Bioinformatic analysis of lncRNA-associated competing endogenous RNA regulatory networks in synovial tissue of temporomandibular joint osteoarthritis

Background:Temporomandibular joint osteoarthritis(TMJOA)is an end-stage disease that seriously affects the patients’quality of life.Molecular insights in advancing our understanding of TMJOA are the need of the hour.Methods:We performed RNA high-throughput sequencing and bioinformatics analysis of differentially expressed(DE)long non-coding RNA(lncRNAs),microRNAs(miRNAs),and messenger RNA(mRNAs)in human synovial TMJOA tissues.Firstly,synovium samples of TMJOA patients and non-TMJOA controls were collected for highthroughput sequencing of lncRNAs,miRNAs,and mRNAs.We then performed biological function analysis of the top 100 mRNAs with more than 2-fold differential expression,and their upstream regulated miRNAs and lncRNAs were predicted separately.Intersections between predicted miRNAs/lncRNAs and differentially expressed miRNAs/lncRNAs were determined,respectively.Regulatory networks among the selected lncRNAs,miRNAs,and mRNAs were constructed.Finally,Western Blotting and reverse transcription-quantitative polymerase chain reaction(RT-qPCR)were used to explore the function of selected lncRNA and mRNAs.Results:Our analysis showed that the only upregulated lncRNAxist,was involved in intracellular protein degradation,cartilage matrix degradation,and osteoclast differentiation through four regulatory axes:miR-1271-5p/ctsb,miR-365a-3p/mmp3,miR-199a-3p/fos,and miR-27b-3p/miR-1271-5p/grb2.RT-qPCR results showed that xist expression increased in both TMJOA synovial tissue and inflammatory-stimulated synovial cells.Inhibition of xist could promote the proliferation of synovial cells upon inflammatory stimulation,and xist could positively regulate the expression of GRB2.Targeting GRB2 could inhibit the expression of matrix degrading enzymes in synovial cells,thereby attenuating the inflammatory environment.Conclusion:Given the current lack of reports of lncRNA regulation in TMJOA synovitis,our results revealed that xist was significantly differentially expressed in human synovial TMJOA and could regulate the expression of GRB2,which may play a role in the progression of TMJOA.

Relationship of distraction rate with inferior alveolar nerve degeneration-regeneration shift

Distraction osteogenesis is an important technique for the treatment of maxillofacial abnormities and defects. However, distraction osteo- genesis may cause the injury of the inferior alveolar nerve. The relationship between distraction rate and nerve degeneration-regeneration shift remains poorly understood. In this study, 24 rabbits were randomly divided into four groups. To establish the rabbit mandibular distraction osteogenesis model, the mandibles of rabbits in distraction osteogenesis groups were subjected to continuous osteogenesis dis- traction at a rate of 1.0, 1.5 and 2.0 mm/d, respectively, by controlling rounds of screwing each day in the distractors. In the sham group, mandible osteotomy was performed without distraction, Pin-prick test with a 10 g blunt pin on the labium, histological and histomorpho- metric analyses with methylene blue staining, Bodian＇s silver staining, transmission electron microscopy and myelinated fiber density of inferior alveolar nerve cross-sections were performed to assess inferior alveolar nerve conditions. At 28 days after model establishment, in the pin-prick test, the inferior alveolar nerve showed no response in the labium to a pin pricks in the 2 mm/d group, indicating a severe dysfunction. Histological and histomorphometric analyses indicated that the inferior alveolar nerve suffered more degeneration and in- juries at a high distraction rate （2 mm/d）. Importantly, the nerve regeneration, indicated by newborn Schwann cells and axons, was more abundant in 1.0 and 1.5 mm/d groups than in 2.0 mm/d group. We concluded that the distraction rate was strongly associated with the inferior alveolar nerve function, and the distraction rates of !.0 and 1.5 mm/d had regenerative effects on the inferior alveolar nerve. This study provides an experimental basis for the relationship between distraction rate and nerve degeneration-regeneration shift during dis- traction osteogenesis, and may facilitate reducing nerve complications during distraction osteogenesis.

Automated classification of dual channel dental imaging of auto-fluorescence and white lightby convolutional neural networks

Prevention is the most effective way to reduce dental caries.In order to provide a simple way to achieve oral healthcare direction in daily life,dual Channel,portable dental Imaging system that combine white light with autofluorescence techniques was established,and then,a group of volunteers were recruited,7200 tooth pictures of different dental caries stage and dental plaque were taken and collected.In this work,a customized Convolutional Neural Networks(CNNs)have been designed to classify dental image with early stage caries and dental plaque.Eighty percentage(n=6000)of the pictures taken were used to supervised training of the CNNs based on the experienced dentists'advice and the rest 20%(n=1200)were used to a test dataset to test the trained CNNs.The accuracy,sensitivity and specificity were calculated to evaluate perfor-mance of the CNNs.The accuracy for the early stage caries and dental plaque were 95.3%and 95.9%,respectively.These results shown that the designed image system combined the cus-tomized CNNs that could automatically and efficiently find early caries and dental plaque on occlusal,lingual and buccal surfaces.Therefore,this will provide a novel approach to dental caries prevention for everyone in daily life.

In vitro study of the PLLA-Mg_(65)Zn_(30)Ca_(5)composites as potential biodegradable materials for bone implants

PLLA-magnesium composites have been widely investigated as potential biodegradable materials for bone implants.Lower/higher corrosion resistance of the crystalized/amorphous magnesium alloys allows tailoring of biodegradability rate.In this work,the amorphous Mg_(65)Zn_(30)Ca_(5)was investigated versus traditional crystalized Mg_(65)Zn_(30)Ca_(5),and a PLLA-Mg_(65)Zn_(30)Ca_(5)composite has been successfully fabricated using hot injection process.Furthermore,the high corrosion resistance of the amorphous Mg_(65)Zn_(30)Ca_(5)prevented the high alkalization and deterioration of mechanical strength.In addition,the high Zn content intended to improve the glass forming ability,also enhances the anti-bacterial property of the PLLA-Mg_(65)Zn_(30)Ca_(5)composite.The remarkable performance of the PLLA-Mg_(65)Zn_(30)Ca_(5)composite shows its promising application in bone repair and tissue regeneration.

Improvement of bone formation by bionic hydroxyapatite nanorod via the regulation of macrophage polarization

Bone defects are common clinical problems in the world,and there are many biomaterials used for treat-ing them.However,there is still a paucity of bioactive materials capable of modulating the immune mi-croenvironment.Therefore,it is necessary to identify new therapeutic strategies to regulate the immune microenvironment of the bone defect to further promote osteogenesis.Hydroxyapatite(HAP)is an impor-tant mineral for the framework of the human body.Recently,HAP has become a key research object for bone tissue engineering applications due to its unique tailored properties and similarity to bone tissue.Here,we prepared rod-shaped HAP(rHAP)with different concentrations(0,100,200,and 300μg/mL).The slowly released Ca^(2+)of 200μg/mL rHAP can induce macrophage phenotype 2(M2)polarization to decrease inflammatory cytokine secretion via the PI3K-Akt and Wnt/β-catenin pathways.In addition,rHAP can induce osteogenesis through the osteogenic differentiation of rat bone marrow mesenchymal stem cells.In conclusion,the 200μg/mL rHAP shows the potential for osteoimmunomodulation in a bone defect in vitro and in vivo,which is beneficial to the treatment of bone defects.

KIF18A is a potential prognostic factor and promotes tumor progression in oral tongue squamous cell carcinoma

The kinesin family member 18A protein was dysregulated in several human cancers and involved in cancer progression.However,the significance in oral tongue squamous cell carcinoma(OTSCC)has not been studied.The present study was intended to explore the functions of KIF18A in oral tongue squamous cell carcinoma.The immunohistochemistry(IHC)assay was performed to assess the relationships between the KIF18A protein expression level and clinical-pathological features of the patients.The biological functions of KIF18A in OTSCC cells were investigated by the experiments in vitro and in vivo.Based on immunohistochemistry,we found that KIF18A was correlated with the clinical-pathological features of OTSCC patients.High expression of KIF18A was associated with the lymph node metastasis,and clinical stages.In vitro experiments revealed that silencing of KIF18A significantly inhibited the expression of the proliferation and migration related proteins such as Ki67,proliferating cell nuclear antigen,matrix metalloproteinase-7 and matrix metalloproteinase-9,and thereby inhibiting the proliferation,migration and invasion of tumor cells.In vivo,knocking-down of KIF18A could inhibit the tumor growth in nude mice.In conclusion,we found KIF18A promoted tumor progression in vivo and in vitro and might become an effective target for the treatment of OTSCC.

Community Workers’Social Support and Sleep Quality during the Coronavirus Disease 2019(COVID-19):A Moderated Mediation Model

To explore the relationship between social support and sleep quality of community workers in Wuhan during the coronavirus disease 2019(the COVID-19 infection epidemic),this research constructed a mediating effect model to explore the mediating psychological mechanism of social support influencing sleep quality of front-line community workers.A total of 500 front-line community workers in Wuhan were investigated.We used the perceived social support scale(PSSS),the Connor-Davidson Resilience Scale(CD-RISC),the perceived stress scale(PSS),and the Pittsburgh sleep quality index(PSQI)to measure social support,psychological resilience,perceived stress and sleep quality.Specifically,the higher the PSQI,the worse the sleep quality.Pearson correlation structural equation model was used to analyze the relationship between these factors.The results showed that:(1)There was a significant negative correlation between social support,psychological resilience,and perceived stress of community workers and PSQI,that means,the higher the level of social support,psychological resilience,and perceived stress,the higher the sleep quality.(2)Social support positively predicted psychological resilience and perceived stress,and perceived stress negatively predicted PSQI.(3)Social support can affect sleep quality through the mediating role of psychological resilience and perceived stress,and the mediating role includes two paths:the single mediating role of perceived stress and the chain mediating role of psychological resilience-perceived stress.(4)Gender moderates the relation-ship between social support and perceived stress,and the influence of social support on perceived stress of women is higher than that of men.Gender moderates the relationship between psychological resilience and PSQI,and only women’s psychological resilience had a negatively predictive effect on PSQI,while men did not,which means that psychological resilience of female frontline community workers can positively predict sleep quality.This research reveals the relationship between social support and sleep quality and its mechanism and verifies that social support can indirectly affect physical health through psychological resilience and perceived stress.It provides reference suggestions and intervention guidance for improving the sleep quality of community workers.

A novel intronic circular RNA,circGNG7,inhibits head and neck squamous cell carcinoma progression by blocking the phosphorylation of heat shock protein 27 at Ser78 and Ser82

Background:There is increasing evidence that circular RNAs(circRNAs)play a significant role in pathological processes including tumorigenesis.In contrast to exonic circRNAs,which are the most frequently reported circRNAs in cancer so far,the studies of intronic circRNAs have been greatly lagged behind.Here,we aimed to investigate the regulatory role of intronic circRNAs in head and neck squamous cell carcinoma(HNSCC).Methods:We conducted whole-transcriptome sequencing with four pairs of primary tumor tissues and adjacent normal tissues from HNSCC patients.Then,we characterized circGNG7 expression in HNSCC tissues and cell lines and explored its association with the prognosis of HNSCC patients.We also identified interactions between circGNG7 and functional proteins,which alter downstream signaling that regulate HNSCC progression.Results:In this study,we identified a new intronic circRNA,circGNG7,and validated its functional roles in HNSCC progression.CircGNG7 was predominately localized to the cytoplasm,and its expression was downregulated in both HNSCC tissues andCAL27,CAL33,SCC4,SCC9,HN6,and HN30 cells.Low expression of circGNG7 was significantly correlated with poor prognosis in HNSCC patients.Consistent with this finding,overexpression of circGNG7 strongly inhibited tumor cell proliferation,colony formation,in vitro migration,and in vivo tumor growth.Mechanistically,the expression of circGNG7 in HNSCC cells was regulated by the transcription factor SMAD family member 4(SMAD4).Importantly,we discovered that circGNG7 could bind to serine residues 78 and 82 of the functional heat shock protein 27(HSP27),occupying its phosphorylation sites and hindering its phosphorylation,which reduced HSP27-JNK/P38 mitogen-activated protein kinase(MAPK)oncogenic signaling.Downregulation of circGNG7 expression in HNSCC increased HSP27-JNK/P38 MAPK signaling and promoted tumor progression.Conclusions:Our results revealed that a new intronic circRNA,circGNG7,functions as a strong tumor suppressor and that circGNG7/HSP27-JNK/P38 MAPK signaling is a novel mechanism by which HNSCC progression can be controlled.

Stimuli responsive co-delivery of celecoxib and BMP2 from micro-scaffold for periodontal disease treatment

Controlling inflammation meanwhile facilitating tissue regeneration has been considered as a promising strategy to treat inflammatory bone defect. Herein, we describe the synthesis of a bio-sensitive poly(lactic-co-glycolic acid)/mesoporous silica nanocarriers core-shell porous microsphere(PLGA/MSNsPMS) encapsulated poly(L-lactic acid)(PLLA) spongy nanofibrous micro-scaffold as a new generation of therapeutic platform for effective reconstruction of bone defects caused by periodontal diseases.The PLGA/MSNs-PMS were designed as stimuli-responsive carriers for on-demand co-delivery of multiple biomolecules to provide proper physiological environment, while the multi-level(from macro-,micro-to nanometers) nanofibrous and porous structures in PLLA micro-scaffold were in charge of the reconstruction of ECM, which synergistically contribute to the enhancement of new tissue formation under inflammatory condition. After local injection into periodontal tissue, this construct could sequentially release bone growth factor(BMP-2) as well as anti-inflammatory drug(celecoxib) loaded MSNs in response to the over-expressed matrix metalloproteinases(MMP) in periodontal region. During alveolar bone regeneration induced by BMP-2 and ECM like structure, the MSNs would further deliver celecoxib in target cells to achieve inflammation inhibition, resulting in effective treatment of periodontal disease.

Death caused by Head and Neck Osteosarcoma:A Retrospective Study from a Single Institute

Objective: To investigate factors that benefit patients with head and neck osteosarcoma( HNOS) before death. Methods: Patients admitted in our department from 2007 to 2015 who died during follow-up after surgery for HNOS were selected. Information concerning demographics,disease,treatment and follow-up were collected and analyzed. Results: A total of 77 patients died at a median age of 42 years old,of whom 33 were male and 44 female. Thirty-nine tumors were identified in the maxilla and skull base region while 38 in the mandible. Positive surgical margins were observed in 7 cases. Twenty patients received adjuvant chemotherapy,and 36 received postoperative radiotherapy. Local recurrence,as an initial cause of death,occurred in 25 cases,whilst metastasis occurred in the rest. Conclusion: Patients with HNOS benefit from negative surgical margins and adjuvant chemotherapy before death. Patients above 30 years old have longer disease-free survival,and patients with tumors of low pathological grade have longer overall survival. Tumor size and postoperative radiotherapy are negative prognostic factors. Frequent follow-up should be conducted for at least 48 postoperative months.

Activating proper inflammation for wound-healing acceleration via mesoporous silica nanoparticle tissue adhesive

Efficient initiation and resolution of inflammation are crucial for wound repair.However,with using tissue adhesives for wound repair,patients occasionally suffered from delayed healing process because slow elimination of those exogenous adhesives generally leads to chronic inflammation.As the demand for minimal invasive therapy continues to rise,desire for adhesive materials that can effectively reconnect surgical gaps and promote wound regeneration becomes increasingly urgent.Herein,by exploiting the inherent porous structure and performance of adhesion to tissue of mesoporous silica nanoparticles(MSNs),we demonstrate a tissue adhesive that can elicit acute inflammatory response and get eliminated after tissue reformation.With formation of nanocomposites in wound gaps,the injured tissues can get reconnected conveniently.The resultant accelerated healing process verifty that the strategy of exploiting unique properties of nanomaterials can effectively promote inflammation resolution and wound repair.This design strategy will inspire more innovative tissue adhesives for clinical applications.

PRKG1 mutation identified by whole-exome sequencing:a potential genetic etiology for He-Zhao deficiency

Objective:He-Zhao deficiency was originally described as a severe type of nonsyndromic hypodontia,and the causative gene locus was mapped to chromosome 10q11.2.The aim of this study was to identify potential genetic mutations that could cause He-Zhao deficiency.Methods:Patients with He-Zhao deficiency and their unaffected relatives of the large pedigree were investigated.The whole-exome sequencing using next-generation sequencing was employed to identify genetic variants.The data generated from the whole-exome sequencing using the Illumina Novaseq 6000 system were further analyzed by Burrows-Wheeler Aligner software,Sequence Alignment/Map tools and ANNOVAR tool.In vitro luciferase assay was used to investigate the effect of the detected mutation on gene expression.R environment was used to conduct t-tests.The study protocol was approved by the Research Ethics Committee of Bio-X Institutes,Shanghai Jiao Tong University(M2011004).Results:The exomes of five patients with He-Zhao deficiency and two of their unaffected relatives identified a mutation in PRKG1αas the molecular etiology of the disease.The variant c.-144 C>A of PRKG1 isoform 1 cosegregated with permanent tooth agenesis in 93 family members who were older than 12,at which time the primary teeth should have been replaced with permanent teeth.Functional studies suggested that the mutant allele promotes gene transcription by increasing its promoter activity.Conclusion:c.-144 C>A variant of PRKG1αinvolving odontoclast-associated root resorption is responsible for He-Zhao deficiency,unlike other forms of hypodontia,which typically involve odontoblast dysfunction.