Unmasking the halide effect in diastereoselective Grignard reactions applied to C4´ modified nucleoside synthesis.

The Grignard reaction represents one of the most powerful carbon-carbon bond forming reactions and is the subject of continual study. Investigations of alkyl magnesium halide additions to β-hydroxy ketones identified a unique effect of the magnesium halide on diastereoselectivity, with alkylmagnesium iodide reagents demonstrating high levels of selectivity for the formation of 1,3-syn diols. Density functional theory (DFT) calculations and mechanistic studies suggest that the Lewis acidity of a chelated magnesium alkoxide can be tuned by the choice of halide, with the highest levels of diasteroselectivity achieved using alkyl magnesium iodide reagents.

Interleukin-2 improves insulin sensitivity through hypothalamic sympathetic activation in obese mice.

Background: IL-2 regulates T cell differentiation: low-dose IL-2 induces immunoregulatory Treg differentiation, while high-dose IL-2 acts as a potent activator of cytotoxic T cells and NK cells. Therefore, high-dose IL-2 has been studied for use in cancer immunotherapy. We aimed to utilize low-dose IL-2 to treat inflammatory diseases such as obesity and insulin resistance, which involve low-grade chronic inflammation.

Tau is required for glial lipid droplet formation and resistance to neuronal oxidative stress.

The accumulation of reactive oxygen species (ROS) is a common feature of tauopathies, defined by Tau accumulations in neurons and glia. High ROS in neurons causes lipid production and the export of toxic peroxidated lipids (LPOs). Glia uptake these LPOs and incorporate them into lipid droplets (LDs) for storage and catabolism.

CRISPR-mediated ablation of TP53 and EGFR mutations enhances gefitinib sensitivity and anti-tumor efficacy in lung cancer.

Multiple pathogenic single-nucleotide polymorphisms (SNPs) have been identified as contributing factors in the aggravation of cancer prognosis and emergence of drug resistance in various cancers. Here, we targeted mutated EGFR and TP53 oncogenes harboring single-nucleotide missense mutations (EGFR-T790M and TP53-R273H) that are associated with gefitinib resistance. Co-delivery of adenine base editor (ABE) and EGFR- and TP53-SNP specific single-guide RNA via adenovirus (Ad) resulted in precise correction of the oncogenic mutations with high accuracy and efficiency in vitro and in vivo.

Ghosting: Social rejection without explanation, but not without care.

Many social ties end when one side rejects the other, but rejection does not need to happen directly. Ghosting-the act of ending a relationship by ignoring another person's attempts to connect-is a common way of ending social ties. The present experiments first establish the key characteristics of ghosting and distinguish it from other rejection behaviors (Pilot Studies 1a-1c).

Cdk8/CDK19 promotes mitochondrial fission through Drp1 phosphorylation and can phenotypically suppress pink1 deficiency in Drosophila.

Cdk8 in Drosophila is the orthologue of vertebrate CDK8 and CDK19. These proteins have been shown to modulate transcriptional control by RNA polymerase II. We found that neuronal loss of Cdk8 severely reduces fly lifespan and causes bang sensitivity.

Whole organism snRNA-seq reveals systemic peripheral changes in Alzheimer's Disease fly models.

Peripheral tissues become disrupted in Alzheimer's Disease (AD). However, a comprehensive understanding of how the expression of AD-associated toxic proteins, Aβ42 and Tau, in neurons impacts the periphery is lacking. Using , a prime model organism for studying aging and neurodegeneration, we generated the Alzheimer's Disease Fly Cell Atlas (AD-FCA): whole-organism single-nucleus transcriptomes of 219 cell types from adult flies neuronally expressing human Aβ42 or Tau.

Targeted deletion of CD244 on monocytes promotes differentiation into anti-tumorigenic macrophages and potentiates PD-L1 blockade in melanoma.

Background: In the myeloid compartment of the tumor microenvironment, CD244 signaling has been implicated in immunosuppressive phenotype of monocytes. However, the precise molecular mechanism and contribution of CD244 to tumor immunity in monocytes/macrophages remains elusive due to the co-existing lymphoid cells expressing CD244.

Methods: To directly assess the role of CD244 in tumor-associated macrophages, monocyte-lineage-specific CD244-deficient mice were generated using cre-lox recombination and challenged with B16F10 melanoma.

Novel Single Nucleotide Variations Alter Pathogenicity in Korean Isolates of .

, the causal agent of fire blight disease, has become a serious threat to the pome fruit industry in Korea since 2015. In this study, we showed that two new isolates of , Ea17-2187 and Ea19-7, obtained from pear orchards in Anseong, Korea, exhibited unique pathogenicity compared with other isolates thus far. Both were nonpathogenic to immature apple fruits but occasionally caused disease on immature pear fruits at varying reduced rates.

Dielectrophoretic force-induced wrinkling of graphene oxide: Enhancing electrical conductivity and expanding biosensing applications.

Graphene oxide (GO) has many advantages, making it suitable for various applications. However, it has low electrical conductivity, restricting its applicability to electrochemical biosensors. This study used dielectrophoretic (DEP) force to control the movement and deformation of GO nanosheets to achieve high electrical conductivity without the chemical reduction of oxygen functional groups.

Inactivation of Salmonella Typhimurium and Listeria monocytogenes on buckwheat seeds through combination treatment with plasma, vacuum packaging, and hot water.

Aims: The objectives of this study were to evaluate the effect of combination treatment with cold plasma (CP), vacuum packaging (VP), and hot water (HW) on the inactivation of foodborne pathogens on buckwheat seeds, and determined the germination rates of seeds and the quality of sprouts following combination treatment.

Methods And Results: Buckwheat seeds inoculated with Salmonella Typhimurium and Listeria monocytogenes were treated with CP, HW, CP + HW, VP + HW, or CP + VP + HW. The germination rates of the HW-, CP + HW-, VP + HW-, and CP + VP + HW-treated seeds and the antioxidant activities and rutin contents of the CP + HW- and CP + VP + HW-treated sprouts were determined.

Fatal outcome of severe fever with thrombocytopenia syndrome (SFTS) and severe and critical COVID-19 is associated with the hyperproduction of IL-10 and IL-6 and the low production of TGF-β.

Severe fever with thrombocytopenia syndrome virus (SFTSV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause the hyperproduction of inflammatory cytokines, which have pathological effects in patient including severe or fatal cytokine storms. To characterize the effect of SFTSV and SARS-CoV-2 infection on the production of cytokines in severe fever with thrombocytopenia syndrome (SFTS) and COVID-19 patients, we performed an analysis of cytokines in SFTS and COVID-19 patients and also investigated the role of interleukin-10 (IL-10) in vitro studies: lipopolysaccharide-induced THP-1-derived macrophages, SFTSV infection of THP-1 cells, and SARS-CoV-2 infection of THP-1 cells. In this study, we found that levels of both IL-10 and IL-6 were significantly elevated, the level of transforming growth factor-β (TGF-β) was significantly decreased and IL-10 was elevated earlier than IL-6 in severe and critical COVID-19 and fatal SFTS patients, and inhibition of IL-10 signaling decreased the production of IL-6 and elevated that of TGF-β.

Aging Fly Cell Atlas identifies exhaustive aging features at cellular resolution.

Aging is characterized by a decline in tissue function, but the underlying changes at cellular resolution across the organism remain unclear. Here, we present the Aging Fly Cell Atlas, a single-nucleus transcriptomic map of the whole aging . We characterized 163 distinct cell types and performed an in-depth analysis of changes in tissue cell composition, gene expression, and cell identities.

Recent Advances in Multiplexed Wearable Sensor Platforms for Real-Time Monitoring Lifetime Stress: A Review.

Researchers are interested in measuring mental stress because it is linked to a variety of diseases. Real-time stress monitoring via wearable sensor systems can aid in the prevention of stress-related diseases by allowing stressors to be controlled immediately. Physical tests, such as heart rate or skin conductance, have recently been used to assess stress; however, these methods are easily influenced by daily life activities.

Self-Formation of a Ru/ZnO Multifunctional Bilayer for the Next-Generation Interconnect Technology via Area-Selective Atomic Layer Deposition.

This study suggests a Ru/ZnO bilayer grown using area-selective atomic layer deposition (AS-ALD) as a multifunctional layer for advanced Cu metallization. As a diffusion barrier and glue layer, ZnO is selectively grown on SiO , excluding Cu, where Ru, as a liner and seed layer, is grown on both surfaces. Dodecanethiol (DDT) is used as an inhibitor for the AS-ALD of ZnO using diethylzinc and H O at 120 °C.

Visualizing extracellular vesicle biogenesis in gram-positive bacteria using super-resolution microscopy.

Background: Recently, bacterial extracellular vesicles (EVs) have been considered to play crucial roles in various biological processes and have great potential for developing cancer therapeutics and biomedicine. However, studies on bacterial EVs have mainly focused on outer membrane vesicles released from gram-negative bacteria since the outermost peptidoglycan layer in gram-positive bacteria is thought to preclude the release of EVs as a physical barrier.

Results: Here, we examined the ultrastructural organization of the EV produced by gram-positive bacteria using super-resolution stochastic optical reconstruction microscopy (STORM) at the nanoscale, which has not been resolved using conventional microscopy.

Comparison of Optical and Electrical Sensor Characteristics for Efficient Analysis of Attachment and Detachment of Aptamer.

Nucleic acid aptamer-based research has focused on achieving the highest performance for bioassays. However, there are limitations in evaluating the affinity for the target analytes in these nucleic acid aptamer-based bioassays. In this study, we mainly propose graphene oxide (GO)-based electrical and optical analyses to efficiently evaluate the affinity between an aptamer and its target.

Polarity Nano-Mapping of Polymer Film Using Spectrally Resolved Super-Resolution Imaging.

With the rapid development of the nanofabrication of polymer materials, the local measurement of the chemical properties of polymer nanostructures has become crucial because they can be highly heterogeneous at the nanoscale. We developed a spectroscopic imaging approach to characterize the nanoscale local polarity of polymer films via spectrally resolved super-resolution microscopy. We demonstrate the capability of the recently developed single-molecule sensing and imaging method to probe the polarity of polymers either inside a polymer matrix or on the external surface of a polymer.

Calcipotriol, a synthetic Vitamin D analog, promotes antitumor immunity via CD4+T-dependent CTL/NK cell activation.

To overcome the hurdles of immunotherapy, we investigated whether calcipotriol, a synthetic vitamin D analog, could overcome the immune evasion of glioblastoma multiforme (GBM) by modulating immune responses and the immunosuppressive tumor microenvironment. Administration of calcipotriol considerably reduced tumor growth. Both in vivo and in vitro studies revealed that CD8+T and natural killer (NK) cell gene signatures were enriched and activated, producing high levels of IFN-γ and granzyme B.

Electric-Field-Mediated In-Sensor Alignment of Antibody's Orientation to Enhance the Antibody-Antigen Binding for Ultrahigh Sensitivity Sensors.

Applying an electric-field (-field) during antibody immobilization aligns the orientation of the antibody on the biosensor surface, thereby enhancing the binding probability between the antibody and antigen and maximizing the sensitivity of the biosensor. In this study, a biosensor with enhanced antibody-antigen binding probability was developed using the alignment of polar antibodies (immunoglobulin G [IgG]) under an -field applied inside the interdigitated electrodes. The optimal alignment condition was first theoretically calculated and then experimentally confirmed by comparing the impedance change before and after the alignment of IgG (a purified anti-β-amyloid antibody).

Effect of Surrounding Solvents on Interfacial Behavior of Gallium-Based Liquid Metal Droplets.

Gallium-based liquid metal (GaLM) alloys have been extensively used in applications ranging from electronics to drug delivery systems. To broaden the understanding and applications of GaLMs, this paper discusses the interfacial behavior of eutectic gallium-indium liquid metal (EGaIn) droplets in various solvents. No significant difference in contact angles of EGaIn is observed regardless of the solvent types.

A Bioprinted Tubular Intestine Model Using a Colon-Specific Extracellular Matrix Bioink.

Tremendous advances have been made toward accurate recapitulation of the human intestinal system in vitro to understand its developmental process, and disease progression. However, current in vitro models are often confined to 2D or 2.5D microarchitectures, which is difficult to mimic the systemic level of complexity of the native tissue.