化学最新文献

Soilless cultivation relies on hydrogel matrices for water and nutrient management, but conventional hydrogels lose performance at low temperature and show unstable sustained release. Here this study develops an antifreeze sustained-release hydrogel (P-GTCH) that integrates l-proline (L-P) with a humic-acid-modified cellulose nanocrystal nanocomposite (CNCs-HA) for nanoenabled controlled release. L-P suppresses ice nucleation via hydrogen bonding, while CNCs-HA boosts HA loading and enables controlled transport within the cross-linked network. HA shows slow, continuous release governed by Fickian diffusion, achieving 96.7% cumulative release over 12 days at 0 °C and mitigating poor fertilizer release in cold environments. P-GTCH provides mechanical support for plant roots, and the synergistic effects of L-P and HA maintain lettuce germination above 86% at 0 °C while promoting root growth. This biobased, biodegradable platform is scalable for low-temperature soilless cultivation.

Enzymes such as oxidases are sustainable tools for hydrogel synthesis, but complex competing reactions have limited the mechanistic understanding and biomedical applications of these materials. Guided by molecular docking and MM-GBSA calculations, we identified two artificial substrates, desaminotyrosine (DAT) and desaminotyrosyltyrosine (DATT), that were experimentally more efficiently converted by mushroom tyrosinase (mTyr) than the natural substrate tyrosine. These substrates were used to synthesize hydrogels from DAT/DATT-functionalized star-shaped oligoethylene glycol (sOEG). Model reactions elucidated the chemical nature and functionality of the hydrogel netpoints. Material properties were systematically investigated depending on sOEG molecular weight (5, 10, 20 kDa), substrate type, and mTyr concentration. Functional mesh sizes and controlled release functions were investigated with fluorescent dextrans (4-500 kDa) and heparin. Cell culture studies with L929 fibroblasts and THP-1 monocytes suggested inertness of the material. These findings provide fundamental insight into mTyr-catalyzed hydrogel formation and support further exploration for in situ hydrogel synthesis.

Conventional gelatin-based hydrogel wound dressings suffer from weak mechanical properties, poor temperature stability, and slow wound healing, limiting their practical application. Herein, a novel multifunctional gelatin-based eutectogel dressing (PGEWD) was developed via a multicross-linked network constructed from porcine skin gelatin (PG), ε-polylysine (EPL), waterborne polyurethane (WPU), and deep eutectic solvent (DES, choline chloride-glycerol). DES induced PG molecular chain rearrangement to form a dense triple-helix structure. With the optimal formulation of 10% EPL, 0.3% WPU, and 10 min DES immersion, the PGE_0.1W_0.3D₁₀ composite exhibited high tensile strength (290 kPa), intrinsic conductivity (0.798 mS/cm), wide thermal tolerance (-20 to 60 °C), and ∼100% antibacterial activity. Combined with electrical stimulation (ES), it accelerated wound healing with ∼94.47% closure rate in 14 days. This study provides a versatile strategy for designing multifunctional gelatin-based wound dressings with significant potential in wound regeneration.

Liquid-liquid phase separation (LLPS) is involved in both the self-assembly of vital cellular organelles and the disease-associated protein misfolding, where LLPS precedes a liquid-solid phase transition (LSPT) leading to amyloid aggregates. Chimeric ACC_1-13K_n peptides are insightful models to study coupled LLPS/LSPT processes triggered by ATP-binding. Here, we investigated the impact of macromolecular crowding on the selection of the aggregation pathway in the ACC_1-13K₈-ATP system. While it has been previously shown that peptides with relatively short oligolysine segments (K₁₆ and shorter) skip the LLPS stage on their pathway to amyloid fibrils, we show here that concentrated polyethylene glycol (PEG), mimicking intracellular crowding conditions, induces prior formation of liquid droplets that subsequently facilitate fibril formation. The influence of PEG contrasts with the behavior of other types of macromolecular crowding agents, Dextran and Ficoll, which accelerate aggregation without a detectable LLPS phase, and that of serum albumin, which prolongs the nucleation phase. In the presence of PEG-induced macromolecular crowding, the fibrillization in the ACC_1-13K₈-ATP system appears to reach a maximal rate limited by diffusion coupled to the conformational dynamics of the polypeptide chains within the droplets. Importantly, the ACC_1-13K₈-ATP fibrils formed in the presence of PEG are distinct from those of the ACC_1-13K₈-ATP amyloid formed in the absence of crowding in terms of their infrared characteristics, morphological features, and overall stability. Our findings suggest that macromolecular crowding can switch between kinetically and thermodynamically favored amyloid polymorphs and that the chemical properties of the crowding agents are key factors in their impact on protein aggregation processes. The results are discussed in the context of the mechanisms of LLPS-dependent protein misfolding and amyloid formation.

Therapeutic interventions for complex diseases depend on the targeted modulation of key pathological pathways. While growing clinical needs continue to drive advancements in the drug discovery space, current strategies primarily rely on searching large volumes of chemical data without addressing the specific contributions of molecular features. Moreover, both clinicians and researchers recognize the need for improved drug discovery methods and characterization that could aid in clinical strategy selection. To address these challenges, we propose a new perspective on targeted therapy development as well as interactome mapping, utilizing molecular fragments. The present study focuses on therapeutic areas that represent emerging targets, namely JAK2 and GLP-1R, both of which have broad clinical potential. We developed a new self-adjusting neural network that enabled us to discover novel therapeutic candidates with improved in silico binding profiles, gain additional insights into drug-target binding that were not previously reported, and identify new metabolic trajectories. Importantly, our work revealed that even a small compound library can effectively generate lead candidates, expediting the search and exploration process. In addition, the fragment-guided bridging of chemical and biological spaces has revealed new opportunities for drug repurposing efforts and a means of improving the prediction of side effects. We concluded our study with insights into the recent high-profile clinical trial failure of danuglipron and how this could have been prevented with our methodology. Thus, building a robust in silico pipeline with integrated screening data can significantly reduce costs and guide therapy adoption. Furthermore, our proposed strategy highlights promising avenues for the discovery of new therapeutics and the development of clinical interventions.