Soft radially contracting actuators, inspired by biological circular muscles, enable diverse robotic functions, including manipulation, gut simulation, locomotion, and haptics. The combination of electrohydraulic actuation with radially contracting actuators holds promise for the development of high-performance radial contraction in a compact form factor. In this paper, we introduce an electrohydraulic folding ring actuator (EFRA) that utilizes folding motion to actively close its inner lumen. The EFRA is lightweight (∼25.9 g) and compact, consisting of a triangular ring with sides of ∼65 mm. Under 7 kV actuation, the EFRA achieves a high contraction ratio of 0.89 sustained over 5 s of actuation. This performance is enabled by the multiple synchronously bending segments in the folding mechanism, which enhances radial contraction compared with prior electrohydraulic radially contracting actuator designs. The EFRA also produces ∼0.96 N of inward-directed force measured at a single inner vertex under 7 kV actuation, yielding high force output relative to its low mass. Finally, we demonstrate the advantages of the high performance and compact nature of the EFRA in multiple applications, including robotic manipulation, locomotion, as well as an artificial robotic sphincter.

Microscopic mechanisms of helical protein unfolding under thermal and confinement effects.

Antiprism folding mechanisms for enhanced energy absorption

In daily life, flatbed and framed carts, the two most common hand carts, have their own strengths but clear functional flaws: flatbed carts are ideal for large items yet cannot fix small goods steadily, while frame carts hold small items properly but cannot handle oversized loads. Current optimization mainly focuses on better functionality and folding performance, but none achieves switch between the two configurations, leaving a practical gap. This study designs a multifunctional foldable cart that combines the merits of both types, inspired by the folding mechanism of paper shopping bags and taking thin plates and hinges as core components. We established a 3D model with SolidWorks, analyzed key angles (∠θ, ∠a, ∠c, etc.) and their kinematic relationships, and calculated the degree of freedom as 4 via the Kutzbach-Grübler Equation. Two cardboard prototypes were made; the first had folding interference, which was solved by adjusting hinges and adding movable linkages to improve structural stability. This new cart enables smooth conversion between flatbed and frame modes and saves storage space, suiting shopping, moving and other scenarios well. However, it has drawbacks: multiple DOFs bring operational complexity, hinges may fatigue after long-term use, and structural stiffness is insufficient under overload. Future improvements will focus on reducing DOFs, reinforcing hinges and adopting modular design to boost usability, durability and maintainability.

The eukaryotic genome is organized into distinct structural units dictated by architectural proteins. The major host architectural protein CCCTC-binding factor (CTCF) is usurped by DNA viruses to regulate viral gene expression. This review will discuss the major ways large (EBV, HSV, HCMV) and small (HPV, HBV, AAV) DNA viruses mimic eukaryotic genome topology using CTCF to regulate viral gene expression. We will further discuss how changes in genome topology can drive virally induced oncogenic progression. Knowledge gained from studying viral genome folding mechanisms will inform the development of targeted anti-viral agents and inform the modification of viruses to serve as gene therapy vectors.

Origami-inspired materials enable sophisticated three-dimensional (3D) structural designs, yet conventional materials face an intrinsic conflict between strength and flexibility. Herein, foldable bamboo (FB) is fabricated by mimicking the rove beetle wing's microstructure and bidirectional folding mechanism, coupled with a microwrinkling engineering and waterborne polyurethane (WPU) loading strategy to decouple mechanical trade-offs. Selective lignin removal and cellulose framework softening induce rearrangement of the hydrogen bond network, driving microfibril aggregation and formation of surface microwrinkles. These features enhance interfacial friction and mechanical interlocking. Reinforced by WPU penetration and film formation, this multiscale structure (from molecular to macro levels) endows FB with exceptional folding endurance (24,793 cycles, >24× higher than bamboo veneer, BV). Simultaneously, FB achieves a 59.18% increase in transverse tensile strength, 16.06% higher elongation at break, and 54.48% improved bursting strength. These properties, especially folding endurance, not only surpass most biobased materials but also compete favorably with many polymers and metals. Notably, FB further demonstrates enhanced hydrophobicity, tunable light transmittance, inkjet compatibility, and unlimited splicing capability, enabling robust performance under tension, compression, and folding. These advantages underpin FB's large-scale applications in sustainable, sophisticated 3D structural designs, such as packaging, decoration, and outdoor engineering.

Mitochondrial outer membrane proteins (β-OMPs) serve as the first line of communication with the cellular milieu. A crucial β-OMP, the sorting and assembly machinery Sam50, is a 16-stranded transmembrane β-barrel highly conserved in all eukaryotes. Sam50 dysregulation is lethal; yet, molecular elements that regulate Sam50 remain poorly understood. Here, we identify and characterize residues that regulate Sam50 structure and function. Using single-molecule electrophysiology, in vivo function, and stability measurements, we demonstrate that the POlypeptide-TRansport Associated domain is dispensable for Sam50. Complete characterization of the folding mechanism using 165 Xaa→Ala substitutions reveals that Sam50 folds through parallel pathways, with at least two transition states. The folding nucleus is towards the N-terminus, whereas frustrated folding at the C-terminal region kinetically traps the structure. We correlate this unexpected folding of Sam50 with its SAM-assisted assembly. Additionally, our per-residue stability measurements show that destabilizing hotspots in Sam50 are linked to its gating function. Our findings suggest how the dynamic structure of Sam50 offers a functional advantage, with specific residues that regulate folding, stability, and function, also determine the protein's sensitivity to mutations.

Cotranslational subunit assembly is thought to be a prominent feature throughout the proteome, but, in bacteria, there are only a limited number of experimentally confirmed examples and most involve the addition of extraneous tag sequences for experimental convenience. Toxin CcdA and Antitoxin CcdB are components of the ccdAB operon. They assemble in a hetero-multimeric complex in vivo. Building on a previously characterised saturation mutagenesis dataset of CcdB, we investigated how operonic gene organisation influences the cotranslational folding and assembly of the toxin-antitoxin complex. We compared the phenotypic effects of CcdB mutations when expressed alone versus in the native operonic context downstream of CcdA. Although several charged and polar mutations in the CcdB core result in loss of function in the absence of CcdA, many of these are functionally rescued in the operonic context. Furthermore, we show that the efficiency of rescue is substantially reduced when ccdA and ccdB are expressed from separate mRNAs rather than from a single polycistronic transcript. Our results highlight a direct role for cotranslational interactions in enabling correct folding of CcdB and suggest that bacterial operon structure may have evolved, in part, to facilitate such chaperone-like rescue of unstable protein variants. Gene organisation in operons in bacteria may thus reflect a fundamental cotranslational mechanism that is important for the effective assembly of protein complexes and can potentially buffer substantial genetic variation.

Abstract The wing, as an important component of an aircraft, provides the main lift for the flight. In response to the problem of overly long wings of unmanned aerial vehicles (UAVs) for storage and transportation in limited spaces, conducting design research on the wing folding mechanism is of great significance. This paper is based on a certain tail-sitter quad ducted fan (TQDF) vertical take-off and landing (VTOL) folding-wing UAV. The selection of a crank-slider wing folding mechanism for this paper was made based on a comparative analysis. The proposed mechanism facilitates a 90-degree wing folding motion, with its functional performance validated through kinematic, dynamic, and structural strength analyses, thus providing a basis for future studies on wing folding systems.

Research on the repeated folding mechanism of membrane antennas based on crease endurance degradation

The unique and intricate pattern of human cortical folding is rooted in fetal neurodevelopmental processes and can now be comprehensively quantified by new neuroimaging-derived measures of sulcal complexity. Here, we provide the first genetic maps of human sulcal complexity. Beginning with large effects of rare variants, we survey nine different neurogenetic syndromes (n=615), detecting visible changes in sulcal complexity on a shared axis of sulcal change coupled to the prenatal timing of sulcation. Turning to common genetic variants, we use genome-wide association studies of complexity scores for 40 sulci in the UK Biobank (n~29,000) to (i) resolve variable heritability across sulci, (ii) reveal both local and remote shared genetic effects with cortical morphology, and (iii) identify complexity-associated genes and their embedding in brain maps of prenatal gene expression. These reference genetic maps uncover multiple new mechanistic pathways for cortical morphogenesis in health and disease.

Understanding the folding mechanisms of biomolecules, such as proteins and nucleic acids, requires probing time-dependent changes of conformations, including secondary and tertiary structure formation. All these mechanism-relevant structural transitions, typically seen as coarse-grained descriptions in molecular dynamics simulations, occur in the tiny fraction of a molecular trajectory called the transition path (TP). However, TPs have been inaccessible for most proteins due to the limited time resolution of single-molecule techniques. Here, we measure the TP times of eight two-state single-domain proteins in aqueous solution using nanophotonics-enhanced single-molecule fluorescence spectroscopy. We found that the TP times are extremely short, ranging from 0.7 to 4 μs, and insensitive to most protein properties. Surprisingly, however, the extracted diffusion coefficient at the free energy barrier on the number of native contacts coordinate increases with protein length. This facilitation of diffusion in larger proteins is explained by increased cooperative native contact formation during folding, which reduces the roughness of the energy landscape. Our results reveal that evolutionary optimization of the energy landscape is much more efficient for protein folding than for other biomolecular processes.

Revealing the complex mechanisms of protein folding, including the transient intermediate states that govern the process, is a fundamental goal in computational biophysics. While molecular dynamics (MD) simulations generate vast amounts of data to this end, extracting a clear kinetic model from these complex, high-dimensional trajectories remains a significant challenge. We present AI-Based conditional transition clustering (CTC), a framework for analyzing MD trajectories that directly addresses the limitations of state-centric methods. Conventional approaches, such as Markov state models, rely on predefined geometric clustering or assume fixed linear dynamics, which can bias the discovery of protein conformational states. CTC operates on a "dynamics-centric" principle, defining a conformational state as a kinetically trapped region identified after analyzing the system dynamics, not before. By leveraging AI-based normalizing flows to estimate conditional transition probabilities from the MD data, CTC identifies states as "kinetic islands" with low escape probabilities. Applying CTC to protein-folding simulations successfully identifies critical intermediate and transition states, revealing folding pathways without prior assumptions about the number of states or their kinetic properties. This approach provides a more objective and physically grounded method for uncovering the complex mechanisms of biomolecular systems.

The cooperative nature of protein folding limits the experimental dissection of the reaction mechanism. PDZ domains, with conserved folds, numerous homologs, and accessible folding intermediates, offer an ideal model to study folding pathways. Here, we present a detailed structural and kinetic characterization of the folding pathway of PDZ6 from PDZD2. Using kinetic folding experiments under different salt conditions combined with φ-value analysis, we revealed a complex energy landscape for PDZ6, featuring three distinct transition states (TS1-TS3) and the progressive acquisition of native-like structure along the reaction coordinate. Taking advantage of the large number of homologous PDZ domains, we compared φ-values at conserved structural positions with those previous obtained for PDZ3 of PSD-95 and PDZ2 of PTP-BL. This analysis revealed a shared, conserved folding mechanism among PDZ domains, in which the central β-strands act as nucleation cores for folding. Overall, this work provides the first structural dissection of the three transition states governing PDZ6 folding and highlights a conserved, hierarchical folding mechanism among PDZ domains. These findings expand our understanding of PDZ folding principles and may inform studies on their functional modulation and evolutionary adaptation.

Protonation and protein folding: Insights from single-molecule fluorescence.

Riboswitches are regulatory RNA elements that control gene expression by undergoing conformational changes upon metabolite binding. Understanding their folding and unfolding dynamics is key to elucidating their regulatory roles and therapeutic potential. This study investigates the unfolding dynamics of the adenosine deaminase (add) A-riboswitch aptamer using steered molecular dynamics (SMD) simulations with constant-velocity (CV) pulling. The Jarzynski equality is applied to derive potential of mean force (PMF) profiles and force-extension curves for ligand-bound and unbound states, revealing distinct conformational transitions. CV-SMD coupled with Jarzynski equality enables quantitative reconstruction of free-energy profiles from multiple non-equilibrium realizations and computes the thermodynamic parameters. Unfolding occurs through a sequential multistep pathway, with adenine binding stabilizing the folded state and enhancing energetic stability. Force-extension data show a linear relationship between simulation time and molecular extension, while analyses of radius of gyration (R g ) and root mean square deviation (RMSD) highlight ligand-induced structural stability. Lower pulling velocities capture intermediate states more effectively than higher velocities. These results provide computational insights into RNA folding mechanisms consistent with experimental observations.

Enhancers have been proposed to act as privileged loading sites for cohesin, raising the idea that they actively fold the genome to engage distal target promoters for transcription. Supporting this idea, NIPBL/MAU2, which is required for cohesin loading, binds at enhancers in mouse embryonic stem cells. However, we find that driving cohesin recruitment near an enhancer strongly inhibits transcription from its target distal promoter, indicating that strong focal cohesin loading at enhancers is not compatible with their long-range regulatory functions. Quantitative experiments and biophysical modeling further indicate that cohesin loading at enhancers does not make major contributions to genome-wide cohesin binding and chromosome folding patterns. Instead, cohesin must load throughout the genome to extrude it, regardless of enhancer proximity, with the major determinants of cohesin traffic being extrusion barriers such as transcription and clustered CTCF sites. These findings indicate that enhancer function is largely ancillary to the general mechanisms of chromosome folding, informing further study of the relationship between genome architecture and transcriptional regulation.

This review critically evaluates recent advances in understanding the adverse effects of thermal pollution on rainbow trout (Oncorhynchus mykiss), focusing on the integrated roles of heat shock proteins (HSPs) and acute-phase proteins (APPs) in stress adaptation. The primary objective is to clarify mechanistic pathways through which temperature elevation and fluctuations, often driven by anthropogenic activities, disrupt homeostasis and trigger molecular and systemic stress responses in this cold-water species. The review synthesizes experimental and field findings to outline how distinct thermal stressors influence the expression, induction and functional modulation of HSPs and APPs, which act as biomarkers and mediators of resilience through protein folding, oxidative balance, immune signaling and survival mechanisms. Major topics include: (i) characterization of HSP families (e.g., HSP70, HSP90) in thermal responses; (ii) APP-mediated inflammation and immune modulation and (iii) molecular networks linking heat shock signaling to physiological outcomes such as altered growth and reproduction. Although considerable progress has been made, variability across study conditions restricts generalization. Future research should focus on (i) defining the specific functional roles and cross-talk of small HSPs (sHSPs) under chronic stress, (ii) investigating epigenetic mechanisms underlying intergenerational thermotolerance and (iii) applying integrated multi-omics approaches to map regulatory interactions between HSPs, APPs and overall stress physiology under climate-driven warming. These efforts will guide strategies to strengthen thermal resilience and welfare in aquaculture and conservation.

Folding Mechanism Within a Prestrained Composite Tape-Spring Structure

Harnessing waves with folds: a flexible origami-inspired wave energy converter