A two-step synthetic strategy (combining coordination polymerization and radical polymerization) was developed to produce a novel kind of branched functional polyethylene (PE) with multiple polar segments (integrating block and branched architectures). Using a binuclear nickel catalyst, the copolymerization of ethylene with polar diene generates PE bearing methacrylate pendants (up to 4.62 mol %, 60/chain), which can serve as a macromolecular branching agent (PE branching agent). Subsequent radical copolymerization with methyl methacrylate (MMA) efficiently introduced PMMA segments into the PE backbone, yielding branched functional PE with highly tailored molecular weights (350-2300 kg/mol) and polar/nonpolar unit ratios (1/38-1/3 molar). The incorporation of PMMA segments confers a pronounced mechanical reinforcement effect, elevating the fracture strength from 6.18 to 19.64 MPa. The resultant material boasts mechanical properties on par with those of polar polyolefin elastomers (POEs) and exhibits versatile application capabilities, functioning both as a toughener for PMMA and as a compatibilizer for POE/PMMA blends.

We have streamlined a dipolar cycloaddition approach to assemble the core of malayamycin A and other related uracil nucleosides possessing the common bicyclic perhydrofuropyran framework. The latent functionality strategy employing oxazoline to unmask the 1,2-hydroxyamine moiety proves feasible, eliminating the need for alkene functionalization required in previous endeavours. This current strategy provides a reliable platform for accessing diverse uracil nucleosides and their derivatives, facilitating the development of potent fungicides.

The p97-UFD1L-NPLOC4 ATPase unfolds numerous proteins for proteasomal degradation, but whether it suffices to pull proteins out of lipid bilayer remains unclear. Here, we identify a conserved ubiquitin-binding helix (UBH) in many UBX-containing p97 adapters, including FAF2, across yeast, plants, and metazoans. The UBH-UBX substantially facilitates the engagement of ubiquitinated substrates with p97-UFD1L-NPLOC4, and enhances p97 motor's working ATPase and unfolding activities by approximately twofold. Using purified p97-UFD1L-NPLOC4-FAF2UBH-UBX, we reconstitute membrane protein extraction from the ER and mitochondria, establishing p97-UFD1L-NPLOC4-FAF2 (p97-UNF) as a power-enhanced unfoldase. Deleting UBH or disrupting UBH-ubiquitin interaction impairs substrate targeting, reduces p97-UNF's working ATPase and unfolding activities, and abolishes membrane protein extraction and degradation. We propose that UBH-UBX module amplifies p97's mechanical output power, enabling the removal of challenging substrates from large assemblies and ensuring rapid responses to protein misfolding or regulatory signals in diverse physiological processes.

Amines are among the most common functional groups in bioactive molecules1. Despite this prevalence, conventional means of converting aromatic amines rely heavily on diazonium intermediates2, which pose significant safety risks due to the explosive nature of these salts3,4. Here we report a direct deaminative strategy through the formation of N-nitroamines, allowing the direct conversion of inert aromatic C-N bonds into an array of other functional groups, including C-X (C-Br, C-Cl, C-I, C-F, C-N, C-S, C-Se, C-O) and C-C bonds. This operationally simple, general protocol establishes a unified strategy for one-pot deaminative cross-couplings by integrating deaminative functionalization with transition-metal-catalysed arylation, thereby streamlining synthesis and late-stage functionalization. The key advantage of this transformation over other deaminative functionalization methods lies in its versatility across nearly all classes of medicinally relevant heteroaromatic amines, as well as electronically and structurally diverse aniline derivatives, regardless of the position of the amino group. Mechanistic studies, supported by both experimental observations and theoretical analysis, suggest that the aryl cation equivalent reactivity of N-nitroamines is generally favoured in this deaminative process. This study highlights the potential of the direct deamination approach in synthetic chemistry, offering a safer alternative to the traditionally explosive and hazardous aryldiazonium chemistry.

Coupling carbon dioxide (CO2) with organic molecules through the electrocarboxylation reaction constitutes a promising approach for generating value-added carboxylic acids. Up to now, activated substrates (such as styrene and butadiene derivatives) have been predominantly focused on due to their high activity. In contrast, the unactivated substrates, with low reductive potentials and unstable radical intermediates but more abundant in nature and industry, have rarely been employed. Herein, we proposed a nickel-electrocatalytic system for the regioconvergent carboxylation of unactivated olefins or halides. Various carboxylic acids were obtained by the remote hydro- or di-carboxylation under mild reaction conditions with inexpensive catalysts and electrodes. It was noteworthy that readily available alkanes could also be utilized as starting substrates for the site-selective electrocarboxylation process by the unified catalytic strategy. This method expands the scope of organic molecules coupled with CO2, and demonstrates the possibility of ectopic and remote C & horbar;H carboxylation. Mechanistic investigations indicated that the Ni & horbar;H species generated in the Ni-electrocatalytic system play a key role for promoting chain walking to efficiently produce activated olefin intermediates, which subsequently undergo radical addition with CO2 radical anion and further transform into the desired products.

Metformin, a first-line therapy for type 2 diabetes, has also been implicated in regulating diverse physiological and pathological processes, including lifespan extension, cancer, and other disease-related conditions. However, its mechanisms of action remain incompletely understood, with many effects still unexplained. In this study, we investigated the impact of metformin on the cellular ubiquitinome and associated protein turnover. Through an integrated analysis combining ubiquitinome profiling with pulsed metabolic labeling, we found that metformin markedly suppresses global protein ubiquitination, including various types of ubiquitin chain linkages, and concurrently inhibits both protein synthesis and degradation. Notably, metformin induces a marked reduction in the ubiquitination of histone H4, a modification closely associated with DNA damage repair. We further establish a mechanistic link whereby metformin regulates DNA damage repair and cell cycle progression through downregulating ubiquitination. Together, our findings demonstrate that metformin modulates ubiquitination and proteostasis, central processes that regulate numerous cellular functions. By identifying histone H4 ubiquitination as a key target, we elucidate a potential mechanism through which metformin influences DNA repair and cell cycle progression. This comprehensive dataset advances understanding of the drug's multifaceted pharmacological activities and provides a valuable resource for future drug development.

Oxyallenes are valuable building blocks in organic synthesis, most commonly exploited as pi-allyl metal precursors in transition-metal-catalyzed allylation reactions. In contrast, their engagement in radical processes remains largely unexplored. Herein, we disclose a Giese-type radical addition protocol in which acyl-substituted oxyallenes function as in situ precursors to alpha,beta-unsaturated ketones, enabling efficient coupling with 2-azaallyl radicals. This metal-free method delivers a wide range of gamma-amino ketones in high yields with broad functional group tolerance, mild conditions, and scalability to gram quantities. Mechanistic studies, including radical trapping and isotopic labeling, support a pathway involving radical addition of the 2-azaallyl radical to transient enone intermediates. These findings establish a new reactivity mode of oxyallenes in radical chemistry and provide an efficient route to synthetically and pharmaceutically valuable amino ketones.

Two acceptor-donor-acceptor (A-D-A) type of hydrogen bonded thiophene azomethine building blocks, TTAZ and BTAZ, were synthesized. Both compounds incorporated the electron-withdrawing unit 3-cyanothiophene, with the electron-rich moieties consisting of carbamate functionalized thieno[3,2-b]thiophene for TTAZ and carbamate functionalized 2,2'-bithiophene for BTAZ, respectively. The corresponding polymer PTTAZ and PBTAZ were synthesized via Stille cross-coupling reaction. Although the absorption spectra of the two polyazomehines exhibited distinct aggregation behaviors, both showed broad full width at half maximum (FWHM) and similar electrochemical energy levels. Organic field-effect transistors (OFETs) fabricated using PTTAZ and PBTAZ as electroactive layers demonstrated p-type charge transport characteristic, with maximum hole mobility of 4.32 x 10-3 for PTTAZ and 3.64 x 10-3 cm2 V- 1 s- 1 for PBTAZ. The microstructures of the polymer thin films were further analyzed using atomic force microscope (AFM) and two-dimensional grazing incidence wide-angle X-ray scattering (2D-GIWAXS).

Radical reactions offer transformative potential in biological contexts but remain constrained by poor selectivity and off-target reactivity. We address these limitations through visible-light photocatalytic generation of diaryl ketyl radicals from benzophenones. This strategy circumvents traditional UV excitation pathways by suppressing triplet diradical formation-which drives nonspecific [2 + 2] cycloadditions and H atom abstraction-in favor of bioorthogonal radical-radical coupling. Our platform enables precise live-cell protein labeling with minimal cytotoxicity, including in sensitive primary neuronal cultures, and achieves site-specific modification via genetically incorporated benzophenone-based unnatural amino acids Bpa. The spatial selectivity of this approach exceeds conventional UV-based cross-linking methods, facilitating site-to-site analysis of tertiary protein interactions in structurally defined complexes. We demonstrate these capabilities by (1) quantifying dimerization interfaces of the Diels-Alderase PyrI4 and (2) resolving Bcl-XL/Bid interactions critical for apoptotic regulation. This photocatalysis-driven methodology establishes a robust alternative to cycloaddition-based bioorthogonal chemistry for spatiotemporally controlled interrogation of dynamic biomolecular processes.