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To investigate the effects of young human red blood cell-derived extracellular vesicles (Y-RBCEVs) on fracture healing. Associations of RBC-related indicators with bone mineral density and mortality in fracture populations were analyzed using NHANES data (1999-2020). A murine femoral fracture model was established to investigate RBC transfusion effects. Y-RBCEVs and O-RBCEVs were isolated to examine their effects on osteogenic differentiation and BMM polarization in vitro. In vivo distribution was assessed by IVIS, and therapeutic efficacy was evaluated in fracture mice. Proteomic sequencing identified differentially expressed proteins between Y-RBCEVs and O-RBCEVs, and key protein function was investigated by transcriptomic analysis and in vitro validation. The observational study revealed associations between RBC count and bone mineral density with fracture populations mortality. RBC transfusion modulated the expression of osteogenic and M2 macrophage polarization-related genes. In vitro, RBCEVs were efficiently internalized by BMSCs and BMMs, with Y-RBCEVs enhancing osteogenic activity in BMSCs and promoting M2 macrophage polarization, thereby partially restoring osteogenesis impaired by inflammatory conditions. In vivo, Y-RBCEVs accumulated at fracture sites and enhanced bone regeneration without detectable toxicity, accompanied by increased OCN and CD206 expression. Proteomic analysis identified VCAN as one of the potential functional cargos. Mechanistically, Y-RBCEV-derived VCAN interacted with CD44 on macrophages and was associated with activation of the PI3K/AKT pathway, contributing to M2 polarization. Y-RBCEVs enhance fracture repair by modulating osteogenesis and macrophage polarization, with VCAN-associated CD44/PI3K/AKT signaling contributing to their osteo-immunomodulatory effects. These findings highlight RBCEVs as a potential therapeutic strategy for bone regeneration.

Escherichia coli is the most commonly isolated bacterium in cases of diarrhoea in calves under the age of 2 months. This study aimed to identify E. coli strains with immunogenic potential by characterizing isolates from diarrheic calves through antigenic profiling and genotyping. The phenotypic and genotypic antibiotic resistance characteristics and virulence genes of the E. coli strains isolated from 500 faecal samples were examined, of which 88 were further genotyped using the Multiple-Locus Variable-Number Tandem Repeat Analysis (MLVA) method. Subsequently, 20 E. coli strains were selected based on their antibiotic resistance patterns and genetic typing (MLVA) results, and subjected to an analysis of their outer membrane vesicle profile. Among these, strains Ec048 and Ec026 exhibited high OMV diversity and were identified as promising candidates for further immunogenic evaluation. Immunization of experimental animals with these strains enhanced humoural immune responses (IgG, IgM, CD20), whereas cellular immune parameters (CD4, CD8) showed no significant change. In conclusion, the study demonstrates that strains Ec048 and Ec026 elicit strong humoural immune responses, indicating their potential for vaccine development. However, protective efficacy was not assessed, and further studies including challenge experiments are required to confirm their suitability as vaccine strains.

Flow diverters (FDs) have revolutionized intracranial aneurysm management, but current permanent metallic devices remain constrained by their bulk and surface properties, which induce chronic inflammation, thrombotic risk, and impaired vessel-wall integration. In this review we address these material-driven design challenges, examining how bioactive bioabsorbable biomaterials can overcome current limitations by balancing scaffold resorption with aneurysm occlusion. Moving beyond the clinical focus of existing literature, we establish a rational design roadmap bridging the gap between bulk material properties and FD architecture. We analyze how synchronized degradation kinetics and neointimal encapsulation govern device functionality, identifying this biological isolation as a necessary safety requirement to ensure resorption occurs only after the scaffold is shielded from the active flow. We analyze the mechanical-biological trade-offs of current platforms, whereby bioabsorbable polymers offer superior flexibility but limited radial support, whereas bioabsorbable metals provide higher mechanical integrity but require precision control over degradation. Hybrid strategies, combining transient and permanent components, emerge as effective solutions to balance mechanical reliability with controlled resorption. Across material classes, sustained flow diversion and vascular healing are primarily dictated by the interplay of scaffold architecture, material composition, and time-dependent surface evolution. Our analysis highlights that converging bulk material selection with advanced interfacial engineering enables the rational design of bioabsorbable FDs that maintain temporary mechanical integrity, while ensuring predictable aneurysm occlusion. These design principles establish a scientific framework for next-generation bioactive neurovascular implants, emphasizing a materials-driven approach to optimize safety and translational potential.

Recurrence of posterior tibial translation (PTT) is one of the challenges of posterior cruciate ligament (PCL) reconstruction. Several studies have emphasized the importance of protecting the transplanted graft. However, the impact of such protective measures on clinical outcomes has rarely been investigated. The purpose of this study was to compare postoperative outcomes between conventional and modified rehabilitation (CR and MR, respectively) protocols after double-bundle PCL reconstruction. It was hypothesized that an MR protocol designed to protect the transplanted graft, combined with a dynamic PCL brace, would improve PTT and patient-reported outcomes (PROs) compared with CR. Cohort study; Level of evidence, 3. This study included 25 patients with isolated grade 2 or 3 PCL injuries who underwent double-bundle reconstruction using autogenous hamstring grafts between 2017 and 2022. Patients were categorized into 2 groups: the CR group (n = 14), which received CR without a dynamic PCL brace, and the MR group (n = 11), which received MR with a dynamic PCL brace. PTT was evaluated by gravity sag view radiographs preoperatively, immediately after surgery, and at 3 months, 6 months, 1 year, and 2 years after surgery. PROs were assessed using the Knee injury and Osteoarthritis Outcome Score (KOOS) at 2 years. PTT decreased from preoperative to immediate postoperative evaluation in both groups without a significant difference between the 2 groups (CR group: 9.9 &#xb1; 3.0 mm to -1.0 &#xb1; 1.9 mm; MR group: 9.6 &#xb1; 3.5 mm to -1.4 &#xb1; 0.5 mm). At 3 months, 6 months, 1 year, and 2 years after surgery, the CR group demonstrated PTT of 3.7 &#xb1; 1.5, 4.0 &#xb1; 1.7, 4.4 &#xb1; 1.6, and 4.7 &#xb1; 1.7 mm, respectively, whereas the MR group demonstrated significantly smaller values of 0.8 &#xb1; 1.9, 1.9 &#xb1; 1.6, 2.6 &#xb1; 2.1, and 2.6 &#xb1; 2.2 mm, respectively (P < .05). Residual posterior sagging (PTT >5 mm) occurred in 29% of the CR group and 9% of the MR group (P = .34). No major complications were observed. The KOOS Sport and Recreation subscale score tended to be higher in the MR group. MR with a dynamic PCL brace to protect the graft significantly improved tibial position after PCL reconstruction compared with CR, without increasing the risk of complications.

Dicentrine, an aporphine alkaloid isolated from Ocotea langsdorffii, was evaluated for its in vitro antileishmanial activity against Leishmania (L.) infantum, Leishmania (L.) amazonensis, and Leishmania (V.) braziliensis. Cytotoxicity was assessed in murine peritoneal macrophages, and the mechanism of action was investigated in L. (L.) infantum promastigotes by evaluating mitochondrial membrane potential (&#x394;&#x3a8;m), reactive oxygen species (ROS) production, and plasma membrane integrity. Dicentrine exhibited potent activity against promastigote and intracellular amastigote forms, with EC50 values ranging from 0.86 to 1.64 &#xb5;g/mL. The compound showed low cytotoxicity toward macrophages (CC50 = 162.5 &#xb5;g/mL), resulting in high selectivity indices (up to 188.3). Mechanistic studies revealed significant disruption of &#x394;&#x3a8;m and a dose-dependent increase in ROS production, indicating mitochondrial dysfunction and oxidative stress as key events in parasite death. These findings highlight dicentrine as a promising lead for antileishmanial drug development.

To establish normative reference ranges for diencephalon diameter, falx cerebri length, and the diencephalon/falx (D/F) ratio between 11&#x2009;+&#x2009;6 and 13&#x2009;+&#x2009;6&#x2009;weeks of gestation and to evaluate their relationship with crown-rump length (CRL). This prospective observational study included 676 fetuses during routine first-trimester screening; three fetuses were excluded from this study with major cerebral anatomical defects. Using a standardized mid-sagittal plane, the diencephalon (maximum anteroposterior distance) and falx cerebri were measured. The D/F ratio was calculated, and quantile regression was used to generate 5th, 50th, and 95th percentile curves associated with CRL. Diencephalon diameter increased progressively with CRL, while falx cerebri length showed modest growth. The D/F ratio demonstrated a slight inverse relationship with CRL. Two cases of midline defects (agenesis of the corpus callosum) were identified; the D/F ratio was abnormal in one case but remained within normal limits in the second. Diencephalon and falx measurements are reproducible during the first trimester. While the proposed quantile-based nomograms provide a robust normative framework, the isolated use of the D/F ratio may have limitations in detecting certain midline anomalies. These landmarks should be regarded as adjunctive markers and should be interpreted as part of a comprehensive first-trimester fetal neurosonographic assessment.

Multidrug-resistant Klebsiella aerogenes poses a significant clinical challenge due to its antimicrobial resistance and biofilm-forming capacity in chronic wounds and device-associated infections. Bacteriophage therapy offers a promising alternative to conventional antibiotics, though effective delivery systems remain critical for clinical translation. This study reports the isolation, genomic characterization, and alginate hydrogel-based formulation of a lytic bacteriophage, KA_SGEB_01, targeting multidrug-resistant K. aerogenes. The phage was isolated from hospital sewage using multidrug-resistant K. aerogenes as a host. Comprehensive characterizations included plaque morphology and host range determination, multiplicity of infection (MOI) optimization, one-step growth kinetics, antibiofilm activity assays, and environmental stability testing. Complete genome sequencing and annotation were performed. Phage-loaded alginate hydrogels were developed and evaluated for release kinetics, long-term viability, and antibiofilm efficacy. KA_SGEB_01 produced clear plaques (1 &#xb1; 0.1 mm) with halos indicative of depolymerase activity and exhibited strict host specificity. The optimal MOI was 0.01 with a 15-minute latent period and the phage remained stable between -20 &#xb0;C and 50 &#xb0;C; and across a pH range 6-9. Biofilm assays demonstrated around 60% Crystal-Violet-stained biomass reduction as well as significant biofilm disruption visualized by Scanning Electron Microscopy. Whole-genome sequencing revealed a 175,095 bp double-stranded DNA genome encoding 289 predicted coding sequences, classified within the family Straboviridae, genus Slopekvirus, and lacking any virulence or AMR genes. Encapsulation in alginate hydrogels preserved viability (>10&#x2079; PFU/mL) for 14 days and enabled sustained release (&#x223c; 67% at 72 h), resulting in significant biofilm biomass inhibition. Collectively, KA_SGEB_01-loaded alginate hydrogels represent a promising platform for treating multidrug-resistant K. aerogenes in wound and device-associated infections caused by the bacterium.

A new diketomorpholine, myromopholine A (1), was isolated from the wetland fungus Myrothecium gramineum (ZLW0801-19). Through extensive spectroscopic analyses, including IR, MS, NMR, and X-ray single crystal diffraction, the planar structure and absolute configuration of the compound were determined, revealing the presence of a rare D-phenyllactic acid moiety. The investigation represents the first reported isolation of a diketomorpholine compound from the genus Myrothecium. Furthermore, it is the first identification of a diketomorpholine bearing a D-phenyllactic acid unit from a natural source, challenging the conventional understanding that such natural products exist exclusively as L-form derivatives.

Non-Hodgkin lymphoma (NHL), predominantly B cell lymphomas (B-NHL), is currently treated with chemotherapy combined with rituximab (RTX), an anti-CD20 monoclonal antibody. Despite substantial therapeutic advances, treatment resistance and disease relapse continue to affect a significant fraction of patients. The mechanisms by which the tumour microenvironment and other factors influence RTX efficacy are not fully elucidated. Herein, we hypothesized that CD20+ extracellular vesicles (EVs) shed by B cell lymphomas are recognized by RTX forming immune complexes that modulate natural killer (NK) cell activity via Fc&#x3b3; receptor (Fc&#x3b3;R) interactions. EVs isolated from lymph node explants and plasma samples of B-NHL patients contained abundant CD20+ vesicles, which were particularly enriched in advanced disease. RTX specifically bound CD20 on these EVs, generating EV-RTX immune complexes. Functional studies employing EVs from a B-NHL cell line and from patient-derived samples demonstrated that, whereas EVs suppressed NK cell activation and cytotoxicity, EV-RTX immune complexes reversed this inhibitory effect and enhanced NK cell effector functions. Indeed, EV-RTX immune complexes specifically triggered Fc&#x3b3;RIIIa-dependent NK cell activation, evidenced by increased Syk phosphorylation, CD69 expression, and enhanced lytic activity against target cells. Our findings uncover a previously unrecognized mechanism by which RTX, through the formation of immune complexes with CD20+ EVs, promotes NK cell activation and may enhance therapeutic efficacy. More broadly, these results demonstrate that antibody binding can endow EVs with novel immunomodulatory properties, revealing a potential mechanism by which therapeutic antibodies reshape EV function and influence anti-tumour immunity.

Perilunate dislocations (PLD) and perilunate fracture-dislocations (PLFD) are uncommon but severe carpal injuries. Although open or arthroscopic-assisted reduction with capsuloligamentous repair is recommended when feasible, access to suture anchors, appropriate nonabsorbable sutures, wrist arthroscopy, and advanced imaging may be inconsistent in resource-limited trauma settings. In such circumstances, temporary K-wire stabilization without formal ligament repair may represent a pragmatic stabilization strategy. We retrospectively reviewed 11 consecutive patients with acute PLD or PLFD treated between July 2019 and June 2024 in a single-center retrospective therapeutic case series (Level IV evidence). All patients underwent attempted fluoroscopic closed reduction followed, when necessary, by open reduction. Stabilization consisted of scapholunate and lunotriquetral pinning using two 1.6-mm&#x2009;K-wires, without formal ligament repair; associated fractures were fixed with K-wires as indicated. Outcomes included pain (VAS), QuickDASH, PRWE, Mayo Wrist Score (MWS), wrist range of motion, and grip strength. Radiographs assessed scapholunate distance (SLD) and scapholunate angle (SLA). Mean age was 36.9 years and 81.8% of patients were male. All injuries resulted from high-energy trauma (nine road-traffic accidents and two sports-related injuries). Five patients had PLD and six had PLFD. Closed reduction was successful in three cases; eight required open reduction (six dorsal and two combined dorsal-volar). Mean follow-up was 50.5 months. Mean VAS was 3. Mean QuickDASH was 30.4, PRWE 37.5, and MWS 78.5. Mean flexion-extension arc was 101.8&#xb0; and mean grip strength was 75.2% of the contralateral side. Mean SLD was 3.0&#x2009;mm and mean SLA was 61.8&#xb0;. No pin-tract infection, K-wire migration, avascular necrosis, or radiographic osteoarthritis was observed at mid-term follow-up. In this small Level IV case series, isolated K-wire stabilization without formal ligament repair was associated with heterogeneous mid-term outcomes after acute PLD and fracture-dislocations. Partial functional recovery was observed in many patients, but residual scapholunate malalignment persisted in some cases. These findings are descriptive and hypothesis-generating and should be interpreted cautiously in the absence of a comparative cohort. They should not be viewed as evidence of equivalence to ligament-repair techniques.

This dataset reports the isolation and genomic characterization of vB_RsoP_PBa1, a novel Caudoviricetes phage that infects Ralstonia pseudosolanacearum GMI1000. The phage was isolated and enriched using double-layer agar plaque assays. Genomic analysis revealed that vB_RsoP_PBa1 possesses a linear double-stranded DNA genome of 42,068 bp with a G+C content of 62.44%, encoding 53 predicted coding sequences, of which 18 were assigned putative functions. The annotated open reading frames include functional modules for genome packaging, virion assembly, host lysis (holin, lysozyme, and a helix-turn-helix domain-containing protein), host infection, genome replication, and phage integration. Phylogenetic analyses based on the proteomic and the terminase large subunit amino acid sequences demonstrated that vB_RsoP_PBa1 is most closely related to Ralstonia phage DU_RP_II (MF150911.1), with which it shares 78.8% average nucleotide identity. Overall, this dataset provides a valuable genomic resource for comparative phage genomics and supports the development of phage-based biocontrol strategies against bacterial wilt caused by R. pseudosolanacearum.

Traumatic brain injury (TBI) involves both primary and secondary pathological processes, including hemorrhage, ischemia, edema, and neuroinflammation. Although tissue-derived exosomes have emerged as important mediators of intercellular communication within local tissue microenvironments, their role in TBI-associated inflammatory responses remains incompletely understood. This study integrated brain tissue-derived exosomal proteomics with publicly available hippocampal transcriptomic data to investigate the potential association between tissue-derived exosomes and chemotaxis-related inflammatory responses after TBI. Brain tissue-derived exosomes were isolated, characterized, and subjected to label-free proteomic analysis. Public hippocampal transcriptomic data from GSE173975 were analyzed, and differentially expressed proteins (DEPs) and genes (DEGs) were identified from the exosomal proteomic and transcriptomic datasets, respectively. Functional enrichment, co-enrichment, and protein-protein interaction network analyses were performed, followed by quantitative real-time PCR, exosomal western blotting, and Transwell migration assays for validation and functional assessment. In total, 190 DEPs and 465 DEGs were identified. Co-enrichment analyses highlighted immune- and inflammation-related processes, particularly chemotaxis-related processes and chemokine signaling. LGALS3 and ITGB2 were increased at the exosomal protein level in brain tissue-derived exosomes from TBI rats and also showed increased hippocampal mRNA expression, whereas CCL2, CCL3, and CCR5 were upregulated at the hippocampal mRNA level. Functionally, TBI-derived exosomes enhanced BV2 microglial migration in vitro. Overall, these findings suggest that injury-associated brain tissue-derived exosomes may be associated with chemotaxis-related inflammatory and pro-migratory responses after TBI.

Periodontitis is a common disorder that causes tooth loss. Osteogenic differentiation of periodontal ligament stem cells (PDLSCs) is crucial for repairing periodontal defects. This study aimed to investigate the underlying mechanism by which Shikonin promotes the osteogenic differentiation of PDLSCs. PDLSCs were isolated from the periodontal ligaments of orthodontically extracted premolars. Flow cytometry was used to characterize the cell surface markers of PDLSCs. PDLSCs were cultured in osteogenic induction medium and treated with Shikonin. Alkaline phosphatase (ALP) and Alizarin Red&#xa0;S (ARS) staining were used to evaluate ALP activity and assess calcium nodule formation, respectively. Protein levels were determined by Western blot analysis. A dual-luciferase reporter assay and chromatin immunoprecipitation analysis confirmed the interaction between the ETS transcription factor 1 (ELK1) and cementum protein 1 (CEMP1) promoter. Shikonin promoted the osteogenic differentiation of PDLSCs (about 7.6 folds for ALP staining and about 6.9 folds for ARS staining with 1&#xa0;&#x3bc;m Shikonin, p&#xa0;<&#xa0;0.01). Shikonin-mediated enhancement of osteogenic differentiation was achieved by promoting the phosphorylation of ELK1 through the activation of the p38 MAPK signaling pathway (p&#xa0;<&#xa0;0.05). Moreover, ELK1 accelerated osteogenic differentiation and transcriptionally activated CEMP1 expression (p&#xa0;<&#xa0;0.05). Activation of the ELK1/CEMP1 axis contributed to Shikonin-induced osteogenic differentiation of PDLSCs (p&#xa0;<&#xa0;0.05). Shikonin promotes the osteogenic differentiation of PDLSCs in vitro by modulating the p38 MAPK/ELK1/CEMP1 axis.