Unmodificated stepless regulation of CRISPR/Cas12a multi-performance.

As CRISPR technology is promoted to more fine-divided molecular biology applications, its inherent performance finds it increasingly difficult to cope with diverse needs in these different fields, and how to more accurately control the performance has become a key issue to develop CRISPR technology to a new stage. Herein, we propose a CRISPR/Cas12a regulation strategy based on the powerful programmability of nucleic acid nanotechnology. Unlike previous difficult and rigid regulation of core components Cas nuclease and crRNA, only a simple switch of different external RNA accessories is required to change the reaction kinetics or thermodynamics, thereby finely and almost steplessly regulating multi-performance of CRISPR/Cas12a including activity, speed, specificity, compatibility, programmability and sensitivity. In particular, the significantly improved specificity is expected to mark advance the accuracy of molecular detection and the safety of gene editing. In addition, this strategy was applied to regulate the delayed activation of Cas12a, overcoming the compatibility problem of the one-pot assay without any physical separation or external stimulation, and demonstrating great potential for fine-grained control of CRISPR. This simple but powerful CRISPR regulation strategy without any component modification has pioneering flexibility and versatility, and will unlock the potential for deeper applications of CRISPR technology in many finely divided fields.

Analysis on the minimum structure of harmonic spectra from MgO crystals.

Recent theoretical and experimental findings have demonstrated the minimum characteristic in the harmonic spectrum of bulk MgO crystals subjected to intense laser pulses. However, the dominant mechanism behind this minimum structure is still under debate. This study simulates the harmonic spectrum from a MgO crystal in a linearly polarized laser pulse by solving multi-band semiconductor Bloch equations. The results show that the minimum feature at 20 eV in the MgO harmonic spectra from 1700 and 800 nm laser pulses is due to band dispersion and interference between interband harmonics. Notably, the disappearance of the minimum structure at 14 eV in the harmonic spectrum from the 800 nm laser is attributed to the intensity suppression of higher energy harmonics, caused by decreased electron population at the boundary of the first Brillouin zone in the multi-band case. These findings offer insights into the spectral structure of solid-state harmonics, contributing to the all-optical reconstruction of the crystal band based on its harmonic spectrum.

A PAM-free CRISPR/Cas12a ultra-specific activation mode based on toehold-mediated strand displacement and branch migration.

CRISPR (clustered regularly interspaced short palindromic repeats) technology has achieved great breakthroughs in terms of convenience and sensitivity; it is becoming the most promising molecular tool. However, only two CRISPR activation modes (single and double stranded) are available, and they have specificity and universality bottlenecks that limit the application of CRISPR technology in high-precision molecular recognition. Herein, we proposed a novel CRISPR/Cas12a unrestricted activation mode to greatly improve its performance. The new mode totally eliminates the need for a protospacer adjacent motif and accurately activates Cas12a through toehold-mediated strand displacement and branch migration, which is highly universal and ultra-specific. With this mode, we discriminated all mismatch types and detected the EGFR T790M and L858R mutations in very low abundance. Taken together, our activation mode is deeply incorporated with DNA nanotechnology and extensively broadens the application boundaries of CRISPR technology in biomedical and molecular reaction networks.

Effect of pulse duration on the above-threshold ionization of a hydrogen atom irradiated by a 400 nm intense laser.

The photoelectron emission spectra generated by the interaction between ultrashort intense laser pulses and atoms can reveal the ultrafast dynamics of electrons. By using the numerical solution of the time-dependent Schrödinger equation in momentum space, the photoelectron emission spectra of atoms irradiated by 400 nm intense lasers with different durations of the pulse has been investigated. In the photoelectron emission spectrum, in addition to the above-threshold ionization peaks due to ionization interference in multiple cycles and the sideband peaks mainly due to the interference of ionized electrons at different moments along the rising edge of the laser pulse envelope, additional peaks of photoelectron emission whose intensity appears to oscillate with the increasing duration of the laser pulse can also be observed. Based on strong-field approximation and the population's analysis of the bound state, it is found that these photoelectron peaks originate from the ionization of the excited state and the oscillations of these peaks are due to the superposition of their peak energy positions with the sideband energy positions. Furthermore, it is demonstrated that the energy positions of the maximum intensity of the photoelectron emission spectra move towards the higher energy end as the duration of the driving laser pulse extends. This phenomenon can be attributed to the fact that the main moment of ionization of atoms changes with the increasing duration of the driving laser pulse, thus allowing the real-time ionization of atoms to be probed using photoelectron emission spectra.

Minimum structure of high-order harmonic spectrum from molecular multi-orbital effects involving inner-shell orbitals.

The spectral features of high-order harmonic spectra can provide rich information for probing the structure and dynamics of molecules in intense laser fields. We theoretically study the high harmonic spectrum with the laser polarization direction perpendicular to the N2O molecule and find a minimum structure in the plateau region of the harmonic spectrum. Through analyzing the time-dependent survival probability of different electronic orbitals and the time-dependent wave packet evolution, it is found that this minimum position is caused by the harmonic interference of HOMO a, HOMO-1, and HOMO-3 a orbitals. Moreover, this interference minimum is discovered over a wide frequency range of 0.087 a.u. to 0.093 a.u., as well as a range of driving laser intensities with peak amplitudes between 0.056 a.u. and 0.059 a.u.. This study sheds light on the multi-electron effects and ultrafast dynamics of inner-shell electrons in intense laser pulses, which are crucial for understanding and controlling chemical reactions in molecules.

Enhancing harmonic brightness near the cutoff region by using laser pulses with a small positive chirp.

Efficient enhancement of harmonic brightness near the cutoff region is achieved by employing laser pulses with a small positive chirp in theory, where the laser intensity and frequency near the peak of the laser pulse are almost unchanged relative to the chirp-free field. The improvement of harmonic brightness is achieved under the condition that the ionization probability is almost unchanged. Through the analysis of the harmonics contributed by the rising and falling parts of the laser pulse, we have uncovered a "frequency compensation" mechanism that leads to an enhanced harmonic brightness near the cutoff region. Under appropriate chirp parameters, the harmonics contributed by the rising and falling parts can be constructively interfered in a smaller frequency range with greater intensity, thereby obtaining harmonics with good monochromaticity and high brightness. This study explains the mechanism of harmonic brightness enhancement from a new perspective, and provides a new idea for harmonic regulation without changing the ionization.

Circularly polarized attosecond light generation from OCS molecules irradiated by the combination of linear polarized infrared and orthogonal terahertz fields.

Researching ultrafast dynamics and creating coherent light sources will both benefit significantly from the establishment of polarization control in high-order harmonic generation (HHG). By employing the time-dependent density functional theory method, we investigate HHG of carbonyl sulfide molecules using a combination of a linear polarized infrared (IR) laser and a weaker orthogonal Terahertz (THz) field. Our findings show that by adjusting the amplitude of the THz field, the movement scale of electrons in the THz direction can be tuned, thereby one can control the harmonic intensity in the IR laser direction. This method allows for the creation of near-circularly polarized attosecond pulses. Furthermore, the ellipticity of the attosecond pulse may be changed by modifying the carrier-envelope phase of the IR laser pulse.

Influence of multiphoton resonance excitation on the above-threshold ionization of a hydrogen atom.

The photo-electron emission of a hydrogen atom irradiated by an ultraviolet laser pulse is investigated by numerically solving the time-dependent Schrödinger equation in momentum space. A subpeak structure with high intensity is observed in the photo-electron emission spectrum, and the peak of the enhanced structure shifts to a higher energy as the laser intensity increases. Through the strong-field approximation and the analysis of the population of the bound state , it is found that this subpeak structure is generated from the interference between the ionized electrons from the ground state and the ionized electrons from the 2p state after the resonant transition from the ground state to the 2p state. Analyzing the change rule of the photo-electron emission spectrum can further deepen the understanding of the energy change of the dressed bound state for an atom irradiated by an intense laser pulse.

Explanation of the anomalous redshift on a nonlinear X-ray Compton scattering spectrum by a bound electron.

Nonlinear Compton scattering is an inelastic scattering process where a photon is emitted due to the interaction between an electron and an intense laser field. With the development of X-ray free-electron lasers, the intensity of X-ray laser is greatly enhanced, and the signal from X-ray nonlinear Compton scattering is no longer weak. Although the nonlinear Compton scattering by an initially free electron has been thoroughly investigated, the mechanism of nonrelativistic nonlinear Compton scattering of X-ray photons by bound electrons is unclear yet. Here, we present a frequency-domain formulation based on the nonperturbative quantum electrodynamics to study nonlinear Compton scattering of two photons by an atom in a strong X-ray laser field. In contrast to previous theoretical works, our results clearly reveal the existence of a redshift phenomenon observed experimentally by Fuchs et al.(Nat. Phys.)11, 964(2015) and suggest its origin as the binding energy of the electron as well as the momentum transfer from incident photons to the electron during the scattering process. Our work builds a bridge between intense-laser atomic physics and Compton scattering processes that can be used to study atomic structure and dynamics at high laser intensities.

All-optical reconstruction of three-band transition dipole moments by the crystal harmonic spectrum from a two-color laser pulse.

When a bulk solid is irradiated by an intense laser pulse, transition dipole moments (TDMs) between different energy bands have an important influence on the ultra-fast dynamic process. In this paper, we propose a new all-optical method to reconstruct the k-dependent TDMs between multi-bands using a crystal high-order harmonic generation (HHG). Taking advantage of an obvious separation of bandgaps between three energy bands of an MgO crystal along the <001 > direction, a continuous harmonic spectrum with two plateaus can be generated by a two-color laser pulse. Furthermore, the first harmonic platform is mainly dominated by the polarization between the first conduction band and the valence band, and the second one is largely attributed to the interband HHG from the second conduction band and the valence band. Therefore, the harmonic spectrum from a single quantum trajectory can be adopted to map TDMs between the first, second conduction bands, and the valence one. Our work is of great significance for understanding the instantaneous properties of solid materials in the strong laser field, and will strongly promote the development of the HHG detection technology.