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Direct asymmetric α C(sp3)‒H alkylation of benzylamines with MBH acetates enabled by bifunctional pyridoxal catalysts
Abstract Organocatalytic allylic substitution of Morita-Baylis-Hillman (MBH) adducts is widely regarded as one of the most powerful transformations in organic synthesis. A range of activated carbon nucleophiles have been successfully employed in this reaction, enabling the incorporation of diverse functional moieties. Despite its potential, the use of inert C–H nucleophiles—critical for broadening the reaction’s versatility and synthetic utility—remains a significant challenge in the field. Direct α-C–H functionalization of benzyl amines with MBH adducts offers a promising route to form a new C–C bond while simultaneously establishing a chiral amine moiety, a feature highly attractive from the perspective of organic synthesis. However, this transformation is particularly challenging due to the inherent inertness of the α-C( sp ³)–H bonds, significant nucleophilic interference from the NH₂ group, and the complexity of selectivity control. Herein, we have successfully achieved an asymmetric direct α-C–H allylic alkylation of NH₂-unprotected benzylamines with MBH adducts using a bifunctional chiral pyridoxal catalyst, producing biologically important chiral γ-amino acid derivatives in good yields with excellent diastereo- and enantioselectivities. The reaction offers a distinct strategy for synthesizing multiply functionalized compounds from readily available starting materials, significantly expanding access to complex chiral architectures.
Calcium–L-aspartate nanoparticles mitigate Boron toxicity in rice seedlings by modulating physiological, antioxidant, and cell wall mechanisms
Prioritization of patients at risk of heart attack using a novel full-objective ITARA based on Random Forest and Decision tree
Wildfire smoke exposure and mortality burden in the USA under climate change
Iridium(III)-catalyzed remote B(9)−H alkylation of o-carboranes with nitrile template
Efficacy of seed priming and foliar application of seaweed extracts on the performance of summer mung bean [(Vigna radiata (L.) Wilczek]
Evaluating diagnostic accuracy of large language models in neuroradiology cases using image inputs from JAMA neurology and JAMA clinical challenges
Loss of cell-autonomously secreted laminin-α2 drives muscle stem cell dysfunction in LAMA2-related muscular dystrophy
Abstract The extracellular matrix protein laminin-α2 is essential for preserving the integrity of skeletal muscle fibers during contraction. Its importance is reflected by the severe, congenital LAMA2-related muscular dystrophy (LAMA2 MD) caused by loss-of-function mutations in the LAMA2 gene. While laminin-α2 has an established role in structurally supporting muscle fibers, it remains unclear whether it exerts additional functions that contribute to the maintenance of skeletal muscle integrity. Here, we report that in healthy muscle, activated muscle stem cells (MuSCs) express Lama2 and remodel their microenvironment with laminin-α2. By characterizing LAMA2 MD-afflicted MuSCs and generating MuSC-specific Lama2 knockouts, we show that MuSC-derived laminin-α2 is essential for rapid MuSC expansion and regeneration. In humans, we identify LAMA2 expression in MuSCs and demonstrate that loss-of-function mutations impair cell-cycle progression of myogenic precursors. In summary, we show that self-secreted laminin-α2 supports MuSC proliferation post-injury, thus implicating MuSC dysfunction in LAMA2 MD pathology.
Rotating compensator spectroscopic ellipsometry based on frequency division multiplexing with retardation calibration
Spatially adaptive modeling of soil erosion susceptibility using geographically weighted regression integrated with remote sensing and GIS techniques
Fe2+ disproportionation within iron-rich alkaline vent analogues reveals proto-bioenergetic systems
Prediction of longitudinal outcomes and novel cluster identification in epilepsy
Study on temperature field of parallel perforated ventilation subgrade in the permafrost region
Flexible perceptual encoding by discrete gamma events
Highly oriented semiconducting polymer nanofilm with enhanced crystallinity
Enhanced early chronic kidney disease prediction using hybrid waterwheel plant algorithm for deep neural network optimization
Abstract Chronic Kidney Disease (CKD) is a progressive condition primarily caused by diabetes and hypertension, affecting millions worldwide. Early diagnosis remains a clinical challenge since traditional approaches, such as Glomerular Filtration Rate (GFR) estimation and kidney damage indicators, often fail to detect CKD in its initial stages. This study aims to enhance early CKD prediction by developing a deep neural network optimized with a novel hybrid metaheuristic that combines the Waterwheel Plant Algorithm (WWPA) with Grey Wolf Optimization (GWO). Using the UCI CKD dataset, rigorous preprocessing techniques-including data imputation, normalization, and synthetic oversampling-were employed to enhance data quality and mitigate class imbalance. A multilayer perceptron (MLP) regression model was trained and optimized through the WWPA-GWO framework and benchmarked against other optimization algorithms, including PSO, GA, and WOA. Results demonstrated that the standard MLP achieved moderate performance (MSE = 0.00177, RMSE = 0.0420, MAE = 0.0100, $$R^2$$ = 0.8793), whereas the optimized model achieved significant improvements (MSE = $$3.06 \times 10^{-6}$$ , RMSE = 0.00175, $$R^2$$ = 0.9730) with reduced computational time (0.0999 s). Statistical validation using ANOVA ( $$p < 0.0001$$ ) and Wilcoxon signed-rank testing ( $$p = 0.002$$ ) confirmed the robustness of the approach. These findings highlight the effectiveness of the WWPA-GWO hybrid optimization strategy for deep neural networks, offering a reliable and efficient pathway for early CKD detection. Future work will explore the integration of advanced imputation methods, multi-modal data sources, and federated learning frameworks to enhance the model’s generalizability and clinical utility in diverse healthcare settings.
The stem ethyl acetate extract of Costus pictus D.DON exhibits cytotoxic activity in human cancer cells via. intrinsic apoptotic caspase pathway as a first report
Covalent-bonding chiroptical network structures for circular polarization differential imaging
Riverscape dynamics and habitat utilization structure evolutionary diversification in a clade of Amazonian electric fishes
Abstract Rivers have long been implicated in the processes of macroevolutionary diversification, but only recently have tools emerged to quantify habitat volume and connectivity across modern and ancient landscapes. Here we compare biodiversity patterns in a diverse clade of Amazonian electric fishes with the predictions of three alternative hypotheses of rivers as: (1) semi-permeable dispersal barriers, (2) branching drainage networks, and (3) dynamic with a reticulated history of connections; i.e., river capture. We found support for all three hypotheses, with large river corridors as partial dispersal barriers to small-river species, interfluves as barriers to large-river species, and contrasting patterns of local (alpha) diversity and species-turnover (beta diversity) in large and small rivers. River captures are faster in smaller rivers with rare but expansive mega-river capture events, facilitating dispersal of small-river clades across watersheds. These results support the role of riverine dynamics as principle agents driving continental diversification of megadiverse tropical aquatic faunas.