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We introduced a microfluidic device for high-efficiency single cell capture and their subsequent extraction. It was fabricated by using a deep reactive ion etching process taking advantage of the lag effect. We accomplished single cell capture based on the least flow resistance path principle as well as independent extraction of individual captured cells to perform their subsequent analysis. The device was performed with >99% single cell capture efficiency.

Migration and metastasis of tumor cells greatly contributes to the failure of cancer treatment. Recently, the extracellular protein secreted protein acidic and rich in cysteine (SPARC) has been reported closely related to tumorigenesis. Some articles have suggested that SPARC promoted metastasis in several highly metastatic tumors. However, there are also some studies shown that SPARC acted as an antitumor factor. SPARC-induced epithelial-to-mesenchymal transition (EMT) in melanoma cells and promoted EMT in hepatocellular carcinoma. Therefore, the role of SPARC in tumorigenesis and its relationship with EMT is still unclear. In this study, we investigated the expression change of SPARC in A549 and H1299 lung cancer cells undergoing EMT process. Our study indicated that SPARC was upregulated in A549 and H1299 cells EMT process. We further investigated the function of SPARC on proliferation, migration, and EMT process of A549 and H1299 cells. Overexpression of SPARC promoted the migration and EMT of A549 and H1299 cells. Knockdown SPARC inhibited the EMT of A549 cells. Overexpression of SPARC induced the increased expression of p-Akt and P-ERK. Furthermore, exogenous SPARC peptide promoted transforming growth factor (TGF)-β1-induced EMT of A549 and H1299 cells. SPARC knockdown partially eliminated TGF-β1 function in inducing EMT of A549 cells. SPARC follistatin-like functional domain reduced the expression of E-cadherin, but had no effect on the expression of p-Akt and p-ERK. In conclusion, we elucidated that SPARC contributes to tumorigenesis by promoting migration and EMT of A549 and H1299 lung cancer cells. These results will provide some new suggestion for lung cancer treatment. © 2018 BioFactors, 44(5):453-464, 2018.

Microcapsulses can be designed to effectively encapsulate, protect, and control the release of pesticides. In this study, emulsion-solvent evaporation method was used to fabricate microcapsules using dichloromethane as the solvent, polylactic acid (PLA) as the carrier materials, poly(vinyl alcohol) as the emulsifier, and β-cypermethrin as the entrapped pesticide. The effects of process parameters on the microcapsules characteristics (size, loading content, and encapsulation efficiency) were investigated. Also, the release behavior of the β-cypermethrin was measured experimentally and modeled mathematically. Kinetic analysis indicated that release mechanism of β-cypermethrin was compatible to Fickian diffusion. By optimizing the process parameters, β-cypermethrin-loaded microcapsules were successfully produced with spherical shape, smooth surface, high encapsulation efficiency (> 80%), and a range of pesticide contents. These parameters could be adjusted to achieve delivery systems with desirable release profiles. The results are beneficial to develop delivery systems for rational and effective usage of pesticides.

Recent evidence suggests potential benefits of applying local anesthetics in cancer patients. Specifically, tetracaine has a potent antitumor effect in diverse cancers, including neuroblastoma, breast cancer, and melanoma; however, the underlying molecular mechanisms remain unclear. Here, we reported that tetracaine hydrochloride inhibited the growth of melanoma cells and arrested melanoma cells in the G0/G1 phase. Tetracaine hydrochloride treatment resulted in translocation of hnRNPA1 from the nucleoplasm to the nuclear envelope and reduced the protein stability of hnRNPA1 possibly by disrupting the dynamic balance of ubiquitination and neddylation. Elevated hnRNPA1 upregulated cyclin D1 to promote cell cycle in melanoma. The hnRNPA1 overexpression attenuated the effect of tetracaine hydrochloride on melanoma cell growth suppression and cell cycle arrest. Furthermore, melanoma homograft experiments demonstrated that tetracaine hydrochloride suppressed melanoma growth, while hnRNPA1 overexpression alleviated tetracaine's antitumor effect on melanoma. Taken together, our findings suggest that tetracaine hydrochloride exerts a potent antitumor effect on melanoma both in vitro and in vivo, and the effect involves cell cycle arrest induction via downregulation of hnRNPA1.

Alternative splicing is one of the most common mechanisms of human gene regulation and plays a crucial role in increasing the diversity of functional proteins. Many diseases are linked to alternative splicing, especially cancer. SMAD4 is a member of the SMAD family and plays a critical role in mediating of TGF-β signal transduction and gene regulatory events. Smad4 is a tumour suppressor and acts as a shuttling protein between nucleus and cytoplasm. The splicing variants of Smad4 have been found in many cancers. The present study performed nested PCR to detect alternative splicing of Smad4 in HaCaT cells lines in response to UVB irradiation. The UVB induced a novel Smad4B isoform that led to decrease the Smad4 expression. The hnRNPA1 splicing factor is responsible for Smad4 alternative splicing in response to UVB. The UVB increased the expression of SF2 and hnRNPA1 Splicing factors. The hnRNPA1 overexpression induced Smad4B by regulating Smad4 alternative splicing. The Smad4B isoform supported the function of Smad4 full length in UVB resistance with certain limitation. The western blot analyses showed that the overexpressed Smad4 full length significantly increased N-cadherin expression while Smad4B overexpression decreased the expression the N-cadherin (P

hnRNP A1 acts as a critical splicing factor in regulating many alternative splicing events in various physiological and pathophysiological progressions. hnRNP A1 is capable of regulating UVB-induced hdm2 gene alternative splicing according to our previous study. However, the biological function and underlying molecular mechanism of hnRNP A1 in cell survival and cell cycle in response to UVB irradiation are still unclear. In this study, silencing hnRNP A1 expression by siRNA transfection led to decreased cell survival after UVB treatment, while promoting hnRNP A1 by lentiviruse vector resulted in increased cell survival. hnRNP A1 remarkably enhanced PI3K/Akt/mTOR signaling pathway by increasing phosphorylation of Akt, mTOR and P70S6 protein. Inhibition of PI3K/Akt signaling by LY294002 suppressed the expression of hnRNP A1. While mTOR signaling inhibitors, rapamycin and AZD8055, did not influence hnRNP A1 expression in HaCaT cells, suggesting that hnRNP A1 may be an upstream mediator of mTOR signaling. Furthermore, hnRNP A1 could alleviate UVB-provoked cell cycle arrest at G0/G1 phase and promoted cell cycle progression at G2/M phase. Our results indicate that hnRNP A1 promotes cell survival and cell cycle progression following UVB radiation.

Cellular metabolic heat (ΔPM) is produced from intracellular reactions, carrying information about particular processes thus indicating the status of organisms. ΔPM originating from a single cell is at pW level, making its determination based on the calorimetry technique challenging. Microcalorimetry, evolved from original calorimetry, provides an opportunity to look inside the cell by monitoring ΔPM at single-cell level due to its high resolution. In this review, we discuss the microcalorimetry-based techniques utilized to measure ΔPM, as well as its extended applications. We first introduce the characterization of microcalorimeters and propose potential methods to improve the performance of these devices. Then we focus on ΔPM measurements using microcalorimeters both in microorganisms and mammalian cells. We also review the applications of ΔPM measurements for fundamental metabolism research and drug susceptibility tests. The measurement of ΔPM at single-cell level is challenging shedding light on cellular processes and enhance our knowledge in this field.

Both consumers and producers of food products are looking for natural ingredients and efficient formulation strategies to improve the shelf life of final products. Natural antimicrobial ingredients such as essential oils can be applied as alternatives to synthetic preservatives, but their main challenge is low stability, adverse effects on sensory properties, low solubility, high needed doses, etc. Formulation of these bioactive compounds into nanoemulsions can be an efficient strategy to improve their properties and practical applications in food products. In this review, after an overview on nanoemulsion formulation, ingredients and fabrication methods, different types of natural antimicrobial agents have been discussed briefly. In addition, properties and action mechanisms of antimicrobial-loaded nanoemulsions, along with their application in preservation and shelf life improvement of different food products have been explained. Finally, safety and regulatory issues of antimicrobial delivery via nanoemulsions have been examined. As a conclusion antimicrobial-loaded nanoemulsions can be promising candidates and alternatives for common synthetic preservatives in real food systems.

SWI/SNF complex is an evolutionarily well-conserved chromatin-remodeling complex, which is implicated in the nucleosomes removing or sliding, impacting on the DNA repair, replication and genes expression regulation. The SWI/SNF complex consists up to 12 protein subunits. The catalytic subunits are BRG1 or BRM, which are exclusive ATPase subunits. BRG1 has been reported to play an important role in cellular senescence. However, The function of non-catalytic subunits involved in cellular senescence is rarely investigated. Therefore, we focused on the senescence regulation roles of SWI/SNF non-catalytic subunits in cellular senescent model induced by H2O2. H2O2 treatment was used to induce cellular senescence models in vitro. Screening the candidate subunits involved in this process by comparing the expression levels of SWI/SNF subunits with/without H2O2 treatment. Over-expression and knockdown the candidate subunits were utilized to investigate the functions and mechanism of the subunits involved in senescence regulation. The expressions of BAF57, BAF60a and SNF5 were changed significantly after H2O2 treatment. Overexpression of the three subunits separately induced cell growth arrest in both HaCaT and GLL19 cells, while knockdown of the subunits separately eased the senescence induced by H2O2 treatment. Results further showed that BAF57, BAF60a and SNF5 regulated cellular senescence via both p53/p21 and p16/pRB pathways, and the three subunits all had a directly interaction with p53. These results indicated that BAF57, BAF60a and SNF5 might act as novel pro-senescence factors in both normal and tumor human skin cells. Therefore, inhibiting expression of the three factors might delay the cellular senescence process.

// Xia Li 1, 2 , Zhiming Jiang 1, 3 , Jianguo Feng 1, 2 , Xiaoying Zhang 4 , Junzhou Wu 1, 2 and Wei Chen 1, 3 1 Zhejiang Cancer Research Institute, Zhejiang Cancer Hospital, Zhejiang Cancer Center, Hangzhou, Zhejiang 310022, China 2 Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology (Lung and Esophagus), Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, China 3 Zhejiang Key Laboratory of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, China 4 ACEA Bio CO., Ltd., Hangzhou, Zhejiang 310030, China Correspondence to: Wei Chen, email: chenwei@zjcc.org.cn Keywords: glutathione reductase, oxidative stress, S -glutathionylation, cell cycle arrest, microtubule depolymerization Received: January 10, 2017 Accepted: May 22, 2017 Published: June 27, 2017 ABSTRACT Esophageal squamous cell carcinoma (ESCC) is a highly malignant cancer with poor response to both of chemotherapy and radiotherapy. 2-Acetylamino-3-[4-(2-acetylamino-2-carboxyethylsulfanylcarbonylamino) phenyl carbamoylsulfanyl] propionic acid (2-AAPA), an irreversible inhibitor of glutathione reductase (GR), is able to induce intracellular oxidative stress, and has shown anticancer activity in many cancer cell lines. In this study, we investigated the effects of 2-AAPA on the cell proliferation, cell cycle and apoptosis and aimed to explore its mechanism of action in human esophageal cancer TE-13 cells. It was found that 2-AAPA inhibited growth of ESCC cells in a dose-dependent manner and it did not deplete reduced glutathione (GSH), but significantly increased the oxidized form glutathione (GSSG), resulting in decreased GSH/GSSG ratio. In consequence, significant reactive oxygen species (ROS) production was observed. The flow cytometric analysis revealed that 2-AAPA inhibited growth of esophageal cancer cells through arresting cell cycle in G 2 /M phase, but apoptosis-independent mechanism. The G 2 /M arrest was partially contributed by down-regulation of protein expression of Cdc-25c and up-regulation of phosphorylated Cdc-2 (Tyr15), Cyclin B1 (Ser147) and p53. Meanwhile, 2-AAPA-induced thiol oxidative stress led to increased protein S -glutathionylation, which resulted in α-tubulin S -glutathionylation-dependent depolymerization of microtubule in the TE-13 cells. In conclusion, we identified that 2-AAPA as an effective thiol oxidative stress inducer and proliferation of TE-13 cells were suppressed by G 2 /M phase cell cycle arrest, mainly, through α-tubulin S -glutathionylation-mediated microtubule depolymerization. Our results may introduce new target and approach for esophageal cancer therapy through generation of GR-mediated thiol oxidative stress.

Intestinal ischemia/reperfusion (I/R) can cause multiple organ damage with extremely high morbidity and mortality. Melatonin has anti-inflammatory, anti-oxidative and anti-apoptotic effects against various diseases. This study aimed to explore whether melatonin had a protective effect against intestinal I/R-induced neuroinflammation and cognitive dysfunction, and investigate its potential mechanisms. In this study, melatonin was administered to the rats with intestinal I/R, then histological changes in intestine and brain (frontal cortex and hippocampal CA1 area) tissues and cognitive function were detected, respectively. The encephaledema and blood-brain barrier (BBB) permeability were observed. Moreover, the alterations of proinflammatory factors (tumor necrosis factor-α, interleukin-6 and interleukin-1β), oxidative response (malondialdehyde, superoxide dismutase, and reactive oxygen species), apoptosis and proteins associated with inflammation,including Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (Myd88) and phosphorylated nuclear factor kappa beta (NF-κB), and apoptosis (cleaved caspase-3) in brain tissues were examined. Furthermore, the expressions of TLR4, Myd88, and microglial activity were observed by multiple immunofluorescence staining. The results showed that intestinal I/R-induced abnormal neurobehavior and cerebral damage were ameliorated after melatonin treatment, which were demonstrated by improved cognitive dysfunction and aggravated histology. Furthermore, melatonin decreased the levels of proinflammatory factors and oxidative stress in plasma, intestine and brain tissues, attenuated apoptotic cell, and inhibited the expressions of related proteins and the immunoreactivity of TLR4 or Myd88 in microglia in brain tissues. These findings showed that melatonin might relieve neuroinflammation and cognitive dysfunction caused by intestinal I/R, which could be, at least partially, related to the inhibition of the TLR4/Myd88 signaling in microglia.

This paper analyzes the origin, status, changes and characteristics of the automotive electromechanical maintenance skills competition in China, and presents the developing trend in the future.

A typical area, Gaomi City in China, was chosen to discuss the enrichment process of groundwater fluorine in seawater intrusion area. The groundwater had fluorine levels of 0.09-10.99 mg/L, with an average concentration of 1.38 mg/L. The high-fluorine groundwater was mainly distributed in the unconsolidated Quaternary sediments, where concentrations in 83.6% of the samples exceeded the national limit of 1.0 mg/L. The groundwater in the Quaternary sediments also had higher levels of Cl

Groundwater is the major source of water for drinking and irrigation purposes in the Futuan River Basin, China. In this paper, 118 groundwater samples were collected and analyzed following standard methods to decipher the sodium adsorption ratio (SAR), sodium percentage (Na%), and residual sodium carbonate (RSC). The groundwater is classified as slightly acidic freshwater with medium hardness, and most of the samples are Ca–HCO3 and Ca–Cl types. The dominance of cations and anions follows the trend Ca2+ > Na+ > Mg2+ > K+ and HCO3− > Cl− > SO42− > NO3−, respectively. The total dissolved solids (TDS) values are higher in the coastal areas and near the townships. Gibbs plots and end-member diagrams indicate that the groundwater chemistry in the Futuan River Basin is mainly controlled by rock weathering, and most of the water chemistry originates from the weathering of silicate, as well as cation exchange. The groundwater of the study area is affected by a certain extent of evaporation, and three samples were influenced by sea water intrusion. Fuzzy comprehensive assessment showed that most of the samples were good to excellent for potable purposes and the SAR, Na%, and RSC indicate that most of the groundwater is suitable for irrigation. Controlling pollution sources, strengthening groundwater dynamic monitoring, optimizing the layout of groundwater exploitation, and reducing the amount of groundwater extraction are of great significance for the rational development and utilization of the groundwater resources in the Futuan River Basin.

The alluvial-diluvial plain of southwest Shandong Province is an important agricultural economic zone and energy base in Shandong Province. Groundwater plays an extremely significant role in the development of the regional social economy. In this study, 50 sets of water samples, collected from 25 wells during October 2016 and June 2017, were utilized to determine the hydrogeochemistry and the suitability of groundwater in the alluvial-diluvial plain of southwest Shandong Province for different applications, such as drinking and irrigation. Most of the water samples could be classified as hard-fresh water or hard-brackish water, and the dominant water types were HCO3-Na and mixed types. Water-rock interactions and evaporation were the dominant controlling factors in the formation of the hydrochemical components in the groundwater. Dissolutions of silicate, calcite, dolomite, and gypsum are the major reactions contributing and defining the groundwater chemistry in this plain. Moreover, cation exchange is a non-negligible hydrogeochemical process in this plain. Calculated saturation index (SI) values indicate that aragonite, calcite and dolomite are saturated, while the SI values for gypsum and halite are unsaturated. Based on fuzzy comprehensive evaluation, the groundwater quality ranges from excellent to very poor. More than 50% of all groundwater samples from 2016 are categorized as poor or very poor, suggesting that the water from these wells is not suitable for drinking. According to the sodium adsorption ratio and percentage sodium, most of the samples are suitable for agricultural irrigation. Overall, the quality of the groundwater in 2017 was found to be better than in 2016.

The occurrence and progress of minimal hepatic encephalopathy (MHE) is closely related to the inflammatory response; however, inflammation contributes to behavioral abnormalities and sleep disorders. Dexmedetomidine has anti-inflammatory effects against various diseases. Whether dexmedetomidine improves MHE and the underlying mechanism is yet unclear. The present study aimed to explore the effects of dexmedetomidine on sleep structure, neurobehavior, and brain morphology of MHE rats and investigate its underlying mechanism. A rat MHE model was established by intraperitoneal injection of thioacetamide (TAA). Dexmedetomidine or yohimbine was administered intraperitoneally to investigate the role of α2 adrenoreceptor in the protection conferred by dexmedetomidine. The 24-h sleep, neurobehavioral changes, the liver function, blood ammonia and morphological changes of the liver and brain were assessed. Also, the microglia, astrocytes, neurons, the expression of pro-inflammatory factors (IL-1β, TNF-α, IL-18), and NLRP3 inflammasomes were detected. The results showed that marked sleep disorders, cognitive impairment, anxiety, abnormal liver function and pathological damage of liver and brain were detected in the MHE rats. The microglia in the prefrontal cortex was highly activated along with the increased expression of pro-inflammatory factors and NLRP3 inflammasomes. Interestingly, dexmedetomidine improved above indicators, however, yohimbine significantly abolished the protection of dexmedetomidine. These findings showed that dexmedetomidine restored the changes in the sleep disorders and neurobehavior in rats and reduced brain damage. The mechanism might be partially related to the activation of α2 adrenergic receptors, reduction of neuroinflammatory response, and inhibition of the activation of microglia and NLRP3/Caspase1 signaling pathway.

Microcalorimetry has been widely used in measuring cellular metabolic heat to study bioprocesses, such as metabolism. However, it is still limited by insufficient sensitivity and system complexity, especially for the direct measurements of individual cells. Here, we present a droplet-based simple differential microcalorimetric system for determining the real-time energy balance of the ciliate protist, Paramecium caudatum. We utilized the platform to dynamically monitor its defensive behavior and measured the temperature change. Then we used heat balance equation and calculated corresponding dissipated power and energy with an ultimate resolution of ≈14 nW. The results showed that the defensive behavior by the ejection of the trichocysts’ content consumed energy of ≈0.75 mJ per cell, and the dissipated power was ≈303.8 μW. This differential microcalorimetric platform can be used to study the metabolic heat of protist metabolism as well as other individual cells, helping us to understand this widespread, yet little-known, biological phenomenon from a new perspective.

Peppermint oil (PO) is one of the most popular and widely used essential oils. However, due to volatile and poor water solubility of volatile oil, its application in the fields of medicine and food is limited. In order to solve this problem, the high speed shearing technology was used to prepare the nanoemulsion from PO. By using a series of characterization methods, such as turbiscan scanning spectrum, dynamic light scattering (DLS), confocal laser scanning microscope (CLSM), the best nanoemulsion formula was identified as PO 10 %, surfactant 8 % (Tween-60: EL-20 = 3:1) and deionized water 82 % (w/w). The inhibition strength of nanoemulsion on bacteria was evaluated by detecting the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) in Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) treated with peppermint oil nanoemulsion (PON) and observing the morphology of bacteria with biological scanning electron microscope (SEM). The results showed that PON had strong inhibitory effect on E. coli. At the concentration range of 0.02 μg/μL–0.2 μg/μL, the apoptosis rate of BEAS-2B cells was less than 10 % compared with control cells. All in all, the PON prepared under this formula is stable, which provides a reference for further exploration of essential oil as natural antibacterial materials in the future.

UV induces CIRP expression and subsequent Stat3 activation, but the biological function and mechanism of CIRP and Stat3 in mediating UVB-induced skin carcinogenesis have not been fully elucidated. In this study, we demonstrate that CIRP is elevated in all tested melanoma and non-melanoma skin cancer cell lines; and the expression of CIRP is upregulated in keratinocytes after being irradiated with relatively low dose (

Estradiol plays important roles in many biological responses inducing tumor genesis and cancer treatment. However, the effects of estradiol on tumors were inconsistent among a lot of researches and the mechanism is not fully understood. Our previous study indicated that splicing factor hnRNPA1 could bind to the human homologue of mouse double minute (MDM2), an oncogene which has been observed to be over-expressed in numerous types of cancers. In this research, we investigated whether and how estradiol correlate to cancer cell behaviors through heterogeneous nuclear ribonucleoprotein (hnRNPA1) and MDM2. Results showed that 10×10-13Mestradiol elevated the expression of hnRNPA1 regardless ER expression in cells, and then down-regulated the expression of MDM2. At the same time, estradiol inhibited cell proliferation, migration and epithelial-mesenchymal transition progression of A375 and GLL19 cells. While, knocking down hnRNPA1 through the transfection of hnRNPA1 siRNA led to the increase of MDM2 at both protein level and gene level In vivo experiment, subcutaneous injection with estradiol every two days near the tumor at doses of 2.5mg/kg/d suppressed tumor growth and reduced MDM2 expression. In a word, via increasing hnRNPA1 level and then reducing the expression of MDM2, estradiol prevented carcinogenesis in melanomas. We confirmed therapeutic effect of estradiol, as well as a new way for estradiol to resist skin cancer.

// Lisha Ying 1, 2, * , Fanrong Zhang 2, * , Xiaodan Pan 3 , Kaiyan Chen 2 , Nan Zhang 2 , Jiaoyue Jin 2 , Junzhou Wu 2 , Jianguo Feng 2 , Herbert Yu 4 , Hongchuan Jin 1 , Dan Su 2 1 Laboratory of Cancer Biology, Provincial Key Lab of Biotherapy in Zhejiang, Sir Runrun Shaw Hospital, Medical School of Zhejiang University, Hangzhou, China 2 Cancer Research Institute, Zhejiang Cancer Hospital & Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology of Zhejiang Province, Hangzhou, China 3 Tissue Bank of Zhejiang Cancer Hospital, Hangzhou, China 4 Cancer Epidemiology Program, University of Hawaii Cancer Center, Hawaii, USA * These authors have contributed equally to this work Correspondence to: Dan Su, email: sudan@zjcc.org.cn Hongchuan Jin, email: jinhc@zju.edu.cn Keywords: complement component 7, tumor progression, prognosis, ovarian cancer, non-small cell lung cancer Received: September 02, 2016 Accepted: October 29, 2016 Published: November 11, 2016 ABSTRACT Our previous study found copy number variation of chromosome fragment 5p13.1-13.3 might involve in the progression of ovarian cancer. In the current study, the alteration was validated and complement component 7 (C7), located on 5p13.1, was identified. To further explore the clinical value of C7 in tumors, 156 malignant, 22 borderline, 33 benign and 24 normal ovarian tissues, as well as 173 non-small cell lung cancer (NSCLC) tissues along with corresponding adjacent and normal tissues from the tissue bank of Zhejiang Cancer Hospital were collected. The expression of C7 was analyzed using reverse transcriptase quantitative polymerase chain reaction. As a result, the C7 expression displayed a gradual downward trend in normal, benign, borderline and malignant ovarian tissues, and the decreased expression of C7 was correlative to poor differentiation in patients with ovarian cancer. Interestingly, a similar change of expression of C7 was found in normal, adjacent and malignant tissues in patients with NSCLC, and low expression of C7 was associated with worse grade and advanced clinical stage. Both results from this cohort and the public database indicated that NSCLC patients with low expression of C7 had a worse outcome. Furthermore, multivariate cox regression analysis showed NSCLC patients with low C7 had a 3.09 or 5.65-fold higher risk for relapse or death than those with high C7 respectively, suggesting C7 was an independent prognostic predictor for prognoses of patients with NSCLC. Additionally, overexpression of C7 inhibited colony formation of NSCLC cells, which hints C7 might be a potential tumor suppressor.

// Jianguo Feng 1, 2, * , Huaying Sheng 3, * , Chihong Zhu 2 , Xiaoqian Qian 2 , Danying Wan 2 , Dan Su 1, 2 , Xufeng Chen 4 , Liming Zhu 5 1 Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology, Hangzhou, Zhejiang 310022, China 2 Cancer Research Institute, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, China 3 Department of Thoracic Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, China 4 Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA 5 Department of Chemotherapy, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, China * These authors contributed equally to this work Correspondence to: Liming Zhu, email: mdtlab@zjcc.org.cn Keywords: non-small cell lung cancer, neuroendocrine, CD56, CgA, Syn Received: June 20, 2016 Accepted: September 21, 2016 Published: September 28, 2016 ABSTRACT The improvement in histological diagnostic tools, including neuroendocrine markers by immunohistochemistry (IHC), has led to increased recognition of non-small cell lung cancer (NSCLC) with neuroendocrine (NE) feature. However, little is known regarding the prevalence and clinical implications of NE feature in patients with NSCLC. In this study, we performed IHC in a tissue microarray containing 451 Chinese NSCLC cases, and analyzed correlation of the expression of neuroendocrine marker with pathological and clinical features of NSCLC. The result showed that NE feature in NSCLC was detectable in almost 30% of studied patients, and tumors with NE feature were significantly correlated with pathological classification, clinical stages and cell differentiation of NSCLC. Our data also revealed that NE feature indicated worse overall survival and disease free survival. Compared with mutant p53, NE markers showed more significance as for prognostic evaluation. Multi-factor COX analysis further suggested a potential clinical impact for NE feature as an independent indicator of poor prognosis for NSCLC patients.

// Shirong Zhang 1, * , Kan Wu 2, 3, * , Jianguo Feng 4, * , Zhibing Wu 3 , Qinghua Deng 3 , Chao Guo 5 , Bing Xia 3 , Jing Zhang 1 , Haixiu Huang 1 , Lucheng Zhu 1 , Ke Zhang 3 , Binghui Shen 5 , Xufeng Chen 6 , Shenglin Ma 1 1 Department of Oncology, Hangzhou First People’s Hospital, Nanjing Medical University, Hangzhou, China 2 Department of Oncology, Affiliated Hangzhou First People’s Hospital of Zhejiang Chinese Medical University, Hangzhou, China 3 Department of Oncology, Hangzhou Cancer Hospital, Hangzhou, China 4 Cancer Research institute, Zhejiang Cancer Hospital, Hangzhou, China 5 Department of Cancer Genetics and Epigenetics, City of Hope National Medical Center, Duarte, CA, USA 6 Department of Pathology and Laboratory Medicine, University of California at Los Angeles, Los Angeles, CA, USA * These authors have contributed equally to this work Correspondence to: Shenglin Ma, email: mashenglin@medmail.com.cn Keywords: non-small cell lung cancer, invasion, epigenetics, suberoylanilide hydroxamic acid, epigenetic therapy Received: March 29, 2016 Accepted: August 24, 2016 Published: September 12, 2016 ABSTRACT Metastasis is the reason for most cancer death, and a crucial primary step for cancer metastasis is invasion of the surrounding tissue, which may be initiated by some rare tumor cells that escape the heterogeneous primary tumor. In this study, we isolated invasive subpopulations of cancer cells from human non-small cell lung cancer (NSCLC) H460 and H1299 cell lines, and determined the gene expression profiles and the responses of these invasive cancer cells to treatments of ionizing radiation and chemotherapeutic agents. The subpopulation of highly invasive NSCLC cells showed epigenetic signatures of epithelial-mesenchymal transition, cancer cell stemness, increased DNA damage repair and cell survival signaling. We also investigated the epigenetic therapy potential of suberoylanilide hydroxamic acid (SAHA) on invasive cancer cells, and found that SAHA suppresses cancer cell invasiveness and sensitizes cancer cells to treatments of IR and chemotherapeutic agents. Our results provide guidelines for identification of metastatic predictors and for clinical management of NSCLC. This study also suggests a beneficial clinical potential of SAHA as a chemotherapeutic agent for NSCLC patients.

Lung cancer is a leading cause of cancer-related mortality worldwide, and concurrent chemoradiotherapy has been explored as a therapeutic option. However, the chemotherapeutic agents cannot be administered for most patients at full doses safely with radical doses of thoracic radiation, and further optimizations of the chemotherapy regimen to be given with radiation are needed. In this study, we examined the effects of suberoylanilide hydroxamic acid (SAHA) and cisplatin on DNA damage repairs, and determined the combination effects of SAHA and cisplatin on human non–small cell lung cancer (NSCLC) cells in response to treatment of ionizing radiation (IR), and on tumor growth of lung cancer H460 xenografts receiving radiotherapy. We also investigated the potential differentiation effect of SAHA and its consequences on cancer cell invasion. Our results showed that SAHA and cisplatin compromise distinct DNA damage repair pathways, and treatment with SAHA enhanced synergistic radiosensitization effects of cisplatin in established NSCLC cell lines in a p53-independent manner, and decreased the DNA damage repair capability in cisplatin-treated primary NSCLC tumor tissues in response to IR. SAHA combined with cisplatin also significantly increased inhibitory effect of radiotherapy on tumor growth in the mouse xenograft model. In addition, SAHA can induce differentiation in stem cell–like cancer cell population, reduce tumorigenicity, and decrease invasiveness of human lung cancer cells. In conclusion, our data suggest a potential clinical impact for SAHA as a radiosensitizer and as a part of a chemoradiotherapy regimen for NSCLC. Mol Cancer Ther; 15(5); 842–53. ©2016 AACR.

Using mesoporous silica nanoparticles (MSNs) to load pesticides has become a research hotspot. In this study, MSNs loaded with abamectin were successfully prepared by a one-pot method, which synchronized the synthesis of nanoparticles with pesticide loading. The preparation cycle shortened, reaction requirement is reduced, and drug loading rate is increased, and the drug can protect abamectin from natural light damage. Moreover, alkaline conditions accelerate the release of abamectin owing to the destruction of mesoporous structures, and increase in temperature promotes molecular movement and accelerates the release of abamectin. Compared with traditional abamectin formulations, MSNs loaded with abamectin prolong the duration of abamectin against Plutella xylostella and significantly reduce toxicity to A549 cells. The preparation of MSNs by the one-pot method provides important help for the further promotion of MSNs as a pesticide delivery system.

Background Immune checkpoint inhibitors play a vital role in triple-negative breast cancer (TNBC) immunotherapy. A recent study showed that chemokine-like factor (CKLF)-like MARVEL transmembrane domain containing 6 (CMTM6) has a crucial role in programmed death-ligand 1 (PD-L1) stability. The aim of this study was to investigate the relationship between CMTM6 and PD-L1 in TNBC and the association with clinical characteristics. Methods A total of 143 patients, including 75 with human epidermal growth factor receptor 2 (HER2)-driven breast cancer and 68 with TNBC, were included in this study. In 83 paired primary breast cancers (PBCs) and metastatic breast cancers (MBC) comprising 45 HER2-driven breast cancers and 38 TNBC, CMTM6 and PD-L1 were detected based on immunohistochemistry (IHC) with FFPE tissues. Another 60 PBCs comprising 30 HER2-driven breast cancers and 30 TNBC in order to detect CMTM6 and PD-L1 mRNA expressions based on real-time polymerase chain reaction (RT-PCR) using frozen tissues. Furthermore, 153 patients comprising 30 TNBC and 123 HER2-driven breast cancer based on The Cancer Genome Atlas (TCGA) database were used to confirm the difference mRNA expression. Results The expression of CMTM6 in patients with TNBC was significantly higher than in those with HER2-driven PBC (IHC, P=0.036, mRNA, P=0.036, TCGA dataset, P=0.039). CMTM6 was correlated with PD-L1 based on IHC in triple-negative MBC (P=0.004); the same result was found based on mRNA data in triple- negative PBC (P=0.021). Moreover, a high expression of CMTM6 in TNBC was associated with poor progression-free survival (PFS) (P=0.030, 95% CI: 1.08-4.57, HR =2.22). After multiple Cox regression analysis, CMTM6 in TNBC emerged as an independent risk factor for PFS (P=0.027, 95% CI: 1.11-5.20, HR =2.40). The expression of PD-L1 was negatively correlated with lymph node metastasis (P=0.026) and was not associated with PFS. Conclusions The expression of CMTM6 was higher in TNBC than in HER2-driven breast cancer. In TNBC, CMTM6 was correlated with PD-L1 expression, and potentially could be used as an independent risk factor for predicting PFS.

Microfluidic devices typically require complex shapes such as funnels, spirals, splitters, channels with different widths, or customized objects of arbitrary complexity with a smooth transition between these elements. Device layouts are generally designed by software developed for the design of integrated circuits or by general computer-aided design drawing tools. Both methods have their limitations, making these tasks time consuming. Here, a script-based, time-effective method to generate the layout of various microfluidic chips with complex geometries is presented. The present work uses the nanolithography toolbox (NT), a platform-independent software package, which employs parameterized fundamental blocks (cells) to create microscale and nanoscale structures. In order to demonstrate the functionality and efficiency of the NT, a few classical microfluidic devices were designed using the NT and then fabricated in glass/silicon using standard microfabrication techniques and in poly(dimethylsiloxane) using soft lithography as well as more complex techniques used for flow-through calorimetry. In addition, the functionality of a few of the fabricated devices was tested. The powerful method proposed allows the creation of microfluidic devices with complex layouts in an easy way, simplifying the design process and improving design efficiency. Thus, it holds great potential for broad applications in microfluidic device design.

Recently, antibiotic resistance of pathogens has grown given the excessive and inappropriate usage of common antimicrobial agents. Hence, producing novel antimicrobial compounds is a necessity. Carbon nanomaterials (CNMs) such as carbon nanotubes, graphene/graphene oxide, and fullerenes, as an emerging class of novel materials, can exhibit a considerable antimicrobial activity, especially in the nanocomposite forms suitable for different fields including biomedical and food applications. These nanomaterials have attracted a great deal of interest due to their broad efficiency and novel features. The most important factor affecting the antimicrobial activity of CNMs is their size. Smaller particles with a higher surface to volume ratio can easily attach onto the microbial cells and affect their cell membrane integrity, metabolic procedures, and structural components. As these unique characteristics are found in CNMs, a wide range of possibilities have raised in terms of antimicrobial applications. This study aims to cover the antimicrobial activities of CNMs (both as individual forms and in nanocomposites) and comprehensively explain their mechanisms of action. The results of this review will present a broad perspective, summarizes the most remarkable findings, and provides an outlook regarding the antimicrobial properties of CNMs and their potential applications.

This study aimed to determine the hydrochemical characteristics and hydrogeochemical processes of shallow groundwater in the Jinta Basin, northwest China, and to evaluate the suitability of groundwater quality for drinking water and agricultural irrigation. A systematic hydrogeological survey was conducted in the study area from May 2017 to October 2018, during which 123 representative samples of groundwater were selected for analysis of chemical parameters and determination of the water quality index. The results showed that the pH of groundwater in the study area was weakly alkaline and ranged between 7.21&ndash, 8.93. Dominant cations were Mg2+ and Na+ and the dominant anion was SO42&minus, Along the groundwater flow from the southwest to northeast, the dominant groundwater chemistry type in the recharge area was Mg-HCO3&middot, SO4. After the transition of the groundwater types in the runoff area to Mg-SO4&middot, HCO3 and Mg&middot, Na-SO4, the groundwater type in the discharge area evolved into Na&middot, Mg-SO4&middot, Cl. The major factors driving the evolution of groundwater chemical types in the Jinta Basin were found to be rock weathering, evaporation and precipitation. The chemical components of groundwater mainly originated from the dissolution of silicate rock and evaporative concentration of salt under water-rock interaction, whereas the dissolution of carbonate had little influence. The quality of drinking water was divided into five groups, and 39.84% of samples fell within the high and good quality groups. The quality of agricultural irrigation water was divided into different grades according to different methods.

D-limonene is an important constituent of citrus fruits, such as oranges and lemons, and can be extracted as a natural essential oil for controlling the agricultural pests because of its antifungal and insecticidal activities. However, the hydrophobicity of D-limonene hinders its full potential and excellent performance. In this research, the effect of emulsifier type, dosage, and emulsification method on the formation and stability of D-limonene-loaded nanoemulsions was investigated by sample appearance, microstructural observations, droplet size measurement, and multiple light scattering analysis. Nanoemulsions prepared with emulsifier (EL-40) exhibited the highest stability, with an appropriate HLB (Hydrophilic Lipophilic Balance) value of 13.5. The stability of nanoemulsions increased at higher emulsifier dosage from 2% to 6%. Also, nanoemulsions fabricated by dropwise addition of aqueous phase (deionized water) into D-limonene as the oil phase premixed with emulsifier were the most stable samples. The optimized formulation of D-limonene-loaded nanoemulsions was determined as: 10 % D-limonene, 6% EL-40, and 84 % deionized water. The quality indicators of this formulation were acceptable in terms of FAO standards. Finally, D-limonene-loaded nanoemulsions could inhibit the growth of various fungal pathogens, including Pyricularia oryzae (rice blast), Rhizoctonia solani (rice sheath blight), Colletortrichum gloeosporiodes (pepper anthracnose), and Phomopsis amygdali (peach shoot blight). This research provides a practical solution for the formulation of stable and effective nanoemulsions containing D-limonene for the control of agricultural crop diseases.

Microcalorimeters have been widely used for characterizing molecular interactions in physical, chemical and biological research. Here, we report on a droplet-based micromachined calorimeter for real-time energy balance monitoring. The microcalorimeter was fabricated by a single lithography process and wafer dicing using glass substrate with a diameter and a thickness of ≈ 100 mm and ≈ 100 μm, respectively. The sample with volume of ≈ 0.5 μL was placed on the microcalorimeter and covered with mineral oil to avoid evaporation. The microcalorimeter was operated in differential mode having the temperature and power resolution of ≈ 148 μK and ≈ 42 nW, respectively. With this system, we monitored the energy balance of H2O2 decomposition catalyzed by few self-propelled Pt microrobots. Such a simple microcalorimeter has tremendous potential for chemical and biological research such as monitoring the energy balance of living cells or microorganisms and correlating the energy changes with their activities and status.

Background Recent studies have shown that circular RNA (circRNA) is rich in microRNA (miRNA) binding sites. We have previously demonstrated that the antidepressant effect of ketamine is related to the abnormal expression of various miRNAs in the brain. This study determined the expression profile of circRNAs in the hippocampus of rats treated with ketamine. Methods The aberrantly expressed circRNAs in rat hippocampus after ketamine injection were analyzed by microarray chip, and we further validated these circRNAs by quantitative reverse-transcription PCR (qRT-PCR). The target genes of the different circRNAs were predicted using bioinformatic analyses, and the functions and signal pathways of these target genes were investigated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Results Microarray analysis showed that five circRNAs were aberrantly expressed in rat hippocampus after ketamine injection (fold change > 2.0, p p = 0.03), while one was significantly reduced (rno_circRNA_005442; fold change = 0.37; p = 0.01). We discovered a significant enrichment in several GO terms and pathways associated with depression. Conclusion Our findings showed the abnormal expression of ketamine-induced hippocampal circRNAs in rats.

We developed an advanced method for fabricating microfluidic structures comprising channels and inputs/outputs buried within a silicon wafer based on single level lithography. We etched trenches into a silicon substrate, covered these trenches with parylene-C, and selectively opened their bottoms using femtosecond laser photoablation, forming channels and inputs/outputs by isotropic etching of silicon by xenon difluoride vapors. We subsequently sealed the channels with a second parylene-C layer. Unlike in previously published works, this entire process is conducted at ambient temperature to allow for integration with complementary metal oxide semiconductor devices for smart readout electronics. We also demonstrated a method of chip cryo-cleaving with parylene presence that allows for monitoring of the process development. We also created an observation window for in situ visualization inside the opaque silicon substrate by forming a hole in the parylene layer at the silicon backside and with local silicon removal by xenon difluoride vapor etching. We verified the microfluidic chip performance by forming a segmented flow of a fluorescein solution in an oil stream. This proposed technique provides opportunities for forming simple microfluidic systems with buried channels at ambient temperature.

Background Brain metastasis is an extremely serious sequela with a dismal prognosis in non-small cell lung cancer (NSCLC). The present study aimed to identify novel biomarkers and potential therapeutic targets for brain metastases of NSCLC. Methods We performed high-throughput Luminex assays to profile the transcriptional levels of 36 genes in 70 operable NSCLC patients, among whom 37 developed brain metastases as the first relapse within 3 years after surgery. The Cox proportional hazards regression model was used to evaluate the association between genes and brain metastases. Wound healing assay and transwell assay was carried out to estimate the function of target gene in vitro. And left ventricular injection on nude mice was used to evaluate the effect of target gene in vivo. Results Growth-associated protein 43 (GAP43) was found to be related to brain metastasis. Multivariate Cox regression analysis showed that NSCLC patients with elevated GAP43 had a 3.29-fold increase in the risk for brain metastasis compared with those with low levels (95% confidence interval: 1.55–7.00; P = 0.002). Kaplan–Meier survival curves revealed that GAP43 was also associated with overall survival. Analysis of a cohort of 1926 NSCLC patients showed similar results: patients with high levels of GAP43 had worse progression-free and overall survival rates. Furthermore, in vitro experiments showed that GAP43 facilitated cell migration. Animal studies demonstrated that GAP43-silenced NSCLC cells were less likely to metastasize to the brain and bone than control cells. Immunofluorescence and F-actin/G-actin in vivo assays indicated that GAP43 knockdown triggered depolymerization of the F-actin cytoskeleton. Rho GTPase activation assays showed that Rac1 was deactivated after GAP43 was silenced. Conclusions Our findings suggest that GAP43 is an independent predictor of NSCLC brain metastasis and that it may facilitate metastasis by regulating the Rac1/F-actin pathway.

How to improve urban traffic and achieve the sustainable development of the city, is a very challenging task in front of the traffic workers. The core idea of urban transportation infrastructure construction is to improve the quality of resident life and protect the environment. Development and construction of a high -volume, low-cost, high-quality form of public transport, which can meet the above requirements of the construction. A large number of practice has proved that the rapid transit system has better combine the strengths of rail transit and bus. Its relatively low cost and high efficiency is indeed a very good mode of public transport. In this paper, the applicability of BRT system in Zibo is studied based on Zibo traffic and environment status.

Human homolog double minute 2 (hdm2), an oncoprotein, which binds to tumor suppressor p53 to facilitate its degradation, has been known to contribute to tumorigenesis. Its splicing variants are reported to be highly expressed in many cancers and can be induced by ultraviolet B light (UVB). However, the mechanisms of how UVB radiation induces hdm2 alternative splicing still remain unclear. In this study, we investigated the roles of two common splicing factors, heterogeneous nuclear ribonucleoproteins (hnRNP) A1 and serine/arginine-rich splicing factor 1 (SRSF1), in regulating UVB-induced hdm2 splicing. Our study indicated that while the expression of both hnRNP A1 and SRSF1 are induced, only hnRNP A1 is involved in hdm2 alternative splicing upon UVB irradiation. Overexpression of hnRNP A1 resulted in decrease of full-length hdm2 (hdm2-FL) and increase of hdm2B, one of hdm2 alternate-splicing forms; while down-regulated hnRNP A1 expression led to the decrease of the hdm2-FL and hdm2B in HaCaT cells. Protein-mRNA binding assay confirmed that UVB irradiation could increase the binding of hnRNP A1 to hdm2 pre-mRNA. In conclusion, we elucidated that UVB induces alternative splicing of hdm2 via increasing the expression and the binding of hnRNP A1 to hdm2 full-length mRNA.

In this paper, we present a microflow cytometer based on a polydimethylsiloxane (PDMS) microfluidic chip. The PDMS chip has a smooth sidewall because of the proposed double molding process. Thus, the side scatter (SSC) detection can be used for the cytometer. The coincidence error using the sheathless focus mechanism is less than 0.069%. Using Flow-Check alignment beads for the counting experiment, the coefficient of variation (CV) of the SSC and the fluorescein isothiocyanate (FITC) channel can reach 8.37% and 2.46%, respectively. The gating of the lymphocytes according to CD45/SSC was also demonstrated successfully. It proves that the chip is a promising solution for point of care (POC) microflow cytometers.

Mechano-growth factor (MGF), an alternative splicing variant of insulin-like growth factor-1 (IGF-1) gene, promotes cell proliferation and inhibits cell differentiation. It also plays an important role in tumor development. It is important to optimize the production process and achieve MGF protein because there is no commercial MGF protein available. In this study, the human MGF gene is cloned into pGEX-4T-1 and the recombinant human MGF (rhMGF) protein could be expressed in Rosetta (DE3) by isopropyl β-d-1-thiogalactopyranoside induction but not in BL21 (DE3). Mutation from rare codons to Escherichia coli preferred ones is performed. We obtain MGF(Mut54–56) and MGF(Mut-total) fragments through site-directed mutagenesis and overlapping PCR. Both pGEX-4T-1/MGF(Mut54–56)- and pGEX-4T-1/MGF(Mut-total)-transformed BL21 (DE3) can be induced to express rhMGF protein. To optimize the production technology, expression and purification of rhMGF are analyzed and compared in Rosetta (DE3) and BL21 (DE3). Results indicate that rhMGF expression in BL21 (DE3) is significantly higher than that in Rosetta (DE3). The protein yield of pGEX-4T-1/MGF(Mut-total) in BL21 (DE3) is higher than that of pGEX-4T-1/MGF(Mut54–56). We test the biological activity of MGF protein purified by affinity chromatography in C2C12 cell line and find that rhMGF promotes cell proliferation significantly. In conclusion, we establish a method to produce rhMGF economically with high biological activity in BL21 (DE3).

Downregulation of fructose-1,6-bisphosphatse-1 (FBP1) was observed in several cancers but its role in the lung cancer still remains unknown. We examined the cancer tissues from 140 patients with nonsmall cell lung cancer patients and found that the relative gene expression of FBP1 was significantly lower in lung cancer tissues as compared to incisal marginal tissues and normal tissues. The patients with higher level of FBP1 RNA expression have significantly longer disease free survival and overall survival as compared to the lower expression groups. There was a negative correlation with the level of FBP1 and recurrence of the lung cancer.

The adsorption of paraquat (PQ) on starfish particles was investigated to calculate the kinetic, isotherm, and thermodynamic parameters. The experiments were carried out as a function of particle size of adsorbent, adsorbent dosage, contact time, initial PQ concentration, stirring speed, and temperature. The kinetic data followed the pseudo-second-order kinetic model, and the equilibrium data were well fitted by the Langmuir isotherm model with the maximum adsorption amount of 10.235 mg g−1 at 288 K. Thermodynamic parameters, including standard Gibbs free energy changes (ΔG0), standard entropy changes (ΔS0), and standard enthalpy changes (ΔH0) were also calculated. The results demonstrated that PQ was adsorbed onto starfish particles spontaneously and exothermically in nature. The adsorption process followed a physisorption mechanism. In addition, the starfish particles were successfully utilized to real sample. Hence, starfish particles are eligible for treating the wastewater containing PQ as an effective and low-cost adsorbent. © 2015 Curtin University of Technology and John Wiley & Sons, Ltd.

Migration and metastasis of tumor cells greatly contributes to the failure of cancer treatment. Recently, the extracellular protein secreted protein acidic and rich in cysteine (SPARC) has been reported closely related to tumorigenesis. Some articles have suggested that SPARC promoted metastasis in several highly metastatic tumors. However, there are also some studies shown that SPARC acted as an antitumor factor. SPARC-induced epithelial-to-mesenchymal transition (EMT) in melanoma cells and promoted EMT in hepatocellular carcinoma. Therefore, the role of SPARC in tumorigenesis and its relationship with EMT is still unclear. In this study, we investigated the expression change of SPARC in A549 and H1299 lung cancer cells undergoing EMT process. Our study indicated that SPARC was upregulated in A549 and H1299 cells EMT process. We further investigated the function of SPARC on proliferation, migration, and EMT process of A549 and H1299 cells. Overexpression of SPARC promoted the migration and EMT of A549 and H1299 cells. Knockdown SPARC inhibited the EMT of A549 cells. Overexpression of SPARC induced the increased expression of p-Akt and P-ERK. Furthermore, exogenous SPARC peptide promoted transforming growth factor (TGF)-β1-induced EMT of A549 and H1299 cells. SPARC knockdown partially eliminated TGF-β1 function in inducing EMT of A549 cells. SPARC follistatin-like functional domain reduced the expression of E-cadherin, but had no effect on the expression of p-Akt and p-ERK. In conclusion, we elucidated that SPARC contributes to tumorigenesis by promoting migration and EMT of A549 and H1299 lung cancer cells. These results will provide some new suggestion for lung cancer treatment. © 2018 BioFactors, 44(5):453-464, 2018.

Background Cholesterol is an essential building block of the cell membrane and an important molecule for cell signaling and function. The dysregulation of cholesterol metabolism has been linked to several diseases, including cancer. The aim of this study is to investigate whether serum cholesterol is associated with the survival outcomes of patients with non-small cell lung cancer (NSCLC). Methods The concentration of total cholesterol (TC) was measured in pre-operative serum samples of 637 NSCLC patients. The associations of TC with recurrence and overall survival were analyzed using a Cox proportional hazard regression model. Kaplan-Meier survival curves were calculated for overall survival analysis. Results Our analyses showed that low serum levels of TC were associated with an increased risk of death. The association between TC and overall survival remained significant after patient age at diagnosis, gender, disease stage, histotype, tumor grade, body mass index (BMI), and smoking status were adjusted in the analysis. The patients with low serum TC had a 61% (95% confidence interval: 1.18 - 2.19) higher risk of death compared to those with normal TC. A Kaplan-Meier survival analysis showed similar results. No association was found between TC and recurrence in NSCLC. Conclusions Our study suggests that the pre-surgical serum level of TC may be an independent prognostic indicator for NSCLC overall survival.

Many of the pesticides that are widely used in agricultural applications are highly hydrophobic molecules with low water solubility, and therefore, they need to be loaded within suitable delivery systems prior to utilization. In this chapter, the application of oil-in-water nanoemulsions for solubilization and delivery of hydrophobic pesticides is reviewed. An overview of the design and formulation of pesticide nanoemulsions is given, and a number of their recent applications are highlighted. In particular, the chapter stresses the importance of carefully designing the composition and structure of pesticide nanoemulsions to ensure their efficacy. Some of the major potential advantages of pesticide nanoemulsions over other methods include their strong adhesion to surfaces, high penetrability, and broad range of applicability.

Oil-in-water (O/W) emulsions can be utilized as effective pesticide delivery systems in the agricultural industry. In this study, the effects of hydrophile-lipophile balance (HLB), concentration, and location of surfactants on the formation and physical stability of O/W emulsions suitable for pesticide applications was investigated using dynamic light scattering and vertical laser profiling. A non-polar pesticide (lambda-cyhalothrin) was used as a model. The pesticide emulsion with the highest stability was obtained using a commercial non-ionic surfactant (polyoxyethylene castor oil ether, EL-20) with a required HLB value of 10.5. Emulsion stability increased as the surfactant concentration was increased from 2 to 6%, which was attributed to the formation of smaller oil droplets during emulsification. Emulsions prepared with the surfactant initially in the oil phase were more stable than those prepared with it initially in the aqueous phase. The optimum formulation of the pesticide emulsion was determined as follows: 5% lambda-cyhalothrin (active ingredient) and 6% EL-20 (surfactant) dissolved in 5% S-200 (aromatic hydrocarbon, as oil phase), then deionized water up to 100%, which met the quality indicators set by the FAO standards. The present study is expected to provide useful information to improve the stability of pesticide emulsions for commercial applications.

The present study aimed to examine the hypothesis that vascular endothelial growth factor (VEGF) has a protective effect against cardiopulmonary bypass (CPB)-associated acute kidney injury (AKI). Eighteen male beagles were randomly allocated to three groups (n=6 per group): Sham group, animals received sternotomy without going through CPB; CPB group, animals received CPB only; VEGF group, animals received CPB and VEGF. VEGF infusion was completed 1 h prior to the initiation of CPB. Renal microcirculation perfusion, serum creatinine (SCr) and blood urea nitrogen (BUN), histopathological injury score and apoptotic index were determined. Hypoxia inducible factor-1α, VEGF, phosphorylated (p)-Akt serine/threonine kinase (Akt), p-endothelial nitric oxide synthase (eNOS), cleaved caspase-3, B-cell lymphoma 2 (Bcl-2) and cluster of differentiation (CD)95 expression levels were assessed by western blot analysis, Enzyme-linked immunosorbent assay quantitative assays were used to evaluate tumor necrosis factor (TNF)-α, interleukin (IL)-6, superoxide dismutase and malondialdehyde levels. Renal microcirculation perfusion of the VEGF group was higher than that of the CPB group (P