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A series of triazolopyridinone derivatives originating from the antidepressant trazodone was designed and pharmacologically evaluated. Most of the compounds with a multireceptor functional profile exhibited high potency at the D2, 5-HT1A, and 5-HT2A receptors. Compounds S1, S3, S9 and S12 were selected for further evaluation of druggable potential. Among these compounds, S1, as a D2 receptor partial agonist, demonstrated very potent inhibition of quipazine-induced head-twitch response, which validated its 5-HT2A receptor antagonistic efficacy in vivo. S1 also demonstrated a dose-dependent effect on PCP-induced hyperactivity when administered orally. Thus, S1 endowed with a triazolopyridinone scaffold represents a valuable lead for the development of novel atypical antipsychotics.

Highly efficient and stimulus-responsive nanomedicines for cancer treatment are currently receiving tremendous attention. In this study, an acid-triggered charge-reversible graphene-based all-in-one nanocomplex is appropriately designed by surface modification with multilayer polymers and simultaneous co-transportation of photosensitizer indocyanine green (ICG) and oligonucleotide inhibitor of miR-21 (miR-21i) to achieve highly efficient genetic phototherapy in a controlled manner. The nanocomplex (denoted as GPCP/miR-21i/ICG) effectively protects miR-21i from degradation and exhibits excellent photothermal/photochemical reactive oxygen species (ROS) generation as well as fluorescence imaging ability. The cargoes ICG and miR-21i can significantly be released at acidic pH compared with normal physiological medium and escaped from endosomes/lysosomes due to the acid-triggered charge reversal effect. Typically, the released miR-21i downregulate the endogenous miR-21 and result in the upregulation of the target proteins PTEN and Bax, thus increasing the phototherapeutic efficiency of ICG. High in vivo anticancer efficiency against the MDA-MB-231 triple-negative breast cancer (TNBC) model is obtained due to the combination of genetic regulation of miR-21i and the photokilling effect of ICG. This work highlights the great potential of this smart nanocomplex as an attractive modality of gene-photo combined treatment of cancer, especially for intractable TNBC.

The efficacy of cancer chemotherapy can be generally restrained by the multiple drug resistance (MDR) of tumors, which is typically attributed to the upregulation of ATP-binding cassette (ABC) transporter proteins, such as P-glycoprotein (P-gp). There is an urgent need to present innovative strategies to reverse MDR and enhance the therapeutic efficacy of chemotherapeutic agents in biomedical applications. Here, we report a novel nanosystem of charge-reversal-functionalized PLGA nanobubbles (denoted as Dox-NBs/PPP/P-gp shRNA) for the co-delivery of Dox and P-gp shRNA for the reversal of drug resistance and for ultrasonic-imaging-guided tumor therapy. 1H NMR, FT-IR, SEM, DLS, and UV-vis spectroscopy characterizations were conducted to determine the structure, morphology, and composition of the as-prepared nanobubbles. Dox-NBs/PPP/P-gp shRNA exhibited an average diameter of about 300 nm with good dispersity, biocompatibility, and pH-responsive release properties through the charge-reversal process. The in vitro experiments showed that Dox-NBs/PPP/P-gp shRNA nanobubbles could co-deliver Dox and P-gp shRNA into tumor cells and could effectively suppress P-gp expression, leading to enhanced overall therapeutic effects against MCF-7/MDR cells by restraining the drug efflux. An in vivo antitumor assay revealed an approximately 65% inhibition rate of Dox-NBs/PPP/P-gp shRNA against MCF-7/ADR tumors in tumor-bearing nude mice. Both the in vitro and in vivo toxicity results indicated the Dox-NBs/PPP/P-gp shRNA are highly biocompatible with reducing side-effects and have negligible systemic toxicity in the in vivo therapy of resistant cancers by combining with a chemotherapeutic agent and P-gp knockdown. Furthermore, the in vivo imaging data substantiated that the functionalized nanobubbles could be used as an efficient contrast agent for the ultrasonic imaging of solid tumors. This works highlights the great potential of Dox-NBs/PPP/P-gp shRNA nanobubbles for enhanced imaging-guided combination therapy for overcoming MDR.

Besides heat stress, the 70 kDa heat shock proteins (HSP70s) have been shown to respond to cold stress. However, the involved cis-acting elements remain unknown. The hsp70 gene from the green macroalga Ulva prolifera (Uphsp70) has been cloned, from which one heat shock element HSE and one low-temperature-responsive element LTR were found in the promoter. Using the established transient expression system and quantitative GUS assay, a series of element deletion experiments were performed to determine the functions of HSE and LTR in response to temperature stress. The results showed that under cold stress, both HSE and LTR were indispensable, since deletion leads to complete loss of promoter activity. Under heat stress, although the HSE could respond independently, coexistence with LTR was essential for high induced activity of the Uphsp70 promoter. Therefore, synergistic effects exist between HSE and LTR elements in response to temperature stress in Ulva, and extensive bioinformatics analysis showed that the mechanism is widespread in algae and plants, since LTR coexists widely with HSE in the promoter region of hsp70. Our findings provide important supplements to the knowledge of algal and plant HSP70s response to temperature stress. We speculated that for algal domestication and artificial breeding, HSE and LTR elements might serve as potential molecular targets to temperature acclimation.

Circulating tumor cells (CTCs) need to acquire resistance to anoikis to survive after they experience fluid shear stress in the circulatory and lymphatic systems. However, the mechanism by which tumor cells resist anoikis under shear stress conditions remains unknown. Here, we found that the application of low shear stress (LSS; 2 dyn/cm2 ) to human breast carcinoma cells (MDA-MB-231) resulted in increased anoikis resistance when tumor cells were grown under anchorage-independent conditions. Caveolin-1 (Cav-1), the major component of plasma membrane caveolae, was overexpressed in LSS-treated cells and prevented tumor cells from anoikis, while depletion of Cav-1 restored sensitivity to anoikis. LSS-induced dissociation of Cav-1-Fas inhibited formation of the death-inducing signaling complex, caspase-8 activation, and rendered tumor cells resistant to anoikis. Likewise, LSS blocked the mitochondrial pathway through promotion of integrin β1-focal adhesion kinase-mediated multicellular aggregation and suppression of truncated BID translocation mediated crosstalk between the extrinsic and intrinsic apoptotic pathways. Our findings provide insights into the mechanisms by which LSS induces anoikis resistance in breast carcinoma cells through inhibition of Cav-1-dependent extrinsic and intrinsic apoptotic pathways, and serves as a potential therapeutic target for CTCs and metastatic breast cancer.

Nanomedicine-based combination therapy has sparked a growing interest in clinical disease treatment and pharmaceutical industry. In this study, a mitochondria-targeted and near-infrared (NIR) light-activable multitasking nanographene (i.e., GT/IR820/DP-CpG) was engineered to in situ trigger highly efficient "triple-punch" strategy of cancer photodynamic therapy, photothermal therapy, and immunotherapy. Modification of triphenylphosphonium on graphene made the vehicle specifically guide the NIR dye IR820 home to mitochondria, followed by lysosomes escape in a time-dependent manner. The photoactive nanocomplex generated an abundant reactive oxygen species as well as photothermal heat to ultimately kill cancer cells by inducing mitochondrial collapse and irreversible cell apoptosis upon the NIR laser irradiation. Further introduction of an immunostimulatory conjugate DP-CpG significantly promoted the secretion of proinflammatory cytokines (i.e., interleukin-6, tumor necrosis factor-α, and interferon-γ) and thus improved the immunogenicity of tumors. In vivo studies demonstrated that GT/IR820/DP-CpG remarkably inhibited tumor growth (tumor inhibition rate, ∼88%) resulting from the combinational phototherapeutic effect of IR820 and immunostimulatory activity of DP-CpG, thereby causing negligible toxic effects on mice. Our work provides a new paradigm of architecting organelle-targeted and stimulative nanocomplex for highly efficient cancer photoimmunotherapy.

Atlantoaxial instability can arise from different disorders, including trauma, congenital and developmental anomalies, rheumatoid arthritis, degenerative disorders, inflammatory or infectious lesions, neoplasms, and secondary to certain surgical interventions. This chapter describes the pathomechanics of atlantoaxial instability resulting from atlas and axis fractures, congenital and developmental abnormalities, and rheumatoid arthritis.

Large-scale green tides caused by the green algae Ulva prolifera have occurred in the Yellow Sea every summer since 2007. The genetic variation and relationships at the intra-species level among floating and attached samples of U. prolifera collected from 2007 to 2011 were analysed using ISSR (inter-simple sequence repeat) markers. The results showed that all of the floating samples collected from the Yellow Sea during the past five years formed a single genetic entity that was different from the attached samples in intertidal zone. A SCAR (sequence characterized amplified region) marker highly specific to the floating samples of U. prolifera was identified and it showed that the same population dominated in the blooms from 2007 to 2013. In combination with the morphology and physiological features, the genetic analysis results suggested that a unique ecotype of U. prolifera was responsible for the largest green tides in the world. These findings indicated that attached U. prolifera along the coast does not seem to be the originator of the green tide in the Yellow Sea and gene flow between attached and floating populations does not readily take place. (C) 2015 Elsevier Ltd. All rights reserved.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers. Cyclopamine (CPA), a potent inhibitor for sonic hedgehog pathway (SHH), shows great promises in PDAC treatment, including the disruption of tumor-associated stroma, and enhancement of radiation therapy. However, CPA is insoluble in water and therefore requires a nanometric delivery platform to achieve satisfactory performance. We herein encapsulated CPA in a core-cross-linked polymeric micelle system (M-CPA). M-CPA was combined with Cs-137 radiation and evaluated in vitro in PDAC cell lines and a human pancreatic stellate cell line. The results showed that M-CPA had higher cytotoxicity than CPA, abolished Gli-1 expression (a key component of SHH), and enhanced the radiation therapy of Cs-137. M-CPA radiosensitization correlated with its ability to disrupt the repair of radiation-induced DNA damage. These findings indicate that the combination therapy of M-CPA and radiation is an effective strategy to simultaneously treat pancreatic tumors and tumor-associated stroma.

A novel stereoscopic snowflake-like CoO material is synthesized via a simple two-step process, including the hydrothermal process for the formation of the stereoscopic snowflake-like Co(OH)F as precursor and thermal conversion process to CoO without altering the original shape of the precursor. The possible formation mechanism of the stereoscopic snowflake-like morphology of CoO was investigated by scanning electron microscopy and X-ray diffraction patterns. The hydrothermal temperature and NH4F were critical to the formation of stereoscopic snowflake-like morphology of CoO. The supercapacitor properties of as-prepared CoO were investigated by the electrochemical measurements on a conventional three-electrode system.

2-Chloro-6-fluorobenzaldehyde was converted to 4-(1-piperazinyl)benzo[b]thiophene dihydrochloride (18), an intermediate in the synthesis of brexpiprazole, via a five-step sequence in 54% overall yield. This procedure requires no expensive catalyst and avoids the side products produced in the coupling step in the reported process. Several kilograms of compound 18 were prepared using this economical and scalable process.

In this paper, we will show that quantum private comparison protocol is secure when a malicious third party is presented. The security of the protocol is considered in a cheat-sensitive model, in which the TP is kept honest by the possibility of being caught cheating. Besides, we enhance the privacy of the quantum private comparison protocol, where the participants' inputs and the comparison result can be preserved. Furthermore, in contrast to pervious protocols requiring a large amount of quantum resources, such as entanglement and quantum memory, our protocol is based on BB84 protocol, which is more feasible for practical applications. Finally, we analyze the security of the presented protocol.

We experimentally demonstrate a high-speed phosphorescent white light emitting diode (LED) visible light communication (VLC) system without utilizing an optical blue filter. Here, the white light response is equalized by using the proposed analog equalizers. The 3 dB bandwidth of the VLC link could be extended from 3 to 132 MHz, which allows 330 Mbit/s non-return-to-zero on–off keying (NRZ-OOK) data transmission with a bit error ratio (BER) of 7.2×10−10 and 672 Mbit/s 64-quadrature amplitude modulation (64-QAM) data transmission with a BER of 3.2×10−3. These resultant BERs are less than the forward error correction (FEC) limit of 3.8×10−3. The VLC link distance is 1 m using a single 1 W LED. The transmitter and receiver modules are integrated to a compact size. Furthermore, the relationships between the signal performance and illumination level or optical power are investigated and analyzed.

A fluorescent dye of a phenolphthalein derivative containing bisphthalonitrile groups was synthesized and subsequently chemically grafted onto dopamine modified silver nanoparticles via the interfacial crosslinking reaction, leading to enhanced fluorescent emission of dye molecules in a solution phase. Specifically, the non-fluorescent phenolphthalein (PP) molecule was end-capped with bisphthalonitrile (BPH) groups through nucleophilic substitution to obtain a violet/blue-emitting fluorescent dye PP-BPH due to the restriction of inter-molecular rotation. Furthermore, the PP-BPH dye can be immobilized on the surface of the dopamine modified silver nanoparticles, given the fact that bisphthalonitrile based monomers can be readily crosslinked in the presence of aromatic amine or phenol compounds (i.e. dopamine). Consequently, the fluorescent emission of the PP-BPH dye can be further enhanced via the plasmonic enhancement effects of silver nanoparticles. The preliminary results obtained in this communication will pave the way for the plasmon controlled photonic properties of PP-BPH based multifunctional polymers.

Large scale green tides have bloomed successively in the Yellow Sea since 2007. The floating ecotype of Ulva prolifera, which is responsible for the environmental disaster, drifted a long distance during the blooming time and was exotic to the coastal area. The Yellow Sea green tide can be a potential source to incur bio-invasion. In this study, the distribution pattern and propagule pressure of the floating ecotype was investigated along the Qingdao coastline, which was seriously impacted by the green tide. Two out of 661 attached Ulva specimens collected in different seasons were identified as the floating ecotype by molecular markers, indicating that a few individuals of the floating ecotype had settled down, and their attached population could have spontaneously established. In seawater and sediments, the proportion of the floating ecotype in Ulva propagules reached up to 32% and 69% respectively when the floating algae was accumulating on seashore, which was a great propagule pressure to the local ecosystem. Results of the field test indicated that the available resources and the competition between the floating ecotype and the local Ulva species might be the main restrictions for settlement. Though the current scale of the established population is still small, the risk of biological invasion by the floating ecotype exists and it deserves more attention.

In previous study, a series of benzamides was identified as potent antipsychotic agents. As a continuation of the program to discover novel antipsychotics, herein we reported the evaluation of a series of pyridinecarboxamide derivatives. The most promising compound 7h not only held good activities on dopamine D2, serotonin 5-HT1A and 5-HT2A receptors, but also exhibited low potency for α1A, H1 and 5-HT2C receptors, indicating a low propensity of side effects like orthostatic hypotension and weight gain. Furthermore, 7h exhibited more potent antipsychotic-like effect than aripiprazole in behavioral studies. The preliminary results were promising enough for further research around this scaffold.

This paper reports the design and fabrication of a planar chip for high-throughput cell trapping and pairing (more than 2400 single cell-cell pairs in a microwell array) in a 1 × 1.5 cm area by positive dielectrophoresis (p-DEP) within only several minutes. The p-DEP was generated by applying an alternating current signal on a novel two-pair interdigitated array (TPIDA) electrode. The TPIDA electrode not only enabled the planar chip to be incorporated with a most often used PDMS microfluidic channel, but also contributed to a high single cell-cell pairing efficiency up to 74.2% by decreasing the induced electric field during consecutive p-DEP trapping of two cell types. Furthermore, the paired cells in each microwell could be "pushed" together into a microbaffle by a liquid flow through a capillary-sized channel, resulting in single cell-cell contact. More importantly, the planar chip could be used repeatedly by a simple water cleaning process. The planar chip offers an effective way for high-throughput single cell-cell pairing, which could provide a facile platform for cell communication and a precise cell pairing step in cell fusion.

In the present study, a series of multi-target N-substituted cyclic imide derivatives which possessed potent dopamine D2, serotonin 5-HT1A and 5-HT2A receptors properties were synthesized and evaluated as potential antipsychotics. Among these compounds, (3aR,4R,7S,7aS)-2-(4-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)butyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione hydrochloride (3d) held a promising pharmacological profile. 3d not only showed potent and balanced in vitro activities on D2/5-HT1A/5-HT2A receptors, but also endowed with low to moderate activities on 5-HT2C, H1, α1A, M3 receptors and hERG channel, suggesting a low liability to induce side effects such as weight gain, orthostatic hypotension and QT prolongation. In animal behavioral studies, 3d reduced phencyclidine-induced hyperlocomotion with a high threshold for catalepsy induction. Compound 3d was selected as a potential antipsychotic candidate for further development.

Notch signaling pathway is evolutionarily conserved in mammals, which plays an important role in cell development and differentiation. In recent years, increasing evidence has shown that aberrant activation of Notch is associated with tumor process. Aberrant activation of Notch signaling pathway has been found in many different solid tumors can induce cell proliferation, metastasis and epithelial-mesenchymal transition. Notch receptor and its ligand are both single transmembrane protein, and Notch is activated when it binds to the Notch ligand of neighbor cells. The signal transduction of Notch signaling pathway is only between cells that are in contact with each other, which is independent of second messengers. Thus, Notch needs to cross talk with other signaling pathways, including PI3K/AKT, NF-κB, integrin and miRNAs, to precisely regulate cell fate. In this review, we summarize the roles of Notch signaling pathway in tumor metastasis and its regulatory mechanisms and discuss the current treatment strategies targeting Notch signal pathway.

Single-cell analysis of cancer cells is important to improve our understanding of tumor heterogeneity, which could contribute to various clinical applications, such as diagnosis, prognosis, and choice of therapy. In order to improve single-cell analysis throughput, cell-sized microwells in an array are often fabricated and single cells are trapped via various methods such as dielectrophoresis, magnetic and optical techniques. After trapped individually, the cells are either lysed to get intracellular materials or directly analyzed to investigate various intracellular responses to external stimuli. However, besides confinement of each cell in an individual microwell, a real single-cell analysis needs to give individual stimuli to each cell, which prevents the cross-contamination of the intracellular materials among each cell. In this study, we firstly trapped individual cells in cell-sized microwells and obtained a high trapping yield via a dielectrophoresis electrode array. Moreover, an analysis microwell array with photolithographically patterned microgaskets was used for high throughput single cell analysis. The droplets containing stimuli were accurately injected into individual analysis microwells by using an inkjet spotter and the analysis microwells with stimuli were reversibly sealled for liquid tight and were aligned to the trapped cells for single cell analysis. For example, we demonstrated the utility of the developed platform by monitoring the kinetics of calcium fluxes and oscillations in individual Hela cells under the stimulation of drugs. As a universal second messenger in virtually all eukaryotic cells, calcium ions (Ca2+) plays a vital role in cellular responses to stimuli and mediates various physiological processes, including neurosecretion, skeletal muscle contraction, cell growth and differentiation. The resulted calcium imaging data revealed significant difference between different cells under the stimulation of drugs. We believe that such a technology will be an essential tool for obtaining high throughput single cell analysis data, in order to indentify statistically significant trends and achieve significant improvements in reagent consumption and analysis time.

Biocompatible fluorescent polymeric nanoparticles (FPNs) are promising luminescent probes in cellular bioimaging, while the fabrication of high-quantum-yield FPN using nonconjugated heterochain polymers derived from step-growth polymerization is still in its infancy. Herein, the nonconjugated polyarylene ether nitrile (PEN) is endowed with aggregation-induced emission (AIE) feature by incorporation of an AIEgen named of 1,2-di(4-hydroxyphenyl)-1,2-diphenylethene into macromolecular backbone. Furthermore, the AIE-active PEN is crosslinked into water soluble fluorescent nanospheres showing good biocompatibility and strong emission ≈480 nm with a quantum yield of 21% in the presence of Ca

Ulva prolifera is a green macroalgae with an extremely high growth rate that can accumulate biomass with considerable protein content. To set up an available seaweed expression system, a prior step is to isolate endogenous and strong constitutive promoters. For this reason, the full-length genomic actin1 gene from U. prolifera (Upactin1) was cloned and its 5′ flanking sequence was obtained by genome walking. The Upactin1 open reading frame consisted of 1134 nucleotides encoding 377 amino acid residues. Besides 4 exons and 3 introns in the coding region, an extra leader intron was identified in the 5′ untranslated region. According to quantitative GUS assays based on transient expression, the promoter activity of the Upactin1 5′ flanking region was found to be several times higher than that of the widely-used cauliflower mosaic virus 35S (CaMV35S) in all tested species of Ulva. In addition, precise deletion of the leader intron led to a significant decrease of promoter strength in U. prolifera, and almost entire loss of strength in U. linza and U. pertusa. To our knowledge, this is the first report to prove function of a leader intron in algae. The 5′ flanking region of Upactin1 was shown to be a much stronger promoter than the foreign CaMV35S, and its activity was highly dependent on the presence of the leader intron. We propose that the Upactin1 promoter could serve as an endogenous and strong constitutive element for genetic engineering of U. prolifera.

We designed a communication system for law enforcement officers to use when conducting explosive detection searches with multiple agencies. Dogs trained in explosive detection work alongside human handlers to form a K9 team, which are an integral part of these searches. Officers in K9 teams have a strong bond and communication with these dogs, but noisy locations, long distances, and crowded spaces present challenges. In addition, other officers assigned as backup often lack the experience to read the cues from the canine, which hinders the speed and effectiveness of the team. Coordinating a search with teams from different municipalities presents challenges due to a lack of standard collaboration tools. Getting the right information as quickly as possible saves lives, whether this information is about the areas that have been searched or the location of an explosive device. We hope that in addition to increasing public safety, our system will make working conditions safer for law enforcement officers and their canines.

Ulva spp. dominates green tides around the world, which are occurring at an accelerated rate. The competitive nitrogen assimilation efficiency in Ulva is suggested to result in ecological success against other seaweeds. However, molecular characterization of genes involved in nitrogen assimilation have not been conducted. Here, we describe the identification of the nitrate reductase (NR) gene from a green seaweed Ulva prolifera, an alga which is responsible for the world's largest green tide in the Yellow Sea. By using rapid amplification of cDNA ends (RACE) and genome walking, the NR gene from U. prolifera (UpNR) was cloned, which consisted of six introns and seven exons encoding 863 amino acids. According to sequence alignment, the NR in U. prolifera was shown to possess all five essential domains and 21 key invariant residues in plant NRs. The GC content of third codon position of UpNR (82.75%) was as high as those of green microalgae, and the intron number supported a potential loss issue from green microalga to land plant. Real-time quantitative PCR results showed that UpNR transcript level was induced by nitrate and repressed by ammonium, which could not be removed by addition of extra nitrate, indicating that U. prolifera preferred ammonium to nitrate. Urea would not repress NR transcription by itself, while it weakened the induction effect of nitrate, implying it possibly inhibited nitrate uptake rather than nitrate reduction. These results suggest the use of UpNR as a gene-sensor to probe the N assimilation process in green tides caused by Ulva. This article is protected by copyright. All rights reserved.

Multimodal therapeutic agents based on nanomaterials for cancer combination therapy have attracted increasing attention. In this report, a novel photo- and chemoactive nanohybrid was fabricated by assembling photosensitizer Zn(II)-phthalocyanine (ZnPc) and anticancer drug doxorubicin (DOX) on the biocompatible poly-l-lysine (PLL)-grafted graphene (G-PLL). This nanocomplex of G-PLL/DOX/ZnPc showed excellent physiochemical properties, including high solubility and stability in biological solutions, high drug loading efficiency, pH-triggered drug release, and ability to generalize (1)O2 under light excitation. Compared to free drug molecules, cells treated with G-PLL/DOX/ZnPc showed a higher cellular uptake. In particular, G-PLL/DOX/ZnPc elicited a remarkable synergistic anticancer activity owing to combined photodynamic and chemotherapeutic effects. The combination dose reduction indexes revealed that combining DOX with ZnPc provided strong synergistic effects (combination index0.1) against three cancer cell lines tested (HeLa, MCF-7, and B16). Thus, this study demonstrates programmable dual-modality therapy exemplified by G-PLL/DOX/ZnPc to synergistically treat cancers.

We report in this study the effects of red-emitting CdTe QDs capped with cysteamine (Cys-CdTe) on the in vitro anticancer activity of the well-known flavenoid quercetin (Qu). Various techniques, including the methylthiazolyldiphenyl-tetrazolium bromide assay, the real-time cell electronic sensing system, the optical and fluorescence imaging, and electrochemical methods have been utilized to study the potential interactions of Cys-CdTe QDs with Qu. The observations demonstrate that the safe-dosage Cys-CdTe QDs can greatly improve the drug uptake and enhance the inhibition efficiency of Qu towards the proliferation of cancer cells such as HepG2 cells. This study implies that Cys-CdTe QDs may be used for cancer therapy and that they exert a synergic anticancer effect when bound to drug molecules.

A novel Co3O4/flocculent graphene (FG) hybrid on commercial Ni foam (NF) has been prepared. The unique flocculent graphene structure is prepared by combining a rapid filtering approach through Ni foam and a template method, in which the thermally expanded graphite is used as precursor and polystyrene (PS) microspheres are used as templates. The PS spheres play an important role in preventing the re-stacking of graphene nanosheets and the formation of flocculent graphene on NF. The PS spheres were first introduced as a guest material and were subsequently removed by calcination. The resulting free-standing FG/NF provides a three-dimensional and high conductivity scaffold for the hydrothermal growth of Co3O4 nanoclusters. The obtained Co3O4/FG/NF hybrid could be directly used as a binder-free supercapacitor electrode. Moreover, the Co3O4 nanoclusters on FG/NF scaffold exhibit improved specific capacitance of 1615 F g−1 compared to that of the bare NF. The 3D active material layer of Co3O4/FG/NF hybrid, high conductivity of 3D FG/NF scaffold and functional features of the Co3O4 nanocluster morphology synergistically result in an improved electrochemical performance.

Objective To evaluate the effect of surgical treatment on health related quality of life (HRQOL) and radiographic variables in patients with adult scoliosis. Methods Sixty-eight patients with adult spinal deformities underwent radiographic analysis. The enrollment criteria were as follows: age older than 18 years, adult degenerative or progressive idiopathic scoliosis (Cobb angle >10°), and surgical treatment within one year before this study was undertaken. The following variables were measured: curve type, apical level, curve magnitude, coronal and sagittal balance using a C7 plumb line (C7PL) and gravity line, lateral intervertebral olisthesis, lumbar lordosis, sacral slope and pelvic tilt. HRQOL was assessed by the Oswestry Disability Index (ODI). Both preoperative and postoperative data were collected and changes in radiographically assessed variables and ODI scores attributable to surgery calculated; correlations between these changes were then assessed. The radiographically assessed variables and ODI scores were analyzed with SigmaStat (SPSS, Chicago, IL, USA). The level of statistical significance was set at P < 0.05. Results Surgical treatment resulted in improvements in ODI scores and several radiographically assessed variables, including sagittal balance, lumbar lordosis, lateral olisthesis and coronal Cobb angle. Only sagittal balance expressed as C7PL was correlated to both preoperative and postoperative ODI. Gravity line, an alternative measurement of spinal balance, did not provide better correlations with HRQOL than C7PL. Conclusions Spinal balance assessed by gravity line did not provide a better correlation with HRQOL than C7PL. Loss of sacral slope and retroverted pelvis are commonly seen in adult scoliosis and are not significantly changed by surgical treatment, including restoration of lumbar lordosis and sagittal balance.

Microbubbles (MBs, usually 2-8 microm) as ultrasound contrast agent and drug carrier are promising for ultrasonic imaging and drug delivery. However, MBs posed some limitations due to their large diameters. In the current study, we developed a nanoscale bubbles (nanobubbles, NBs) by encapsulating the doxorubicin (DOX) into poly(lactic-co-glycolic acid) (PLGA) shells (denoted as DOX-PLGA NBs) for drug delivery into cancer cells. The size, morphology, particle stability, drug encapsulation efficiency, and drug payload were determined. The results showed that the DOX-PLGA NBs were uniform (270 +/- 3 nm) and spherical with a smooth surface, and were well dispersed and stable in water. The encapsulation efficiency and payload of DOX increased with its initial loading concentrations. The release behavior of DOX from the DOX-PLGA NBs exhibited a biphasic pattern characterized by an initial burst release followed by a slower and continuous release at both pH 7.4 and pH 4.4, and also presented in a pH-triggered releasing profile. The qualitative analysis of cellular internalization into HeLa cells by inverted fluorescence microscope showed that the cellular uptake of DOX-PLGA NBs was both concentration- and time-dependent. Moreover, the cell viability was also investigated using CCK-8 assay. It was found that DOX-PLGA NBs showed greater HeLa cell growth inhibition effect in vitro compared with free DOX. It was concluded that the DOX-PLGA NBs were biocompatible and appropriate for anti-cancer drug delivery, and were potentially promising as a new therapeutic system for cancer treatment.

A new type of three-dimensional (3D) NiO/ultrathin derived graphene (UDG) hybrid on commercial Ni foam (NF) for a binder-free pseudocapacitor electrode is presented. NiO nanoflakes are in situ grown by a chemical bath deposition (CBD) technique on the free-standing 3D UDG/NF scaffold, which is first prepared by a simple nanocasting process consisting of hydrothermal reaction and subsequent thermal transformation. The 3D UDG/NF scaffold with interconnected network affords a high conductivity due to the high graphitization degree and efficiently facilitates the electron transport to NiO. Moreover, the 3D NiO/UDG/NF hybrid allows for a thinner 3D active material layer under the same loading density, which could shorten the diffusion paths of ions. The NiO/UDG/NF hybrid is directly used as a binder-free supercapacitor electrode, which exhibited significantly improved supercapacitor performance compared to the bare CBD prepared NiO/NF electrode.

A series of benzamide derivatives possessing potent dopamine D2 , serotonin 5-HT1A , and 5-HT2A receptor properties were synthesized and evaluated as potential antipsychotics. Among them, 5-(4-(4-(benzo[d]isothiazol-3-yl)piperazin-1-yl)butoxy)-N-cyclopropyl-2-fluorobenzamide (4k) held the best pharmacological profile. It not only exhibited potent and balanced activities for the D2 , 5-HT1A , and 5-HT2A receptors, but was also endowed with low to moderate activities for the 5-HT2C , H1 , and M3 receptors, suggesting a low propensity for inducing weight gain or diabetes. In animal models, compound 4k reduced phencyclidine-induced hyperactivity with a high threshold for catalepsy or muscle relaxation induction. On the basis of its robust in vitro potency and in vivo efficacy in preclinical models of schizophrenia, 4k was selected as a candidate for further development.

MnO2 nanorods/graphene composite materials have been fabricated using a facile hydrothermal method for supercapacitor applications. The prepared composite materials are characterized by means of X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and transmission electron microscope (TEM). Electrochemical performances are evaluated using cyclic voltammetry (CV), galvanostatic charge–discharge and electrochemical impedance spectrometry (EIS). It indicates that ratio of MnO2 nanorods to graphene in composite materials has significant influence on the electrochemical performance of composite electrodes. We have achieved the maximum specific capacitance of 218 F g−1 at the scan rate of 5 mV s−1 in 1 M Na2SO4 aqueous solution. Additionally, MnO2 nanorods/graphene composite materials exhibit highest energy density of 16 Wh kg−1 at power density of 95 W kg−1 and excellent capacitance retention with no more than 6% capacitance loss after 1000 cycles at the most favorable composites ratio.

A series of aza-boron-diquinomethene (aza-BODIQU) complexes with different aryl-substituents (B1–B6) were synthesized and characterized. Their photophysical properties were investigated systematically via spectroscopic and theoretical methods. All complexes exhibit strong 1π–π* absorption bands and intense fluorescent emission bands in the visible spectral region at room temperature. The fluorescence spectra in solution show the mirror image features of the S0→S1 absorption bands, which can be assigned to the 1π–π*/1ICT (intramolecular charge transfer) emitting states. Except for B6, all complexes exhibit high photoluminescence quantum yields (ΦPL = 0.47–0.93). The spectroscopic studies and theoretical calculations indicate that the photophysical properties of these aza-BODIQUs can be tuned by the appended aryl-substituents, which would be useful for rational design of boron–fluorine complexes with high emission quantum yield for organic light-emitting applications.

Diverse titanium dioxide (TiO2 ) nanostructures have attracted much attention recently due to their potential application in photocatalytic and photovoltaic fields. Here, the synthesis of a TiO2 single crystal with a novel four-truncated-bipyramid morphology is reported for the first time, produced by a simple hydrothermal method. Both peroxo titanic acid precursor and hydrofluoric acid capping agent are essential for the formation of this unique morphology. Moreover, the as-prepared TiO2 photocatalyst exhibits excellent hydrogen production activity from an ethanol-water solution, which is attributed to exposure of both high-energy {001} oxidative and low-energy {101} reductive facets in an optimal ratio. The current findings will contribute greatly to development of more novel photocatalysts with controllable microscopic structures for hydrogen production.

A biaxially wave-shaped polydimethylsiloxane (PDMS) surface was developed simply by using a taro leaf as the template. The resulting leaf-templated PDMS (L-PDMS) possesses a micro-sized curved interface structure, which is greatly beneficial for the exact embedding of a silver nanowire (AgNW) network conductive film covering the L-PDMS surface. The intrinsically curved AgNW/L-PDMS film surface, without any dangling nanowire, could prevent the fracture of AgNWs due to stretching stress even after cyclic stretching. More importantly, it also exhibited a biaxial stretchability, which showed ultra-stable resistance after continuous stretching for 100 cycles each in X- and Y-directions. This biaxially stretchable AgNW/L-PDMS film could extend the application fields in stretchable electronics.

Light-triggered nanotheranostics opens a fascinating but challenging avenue to achieve simultaneous and highly efficient anticancer outcomes for multimodal therapeutic and diagnostic modalities. Herein, a multifunctional phototheranostics based on a photosensitizer-assembled graphene/gold nanostar hybrid (GO/AuNS-PEG) was developed for cancer synergistic photodynamic (PDT) and photothermal therapy (PTT) as well as effective photothermal imaging. The stable and biocompatible GO/AuNS-PEG composite displayed a high photothermal conversion efficiency due to the enhanced optical absorbance of both graphene and gold nanostars in the near-infrared (NIR) range. By tuning the absorption wavelength of GO/AuNS-PEG to that of Chlorin e6 (Ce6), GO/AuNS-PEG/Ce6 completely eliminated the EMT6 xenograft tumors by the tremendous synergistic anticancer efficiency of simultaneous PDT and PTT under a single NIR laser irradiation (660 nm) in vivo . The underlying mechanism may be the enhanced cytoplasmic uptake and accumulation of GO/AuNS-PEG/Ce6 and the subsequent photodestruction of the lysosomal membrane and mitochondria. Moreover, GO/AuNS-PEG/Ce6 exhibited negligible side-effects on the body and other organs. These results demonstrate that the graphene/gold nanostar nanoconstruct provides a versatile and reliable integrated platform for the photo-controlled cancer theragnostic applications. Statement of Significance This work demonstrated the application of graphene-Au Nanostars hybridized system (denoted as GO/AuNS-PEG) in single wavelength laser induced synergistic photodynamic (PDT) and photothermal therapy (PTT) and effective cancer photothermal/fluorescence multimode imaging. GO/AuNS-PEG showed excellent biocompatibility and high dual-enhanced photothermal efficiency under the near-infrared laser irradiation that was very promise for deep tumor imaging. By combining with the photosensitizer Chlorin e6, both in vitro and in vivo data confirmed the efficient photoablation of the EMT6 tumors through the synergistic PDT and PTT effect under the activation of a single wavelength laser.

Rapid improvement in the efficiency of GaN-based LEDs not only speed up its applications for general illumination, but offer the possibilities for data transmission. This review is to provide an overview of current progresses of GaN-based LEDs for light communications. The modulation bandwidth of GaN-based LEDs has been first improved by optimizing the LED epilayer structures and the modulation bandwidth of 73 MHz was achieved at the driving current density of 40 A/cm2 by changing the multi-quantum well structures. After that, in order to increase the current density tolerance, different parallel flip-chip micro-LED arrays were fabricated. With a high injected current density of ~7900 A/cm2, a maximum modulation bandwidth of ~227 MHz was obtained with optical power greater than 30 mW. Besides the increase of carrier concentrations, the radiative recombination coefficient B was also enhanced by modifying the photon surrounding environment based on some novel nanostructures such as resonant cavity, surface plasmon, and photonic crystals. The optical 3 dB modulation bandwidth of GaN-based nanostructure LEDs with Ag nanoparticles was enhanced by 2 times compared with GaN-based nanostructure LEDs without Ag nanoparticles. Our results demonstrate that using the QW-SP coupling can effectively help to enhance the carrier spontaneous emission rate and also increase the modulation bandwidth for LEDs, especially for LEDs with high intrinsic IQE. In addition, we discuss the progress of the faster color conversion stimulated by GaN-based LEDs.

Tumor cells translocating to distant sites are subjected to hemodynamic shear forces during their passage in the blood vessels. Low shear stress (LSS) plays a critical role in the regulation of various aspects of tumor cells functions, including motility and adhesion. Beyond its structural role, caveolin-1 (Cav-1), the important component of caveolae, represents a modulator of several cancer-associated functions as tumor progression and metastasis. However, the role of Cav-1 in regulating tumor cells response to shear stress remains poorly explored. Here, we characterized the role of LSS and Cav-1 in mediating cell motility and adhesion on human breast carcinoma MDA-MB-231 cells. We first showed that LSS exposure promoted cell polarity and focal adhesion (FA) dynamics, thus indicating elevated cell migration. Silencing of Cav-1 leaded to a significantly lower formation of stress fibers. However, LSS exposure was able to rescue it via the alteration of actin-associated proteins expression, including ROCK, p-MLC, cofilin and filamin A. Time-lapse migration assay indicated that Cav-1 expression fostered MDA-MB-231 cells motility and LSS triggered cells to rapidly generate new lamellipodia. Furthermore, Cav-1 and LSS significantly influenced cell adhesion. Taken together, our findings provide insights into mechanisms underlying LSS triggered events mediated by downstream Cav-1, including FAK/Src and ROCK/p-MLC pathways, involved in the reorganization of the cytoskeleton, cell motility, FA dynamics and breast cancer cell adhesion.

This paper describes an 8.5–11.5 Gb/s transceiver with a dual path receiver and a voltage-mode transmitter. The RX can operate either in ADC mode for complex loss channels such as optical multimode fiber or in DFE mode for copper-based backplane links. The ADC path implements a 2X interleaved 6-bit rectifying flash ADC using a programmable gain amplifier (PGA) with controlled bandwidth and peaking, comparator pipelining, and super-source follower circuit techniques. The LRM optical sensitivity requirements are met with a > 6 dB margin while achieving an ENOB of 4.59 bits at a 5 GHz input frequency. The TX/RX DFE path achieves copper channel loss compensation of 38 dB with BER < 10−12 at 11.5 Gb/s consuming 46mW from a 0.9V supply. The TX/RX ADC path consumes 125 mW at 10.3125 Gb/s. The TX/RX occupies 0.56 mm2 in a 28nm standard CMOS process.

Breast cancer has a high incidence in the world and is becoming a leading cause of death in female patients due to its high metastatic ability. High expression of Notch-1 and its ligand Jagged-1 correlates with poor prognosis in breast cancer. Our previous work has shown that Notch-1 signaling pathway upregulates NF-κB transcriptional activity and induces the adhesion, migration and invasion of human breast cancer cell line MDA-MB-231. However, the role of Notch-1 in NF-κB activation is still poorly understood. Here, we aim to understand the exact mechanism that Notch-1 regulates NF-κB activity. In MDA-MB-231 cells where Notch-1 is constitutively activated, the phosphorylation of p85 and AKT (Tyr308/Ser473) is upregulated, indicating PI3K/AKT pathway is activated. Notch-1 activation caused the increase of PP2A phosphorylation at Tyr307, indicating Notch-1 inhibits PP2A activity. NF-κB transcriptional activity was evaluated by dual-luciferase reporter assay, and the results showed that, while silencing of Notch-1, PP2A activity was upregulated and NF-κB activity was downregulated, whereas PP2A inhibitor okadaic acid (OA) restored NF-κB activity. Immunofluorescence and Western blots showed that OA treatment antagonized the decrease of p65 nuclear translocation caused by Notch-1 silencing. Moreover, OA treatment also upregulated MMP-2, MMP-9 and VEGF mRNA expression levels, indicating OA rescues Notch-1 silencing that caused low cell invasion. Taken together, our results suggest that Notch-1-activating PI3K/AKT/NF-κB pathway is PP2A dependent; PP2A may be a potential therapeutic target in breast cancer.

In the present study, a series of benzamides, endowed with potent dopamine D2, serotonin 5-HT1A and 5-HT2A receptors properties, was synthesized and evaluated as potential antipsychotics. Among them, 3-(4-(4-(6-fluorobenzo[d]isoxazol-3-yl)-piperidin-1-yl)butoxy)-N-methylbenzamide (21) and its fluoro-substituted analogue (22) held the best pharmacological binding profiles. They not only presented potent activities for D2, 5-HT1A, and 5-HT2A receptors, but were also endowed with low activities for 5-HT2C, H1 receptors and hERG channels, suggesting a low propensity of inducing weight gain and QT prolongation. In animal models, compounds 21 and 22 reduced phencyclidine-induced hyperactivity with a high threshold for catalepsy induction. It thus provides potential candidates for further preclinical studies.

We have previously investigated electromyographic (EMG) and transcranial motor evoked potential (MEP) abnormalities after mechanical spinal cord injury. We now report thermally generated porcine spinal cord injury, characterized by spinal cord generated hindlimb EMG injury activity and spinal cord motor conduction block (MEP loss). Electrocautery (EC) was delivered to thoracic level dural root sleeves within 6-8 mm of the spinal cord (n = 6). Temperature recordings were made near the spinal cord. EMG and MEP were recorded by multiple gluteobiceps intramuscular electrodes before, during, and after EC. Duration of EC was titrated to an end-point of spinal motor conduction block (MEP loss). In 5/6 roots, ipsilateral EMG injury activity was induced by EC. In 4/5 roots, EMG injury activity was identified before MEP loss. In all roots, a minimum of 20 s EC and a temperature maximum of at least 57 °C at the dural root sleeve were required to induce MEP loss. Unexpectedly, conduction block was preceded by an enhanced MEP in 4/6 trials. EMG injury activity, preceding MEP loss, can be seen during near spinal cord EC. Depolarization and facilitation of lumbar motor neurons by thermally excited descending spinal tracts likely explains both hindlimb EMG and an enhanced MEP signal (seen before conduction block) respectively. A thermal mechanism may play a role in some unexplained MEP losses during intraoperative monitoring. EMG recordings might help to detect abnormal discharges and forewarn the monitorist during both mechanical and thermal injury to the spinal cord.

Non-malleability is an important property in commitment schemes, which can resist to the person-in-the-middle (PIM) attacks within the interaction. In this paper, we focus on the non-malleability of ID-based trapdoor commitment. We first point out some weakness of the definition for Fischlin's ID-based trapdoor commitments, which we call the partial ID-based trapdoor commitments. Moreover, we present the formal definition for the full ID-based trapdoor commitment and give a concrete construction based on the computational Diffie-Hellman (CDH) assumption. Finally, we use the idea of multi-trapdoor commitments and the technique of non-malleability to propose two efficient interactive full ID-based non-malleable trapdoor commitments in discrete logarithm (DL) system, with/without random oracle respectively.