Noncanonical Amino Acid Incorporation in Animals and Animal Cells.

Noncanonical amino acids (ncAAs) are synthetic building blocks that, when incorporated into proteins, confer novel functions and enable precise control over biological processes. These small yet powerful tools offer unprecedented opportunities to investigate and manipulate various complex life forms. In particular, ncAA incorporation technology has garnered significant attention in the study of animals and their constituent cells, which serve as invaluable model organisms for gaining insights into human physiology, genetics, and diseases.

Autocrine Motility Factor and Its Peptide Derivative Inhibit Triple-Negative Breast Cancer by Regulating Wound Repair, Survival, and Drug Efflux.

Triple-negative breast cancer (TNBC) presents a significant challenge in oncology due to its aggressive nature and limited targeted therapeutic options. This study explores the potential of autocrine motility factor (AMF) and an AMF-derived peptide as novel treatments for TNBC. AMF, primarily secreted by neoplastic cells, plays a crucial role in cancer cell motility, metastasis, and proliferation.

The BAF complex enhances transcription through interaction with H3K56ac in the histone globular domain.

Histone post-translational modifications play pivotal roles in eukaryotic gene expression. To date, most studies have focused on modifications in unstructured histone N-terminal tail domains and their binding proteins. However, transcriptional regulation by chromatin-effector proteins that directly recognize modifications in histone globular domains has yet to be clearly demonstrated, despite the richness of their multiple modifications.

The Immobilization of an FGF2-Derived Peptide on Culture Plates Improves the Production and Therapeutic Potential of Extracellular Vesicles from Wharton's Jelly Mesenchymal Stem Cells.

The skin is an essential organ that protects the body from external aggressions; therefore, damage from various wounds can significantly impair its function, and effective methods for regenerating and restoring its barrier function are crucial. This study aimed to mass-produce wound-healing exosomes using a fragment of the fibroblast growth factor 2 (FGF2)-derived peptide (FP2) to enhance cell proliferation and exosome production. Our experiments demonstrated increased cell proliferation when Wharton's jelly mesenchymal stem cells (WJ MSCs) were coated with FP2.

tRNA engineering strategies for genetic code expansion.

The advancement of genetic code expansion (GCE) technology is attributed to the establishment of specific aminoacyl-tRNA synthetase/tRNA pairs. While earlier improvements mainly focused on aminoacyl-tRNA synthetases, recent studies have highlighted the importance of optimizing tRNA sequences to enhance both unnatural amino acid incorporation efficiency and orthogonality. Given the crucial role of tRNAs in the translation process and their substantial impact on overall GCE efficiency, ongoing efforts are dedicated to the development of tRNA engineering techniques.

Bioorthogonal CRISPR/Cas9-Drug Conjugate: A Combinatorial Nanomedicine Platform.

Bioconjugation of proteins can substantially expand the opportunities in biopharmaceutical development, however, applications are limited for the gene editing machinery despite its tremendous therapeutic potential. Here, a self-delivered nanomedicine platform based on bioorthogonal CRISPR/Cas9 conjugates, which can be armed with a chemotherapeutic drug for combinatorial therapy is introduced. It is demonstrated that multi-functionalized Cas9 with a drug and polymer can form self-condensed nanocomplexes, and induce significant gene editing upon delivery while avoiding the use of a conventional carrier formulation.

"Lighting up" fluoride: cellular imaging and zebrafish model interrogations using a simple ESIPT-based mycophenolic acid precursor-based probe.

The discovery and implementation of media that derive from bioinspired designs and bear optical readouts featuring large Stokes shifts are of continued interest to a wide variety of researchers and clinicians. Myco-F, a novel mycophenolic acid precursor-based probe features a cleavable -butyldimethylsiloxy group to allow for fluoride detection. Myco-F exhibits high selectivity and specificity towards F (Stokes shift = 120 nm).

A Versatile Strategy for Screening Custom-Designed Warhead-Armed Cyclic Peptide Inhibitors.

Demand for peptide-based pharmaceuticals has been steadily increasing, but only limited success has been achieved to date. To expedite peptide-based drug discovery, we developed a general scheme for cell-based screening of cyclic peptide inhibitors armed with a user-designed warhead. We combined unnatural amino acid incorporation and split intein-mediated peptide cyclization techniques and integrated a yeast-based colorimetric screening assay to generate a new scheme that we call the custom-designed warhead-armed cyclic peptide screening platform (CWCPS).

Computational design of an apoptogenic protein that binds BCL-xL and MCL-1 simultaneously and potently.

One of the hallmarks of cancer cells is their ability to evade apoptosis, which confers survival advantages and resistance to anti-cancer drugs. Cancers often exhibit overexpression of anti-apoptotic BCL-2 proteins, the loss of which triggers apoptosis. In particular, the inhibition of both BCL-xL and MCL-1, but neither one individually, synergistically enhances apoptotic cell death.

Effects of Ti-doping amount and annealing temperature on electrochromic performance of sol-gel derived WO.

Fine control of structural and morphological features in electrochromic materials is of paramount importance for realizing practical electrochromic devices (ECDs), which can dynamically adjust indoor light and temperature of buildings. To this end, herein we investigate impacts of two variants such as Ti-doping amount and the annealing temperature on physical and chemical properties of sol-gel derived electrochromic WO films. We use a wide range of titanium coupling agents (TCAs) as Ti-dopants ranging from 0 wt% to 20 wt% and vary the annealing temperature between 200 °C and 400 °C with 50 °C interval.

Predicting the Cochlear Dead Regions Using a Machine Learning-Based Approach with Oversampling Techniques.

: Determining the presence or absence of cochlear dead regions (DRs) is essential in clinical practice. This study proposes a machine learning (ML)-based model that applies oversampling techniques for predicting DRs in patients. : We used recursive partitioning and regression for classification tree (CT) and logistic regression (LR) as prediction models.

Phosphinate-benzoindocyanin fluorescent probe for endogenous mitochondrial peroxynitrite detection in living cells and gallbladder access in inflammatory zebrafish animal models.

Potent oxidants such as peroxynitrite (ONOO) play important roles in the regulation of different physiopathological processes; their overproduction is thought to potentially cause several diseases in living organisms. Hence, the precise and selective monitoring of ONOO is imperative for elucidating its interplay and roles in pathological and physiological processes. Herein, we present a novel diphenyl phosphinate-masked benzoindocyanin "turn-on" fluorogenic probe to help detect mitochondrial ONOO in living cells and zebrafish models.

The effect of autocrine motility factor alone and in combination with methyl jasmonate on liver cancer cell growth.

Neoplastic cells secrete autocrine motility factor (AMF) to stimulate the motility of cancer cells. In this study, AMF secreted from HT-29 colorectal cancer cells selectively suppressed liver cancer cells by downregulating pAKT and β-catenin. In addition, HT-29 AMF significantly augmented the activity of methyl jasmonate against liver cancer cells and is a promising alternative for liver cancer therapy.

Synergistic effects of autocrine motility factor and methyl jasmonate on human breast cancer cells.

Autocrine motility factor (AMF) stimulates the motility of cancer cells via an autocrine route and has been implicated in tumor progression and metastasis. Overexpression of AMF is correlated with the aggressive nature of breast cancer and is negatively associated with clinical outcomes. In contrast, AMF also has the ability to suppress cancer cells.

Noncanonical Amino Acids in Synthetic Biosafety and Post-translational Modification Studies.

The incorporation of noncanonical amino acids (ncAAs) has been extensively studied because of its broad applicability. In the past decades, various in vitro and in vivo ncAA incorporation approaches have been developed to generate synthetic recombinant proteins. Herein, we discuss the methodologies for ncAA incorporation, and their use in diverse research areas, such as in synthetic biosafety and for studies of post-translational modifications.

The interaction between ubiquitin and yeast polymerase η C terminus does not require the UBZ domain.

Polymerase η (Polη) is one of the Y-family polymerases that is recruited by monoubiquitinated proliferating cell nuclear antigen (Ub-PCNA) to DNA damage sites during translesion synthesis (TLS). This interaction is mediated by an ubiquitin-binding zinc-finger (UBZ) domain and a PCNA-interacting protein (PIP) box in Polη, which binds to ubiquitin and PCNA, respectively. Here, we show that without the UBZ domain, the PIP box of yeast Polη has a novel binding function with ubiquitin.

Autocrine motility factor secreted by HeLa cells inhibits the growth of many cancer cells by regulating AKT/ERK signaling.

In cell competition, a secreted death signal can determine cell fate. However, the nature of such a signal remains unclear. In this study, conditioned medium from HeLa cells (HeLa CM) inhibited growth of A549 and MCF-7 cells.

Glucose-dependent control of leucine metabolism by leucyl-tRNA synthetase 1.

Despite the importance of glucose and amino acids for energy metabolism, interactions between the two nutrients are not well understood. We provide evidence for a role of leucyl-tRNA synthetase 1 (LARS1) in glucose-dependent control of leucine usage. Upon glucose starvation, LARS1 was phosphorylated by Unc-51 like autophagy activating kinase 1 (ULK1) at the residues crucial for leucine binding.

Clinical characteristics and associated factors of canal switch in benign paroxysmal positional vertigo.

Background: Canal switch benign paroxysmal positional vertigo (CS-BPPV) is a transition of BPPV involving one canal to another canal during or after canalith repositioning procedures (CRP).

Objective: To investigate the clinical characteristics of CS-BPPV and its associated factors.

Methods: The data of 2,303 patients with BPPV involving the lateral canal (LC) or posterior canal (PC) were retrospectively analyzed.

Site-Specific Labeling of Proteins Using Unnatural Amino Acids.

Labeling of a protein with a specific dye or tag at defined positions is a critical step in tracing the subtle behavior of the protein and assessing its cellular function. Over the last decade, many strategies have been developed to achieve selective labeling of proteins in living cells. In particular, the site-specific unnatural amino acid (UAA) incorporation technique has gained increasing attention since it enables attachment of various organic probes to a specific position of a protein in a more precise way.

Efficacy of three proton-pump inhibitor therapeutic strategies on laryngopharyngeal reflux disease; a prospective randomized double-blind study.

Objectives: Proton-pump inhibitor (PPI) prescribing practices in laryngopharyngeal reflux disease (LPR) differ among physicians. We assessed the improvement in reflux symptom index (RSI) and reflux finding score (RFS) after treating LPR with three different regimens.

Design: A prospective, double-blind, randomized clinical trial.

Cyclic Peptides: Promising Scaffolds for Biopharmaceuticals.

To date, small molecules and macromolecules, including antibodies, have been the most pursued substances in drug screening and development efforts. Despite numerous favorable features as a drug, these molecules still have limitations and are not complementary in many regards. Recently, peptide-based chemical structures that lie between these two categories in terms of both structural and functional properties have gained increasing attention as potential alternatives.

Overriding Phthalate Decomposition When Exploring Mycophenolic Acid Intermediates as Selenium-Based ROS Biological Probes.

Hypochlorous (OCl) acid is the most well-known bacterial oxidant to be produced by neutrophils. Excess amounts of OCl can cause various disorders in living systems. Herein, we have designed, synthesized, and characterized two novel organoselenium-based target molecules ( and ) based on a synthetic intermediate of mycophenolic acid for the aqueous detection of OCl.

MSK1 functions as a transcriptional coactivator of p53 in the regulation of p21 gene expression.

Mitogen- and stress-activated kinase 1 (MSK1) is a chromatin kinase that facilitates activator-dependent transcription by altering chromatin structure through histone H3 phosphorylation. The kinase activity of MSK1 is activated by intramolecular autophosphorylation, which is initially triggered by the activation of upstream mitogen-activated protein kinases (MAPKs), such as p38 and ERK1/2. MSK1 has been implicated in the expression of p21, a p53 target gene; however, the precise connection between MSK1 and p53 has not been clearly elucidated.