Browse Articles

Ductile and scalable 3 GPa steel via a hierarchical microstructural architecture

The 10-year RELEVANCE trial analysis

Valorization of agro-industrial and forestry biomass ashes as soil amendments: integrating chemical screening, leaching dynamics, and Beta vulgaris L. response

Abstract Sustainable management of biomass combustion ash is critical for circular economy transitions. This study provides a comprehensive evaluation of six biomass ashes (wood chips, forest residues, maize cobs, plum pits, sugar beet pulp, and distillery decoction) as potential soil amendments. Chemical characterization and leaching tests revealed high concentrations of Ca, K, Mg, and P, confirming significant agronomic potential. However, ashes from beet pulp and distillery decoction exceeded EU arsenic limits by up to 5.5-fold, with distillery decoction ash releasing 69% of its As during leaching. A pot experiment with Beta vulgaris L. demonstrated that ash application at 2–8 Mg ha⁻¹ consistently increased soil pH and enhanced fresh biomass by up to 59%, particularly when combining nutrient-rich and Ca-rich ashes. Nevertheless, high application rates of specific blended variants increased Pb and Cd uptake in roots, likely driven by dissolved organic carbon (DOC) mobilization. These findings indicate that while biomass ashes effectively correct soil acidity and improve crop yields, their valorization requires rigorous feedstock screening and dose control to ensure regulatory compliance and food safety.

SplitSeek-Pro: accurate prediction of splittable sites on protein structures

A novel G13-RAPGEF2-RAP1 signaling pathway critical for platelet adhesion and aggregation

Abstract Hemostasis and thrombosis are strongly dependent on the unique ability of platelets to rapidly activate integrin receptors and to firmly adhere to sites of injury under shear stress conditions. Central to integrin activation is the small GTPase RAP1, which itself is activated by guanine nucleotide exchange factors (GEFs). CalDAG-GEFI (RASGRP2) is the highest expressed and functionally dominant platelet RAP-GEF. However, a genome-wide association study also suggested a significant role for RAPGEF2 (PDZ-GEFI), a low-expressed RAP-GEF, in human platelet aggregation. Here, we used mice deficient in RAPGEF2 (megakaryocyte-specific, Rapgef2mKO), CalDAG-GEFI (Caldaggef1˗/˗), or both RAPGEF2 and CalDAG-GEFI (DKO) to characterize the contribution of RAPGEF2 signaling to platelet function, hemostasis, and thrombosis. RAPGEF2 protein was detected in murine and human platelets. Compared with control or Caldaggef1˗/˗ platelets, both RAP1 activation and integrin αIIbβ3-mediated aggregation were significantly diminished in DKO platelets. When compared with controls, Rapgef2mKO platelets exhibited reduced integrin activation, a more reversible aggregation response, and impaired adhesion under conditions of shear stress ex vivo and in vivo. Mechanistic studies strongly suggest that RAPGEF2 operates downstream of receptors coupled to the heterotrimeric G protein G13 (GNA13), such as αIIbβ3 and the thromboxane receptor. Together, our studies provide genetic evidence that RAPGEF2 in platelets operates downstream of G13 as an important regulator of RAP1 signaling and integrin activation, especially under conditions of elevated shear stress. These findings markedly improve our understanding of G protein signaling and integrin function in platelets, with potential implications for the development of improved platelet-targeted therapies for cardiovascular disease.

Synergistic use of brick and ceramic wastes with polyethylene glycol in high-performance fiber-reinforced composites

POLY-Senolytic nanoplatform for tumor-specific eradication of senescent tumor cells and mitigation of radiotherapy-induced immune resistance of cancer

Severe allergic transfusion reactions to group B/AB plasma or platelets in group O recipients are linked to α-Gal sensitization

Abstract Allergic transfusion reactions (ATR) are potentially lethal adverse events that occur in ∼0.3% to 6% of plasma or platelet transfusions. The main mechanism described is an immunoglobulin E (IgE)–mediated response to donor proteins, such as IgA and haptoglobin in deficient patients. Recently, in a nationwide retrospective observational study, we reported that group O recipients of group B or AB platelet concentrates or plasma were at significantly higher risk of severe ATR than recipients with other ABO combinations. Given the antigenic proximity between group B determinant and the galactose-α-1,3-galactose (α-Gal) epitope, we hypothesize a role for α-Gal IgE–mediated sensitization in these ATR. In this report, we investigated the presence of anti–α-Gal IgE in a cohort of 59 patients with severe ATR. We found that group O recipients of group B or AB blood components (plasma or platelet concentrates) were substantially more likely to exhibit high titers of group B cross-reactive anti–α-Gal IgE than other patients, supporting our hypothesis that α-Gal sensitization underlies these severe ATR. These findings suggest that α-Gal sensitization is an additional mechanism responsible for ATR in major ABO-incompatible transfusion and should be systematically explored in group O patients having received group B/AB plasma or platelets.

Novel biomass-based cellulosic biofiller from Artocarpus heterophyllus fruit seed outer peel: Extraction and characterization

Strain sharing and persistence of microbial pathogens colonizing the skin of residents in a regional nursing home network

Abstract Antimicrobial resistance (AMR) is a health threat disproportionately affecting nursing home (NH) residents. Surveillance and infection control in NHs are restricted to nares or perirectal cultures, overlooking skin colonization and multidrug-resistant organisms (MDROs) not recovered by selective media. Here, within the PROTECT trial NCT03118232, we show, that NH residents’ skin serves as a reservoir of transmissible MDROs. We analyzed 207 groin and axilla swabs from 38 residents across 15 California NHs using metagenomics, culturing, and genome sequencing. Culture detected MDROs in 10 of 38 residents (26.3%), including 4 (10.5%) with ESBL-producing Escherichia coli sequence type (ST)131/ST648 and 7 (18.4%) with methicillin-resistant Staphylococcus aureus . Skin microbiome analysis by metagenome-assembled genomes identified broader MDRO colonization, including 27 (71.1%) with E. coli ST93, 14 (36.8%) with Staphylococcus epidermidis ST2, 16 (42.1%) with Proteus mirabilis , 7 (18.4%) with Providencia stuartii , 7 (18.4%) with Enterococcus faecalis , and 5 (13.2%) with Pseudomonas aeruginosa . Colonization persisted after bathing. Clonal E. coli ST93 was shared by 27 residents across 9 facilities, and 5 resident pairs carried clonally related strains of ≥2 MDRO species, suggesting polymicrobial transmission. We confirmed skin as a reservoir of MDROs, utilizing metagenomics to detect colonization and transmission pathways, supporting AMR surveillance in long-term care.

Study on failure law and repair technology of weak surrounding rock in adjacent roadway under excavation disturbance

TRIM21-mediated ubiquitination of PARP1 regulated by the PI3K/AKT-STAT5A axis suppresses small cell lung cancer

Abstract Abnormal accumulation of Poly(ADP-ribose) polymerase 1 (PARP1) promotes cancer progression, yet its stabilization mechanisms remain unclear. Here, we identify E3 ubiquitin ligase tripartite motif-containing 21 (TRIM21) as a PARP1-binding partner. PARP1 interacts directly with TRIM21 via its 662-908 domain, while the PRY-SPRY domain of TRIM21 is essential for this binding. TRIM21 facilitates PARP1 polyubiquitination at residue K654, leading to its degradation. In small cell lung cancer (SCLC), TRIM21 is significantly downregulated, and its tumor-suppressive function is partly mediated through the degradation of PARP1, supporting genomic stability. Additionally, the PI3K/AKT pathway transcriptionally suppresses TRIM21 via transcription factor STAT5A, thereby stabilizing PARP1. Importantly, combining the PI3K/AKT inhibitor PKI-587 with the PARP inhibitor BMN673 synergistically inhibits tumor growth across multiple SCLC models, including cell lines, patient-derived organoids, and xenograft models. Collectively, our findings define a “PI3K/AKT-STAT5A-TRIM21-PARP1” axis critical for SCLC progression and propose its dual inhibition as a promising therapeutic strategy.

Effects of Rosa roxburghii and kiwifruit composite supplements on improving exercise performance and anti-fatigue in mice

A functional map of phosphoprotein phosphatase regulation identifies an evolutionarily conserved reductase for the catalytic metal ions

Retrobulbar microvascular and biomechanical changes associated with axial elongation in myopic eyes

Cu-Catalyzed dynamic kinetic asymmetric allylation enabled enantioselective assembly of sterically congested triaryl tertiary alcohols

The relationship between memorable tourist experiences and subjective well-being, the mediating role of emotions, and the moderating role of psychological resilience

Atomically precise Au8Pd1(DPPF)42+ catalyst orchestrates the synthesis and utilization of hydrogen peroxide

Progressive fusion and guidance-aware denoising for robust multimodal sentiment analysis

Supramolecular strategy for compartment pathogen clearance and immuno-metabolic homeostasis to treat periodontitis

Abstract Periodontitis is an inflammatory disease driven by bacterial infection and immune dysfunction. Immune-subversive bacteria in the periodontitis microenvironment, such as Porphyromonas gingivalis , can evade conventional therapies by invading cells and inducing lysosomal dysfunction. Here we develop an injectable supramolecular hydrogel through the co-assembly of recombinant human type I collagen (COL), poly-ε-lysine (PL), and puerarin (PUE). Supramolecular amorphization improves PUE’s solubility and permeability, enabling a dual-compartment antibacterial strategy via effective trans-barrier delivery. Extracellularly, PL and PUE synergistically disrupt bacterial membranes and metabolism, while concurrently mitigating bacterial toxin induced pro-inflammatory macrophage polarization. Intracellularly, the supramolecular complexes facilitate PUE accumulation in phagolysosomes. By counteracting local oxidative stress, the internalized PUE restores lysosomal acidification and alleviates bacteria-induced immuno-metabolic dysregulation. In vivo, the hydrogel manipulates the local inflammatory microenvironment and facilitates periodontal tissue repair. This study provides a clinically translatable supramolecular strategy for treating intracellular infections and restoring tissue homeostasis.