Reelin Promotes Cisplatin Resistance by Induction of Epithelial-Mesenchymal Transition via p38/GSK3ß/Snail Signaling in Non-Small Cell Lung Cancer.

BACKGROUND Emerging evidence suggests the involvement of Reelin in chemoresistance in various cancers. However, its function in cisplatin (DDP) sensitivity of non-small cell lung cancer (NSCLC) needs to be investigated. MATERIAL AND METHODS Reelin expression in cisplatin-sensitive A549 cells and cisplatin-resistant NSCLC (A549/DDP) cells was analyzed by western blot analysis. qRT-PCR, western blotting, immunofluorescence, CCK-8 assays, Annexin V/propidium iodide apoptosis assay, and Transwell migration assays were carried out to determine the function of Reelin on DDP resistance. RESULTS Reelin was markedly increased in A549/DDP cells relative to A549 cells. Knockdown of Reelin enhanced DDP chemosensitivity of A549/DDP cells, whereas overexpression of Reelin enhanced DDP resistance of A549, H1299, and H460 cells. Reelin induced DDP resistance in NSCLC cells via facilitating epithelial-mesenchymal transition (EMT). Furthermore, Reelin modulated p38/GSK3ß signal transduction and promoted Snail (EMT-associated transcription factor) expression. Suppression of p38/Snail reversed Reelin-induced EMT and resistance of NSCLC cells to DDP. CONCLUSIONS These data indicated that Reelin induces DDP resistance of NSCLC by regulation of the p38/GSK3ß/Snail/EMT signaling pathway and provide evidence that Reelin suppression can be an effective strategy to suppress DDP resistance in NSCLC.

Dynamic Partition Gaussian Crack Detection Algorithm Based on Projection Curve Distribution.

When detecting the cracks in the tunnel lining image, due to uneven illumination, there are generally differences in brightness and contrast between the cracked pixels and the surrounding background pixels as well as differences in the widths of the cracked pixels, which bring difficulty in detecting and extracting cracks. Therefore, this paper proposes a dynamic partitioned Gaussian crack detection algorithm based on the projection curve distribution. First, according to the distribution of the image projection curve, the background pixels are dynamically partitioned. Second, a new dynamic partitioned Gaussian (DPG) model was established, and the set rules of partition boundary conditions, partition number, and partition corresponding threshold were defined. Then, the threshold and multi-scale Gaussian factors corresponding to different crack widths were substituted into the Gaussian model to detect cracks. Finally, crack morphology and the breakpoint connection algorithm were combined to complete the crack extraction. The algorithm was tested on the lining gallery captured on the site of the Tang-Ling-Shan Tunnel in Liaoning Province, China. The optimal parameters in the algorithm were estimated through the Recall, Precision, and Time curves. From two aspects of qualitative and quantitative analysis, the experimental results demonstrate that this algorithm could effectively eliminate the effect of uneven illumination on crack detection. After detection, Recall could reach more than 96%, and after extraction, Precision was increased by more than 70%.

Trichostatin A, a histone deacetylase inhibitor, reverses epithelial-mesenchymal transition in colorectal cancer SW480 and prostate cancer PC3 cells.

Trichostatin A (TSA) is a kind of classical histone deacetylase (HDAC) inhibitor. In this study, we reported the reversal effects of TSA on EMT and investigated the possible involved molecular mechanisms in SW480 and PC3 cells. Firstly, we observed that TSA induced the reversal process of epithelial-mesenchymal transition (EMT) in SW480 and PC3 cells, resulting in attenuated cell invasion and migration abilities. TSA-induced EMT reversal was characterized by up-regulation of E-cadherin and down-regulation of Vimentin. Then, treatment with TSA also decreased the expression of transcription factor Slug. Furthermore, over-expression of Slug significantly caused down-regulation of E-cadherin and up-regulation of Vimentin. Meanwhile, TSA treatment in Slug-expressing cells could prevent these changes. These findings suggested that Slug played a crucial role in TSA-induced EMT reversal. Additionally, the study showed that TSA could induce the increase of HDAC1 and HDAC2 on the Slug gene promoter, which might be responsible for the suppression of Slug. Overall, TSA could reverse EMT in SW480 and PC3 cells and TSA-mediated down-regulation of Slug was involved in the reversal process.

The spatial variation of hydrological conditions and their impact on wetland vegetation in connected floodplain wetlands: Dongting Lake Basin.

Wetland vegetation plays a crucial role in wetland conservation policy formulation and global climate change research. This study analyzed remotely sensed images of West Dongting Lake (DTL) Wetland from 1994 to 2020. This wetland is one of the most important wetlands in the world. At the pixel scale, we applied the histogram comparison approach, the range variability analysis (RVA) method, and the structural equation model (SEM) to quantify spatial changes in the hydrological conditions of wetland lakes and the ecological effects of environmental factors (precipitation, temperature, nutrients, water coverage) on vegetation. We propose a climate (C) - hydrological status (S) - vegetation response (R) (CSR) framework to elucidate the propagation relationships between climate, hydrology, and wetland vegetation conditions. The study found that the hydrological degradation promotes the succession of vegetation into the lake, and the distribution is concentrated in the northern Yangtze River inflow area. And the extent of hydrological changes in the West DTL region reached 34.5% during the flood period. In addition, the post-dam period showed a high degree of hydro-ecological failure, accounting for 65% of the total. Within the wetland area, there was a significant negative correlation between water coverage nutrient levels and bare vegetation within the lake area. Nutrient levels were also significantly negatively correlated with wetland vegetation conditions. Rainfall and temperature influence wetland vegetation by affecting the condition of the water body. This research provides valuable insights into managing wetland water resources and ecological restoration under the influence of climate change and human activities and provides a basis for decision-making.

Evolution and attribution of ecological flow in the Xiangjiang River basin since 1961.

Climate change and human activities have greatly altered the ecological flow of rivers, and the conflict between human water use and natural water demand is becoming more and more prominent. Using two ecological flow indicators (ecodeficit and ecosurplus), this study focuses on assessing the characteristics of ecological flow changes at multiple time scales and introduces the Long Short-Term Memory model to construct a meteorological streamflow model for the Xiangjiang River (XJR) basin, using a separation framework to quantify the effects of human disturbance and climate change on ecological flow at multiple time scales. In addition, the fluvial biodiversity Shannon Index (SI) was used to assess the response processes of riverine ecosystems under changing conditions. The results show that the increase of XJR flow is larger (11%) after 1991, the increase in precipitation and potential evapotranspiration in the basin is 5.60%, and the decrease is 3.09%, respectively, and there are obvious cycles of all three on annual and seasonal scales. The annual ecosurplus increased, and the annual ecodeficit decreased after the hydrological variation; on the seasonal scale, the ecodeficit decreased significantly in summer and autumn, and the ecosurplus increased substantially in winter. Climatic factors were the main drivers of the increased frequency and magnitude of annual, summer, and fall high flows (91%, 94%, and 65% contributions, respectively), while urbanization expansion and reservoir diversions drove the increase in spring ecodeficit. Changes in river flow maintained the ecosurplus at a low level after 2002, further causing a decrease in river biodiversity, and the annual and summer ecosurplus were highly correlated with SI indicators (0.824 and 0.711, respectively). Our study contributes to the development of effective ecological flow regulation policies for the XJR basin.

Sustained Biotic-Abiotic Hybrids Methanogenesis Enabled Using Metal-Free Black Phosphorus/Carbon Nitride.

Biotic-abiotic hybrid systems (BAHs) constructed by integrating biological methanogens with photocatalysts offer novel approaches for the effective solar-driven conversion of CO2 to CH4, providing significant inspiration for achieving carbon neutrality and alleviating the energy crisis. As metal photocatalysts would cause photocorrosion that damages microbial cells and lead to system imbalance. Therefore, exploring suitable metal-free photocatalysts is of particular importance in the search for more efficient and sustainable BAHs to improve the actual operability and applicability. Herein, black phosphorus/carbon nitride (BPCN x ) as an alternative metal-free heterostructure was combined with Methanosarcina barkeri (M. barkeri) to construct M. barkeri-BPCN x hybrid systems, and their cyclic methanogenesis performance was investigated. Our results demonstrated that BPCN x promotes the separation of photogenerated charges and enhances the quantum yield, providing a sustained energy source for the cyclically driven M. barkeri reduction of CO2 to CH4 under visible light. Our system achieved a total CH4 yield of 1087.45 ± 29.14 µmol gcat -1 after three cycles, 1.96 times higher than that of M. barkeri-Ni@CdS. M. barkeri-BPCN x overcame the defects of the metal photocatalyst and kept cell permeability, achieving cyclic stability and effectively maintaining the activity of M. barkeri. These results highlight the viable role of BPCN x as a metal-free photocatalysts in the construction of BAHs for the sustained and efficient methanation of CO2, which is conducive to the development of an environmentally-friendly, low-cost, and efficient strategy for the conversion of CO2 to CH4.

Knockdown of METTL14 suppresses the malignant progression of non-small cell lung cancer by reducing Twist expression.

Non-small cell lung cancer (NSCLC) is one of the most malignant cancer types. N6-methyladenosine (m6A), an abundant eukaryotic mRNA modification, has been observed in multiple diseases, particularly cancer. Methyltransferase-like 14 (METTL14) is a central component of the m6A methyltransferase complex and has been reported to promote tumor development in several cancer types. The present study aimed to investigate the role of METTL14 in NSCLC. Relevant clinical and mRNA sequencing data for m6A-related genes were downloaded from The Cancer Genome Atlas database. R software was used to evaluate the expression of m6A regulators in NSCLC. The biological functions of METTL14 were evaluated using Cell Counting Kit-8, colony formation, Transwell migration and western blot analyses. The results demonstrated that METTL14 expression was upregulated in NSCLC tissues and cell lines, and its expression was high in cancer tissues from patients with NSCLC with all four stages (I, II, III and IV) of disease. METTL14 downregulation inhibited cell proliferation and migration in A549 and SK-MES-1 lung cancer cell lines. Knockdown of METTL14 in lung cancer cell lines increased E-cadherin expression and suppressed N-cadherin expression. Furthermore, METTL14 downregulation reduced the expression levels of the transcription factor Twist and the p-AKT/AKT ratio. In conclusion, the present findings revealed that silencing of METTL14 suppressed NSCLC malignancy by inhibiting Twist-mediated activation of AKT signaling. These data suggest that METTL14 may be a potential therapeutic target for NSCLC.

Dehydrogenase/reductase SDR family member 2 silencing sensitizes an oxaliplatin­resistant cell line to oxaliplatin by inhibiting excision repair cross­complementing group 1 protein expression.

Oxaliplatin (Oxa)­based chemotherapy is widely used as the first­line treatment for colorectal cancer (CRC). However, Oxa­resistance is common for many postoperative CRC patients. To explore drug resistance in CRC, an Oxa­resistant cell line, HCT116/Oxa, was established from parental HCT116 cells. These Oxa­resistant cells exhibited characteristics of epithelial­mesenchymal transition (EMT) and a higher migratory capacity than parental cells. Protein profiles of HCT116/Oxa and HCT116 cells were compared using a tandem mass tag­based quantitative proteomics technique. The protein dehydrogenase/reductase SDR family member 2 (DHRS2) was revealed to be highly expressed in HCT116/Oxa cells. Silencing of DHRS2 in HCT116/Oxa cells effectively restored Oxa­sensitivity by suppressing the expression of excision repair cross­complementing group 1 protein via a p53­dependent pathway, and reversed the EMT phenotype. Overall, the suppression of DHRS2 expression may be a promising strategy for the prevention of Oxa­resistance in CRC.

A novel FAPα-based Z-Gly-Pro epirubicin prodrug for improving tumor-targeting chemotherapy.

Fibroblast activation protein-α (FAPα) is a serine protease of the post-prolyl peptidase family that is specifically expressed in the majority of human epithelial tumors, but not in normal tissues. In this study, we demonstrated the anti-tumor activity of a novel targeting drug formed by conjugating epirubicin (EPI) with an FAPα-specific dipeptide (Z-Gly-Pro) and named it Z-GP-EPI. Consistent with this tumor-targeting delivery strategy, the results illustrated that Z-GP-EPI could release EPI efficiently after incubating with FAPα and could exhibit similar antitumor effects as EPI in vitro in FAPα over-expressed tumor cells (4T1/FAPα+). Furthermore, the evaluation of antitumor activity of Z-GP-EPI in vivo was implemented in a 4T1/FAPα+ tumor-bearing mice xenograft model. Our results illustrated that Z-GP-EPI had similar antitumor effects in 4T1/FAPα+ tumor-bearing mice and showed no visible cardiotoxicity side effects compared with free EPI. Thus, our study indicated that this FAPα-activated prodrug targeting strategy may provide a new mechanism for the targeted delivery of antitumor agents and improve their safety levels.

Asclepiasterol, a novel C21 steroidal glycoside derived from Asclepias curassavica, reverses tumor multidrug resistance by down-regulating P-glycoprotein expression.

Multidrug resistance (MDR) mediated by P-glycoprotein (P-gp) is a major cause of cancer therapy failure. In this study, we identified a novel C21 steroidal glycoside, asclepiasterol, capable of reversing P-gp-mediated MDR. Asclepiasterol (2.5 and 5.0µM) enhanced the cytotoxity of P-gp substrate anticancer drugs in MCF-7/ADR and HepG-2/ADM cells. MDR cells were more responsive to paclitaxel in the presence of asclepiasterol, and colony formation of MDR cells was only reduced upon treatment with a combination of asclepiasterol and doxorubicin. Consistent with these findings, asclepiasterol treatment increased the intracellular accumulation of doxorubicin and rhodamine 123 (Rh123) in MDR cells. Asclepiasterol decreased expression of P-gp protein without stimulating or suppressing MDR1 mRNA levels. Asclepiasterol-mediated P-gp suppression caused inhibition of ERK1/2 phosphorylation in two MDR cell types, and EGF, an activator of the MAPK/ERK pathway, reversed the P-gp down-regulation, implicating the MAPK/ERK pathway in asclepiasterol-mediated P-gp down-regulation. These results suggest that asclepiasterol could be developed as a modulator for reversing P-gp-mediated MDR in P-gp-overexpressing cancer variants.

The reversal effects of 3-bromopyruvate on multidrug resistance in vitro and in vivo derived from human breast MCF-7/ADR cells.

PURPOSE: P-glycoprotein mediated efflux is one of the main mechanisms for multidrug resistance in cancers, and 3-Bromopyruvate acts as a promising multidrug resistance reversal compound in our study. To test the ability of 3-Bromopyruvate to overcome P-glycoprotein-mediated multidrug resistance and to explore its mechanisms of multidrug resistance reversal in MCF-7/ADR cells, we evaluate the in vitro and in vivo modulatory activity of this compound. METHODS: The in vitro and in vivo activity was determined using the MTT assay and human breast cancer xenograft models. The gene and protein expression of P-glycoprotein were determined using real-time polymerase chain reaction and the Western blotting technique, respectively. ABCB-1 bioactivity was tested by fluorescence microscopy, multi-mode microplate reader, and flow cytometry. The intracellular levels of ATP, HK-II, and ATPase activity were based on an assay kit according to the manufacturer's instructions. RESULTS: 3-Bromopyruvate treatment led to marked decreases in the IC50 values of selected chemotherapeutic drugs [e.g., doxorubicin (283 folds), paclitaxel (85 folds), daunorubicin (201 folds), and epirubicin (171 folds)] in MCF-7/ADR cells. 3-Bromopyruvate was found also to potentiate significantly the antitumor activity of epirubicin against MCF-7/ADR xenografts. The intracellular level of ATP decreased 44%, 46% in the presence of 12.5.25 µM 3-Bromopyruvate, whereas the accumulation of rhodamine 123 and epirubicin (two typical P-glycoprotein substrates) in cells was significantly increased. Furthermore, we found that the mRNA and the total protein level of P-glycoprotein were slightly altered by 3-Bromopyruvate. Moreover, the ATPase activity was significantly inhibited when 3-Bromopyruvate was applied. CONCLUSION: We demonstrated that 3-Bromopyruvate can reverse P-glycoprotein-mediated efflux in MCF-7/ADR cells. Multidrug resistance reversal by 3-Bromopyruvate occurred through at least three approaches, namely, a decrease in the intracellular level of ATP and HK-II bioactivity, the inhibition of ATPase activity, and the slight decrease in P-glycoprotein expression in MCF-7/ADR cells.

A novel eyelash detection method for iris recognition.

Iris is often affected by the eyelash noise, when captured under unfavorable condition. Not only the iris localization of inner and outer boundaries, but also iris feature extraction can be affected by eyelash. Therefore, in an iris recognition system, eyelash detection is of great importance for accurate iris recognition. Eyelash can be classified into two classes: (1) separable eyelashes (2) multiple eyelashes. The former are detected by local intensity minimum algorithm, and the latter are detected according to the template mean and standard deviation. Experimental results show that the proposed method can detect eyelash accurately.

A novel iris localization algorithm based on the gray distributions of eye images.

In this paper, we proposed a novel iris localization algorithm based on the gray distributions of eye images. Firstly, according to the gray features, find a point inside the pupil using a gray value summing operator. Next, starting from this point, find three inner boundary points using a boundary detection template, and then calculate the circle parameters of inner boundary according to the principle that three points which are not on the same line can define a cricle. Finally, find three iris outer boundary points utilizing the similar algorithm and obtain the circle parameters. A large number of experiments on the CASIA iris image database demonstrated that the localization results of proposed algorithm are more accurate and more rapid than any other classical algorithms, such as Daugman's algorithm and Hough transform.

A rapid iris location method based on the structure of human eyes.

Iris location is an important part of iris recognition. Speed of location and robustness of arithmetic of location are factors which we must pay attention to especially. In this paper we analyse eye images that we have based on structure characteristics of eyes, we put forward a rapid iris location arithmetic. Firstly, we get an approximative center by gray projection, we get two points that locate at left and right boundary by threshold value respectively, and we get a point that locates at the lower boundary by direction edge detection operators, then we can ensure the boundary of pupil and probable center. Secondly, we get exact pupil boundary and center by Hough transform that is processed at a small scope surrounding the probable center. Thirdly, we search two points that locate at left and right boundaries between iris and sclera along horizontal direction by using the exact center and direction edge detection operators. Then we ensure the horizontal coordinate of the center of iris based on the above two point accurately. Finally, we search two points that locate at upper and lower boundaries between iris and sclera beginning at the horizontal coordinate of the center of iris along the directions that making plus and minus thirty angles between horizontal direction respectively by using direction edge detection operators, so we ensure the coordinate of the center of iris and the boundary between iris and sclera. The experiments indicate that this method reaches about zero point two second at speed and percentage of ninety nine point forty five at precision. This method is faster than existing methods at speed.