Browse Articles

Spatial segregation and cross-kingdom interactions drive stingless bee hive microbiome assembly

Clinicoradiologic characteristics and management of orbital incidentaloma

Antiproliferative effect of Filopaludina bengalensis fluid inducing apoptosis-necroptosis synergy with immunogenic remodelling in triple-negative breast cancer

FGF4-FGFR1 signaling promotes podocyte survival and glomerular function to ameliorate diabetic kidney disease in male mice

Abstract Podocyte injury is central to diabetic kidney disease (DKD) pathogenesis, however, the mechanisms underlying podocyte loss remain unclear. Emerging evidence underscores the involvement of fibroblast growth factors (FGFs) in renal pathophysiology. Here we reveal a previously unappreciated role of podocyte-secreted FGF4 in safeguarding renal function. FGF4 expression is downregulated in renal tissues from DKD patients and animal models, correlating with disease severity. Podocyte-specific deletion of Fgf4 exacerbated podocyte loss and accelerated DKD progression in mice. Conversely, treatment with recombinant FGF4 (rFGF4) improved glomerular filtration and reduced renal injury and fibrosis in diabetic male mice. These effects are primary mediated by activating the FGFR1-AMPK-FOXO1 signaling cascade in podocytes, which mitigates oxidative stress, suppresses apoptosis, and fosters podocyte survival. Notably, rFGF4 also restores the morphology and function of human podocytes exposed to high glucose. Our findings establish FGF4 as a critical regulator of podocyte homeostasis and a potential therapeutic target for DKD.

In vitro study of retention forces in traditional and PEEK milled ball attachments with two retentive caps

Detecting automobile insurance fraud using a novel penalty-driven feature selection method with particle swarm optimization and machine learning classifiers

Active foam dynamics of tissue spheroid fusion

Hull form optimization with a new three-dimensional deformation strategy

Outbreaks of post-weaning diarrhea caused by ETEC F4 are strongly associated with CHCF1 genotype in Danish pigs

Evolving Southern Ocean overturning in warming climates

Abstract The Southern Ocean Meridional Overturning Circulation (MOC) has intensified in recent decades, yet the interplay between its Eulerian and eddy components under future warming remains uncertain. Using ensemble climate simulations, here we show that the Eulerian-mean MOC shifts poleward under high-emission scenarios during the twenty-first century, with compensating eddy-induced MOC sustaining a uniformly intensified residual overturning. This response is less pronounced under low-emission scenarios with climate mitigation. Likewise, a poleward-shifted Eulerian-mean MOC occurred during the Mid-Pliocene Warm Period, but with weaker, broader eddy compensation, leading to non-uniform intensified residual overturning. Across past and future warming climates, the eddy-induced MOC is primarily modulated by surface heat flux changes at lower latitudes and by freshwater flux changes at higher latitudes over the Southern Ocean. The buoyancy forcing changes drive northward Antarctic upwelling, promoting Antarctic bottom water formation. Along with MOC changes, ventilation intensifies in the lower latitudes of the Southern Ocean as related to the subduction branch, especially during the past warm period.

Quality by design optimisation of isothermal dry particle coating for enhanced buccal permeation of vancomycin

Abstract The formulation and manufacture of macromolecules for oral delivery present persistent challenges owing to high molecular weight, pH sensitivity and manufacturing complexity. Consequently, over 90% of FDA-approved biologics are administered by invasive methods. Buccal delivery offers a promising non-invasive alternative, as it bypasses first-pass metabolism, avoids gastrointestinal degradation, and can improve patient compliance. Here we evaluate isothermal dry particle coating (iDPC) as a scalable, solvent-free approach to enhance buccal permeation by forming ion-pair coatings on drug particles. In iDPC, centrifugal and gas-drag forces promote systematic collisions between host and guest particles, here vancomycin and L-glutamic acid, yielding uniform surface coverage that facilitates buccal permeation. This study utilised a Design of Experiments (DoE) methodology within a Quality by Design (QbD) framework to optimise iDPC processing for vancomycin, a Biopharmaceutics Classification System (BCS) Class III glycopeptide with poor oral bioavailability. A Central Composite Face (CCF) design was utilised to investigate the interactive effects of five critical process parameters (CPPs): pre-processing time, processing time, nitrogen flow rate, drum speed and amino acid concentration, on two critical quality attributes (CQAs): content uniformity and 60-minute permeation across TR146 buccal epithelium. Regression modelling identified that increases in L-glutamic acid concentration and drum speed were the key factors enhancing permeation, while processing time and drum speed were the key variables improving content uniformity. A predictive 4D design space identified operating regions with a high probability of simultaneously meeting prespecified targets (permeation ≥ 40% and RSD ≤ 5%). The models demonstrated strong fit (R 2 = 0.767 for permeation; 0.774 for content uniformity), with non-significant lack-of-fit, and performance improved markedly, with content uniformity ranging from 0.93 to 6.29% RSD and permeation increasing from 36% to 60% under optimised conditions. Mechanistic analysis indicated that drag from the nitrogen curtain impacted the fluidisation of cohesive L-glutamic acid fine particles, while total energy input promoted deagglomeration and dispersion, thereby improving uniformity. These findings demonstrate that iDPC is a robust manufacturing approach for buccal delivery of biologics, providing controlled particle level modification without the use of solvents. The QbD-driven DoE establishes clear links between CPPs and CQAs, supports the development of control strategies, and provides a basis for regulatory flexibility in the non-invasive delivery of large molecule therapeutics.

Design improvements and clinical evaluation of an adjustable clubfoot splint

Soft magnetic microrobots with remote sensing and communication capabilities

Abstract Remote communication in small-scale robotics offers a powerful way to enhance their capabilities, introducing options for state monitoring, multi-agent collaboration, and autonomous operation. Integrating common remote communication tools, such as antennas, into microrobots is challenging with conventional design and manufacturing techniques. We propose a concept that integrates shape-reconfigurable soft microrobots with flexible electronics, leveraging their elastic mechanical properties to enable remote communication. This approach, based on photolithography processes, is scalable and adaptable to various sensing applications. As a proof of concept, we present a microrobot, which integrates a thermoresponsive magnetic hydrogel, an anisotropic support structure, and a flexible dipole antenna into a cohesive three-layered design. The microrobot can morph from a helical shape at low-temperatures to a planar shape at high-temperatures. This shape transformation can be remotely detected by external radio communication receivers, enabling shape-state recognition and environmental temperature sensing. Furthermore, we show that the collective behavior of multiple microrobots enhances the recognition performance by amplifying the signal. The concept represents a significant advancement in co-engineering smart materials and flexible electronics, illustrating an approach of microrobotic embodied intelligence by integrating environmental monitoring, magnetic navigation, and remote signaling.

Antitumor effects of a novel glucose-conjugated bacteriochlorin for photodynamic therapy

Abstract Photodynamic therapy (PDT) is a minimally invasive cancer treatment that employs photosensitizers (PSs) activated by light to generate cytotoxic reactive oxygen species (ROS). Talaporfin sodium (TS), widely used in Japan, has shown limited efficacy in advanced tumors, highlighting the need for novel PSs. We developed a glucose-conjugated bacteriochlorin derivative, Glc-TFPB, designed to enhance tumor selectivity via the Warburg effect and to enable deep tissue penetration owing to its near-infrared absorption. In vitro, Glc-TFPB exhibited time-dependent cellular uptake, predominantly in lysosomes, and induced significant ROS generation and apoptosis upon PDT. Compared with TS, Glc-TFPB-PDT demonstrated markedly higher cytotoxicity 24 h after administration (IC50: 1.10 µM vs 13.60 µM). In vivo fluorescence analysis revealed peak tumor accumulation at 24 h after administration, consistent with optimal treatment timing. PDT with Glc-TFPB significantly suppressed tumor growth in xenografted mice, with greater efficacy at 24 h than at 2 h after administration. These findings indicate that Glc-TFPB is a promising next-generation PS with improved tumor selectivity, deeper tissue penetration, and superior photodynamic efficacy, supporting its potential for clinical translation.

eSolubilized amniotic membrane ECM as a promising biological surface treatment approach for 3D-printed bone tissue engineering scaffolds

Rational synthesis of dual-atom catalysts for optimized thermochemical CO2 reduction

Parental educational aspirations and children’s sleep: a mediation analysis

Intelligent prediction of air quality index based on the transformer-BiLSTM model

Topological turning points across the human lifespan

Abstract Structural topology develops non-linearly across the lifespan and is strongly related to cognitive trajectories. We gathered diffusion imaging from datasets with a collective age range of zero to 90 years old ( N  = 4,216). We analyzed how 12 graph theory metrics of organization change with age and projected these data into manifold spaces using Uniform Manifold Projection and Approximation. With these manifolds, we identified four major topological turning points across the lifespan – around nine, 32, 66, and 83 years old. These ages defined five major epochs of topological development, each with distinctive age-related changes in topology. These lifespan epochs each have a distinct direction of topological development and specific changes in the organizational properties driving the age-topology relationship. This study underscores the complex, non-linear nature of human development, with unique phases of topological maturation, which can only be illuminated with a multivariate, lifespan, population-level perspective.

A computational model of the cerebellar granular layer calibrated to experimental data for studying inhibition and sensory encoding

Abstract The cerebellar granular layer plays a central role in sensory processing and pattern separation through its distinctive feedforward architecture. Here, we present a biologically realistic computational model of the granular layer designed to explore the functional impact of synaptic inhibition mediated by Golgi cells. The model integrates anatomical and physiological constraints to simulate realistic mossy fiber activity patterns, including spatial correlations and varying activation levels. We validate the model by replicating key findings from recent in vivo experiments, such as the role of inhibition in shaping granule cell responsiveness and the emergence of nonlinear suppression during multisensory integration. Beyond validation, the model provides a robust computational tool for studying how inhibition contributes to energy-efficient and noise-resilient sensory encoding. Mechanistic analyses revealed that moderate inhibition levels optimize pattern separation performance, with feedforward and feedback inhibitory circuits exerting distinct effects on coding expansion and decorrelation. All model code and simulation scripts are openly available, offering a framework for generating testable hypotheses and further investigating cerebellar computation and learning mechanisms in divergent feedforward networks.