Titanium is widely acknowledged as the "gold standard" for dental implants because of its superior biocompatibility and osseointegration capabilities. However, it is limited by the possibility of metal allergies, aesthetic concerns such as gray discoloration visible through the thin gingiva, and the risk of corrosion. To overcome these limitations, metal-free implant materials, particularly yttria-niobia-stabilized tetragonal zirconia polycrystals ((Y,Nb)-TZP), have attracted increasing attention. Zirconia has been noted for its advantages, including promising mechanical properties, biocompatibility, aesthetics, and reduced bacterial adhesion. Despite these findings, comparative studies of sandblasted, large-grit, acid-etched (SLA) titanium and (Y,Nb)-TZP are limited. This study aimed to compare the in vitro osteogenic potential and in vivo osseointegration of sandblasted (Y,Nb)-TZP implants with those of conventional SLA titanium implants using 3-dimensional evaluation. (Y,Nb)-TZP implants demonstrated comparable in vitro and in vivo results to SLA titanium, despite significantly lower surface roughness. Early cell attachment and spreading were observed on (Y,Nb)-TZP, whereas alkaline phosphatase activity and late-stage osteogenic gene expression increased over time in both groups without intergroup differences. In in vivo experiments, no significant between-group differences were observed in bone-to-implant contact, bone area, and dynamic bone remodeling indices. Three-dimensional-based analysis revealed similar overall bone remodeling volumes but distinct spatial distributions of newly formed bone around the implant threads, providing additional insights into the subcortical peri-implant bone area. In conclusion, sandblasted (Y,Nb)-TZP implants exhibited osteogenic potential and osseointegration comparable to those of SLA titanium implants, supporting the potential clinical applicability of (Y,Nb)-TZP as an alternative implant material.

Bone and cartilage regeneration remains a major clinical challenge due to the limited intrinsic repair capacity of musculoskeletal tissues. Biomaterial strategies capable of regulating stem cell behavior at the single-cell level offer new opportunities for precise control of tissue regeneration. Herein, we developed tannic acid-metal (TA-metal) coordination systems incorporating Fe[3+], Sr[2+], and Mg[2+] ions as single-cell nano-coatings to modulate the pericellular microenvironment of bone marrow-derived mesenchymal stem cells (BMSCs). The physicochemical properties of the TA-metal coatings, including protein adsorption, surface morphology, surface charge, ion release behavior, and elemental composition, were systematically characterized. All TA-metal systems formed conformal coatings on individual cells with excellent cytocompatibility and showed detectable retention during early culture. The TA-metal nano-coatings significantly regulated cell morphology and cytoskeletal organization in a metal ion-dependent manner. Notably, TA-Sr and TA-Mg coatings promoted enhanced cell spreading and well-organized actin structures. Tri-lineage differentiation assays revealed distinct lineage-specific regulatory effects. TA-Fe nano-coatings preferentially enhanced adipogenic differentiation, whereas TA-Sr coatings significantly promoted chondrogenic matrix production while supporting osteogenic differentiation. TA-Mg nano-coatings exhibited the strongest osteogenic potential, as evidenced by increased alkaline phosphatase activity and extracellular matrix mineralization. Collectively, these results demonstrate that TA-metal single-cell nano-coatings enable programmable, ion-specific regulation of stem cell fate within an identical coordination framework. This cell-level biomaterial strategy provides a versatile platform for skeletal tissue engineering and cell-based regenerative therapies.

Small extracellular vesicles (sEVs) derived from mesenchymal stem/stromal cells (MSCs) contain microRNAs (miRNAs) that can modulate the cellular behavior of recipient cells. Human periodontal ligament mesenchymal stem/stromal cells (hPDL-MSCs) are a unique MSC population involved in periodontal tissue regeneration; however, the specific miRNAs that regulate their proliferative and differentiation-related properties remain incompletely understood. In this study, we profiled miRNAs enriched in sEVs secreted by highly proliferative human PDL-MSCs and identified hsa-let-7c-3p as a candidate regulator of hPDL-MSC behavior. Functional assays demonstrated that hsa-let-7c-3p enhanced proliferative and migratory behavior, reflected by an approximately 1.5-fold increase in metabolic activity and a 2-fold increase in migration, while suppressing osteogenic differentiation, with approximately 50% reductions in alkaline phosphatase activity and mineralization. To identify functionally relevant downstream targets, we intersected AGO2-RIP-seq-enriched transcripts, RNA-seq-defined genes altered by hsa-let-7c-3p overexpression, and in silico target predictions, identifying NT5E/CD73 as a candidate downstream target with experimental validation. Furthermore, NT5E knockdown partially phenocopied the effects of hsa-let-7c-3p overexpression on hPDL-MSC proliferation, migration, and osteogenic differentiation, supporting a functional link between hsa-let-7c-3p and NT5E/CD73. These findings highlight hsa-let-7c-3p as an underexplored sEV-associated 3p miRNA strand that restrains the proliferation-to-osteogenesis transition of hPDL-MSCs and identify NT5E/CD73 as a functionally relevant downstream target. Clinical trial number. Not applicable.

Drug-induced liver injury is a significant cause of acute liver failure, and sex-related biological differences may affect hepatic responses to xenobiotics. This study examined the sex- and dose-dependent effects of morphine on liver function, oxidative stress, inflammation, apoptosis, and histology in Wistar rats. Forty rats (20 males and 20 females) were administered distilled water or morphine at doses of 20, 40, or 60 mg/kg orally once daily for 30 days. Plasma liver enzyme levels and markers of hepatic oxidative stress, inflammation, and apoptosis were assessed, and liver tissues were analyzed histologically. Morphine significantly elevated alanine aminotransferase (ALT) activity in both sexes at most dose levels, with female rats exhibiting greater increases than males at 20 and 40 mg/kg. Alterations in aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT) were most pronounced in the low-dose groups. Low-dose morphine also led to significant increases in tumor necrosis factor-alpha (TNF-α), caspase-3, malondialdehyde (MDA), and nitric oxide (NO), indicating enhanced inflammatory, pro-apoptotic, and oxidative responses. While superoxide dismutase (SOD) and catalase (CAT) levels were not significantly altered, glutathione (GSH) demonstrated sex-related variation. Histological analysis revealed that male livers were largely preserved, whereas female livers displayed widened sinusoids and hepatocellular erosion. Overall, morphine induced sex- and dose-dependent hepatotoxicity, with females exhibiting greater susceptibility, particularly at low-dose exposure, which resulted in the most pronounced biochemical disturbances.

Excessive use of chemical fertilizers leads to soil degradation during chili cultivation, particularly in acidic red soils with low phosphorus (P) availability, which limits yield and quality.

The design of magnetoactive hybrid scaffolds based on biocompatible piezoelectric polymers and magnetic nanoparticles (NPs) holds great promise for advanced bone tissue regeneration applications. In this study, electrospun magnetoactive poly(vinylidene fluoride-co-trifluoroethylene) [P(VDF-TrFE)] composite fibrous membranes doped with different concentrations of oleic acid-modified Fe3O4 (Fe3O4-OA) NPs were successfully fabricated via the electrospinning technology. The as-prepared P(VDF-TrFE)/Fe3O4-OA composite membranes exhibited a uniform fibrous morphology with an average fiber diameter of approximately 0.2 µm, and the piezoelectric crystalline β-phase was predominant. The homogeneous dispersion of Fe3O4-OA NPs endowed the composite fibrous membranes with typical ferromagnetic behaviour and tunable saturation magnetisation. In vitro biological evaluations confirmed the excellent biocompatibility of the composite membranes with bone marrow mesenchymal stem cells (BMSCs). CCK-8 assays indicated that the viability of BMSCs cultured on all composite membrane groups increased over time, and live/dead staining further verified that all composite membranes supported high BMSC viability. F-actin staining results revealed that BMSCs could effectively attach and spread on the composite membranes with well-developed cytoskeletal structures. Moreover, the osteogenic differentiation potential of the BMSCs on the composite membranes was systematically evaluated at the early, middle and late stages of osteogenic induction. Alkaline phosphatase (ALP) activity assays revealed that the composite membranes containing Fe3O4-OA NPs exhibited significantly elevated ALP activity compared with the pure P(VDF-TrFE) membrane, and RUNX2 immunofluorescence staining confirmed enhanced early osteogenic transcriptional activation in the BMSCs cultured on the Fe3O4-OA-doped composite membranes. Collectively, these findings suggest that the electrospun magnetic P(VDF-TrFE)/Fe3O4-OA composite fibrous membranes exhibit good cytocompatibility and support the osteogenic differentiation of BMSCs, indicating their potential as scaffold materials for bone tissue engineering.

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by renal phosphate wasting, hypophosphatemia, and impaired bone mineralization, primarily caused by phosphaturic mesenchymal tumors (PMTs). Due to the small size and non-specific clinical presentation, PMTs are often difficult to localize, resulting in delayed diagnosis. This study presents a case of a 54-year-old man who experienced a 2-year history of progressive polyarthralgia affecting the knees, hips, and lower back, which exacerbated over the past 3 months. Laboratory tests revealed hypophosphatemia, elevated alkaline phosphatase (ALP) levels, and increased parathyroid hormone (PTH) levels. Moreover, a dual-energy X-ray absorptiometry (DXA) scan indicated low bone mineral density (BMD), while a whole-body bone scintigraphy revealed multiple rib pathological fractures, indicative of osteomalacia. Although serum fibroblast growth factor 23 (FGF23) was not measured, the clinical and biochemical profiles were highly consistent with tumor-induced osteomalacia (TIO). Subsequent Gallium-68 1,4,7,10-tetraazacyclododecane 1,4,7,10-tetraacetic acid tyrosine-3-octreotate positron emission tomography/computed tomography (68Ga-DOTA-TATE) positron emission tomography/computed tomography (PET/CT) confirmed a hypermetabolic lesion in the left temporalis muscle. The lesion was completely resected, and histopathological examination confirmed the diagnosis of PMT, with positive immunostaining for special AT-rich sequence-binding protein 2 (SATB2), neural cell adhesion molecule (CD56), and somatostatin receptor type 2 (SSTR2). No tumor recurrence was observed during follow-up at 6 months after surgery. Clinicians should consider occult PMTs in patients with unexplained hypophosphatemia, bone pain, or pathological fractures, and employ functional imaging modalities such as 68Ga-DOTA-TATE PET/CT for early tumor localization and potential cure through resection.

Heavy metal contamination in saline-alkali soils poses a dual challenge of excessive alkalinity and nutrient deficiency, particularly phosphorus (P). Traditional biochar remediation often exhibits limited efficacy in these complex matrices due to the high ionic strength and recalcitrant P fractions. In this study, a bamboo vinegar-modified biochar (MB) was developed to simultaneously remediate cadmium (Cd) and activate P in saline-alkali soil. Modification significantly enhanced biochar textural properties, increasing the specific surface area and pore volume by 330.6% and 298.6%, respectively. MB application substantially ameliorated soil alkalinity and salinity, achieving superior reductions in pH (12.2%), ionic strength (48.8%), and sodium adsorption ratio (41.2%) compared to pristine biochar. MB induced a profound redistribution of Cd speciation, decreasing bioavailable Cd by 42.3% and expanding the residual pool by 29.6%. Simultaneously, the P availability coefficient was enhanced by 166.2%, driven by the dissolution of recalcitrant calcium-bound P and the mineralization of organic P. Mechanistic investigations reveal that MB establishes a synergistic remediation pathway integrating persistent acidification, desalination-driven immobilization, and microbial revitalization. The reduction in Cd toxicity and improved physiochemical environment stimulated the absolute abundance of P-solubilizing bacteria and phosphatase-encoding genes (phoC and phoD). Overall, our study highlights the potential of multifunctional modified biochar to overcome chemical and biological barriers, offering a sustainable strategy for the integrated management of nutrient cycles and heavy metal risks.