Structural basis of ELKS/Rab6B interaction and its role in vesicle capturing enhanced by liquid-liquid phase separation.

ELKS proteins play a key role in organizing intracellular vesicle trafficking and targeting in both neurons and non-neuronal cells. While it is known that ELKS interacts with the vesicular traffic regulator, the Rab6 GTPase, the molecular basis governing ELKS-mediated trafficking of Rab6-coated vesicles, has remained unclear. In this study, we solved the Rab6B structure in complex with the Rab6-binding domain of ELKS1, revealing that a C-terminal segment of ELKS1 forms a helical hairpin to recognize Rab6B through a unique binding mode. We further showed that liquid-liquid phase separation (LLPS) of ELKS1 allows it to compete with other Rab6 effectors for binding to Rab6B and accumulate Rab6B-coated liposomes to the protein condensate formed by ELKS1. We also found that the ELKS1 condensate recruits Rab6B-coated vesicles to vesicle-releasing sites and promotes vesicle exocytosis. Together, our structural, biochemical, and cellular analyses suggest that ELKS1, via the LLPS-enhanced interaction with Rab6, captures Rab6-coated vesicles from the cargo transport machine for efficient vesicle release at exocytotic sites. These findings shed new light on the understanding of spatiotemporal regulation of vesicle trafficking through the interplay between membranous structures and membraneless condensates.

The Effect of NPWT on Odontogenic Cervical Necrotizing Fasciitis.

OBJECTIVE: To investigate the clinical efficacy of negative pressure wound therapy (NPWT) in the treatment of odontogenic cervical Necrotizing fasciitis (CNF). METHODS: Sixteen cases of odontogenic cervical necrotizing fasciitis were randomly divided into observation group and control group after routine debridement and disinfection. The patients in the control group were treated with drainage tube and regular dressing changes, while those in the observation group were treated with NPWT. The therapeutic effects of the 2 groups were compared. RESULTS: The frequency of operation, treatment length, and cost of treatment in the observation group were significantly less than those in the control group (P<0.05). During the treatment, the VAS (visual analog scale of pain) in the observation group was significantly lower than that in the control group (P<0.05). The levels of WBC, CRP, PCT, IL-6, and TNF-α in the observation group were lower than those in the control group (P<0.05). The levels of Il-10 and VEGF in the observation group were higher than those in the control group (P<0.05), the difference was statistically significant. CONCLUSIONS: The condition of odontogenic cervical necrotizing fasciitis progresses rapidly. Compared with conventional drainage and dressing change, NPWT can control infection in a short time, reduce operation frequency and treatment cost, and promote wound healing, shorten the treatment time, ease the pain of patients, improve the quality of life. The therapeutic scheme is safe, effective, and suitable for clinical application.

Clinical Study of Damage Control Surgery in the Management of Odontogenic Cervical Necrotizing Fasciitis with Septic Shock.

Objective: To evaluate the clinical efficacy of damage control surgery (DCS) in the treatment of odontogenic cervical Necrotizing Fasciitis (CNF) complicated with septic shock. Methods: From January 2019 to January 2022, 8 cases with odontogenic cervical Necrotizing Fasciitis (CNF) complicated with septic shock were selected. According to the concept of damage control surgery (DCS), they were treated with incision and decompression, debridement and sealing vacuum suction (VSD) at the early stage, anti-shock, anti-infection, life support. At the later stage, the patients were treated by skin autograft combined with early rehabilitation. Results: In 8 cases, shock was corrected in a short time, lac decreased rapidly, infection index including white blood cell (WBC), C-reactive protein (CRP), thrombocytocrit (PCT) decreased rapidly, organ function including blood urea nitrogen (BUN), total bilirubin (Tbil), Aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin (Alb), creatine kinase (CK) was improved effectively, P < .05. The wounds of all the patients were effectively closed and cured. The average days of hospitalization were 21-42 days (27.00±3.20 days). No recurrence was found in the follow-up of 6 months. Conclusion: Odontogenic cervical Necrotizing fasciitis with septic shock progresses rapidly. Damage control surgery can effectively control infection, correct shock and avoid further deterioration of organ function. This scheme has unique advantages, which can make the wound repaired in time and improve the success rate of treatment. It is worth popularizing in clinic.

Application of Autogenous Dermis Combined With Local Flap Transplantation in Repair of Titanium Mesh Exposure After Cranioplasty.

OBJECTIVES: To investigate the clinical outcome of autogenous dermis combined with local flap transplantation in the treatment of titanium mesh exposure after cranioplasty. METHODS: We studied a total of 8 patients with titanium mesh exposure after cranioplasty. After debridement of the head wound, the autogenous dermal tissue from the lateral thigh was transplanted to the surface of titanium mesh, and the local skin flap was then applied after suturing and fixation to repair the wound on the surface of the dermis. To repair the lateral thigh dermal tissue area, a local skin flap was obtained, and a blade thick skin graft was used. RESULTS: Both dermal tissue and local skin flap survived. In the meanwhile, the donor skin area of the lateral thigh healed well, with only slight scar hyperplasia, and the titanium mesh was preserved. There was no recurrence after 6 months of follow-up. CONCLUSIONS: The application of autogenous dermis combined with local skin flap to repair titanium mesh exposure can effectively avoid skin flap necrosis, potential re-exposure of titanium mesh, sub-flap effusion, infection, and other problems. This method has an ideal effect, has easy access to materials, and reduces patients' economic burden. It is worth popularizing.

Effects and underlying mechanism of micro-nano-structured zirconia surfaces on biological behaviors of human gingival fibroblasts under inflammatory conditions.

Zirconia is one of the most commonly used materials for abutments of dental implants, especially in the anterior region. Soft tissue integration to the zirconia abutment surface remains a challenge. Peri-implant soft tissue integration serves as a physiological barrier, attenuating pathogen penetration and preventing peri­implant disease. The surface microstructure of zirconia has significant effects on the biological behaviors of human gingival fibroblasts (HGFs), but the effects under inflammatory conditions are still unclear. In this study, we established two micro-nano structures on zirconia surfaces using a femtosecond laser, including microgrooves with widths of 30 µm (G3) and 60 µm (G6) and depths of 5 µm, and nanoparticles inside the microgrooves. Polished surfaces were used as controls. HGFs were seeded onto the three groups of zirconia specimens and stimulated with lipopolysaccharide. The HGFs on micro-nano-structured zirconia surfaces exhibited lower inflammatory responses and higher cell adhesion, proliferation, and migration under inflammatory conditions compared with the polished surfaces. Additionally, the G3 group exhibited lower inflammatory responses and higher cell adhesion and migration than the G6 group. The micro-nano-structured zirconia surface exhibited decreased neutrophil infiltration and increased M2-type macrophage polarization in vivo. To explore the molecular mechanism, RNA sequencing and gene silencing were utilized, which revealed two critical target genes regulated by the G3 group. Overall, we proposed an innovative micro-nano-structured zirconia surface that reduced the in vitro and in vivo inflammatory responses and promoted HGF adhesion, migration, and proliferation under inflammatory conditions, in which TRAFD1 and NLRC5 were the underlying key genes. STATEMENT OF SIGNIFICANCE: Zirconia is one of the most commonly used materials for abutments, especially in the anterior region. The surface microstructure of zirconia has significant effects on the biological behaviors of human gingival fibroblasts (HGFs), but few studies have investigated these effects under inflammatory conditions, and the mechanism remains unclear. In this study, we developed an innovative micro-nano-structured zirconia surface using a femtosecond laser, which reduces the in vitro and in vivo pro-inflammatory responses and promotes HGFs adhesion, migration, and proliferation under inflammatory conditions compared with the polished zirconia surface. The potential underlying mechanism was also investigated. This work has provided some theoretical basis for the micro-nano-structured zirconia surface in potentially reducing the inflammation and enhancing peri­implant soft-tissue integration under inflammatory conditions.