Room-temperature phosphorescence (RTP) and organic long-persistent luminescent (OLPL) materials inherently possess significant potential in information encryption, anti-counterfeiting, and optoelectronic devices. The integration of these materials with wood to fabricate such materials to enrich multifunctionality and broaden its application scope. Herein, we present a dual-component room-temperature phosphorescence/thermally activated delayed fluorescence (RTP/TADF) afterglow system composed of a difluoroboron beta-diketonate (BF2bdk) dopants and an organic matrix. In this dual-component system, the introduction of an electron-donating component enables charge separation, enhancing the afterglow performance. The resulting three-component material demonstrates visible-light-excitable OLPL properties, exhibiting long-afterglow that lasts for several hours under ambient conditions. When this three-component material is melt-cast into a wood framework, a novel wood with OLPL properties is created. This fusion of wood and luminescent technology not only enhances the aesthetic and practical qualities of wood products but also drives technological innovation and development in areas such as anti-counterfeiting, data encryption, green building materials, and emergency lighting.

HOIP, an RBR-type E3 ligase and the catalytic subunit of the linear ubiquitin chain assembly complex (LUBAC), plays crucial roles in various cellular processes, including the NF-kappa B signaling pathway. The E3 activity of HOIP can be inhibited by the kinase STK4-mediated phosphorylation, although the mechanism is poorly understood. In this study, using biochemical, mass spectrometry and structural approaches, we systemically characterize the association of STK4 with HOIP, and unveil that STK4 can directly bind to the RING2-LDD module of HOIP through its kinase domain. The determined crystal structure of STK4 in complex with HOIP RING2-LDD not only elucidates the detailed binding mechanism of STK4 with HOIP, but also uncovers, for the first time, a unique binding mode of STK4 with its substrate. Moreover, we reveal that STK4 can directly phosphorylate the T786 residue of HOIP that is located in the allosteric ubiquitin-binding site of HOIP. Importantly, the phosphorylation of HOIP T786 mediated by STK4 can block the binding of ubiquitin to the allosteric site of HOIP, thereby attenuating the E3 activity of HOIP. In all, our findings provide mechanistic insights into the interaction between STK4 and HOIP as well as the negative regulation of HOIP's E3 activity by STK4-mediated phosphorylation, which are valuable for further understanding the regulatory modes of RBR-type E3 ligases.

Tsuji-Trost reaction typically relies on the use of alkenes containing an alpha-leaving group as the substrates. In comparison, an in situ assembling model from feedstock chemicals represents a distinctive and practically valuable route, yet remains undeveloped. Here we report an unprecedented excited Pd-catalyzed in situ assembling Tsuji-Trost reaction by using readily available alkenes, esters, and nucleophiles as substrates. With the development of a HAT/Heck/allylation cascade protocol, various (E)-allyl compounds are prepared in good yields and stereoselectivities. Meanwhile, a novel photoinduced Pd/Ir relay catalysis is designed to enable stereoselective preparation of challenging (Z)-allyl compounds. Stereodivergent synthesis of all four stereoisomers [(E,R), (E,S), (Z,R), and (Z,S)] is also realized via this excited-state Pd chemistry, different from typical ground-state catalytic models. A broad range of N-, C-, O-, and S-derived nucleophiles and different alkenes and esters show high compatibility with the transformation. The protocol is further applied to the concise synthesis of seven bioactive molecules from bulk materials, highlighting the reliability, generality, and practical value of the design. Mechanistic studies support the present design.

The active Cu(I) species Q+ [CuI (CF2 CO2 Et)(Cl)]- 1a and Q+ [CuI (CF2 CO2 Et)2 ]- 1b (Q = Ph4 P), which played an important role in the copper mediated ethoxycarbonyl difluoromethylation of organic halides, have been isolated and characterized for the first time. Stoichiometric reaction showed complex 1b is much more reactive than 1a . Furthermore, while oxidative addition of complex 1b with aryl iodide resulted in the formation of the reductive elimination product without the observation of the Cu(III) intermediate, the oxidative addition of iodoacetronitrile to 1b successfully generated Cu(III) intermediates that reductively eliminate to give the products. Building on the stoichiometric reaction, a copper-catalyzed ethoxycarbonyl difluoromethylation of benzylic, allylic halides was developed. Additionally, it has been found that complex 1b serves as a powerful ethoxycarbonyl difluoromethylation reagent capable of ethoxycarbonyl difluoromethylating a variety of electrophiles including (hetero)aryl electrophiles, alkyl electrophiles and acid chloride, disulfide. Moreover, the oxidative ethoxycarbonyl difluoromethylation of complex 1b with various lithium n -butyl (hetero)aryl boronic acid pinacol esters has been achieved in the presence of an oxidant. (c) 2025 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.

Small-molecule intervention and stabilization of G-quadruplexes (G4s) have been investigated for the potential as therapeutic approaches. MYC plays diverse roles in cellular functions, making it a highly desirable yet challenging target. One promising strategy includes DNA G4 structures, which mediate transcriptional control over MYC in the presence of small-molecule ligands. Unraveling the effects of these ligands on G4 stability and functionality is seldom achieved yet essential for designing potent ligands against these intractable targets. This study introduces BTO-28, a benzothiazole-based ligand that binds with high affinity to the MYC G4. In vitro experiments, NMR analysis, and intracellular assays collectively indicate that BTO-28 potentially downregulates MYC transcription through a G4-mediated mechanism. Structural determination of the 2:1 benzothiazole-MYC G4 complex provides insights into unexpected molecular interactions, highlighting for the first time a unique hydrogen-bonding pattern involving the nucleobase surrogate and flanking residues. The protonated pyrrolidine side chains of BTO-28 reorient to form hydrogen bonding with the external G-tetrad, establishing a previously uncharacterized ligand-G4 interface. This work advances the rational design of G4-binding ligands and clarifies the molecular basis underlying MYC recognition.

Terphenyl phosphines are rising as powerful supporting ligands in the palladium-catalyzed C-N cross-coupling reactions, leading to reduced catalyst loadings and broadened substrate scope. To extend the terphenyl phosphine family, TRuPhos and TSPhos along with their 2-amino-biphenyl-eta(2)-C,N palladium precatalysts have been synthesized and characterized, including one complex by single-crystal diffraction. TRuPhos exhibits unprecedented efficiency in the palladium-catalyzed arylation of many hindered primary alkyl amines. Mechanism studies have clarified that: 1) the transmetalation path A involving amine adducts of oxidative addition product does not work by the TRuPhos-supported palladium catalyst in the arylation of hindered primary alkyl amines, but works for that in small bulk amines; 2) the path C involving the substitution of halogen atoms on oxidative addition products by tBuO groups seems impossible as well; 3) the reaction occurred between oxidative addition products and sodium amides forming C-N coupling products suggests that path B is a possible transmetalation pathway in Pd/TRuPhos-catalyzed arylation of hindered primary alkyl amines.

Covalent organic frameworks (COFs) are crystalline porous polymers with diverse structures and tunable functions. Building hierarchical porosity in 2D COFs allows integration of complex pores with adjustable metal centers for precise charge modulation-key for enhancing light-driven catalysis, though still challenging. Herein, a bipyridine-based COF (TB-COF) featuring three distinct types of pores is achieved using a desymmetrization strategy based on a modified D2h-symmetric monomer. The high crystallinity and uniform triple pores of TB-COF are unequivocally characterized via high-resolution transmission electron microscopy (HR-TEM). Post-synthetic metalation with Co2(+), Ni2(+), and Cu2(+) incorporates active sites into the bipyridine units. Leveraging their well-ordered hierarchical porous structure and active metal sites, these metalated COFs are investigated as photocatalysts for CO2 reduction. Notably, the Co-functionalized COF (Co-TB-COF) exhibits a high CO production rate of 12385 mu mol g-1 h-1 with a selectivity of 88.4% over H2. Mechanistic investigations, supported by experimental data and theoretical calculations, confirm that the embedded metal sites are crucial to enhance photoinduced charge separation and lower the activation energy for intermediate *COOH formation, thereby boosting photoreduction efficiency. This study presents a novel strategy for the design of intricate COF architectures and elucidates the previously unexplored functionalities of hierarchically porous COFs.

Pathological aggregation of transactive response DNA binding protein of 43 kDa (TDP-43), primarily driven by its low-complexity domain, is closely associated with various neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Despite the therapeutic potential of preventing TDP-43 aggregation, no effective small molecule or biomacromolecule therapeutics have been successfully developed so far. Here, we introduce a protein design strategy that yields de novo designed proteins capable of stabilizing the key amyloidogenic region of TDP-43 in its native helical conformation with nanomolar binding affinity. The binding mechanism was further characterized by the NMR and mutagenesis study. More importantly, we demonstrated that our designed protein binders efficiently reduced TDP-43 amyloid aggregation both in vitro and in cells. Our work provides a strategy for designing protein stabilizer of the native conformation of pathological proteins for preventing its amyloid aggregation, shedding light on the development of potential therapeutic approaches for ALS, FTLD, and other protein aggregation-associated diseases.

a-synuclein transmission and propagation are hallmarks of synucleinopathies, yet the molecular mechanisms remain elusive. Using a-synuclein preformed fibrils as pathological seeds, we observed a gradual decline in neuronal transmission activity during serial propagation. Fibril polymorphisms were identified from the initial generation: mini-P, with higher neuronal seeding activity, and mini-S, which accelerated recombinant a-synuclein aggregation. Changes in their proportions during propagation explained the overall decline in transmission activity. Cryoelectron microscopy and solid-state nuclear magnetic resonance revealed that both fibrils shared similar core regions but differed in their fuzzy coat flexibilities. The interaction between the fuzzy coat and fibril core substantially influenced neuronal transmission, a model further supported by hydrogen/deuterium exchange mass spectrometry. A mini-P-selective antibody identified active fibril types in newly propagated brain regions in human synucleinopathies. This study highlights the fuzzy coat's pivotal role in pathological protein transmission and suggests it as a potential therapeutic target for synucleinopathies.