Copper-Catalyzed C(sp)-H α-Acetylation: Generation of Quaternary Centers.

α-substituted ketones are important chemical targets as synthetic intermediates as well as functionalities in natural products and pharmaceuticals. We report the α-acetylation of C(sp)-H substrates R-H with arylmethyl ketones ArC(O)Me to provide α-alkylated ketones ArC(O)CHR at RT with BuOOBu as oxidant via copper(I) -diketiminato catalysts. Proceeding via alkyl radicals R•, this method enables α-substitution with bulky substituents without competing elimination that occurs in more traditional alkylation reactions between enolates and alkyl electrophiles.

Copper catalyzed benzylic sp C-H alkenylation.

The prenyl group is present in numerous biologically active small molecule drugs and natural products. We introduce benzylic C-H alkenylation of substrates Ar-CH with alkenylboronic esters (CH)OB-CH[double bond, length as m-dash]CMe as a pathway to form prenyl functionalized arenes Ar-CHCH[double bond, length as m-dash]CMe. Mechanistic studies of this radical relay catalytic protocol reveal diverse reactivity pathways exhibited by the copper(ii) alkenyl intermediate [Cu]-CH[double bond, length as m-dash]CMe that involve radical capture, bimolecular C-C bond formation, and hydrogen atom transfer (HAT).

Quantification Quality Control Emerges as a Crucial Factor to Enhance Single-Cell Proteomics Data Analysis.

Mass spectrometry (MS)-based single-cell proteomics (SCP) provides us the opportunity to unbiasedly explore biological variability within cells without the limitation of antibody availability. This field is rapidly developed with the main focuses on instrument advancement, sample preparation refinement, and signal boosting methods; however, the optimal data processing and analysis are rarely investigated which holds an arduous challenge because of the high proportion of missing values and batch effect. Here, we introduced a quantification quality control to intensify the identification of differentially expressed proteins (DEPs) by considering both within and across SCP data.

Circ_0000877 accelerates proliferation and immune escape of non-small cell lung cancer cells by regulating microRNA-637/E2F2 axis.

Background: Recently, circular RNA (circRNA) has become a vital targeted therapy gene for non-small-cell lung cancer (NSCLC) cells. CircRNA_0000877 (Circ_0000877) has been researched in diffuse large B-cell lymphoma (DLBCL). However, whether circ_0000877 regulated NSCLC cell progression is still poorly investigated.

Effects of ceramic thickness, ceramic translucency, and light transmission on light-cured bulk-fill resin composites as luting cement of lithium disilicate based-ceramics.

Purpose: To assess the effects of ceramic thickness, ceramic translucency, and light transmission on restorative composites used as luting cement for lithium disilicate-based ceramics.

Methods: Four luting types of cement were tested (n=8); a dual-cured resin cement (Multilink N), a light-cured conventional flowable composite (Tetric N-Flow), and two light-cured bulk-fill flowable composites (Tetric N-Flow Bulk Fill and X-tra base). The 20 s- or 40 s-light (1000 mW/cm) was transmitted through 1- or 2-mm-thick high- or low-translucency (HT- or LT-) ceramic discs (IPS e.

Imaging Genetic Based Mediation Analysis for Human Cognition.

The brain connectome maps the structural and functional connectivity that forms an important neurobiological basis for the analysis of human cognitive traits while the genetic predisposition and our cognition ability are frequently found in close association. The issue of how genetic architecture and brain connectome causally affect human behaviors remains unknown. To seek for the potential causal relationship, in this paper, we carried out the causal pathway analysis from single nucleotide polymorphism (SNP) data to four common human cognitive traits, mediated by the brain connectome.

Canonical Wnt Signaling Promotes Formation of Somatic Permeability Barrier for Proper Germ Cell Differentiation.

Morphogen-mediated signaling is critical for proper organ development and stem cell function, and well-characterized mechanisms spatiotemporally limit the expression of ligands, receptors, and ligand-binding cell-surface glypicans. Here, we show that in the developing ovary, canonical Wnt signaling promotes the formation of somatic escort cells (ECs) and their protrusions, which establish a physical permeability barrier to define morphogen territories for proper germ cell differentiation. The protrusions shield germ cells from Dpp and Wingless morphogens produced by the germline stem cell (GSC) niche and normally only received by GSCs.

Color-complexity enabled exhaustive color-dots identification and spatial patterns testing in images.

Our computational developments and analyses on experimental images are designed to evaluate the effectiveness of chemical spraying via unmanned aerial vehicle (UAV). Our evaluations are in accord with the two perspectives of color-complexity: color variety within a color system and color distributional geometry on an image. First, by working within RGB and HSV color systems, we develop a new color-identification algorithm relying on highly associative relations among three color-coordinates to lead us to exhaustively identify all targeted color-pixels.

Role of Pneumococcal NanC in the Severe Disease of Superinfection with Influenza.

Bacterial superinfection aggravates the disease of influenza. is the most common bacterial pathogen. Synergistic virulence has been demonstrated between influenza neuraminidase and pneumococcal NanA and NanB.

Collagen production and niche engineering: A novel strategy for cancer cells to survive acidosis in DCIS and evolve.

Growing tumors are dynamic and nonlinear ecosystems, wherein cancer cells adapt to their local microenvironment, and these adaptations further modify the environment, inducing more changes. From nascent intraductal neoplasms to disseminated metastatic disease, several levels of evolutionary adaptations and selections occur. Here, we focus on one example of such an adaptation mechanism, namely, "niche construction" promoted by adaptation to acidosis, which is a metabolic adaptation to the early harsh environment in intraductal neoplasms.

Artificial selection for host resistance to tumour growth and subsequent cancer cell adaptations: an evolutionary arms race.

Background: Cancer progression is governed by evolutionary dynamics in both the tumour population and its host. Since cancers die with the host, each new population of cancer cells must reinvent strategies to overcome the host's heritable defences. In contrast, host species evolve defence strategies over generations if tumour development limits procreation.

Protective Evaluation of Compounds Extracted from Root of L. against Methylglyoxal-Induced Toxicity in a Neuronal Cell Line.

L. () is one of the most beneficial medicinal plants and it is studied as an adaptogen. This study aims to evaluate the neuroprotective activity of compounds extracted from the root of against methylglyoxal (MG)-induced apoptosis in neuro-2A (N2A) cells.

Effect of aloin on viral neuraminidase and hemagglutinin-specific T cell immunity in acute influenza.

Background: Millions of people are infected by the influenza virus worldwide every year. Current selections of anti-influenza agents are limited and their effectiveness and drug resistance are still of concern.

Purpose: Investigation on in vitro and in vivo effect of aloin from Aloe vera leaves against influenza virus infection.

Alkanethiolate-Capped Palladium Nanoparticles for Regio- and Stereoselective Hydrogenation of Allenes.

Colloidal Pd nanoparticles capped with octanethiolate ligands have previously shown an excellent selectivity toward the mono-hydrogenation of both isolated and conjugated dienes to internal alkenes. This paper reports an efficient stereoselective mono-hydrogenation of cumulated dienes (allenes) to either Z or E olefinic isomers, depending on the substitution pattern around C=C bonds. Kinetic studies indicate that the reaction progresses through the hydrogenation of less hindered C=C bonds to produce internal Z olefinic isomers.

Management of Giant Retinal Tear with microincision vitrectomy and metallic retinal tacks fixation-a case report.

Background: Giant retinal tear is usually challenging among retinal detachment with recurrent rate up to 45%. Here we presented a case of giant retinal tear being treated by microincision vitrectomy and retinal tacks fixation.

Case Presentation: A 53-year-old male presented to our hospital with blurred vision of his right eye for one week with floaters and obscured sensation over nasal visual field.

Ultrasound-assisted emulsification microextraction for rapid determination of unmetabolized synthetic polycyclic and nitro-aromatic musks in human urine.

An effective method to rapidly determine the presence of seven unmetabolized synthetic musks in human urine samples is developed. The target musks are five synthetic polycyclic musks (i.e.

Alkanethiolate-capped palladium nanoparticles for selective catalytic hydrogenation of dienes and trienes.

Selective hydrogenation of dienes and trienes is an important process in the pharmaceutical and chemical industries. Our group previously reported that the thiosulfate protocol using a sodium -alkylthiosulfate ligand could generate catalytically active Pd nanoparticles (PdNP) capped with a lower density of alkanethio-late ligands. This homogeneously soluble PdNP catalyst offers several advantages such as little contamination Pd leaching and easy separation and recycling.

Targeting Ligand Specificity Linked to Tumor Tissue Topological Heterogeneity via Single-Cell Micro-Pharmacological Modeling.

Targeted therapy has held promise to be a successful anticancer treatment due to its specificity towards tumor cells that express the target receptors. However, not all targeting drugs used in the clinic are equally effective in tumor eradication. To examine which biochemical and biophysical properties of targeted agents are pivotal for their effective distribution inside the tumor and their efficient cellular uptake, we combine mathematical micro-pharmacological modeling with in vivo imaging of targeted human xenograft tumors in SCID mice.

Tumor Targeting and Pharmacokinetics of a Near-Infrared Fluorescent-Labeled δ-Opioid Receptor Antagonist Agent, Dmt-Tic-Cy5.

Fluorescence molecular imaging can be employed for the development of novel cancer targeting agents. Herein, we investigated the pharmacokinetics (PK) and cellular uptake of Dmt-Tic-Cy5, a delta-opioid receptor (δOR) antagonist-fluorescent dye conjugate, as a tumor-targeting molecular imaging agent. δOR expression is observed normally in the CNS, and pathologically in some tumors, including lung liver and breast cancers.

Delta-Opioid Receptor (δOR) Targeted Near-Infrared Fluorescent Agent for Imaging of Lung Cancer: Synthesis and Evaluation In Vitro and In Vivo.

In the United States, lung cancer is the leading cause of cancer death and ranks second in the number of new cases annually among all types of cancers. Better methods or tools for diagnosing and treating this disease are needed to improve patient outcomes. The delta-opioid receptor (δOR) is reported to be overexpressed in lung cancers and not expressed in normal lung.

In vivo and in silico pharmacokinetics and biodistribution of a melanocortin receptor 1 targeted agent in preclinical models of melanoma.

The melanocortin 1 receptor (MC1R) is overexpressed in most melanoma metastases, making it a promising target for imaging of melanomas. In this study, the expression of MC1R in a large fraction of patients with melanoma was confirmed using mRNA and tissue microarray. Here, we have characterized the in vivo tumor and tissue distribution and pharmacokinetics (PK) of uptake and clearance of a MC1R specific peptidomimetic ligand conjugated to a near-infrared fluorescent dye.

The role of tumor tissue architecture in treatment penetration and efficacy: an integrative study.

Despite the great progress that has been made in understanding cancer biology and the potential molecular targets for its treatment, the majority of drugs fail in the clinical trials. This may be attributed (at least in part) to the complexity of interstitial drug transport in the patient's body, which is hard to test experimentally. Similarly, recent advances in molecular imaging have led to the development of targeted biomarkers that can predict pharmacological responses to therapeutic interventions.

Acidity generated by the tumor microenvironment drives local invasion.

The pH of solid tumors is acidic due to increased fermentative metabolism and poor perfusion. It has been hypothesized that acid pH promotes local invasive growth and metastasis. The hypothesis that acid mediates invasion proposes that H(+) diffuses from the proximal tumor microenvironment into adjacent normal tissues where it causes tissue remodeling that permits local invasion.