Kelch-like Protein 21 (KLHL21) Targets IκB Kinase-ß to Regulate Nuclear Factor κ-Light Chain Enhancer of Activated B Cells (NF-κB) Signaling Negatively.

Activation of IKKß is the key step in canonical activation of NF-κB signaling. Extensive work has provided insight into the mechanisms underlying IKKß activation through the identification of context-specific regulators. However, the molecular processes responsible for its negative regulation are not completely understood. Here, we identified KLHL21, a member of the Kelch-like gene family, as a novel negative regulator of IKKß. The expression of KLHL21 was rapidly down-regulated in macrophages upon treatment with proinflammatory stimuli. Overexpression of KLHL21 inhibited the activation of IKKß and degradation of IκBα, whereas KLHL21 depletion via siRNA showed the opposite results. Coimmunoprecipitation assays revealed that KLHL21 specifically bound to the kinase domain of IKKß via its Kelch domains and that this interaction was gradually attenuated upon TNFα treatment. Furthermore, KLHL21 did not disrupt the interaction between IKKß and TAK1, TRAF2, or IκBα. Also, KLHL21 did not require its E3 ubiquitin ligase activity for IKKß inhibition. Our findings suggest that KLHL21 may exert its inhibitory function by binding to the kinase domain and sequestering the region from potential IKKß inducers. Taken together, our data clearly demonstrate that KLHL21 negatively regulates TNFα-activated NF-κB signaling via targeting IKKß, providing new insight into the mechanisms underlying NF-κB regulation in cells.

[Study on fatigue resistance of mechanical nickel-titanium files by phase-locked infrared flaw detection method].

PURPOSE: The movement trend of the posterior teeth and the distribution of the periodontal membrane stress were studied by using three-dimensional digital technology. METHODS: CBCT data of 88 patients admitted to our hospital from June 2017 to June 2022 were selected, and input into Mimics20.0 software for preliminary extraction of all parts and stored with STL files; then the data were repaired and optimized through Geomagic Studio 2014 software. With the help of normal phase extension, the invisible appliance and periodontal membrane were constructed. Finally, the six FEM models were simulated and observed by the current teeth in different groups. Statistical analysis was performed with SPSS 21.0 software package. RESULTS: The effect force of the largest periodontal membrane was distributed in the neck of the tooth, followed by the apical area, with the maximum effect force value in the NA group. In all accessory groups, the periodontal membrane maximum paradigm isoeffect force values of all patients in the accessory vertical rectangular group were significantly smaller than the values obtained in the horizontal rectangular group. CONCLUSIONS: The design of orthodontic tooth accessories has a strong inhibition effect on the position movement of anterior teeth during recovery, which improves the accuracy of tooth three-dimensional movement to a certain extent. Meanwhile, the normal equivalent stress of the periodontal membrane of patients in the initial application of the invisible appliance without brackets is large.

[Treatment of skeletal Class II adult patients with microscrew implant anchorage and multi-loop edgewise arch wire].

OBJECTIVE: To evaluate the effects and mechanisms of the microscrew implant anchorage (MIA) combined with multi-loop edgewise arch wire (MEAW) technique in the treatment of skeletal Class II adult patients. METHODS: Eleven adult patients with skeletal Class II high-angle malocclusions were treated with fixed appliances. The spaces were closed by the springs from the MIA to the hook on the archwire. The height of the hook and the direction of the force were different according to the intrusion and retraction of upper anterior teeth. In the finishing stage, MEAW technique and modified class II elastics (from the first loop of MEAW to the MIA) were used for final detailing. Cephalometric analysis was used to evaluate the effect after treatment. RESULTS: After treatment, the decrease of SNA, ANB and FMA were (2.86 +/- 1.05) degrees , (2.82 +/- 0.96) degrees and (2.95 +/- 1.35) degrees , respectively. The torque control of upper anterior teeth was good. The protrusion of lower incisors and the molar extrusion were avoided. The upper molars were moved distally by (3.00 +/- 2.19) mm. CONCLUSIONS: The treatment of adult patients with skeletal Class II high angle malocclusions with MIA and MEAW technique could not only improve the facial esthetics but also avoided the common side effects of traditional Class II elastics.