Browse Articles
Discover research articles across all indexed journals
Monocarboxylate transporter 2 regulates maintenance of myelin and axonal integrity by oligodendrocytes
Platelets under pressure: a sticky outside-in problem
Enhancing performance of gravitational water vortex turbines through airfoil design and basin parameters
Abstract Gravitational water vortex turbines (GWVTs) have emerged as promising hydrokinetic technology for energy extraction in riverine systems characterized by low flow velocity and ultra-low head, where conventional hydropower solutions are not feasible. In this study, a three-dimensional computational fluid dynamics (CFD) model is developed to investigate turbine performance within a conical basin configuration. The numerical framework, validated against published reference data, is used to systematically evaluate the influence of airfoil axial spacing, chord sizing, and airfoil profile, on vortex structure and power coefficient. The results demonstrate that basin-induced flow control plays a critical role in enhancing tangential momentum transfer to the rotor. Among the investigated cases, a configuration employing a NACA0024 ducted airfoil with a chord size of 35 mm and an axial spacing of 50 mm yielded the highest power coefficient of 0.419 compared to the baseline basin power coefficient of 0.313 and reached a maximum value of 0.736 at higher inlet velocities. Performance analysis based on tip speed ratio (TSR) further identified an optimal low-TSR operating range consistent with gravitational water vortex turbine characteristics. Compared with previous GWVT studies that focus on turbine geometry, the present work highlights the effectiveness of basin wall airfoil design as an impactful strategy for performance enhancement in low-head hydrokinetic applications.
Stewardship without walls: taming the unregulated antibiotic economy to contain antimicrobial resistance in Ethiopia
Ibrutinib in early stage CLL: Genetic risk factors and treatment outcome in the GCLLSG CLL12 trial
Watch & wait is the standard of care in asymptomatic early-stage chronic lymphocytic leukemia (CLL). The CLL12 trial investigated ibrutinib versus placebo in early-stage patients with intermediate to very high risk of progression, showing improved event-free survival (EFS) but no overall survival (OS) benefit10. Building on these findings, our analysis examined whether a significant benefit could be identified within distinct genetic subgroups. After a median follow-up of 69.3 months, there were 166 EFS and 32 OS events in 515 trial patients. In the placebo arm, del(17p), del(11q), +12, U-IGHV, and mutations in NOTCH1, ATM, NRAS/KRAS/BRAF, and NFKBIE correlated with shorter EFS. With ibrutinib, only del(17p) and TP53 and NFKBIE mutations significantly compromised EFS. Ibrutinib offered substantial EFS benefit in subgroups with U-IGHV, del(11q), +12, NOTCH1, ATM, and NFKBIE mutations. No EFS improvement was seen for asymptomatic early-stage patients with del(17p) or TP53 mutations. Ibrutinib provided no OS benefits in any genetic subgroup. Multivariable analysis revealed ibrutinib treatment as an independent favorable factor for EFS, while U-IGHV, del(17p), POT1, RAS/RAF, and NFKBIE mutations were adverse prognostic factors. The results confirm watch-and-wait as standard of care for early-stage CLL patients, especially in high-risk CLL characterized by del(17p) and/or mutated TP53. EudraCT Number: 2013-003211-22
Synthesis, structure, fluorescence properties and catalytic application of uranyl complexes supported by salen ligands
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.