Dali University

The global rise in aging populations has substantially increased the clinical and socioeconomic burden of osteoporosis (OP), a disorder characterized by impaired bone formation and excessive resorption. Disruption of circadian rhythmicity is increasingly recognized as a significant contributor to skeletal fragility and fracture risk. The retinoic acid-related orphan receptor (ROR) family-RORα, RORβ, and RORγ-integrates circadian regulation with immune and metabolic pathways essential to bone remodeling, presenting emerging therapeutic opportunities.

We systematically synthesized current evidence spanning four major dimensions of ROR biology relevant to skeletal physiology: (1) structural characteristics and ligand specificity, (2) subtype-dependent roles in bone homeostasis, (3) molecular and cellular regulatory mechanisms, and (4) translational progress and therapeutic potential, including chronopharmacological strategies.

RORα/β/γ exhibit distinct ligand-binding architectures that confer subtype-specific transcriptional regulation, enabling coordinated control over osteoblast, osteoclast, and osteocyte activity. Functionally, RORα promotes osteogenesis and supports circadian transcriptional oscillation; RORβ acts as a transcriptional repressor limiting osteoblast differentiation; and RORγt mediates osteoimmune crosstalk via the IL-17 axis to modulate osteoclastogenesis. Preclinical studies demonstrate promising efficacy of ROR-directed agents-including agonists, inverse agonists, and isoform-selective inhibitors-and highlight the importance of circadian-aligned therapeutic administration.

RORα, RORβ, and RORγ function as complementary regulators of bone homeostasis and represent compelling targets for precision therapeutics against OP and related skeletal disorders. Future research should prioritize defining spatiotemporal regulation within bone microenvironments, quantifying immune-mediated RORγt signaling, and optimizing chronopharmacological strategies to enable time-synchronized, subtype-selective interventions.

Blaps rynchopetera Fairmaire (Coleoptera: Tenebrionidae), a traditional medicinal insect employed by the Yi and Dai ethnic communities in Yunnan, China, has long been utilized for treating inflammatory conditions such as fever, mumps, and gastritis. Its potential application in managing symptoms akin to neuroinflammatory disorders provides an ethnopharmacological basis for this investigation. However, the bioactive components underpinning its anti-inflammatory properties, particularly its polysaccharides, remain poorly investigated.

This study aimed to isolate the polysaccharide fraction from Blaps rynchopetera Fairmaire (BRPs), characterize its structure, and evaluate its anti-neuroinflammatory activity in cellular and animal models, with a focus on the TLR4/NF-κB pathway.

BRPs were extracted from whole insects using hot water and purified by ethanol precipitation. Structural characterization was performed via HPAEC-PAD, GPC-RI-MALS, SEM, and FT-IR. The anti-neuroinflammatory effects and TLR4/NF-κB or MAPK signaling pathway were investigated in LPS-stimulated primary microglia and a TLR4-overexpressing (TLR4-OE) HEK293 cell model for target validation. TLR4-binding components within BRPs were identified using the affinity-based technique of biolayer interferometry-mass spectrometry (BLI-MS). The in vivo efficacy of the TLR4-affinity enriched fraction (BRPs-AEF) was further assessed in a mouse model of transient middle cerebral artery occlusion/reperfusion (MCAO/R).

BRPs was a polysaccharide-glycoprotein complex containing 77.88% carbohydrates (dominant glucose and galactose) and 8.51% protein, with a porous microstructure and α-glycosidic linkages. In primary microglia, BRPs dose-dependently suppressed LPS-induced production of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), and inhibited the activation of TLR4/NF-κB activation and MAPK signaling pathways. Using a BLI-MS strategy, 10 unique TLR4-binding proteins (e.g., WH2 domain proteins and calreticulin) and 21 interaction peptides were identified within BRPs. This TLR4-mediated mechanism was functionally validated in TLR4-OE cells. In MCAO/R mice, BRPs-AEF significantly reduced cerebral infarction, improved neurological deficits, attenuated neuroinflammation, and preserved neuronal integrity in a murine stroke model.

These results demonstrate that BRPs from B. rynchopetera alleviate neuroinflammation through multi-target mechanisms, with the TLR4/NF-κB pathway being a major and directly validated target. This work provides pharmacological insights supporting the traditional use of this insect and illustrates a targeted approach for identifying bioactive constituents from complex mixtures.

Masquelet induced membrane surgery is a viable option for the reconstruction of extensive bone defects. This study aimed to comprehensively compare the clinical efficacy of 3D printed microporous tantalum prosthesis and autologous bone graft in the final stage of Masquelet induced membrane surgery during the treatment of lower extremity fracture-related infections(FRI) with large segmental bone defect.

We retrospectively analyzed the clinical data of 43 patients with large segmental bone defect caused by lower extremity FRI treated with Masquelet induced membrane surgery. Among these, 21 patients were implanted 3D printed microporous tantalum prosthesis (Prosthesis group), while 22 patients were implanted autologous bone graft (Autologous bone group) in the final-stage surgery. Follow-up was conducted for 12 months postoperatively. Clinical efficacy was evaluated using the Paley grade for bone defect healing, Visual analog scale (VAS), Lower extremity functional scale (LEFS), Fernandez-Esteve eschar score, and time to full weight-bearing. The clinical outcomes between the two treatment groups were compared.

Postoperatively, the scores of VAS and LEFS significantly improved compared to preoperative values in both groups (all P < 0.001). Compared to the Autologous bone group, the Prosthesis group demonstrated significantly higher LEFS scores and Fernandez-Esteve eschar scores, along with a significantly shorter time to full weight-bearing (all P < 0.05). The complication rate was 19.0% (4/21) in the Prosthesis group and 9.1% (2/22) in the Autologous bone group; there was no statistically significant difference between the two groups (P > 0.05). Patients experiencing complications received effective and targeted interventions.

Both implants show remarkable efficacy in the reconstruction of large segmental bone defect caused by lower limb FRI. However, 3D printed microporous tantalum prosthesis exhibits certain advantages over the autologous bone graft in terms of limb function recovery, bone callus growth, and early weight-bearing. However, when using this technique, one should be vigilant about the risk of complications.