Browse Articles

pH-dependent activation of the Na+/H+ antiporter NhaA and conformational dynamics of its N-terminus

Abstract Na⁺/H⁺ antiporters are vital for regulating intracellular pH and sodium ion levels across all domains of life. In Escherichia coli , NhaA is the principal Na⁺/H⁺ antiporter, exhibiting strong pH sensitivity and rapid turnover, yet the structural transitions underlying its activation and substrate recognition have remained obscure. Here, we use single-particle cryo-electron microscopy to determine the conformational ensemble of NhaA across a physiological pH range and in the presence of Na⁺, complemented by constant-pH molecular dynamics simulations. High-resolution structures of apo and Na⁺-bound NhaA reconstituted in lipid nanodiscs reveal progressive opening of the cytoplasmic funnel with increasing pH. We also visualize the previously unresolved N-terminal tail, which forms a dynamic plug at the cytoplasmic entrance under low-pH conditions and disengages at alkaline pH, coinciding with activation. The Na⁺-bound structure captures Na⁺ coordination at the ion-binding site, and simulations suggest potential roles for the conserved charged residues. Together, these findings illuminate how pH sensing, N-terminal gating, and substrate binding are structurally coordinated in NhaA, providing a framework for understanding Na⁺/H⁺ antiporter activation and regulation, and the basis for targeting clinical important antiporters.

Hybrid cooperative complex treatment is associated with reduced facial pore size in a pilot study

Abstract Enlarged facial pores are a common aesthetic concern associated with aging and reduced dermal support. Hybrid Cooperative Complex (HCC), a stabilized hyaluronic acid formulation, has been proposed to improve skin quality through bioremodeling. This prospective observational pilot study evaluated changes in facial pore size after treatment with Hybrid Cooperative Complex (HCC) using standardized photography, clinical assessment, and validated rating scales. Ten healthy adult participants received two treatment sessions according to the Bio Aesthetic Points protocol, and outcomes were assessed at baseline and on Days 30, 60, 120, and 180. Visible improvement in facial pore size and skin texture was observed after treatment. Peak pore refinement was noted at Day 120 in most participants, while partial regression was observed in many cases by Day 180, although skin quality remained improved compared with baseline. HCC may be associated with visible improvement in facial pore size and skin quality in this pilot cohort. Changes in pore morphology may represent a practical clinical marker for estimating maintenance treatment timing, although larger controlled studies are needed.

Efficacy of Pam3CSK4 as a cross-species adjuvant for polysaccharide vaccines in humanized mouse and non-human primate models

Abstract Polysaccharide-based vaccines are essential for preventing bacterial infections, but their effectiveness is limited by weak antibody responses and lack of suitable adjuvants. TLR4 agonists enhance polysaccharide-specific antibody responses through B cell–intrinsic TLR4-MyD88 signaling in mice, but this mechanism is not conserved in primates, prompting the search for alternative MyD88-activating agonists. In vitro, the TLR1/2 agonist Pam3CSK4 synergizes with strong BCR crosslinking to enhance activation and antibody secretion by mouse and human B cells. In vivo, Pam3CSK4 in squalene emulsion increases protective pneumococcal polysaccharide–specific antibody responses in both immunocompetent and humanized mice. Although a dual TLR2/7 agonist shows strong in vitro activity, it fails to enhance polysaccharide-specific IgG responses in vivo, consistent with antagonism observed when Pam3CSK4 and TLR7 agonists are combined. In contrast, incorporating Pam3CSK4 into an adjuvant containing a TLR4 agonist, synthetic cord factor, and squalene emulsion further enhances memory B cell generation and protective antibody responses in mice and restores adjuvant activity in non-human primates, supporting Pam3CSK4-based formulations as promising adjuvants for polysaccharide vaccines.

Luminescent heparin-functionalized carbon dots with potential applications in nanoparticle-protein interactions and cell imaging

Basolateral amygdala dopamine transmits emotional salience

Influence of microwave excitation mode and antenna-sample orientation on rebar detection using microwave infrared thermography

Reducing P-O bond covalency in polyanionic groups to increase the intrinsic electronic conductivity in sodium positive electrodes

Collagen-derived biomarkers reveal distinct fibrotic responses among cancer-associated fibroblasts

Recognition of non-standard base pairs by triplex-forming oligonucleotides containing an expanded genetic alphabet

Abstract The sequence-specific recognition of double-stranded DNA by biocompatible molecules is fundamental to molecular medicine and synthetic biology. Triplex-forming oligonucleotides (TFOs) enable programmable major groove recognition via Hoogsteen base pairing; however, the limited repertoire of natural nucleobases imposes strict constraints on target sequences and parallel motif triplexes require acidic conditions for stability. Here, we have expanded the triplex recognition space using nucleobases from an artificially expanded genetic information system (AEGIS). Through a systematic evaluation of 120 base triad combinations, we identify at least 12 modular triads that can be combined interchangeably to target duplex DNA containing standard, damaged, or synthetic base pairs with nanomolar affinity at neutral pH. We further demonstrate the versatility of this expanded recognition code by detecting oxidative lesions or AEGIS base pairs in enzymatically assembled duplex constructs using both chemically and enzymatically synthesized TFOs. This generalized framework provides a robust platform for precision gene-targeting, molecular sensing, and nucleic acid nanotechnology.

Identification of cannabichromevarin as a potent stabilizer of the measles virus prefusion F protein: structural insights from long-timescale molecular dynamics

Rethinking the use of deep learning methods for photovoltaic power forecasting

Abstract Accurate photovoltaic power forecasting is critical for grid stability, but remains challenged by weather uncertainties and difficulty integrating historical observations with forward-looking forecasts. We re-evaluate existing architectural choices in deep-learning models for time-series forecasting and demonstrate the importance of full encoder-decoder architectures and channel dependence modeling when both weather forecasts and historical data are available. Based on this insight, we propose Cross-Unet, a Transformer-based architecture featuring multi-scale temporal encoding, correlation-aware channel attention, and hierarchical cross-attention decoding to fuse historical generation data with weather forecasts. Evaluated on open-source datasets from four utility-scale plants in northern China and one aggregated plant in central Australia, using three types of forward-looking inputs: numerical weather prediction, satellite-derived irradiance, and AI-based weather model forecasts. Across the majority of evaluated configurations spanning five photovoltaic power stations, five forecasting horizons (4 hours to 7 days), and three forecast sources, Cross-Unet outperforms ten deep learning baselines and traditional operational benchmarks. By integrating advanced forecasting systems, such as modern AI weather models, into an end-to-end forecasting pipeline, Cross-Unet enables operational 15-minute-resolution predictions over 4-hour to 7-day horizons, supporting grid scheduling and energy trading.

ViT-ConvGAN: a hybrid model for spatiotemporal action recognition using video transformer and 3D CNN

Relief of GbDEAH12G repression on the GbNAC072C-GbHOX3 axis improves lint percentage in Gossypium barbadense

Depressive symptoms hopelessness self-efficacy and COVID-19-related stressors among pregnant women in Hungary across two pandemic waves

Abstract Depression and hopelessness during pregnancy may be intensified by public health crises, yet less is known about how pregnancy- and pandemic-related stressors differ across successive COVID-19 waves. This study examined depressive symptoms, hopelessness, self-efficacy, and COVID-19-related concerns among pregnant women in Hungary during two independent cross-sectional pandemic waves. A total of 692 pregnant women participated in Wave 1 and 459 in Wave 2. Participants completed the Edinburgh Postnatal Depression Scale, Beck Hopelessness Scale, General Self-Efficacy Scale, and the study-specific „Pregnancy during the coronavirus” questionnaire. EPDS categories did not differ significantly between waves; 11.8% of participants in Wave 1 and 10.5% in Wave 2 fell into the major depressive symptom range. Mild hopelessness was reported by 31.1% and 26.4%, and moderate/severe hopelessness by 3.2% and 3.3%, respectively. Confinement-related difficulties and daily disruption, as well as perceived support and positive reappraisal, were higher in Wave 1 than Wave 2, both p < 0.001. In Wave 2, unplanned or unwanted pregnancy was associated with higher depressive symptoms, hopelessness, and financial/housing concerns. Emotional distress and impaired coping was the strongest predictor of EPDS and BHS scores, while self-efficacy was a consistent negative predictor. These findings support pregnancy-sensitive mental health screening during public health crises.

Engineering human PEG10-based nanoparticles for RNA self-packaging, delivery and cancer therapy

Temporal dynamics of ammonia and nitrous oxide emissions following green crop residue recycling in soils

Abstract The recycling of green crop residues is promoted for enhancing soil organic carbon sequestration and health, but can also stimulate emissions of nitrous oxide (N₂O) and ammonia (NH₃). Soil tillage can lead to different residue distributions which affect contact with decomposers and local gas and solute diffusion. This study aims to quantify N₂O, NH₃, and carbon dioxide emissions from N-rich red clover residue subjected to three different distributions in the soil—surface, layered, and mixed—across three contrasting agricultural soils. The incubations were performed under laboratory conditions for 50 days at 15 °C, with a water-filled pore space of 60%. Gas fluxes as well as soil ammonium and nitrate contents were measured. Results showed that N₂O emissions were strongly influenced by soil type and residue placement, with sandy loam producing the highest cumulative fluxes, particularly in the mixed (17.4 kg N ha⁻ 1 ) and layered (11.5 kg N ha⁻ 1 ) treatments. NH₃ volatilization occurred almost exclusively from surface residues, peaking at 10.2 kg N ha⁻ 1 in sandy loam soil. Emission for N 2 O were significantly higher than previously reported for residues. These findings highlight that both residue placement and soil properties critically determine gaseous emission patterns.

Adaptive kNN graph model

Evolutionary transition from single-cell to multi-cell organisms: the role of surface waters and their hydrodynamics

Abstract The evolutionary transition from unicellular to multicellular organisms exhibited a sharp increase in metabolic rates, yet the physical conditions supporting this transition remain poorly understood. Here we propose that wide-spread hydrodynamic enhancement of nutrient delivery to the microorganisms in the Neoproterozoic Era constituted a necessary enabling condition for early multicellularity, complementing the effect of rising oxygen levels occurring at the same time. Along with conceptual arguments in support of this hypothesis, we define three testable hydrodynamic mechanisms (viscous-diffusive, viscous-convective, and inertial-convective) controlling nutrient uptake and largely applicable for both bed-attached and free-floating microorganisms. We also highlight a flow-bed interface in surface streams as potentially important hotbed for multicellularity breeding, complementing the mainstream perception on the defining role of early oceans. Overall, our results emphasize hydrodynamics as under-represented physical component in existing evolutionary frameworks and generate testable predictions linking organism size, flow conditions, and habitat type.

Bidirectional integrin β1 activation synergizes neurovascular coupling and enhances bone regeneration

Abstract Reconstruction of large segmental bone defects remains challenging because current grafting strategies often fail to coordinate angiogenesis, neurogenesis, and osteogenesis. Here we developed a functional scaffold (peptide/Talin1 plasmid/PLA–HA/GelMA, PTPG) capable of simultaneously delivering peptides and Talin1 plasmids. We hypothesized that this scaffold enables neurovascularized bone regeneration through bidirectional activation of integrin β1 (ITGB1). The REDV–IKVAV (Arg-Glu-Asp-Val-Gly-Gly-Gly-Ile-Lys-Val-Ala-Val) peptide triggers “outside-in” ITGB1 signaling in endothelial and Schwann cells, while Talin1 plasmid-mediated “inside-out” activation. This PTPG scaffold synergistically enhances cell proliferation, migration and secretion, which are eliminated by ITGB1 silencing. In vivo, PTPG scaffold promotes aligned neurovascular networks guiding bone deposition. Single-cell RNA sequencing demonstrates enrichment of endothelial H-type signatures and repair-associated Schwann cell phenotypes, with activation of ITGB1–focal adhesion kinase–paxillin signaling. Collectively, this scaffold integrates structural support with peptide and genetic cues to promote coordinated angiogenesis, neurogenesis, and osteogenesis, offering a promising strategy for functional bone regeneration.

Lattice boltzmann method for investigation of flow through square in-line cylinders with transverse oscillation