Search Results (206)

Long bone formation in vertebrates proceeds via endochondral ossification, a sequential process that begins with mesenchymal condensation, advances through cartilage anlage formation, and culminates in its replacement by mineralized bone. Recent advances in inducible lineage tracing and single-cell genomics have revealed that, rather than being a uniform event, mesenchymal condensation rapidly segregates into progenitor pools with distinct fates. Centrally located Sox9⁺/Fgfr3⁺ chondroprogenitors expand into the growth plate and metaphyseal stroma, peripheral Hes1⁺ boundary cells refine condensation via asymmetric division, and outer-layer Dlx5⁺ perichondrial cells generate the bone collar and cortical bone. Concurrently, dorsoventral polarity established by Wnt7a–Lmx1b and En1 ensures that dorsal progenitors retain positional identity throughout development. These lineage divergences integrate with signaling networks, including the Ihh–PTHrP, FGF, BMPs, and WNT/β-catenin networks, which impose temporal control over chondrocyte proliferation, hypertrophy, and vascular invasion. Perturbations in these programs, exemplified by mutations in Fgfr3, Sox9, and Dlx5, underlie region-specific skeletal dysplasias, such as achondroplasia, campomelic dysplasia, and split-hand/foot malformation, demonstrating the lasting impacts of embryonic patterning errors. Based on these insights, regenerative strategies are increasingly drawing upon developmental principles, with organoid cultures recapitulating ossification centers, biomimetic hydrogels engineered for spatiotemporal morphogen delivery, and stem cell- or exosome-based therapies harnessing developmental microRNA networks. By bridging developmental biology with biomaterials science, these approaches provide both a roadmap to unravel skeletal disorders and a blueprint for next-generation therapies to reconstruct functional bones with the precision of the embryonic blueprint. Full article

SiC/Al matrix composites are prone to forming brittle Al₄C₃ phase via interfacial reactions during fabrication, which severely limits their mechanical properties and engineering applications. Microalloying is an effective method to inhibit this brittle phase, yet the interfacial mechanism of alloying elements at the atomic scale remains unclear. Centered on molecular dynamics simulation combined with experimental verification, this study systematically investigates the laws of Fe and Ni microalloying on the interface regulation and mechanical property optimization of SiC/Al composites. Simulation results show that Fe and Ni atoms tend to segregate at the SiC/Al interface, which can suppress interfacial reactions, promote dislocation nucleation and proliferation, induce new dislocation types, and achieve the synergistic improvement of strength and ductility—with Ni exhibiting a more prominent strengthening effect. Composites prepared by the pressure infiltration-hot extrusion process show no Al₄C₃ phase in phase detection. Mechanical property tests confirm that Fe and Ni microalloying can effectively enhance the comprehensive performance of the materials, among which Ni increases the strength–ductility product by 54%. This study clarifies the interfacial regulation mechanism of Fe and Ni microalloying at the atomic scale, providing theoretical guidance and experimental support for the microalloying design of SiC/Al composites. Full article

Al–Zn–Ca alloys are good candidates for industrial electronics and electric vehicles due to their high thermal conductivity, castability, and corrosion resistance, but their strength requires improvement. This study investigates how Sc and Zr additions affect the microstructure, thermal, mechanical, and corrosion properties of an Al–3 wt% Zn–3 wt% Ca base alloy. Microstructural analysis showed that substituting Sc with Zr did not drastically alter the phase composition but changed the elemental distribution: Sc was uniform, while Zr segregated to center of dendritic cell. Zr addition also refined the grain size from 488 to 338 μm. An optimal aging treatment at 300 °C for 3 h was established, which enhanced hardness for all alloys via precipitation of Al₃Sc/Al₃(Sc,Zr) particles. However, this Zr substitution reduced thermal conductivity (from 184.7 to 168.0 W/mK) and ultimate tensile strength (from 269 to 206 MPa), though it improved elongation at fracture (from 4.6 to 7.1%). All aged alloys exhibited high corrosion resistance in 5.7% NaCl + 0.3% H₂O₂ water solution, with Zr-containing variants showing a lower corrosion rate and better pitting resistance. The study confirms the potential of tuning Sc/Zr ratios in Al–Zn–Ca alloys to achieve a favorable balance of strength, ductility, thermal conductivity, and corrosion resistance. Full article

Urban fragmentation has emerged as a central issue in the study of socio-spatial dynamics in contemporary cities, reflecting processes of inequality, segregation, and spatial discontinuities. This article introduces a new methodological approach to measure fragmentation by focusing on discontinuities at limits rather than on the content of statistical units alone. The method applies robust standardization of selected socioeconomic variables—higher education, foreign-born population, and low-income population—at the census tract scale in the city of Lleida, Spain. Rupture intensity is measured through a Rupture Intensity Index, which integrates standardized differences across 217 limits. Principal component analysis identifies the most influential variables, while cluster analysis characterizes the multidimensional nature of limits. Results show that fragmentation in Lleida does not follow a simple center–periphery model but a tessellated pattern of fracture lines and gradient zones. Intense fractures emerge at borders between advantaged and disadvantaged neighborhoods, whereas gradients mark gradual transitions. The study demonstrates that limits are critical sites for observing and quantifying urban fragmentation and proposes a transferable methodology for comparative research and urban policy design in diverse urban contexts. This approach provides a replicable tool for urban analysis and the design of cohesion-oriented policies. Full article

Aiming at the drawbacks of the classic CoCrFeNi high-entropy alloy (HEA)—low room-temperature strength and softening above 600 °C, which fail to meet strict material requirements in high-end fields like aerospace—this study used the vacuum hot-pressing sintering process to prepare CoCrFeNiTa_x HEAs (x = 0, 0.5, 1.0, 1.5, 2.0 atom, designated as H4, Ta_0.5, Ta_1.0, Ta_1.5, Ta_2.0, respectively). This process effectively inhibits Ta segregation (a key issue in casting) and facilitates the presence uniform microstructures with relative density ≥ 96%, while this study systematically investigates a broader Ta content range (x = 0–2.0 atom) to quantify phase–property evolution, differing from prior works focusing on limited Ta content or casting/spark plasma sintering (SPS). Via X-ray diffraction (XRD), scanning electron microscopy–energy-dispersive spectroscopy (SEM-EDS), microhardness testing, and room-temperature compression experiments, Ta’s regulatory effect on the alloy’s microstructure and mechanical properties was systematically explored. Results show all alloys have a relative density ≥ 96%, verifying the preparation process’s effectiveness. H4 exhibits a single face-centered cubic (FCC) phase. Ta addition transforms it into a “FCC + hexagonal close-packed (HCP) Laves phase” dual-phase system. Mechanically, the alloy’s inner hardness (reflecting the intrinsic property of the material) increases from 280 HV to 1080 HV, the yield strength from 760 MPa to 1750 MPa, and maximum fracture strength reaches 2280 MPa, while plasticity drops to 12%. Its strengthening mainly comes from the combined action of Ta’s solid-solution strengthening (via lattice distortion hindering dislocation motion) and the Laves phase’s second-phase strengthening (further inhibiting dislocation slip). Full article

Background: Early relapse in multiple myeloma (MM) is a major predictor of poor prognosis, regardless of cytogenetic risk or treatment intensity. Methods: Here we analyzed 1026 MM patients treated across 12 Italian hematology centers. FHR was defined as progression-free survival (PFS) ≤18 months in transplant-eligible (TE) and ≤12 months in non-transplant-eligible (NTE) patients. Logistic regression and ROC analysis were used to identify significant predictors of FHR and build a risk score. Results: FHR status was identified in 175 patients (17%). These patients had significantly shorter PFS (7 vs. 57.5 months) and overall survival (19 months vs. not reached; p < 0.001). FHR status was associated with higher median LDH, lower Hb level, higher creatinine level and lower platelets count. Modified EASIX formula was built by these significant continuous variables, to be tested in a logistic analysis: [(LDH × creatinine)/(Hb × PLT) × 100]. A significantly higher rate of FHR was found with a score > 2.0 (89% vs. 11%, p < 0.001). Multivariate logistic analysis selected the above formula, ECOG PS ≥ 2 and ISS III as factors associated with FHR. Scoring these variables according to OR, three groups of patients were segregated with a rate of FHR patients of 7%, 29.5%, and 63.5%, respectively. Treatment with anti-CD38 monoclonal antibodies was associated with lower FHR frequency. Conclusions: This study proposes a simple, clinically applicable model to identify FHR MM patients early in their disease course. However, very in-depth biological tools, not available in clinical practice, are needed to identify singularly risk of becoming FHR. Full article

The distribution of grain particles within a silo influences heat and moisture transfer during stored grain ventilation, leading to grain quality losses. A study on porosity distribution analysis and ventilation tests was conducted in a pilot silo with a height of 3 m, a diameter of 1.5 m, and a conical dome height of 0.85 m. The E-B constitutive model was incorporated into the secondary development of FLAC^3D 5.0 to analyze the vertical pressure distribution in the grain bulk. An anisotropic porosity distribution model for the maize bulk was developed, accounting for both vertical pressure and segregation mechanisms. The differences in airflow and heat transfer during ventilation between isotropic and anisotropic porosity distributions were quantified. A nonlinear model was innovatively proposed to predict the temperature front curve (TFC) during ventilation as affected by porosity variation. The results indicate that friction between the maize kernel and the silo wall led to vertical pressure at the center of the bottom that was 10.7% higher than that near the wall. The average surface porosity of the maize bulk was 2.8% higher than at the bottom. This led to a minimum porosity of 0.409 at the center of the silo bottom, due to the combined effect of impact during the loading process and vertical pressure. The numerical simulation demonstrated excellent consistency with the experimental data. At a supply vent air velocity of 0.126 m/s, an increase in the maize bulk height from 0.725 m to 2.9 m resulted in reductions in airflow rate and average relative humidity of 20.3% and 9.67%. The airflow velocity near the wall was 13.4% higher than that in the center, leading to a faster cooling rate in the peripheral region compared to the center of the maize bulk. The airflow velocity based on the isotropic porosity model was higher at the center than that predicted by the anisotropic model, whereas the opposite trend was observed near the wall. The temperature front during ventilation based on the anisotropic porosity model exhibited a concave curve. A nonlinear model was developed to predict this temperature front, showing strong agreement with computational data. Full article

Background/Objectives: Inborn errors of immunity (IEIs), formerly known as primary immunodeficiency disorders, are a heterogeneous group of genetic diseases characterized by recurrent infections and multisystem involvement. Although more than 500 distinct entities have been identified, reports from Central Asia remain scarce. This study describes two rare pediatric IEI cases from Kazakhstan, highlighting the importance of genomic diagnostics in underrepresented regions. Methods: Two unrelated male patients with early-onset recurrent infections and systemic complications were evaluated at the University Medical Center, Astana. Clinical and laboratory assessments included immunophenotyping, imaging, and histopathology. Whole-genome sequencing (WGS) was performed, followed by Sanger confirmation and segregation analysis when feasible. Variants were classified according to ACMG/AMP guidelines. Results: The first case involved a child with recurrent bronchopulmonary disease, pulmonary fibrosis, and connective tissue abnormalities, found to carry a novel homozygous FBLN5:c.53del frameshift variant consistent with autosomal recessive cutis laxa type 1A. The second case concerned an adolescent with progressive neurodegeneration, granulomatous skin lesions, and chronic pancreatitis, who was identified with a heterozygous pathogenic ATM:c.4828dup variant, confirming ataxia–telangiectasia. Both patients required lifelong subcutaneous immunoglobulin therapy. Consanguinity contributed to the genetic risk in the first case, while the second case demonstrated diagnostic delays that emphasized the value of genetic testing. Conclusions: These cases underscore the clinical heterogeneity of IEIs and illustrate the essential role of genomic diagnostics in elucidating atypical presentations. Documenting rare variants and unconventional phenotypes enhances global knowledge, elevates awareness in resource-limited regions, and emphasizes the necessity for early, multidisciplinary care and the enhancement of national registries for rare immunogenetic disorders. Full article

This study examines the statistical and spatial alignment between urban place perceptions and the census-based evidence of socio-spatial segregation. We process a large dataset of geotagged images from Mapillary and KartaView with ZenSVI to score six place perception dimensions (safety, liveliness, wealth, beauty, boredom, depression) for the metropolitan area of Thessaloniki, Greece. The socio-economic structure is derived from census indicators and property values using Location Quotients and principal component analysis. We assess alignment through Pearson’s correlation (r) to capture statistical association, and bivariate Moran’s I to test spatial correspondence while accounting for spatial dependence. Results reveal a robust northwest–southeast divide: southeastern and central districts are perceived as safer, livelier, wealthier, and more beautiful, while northwestern and industrial zones score higher on boredom and depression. The historic city center emerges as vibrant and affluent, acting as a key interface between social groups, especially students, the elderly, and migrants. Perceptual dimensions vary in spatial form: safety, beauty, and depression cluster locally, whereas wealth and vibrancy extend over broader sectors. The study demonstrates the combined use of perceptual and socio-economic data for urban analysis and provides a replicable framework for monitoring inequalities and guiding participatory and inclusive planning. Full article

Background: The current assessment method of the protective efficacy of adjuvanted vaccines remains slow and labor-intensive, hindered by prolonged immunization protocols and complex assays. Methods: To overcome this bottleneck, we demonstrate that early segregated cellular biomarkers enable rapid prediction of protection, using a respiratory syncytial virus (RSV) pre-fusion F (pre-F) protein model with diverse adjuvants in mice. Results: We identified that germinal center (GC) B cell responses (Days 7 and 9 post-immunization) strongly aligned with protective efficacy, except for Alum, which achieved MF59-level protection despite lower GC responses. Crucially, follicular dendritic cell (FDC) abundance at day 7 universally predicted protection across all adjuvants, including Alum, drastically shortening discovery time and effort from at least 4–6 weeks to within 1 week. Conclusions: FDCs and GC B cells serve as complementary early biomarkers that accurately forecast vaccine efficacy. This approach could potentially reduce the need for prolonged immunization regimens by cellular profiling on days 7–9, offering a modest step toward streamlining adjuvant selection and informing vaccine design. Full article

This paper investigates the effects of Ti and Nb addition with varying Mn content on the solidification macrostructure and microstructure in the continuous casting slab of Q355 steel using optical microscopy, scanning electron microscopy, transmission electron microscopy, and electron probe microanalysis. The evolution of central segregation and MnS inclusions during thermal simulation compress deformation has been clearly established using Gleeble-1500 thermal simulation tester. The results indicate that by reducing the Mn content and adding a small amount of Ti and Nb, it is possible to refine the grain and mitigate the center segregation of Q355 steel. Mn steel with 1.25% Mn and without Ti and Nb addition exhibits the most severe center segregation. The TiNb steel with 0.52% Mn and a small amount of Ti and Nb addition showed a marked improvement in the center segregation of the slab. The Nb steel with 0.56% Mn and 0.009% Nb shows the presence of thin film ferrite along prior grain boundaries surrounded by Widmanstätten ferrite, and the central segregation has not shown significant improvement. The thermal simulation samples of the three steel types inherit the characteristics of their respective casting structures. Full article

Introduction: Dengue virus (DENV) remains a global health threat, with four distinct serotypes (DENV1-4) that complicate vaccine development due to low-affinity, cross-reactive antibodies that increase the risk of antibody-dependent enhancement (ADE). Objective: To address the challenge of inducing strictly serotype-specific immune responses, this study explored the use of targeting individual lymph nodes (LNs) for the creation of simultaneous but independent immune responses as a targeted approach to reduce cross-reactivity and improve vaccine specificity. Methods: In the initial experiments, targeting individual LN successfully induced specific germinal centers (GCs) for different antigens in distinct LNs, highlighting its potential to enhance immune specificity. This approach was further tested using two virus-like particle (VLP)-based vaccines based on AP205 for DENV1 and DENV4, selected due to their genetic divergence and to probe the potential to minimize cross-reactive immune responses. In this setup, AP205-DV1 and AP205-DV4 were administered in targeted separate LNs, and the specificity of the immune response was compared to subcutaneous administration of a mixture of both vaccines. Results: Our data show that targeting distinct LNs elicited antibodies with significantly higher avidity, which is a critical factor in determining the neutralizing capacity of the immune response. Avidity measurements confirmed that this segregation approach results in a more refined selection of high-affinity B cells. Neutralization experiments demonstrated that targeting distinct LNs with individual vaccines induced a more potent and serotype-specific neutralizing response, compared to the injection of a vaccine mixture. Conclusions: These findings suggest that targeting individual LNs could be a promising method for enhancing both the specificity and potency of immune responses, particularly for flaviviruses. Targeting distinct LNs by direct administration of individual vaccines into distinct watersheds rather than individual lymph nodes will offer the opportunity to facilitate the approach in humans. Full article

This study investigates the influence of Cu addition on the nanostructural evolution and mechanical performance of a heavily drawn non-equiatomic CoCu_1.71FeMnNi high-entropy alloy (HEA) wire. Through systematic microstructural and compositional analysis, we examine how Cu constituent affects phase separation behavior and promotes deformation-induced nano-twinning in another phase counterpart. The designed HEA wire exhibits an elongated ultrafine dual face-centered cubic (fcc) lamella structure (i.e., Co-Fe-rich and Cu-rich phases) that emerges through compositional segregation by spontaneous phase separation from the as-cast state. High-resolution electron microscopy reveals the dislocation wall boundaries stabilized by nanoscale phase interfaces. The cold-drawn CoCu_1.71FeMnNi wire features an impressive combination of strength and ductility, as well as an ultimate tensile strength of nearly ~2 GPa with an elongation of over ~6%. These findings highlight the critical role of compositional tuning in controlling the ultrafine lamella structure stabilized by spinodal-like phase decomposition, offering a pathway to engineering high-performance HEA wires for advanced structural applications. Full article

Surface and sub-surface atomic configurations are critical for catalysis as they host the active sites governing electrochemical processes. This study employs density functional theory (DFT) calculations and Monte Carlo simulations combined with the cluster-expansion approach to investigate atom distribution and Pt segregation in Pt-Fe alloys across varying Pt/Fe ratios. Our simulations reveal a strong tendency for Pt atoms to segregate to the surface layer while Fe atoms enrich the sub-surface region. Crucially, the calculations predict the stability of a periodic Pt₂Fe alloy surface model, characterized by specific defect structures, at low platinum content and low annealing temperatures. Electronic structure analysis indicates that forming this Pt₂Fe surface alloy lowers the d-band center of Pt atoms, weakening CO adsorption and thereby enhancing resistance to CO poisoning. Although defect-induced strains can modulate the d-band center, crystal orbital Hamilton population (COHP) analysis confirms that such strains generally strengthen Pt-CO interactions. Therefore, the theoretical design of Pt₂Fe alloy surfaces and controlling defect density are predicted to be effective strategies for enhancing catalyst resistance to CO poisoning. This work highlights the advantages of periodic Pt₂Fe surface models for anti-CO poisoning and provides computational guidance for designing efficient Pt-based electrocatalysts. Full article

High-titanium steel contains an elevated titanium content, which promotes the formation of abundant non-metallic inclusions in molten steel at high temperatures, including titanium oxides, sulfides, and nitrides. These inclusions adversely affect continuous casting operations and generate substantial internal/surface defects in cast slabs, ultimately compromising product performance and service reliability. Therefore, stringent control over the size, distribution, and population density of inclusions is imperative during the smelting of high-titanium steel to minimize their detrimental effects. In this paper, samples of high titanium steel (0.4% Ti, 0.004% N) casting billets were analyzed by industrial test sampling and full section comparative analysis of the samples at the center and quarter position. Using the Particle X inclusions, as well as automatic scanning and analyzing equipment, the number, size, location distribution, type and morphology of inclusions in different positions were systematically and comprehensively investigated. The results revealed that the primary inclusions in the steel consisted of TiN, TiS, TiC and their composite forms. TiN inclusions exhibited a size range of 1–5 µm on the slab surface, while larger particles of 2–10 μm were predominantly observed in the interior regions. Large-sized TiN inclusions (5–10 μm) are particularly detrimental, and this problematic type of inclusion predominantly concentrates in the interior regions of the steel slab. A gradual decrease in TiN inclusion number density was identified from the surface toward the core of the slab. Thermodynamic and kinetic calculations incorporating solute segregation effects demonstrated that TiN precipitates primarily in the liquid phase. The computational results showed excellent agreement with experimental data regarding the relationship between TiN size and solidification rate under different cooling conditions, confirming that increased cooling rates lead to reduced TiN particle sizes. Both enhanced cooling rates and reduced titanium content were found to effectively delay TiN precipitation, thereby suppressing the formation of large-sized TiN inclusions in high-titanium steels. Full article