The near-universal adoption of electron cryo-microscopy (cryo-EM) by structural and cell biologists has led to exponential growth of the field, especially over the last two decades, with a doubling in the number of deposited electron-microscopy density maps every 2.5 years. This exponential growth has changed in recent years to become linear. Cryo-EM methods are now able to contribute to our structural understanding of biological complexity ranging from atomic resolution maps of assemblies of multiprotein complexes to in situ investigation of protein structures in the context of intact cells, snapshots of multiple conformations and insights into fundamental chemical mechanisms underlying biological function. Combined with dramatic advances in artificial intelligence, the increasing democratization and implementation of cryo-EM appears poised to drive a new revolution in digital biology.

Preeclampsia is a pregnancy-specific hypertensive disorder, clinically defined by new-onset hypertension with proteinuria or other maternal organ dysfunction. It is a leading cause of maternal and perinatal mortality worldwide and remains an incurable condition, with delivery as the only definitive treatment. Although heterogenous, the disorder originates in placental dysfunction, characterized by inadequate trophoblast invasion and impaired spiral uterine artery remodeling, resulting in syncytiotrophoblast stress and the release of placenta-derived factors. Increased placental secretion of antiangiogenic factors, including soluble fms-like tyrosine kinase-1 and soluble endoglin, promotes angiogenic imbalance and drives widespread maternal endothelial dysfunction. This narrative review synthesizes findings from human studies and experimental research models used to investigate angiogenic dysregulation in preeclampsia, with particular focus on in vitro and in vivo models, and emerging 3-dimensional placental platforms. In vitro models, such as trophoblast organoids, placenta-on-a-chip devices, and 3-dimensional bioprinted constructs, recapitulate key aspects of the placental microenvironment and enable detailed study of aberrant angiogenesis and how to target it, while reducing reliance on limited primary tissue and improving experimental control. Complementing in vitro models, in vivo models are essential for linking placenta-derived angiogenic imbalance to maternal disease phenotypes, therapeutic responses, and fetal outcomes. This review provides a comprehensive assessment of current literature on models that recapitulate angiogenic imbalance in preeclampsia. We emphasize the importance of integrating bioengineering, cell biology, and clinical insights to improve our understanding of preeclampsia pathogenesis and to develop predictive tools and therapeutic strategies to manage angiogenic dysregulation in preeclampsia.

Cells, bacteria, and other bioparticles exist in diverse shapes, and their morphology plays a pivotal role in biological functions and clinical significance. Various microfluidic approaches have been developed for shape-based separation of bioparticles with the same or similar volume; however, most of them were limited to separation of prolate spheroids from spheres or required a priori labeling and consequent detection. Here, we propose a vertical-type acoustofluidic method for the first separation of oblate spheroids from spheres in a label-free manner. The acoustic radiation torque suppresses the rotational motion of oblate micro-objects, leading to horizontal alignment with an increase in projected surface area compared to that of isovolumetric spheres. The enhanced acoustic radiation force, proportional to the projected surface area normal to the wave propagation, allows the oblate spheroids to have greater vertical migration inside a microchannel, resulting in distinct trajectories for shape-based separation. We conduct numerical simulations of asymmetric wave scattering to elucidate the working principle and experiments to demonstrate the separation of polystyrene microparticles and red blood cells of spherical and oblate shapes at high purity and recovery rate. The proposed acoustofluidic approach holds promise for label-free, shape-based manipulation of bioparticles in cell biology and microbiology.

Targeting TREM2 to disentangle neuroinflammation and α-Syn pathological propagation in Parkinson's disease.

A function-first legacy in hematopoietic stem cell biology: the scientific impact of Hal E. Broxmeyer.

Double-negative T cells in systemic lupus erythematosus: From immunopathology to therapeutic target.

Cytokine-based NK cell engineering for cancer immunotherapy.

Gold nanoparticles (AuNPs) are widely applied in nanomedicine, cellular and tissue biology, nanoscopy, photothermal therapy, and a range of diagnostic and clinical technologies. Among them, gold nanostars (AuNSs) have emerged as particularly promising due to their highly tunable optical and chemical properties. However, like other nanostructures, the stability of AuNSs remains a key challenge, especially within complex cellular microenvironments. Here, wide-field hyperspectral microscopy is evaluated for the real-time characterization of the morphology-dependent stability of AuNS formulations in immune-cell microenvironments. A computationally efficient image processing pipeline extracts statistical features from reflectance images, enabling the real-time analysis of hyperspectral data. UMAP-based visualization of spectral data revealed distinct, time- and formulation-dependent spectral shifts, with smaller seed volume formulations (larger overall diameter) for AuNSs exhibiting rapid destabilization and aggregation in THP-1 cells. In contrast, larger seed volume formulations (smaller overall diameter) for AuNS demonstrated enhanced colloidal stability and spectral uniformity. Compared to conventional ensemble measurements, hyperspectral reflectance measurements provided a rapid and resource-efficient approach that enabled macroscale imaging while retaining the spectral detail necessary to resolve AuNS transformations. Overall, the hyperspectral microscopy techniques presented here provide a label-free, high-throughput platform for evaluating AuNS stability and biocompatibility, with strong potential to guide the rational design of AuNSs for immunotherapeutic and diagnostic applications.

Systematic discovery of pathogen effector functions across human pathogens and pathways.

A blind spot of human T cell immunology: epitope specificity in secondary lymphoid organs.

Integrin-linked kinase (ILK) and kindlin-2 (K2) are key components of focal adhesions (FAs) that regulate cell-matrix adhesion and integrin signaling. Both proteins directly bind each other, but how they influence each other's localization to FAs and binding to integrins remains a subject of ongoing debate. Here, we establish a sensitive workflow to study protein-protein interactions in cells by combining methods from biochemistry, cell biology, and superresolution microscopy. Together with an analytical framework, this approach allowed us to distinguish direct from indirect molecular interactions and construct detailed interaction networks. Disrupting the ILK-K2 interaction reduced ILK localization to FAs and compromised integrin function, whereas K2 recruitment was unaffected. Our interdisciplinary approach also revealed that ILK does not directly bind β1-integrin cytosolic domains in vitro and in cells. Instead, ILK was recruited to integrins exclusively through a K2-dependent mechanism, primarily via K2 bridging ILK and β1 integrins. These findings define the hierarchical relationship between ILK and K2 in FAs and highlight the essential role of K2-mediated ILK recruitment for integrin adhesion and signaling.

Fibrosis represents a pathological wound-healing response that occurs after nearly any type of organ injury and has been estimated to lead to half of all deaths in the industrialized world. Current evidence indicates that the extracellular matrix in the fibrotic lesion is primarily produced by activated fibroblasts and/or myofibroblasts. In the liver, the key fibrosis effector cell is the hepatic stellate cell (HSC), which undergoes phenotypic switching from a quiescent (normal) state to a hepatic myofibroblast (activated state). The classic signature for the activated HSC is not only upregulation of various extracellular matrix mRNAs and proteins, particularly type 1 collagen, but also the de novo expression of multiple smooth muscle mRNAs and proteins, including the smooth muscle isoform of actin (smooth muscle α-actin), which supports a robust actin cytoskeleton. Growing evidence indicates that the actin cytoskeleton has a critical role in multiple essential HSC activities during the wound-healing response, including cell migration, contraction, signal transduction and matrix gene expression. In this Review, we focus on the role of the actin cytoskeleton and the molecular processes linking this critically important cellular structure to the cell biology of fibrosis.

Mechanical cues are increasingly recognized as master regulators of cell behavior in development, regeneration and disease. In fibrotic tissues and solid tumors, aberrant extracellular matrix (ECM) stiffening activates mechanotransduction pathways that reprogram gene expression, metabolism and chromatin architecture. This stiffened microenvironment does not merely act as a transient signal but may also create a mechanotransductive imprint that reinforces signaling pathways, establishing a positive feedback loop that modulates cell behavior through mechanical memory. The concept of mechanomemory, defined as the cellular ability to retain and adaptively respond to past mechanical stimuli, has emerged as a critical player in cell biology offering new insights into how cells interpret and perpetuate biomechanical cues. This "memory" of mechanical stress modulates key processes such as cellular proliferation, epithelial-mesenchymal transition and invasion, contributing to disease progression and resistance against conventional therapies. This review explores the potential role of mechanomemory in the progression of lung diseases. We examine how sustained mechanical signals are encoded through molecular pathways, cytoskeletal adaptations, and epigenetic modifications, leading to persistent pathological cell states. We discuss how this imprinted memory may drive key features of lung disease, including the perpetuation of fibrosis and the acquisition of therapeutic resistance. We propose that targeting mechanomemory could open novel pathways for disrupting the vicious cycle of mechanical stress and lung disease while identifying novel areas for future research.

Immune checkpoint molecules, inhibitory receptors originally characterized in T cell biology, have recently emerged as regulators of microglial function in neurodegeneration, yet their roles in amyotrophic lateral sclerosis (ALS) remain unexplored. Here, we investigated LAG-3, an inhibitory immune checkpoint receptor, in microglial regulation during ALS pathogenesis using SOD1G93A mice. LAG-3 expression was progressively upregulated in spinal cord microglia during disease progression, and LAG-3-high microglia exhibited a disease-associated microglia (DAM) transcriptional signature. Genetic deletion of LAG-3 produced a biphasic phenotype, with accelerated disease onset but significantly prolonged disease duration. LAG-3 deficiency enhanced inflammatory microglial responses at the early disease stage, whereas at the late stage it suppressed inflammatory signaling while selectively preserving phagocytic effector gene expression, demonstrating that LAG-3 dissociates the inflammatory and phagocytic modules within the DAM program in a stage-dependent manner. These transcriptional changes translated into enhanced phagocytic capacity in primary microglia and amelioration of the spinal cord environment through suppression of inflammatory pathways and restoration of oxidative phosphorylation. Our findings identify LAG-3 as a stage-dependent regulator of microglial functional states in ALS and support the concept that immune checkpoint molecules constitute a class of module-level regulators of microglial function in neurodegeneration.

Zebrafish (Danio rerio) is used as a model to study adrenergic signaling and pigment cell development because their genetic structure matches human genetics and enables advanced scientific research methods. Researchers use zebrafish to conduct their studies in three different research areas which include cellular signaling studies and toxicology research and pharmacology investigations and translational scientific work. Hormonal processes through alpha-MSH MCH and melatonin interact with each other to regulate pigment distribution. The GPCR-mediated pathways initiate melanosome aggregation and dispersion processes through catecholamine binding which leads to cyclic AMP (cAMP) and calcium (Ca2+) pathway activation. The adrenergic signaling system adjusts to different environmental factors and endocrine disruptors which then creates changes to both pigmentation and behavioral patterns. The review examines how adrenergic receptor signaling works in the body and demonstrates its role in controlling melanophore functions. This review underscores the importance of adrenergic signaling in zebrafish as a model system that bridges fundamental cellular biology with translational applications in human health, drug development, and environmental toxicology, offering valuable perspectives for future interdisciplinary research.

The rules of prokaryotic cell design remain elusive. Here, a theory is presented for interpreting growth rate, overflow metabolism, respiration efficiency, and maintenance energy flux based on cell dimensions, membrane protein crowding, and metabolism. The theory employs biophysical properties and systems analysis to successfully interpret phenotypes of Escherichia coli K-12 strains MG1655 and NCM3722. These strains are genetically similar but differ in surface area-to-volume (SA : V) ratios (~ 30%), growth rate on glucose (~ 40%), and overflow-inducing growth rates (~ 80%). Six predictions were tested and validated using experimental phenomics, proteomics, and mutant data. Analyses did not require assumptions regarding cytosolic macromolecular crowding, highlighting the distinct properties of the theory. Cell geometry and membrane protein crowding are significant biophysical constraints of cell biology.

Hydrogel-based cellular drug delivery systems as living therapeutics: Micro/nanogel design, fabrication, and controlled release.

Mitochondria across the globe: Diverse voices, shared energy.

Engineering the esophagus: advances, challenges, and translational pathways in esophageal tissue reconstruction.

Abstract Introduction and aims Skin being the largest organ in the body has three layers: epidermis, dermis and hypodermis. The epidermal layer itself has multiple layers with self-renewal capabilities. Malignant transformation of keratinocyte carcinoma occurs owing to failure in the completion of differentiation programme, which can lead to dysplastic epithelium and precancerous cells in skin. E74-like factor (ELF)5 is a member of the E26 transformation-specific (ETS) family of transcription factors, predominantly expressed in some epithelial tissues including skin and is known to have an antitumorigenic role in other epithelial tissues. We have shown that ELF5 is essential for normal keratinocytes proliferation, differentiation and stem/progenitor maintenance in mouse skin and loss of ELF5 in human immortalized keratinocytes can lead to tumorigenesis. Further analysis is required to clearly define the role of ELF5 in malignant keratinocyte development. Methods Our investigations provide novel approach into the role of ELF5 in keratinocytes activities and its malignant transformation. Using cancer cell lines such as SCC-13, A431 and SCC-9, we transduced cells lentiviral particles (ELF5 control and ELF5 overexpression) with subsequent Fluorescence-activated cell sorting live cell sorting, followed by transcriptomic (RNA sequencing analysis) and proteomic analyses (quantitative polymerase chain reaction, Western blot analysis) and functional studies (migration transwell assay, soft agar and three-dimensional colony-forming assay) in vitro. Results Our findings suggest that overexpression of ELF5 is instrumental in reducing migrations and inhibiting skin tumorigenesis, thus representing a potential target for future therapeutic interventions in malignant. Conclusions Our data demonstrate an important understanding of ELF5 as a crucial regulator of keratinocyte malignant transformation and will provide better understanding of the novel transcriptional regulator in skin in many areas of research, including stem cell and cancer biology.