Browse Articles

Unveiling the synergistic mechanism of C-F and C-Cl bonds in enhancing the triboelectric performance of fluorinated polymers

Convergence of external and internal stressors on a stress-responsive enhancer of the <i>Sonic hedgehog</i> gene to induce hair disorders

Mammals are constantly exposed to various stressors of internal and external origin. Though hair follicles (HFs) are exquisitely sensitive to stress, it remains largely unknown how stress-induced responses are linked with the intrinsic regulators of HF growth, cycling, and regeneration. Here, we characterize the long-range enhancer of Sonic hedgehog ( Shh ) gene which encodes a crucial mitogen in the HF, and identify a hair stress-responsive enhancer ( HSRE ) as a unified target on which various internal and external stressors converge. Together with the immediate early gene Early growth response 1 ( Egr1 ), this combination of enhancer and transcription factor mediates hair growth arrest and regeneration defects under several stress conditions, including chemotherapy-induced hair loss, noise-induced hair dystrophy, and retarded hair regeneration in aging and obesity. Under stress, the increased expression of Egr1 suppresses Shh gene expression; however, this suppression does not occur when the HSRE is absent. Furthermore, two chemical agents SR11302 and T-5224 which suppress Egr1 expression both rescued the hair disorders under the various stressors. We propose that an Egr1 – Shh axis integrates distinct stress signals and induces hair disorders via suppression of Shh gene expression, and provide a plausible strategy for therapeutic intervention. Our results establish a paradigm of how stress perturbs organ growth and regeneration through the regulation of key intrinsic morphogenetic factors.

FRZB-induced anti-angiogenic effect via Caveolin-1-mediated TGFβ signalling

Neural circuits for decision-making based on pineal photoreception in zebrafish

Nonmammalian vertebrates possess photosensitive pineal organs. We previously found that in the zebrafish pineal organ, photoreceptor cells expressing parapinopsin 1 (PP1), a bistable opsin, exhibit “chromatic” responses to ultraviolet (UV) and visible light through a unique mechanism based on the photo-interconvertibility between UV-sensitive (inactive) and visible light-sensitive (active) states of PP1. However, it remains unclear whether PP1-based chromatic responses are transmitted to pineal ganglion cells and further to the brain. In this study, we designed light stimuli by exploiting the spectral properties of the two states of PP1 and found that pineal ganglion cells exhibited chromatic responses, characterized by opposing changes to UV and visible light, using calcium imaging. These responses were significantly reduced in PP1-deficient fish compared to wild-type fish, indicating that PP1-derived signals are transmitted to pineal ganglion cells. This spectral stimulation approach enables selective analysis of PP1-specific responses. Using these stimuli, we further identified the tegmentum as a central brain region receiving pineal-derived “color” information, although it is also indirectly influenced by retinal photoreception. Both PP1-deficient fish and tegmentum neuron-ablated fish showed impaired vertical movements in response to sequential wavelength component changes. These results suggest that the neural circuit from the pineal organ to the tegmentum, which processes PP1-based chromatic information, contributes to the decision-making process for wavelength-dependent vertical behavior that is also driven by visual input. These findings provide insights into the neural circuits integrating pineal and retinal light information and how PP1-based color opponency affects behavior via tegmentum neurons.

Bubble explosion induced melt pool instabilities in electron beam melting of aluminum alloy

Abstract Electron beam melting (EBM) is an additive manufacturing technology that can process materials and manufacture components otherwise impossible or uneconomical. However, defects, including porosity and surface irregularities, are widely reported in EBM-built components, and their formation mechanisms are not fully understood. Here, using in-situ high-speed synchrotron X-ray imaging, we reveal that bubble explosions in Al6061 during EBM induce melt pool instabilities contributing to defect formation. The melt pool and keyhole evolve through three stages: (1) initial formation of a melt pool, (2) subsurface bubble formation and explosion, and (3) periodic keyhole oscillation. During scanning, periodic bubble explosions can eject molten liquid as spatters and disturb the vapor depression and melt pool, contributing to surface humping, that may trigger lack-of-fusion defects in subsequent layers. The physical insights we report could provide guidance for EBM machine development, process innovation, alloy design and model development.

WFDC21P is essential for G3BP1-mediated RIG-I activation and antitumor immunity in triple-negative breast cancer

Deciphering the mechanisms underlying antitumor immunity is critical for improving cancer immunotherapy efficacy. Here, we identify WFDC21P (lnc-DC) as a positive regulator of antitumor immunity through promoting the activation of the RNA-sensing retinoic acid-inducible gene-I (RIG-I) pathway in triple-negative breast cancer (TNBC). WFDC21P directly binds to RIG-I-interacting protein G3BP1 and is required for a rapid assembly of functional G3BP1-RIG-I-double-stranded RNAs condensates via phase separation, which enables robust activation of RIG-I. WFDC21P is downregulated in TNBC tissues and correlates with less CD8 + T cell infiltration in tumors and worse outcome of patients. WFDC21P knockdown in TNBC cells markedly dampens RIG-I activation and reduces the expression of IFN-stimulated genes, including MHC-I and PD-L1. In syngeneic tumor models, WFDC21P expression not only suppresses tumor growth by augmenting the infiltration and cytotoxic function of CD8 + T cells but also improves the response to immune checkpoint blockade, thus providing a compelling combination immunotherapy strategy for treating triple-negative breast cancer.

Osteoarthritis and analgesic consumption in haemochromatosis HFE C282Y homozygotes with normal or low iron parameters

Jamming as a topological satisfiability transition with contact number hyperuniformity and criticality

The jamming transition between flow and amorphous-solid states exhibits paradoxical properties characterized by hyperuniformity (suppressed spatial fluctuations) and criticality (hyperfluctuations), whose origin remains unclear. Here, we model the jamming transition by a topological satisfiability transition in a minimum network model with simultaneously hyperuniform distributions of contacts, diverging length scales and scale-free clusters. We show that these phenomena stem from isostaticity and mechanical stability: The former imposes a global equality, and the latter local inequalities on arbitrary subsystems. This dual constraint bounds contact number fluctuations from both above and below, limiting them to scale with the surface area. The hyperuniform and critical exponents of the network model align with those of frictionless jamming, suggesting a universality class of nonequilibrium phase transitions. Our results provide a minimal, dynamics-independent framework for jamming criticality and hyperuniformity in disordered systems.

Regulating interface electric field to stabilize high-voltage KVPO4F positive electrode for sustainable potassium-ion batteries

Proton-activated chloride channel PACC1 as acid sensor in epidermal desquamation

The acidic microenvironment of the stratum corneum is crucial for epidermal desquamation and barrier homeostasis, yet the primary proton sensor that triggers this process remains unknown. Here, we report that the proton-activated chloride channel PACC1 is essential for acid-induced upregulation of kallikreins (KLKs) and desmosomal degradation, two key steps in skin exfoliation. Functional and protein expression analyses revealed that PACC1 is the predominant acid-sensitive ion channel in keratinocytes. Proton-mediated PACC1 activation evokes chloride efflux and initiates a signaling cascade via the c-Jun N-terminal Kinase/AP-1 (JNK/AP-1) pathway. This cascade significantly enhances the expression and secretion of KLKs (KLK5/7), thereby facilitating desquamation through corneodesmosomal degradation. Notably, acid-induced KLK upregulation was abolished by PACC1 knockdown, knockout, or mutants that are deficient in proton sensing. This effect was also observed with pharmacological channel inhibition and was specifically restored by reconstitution with functional PACC1. These findings establish PACC1 as the core sensor that converts epidermal acidification into a desquamation signal, providing a mechanistic foundation for developing targeted therapeutic and cosmetic strategies that modulate skin barrier function.

Recruitment of Mre11 to recombination sites during meiosis

Abstract The Mre11 nuclease is part of the conserved MRX complex involved in DNA double-strand break (DSB) repair. During meiosis in budding yeast, MRX is also required for Spo11-mediated programmed DSB formation to initiate homologous recombination. Recruitment of Mre11 to meiotic DSB sites depends on Rec114-Mei4 and Mer2, proposed to organize the DSB machinery via biomolecular condensation. Here, we show that Mre11 and MRX complexes form DNA-dependent, hexanediol-sensitive condensates in vitro. In vivo, Mre11 assembles into DNA damage-dependent foci during mitosis and DSB-independent foci during meiosis. Both in vitro condensates and in vivo foci require Mre11 C-terminal intrinsically-disordered region (IDR). While dispensable for vegetative DNA repair, Mre11 IDR is essential during meiosis, where it mediates interaction with Mer2 via a short α-helix and contains a SUMO-interacting motif that enhances Mre11 recruitment and DSB formation. Together, these findings provide insights into the biophysical properties of Mre11 and its role in initiating meiotic recombination.

Model evidence for distinct origins of glacial–interglacial and millennial signals in Greenland dust

Greenland ice-core records show that the mineral dust flux during the last glacial maximum was twenty times greater than present and it responded rapidly during North Atlantic abrupt climate events. Both glacial–interglacial and rapid modes of dust variability have been suggested to originate from changes in storminess over Asian deserts. However, geochemical measurements do not rule out sources in Africa and Europe, and rapid changes in the source strength over Asia are yet to be unambiguously identified in North Pacific dust flux records. With a suite of Earth System model simulations of the last glacial period we show that latitudinal rainbelt shifts characteristic of abrupt events may have had an important impact on dust across the Atlantic region. Unlike for the glacial–interglacial difference, these faster, decadal to centennial scale transitions drive significant dust generation and meridional dust transport which enhances dust delivery over Greenland. These results help reconcile several features of the glacial dust cycle and thereby question the paradigm that Asian desert conditions can explain both modes of variability in Greenland dust records. The model points to a greater sensitivity of the poleward dust transport to climate change and provides a basis for investigating the potential role of dust radiative feedbacks during abrupt climate change.

Identification of stem cell marker-positive subpopulations in the vocal fold of the larynx through transcriptomic analyses

Mitochondrial remodeling in skeletal muscle underlies exercise-induced reversal of age-associated functional decline in mice and humans

Loss of skeletal muscle mass and strength are common manifestations of frailty in older people and are linked to reduced quality of life. However, whether mitochondria are mechanistically linked to frailty and how physical activity, or lack thereof, is involved in age-related functional decline are still unknown. We report that exercise-induced improvements in functional capacity, including reduced frailty in old mice, are dependent on mitochondrial adaptations in skeletal muscle at structural, enzymatic, and functional levels. Our preclinical study included a healthy aging mouse line, a transgenic model of robustness, and a muscle-specific mitochondrial-deficient mutant mice, allowing us to assess both mitochondrial plasticity with aging and the necessity of intact mitochondrial function for exercise-induced adaptations. These findings were corroborated by a cross-sectional human study examining the relationship between skeletal muscle mitochondrial function, age, and physical capacity. We analyzed biopsies from 30 donors (men and women, aged 17 to 99 y) stratified into young and older adults with varying functional statuses. Our results indicate that mitochondrial dysfunction in skeletal muscle is associated with the decline in locomotor muscle function in the elderly, highlighting the potential role of exercise or habitual physical activity in mitigating this phenotype. Notably, we demonstrate that skeletal muscle mitochondria maintain plasticity during aging in mice and humans, and that this preserved adaptability can be leveraged to improve muscle performance and overall functional capacity.

Specialised and persistent raw material procurement by humans in the Middle Pleistocene

Abstract The selection and acquisition of suitable raw material constitute the first steps in stone tool technology. Previous ethnographical and archaeological research suggests that hominins in the Pleistocene primarily collected their stone materials while carrying out other activities. Direct provisioning for this purpose alone remains an outlier and is rarely demonstrated. Archaeological excavations coupled with multidisciplinary analyses at Jojosi in South Africa demonstrate that early modern humans undertook specific, repeated visits to a raw material source over tens of thousands of years for the exclusive purpose of obtaining hornfels. This rare, stratified, open-air locality features uniquely preserved lithic assemblages with abundant refits dating from ~220 ka to ~110 ka for the reduction and export of a single tool stone. The scope of these knapping activities is underscored by millions of Middle Stone Age hornfels artefacts paving the modern landscape. The consistent, specialised procurement of a single raw material at Jojosi already during the Middle Pleistocene challenges the standard model of embedded procurement for this period. These findings further show that key capacities of Homo sapiens , including increased long-term planning and behavioural plasticity in the interaction with the material world, emerged early in their evolutionary history.

Divergence of ontogenetic dietary shifts in adaptive radiation

The availability of trophic niches is a key driver of biodiversity, promoting adaptive radiation through evolutionary processes. However, most research has focused on how species adapt to trophic niches as adults, largely overlooking the fact that many taxa undergo significant ontogenetic dietary shifts. Here, we address this gap by investigating individual dietary shifts in an incipient adaptive radiation of Arctic charr ( Salvelinus alpinus ), where distinct piscivorous and planktivorous lacustrine morphs have diverged. Using eye lens isotopes, we reconstructed dietary histories at the individual level, tracing resource use from maternal nutrients to adult diet. Our analyses revealed three key dimensions in which ontogenetic dietary shifts diverge: early-life diets, the stability of dietary transitions, and the degree of plasticity in dietary shifts. These findings suggest that the early phases of adaptive radiation are accompanied by a complete divergence of ontogenetic dietary shifts. We advocate for a more integrated approach to understanding dietary shifts within evolutionary processes and call for further exploration of these patterns across diverse taxa.

Spatiotemporal dynamics of the human cortical functional hierarchy across the lifespan

Building the Bergmann glial scaffold: Early arrivals and stops along the way in human cerebellar development

A hypothalamic circuit for circadian regulation of corticosterone secretion

Abstract There is a strong circadian rhythm of corticosteroid secretion in animals and humans, but the circuit for translating the suprachiasmatic (SCN) clock light-dark cycle rhythm into an increase in corticosteroid secretion beginning several hours before the active period is not known. We show here that in male mice, this rhythm depends upon input from the SCN to the subparaventricular zone (SPZ), and then to the dorsomedial nucleus of the hypothalamus (DMH). Both glutamatergic and GABAergic DMH neurons are required for the daily surge of corticosteroid secretion in anticipation of the active period. Glutamatergic DMH neurons directly excite paraventricular nucleus corticotrophin-releasing hormone (PVH-CRH) neurons, whereas DMH GABA neurons disinhibit PVH-CRH neurons via a relay in GABAergic neurons in the caudoventral PVH. This circuit underlies the daily surge in corticosteroid secretion that is temporally linked but phase advanced compared to the SCN activity cycle.

Biomechanical anticoagulation by spherical platelets in extracorporeal systems

Extracorporeal life support, such as hemodialysis, often face the risk of blood coagulation, where systemic anticoagulation with heparin is routinely administered. However, this strategy is contraindicated in patients at high risk of bleeding. Inspired by the observation that rolling motion of spherical platelets avoids their exposure to tangential forces, an anticoagulation strategy is proposed based on platelet spherification for extracorporeal systems. Experimental results prove that spherical platelets retain activation pathways and capacity compared to discoid platelets. Mechanical activation is driven by tangential rather than normal forces, and maintaining rolling instead of sliding effectively prevents tangential force-induced activation. Molecular dynamics simulations reveal that tangential force acting on sliding discoid platelets separates the integrin α IIb β 3 head from the lower leg region to unfold and activate the integrin, while the normal force acting on rolling spherical platelets induces headpiece rotation without triggering unfolding, which effectively reduces integrin α IIb β 3 activation. In in vitro hemodialysis experiments, platelet spherification effectively minimized coagulation, while avoiding bleeding complications.