Partial differentiation of Europa and implications for the origin of materials in the Jupiter system
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A system-level model reveals that transcriptional stochasticity is required for hematopoietic stem cell differentiation
HSCs differentiation has been difficult to study experimentally due to the high number of components and interactions involved, as well as the impact of diverse physiological conditions. From a 200-node network, that was grounded on experimental data, we derived a 21-node regulatory network by collapsing linear pathways and retaining the functional feedback loops. This regulatory network core integrates key nodes and interactions underlying HSCs differentiation, including transcription factors, metabolic, and redox signaling pathways. We used Boolean, continuous, and stochastic dynamic models to simulate the hypoxic conditions of the HSCs niche, as well as the patterns and temporal sequences of HSCs transitions and differentiation. Our findings indicate that HSCs differentiation is a plastic process in which cell fates can transdifferentiate among themselves. Additionally, we found that cell heterogeneity is fundamental for HSCs differentiation. Lastly, we found that oxygen activates ROS production, inhibiting quiescence and promoting growth and differentiation pathways of HSCs.
Efficient GPU-computing simulation platform JAX-CPFEM for differentiable crystal plasticity finite element method
We present the formulation and applications of JAX-CPFEM, an open-source, GPU-accelerated, and differentiable 3-D crystal plasticity finite element method (CPFEM) software package. Leveraging the modern computing architecture JAX, JAX-CPFEM features high performance through array programming and GPU acceleration, achieving a 39× speedup in a polycrystal case with ~52,000 degrees of freedom compared to MOOSE with MPI (8 cores). Furthermore, JAX-CPFEM utilizes the automatic differentiation technique, enabling users to handle complex, non-linear constitutive materials laws without manually deriving the case-specific Jacobian matrix. Beyond solving forward problems, JAX-CPFEM demonstrates its potential in an inverse design pipeline, where initial crystallographic orientations of polycrystal copper are optimized to achieve targeted mechanical properties under deformations. The end-to-end differentiability of JAX-CPFEM allows automatic sensitivity calculations and high-dimensional inverse design using gradient-based optimization. The concept of differentiable JAX-CPFEM provides an affordable, flexible, and multi-purpose tool, advancing efficient and accessible computational tools for inverse design in smart manufacturing.
Tissue macrophages: origin, heterogenity, biological functions, diseases and therapeutic targets
Macrophages are immune cells belonging to the mononuclear phagocyte system. They play crucial roles in immune defense, surveillance, and homeostasis. This review systematically discusses the types of hematopoietic progenitors that give rise to macrophages, including primitive hematopoietic progenitors, erythro-myeloid progenitors, and hematopoietic stem cells. These progenitors have distinct genetic backgrounds and developmental processes. Accordingly, macrophages exhibit complex and diverse functions in the body, including phagocytosis and clearance of cellular debris, antigen presentation, and immune response, regulation of inflammation and cytokine production, tissue remodeling and repair, and multi-level regulatory signaling pathways/crosstalk involved in homeostasis and physiology. Besides, tumor-associated macrophages are a key component of the TME, exhibiting both anti-tumor and pro-tumor properties. Furthermore, the functional status of macrophages is closely linked to the development of various diseases, including cancer, autoimmune disorders, cardiovascular disease, neurodegenerative diseases, metabolic conditions, and trauma. Targeting macrophages has emerged as a promising therapeutic strategy in these contexts. Clinical trials of macrophage-based targeted drugs, macrophage-based immunotherapies, and nanoparticle-based therapy were comprehensively summarized. Potential challenges and future directions in targeting macrophages have also been discussed. Overall, our review highlights the significance of this versatile immune cell in human health and disease, which is expected to inform future research and clinical practice.
Energy metabolism in health and diseases
Energy metabolism is indispensable for sustaining physiological functions in living organisms and assumes a pivotal role across physiological and pathological conditions. This review provides an extensive overview of advancements in energy metabolism research, elucidating critical pathways such as glycolysis, oxidative phosphorylation, fatty acid metabolism, and amino acid metabolism, along with their intricate regulatory mechanisms. The homeostatic balance of these processes is crucial; however, in pathological states such as neurodegenerative diseases, autoimmune disorders, and cancer, extensive metabolic reprogramming occurs, resulting in impaired glucose metabolism and mitochondrial dysfunction, which accelerate disease progression. Recent investigations into key regulatory pathways, including mechanistic target of rapamycin, sirtuins, and adenosine monophosphate-activated protein kinase, have considerably deepened our understanding of metabolic dysregulation and opened new avenues for therapeutic innovation. Emerging technologies, such as fluorescent probes, nano-biomaterials, and metabolomic analyses, promise substantial improvements in diagnostic precision. This review critically examines recent advancements and ongoing challenges in metabolism research, emphasizing its potential for precision diagnostics and personalized therapeutic interventions. Future studies should prioritize unraveling the regulatory mechanisms of energy metabolism and the dynamics of intercellular energy interactions. Integrating cutting-edge gene-editing technologies and multi-omics approaches, the development of multi-target pharmaceuticals in synergy with existing therapies such as immunotherapy and dietary interventions could enhance therapeutic efficacy. Personalized metabolic analysis is indispensable for crafting tailored treatment protocols, ultimately providing more accurate medical solutions for patients. This review aims to deepen the understanding and improve the application of energy metabolism to drive innovative diagnostic and therapeutic strategies.
Unraveling the dynamics of magnetization in topological insulator-ferromagnet heterostructures via spin-orbit torque
Spin–orbit coupling is a relativistic effect coupling the orbital angular momentum with the spin, which determines the physical properties of condensed matter. For instance, the spin–orbit coupling strongly influences spin dynamics, opening the possibility for promising applications. The topological insulator–ferromagnet heterostructure is a typical example exhibiting spin dynamics driven by current-induced spin–orbit torque. Recent observations of the sign flip of Hall conductivity imply that the spin–orbit torque is strong enough to flip magnetization within this heterostructure. Motivated by this, our study elucidates the conditions governing spin flips by studying the magnetization dynamics. We establish that the interplay between spin-anisotropy and spin–orbit torque plays a crucial role in the magnetization dynamics. Furthermore, we categorize various modes of magnetization dynamics, constructing a comprehensive phase diagram across distinct energy scales, damping constants, and applied frequencies. We also consider the effect of a magnetic field on the magnetization dynamics. This research not only offers insights into controlling spin direction but also charts a new pathway to the practical application of spin–orbit coupled systems.
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