Additional file 3: Table S2. of Development of a 4-aminopyrazolo[3,4-d]pyrimidine-based dual IGF1R/Src inhibitor as a novel anticancer agent with minimal toxicity

The IC50 values showing the inhibitory effect of LL28 on the viability of a panel of human lung cancer cells. (PDF 177 kb

Food-fodder traits in groundnut

Changes in the level of GPT, BUN, and creatinine by treatment with LL28 in mice. (PDF 109 kb

Additional file 5: Table S4. of Development of a 4-aminopyrazolo[3,4-d]pyrimidine-based dual IGF1R/Src inhibitor as a novel anticancer agent with minimal toxicity

Changes in the level of GPT, BUN, and creatinine by treatment with LL28 in mice. (PDF 109 kb

Additional file 4: Table S3. of Development of a 4-aminopyrazolo[3,4-d]pyrimidine-based dual IGF1R/Src inhibitor as a novel anticancer agent with minimal toxicity

The IC50 values showing the inhibitory effect of LL28 on the anchorage-dependent colony -forming ability of a panel of human lung cancer cells. (PDF 176 kb

PSA Detection with Femtomolar Sensitivity and a Broad Dynamic Range Using SERS Nanoprobes and an Area-Scanning Method

Recently, surface-enhanced Raman scattering (SERS)-based immunoassays (SIA) have drawn much attention as diagnostic tools with large multiplex capacity and high sensitivity. However, several challengessuch as a low reproducibility, a time-consuming read-out process, and limited dynamic rangeremain. In this study, we report a reliable and sensitive SIA platform for prostate specific antigen (PSA) detection. Reliability and sensitivity were achieved by two approaches: (1) well-established SERS probes, so-called SERS dots that have high sensitivity (single particle detection) and little particle-to-particle variation in SERS intensity; and (2) a whole area-scanning readout method for rapid and reliable chip analysis rather than point scanning. As a feasibility test, PSA could be detected with high sensitivity (ca. 0.11 pg/mL, 3.4 fM LOD), with a wide dynamic range (0.001–1000 ng/mL). Thus, the developed platform will facilitate development of reliable immunoassays with high sensitivity and a wide dynamic range

Ag Shell–Au Satellite Hetero-Nanostructure for Ultra-Sensitive, Reproducible, and Homogeneous NIR SERS Activity

It is critical to create isotropic hot spots in developing a reproducible, homogeneous, and ultrasensitive SERS probe. Here, an Ag shell–Au satellite (Ag–Au SS) nanostructure composed of an Ag shell and surrounding Au nanoparticles was developed as a near-IR active SERS probe. The heterometallic shell-satellite structure based SERS probe produced intense and uniform SERS signals (SERS enhancement factor ∼1.4 × 10⁶ with 11% relative standard deviation) with high detectability (100% under current measurement condition) by 785 nm photoexcitation. This signal enhancement was independent of the laser polarizations, which reflects the isotropic feature of the SERS activity of Ag–Au SS from the three-dimensional (3D) distribution of SERS hot spots between the shell and the surrounding satellite particles. The Ag–Au SS nanostructure shows a great potential as a reproducible and quantifiable NIR SERS probe for in vivo targets

[¹⁸F]Fluoromethyl-PBR28 as a Potential Radiotracer for TSPO: Preclinical Comparison with [¹¹C]PBR28 in a Rat Model of Neuroinflammation

To develop radiotracer for the translocator protein 18 kDa (TSPO) in vivo, <i>N</i>-(2-[¹⁸F]­fluoromethoxybenzyl)-<i>N</i>-(4-phenoxypyridin-3-yl)­acetamide ([¹⁸F]<b>1</b>, [¹⁸F]­fluoromethyl-PBR28) was prepared by incorporating of fluorine-18 into triazolium triflate-PBR28 precursor (<b>7</b>). The radiochemical yield of [¹⁸F]<b>1</b> after HPLC purification was 35.8 ± 3.2% (<i>n</i> = 11, decay corrected). Radiotracer [¹⁸F]<b>1</b> was found to be chemically stable when incubated in human serum for 4 h at 37 °C. Both aryloxyanilide analogs (<b>1</b> and <b>2</b>) behaved similarly in terms of lipophilicity and in vitro affinity for TSPO. Here, both radiotracers were directly compared in the same inflammatory rat to determine whether either radiotracer provides more promising in vivo TSPO binding. Uptake of [¹⁸F]<b>1</b> in the inflammatory lesion was comparable to that of [¹¹C]­PBR28, and [¹⁸F]<b>1</b> rapidly approached the highest target-to-background ratio at early imaging time (35 min postinjection versus 85 min postinjection for [¹¹C]­PBR28). These results suggest that [¹⁸F]<b>1</b> is a promising radiotracer for imaging acute neuroinflammation in rat. In addition, our use of a triazolium triflate precursor for [¹⁸F]­fluoromethyl ether group provides the convenient application for radiofluorination of radiotracer containing a methoxy group

Single-Step and Rapid Growth of Silver Nanoshells as SERS-Active Nanostructures for Label-Free Detection of Pesticides

We explored a single-step approach for the rapid growth of Ag nanoshells (Ag NSs) under mild conditions. Without predeposition of seed metals, a uniform and complete layer of Ag shells was rapidly formed on silica core particles within 2 min at 25 °C via single electron transfer from octylamine to Ag⁺ ions. The size and thickness of the Ag NSs were effectively tuned by adjusting the concentration of silica nanoparticles (silica NPs) with optimal concentrations of AgNO₃ and octylamine. This unusually rapid growth of Ag NSs was attributed to a significant increase in the reduction potential of the Ag⁺ ions in ethylene glycol (EG) through the formation of an Ag/EG complex, which in turn led to their facile reduction by octylamine, even at room temperature. A substantial enhancement in the surface-enhanced Raman scattering (SERS) of the prepared Ag NSs was demonstrated. The Ag NSs were also utilized as SERS-active nanostructures for label-free detection of the pesticide thiram. The Ag NS-based SERS approach successfully detected thiram on apple peel down to the level of 38 ng/cm² in a label-free manner, which is very promising with respect to its potential use for the on-site detection of residual pesticides

A Potential PET Radiotracer for the 5‑HT_2C Receptor: Synthesis and in Vivo Evaluation of 4‑(3‑[¹⁸F]fluorophenethoxy)pyrimidine

The serotonin 2C receptor subtype (5-HT_2C) is an excitatory 5-HT receptor widely distributed throughout the central nervous system. As the 5-HT_2C receptor displays multiple actions on various neurotransmitter systems including glutamate, dopamine, epinephrine, and γ-aminobutyric acid (GABA), abnormalities of the 5-HT_2C receptor are associated with psychiatric diseases such as depression, schizophrenia, drug abuse, and anxiety. Up to date, three kinds of 5-HT_2C PET radiotracers such as [¹¹C]<i>N</i>-methylated arylazepine (<b>1</b>), [¹¹C]­WAY-163909 (<b>2</b>), and [¹⁸F]­fluorophenylcyclopropane (<b>3</b>) have been developed, but they may not be suitable for in vivo 5-HT_2C imaging study due to their modest specific binding. Herein, the synthesis and in vivo evaluation of 4-(3-[¹⁸F]­fluorophenethoxy)­pyrimidine <b>[</b>^<b>18</b><b>F]­4</b> as a potential PET radiotracer for the 5-HT_2C receptor is described. <b>[</b>^<b>18</b><b>F]­4</b> was synthesized by nucleophilic aromatic substitution of diaryliodonium precursor <b>17a</b> with a 7.8 ± 2.7% (<i>n</i> = 6, decay corrected) radiochemical yield and over 99% radiochemical purity, showing an 89 ± 14 GBq/μmol specific radioactivity. The in vivo PET imaging studies of <b>[</b>^<b>18</b><b>F]­4</b> with or without lorcaserin, a U.S. Food and Drug Administration approved selective 5-HT_2C agonist, demonstrated that <b>[</b>^<b>18</b><b>F]­4</b> exhibits a high level of specific binding to 5-HT_2C receptors in the rat brain

DataSheet_1_A novel bispecific antibody dual-targeting approach for enhanced neutralization against fast-evolving SARS-CoV-2 variants.docx

IntroductionThe emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has caused unprecedented health and socioeconomic crises, necessitating the immediate development of highly effective neutralizing antibodies. Despite recent advancements in anti-SARS-CoV-2 receptor-binding domain (RBD)-specific monoclonal antibodies (mAbs) derived from convalescent patient samples, their efficacy against emerging variants has been limited. In this study, we present a novel dual-targeting strategy using bispecific antibodies (bsAbs) that specifically recognize both the SARS-CoV-2 RBD and fusion peptide (FP), crucial domains for viral attachment to the host cell membrane and fusion in SARS-CoV-2 infection. MethodsUsing phage display technology, we rapidly isolated FP-specific mAbs from an established human recombinant antibody library, identifying K107.1 with a nanomolar affinity for SARS-CoV-2 FP. Furthermore, we generated K203.A, a new bsAb built in immunoglobulin G4-(single-chain variable fragment)2 forms and demonstrating a high manufacturing yield and nanomolar affinity to both the RBD and FP, by fusing K102.1, our previously reported RBD-specific mAb, with K107.1. ResultsOur comprehensive in vitro functional analyses revealed that the K203.A bsAb significantly outperformed the parental RBD-specific mAb in terms of neutralization efficacy against SARS-CoV-2 variants. Furthermore, intravenous monotherapy with K203.A demonstrated potent in vivo neutralizing activity without significant in vivo toxicity in a mouse model infected with a SARS-CoV-2 variant. ConclusionThese findings present a novel bsAb dual-targeting strategy, directed at SARS-CoV-2 RBD and FP, as an effective approach for rapid development and management against continuously evolving SARS-CoV-2 variants.</p