Abstract Polymer crystallization under nanoscale confinement is governed by finite-size and interfacial effects, yet its behavior at length scales approaching the lamellar thickness remains poorly understood. Here, we investigate the crystallization of poly(ethylene oxide) (PEO) with varying molecular weights confined within silicon nanopores (d ∼ 7–8 nm). Crystallization is strongly suppressed, with the crystallization temperature approaching the homogeneous nucleation regime while deviating from conventional volume scaling. Furthermore, the melting temperature exhibits a pronounced reduction (∼20 K), indicating that lamellar thickness is directly constrained by the geometry. Interestingly, a transition from an extended-chain crystal to a folded-chain crystal occurs in PEO with a molecular weight of 2000 g/mol (PEO2k), while PEO with a molecular weight of 1000 g/mol (PEO1k) maintains an extended-chain crystal, because the contour length of the PEO2k chain exceeds d, whereas that of the PEO1k is comparable to d. These results demonstrate that, when the confinement dimension approaches the lamellar thickness, geometric confinement dictates nucleation and attainable crystal dimensions, whereas interfacial interactions govern crystal orientation, thereby defining the fundamental limits of polymer crystallization under extreme nanoconfinement.

Hydroxyapatite (HA) ceramics are one of the most widely used biomaterials due to their high biocompatibility and bioactivity. However, the inherent brittleness limits their biomedical applications as load-bearing components for hard tissue repair. Herein, we reported a 127% enhancement in fracture toughness (K-IC increased from 0.62 to 1.41 MPam(1/2)) of defective Al-doped HA (D-Al-HA) ceramics through defect-engineering mechanism. The theoretical and experimental studies indicated that Al substitution induced lattice distortion and defects such as generation of Ca vacancy, rotation of PO43- group, dislocation of Ca ions and disorder of OH- chains. These defects acted as potent Zener pinning sites, suppressing grain boundary mobility during sintering and yielding a refined microstructure. The average grain size decreased from 2.2 mu m for HA to 1.3 mu m for D-Al-HA ceramics. This grain refinement caused a remarkable increase in fracture toughness of D-Al-HA ceramics through crack deflection, branching, and bridging mechanism. Concurrently, the compressive strength and flexural strength increased by 43% and 21%, achieving 363 +/- 86 MPa and 77.4 +/- 14.0 MPa, respectively, through Hall-Petch mechanism. This study not only provided the first insights into the effects of Al-induced defects on the enhanced mechanical performances of HA and the positive role of Al element for HA materials, but also offered a promising pathway for developing stronger and tougher bioceramics for demanding hard tissue implants.

Chronic activation of the cGAS-STING pathway drives inflammaging and cellular senescence. Although nuclear envelope (NE) barrier failure leading to cytoplasmic chromatin leakage is a key trigger, the molecular mechanisms governing STING activity at the NE during aging remain poorly understood. Here, we identify lamin A/C (LMNA) as a critical NE scaffold that orchestrates STING regulation by recruiting both STING and Casein Kinase 2 (CK2α). We demonstrate that LMNA facilitates the phosphorylation of STING at Ser366 by CK2α, which promotes STING turnover and restricts its accumulation, thereby attenuating pathway activation and mitigating senescence in myeloid cells as well as systemic aging. Strikingly, pharmacologic STING inhibition in vivo robustly rescues progeroid phenotypes—including loss of bone density and multi-tissue senescence—and extends lifespan in progeroid mouse models. Moreover, H-151 treatment also ameliorates the premature aging phenotypes induced by myeloid-specific CK2α ablation. In contrast, constitutive STING ablation yields limited survival benefits, revealing that controlled attenuation of STING signaling, rather than complete elimination, drives therapeutic efficacy. Our findings establish the LMNA-CK2-STING axis as a key biochemical mechanism that suppresses innate immune activation at the NE, offering a promising strategy for ameliorating aging and progeroid pathologies. Lamin A/C scaffolds STING and CK2α at the nuclear periphery, promoting STING phosphorylation and turnover to reduce cGAS-STING-driven inflammaging, and this LMNA–CK2–STING axis curbs senescence in myeloid cells and systemic aging.

Dynamic disassembly and reconstruction of the nuclear lamina during entry and exit of mitosis, respectively, are pivotal steps in the proliferation of higher eukaryotic cells. Although numerous post-translational modifications of lamin proteins have been identified, key factors driving the nuclear lamina dynamics remain elusive. Here we identified CDK1-elicited phosphorylation sites on endogenous Lamin A/C and characterized their functions in regulation of the nuclear lamina. Specifically, mass spectrometry revealed CDK1-mediated phosphorylation of Lamin A/C at the N-terminal Thr19/Ser22 and the C-terminal Ser390/Ser392 during mitosis. Importantly, the phospho-mimicking 4D mutant T19D/S22D/S390D/S392D completely disrupted Lamin A filamentous structure in interphase cells. Conversely, the non-phosphorylatable mutant T19A/S22A and especially the 4A mutant T19A/S22A/S390A/S392A protected Lamin A from depolymerization during mitosis. These results suggest that phosphorylation and dephosphorylation of both N- and C-terminal sites regulate the nuclear lamina dynamics. Engineering the non-phosphorylatable mutant T19A/S22A into the endogenous LMNA gene resulted in nuclear abnormalities and micronucleus formation during telophase. Perturbation of the Lamin A phosphorylation is shown to prevent proper nuclear envelope dynamics and impair nuclear integrity. These findings reveal a previously undefined link between the CDK1-elicited Lamin A phosphorylation dynamics, nuclear envelope plasticity, and genomic stability during the cell cycle.

Polymers confined within nanopores typically exhibit strongly depressed crystallization temperatures (T c) while their melting temperatures (T m) remain nearly unchanged, resulting in an apparent deviation from the classical Hoffman-Weeks relationship. Using isotactic polypropylene (iPP) confined within anodic aluminum oxide (AAO) nanopores as a model system, we demonstrate that the endothermic peak during heating measured by conventional differential scanning calorimetry (DSC) does not reflect the melting of the imperfect crystals initially formed during cooling. X-ray diffraction (XRD) and scanning electron microscopy (SEM) analyses further reveal continuous structural and morphological evolution during heating, indicating extensive crystal reorganization over a broad temperature range (similar to 60-140 degrees C). As a result, the observed melting behavior predominantly reflects the reorganized crystals formed during subsequent heating and is nearly independent of the preceding cooling conditions. By kinetically suppressing recrystallization through ultrafast heating using fast scanning calorimetry (FSC), the intrinsic T c-T m relationship is recovered, consistent with the classical Hoffman-Weeks framework. These results reveal the critical role of crystal reorganization in determining the apparent melting behavior of nanoconfined polymers and provide a physically consistent interpretation of melting in confined polymer systems.

Adipose tissues are highly dynamic in response to environmental temperature changes. During aging, subcutaneous white adipose tissues (WAT) decreases, yet whether this atrophy exacerbates cold stress and triggers systemic aging remains unclear. Here we show that adipocyte-specific expression of the LmnaG609G mutation in male mice leads to progressive WAT atrophy, accelerates aging, and shortens lifespan, whereas female mice remain unaffected. This lipoatrophy exacerbates cold stress, triggering cyclooxygenase-2 (COX-2) upregulation in WAT, and increased prostaglandin E2 production, which mediates the elevation of core body temperature (CBT). Inhibiting COX-2 by celecoxib or thermotherapy by housing the lipoatrophic mice at 26 °C (normally 22 °C) ameliorates cold stress, restores CBT, reduces aging features, and extends lifespan. Our findings reveal that subcutaneous WAT atrophy and subsequent CBT elevation induced by chronic mild cold stress are drivers of systemic aging in male mice, identifying thermotherapy as a potential regimen for progeria.

Ras-related protein 2 (Rras2) mutations are linked to Noonan syndrome, a disorder characterized by skeletal dysplasia and growth deficits. However, the role of Rras2 in bone homeostasis remains poorly defined, hindering the development of clinical interventions. Here, we show that Rras2 deficiency in mice leads to osteopenia, reduced bone strength, and impaired osteogenesis, recapitulating the clinical features of human patients. Mechanistically, Rras2 promotes osteogenic differentiation of bone marrow mesenchymal stem cells and supports bone regeneration. At the molecular level, Rras2 sustains BMP signaling by blocking Smurf1-dependent ubiquitination and degradation of BMPR2; in turn, BMP signaling enhances Rras2 transcription. Osteoporotic mice exhibit marked reduction in Rras2 expression in bone, and adeno-associated virus 9 (AAV9)-mediated restoration of Rras2 rescues bone loss. Our findings identify a Rras2-BMPR2 positive feedback loop that is critical for bone homeostasis and provide a therapeutic avenue for osteoporosis and Noonan syndrome.

Physical aging in amorphous polymers reflects the slow structural relaxation toward equilibrium below the glass transition. Isoconversional analysis suggests that progressively larger activation barriers are explored during aging, approaching that of α-relaxation near equilibrium. Yet the molecular origin of the low-barrier regime that defines the onset of aging, where the recovered enthalpy is only a few percent of the total, remains poorly understood. Here, we combine calorimetry and broadband dielectric spectroscopy on bulk and nanopore-confined poly(methyl methacrylate) (PMMA) to isolate the earliest stage of aging through the identification of the induction time of the kinetics (tind). We find that tind follows a clear Arrhenius dependence with an activation energy that, for both bulk and confined PMMA, is more aligned with that of the slow Arrhenius process, rather than that of the β-relaxation mode resolved in the dielectric spectra. These findings challenge the prevailing assumption that Arrhenius-like behavior is a unique signature of the β-relaxation, suggesting that additional localized modes play key roles in the dynamics of disordered solids and calling for a reassessment of how low-barrier processes are assigned.

YTH domain-containing family (YTHDF1/2/3) recognizes m6A modified mRNAs and regulates their stability, translation and function. We found loss of Ythdf3 in mice caused cardiac hypotrophy, myopathy, and intellectual abnormalities, resembling the clinical features of a rare inherited X-linked disorder Danon disease (DD). Mechanistically, this was attributable to the compromised mRNA decay of sex-determining region Y (SRY)-box 9 ( Sox9 ), mediated by YTHDF3 m6A reader function. Targeted therapy with AAV-shRNA against Sox9 ameliorated fibrosis, increased neuron number, and significantly improved heart and brain function in Ythdf3 −/− mice. Our data reveal that loss of murine Ythdf3 recapitulates systemic DD-like features, attributable to impaired Sox9 decay, and highlight a novel therapeutic target for DD.

The mechanistic target of rapamycin (mTOR) serves as an essential hub in sensing metabolic stress and regulating aging, although the differential contributions of mTOR-regulated protein and cholesterol synthesis are unclear. Post-transcriptional modifications of mRNAs, such as N6-methyladenosine (m6A), occur rapidly in response to acute environmental changes to maintain tissue homeostasis. Here, we showed that loss of YTH m6A RNA-binding protein 1 (YTHDF1) accelerated murine aging. Mechanistically, YTHDF1 is anchored to the lysosome surface by lysosome-associated membrane protein (LAMP2), whereby it recruits tuberous sclerosis complex (TSC2) to inhibit mTOR complex 1 (mTORC1). Ythdf1 loss activated mTORC1-sterol regulatory element-binding protein 2 (SREBP2)-axis-mediated cholesterol biosynthesis but not m6A-reader-regulated protein translation. Rapamycin restored murine healthspan in contrast to the maximum lifespan shortening caused by Ythdf1 depletion. Our data reveal an m6A-independent function of YTHDF1, which differentiates the contributing roles of mTORC1 in the regulation of aging.

Nucleation, which is the initial step of crystallization, critically governs the polymer crystallization behavior, influencing the crystallization temperature, kinetics, and morphology. However, the direct observation of the nucleation process in polymers remains elusive owing to spatial and temporal resolution limitations. This feature article summarizes the recent progress in understanding polymer nucleation within confined and interface-dominated environments, focusing on three representative systems: anodic aluminum oxide templates and nanocomposites containing nanoparticles or nanosheets. The interplay between finite size and interfacial effects has revealed some novel phenomena, such as homogeneous nucleation, surface nucleation, prefreezing, and supernucleation.

Interfaces play a pivotal role in various physical, chemical, and biological processes. In polymer crystallization, nucleation often occurs at solid interfaces due to the reduced barrier for heterogeneous nucleation, with the chain conformations and dynamics deviating significantly from their undisturbed (bulk) state. In this Letter, we employed a nanopore-confined system to differentiate between two nucleation scenarios: surface nucleation and homogeneous nucleation, through comprehensive crystal orientation analysis. Experimental findings reveal that surface-induced nucleation in polymers is predominantly driven by an entropic effect, arising from the loss of conformational entropy as polymer chains flatten at weakly interacting solid interfaces. Homogeneous nucleation is, instead, predominant in cases of strong interfacial interactions.

To understand how the processing conditions influence the formation of the crater-like surface morphology of biaxially oriented polypropylene (BOPP) capacitor films, in this work, we investigated the structure of cast sheets and BOPP films obtained by a five-layer co-extrusion equipment under different sheet cast-extrusion conditions (thickness of cast sheet and chill-roll temperature) and biaxial stretching temperatures. Multiple characterization techniques, including wide/small angle X-ray scattering (WAXS/SAXS), differential scanning calorimetry (DSC), and polarized light optical microscopy (PLOM) were used to establish the relationship between the structure of the cast sheet and the surface morphology. The results indicate that, within the process conditions investigated in this study, higher thickness (300 and 500 mu m), higher chill-roll temperature (90 degrees C), and appropriate stretching temperature (145 and 150 degrees C) are beneficial to the formation of crater-like surfaces. By micro-focus X-ray diffraction mapping, the spatial distribution of /3 crystal along the normal direction of the cast sheet was characterized, thus further elucidating the role of the /3 crystal in the roughening process of BOPP capacitor films.

The formation mechanism of the crater-like surface of biaxially oriented polypropylene (BOPP) film remains controversial. To clarify this issue, in this work, three isotactic polypropylene (iPP) samples with different tacticities are selected to prepare BOPP films. It is shown that the relative beta crystal content (k(beta)) in the cast sheet increases with tacticity. The beta crystal transforms to the alpha crystal when stretched at 145 degrees C along the machine direction. For all the samples, rough surfaces are obtained even if the k(beta) value of the cast sheet is very low (k(beta) < 0.1). The arithmetic mean roughness (R-a) of the BOPP films increases with the increase of the k(beta) in the cast sheet. While higher k(beta) in the iPP cast sheet contributes to a higher R-a value, the beta crystallites hinder the enlargement of roughening rings, and cause surface defects (cavitation), which are detrimental to applications. Our results indicate that the beta crystal in the cast sheet is not essential for the crater formation and a higher beta crystal content is not always beneficial for BOPP capacitor films.

We propose a methodology to characterize the crystalline content of interfacial polymer layers in systems confined at the nanoscale level in a 2D geometry. Based on the crystallinity data of a set of polymers, we introduce a simple model to describe the gradient in crystallinity introduced by confining polymer chains in nanopores. Our model underscores the pivotal role that interfaces play in crystallization and unequivocally contradicts the existence of interfacial "dead" layers where crystallization cannot take place. Further, we verified that the organization of crystals near the pore walls resembles the macromolecular architecture of adsorbed layers, hinting at a strong interplay between crystallization and adsorption.

Beyond the antimicrobial activity, doxycycline (DOX) exhibits longevity-promoting effect in nematodes, while its effect on mammals is unclear. Here, we applied a mouse model of Hutchinson-Gilford progeria syndrome (HGPS), Zmpste24 knockout (KO) mice, and analyzed the antiaging effect of DOX. We found that the DOX treatment prolongs lifespan and ameliorates progeroid features of Zmpste24 KO mice, including the decline of body and tissue weight, exercise capacity and cortical bone density, and the shortened colon length. DOX treatment alleviates the abnormal nuclear envelope in multiple tissues, and attenuates cellular senescence and cell death of Zmpste24 KO and HGPS fibroblasts. DOX downregulates the level of proinflammatory IL6 in both serum and tissues. Moreover, the elevated α-tubulin (K40) acetylation mediated by NAT10 in progeria, is rescued by DOX treatment in the aorta tissues in Zmpste24 KO mice and fibroblasts. Collectively, our study uncovers that DOX can decelerate aging in progeria mice via counteracting IL6 expression and NAT10-mediated acetylation of α-tubulin.

Brain waves of different frequencies are generated when the human brain functions, and γ waves are closely associated with higher cognitive functions, such as learning and memory. It has been observed that an electromagnetic field with specific frequency, amplitude, and duty cycle can enhance γ wave oscillation, thereby effectively improving human cognitive function. Building upon this discovery, this paper introduces a wearable pulsed magnetic field generator designed to enhance human cognitive abilities. The device allows for adjustable magnetic induction intensity of the output pulse magnetic field within the range of 0–5 mT, adjustable frequency of the output magnetic field within the range of 0–50 Hz, and adjustable duty cycle of the output magnetic field within the range of 1–50

Herein a split-type photoelectrochemical (PEC) immunosensor based on in situ grown gold nanoparticles (Au NPs) on the surface of ZnO microrods (ZnO MRs) was devised for the detection of alpha-fetoprotein (AFP) by employing dopamine (DA)-loaded liposomes as the signal amplification strategy. Specifically, as the level of AFP rises, a proportional number of sandwich-type immunocomplexes form in the well of the microplate, which can introduce a corresponding amount of DA-encapsulated liposomes at the same time. Encapsulated DA molecules will be released with the stimulation of Triton X-100, thereby resulting in the marked enhancement of the PEC signal. Under optimized conditions, the proposed PEC immunosensing platform displays specific photocurrent responses toward AFP in a broad dynamic working range of 0.05 -50 ng mL-1, achieving an impressively low limit of detection (LOD) of 18.7 pg mL-1. Furthermore, this methodology not only displays high specificity, and satisfactory storage stability but also ensures acceptable accuracy and practicality for the analytical applications of human serum samples. image