High-peak-power picosecond deep-UV laser sources.

Ultrafast deep-UV laser sources have extensive applications across a wide number of fields, whether biomedicine, photolithography, industrial processing, or state-of-the-art scientific research. However, it has been challenging to obtain deep-UV laser sources with high conversion efficiency and output peak power. Here, we simultaneously demonstrated high-peak-power picosecond deep-UV laser sources at two typical wavebands of 263.2 and 210.5 nm via the efficient fourth- and fifth-harmonic generation. The highest peak power of 263.2 and 210.5 nm laser radiations were up to 2.13 GW (6.72 ps) and 1.38 GW (5.08 ps). The overall conversion efficiencies from the fundamental wave to the fourth and fifth harmonic were up to 42.9% and 28.8%, respectively. The demonstrated results represent the highest conversion efficiencies and output peak powers of picosecond deep-UV laser sources at present to our knowledge. Additionally, we also systematically characterized the deep-UV optical properties of typical birefringent and nonlinear borate crystals, including α-BaB2O4, ß-BaB2O4, LiB3O5, and CsLiB6O10 crystals. The experiments and obtained numerous new optical data in this work will contribute to the generation of ultrahigh-peak-power deep-UV and vacuum-UV laser sources and crucial applications in both science and industry, such as high-energy-density physics, material science, and laser machining.

Noncritical phase-matching fourth- and fifth-harmonic generation of 1077 nm laser using KDP-family crystals.

We systematically demonstrated the angular and temperature acceptances of noncritical phase-matching (NCPM) fourth- and fifth-harmonic generation (FHG and FiHG) of a 1077 nm laser in NH4H2PO4 (ADP), KH2PO4 (KDP), and KD2PO4 (DKDP) crystals. In this work, a new, to the best of our knowledge, laser frequency with a wavelength of 1077 nm was generated by optical parametric amplification, in which the pump light (526.3 nm) was generated by the frequency doubling of a Nd:YLF laser (1052.7 nm), and the signal light was a Yb:YAG laser (1029.5 nm). Subsequently, the 1077 nm laser was used as the fundamental wave for FHG and FiHG to obtain a deep-ultraviolet laser source. For ADP and DKDP crystals, NCPM FHG of a 1077 nm laser was realized at 74.0∘C and 132.5∘C, respectively, and large angular acceptances of 59.8 and 61.6 mrad were measured. For the FiHG, NCPM was realized in a KDP crystal at 48.5∘C with an angular acceptance of 56.4 mrad. The results pave the way for high-energy and high-power deep-ultraviolet laser generation using KDP-family crystals under noncryogenic conditions.

Electro-optic coefficient measurement of a K(H1-xDx)2PO4 crystal based on χ(2) nonlinear optical technology.

We present a novel method utilizing the χ(2) nonlinear optical technology, which can realize high precision measurement of linear electro-optic (EO) coefficients of nonlinear materials. By applying the linear EO effect to the nonlinear optical process, the theoretical model of this measurement method was established, and the calculation formula of the linear EO coefficient was given. In the proof-of-principle experiment, by introducing an external electric field into the fourth harmonic generation (FHG) process, we comprehensively obtained the linear EO coefficients of K(H1-xDx)2PO4 crystals and revealed the relationship between deuterium content (x) and EO coefficient (γ63): γ63 = -9.789 - 16.53x. Meanwhile, the stability of FHG was greatly improved, and the angular range of efficiency stability was increased to 4.4 times in maximum. This work not only systematically demonstrates the FHG characteristics of KDP-family crystals, which provides a good reference for the deep ultraviolet laser generation, but also offers a new way to measure the basic parameters of nonlinear optical materials.

Epigenetic regulation of the miR142-3p/interleukin-6 circuit in glioblastoma.

Epigenetic regulation plays a critical role in glioblastoma (GBM) tumorigenesis. However, how microRNAs (miRNAs) and cytokines cooperate to regulate GBM tumor progression is still unclear. Here, we show that interleukin-6 (IL-6) inhibits miR142-3p expression and promotes GBM propagation by inducing DNA methyltransferase 1-mediated hypermethylation of the miR142-3p promoter. Interestingly, miR142-3p also suppresses IL-6 secretion by targeting the 3' UTR of IL-6. In addition, miR142-3p also targets the 3' UTR and suppresses the expression of high-mobility group AT-hook 2 (HMGA2), leading to inhibition of Sox2-related stemness. We further show that HMGA2 enhances Sox2 expression by directly binding to the Sox2 promoter. Clinically, GBM patients whose tumors present upregulated IL-6, HMGA2, and Sox2 protein expressions and hypermethylated miR142-3p promoter also demonstrate poor survival outcome. Orthotopic delivery of miR142-3p blocks IL-6/HMGA2/Sox2 expression and suppresses stem-like properties in GBM-xenotransplanted mice. Collectively, we discovered an IL-6/miR142-3p feedback-loop-dependent regulation of GBM malignancy that could be a potential therapeutic target.

Universal nanosecond range pulse contrast measurement for a kJ-class petawatt laser.

A single-shot measuring apparatus with optical limiting for temporal pulse contrast of kJ-class petawatt lasers in the nanosecond range is proposed. A temporal linear filter comprising an electro-optical switch, a polarizer, a temporal nonlinear filter composed of cascaded SHG crystals, and a dichromatic mirror are, respectively, used as an optical limiting apparatus for contrast measurement of nanosecond and picosecond pulses to improve dynamic range and temporal resolution. The apparatus has been applied to pulse contrast measurements at the SG-II petawatt facility, achieving a high dynamic range of 1010 and a fast time resolution of 107 ps in the 350 ns range. This technique can also be universally applied to the limiting of the main pulse of varying pulse widths to diagnose pre-pulses during generation and transmission.

Three-dimensional laser damage positioning by a deep-learning method.

A holographic and deep learning-based method is presented for three-dimensional laser damage location. The axial damage position is obtained by numerically focusing the diffraction ring into the conjugate position. A neural network Diffraction-Net is proposed to distinguish the diffraction ring from different surfaces and positions and obtain the lateral position. Diffraction-Net, which is completely trained by simulative data, can distinguish the diffraction rings with an overlap rate greater than 61% which is the best of results reported. In experiments, the proposed method first achieves the damage pointing on each surface of cascade slabs using diffraction rings, and the smallest inspect damage size is 8µm. A high precision result with the lateral positioning error less than 38.5µm and axial positioning error less than 2.85mm illustrates the practicability for locating the damage sites at online damage inspection.

Fast compensation for arbitrary focusing through scattering media.

We introduce a fast compensation scheme to realize arbitrary focusing after propagation through a scattering sample. Theoretical analysis of the effect of cross terms on multi-point focusing is conducted based on the transmission matrix theory. The results show that the cross-term influence is very significant, which needs to be considered. The Multi-Population Genetic Algorithm is adopted to retrieve the input mode for the suppression of the cross-term effect. In order to realize fast compensation and reduce measurement noise, the off-axis holographic method is used to measure the large transmission matrix, which reduces the number of measurements compared with the traditional method. In the experiment, after retrieving the input phase, we obtain a high-quality focal output, and the signal-to-noise ratio is increased by 13.6 dB.

Demethoxycurcumin-Loaded Chitosan Nanoparticle Downregulates DNA Repair Pathway to Improve Cisplatin-Induced Apoptosis in Non-Small Cell Lung Cancer.

Demethoxycurcumin (DMC), through a self-assembled amphiphilic carbomethyl-hexanoyl chitosan (CHC) nanomatrix has been successfully developed and used as a therapeutic approach to inhibit cisplatin-induced drug resistance by suppressing excision repair cross-complementary 1 (ERCC1) in non-small cell lung carcinoma cells (NSCLC). Previously, DMC significantly inhibited on-target cisplatin resistance protein, ERCC1, via PI3K-Akt-snail pathways in NSCLC. However, low water solubility and bioavailability of DMC causes systemic elimination and prevents its clinical application. To increase its bioavailability and targeting capacity toward cancer cells, a DMC-polyvinylpyrrolidone core phase was prepared, followed by encapsulating in a CHC shell to form a DMC-loaded core-shell hydrogel nanoparticles (DMC-CHC NPs). We aimed to understand whether DMC-CHC NPs efficiently potentiate cisplatin-induced apoptosis through downregulation of ERCC1 in NSCLC. DMC-CHC NPs displayed good cellular uptake efficiency. Dissolved in water, DMC-CHC NPs showed comparable cytotoxic potency with free DMC (dissolved in DMSO). A sulforhodamine B (SRB) assay indicated that DMC-CHC NPs significantly increased cisplatin-induced cytotoxicity by highly efficient intracellular delivery of the encapsulated DMC. A combination of DMC-CHC NPs and cisplatin significantly inhibited on-target cisplatin resistance protein, ERCC1, via the PI3K-Akt pathway. Also, this combination treatment markedly increased the post-target cisplatin resistance pathway including bax, and cytochrome c expressions. Thymidine phosphorylase (TP), a main role of the pyrimidine salvage pathway, was also highly inhibited by the combination treatment. The results suggested that enhancement of the cytotoxicity to cisplatin via administration of DMC-CHC NPs was mediated by down-regulation of the expression of TP, and ERCC1, regulated via the PI3K-Akt pathway.

Temperature-insensitive frequency conversion by phase mismatch self-compensation in the same type of crystals.

Aiming at high-power laser frequency conversion, we present a new scheme that can self-compensate for the thermally induced phase mismatch. The basic design of the scheme is that three crystals with the same type are cascaded, of which the crystals at both ends are used for frequency conversion and the middle crystal is used for compensating phase mismatch. By configuring the polarization states of the interacting waves in the middle crystal, the sign of the first temperature derivative of the phase mismatch is opposite to that of the frequency conversion crystals. The thermally induced phase mismatch in the first crystal can thus be self-compensated in the middle crystal. To verify the utility of the proposed scheme, we experimentally demonstrated temperature-insensitive second and third harmonic generation using KH2PO4 crystals. The results show that the temperature acceptance bandwidth is about two times larger than that of using a single crystal. Since the crystals used are of the same type, this scheme has excellent universal applicability and is almost completely free from the limitations of the laser wavelength, crystal and phase-matching type. Therefore, the scheme can be widely applied to various frequency conversion processes and is scarcely any limitations.

Phase Matching Using the Linear Electro-Optic Effect.

Phase matching is a necessary condition for achieving high-efficiency optical-frequency conversion. To date, practical means of accomplishing phase matching in homogeneous crystals remain limited, despite considerable efforts. Herein, we report a new class of methods aimed at achieving quasiperfect phase matching, based on controllable birefringence produced via the linear electro-optic effect, termed "voltage-tuning phase matching." The wave vectors of the induced polarization and the generated fields can be matched and maintained along the direction of propagation by introducing an external electric field. We analyze the validity and feasibility of this method theoretically and demonstrate it experimentally by applying the linear electro-optic effect and fourth-harmonic generation simultaneously in a partially deuterated KH_{2}PO_{4} crystal. Quasiperfect phase matching is achieved systematically over a temperature range of the initial phase-matching temperature ±2 °C. Moreover, this method can overcome the limitation of the birefringence in traditional technologies and provides new functionalities for conventional nonlinear materials as well as low-birefringence and isotropic materials. This technology may significantly impact the study of optical-frequency conversion and has promise for a broad range of applications in nonlinear optics.

Demethoxycurcumin-carrying chitosan-antibody core-shell nanoparticles with multitherapeutic efficacy toward malignant A549 lung tumor: from in vitro characterization to in vivo evaluation.

Targeting controlled release core-shell nanocarriers with the potential to overcome multidrug resistant (MDR) lung cancer were prepared based on demethoxycurcumin (DMC) loaded amphiphilic chitosan nanoparticles coated with an anti-EGFR antibody layer. The nanocarriers were characterized with regard to size with dynamic light scattering, SEM, and TEM. The characterization confirmed the nanocarriers to have a surface coating of the anti-EGFR antibody and a final size excellently suited for circulating targeting nanocarriers, i.e., <200 nm in diameter. In vitro drug release revealed extended quasi-Fickian release from the nanocarriers, with the anti-EGFR layer further reducing the release rate. Cell culture experiments using normoxic and MDR hypoxic cells overexpressing EGFR confirmed improved DMC delivery for anti-EGFR coated particles and revealed that the DMC was delivered to the cytoplasmic region of the cells, forming nanoprecipitates in lysosomes and endosomes. The effective endocytosis and targeting of the core-shell nanoparticles resulted in the nanocarriers achieving high cytotoxicity also against MDR cells. The therapeutic potential was further confirmed in an A549 xenograft lung tumor mouse model, where DMC loaded core-shell nanocarriers achieved about 8-fold reduction in tumor volume compared with control group over the 8 weeks of the investigation. Both in vitro and in vivo data suggest the anti-EGFR coated core-shell nanocarriers as highly promising for treatment of hypoxic MDR cancers, especially for non-small cell lung cancer.

Forming of demethoxycurcumin nanocrystallite-chitosan nanocarrier for controlled low dose cellular release for inhibition of the migration of vascular smooth muscle cells.

We report an efficient therapeutic approach to inhibit the migration and growth of vascular smooth muscle cells (VSMCs) via a low-dose sustained elution of a water-insoluble drug, demethoxycurcumin (DMC), through a self-assembled amphiphilic carbomethyl-hexanol chitosan (CHC) nanomatrix. Manipulating the cellular internalization and controlled cytotoxic effect of DMC-CHC nanoparticles over the VSMCs was elucidated. The DMC-CHC nanoparticles, which were systematically characterized in terms of structural morphology, surface potential, encapsulation efficiency, and DMC nanocrystallite distribution, exhibited rapid cellular uptake efficiency and considerably improved cytotoxic potency by 2.8 times compared to the free DMC. Under a cytotoxic evaluation, an improved antiproliferative effect and effective inhibition of VSMC migration as a result of highly efficient intracellular delivery of the encapsulated DMC in comparison to free DMC was achieved, which also was confirmed with a subsequent protein analysis. Cellular drug release and distribution of DMC after internalization into VSMCs was experimentally determined. This work may open a potential intracellular medicinal strategy with improved biological and therapeutic efficacy using the DMC-CHC nanoparticles illustrated in this work.

Use of irinotecan for treatment of small cell carcinoma of the prostate.

BACKGROUND: Prostatic small cell carcinoma (SCC) is a rare variant of prostate cancer. It is extremely aggressive and resistant to available therapies with a median survival range of 5-17 months. No standard chemotherapeutic regimen has been established for its treatment. In search of a new therapeutic approach, we examined the response of patient-derived prostatic SCC tissue xenografts to irinotecan, a topoisomerase I inhibitor. METHODS: A tumor tissue line was established from a patient's prostatic SCC by subrenal capsule grafting using NOD-SCID mice. Mice carrying subcutaneous transplants of the tumor line were then treated for 2 weeks with irinotecan alone and in combination with cisplatin. The effect on tumor volume, histopathology, and apoptosis were determined. RESULTS: The prostatic SCC tissue line resembled the donor tissue in morphologic and immunohistochemical features. Irinotecan (20 mg/kg/day; days 1-3, 8-10) completely arrested xenograft growth with a small reduction in tumor volume and only minor weight loss of the hosts (7%); irinotecan (12 mg/kg; same schedule) + cisplatin (2.5 mg/kg/day; days 1 and 8) had a similar effect, but with lower weight loss. While the growth inhibition involved apoptosis, it was also associated with a marked increase in autophagy. CONCLUSIONS: Tumor tissue lines established via subrenal capsule xenografting provide models with clinical relevance and the present study suggests that irinotecan could be useful for therapy of refractory prostatic SCC, in particular in combination with cisplatin.

Magnolol-loaded core-shell hydrogel nanoparticles: drug release, intracellular uptake, and controlled cytotoxicity for the inhibition of migration of vascular smooth muscle cells.

Encapsulation and release behavior of a water-insoluble drug, magnolol, using a core-shell polysaccharide-based nanoparticle, manipulating the cellular internalization and controlled cytotoxic effect of magnolol-loaded nanoparticles over the A10 vascular smooth muscle cells (VSMCs) was reported. A magnolol-polyvinylpyrrolidone (PVP) core phase was prepared, followed encapsulating by an amphiphilic carboxymethyl-hexanoyl chitosan (CHC) shell to form a magnolol-loaded core-shell hydrogel nanoparticles (termed magnolol-CHC nanoparticles). The resulting magnolol-CHC nanoparticles were employed for evaluation of drug release and controlled cytotoxic inhibition of VSMCs migration in vitro. A sustained release of the magnolol from the nanoparticles was determined. The magnolol-CHC nanoparticles exhibited outstanding cellular uptake efficiency, and under a cytotoxic evaluation, an increased antiproliferative effect and effective inhibition of VSMC migration as a result of efficient intracellular delivery of the encapsulated magnolol in comparison to free magnolol was achieved. We then envision a potential intracellular medication strategy with improved biological and therapeutic efficacy using the magnolol-CHC nanoparticles illustrated in this work.

Characterization and structure evolution of Ca-Al-CO3 hydrotalcite film for high temperature CO2 adsorption.

In this work, monodispersed layered double hydroxide (Ca-Al LDHs) nanoparticles were synthesized by hydrothermal coprecipitation. Uniform thin films of layered double hydroxide on porous anodic aluminum oxide (AAO) substrates were formed by a direct precipitation process in a homogeneous suspension containing monodispersed Ca-Al layered double hydroxide nanoparticles. It was found that the formation of a designed hydrotalcite-like phase is strongly dependent on the [Ca(2+)]/[Al(3+)] ratios, and that a minor CaCO3 phase could possibly form simultaneously, which is attributed to the greater insolubility of CaCO3 and the incompatibility of the ionic size of Al and Ca. The optimal CO2 adsorption capacity appears in the layered Ca-OH-Al structure with the composition ratio of 3:1. Furthermore, the CO2 adsorption mechanism varies with treatment temperature. Below 400 degrees C, the CO2 adsorption is attributed to the LDH structure with a large surface area and pore volume, but above that the adsorption is due to the formation of CaCO3 and CaO. The permeation behavior and CO2 absorption can be explained by a preferable chemical and physical absorption of CO2 on the layered double hydroxide and porous structure of the membrane.

Self-assembly behavior and doxorubicin-loading capacity of acylated carboxymethyl chitosans.

A new type of acylated carboxymethyl amphiphilic chitosan (ACC) with the use of acyl chain of varying lengths, from C(2) to C(12), and various degrees of acyl substitution was successfully synthesized and has been characterized in terms of its self-assembly behavior, structural stability, and drug encapsulation. The resulting nanostructure of the ACC nanoaggregates can be well manipulated through a control of hydrophobicity. Structural evolution of the self-assembled nanoaggregates is extensively characterized via (1)H NMR, FTIR, DSC, and TEM. A critical value of the hydrophobic effect, (X(DH) x X(Cn)), i.e., a product of "degree of acyl substitution" and "carbon number of acyl chain", can be employed as an indicator for structural variation of the nanoaggregates: when (X(DH) x X(Cn)) exceeded 1.5, the architecture of the nanoaggregates underwent a structural transformation from solid nanoparticle to hollow nanocapsules. The nanoaggregates exhibited an excellent colloidal and structural stability in aqueous medium. An improved affinity toward drug encapsulation, i.e., doxorubicin, can be technically designed according to the amphiphilic nature of the resulting nanoaggregates for drug delivery.

A nanoporous optically transparent CdS-pHEMA hybrid with high optical sensing capability to dielectric liquids.

A hydrogel-based functional hybrid with highly uniformly dispersed nanoparticulate CdS semiconductors is proposed. The hybrid is synthesized using an in situ polymerization following an in situ chemical reduction, where the resulting particle size and the distribution of CdS nanocrystals (NCs) can be narrowly manipulated. The hybrids, containing a relatively small amount of the CdS NCs, exhibit a pronounced photoluminescence spectrum shift when in contact with a number of dielectric liquids and such a pronounced dielectric-confinement effect has been experimentally verified and modeled in this study. The sensing capability of the hybrids with respect to dielectric liquids or molecules can be optically characterized and varied depending upon the intensity of the dielectric environment surrounding the hybrids. This work suggests that the transparent, nanoporous CdS-pHEMA hybrids can be used as highly efficient optical sensing materials.

Electrochemical behavior of nano Cu/poly(2-hydroxyethyl methacrylate) composite.

A novel electro-activated Cu/pHEMA nanocomposite was fabricated by coupling nano copper particles with poly(2-hydroxyethyl methacrylate) (pHEMA) matrix. The nano-sized copper particles ranging from 5 nm to 10 nm were in-situ synthesized in the presence of three-dimensional polymer matrixes by photo-polymerization of the copper ions with the HEMA monomer and followed by a strong reducing reaction. The electrochemical behaviors of the Cu/pHEMA nanocomposite were charcterized by cyclic voltammetry and alternating current impedance method. The results showed that the redox behavior of Cu/pHEMA nanocomposite was controlled by the crystallinity of copper particles and the interaction between copper and pHEMA.

Electrical-sensitive nanoparticle composed of chitosan and tetraethyl orthosilicate for controlled drug release.

In the present study, the nanoparticles with size of 50-130 nm composed of chitosan (CS) and tetraethyl orthosilicate (TEOS), which showed electrically-controlled release profile, were prepared. Myoglobin was encapsulated into the nanoparticles with an encapsulation efficiency as high as 91.5% and a maximum loading capacity of 70.2% that can be achieved. Here, TEOS was hydrolyzed and condensed to form interpenetration network with CS. Increase of TEOS content results in a shift of the release profile from swelling-controlled towards diffusion-controlled mechanism. The "slow-to-burst" and "near-zero" release of the myoglobin can be effectively controlled by applying DC electric field between "on" and "off".

Stimuli-responsive controlled drug release from magnetic-sensitive silica nanospheres.

A novel method for control burst releasing of drug via a high frequency magnetic field (HFMF) from magnetic-sensitive silica nanospheres was developed. The nanospheres were synthesized by a combination of emulsion and sol-gel process with the particles controlled at about 80 nm in diameter. Under repeated exposures to the high frequency magnetic stimulus, the drug release behaviors showed reproducible slow-to-burst profiles while consecutively applying the magnetic stimulus at 10-min switching time and the release profile restored immediately when the stimulus was removed. By taking this non-contact control-burst method, the magnetic silica nanospheres can be designed to treat the cancer therapy and urgent physiological needs.