Search Results (175)

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

Hydraulic manipulators are vital for heavy-duty applications such as rescue robotics due to their high power density, yet these scenarios increasingly demand safe and compliant physical interaction. Impedance control is a key enabling technology for such capabilities. However, a significant challenge arises when implementing impedance control on Independent Metering Systems (IMS), which are widely adopted for their energy efficiency. The inherent multi-mode operation of IMS relies on discrete switching logic. Crucially, when mode switching occurs during physical interaction with the environment, the unpredictable external forces can trigger frequent and abrupt switching between operating modes (e.g., resistive and overrunning), leading to severe chattering. This phenomenon not only undermines the smooth interaction that impedance control aims to achieve but also jeopardizes overall system stability. To address this critical issue, this paper proposes a seamless control framework based on a Takagi–Sugeno (T-S) fuzzy model. Two premise variables based on the physical characteristics of the system are innovatively designed to make the rule division highly consistent with the dynamic nature of the system. Asymmetric membership functions are introduced to handle direction-dependent switching, with orthogonal functions ensuring logical exclusivity between extension and retraction, and smooth complementary functions enabling seamless transitions between resistance and overrunning modes. Experimental validation on a small hydraulic manipulator validates the effectiveness of the proposed method. The controller eliminates switching-induced instability and smooths velocity transitions, even under dynamic external force disturbances. This work provides a crucial solution for high-performance, stable hydraulic interaction control, paving the way for the application of hydraulic robots in complex and dynamic environments. Full article

Antibiotic persistence is a transient phenotype in which a subset of genetically susceptible bacteria survives lethal antibiotic exposure without acquiring resistance. However, survival alone does not define a persister cell—only cells that successfully recover, resume growth, and produce viable progeny complete the persister cycle. Recent studies in Escherichia coli show that persister awakening is a multistage process shaped by dormancy depth, metabolic state, and antibiotic-induced damage. Upstream induction mechanisms, including stringent-response signaling and toxin–antitoxin–mediated growth arrest, primarily determine dormancy depth but do not directly control awakening kinetics. During the lag phase, persister cells undergo coordinated recovery involving detoxification of residual antibiotics, ATP restoration, dissolution of protein aggregates, and ribosome reactivation. After exposure to fluoroquinolones, awakening additionally requires SOS-driven DNA repair via homologous recombination or transcription-coupled repair. In contrast, β-lactam–exposed persister cells rely mainly on efflux-mediated detoxification and asymmetric damage partitioning. Failure to restore proteostasis or resolve damage results in abortive recovery or cell death. Only after damage processing and metabolic reactivation can persister cells resume division and generate viable progeny. This review integrates current molecular insights into persister cell recovery in E. coli, highlighting the lag phase as the critical barrier between survival and true persistence. Full article

Visible Light Communication (VLC) systems commonly employ optical orthogonal frequency division multiplexing (O-OFDM) to achieve high data rates, benefiting from its robustness against multipath effects and intersymbol interference (ISI). However, a key limitation of asymmetrically clipped direct current biased optical–OFDM (ACO-OFDM) systems lies in their inherently high peak-to-average power ratio (PAPR), which significantly affects signal quality and system performance. This paper proposes a joint chaotic encryption and modified μ-non-linear logarithmic companding (μ-MLCT) scheme for ACO-OFDM–based VLC systems to simultaneously enhance security and reduce PAPR. First, image data is encrypted at the upper layer using a hybrid chaotic system (HCS) combined with Arnold’s cat map (ACM), mapped to quadrature amplitude modulation (QAM) symbols and further encrypted through chaos-based symbol scrambling to strengthen security. A μ-MLCT transformation is then applied to mitigate PAPR and enhance both peak signal-to-noise ratio (PSNR) and bit-error-ratio (BER) performance. A mathematical model of the proposed secured ACO-OFDM system is developed, and the corresponding BER expression is derived and validated through simulation. Simulation results and security analyses confirm the effectiveness of the proposed solution, showing gains of approximately 13 dB improvement in PSNR, 2 dB in BER performance, and a PAPR reduction of about 9.2 dB. The secured μ-MLCT-ACO-OFDM not only enhances transmission security but also effectively reduces PAPR without degrading PSNR and BER. As a result, it offers a robust and efficient solution for secure image transmission with low PAPR, making it well-suitable for emerging wireless networks such as cognitive and 5G/6G systems. Full article

Bias and hallucinations in low-resource cultural artefacts significantly impede text-to-image generation models from understanding and disseminating. Focusing on Tibetan as a Chinese minority culture, we produced a children’s picture book through two methods: AI generation and human illustrator. Eye-tracking experiments were employed to investigate participants’ implicit attitudes, aesthetic biases, and cultural perceptions towards these two sources. The results revealed that (1) the hand-drawn group demonstrated higher fidelity to Tibetan culture, exhibiting a positive aesthetic calibration effect in terms of cultural adaptability owing to viewers’ attention duration to the cultural symbols details. (2) The AI-generated group elicited greater viewer interest and emotional engagement through its asymmetric color palettes, especially in color richness and stylistic rendering, and achieved professional-level compositional maturity in multi-character scene generation. This study provides empirical evidence to inform the division of labor between humans and AI in children’s book illustration and explores potential models for future human-AI collaboration. Full article

The accurate division of operating periods in urban rail transit (URT) is crucial for reasonable scheduling. However, the current determination of operating breakpoints largely relies on the empirical judgment of operators, and symmetric period schemes are usually adopted, which fail to effectively reflect the uneven temporal distribution of passenger flow across different lines and directions. This study proposes a hybrid SOM–K-means framework for dividing daily operating periods based on automatic fare collection (AFC) data, the method extracts features from three dimensions of passenger flow, total volume, microscopic fluctuations and macroscopic distribution. A case study is conducted based on data from Tianjin URT Lines 1 and 2. The results demonstrate that the clustering-based operating period division effectively reveals transition periods between peak and off-peak hours, as well as late-night periods that are not captured by the existing scheme, while also reflecting temporal asymmetry across lines and directions. Consequently, compared to current schemes, this division offers a more accurate representation of passenger flow characteristics, enhancing the precision of scheduling work and operational efficiency. Moreover, the SOM–K-means method shows robust clustering performance and stability across various scenarios and sample sizes. This study offers insights for URT to achieve refined scheduling and demand-responsive operations based on passenger flow. Full article

This paper investigates the dual-functional broadband properties of an asymmetric piezoelectric metamaterial beam for simultaneous vibration reduction and energy harvesting. Firstly, a grading method is proposed, and an asymmetric piezoelectric metamaterial beam structure model with the gradient mode is established. The effects of various gradient modes on the grading parameters of each segment are examined. Subsequently, the band structure and group velocity of each segment are examined to elucidate the propagation and energy harvesting mechanisms for the bending-dominated wave. Furthermore, the evaluation criteria for dual-functional properties in the gradient mode are introduced, revealing the broadening law of the dual-functional band under various gradient modes. Finally, the theoretical results are analyzed and compared with the finite element method (FEM). The results show that in gradient mode, the bending-dominated wave in the asymmetric piezoelectric metamaterial beam generates the spatial frequency division and enhances wave field energy. Compared with the uniform mode, the gradient modes can simultaneously achieve dual-functional effects in both the low-frequency and broadband ranges, significantly improving performance. Parameters such as gradient modes and grading variation ranges significantly impact the dual-functional performance. By reasonably selecting the grading parameters, enhanced dual-functional performance can be achieved. Full article

The ciliary marginal zone (CMZ) is a region in the peripheral-most retina that displays ongoing retinogenesis during growth and expansion of the eye in adulthood. While there is evidence that this capacity also exists in birds and mammals, it is far more robust in fish and amphibians. The process of CMZ retinogenesis is essentially equivalent to that seen early in the central retina; however, its regulation is not fully understood. In a previous study, we attempted to uncover novel regulatory genes by using a forward genetics screen in zebrafish, looking for recessive CMZ mutants. One of the mutants found was called no marginal zone (nmz). The nmz mutant showed relatively normal central retina development, but a lack of cells in the CMZ by 5 days post fertilization (dpf). Mapping, genomic sequencing, and complementation analysis using a second mutant line (m863) isolated in another laboratory showed that a mutation in damage-specific DNA binding protein-1 (ddb-1) gene underlies the phenotype seen in nmz. BrdU labeling suggested that later expansion and differentiation of CMZ retinal progenitors is more affected by ddb-1 loss than the earlier process of stem cell asymmetric division. As was seen for the m863 mutant and in other studies with mice, one profound effect of ddb-1 loss in nmz was the upregulation in expression of tp53 and several of its downstream effectors. Several important genes important in CMZ retinogenesis are also downregulated in the nmz mutant. The change in gene expression would suggest that ddb-1 loss leads to increased cell cycle disruption and apoptosis at the expense of CMZ retinogenesis. While homozygosity is lethal, heterozygous fish appear to be completely normal in morphology, visual function, and behavior. Full article

Estrogen metabolites (EMs) play a local regulatory role in mammalian ovarian function. Among them, 2-hydroxyestradiol (2-OHE2) exerts dose-dependent effects on reproductive physiology, supporting either normal ovarian processes or contributing to pathological conditions. Specifically, 2-OHE2 modulates ovarian vasculature and progesterone biosynthesis, and at 1–10 nM concentrations, it enhances in vitro developmental competence and blastocyst quality in mouse oocytes. Conversely, doses below 1 nM show no appreciable effects, suggesting the existence of a biological activity threshold. However, the impact of supra-physiological concentrations remains largely unexplored. In this study, we investigated the effects of increasing 2-OHE2 doses (0.05, 0.50, and 5.00 µM) on oocyte meiotic progression and quality. Exposure to 0.50 and 5.00 µM significantly impaired oocyte maturation, while only the highest dose notably reduced the percentage of embryos developing to the blastocyst stage. Morphometric analysis during the GV-to-MII transition revealed altered first polar body morphology, defective asymmetric division, and disruptions in cytoskeletal organization, including enlarged meiotic spindles, increased F-actin cap angles, and aberrant microtubule-organizing centers distribution. These structural alterations were paralleled by distinct changes in cytoplasmic movement velocity patterns observed through time-lapse imaging during meiotic resumption. Together, these findings demonstrate that supra-physiological exposure to 2-OHE2 compromises oocyte maturation and developmental competence by perturbing key cytoskeletal dynamics and cellular architecture necessary for successful meiosis and early embryogenesis. Full article

GpsB is a conserved cell-cycle regulator in the Firmicute clade of Gram-positive bacteria that coordinates multiple aspects of envelope biogenesis. Recent studies demonstrate interactions between GpsB and the key division cytoskeleton FtsZ, suggesting that GpsB links cell division to various aspects of cell envelope biogenesis in Staphylococcus aureus and potentially other Firmicutes. We determined a 1.7 Å resolution crystal structure of the N-terminal domain of Staphylococcus aureus GpsB, revealing an asymmetric dimer with a bent conformation. This conformation is nearly identical to one of two conformations reported by Sacco et al., confirming the unique conformation of S. aureus GpsB compared to other Gram-positive bacteria. This structural agreement provides strong validation of the S. aureus GpsB fold and supports its proposed role in organizing the cell division machinery. Full article

In this work, one-to-two-port beam division is achieved in a five-channel acoustic system. The adjacent composing channels are connected by space-varying air slits, thus realizing quantum-like adiabatic energy transfer. Equal-weight beam splitting with opposite phases from two different output ports is obtained in a broadband signal of 6 kHz-10.5 kHz. In addition, owing to the existence of distinct evolution paths, one-way beam division is exhibited when a certain loss is evenly exerted inside the system. Furthermore, one-to-m-port beam division can also be achieved by extending the composing channels, thus making it possible to construct an asymmetric acoustic beam splitter. The simulated results verify that the incident waves can be split into opposite directions unidirectionally, which may have potential applications in concealed information transmission and eavesdropping. Full article

Curved roofs constructed using hyperbolic paraboloid (HP) modules are gaining popularity in structural engineering due to their unique aesthetic and structural advantages. Consequently, these studies have investigated steel bar modules based on HP geometry, focusing on how variations in geometric configuration and bar topology affect internal force distribution and overall structural performance. Each module was designed on a 4 × 4 m square plan, incorporating external bars that formed the spatial frame and internal grid bars that filled the frame’s interior. Parametric modeling was conducted using Dynamo, while structural analysis and design were performed in Autodesk Robot Structural Analysis Professional (ARSAP). Key variables included the vertical displacement of frame corners (0–1.0 m at 0.25 m intervals), the orientation and spacing of internal bar divisions, and the overall mesh topology. A total of 126 structural models were analyzed, representing four distinct bar topology variants, including both planar and non-planar mesh configurations. The results demonstrate that structural efficiency is significantly influenced by the geometry and topology of the internal bar system, with notable differences observed across the various structural types. Computational analysis revealed that asymmetric configurations of non-planar quadrilateral subdivisions yielded the highest efficiency, while symmetric arrangements proved optimal for planar panel applications. These findings, along with observed design trends, offer valuable guidance for the development and optimization of steel bar structures based on HP geometry, applicable to both single-module and multi-module configurations. Full article

(1) Background: Chronic myeloid leukemia (CML) is a myeloproliferative disorder driven by the BCR::ABL oncoprotein. During the chronic phase, Philadelphia chromosome-positive hematopoietic stem cells generate proliferative myeloid cells with various stages of maturation. Despite this expansion, leukemic stem cells (LSCs) retain self-renewal capacity via asymmetric cell divisions, sustaining the stem cell pool. Quiescent LSCs are known to be resistant to tyrosine kinase inhibitors (TKIs), potentially through BCR::ABL-independent signaling pathways. We hypothesize that dysregulation of genes governing asymmetric division in LSCs contributes to disease progression, and that their expression pattern may serve as a prognostic marker during the chronic phase of CML. (2) Methods: Genes related to asymmetric cell division in the context of hematopoietic stem cells were extracted from the PubMed database with the keyword “asymmetric hematopoietic stem cell”. The collected relative gene set was tested on two independent bulk transcriptome cohorts and the results were confirmed by single-cell RNA sequencing. (3) Results: The expression of genes involved in asymmetric hematopoietic stem cell division was found to discriminate disease phases during CML progression in the two independent transcriptome cohorts. Concordance between cohorts was observed on asymmetric molecules downregulated during blast crisis (BC) as compared to the chronic phase (CP). This downregulation during the BC phase was confirmed at single-cell level for SELL, CD63, NUMB, HK2, and LAMP2 genes. Single-cell analysis during the CP found that CD63 is associated with a poor prognosis phenotype, with the opposite prediction revealed by HK2 and NUMB expression. The single-cell trajectory reconstitution analysis in CP samples showed CD63 regulation highlighting a trajectory cluster implicating HSPB1, PIM2, ANXA5, LAMTOR1, CFL1, CD52, RAD52, MEIS1, and PDIA3, known to be implicated in hematopoietic malignancies. (4) Conclusion: Regulation of CD63, a tetraspanin involved in the asymmetric division of hematopoietic stem cells, was found to be associated with poor prognosis during CML progression and could be a potential new therapeutic target. Full article

Background: Duchenne muscular dystrophy (DMD), which affects 1 in 3500 to 5000 newborn boys worldwide, is characterized by progressive skeletal muscle weakness and degeneration. The reduced muscle regeneration capacity presented by patients is associated with increased fibrosis. Satellite cells (SCs) are skeletal muscle stem cells that play an important role in adult muscle maintenance and regeneration. The absence or mutation of dystrophin in DMD is hypothesized to impair SC asymmetric division, leading to cell cycle arrest. Methods: To overcome the limited availability of biopsies from DMD patients, we used our 3D skeletal muscle organoid (SMO) system, which delivers a stable population of myogenic progenitors (MPs) in dormant, activated, and committed stages, to perform SMO cultures using three DMD patient-derived iPSC lines. Results: The results of scRNA-seq analysis of three DMD SMO cultures versus two healthy, non-isogenic, SMO cultures indicate reduced MP populations with constant activation and differentiation, trending toward embryonic and immature myotubes. Mapping our data onto the human myogenic reference atlas, together with primary SC scRNA-seq data, indicated a more immature developmental stage of DMD organoid-derived MPs. DMD fibro-adipogenic progenitors (FAPs) appear to be activated in SMOs. Conclusions: Our organoid system provides a promising model for studying muscular dystrophies in vitro, especially in the case of early developmental onset, and a methodology for overcoming the bottleneck of limited patient material for skeletal muscle disease modeling. Full article

This article reports on the interrogation of fiber Bragg grating (FBG)-based sensors that are multiplexed in an asymmetric tree topology. At each stage in the topology, FBGs are connected at one output port of a 50:50 coupler with fibers of different lengths. This asymmetric structure allows the simultaneous interrogation of long-distance and parallel sensor networks to be realized. Time- and wavelength-division multiplexing techniques are used to multiplex the FBGs. Using the heterodyne detection technique, high-sensitivity detection of reflection signals that have been weakened by losses induced by a round-trip transmission through the couplers and long-distance propagation is performed. Quasi-distributed FBGs are interrogated simultaneously, over distances ranging from 15 m to 80 km. Full article