Introducing functional groups to skeletons of covalent organic frameworks (COFs) is fundamentally important to create specific properties and functions for this class of crystalline porous polymers. The strategy of multi-functionalization could introduce multiple functional groups in one-step but has rarely been developed for polymers. Herein, we report a novel linkage conversion strategy which could simultaneously install multiple functional groups into a single site of azine-linked COFs. This strategy is based on criss-cross 1,3-dipolar cycloaddition reaction between azine linkages in COFs and multifarious alkynes carrying different functional groups. Its general applicability and high efficiency have been demonstrated by the successful construction of more than 10 COFs with widespread functional groups, for which homo-type and hetero-type functional groups could be introduced. This study provides a general and powerful tool to introduce highly dense functional groups into nanopores of COFs, enabling the further exploration of their applications bestowed by the functional groups.

Organic room-temperature phosphorescent (RTP) materials are of increasing interest due to their unique triplet-state emission and potential applications in anti-counterfeiting, bioimaging, and optical storage. However, challenges such as low emission efficiency, short lifetimes, and limited scalability have hindered their practical use. Herein, we report a facile and scalable synthesis of difluoroboron beta-diketonate (BF2bdk) compounds and their incorporation into a poly(methyl methacrylate) (PMMA) matrix via emulsion polymerization. The rigid microenvironment of PMMA effectively suppresses non-radiative decay of the triplet state, yielding an RTP emulsion with a phosphorescence lifetime of up to 1.38 s. Blending with commercial emulsions enables the fabrication of uniform, transparent RTP coatings that can be obtained with bright afterglow exceeding 10 s. These coatings exhibit excellent environmental stability, thermal and chemical resistance, and industrial applicability. This study addresses the long-standing challenge of the scalable fabrication of aqueous afterglow materials, and offers a promising route for the large-scale production of high-performance organic RTP materials, paving the way for their integration into diverse application scenarios such as advanced optical and security technologies.

All-carbon quaternary centers are prevalent structural motifs, thus attracting increasing interest from the organic community. We present here a nickel-catalyzed, Markovnikov-selective addition of stable organoborons to simple alkenes, enabled by a diimine ligand. This robust method provides efficient access to quaternary carbon centers with high yields. Furthermore, with a bulky chiral diimine ligand, quaternary carbon stereocenters can be readily prepared. Mechanistic investigations indicate the involvement of an unusual nickel migration from an alkyl nickel to an aryl nickel species.

To help alleviate resource waste and environmental pollution from discarded poly(methyl methacrylate) (PMMA), we demonstrate facile synthesis and efficient catalytic depolymerization of high-molecular-weight PMMA. A small fraction of C-Me bonds are replaced with catalytically activatable C-Cl bonds via free radical copolymerization of MMA with readily available methyl alpha-chloroacrylate. Leveraging low-temperature efficient catalysis by Cu(0), the synthesized polymers achieve high recyclability while maintaining ideal intrinsic properties. For PMMA with Mn exceeding 300 kg mol-1 (380-1010 kg mol-1), Cu(0)-catalyzed depolymerizations attain the highest reported depolymerization efficiency (similar to 90% in 4 hours) at a temperature well below 200 degrees C (160 degrees C) and high concentrations ([MMA unit]0 = 400-8800 mM). The recovered MMA monomer can be effectively repolymerized into a polymer with molecular weight and properties comparable to those of the polymer synthesized from a virgin monomer, and both catalysts and solvents used in this approach exhibit potential for recyclability.

Hydrocarbon polymers are ideal dielectric materials in microelectronic industry due to their extraordinarily low dielectric constant (D-k) and dielectric loss (D-f). However, a challenge remains in improving their intrinsic thermal conductivity. This work establishes a novel method to develop hydrocarbon polymers with enhanced thermal conductivity by a liquid crystal (LC) ordering effect. An LC molecule is designed with triphenyl mesogen and styrene end groups (ST38), cross-linking in polybutadiene to form an LC polymer (ST38PB). The exploration of LC arrangement reveals that the formation of well-ordered LC domains is induced by pi-pi stacking of triphenyl group, with its orientation being fixed by the cross-linking reaction. The LC domains demonstrate exceptional thermal stability, maintaining their structural integrity even at 260 degrees C. ST38PB exhibits an enhanced intrinsic thermal conductivity coefficient (lambda) of 0.62 W m(-1) K-1, which is 3.4 times that of pristine polybutadiene. Meanwhile, it displays excellent dielectric properties (D-k = 2.40, D-f = 3.3 x 10(-3) at 10 GHz). The use of ST38PB as thermal management materials for chip cooling and dielectric substrates for printed circuit boards is investigated. The findings confirm its promising potential for applications, and this strategy can be further extended to develop other LC-based thermally conductive polymers for demanding high-temperature applications.

Parkinson's disease (PD) is a prevalent neurodegenerative disorder characterized by progressive neuronal loss and pathological aggregation of a-synuclein (a-syn) into amyloid fibrils, which propagate between cells and drive disease progression. Over the past decade, our laboratory has implemented an integrated strategy-combining high-resolution structural biology, molecular biophysics, biochemical and cellular analyses, chemical biology approaches, and in vivo disease models-to elucidate the molecular basis of a-syn pathology. We first determined atomic-resolution structures of full-length a-syn fibrils, revealing diverse polymorphs shaped by familial mutations and post-translational modifications, and linking conformational heterogeneity to phenotypic and pathological diversity. We further elucidated the structural basis underlying the interaction between amyloid fibril and chemical ligands, enabling the rational development of imaging probes and therapeutic modulators. In parallel, we found that the conserved acidic C-terminal region of a-syn fibrils acts as a central interface for driving pathogenic engagement with multiple receptors for neural propagation and inflammation induction, while also binding the autophagy adaptor LC3B to disrupt p62-mediated selective autophagy. Targeting this interface with small molecule inhibitors alleviates a-syn-induced toxicity in cellular models. Together, these findings provide an integrated molecular roadmap for understanding a-syn pathology and advancing precision diagnostics and targeted interventions in PD and related synucleinopathies. (c) 2025 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC license. (http://crea-tivecommons.org/licenses/by-nc/4.0/)

Metal ions are essential in regulating protein functions through interactions with residues such as cysteine, but comprehensive mapping of metal-specific metalloproteomes in mammals remains limited. Here, we introduce CysMP, a cysteine-centered metalloprotein profiling strategy to profile the metalloproteomes of 11 key metal ions. CysMP identified 8895 metal-binding sites across 4150 proteins, enabling quantitative comparisons between different metals and revealing both their binding promiscuity and preferences. Notably, zinc and copper ions exhibit the broadest protein interaction profiles. CysMP uncovers numerous potential metalloproteins. We demonstrate that copper and zinc bind to and inhibit 5 '-methylthioadenosine phosphorylase, resulting in the accumulation of 5 '-methylthioadenosine. Furthermore, copper binding suppresses phosphoglycerate kinase 1 activity, leading to a down-regulation of glycolysis. Our work not only establishes a valuable resource for a dual-specific metalloproteome database but also paves the way for understanding the molecular insights of metalloprotein functions.

Halogen bonding offers a directional and tunable noncovalent interaction that remains underexplored in the design of porous molecular materials. Here, we report FPMC-1-beta, a porous molecular crystal that uniquely integrates permanent porosity, high thermal stability, solution processability, and halogen bonding capability. Upon desolvation, FPMC-1-alpha undergoes a structural transformation into the denser FPMC-1-beta phase, featuring distorted 1D channels lined with exposed sigma-holes on bromine atoms. This architecture enables selective halogen bond-mediated interactions with fluorinated gases. FPMC-1-beta exhibits a sulfur hexafluoride (SF6)/N2 selectivity of 178.6 at 298 K and 1 bar-setting a new record among all reported porous molecular crystals and soluble porous materials. Combined experimental and computational studies reveal that the high selectivity arises from strong F & ctdot;Br halogen bonding with SF6, in contrast to the weak, nonspecific interactions observed for N2.

The substantial ring strain and activated double bonds render methylenecyclopropanes (MCPs) potential substrates for Diels-Alder (DA) reactions. In this work, we present a thermally induced intramolecular Diels-Alder (IMDA) reaction utilizing furan-tethered MCPs. The reactions were carried out smoothly with respect to a wide variety of substrates with good functional group compatibility, affording the desired products in moderate to excellent yields. The synthetic utility of these products was successfully demonstrated. Mechanistic studies involving radical scavenger control experiments and density functional theory (DFT) calculations revealed a concerted mechanism involving an asynchronous one-step pathway.

Migraine is a complex neurological disorder influenced by multiple genetic susceptibility factors, yet current animal models fail to fully recapitulate its human-specific pathophysiology. In this study, we explored the potential mechanisms underlying migraine by examining functional abnormalities and molecular dysregulation in glutamatergic neurons derived from induced pluripotent stem cells (iPSCs) of migraine patients. As key excitatory cells in the central nervous system, glutamatergic neurons are implicated in migraine through altered excitability, ion channel dysfunction, and dysregulation of nociceptive signaling molecules. iPSCs from both migraine patients and healthy controls were differentiated into glutamatergic neurons. Electrophysiological properties and sodium and potassium channel functions were assessed using whole-cell patch-clamp recordings. Expression levels of migraine-associated molecules, including P2RX3, calcitonin gene-related peptide (CGRP), and c-Fos, were evaluated via immunofluorescence and quantitative real-time PCR. Dysfunction of glutamatergic neurons, involving ion channel dysregulation and abnormal molecular expression, may be implicated in migraine pathology and may provide potential targets for therapeutic intervention. The iPSC-based model may help to address some limitations of animal studies and offers a potential platform for migraine precision medicine research. As a proof-of-principle study, these findings highlight the feasibility of using iPSC-derived glutamatergic neurons to explore migraine mechanisms. While preliminary, this model may serve as a valuable foundation for future translational and precision medicine research.

Dehydroxylative trifluoromethylthiolation of alcohols has garnered significant attention yet remains a challenging transformation due to the high bond dissociation energy of the C-OH bond. In this work, we report the use of tris(trifluoromethylthio)-1,3,5-triazine as a dual-function reagent that serves both as a CF3S source and an activator of hydroxyl groups. The reaction proceeds under mild conditions, does not require Lewis acid activators, and converts a range of primary alcohols to the corresponding products in good to excellent yields.

Neuroinflammation drives Alzheimer's disease (AD) pathogenesis. Z-DNA, a non-canonical left-handed DNA structure, activates innate immune signaling through Z-DNA-binding protein 1 (ZBP1). However, the functional significance of ZBP1-mediated Z-DNA detection in AD remains undefined. Here, we found that ZBP1 is amplified in AD microglia, driving innate immune responses and neuroinflammation through sensing Z-form mitochondrial DNA (mtDNA). We show that oxidized mtDNA, generated by amyloid-beta(A beta)-induced oxidative stress, was fragmented and released into the cytoplasm, forming Z-DNA. Z-DNA-activated ZBP1 engaged receptor-interacting protein kinase 1 (RIPK1), promoting its kinase activation and inducing transcription of pro-inflammatory molecules and inflammatory signaling mediators. Genetic deletion of Zbp1 or inhibition of RIPK1 attenuated neuroinflammation, A beta pathology, and behavioral deficits in an AD mouse model. Our findings reveal that oxidation induces the Z conformer in mtDNA and establish the ZBP1-RIPK1 axis as a key driver of AD neuroinflammation, providing insights into the immune mechanisms underlying AD pathogenesis and identifying a potential therapeutic target.

The ring-opening polymerization (ROP) of O-carboxyanhydrides (OCAs) efficiently produces diverse poly(alpha-hydroxyalkanoic acid) (PAHA) with functional groups that are difficult to achieve via lactone polymerization. Poly(mandelic acid) (PMA), synthesized from manOCA (OCA derived from mandelic acid), is a promising polymeric material because of its high glass transition (T g) and thermal decomposition temperatures (T d). However, the synthesis of highly isotactic PMA remains challenging due to the inherent tendency to undergo epimerization during polymerization. Herein, the simple bimetallic rare-earth metal amide complex [(Me3Si)2N]3La(mu-Cl)Li(THF)3 was developed as an efficient catalyst to catalyze the ROP of L-manOCA. This catalyst effectively suppressed epimerization with high activity to afford highly isotactic PMA. The remarkable activity and isomerization selectivity were attributed to the synergistic effect between the rare-earth metal and lithium atoms in [(Me3Si)2N]3La(mu-Cl)Li(THF)3, as confirmed by density functional theory (DFT) calculations. Furthermore, the catalyst enabled precise control over polymer topology (cyclic vs linear) by modulating BnOH addition and reaction temperature. This catalyst also exhibited remarkable polymerization activity toward OCA derivatives with high isotactic selectivity. These findings lay the foundation for the development of efficient catalysts for the synthesis of highly isotactic PAHA polymers from OCA monomers.