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Herein, we describe a highly effective 1,8-conjugate-addition-mediated formal (3+3)-annulation of (aza)-para-quinone methides in situ generated from propargylic alcohols with 4-hydroxycoumarins and 1,3-dicarbonyl compounds under the catalysis of a Bronsted acid. This methodology affords efficient and practical access to synthetically important and highly functionalized pyranocoumarins and pyrans in excellent yields under mild conditions. Importantly, these products exhibit impressive inhibitory activity toward α-glucosidase.

Collective total synthesis of five tetrahydroisoquinoline alkaloids including the first total synthesis of (-)-fennebricin A and (-)-renieramycin J has been accomplished. The synthesis features employing a single common amino acid to symmetrically construct the pentacycle of title alkaloids. The palladium-catalyzed arylation of alanine-derived amide developed by Yu was tactically utilized to afford unnatural amino acid building block rapidly and practically. The structure of synthetic (-)-renieramycin M has been confirmed by single crystal X-ray analysis for the first time.

Background & aims The mechanisms involved in liver regeneration after partial hepatectomy (PHx) are complicated. Cellular senescence, once linked to aging, plays a pivotal role in wound repair. However, the regulatory effects of cellular senescence on liver regeneration have not been fully elucidated. Approach & results Mice subjected to PHx were analyzed 14 days after surgery. The incomplete remodeling of liver sinusoids affected shear stress-induced eNOS signaling on day 14, resulting in the accumulation of senescent liver sinusoidal endothelial cells (LSECs). Removing macrophages to augment LSEC senescence led to a malfunction of the regenerating liver. A dynamic fluctuation in Notch activity accompanied senescent LSEC accumulation during liver regeneration. Endothelial Notch activation by using Cdh5-CreERT NICeCA mice triggered LSEC senescence and senescence-associated secretory phenotype (SASP), which disrupted liver regeneration. Blocking the Notch by γ-secretase inhibitor (GSI) diminished senescence and promoted LSEC expansion. Mechanically, Notch-Hes1 signaling inhibited Sirt1 transcription by binding to its promoter region. Activation of Sirt1 by SRT1720 neutralized the up-regulation of P53, P21, and P16 caused by Notch activation, and eliminated Notch-driven LSEC senescence. Finally, Sirt1 activator promoted liver regeneration by abrogating LSEC senescence and improving sinusoid remodeling. Conclusions Shear stress-induced LSEC senescence driven by Notch interferes with liver regeneration after PHx. Sirt1 inhibition accelerates liver regeneration by abrogating Notch-driven senescence, providing a potential opportunity to target senescent cells and facilitate liver repair after injury.

A copper-catalyzed mono-selective C–H amination of ferrocenes assisted by 8-aminoquinoline is presented here. A range of amines, including bioactive molecules, were successfully installed to the ortho-position of ferrocene amides with high efficiency under mild conditions. A range of functionalized ferrocenes were compatible to give the aminated products in moderate to good yields. The gram-scale reaction was smoothly conducted and the directing group could be removed easily under basic conditions.

Based on the phase separation phenomenon in micro-droplets, polymer-lipid Janus particles were prepared on a microfluidic flow focusing chip. Phase separation of droplets was caused by solvent volatilization and Janus morphology was formed under the action of interfacial tension. Because phase change from solid to liquid of the lipid hemisphere could be triggered by physiological temperature, the lipid hemisphere could be used for rapid release of drugs. While the polymer we selected was pH sensitive that the polymer hemisphere could degrade under acidic conditions, making it possible to release drugs in a specific pH environment, such as tumor tissues. Janus particles with different structures were obtained by changing the experimental conditions. To widen the application range of the particles, fatty alcohol and fatty acid-based phase change materials were also employed to prepare the particles, such as 1-tetradecanol, 1-hexadecanol and lauric acid. The melting points of these substances are higher than the physiological temperature, which can be applied in fever triggered drug release or in thermotherapy. The introduction of poly (lactic-co-glycolic acid) enabled the formation of multicompartment particles with three distinct materials. With different degradation properties of each compartment, the particles generated in this work may find applications in programmed and sequential drug release triggered by multiple stimuli.

BackgroundDesigning combination drugs for malignant cancers has been restricted due to the scarcity of synergy-medicated targets, while some natural compounds have demonstrated potential to enhance anticancer effects.MethodsWe here explored the feasibility of probing synergy-mediated targets by Berberine (BER) and Evodiamine (EVO) in hepatocellular carcinoma (HCC). Using the genomics-derived HCC signaling networks of compound treatment, NF-κB and c-JUN were inferred as key responding elements with transcriptional activity coinhibited during the synergistic cytotoxicity induction in BEL-7402 cells. Then, selective coinhibitors of NF-κB and c-JUN were tested demonstrating similar synergistic antiproliferation activity.ResultsConsistent with in vivo experiments of zebrafish, coinhibitors were found to significantly reduce tumor growth by 79% and metastasis by 96% compared to blank control, accompanied by anti-angiogenic activity. In an analysis of 365 HCC individuals, the low expression group showed significantly lower malignancies and better prognosis, with the median survival time increased from 67 to 213%, compared to the rest of the groups.ConclusionTogether, NF-κB and c-JUN were identified as promising synergistic inducers in developing anti-HCC therapies. Also, our method may provide a feasible strategy to explore new targeting space from natural compounds, opening opportunities for the rational design of combinational formulations in combatting malignant cancers.

Polarization sensitivity is a severe problem in photonic integration devices and chips based on the high-index contrast Si/SiO2 system. In this paper, a broadband silicon polarization splitter-rotator (PSR) comprised of a bi-level taper and a counter-tapered coupler is proposed with a large fabrication tolerance. The measured insertion loss is lower than 0.7 dB/0.73 dB for the wavelength range from 1470 to 1580 nm with a crosstalk lower than -12.1 dB/-14.7 dB for TE and TM polarization input, respectively. By integrating the PSR with silicon arrayed waveguide gratings and germanium photodetectors (PDs) on a single chip, a polarization-insensitive wavelength-division-multiplexing (WDM) receiver is demonstrated with a polarization-dependent loss as low as 1.21 dB. High-speed operations are also achieved with clear eyes at 10 Gb/s.

Hepatocellular carcinoma (HCC) is the most common cancer and its prognosis is poor due to metastasis and recurrence. EMT is associated with metastasis. A deep understanding of regulatory mechanism of EMT is critical. LncRNA is involved in regulation of various biological processes including EMT. This study aimed to investigate the regulatory signal axis among lncRNA SNHG12, miR-516a-5p and the target gene HEG1 during EMT. Cell cycle and apoptosis were analyzed by flow cytometry. Tumorigenesis was analyzed by clone formation assay. Wound healing assay and transwell assay was performed to detect migration and invasion, respectively. Interaction among SNHG12, miR-516a-5p and HEG1 were analyzed by dual luciferase assay and RIP assay. We also detected expression of RNA and protein by QPCR and western blotting. Finally, tumor growth was analyzed by tumorigenesis assay in vivo. Ki-67 and HEG1 level in tumor tissues was analyzed by IHC. SNHG12 and HEG1 were upregulated, miR-516a-5p was downregulated in HCC cell lines. SNHG12 could interact with and inhibit miR-516a-5p. MiR-516a-5p could interact with HEG1 and inhibit HEG1 expression. Knock down SNHG12 inhibited proliferation, migration, invasion, EMT and promoted apoptosis of HCC cells. Such effects were antagonized by inhibiting miR-516a-5p. SNHG12 overexpression lead to opposite results. Similar results were observed in mice. SNHG12 could promote EMT in HCC through targeting and inhibiting miR-516a-5p, which eventually upregulated HEG1 expression, in both cell and mice.

Transition-metal-catalyzed dehydrogenative C-H allylation with 1,1-disubstituted alkenes via β-H elimination remains challenging, because of the low reactivity and difficulty of controlling selectivity. Herein, the development of a Pd(II)-catalyzed directed atroposelective C-H allylation with methacrylates is described. Exclusive allylic selectivity was achieved. A vast array of axially chiral biaryl-2-amines are efficiently synthesized with excellent enantioselectivities (up to99% enantiomeric excess).

Here, we designed a broadband, low loss, compact, and fabrication-tolerant silicon-based four-mode edge coupler, composed of a 1×3 adiabatic mode-evolution counter-taper splitter and a triple-tip inverse taper. Based on mode conversion and power splitting, the proposed structure can simultaneously realize efficient mode coupling from TE0, TM0, TE1, and TM1 modes of multimode silicon waveguides to linearly polarized (LP), LP01,x , LP01,y , LP11a,x , and LP11a,y , modes in the few-mode fiber. To the best of our knowledge, we proposed the first scheme of four LP modes coupling, which is fully compatible with standard fabrication process. The 3D finite-difference time-domain simulation results show that the on-chip conversion losses of the four modes remain lower than 0.62 dB over the 200 nm wavelength range, and total coupling losses are 4.1 dB, 5.1 dB, 2.1 dB, and 2.9 dB for TE0-to-LP01,x , TM0-to-LP01,y , TE1-to-LP11a,x , and TM1-to-LP11a,y , respectively. Good fabrication tolerance and relaxed critical dimensions make the four-mode edge coupler compatible with standard fabrication process of commercial silicon photonic foundries.

Tantalum (Ta)-coated porous Ti-6A1-4V scaffolds have better bioactivity than Ti-6A1-4V scaffolds; however, their bioperformance as an artificial vertebral body (AVB) is unknown. In the present study, we combined a Ta-coated Ti-6A1-4V scaffold with rabbit bone marrow stromal cells (BMSCs) for tissue-engineered AVB (TEAVB) construction and evaluated the healing and fusion efficacy of this scaffold in lumbar vertebral defects after corpectomy in rabbits. The results showed that BMSCs on the surface of the Ta-coated Ti scaffolds proliferated better than BMSCs on Ti scaffolds. Histomorphometry showed better bone formation when using Ta-coated TEAVBs than that with Ti TEAVBs at both 8 and 12 weeks after implantation. In addition, the vertical and rotational stiffness results showed that, compared with uncoated TEAVBs, Ta-coated TEAVBs enhanced rabbit lumbar vertebral defect repair. Our findings demonstrate that Ta-coated TEAVBs have better healing and fusion efficacy than Ti TEAVBs in rabbit lumbar vertebral defects, which indicates their good prospects for clinical application.

A two-beam laser fabrication technique is introduced to fabricate the single silver nanowire (AgNW) on polyethylene terephthalate (PET) substrate. The resistivity of the AgNW is (1.31 ± 0.05) × 10−7 Ω·m, which is about 8 times of the bulk silver resistivity (1.65 × 10−8 Ω·m). The AgNW electrical resistance is measured in temperature range of 10–300 K and fitted with the Bloch-Gruneisen formula. The fitting results show that the residue resistance is 153 Ω, the Debye temperature is 210 K and the electron-phonon coupling constant is (5.72 ± 0.24) × 10−8 Ω·m. Due to the surface scattering, the Debye temperature and the electron-phonon coupling constant are lower than those of bulk silver, and the residue resistance is bigger than that of bulk silver. Thermal conductivity of the single AgNW is calculated in the corresponding temperature range, which is the biggest at the temperature approaching the Debye temperature. The AgNW on PET substrate is the low temperature resistance material and is able to be operated stably at such a low temperature of 10 K.

Aim of Study: Results on the association of Vitamin D receptor (VDR) gene polymorphism with renal cell carcinoma (RCC) susceptibility from the present reports are still debating. This meta-analysis was conducted to assess the association of VDR ApaI (rs7975232), BsmI (rs1544410), TaqI (rs731236), and Fok1 (rs2228570) gene polymorphisms with RCC risk. Materials and Methods: The association studies were recruited from PubMed on May 1, 2016, and eligible reports were extracted and data were synthesized using meta-analysis method. Result: Six investigations were included into this meta-analysis for the relationship between VDR gene polymorphism and RCC susceptibility. In this meta-analysis, the ApaI A allele, AA genotype, aa genotype, and Fok1 FF genotype were associated with RCC susceptibility in Asians. However, VDR BsmI and TaqI gene polymorphisms were not associated with the RCC risk in Asians, Caucasians, and overall populations. Furthermore, Fok1 gene polymorphism was not associated with the RCC risk in Caucasians and overall populations. Conclusion: ApaI gene polymorphism and Fok1 FF genotype were associated with RCC susceptibility in Asians.

A silicon-on-insulator polarization diversity scheme is proposed. Based on an asymmetrical evanescent coupler, a broadband and compact polarization splitter–rotator comprising mode conversion tapers and mode sorting asymmetric Y junctions is optimized with silicon dioxide upper cladding and a silicon nitride waveguide. The simulation results show mode conversion loss is less than 0.2 dB, and the extinction ratio is lower than − 17 d B in the wavelength range of 1.48 µ m to 1.67 µ m .

Nonalcoholic steatohepatitis (NASH)-related hepatocellular carcinoma and liver disorders have become the leading causes for the need of liver transplantation in developed countries. Lipotoxicity plays a central role in NASH progression by causing endoplasmic reticulum stress and disrupting protein homeostasis. To identify key molecules that mitigate the detrimental consequences of lipotoxicity, we performed integrative multiomics analysis and identified the E3 ligase tripartite motif 16 (TRIM16) as a candidate molecule. In particular, we found that lipid accumulation and inflammation in a mouse NASH model is mitigated by TRIM16 overexpression but aggravated by its depletion. Multiomics analysis showed that TRIM16 suppressed NASH progression by attenuating the activation of the mitogen-activated protein kinase (MAPK) signaling pathway; specifically, by preferentially interacting with phospho-TAK1 to promote its degradation. Together, these results identify TRIM16 as a promising therapeutic target for the treatment of NASH.

G-quadruplex structures are attractive targets for the development of anticancer drugs, as their formation in human telomere could impair telomerase activity, thus inducing apoptosis in cancer cells. In this work, a thiophene-containing dinuclear ruthenium(II) complex, [Ru2(bpy)4(H2bipt)]4+ {bpy = 2,2′-bipyridine, H2bipt = 2,5-bis[1,10]phenanthrolin[4,5-f]-(imidazol-2-yl)thiophene}, was prepared and the interaction between the complex and human telomeric DNA oligomers 5′-G3(T2AG3)3-3′ (HTG21) has been investigated by UV-Vis, fluorescence and circular dichroism (CD) spectroscopy, fluorescence resonance energy transfer (FRET) melting assay, polymerase chain reaction (PCR) stop assay, fluorescent intercalator displacement (FID) titrations, Job plot and color reaction studies. The results indicate that the complex can well induce and stabilize the formation of antiparallel G-quadruplex of telomeric DNA in the presence or absence of metal cations, and the ΔTm value of the G-quadruplex DNA treated with ...

Magnesium has been investigated as a biodegradable metallic material. Increased concentrations of Mg2+ around magnesium implants due to biodegradation contribute to its satisfactory osteogenic capacity. However, the mechanisms underlying this process remain elusive. We propose that activation of the PI3K/Akt signalling pathway plays a role in the Mg2+-enhanced biological behaviours of osteoblasts. To test this hypothesis, 6, 10 and 18 mM Mg2+ was used to evaluate the stimulatory effect of Mg2+ on osteogenesis, which was assessed by evaluating cell adhesion, cell viability, ALP activity, extracellular matrix mineralisation and RT-PCR. The expression of p-Akt was also determined by western blotting. The results showed that 6 and 10 mM Mg2+ elicited the highest stimulatory effect on cell adhesion, cell viability and osteogenic differentiation as evidenced by cytoskeletal staining, MTT assay results, ALP activity, extracellular matrix mineralisation and expression of osteogenic differentiation-related genes. In contrast, 18 mM Mg2+ had an inhibitory effect on the behaviour of osteoblasts. Furthermore, 10 mM Mg2+ significantly increased the phosphorylation of Akt in osteoblasts. Notably, the aforementioned beneficial effects produced by 10 mM Mg2+ were abolished by blocking the PI3K/Akt signalling pathway through the addition of wortmannin. In conclusion, these results demonstrate that 6 mM and 10 mM Mg2+ can enhance the behaviour of osteoblasts, which is at least partially attributed to activation of the PI3K/Akt signalling pathway. Furthermore, a high concentration (18 mM Mg2+) showed an inhibitory effect on the biological behaviour of osteoblasts. These findings advance the understanding of cellular responses to biodegradable metallic materials and may attract greater clinical interest in magnesium.

Objective To investigate the antagonistic effects of different doses of Lianhua Qingwen on pulmonary injury induced by fine particulates PM2.5 in rats. Methods Fine particulates suspended in the environment were collected. Forty-eight healthy adult wistar rats were randomly divided into 6 groups with 8 rats in each group. Four groups of rats were exposed to PM2.5 by intratracheally dripping suspensions of fine particulates PM2.5 (7.5 mg/kg) as dust-exposed model rats. Among them 24 rats in three groups received Lianhua Qingwen treatment (crude drug) at a dose of 2 g/kg, 4 g/kg, 8 g/kg per day for 3 days before dust exposure and were defined as low-dose, middle-dose and high-dose Lianhua Qingwen treatment groups respectively. The other dust-exposed model rats without treatment were assigned as PM2.5 control group. The un-exposed rats were set as saline control group (1.5 ml/kg saline) and blank control group. All rats were killed after 24 hours of the exposure. Lung tissue, serum and bronchoalveolar lavage fluid (BALF) were collected. The levels of malonaldehyde (MDA), lactate dehydrogenase (LDH), and glutathione peroxidase (GSH-PX) in blood serum and BALF, and superoxide dismutase (SOD) in blood surum were measured using fluorescent quantitation PCR; Expression of NF-E2-related factor 2(NRF-2), heme oxygenase 1 (HO-1) and quinone oxidoreductase 1 (NQO1) in lung tissues were measured using Western blot. Pathological changes of lung tissues in each group were also examined. Results Pathology revealed thickened alveolar septum, congestion of capillary, interstitial edema and infiltration of lymphocyte and neutrophil surrounding bronchiole in the PM2.5 control group, which were significantly relieved in the Lianhua Qingwen treatment groups. Compared to the blank and saline control groups, the PM2.5 control group had significantly higher levels of LDH and MDA (p

We have demonstrated an approach of silver nanostructure microfabrication by femtosecond laser direct writing of silver ion aqueous solution containing biocompatible amino acids with different molecular architectures. The amino acids-assisted multiphoton photoreduction (MPR) lowers the incident femtosecond laser threshold to 0.32 mW for glycine, 0.72 mW for valine, 0.6 mW for proline, and 0.35 mW for leucine. The line widths of the silver nanowires are varied with the composition of the biocompatible amino acids. The highest resolution of 186 nm has been achieved. Furthermore, the corresponding electrical conductivities of silver nanowires are determined to be 1.48 × 10–6, 4.1 × 10–7, 7.04 × 10–7, and 1.35 × 10–6 Ω m, which have been significantly improved compared to that of the previously reported silver wires fabricated by MPR microfabrication. The proposed protocol for fabricating silver nanostructure would pave the way for fabricating metallic nanostructures and play an extremely important role in th...

Chemo-selectivity is always a hard problem in preparing 2-pyridinones. Silica sulfuric acid (SSA) modified with zinc chloride (Zn–SSA) was found to be a high efficient heterogeneous catalyst to solve this problem. Under Zn–SSA and solvent-free conditions, the one-pot cyclocondensation of 1,3-dicarbonyl compounds, malononitrile and arylaldehydes to afford 2-pyridinones was conveniently implemented. The heterogeneous reaction was much efficient and promising in pharmaceutical study and industrial production. Improving chemo-selectivity is always a hard problem in preparing 2-pyridinones. Silica sulfuric acid (SSA) modified with zinc chloride (Zn–SSA) was found to be efficient heterogeneous catalyst to solve this problem. Under Zn-SSA and solvent-free conditions, the one-pot cyclocondensation of 1,3-dicarbonyl compounds, malononitrile and arylaldehydes to afford 2-pyridinones was conveniently implemented. The heterogeneous reaction was much efficient and promising in pharmaceutical study and industrial production.

A Gram-stain-negative, short rod-shaped bacterium, designated 9-2T, was isolated from a sediment sample collected from a hydrothermal vent field on the south-west Indian Ridge. It formed red colonies, produced carotenoid-like pigments and did not produce bacteriochlorophyll a. Strain 9-2T was positive for hydrolysis of DNA, gelatin and starch, but negative for hydrolysis of aesculin and Tween 60. The sole respiratory quinone was menaquinone-7 (MK-7). The main polar lipids consisted of phosphatidylethanolamine, one unidentified phospholipid and two unidentified polar lipids. The principal fatty acids (>5 %) were summed feature 4 (iso-C17 : 1 I and/or anteiso-C17 : 1 B), iso-C15 : 0 and iso-C17 : 0 3-OH. The genomic DNA G+C content was 49.2 mol%. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain 9-2T should be assigned to the genus Pontibacter. Levels of 16S rRNA gene sequence similarity between the new isolate and the type strains of Pontibacter species with validly published names were in the range 94.0–96.5 %. On the basis of phenotypic and genotypic data, strain 9-2T represents a novel species of the genus Pontibacter, for which the name Pontibacter amylolyticus sp. nov. is proposed. The type strain is 9-2T ( = CGMCC 1.12749T = JCM 19653T = MCCC 1K00278T).

Optical antennas are utilized to link free-space optical radiation with localized energy, enabling varied applications such as beam focusing, freewheeling steering, biosensing, and optical communications. Here, we demonstrate a novel silicon nanoantenna array (SNA), comprising subwavelength silicon nanorods that direct light emission vertically. When the array of nanorods was positioned optimally, the efficiency of the upward light emission reached 46%. In addition, the rigorous design of the array of nanorods resulted in a well-confined profile of the vertically emitting beam. The SNA, therefore, provides a new approach for 3D optical interconnections between different decks of integrated photonics circuits.

The in-plane tailoring of light propagation is significant in on-chip optical interconnections. Recently, an in-plane negative-angle refraction was realized with a thin line of silicon nanoposts, which are at resonance in the first angular momentum channel. This advancement is different from metasurface research, which mostly focuses on out-of-plane operations. In this paper, we experimentally demonstrate that a thin array of doublet silicon nanoposts, in which each unit comprises two tangent nanoposts functioning as an upright interface, remarkably improve efficiency for molding light. The designed upright interface exhibits a broadband response featuring high efficiency in a negative-angle light bending in the wavelength of 1480–1600 nm. The broadband, compactness, low loss, and complementary metal–oxide semiconductor (CMOS) compatibility enable the use of the subwavelength array as an alternative component for on-chip optical control.

We demonstrate low threshold lasing oscillation in a photonic crystal (PhC) laser by using tert-butyl Rhodamine B (t-Bu-RhB) doped gain media. Lactonic t-Bu-RhB is synthesized to improve doping concentration in polymethylmethacrylate (PMMA) films, and then isomerized to the zwitterion form to achieve highly fluorescent gain medium. The t-Bu-RhB doped PMMA film is sandwiched by a pair of polystyrene colloidal crystals to construct a PhC resonating cavity. Single-mode laser oscillation at 592 nm is observed when the PhC resonating cavity is pumped by a Nd:YAG laser. The lasing threshold is 0.12 MW cm(-2) utilizing 6.9 wt% t-Bu-RhB doped PMMA films, which is only 1/60 of that with 3 wt% t-Bu-RhB doped PMMA films. The concentration-dependent lasing action is attributed to different gain factors of the t-Bu-RhB doped PMMA films. Furthermore, a spatially and spectrally coherent laser beam from the PhC resonating cavity is verified by exploring the far-field image and angular dependence of the lasing emission. The approach provides a facile and efficient strategy to reduce the lasing threshold for fabricating low threshold PhC lasers.

The development of new, sensitive and simple methods for the rapid detection of dimethoate (DMT) in water is vitally important. A fluorescent probe technique has been developed for the rapid trace detection of pesticide residues. In our study, the method used is based on the fluorescence resonance energy transfer, which is also known as FRET. Dithizone (DZ) was bound to cadmium (Cd) on the surface of CdTe QDs to form a DZ–Cd complex. Then, the fluorescence of the CdTe QDs was immediately quenched because of the FRET between the CdTe QDs and the surface of DZ–Cd complex. After the addition of DMT to the DZ-functionalized QDs, DZ was separated from the surface of the QDs and was replaced by DMT, and the fluorescence of the QDs was restored. This method was validated using water samples spiked with DMT. Two good linear relationships were obtained in the range from 0.01 to 5.0 μg mL−1 and 5.0 to 40 μg mL−1; the detection limit was calculated to be 0.005 μg mL−1, and reasonable recoveries (88.6–95.3%) were achieved for the direct detection of DMT in water samples. This method is rapid, convenient and environmentally acceptable and shows potential for the rapid detection of DTM in water samples.

This work aims to study the roles and related mechanisms of six2 in 5-FU sensitivity of hepatocellular carcinoma (HCC) cells. KM-Plotter analysis showed that HCC patients with higher six2 expression levels had shorter overall survival. Six2 expression was higher in clinical HCC tissues than in normal tissues, and was negatively correlated with E-cadherin expression. Additionally, six2 overexpression decreased the sensitivity of HCC cells to 5-Fu, characterized as attenuating 5-FU-induced cell apoptosis and downregulation of cell viability, and promoted HCC cells stemness. Mechanistically, six2 overexpression repressed E-cadherin expression via stimulating promoter methylation of the E-cadherin. And E-cadherin overexpression rescued six2-induced decrease of 5-FU sensitivity and promotion on HCC cells stemness. Therefore, our results suggest that Six2 is negatively correlated with good prognosis and decreases 5-FU sensitivity via suppressing E-cadherin expression in HCC cells.

Two novel carbazole derivatives, BMEPC and BMEMC, were designed, synthesized and first reported as two-photon photosensitizers for DNA photodamage, which showed efficient DNA photocleavage ability under near-infrared light exposure via a two-photon process in anaerobic condition.

Chitosan coated porous titanium alloy implant (CTI) is demonstrated a promising approach to improve osseointegration capacity of pure porous titanium alloy implant (TI). Since chitosan has been demonstrated to exhibit antioxidant activity, we propose CTI may ameliorate the ROS overproduction, thus reverse the poor osseointegration under diabetic conditions, and investigate the underlying mechanisms. Primary rat osteoblasts incubated on the TI and the CTI were subjected to normal serum (NS), diabetic serum (DS), DS + NAC (a potent ROS inhibitor) and DS + LY294002 (a PI3K/AKT-specific inhibitor). In vivo study was performed on diabetic sheep implanted with TI or CTI into the bone defects on crista iliaca. Results showed that diabetes-induced ROS overproduction led to osteoblast dysfunction and apoptosis, concomitant with the inhibition of AKT in osteoblasts on the TI substrate. While CTI stimulated AKT phosphorylation through ROS attenuation, thus reversed osteoblast dysfunction evidenced by improved osteoblast adhesion, increased proliferation and ALP activity, and decreased cytotoxicity and apoptotic rate, which exerted same effect to NAC treatment on the TI. These effects were further confirmed by the improved osseointegration within the CTI in vivo evidenced by Micro-CT and histological examinations. In addition, the aforementioned promotive effects afforded by CTI were abolished by blocking PI3K/AKT pathway with addition of LY294002. These results demonstrate that the chitosan coating markedly ameliorates diabetes-induced impaired bio-performance of TI via ROS-mediated reactivation of PI3K/AKT pathway, which elicits a new surface functionalization strategy for better clinical performance of titanium implant in diabetic patients.

A broadband silicon PSR is presented with an insertion loss lower than ∼0.7dB/0.3dB and crosstalk lower than 12.1dB/14.7dB for TE and TM mode respectively. By combining the PSR with AWG and Germanium PDs, an integrated polarization insensitive DWDM receiver is further demonstrated.

The concentration of L-cysteine (Cys) and glutathione (GSH) is closely related to the critical risk of various diseases. In our study, a new rapid method for the determination of Cys and GSH in water and urine samples has been developed using a fluorescent probe technique, which was based on crystal violet (CV)-functionalized CdTe quantum dots (QDs). The original QDs emitted fluorescence light, which was turned off upon adding CV. This conjugation of CV and QDs could be attributed to electrostatic interaction between COO− of mercaptopropionic acid (MPA) on the surface of QDs and N+ of CV in aqueous solution. In addition, Forster resonance energy transfer (FRET) also occurred between CdTe QDs and CV. After adding Cys or GSH to the solution, Cys or GSH exhibited a stronger binding preference toward Cd2+ than Cd2+-MPA, which disturbed the interaction between MPA and QDs. Thus, most MPA was able to be separated from the surface of QDs because of the participation of Cys or GSH. Then, the fluorescence intensity of the CdTe QDs was enhanced. Good linear relationships were obtained in the range of 0.02–40 μg mL−1 and 0.02–50 μg mL−1, and the detection limits were calculated as 10.5 ng mL−1 and 8.2 ng mL−1, for Cys and GSH, respectively. In addition, the concentrations of biological thiols in water and urine samples were determined by the standard addition method using Cys as the standard; the quantitative recoveries were in the range of 97.3–105.8%, and relative standard deviations (RSDs) ranged from 2.5 to 3.7%. The method had several unique properties, such as simplicity, lower cost, high sensitivity, and environmental acceptability.

A five-channel silicon etched diffraction gratings (EDGs) working in the O-band was demonstrated in this paper. The device has a channel spacing of 20 nm and occupies a footprint of 180μm×120μm with an insertion loss of 5.3dB. Integrated heaters were designed to compensate the center wavelength shifts brought from fabrication errors. A tuning efficiency of 0.358nm/mA was obtained finally.

We present an O-band silicon PSR based on a bi-level mode-converter and cascaded MMI couplers. The device shows an insertion loss less than 0.5dB/0.65dB and crosstalk lower than -14dB/-13dB for TE/TM input polarizations respectively.

The process of molecules translocation through nanopore is important to understand many interesting phenomena. Molecular dynamics simulations have been carried out to study the translocation of alkane through graphene nanopore. The results detail relative distance, average translation time, etc. The translocation process can be divided into three stages: finding-entering-moving through the nanopore. Alkane must climb an energy barrier in every stage. The dependence of translocation on chain length is also discussed. Shorter alkanes are easy to transport through the nanopore and the average translocation time is short when alkane translocates through nanopore one by one. Our simulations show a visualized translocation process, which can favor our understanding of this important process.

In this work, we simulated the diffusion of polymers with different length (N) among single wall carbon nanotubes (SWCNTs) by using molecular dynamics (MD) simulation. The scaling relation between the diffusion coefficient (D) and the chain length (N) was investigated. The effect of the distance between SWCNTs on the scaling relation was also discussed. The polymers diffusion follows D ∝ N−1.14±0.03 among the SWCNTs with large distance. On the other hand, the scaling is D ∝ N−1.90±0.09 when polymers are among the SWCNTs with small distance. The exponent in the scaling relation increases with the distance between SWCNTs decreasing. Moreover the diffusion shows anisotropy in our simulations.

In the tribe Triticeae, several Thinopyrum species have been used as sources of resistance to stem rust (caused by Puccinia graminis Pers.:Pers. f. sp. tritici Eriks. & E. Henn., abbreviated as Pgt) and other wheat (Triticum aestivum L.) diseases. To identify novel sources of resistance to Pgt race TTKSK (Ug99), we evaluated and characterized the stem rust resistance of 242 accessions belonging to five Thinopyrum species, including beach wheatgrass [Th. bessarabicum (Savul. & Rayss) A. Love], diploid tall wheatgrass [Th. elongatum (Host) D.R. Dewey], intermediate wheatgrass [Th. intermedium (Host) Barkworth & D. R. Dewey], sand cough or sea wheatgrass [Th. junceum (L.) A. Love], and decaploid tall wheatgrass [Th. ponticum (Podp.) Barkworth & D.R. Dewey]. These accessions were evaluated for seedling reactions to nine Pgt races (TTKSK, TTTTF, TRTTF, RTQQC, QFCSC, TCMJC, TPMKC, TMLKC, and TPPKC), genotyped with molecular markers linked to four stem rust resistance genes (Sr24, Sr25, Sr26, and Sr43) derived from Thinopyrum species, and examined for ploidy levels. All accessions but one (Th. elongatum PI 531718) were resistant to all or most races. Most of the Th. elongatum and Th. ponticum accessions showed near-immunity to all of the races while the accessions of the other three species (Th. bessarabicum, Th. intermedium, and Th. junceum) had varied levels of resistance ranging from near immunity to moderate resistance. Molecular marker analysis showed that most of the markers appeared to be species- or genus-specific rather than linked to a gene of interest, and thus genotyping analysis was of limited value. Comparisons of infection types of accessions based on ploidy level suggested that higher ploidy level was associated with higher levels of stem rust resistance. The results from this study substantiate that the Thinopyrum species are a rich source of stem rust resistance.

Two new Ru(II) complexes, [Ru(Htip)3]Cl2 (1) and [Ru(Htip)2(dppz)]Cl2 (2), were synthesised and were characterised. The ground- and excited-state acid–base properties of 1 and 2 were studied and demonstrated that 1 acted as a pH-induced “on–off–on” luminescence switch. The binding behaviours of 1 and 2 to calf thymus DNA were studied with absorption and emission spectroscopy, DNA viscosities and density functional theory calculations. 2 was found to act as a DNA molecular light switch and as an efficient photocleaver of pUC 18 DNA. The cytotoxicities of the complexes were evaluated with the MTT method and it was found that 1 displayed apparent anticancer activity against MCF-7 cell, whereas 2 exhibited more potent and wider-spectrum antitumor activities against all cancer cell lines tested.

Six purple corn grains were chosen to investigate their antioxidant activities and the relationships between anthocyanins and phenolics contents with antioxidant activities. Purple grains were screened for their antioxidant potentials using various in-vitro models such as superoxide anion radical scavenging activity and reducing power at various concentrations. The result showed that ZS39 and FS11 exhibited the highest anthocyanins and total phenolics contents. ZS39 and FS11 also exhibited the highest superoxide anion radical scavenging activity. There was no significant difference among the reducing power of six different purple corn grain extracts. It was found that there were positive correlations between anthocyanins and superoxide anion radical scavenging activity or reducing power, R2=0.9911, R2=0.9873, respectively. Whereas the correlations between total phenolics and superoxide anion radical scavenging activity or reducing power, R2=0.9863, R2=0.9826, respectively. It suggested that purple corn appeared to be a rich and interesting source of natural antioxidants.

Low loss silicon waveguides are the key to the realization of high performance photonic integrated circuits. In this paper, fabrication, characterization and loss analysis of silicon nanowaveguides are presented. Silicon nanowaveguides are fabricated on silicon-on-insulator (SOI) wafers with 0.13 μm complementary metal-oxide-semiconductor (CMOS) technology. To reduce the propagation loss, both photolithography and etching processes are optimized to make the waveguide sidewalls smooth. Propagation losses of 2.4 ± 0.2 and 0.59 ± 0.32 dB/cm are obtained at 1550 nm wavelength for TE and TM modes, respectively. A theoretical method is used to estimate the propagation losses for TE and TM modes. Scattering losses from both sidewalls and top/bottom surface are considered. The calculated results show that loss comes from sidewall roughness is the main source of propagation loss for TE mode while for TM mode, losses from both sidewall and top/bottom surface contribute comparably to the total propagation loss. The theoretically estimated propagation loss agrees well with the measured results.

Here, we have introduced a novel biscarbazolylmethane-based cyanine as a two-photon excited fluorescent probe, 6,6'-bis[2-(1-methylpyridinium)vinyl]-bis(9-methyl-carbazol-3-yl)methane diiodide, which has two vinylpyridinium carbazole moieties connected by a non-rigid methylene bridge. This molecule possesses a larger Stokes shift and enhanced two-photon absorption cross-section than the previously reported vinylpyridinium carbazole monocyanine, which is mainly attributed to the "through-space" type intramolecular charge transfer. The low fluorescence quantum yield and 30-fold fluorescence enhancement once binding with calf thymus DNA highlight this molecule as a promising fluorescence light-up probe for DNA. The obvious induced circular dichroism signals have proved that the molecule with soft-connected bis-cationic centers can specifically interact with various DNA structures. Cell viability study shows that the probe has very low cytotoxicity. The probe exhibits high staining selectivity for mitochondria in living HeLa cells. Its capability to stain nuclear DNA has been confirmed by fixed cell staining. Furthermore, the application for two-photon excited fluorescence imaging demonstrates high potential of the probe for nonlinear bioimaging with 3D resolution.

The isothermal crystallisation of polyethylene (PE) chains around single PE lamella in vacuum is investigated by molecular dynamic simulation. The crystallisation process is analysed in terms of the orientational order parameters, principal moments of inertia for the simulated systems. The effects of charge interactions between the polymer chains and lamella are discussed. It is found that the crystallisation process for uncharged systems can be divided into three stages: (1) adsorption, (2) orientation and (3) arrangement. The single polymer lamella changes a little during the three stages. PE chains are arranged parallel to the chain direction of the stems in the crystalline state. When considering the effect of charge interactions between the polymer chains and lamella, a different crystallisation process appears. The single polymer lamella is affected by the charged polymer chains.

We have investigated the photoinitiating properties of the photoinitiator 3,6-bis[2-(4-nitrophenyl)-ethynyl]-9-(4-methoxy-benzyl)-carbazole (BNMBC), which has an intramolecular radical quenching group "p-methoxybenzyl," in the substrate lines fabrication of two-photon induced photopolymerization (TPIP). Another photoinitiator 3,6-bis[2-(4-nitrophenyl)-ethynyl]-9-benzyl-carbazole (BNBC) with similar chemical structure but not radical quenching group was studied for comparison. Their photopolymerization properties were studied with resins in which BNBC and BNMBC were used as photoinitiators with a molar ratio of 0.02%, respectively. The linewidth of polymer lines fabricated by TPIP of the photoresist that contained BNMBC could be decreased to 65% of those using BNBC. Besides, we introduced a radical quencher, phenyl methyl ether (PhOCH3), to BNBC and further studied the photopolymerization properties by using BNBC, BNBC/PhOCH3 and BNMBC as photoinitiators with a molar ratio of 0.1%. The results further indicated that BNMBC was effective to confine the radical diffusion in polymerization due to the radical quenching effect of moiety. This intramolecular radical quenching moiety exhibited more effective confining effect of radical diffusion compared to the intermolecular radical quencher PhOCH3. Furthermore, arbitrary complex three-dimensional (3D) microstructure was achieved using the photoresist with photoinitiator BNMBC. The approach could open up broad prospect for improving the resolution in TPIP.

Clinical evidence indicates a high failure rate for titanium implants (TiI) in diabetic patients, involving the overproduction of reactive oxygen species (ROS) at the implant/bone interface. Tantalum coating on titanium (TaTi) has exerted better tissue integration properties than TiI, but its biological performance under diabetic conditions remains elusive. To investigate whether TaTi may ameliorate diabetes-induced implant destabilization and the underlying mechanisms, primary rabbit osteoblasts cultured on 3-dimensional printed TiI and TaTi were exposed to normal serum (NS), diabetic serum (DS), DS+NAC (a potent ROS inhibitor), and DS+SB203580 (a specific p38 MAPK inhibitor). An in vivo study was performed on diabetic sheep implanted with TiI or TaTi. Diabetes induced mitochondrial-derived ROS overproduction and caused cellular dysfunction and apoptosis, together with the activation of p38 MAPK in osteoblasts on TiI surface. Importantly, TaTi significantly attenuated ROS production and p38 MAPK phosphorylation and exerted more osseointegrative cell behavior than TiI, as shown by improved osteoblast adhesion, increased cell proliferation and differentiation and decreased apoptosis. These results were confirmed in vivo by the enhanced bone healing efficacy of TaTi. Moreover, treatment with NAC or SB203580 on TiI not only inhibited the activation of p38 MAPK but also improved cell function and alleviated apoptotic injury, whereas TaTi combined with NAC or SB203580 failed to further improve osteoblast functional recovery compared with TaTi alone. These results demonstrated that the tantalum coating markedly improved diabetes-induced impaired osteogenesis of TiI, which may be attributed to the suppression of the ROS-mediated p38 MAPK pathway.

Regulatory T cells (Tregs) and interleukin-17-producing T helper (Th17) cells were mutually antagonistic in the pathogenesis of chronic hepatitis C virus (HCV) infection. However, the regulation of imbalance between Tregs and Th17 cells was poorly understood in HCV infection. A recent report revealed the immunomodulatory role of Toll-like receptor (TLR) 2 in regulating the balance of Tregs/Th17 functions in multiple sclerosis. Thus, the aim of the current study was to assess the effect of TLR2 stimulation on the suppressive function of Tregs and Th17 differentiation in chronic hepatitis C. A total of 65 patients with chronic hepatitis C receiving pegylated interferon-a2a and ribavirin therapy for 48 weeks, as well as 20 of normal controls (NCs) were enrolled. Cellular proliferation and cytokine production was tested in purified CD4(+)CD25(+)CD127(dim/-) Tregs in response to the stimulation of Pam3Csk4, an agonist of TLR2. In treatment-naive patients, Tregs, but not Th17 cells, from chronic hepatitis C patients expressed higher levels of TLR2 compared with NCs. Stimulation with Pam3Csk4 enhanced the suppressive function of Tregs and production of IL-10 in chronic hepatitis C more than in NCs. However, TLR2 stimulation did not promote Th17 differentiation of Tregs in chronic hepatitis C patients. Moreover, effective anti-HCV therapy resulted in the induction of IL-17-secreting phenotypic shift of Tregs without loss of inhibitive function upon TLR2 stimulation. These data provided a novel mechanism underlying modulating the balance of Tregs/Th17 cells in chronic hepatitis C. HCV infection shifted Tregs/Th17 cells through TLR2 stimulation by inducing Tregs to produce IL-10 and enhancing inhibitive function of effector T cells, resulting in viral persistence.

A subwavelength silicon nanoposts array featuring high bending efficiencies in the wavelength of 1480–1600 nm are demonstrated. The compactness, low loss, and CMOS compatibility enable the structure a promising component for on-chip optical control.

Herbal compounds that have notable therapeutic effect upon Alzheimer's disease (AD) have frequently been found, despite the recent failure of late-stage clinical drugs. Icariin, which is isolated from Epimedium brevicornum, is widely reported to exhibit significant anti-AD effects in in vitro and in vivo studies. However, the molecular mechanism remains thus far unclear. In this work, the anti-AD mechanisms of icariin were investigated at a target network level assisted by an in silico target identification program (INVDOCK). The results suggested that the anti-AD effects of icariin may be contributed by: attenuation of hyperphosphorylation of tau protein, anti-inflammation and regulation of Ca(2+) homeostasis. Our results may provide assistance in understanding the molecular mechanism and further developing icariin into promising anti-AD agents.

In order to improve ZnWO4 photocatalytic activity under visible light, the C, N-codoped ZnWO4 nanoparticles have been successfully synthesized by choosing C3N4 generated from tripolycyanamide pyrolysis as the source of Carbon and Nitrogen and the influence of C3N4 concentration on structural, optical and morphological properties of C, N-codoped ZnWO4 using X-ray diffraction (XRD), UV-visible spectroscopy, scanning electron microscopy (SEM) and photocatalytic decoloration of rhodamine B (RhB) aqueous solution under visible light. It was found that the presence of carbon and nitrogen could not improve the crystallization of ZnWO4 species but could enhance their photoabsorption property in the visible region. The results also showed that the photocatalytic activity of the as-prepared ZnWO4 is higher than that of pure ZnWO4 with the optimum effect occurring at RC3N4 = 9 % (the weight ratio of tripolycyanamide to ZnWO4)

Poly(acrylic acid-b-styrene) (PAA-b-PS) amphiphilic block copolymers were synthesized by consecutive telomerization of tert-butyl acrylate, atom transfer radical polymerization (ATRP) of styrene, and hydrolysis. The resulting block copolymers were characterized by 1H NMR and GPC. These amphiphilic block copolymeric micelles were prepared by dialysis against water. Transmission electron micrograph (TEM) and laser particle sizer measurements were used to determine the morphology and size of these micelles. The results showed that these amphiphilic block copolymers formed spherical micelles with average size of 140–190 nm. The critical micelle concentration (CMC) and the kinetic stability of these micelles were investigated by fluorescence technique, using pyrene as a fluorescence probe. The observed CMC value was in the range of 0.075–0.351 mg/L. Kinetic stability studies showed that the stability of micelles increased with the decrease of the pH value of the solution.