Structure-Based Design of 2-Aminopyrazolpyrimidopyridone Derivatives as New Rearranged During Transfection (RET) Kinase Inhibitors.

RET (Rearranged during transfection) kinase is a validated target for non-small cell lung cancer (NSCLC). In 2020, two selective RET inhibitors, selpercatinib and pralsetinib were approved by the US FDA. However, high treatment costs and clinically acquired resistance (e.

Two-dimensional flat-band solitons in superhoneycomb lattices.

Flat-band periodic materials are characterized by a linear spectrum containing at least one band where the propagation constant remains nearly constant irrespective of the Bloch momentum across the Brillouin zone. These materials provide a unique platform for investigating phenomena related to light localization. Meantime, the interaction between flat-band physics and nonlinearity in continuous systems remains largely unexplored, particularly in continuous systems where the band flatness deviates slightly from zero, in contrast to simplified discrete systems with exactly flat bands.

Mamastrovirus spike protein: Sequence and structural characterization as a basis for understanding cross-species transmission.

Astroviruses (AstVs) are notable for their propensity for cross-species transmission; however, the molecular determinants underlying this phenomenon remain poorly understood. The spike protein, which is responsible for host cell entry and is a major antigenic determinant, is hypothesized to play a pivotal role. In this study, we observed high sequence variability in the spike region of AstV.

Observation of nonlinear fractal higher order topological insulator.

Higher-order topological insulators (HOTIs) are unique materials hosting topologically protected states, whose dimensionality is at least by 2 lower than that of the bulk. Topological states in such insulators may be strongly confined in their corners which leads to considerable enhancement of nonlinear processes involving such states. However, all nonlinear HOTIs demonstrated so far were built on periodic bulk lattice materials.

Development of RPA-Cas12a assay for rapid and sensitive detection of Pneumocystis jirovecii.

Pneumocystis jirovecii is a prevalent opportunistic fungal pathogen that can lead to life-threatening Pneumocystis pneumonia in immunocompromised individuals. Given that timely and accurate diagnosis is essential for initiating prompt treatment and enhancing patient outcomes, it is vital to develop a rapid, simple, and sensitive method for P. jirovecii detection.

-symmetric photonic lattices with type-II Dirac cones.

The type-II Dirac cone is a special feature of the band structure, whose Fermi level is represented by a pair of crossing lines. It has been demonstrated that such a structure is useful for investigating topological edge solitons and, more specifically, for mimicking the Klein tunneling. However, it is still not clear what the interplay between type-II Dirac cones and the non-Hermiticity mechanism will result in.

HR-MRI-based nomogram network calculator to predict stroke recurrence in high-risk non-disabling ischemic cerebrovascular events patients.

Background And Objective: To investigate the use of high-resolution magnetic resonance imaging (HR-MRI) to identify the characteristics of culprit plaques in intracranial arteries, and to evaluate the predictive value of the characteristics of culprit plaques combined with the modified Essen score for the recurrence risk of high-risk non-disabling ischemic cerebrovascular events (HR-NICE) patients.

Methods: A retrospective analysis was conducted on 180 patients with HR-NICE at the First Affiliated Hospital of Xinxiang Medical University, including 128 patients with no recurrence (non-recurrence group) and 52 patients with recurrence (recurrence group). A total of 65 patients with HR-NICE were collected from the Sixth Affiliated Hospital of Shanghai Jiaotong University as a validation group, and their modified Essen scores, high-resolution magnetic resonance vessel wall images, and clinical data were collected.

EGFR degraders in non-small-cell lung cancer: Breakthrough and unresolved issue.

The epidermal growth factor receptor (EGFR) has been well validated as a therapeutic target for anticancer drug discovery. Osimertinib has become the first globally accessible third-generation EGFR inhibitor, representing one of the most advanced developments in non-small-cell lung cancer (NSCLC) therapy. However, a tertiary Cys797 to Ser797 (C797S) point mutation has hampered osimertinib treatment in patients with advanced EGFR-mutated NSCLC.

Deciphering antifungal and antibiofilm mechanisms of isobavachalcone against Cryptococcus neoformans through RNA-seq and functional analyses.

Cryptococcus neoformans has been designated as critical fungal pathogens by the World Health Organization, mainly due to limited treatment options and the prevalence of antifungal resistance. Consequently, the utilization of novel antifungal agents is crucial for the effective treatment of C. neoformans infections.

An annular pulse forming line based on coaxial transmission lines.

The miniaturization, lightweight, and solidification of pulse forming lines (PFLs) are of prime significance during the evolution of pulsed power technology. In this paper, an all-solid-state annular pulse forming line (APFL) based on film-insulated coaxial transmission lines is developed to generate fast-rise time quasi-square pulses. First, a coiled coaxial transmission line (CCTL) comprised of multilayer polypropylene films with outstanding insulating properties is constructed.

Establishment of RPA-Cas12a-Based Fluorescence Assay for Rapid Detection of Feline Parvovirus.

Feline parvovirus (FPV) is highly infectious for cats and other Felidae and often causes severe damage to young kittens. In this study, we incorporated recombinase polymerase amplification (RPA) and Cas12a-mediated detection and developed an RPA-Cas12a-based real-time or end-point fluorescence detection method to identify the NS1 gene of FPV. The total time of RPA-Cas12a-based fluorescence assay is approximately 25 min.

Structural Insights and Influence of Terahertz Waves in Midinfrared Region on Kv1.2 Channel Selectivity Filter.

Potassium ion channels are the structural basis for excitation transmission, heartbeat, and other biological processes. The selectivity filter is a critical structural component of potassium ion channels, whose structure is crucial to realizing their function. As biomolecules vibrate and rotate at frequencies in the terahertz band, potassium ion channels are sensitive to terahertz waves.

Comprehensive analysis of sesame LRR-RLKs: structure, evolution and dynamic expression profiles under stress.

Leucine-rich repeat receptor-like kinases (LRR-RLKs) can participate in the regulation of plant growth and development, immunity and signal transduction. , one of the most important oil crops, has a significant role in promoting human health. In this study, 175 genes were identified in , and they were subdivided into 12 subfamilies by phylogenetic analysis.

Hsa_circ_0021205 enhances lipolysis via regulating miR-195-5p/HSL axis and drives malignant progression of glioblastoma.

Abnormal lipid metabolism is an essential hallmark of glioblastoma. Hormone sensitive lipase (HSL), an important rate-limiting enzyme contributed to lipolysis, which was involved in aberrant lipolysis of glioblastoma, however, its definite roles and the relevant regulatory pathway have not been fully elucidated. Our investigations disclosed high expression of HSL in glioblastoma.

Effect of THz Waves of Different Orientations on K Permeation Efficiency in the KcsA Channel.

Potassium (K) channels show the highest variability and most frequent alterations in expression in many tumor types, and modulation of K channels may represent a new window for cancer therapy. In previous work, we found that a terahertz (THz) field incident along the -axis with a frequency of 51.87 THz increased the ion flux through K channels.

An integrative analysis of single-cell and bulk transcriptome and bidirectional mendelian randomization analysis identified C1Q as a novel stimulated risk gene for Atherosclerosis.

Background: The role of complement component 1q (C1Q) related genes on human atherosclerotic plaques (HAP) is less known. Our aim is to establish C1Q associated hub genes using single-cell RNA sequencing (scRNA-seq) and bulk RNA analysis to diagnose and predict HAP patients more effectively and investigate the association between C1Q and HAP (ischemic stroke) using bidirectional Mendelian randomization (MR) analysis.

Methods: HAP scRNA-seq and bulk-RNA data were download from the Gene Expression Omnibus (GEO) database.

Establishment of RT-RPA-Cas12a assay for rapid and sensitive detection of human rhinovirus B.

Human rhinovirus B (HRV-B) is a major human viral pathogen that can be responsible for various kinds of infections. Due to the health risks associated with HRV-B, it is therefore crucial to explore a rapid, specific, and sensitive method for surveillance. Herein, we exploited a novel detection method for HRV-B by combining reverse-transcription recombinase polymerase amplification (RT-RPA) of nucleic acids isothermal amplification and the trans-cleavage activity of Cas12a.

Suppression of Secondary Electron Emission from Nickel Surface by Graphene Composites Based on First-Principles Method.

Secondary electron emission (SEE) is a fundamental phenomenon of particle/surface interaction, and the multipactor effect induced by SEE can result in disastrous impacts on the performance of microwave devices. To suppress the SEE-induced multipactor, an Ni (111) surface covered with a monolayer of graphene was proposed and studied theoretically via the density functional theory (DFT) method. The calculation results indicated that redistribution of the electron density at the graphene/Ni (111) interface led to variations in the work function and the probability of SEE.

Association of the L3MBTL3 rs1125970 and rs4897367 Gene Polymorphisms With Coronary Heart Disease Susceptibility in the Chinese Population: A Case-Control Study.

Coronary heart disease (CHD) is a prevalent heart disease with high incidence and mortality rates worldwide, and its pathogenesis is related to genetic factors. L3MBTL3 has been reported to be potentially linked to CHD susceptibility. This study aims to explore the correlation between L3MBTL3 single nucleotide polymorphisms (SNPs) and CHD risk in the Chinese population.

Non-adaptive evolution in codon usage of human-origin monkeypox virus.

Monkeypox virus (Mpox) is a zoonotic infectious disease that threatens human and animal health, with a global outbreak of the low-pathogenic Mpox beginning from 2022. In this study, we analyzed the codon usage of Mpox between two clades, Clade-I and Clade-IIb-B, to understand changes in host adaptation. Clade-IIb-B of the Mpox genome underwent non-adaptive evolution making it less adapted to its host than Clade-I.

Permeability enhancement of Kv1.2 potassium channel by a terahertz electromagnetic field.

As biomolecules vibrate and rotate in the terahertz band, the biological effects of terahertz electromagnetic fields have drawn considerable attention from the physiological and medical communities. Ion channels are the basis of biological electrical signals, so studying the effect of terahertz electromagnetic fields on ion channels is significant. In this paper, the effect of a terahertz electromagnetic field with three different frequencies, 6, 15, and 25 THz, on the Kv1.

Vector valley Hall edge solitons in distorted type-II Dirac photonic lattices.

Topological edge states have recently garnered a lot of attention across various fields of physics. The topological edge soliton is a hybrid edge state that is both topologically protected and immune to defects or disorders, and a localized bound state that is diffraction-free, owing to the self-balance of diffraction by nonlinearity. Topological edge solitons hold great potential for on-chip optical functional device fabrication.

Effect of Terahertz Electromagnetic Field on the Permeability of Potassium Channel Kv1.2.

In this paper, the influence of external terahertz electromagnetic fields with different frequencies of 4 THz, 10 THz, 15 THz, and 20 THz on the permeability of the Kv1.2 voltage-gated potassium ion channel on the nerve cell membrane was studied using the combined model of the "Constant Electric Field-Ion Imbalance" method by molecular dynamics. We found that although the applied terahertz electric field does not produce strong resonance with the -C=O groups of the conservative sequence T-V-G-Y-G amino acid residue of the selective filter (SF) of the channel, it would affect the stability of the electrostatic bond between potassium ions and the carbonyl group of T-V-G-Y-G of SF, and it would affect the stability of the hydrogen bond between water molecules and oxygen atoms of the hydroxyl group of the 374THR side chain at the SF entrance, changing the potential and occupied states of ions in the SF and the occurrence probability of the permeation mode of ions and resulting in the change in the permeability of the channel.

Exosomal miR-6733-5p mediates cross-talk between glioblastoma stem cells and macrophages and promotes glioblastoma multiform progression synergistically.

Aim: Exosomal miRNAs derived from glioblastoma stem cells (GSCs) are important mediators of immunosuppressive microenvironment formation in glioblastoma multiform (GBM), especially in M2-like polarization of tumor-associated macrophages (TAMs). However, the exact mechanisms by which GSCs-derived exosomes (GSCs-exo) facilitate the remodeling of the immunosuppressive microenvironment of GBM have not been elucidated.

Methods: Transmission electron microscopy (TME) and nanoparticle tracking analysis (NTA) were applied to verify the existence of GSCs-derived exosomes.