Discovery of selective LATS inhibitors scaffold hopping: enhancing drug-likeness and kinase selectivity for potential applications in regenerative medicine.

Due to its essential roles in cell proliferation and apoptosis, the precise regulation of the Hippo pathway through LATS presents a viable biological target for developing new drugs for cancer and regenerative diseases. However, currently available probes for selective and highly drug-like inhibition of LATS require further improvement in terms of both activity, selectivity and drug-like properties. Through scaffold hopping aided by docking studies and AI-assisted prediction of metabolic stabilities, we successfully identified an advanced LATS inhibitor demonstrating potent kinase activity, exceptional selectivity against other kinases, and superior oral pharmacokinetic profiles.

NUAK2 Inhibitors, KHKI-01128 and KHKI-01215, Exhibit Potent Anticancer Activity Against SW480 Colorectal Cancer Cells.

Background/aim: NUAK family kinase 2 (NUAK2) is a promising target for cancer therapeutics due to its reported role in protein phosphorylation, a critical process in cancer cell survival, proliferation, invasion, and senescence. This study aimed to identify novel inhibitors that disrupt NUAK2 activity. We have already identified two KRICT Hippo kinase inhibitor (KHKI) compounds, such as KHKI-01128 and KHKI-01215.

Preoperative Serum Copeptin Can Predict Delayed Hyponatremia after Pituitary Surgery in the Absence of Arginine Vasopressin Deficiency.

Backgruound: Delayed postoperative hyponatremia (DPH) is the most common cause of readmission after pituitary surgery. In this study, we aimed to evaluate the cutoff values of serum copeptin and determine the optimal timing for copeptin measurement for the prediction of the occurrence of DPH in patients who undergo endoscopic transsphenoidal approach (eTSA) surgery and tumor resection.

Methods: This was a prospective observational study of 73 patients who underwent eTSA surgery for pituitary or stalk lesions.

Intramolecular cyclization of -cyano sulfoximines by N-CN bond activation.

Metal-free halogenated anhydrides promote the intramolecular cyclization of -cyano sulfoximines. Trifluoro- or trichloroacetic anhydride (TFAA or TCAA, respectively) activate the -cyano groups of -cyano sulfoximines, leading to the intramolecular cyclization of 2-benzamide--cyano sulfoximines 1. This method results in excellent yields of thiadiazinone 1-oxides 2.

Interpreting changes in consecutive laboratory results: clinician's perspectives on clinically significant change.

Background: Clinical laboratory tests are inevitably affected by various factors. Therefore, when comparing consecutive test results, it is crucial to consider the inherent uncertainty of the test. Clinical laboratories use reference change value (RCV) to determine a significant change between 2 results.

-Cyano sulfilimine functional group as a nonclassical amide bond bioisostere in the design of a potent analogue to anthranilic diamide insecticide.

To explore the potential of the -cyano sulfilimine group as an amide bond isostere, a derivative of the blockbuster anthranilic diamide, chlorantramiliprole, was synthesized and evaluated with regard to its physicochemical properties, permeability, and biological activity. Given the combination of -cyano sulfilimine chlorantraniliprole 1 and its strong hydrogen bond acceptor character, high permeability, and excellent insecticidal activity, the -cyano sulfilimine functional group could be considered as an amide bond isostere.

Serum copeptin levels at day two after pituitary surgery and ratio to baseline predict postoperative central diabetes insipidus.

Purpose: Central diabetes insipidus is a complication that may occur after pituitary surgery and has been difficult to predict. This study aimed to identify the cutoff levels of serum copeptin and its optimal timing for predicting the occurrence of central diabetes insipidus in patients who underwent transsphenoidal surgery.

Methods: This was a prospective observational study of patients who underwent transsphenoidal surgery for pituitary gland or stalk lesions.

>50 MW peak power, high brightness Nd:YAG/Cr:YAG microchip laser with unstable resonator.

We demonstrated a flat-convex unstable cavity Nd:YAG/Cr:YAG ceramic air-cooled microchip laser (MCL) generating a record 37.6 and 59.2 MW peak power pulses with an energy of 17.

Acid-Catalyzed Hydrolysis and Intramolecular Cyclization of -Cyano Sulfoximines for the Synthesis of Thiadiazine 1-Oxides.

Herein, we describe a novel approach for the practical synthesis of thiadiazine 1-oxides . The first example of an intramolecular cyclization with 2--cyano-sulfonimidoyl amides to form the desired thiadiazine 1-oxides was developed. One-pot acid-induced hydrolysis of the cyano group and the intramolecular cyclocondensation protocol readily provided various heterocyclic frameworks in good to moderate yields.

Changes in copeptin levels before and 3 months after transsphenoidal surgery according to the presence of postoperative central diabetes insipidus.

Copeptin levels reflect arginine vasopressin (AVP) release from the hypothalamus. Pituitary surgery often impairs AVP release and results in central diabetes insipidus (CDI). Here, we aimed to investigate how serum copeptin level changes 3 months after pituitary surgery and whether it has a diagnostic value for postoperative permanent CDI.

Synthesis and Properties of Pentafluorosulfanyl Group (SF)-Containing Meta-Diamide Insecticides.

Herein, we describe novel pentafluorosulfanyl (SF) group-containing meta-diamide insecticides. For the facile preparation of the SF-based compounds -, practical synthetic methods were applied. Among newly synthesized compounds, 3-benzamido--(2,6-dimethyl-4-(pentafluoro-λ-sulfanyl)phenyl)-2-fluorobenzamide showed (i) a high insecticidal activity, (ii) an excellent selectivity to insects, and (iii) good levels of water solubility and log P values.

Selective Synthesis of -Cyano Sulfilimines by Dearomatizing Stable Thionium Ions.

For the selective synthesis of -cyano sulfilimines, we have developed a new method based on the soft-soft interaction between thionium ion electrophiles and cyanonitrene nucleophiles. The stable thionium ion was successfully obtained by oxidative dearomatization using phenyliodine (III) diacetate (PIDA) in ,-dimethylformamide (DMF). The sulfur imination reactions were tolerant to a wide range of functional groups and exhibited high selectivities and excellent yields.

High peak power Nd:YAG/Cr:YAG ceramic microchip laser with unstable resonator.

A doughnut mode microchip laser was demonstrated by introducing a monolithic ceramic Nd:YAG/Cr:YAG chip in an unstable resonator to deliver laser pulses with an energy of 13.2 mJ and a pulse width of 476 ps, corresponding to a record peak power of 27.7 MW.

Synthesis, Physicochemical Properties, and Biological Activities of 4-(-Methyl--(2,2,2-Trifluoroacetyl)Sulfilimidoyl) Anthranilic Diamide.

Novel anthranilic diamides with sulfilimidoyl and sulfoximidoyl functionalities were successfully prepared. Among newly-prepared organosulfur compounds, 3-bromo-1-(3-chloropyridin-2-yl)--(2-methyl-6-(methylcarbamoyl)-4-(methylthio)phenyl)-1-pyrazole-5-carboxamide and (,)-3-bromo-1-(3-chloropyridin-2-yl)--(2-methyl-4-(S-methyl--(2,2,2-trifluoroacetyl)sulfinimidoyl)-6-(methylcarbamoyl)phenyl)-1-pyrazole-5-carboxamide showed good levels of efficacy and a strong correlation between insecticidal activities and physical properties, respectively. In particular, available data indicated that the -trifluoroacetyl sulfilimine moiety could be an appealing structural scaffold for the discovery of a new crop-protecting agent.

Performance Evaluation of the QXDx BCR-ABL %IS Droplet Digital PCR Assay.

Accurate detection of fusion transcripts at and below molecular response (MR) 4 (0.01% International Scale [IS]) is required for disease monitoring in patients with chronic myeloid leukemia (CML). We evaluated the analytical performance of the QXDx BCR-ABL %IS (Bio-Rad, Hercules, CA, USA) droplet digital PCR (ddPCR) assay, which is the first commercially available ddPCR-based diagnostics product.

Effects of weaning and castration ages on growth performance, blood metabolites, and carcass characteristics in Hanwoo steers.

Background: Recently, as production costs have been increasing owing to rising feed prices worldwide, shortening the age of slaughter has been recognized as a way to increase farm income. In Korea, the raising period for Hanwoo steers is over 31 months with the delay of weaning and castration stated as one of the reasons for the increase in the raising period. Thus far, studies on age of weaning and castration have been conducted individually, and there have been no studies on the combined effects of weaning and castration ages on the growth performance and carcass characteristics in Hanwoo steers.

Revealing of Core Shell Effect on Frequency-Dependent Properties of Bi-based Relaxor/Ferroelectric Ceramic Composites.

In this study, electromechanical characteristics of (1-x) BiNaTiO-xSrTiO (ST26, x = 0.26)/(1-y) BiNaTiO-ySrTiO (ST10, y = 0.1) (matrix/seed) composites were studied.

Broadly Applicable Stereoselective Syntheses of Serrulatane, Amphilectane Diterpenes, and Their Diastereoisomeric Congeners Using Asymmetric Hydrovinylation for Absolute Stereochemical Control.

A stereogenic center, placed at an exocyclic location next to a chiral carbon in a ring to which it is attached, is a ubiquitous structural motif seen in many bioactive natural products, including di- and triterpenes and steroids. Installation of these centers has been a long-standing problem in organic chemistry. Few classes of compounds illustrate this problem better than serrulatanes and amphilectanes, which carry multiple methyl-bearing exocyclic chiral centers.

One-pot sequential synthesis of tetrasubstituted thiophenes via sulfur ylide-like intermediates.

Herein, we describe a novel approach for the practical synthesis of tetrasubstituted thiophenes . The developed method was particularly used for the facile preparation of thienyl heterocycles . The mechanism for this reaction is based on the formation of a sulfur ylide-like intermediate.

Sialidase inhibitory activity of diarylnonanoid and neolignan compounds extracted from the seeds of Myristica fragrans.

Sialidases are key virulence factors that remove sialic acid from host cell surface glycans, thus unmasking receptors to facilitate bacterial adherence and colonization. In this study, we report the isolation and characterization of novel inhibitors of the Streptococcus pneumoniae sialidases NanA, NanB, and NanC from Myristica fragrans seeds. Of the isolated compounds (1-12), malabaricone C showed the most pneumococcal sialidases inhibition (IC of 0.

Sub-nanosecond laser induced air-breakdown with giant-pulse duration tuned Nd:YAG ceramic micro-laser by cavity-length control.

We first demonstrated a continuously and widely giant-pulse duration tunable laser based on a short monolithic Nd:YAG/Cr:YAG ceramic by cavity-length control in 100 Hz operation. The tuning range of pulse duration τ was from 0.5 to 9 ns as keeping peak powers of over 0.

Small molecule inhibitors of the Dishevelled-CXXC5 interaction are new drug candidates for bone anabolic osteoporosis therapy.

Bone anabolic agents promoting bone formation and rebuilding damaged bones would ideally overcome the limitations of anti-resorptive therapy, the current standard prescription for osteoporosis. However, the currently prescribed parathyroid hormone (PTH)-based anabolic drugs present limitations and adverse effects including osteosarcoma during long-term use. Also, the antibody-based anabolic drugs that are currently being developed present the potential limits in clinical application typical of macromolecule drugs.

0.54 μm resolution two-photon interference with dispersion cancellation for quantum optical coherence tomography.

Quantum information technologies harness the intrinsic nature of quantum theory to beat the limitations of the classical methods for information processing and communication. Recently, the application of quantum features to metrology has attracted much attention. Quantum optical coherence tomography (QOCT), which utilizes two-photon interference between entangled photon pairs, is a promising approach to overcome the problem with optical coherence tomography (OCT): As the resolution of OCT becomes higher, degradation of the resolution due to dispersion within the medium becomes more critical.