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Pre-frailty is a transitional stage between health and frailty. Previous studies have demonstrated that individuals with pre-frailty experience declines in cognitive and gait performances compared with healthy individuals. However, the basic neural mechanism underlying this needs to be clarified. In this cross-sectional study, twenty-one healthy older adults and fifteen with pre-frailty underwent three conditions, including a single cognitive task (SC), single walking task (SW), and dual-task (DT), while cortical hemodynamic reactions were measured using functional near-infrared spectroscopy (fNIRS). The prefrail group (PG) showed a significantly lower activation of the left dorsolateral prefrontal cortex (L-DLPFC) than the healthy group (HG) when performing SC (p < 0.05). The PG showed a significantly lower Timed Up and Go test and step speed than the HG during SW (p < 0.05). The coefficient of variation (CV) of the step length of the PG was significantly higher than that of the HG when performing DT (p < 0.05). No significant correlation in cerebral cortex activation and gait parameters in the HG when performing SW and DT was noted (p > 0.05). Participants of the PG with a higher oxygenated area in the left anterior prefrontal cortex (L-APFC) had a lower step frequency during SW (r = −0.533, p = 0.041), and so did the following indicators of the PG during DT: L-APFC and step speed (r = −0.557, p = 0.031); right anterior prefrontal cortex and step speed (r = −0.610, p = 0.016); left motor cortex and step speed (r = −0.674, p = 0.006); step frequency (r = −0.656, p = 0.008); and step length (r = −0.535, p = 0.040). The negative correlations between the cerebral cortex and gait parameters of the PG indicated a neural compensatory effect of pre-frailty. Therefore, older adults with pre-frailty promote prefrontal activation to compensate for the impaired sensorimotor systems.

Patients with intrahepatic cholangiocarcinoma (ICC) require chemotherapy due to late detection, rapid disease progression, and low surgical resection rate. Tumor cell lines are extremely important in cancer research for drug discovery and development. Here, we established and characterized a new intrahepatic cholangiocarcinoma cell line, ICC-X1. STR testing confirmed the absence of cross-contamination and high similarity to the original tissue. ICC-X1 exhibited typical epithelial morphology and formed tumor spheres in the suspension culture. The population doubling time was approximately 48 h. The cell line had a complex hypotriploid karyotype. The cell line exhibited a strong migration ability in vitro and cell inoculation into BALB/c nude mice led to the formation of xenografts. Additionally, ICC-X1 cells were sensitive to gemcitabine and paclitaxel but resistant to 5-fluorouracil and oxaliplatin. RNA sequencing revealed that the upregulated cancer-related genes were mainly enriched in several signaling pathways, including the TNF signaling pathway, NOD-like receptor signaling pathway, and NF-κB signaling pathway. The downregulated cancer-related genes were mainly enriched in the Rap1 signaling pathway and Hippo signaling pathway among other pathways. In conclusion, we have created a new ICC cell line derived from Chinese patients. This cell line can be used as a preclinical model to study ICC, specifically tumor metastasis and drug resistance mechanisms.

Hepatocellular carcinoma (HCC) is a highly aggressive and heterogeneous disease. Cell lines are commonly employed as in vitro models for cell type studies. However, the success rate of HCC primary culture establishment is low. In this study, we successfully established a liver cancer cell line, Hep-X1. Primary culture and passage of surgically removed tissues were used to establish hepatoma cell lines. Morphological examination, short tandem repeat (STR) analysis, immunohistochemical staining, doubling time, karyotype analysis, plate tumor formation experiments, organoid culture, and in vivo tumor formation investigations in animals were used to identify the cell lines. A novel liver cancer cell line, Hep-X1, was established based on morphology, immunophenotype, cytogenetics, and STR analysis. The novel cell line can be a valuable model for studying primary liver cancer.

A kind of smart calcium alginate fiber having pH indicating properties was proposed to monitor wound healing. The smart calcium alginate fiber was prepared by dyeing the hydroxypropyl trimethyl ammonium chloride chitosan (HACC) modified calcium alginate fiber with alizarin dye and anthocyanin dye, respectively. It was worth noting that modification of calcium alginate fibers with HACC enhanced the dyeing and antibacterial properties, simultaneously. When the concentration of HACC was 10 g/L, the modified calcium alginate fiber had the best dyeing performance. At the same time, the dyeing process had no significant influence on the mechanical properties of the fibers with the strength loss only around 0.2 cN/dtex. The smart calcium alginate fibers exhibited a rapid and significant color change and reversible color response at pH 2–11. Moreover, the color change could be easily observed by naked eye. Therefore, the prepared calcium alginate fibers could be a good candidate for intelligent wound dressings for visual monitoring of wound healing.

The electrospinning of poly(L-lactic acid)/poly(D-lactic acid) (PLLA/PDLA) microfiber membranes were carried out with dichloromethane (DCM), DCM/ethanol, DCM/acetone, DCM/hexane as the spinning solvent. Scanning electron microscope observation showed that the electrospun fiber obtained using DCM/ethanol (L/D-DE) mixed solvent was homogeneous without visible bead, which was better than any others. Moreover, plenty of pores could be found on the surface of the fibers obtained using the mixed solvents. The porous structure of fibers was significantly influenced by the ethanol (non-solvent) content. When the DCM/ethanol was 50:10 (v/v), the fibers were uniform and had isolated pores. XRD and DSC results indicated that the exclusive stereocomplex poly(lactide acid) (sc-PLA) crystallites without any homocrystallites poly(lactide acid) (hc-PLA) did form in all types of fibers. The crystallinity of sc-PLA in the L/D-DE fiber was higher than other samples due to the slowest evaporation rate. TGA test further indicated that the thermal stabilities of PLLA/PDLA electrospun fibers were slightly better than the PLLA. Furthermore, L/D-DE had the excellent mechanical properties and underwent the course of ductile fracture. Possible mechanisms accounting for the morphologies and tensile properties were also proposed in this study.

Hepatocellular carcinoma (HCC) is the most common primary human liver malignancy with high mortality. Liver cancer stem cells (CSCs) have been demonstrated to contribute to the recurrence, metastasis and drug resistance of liver cancer. Human HCC cohort analysis indicated that the epigenetic regulator polycomb chromobox homologue 4 (CBX4) was overexpressed in human HCC. Moreover, we found that CBX4 expression was significantly higher in CD44+ CD133+ Hep3B CSCs. Functionally, we demonstrated that CBX4 regulated cell proliferation, self-renewal, and metastasis ability of Hep3B CSCs. Bioinformatics analysis predicted that CBX4 was a direct target of microRNA-6838-5p (miR-6838-5p), which was further confirmed by luciferase reporter assay. MiR-6838-6p was down-regulated in HCC tumors and overexpression of miR-6838-5p attenuated the malignant traits of human liver CSCs in vitro. In addition, we found that miR-6838-5p/CBX4 axis modulates the biological properties of human liver CSCs via regulating ERK signaling. Overexpression of miR-6838-5p suppressed Hep3B xenograft tumor growth in vivo, while CBX4 overexpression abrogated the suppression effect, restored the angiogenesis, epithelial-to-mesenchymal transition (EMT), and ERK signaling in Hep3B tumor. In summary, our findings suggest that miR-6838-5p/CBX4 axis regulates liver tumor development and metastasis, which could be utilized as potential therapeutic target for HCC treatment.

Background: PCGF4 as a cancer stem cells (CSC) marker displays stem cell-like properties, and drug resistance in hepatocellular carcinoma (HCC). PCGF2, a homologue of PCGF4, the effect of PCGF2 on liver CSCs (LCSCs) and drug resistance and the molecular mechanism of this effect have not been documented.Methods: To measure the cell viability, CSCs properties of the cells, the Cell Counting Kit-8, spheroid assay, and flow cytometry assays were applied in the HCC cell lines, respectively. The self-renewal was determined by limiting dilution assay. Also, IHC and western blotting were used to detect protein expression of PCGF2 and PCGF4 in human HCC tissues, cell lines and the effects of PCGF2 overexpression on the p38 MAPK genes expression. Kaplan-Meier curves were generated for overall survival (OS) and disease-free survival (DFS). We performed KEGG analysis on target genes through the R language cluster profiler package.Results: IHC showed that expression of PCGF4 and PCGF2 correlate inversely in HCC cell lines and HCC tumors. Overexpression of PCGF2 inhibited the stemness of HCC cells refected by decreasing sphere-forming and self-renewal capacities as well as the expression of CSCs markers. Interestingly, down-regulating PCGF4 led to similar results as up-regulating PCGF2. We also found that PCGF2 and PCGF4 oppositely regulated the stem-like properties driven by the p38 MAPK signalling pathway.Conclusion: Our results suggest that PCGF2 inhibits the stem cell population, reduces the sphere formation ability in HCC cell lines, and increases sensitivity to sorafenib by targeting p38 MAPK signalling.

Object detection algorithm has high recognition accuracy and fast detection speed, but there are also obvious problems. The positioning is inaccurate because the network uses an end-to-end model that generates the resulting final framework directly after regression without matching and preselecting the main framework. The YOLO network can resize the entire image to a fixed size and divide it into a grid. When there is more than one object in a grid, it is likely to cause missed detection. The DenseNet network can combine the information of the front feature layer and adopt a new network structure, which improves the detection accuracy of objects to a certain extent. Therefore, THE YOLO-D algorithm is proposed, which combines the information of the front characteristic layer to improve the vehicle detection accuracy and positioning accuracy while maintaining the vehicle detection speed.

In the present study, ultrasound-assisted extraction was employed to extract the general flavone from celery leaves using response surface methodology and BP neural network model with a genetic algorithm (GA). The effects of temperature, time, solid-liquid ratio, and ethanol concentration on the extraction results were assessed by Box-Behnken design. Further optimization of the process was performed by GA-BP. Our results showed that the optimal conditions were an ethanol concentration of 70.31%, a temperature of 67.2 °C and an extraction time of 26.6 min. In addition, significant antioxidant activity and in vitro bacteriostasis were observed. We found that the total flavonoids of the celery leaves exerted a strong inhibitory effect on Escherichia coli, Staphylococcus aureus, and Bacillus subtilis. Additionally, considerable DPPH· and ·OH scavenging effects were exerted by flavonoids. Therefore, flavonoids from celery leaves can be considered natural antioxidants and bacterial inhibitors.

Background Accumulating evidence demonstrates that tRFs (tRNA-derived small RNA fragments) and tiRNAs (tRNA-derived stress-induced RNA), an emerging category of regulatory RNA molecules derived from transfer RNAs (tRNAs), are dysregulated in in various human cancer types and play crucial roles. However, their roles and mechanisms in hepatocellular carcinoma (HCC) and liver cancer stem cells (LCSCs) are still unknown. Methods The expression of glycine tRNA-derived fragment (Gly-tRF) was measured by qRT-PCR. Flow cytometric analysis and sphere formation assays were used to determine the properties of LCSCs. Transwell assays and scratch wound assays were performed to detect HCC cell migration. Western blotting was conducted to evaluate the abundance change of Epithelial-mesenchymal transition (EMT)-related proteins. Dual luciferase reporter assays and signalling pathway analysis were performed to explore the underlying mechanism of Gly-tRF functions. Results Gly-tRF was highly expressed in HCC cell lines and tumour tissues. Gly-tRF mimic increased the LCSC subpopulation proportion and LCSC-like cell properties. Gly-tRF mimic promoted HCC cell migration and EMT. Loss of Gly-tRF inhibited HCC cell migration and EMT. Mechanistically, Gly-tRF decreased the level of NDFIP2 mRNA by binding to the NDFIP2 mRNA 3′ UTR. Importantly, overexpression of NDFIP2 weakened the promotive effects of Gly-tRF on LCSC-like cell sphere formation and HCC cell migration. Signalling pathway analysis showed that Gly-tRF increased the abundance of phosphorylated AKT. Conclusions Gly-tRF enhances LCSC-like cell properties and promotes EMT by targeting NDFIP2 and activating the AKT signalling pathway. Gly-tRF plays tumor-promoting role in HCC and may lead to a potential therapeutic target for HCC.

Background: PCGF4 is highly expressed in liver cancer and can be used as a marker for liver cancer stem cells. However, PCGF2, a homologue of PCGF4, is not clear whether it is expressed in HCC, and whether it regulates the stemness of liver cancer stem cells.Methods: IHC and Western blot were used to detect the expression of PCGF2 and PCGF4 protein in human HCC tissues and cell lines. Flow cytometry and sphere formation were performed to detect the effect of PCGF2 or PCGF4 on the stem-like properties of liver cancer stem cells. Kaplan-Meier curves were conducted for OS and DFS. Cell viability was measured at the indicated time points using Cell Counting Kit-8. We performed KEGG analysis on these target genes through the cluster profiler package of the R language.Results: IHC results showed that PCGF2 was lower expressed in HCC, while PCGF4 was higher expressed in HCC compared with matched paracancerous, and this higher expression exhibited poor prognosis in HCC. Up regulation of PCGF2 was also accompanied with decreased stem-like properties and sphere formation in HCC cell lines. Interestingly, down regulating PCGF4 got the similar results as up regulating PCGF2. Furthermore, up regulating PCGF2 or down regulating PCGF4 cells performed more sensitivity to sorafenib. We also found that PCGF2 and PCGF4 oppositely regulated the drives stem-like properties by p38 MAPK signal pathway.Conclusion: PCGF2 was a novel negative regulator of LCSCs that inhibiting the stem cell population, reducing the sphere formation ability of liver cancer stem cells, and increasing the sensitivity of sorafenib by targeting p38 MAPK signaling. PCGF2 was supposed to be a novel therapeutic target for Liver cancer stem cell.

Background: The existence of liver cancer stem cells (LCSCs) and the occurrence of epithelial-mesenchymal transition (EMT) are generally considered to be the primary causes for migration and metastasis of Hepatocellular carcinoma (HCC). Accumulating evidences demonstrate that tRFs and tiRNAs, are an emerging category of regulatory RNA molecules derived from transfer RNA (tRNA), are dysregulated in in various human cancer types and play crucial roles. However, their impact on tumorigenesis is still in the exploratory stage, their roles and mechanisms in HCC and LCSCs are still unknown.Methods: Quantitative real-time PCR (qRT-PCR) was performed to detect the expression of glycine tRNA-derived fragments (Gly-tRF) in HCC cell lines and tumor tissues. Inhibitor and mimic were performed to weaken and enhance the function of Gly-tRF. Flow cytometry and sphere formation assay to detect the representative surface markers (CD133, CD13, EpCAM, CD44) proportion and stemness of LCSCs. Transwell assay and scratched wound assay were performed to detect HCC cells migration. Western blot was used to detect the expression of EMT-related proteins. Dual luciferase reporter assay and signaling pathway analysis were performed to explore the underlying mechanism of Gly-tRF functions.Results: Gly-tRF is highly expressed in HCC cell lines and tumor tissues, compared to L02 hepatocytes and adjacent normal tissues. Flow cytometry and sphere formation assay found that Gly-tRF mimic promotes LCSCs subpopulation proportion and LCSCs-like cells stemness. Next, functional experiments confirmed that Gly-tRF mimic promotes HCC cells migration and EMT. Consistently, Loss of Gly-tRF inhibits HCC cells migration and EMT. Mechanistically, Gly-tRF inhibits the level of NDFIP2 mRNA by binding to the NDFIP2 3′ UTR. Importantly, overexpression of NDFIP2 can weaken the effect of Gly-tRF in promoting LCSCs-like cells sphere formation and HCC cells migration, NDFIP2 is the direct target of Gly-tRF. Signaling pathway exploration found that Gly-tRF enhances the abundance of phosphorylated AKT.Conclusions: Gly-tRF promotes EMT of HCC cells and enhances LCSCs-like cells stemness via targeting NDFIP2 and activating AKT signaling pathway. The tRNA-derived fragments provide a new perspective of oncology research, and can be the direction of future oncology research.

Adaptive dynamic programming (ADP), which belongs to the field of computational intelligence, is a powerful tool to address optimal control problems. To overcome the bottleneck of solving Hamilton–Jacobi–Bellman equations, several state-of-the-art ADP approaches are reviewed in this paper. First, two model-based offline iterative ADP methods including policy iteration (PI) and value iteration (VI) are given, and their respective advantages and shortcomings are discussed in detail. Second, the multistep heuristic dynamic programming (HDP) method is introduced, which avoids the requirement of initial admissible control and achieves fast convergence. This method successfully utilizes the advantages of PI and VI and overcomes their drawbacks at the same time. Finally, the discrete-time optimal control strategy is tested on a power system.

When dental pulp needs to be removed in individuals who require root canal therapy, dental pulp segmentation from cone-beam computed tomography (CBCT) images plays a vital role in assisting clinical decisions by making through simulation of dental pulp removal. Dental pulp has complex topological shapes and inhomogeneous intensity distribution, so we propose a level set method to incorporate the piecewise area energy with the local edge energy into semiautomatically segment dental pulps in the three-dimensional domain. The minimization of the piecewise area energy approximates a separation between the target and the intricate background region. In the local edge energy, our edge indicator function highlights the dental pulp boundaries with weak ramps. We compared our approach with the start-of-the-art method of dental pulp segmentation, the well-known DRLSE model for image segmentation, and the manual delineation by the trained operator. The DRLSE model was not successful in segmenting dental pulps of some teeth, and our method outperformed the start-of-the-art method. Four quantitative metrics were applied between our method and the manual delineation, and our results on 29 dental pulps showed that our approach has a root-mean-square surface distance of 1.22 ± 0.31 mm, 3.13 ± 1.35 mm, 2.63 ± 1.92 mm, 2.03 ± 0.82 mm, and 2.06 ± 1.48 mm in dental pulps of wisdom teeth, molars, premolars, canines, and incisors, respectively.

It is generally believed that the existence of cancer stem cells (CSCs) is related to tumor recurrence and metastasis of hepatocellular carcinoma (HCC). Neuropilin1 (NRP1) is involved in numerous pathophysiological processes of tumor progression, however, whether NRP1 is involved in the regulation of liver CSCs and metastasis of HCC is still unknown. In the present study, we examined the effect of NRP1 on the population of liver CSCs and the metastasis mechanism of HCC. In NRP1 small hairpin RNA (shRNA)-transduced HCC cells, liver CSCs surface markers (CD133+/ EpCAM+/CD13+/CD44+) expressing cells, which imply the CSCs population, were decreased. Transwell assay and nude mouse liver orthotopic transplantation model confirmed that NRP1 knockdown inhibited HCC cells' migration and lung metastasis. Our data showed that the expression of NRP1 was upregulated in 5 independent cohorts of HCC patients, consequently, high levels of NRP1 correlated with recurrence and poor prognosis in HCC. Mechanism research showed that NRP1 promotes cell spreading through the epithelial-mesenchymal transition (EMT) signaling pathway. In summary, NRP1 enhanced the population of liver CSCs and migration of HCC via EMT, indicating that NRP1 might be a novel target for HCC treatments.

In recent decades, the melting of the Greenland Ice Sheet (GrIS) has become one of the major causes of global sea-level rise. Supraglacial lakes (SGLs) are typical hydrological features produced on the surface of the GrIS during the melt seasons. The existence and evolution of SGLs play an important role in the melting process of the ice sheet surface. To understand the distribution and recent changes of SGLs in Greenland, this study developed a random forest (RF) algorithm incorporating the texture and morphological features to automatically identify SGLs based on the Google Earth Engine (GEE) platform. Sentinel-2 imagery was used to map the SGLs inventory in Greenland during the 2016–2018 melt seasons and to explore the spatial and temporal variability characteristics of SGLs. Our results show changes in SGLs from 2016 to 2018, with the total area decreasing by ~1152.22 km2 and the number increasing by 1134; SGLs are mainly distributed in western Greenland (SW, CW, NW) and northeastern Greenland (NE), where the NE region has the largest number of observed SGLs and the largest SGL was with the surface area of 16.60 km2 (2016). SGLs were found to be most active in the area with the elevation of 800–1600 m and the slope of 0–5°, and showed a phenomenon of retreating to lower elevation areas and developing to steeper slope areas. Our work provided a method for rapid inventory of SGLs. This study will help monitor the mass balance of the GrIS and predict future rapid ice loss from Greenland.

In this paper, the influence of nanocellulose with different aspect ratio on the performance of PLLA/PDLA was explicit through a quantity of test results. Three different aspect ratio nanocelluloses were chemically extracted from waste colored cotton fibers. After acetylated and adding to PLLA/PDLA solution, PLLA/PDLA (LD) composites films were prepared by solution casting method and their properties were investigated by differential scanning calorimetry (DSC), polarized optical microscopy (POM), tensile testing, oxygen permeability and optical measurement. It was found that nanocellulose play a role as nucleating agent to promote crystallization and was also helpful to form the stereocomplexs crystallites. Wherein, the acetylated cellulose nanospheres (ACNS) had the most obvious effect on crystallinity enhancing. The best oxygen barrier performance of LD composites films was occurred after addition acetylated cellulose nanocrystals (ACNC). Fibrous acetylated cellulose nanofiber (ACNF) had the most influence on tensile property. Furthermore, addition of ACNS, ACNC and ACNF had hardly impact on transmittance and haze of films. It is of guiding significance for the preparation of PLA composite materials applied in different fields.

In order to safeguard their own energy security, strengthen environmental protection and prevent climate change, many countries in the world are vigorously developing renewable energy to replace traditional fossil energy. As the largest developing country in the world, China’s energy structure and development situation are in a very serious situation, and the energy security problems are threatening the smooth implementation of the national energy strategy. Accelerating the development and utilization of renewable energy has become the best choice to solve the energy crisis in China. Wind and solar energy, as an important part of new energy, are gradually infiltrating into China’s power system. However, due to their great randomness, they are bound to bring severe challenges and a series of difficulties to the traditional power system optimal scheduling problem. China is rich in water energy resources, hydropower is the largest renewable energy that can be developed on a large scale at present, vigorously developing hydropower can significantly reduce the consumption of traditional fossil energy, and at the same time it will absorb some negative effects of new energy power generation through controllable adjustment. Therefore, it is necessary to rationally formulate the optimal dispatching strategy of multi-energy complementary power system for the development of China’s energy strategy. This paper has carried on a series of discussions and carried out the following work. (1) Comprehensively analyze the reasons for the uncertainty of new energy power generation, study the probability distribution model of prediction error, and discuss the new energy power generation scenario with the scenario analysis method. (2) The traditional combined optimal dispatching model, the combined dispatching model with new energy generation system and the multi-energy complementary power system are calculated respectively, and the optimal dispatching strategy is given through an example analysis. (3) Complex models need efficient algorithms to solve, so this paper proposes a new intelligent optimization algorithm.

It has been revealed by our previous proteomic study that the expression profile is different between well‑differentiated and poorly differentiated hepatocellular carcinoma (HCC). Among those differently expressed proteins, peroxiredoxin2 (PRDX2) was our protein of interest. The present study aimed to further investigate the value of PRDX2 as a prognostic factor in HCC. Tissue microarrays were used to investigate the expression difference between HCC tissues and their adjacent normal liver tissues. The expression of PRDX2 at both mRNA and protein levels was examined by q‑RT‑PCR, western blotting and immunohistochemical assessment in HCC tissues and cell line HCCLM3. Silencing of PRDX2 in HCCLM3 was achieved usingpGMLV‑SC1 lentiviral vectors. Cell Counting Kit‑8 (CCK‑8) and Transwell migration assays were used to assess cell proliferation and migration, respectively. Categorical variables were assessed using the Chi‑square test, and ordinal variables were examined using the Mann‑Whitney U test. The difference of continuous variables between groups were compared with t‑tests. The Kaplan‑Meier method was used to calculate the overall survival (OS) and disease‑free survival (DFS) of patients, and the log‑rank test was used to analyze the differences between groups. The results revealed that the expression of PRDX2 was decreased at both the mRNA and protein levels in an HCC cell line compared to that of a normal human liver cell line. PRDX2 protein expression levels were significantly downregulated in HCC tissues and were positively linked to overall survival (OS) and disease‑free survival (DFS) of HCC patients. Patients with high PRDX2 expression levels had longer OS and DFS times than those with lower PRDX2 expression. Silencing of PRDX2 in the HCC cell line HCCLM3 promoted cancer cell proliferation and migration. Our findings indicated that PRDX2 may play an important role in HCC development; PRDX2 may serve as a useful prognostic factor and a therapeutic target.

Neuropilin-1 (NRP1) is a type I transmembrane glycoprotein that was originally found playing a role in neuronal axon guidance and embryonic angiogenesis. NRP1 can promote various aspects of tumorigenesis, such as angiogenesis, cell survival, migration, invasion and chemo-resistance, but little is known about the nanomechanica signature of NRP1 inregulating hepatocellular carcinoma(HCC) cells. Our study found that NRP1 was overexpressed in HCC and high expression of NRP1 was associated with poor prognosis in HCC patients.but there are no correlation between NRP1 and liver cirrhosis. In vivo and vitro experiments knockdown of NRP1 reduced proliferation and invasion of HCC. We quantified the Young's modulus, RMS residuals of HCC cell lines and normal liver cell line L02 using Atomic force microscopy (AFM). AFM data indicated that Young's modulus decreased in highly metastatic HCC cells, which is consistent with the verification results of NRP1 knockdown. Our analyses revealed that down regulation of NRP1 negatively correlated with increased Young's modulus in cells exhibiting differing degrees of invasiveness. Our molecular data showed that NRP1 activated AKT, ERK1/2, and epithelial-mesenchymal transition (EMT)-related signals in HCC cells and promoted tumor apoptosis and invasion. As an important biophysical property of cells, the membrane stiffness of HCC cells was further quantified by AFM force measurements, which indicated that these cells became much stiffer after NRP1 knockdown. These results collectively illuminated that Neuropilin-1 alterrated namomechanica signature in hepatocellular carcinoma cells and can be a potential therapeutic agent for HCC. Funding Statement: The present study was supported by the National Natural Science Fund of China (grant nos. 31570509 and 81702326), Science and Technology Major Project of Gansu province(1602FKDA001), the Talent innovation and Entrepreneurship Program of Lanzhou City (grant no. 2016-RC57) and the science and technology project of Chenguan District (2017SHFZ0014); Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: The study was approved by the Zhongshan Hospital Ethics Committee and informed consent was obtained from each patient under Institutional Reviewer Board protocols. The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a prior approval by the institution's human research committee.

A possible association between multiple drug resistance 1 gene (MDR1) polymorphisms and the risk of developing hepatocellular carcinoma (HCC) is currently under debate, and evidence from various epidemiological studies has yielded controversial results. To derive a more precise estimation of the association between MDR1 polymorphisms and HCC risk, the present meta-analysis was performed. A total of 8 studies containing 11 cohorts with 4407 cases and 4436 controls were included by systematic literature search of EMBASE, PubMed, Web of Science, and CNKI. All polymorphisms were classified as mutant/wild-type alleles. In particular, the variation type, functional impact, and protein domain location of the polymorphisms were assessed and used as stratified indicators. The pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated to evaluate the association. Overall, our results suggested that the mutant alleles of the MDR1 gene were associated with a significantly increased risk for HCC under all genetic models (allelic model: OR = 1.28, 95 % CI = 1.20–1.36, P

Curcumol is the major component extracted from root of Rhizoma Curcumae. Recent studies have shown that curcumol exerts therapeutic effects against multiple conditions, particularly cancers. However, the therapeutic role and mechanism of curcumol against cholangiocarcinoma cells are still unclear. In our current research, we tested the effect of curcumol in cholangiocarcinoma cells, and using two-dimensional electrophoresis, proteomics and bioinformatics, we identified cyclin-dependent kinase like 3 (CDKL3) as a potential target for curcumol. We have demonstrated that curcumol can evidently suppress growth and migration of cholangiocarcinoma cells. Furthermore, curcumol could significantly block the cell cycle progression of the cholangiocarcinoma cells. These effects could be largely attributed to the inhibition of CDKL3 by curcumol. Further studies have recapitulated the oncogenic role of CDKL3 in that knockdown of CDKL3 by lentiviral mediated transfection of shRNA against CDKL3 also led to a significant inhibition on cell proliferation, migration, invasion, and cell cycle progression. Given the high level of CDKL3 expression in human cholangiocarcinoma tissues and cell lines, we speculated that CDKL3 may constitute a potential biological target for curcumol in cholangiocarcinoma.

In recent years, with the continuous development of China's social and economic life of the people in the industry has been rapid infrastructure development. In these people's livelihood industries, the pace of development of the power industry is particularly fast. With the continuous improvement and continuous development of society and the improvement of people's living standards, electrical equipment has become an indispensable part of our lives, but what good foundation, a growing number of power system to enhance and improve our lives At the same time, there are many attendant problems, China's various regions have experienced varying degrees of power shortage problem, in order to alleviate the power shortage situation in the country and even less in some areas have taken brownouts and blackouts solutions. The relay technology has just the right solution to this thorny problem, the principle of protection technology, when the power system for some reason there is a problem, relay technology can automatically be repaired, so that the power system can stable and secure operation, which has a strong automation features. The protection of these power systems, the protection technology is a very important measure[1].