon modified titanium dioxide/bismuth trioxide adsorbent: One-pot synthesis, high removal efficiency of organic pollutants, and good recyclability.

Considerable endeavors have focused on tightly combining adsorption with photocatalysis in designing composite materials for environmental pollution treatment. Recent advances in coupling titanium dioxide/bismuth trioxide (TiO2/Bi2O3) with activated carbon (AC) show significantly enhanced photocatalytic performance but face critical limitations including low adsorption capacity and multi-step synthesis. In this work, we introduce a one-pot synthesis of activated carbon modified TiO2/Bi2O3 composite materials (TiO2/Bi2O3/AC). Thanks to the integrated adsorbent/photocatalyst system, TiO2/Bi2O3/AC shows a drastically enhanced removal efficiency for sulfamethazine (>81%), far beyond the corresponding value of the reported AC/TiO2/Bi2O3 adsorbent (<40%). Notably, the removal rates of other typical pollutants including tetracyclines, methyl orange, and rhodamine B are as high as >98%. Furthermore, TiO2/Bi2O3/AC obtains >80% of its adsorption rate for the fifth cycle after simple photo-regeneration without any other post-treatments. Kinetic analysis and photoelectric characterization are carried out to provide insight into adsorption mechanism. Therefore, this work demonstrates a considerable potential to design and construct other multifunctional adsorbents with advanced performance.

miR-31/QKI-5 axis facilitates cell cycle progression of non-small-cell lung cancer cells by interacting and regulating p21 and CDK4/6 expressions.

BACKGROUND: RNA-binding protein Quaking-5 (QKI-5), a major isoform of QKIs, inhibits tumor progression in non-small cell lung cancer (NSCLC). However, the underlying molecular mechanisms of QKI-5 in the cell cycle of NSCLC are still largely unknown. METHODS: MTT, flow cytometry, and colony formation assays were used to investigate cellular phenotypic changes. Mice xenograft model was used to evaluate the antitumor activities of QKI-5. Co-immunoprecipitation, RNA immunoprecipitation (RIP), and RIP sequencing were used to investigate protein-protein interaction and protein-mRNA interaction. RESULTS: The QKI-5 expression was downregulated in NSCLC tissues compared with that in paired normal adjacent lung tissues. Overexpression of QKI-5 inhibited NSCLC cell proliferative and colony forming ability. In addition, QKI-5 induced cell cycle arrest at G0/G1 phase through upregulating p21Waf1/Cip1 (p21) expression and downregulating cyclin D1, cyclin-dependent kinase 4 (CDK4), and CDK6 expressions. Further analyses showed that QKI-5 interacts with p21 protein and CDK4, CDK6 mRNAs, suggesting a critical function of QKI-5 in cell cycle regulation. In agreement with in vitro study, the mouse xenograft models validated tumor suppressive functions of QKI-5 in vivo through altering cell cycle G1-phase-associated proteins. Moreover, we demonstrated that QKI-5 is a direct target of miR-31. The QKI-5 expression was anticorrelated with the miR-31 expression in NSCLC patient samples. CONCLUSION: Our results suggest that the miR-31/QKI-5/p21-CDK4-CDK6 axis might have critical functions in the progression of NSCLC, and targeting this axis could serve as a potential therapeutic strategy for NSCLC.

Regorafenib induces NOX5-mediated endoplasmic reticulum stress and potentiates the anti-tumor activity of cisplatin in non-small cell lung cancer cells.

Lung cancer is one of the most commonly diagnosed cancers worldwide. Although cisplatin-based chemotherapy regimens serve a pivotal role in non-small cell lung cancer (NSCLC) treatment, drug resistance and serious side effects limited its further clinical application. Regorafenib, a small-molecule multi-kinase inhibitor, was demonstrated to have promising anti-tumor activity in various solid tumors. In the present study, we found that regorafenib markedly enhanced cisplatin-induced cytotoxicity in lung cancer cells by activating reactive oxygen species (ROS)-mediated endoplasmic reticulum stress (ER Stress), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) signaling pathways. Regorafenib increased ROS generation by promoting NADPH oxidase 5 (NOX5) expression, and knocking down NOX5 attenuated ROS-mediated cytotoxicity of regorafenib in lung cancer cells. Additionally, mice xenograft model validated that synergistic anti-tumor effects of combined treatment with regorafenib and cisplatin. Our results suggested that combination therapy with regorafenib and cisplatin may serve as a potential therapeutic strategy for some NSCLC patients.

Activation of persulfate by a water falling film DBD process for the enhancement of enrofloxacin degradation.

A synergetic system of water falling film dielectric barrier discharge (DBD) plasma and persulfate (PS) was established and applied to enhance the enrofloxacin (EFA) degradation in this study. The simultaneous existence of electrons, reactive species, heat and UV-visible light in the DBD plasma system were utilized together to activate the PS to form SO4-· and other reactive oxygen species (ROS), and then worked in synergy with the DBD plasma to oxidize the EFA. The obtained results verified that there was a significant increase in the degradation percentages of EFA (20 mg L-1) in the DBD/PS system, and the trend was more obvious under the condition of larger discharge power input. When 0.8 mM PS was added into the DBD system with 0.8 kW discharge power, the degradation percentage of EFA could reach 99.35% after 60 min treatment, the corresponding synergetic factor (SF) was 7.94. Analysis of the O3 and the H2O2 concentrations in the DBD plasma system before and after the PS addition explained the activation of the PS by the HO·. The quenching experiments on reactive species suggested that SO4-·, HO·, and 1O2 were all important reactive species for EFA degradation. The intermediates formed by the EFA degradation were detected and the degradation pathways were speculated. Results of toxicity analysis illustrated that the toxicity of the initial EFA solution decreased after degradation in the synergetic system of DBD/PS.

Dihydroartemisinin enhances the anti-tumor activity of oxaliplatin in colorectal cancer cells by altering PRDX2-reactive oxygen species-mediated multiple signaling pathways.

BACKGROUND: Globally, colorectal cancer (CRC) is one of the leading causes of cancer-related deaths. Oxaliplatin based treatments are frequently used as chemotherapeutic methods for CRC, however, associated side effects and drug resistance often limit their clinical application. Dihydroartemisinin (DHA) induces apoptosis in various cancer cells by increasing reactive oxygen species (ROS) production. However, the direct target of DHA and underlying molecular mechanisms in oxaliplatin-mediated anti-tumor activities against CRC are unclear. METHODS: We used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), flow cytometry, and colony formation assays to investigate cell phenotype alterations and ROS generation. We also used quantitative Real-Time PCR (qRT-PCR) and western blotting to measure relative gene and protein expression. Finally, an in vivo mouse xenograft model was used to assess the anti-tumor activity of oxaliplatin and DHA alone, and combinations. RESULTS: DHA synergistically enhanced the anti-tumor activity of oxaliplatin in colon cancer cells by regulating ROS-mediated ER stress, signal transducer and activator of transcription 3 (STAT3), C-Jun-amino-terminal kinase (JNK), and p38 signaling pathways. Mechanistically, DHA increased ROS levels by inhibiting peroxiredoxin 2 (PRDX2) expression, and PRDX2 knockdown sensitized DHA-mediated cell growth inhibition and ROS production in CRC cells. A mouse xenograft model showed strong anti-tumor effects from combination treatments when compared with single agents. CONCLUSIONS: We demonstrated an improved therapeutic strategy for CRC patients by combining DHA and oxaliplatin treatments.

Cynaropicrin Shows Antitumor Progression Potential in Colorectal Cancer Through Mediation of the LIFR/STATs Axis.

BACKGROUND: Colorectal cancer (CRC) is the second deadliest malignant disease in the world and the leukemia inhibitory factor receptor/signal transducers and activators of transcriptions (LIFR/STATs) signaling axis plays an important role in the molecular biology of CRC. METHODS: Cell function tests were performed to observe the inhibitory effect of cynaropicrin on human CRC cells (RKO, HCT116, and DLD-1). Expression levels of LIFR, P-STAT3, P-STAT4, and apoptotic proteins were detected by Western blotting. Immunoprecipitation confirmed the presence of LIFR/STAT3/STAT4 complex. Cell immunofluorescence assay was used to observe the subcellular localization of STAT3 and STAT4. In vivo efficacy of cynaropicrin was evaluated by a xenotransplantation model in nude mice. RESULTS: Cynaropicrin significantly reduced the survival ability of human CRC cells and promoted apoptosis in a dose-dependent manner. Western blotting results suggested that the antitumor effects of cynaropicrin might be mediated by inhibition of the LIFR/STATs axis. Cynaropicrin reduced the formation of STAT3/STAT4 heterodimers and blocked their entry into the nucleus. Cynaropicrin also suppressed tumor growth in the xenograft model. CONCLUSION: The results showed that cynaropicrin exerted a strong inhibitory effect on CRC in vitro and in vivo. Our study concluded that cynaropicrin has potential application prospects in the field of anti-CRC therapy.

miR-196b-5p-mediated downregulation of FAS promotes NSCLC progression by activating IL6-STAT3 signaling.

Our recent study demonstrated that the QKI-5 regulated miRNA, miR-196b-5p, and it functions as an onco-microRNA in non-small cell lung cancer (NSCLC) by directly targeting GATA6 and TSPAN12. However, the role of miR-196b-5p in NSCLC progression and metastasis still remains unclear. We found that miR-196b-5p promotes lung cancer cell proliferation and colony formation by directly targeting tumor suppressor, FAS. The expression of FAS was significantly downregulated in NSCLC tissue samples and was negatively correlated with the miR-196b-5p expression. Knocking down FAS activates NFkB signaling and subsequent IL6 secretion, resulting in phosphorylation of signal transducer and activator of transcription 3 (STAT3) to promote lung cancer cell growth. Our findings indicated that miR-196b-5p might exhibit novel oncogenic function by FAS-mediated STAT3 activation in NSCLC, and suggested that targeting the miR-196b-5p/FAS/NFkB/IL6/STAT3 pathway might be a promising therapeutic strategy in treating NSCLC.

[Nitrogen and organic matter vertical distribution characteristics and evaluation in ancient canal sediments of Zhenjiang old town].

In order to reveal vertical distribution characteristics of nitrogen and organic matter in the ancient canal sediments of Zhenjiang old town, the columnar sediment samples in Dianli road bridge (D) and Nanshui bridge (B) were collected, contents of total nitrogen (TN), organic nitrogen (Org-N), ammonia nitrogen (NH4(+)-N), nitrate nitrogen (NO3(-)-N) and organic matter (O. M) were determined, and C/N, nutrient concentration coefficient and the correlation of nitrogen, O. M and environmental factors had been analyzed, and organic nitrogen and organic index had also been evaluated. The results showed that (1) The average contents of TN, Org-N, NH4(+) -N, NO3(-) -N and O. M were 366.33 mg x kg(-1), 348.02 mg x kg(-), 89.47 mg x kg(-1), 13.51 mg x kg(-1), 0.43%, respectively, in Dianli road bridge (D). And the average contents of TN, Org-N, NH4(+) -N, NO3(-) -N and O. M were 940.23 mg x kg(-1), 893.22 mg x kg(-1), 169.48 mg x kg(-1), 15.19 mg x kg(-1), 0.76%, respectively, in Nanshui bridge (B). The ranked order of average N and O. M was D < B, which indicated that nitrogen and organic matter pollution in Nanshui bridge (B) was more serious than that in Dianli road bridge (D). (2) The results of C/N indicated that the O. M source of sediment was zooplankton and phytoplankton in ancient canal. (3) There was no significant difference (P > 0.05) of nutrient concentration coefficient between D and B sampling points, which indicated that the concentration process of nitrogen and organic matter was similar in D and B sampling points. (4) TN and O. M were not significantly correlated, which indicated that TN might come from exogenous pollution. (5) The organic index evaluation results showed that ancient canal sediments of Zhenjiang old town were in a cleaning situation, and organic nitrogen still belonged to fairly cleaning and slight cleaning categories.

[Effect of submerging and wetting-redrying on Cd speciation and uptake by Sorghum hybrid Sudangrass in two paddy soils under spiked Cd].

Effect of continuous submerging and wetting-redrying on cadmium speciation and uptake by Sorghum hybrid Sudangrass in a Ferric-accumulic Stagnic Anthrosol and a Tipical Hapludult collected from the Taihu Lake region and the rolling downs of Yingtan, Jiangxi, China respectively, was studied by pot experiment with Cd spike in 2003. Compared to that under wetting-redrying treatment, the MgCl2-extracted pool of Cd in Huangnitu with spiked Cd of 5mg x kg(-1) and 10mg x kg(-1) was decreased from 21.8% and 28.5% to 8.0% and 16.9% while NH2OH x HCl-extracted pool increased from 17.7% and 17.3% to28.1% and 37.5% under continuous submerging. However, in the Typical Halpudult, NaAC-extracted pool of Cd decreased from 20.8% and 29.6% to 11.6% and 12.6%. Cd uptake by Sorghum hybrid Sudangrass was found in negative correlation with the MgCl2 extracted pool of Cd. Total Cd uptake was significantly reduced by the pretreatment of continuously submerging in Huangnitu.

Dual-pathway charge transfer mechanism of anatase/rutile TiO2-Ag3PO4 hollow photocatalyst promotes efficient degradation of pesticides.

Exploring high-performance photocatalysts still remains a big challenge due to poor charge separation efficiency. Herein, we prepare a novel anatase/rutile TiO2-Ag3PO4 hollow photocatalyst (A/R-TiO2-Ag3PO4) for addressing this challenge. Microstructural characterization and photoelectric measurements confirm that the synergy of hollow structure and dual-heterojunction can provide abundant active sites and boost efficient charge separation through dual-pathway charge transfer mechanism. The A/R-TiO2-Ag3PO4 photocatalyst exhibits the highest photocurrent density (15.25 µA cm-2), which is 8.4 and 5.2 times than that of A-TiO2-Ag3PO4 (1.82 µA cm-2) and P25-Ag3PO4 (2.93 µA cm-2), respectively. Photo-degradation experiment shows that A/R-TiO2-Ag3PO4 presents a high degradation percentage (98.7 %) of thiamethoxam (THX) within 30 min, which is 1.45 and 1.23 times than that of A-TiO2-Ag3PO4 (68.1 %) and P25-Ag3PO4 (80.7 %), respectively. Furthermore, the degradation percentage of THX by A/R-TiO2-Ag3PO4 is as high as 96.4 % after seven successive cycles, indicating excellent cycling stability. Therefore, this work provides a new insight into exploring other high-performance photocatalysts by combining hollow structure and dual-heterojunction.