Browse Articles

PALLADIN regulates osteogenic differentiation of bone marrow mesenchymal stem cells and protects against bone loss in ovariectomized mice

Abstract Osteoporosis is a systemic skeletal disease associated with reduced bone density and impaired bone quality, which leading to a greater risk of fracture. The pathogenesis of osteoporosis is closely associated with compromised osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). The actin-cytoskeleton associated protein PALLADIN has been reported to play a central role in the remodeling of the actin-cytoskeleton. However, no studies to date have established whether PALLADIN can influence osteogenic differentiation of BMSCs or the onset of osteoporosis. Here, PALLADIN knockdown was observed to reduce osteogenic differentiation of BMSCs, confirming the involvement of the gene in osteoporosis. Knockdown also altered the cytoskeletal organization and reduced Ras homolog family member A (RhoA) activity to inhibit osteogenic differentiation. The results of the in vivo experiments showed that overexpression of Palladin reversed bone loss and marrow adipose tissue (MAT) accumulation in OVX mice, while Palladin knockdown increased both bone loss and MAT accumulation in OVX mice. Together, these results suggest a model in which Palladin protects against bone loss induced by OVX through the promotion of BMSCs osteogenesis. In human osteoporotic BMSCs, PALLADIN expression is significantly downregulated, correlating with disease status. While functional validation in primary human osteoporotic BMSCs remains to be performed, these preclinical findings establish Palladin as a novel regulator of BMSCs osteogenic differentiation and provide a foundation for future efforts to characterize the pathogenesis of osteoporosis and identify new therapeutic targets.

Aneuploidy selects for the acquisition of driver genes in breast cancer

Uncovering Electron-Transfer Mechanisms of Sulfur Anion Photosensitizers with Intramolecular Charge Transfer

Integrating spatial, temporal and magnitude probabilities for landslide hazard assessment along a major road corridor in Darjeeling Himalayas

Broad-Spectrum Absorption and Microsecond Excited State in Copper-MOFs for Boosting Organic Photosynthesis

An enhanced YOLOv10 framework for small-object safety helmet detection on construction sites

Quaternary <i>N</i> -Heterobenzylic Carbon Centers via Allene-Mediated C–H Functionalization of Azines/Azoles: Ruthenium-Catalyzed Dearomative Addition-Hydrogen Auto-Transfer

Predicting fuzzy topological indices from crisp indices in hexagonal and honeycomb networks using linear regression

Understanding the landscape of hereditary breast and ovarian cancer testing in Brazil

Judicious use of LLMs could speed up progress in the social sciences

Correction: 1H-NMR serum metabolomic profiling from clinical routine identifies signatures of progressive melanoma metastasis

Atroposelective Bromination for the Synthesis of Chiral Biaryl Phosphines via Cross-Assembled Catalysis with Chiral Phosphoric Acid and Achiral Phenol

Efficacy of mental and physical training on blood pressure and resting heart rate among physically inactive young adults with elevated blood pressure: a randomized controlled trial

Endowing Metal Oxychloride Solid Electrolytes with Improved Li Compatibility

Modeling the resilient modulus of railway subgrade material considering the effects of initial stress state under long-term cyclic loading

Universal cell embedding provides a foundation model for cell biology

Visible-Light-Enabled Ir-Catalyzed Asymmetric Allylic Etherification and Dearomative Photocycloaddition

Effects of dynamic neuromuscular stabilization on balance, gait, and quality of life in older adults: a randomized controlled trial

Abstract Age-related declines in neuromuscular and sensory systems substantially increase fall risk and impair independence in older adults. Exercise interventions improve balance and gait; however, the maintenance of these training-induced gains over time remains uncertain, as most benefits may diminish within months after training ceases. This study determined whether an 8-week Dynamic Neuromuscular Stabilization (DNS) programme produces post-intervention and short-term follow-up improvements in balance, gait speed, fear of falling, and health-related quality of life in community-dwelling older adults. In this assessor-blinded randomised controlled trial, 44 older adults aged 60–75 years were randomly allocated to either supervised DNS (totaling 24 sessions: three sessions per week for 8 weeks, 40–50 min per session) or a usual-activity control group. Outcomes were measured at baseline, immediately post-intervention, and at 2-month follow-up using validated clinical instruments. Thirty-nine participants completed the trial (DNS group, n  = 19; control group, n  = 20). Mixed-design ANOVA showed significant group × time interactions for all outcomes (all P  &lt; 0.001). At post-test, the DNS group exhibited large effect-size improvements compared with controls: static balance errors decreased by 58–74% (Cohen’s d = 2–2.65), dynamic balance scores increased by 36% (d = 2.05), gait speed increased by 28% (d = 1.54), fear of falling decreased by 42% (d = 1.92), and physical and mental health-related quality of life (HRQOL) components improved substantially (d = 2.20–2.28). At 2-month follow-up, these improvements were largely maintained without significant deterioration within the follow-up period ( P  &gt; 0.05). The control group exhibited no meaningful changes. An 8-week DNS intervention yields robust, clinically meaningful, and sustained short-term improvements across multiple domains related to fall risk in older adults. These short-term retained adaptations position DNS as an effective neurophysiologically based approach for fall prevention within the observed follow-up period. Trial registration: RTC, prospectively registered in the Clinical Trial Registry (UMIN000055127) on 29/12/2024.

An intrinsic cytoskeletal oscillator establishes neuronal polarity

Abstract Neurons acquire polarity by specifying one neurite as the axon, whereas the others become dendrites. But how this fundamental asymmetry is established remains unclear 1 . Neuronal polarization has been thought to rely primarily on growth cones that sense external cues 2 . Here we show that growth cones alone do not direct this process and that the soma acts as a central organizer of neuronal polarization. Using live imaging and genetic loss-of-function approaches in vivo, combined with optogenetic control and local cytoskeletal perturbations in cultured neurons, we uncover a soma-initiated oscillatory program that primes axon selection. Periodic actin branching that depends on the actin-related protein 2/3 (ARP2/3) complex at the soma remodels a global actomyosin network, thereby generating an actin wave that retracts neurites before propagating into a single neurite tip. Exposure to this wave relaxes local actomyosin contractility, which drives a transient microtubule-based protrusion and biases this neurite towards axon fate. As the cell exits this oscillatory stage, this neurite can overcome global inhibition and extend independently of ARP2/3, whereas actomyosin activity suppresses axon formation in the remaining neurites so that they subsequently become dendrites. This soma-driven mechanism ensures the emergence of a single axon independent of environmental cues and underpins the unidirectional information flow in neuronal circuits.

Ligand-Regulated Metallaphotoredox Aminoarylation for the Valorization of Feedstock Alkenes