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A novel integrated surface plasmon resonance (SPR) sensor that combines an optical waveguide platform and an ultra-thin spectrometer is proposed. The core of the proposed method is a special-shaped optical waveguide structure that employs a wedge-shaped incident surface, which changes the position of the total reflection of the incident light on the sagittal plane without affecting the direction of propagation on the tangential plane. The parameters of the sensing module with the integrated SPR sensor and spectrometer module were designed and optimized to achieve higher performance in a compact optical waveguide platform. An experimental system was built based on the theoretical model, and the spectral sensitivity of the system was analyzed before sample detection, and the results showed that the spectral resolution in the working range could reach 9.9 nm. The refractive index sensitivity of this novel SPR sensor was 3186 nm/RIU with good stability by detecting different concentrations of sodium chloride samples. This new structure does not require an external spectrometer, thereby enabling an increase in the compactness of the SPR sensing system. The proposed method can provide a novel idea for the miniaturization of SPR sensors.

A Fourier transform spectrometer (FTS) has been used to observe solar activities due to its ultra-high spectral resolution. However, the FTS in-band spectra are usually distorted and some artifacts appear in out-of-band regions due to nonlinear effects. Therefore, the FTS nonlinear problem must be corrected. In this study, we proposed a novel method to correct the nonlinear effects using simulated annealing. We simulated several nonlinear spectra to evaluate the performance of our method. The calculated quadratic coefficients are extremely close to the given values, demonstrating that the method is effective and accurate. The proposed method is further used to correct the blackbody and solar spectra with nonlinearity obtained by Bruker IFS-125HR installed at the Huairou Solar Observing Station, which is a pathfinder for the accurate infrared magnetic field measurements of the Sun project. To the blackbody spectra, the nonlinearity in low- and high-frequency regions are corrected by 89.09% and 60.84%. The nonlinear correction of the solar spectra in the low- and high-frequency regions have reached 65.34% and 81.04%, respectively. These results prove that our method can correct the nonlinear problem to improve the data accuracy.

Benzoylaconitine (BAC), the main hydrolysate of aconitine, is a lower toxic monoester type alkaloid considered as the pharmacodynamic constituent in Aconitum species. In this study, the effects and mechanisms of BAC on production of inflammatory cytokines interleukin (IL)-6 and IL-8 were investigated in IL-1β-stimulated human synovial SW982 cells. The SW982 cells were incubated with BAC (0, 5 and 10 µM) before stimulating with IL-1β (10 ng/mL). The results revealed that BAC suppressed gene and protein expression of IL-6 and IL-8 induced by IL-1β. BAC decreased activation of mitogen-activated protein kinase (MAPK) and phosphorylation of Akt. BAC also inhibited degradation of inhibitor of kappaB (IκB)-α, phosphorylation and nuclear transposition of p65 protein. The results demonstrate that BAC exerts an anti-inflammatory effect dependent on MAPK, Akt and nuclear factor-κB (NF-κB) pathways in human synovial cells stimulated with IL-1β, suggesting that BAC may be exploited as a potential therapeutic agent for rheumatoid arthritis (RA) treatment.

The novel coronavirus disease 2019 (COVID-19) infection broke out in December 2019 in Wuhan, and rapidly overspread 31 provinces in mainland China on 31 January 2020. In the face of the increasing number of daily confirmed infected cases, it has become a common concern and worthy of pondering when the infection will appear the turning points, what is the final size and when the infection would be ultimately controlled. Based on the current control measures, we proposed a dynamical transmission model with contact trace and quarantine and predicted the peak time and final size for daily confirmed infected cases by employing Markov Chain Monte Carlo algorithm. We estimate the basic reproductive number of COVID-19 is 5.78 (95%CI: 5.71–5.89). Under the current intervention before 31 January, the number of daily confirmed infected cases is expected to peak on around 11 February 2020 with the size of 4066 (95%CI: 3898–4472). The infection of COVID-19 might be controlled approximately after 18 May 2020. Reducing contact and increasing trace about the risk population are likely to be the present effective measures.

Sine oculis homeobox 1 (Six1) is a homeodomain transcription factor that is aberrantly expressed in a variety of human cancers, including colorectal cancer (CRC). Six1 has been reported to play a key role in the proliferation and migration of CRC cells but the underlying molecular mechanisms are still poorly characterized. In the present study, we found that Six1 overexpression promoted the proliferation and migration of CRC cells. Consistently, Six1 knockdown (KD) significantly inhibited proliferation and migration of CRC cells. In addition, we showed that Six1 promoted proliferation and migration of CRC cells through activation of Wnt/β-catenin signaling, as evidenced by promotion of nuclear localization of β-catenin. Silencing of β-catenin expression with siRNA or inhibiting Wnt signaling with a specific inhibitor, xav939, significantly blocked Six1-induced nuclear localization of β-catenin and mitigated Six1-promoted proliferation and migration of CRC cells. We further confirmed the involvement of β-catenin in Six1-promoted proliferation and migration of CRC cells by activation of Wnt signaling with lithium chloride (LiCl) in Six1 KD CRC cells and results showed that LiCl restores defective β-catenin nuclear localization and proliferation and migration of CRC cells. Taken together, these results suggest that Six1 homeoprotein promotes the proliferation and migration of CRC cells by activating the Wnt/β-catenin signaling pathway, and strategies targeting Six1 may be promising for the treatment of CRC.

Cocaine abuse remains a public health threat around the world. There are no pharmacological treatments approved for cocaine use disorder. Cannabis has received growing attention as a treatment for many conditions, including addiction. Most cannabis-based medication development has focused on cannabinoid CB(1) receptor (CB(1)R) antagonists (and also inverse agonists) such as rimonabant, but clinical trials with rimonabant have failed due to its significant side-effects. Here we sought to determine whether a novel and selective CB(2)R inverse agonist, Xie2-64, has similar therapeutic potential for cocaine use disorder. Computational modeling indicated that Xie2-64 binds to CB(2)R in a way similar to SR144528, another well-characterized but less selective CB(2)R antagonist/inverse agonist, suggesting that Xie2-64 may also have CB(2)R antagonist profiles. Unexpectedly, systemic administration of Xie2-64 or SR144528 dose-dependently inhibited intravenous cocaine self-administration and shifted cocaine dose-response curves downward in rats and wild-type, but not in CB(2)R-knockout, mice. Xie2-64 also dose-dependently attenuated cocaine-enhanced brain-stimulation reward maintained by optical stimulation of ventral tegmental area dopamine neurons in DAT-Cre mice, while Xie2-64 or SR144528 alone inhibited optical brain-stimulation reward. In vivo microdialysis revealed that systemic or local administration of Xie2-64 into the nucleus accumbens reduced extracellular dopamine levels in a dose-dependent manner in rats. Together, these results suggest that Xie2-64 has significant anti-cocaine reward effects likely through a dopamine-dependent mechanism, and therefore, deserves further study as a new pharmacotherapy for cocaine use disorder.

The present study shows the basis for the anti-inflammatory effects of pitavastatin in interleukin (IL)-1β-induced human synovial cells. The SW982 cells were pretreated with pitavastatin at different concentrations (5μM and 10μM), followed by IL-1β (10ng/mL) stimulation. The results showed that pitavastatin inhibited the expression of inflammatory mediators IL-6 and IL-8. Furthermore, pitavastatin inhibited the phosphorylation of p38, extracellular signal-related kinase (ERK), c-jun N-terminal kinase (JNK) and protein kinase B (Akt). It also suppressed the degradation of I kappa B alpha and blocked p65 translocation into the nucleus. These findings suggest that the mechanism underlying the inhibitory effects of pitavastatin on IL-1β-induced IL-6 and IL-8 release might be mediated by the suppression of mitogen-activated protein kinase (MAPK), Akt, and nuclear factor-κB (NF-κB) signaling pathways. These results may also indicate that pitavastatin may be potentially utilized as an effective therapeutic agent for the treatment of osteoarthritis.

Induced by hypothermia, cold-inducible protein RBM3 (RNA-binding protein motif 3), has been implicated in neuroprotection against various toxic insults such as hypoxia and ischemia. However, whether mild hypothermia and RBM3 prevent neural cells from UV irradiation-elicited apoptosis is unclear. In the present study, human neuroblastoma cell line SH-SY5Y was used as a cell model for neural cell death, and it was demonstrated that mild hypothermia protects SH-SY5Y cells from UV irradiation-induced apoptosis. However, the protective effect of mild hypothermia was abrogated when RBM3 was silenced. Conversely, the overexpression of RBM3 rescued SH-SY5Y cells from UV-induced apoptosis, as indicated by the decreased levels of cleaved caspase-3 and PARP, and increased cell survival. The analysis on the mechanism underlying RBM3-mediated neuroprotection against UV insult showed that RBM3 could substantially block the activation of p38 and JNK signaling pathways. In addition, the overexpression of RBM3 reduced the expression of pro-apoptotic proteins Bax and Bad, leaving the pro-survival protein Bcl-2 unaffected. In conclusion, RBM3 is the key mediator of mild hypothermia-related protection against UV in neuroblastoma cells, and the neuroprotective effect might be exerted through interfering with pro-apoptotic signaling pathways p38 and JNK and regulating pro-apoptotic proteins Bax and Bad.

As a result of vitamin A abuse, excessive retinoic acid can induce apoptosis in neural cells. Mild-hypothermia and cold-inducible protein RBM3 protect neural cells from apoptosis. However, whether hypothermia/RBM3 protect neural cells from retinoic acid-induced apoptosis remains unclear. The SH-SY5Y neuroblastoma cell line, a common neural cell model of apoptosis, was employed here. Interestingly, retinoic acid overdose induced apoptosis in SH-SY5Y cells, which was prevented by mild-hypothermia. When RBM3 was silenced, hypothermia-related protection was completely abolished. RBM3 overexpression significantly prevented retinoic acid-induced apoptosis. Screening of signaling pathways revealed that RBM3 overexpression markedly inhibited retinoic acid-induced upregulation of p38 and JNK signaling, and antagonized downregulation of AMPK signaling. Subsequent assays demonstrated that p38 and JNK signaling were pro-apoptotic, while AMPK was anti-apoptotic. Overall, these data showed that mild-hypothermia protects neural cells from retinoic acid-induced apoptosis via induction of RBM3, which subsequently mediates the neuroprotective effects via AMPK, p38 and JNK signaling.

Liquiritin is one of flavone compounds derived from licorice, a common flavoring and sweetening agent in food products. This study investigated the effects and mechanisms of liquiritin in interleukin (IL)-1β-stimulated SW982 human synovial cells, which is a useful tool to study the inflammatory response of rheumatoid arthritis (RA). The SW982 cells were pretreated with various concentrations (0, 10 and 40 μM) of liquiritin, followed by IL-1β (10 ng/mL) stimulation. Liquiritin significantly inhibited protein and mRNA levels of inflammatory cytokines IL-6 and IL-8 in IL-1β-stimulated SW982 cells. Liquiritin suppressed IL-1β-induced phosphorylation of p38, c-jun N-terminal kinase (JNK), and adenosine monophosphate-activated protein kinase (AMPK), inhibited p-c-Jun activation and decreased p65 protein translocation into the nucleus induced by IL-1β. These results indicate that liquiritin exerts an anti-inflammatory effect via modulating JNK, p38, activator protein-1 (AP-1), AMPK and nuclear factor-κB (NF-κB) pathways in IL-1β-induced human synovial cells.

The neural cell adhesion molecule (NCAM), a key member of the immunoglobulin-like CAM family, was reported to regulate the migration of bone marrow-derived mesenchymal stem cells (BMSCs). However, the detailed cellular behaviors including lamellipodia formation in the initial step of directional migration remain largely unknown. In the present study, we reported that NCAM affects the lamellipodia formation of BMSCs. Using BMSCs from Ncam knockout mice we found that Ncam deficiency significantly impaired the migration and the directional lamellipodia formation of BMSCs. Further studies revealed that Ncam knockout decreased the activity of cofilin, an actin-cleaving protein, which was involved in directional protrusions. To explore the molecular mechanisms involved, we examined protein tyrosine phosphorylation levels in Ncam knockout BMSCs by phosphotyrosine peptide array analyses, and found that the tyrosine phosphorylation level of β1 integrin, a protein upstream of cofilin, was greatly upregulated in Ncam-deficient BMSCs. Notably, by blocking the function of β1 integrin with RGD peptide or ROCK inhibitor, the cofilin activity and directional lamellipodia formation of Ncam knockout BMSCs could be rescued. Finally, we found that the effect of NCAM on tyrosine phosphorylation of β1 integrin was independent of the fibroblast growth factor receptor. These results indicated that NCAM regulates directional lamellipodia formation of BMSCs through β1 integrin signal-mediated cofilin activity.

Benzoylaconitine (BAC), the main hydrolysate of aconitine, is a lower toxic monoester type alkaloid considered as the pharmacodynamic constituent in Aconitum species. In this study, the effects and mechanisms of BAC on production of inflammatory cytokines interleukin (IL)-6 and IL-8 were investigated in IL-1β-stimulated human synovial SW982 cells. The SW982 cells were incubated with BAC (0, 5 and 10 µM) before stimulating with IL-1β (10 ng/mL). The results revealed that BAC suppressed gene and protein expression of IL-6 and IL-8 induced by IL-1β. BAC decreased activation of mitogen-activated protein kinase (MAPK) and phosphorylation of Akt. BAC also inhibited degradation of inhibitor of kappaB (IκB)-α, phosphorylation and nuclear transposition of p65 protein. The results demonstrate that BAC exerts an anti-inflammatory effect dependent on MAPK, Akt and nuclear factor-κB (NF-κB) pathways in human synovial cells stimulated with IL-1β, suggesting that BAC may be exploited as a potential therapeutic agent for rheumatoid arthritis (RA) treatment.

Chondrocyte hypertrophy‐like change is an important pathological process of osteoarthritis (OA), but the mechanism remains largely unknown. Neural cell adhesion molecule (NCAM) is highly expressed and involved in the chondrocyte differentiation of mesenchymal stem cells (MSCs). In this study, we found that NCAM deficiency accelerates chondrocyte hypertrophy in articular cartilage and growth plate of OA mice. NCAM deficiency leads to hypertrophic chondrocyte differentiation in both murine MSCs and chondrogenic cells, in which extracellular signal‐regulated kinase (ERK) signaling plays an important role. Moreover, NCAM expression is downregulated in an interleukin‐1β‐stimulated OA cellular model and monosodium iodoacetate‐induced OA rats. Overexpression of NCAM substantially inhibits hypertrophic differentiation in the OA cellular model. In conclusion, NCAM could inhibit hypertrophic chondrocyte differentiation of MSCs by inhibiting ERK signaling and reduce chondrocyte hypertrophy in experimental OA model, suggesting the potential utility of NCAM as a novel therapeutic target for alleviating chondrocyte hypertrophy of OA., NCAM deficiency enhances hypertrophic chondrocyte differentiation of MSCs by increasing ERK signaling, and accelerates chondrocyte hypertrophy in experimental osteoarthritis.

As the areas of CCD detectors and CCD mosaics have become larger and larger, the number of readout channels in astronomical cameras has increased accordingly to keep the image readout time within an acceptable range. For the large area cameras or the mosaic cameras, the analog Correlated Double Sampling (aCDS) circuit used in traditional astronomical cameras for suppressing readout noise is difficult to integrate into the camera controllers within the constraints of the space and energy consumption. Recently, digital CDS (dCDS) technology has been developed to solve this problem, which also offers novel analysis and noise suppression methods. In this study, a mathematical model is presented to conveniently analyze the frequency characteristic of a dCDS circuit, which is then simulated by a numerical method for investigating the noise suppression capability with different sampling weights. Importantly, using this model, the extreme point with lowest readout noise can be predicted for a certain dCDS model; and for a specific CCD readout frequency, readout noise can be suppressed by selecting the proper dCDS model. A testing system is then constructed for validating the efficiency of the proposed method.

Effects and mechanisms of kaempferol, identified in a wide variety of dietary sources, on the expression of interleukin (IL)-6, IL-8, matrix metallo proteinase (MMP)-1, and cyclooxygenase (COX)-2 were evaluated in IL-1β-induced SW982 cells. The cells were pretreated with kaempferol of various concentrations (2, 10 and 50 µmol/L) followed by IL-1β (10 ng/mL) stimulation. Kaempferol significantly suppressed mRNA and protein levels of IL-6, IL-8, MMP-1, and COX-2 induced by IL-1β. Kaempferol also inhibited mitogen-activated protein kinase (MAPK) and protein kinase B (Akt) phosphorylation and decreased IκB-α degradation and p65 protein translocation into the nucleus. Moreover, adenosine monophosphate-activated protein kinase (AMPK) does not contribute to the anti-inflammatory effects in SW982 cells, although its phosphorylation is significantly increased by kaempferol. These results indicate that kaempferol may have an anti-inflammatory effect by inhibiting expression of IL-6, IL-8, MMP-1 and COX-2 via suppressing MAPK, Akt, and nuclear factor (NF)-κB signalling but not activating AMPK signalling.

NG2-expressing neural progenitors can produce neurons in the central nervous system, providing a potential cell resource of therapy for neurological disorders. However, the mechanism underlying neuronal differentiation of NG2 cells remains largely unknown. In this report, we found that a thrombospondin (TSP) family member, TSP4, is involved in the neuronal differentiation of NG2 cells. When TSP4 was overexpressed, NG2 cells underwent spontaneous neuronal differentiation, as demonstrated by the induction of various neuronal differentiation markers such as NeuN, Tuj1, and NF200, at the messenger RNA and protein levels. In contrast, TSP4 silencing had an opposite effect on the expression of neuronal differentiation markers in NG2 cells. Next, the signaling pathway responsible for TSP4-mediated NG2 cell differentiation was investigated. We found that ERK but not p38 and AKT signaling was affected by TSP4 overexpression. Furthermore, when ERK signaling was blocked by the inhibitor U0126, the neuronal marker expression of NG2 cells was substantially increased. Together, these findings suggested that TSP4 promoted neuronal differentiation of NG2 cells by inhibiting ERK/MAPK signaling, revealing a novel role of TSP4 in cell fate specification of NG2 cells.

PRDM (PRDI‐BF1 and RIZ domain‐containing) proteins constitute a family of zinc finger proteins and play important roles in multiple cellular processes by acting as epigenetic modifiers. PRDM5 is a recently identified member of the PRDM family and may function as a tumor suppressor in several types of cancer. However, the role of PRDM5 in murine melanoma remains largely unknown. In our study, effect of PRDM5 on murine melanoma cells was determined and results showed that PRDM5 overexpression significantly promoted proliferation, migration, and invasion of murine melanoma B16F10 cells. Consistently, silencing of PRDM5 expression significantly inhibited proliferation, invasion, and migration of B16F10 cells. In vivo study also showed that PRDM5 silencing significantly inhibited the growth and metastasis of melanoma in mice. PRDM5 was then found to increase the expression and activation of JNK in B16F10 cells. JNK silencing significantly reduced PRDM5‐mediated up‐regulation of JNK expression and blocked the PRDM5‐induced proliferation and invasion of B16F10 cells. To further verify the involvement of JNK signaling in PRDM5‐induced progression of B16F10 cells, a specific JNK inhibitor was employed to inhibit the JNK signaling pathway, and results showed that PRDM5‐induced proliferation and invasion of B16F10 cells were abolished. We conclude that PRDM5 promotes the proliferation and invasion of murine melanoma cells through up‐regulating JNK expression and strategies targeting PRDM5 may be promising for the therapy of melanoma.

Hydroxysafflor yellow A (HSYA), the main active ingredient in medical and edible dual purpose plant safflower, is reported to have multiple bioactivities. In the present study, the anti-inflammatory effects of HSYA and the underlying mechanisms were investigated in interleukin (IL)-1β-induced SW982 human synovial cells. The cells were pretreated with HSYA at various concentrations (2.5, 10 and 40 μM) followed by IL-1β (10 ng mL−1) stimulation. HSYA significantly inhibited the expression of IL-6, IL-8 and matrix metalloproteinase (MMP)-1 in IL-1β-stimulated SW982 cells. HSYA also inhibited the phosphorylation of extracellular signal-regulated kinase (ERK), p65 and c-Jun. It also suppressed the degradation of IκBα and blocked p65 translocation into the nucleus. These results indicate that the inhibitory effects of HSYA on IL-1β-induced IL-6, IL-8 and MMP-1 release might be mediated via suppression of ERK, nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) signaling pathways. The present data support the potential role of HSYA as an effective therapeutic agent in osteoarthritis.

To study the role of oleanolic acid on interleukin (IL)-1β-stimulated expression of inflammatory cytokines, and to explore its anti-inflammatory mechanism in SW982 cells, the toxicity of oleanolic acid on SW982 cells was detected by MTT; effects of different concentrations of oleanolic acid(5, 10, 20 μmol·L(-1)) on the expression of inflammatory factors IL-6, IL-8 and matrix metalloproteinase-1 (MMP-1) was tested at protein and m RNA levels. The study was performed in IL-1β-stimulated SW982 cells together with enzyme-linked immunosorbent assay (ELISA) and real-time fluorescence quantitative PCR (real-time PCR) methods; the influence of oleanolic acid on the phosphorylation of mitogen-activated protein kinase (MAPK), phosphatidyl inositol-3-kinase/Akt (PI3K/Akt) and nuclear transcription factor-κB (NF-κB) signaling pathways related protein was analyzed by Western blot. Results showed that different concentrations of oleanolic acid(≤40 μmol·L(-1)) were almost non-toxicity to SW982 cells; oleanolic acid significantly inhibited the expression of inflammatory factors in a dose-dependent manner; oleanolic acid restrained extracellular signal-related kinase (ERK), p38, c-jun N-terminal kinase (JNK) and Akt protein phosphorylation and IκB-α protein degradation obviously. The inhibition effect of oleanolic acid on inflammatory factors stimulated by IL-1β may be worked through MAPK, PI3K/Akt and NF-κB signaling pathways.

Nitric oxide (NO), a gaseous signaling molecule, induces apoptosis and mediates neurodegenerative diseases and brain injury. Biglycan (BGN), a member of the small leucine-rich proteoglycan family, was demonstrated to exert anti-apoptosis function in various disease models. However, little is known about the effect of BGN on NO-induced neurotoxicity. Here, for the first time, we reported that BGN protects against NO-induced apoptosis in human neuroblastoma SH-EP1 cells. This is supported by the finding that sodium nitroprusside (SNP), a NO donor, triggered downregulation of BGN in SH-EP1 cells, and over-expression of BGN strikingly attenuated NO-induced nuclear fragmentation and apoptosis of neuronal cells. More importantly, BGN remarkably blocked NO-induced phosphorylation of Erk1/2 and p38 signaling, but not JNK MAPK pathway in neuronal cells. Furthermore, inhibiting Erk1/2 by U0126 or p38 by SB203580 partially protected against NO-induced cell death. Conversely, downregulation of BGN by siRNA aggravated NO-induced neuronal cell death, which was not attenuated by U0126 or SB203580. These findings indicated that BGN, downregulated by NO, prevents NO-induced neuronal cell apoptosis via targeting Erk1/2 and p38 signaling pathways. Our results strongly suggest that BGN could be explored for the prevention of NO-induced neurodegenerative disorders.

A double-structured microporous polymer composite support consisting of a microporous skeleton for protection of immobilized enzymes and a gel-like polymer bearing different functionalities has been synthesized for immobilization of various enzymes. Among three approaches based on two types of interactions (physical and chemical), we found that under our experimental conditions the covalent bonding between amine moieties of enzymes and epoxide groups of the support was the best, with enzyme leaching being reduced to as low as zero for nine enzymes and catalytic activities increased by factors of 1–4 for two lipases. The improvement in catalytic activity could be attributed to the amphiphilic soft gel which might create a kind of lipid–water interface or microenvironment in aqueous solution, favoring the interfacial activation of certain lipases. Furthermore, the thermal and operational stability, and reusability of all the enzymes could be enhanced to varying degrees. We also found that enzyme aggregates of different sizes could be formed on the spherical support surface at quite low enzyme concentrations, which might also influence the final catalytic activities of the immobilized enzymes. © 2015 Society of Chemical Industry

Polyethyleneimine (PEI) is a cost-effective and non-viral vector for gene transfer, but the factors determining gene transfer efficiency and cytotoxicity of PEI in different mammalian cell lines remain largely unknown. In the present study, three different cell lines were chosen for investigation. Using pEGFP DNA and PEI, 21.5, 29.2, and 92.1 % of GFP-positive cells were obtained in BMSC, Hela, and 293T, respectively. In luciferase reporter assay, similar results were obtained (for luciferase activity, BMSC < Hela < 293T cells). By MTT test and cell apoptotic marker analysis, we demonstrated that high gene transfer efficiency is accompanied with high cytotoxicity of PEI. Moreover, we found that high expression level of caveolin-1 was accompanied with high gene transfer efficiency and cytotoxicity of PEI in 293T cells. More convincingly, caveolin-1 silencing in 293T could reduce both gene transfer efficiency and cytotoxicity of PEI. In contrast, caveolin-1 overexpression in BMSCs increases both gene transfer efficiency and cytotoxicity of PEI. Taken together, our study suggests that caveolin-1 may at least in part determine gene transfer efficiency and cytotoxicity of PEI in mammalian cell lines, providing caveolin-1 as a potential target for improving gene transfer efficiency when applying positively charged polyplexes to cell transfection.

Nitric oxide (NO)-induced apoptosis in neurons is an important cause of neurodegenerative disease in humans. The cold-inducible protein RBM3 mediates the protective effects of cooling on apoptosis induced by various insults. However, whether RBM3 protects neural cells from NO-induced apoptosis is unclear. This study aimed to investigate the neuroprotective effect of RBM3 on NO-induced apoptosis in human SH-SY5Y neuroblastoma cells. Firstly, we demonstrated that mild hypothermia (32 °C) induces RBM3 expression and confers a potent neuroprotective effect on NO-induced apoptosis, which was substantially diminished when RBM3 was silenced by siRNA. Moreover, overexpression of RBM3 exhibited a strong protective effect against NO-induced apoptosis. Signaling pathway screening demonstrated that only p38 inhibition by RBM3 provided neuroprotective effect, although RBM3 overexpression could affect the activation of p38, JNK, ERK, and AKT signaling in response to NO stimuli. Notably, RBM3 overexpression also blocked the activation of p38 signaling induced by transforming growth factor-β1. Furthermore, both RBM3 overexpression and mild hypothermia abolished the induction of miR-143 by NO, which was shown to mediate the cytotoxicity of NO in a p38-dependent way. These findings suggest that RBM3 protects neuroblastoma cells from NO-induced apoptosis by suppressing p38 signaling, which mediates apoptosis through miR-143 induction.

It is challenging to reinforce and toughen thermoset epoxy resins. We describe a slurry-compounding technique to transfer a uniform dispersion of chitin nanowhiskers (CW) in ethanol into an epoxy matrix. The incorporation of the hydrophilic CW reinforces the oil-soluble diglycidyl ether of bisphenol A (DGEBA). The resultant CW/epoxy bionanocomposites were transparent and showed considerably enhanced thermal and mechanical properties with tensile strength, modulus, toughness, and elongation at break being increased by 49%, 16%, 457%, and 250%, with only 2.5 wt.% CW. This improvement in strength and toughness is rare for thermoset epoxy/rigid nanofiller systems. We hypothesize that CW with many free amine groups could function not only as a nanofiller but also as a macromolecular polyamine hardener that participates in epoxy curing. The strong covalent interaction between the filler and the matrix allowed for efficient load transfer across the interfaces, which accounted for the greater strength and toughness.

Oligodendrocytes (OLs) are derived oligodendrocyte progenitor cells (OPCs), and their differentiation is a tightly regulated process. It is known that cyclin-dependent kinases (CDKs) play an essential role as regulators of OPC differentiation. Here, we newly identified a CDK-like protein, PFTK1, to be involved in OPC differentiation. With serum-deprivation, OLN-93 undergoes OL differentiation, and PFTK1 expression is markedly decreased during differentiation. When PFTK1 is silenced, OL differentiation is potentiated, as suggested by the increase of various differentiation markers CNPase, MOG, CGT, and MBP, by qPCR and Western blotting analysis. Vice versa, PTTK1 overexpression has opposite effects on OL differentiation of OLN-93 in vitro. Next, the modulation mechanism underlying OL differentiation of OLN-93 was investigated. Significantly, PFTK1 silencing leads to the activation of PI3K/AKT pathway, but no activation of MAPK/ERK pathway. The inhibition of AKT by its specific inhibitor abrogates PFTK1 silencing-promoted OL differentiation, indicating that PFTK1 negatively regulates OL differentiation through PI3K/AKT pathway. Together, these findings indicate a novel role played by PFTK1 in OL development, thus presenting opportunities to establish therapeutic approaches in improving neurological recovery related to demyelinating disorders.

Objective To investigate the clinical efficacy of acupuncture combined with tuina in treating patients with cervical vertigo.

GATA-2, a member of zinc finger GATA transcription factor family, plays key role in the hematopoietic stem cells self-renewal and differentiation. The transforming growth factor-β (TGFβ) signaling pathway is a major signaling network that controls cell proliferation, differentiation and tumor suppression. Here we found that GATA-2 negatively regulated TGF-β signaling pathway in Smad4-dependent manner. GATA-2 specifically interacts with Smad4 with its N-terminal while the zinc finger domain of GATA-2 is essential for negative regulation of TGFβ. Although GATA-2 did not affect the phosphorylation of Smad2/3 and the complex Smad2/3/4 formation in response to TGFβ, the DNA binding activity of Smad4 was decreased significantly by GATA-2 overexpression. Overexpression of GATA-2 in K562 cells led to reduced TGFβ-induced erythroid differentiation while knockdown of GATA-2 enhanced TGFβ-induced erythroid differentiation. All these results suggest that GATA-2 is a novel negative regulator of TGFβ signal pathway.

Aiming at the fire type and evolution of large ship cabins, a fire risk analysis method of large ship cabins based on fire scene analysis was established, which is basing on the International Maritime Organization (IMO) SOLAS Convention and International fire procedures (FTP ) by combining Chinas ship cabins fire protection technology and fire safety management features. The purpose is to improve technical level of the fire risk management and fireproof disposal basing on fire prevention with warning disposal by dynamic risk management of ship cabins fire hazard and fire control technology.

The panel flutter on hypersonic vehicle is investigated. Based on third-order local flow piston theory and reference enthalpy method, the aerodynamic force and aerodynamic heat model are established respectively. Taking temperature conduct in the panel and radiation to ambience into account, hierarchical solution process is adopted in time-domain to analyze the flutter character in different flow with thermal effects. The results shows that, the flight height and mach number of the hypersonic vehicle can make notable influence on the flutter frequency, amplitude and starting time. This will support the design of panel structures on hypersonic vehicle.

Three species of the family Noctuidae –Phlogophora striatovirens (Moore, 1867), Usbeca kulmburgi (Rebel, 1918) and Feliniopsis leucostigma (Moore, 1867) – are reported for the first time from China. Photographs of adults and genital characteristics are provided.

Leptomeningeal fibrosis is important in the pathogenesis of communicating hydrocephalus following subarachnoid hemorrhage; however, the underlying mechanisms of leptomeningeal fibrosis remain largely unclear. In the present study, primary meningeal mesothelial cells (MMCs) were used as a cell model to investigate the effect of transforming growth factor‑β1 (TGF‑β1) on leptomeningeal fibrosis. Firstly, primary MMCs were isolated from rat brains and characterized by immunofluorescene, staining positive for keratin and vimentin, but negative for factor VIII. Upon TGF‑β1 treatment, MMCs were induced to express connective tissue growth factor (CTGF), an indicator of fibrosis, in a dose‑dependent manner. Furthermore, p38 mitogen‑activated protein kinase (MAPK) signaling was significantly activated by TGF‑β1. However, in the presence of a p38 MAPK inhibitor, TGF‑β1‑induced CTGF expression was markedly suppressed. Together, these data suggest that TGF‑β1 could induce fibrosis of MMCs via the p38 MAPK signaling pathway, providing a novel potential target for intervention in TGF‑β1‑induced leptomeningeal fibrosis.

The research of hypersonic gliding lifting body vehicle is so complicated that its aerodynamic characteristics prediction is very time-consuming. To solve the problem, the parametric design method based on class function/shape function transformation and power function is employed, and a lifting body shape with five configuration parameters which is convenient for analysis and design is proposed. At the same time, we calculate hypersonic aerodynamic based on panel element with kinds of engineering-estimation methods according to compression or expansion elements. Compared with numerical computation results, the fast computation we used was high efficient and sufficiently accurate for engineering demand, even more important, we summarize the best method combination for typical configuration. The investigation shows that the fast computation method consist of configuration parameters and hypersonic aerodynamic estimation based on panel element can give better results for hypersonic gliding lifting body design and optimization problems.

Melanoma is the leading cause of skin cancer death owing to its highly metastatic nature and resistance to chemotherapy. It may account for 80% of the deaths relating to skin cancers. Once it progressed to metastatic stage, no current effective treatment is available for melanoma. Therefore, in-depth understanding of the mechanism underlying the metastatic process is imperative and would be of great help for improving the treatment of melanoma. Here, wedemonstrate that RING finger protein 11 (RNF11) disruption by insertional mutagenesis impairs the metastatic potential of murine melanoma B16F10 cells. The requirement of RNF11 in the migration of melanoma cells is further confirmed by gene knockdown and overexpression experiments in vitro. Together, our findings suggest a novel role of RNF11 in promoting the metastasis of melanoma cells which may potentially be useful for the treatment of melanoma by developing a new intervention target.

Found in neurons and neuroblastoma cells, Fas-induced apoptosis and accompanied activation of NF-κB signaling were thought to be associated with neurodegenerative diseases. However, the detailed functions of NF-κB activation in Fas killing and the effect of NF-κB activation on its downstream events remain unclear. Here, we demonstrated that agonistic Fas antibody induces cell death in a dose-dependent way and NF-κB signaling is activated as well, in neuroblastoma cells SH-EP1. Unexpectedly, NF-κB activation was shown to be pro-apoptotic, as suggested by the reduction of Fas-induced cell death with either a dominant negative form of IκBα (DN-IκBα) or an IκB kinase-specific inhibitor. To our interest, when analyzing downstream events of NF-κB signaling, we found that DN-IκBα only suppressed the expression of caspase-4, but not other caspases. Vice versa, enhancement of NF-κB activity by p65 (RelA) overexpression increased the expression of caspase-4 at both mRNA and protein levels. More directly, results from dual luciferase reporter assay demonstrated the regulation of caspase-4 promoter activity by NF-κB. When caspase-4 activity was blocked by its dominant negative (DN) form, Fas-induced cell death was substantially reduced. Consistently, the cleavage of PARP and caspase-3 induced by Fas was also reduced. In contrast, the cleavage of caspase-8 remained unaffected in caspase-4 DN cells, although caspase-8 inhibitor could rescue Fas-induced cell death. Collectively, these data suggest that caspase-4 activity is required for Fas-induced cell apoptosis and caspase-4 may act upstream of PARP and caspase-3 and downstream of caspase-8. Overall, we demonstrate that NF-κB can mediate Fas-induced apoptosis through caspase-4 protease, indicating that caspase-4 is a new mediator of NF-κB pro-apoptotic pathway in neuroblastoma cells.

This article shows that ultra violet (UV) micro-embossing can be successfully used for fabricating biocompatible micropatterned films with microchannels separated by high aspect ratio microwalls. Eight series of micropatterns were investigated; the width of the microwall was either 10 or 25 μm and that of the microchannel either 40, 80, 120, or 160 μm. The material investigated was principally polyurethane diacrylate. The UV-embossed micropattern was extracted with methanol, converting the micropatterns from cytotoxic to biocompatible. The typical UV embossing method was modified by using a marginally adhesive polyester substrate, which facilitates demolding but is removable before methanol extraction to avoid fragmentation of the embossed micropatterns. The effect of the micropatterns on A7r5 smooth muscle cells and C2C12 skeletal muscle cells was investigated. The dimensions of both channel and wall have significant effects on the elongation of both muscle cells. In the narrower 40-μm channel, the C2C12 cells merged together to form myofibers. These results indicate that UV-embossed micropatterns may present a useful scaffold for in vitro cell shape and orientation control needed in vascular and muscle tissue engineering. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006