Generation of high-order harmonics and attosecond pulses in the water window via nonlinear propagation of a few-cycle laser pulse.

We theoretically and computationally study the generation of high-order harmonics in the water window from a semi-infinite gas cell where a few-cycle, carrier-envelope-phase-controlled 1.7-µm driving laser pulse undergoes nonlinear propagation via optical Kerr effect (self-focusing) and plasma defocusing. Our calculation shows that high harmonic signals are enhanced for extended propagation distances and furthermore, isolated attosecond pulses in the water window can be generated from the semi-infinite gas cell. This enhancement is attributed mainly to better phase matching for extended propagation distances achieved via nonlinear propagation and resulting intensity stabilization.

Breast Cancer Therapeutics and Hippo Signaling Pathway: Novel MicroRNA-Gene-Protein Interaction Networks.

The Hippo signaling pathway is a master regulator of development, cell proliferation, and apoptosis in particular, and it plays an important role in tissue regeneration, controlling organ size, and cancer suppression. Dysregulation of the Hippo signaling pathway has been implicated in breast cancer, a highly prevalent cancer affecting 1 out of every 15 women worldwide. While the Hippo signaling pathway inhibitors are available, they are suboptimal, for example, due to chemoresistance, mutation, and signal leakage. Inadequate knowledge about the Hippo pathway connections and their regulators limits our ability to uncover novel molecular targets for drug development. We report here novel microRNA (miRNA)-gene and protein-protein interaction networks in the Hippo signaling pathway. We employed the GSE miRNA dataset for the present study. The GSE57897 dataset was normalized and searched for differentially expressed miRNAs, and their targets were searched using the miRWalk2.0 tool. From the upregulated miRNAs, we observed that the hsa-miR-205-5p forms the biggest cluster and targets four genes involved in the Hippo signaling pathway. Interestingly, we found a novel connection between two Hippo signaling pathway proteins, angiomotin (AMOT) and mothers against decapentaplegic homolog 4 (SMAD4). From the downregulated miRNAs, hsa-miR-16-5p, hsa-miR-7g-5p, hsa-miR-141-3p, hsa-miR-103a-3p, hsa-miR-21-5p, and hsa-miR-200c-3p, target genes were present in the pathway. We found that PTEN, EP300, and BTRC were important cancer-inhibiting proteins, form hubs, and their genes interact with downregulating miRNAs. We suggest that targeting proteins from these newly unraveled networks in the Hippo signaling pathway and further research on the interaction of hub-forming cancer-inhibiting proteins can open up new avenues for next-generation breast cancer therapeutics.

Multi-omics therapeutic perspective on ACVR1 gene: from genetic alterations to potential targeting.

Activin A receptor type I (ACVR1), a transmembrane serine/threonine kinase, belongs to the transforming growth factor-ß superfamily, which signals via phosphorylating the downstream effectors and SMAD transcription factors. Its central role in several biological processes and intracellular signaling is well known. Genetic variation in ACVR1 has been associated with a rare disease, fibrodysplasia ossificans progressive, and its somatic alteration is reported in rare cancer diffuse intrinsic pontine glioma. Furthermore, altered expression or variation of ACVR1 is associated with multiple pathologies such as polycystic ovary syndrome, congenital heart defects, diffuse idiopathic skeletal hyperostosis, posterior fossa ependymoma and other malignancies. Recent advancements have witnessed ACVR1 as a potential pharmacological target, and divergent promising approaches for its therapeutic targeting have been explored. This review highlights the structural and functional characteristics of receptor ACVR1, associated signaling pathways, genetic variants in several diseases and cancers, protein-protein interaction, gene expression, regulatory miRNA prediction and potential therapeutic targeting approaches. The comprehensive knowledge will offer new horizons and insights into future strategies harnessing its therapeutic potential.

How to Cope with the Challenges of Environmental Stresses in the Era of Global Climate Change: An Update on ROS Stave off in Plants.

With the advent of human civilization and anthropogenic activities in the shade of urbanization and global climate change, plants are exposed to a complex set of abiotic stresses. These stresses affect plants' growth, development, and yield and cause enormous crop losses worldwide. In this alarming scenario of global climate conditions, plants respond to such stresses through a highly balanced and finely tuned interaction between signaling molecules. The abiotic stresses initiate the quick release of reactive oxygen species (ROS) as toxic by-products of altered aerobic metabolism during different stress conditions at the cellular level. ROS includes both free oxygen radicals {superoxide (O2•-) and hydroxyl (OH-)} as well as non-radicals [hydrogen peroxide (H2O2) and singlet oxygen (1O2)]. ROS can be generated and scavenged in different cell organelles and cytoplasm depending on the type of stimulus. At high concentrations, ROS cause lipid peroxidation, DNA damage, protein oxidation, and necrosis, but at low to moderate concentrations, they play a crucial role as secondary messengers in intracellular signaling cascades. Because of their concentration-dependent dual role, a huge number of molecules tightly control the level of ROS in cells. The plants have evolved antioxidants and scavenging machinery equipped with different enzymes to maintain the equilibrium between the production and detoxification of ROS generated during stress. In this present article, we have focused on current insights on generation and scavenging of ROS during abiotic stresses. Moreover, the article will act as a knowledge base for new and pivotal studies on ROS generation and scavenging.

Study of wavelength-dependent pulse self-compression for high intensity pulse propagation in gas-filled capillaries.

We theoretically investigate the wavelength-dependent pulse self-compression dynamics of intense femtosecond laser pulses in gas-filled capillaries. Simulations with λ = 1, 2, 3 and 4 µm using the multimode carrier-resolved unidirectional pulse propagation equation reveal pulse self-compression or pulse broadening depending on plasma and modal dispersion. Our study shows that the pulse at 1 µm exhibits better pulse self-compression compared with longer wavelengths due to smaller group velocity mismatch between fundamental and higher-order capillary modes.

Multioctave supercontinuum generation and frequency conversion based on rotational nonlinearity.

The field of attosecond science was first enabled by nonlinear compression of intense laser pulses to a duration below two optical cycles. Twenty years later, creating such short pulses still requires state-of-the-art few-cycle laser amplifiers to most efficiently exploit "instantaneous" optical nonlinearities in noble gases for spectral broadening and parametric frequency conversion. Here, we show that nonlinear compression can be much more efficient when driven in molecular gases by pulses substantially longer than a few cycles because of enhanced optical nonlinearity associated with rotational alignment. We use 80-cycle pulses from an industrial-grade laser amplifier to simultaneously drive molecular alignment and supercontinuum generation in a gas-filled capillary, producing more than two octaves of coherent bandwidth and achieving >45-fold compression to a duration of 1.6 cycles. As the enhanced nonlinearity is linked to rotational motion, the dynamics can be exploited for long-wavelength frequency conversion and compressing picosecond lasers.

Long-wavelength-infrared laser filamentation in solids in the near-single-cycle regime.

We experimentally demonstrate long-wavelength-infrared (LWIR) femtosecond filamentation in solids. Systematic investigations of supercontinuum (SC) generation and self-compression of the LWIR pulses assisted by laser filamentation are performed in bulk KrS-5 and ZnSe, pumped by ${\sim}{145}\;{\rm fs}$∼145fs, 9 µm, 10 µJ pulses from an optical parametric chirped-pulse amplifier operating at 10 kHz of repetition rate. Multi-octave SC spectra are demonstrated in both materials. While forming stable single filament, 1.5 cycle LWIR pulses with 4.5 µJ output pulse energy are produced via soliton-like self-compression in a 5 mm thick KrS-5. The experimental results quantitatively agree well with the numerical simulation based on the unidirectional pulse propagation equation. This work shows the experimental feasibility of high-energy, near-single-cycle LWIR light bullet generation in solids.

Single-shot ultrafast visualization and measurement of laser-matter interactions in flexible glass using frequency domain holography.

We perform single-shot frequency domain holography to measure the ultrafast spatio-temporal phase change induced by the optical Kerr effect and plasma in flexible Corning Willow Glass during femtosecond laser-matter interactions. We measure the nonlinear index of refraction ($ {n_2} $n2) to be $(3.6 \pm 0.1) \times {10^{ - 16}}\;{{\rm cm}^2}/{\rm W} $(3.6±0.1)×10-16cm2/W and visualize the plasma formation and recombination on femtosecond time scales in a single shot. To compare with the experiment, we carry out numerical simulations by solving the nonlinear envelope equation.