Browse Articles

Coordinated active repression operates via transcription factor cooperativity and multiple inactive promoter states in a developing organism

Abstract Refining transcriptional levels via active repression in a euchromatic context represents a critical regulatory process. While the molecular players of active repression are well described, their dynamics remain obscure. Here, we used snail expression dynamics as a paradigm to uncover how repression, mediated by the Snail (Sna) repressor, can be imposed within a developing tissue. Combining live imaging and mathematical modeling, we show that Sna-mediated repression is cooperative and that cooperativity is primarily mediated by the distal enhancer. Repression shifts transcription bursting dynamics from a two-state ON/OFF regime to a three-state repressed regime with two temporally distinct OFF states. Mutating Sna binding sites suggests that repression introduces the long-lasting inactive state, which is stabilized by cooperativity. Our approach offers quantitative insights into the dynamics of repression and how transcription factor cooperativity coordinates cell fate decisions within a tissue.

Synergistic Covalently and Mechanically Interlocked Polymer

Abstract Integrating different polymer types into a unified system in a thoughtful manner leverages their complementary advantages, providing a promising strategy for developing high‐performance materials. Mechanically interlocked polymers (MIPs), characterized by their unique spatial entanglement, exhibit distinctive performance advantages, yet their potential to expand material properties through rational integration with other polymer architectures presents substantial opportunities for continued investigation. Herein, we report a coherent integration of covalent polymers (CPs) and mechanically interlocked polymers through sequential orthogonal polymerizations, developing a novel synergistic covalently and mechanically interlocked polymer (CMIP) featuring both structural stability and force‐induced dynamics. Compared to its structurally similar but noninterlocked control sample, CMIP demonstrates markedly enhanced thermomechanical stability and performance recovery, achieving a 93.4% recovery efficiency at 100% strain after just 5 min of rest, in contrast to 59.7% for the control. This remarkable stability and recovery result from the synergistic interplay between the covalent polymer framework and the interlocked structure, which work in tandem to preserve network integrity and enable rapid host−guest reformation. Notably, despite this significant improvement, CMIP retains a comparable damping capacity (91% versus 87%) and material toughness (14.8 versus 15.1 MJ m −3 ), owing to the efficient energy dissipation mechanisms enabled by host−guest dissociation and subsequent sliding motion. This strategy imparts CMIP with unique characteristics, offering a prospective pathway for the development of a diverse array of advanced synergistic materials with enhanced, multifaceted properties.

Deferral of scheduled transcatheter heart valve interventions strongly increases the risk of congestive heart failure

Abstract Deferral of non-emergency cardiac interventions is associated with worse clinical outcomes, even post-procedurally. Affected patients show signs of congestive heart failure (CHF) after the waiting time. To identify predictors of CHF with clinical progress during prolonged waiting time, and assess the impact of CHF on the actual intervention date and of the identified baseline predictors in case of deferral on subsequent outcomes. Consecutive patients whose non-emergency cardiac intervention was postponed during the first Covid-19 related lockdown between March 19th and April 30th, 2020 were included (n = 178). Binary logistic regression analysis was performed to identify predictors of clinically progredient CHF, indicated by an NT-proBNP level of > 900 pg/ml on the actual intervention date in combination with worsening of dyspnea as assessed by NYHA class, emergency heart failure hospitalization, or declining left ventricular ejection fraction (LVEF) during the waiting time. Clinical outcomes were compared to a seasonal control group undergoing such interventions in 2019 as scheduled (n = 214). 89 of 178 deferred patients (50.0%) had an NT-proBNP level of > 900 pg/ml in combination with clinical symptoms indicating CHF on the actual intervention date. Thereof, repeated data measurement was available for 72 patients, of whom 54 (75%) experienced new-onset or worsening of CHF, while 18 (25%) had stable, pre-existing CHF. Planned transcatheter heart valve intervention was the only independent predictor of CHF with clinical progress (OR 34.632, 95%-CI 3.337–359.404, p = 0.003). Risk was even higher in patients with planned mitral or tricuspid edge-to-edge-repair (M/T-TEER) than in those with transcatheter aortic valve replacement (TAVR) (82.4% vs. 40.0%; p = 0.035 after Bonferroni correction). During the post-procedural 36-month follow-up, rates of emergency hospitalization or death were significantly higher in patients with CHF and time-to event was shorter compared to those without (57.3% vs. 14.0%, p < 0.001; HR 6.432, 95%-CI 3.476–11.868; log rank p < 0.001). Higher event rates and shorter time-to-event in deferred compared to regularly treated patients after the originally planned intervention date were observed only in those with the predictor scheduled heart valve intervention (83.7% vs. 40.4%, p < 0.001; HR 4.37, 95%-CI 2.50–7.64, log rank p < 0.001). Deferral of planned transcatheter heart valve intervention, TAVR and especially M/T-TEER, leads to a highly increased risk of clinically progredient CHF during prolonged waiting time and worse clinical outcomes. Therefore, these procedures should be prioritized and postponement should be avoided.

Forming gas annealing-induced reversible 2D-to-3D bonding transition in 3R-MoS2

We report a method of engineering a reversible change in interlayer bonding between layers of exfoliated thin films of MoS2 by means of hydrogen intercalation through forming gas annealing. Interlayer bonding strength is probed through the behavior of MoS2 under process-induced strain engineering, where two-dimensional (2D) flakes are encapsulated with a deposited stressed thin film layer to transfer strain into the underlying 2D materials. It is shown that after forming gas annealing, the depth of the strain transferred into multilayer MoS2 is enhanced as determined through layer-thickness-dependent Raman spectroscopic mapping. This change represents a transition from a 2D van der Waals-bonded material in the as-exfoliated samples to a more three-dimensional (3D)-bonded system in the annealed samples. We demonstrate the reversibility of this effect by means of vacuum annealing of previously forming gas annealed samples. The process of forming gas annealing itself also imparts strain into MoS2 due to a combination of 2D-to-3D bonding transition with differential thermal mismatch between the MoS2 and the substrate. These strains are shown to be retained after the vacuum annealing process, despite the transition back to 2D bonding. Since forming gas annealing is a common technical process in engineering 2D electronic devices, these results represent an important consideration in understanding non-intentionally applied strains due to changes in the mechanical properties of 2D materials.

Chronic social defeat stress induces meningeal neutrophilia via type I interferon signaling in male mice

Abstract Inflammation is increasingly recognized as a risk factor for psychiatric disorders. Animal models of stress and stress-related disorders are associated with blood neutrophilia. The mechanistic relevance of this to symptoms or behavior is unclear. We characterized the immune response to chronic social defeat (CSD) stress at brain border regions in male mice. Here we show that chronic, but not acute, stress causes neutrophil accumulation in the meninges—i.e., “meningeal neutrophilia”— but not the brain. CSD promotes neutrophil trafficking to meninges via vascular channels originating from skull bone marrow (BM). Transcriptional analysis suggests CSD increases type I interferon (IFN-I) signaling in meningeal neutrophils. Blocking this pathway via the IFN-I receptor (IFNAR) protects against the negative behavioral effects of CSD stress. Our identification of IFN-I signaling as a putative mediator of meningeal neutrophil recruitment may facilitlate development of new therapies for stress-related disorders.

Outside Front Cover: Conditional Stabilization of the Hypoxia‐Inducible Factor HIF1α: Photoswitchable Stapled Peptides Prevent Elongin BC–Mediated Degradation (Angew. Chem. Int. Ed. 36/2025)

Developing a plant based hand sanitizer using antibacterial Apium graveolens leaf extract

Pronounced visible luminescence in GaN by high-temperature anion implantation

Chemically robust III-nitrides (III-N) with bandgaps in the visible spectral range are critical for advancing emerging technologies such as solar-driven photocatalysis and optoelectronics. Conventional methods for bandgap reduction of GaN, such as increasing indium content in InGaN alloys, are limited by lattice mismatch strain-induced defects that compromise device performance. Incorporating small number of anions like arsenic (As) or antimony (Sb) offers an alternative through significant band bowing in GaN; however, achieving high visible emission efficiency remains challenging for in situ epitaxial incorporation due to thermodynamic barriers of limited solubility. This study demonstrates high-temperature (550 and 1000 °C) ion implantation as an effective strategy to tailor the spectral response of various GaN semiconductor structures into the visible range, achieving bright room-temperature photoluminescence at ∼485 and ∼550 nm for As- and Sb-related emissions, respectively. Notably, the implanted impurity concentration is only at the ∼1 × 1019 cm−3 level and localized at a depth of ∼30 nm below the surface. Based on density functional theory calculations, the observed As-related emission arises from a combined effect of valence band edge shifting by As replacing N isoelectronically and an Arsenic interstitial (Asi3+) defect level formation. The Sb-related emission was attributed only to the substitutional Sb in N site (SbN0) related band energy shift, as previously reported for epitaxial incorporation. This work establishes high-temperature ion implantation as a viable technique to enable effective concurrent impurity activation and crystal damage repair, opening pathways for deep-level defect and bandgap engineering in GaN for energy conversion and photonic and quantum applications.

A quadratic paradigm describes the relationship between phenotype severity and variation

Conduction Band Convergence and Modular Nanostructures: Driving High Thermoelectric Performance in <i>n</i> ‐Type PbSe

Abstract n ‐type lead chalcogenides showing high thermoelectric performance are rare due to the larger energy offset between the two lowest energy conduction bands minima, leaving ample opportunity to modulate electronic structure for improving their thermoelectric performance. Here, we present a remarkable thermoelectric figure of merit (zT) of ∼1.8 at 873 K in n ‐type PbSe doped with MoCl 5 by modulation of the conduction bands, while simultaneously suppressing the phonon transport. Doping MoCl 5 in PbSe induces notable convergence of conduction bands and an increased density of states near the Fermi level, mainly due to the contribution of Mo 4 d orbital hybridized with the Se 4 p ‐Pb 6 p . This results in an improved Seebeck coefficient, despite maintaining a high n ‐type charge carrier concentration resulting in an excellent power factor (σS 2 ) of ∼21 µW cm −1 K −2 at 873 K for PbSe + 1 mol% MoCl 5 . When the solid solution limit of the doping exceeds, it forms unique modular nano‐heterostructures (5‐30 nm) of PbSe‐MoSe 2 misfit layered compounds embedded in PbSe matrix. These nano‐heterostructures significantly intensify phonon scattering, leading to an ultralow lattice thermal conductivity (κ lat ) of 0.20 W m −1  K −1 at ∼725 K in PbSe + 1 mol% MoCl 5 sample.

Signature of cooperativity in the stochastic fluctuations of small systems with application to the bacterial flagellar motor

Abstract The cooperative binding of molecular agents onto a substrate is pervasive in living systems. To study whether a system shows cooperativity, one can rely on a fluctuation analysis of quantities such as the number of substrate-bound units and the residence time in an occupancy state. Since the relative standard deviation from the statistical mean monotonically decreases with the number of binding sites, these techniques are only suitable for small enough systems, such as those implicated in stochastic processes inside cells. Here, we employ a general-purpose grand canonical Hamiltonian description of a small one-dimensional (1D) lattice gas with either nearest-neighbor or long-range interactions as prototypical examples of cooperativity-influenced adsorption processes. First, building upon previous work on finite-size one-dimensional Ising-type models, we elucidate how the strength and sign of the interaction potential between neighboring bound particles on the lattice determine the intensity of the fluctuations of the mean occupancy and the nature of bound particle-particle correlations. We present our theoretical results, which extend beyond standard analysis, in a novel, physically transparent form. We explore simple limiting cases of the parameter space in greater detail, examine the complete probability distribution functions for occupation, and relate these to the shape and strength of the fluctuations. Second, we leverage these relationships to compare the theoretical predictions of our model to data from single molecule experiments on bacterial flagellar motors (BFM) of Escherichia coli. In this way, we find evidence that cooperativity controls the mechano-sensitive dynamical assembly of the torque-generating units, the so-called stator units, onto the BFM and thereby arrive at an estimate of the stator-stator interaction potential from our fluctuation analysis. Furthermore, we attempt to clarify the link between occupation fluctuations and the adaptability of the BFM. Finally, we conclude that the system resides in a sweet spot of the parameter space (phase diagram) with characteristics suitable for a smoothly and widely adaptive system, while minimizing fluctuations.

High-efficiency ternary layer-by-layer all-polymer solar cells enabled by a dual-donor alloy strategy

All-polymer solar cells (all-PSCs) exhibit the advantage of superior stability due to the intrinsic properties of the polymer with larger molecular sizes. However, obtaining excellent morphology of the active layer is an important challenge for achieving efficient all-PSCs. In this work, a ternary-assisted layer-by-layer (LbL) strategy is used to optimize the morphology of all-PSCs. The polymers PM6, PM1, and PY-IT are selected as host donor, guest donor, and acceptor to fabricate a series of LbL all-PSCs, respectively. The high compatibility between PM6 and PM1 promotes the formation of an alloy state within the active layer, which enhances molecular arrangement orderliness and crystallinity, and vertical structural phase distribution. The ternary LbL all-PSCs based on PM6:PM1/PY-IT exhibit a higher power conversion efficiency (PCE) of 18.10% and better stability compared to the binary LbL all-PSCs based on PM6/PY-IT with a PCE of 16.96%. The optimized ternary LbL all-PSCs retain over 82% of their initial PCE after 790 h of storage in a glovebox. This research demonstrates that the effective combination of dual-donor ternary strategy and the LbL strategy provides a feasible route for achieving high-performance all-PSCs through regulating the morphology of the active layer.

Low-temperature molten-salt enabled synthesis of highly-efficient solid-state emitting carbon dots optimized using machine learning

A method for constructing digital twins of CNC machine tools feed systems based on hybrid mechanism-data

Geometry-engineered spring-shaped silicon nanowires for directional airflow sensing on flexible substrates

Precise detection of gentle airflow remains challenging for wearable sensors due to low flexibility and limited directional sensitivity in conventional nanowire designs. Inspired by mechanosensory hairs in human skin, we report a flexible, geometry-engineered airflow sensor based on suspended spring-shaped silicon nanowires (SiNWs), synthesized via an in-plane solid–liquid–solid strategy. The spring-shaped architecture is rationally designed to enhance axial compliance and mechanical resilience, significantly outperforming straight SiNWs under airflow-induced strain, as validated by finite element simulations and mechanical testing. The sensor demonstrates a rapid response time of 80 ms and a linear electrical output in response to gentle airflow ranging from 0.5 to 3 m/s under bending conditions. Notably, its unique structural anisotropy enables directional sensing at 0°, 45°, and 90°, with distinct current responses of 56%, 38%, and 16%, respectively. This work highlights geometry engineering as an effective strategy for enabling directional airflow detection in flexible nanowire-based systems.

Isotope-encoded spatial biology identifies plaque-age-dependent maturation and synaptic loss in an Alzheimer’s disease mouse model

Abstract Understanding how amyloid beta (Aβ) plaques develop and lead to neurotoxicity in Alzheimer’s disease remains a major challenge, particularly given the temporal delay and weak correlation between plaque deposition and cognitive decline. This study investigates how the evolving pathology of plaques affects the surrounding tissue, using a knock-in Aβ mouse model ( App NL-F/NL-F ). We combined mass spectrometry imaging with stable isotope labeling to timestamp Aβ plaques from the moment of their initial deposition, enabling us to track their aging spatially. By integrating spatial transcriptomics, we linked changes in gene expression to the age of the plaques, independent of the mice’s chronological age or disease stage. Here we show that older plaques were associated with reduced expression of synaptic genes. Additionally, when correlated with structure-specific dyes, we show that plaque age positively correlated with structural maturation. These more compact and older plaques were linked to greater synapse loss and increased toxicity.

Photoresponsive Slide‐Ring Gels Enable Modulation of Sliding Dynamics

Abstract Cyclodextrin‐based slide‐ring gels (SRGs) have emerged as a promising class of materials owing to their unique topology. Upon mechanical loading, the slidable cross‐links of the polymer network freely translocate along the polymer backbone enabling pronounced energy dissipation in the material, which is associated with exceptional ductility and toughness. Despite the critical role of sliding dynamics in defining SRG mechanical properties, attempts to control them have primarily been limited to tuning the overall loading of macrocycles. Further, SRGs that can be triggered via an external stimulus have yet to be reported. In this work, we present light‐responsive SRGs based on azobenzene‐containing polymers. Reversible photoswitching of the azobenzenes modulates the sliding dynamics of the threaded α‐cyclodextrin (α‐CD) macrocycles. By using UV–Vis and circular dichroism spectroscopy, we show that α‐CDs readily bind to the azobenzenes along the polymer backbone in the E configuration. Upon light irradiation, and thus isomerization to the Z isomer, the macrocycles no longer interact with the azobenzenes, allowing them to freely translocate along the polymer backbone. As a result of this E to Z isomerization and difference in sliding dynamics, the mechanical properties of the SRGs reversibly alternate between a stiff and a soft state.

Harnessing remote sensing and machine learning techniques for detecting and monitoring the invasion of goldenrod invasive species

Cu-doped poly(1,8-diaminonaphthalene) enables high-rate and long-cycle stability for quasi-solid-state supercapacitors

The widespread adoption of aqueous polymer-based supercapacitors is significantly hampered by issues such as limited operating potential windows and low energy density. To address these challenges, this study introduces a straightforward and rapid approach involving the incorporation of an active metal, copper (Cu), into a conductive polymer matrix, poly(1,8-diaminonaphthalene), to fabricate an asymmetric supercapacitor configuration (CP//AC). This strategy aims to broaden the potential window of individual cells within aqueous electrolytes, thereby enhancing energy density. The synthesized polymer composite (CP) features a layered nanoflake morphology that facilitates conduction pathways, substantially boosting electron transfer and ion mobility rates. Notably, the CP electrode (CP-2) achieves a specific capacity of 935 mAh g−1 at 3 A g−1 and demonstrates cycling stability with negligible capacity loss over 10 000 cycles at 20 A g−1 in a three-electrode system, corresponding to a maximum power density of 8249 W kg−1 and energy density of 189 Wh kg−1. Upon fabrication of a flexible quasi-solid-state supercapacitor using CP-2//AC, an 80.3% capacity retention is observed after 1500 charge–discharge cycles at 15 A g−1. This research highlights the potential of polymeric materials for energy storage and demonstrates their feasibility in flexible aqueous supercapacitor technologies.

Single-molecule fluorescence microscopy reveals regulatory mechanisms of MYO7A-driven cargo transport in stereocilia of live inner ear hair cells

Abstract Stereocilia are F-actin-based cylindrical protrusions on the apical surface of inner ear hair cells that function as biological mechanosensors of sound and acceleration. During stereocilia development, specific unconventional myosins transport proteins and phospholipids as cargo and mediate elongation, differentiation and acquisition of the mechanoelectrical transduction (MET). How unconventional myosins localize themselves and cargo in stereocilia using energy from ATP hydrolysis is only partially understood. Here, we developed STELLA-SPIM microscopy to visualize movement of single myosin molecules in live hair cell stereocilia. STELLA-SPIM demonstrated that MYO7A, a component of MET machinery, shows processive movement toward stereocilia tips when chemically dimerized or constitutively activated by missense mutations disabling tail-mediated autoinhibition. Conversely, MYO7A shows step-wise but not processive movement in stereocilia when its tail is tethered to the plasma membrane or F-actin in the presence of MYO7A interacting partners. We posit that MYO7A dimerizes and moves processively in stereocilia when unleashed from autoinhibition.