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 comprehensive study on three typical photoacid generators using photoelectron spectroscopy and ab initio calculations.

Conducting a comprehensive molecular-level evaluation of a photoacid generator (PAG) and its subsequent impact on lithography performance can facilitate the rational design of a promising 193 nm photoresist tailored to specific requirements. In this study, we integrated spectroscopy and computational techniques to meticulously investigate the pivotal factors of three prototypical PAG anions, p-toluenesulfonate (pTS-), 2-(trifluoromethyl)benzene-1-sulfonate (TFMBS-), and triflate (TF-), in the lithography process. Our findings reveal a significant redshift in the absorption spectra caused by specific PAG anions, attributed to their involvement in electronic transition processes, thereby enhancing the transparency of the standard PAG cation, triphenylsulfonium (TPS+), particularly at ∼193 nm. Furthermore, the electronic stability of PAG anions can be enhanced by solvent effects with varying degrees of strength. We observed the lowest vertical detachment energy of 6.6 eV of pTS- in PGMEA solution based on the polarizable continuum model, which prevents anion loss at 193 nm lithography. In addition, our findings indicate gas-phase proton affinity values of 316.4 kcal/mol for pTS-, 308.1 kcal/mol for TFMBS-, and 303.2 kcal/mol for TF-, which suggest the increasing acidity strength, yet even the weakest acid pTS- is still stronger than strong acid HBr. The photolysis of TPS+-based PAG, TPS+·pTS-, generated an excited state leading to homolysis bond cleavage with the lowest reaction energy of 83 kcal/mol. Overall, the PAG anion pTS- displayed moderate acidity, possessed the lowest photolysis reaction energy, and demonstrated an appropriate redshift. These properties collectively render it a promising candidate for an effective acid producer.

Annexin-A1 tripeptide enhances functional recovery and mitigates brain damage in traumatic brain injury by inhibiting neuroinflammation and preventing ANXA1 nuclear translocation in mice.

This study explores the role and mechanism of Annexin-A1 Tripeptide (ANXA1sp) in mitigating neuronal damage and promoting functional recovery in a mouse model of traumatic brain injury (TBI). Our goal is to identify ANXA1sp as a potential therapeutic drug candidate for TBI treatment. Adult male C57BL/6J mice were subjected to controlled cortical impact (CCI) to simulate TBI, supplemented by an in vitro model of glutamate-induced TBI in HT22 cells.  We assessed neurological deficits using the Modified Neurological Severity Score (mNSS), tested sensorimotor functions with beam balance and rotarod tests, and evaluated cognitive performance via the Morris water maze. Neuronal damage was quantified using Nissl and TUNEL staining, while microglial activation and inflammatory responses were measured through immunostaining, quantitative PCR (qPCR), Western blotting, and ELISA. Additionally, we evaluated cell viability in response to glutamate toxicity using the Cell Counting Kit-8 (CCK-8) assay and lactate dehydrogenase (LDH) release. Intraperitoneal administration of ANXA1sp significantly enhanced neurological outcomes, markedly reducing sensorimotor and cognitive impairments caused by TBI. This treatment resulted in a significant reduction in lesion volume and decreased neuronal cell death in the ipsilateral cortex. Moreover, ANXA1sp effectively diminished microglial activation around the brain lesion and decreased the levels of pro-inflammatory markers such as IL-6, IL-1ß, TNF-α, and TGF-ß in the cortex, indicating a significant reduction in neuroinflammation post-TBI. ANXA1sp also offered protection against neuronal cell death induced by glutamate toxicity, primarily by inhibiting the nuclear translocation of ANXA1, highlighting its potential as a neuroprotective strategy in TBI management. Administration of ANXA1sp significantly reduced neuroinflammation and neuronal cell death, primarily by blocking the nuclear translocation of ANXA1. This treatment substantially reduced brain damage and improved neurological functional recovery after TBI. Consequently, ANXA1sp stands out as a promising neuroprotective agent for TBI therapy.

Spatiotemporal aberrations due to the groove density mismatching of compression gratings in ultra-intense femtosecond lasers.

The groove density mismatching of compression gratings, an often-neglected key issue, can induce significant spatiotemporal aberrations especially for super-intense femtosecond lasers. We mainly investigate the angular chirp and the consequent degradation of the effective focused intensity introduced by the groove density mismatching of compression gratings in ultra-intense femtosecond lasers. The results indicate that the tolerances of grating groove density mismatching will rapidly decrease with the beam aperture or spectral bandwidth increases. For our 100PW laser under construction, the grating groove density mismatching should be as small as 0.001 gr/mm if the drop of effective focused intensity has to be controlled below 15%. More importantly, new angular chirp compensation schemes are proposed for both double-grating and four-grating compressors. This work reveals the importance of groove density matching of compression gratings, and can provide helpful guidelines for the design of ultra-intense femtosecond lasers.

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.

Reconfigurable Ag/HfO2/NiO/Pt Memristors with Stable Synchronous Synaptic and Neuronal Functions for Renewable Homogeneous Neuromorphic Computing System.

Artificial synapses and bionic neurons offer great potential in highly efficient computing paradigms. However, complex requirements for specific electronic devices in neuromorphic computing have made memristors face the challenge of process simplification and universality. Herein, reconfigurable Ag/HfO2/NiO/Pt memristors are designed for feasible switching between volatile and nonvolatile modes by compliance current controlled Ag filaments, which enables stable and reconfigurable synaptic and neuronal functions. A neuromorphic computing system effectively replicates the biological synaptic weight alteration and continuously accomplishes excitation and reset of artificial neurons, which consist of bionic synapses and artificial neurons based on isotype Ag/HfO2/NiO/Pt memristors. This reconfigurable electrical performance of the Ag/HfO2/NiO/Pt memristors takes advantage of simplified hardware design and delivers integrated circuits with high density, which exhibits great potency for future neural networks.

Terahertz-triggered ultrafast nonlinear optical activities in two-dimensional centrosymmetric PtSe2.

The nonlinear mechanisms of polarization and optical fields can induce extensive responses in materials. In this study, we report on two kinds of nonlinear mechanisms in the topological semimetal PtSe2 crystal under the excitation of intense terahertz (THz) pulses, which are manipulated by the real and imaginary parts of the nonlinear susceptibility of PtSe2. Regarding the real part, the broken inversion symmetry of PtSe2 is achieved through a THz-electric-field polarization approach, which is characterized by second harmonic generation (SHG) measurements. The transient THz-laser-induced SHG signal occurs within 100 fs and recombines to the equilibrium state within 1 ps, along with a high signal-to-noise ratio (∼51 dB) and a high on/off ratio (∼102). Regarding the imaginary part, a nonlinear absorption change can be generated in the media. We reveal a THz-induced absorption enhancement in PtSe2 via nonlinear transmittance measurements, and the sheet conductivity can be modulated up to 42% by THz electric fields in our experiment. Therefore, the THz-induced ultrafast nonlinear photoresponse reveals the application potential of PtSe2 in photonic and optoelectronic devices in the THz technology.

Characteristics of broadband OPCPA based on DKDP crystals with different deuterations for the SEL-100 PW laser system.

We present the performances of a broadband optical parametric chirped pulse amplification (OPCPA) using partially deuterated potassium dihydrogen phosphate (DKDP) crystals with deuteration levels of 70% and 98%. When pumped by a Nd:glass double frequency laser, the OPCPA system using the 98% deuterated DKDP crystal achieves a broad bandwidth of 189 nm (full width at 1/e2 maximum) from 836 nm to 1025 nm. For the DKDP crystal with length of 43 mm, the pump-to-signal conversion efficiency reaches 28.4% and the compressed pulse duration is 13.7 fs. For a 70% deuterated DKDP crystal with a length of 30 mm, the amplified spectrum ranges from 846-1021 nm, the compressed pulse duration is 15.7 fs, and the conversion efficiency is 25.5%. These results demonstrate the potential of DKDP crystals with higher deuteration as promising nonlinear crystals for use as final amplifiers in 100 Petawatt (PW) laser systems, supporting compression pulse duration shorter than 15 fs.

Gigahertz electromagnetic pulse emission from femtosecond relativistic laser-irradiated solid targets.

The interactions between high-intensity laser and matter produce particle flux and electromagnetic radiation over a wide energy range. The generation of extremely intense transient fields in the radio frequency-microwave regime has been observed in femtosecond-to-nanosecond laser pulses with 1011-1020-W/cm2 intensity on both conductive and dielectric targets. These fields typically cause saturation and damage to electronic equipment inside and near an experimental chamber; nevertheless, they can also be effectively used as diagnostic tools. Accordingly, the characterization of electromagnetic pulses (EMPs) is extremely important and currently a popular topic for present and future laser facilities intended for laser-matter interaction. The picosecond and sub-picosecond laser pulses are considerably shorter than the characteristic electron discharge time (∼0.1 ns) and can be efficient in generating GHz EMPs. The EMP characterization study of femtosecond laser-driven solid targets is currently mainly in the order of 100 mJ laser energy, in this study, the EMP generated by intense (Joule class) femtosecond laser irradiation of solid targets has been measured as a function of laser energy, laser pulse duration, focal spot size, and target materials. And a maximum electric field of the EMP reaching up to 105 V/m was measured. Analyses of experimental results confirm a direct correlation between measured EMP energy and laser parameters in the ultrashort pulse duration regime. The EMP signals generated by femtosecond laser irradiation of solid targets mainly originate from the return current inside the target after hot electron excitation. Numerical simulations of EMP are performed according to the target charging model, which agree well with the experimental results.

Stable, intense supercontinuum light generation at 1 kHz by electric field assisted femtosecond laser filamentation in air.

Supercontinuum (SC) light source has advanced ultrafast laser spectroscopy in condensed matter science, biology, physics, and chemistry. Compared to the frequently used photonic crystal fibers and bulk materials, femtosecond laser filamentation in gases is damage-immune for supercontinuum generation. A bottleneck problem is the strong jitters from filament induced self-heating at kHz repetition rate level. We demonstrated stable kHz supercontinuum generation directly in air with multiple mJ level pulse energy. This was achieved by applying an external DC electric field to the air plasma filament. Beam pointing jitters of the 1 kHz air filament induced SC light were reduced by more than 2 fold. The stabilized high repetition rate laser filament offers the opportunity for stable intense SC generation and its applications in air.

Phase-matching of high-order harmonic generation in the extreme ultraviolet region with orbital angular momentum.

High-order harmonics can generate vortex beams with orbital angular momentum (OAM) in the extreme ultraviolet region. However, experimental research on their phase-matching (PM) characteristics is limited. In this study, vortex high-order harmonic generation (HHG) in the extreme ultraviolet region was generated with Ar gas. Phase-matched HHG with OAM was obtained by optimizing the focus position, laser energy, and gas pressure. The dependence of the PM characteristics on these parameters was analyzed. In addition, we conducted an experimental analysis of the dimensional properties of vortex harmonics under PM conditions. This study is a contribution towards the intense vortex high-order harmonic light sources and their applications.

Dynamic range enhancement of self-referenced spectral interferometry with extended time excursion method by the cascaded Kerr lens process.

Self-referenced spectral interferometry with extended time excursion (SRSI-ETE) is a powerful method for single-shot characterization of the temporal contrast of a high peak power laser, which has high temporal resolution but a low dynamic range. Here, a temporal contrast reduction method is proposed that uses the cascaded Kerr lens process in two thin glass plates. Combined with the SRSI-ETE method, the measurement dynamic range of the method is increased about two orders of magnitude while having a 20 fs temporal resolution and a 40 ps time window in single shot.

417†W, 2.38†mJ Innoslab amplifier compressible to a high pulse quality of 406†fs.

We demonstrate a 417 W, 175 kHz Innoslab chirped pulse amplification laser compressible to short and clean 406 fs pulse duration. A spectral bandwidth (full width at half maximum, FWHM) of ∼3 nm was maintained at full pump power, and the pulses exhibited good pulse quality in a wide tunable pulse energy range from 1.7 mJ to a maximum of 2.38 mJ. At the maximum output power, the compressed pulses were nearly pedestal free. The comprehensive effects of residual high-order dispersion from the front end, the gain shaping effects of the amplifier, and the slight mismatch of third-order dispersion (TOD) between the stretcher (CFBG) and the gating compressor, along with the small nonlinear phase shift accumulated in the amplifier, could have facilitated the high pulse quality. To the best of our knowledge, this is the shortest pulse duration from the Innoslab amplifiers at hundreds of watts average power in the millijoule energy regime.

Frequency shift of even-order high harmonic generation in monolayer MoS2.

Sub-optical-cycle electron dynamics in materials driven by intense laser fields can be investigated by high harmonic generation. We observed frequency shift of high harmonic spectrum near the band gap of monolayer MoS2 experimentally. Through semi-classical quantum trajectory analysis, we demonstrated that the phase of transition dipole moment varies according to the recombination timing and momentum of tunneled electrons. It results in either blue- or red-shift of harmonic frequencies, determined by the modulated energy gap by transition dipole phases (TDPs) and Berry connections. Our finding reveals the effect of TDPs on high harmonic frequency in non-central symmetric materials.

Intense ultraviolet-visible-infrared full-spectrum laser.

A high-brightness ultrabroadband supercontinuum white laser is desirable for various fields of modern science. Here, we present an intense ultraviolet-visible-infrared full-spectrum femtosecond laser source (with 300-5000 nm 25 dB bandwidth) with 0.54 mJ per pulse. The laser is obtained by sending a 3.9 µm, 3.3 mJ mid-infrared pump pulse into a cascaded architecture of gas-filled hollow-core fiber, a bare lithium niobate crystal plate, and a specially designed chirped periodically poled lithium niobate crystal, under the synergic action of second and third order nonlinearities such as high harmonic generation and self-phase modulation. This full-spectrum femtosecond laser source can provide a revolutionary tool for optical spectroscopy and find potential applications in physics, chemistry, biology, material science, industrial processing, and environment monitoring.

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.

400nm ultra-broadband gratings for near-single-cycle 100 Petawatt lasers.

Compressing high-energy laser pulses to a single-cycle and realizing the "λ3 laser concept", where λ is the wavelength of the laser, will break the current limitation of super-scale projects and contribute to the future 100-petawatt and even Exawatt lasers. Here, we have realized ultra-broadband gold gratings, core optics in the chirped pulse amplification, in the 750-1150 nm spectral range with a > 90% -1 order diffraction efficiency for near single-cycle pulse stretching and compression. The grating is also compatible with azimuthal angles from -15° to 15°, making it possible to design a three-dimensional compressor. In developing and manufacturing processes, a crucial grating profile with large base width and sharp ridge is carefully optimized and controlled to dramatically broaden the high diffraction efficiency bandwidth from the current 100-200 nm to over 400 nm. This work has removed a key obstacle to achieving the near single-cycle 100-PW lasers in the future.

Identification immune response genes in psoriasis after treatment with secukinumab.

BACKGROUND: Secukinumab is a fully human IgG1κ MoAb that selectively binds to IL-17A with high affinity, and it has been proven effective for the treatment of psoriasis. However, the immune response pathways and mechanisms during the treatment are still masked. Therefore, the current study was designed to investigate the potential immune response genes via bioinformatics approaches. METHODS: Gene expression data of severe plaque-type psoriasis was retrieved from the GEO database. Quantification of immune infiltration by ssGSEA and identification of differentially infiltrated immune cells were conducted to validate the treatment effect of secukinumab. After data processing, differentially expressed genes were identified between the treatment and untreated group. TC-seq was employed to analyze the trend of gene expression and clustering analysis. IL-17 therapeutic immune response genes were selected by taking the intersection of the genes inside the key cluster set and the MAD3-PSO geneset. Based on these therapeutic response genes, protein-protein interaction networks were built for key hub gene selection. These hub genes would work as potential immune response genes, and be validated via an external dataset. RESULTS: Enrichment scores calculated by ssGSEA illustrated that the immune infiltration level of T cells had a strong difference before and after medication, which validated the treatment effect of Secukinumab. 1525 genes that have significantly different expression patterns before and after treatment were extracted for further analysis, and the enrichment result shows that these genes have the function related to epidermal development, differentiation, and keratinocytes differentiation. After overlapping candidate genes with MAD3-PSO gene set, 695 genes were defined as anti-IL7A treatment immune response genes, which were mainly enriched in receptor signaling and IL-17 signaling pathways. Hub gene were pinpointed from the PPI network constructed by anti-IL7A treatment immune response genes, their expression pattern fits TC-seq gene expression pattern. CONCLUSION: Our study revealed the potential anti-IL7A treatment immune response genes, and the central hub genes, which may act critical roles in Secukinumab, induced immune response. This would open up a novel and effective avenue for the treatment of psoriasis.

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.

Coherent surface plasmon polariton amplification via free-electron pumping.

Surface plasmonics with its unique confinement of light1,2 is expected to be a cornerstone for future compact radiation sources and integrated photonics devices. The energy transfer between light and matter is a defining aspect that underlies recent studies on optical surface-wave-mediated spontaneous emissions3-5. However, coherent stimulated emission of free electrons, which is essential for free-electron light sources, and its dynamical amplification process remain to be disclosed in a clear, unambiguous and calibrated manner. Here we present the coherent amplification of terahertz surface plasmon polaritons via free-electron-stimulated emission: a femtosecond optical pulse creates an in-phase free-electron pulse with an initial terahertz surface wave, and their ensuing interactions intensify the terahertz surface wave coherently. The underlying dynamics of the amplification, including a twofold redshift in the radiation frequency over a one-millimetre interaction length, are resolved as electromagnetic-field-profile evolutions using an optical pump-probe method. By extending the approach to a properly phase-matched electron bunch, our theoretical analysis predicts a super-radiant surface-wave growth, which lays the ground for a stimulated surface-wave light source and may facilitate capable means for matter manipulation, especially in the terahertz band.