Histone deacetylase 3 promotes innate antiviral immunity through deacetylation of TBK1

TANK-binding kinase 1 (TBK1), a core kinase of antiviral pathways, activates the production of interferons (IFNs). It has been reported that deacetylation activates TBK1; however, the precise mechanism still remains to be uncovered. We show here that during the early stage of viral infection, the acetylation of TBK1 was increased, and the acetylation of TBK1 at Lys241 enhanced the recruitment of IRF3 to TBK1. HDAC3 directly deacetylated TBK1 at Lys241 and Lys692, which resulted in the activation of TBK1. Deacetylation at Lys241 and Lys692 was critical for the kinase activity and dimerization of TBK1 respectively. Using knockout cell lines and transgenic mice, we confirmed that a HDAC3 null mutant exhibited enhanced susceptibility to viral challenge via impaired production of type I IFNs. Furthermore, activated TBK1 phosphorylated HDAC3, which promoted the deacetylation activity of HDAC3 and formed a feedback loop. In this study, we illustrated the roles the acetylated and deacetylated forms of TBK1 play in antiviral innate responses and clarified the post-translational modulations involved in the interaction between TBK1 and HDAC3.

Evaluation of Lateral Pterygoid Muscle Contraction in Patients with Temporomandibular Disorders Based on 3D-T2 Weighted Imaging / 中国医学科学院学报

Objective To evaluate lateral pterygoid muscle(LPM)contraction in the patients with temporomandibular disorders(TMD)based on 3D-T2 weighted imaging(3D-T2WI).Multiplanar reconstruction(MPR)was employed to measure the length of LPM in the images taken in closed-and open-mouth positions. Methods Seventeen TMD patients [age of(29.82±10.70)years,males/females=8/9] and 13 normal volunteers [control,age of(23.54±3.31)years,males/females=6/7] received 3D-T2WI of the temporomandibular joints in closed-and open-mouth positions from November 2019 to April 2020 in Department of Radiology,Hainan Hospital of Chinese PLA General Hospital.According to the position of the discs,the subjects were classified into the following groups:TMD with disc displacement without reduction(TMD-DDwoR),TMD with disc displacement with reduction(TMD-DDwR),TMD without disc displacement(TMDwoDD),and normal control without disc displacement(NCwoDD).MPR was employed to measure the maximal length of the superior belly of LPM.One-way analysis of variance,receiver operating characteristic curve,and permutation test were employed for the statistical analyses. Results The contraction of LPM was significantly shorter in TMD-DDwoR group [(3.36±1.96)mm] than in TMDwoDD group [(7.90±3.95)mm],NCwoDD group [(8.77±3.13)mm](

Biomechanical study on repair materials of unilateral maxilla defect based on finite element model / 医用生物力学

Objective To study the biomechanical effect from different prosthetic materials used on unilateral maxillary defect repair by three dimensional finite element (FE) analysis method. Methods The maxillary unilateral defect model was reconstructed by medical image processing software MIMICS. The prosthesis was generated by mirroring technology. After processing, the FE unilateral maxillary defect model and healthy maxillary model were established to simulate stress distributions on the maxilla during occlusion. Results The maximum stress on maxilla using different repair materials was always found concentrated on the edge of maxilla connected with zygoma (the positions attaching zygolabialis and levator anguli oris). The minimum stress of from the maxilla edge on the repair side was 8.471 MPa by using tricalcium phosphate (TCP) composite. The maximum stress from the maxilla edge on the repair side was 17.55 MPa by using hydroxyapatite (HA) material. Conclusions Different repair materials had no significant effect on natural side of the maxilla after restoration, while a greater impact of force status on the repair side was found. The elastic modulus of different repair materials can be used as a basis for maxilla restoration in clinic.

Innate immune responses to DNA viruses

The innate immune system acts as the first line of defense against pathogens, which is also essential for initiation of adaptive immunity. Innate immune responses are initiated by pattern-recognition receptors (PRRs), which recognize conserved molecular structures of pathogens called pathogen-associated molecular patterns (PAMPs). The infection of virus triggers a series of signaling events leading to transcriptional induction of type I interferons (IFNs) and proinflammatory cytokines. In recent years, the mechanisms of viral RNA recognition and RNA virus-triggered signaling pathways have been well studied. However, it remains unclear on how DNA virus infection is sensed by host cells and triggers the host antiviral defense. Although ten potential viral DNA sensors have been reported, none of them is validated as a generally used sensor for distinct DNA viruses in divergent cell types and animals. Here, we provide a summary and perspective on recent advances in innate immune responses to DNA viruses.

Heat shock cognate 71 (HSC71) regulates cellular antiviral response by impairing formation of VISA aggregates

In response to viral infection, RIG-I-like RNA helicases detect viral RNA and signal through the mitochondrial adapter protein VISA. VISA activation leads to rapid activation of transcription factors IRF3 and NF-κB, which collaborate to induce transcription of type I interferon (IFN) genes and cellular antiviral response. It has been demonstrated that VISA is activated by forming prion-like aggregates. However, how this process is regulated remains unknown. Here we show that overexpression of HSC71 resulted in potent inhibition of virus-triggered transcription of IFNB1 gene and cellular antiviral response. Consistently, knockdown of HSC71 had opposite effects. HSC71 interacted with VISA, and negatively regulated virus-triggered VISA aggregation. These findings suggest that HSC71 functions as a check against VISA-mediated antiviral response.

Investigation of the prevalence of temporomandibular disorders in 352 aged edentulous individuals / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To study the prevalence of temporomandibular disorders (TMD) in 352 aged edentulous individuals in Beijing area and to analyze the correlative risk factors.</p><p><b>METHODS</b>Three hundred and fifty-two aged edentulous subjects were included in the study (198 males and 154 females). The adopted questionnaire was designed according to Helkimo index, and the subjects were examined by the same examiner who would record every result as well.</p><p><b>RESULTS</b>The prevalence of TMD's clinical positive signs in the edentulous subjects was 43.2% (152/352), among which temporomandibular joint (TMJ) noise [34.1% (120/352)] was the highest prevalent sign while TMJ pain on movemert was the lowest. The prevalence of mandibular movement deviation [18.2% (64/352)] fitted in between. The prevalence of TMD's clinical positive signs of male individuals was 36.9% (73/198), and the female was 51.3% (79/154). There was a significant difference in prevalence of TMD's clinical positive signs between males and females (P = 0.0067 < 0.01). The prevalence of TMD's clinical positive signs in denture wearing group was 38.6% (91/236) and that in no denture group was 52.6% (61/116). There was a significant correlation between the prevalence of TMD's clinical positive signs and wearing denture [P = 0.0125 < 0.05, OR = 1.767 (1.130 ∼ 2.763)].</p><p><b>CONCLUSIONS</b>Gender and malocclusion may be the risk factors of TMD in edentulous individuals.</p>

Shielding property of different prosthetic materials to shield radiation of (125)I seed / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To investigation the shielding property to (125)I of several different prosthetic materials used in clinical when prostheses are used as carriers of (125)I seed in tumor treatment.</p><p><b>METHODS</b>(125)I seeds were taken as the radiation sources to establish a model in vitro and the radiation doses were measured by thermoluminescent dosemeters (TLD). The shielding property of titanium plate, cochrome plate, and poly methyl methacrylate (PMMA) plate were detected, calculated and compared with that of plumbum plate in the control group.</p><p><b>RESULTS</b>The radiation doses of the radiation source at 10 mm distance through the following materials were measured, and the results are 2.805 mGy (0.09 mm thick titanium plate), 1.082 mGy (0.48 thick titanium plate), 0.390 mGy (0.41 mm thick cochrome plate), and 0.261 mGy (0.67 mm's cochrome plate), and 2.885 mGy (1.685 mm thick PMMA plate).</p><p><b>CONCLUSIONS</b>The shield property of cochrome is optimal. The poly methyl methacrylate behaves to some extend as a shield to the (125)I seed which can shield the radiation as the effects of plumbum when adopted together with the 0.557 mm's (or more) titanium plate.</p>

Using TiNi-SMA distractor for mandibular alveolar ridge augmentation by distraction osteogenesis: a preliminary study / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To study the possibility of mandibular alveolar ridge augmentation by distraction osteogenesis using TiNi-SMA (shape memory alloy) distractor.</p><p><b>METHODS</b>All of the mandibular premolars and the first molar were extracted from ten adult mongrel canines. One month later, box-shaped osteotomies of the alveolar bone were performed out and TiNi-SMA distractors were buried in experimental group. The bone height was measured before and 1, 5, 13 weeks after the operation. The radiographs were taken on the day of, and 1, 5, 13 weeks after operation. The animals were killed at one or three months after distraction and examined histologically.</p><p><b>RESULTS</b>The bone segments were lifted up immediately after the insertion of distractors and the height achieved 7.5 - 11.5 mm one week after the operation. One month after distraction, the radiographs showed there was regeneration of bone in distraction gap. The new bone and the normal bone could not be differentiated clearly three months after distraction. No bone resorption was found during this period. In histological sections, there were collagen bundles in early distraction, then these bundles were calcified and became traeculaes.</p><p><b>CONCLUSION</b>It suggests that the canine mandibular posterior alveolar ridge can be augmented by distraction osteogenesis using TiNi-SMA distractor, and the new bone is formed by intramembranous ossification.</p>