Spatial mode cleaning and efficient nonlinear pulse compression to sub-50†fs in a gas-filled multipass cell.

We demonstrate a gas-filled multipass cell (MPC) that cleaned the spatial mode of a spatial-filter-free 250 W, 100 kHz, 445 fs driven source based on an Innoslab amplifier and compressed the pulse duration to 41 fs simultaneously. The multipass cell acted as a spatial filter and benefited from its discrete waveguide nature, in which the input beam quality factor M2 was improved from 1.53 to a near-diffraction-limited value of 1.21 at 96% transmission.

A nitroreductase-responsive fluorescence turn-on photosensitizer for lysosomes imaging and photodynamic therapy.

Nitroreductase (NTR) is a frequently used biomarker for the assessment of hypoxia level in tumors. As one of the main sources of enzymes, the dysfunction of lysosomes typically leads to various diseases. In this study, an NTR-triggered lysosome-targeting probe, M-TPE-P, was designed based on a tetraphenylethylene core. DFT calculation indicated that the probe possessed a narrow singlet-triplet energy gap (ΔEST), rendering it an efficient photosensitizer. The docking affinity of M-TPE-P to NTR revealed a strong structural match between them. Photophysical properties demonstrated that the probe exhibited high selectivity and sensitivity in a broad pH rang for detecting NTR with kcat/Km as 2.18 × 104 M-1 s-1. The detection limit was determined to be 53.6 ng/mL in 80 % PBS/DMSO solution. Cell imaging studies showed the probe could trace intracellular NTR behavior with green fluorescence. The colocalization analysis indicated its excellent lysosome-targeting specificity. In addition, the probe exhibited effective ROS generation ability and significant PDT effect after NIR irradiation, positioning it as a promising photosensitizer for cancer treatment.

Rational design of a ratiometric fluorescent probe for imaging lysosomal nitroreductase activity.

Overexpressed nitroreductase (NTR) is often utilized to evaluate the hypoxic degree in tumor tissues, thus it is of great importance to develop high selective and efficient optical method to detect NTR. The dynamic fusion and function of lysosome promoted us to explore the possible appearance of NTR inside this organelle and to probe its behavior in a cellular context. In this work, a ratiometric fluorescent probe based on an extended π-π conjugation of a triphenylamine unit was designed for NTR detection and lysosomes imaging. The dual-emission mechanism of the probe in the presence of catalytic NTR was confirmed by theoretical study. The structure-function relationship between probe and NTR was revealed by docking calculations, suggesting a suitable structural and spatial match of them. The photophysical studies showed the probe had high selectivity, rapid response and a wide pH range towards NTR. MTT assay indicated the probe had low cytotoxicity in both normal (HUVEC) and tumor (MCF-7) cells. Furthermore, the inverse fluorescent imaging results confirmed the probe was NTR-active and exhibited time- and concentration-dependent fluorescence signals. In addition, the relatively high Pearson's correlation coefficient (0.99 in HepG2 and 0.97 in MCF-7 cells, compared to Lyso-Tracker Red) demonstrated the probe had excellent lysosomes colocalization. This study illustrates a ratiometric detection of NTR agent for lysosomes fluorescent imaging, which may provide a novel insight in molecular design.

Generation of 13.9-mJ Terahertz Radiation from Lithium Niobate Materials.

Extremely strong-field terahertz (THz) radiation in free space has compelling applications in nonequilibrium condensed matter state regulation, all-optical THz electron acceleration and manipulation, THz biological effects, etc. However, these practical applications are constrained by the absence of high-intensity, high-efficiency, high-beam-quality, and stable solid-state THz light sources. Here, the generation of single-cycle 13.9-mJ extreme THz pulses from cryogenically cooled lithium niobate crystals and a 1.2% energy conversion efficiency from 800 nm to THz are demonstrated experimentally using the tilted pulse-front technique driven by a home-built 30-fs, 1.2-Joule Ti:sapphire laser amplifier. The focused peak electric field strength is estimated to be 7.5 MV cm-1 . A record of 1.1-mJ THz single-pulse energy at a 450 mJ pump at room temperature is produced and observed that the self-phase modulation of the optical pump can induce THz saturation behavior from the crystals in the substantially nonlinear pump regime. This study lays the foundation for the generation of sub-Joule THz radiation from lithium niobate crystals and will inspire more innovations in extreme THz science and applications.

Measurements of microjoule-level, few-femtosecond ultraviolet dispersive-wave pulses generated in gas-filled hollow capillary fibers.

To the best of our knowledge, we demonstrate the first time-domain measurement of µJ-level, few-fs ultraviolet dispersive-wave (DW) pulses generated in gas-filled hollow capillary fibers (HCFs) in an atmosphere environment using several chirped mirrors. The pulse temporal profiles, measured using a self-diffraction frequency-resolved optical gating setup, exhibit full width at half maximum pulse widths of 9.6 fs at 384 nm and 9.4 fs at 430 nm, close to the Fourier-transform limits. Moreover, theoretical and experimental studies reveal the strong influences of driving pulse energy and HCF length on temporal width and shape of the measured DW pulses. The ultraviolet pulses obtained in an atmosphere environment with µJ-level pulse energy, few-fs pulse width, and broadband wavelength tunability are ready to be used in many applications.

Efficacy of irreversible electroporation ablation combined with natural killer cells in treating locally advanced pancreatic cancer.

PURPOSE: To explore the efficacy and safety of irreversible electroporation (IRE) ablation combined with natural killer (NK) cells in the treatment of locally advanced pancreatic cancer (LAPC). METHODS: A total of 92 LAPC patients treated in our hospital from January 2016 to January 2017 were enrolled, and there were 46 cases of percutaneous IRE as IRE group, and 46 cases of IRE combined NK cell therapy as IRE-NK group. The clinical information of all the patients was collected, and the short-term efficacy, changes in the serum immunological indicators after treatment, carbohydrate antigen 19-9 (CA19-9) level, and incidence of adverse reactions were compared between the two groups of patients. Besides, the overall survival (OS) and disease-free survival (DFS) of patients were followed up and recorded. RESULTS: On 1 month after treatment, all the patients underwent efficacy assessment, which showed the overall response rate of patients in IRE-NK group was significantly superior to that in IRE group. One and 7 days after operation, the level of CA19-9 was obviously raised in the two groups, with a statistically significant difference, and it declined 30 days postoperatively. Seven and 30 days after operation IRE-NK group had a notably lower level of CA19-9 than IRE group. After treatment, all the patients exhibited considerably higher lymphocyte count and notably enhanced lymphocyte function, and all the indicators in IRE-NK group were higher than those in IRE group. Besides, the levels of serum interleukin (IL)-2, TNF-ß and IFN-γ in IRE-NK group were remarkably higher than those in IRE group, whereas there were no statistically significant differences in the levels of IL-4, IL-6 and IL-10 between the two groups. All the patients were followed up for 6-29 months, and there were no statistically significant differences in the DFS and OS between IRE group and IRE-NK group. CONCLUSION: IRE ablation combined with NK cells has excellent efficacy in treating LAPC, and they can exert a synergistic treatment effect to enhance the immune function of patients and reduce CA19-9 expression, with tolerable adverse reactions.

Probing electron-atom collision dynamics in gas plasma by high-order harmonic spectroscopy.

Plasma is a complex system involving diverse collisional processes and interactions, such as electron-impact excitation, ionization, recombination, etc. One of the most important methods for studying the properties and dynamics of plasma is to analyze the radiations from plasma. Here, we demonstrate the high-order harmonic (HH) spectroscopy for probing the complex electron-atom collision (EAC) dynamics in a laser-induced gas plasma. These measurements were carried out by using an elliptically polarized pump and a time-delayed linearly polarized probe. The HH spectra from argon and krypton plasmas were recorded by scanning the time delay up to hundreds of picoseconds. We found that the delay-dependent HH yield contains three distinct regions, i.e., the first enhancement, the subsequent suppression, and the final restoration regions. A qualitative analysis shows that these features are clear signatures of the EAC processes and interactions involved in the delay-dependent HH spectroscopy.

Picosecond pulse compression by modulation of intensity envelope in a gas-filled hollow-core fiber.

A method of temporally compressing picosecond pulses is proposed. To increase the spectral broadening, two picosecond pulses at different central wavelengths are overlapped spatiotemporally to induce a modulation on the intensity envelope, thus leading to a high temporal intensity gradient. The combined pulse is then coupled into a gas-filled hollow-core fiber (HCF) to broaden the spectrum through nonlinear propagation. After that the pulse can be compressed by chirp compensation. This method is demonstrated numerically with two 1-ps/5-mJ pulses centered at 1053- and 1064-nm, respectively, which are coupled into a 250-µm-inner-diameter, 1-m-long HCF filled with 5-bar neon. After nonlinear propagation, the spectrum of the combined pulse is broadened significantly compared with the sum of the broadened spectra of a single 1-ps/10-mJ pulse centered at 1053- and 1064-nm. Under proper initial conditions, the pulse can be compressed down to ~16-fs. The influences of the energy ratio, time delay and wavelength gap between two input pulses, as well as the energy scaling are also discussed. These results show an alternative way to obtain ultrashort laser pulses from the picosecond laser technology, which can deliver both high peak power and high average power, and thus will benefit relevant researches in high-field laser physics.

Two new pyrone derivatives from the plant endophytic fungus Exserohilum sp.

Two new a-pyrones, Exserolide G-H (1-2), together with one known metabolite, stemphypyrone (3), were isolated from the solid-substrate fermentation cultures of the plant endophytic fungus Exserohilum sp. The structures of the new compounds were elucidated primarily by analysis of NMR data. Compounds 1-3 were tested for cytotoxicity against a small panel of human carcinoma cell lines. Compound 1 showed cytotoxicity against HeLa, A549 and HCT116 cells.

Waveform-controlled terahertz radiation from the air filament produced by few-cycle laser pulses.

Waveform-controlled terahertz (THz) radiation is of great importance due to its potential application in THz sensing and coherent control of quantum systems. We demonstrated a novel scheme to generate waveform-controlled THz radiation from air plasma produced when carrier-envelope-phase (CEP) stabilized few-cycle laser pulses undergo filamentation in ambient air. We launched CEP-stabilized 10 fs-long (~1.7 optical cycles) laser pulses at 1.8 µm into air and found that the generated THz waveform can be controlled by varying the filament length and the CEP of driving laser pulses. Calculations using the photocurrent model and including the propagation effects well reproduce the experimental results, and the origins of various phase shifts in the filament are elucidated.

Impact of gas backing pressure and geometry of conical nozzle on the formation of methane clusters in supersonic jets.

We present an experimental investigation of the dependence of the production of large methane clusters on the cluster source conditions. The clusters were produced at room temperature through supersonic expansion of methane gas at the backing pressures P(0) ranging from 10 to 84 bar using five conical nozzles of different geometries. The cluster size was characterized by Rayleigh scattering measurements and calibrated with Coulomb explosion of the clusters at P(0) = 44 bar subjected to an ultraintense laser pulse. A quantitative evaluation of the performance of the conical nozzles against the nozzle geometry and the backing pressure was made by introducing a parameter delta. Differ from the idealized case where the performance of the conical nozzle can be described by the equivalent sonic nozzle of diameter d(eq), in the present work, the "effective equivalent sonic-nozzle diameter" of the conical nozzle defined by d(eq)* = deltad(eq) is introduced. delta represents the deviation of the performance in cluster formation of the conical nozzles from that predicted on the basis of the concept of the equivalent diameter d(eq) = d/tan alpha, with d being the throat diameter, and alpha the half-opening angle of the conical nozzle. Experimental results show that the cluster growth process will be restricted when the gas backing pressure P(0) is higher and/or d/tan alpha of the conical nozzle becomes larger, resulting in smaller delta. From the experimental data, delta can be expressed by an empirical relation delta = A/[P(0)(B)(d/tan alpha)(1.36)], where A = 8.4 and B = 0.26 for 24 bar

Supercontinuum generation and pulse compression from gas filamentation of femtosecond laser pulses with different durations.

Self-compression and spectral supercontinuum (SC) generated by filamentation of femtosecond laser pulses with duration from 45 fs down to 6 fs in argon gas have been numerically investigated. A 45-fs pulse can be self-compressed into a few-cycle pulse with duration of 12 fs at the post-filamentation region. By properly employing a high-pass filter to select the broadening high-frequency spectra which are almost in phase, the pulse can be further shortened to about 7 fs. By contrast, a 6-fs pulse cannot be further self-compressed into a shorter pulse by filamentation although it can generate much broader SC extending from 200 nm to 1300 nm. It is also found that a separate and strong SC in the ultraviolet (UV) region extending from 220 nm to 300 nm and peaked at about 255 nm can be generated at proper propagation distances, which corresponds to a pulse with duration of about 5 fs.

Frequency modulation of synchronized Ca2+ spikes in cultured hippocampal networks through G-protein-coupled receptors.

Synchronized spontaneous Ca2+ spikes in networked neurons represent periodic burst firing of action potentials, which are believed to play a major role in the development and plasticity of neuronal circuitry. How these network activities are shaped and modulated by extrinsic factors during development, however, remains to be studied. Here we report that synchronized Ca2+ spikes among cultured hippocampal neurons can be modulated by two small factors that act on G-protein-coupled receptors (GPCRs): the neuropeptide PACAP (pituitary adenylate cyclase-activating polypeptide) and the chemokine SDF-1 (stromal cell-derived factor-1). PACAP effectively increases the frequency of the synchronized Ca2+ spikes when applied acutely; the PACAP potentiation of Ca2+ spikes requires the activation of the PACAP-specific PAC1 GPCRs and is mediated by the activation of cAMP signaling pathway. SDF-1, on the other hand, significantly reduces the frequency of these Ca2+ spikes through the activation of its specific GPCR CXCR4; the inhibitory action of SDF-1 is mediated by the inhibition of cAMP pathway through the Gi component of GPCRs. Taken together, these results demonstrate that synchronized neuronal network activity can be effectively modulated by physiologically and developmentally relevant small factors that act on GPCRs to target the cAMP pathway. Such modulation of neuronal activity through GPCRs may represent a significant mechanism that underlies the neuronal plasticity during neural development and functioning.