Lassa virus Z protein hijacks the autophagy machinery for efficient transportation by interrupting CCT2-mediated cytoskeleton network formation.

The Lassa virus (LASV) is a widely recognized virulent pathogen that frequently results in lethal viral hemorrhagic fever (VHF). Earlier research has indicated that macroautophagy/autophagy plays a role in LASV replication, but, the precise mechanism is unknown. In this present study, we show that LASV matrix protein (LASV-Z) is essential for blocking intracellular autophagic flux.

Biosynthesis of Nanoparticles with Green Tea for Inhibition of β-Amyloid Fibrillation Coupled with Ligands Analysis.

Background: Inhibition of amyloid β protein fragment (Aβ) aggregation is considered to be one of the most effective strategies for the treatment of Alzheimer's disease. (-)-Epigallocatechin-3-gallate (EGCG) has been found to be effective in this regard; however, owing to its low bioavailability, nanodelivery is recommended for practical applications. Compared to chemical reduction methods, biosynthesis avoids possible biotoxicity and cumbersome preparation processes.

Visible-Light-Promoted Radical Cascade Cyclization of 2-Vinyl Benzimidazoles: Access to Benzo[4,5]imidazo[1,2-]isoquinolin- 11(6)-ones.

A visible-light-enabled photoredox radical cascade cyclization of 2-vinyl benzimidazole derivatives is developed. This chemistry is applicable to a wide range of -aroyl 2-vinyl benzimidazoles as acceptors, and halo compounds, including alkyl halides, acyl chlorides and sulfonyl chlorides, as radical precursors. The Langlois reagent also serves as an effective partner in this photocatalytic oxidative cascade process.

Optomechanical Frequency Comb Based on Multiple Nonlinear Dynamics.

Phonon-based frequency combs that can be generated in the optical and microwave frequency domains have attracted much attention due to the small repetition rates and the simple setup. Here, we experimentally demonstrate a new type of phonon-based frequency comb in a silicon optomechanical crystal cavity including both a breathing mechanical mode (∼GHz) and flexural mechanical modes (tens of MHz). We observe strong mode competition between two approximate flexural mechanical modes, i.

Effect of Initial Position and Crystallographic Orientation on Grain Selection Procedure in Z-Form Selector for Ni-Based Single-Crystal Superalloy.

The grain selection process in a Z-form selector for Ni-based single-crystal superalloy was simulated using a macro-scale ProCAST software (2013 version) coupled CAFE module combined with an experiment to investigate the grain selection procedure and mechanism with different grain positions and crystal orientation relationships. A non-stationary solidification process was found in the Z-form selector, and the liquid-solid (L-S) interface was tilted in the same direction as the selector channel during directional solidification. Given that the grain boundary was parallel to the Z-form selector, the overgrowth rate of the bi-crystal in the selector channel was very low.

Neuroinvasive virus facilitates viral replication by employing lipid droplets to reduce arachidonic acid-induced ferroptosis.

Lipids have been previously implicated in the lifecycle of neuroinvasive viruses. However, the role of lipids in programmed cell death and the relationship between programmed cell death and lipid droplets (LDs) in neuroinvasive virus infection remains unclear. Here, we found that the infection of neuroinvasive virus, such as rabies virus and encephalomyocarditis virus could enhance the LD formation in N2a cells, and decreasing LDs production by targeting diacylglycerol acyltransferase could suppress viral replication.

Transcription factor FOXP4 inversely governs tumor suppressor genes and contributes to thyroid cancer progression.

Objective: In recent decades, thyroid cancer (TC) has exhibited a rising incidence pattern. Elevated levels of the transcription factor FOXP4 have been strongly linked to the progression of diverse tumors; nevertheless, its specific role in thyroid cancer remains underexplored. The primary objective of this study was to elucidate the functions of FOXP4 and its associated target gene, FBXW7, in the context of thyroid cancer.

Magnonic Frequency Comb in the Magnomechanical Resonator.

An optical frequency comb is a spectrum of optical radiation which consists of evenly spaced and phase-coherent narrow spectral lines and is initially invented in a laser for frequency metrology purposes. A direct analog of frequency combs in the magnonic systems has not been demonstrated to date. In our experiment, we generate a new magnonic frequency comb in the resonator with giant mechanical oscillations through the magnomechanical interaction.

A modified recombinant adenovirus vector containing dual rabies virus G expression cassettes confers robust and long-lasting humoral immunity in mice, cats, and dogs.

During the COVID-19 epidemic, the incidence of rabies has increased in several countries, especially in remote and disadvantaged areas, due to inadequate surveillance and declining immunization coverage. Multiple vaccinations with inactivated rabies virus vaccines for pre- or post-exposure prophylaxis are considered inefficient, expensive and impractical in developing countries. Herein, three modified human recombinant adenoviruses type 5 designated Adv-RVG, Adv-E1-RVG, and Adv-RVDG, carrying rabies virus G (RVG) expression cassettes in various combinations within or genomic regions, were constructed to serve as rabies vaccine candidates.

Functional polymorphisms in Benzo(a)Pyrene-induced toxicity pathways associated with the risk on laryngeal squamous cell carcinoma.

Benzo(a)Pyrene (BaP) is a well-known environmental carcinogen that poses a significant risk to human health. The pivotal genes and toxicity pathways have been identified as key events to construct the mode of action (MOA) of BaP. In this study, we focused on evaluating the association between genetic variants in BaP-disturbed toxicity pathways and the susceptibility of laryngeal squamous cell carcinoma (LSCC), based on the data of our previous genome-wide association analysis (GWAS).

Specific recognition and sensitive quantification of mRNA splice variants one-pot ligation-dependent loop-mediated isothermal amplification.

Specific recognition and sensitive quantification of mRNA alternative splice variants have been a necessity for exploring the regulatory mechanism of RNA splicing and revealing the association between pre-mRNA splicing and transcriptome function, as well as disease diagnosis. However, their wide abundance range and high sequence homology pose enormous challenges for high sensitivity and selectivity quantification of splice variants. Herein, taking advantage of the excellent specificity of ligation and the powerful nucleic acid replication feature of loop-mediated isothermal amplification (LAMP), we developed a one-pot method (termed one-pot ligation-LAMP) for specific recognition and sensitive quantification of mRNA splicing variants based on two splicing junction-specific stem-loop DNA probe ligation and the subsequently initiating LAMP.

Effects of tris (2-chloroethyl) phosphate exposure on gut microbiome using the simulator of the human intestinal microbial ecosystem (SHIME).

Tris (2-chloroethyl) phosphate (TCEP) has been widely used, and its health risk has received increasing attention. However, the rare research has been conducted on the effects of TCEP exposure on changes in the structure of the human gut microbiome and metabolic functions. In this experiment, Simulator of the human intestinal microbial ecosystem (SHIME) was applied to explore the influences of TCEP on the human gut bacteria community and structure.

The Effects of -3 PUFA Supplementation on Bone Metabolism Markers and Body Bone Mineral Density in Adults: A Systematic Review and Meta-Analysis of RCTs.

Supplemental -3 polyunsaturated fatty acids (PUFA) on bone metabolism have yielded inconsistent results. This study aimed to examine the effects of -3 PUFA supplementation on bone metabolism markers and bone mineral density through a meta-analysis of randomized controlled trials. A systematic literature search was conducted using the PubMed, Web of Science, and EBSCO databases, updated to 1 March 2023.

Immunotherapy for non-small cell lung cancer with EGFR or HER2 exon 20 insertion mutations: a real-world analysis.

Background: Due to less sensitivity to classic tyrosine kinase inhibitors, effective first-line treatment is limited in non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) or human epidermal growth factor receptor 2 (HER2) exon 20 insertion (ex20ins) mutations. Meanwhile, the impact of driver genes on the efficacy of PD-1 inhibitors is discrepant. Our study aimed to assess the clinical response to immunotherapy in NSCLC patients with EGFR or HER2 ex20ins mutations.

A Phase 1 First-in-Human Pharmacokinetic and Pharmacodynamic Study of JNJ-64264681, a Covalent Inhibitor of Bruton's Tyrosine Kinase.

JNJ-64264681 is an irreversible covalent inhibitor of Bruton's tyrosine kinase. This phase 1, first-in-human, 2-part (single-ascending dose [SAD]; multiple-ascending dose [MAD]) study evaluated the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD; Bruton's tyrosine kinase occupancy [BTKO]) of JNJ-64264681 oral solution in healthy participants. For SAD (N = 78), 6 increasing doses of JNJ-64264681 (4-400 mg) or placebo were evaluated in fasted males.

Punicalagin protects against impaired skeletal muscle function in high-fat-diet-induced obese mice by regulating TET2.

The function of skeletal muscles can be markedly hampered by obesity. Ten-eleven translocation 2 (TET2) is an important therapeutic target for ameliorating skeletal muscle dysfunction. Our previous study revealed that punicalagin (PUN) regulated TET2 in obese mice; however, whether PUN can prevent obesity-induced skeletal muscle dysfunction by regulating TET2 remains unclear.

Coherent Coupling between Phonons, Magnons, and Photons.

Mechanical degrees of freedom, which have often been overlooked in various quantum systems, have been studied for applications ranging from quantum information processing to sensing. Here, we develop a hybrid platform consisting of a magnomechanical cavity and an optomechanical cavity, which are coherently coupled by the straightway physical contact. The phonons in the system can be manipulated either with the magnetostrictive interaction or optically through the radiation pressure.

Ringing spectroscopy in the magnomechanical system.

The ringing phenomenon has been studied in optical whispering gallery mode (WGM) resonators and can be used to sense the ultrafast process in spectroscopy. Here we observe the ringing phenomenon in a magnomechanical system for the first time, which is induced by the interference between the microwave photons converted from the damped phonons and the probing microwave photons. This interference eventually appears as a transparency window even along with the ringing phenomenon in the measured microwave reflection spectrum, which is influenced by the scanning speed and the input power.

Long-Term Clinical Outcomes and Safety Analysis of Superficial Esophageal Cancer Patients Treated with Definitive or Adjuvant Radiotherapy.

(1) Background: The role of radiotherapy (RT) in superficial esophageal squamous cell cancer (ESCC) remains unclear. The objective of our study was to perform a detailed outcome and safety analysis of RT as a definitive or adjuvant treatment for T1N0M0 staged ESCC patients. (2) Methods: A total of 55 patients treated with endoscopic resection (ER) + RT/concurrent chemoradiotherapy (CCRT) or RT/CCRT from January 2011 to June 2021 were included in this study.

Ultrasensitive quantification of multiplexed mRNA variants splice-junction anchored DNA probes and SplintR ligase-initiated PCR.

A method based on mRNA-templated ligation of splice-junction anchored DNA probes followed by PCR amplification of the ligated product has been developed for multiplexed detection of mRNA splice variants with high sensitivity and specificity. The proposed assay can detect as low as 10 aM mRNA splicing variants and has been successfully applied to detect real samples.