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Objective To study the effects of saikosaponin D (SSD) on proliferation and apoptosis in human non-small cell lung cancer cell lines, and to explore underlying mechanisms. Methods Following treatment with saikosaponin D, A549 and H1299 cells were assessed for anti-proliferation effects using cell cycle kit-8 assays, changes in nuclear morphology using 4′,6-diamidino-2-phenylindole (DAPI) staining, and cell apoptosis using annexin V/propidium iodide double staining. Proliferation- and apoptosis-related proteins were detected by immunoblotting. Results Saikosaponin D had dose-dependent inhibitory effects on A549 cells (IC 50 , 3.57 µM) and H1299 cells (IC 50 , 8.46 µM). DAPI staining revealed decreased cell numbers, and most H1299 cells became round after treatment with 20 µM saikosaponin D. As saikosaponin D concentration increased, the proportions of cells in G0/G1 phase, and cells undergoing apoptosis, increased. Levels of phosphorylated p44/42 and signal transducer and activator of transcription (STAT)3 were significantly downregulated in both cell lines, while total STAT3 levels were not significantly affected. The cleaved form of caspase 3 was significantly upregulated. Conclusions Saikosaponin D inhibits proliferation, inducing cell cycle arrest and apoptosis, in lung cancer cells in a dose-dependent manner, possibly through inhibition of STAT3 phosphorylation and activation of caspase 3.

Acetaminophen (APAP) overdose induces hepatocyte necrosis and causes liver hepatotoxicity. Currently, the role of galactosyltransferase in APAP-induced liver injury is still unclear. This study assessed the contribution of the GLT25D2 gene, a kind of collagen galactosyltransferase, to the development of APAP-induced liver injury. This study found that the expression of GLT25D2 markedly increased first and then decreased in the liver of mice treated with APAP, however, it downregulated in the liver of APAP overdose-patients compared with normal controls. Knockout of GLT25D2 significantly ameliorated the liver injury, meanwhile, it downregulated the proinflammatory cytokines (IL-6, TNF-α) and chemokines (CXCL-10, MIG and CXCL-1) levels, however, and upregulated the anti-inflammatory cytokines (IL-22, IL-10) levels. Mechanistic explorations showed that (1) GLT25D2 knockout promoted autophagy pathway; and (2) the GLT25D2 knockout-induced autophagy selected to clear damaged mitochondria in APAP-induced liver injury by mitophagy; and (3) the autophagy intervention by Atg 7 siRNA cancelled liver protection by knockout of GLT25D2 through regulating liver inflammation. In conclusion, our study proves that the upregulated expression of GLT25D2 decreased autophagy contributing to APAP-induced hepatotoxicity by mediating the inflammatory immune regulatory mechanism.

Recent studies have revealed that natural plants-derived polysaccharides exhibit potent anti-tumor activity. Our earlier studies suggest that dandelion polysaccharide (DP) inhibits hepatocellular carcinoma (HCC) cell proliferation in vitro and in vivo. Here, we investigated the effects of DP on the angiogenesis of HCC and the potential molecular mechanisms by which DP regulates angiogenesis. Wound-healing and transwell invasion assays revealed that DP inhibited HUVECs migration and invasion in vitro, respectively. Tube formation assay, chick chorioallantoic membrane (CAM) assay, and immunohistochemistry (IHC) demonstrated that DP suppressed vasculogenesis in vitro and in vivo. Moreover, Western blot and immunofluorescence staining verified that DP treatment decreased the protein levels of some key factors involved in angiogenesis of HCC, such as hypoxia-inducible factor 1α (HIF-1α), vascular endothelial growth factor (VEGF), p-PI3K, and p-AKT. However, activation of PI3K/AKT pathway with insulin-like growth factor 1 (IGF-1) treatment attenuated the effect of DP on angiogenesis via lowering the expression of HIF-1α and VEGF. In summary, we found that DP treatment inhibited angiogenesis in vivo and in vitro through suppressing expression of VEGF and HIF-1a. Furthermore, we showed that the expression of VEGF and HIF1-α was modulated by PI3K/AKT signaling. Collectively, our study suggests that DP is a promising anti-cancer drug candidate for treating HCC.

Abstract Background Growing evidence suggests that MiRNAs play essential roles in the initiation and progression of colorectal cancer (CRC). The aberrant expression of miR-384 has been reported in some cancers. However, the role and mechanism of miR-384 in CRC proliferation remains unknown. Methods The expression of miR-384 was detected in CRC and their paired normal tissues by real-time PCR. In vivo and in vitro assays were conducted to confirm the role of miR-384 in the proliferation of CRC. Bioinformatics analysis, luciferase reporter assays, western blot and in vitro assays were used to confirm that AKT3 was the target gene of miR-384. Finally, Spearman’s correlation analyses was carried out to analyze the relationship between miR-384 expression and AKT3 expression in CRC. Results MiR-384 was down‑regulated in CRC tissues. The in vivo and vitro functional assays verified that the ectopic upregulation of miR-384 inhibited the proliferation of CRC and the inhibition of miR-384 promoted the proliferation of CRC. Bioinformatics analysis, luciferase reporter assays, western blot and in vitro functional assays confirmed AKT3 as the target gene of miR-384. The expression of miR-384 was negatively correlated with the expressions of AKT3. Conclusion Our study verified that miR-384 could significantly suppress the proliferation of CRC by directing targeting AKT3.

Abstract Background Crizotinib is a multi-target inhibitor approved for the treatment of advanced non-small-cell lung cancer patients with a ROS1 rearrangement. However, interstitial lung disease is a rare but severe and fatal side effect of crizotinib that should lead to immediate discontinuation of the drug. Unfortunately, the pathophysiology, molecular mechanism and risk factors for crizotinib-induced interstitial lung disease remain poorly understood. Case presentation We first identified and reported interstitial lung disease induced de novo by crizotinib in a 47-year-old female patient who was diagnosed with advanced lung adenocarcinoma with a ROS1 rearrangement in a malignant pleural effusion. Subsequent next-generation sequencing analysis revealed both ROS1 rearrangement and an EGFR exon 19 deletion mutation in lung biopsy specimens, which were histologically confirmed to be interstitial lung disease. Although crizotinib treatment was ceased immediately and a shock treatment with high-dose methylprednisolone as well as other necessary treatment procedures was applied to reverse the interstitial lung disease process, the patient died. Conclusions The present case indicates that while treating non-small-cell lung cancer patients with crizotinib, it is important to constantly monitor any newly emerging respiratory symptoms and unexplained imaging changes, which may suggest an adverse effect related to drug-induced interstitial lung disease or even lethality. Histopathology and molecular pathological examination of lung biopsy specimens may help clinicians understand the development mechanism and exclude other causes.

Background/Aims: Iron plays a fundamental role in cell biology and its concentration must be precisely regulated. It is well documented that excess iron burden contributes to the occurrence and progression of cancer. Hepcidin secreted by liver plays an essential role in orchestrating iron metabolism. In the present study, we aimed to investigate the ability of angelica sinensis polysaccharide (ASP) to decrease iron burden in tumor-bearing mice and the mechanism of ASP regulation hepcidin expression. Methods: Western blot, RT-PCR, immunohistochemistry (IHC), and enzyme-linked immunosorbent assay (ELISA) were used to detect the regulation of hepcidin and related cytokines by ASP. The role of ASP in tumor proliferation was investigated using in vivo assays. Iron depositions and iron concentrations in organs were determined by hematoxylin-eosin (H&E) staining and atomic absorption spectrophotometer. Results: We found that ASP could inhibit tumor growth in mice xenografted with 4T1 and H22 cancer cells. In vivo experiments also showed that ASP could potently regulate hepcidin expression in liver and serum and decrease iron burden in liver, spleen and grafted tumors in mouse model. Treatment with ASP in hepatic cell lines reproduced comparable results in decreasing hepcidin as in mouse liver. Furthermore, we found that ASP markedly suppressed the expression of interleukin-6 (IL-6), JAK2, p-STAT3, and p-SMAD1/5/8 in liver, suggesting that JAK/STAT and BMP-SMAD pathways were involved in the regulation of hepcidin expression by ASP. We also found down-regulation of iron-related cytokines in ASP treated mice. Conclusion: The present study provides new evidence that ASP decreases hepcidin expression, which can reduce iron burden and inhibit tumor proliferation. These findings might aid ASP developed as a potential candidate for cancer treatment in patients with iron overload.

The challenge for a non-linear vibration system in a fractal space is more fractal dimensions than frequency-amplitude relationship, the system energy consumption depends upon its fractal property, so its best-case scenario is to establish a relationship among the fractal dimensions, frequency and amplitude. For this purpose, this paper studies a fractal-fractional vibration system of a mass attached to a stretched elastic wire in a fractal space, and its asymptotic periodic property is elucidated, the effect of the fractal dimensions on the vibration system is discussed. This paper offers a new road to fast and reliable analysis of fractal oscillators with high accuracy. [ABSTRACT FROM AUTHOR]

Abstract We report on the embedded silver (Ag) nanoparticles fabricated by Ag+ ion implantation into the Bi4Ge3O12 (BGO) crystal. Localized surface plasmon resonance (LSPR) phenomenon has been observed by linear optical absorption spectrum, which is accordance with the expectation based on Mie theory calculation. Further proofs are given by SRIM, TEM and SAED analysis, which explain the slight difference between experiment and calculation. Based on the z-scan system, it is found that the nonlinear optical response is converted from two-photon absorption to three-photon absorption under the 515 nm femtosecond pulse excitation within the LSPR band. The nonlinear absorption coefficient is measured to be ~3.1 × 10−9 cm/W (two-photon absorption coefficient) and ~8.9 × 10−14cm3/W2 (three-photon absorption coefficient) for pure BGO crystal and the sample embedded with Ag nanoparticles (Ag:BGO), respectively. Finally, we have proposed a model to explain the asymmetric nonlinear transmittance, which is in good agreement with the experimental results.

Developing high-performance tungsten plasma-facing materials for fusion reactors is an urgent task. In this paper, novel nanochannel structural W films prepared by magnetron sputtering deposition were irradiated using a high-power pulsed electron beam or ion beam to study their edge-localized modes, such as transient thermal shock resistance. Under electron beam irradiation, a 1 μm thick nanochannel W film with 150 watt power showed a higher absorbed power density related cracking threshold (0.28–0.43 GW/m2) than the commercial bulk W (0.16–0.28 GW/m2) at room temperature. With ion beam irradiation with an energy density of 1 J/cm2 for different pulses, the bulk W displayed many large cracks with the increase of pulse number, while only micro-crack networks with a width of tens of nanometers were found in the nanochannel W film. For the mechanism of the high resistance of nanochannel W films to transient thermal shock, a residual stress analysis was made by Grazing-incidence X-ray diffraction (GIXRD), and the results showed that the irradiated nanochannel W films had a much lower stress than that of the irradiated bulk W, which indicates that the nanochannel structure can release more stress, due to its special nanochannel structure and ability for the annihilation of irradiation induced defects.

A series of novel Li+ doped Bi3.46Ho0.04Yb0.5Ti3O12 (BHYTO: xLi, 0 ≤ x ≤ 0.15) upconversion phosphors were prepared through a sol-gel-sintering method. There exist three emission bands centered at 545 nm, 658 nm, and 756 nm in the upconversion emission spectra at 980 nm excitation, corresponding to energy transitions of 5F4/5S2 → 5I8, 5F5 → 5I8 and 5F4/5S2 → 5I7 of Ho3+, and the upconversion emission intensity of BHYTO: 0.05Li is about 2.2 times stronger than that of BHYTO samples. The luminescent lifetime of the strongest emission (545 nm) is in the range of 45.25 to 65.99 μs for the different BHYTO: xLi phosphors. The energy transfers during the upconversion pumping process from Yb3+ to Ho3+ are mainly responsible for all the emissions, each belonging to a double-photon process. Li+ mainly entered into the interspace sites or occupied Bi3+ sites in Bi4Ti3O12 host during the fabrication process according to its dosage, and the possibility is very low for Li+ to take part in the energy transfer process directly due to its lack of matching levels with 4f of Ho3+ and Yb3+. However, Li+ doping can not only increase the size of crystal grains to improve crystallinity through XRD analysis, but also reduced oxygen vacancies to decrease the number of quenching centers through XPS analysis. The improved crystallinity and reduced quenching centers are proposed to be the main causes for the enhanced upconversion luminescence of the Li+ doped BHYTO phosphor.

Phase matching is a crucial condition for nonlinear optical processes. Here, Wang et al. demonstrate that a gradient metasurface composed of phased array antennas allows phase-matching-free frequency conversion over a pump wavelength range of almost 100 nm.

The purpose of this study was to investigate the variations of arch index from static standing to dynamic walking and running; furthermore, the interlimb symmetry was checked in the two populations. A total of eighty male participants were recruited for this study, with forty habitually barefoot and forty habitually shod males, respectively. Arch index (AI) was calculated following the previously established “gold standard” measurement via contact areas recorded from EMED. Repeated measure analysis of variance (ANOVA) was employed to compare the difference between static and dynamic walking and running arch index. Paired-samples t-test and symmetry index (SI) were used to investigate the symmetry of the left foot arch index and right foot arch index. It was found that the dynamic arch index was significantly higher than the static arch index in barefoot and shod males, showing an increase from static weight-bearing standing to dynamic walking and running. However, interlimb (right-left) symmetry in the foot arch index was observed in the two populations. Dynamic changes of the arch index may provide implications that need to be considered while designing shoe lasts or insoles. Knowledge of the healthy arch index range reported from this study could also be used as a standard baseline to probe into foot and arch disorders.

The RH vacuum refining technology is a vitally powerful method of producing clean steel. The inner diameter of traditional circular snorkel is very difficult to be increased owing to the metallurgical refractory thickness around the snorkels and the limitation of the area under the vacuum chamber, limiting the increase in refining efficiency. In order to improve the refining efficiency of the RH reactor, a new designed RH degasser with an optimized arched snorkel is established. This design replaces the traditional two circular snorkels structure with the two arched snorkels and greatly enhances the cross-sectional area of snorkel. In this study, the flow characteristics of this new type RH were studied and analyzed by establishing a 1 : 5.5 physical model of RH with arched snorkels. Results show that the circulation flow rate of RH with arched snorkels can increase by 100% ∼ 180% and the mixing time approximately decreases by 35% compared with RH with circular snorkels under actual production conditions. The circulation flow rate of RH with arched snorkels continues to increase obviously when gas flow rate exceeds the saturated value of RH with circular snorkels. The RH with arched snorkels can increase the refining efficiency significantly and has important application prospect.

Research on ecological total-factor energy efficiency (ETFEE) is conducive to energy conservation, emission reduction, and ecological protection. This paper focuses on the measurement and decomposition of the ETFEE in the Beijing-Tianjin-Hebei (BTH) region in China. In order to measure the ETFEE values, the window technology is combined with a nonradial and nonoriented SBM-undesirable model considering undesirable outputs to overcome the defect of insufficient data of research objects and ensure the calculation process to be implemented. The findings show that Beijing and Tianjin are DEA-efficient, while Hebei is not. The technological progress rates of Beijing and Tianjin reach up to 11.92% and 14.96%, while that of Hebei retrogresses by 4.47%. The scale efficiencies of Beijing, Tianjin, and Hebei are 97.75%, 86.60%, and 93.81%, respectively, which means that there are potentials for further optimization in the energy structures. The impulse response results between the energy structure and the ETFEE show that the proportions of coal and petroleum have negative effects on the ETFEE, while that of natural gas has a positive effect. The research results can provide reference for decision makers to formulate regional development plans.

Acute-on-chronic liver failure (ACLF) carries a significant burden on critical care services and health care resources. However, the exact pathogenesis of ACLF remains to be elucidated, and novel treatments are desperately required. In our previous work, we utilized mice subjected to acute insult in the context of hepatic fibrosis to simulate the development of ACLF and documented the favorable hepatoprotection conferred by M2-like macrophages in vivo and in vitro . In the present study, we focused on the phenotypic switch of human and mouse macrophages and assessed the effects of this switch on apoptosis resistance in hepatocytes. For this purpose, human and mouse macrophages were isolated and polarized into M0, M(IFN-γ), M(IFN-γ→IL-4), M(IL-4) or M(IL-4→IFN-γ) subsets. Conditioned media (CM) from these subsets were applied to human and mouse hepatocytes followed by apoptosis induction. Cell apoptosis was evaluated by immunostaining for cleaved caspase-3. As a result, M(IFN-γ) or M(IL-4) macrophages switched their phenotype into M(IFN-γ→IL-4) or M(IL-4→IFN-γ) through reprogramming with IL-4 or IFN-γ, respectively. Importantly, hepatocytes pre-treated with M(IFN-γ→IL-4) CMs exhibited much weaker expression of cleaved caspase-3, compared to those pre-treated with M(IFN-γ) CM, and vice versa . Together, phenotypic switch of macrophages toward M(IL-4) phenotype confers hepatocytes enhanced resistance to apoptosis.