Category-Specific Topological Learning of Metal-Organic Frameworks.

Metal-organic frameworks (MOFs) are porous, crystalline materials with high surface area, adjustable porosity, and structural tunability, making them ideal for diverse applications. However, traditional experimental and computational methods have limited scalability and interpretability, hindering effective exploration of MOF structure-property relationships. To address these challenges, we introduce, for the first time, a category-specific topological learning (CSTL), which combines algebraic topology with chemical insights for robust property prediction.

Targeting autophagy plus high-dose CDK4/6 inhibitors in advanced HR+HER2- breast cancer: A phase 1b/2 trial.

Background: The unmet needs of managing patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer who progress after cyclin-dependent kinase (CDK)4/6 inhibitor (CDK4/6i) treatment remain unclarified.

Methods: This was a phase 1b/2, single-arm, open-label study that enrolled 29 patients with HR+/HER2- breast cancer who experienced first-line palbociclib treatment failure. The primary endpoint was the incidence of dose-limiting toxicity (DLT).

A molecular view of peptoid-induced acceleration of calcite growth.

The extensive deposits of calcium carbonate (CaCO) generated by marine organisms constitute the largest and oldest carbon dioxide (CO) reservoir. These organisms utilize macromolecules like peptides and proteins to facilitate the nucleation and growth of carbonate minerals, serving as an effective method for CO sequestration. However, the precise mechanisms behind this process remain elusive.

Hierarchical Self-Assembly of Multidimensional Functional Materials from Sequence-Defined Peptoids.

Hierarchical self-assembly represents a powerful strategy for the fabrication of functional materials across various length scales. However, achieving precise formation of functional hierarchical assemblies remains a significant challenge and requires a profound understanding of molecular assembly interactions. In this study, we present a molecular-level understanding of the hierarchical assembly of sequence-defined peptoids into multidimensional functional materials, including twisted nanotube bundles serving as a highly efficient artificial light harvesting system.

Assembly of short amphiphilic peptoids into nanohelices with controllable supramolecular chirality.

A long-standing challenge in bioinspired materials is to design and synthesize synthetic materials that mimic the sophisticated structures and functions of natural biomaterials, such as helical protein assemblies that are important in biological systems. Herein, we report the formation of a series of nanohelices from a type of well-developed protein-mimetics called peptoids. We demonstrate that nanohelix structures and supramolecular chirality can be well-controlled through the side-chain chemistry.

Access to Advanced Functional Materials through Postmodification of Biomimetic Assemblies via Click Chemistry.

The design, synthesis, and fabrication of functional nanomaterials with specific properties remain a long-standing goal for many scientific fields. The self-assembly of sequence-defined biomimetic synthetic polymers presents a fundamental strategy to explore the chemical space beyond biological systems to create advanced nanomaterials. Moreover, subsequent chemical modification of existing nanostructures is a unique approach for accessing increasingly complex nanostructures and introducing functionalities.

Directing polymorph specific calcium carbonate formation with de novo protein templates.

Biomolecules modulate inorganic crystallization to generate hierarchically structured biominerals, but the atomic structure of the organic-inorganic interfaces that regulate mineralization remain largely unknown. We hypothesized that heterogeneous nucleation of calcium carbonate could be achieved by a structured flat molecular template that pre-organizes calcium ions on its surface. To test this hypothesis, we design helical repeat proteins (DHRs) displaying regularly spaced carboxylate arrays on their surfaces and find that both protein monomers and protein-Ca supramolecular assemblies directly nucleate nano-calcite with non-natural {110} or {202} faces while vaterite, which forms first in the absence of the proteins, is bypassed.

DAXX promotes centromeric stability independently of ATRX by preventing the accumulation of R-loop-induced DNA double-stranded breaks.

Maintaining chromatin integrity at the repetitive non-coding DNA sequences underlying centromeres is crucial to prevent replicative stress, DNA breaks and genomic instability. The concerted action of transcriptional repressors, chromatin remodelling complexes and epigenetic factors controls transcription and chromatin structure in these regions. The histone chaperone complex ATRX/DAXX is involved in the establishment and maintenance of centromeric chromatin through the deposition of the histone variant H3.

Insights into the Biomimetic Synthesis of 2D ZnO Nanomaterials through Peptoid Engineering.

Achieving predictable biomimetic crystallization using sequence-defined synthetic molecules in mild conditions represents a long-standing challenge in materials synthesis. Herein we report a peptoid-based approach for biomimetic control over the formation of nanostructured ZnO materials in ambient aqueous conditions. A series of two-dimensional (2D) ZnO nanomaterials have been successfully obtained using amphiphilic peptoids with different numbers, ratios, and patterns of various hydrophilic and hydrophobic side chains.

Designed Metal-Containing Peptoid Membranes as Enzyme Mimetics for Catalytic Organophosphate Degradation.

The detoxification of lethal organophosphate (OP) residues in the environment is crucial to prevent human exposure and protect modern society. Despite serving as excellent catalysts for OP degradation, natural enzymes require costly preparation and readily deactivate upon exposure to environmental conditions. Herein, we designed and prepared a series of phosphotriesterase mimics based on stable, self-assembled peptoid membranes to overcome these limitations of the enzymes and effectively catalyze the hydrolysis of dimethyl -nitrophenyl phosphate (DMNP)─a nerve agent simulant.

Thermodynamic Basis for the Stabilization of Helical Peptoids by Chiral Sidechains.

Peptoids are a class of highly customizable biomimetic foldamers that retain properties from both proteins and polymers. It has been shown that peptoids can adopt peptide-like secondary structures through the careful selection of sidechain chemistries, but the underlying conformational landscapes that drive these assemblies at the molecular level remain poorly understood. Given the high flexibility of the peptoid backbone, it is essential that methods applied to study peptoid secondary structure formation possess the requisite sensitivity to discriminate between structurally similar yet energetically distinct microstates.

Computational and Experimental Determination of the Properties, Structure, and Stability of Peptoid Nanosheets and Nanotubes.

Peptoids (N-substituted glycines) are a group of highly controllable peptidomimetic polymers. Amphiphilic diblock peptoids have been engineered to assemble crystalline nanospheres, nanofibrils, nanosheets, and nanotubes with biochemical, biomedical, and bioengineering applications. The mechanical properties of peptoid nanoaggregates and their relationship to the emergent self-assembled morphologies have been relatively unexplored and are critical for the rational design of peptoid nanomaterials.

Mistimed origin licensing and activation stabilize common fragile sites under tight DNA-replication checkpoint activation.

Genome integrity requires replication to be completed before chromosome segregation. The DNA-replication checkpoint (DRC) contributes to this coordination by inhibiting CDK1, which delays mitotic onset. Under-replication of common fragile sites (CFSs), however, escapes surveillance, resulting in mitotic chromosome breaks.

Study of 60 Adult Patients to Compare Standard Postoperative Clinical Assessment with Train-of-Four Ratio ≥0.9 on Patient Outcomes Using Postoperative Spirometry and Neuromuscular Function Measurements Following Extubation.

BACKGROUND Postoperative tracheal extubation requires optimal timing to ensure patient safety and normal muscle function. The train-of-four ratio (TOFR) of the fourth muscle response compared with the first indicates a non-depolarizing neuromuscular block, and a ratio ≥0.9 can be used as an objective measurement of neuromuscular reversal.

Co-Assembly of Carbon Nanotube Porins into Biomimetic Peptoid Membranes.

Robust and cost-effective membrane-based separations are essential to solving many global crises, such as the lack of clean water. Even though the current polymer-based membranes are widely used for separations, their performance and precision can be enhanced by using a biomimetic membrane architecture that consists of highly permeable and selective channels embedded in a universal membrane matrix. Researchers have shown that artificial water and ion channels, such as carbon nanotube porins (CNTPs), embedded in lipid membranes can deliver strong separation performance.

OKseqHMM: a genome-wide replication fork directionality analysis toolkit.

During each cell division, tens of thousands of DNA replication origins are co-ordinately activated to ensure the complete duplication of the human genome. However, replication fork progression can be challenged by many factors, including co-directional and head-on transcription-replication conflicts (TRC). Head-on TRCs are more dangerous for genome integrity.

The human pre-replication complex is an open complex.

In eukaryotes, DNA replication initiation requires assembly and activation of the minichromosome maintenance (MCM) 2-7 double hexamer (DH) to melt origin DNA strands. However, the mechanism for this initial melting is unknown. Here, we report a 2.

Designing sequence-defined peptoids for fibrillar self-assembly and silicification.

In the biological environment, mineral crystals exquisitely controlled by biomacromolecules often show intricate hierarchical structures and superior mechanical properties. Among these biominerals, spicules, hybrid silica/protein superstructures serving as skeletal elements in demosponges, represent an excellent example for motivating the synthesis of silica materials. Herein, by designing sequence-defined peptoids containing side chains with a strong binding to silica, we demonstrated that self-assembly of these peptoids into fiber structures enables the mimicking of both biocatalytic and templating functions of silicatein filaments for the formation of silica fibers at near-neutral pH and ambient temperature.