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A PLA-based bagasse cellulose composite material with excellent performance and low cost was prepared. As one of the most commonly used thermoplastic materials in fused deposition modeling (FDM), PLA is currently the most widely used three-dimensional (3D) printing technology. It has the natural advantage of being biodegradable. However, due to its poor toughness, it cannot meet the requirements for 3D printing consumables in some areas. Therefore, polylactic acid (PLA) is used as the matrix, tert-butyl peroxybenzoate (TBPB) are used as the free radical initiator, and glycidyl methacrylate (GMA) is used as the reaction monomer to prepare the PLA-GMA graft product, which realizes the toughening of PLA, and the PLA/PLA-GMA/BC (bagasse cellulose) composite material is prepared by the physical blending method, which realizes the reinforcement of PLA; it was proved by fourier transform infrared spectroscopy (FTIR) and 1H NMR that GMA was successfully grafted onto the PLA molecular chain, and the influence of the grafting rate on the toughness of PLA-GMA was explored. It was concluded that the grafting rate of PLA-GMA with the best toughness was 10.33%. The strength is 15.94 MPa, the modulus of elasticity is 969.01 MPa, and the elongation at break is 278.17%, which is about 44 times the elongation at break of pure PLA. The PLA/PLA-GMA/BC composite material with high cellulose loading was prepared by physical blending. The effect of PLA-GMA content, BC particle size and BC content on the properties of composite materials was explored. The results showed that PLA-GMA when the addition amount is 25%, the capacity enhancement effect is the best; when the additional amount of BC is as high as 40%, the PLA/PLA-GMA/BC composite still has good mechanical properties, and the addition of BC can promote the crystallization of PLA; DSC results show that BC can promote the crystallization of PLA, and the addition of PLA-GMA is not conducive to the composite material the formation of PLA crystalline regions; the temperature at the maximum decomposition rate of 40% BCB/25% PLA-GMA/PLA composite material is 355.44 ℃, and the thermal stability is improved. This study proves that the functional group properties of GMA realize the toughening and enhanced dual modification of polylactic acid, which expands the choice and application range of FDM 3D printing materials.

In this paper, the effect of D0 temperature, Kappa factor and the final pH value on bleaching sulfate bleached pine wood pulp was studied. The results showed that the bleaching efficiency was better when the pH value was 4, and the amount of absorbable organic halogen (AOX) in the bleaching wastewater was decreased. The Kappa factor is linear with the whiteness in the range of 0–0.15. With the increase of the Kappa factor, the amount of AOX in bleaching wastewater of D0 and Ep gradually increases. High temperature bleaching can reduce AOX production, but some fibers are hydrolyzed, leading to a decrease in pulp viscosity. The effects of chlorine dioxide solution adding sodium dihydrogen phosphate (NaH2PO4) and dimethylsulfoxide (DMSO) on pulp bleaching were investigated. The results showed that both solutions could reduce the amount of AOX in bleaching wastewater. Among them, the addition of NaH2PO4 in chlorine dioxide increased pulp whiteness, while the addition of DMSO was the opposite. Scanning electron microscope showed that a small amount of hollow cracks and more voids appeared on the surface of pulp fibers after the addition of NaH2PO4. Pulp fibers bleached by the chlorine dioxide adding DMSO have more folds and less voids on the surface. The surface wrinkles of pulp fibers increased with the addition of DMSO and the voids were less. FT-IR showed that the number of chromophore groups in the pulp bleached by chlorine dioxide adding NaH2PO4 were decreased. However, the lignin characteristic absorption peak in the pulp bleached by chlorine dioxide adding DMSO increased at the intensity of 1062 and 1160 cm−1, which indicated that there were more residual chromophore groups.

The modulation p-doping technique has emerged as an effective way to optimize the carrier dynamics process of quantum dot (QD) structures. Here, the laser structures based on the 1.3 μm multiple-layer InAs/GaAs QD were fabricated with and without modulation p-doping. The carrier relaxation rate was increased after modulation p-doping, as demonstrated by transient absorption spectroscopy. The higher relaxation rate in p-doped QDs could be explained by more rapid carrier–carrier scattering process originating from increasing of the hole quasi-Fermi-level movement that increases the probability of occupancy of the valence states. In addition, the lasing behavior of Fabry–Perot lasers with and without modulation p-doping was investigated and compared. It was found that the ground state (GS) lasing in the absence of facet coating was successfully achieved in a p-doped laser diode with short cavity length (400 μm), which can be attributed to the higher GS saturation gain caused by p-doping. With assistance of a designed TiO2/SiO2 facet coating whose central wavelength (∼1480 nm) is far beyond the lasing wavelength of 1310 nm, the GS lasing could be realized in a laser diode with short cavity lengths (300 μm) under continuous wave operation at room temperature, implying great potential for the development of low-cost and high-speed directly modulated lasers.

Ferroelectric materials have multiple characteristics in ferroelectric, piezoelectric, pyroelectric properties, which provide an attractive prospect for simultaneously harvesting multiple energy sources for catalytic applications. However, the crucial challenge for wastewater purification lies in the development of ferroelectric materials with improved functions and the design of advanced oxidation processes. Herein, Sr0.3Ba0.7TiO3 (SBT-0.3) nano-catalysts modified by PVP surfactant could significantly promote water recovery efficiency from the rhodamine B (RhB), which is as high as 98% by simultaneously collecting two types of energy sources of mechanical friction and temperature fluctuation from the natural environment for tribo-/pyro-catalysis under dark conditions. It was found that the samples containing PVP surfactant show significantly improved performance in the separation of charge carriers in comparison with those without PVP surfactant. The permanent polarization in SBT-0.3, coupled with the piezo-/pyro-potential, could generate internal field and therefore reduce charge recombination. It also helps to absorb charged species from the dye solution, which favors the reaction with active oxygen to cause the cleavage and breakdown of organic molecules. The mechanism of RhB decomposition mediated by SBT-0.3 ferroelectric is also discussed. This work favors us to in-depth understanding for the tribo-/pyro-catalysis and hence proposes a new strategy to improve the water purification efficiency of ferroelectric nanocrystals.

A semiconductor polymer with side-chain oxetane groups was synthesized to form highly fluorescent, functionalized, and ultra-stable polymer dots (Pdots). A facile light-induced strategy covalently links functional polyethylene glycol (PEG) molecules to polymer dots while simultaneously providing functional groups for bioconjugation. The influence of photo-crosslinkable side-chains and PEG molecules on the properties and performance of Pdots was systematically investigated. The Pdots functionalized by photo-crosslinking show specific labeling and negligible non-specific binding as compared to non-functionalized Pdots. The results provide a viable strategy for nanoparticle assembly and functionalization.

Light has been widely used for cancer therapeutics such as photodynamic therapy (PDT) and photothermal therapy. This paper describes a strategy called enzyme-enhanced phototherapy (EEPT) for cancer treatment. We constructed a nanoparticle platform by covalent conjugation of glucose oxidase (GOx) to small polymer dots, which could be persistently immobilized into a tumor. While the malignant tumors have high glucose uptake, the GOx efficiently catalyzes the glucose oxidation with simultaneous generation of H2O2. Under light irradiation, the in situ generated H2O2 was photolyzed to produce hydroxyl radical, the most reactive oxygen species, for killing cancer cells. In vitro assays indicated that the cancer cells were destroyed by using a nanoparticle concentration at 0.2 μg/mL and a light dose of ∼120 J/cm2, indicating the significantly enhanced efficiency of the EEPT method when compared to typical PDT that requires a photosensitizer of >10 μg/mL for effective cell killing under the same light dose. Furth...

A self-supporting macroporous graphene foam was prepared by template method. This foam which was fabricated by reduced graphene oxide (rGO) has good conductivity, and it also has large surface both in the foam interior and outside surface. The surface can offer a good platform to introduce active materials into the foam. TiO2 nanorods were grown on the foam framework using hydrothermal synthesized method. Due to a well-ordered macroporous structure and high conductivity of the reduced graphene oxide scaffold, the light utilizing in the composite TiO2/rGO foam will increase, and the photoinduced electron also transports quickly to the substrate. These advantages resulted in a better photocurrent response. Furthermore, the well photo induced electron transports will also lead to better photocatalytic degradation property. The enhanced absorption performance, photocurrent response, photocatalytic degradation property of composite TiO2/rGO foam will make this foam a promising material for practical applications in the environmental protection field.

Photodynamic therapy (PDT) is a promising treatment modality for clinical cancer therapy. However, the therapeutic effect of PDT is strongly dependent on the property of photosensitizer. Here, we developed photo-cross-linkable semiconductor polymer dots doped with photosensitizer Chlorin e6 (Ce6) to construct a nanoparticle platform for photodynamic therapy. Photoreactive oxetane groups were attached to the side chains of the semiconductor polymer. After photo-cross-linking reaction, the Ce6-doped Pdots formed an interpenetrated structure to prevent Ce6 leaching out from the Pdot matrix. Spectroscopic characterizations revealed an efficient energy transfer from the polymer to Ce6 molecules, resulting in amplified generation of singlet oxygen. We evaluated the cellular uptake, cytotoxicity, and photodynamic effect of the Pdots in gastric adenocarcinoma cells. In vitro photodynamic experiments indicated that the Ce6-doped Pdots (∼10 μg/mL) effectively killed the cancer cells under low dose of light irradiation (∼60 J/cm

An operational modal response method for application to the structure health and integrity of pipelines is investigated. The modal response characteristics of externally supported pipe structures are quantified through flow Reynolds number (Red) variation. Pipe flow turbulence and the resulting hydrodynamic pressure fluctuations on the interior pipe wall provide the structural forcing mechanism, and signals from wall-mounted accelerometers provide the system response. During experiments, the Reynolds number is varied from 51,000 to 154,000. Over this Reynolds number range, the pipe flow turbulence was found sufficient enough to excite the structure at frequencies up to 400 Hz. Modal response characteristics obtained through Reynolds number variation were found to be in agreement with results from impact hammer modal testing. The in-situ modal response method developed was applied to two different structural health monitoring investigations, one involving loss-of-material and the other involving loss-of-fluid. The loss-of-material scenario simulated the process of external pipe wall corrosion, and the developed method was able to detect material loss as small as 1.4%. The loss-of-fluid scenario simulated a small leak. Despite the low operating pressure of 0.024 MPa, the methodology was able to detect fluid loss as low as 0.1% of the bulk flow rate. The developed method has the potential to offer in-situ continuous pipeline health monitoring that relies on the continuous changes (flow rate, product viscosity, product density) that are inherent to an operational pipeline system.

Control of stereochemistry plays a key role in medicinal chemistry, material and life science. As a prominent AIE luminogen, tetraphenylethene (TPE) derivatives have E/Z isomers which are challenging to separate even by HPLC. Herein, we designed oxetane-substituted TPE (TPE-2OXE) and separated pure isomers by simple column chromatography with high yields, as confirmed by mass spectrometry, IR and NMR spectroscopy. The isomerization of the two isomers can occur by photo- and thermo-activation. Importantly, (Z)-TPE-2OXE isomer solid shows bathochromic emission with a quantum yield 5 times higher than that of (E)-TPE-2OXE. The differences in emission wavelength and quantum yield are derived from distinct emission mechanisms of locally excited (LE) state emission of (E)-TPE-2OXE and charge transfer (CT) state emission of (Z)-TPE-2OXE. The two isomers are also good piezochromic luminescent materials, which have not only an obvious emission color shift but also significantly enhanced luminescence brightness by ...

A convenient, nontoxic and efficient way is developed for the fabrication of three-dimensional free-standing graphene foam modified with ZnO nanorods arrays. The resulting composite foam (ZnO/rGO foam) has a hierarchical micro-nano structure. The conductive macroporous structure will enhance the light harvesting, the photoinduced electron-hole separation and electrons transport. Moreover, the ZnO nanorods on the graphene surface will act as the active material which show the dramatic improvement in photocurrent generation and photocatalytic activity. This simple and scalable manufacturing technology will open a reasonable design and engineering route for the high-performance photoelectric conversion apparatus and environmental pollutant management.

Nowadays the yellow emissive YAG:Ce phosphors play an important role in fabricating white light-emitting diodes (WLEDs). However, they are deficient in red emission so we proposed polymer dot phosphors to compensate this poor photometric property. The polymer dot phosphors exhibited broad emission bands under excitation of a blue LED chip with weak reabsorption. We demonstrated hybrid white light-emitting diodes with commendable color rendering index (85–95), widely variable color temperatures (3050–7295 K) and high luminous efficacy (72–80 lm W−1 operated at 20 mA) by combining green and red emitting polymer dots on YAG:Ce-based WLEDs. The optical properties suggest the polymer dot phosphors are the suitable color converting materials, which may enable their application in WLED lighting.

Introduction: Small cell lung cancer (SCLC) is one of the two recalcitrant cancers designated by NCI, and its 2-year survival rate has not improved over the past two decades. Novel therapy is urgently needed. BET bromodomain inhibitor (BETi), which targets transcriptional coactivator BET bromodomain proteins, has been reported to be effective in SCLC. However, given that SCLC is notorious for rapid development of drug resistance, it is necessary to identify drugs that can synergize with BETi to form a combinatorial drug regimen. Methods: A high-throughput drug combination matrix screen was performed to identify potential agents that can synergize with BETi. Synergy between the identified candidate drugs and BETi was further validated in various SCLC cell lines by using the CellTiter-Glo assay as well as in several SCLC PDX models by examining tumor growth suppression and survival of tumor-bearing mice. Cleavage of caspase 3 and poly (ADP-ribose) polymerase (PARP) was analyzed by IHC and western blot in SCLC PDX tumors and in vitro cell lines to assess apoptosis after drug treatment, respectively. Results: The high-throughput screen identified multiple inhibitors of the PI-3K/AKT/mTOR pathway to synergize with BETi by causing a significantly higher rate of apoptosis and cell growth inhibition. A comparison among the inhibitors that specifically target PI-3K, AKT or mTOR revealed that the combination of BETi and mTOR inhibitor (mTORi) have the highest level of synergy. The BETi/mTORi combo also showed synergy in several SCLC cell lines that are initially resistant to single agent BETi. The antitumor effect of the BETi/mTORi combinatorial treatment was further confirmed in several SCLC PDX mouse models. When compared to either single agent or vehicle, the BETi/mTORi combo treatment led to a greater degree of tumor growth suppression and a more prolonged survival of the tumor-bearing mice. This enhanced antitumor effect is connected with a significantly more apoptosis (cleaved caspase 3 or PARP) found in SCLC tumor tissues and cell lines treated with the BETi/mTORi combo. Conclusion: mTORi can enhance the antitumor effect of BETi in SCLC by causing more apoptosis. Citation Format: ANJU KUMARI, Lisa Gesumaria, Patricia Fetsch, Markku Miettinen, Keith Hughitt, Beverly Mock, Craig Thomas, David S. Schrump, Haobin Chen. mTOR inhibitor enhances anti-tumor effect of BET bromodomain inhibitor in small cell lung cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5328.

In this study, we investigated the barrier properties of a montmorillonite-reinforced biomass material, starch. Organically modified montmorillonite materials were prepared from natural montmorillonite by reacting it with dodecyl trimethyl ammonium chloride, dodecyl dimethyl benzyl ammonium chloride or octadecyl trimethyl ammonium chloride under ultrasonic conditions. The composite starch films incorporated with these organically modified montmorillonite samples were characterized by scanning electron microscopy, transmission electron microscopy, infrared spectroscopy and X-ray diffraction. The results showed that the introduction of montmorillonite decreases the transmittance of the composite film by 10% in the visible region and significantly inhibits UV-light transmittance. The decomposition temperature of the composite film ranges from 200 to 500 &deg, C, with a weight loss rate of 80%. The distance between the montmorillonite layers increases from 0.14 nm in the non-magnetized state to 1.49 nm after magnetization. The oxygen permeability of the starch film modified by organic montmorillonite (0.067 cm3/m2&middot, d) is lower than that of the montmorillonite starch film without magnetization (0.097cm3/m2&middot, d). The oxygen barrier capacity is close to zero. Particularly in the ordered magnetic montmorillonite starch composite film, the oxygen barrier ability is the best. Therefore, modified montmorillonite could serve as an excellent reinforcing agent for cassava starch films and effectively improve the oxygen barrier performance of the films.

SUMMARY Clonal evolution of osimertinib-resistance mechanisms in EGFR mutant lung adenocarcinoma is poorly understood. Using multi-region whole-exome and RNA sequencing of prospectively collected pre- and post-osimertinib-resistant tumors, including at rapid autopsies, we identify a likely mechanism driving osimertinib resistance in all patients analyzed. The majority of patients acquire two or more resistance mechanisms either concurrently or in temporal sequence. Focal copy-number amplifications occur subclonally and are spatially and temporally separated from common resistance mutations such as EGFR C797S. MET amplification occurs in 66% (n = 6/9) of first-line osimertinib-treated patients, albeit spatially heterogeneous, often co-occurs with additional acquired focal copy-number amplifications and is associated with early progression. Noteworthy osimertinib-resistance mechanisms discovered include neuroendocrine differentiation without histologic transformation, PD-L1, KRAS amplification, and ESR1-AKAP12, MKRN1-BRAF fusions. The subclonal co-occurrence of acquired genomic alterations upon osimertinib resistance will likely require targeting multiple resistance mechanisms by combination therapies., In Brief Roper et al. perform multi-region whole-exome and RNA sequencing of pre- and post-resistant tumors from EGFR mutant lung cancer patients treated with osimertinib. They uncover the subclonal co-occurrence of acquired genomic alterations upon osimertinib resistance suggesting combination first-line therapies may prevent or delay key resistance mechanisms., Graphical Abstract

The modal response characterization of structures is a proven and reliable technique used to monitor system behavior and change, providing information for condition assessment and damage identification. In traditional modal response characterization procedures, an external mass excitation source is used to excite the system, and this is modeled as an impact function. This provides system forcing across a broad range of frequencies. In this investigation, an in-situ method of system excitation is explored. The modal characteristics of externally-supported pipe structures are investigated by varying the flow Reynolds number (Red). Given the increase in flow turbulence with Reynolds number, hydrodynamic pressure fluctuations on the pipe wall provide a varying excitation source. This removes the requirement for an external excitation source. A comparative analysis of data sets collected for both Acrylic and ABS pipe material show similar pressure spectra, while vibration spectra change significantly. Pressure spectra reveal a character whereby the spectral energy increases with increasing Reynolds number. A comparison of in-situ results to those obtained using traditional impact response tests show that vibration spectra collected through Reynolds number variation successfully capture the modal characteristics of the pipe-structure.

Rationale: The effects of hookah smoke on respiratory epithelia have not been well characterized. Objectives: To characterize and compare the effects of hookah tobacco smoke and conventional cigarette smoke on the epigenome and transcriptome of human respiratory epithelia. Methods: Normal human small airway epithelial cells and cyclin-dependent kinase 4/human telomerase reverse transcriptase–immortalized human bronchial epithelial cells were cultured for 5 days in normal media in the presence or absence of water pipe condensates or cigarette smoke condensates under relevant exposure conditions. CyQUANT assay (Thermo Fisher Scientific), RNA sequencing, quantitative reverse transcriptase–polymerase chain reaction, and Western blotting techniques were used to examine/compare the effects of hookah and cigarette smoke on cell proliferation, messenger RNA/microRNA expression, and global histone marks. Results: Water pipe condensates– and cigarette smoke condensates–mediated, dose-dependent growth-inhibitory effects in cultured respiratory epithelial cells were measured. Under conditions mediating equipotent mild to moderate growth-inhibitory effects, water pipe condensates as well as cigarette smoke condensates decreased histone H4 lysine 15 acetylation (H4K16ac) and histone H4 lysine 20 trimethylation (H4K20me3) levels in small airway epithelial cells and human bronchial epithelial cells; these histone alterations are putative “hallmarks of cancer.” RNA sequencing analysis demonstrated that cigarette smoke condensates and water pipe condensates mediated dose-dependent alterations in gene expression in small airway epithelial cells and human bronchial epithelial cells. A total of 873 genes were commonly regulated (fold change >2) by water pipe condensates (1.0 mg/ml) and cigarette smoke condensates (0.05 mg/ml) in small airway epithelial cells, whereas a total of 1,577 genes were commonly regulated by water pipe condensates (1.0 mg/ml) and cigarette smoke condensates (0.05 mg/ml) in human bronchial epithelial cells. Ingenuity Pathway Analysis (QIAGEN Bioinformatics) of the 100 genes commonly regulated by water pipe condensates and cigarette smoke condensates in small airway epithelial cells and human bronchial epithelial cells demonstrated that the top three activated upstream regulators are cigarette smoke (z-score = 2.577), benzo[a]pyrene (z-score = 2.905), and nuclear factor (erythroid-derived 2)-like 2 (NFE2L2, Nrf2) (z-score = 2.531). Analysis of downstream effects indicated that growth of epithelial tissue was predicted to be increased (z-score = 2.813; P

Optical Coherence Tomography (OCT) is a valuable technology that has been used to obtain microstructure images of tissue, and has several advantages, though its applications are limited in high-scattering tissues. Therefore, semiconducting polymer nanoparticles (SPNs) that possess strong absorption characteristics are applied to decrease light scattering in tissues and used as exogenous contrast agents for enhancing the contrast of OCT imaging detection. In this paper, we prepared two kinds of SPNs, termed PIDT-TBZ SPNs and PBDT-TBZ SPNs, as the contrast agents for OCT detection to enhance the signal. Firstly, we proved that they were good contrast agents for OCT imaging in agar-TiO2. After that, the contrast effects of these two SPNs were quantitatively analyzed, and then cerebral blood vessels were monitored by a home-made SD-OCT system. Finally, we created OCT images in vitro and in vivo with these two probes and performed quantitative analysis using the images. The results indicated that these SPNs created a clear contrast enhancement of small vessels in the OCT imaging process, which provides a basis for the application of SPNs as contrast agents for bioimaging studies.

Traditional frequency warping algorithms in speech recognition mainly consider the spectrum offset caused by different vocal tract length. But in addition to the vocal tract length, the pronunciation diversity is also affected by the glottis difference. At the same time, the difference mentioned above is also interconnected. Although piecewise linear frequency warping considers the effect of the glottis and vocal tract, it will lose some information because it is not continuous and it only considers the effect of single factor. This paper proposes a two factor frequency warping algorithm based on the weighted fusion of the glottis resonant factor and the third formant factor. Compared with piecewise linear frequency warping, the method of spectrum aligned in this algorithm is smoother and takes the relationship between the glottis and vocal tract into account. Experimental results show that the recognition rate of the proposed algorithm is improved in the case of training data and testing data both matching and mismatching.

Semiconductor polymer dots (Pdots) were encapsulated into a SiO2 matrix to form fluorescent nanocomposites using a modified Stober method. Significantly, the photostability and thermal stability of the nanocomposites were greatly improved as compared to those of pure Pdots. The luminescent nanocomposites combined with blue LEDs result in white-light emitting devices with a high color-rendering index.

Organic semiconducting materials have attracted significant attention for use in optoelectronic devices, as they can significantly improve device performance. Herein, a donor–acceptor conjugated polymer (poly(isoindigo-thiopheneylbenzothiadiazole, PID-TBT) was synthesized, which has strong and broad absorption in the visible region (400–800 nm). The band gap of PID-TBT is 1.65 eV. The PID-TBT honeycomb film with a porous structure was easily fabricated by the breath figure method. Compared with the smooth PID-TBT film, the honeycomb film shows significant enhancement in light capture capability and the efficiency of photoelectric conversion. The reflectance of the honeycomb film is reduced by 7% and the photocurrent is tenfold higher than that of the smooth film. Apart from designing new molecules by complex reactions, this work demonstrated that photoelectric conversion can be easily improved by introducing micro or nanostructures into devices.

Aggregation induced emission (AIE) has attracted considerable interest for the development of fluorescence probes. However, controlling the bioconjugation and cellular labeling of AIE dots is a challenging problem. Here, this study reports a general approach for preparing small and bioconjugated AIE dots for specific labeling of cellular targets. The strategy is based on the synthesis of oxetane-substituted AIEgens to generate compact and ultrastable AIE dots via photo-crosslinking. A small amount of polymer enriched with oxetane groups is cocondensed with most of the AIEgens to functionalize the nanodot surface for subsequent streptavidin bioconjugation. Due to their small sizes, good stability, and surface functionalization, the cell-surface markers and subcellular structures are specifically labeled by the AIE dot bioconjugates. Remarkably, stimulated emission depletion imaging with AIE dots is achieved for the first time, and the spatial resolution is significantly enhanced to ≈95 nm. This study provides a general approach for small functional molecules for preparing small sized and ultrastable nanodots.

Semiconducting polymer dots (Pdots) have shown great promise in biomedical applications, including biosensing, drug delivery, and live imaging of cells and biomolecules. Insight into the mechanism and regulation of cellular uptake and intracellular metabolism of Pdots is important for the development of superior Pdots-based theranostic nanoconjugates. Herein, we performed real-time imaging of endocytosis and intracellular trafficking of a type of fluorescent Pdots that showed excellent biocompatibility in various types of cells. The endocytic routes and kinetics of Pdots were differently regulated in distinct cell types. Following endocytosis, Pdots were transported in vesicles along microtubule and destined for lysosomes. Furthermore, our results revealed exosome-mediated extracellular release of Pdots and have tracked the dynamic process at the single particle level. These results provide new insight into the design of more effective and selective imaging probes as well as drug carriers.

A new method of mechanical axis planning has recently been suggested to aid in corrective surgery for hallux valgus (HV) deformity, which aims to identify the ideal position for the first metatarsal after correction. We investigated the influence of the mechanical axis angle (MAA) correction on the outcomes of corrective HV surgery. We reviewed 50 radiographs to identify the "normal" MAA range within the population. We also reviewed the medical records of 100 patients who had undergone scarf osteotomy at our institution from January 2011 to December 2013. These patients were segregated into 2 groups according to their postoperative MAA: those within the normal range (normal group) and those outside this range (outlier group). We compared the pre- and postoperative functional scores between the 2 groups using statistical analysis. The normal MAA range within our population was 12.5° ± 0.8° (range 11.0° to 14.3°). We found that the physical component summary score of the short-form 36-item health survey was significantly poorer for the outlier group at 6 and 24 months postoperatively compared with the normal group, although the other postoperative scores were comparable. Surgical correction of the MAA to the normal range of the patient population can be recommended because it provides improved quality of life. However, further studies are required to investigate the influence of MAA planning on other standardized foot and ankle scores.

Human ABH2 repairs DNA lesions by using an Fe(II)- and αKG-dependent oxidative demethylation mechanism. The structure of the active site features the facial triad of protein ligands consisting of the side chains of two histidine residues and one aspartate residue that is common to many non-heme Fe(II) oxygenases. X-ray absorption spectroscopy (XAS) of metallated (Fe and Ni) samples of ABH2 was used to investigate the mechanism of ABH2 and its inhibition by Ni(II) ions. The data are consistent with a sequential mechanism that features a five-coordinate metal center in the presence and absence of the α-ketoglutarate cofactor. This aspect is not altered in the Ni(II)-substituted enzyme, and both metals are shown to bind the cofactor. When the substrate is bound to the native Fe(II) complex with α-ketoglutarate bound, a five-coordinate Fe(II) center is retained that features an open coordination position for O2 binding. However, in the case of the Ni(II)-substituted enzyme, the complex that forms in the prese...

The bandwidth of white light emitting diodes (WLEDs) is an important factor that affects most of the system performances in visible light communication (VLC). It is mainly limited by the down-conversion phosphors. We propose in this paper to employ nanomaterial phosphors with short fluorescence lifetime and high quantum yield in VLC. The white-emitting device of bandwidth-based lifetime was fabricated by using several kinds of nanophosphors with different fluorescence lifetimes. Moreover, we proposed two theoretical models to analyze the factors that affect bandwidth. Compared with the commercial YAG-based WLEDs, the bandwidth of nanophosphor-based WLEDs can be improved over three times and close to the blue excitation sources. Our study indicates that nanophosphors can become promising fluorescent materials in VLC, and provides a new direction for developing wide-bandwidth VLC systems.

Epigenetic silencing of tumor suppressor genes commonly occurs in human cancers via increasing DNA methylation and repressive histone modifications at gene promoters. However, little is known about how pathogenic environmental factors contribute to cancer development by affecting epigenetic regulatory mechanisms. Previously, we reported that both hypoxia and nickel (an environmental carcinogen) increased global histone H3 lysine 9 methylation in cells through inhibiting a novel class of iron- and α-ketoglutarate-dependent histone demethylases. Here, we investigated whether inhibition of histone demethylase JMJD1A by hypoxia and nickel could lead to repression/silencing of JMJD1A-targeted gene(s). By using Affymetrix GeneChip and ChIP-on-chip technologies, we identified Spry2 gene, a key regulator of receptor tyrosine kinase/extracellular signal-regulated kinase (ERK) signaling, as one of the JMJD1A-targeted genes in human bronchial epithelial BEAS-2B cells. Both hypoxia and nickel exposure increased the level of H3K9me2 at the Spry2 promoter by inhibiting JMJD1A, which probably led to a decreased expression of Spry2 in BEAS-2B cells. Repression of Spry2 potentiated the nickel-induced ERK phosphorylation, and forced expression of Spry2 in BEAS-2B cells decreased the nickel-induced ERK phosphorylation and significantly suppressed nickel-induced anchorage-independent growth. Taken together, our results suggest that histone demethylases could be targets of environmental carcinogens and their inhibition may lead to altered gene expression and eventually carcinogenesis.

Nanocavities composed of lipids and block polymers have demonstrated great potential in biomedical applications such as sensors, nanoreactors, and delivery vectors. However, it remains a great challenge to produce nanocavities from fluorescent semiconducting polymers owing to their hydrophobic rigid polymer backbones. Here, we describe a facile, yet general strategy that combines photocrosslinking with nanophase separation to fabricate multicolor, water-dispersible semiconducting polymer nanocavities (PNCs). A photocrosslinkable semiconducting polymer is blended with a porogen such as degradable macromolecule to form compact polymer dots (Pdots). After crosslinking the polymer and removing the porogen, this approach yields semiconducting polymer nanospheres with open cavities that are tunable in diameter. Both small molecules and macromolecules can be loaded in the nanocavities, where molecular size can be differentiated by the efficiency of the energy transfer from host polymer to guest molecules. An anticancer drug doxorubicin (Dox) is loaded into the nanocavities and the intracellular release is monitored in real time by the fluorescence signal. Finally, the efficient delivery of small interfering RNA (siRNA) to silence gene expression without affecting cell viability is demonstrated. The combined features of bright fluorescence, tunable cavity, and efficient drug/siRNA delivery makes these nanostructures promising for biomedical imaging and drug delivery.

Previously we reported that mithramycin represses multiple pathways critical for stem cell signaling and pluripotency in lung cancer cells. This phenomenon coincided with decreased side population fraction and dramatic dose-dependent growth arrest of lung cancer cells in vitro and in vivo. In the present study, microarray, quantitative reverse transcriptase polymerase chain reaction and immunoblot experiments were performed to further examine the effects of mithramycin on stem cell gene expression in lung cancer cells. This analysis revealed that mithramycin significantly inhibited expression of musashi-2 (MSI2), which encodes a RNA binding protein that mediates self-renewal and pluripotency in normal stem cells and has been implicated in mediating aggressive phenotype of a variety of human malignancies. MSI2 expression levels were significantly increased in non–small cell lung cancer lines and were even more dramatically elevated in small-cell lung cancer lines relative to cultured normal human respiratory epithelial cells (small airway epithelial cells / normal human bronchial epithelia / human bronchial epithelial cells; P

Conjugated polymers have recently attracted a great deal of attention for applications in photodynamic therapy (PDT) because of their light-harvesting capability, efficient energy transfer, and singlet oxygen generation properties. This review describes recent advances in PDT development, including therapeutic mechanisms of PDT in cancer treatments, light excitation methods, and especially recent advances of conjugated polyelectrolytes and conjugated polymer nanoparticles as photosensitizers. The future direction on PDT and further development of conjugated polymer photosensitizers are discussed. The aim of this review is to stimulate innovative ideas to synthesize a new generation of conjugated polymer photosensitizers and promote their translation to clinical applications of PDT.

Hexavalent chromium [Cr(VI)] is a mutagen and carcinogen, and occupational exposure can lead to lung cancers and other adverse health effects. Genetic changes resulting from DNA damage have been proposed as an important mechanism that mediates chromate's carcinogenicity. Here we show that chromate exposure of human lung A549 cells increased global levels of di- and tri-methylated histone H3 lysine 9 (H3K9) and lysine 4 (H3K4) but decreased the levels of tri-methylated histone H3 lysine 27 (H3K27) and di-methylated histone H3 arginine 2 (H3R2). Most interestingly, H3K9 dimethylation was enriched in the human MLH1 gene promoter following chromate exposure and this was correlated with decreased MLH1 mRNA expression. Chromate exposure increased the protein as well as mRNA levels of G9a a histone methyltransferase that specifically methylates H3K9. This Cr(VI)-induced increase in G9a may account for the global elevation of H3K9 dimethylation. Furthermore, supplementation with ascorbate, the primary reductant of Cr(VI) and also an essential cofactor for the histone demethylase activity, partially reversed the H3K9 dimethylation induced by chromate. Thus our studies suggest that Cr(VI) may target histone methyltransferases and demethylases, which in turn affect both global and gene promoter specific histone methylation, leading to the silencing of specific tumor suppressor genes such as MLH1.

Nickel compounds are important occupational and environmental pollutants. Chronic exposure to these pollutants has been connected with increased risks of respiratory cancers and cardiovascular diseases. However, it is still not clear what are the specific molecular targets for nickel toxicity and carcinogenicity. Here, we propose that the iron- and 2-oxoglutarate-dependent dioxygenase family enzymes are important intracellular targets that mediate the toxicity and carcinogenicity of nickel. In support of this hypothesis, our data show that three different classes of enzymes in this iron- and 2-oxoglutarate-dependent dioxygenase family, including HIF-prolyl hydroxylase PHD2, histone demethylase JHDM2A/JMJD1A, and DNA repair enzyme ABH3, are all highly sensitive to nickel inhibition. Inactivation of these enzymes accounts for a number of deleterious effects caused by nickel in cells, namely hypoxia-mimic stress and aberrant epigenetic changes. Future studies on nickel’s effects on these iron- and 2-oxoglutarate-dependent dioxygenases would deepen our understanding on nickel toxicity and carcinogenicity.

Post-translational modifications of histones play a critical role in regulating genome structures and integrity. We have focused on the regulatory relationship between covalent modifications of histone H3 lysine 9 (H3K9) and H3S10 during the cell cycle. Immunofluorescence microscopy revealed that H3S10 phosphorylation in HeLa, A549, and HCT116 cells was high during prophase, prometaphase, and metaphase, whereas H3K9 monomethylation (H3K9me1) and dimethylation (H3K9me2), but not H3K9 trimethylation (H3K9me3), were significantly suppressed. When H3S10 phosphorylation started to diminish during anaphase, H3K9me1 and H3K9me2 signals reemerged. Western blot analyses confirmed that mitotic histones, extracted in an SDS-containing buffer, had little H3K9me1 and H3K9me2 signals but abundant H3K9me3 signals. However, when mitotic histones were extracted in the same buffer without SDS, the difference in H3K9me1 and H3K9me2 signals between interphase and mitotic cells disappeared. Removal of H3S10 phosphorylation by pretreatment with lambda-phosphatase unmasked mitotic H3K9me1 and H3K9me2 signals detected by both fluorescence microscopy and Western blotting. Further, H3S10 phosphorylation completely blocked methylation of H3K9 but not demethylation of the same residue in vitro. Given that several conserved motifs consisting of a Lys residue immediately followed by a Ser residue are present in histone tails, our studies reveal a potential new mechanism by which phosphorylation not only regulates selective access of methylated lysines by cellular factors but also serves to preserve methylation patterns and epigenetic programs during cell division.

Arsenic (As) is a well-characterized human carcinogen but is generally not mutagenic. The evidence that As induces both loss of global DNA methylation and gene promoter DNA hypermethylation has suggested that epigenetic mechanisms may play an important role in As-induced carcinogenesis. In the present study, we examined the change in histone methylation by As exposure. In human lung carcinoma A549 cells, exposure to inorganic trivalent As (arsenite) increased H3K9 dimethylation (H3K9me2) and decreased H3K27 trimethylation (H3K27me3), both of which represent gene silencing marks, while increasing the global levels of the H3K4 trimethylation (H3K4me3), a gene-activating mark. The increase in H3K9me2 was mediated by an increase in the histone methyltransferase G9a protein and messenger RNA levels. We also observed strikingly significant altered histone modifications induced by very low-dose (0.1 microM) arsenite. Taken together, these results suggest a potential mechanism by which As induces carcinogenesis through the alteration of specific histone methylations that represent both gene silencing and activating marks. Furthermore, these marks are known to affect DNA methylation, and it is likely that arsenic's effect is not limited to histone modifications alone, but extends, perhaps by them, to DNA methylations as well. Future studies in our laboratory will address the genomic location of these silencing and activating marks using ChIP-on-chip technology.

Fingerprint imaging and recognition represent the most important approach in personal identification. Here we designed and synthesized oxetane-functionalized semiconductor polymer dots (Ox-Pdots) for covalent patterning and rapid visualization of latent fingerprints. The high fluorescence brightness, large Stokes shift, and excellent surface properties of the Ox-Pdots lead to fingerprint imaging with high sensitivity and resolution. Fingerprint ridge structures with the first, second, and third levels of details were clearly developed within minutes. The method was facile and robust for visualization of fingerprints on various surfaces including glass, metal, and plastics. Moreover, the oxetane groups in the Ox-Pdots undergo cross-linking reactions induced by a short-time UV irradiation, yielding 3-D intermolecular polymer network. The resulting fingerprint patterns exhibit unparalleled stability against rigorous treatment, as compared to those by traditional Pdots. Our results demonstrate that the Ox-Pdots hold great promise for latent fingerprint imaging and fluorescence anticounterfeiting applications.

We have previously reported that carcinogenic nickel compounds decreased global histone H4 acetylation and silenced the gpt transgene in G12 Chinese hamster cells. However, the nature of this silencing is still not clear. Here, we report that nickel ion exposure increases global H3K9 mono- and dimethylation, both of which are critical marks for DNA methylation and long-term gene silencing. In contrast to the up-regulation of global H3K9 dimethylation, nickel ions decreased the expression and activity of histone H3K9 specific methyltransferase G9a. Further investigation demonstrated that nickel ions interfered with the removal of histone methylation in vivo and directly decreased the activity of a Fe(II)-2-oxoglutarate-dependent histone H3K9 demethylase in nuclear extract in vitro. These results are the first to show a histone H3K9 demethylase activity dependent on both iron and 2-oxoglutarate. Exposure to nickel ions also increased H3K9 dimethylation at the gpt locus in G12 cells and repressed the expression of the gpt transgene. An extended nickel ion exposure led to increased frequency of the gpt transgene silencing, which was readily reversed by treatment with DNA-demethylating agent 5-aza-2'-deoxycytidine. Collectively, our data strongly indicate that nickel ions induce transgene silencing by increasing histone H3K9 dimethylation, and this effect is mediated by the inhibition of H3K9 demethylation.

Previous studies have demonstrated that exposure to polycyclic aromatic hydrocarbons (PAHs) and its derivatives is associated with an increased risk of skin cancers, and the carcinogenic effect of PAHs is thought to involve both tumor initiation and promotion. Whereas PAH tumor initiation is well characterized, the mechanisms involved in the tumor promotion of PAHs remain elusive. In the present study, we investigated the effects of PAHs on vascular endothelial growth factor (VEGF) expression by comparison of its induction between the active metabolite and its parent compound (B[a]PDE versus B[a]P) or between active compound and its relatively inactive analog (5-MCDE versus CDE). We found that exposure of cells to (+/-)-anti-benzo-[a]pyrene-7,8-diol-9,10-epoxide (B[a]PDE) or (+/-)-anti-5-methylchrysene-1,2-diol-3,4-epoxide (5-MCDE) led to marked induction of VEGF in Cl41 cells, whereas benzo[a]pyrene (B[a]P) or chrysene-1,2-diol-3,4-epoxide (CDE) did not exhibit significant inductive effects. Exposure of cells to B[a]PDE and 5-MCDE did not induce HIF-1alpha activation, whereas AP-1 was significantly activated. Moreover, overexpression of TAM67 (a dominant-negative mutant c-Jun) dramatically blocked that VEGF induction. Electrophoretic mobility shift assay showed that AP-1 was only able to specifically recognize and bind to its AP-1 potential binding site within -1136 and -1115 of the VEGF promoter region. Site-directed mutation of this AP-1 binding site eliminated the VEGF transcriptional activity induced by B[a]PDE, suggesting that the AP-1 binding site between -1136 and -1115 in the VEGF promoter region is critical for VEGF induction by B[a]PDE. In addition, overexpression of Deltap85 (a dominant-negative mutant PI-3K) impaired B[a]PDE- and 5-MCDE-induced VEGF induction. Considering our previous findings that PI-3K is an upstream mediator for c-Jun/AP-1 activation, we conclude that the VEGF induction by B[a]PDE and 5-MCDE is through PI-3K/AP-1-dependent and HIF-1alpha-independent pathways. These findings may help us to understand the mechanisms involved in PAH carcinogenic effects.

Although it has been well established that insoluble nickel compounds are potent carcinogens and soluble nickel compounds are less potent, the mechanisms remain unclear. Nickel compounds are weakly mutagenic, but cause epigenetic effects in cells. Previous studies have shown that insoluble nickel compounds enter cells by phagocytosis and silence gene expression, but the entry of soluble nickel compounds and their effects on gene silencing have not been well studied. Here, we have demonstrated, using a dye that fluoresces when nickel ions bind, that soluble nickel compounds were taken up by cells. Nickel ions localized initially in the cytoplasm, but later entered the nucleus and eventually silenced a transgene. In addition, we described three major changes in histone modification of cells exposed to soluble nickel compounds: (i) loss of acetylation of H2A, H2B, H3 and H4; (ii) increases of H3K9 dimethylation; and (iii) substantial increases of the ubiquitination of H2A and H2B. These effects were observed at nickel exposure conditions that had minimum effects on cell cytotoxicity. Moreover, we demonstrated that nickel-induced transgene silencing was associated with similar changes of histone modifications in their nuclesomes. This study is the first to show that nickel compounds increase histone ubiquitination in cells. These new findings will further our understanding of the epigenetic mechanisms of nickel-mediated carcinogenesis.

Both water soluble and insoluble nickel compounds have been implicated in the etiology of human lung and nasal cancers. Water insoluble nickel compounds have been shown to enter cells by phagocytosis and are contained in cytoplasmic vacuoles, which are acidified thus accelerating the dissolution of soluble nickel from the particles. Using Newport Green, a dye that fluoresces when ionic nickel is bound, we have shown that following exposure (48-72 h) of human lung (A549) cells to NiS particles, most of the nickel is contained in the nucleus, while cells exposed to soluble NiCl2 exhibit most of the ions localized in the cytoplasm. This effect is consistent with previously published reports showing that short-term exposure of cells to crystalline nickel particles (1-3 days) is able to epigenetically silence target genes placed near heterochromatin, while similar short-term exposure to soluble nickel compounds are not able to induce silencing of genes placed near heterochromatin. However, a 3 week exposure of cells to soluble NiCl2 is also able to induce gene silencing. A similar effect was found in yeast cells where nickel was able to silence the URA-3 gene placed near (1.3 kb) a telomere silencing element, but not when the gene was placed farther away from the silencing element (2.0 kb). In addition to epigenetic effects, nickel compounds activate hypoxia signaling pathways. The mechanism of this effect involves the ability of either soluble or insoluble nickel compounds to block iron uptake leading to cellular iron depletion, directly affect iron containing enzymes, or both. This results in the inhibition of a variety of iron-dependent enzymes, such as aconitase and the HIF proline hydroxylases (PHD1-3). The inhibition of the HIF proline hydroxylases stabilizes the HIF protein and activates hypoxic signaling. Additional studies have shown that nickel and hypoxia decrease histone acetylation and increase the methylation of H3 lysine 9. These events are involved in gene silencing and hypoxia can also cause these effects in human cells. It is hypothesised that the state of hypoxia either by low oxygen tension or as a result of agents that signal hypoxia under normal oxygen tension (iron chelation, nickel and cobalt) results in low levels of acetyl CoA, which is a substrate for histone and other protein acetylation. This effect may in part be responsible for the gene silencing following nickel exposure and during hypoxia.

Nickel (Ni) compounds are well-established carcinogens and are known to initiate a hypoxic response in cells via the stabilization and transactivation of hypoxia-inducible factor-1 alpha (HIF-1alpha). This change may be the consequence of nickel's interference with the function of several Fe(II)-dependent enzymes. In this study, the effects of soluble nickel exposure on cellular iron homeostasis were investigated. Nickel treatment decreased both mitochondrial and cytosolic aconitase (c-aconitase) activity in A549 cells. Cytosolic aconitase was converted to iron-regulatory protein 1, a form critical for the regulation of cellular iron homeostasis. The increased activity of iron-regulatory protein 1 after nickel exposure stabilized and increased transferrin receptor (Tfr) mRNA and antagonized the iron-induced ferritin light chain protein synthesis. The decrease of aconitase activity after nickel treatment reflected neither direct interference with aconitase function nor obstruction of [4Fe-4S] cluster reconstitution by nickel. Exposure of A549 cells to soluble nickel decreased total cellular iron by about 40%, a decrease that likely caused the observed decrease in aconitase activity and the increase of iron-regulatory protein 1 activity. Iron treatment reversed the effect of nickel on cytosolic aconitase and iron-regulatory protein 1. To assess the mechanism for the observed effects, human embryonic kidney (HEK) cells over expressing divalent metal transporter-1 (DMT1) were compared to A549 cells expressing only endogenous transporters for inhibition of iron uptake by nickel. The inhibition data suggest that nickel can enter via DMT1 and compete with iron for entry into the cell. This disturbance of cellular iron homeostasis by nickel may have a great impact on the ability of the cell to regulate a variety of cell functions, as well as create a state of hypoxia in cells under normal oxygen tension. These effects may be very important in how nickel exerts phenotypic selection pressure to convert a normal initiated cell into a cancer cell.

We have previously reported that the gpt transgene in G12 Chinese hamster cells could be silenced by water-insoluble nickel compounds nickel sulfide (NiS) or nickel subsulfide (Ni(3)S(2)) and showed that the transgene was silenced by de novo DNA methylation and chromatin condensation. To further understand the nature of this silencing, we used the chromatin immunoprecipitation assay to elucidate the chromatin structure in nickel-induced silenced G12 clones. We also analyzed the effects of the DNA methyltransferase inhibitor 5-azacytidine (5-AzaC) and a histone deacetylase inhibitor trichostatin A (TSA) on histone H3 and H4 acetylation and gpt gene expression in selected nickel-silenced clones. We observed that both histone H3 and H4 were hypoacetylated and a methyl DNA-binding protein MeCP2 was targeted to the gpt gene locus, resulting in a localized inactive chromatin configuration in nickel-silenced cell clones. The histone H3K9 was also found methylated in three of four nickel- silenced cell clones, whereas the histone H3K9 was deacetylated in all four cell clones, indicating that the H3K9 methylation was involved in nickel-induced gene silencing. The acetylation of the gpt gene could be increased by a combination of 5-AzaC and TSA treatment, but not by either 5-AzaC or TSA alone. The gpt transcript was studied by either Northern blot or by semiquantitative RT-PCR following treatment of the silenced clones with TSA or 5-AzaC. An increase in gpt mRNA could be detected by RT-PCR in the clones that regained acetylation of H3 and H4. These data show that gene silencing induced by nickel in the gpt transgenic cell line involved a loss of histone acetylation and an activation of histone methylation. Both H4 and H3 histone acetylation were lost in the silenced clones and these clones exhibited an increase in the methylation of the lysine 9 in histone H3.

Nowadays, nanoparticle probes have received extensive attention largely due to its potential biomedical applications in structural, functional, and molecular imaging. In addition, photoacoustic tomography (PAT), a method based on the photoacoustic effect, is widely recognized as a robust modality to evaluate the structure and function of biological tissues with high optical contrast and high acoustic resolution. The combination of PAT with nanoparticle probes holds promises for detecting and imaging diseased tissues or monitoring their treatments with high sensitivity. This review will introduce the recent advances in the emerging field of nanoparticle probes and their preclinical applications in PAT, as well as relevant perspectives on future development.