Palladium Oxidative Addition Complexes Enabled Synthesis of Amino-Substituted Indolyl-4(3H)-quinazolinones and Their Antitumor Activity Evaluation

The indolyl-4(3H)-quinazolinone core is an important structural motif in functional molecules. However, few methods exist for the direct modification of which limit its potential application. Reported herein is a palladium-mediated...

A sandcastle worm-inspired strategy to functionalize wet hydrogels

Hydrogels have been extensively used in many fields. Current synthesis of functional hydrogels requires incorporation of functional molecules either before or during gelation via the pre-organized reactive site along the polymer chains within hydrogels, which is tedious for polymer synthesis and not flexible for different types of hydrogels. Inspired by sandcastle worm, we develop a simple one-step strategy to functionalize wet hydrogels using molecules bearing an adhesive dibutylamine-DOPA-lysine-DOPA tripeptide. This tripeptide can be easily modified with various functional groups to initiate diverse types of polymerizations and provide functional polymers with a terminal adhesive tripeptide. Such functional molecules enable direct modification of wet hydrogels to acquire biological functions such as antimicrobial, cell adhesion and wound repair. The strategy has a tunable functionalization degree and a stable attachment of functional molecules, which provides a tool for direct and convenient modification of wet hydrogels to provide them with diverse functions and applications.

Direct Surface Modification of Polycaprolactone-Based Shape Memory Materials to Introduce Positive Charge Aiming to Enhance Cell Affinity

In this study, the introduction of a positive charge on the surface of a shape memory material was investigated to enhance cell affinity. To achieve this, the direct chemical modification of a material surface was proposed. Sheet-type, crosslinked poly(caprolactone-co-α-bromo-ɤ-butyrolactone) (poly(CL-co-BrBL)) were prepared, and the direct reaction of amino compounds with bromo groups was conducted on the material surface with a positive charge. Branched poly(CL-co-BrBL) was prepared, followed by the introduction of methacryloyl groups to each chain end. Using the branched macromonomers, stable and sheet-type materials were derived through UV-light irradiation. Then, the materials were soaked in an amino compound solution to react with the bromo groups under various conditions. Differential scanning calorimetry and surface analysis of the modified materials indicated that 10 vol% of N, N-dimethylethylenediamine in n-hexane and 1 h soaking time were optimal to maintain the inherent thermal properties. The achievement of increased luminance and a positive zeta potential proved that the direct modification method effectively introduced the positive charge only on the surface, thereby enhancing cell affinity.

PCSK9 inhibition could be effective for acute myocardial infarction

: In this review, we will explore the role of PCSK9 and inhibition of PCSK9 in patients after acute myocardial infarction (MI). Despite the implementation of evidence-based therapies to improve outcomes, mortality at one-year remains at 12-15% and the need to further reduce complications related to MI persists. Mechanistic and epidemiologic studies suggest that the naturally occurring PCSK9 protein increases coronary plaque vulnerability through several pathways, including pro-inflammatory LDL-C oxidation and direct modification of plaque composition. PCSK9 inhibitors are a class of drugs with proven efficacy in patients with recent MI. The latest guidelines recommend the use of PCSK9 in patients with recent MI early in the process of care to reduce LDL-C values and associated morbidity. The use of PCSK9 inhibition could be beneficial for mortality reduction after an acute MI and should be tested in an appropriately powered randomized controlled trial.

Effect of Depth-Induced Breaking on Wind Wave Simulations in Shallow Nearshore Waters off Northern Taiwan during the Passage of Two Super Typhoons

Super Typhoons Maria (2018) and Lekima (2019) were adopted for this case study, although they only passed the northern offshore waters of Taiwan without making landfall. A direct modification technique was employed to create the atmospheric conditions for a wave-circulation model to hindcast large typhoon-driven waves. The radius of the modified scale (Rtrs) for a hybrid typhoon wind plays an important role in the significant wave height (SWH) simulations during the passage of typhoons. The maximum increment in peak SWH reached 3.0 m and 5.0 m in the deep ocean for Super Typhoons Maria (2018) and Lekima (2019), respectively if the Rtrs was increased from 4 × Rmax (radius of the maximum wind) to 7 × Rmax. The SWHs induced by the typhoon winds in the surf zone were more sensitive to different wave-breaking formulations used in the wave-circulation model. The maximum difference in peak SWH reached 2.5 m and 1.2 m for Super Typhoons Maria (2018) and Lekima (2019), respectively, when the wave-breaking formulations of BJ78 (proposed by Battjes and Janssen in 1978) and CT93 (proposed by Church and Thornton in 1993) were introduced to the wave-circulation model. The SWH simulations in the surf zone were insensitive to the wave-breaking criterion (γ) during the passage of typhoons. In shallow nearshore waters, the utilization of a constant γ for the wave-circulation model always produces peak SWHs that are smaller than those using γ based on local steepness or peak steepness.

Coumarin Luciferins and Mutant Luciferases for Robust Multicomponent Bioluminescence Imaging

We prepared a new class of luciferins based on a red-shifted coumarin scaffold. These probes (CouLuc-1s) were accessed in a two-step sequence via direct modification of commercial dyes. The bioluminescent properties of the CouLuc-1 analogs were also characterized, and complementary luciferase enzymes were identified using a two-pronged screening strategy. The optimized enzyme-substrate pairs displayed robust photon outputs and emitted a significant portion of near-infrared light. The CouLuc-1 scaffolds are also structurally distinct from existing probes, enabling rapid multicomponent imaging. Collectively, this work provides novel bioluminescent tools along with a blueprint for crafting additional probes for multiplexed imaging