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Varroa mite resistance in a hybrid honey bee (Apis mellifera) population in Southern California
Abstract Honey bees ( Apis mellifera ) are important ecological and agricultural pollinators. In the United States, beekeepers experience substantial annual colony losses, largely driven by parasites such as the mite Varroa destructor . We studied a Californian hybrid honey bee population in Southern California, a genetic mix of Western European, Eastern European, Middle Eastern, and African lineages. We predicted that these bees would show lower mite infestation levels because they survive and persist without human intervention. To test this, we monitored 236 colonies over a four-year period. We found that Californian hybrid honey bee colonies consistently had lower mite infestation rates compared to colonies headed by queens from a commercial stock. Consequently, they exceeded standard treatment thresholds (≥ 3 mites per 100 worker bees) less frequently and therefore received fewer miticide treatments. We then conducted laboratory-based-choice assays to test whether colony-level differences were reflected at the brood level. Mites were significantly less attracted to seven-day-old larvae of the Californian hybrid genotype compared to commercial larvae, indicating reduced brood attractiveness. Together, our findings indicate that this Californian hybrid population experiences lower Varroa burdens under field conditions and exhibits reduced brood attractiveness to mites under controlled laboratory conditions. This population represents a valuable resource for investigating ecological, genetic, and behavioral mechanisms underlying host resistance.
Questioning the near-intrinsic thermal conductivity of suspended graphene membranes fabricated via a cyclododecane-based transfer method
Macromolecular Condensates as Tunable Scaffolds for Bio‐Inspired Silica Hybrids
ABSTRACT Silica‐based materials are of immense functionality as their production is versatile and can accommodate a wide range of properties. Nevertheless, no synthetic system can reproduce the ability of organisms to precipitate dense silica under ambient conditions and from dilute soluble precursors, leaving a substantial gap in our understanding of silica chemistry. It is widely accepted that a key feature of biosilicification is the activity of amine‐rich macromolecules, but their biomimetic use in silica synthesis currently fails to reproduce biological processes. Here, we take inspiration from some properties of biological processes and demonstrate that phase separated polyamine condensates drive the formation of hybrid silica materials. We further show that the pH of the reaction is a regulator that allows to control the architecture and composition of the silica material. These results point to the fundamental role of condensates in driving silicification from dilute aqueous environments that characterize physiological conditions. Applying these sets of rules to synthetic systems may open the road for the production of a new class of dense and biocompatible silica hybrids.
Neo‐Cysteine Molecular Glues for Targeting Mutated SMAD4 Protein
Abstract Neo‐protein‐protein interactions (neoPPIs), directed by genetic mutation‐encoded neo‐amino acid residues, represent a promising class of precision medicine targets. Small molecules can mimic genetic mutational effects, creating neo‐surfaces and acting as molecular glues to mediate neoPPIs and reprogram biological circuitry. This convergence of genomic alterations and chemical interventions highlights a strategy for targeting disease‐associated mutations using neo‐amino acid residue‐directed molecular glues. Among these, neo‐cysteine at the protein‐protein interaction (PPI) interface represents unique opportunities to develop covalent molecular glues. Despite this promise, identifying neo‐cysteine molecular glues (neoCMGs) remains challenging. Here, we report the discovery of a neoCMG through a systematic chemical screening approach, using SMAD4, a frequently mutated tumor suppressor gene, as a model system. We established a robust PPI biosensor assay for high‐throughput chemical screening, leading to the identification of neoCMG101. Biophysical and biochemical characterization revealed that neoCMG101 selectively and covalently modifies the neo‐C361 residue on SMAD4, enhance SMAD4‐R361C/SMAD3 PPI and restore SMAD‐dependent transcriptional activity. This work establishes the feasibility of leveraging neo‐cysteine‐directed molecular glues to restore mutant PPIs, supporting a generalizable strategy for identifying neoCMG hits through unbiased screening. Such an approach provides a framework for targeting mutation‐disrupted signaling networks in cancer and other diseases.
Zinc finger protein Y - linked as a potential biomarker for autoimmune hepatitis and multiple sclerosis which overlap with immune infiltration
Abstract Autoimmune Hepatitis (AIH) and Multiple Sclerosis (MS) are chronic inflammatory diseases with abnormal immune responses. This study aims to identify common biomarkers for AIH and MS using bioinformatics analysis. Gene expression data of AIH (GSE159676) and MS (GSE131279 and GSE131281) were obtained from the GEO database. Differentially Expressed Genes (DEGs) were identified using the limma package in R. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, Protein-Protein Interaction (PPI) network, and machine learning algorithm Least Absolute Shrinkage and Selection Operator (LASSO) regression were used to evaluate potential biomarkers. The common biomarker gene Zinc Finger Protein Y-linked (ZFY) was identified. KEGG analysis showed significant enrichment of the Phosphatidylinositol 3-Kinase/Protein Kinase B (PI3K/Akt) pathway in both diseases. LASSO regression identified ZFY as a potential diagnostic marker, with decreased expression in both AIH and MS groups. Single-gene immune infiltration analysis indicated a significant association between ZFY expression and immune cell infiltration levels. Experimental validation in ConA-induced hepatitis and CPZ-mediated demyelination model mice further verified the diagnostic potential of ZFY. This study reveals the potential of ZFY as a biomarker for AIH and MS, highlighting its role in the PI3K/Akt pathway and immune infiltration. These findings provide new insights into the common pathological mechanisms of AIH and MS and suggest potential targets for future therapeutic strategies.
Structural basis for the carboxylation and epoxidation of human gamma-glutamyl carboxylase
Corilagin alleviates Staphylococcus aureus pathogenicity by interacting with amidase and α-hemolysin
Energetic diversity in retinal ganglion cells is modulated by neuronal activity and correlates with resilience to degeneration
Forensic examination to determine the correlation between fingerprint patterns and blood groups in the population of Assam
High-risk EBV promotes immune evasion in nasopharyngeal carcinoma by upregulating HLA-DP via the encoded BALF2-HR variant
A Chemoselective and Stereodivergent Platform of Heme‐Nitrene Transferases to Access Chiral Aryl‐β‐Amino Esters and An Investigation of the Sequence‐Activity Landscape
ABSTRACT Engineered biocatalysts can utilize nitrene precursors to access enantioenriched amination products, yet they have not been applied to produce valuable, enantiomerically enriched noncanonical β‐amino esters. Current approaches to synthesizing β‐amino acids rely on pre‐oxidized precursors and multistep synthetic approaches involving various protecting groups. We engineered a platform of heme enzymes for stereoselective C–H bond amination of readily available carboxylic ester derivatives to install primary amines. A directed evolution campaign coupled with sequencing of over 1000 variants enabled us to develop engineered variants that use either O ‐pivaloylhydroxylamine triflic acid (PONT) or hydroxylamine hydrochloride (H 2 NOH∙HCl) as aminating reagents. An analysis of the resulting sequence–activity dataset revealed additional improvements that could be made to the final variant, highlighting the utility of sequencing data to guide future steps in directed evolution campaigns. The evolved nitrene transferases expand the scope of accessible chiral β‐amino acid building blocks for peptidomimetic applications and provide new starting points for the design and synthesis of enantioenriched β‐amino acid motifs.
Experimental, spectroscopic, thermodynamic, and DFT study of a novel cyanomethylchrome nopyridinecarbonitrile (CCPC)
Abstract A novel heterocyclic system, 5-cyanomethylchromeno[4,3- b ]pyridine-3-carbonitrile ( CCPC , 3 ), was synthesized via the reaction of 3-(6,8-dimethylchromonyl)acrylonitrile ( 1 ) with cyanoacetamide ( 2 ) under basic conditions. The transformation proceeds through a cascade mechanism involving Michael addition, γ-pyrone ring opening, and double recyclization. The structure of CCPC was confirmed by analytical and spectral data. Density functional theory (DFT/B3LYP/6-311 + + G(d, p)) was used to optimize its molecular geometry and investigate electronic properties, global reactivity descriptors, molecular electrostatic potential, and intramolecular charge transfer characteristics. Thermokinetic behavior was evaluated using KiSThelP, while UV–Vis spectra were simulated via TDDFT, showing solvent-dependent absorption shifts. SwissADME analysis indicated favorable drug-likeness according to Lipinski’s and Veber’s rules. Overall, the combined experimental and computational study provides insight into the structure, reactivity, stability, and potential applications of CCPC .
Targeting a super-enhancer induced aldehyde dehydrogenase metabolic loop mitigates CDK4/6 inhibitor resistance in estrogen receptor-positive cancers
Electrocatalytic C─N Coupling in Aqueous Solutions for High‐Value Product Synthesis
ABSTRACT Organic nitrogen‐containing compounds, such as urea, amines, amides, and amino acids, play a crucial role in global biogeochemical cycles and industrial systems. Electrocatalytic C─N coupling, enabling reactions under mild conditions (room temperature/pressure) and utilizing a range of feedstocks (CO 2 , CO, N 2 , NO 3 − , and NH 3 , etc.), has emerged as a sustainable alternative for the synthesis of these chemicals. Recent advancements in diversifying product scopes via C─N coupling methodologies have significantly enhanced reaction versatility and conversion efficiency. These developments enable novel reaction pathways while addressing critical challenges, such as slow kinetics (e.g., high bond dissociation energies in N≡N or C═O bonds) and competing reactions. This review comprehensively examines the progress in electrochemical C─N coupling, with a focus on reaction mechanisms across diverse systems and the advanced catalysts driving these transformations. Furthermore, we summarize the integrated electrolytic cell design to bridge laboratory‐scale breakthroughs with sustainable large‐scale production. By overcoming existing limitations, electrocatalytic synthesis holds the potential to transform chemical manufacturing while mitigating environmental impacts.
A novel fine-scale identification method for coal mining subsidence basin based on TS-InSAR and subsidence curve characteristics
Photoinduced Mn catalysis for efficient platform for C-heteroatom bond coupling of aryl halides
Abstract Photoinduced transition metal catalysis offers innovative strategies for fostering novel chemical reactions and improving established ones. In this work, we present a highly efficient, photoinduced Mn(II)-bipyridine catalyzed C–N, C-O and C-S coupling reaction between aryl halides—particularly less reactive aryl chlorides—and nucleophiles containing nitrogen, oxygen, and sulfur. This protocol does not need an external photocatalyst, as the single Mn(II)–bipyridine complex simultaneously serves as both the light-harvester and the metal catalyst. This method exhibits excellent substrate scope, covering eight different nitrogen sources for C-N coupling, as well as C-O coupling with alcohols, C-S coupling with thiophenols, encompassing more than 150 examples, with yields reaching up to 94%. Mechanistic studies suggest that this reaction may be initiated and sustained by the Mn(I) species through the photoinduced homolysis of the catalyst precursor bipyridine-Mn(II)(OAc) 2 , likely proceeding via a Mn(I)/Mn(III) catalytic cycle.