Browse Articles

Direct Cellular Screening of Pd-Mediated Arylation of Cyclic Peptide Binders Targeting Ubiquitin Chains: Toward Modulating NEMO Liquid–Liquid Phase Separation

How thoughtful experimental design can empower biologists in the omics era

Ginkgolide B attenuates hyperlipidemia by restoring sphingolipid homeostasis and activating PPARα and Nrf2 pathways

A Covalent Self-Reporting Peptide Degrader Enables Real-Time Monitoring of Targeted Protein Degradation In Vivo

Self-sustained frictional cooling in active matter

Abstract Cooling processes in nature are typically generated by external contact with a cold reservoir or bath. According to the laws of thermodynamics, the final temperature of a system is determined by the temperature of the environment. Here, we report a spontaneous internal cooling phenomenon for active particles, occurring without external contact. This effect, termed self-sustained frictional cooling, arises from the interplay between activity and dry (Coulomb) friction, and in addition is self-sustained from particles densely caged by their neighbors. If an active particle moves in its cage, dry friction will stop any further motion after a collision with a neighbor particle thus cooling the particle down to an extremely low temperature. We demonstrate and verify this self-sustained cooling through experiments and simulations on active granular robots and identify dense frictional arrested clusters coexisting with hot, dilute regions. Our findings offer potential applications in two-dimensional swarm robotics, where activity and dry friction can serve as externally tunable mechanisms to regulate the swarm’s dynamical and structural properties.

Multiscale investigation of thermally activated coal gangue aggregate concrete interfacial transition zone evolution and failure mechanisms

Ultra-Narrow Homogeneous Photoluminescence Line Width of Zinc-Blende CdSe-Based Core/Shell Nanocrystals: Dominating Role of Lattice–Ligands Interface

Quarter- and half-filled quantum Hall states and their topological orders revealed by daughter states in bilayer graphene

In silico decrypting of the bystander effect in antibody–drug conjugates for breast cancer therapy

Abstract Antibody–Drug Conjugates (ADCs) are a promising cancer treatment that deliver toxic drugs directly to cancer cells, reducing harm to healthy tissue. A key feature of newer ADCs is the “bystander effect,” in which nearby cancer cells are also affected by passive diffusion. However, the mechanisms underlying this effect remain unclear. Using computer simulations, this study investigates how the drug’s ionization state and the linker connecting it to the antibody influence its ability to cross cell membranes. The results show that the ionization state of the drug impacts its membrane permeability, as charged molecules encounter resistance when moving through the membrane’s hydrophobic core. Moreover, the study reveals that the linker increases the drug’s overall size and hydrophobicity, thereby hindering its diffusion to adjacent cells. This finding suggests that linker design can significantly influence the efficacy of antibody–drug conjugates (ADCs) by limiting their ability to reach neighboring cancer cells. These insights enhance our understanding of ADC mechanisms and provide a valuable foundation for the optimization of next-generation ADC therapies targeting breast cancer.

Asymmetric C–H Functionalization of <i>N</i>-Boc-2,5-dihydro-1<i>H</i>-pyrrole and Its Application as a Key Step in the Synthesis of (−)-Dragocin D

Plasmodium falciparum egress disrupts endothelial junctions and activates JAK-STAT signaling in a microvascular 3D blood-brain barrier model

Abstract Cerebral malaria is a severe neurovascular complication of Plasmodium falciparum infection, with high mortality rates even after treatment with effective antimalarials. Limitations in current experimental models have hindered our knowledge of the disease. We developed a 3D blood-brain barrier (BBB) model with enhanced barrier properties using primary brain endothelial cells, astrocytes, and pericytes. Exposure to parasite egress products increases microvascular permeability, likely due to transcriptional downregulation of junctional and vascular development genes in endothelial cells. In addition, it increases the expression of ferroptosis markers, antigen presentation and type I interferon genes and upregulates the JAK-STAT pathway across all BBB cell types. Incubation with cytoadherent schizont-stage P. falciparum -infected erythrocytes induces a similar, but highly localized transcriptional shift, along with inter-endothelial gaps at sites of parasite egress, leading to enhanced permeability. Treatment with the JAK-STAT inhibitor Ruxolitinib prevents the increase in permeability induced by P. falciparum egress products. These findings provide key insights into the parasite-mediated mechanisms driving brain microvascular pathogenesis in cerebral malaria and suggest potential avenues for adjunctive therapies.

Experimental study of strength degradation in fractured surrounding rock of deep high-temperature tunnels

Iridium–Lewis Acid Bifunctional Catalyst-Enabled Regio- and Enantioselective C(sp ² )–H <i>meta</i> -Borylation of α,α-Diarylcarboxamides

Transformation of CO2 to C2+ alcohols by tailoring the oxygen bonding via Fe-based tandem catalyst

Transductive zero-shot learning via knowledge graph and graph convolutional networks

Enabling Ethanol Dehydrogenation Catalysis by Postsynthetic Anion Exchange of Triazolate-Based Metal–Organic Frameworks

Phase synchrony between prefrontal noradrenergic and cholinergic signals indexes inhibitory control

Graph representation learning via enhanced GNNs and transformers

Near-Infrared to Visible Photon Upconversion with Gold Quantum Rods and Aqueous Photo-Driven Polymerization

Antimicrobial peptide class that forms discrete β-barrel stable pores anchored by transmembrane helices

Abstract Bacteriocin peptides are weapons of inter-bacterial warfare and belong to the larger group of antimicrobial peptides (AMPs), which are frequently proposed as alternatives to antibiotics. Many AMPs kill by destroying the target’s cytoplasmic membrane using short-lived membrane perturbations. Contrastingly, protein toxins form large pores by stably assembling in the target membrane. Here we describe an AMP class termed TMcins (for transmembrane helix-containing bacteriocin), in which half of the AMP forms a transmembrane helix. This characteristic allows TMcin to assemble into stable and large oligomeric pores. The biosynthetic locus of TMcin, which was broadly active against Gram-positive bacteria, is distributed throughout two major bacterial phyla, yet bears no homology to previously reported bacteriocin biosynthetic gene clusters. Our discovery of an AMP class that achieves pore stability otherwise only found in protein toxins transforms our current understanding of AMP structure and function and underscores the continuing importance of phenotype-initiated investigations in uncovering wholly uncharacterized antimicrobials.