Aging and its associated diseases are characterized by a complex interplay of cellular dysfunction, chronic inflammation, and tissue degeneration. Dysregulated cell death and the resulting inflammatory responses are pivotal drivers of this pathological synergy. Among various cell demise pathways, programmed cell death (PCD) mechanisms, including apoptosis, necroptosis, and pyroptosis, are critical for maintaining homeostasis but can drive pathology when aberrantly activated. Crucially, they leave specific and reliable biomarkers, allowing for their distinct assessment in complex aging tissues. This review synthesizes recent insights into the intricate regulation and execution of these PCD pathways, their interconnections with inflammatory signaling, and their impact on the pathogenesis of aging and aging-related diseases. We further highlight how the integrated understanding of these cell death pathways opens avenues for targeted therapies in aging-associated disorders.

The synthesis of multisubstituted cubane derivatives remains challenging due to the limitations of current synthetic methods. Therefore, developing site-selective C-H halogenation reactions starting from simple 1,4-substituted cubane compounds is highly desirable. Herein, we report an efficient strategy for the C-H halogenation of cubane using sodium decatungstate (NaDT) as a hydrogen atom transfer photocatalyst to produce cubyl radicals which could undergo halogenation with different halogen sources to achieve chloro-, bromo-, and iodo-substituted cubane derivatives in poor-to-excellent yields ranging from 12% to 94%. This method offers a practical route for accessing multifunctionalized cubanes for further research.

Noncovalent interactions are the fundamental forces governing crystal packing and the generation of intrinsic porosity in noncovalent porous crystals (NPCs); however, the comparative efficacy of distinct interaction types remains insufficiently characterized. This study presents a systematic, direct comparison between hydrogen bonding and halogen bonding within single-component NPCs, utilizing triptycene-based molecular scaffolds with identical geometric parameters. By selectively incorporating hydrogen-bonding (H & centerdot;& centerdot;& centerdot;N) or halogen-bonding (X & centerdot;& centerdot;& centerdot;N) motifs, we observe strikingly divergent crystallization behaviors. The hydrogen-bonded system displays pronounced polymorphism, yielding multiple crystal forms due to competing, nonspecific interaction modes. Conversely, the halogen-bonded analogue crystallizes exclusively into a single, highly porous structure. This sharp contrast is attributed to the unique nature of halogen bonding, which enforces highly directional and specific intermolecular interactions. This specificity enhances porosity, suppresses polymorphism, and significantly improves structural predictability. Consequently, these findings establish halogen bonding as an advantageous supramolecular design element within specific molecular scaffolds for constructing single-component NPCs.

Breaking the development bottlenecks of traditional energetic materials has become an urgent problem to be solved in recent years. In general, energetic materials are composed of energetic groups and molecular skeletons. At present, most design strategies for energetic molecules focus on the construction of novel molecular skeletons. Inspired by the unconventional complex energetic groups reported in the literature, this study focused on the design of new "composite energetic groups". A total of 72 initial structures were obtained by combining traditional energetic groups. Theoretical calculations on their molecular structures, initial thermal decomposition mechanisms were performed via density functional theory (DFT) using the Gaussian16 program. Excellent kinetic stability ensures a sufficiently high thermal decomposition temperature and favorable chemical stability, which are essential prerequisites for the practical application of energetic molecules. Identifying accurate trigger bonds and reliable decomposition mechanisms is critical for determining the initial decomposition energy barriers. Multiple potentially fractured chemical bonds and various cleavage pathways were considered, including homolysis, heterolysis, group migration, and elimination. The Kamlet-Jacobs (KJ) equation and the EXPLO5 program were adopted to calculate detonation velocity and detonation pressure. Subsequently, 39 energetic groups were screened out based on energetic performance and kinetic stability, all possessing an initial decomposition energy barrier of >= 30 kcal center dot mol-1, among which 34 were unprecedented new groups. For five experimentally synthesized structures, detailed comparisons demonstrated that the calculated thermal stability results were in excellent agreement with experimental data. Furthermore, molecular design was carried out using alkane skeletons and polyamine skeletons. It is revealed that the intramolecular strain and steric hindrance dominated by alkane skeletons, as well as the hyperconjugation effect, exert a significant influence on the kinetic stability of the final energetic molecules. All these molecules exhibit a density >2.0 g center dot cm(-3), a detonation velocity >8000 m center dot s(-1), and a detonation pressure >33 GPa.

Macrocyclic molecules (cyclodextrins, calixarenes, cucurbiturils, and pillararenes) have demonstrated significant potential in energy storage applications owing to their unique cavity structures and molecular recognition capabilities. This review focuses on the core molecular-level mechanisms, systematically elaborating four key pathways: cavity confinement, redox activity, host-guest transport, and supramolecular assembly which synergistically regulate ion/electron behavior. We further establish the structure-activity relationships that govern energy storage device performance, elucidating how molecular-level design parameters translate into macroscopic device metrics. Different from traditional material synthesis-oriented reviews, this work emphasizes "design guidelines for macrocyclic molecules", providing new insights and theoretical support for the development of next-generation high-performance energy storage materials.

Enantioselective hydrosilylation of allenes remains a significant challenge with a limited scope due to the difficulties in controlling both regioselectivities and enantioselectivities, despite it representing one of the most efficient manners for the preparation of optically pure allylsilanes. Here, we report a general platform for the efficient and modular preparation of diverse allylsilanes via nickel-catalyzed hydrosilylation of various allene derivatives, including mono-substituted allenes and 1,3-disubstituted allenes. Enabled by a newly developed SPSiOL-derived diphosphinite ligand (SPSiOP), hydrosilylation of mono-substituted allenes has been realized with excellent regioselectivity and enantioselectivity. Moreover, the first kinetic resolution of racemic 1,3-disubstituted allenes has been disclosed using a commercially available chiral QuinoxP* ligand, affording a series of secondary allylsilanes with high stereo induction (S factor up to 133). The resulting enantioenriched allylsilanes are highly synthetically useful, which has been demonstrated by a variety of transformations of the silyl and alkene functional groups, culminating in efficient synthesis of silacycles and formal synthesis of several bioactive molecules.

Necroptosis is a programmed lytic cell death pathway executed through mixed lineage kinase domain-like protein (MLKL)-driven plasma membrane disruption and has pivotal roles in both health and disease. Recent advances have led us to propose the classification of mammalian necroptosis into two subtypes: extrinsic and intrinsic necroptosis, which differ in their mechanisms of trigger sensing and signal integration. Extrinsic necroptosis is initiated by membrane-bound receptors, including cell-surface receptors such as tumour necrosis factor receptor 1 (TNFR1) and Toll-like receptor 4 (TLR4), as well as endosomal receptors such as TLR3, whereas intrinsic necroptosis is initiated intracellularly through sensors such as Z-DNA-binding protein 1 (ZBP1) detecting cytosolic Z-nucleic acids. In this Review, we provide an overview of the molecular mechanisms of necroptosis, highlighting the latest insights into their complex regulatory networks, execution pathways, and the growing clinical relevance and therapeutic potential of targeting necroptosis in human diseases.

CO2, one of the major contributors to global climate change, is a promising carbon feedstock for graphite synthesis. Graphite is the only carbon-based critical material recognized by numerous countries and international organizations, with various applications including energy storage on Earth and Mars. Herein, this study realizes the mild, efficient in situ synthesis of graphite from CO2, H2O, and borate, which are abundant on both planets. At 220 degrees C and 5.0 MPa with NaBH4, graphite is obtained with 79.2% selectivity and 93.1 wt.% purity, and byproduct NaBO2 can be electrochemically recycled for sustainable material utilization. Mechanistic investigations reveal that CO2 reacts with NaBH4 to form methane, ethylene, and propadiene. Methane and ethylene generate aromatics, while propadiene promotes polymerization into graphite. As a Zn-based battery anode, the graphite retains 90.9% capacity after 2500 cycles at 1.0 A & centerdot;g-1 for Zn-CO2||MnO2, confirming excellent energy storage performance. This work not only provides a novel, sustainable strategy for CO2 utilization and storage but also aims to bridge terrestrial environmental crisis mitigation and extraterrestrial in-situ resource utilization, laying a foundational basis for material, environmental, and energy sustainability on Earth and Mars.

Neuronal intranuclear inclusion disease (NIID) arises from GGC repeat expansions in NOTCH2NLC. These expanded repeats produce polyglycine (polyG) proteins, and the accumulation of these polyG proteins in neuronal nuclei serves as the characteristic pathological hallmark of NIID. However, the native cellular ultrastructure of polyG and its contribution to pathology remain poorly understood. Here, using a transgenic NIID mouse model, we extract polyG assemblies from diseased brain and characterize their architecture by cryo-electron tomography (cryo-ET). We further examine their native organization by tracer-guided in situ cryo-ET in vitrified mouse brain. We find that polyG forms highly branched similar to 5 nm fibrils that laterally coalesce into densely packed ribbons, which represent the predominant polyG state within neuronal nuclei in situ. In parallel, proximity-dependent labeling coupled to mass spectrometry reveals selective enrichment of proteostasis factors-including proteasome subunits and molecular chaperones-at polyG assemblies in mouse brain. Consistent with this, cryo-ET visualizes proteasome-like particles decorating ribbon-shaped surfaces and edges in cells. Together, these findings uncover an unexpected ribbon-shaped supramolecular architecture for a low-complexity disease protein and suggest that nuclear polyG ribbons act as scaffolds that engage proteostasis machinery, providing mechanistic insight into NIID.