Growing evidence suggests close associations between periodontitis and atherosclerosis.To further understand the pathological relationships of these associations,we developed periodontitis with ligature placement arou...Growing evidence suggests close associations between periodontitis and atherosclerosis.To further understand the pathological relationships of these associations,we developed periodontitis with ligature placement around maxillary molars or ligature placement in conjunction with Porphyromonas gingivalis lipopolysaccharide injection at the ligature sites (ligature/P.g.LPS) in Apolipoprotein E knock out mice and studied the atherogenesis process in these animals.The mice were fed with high fat diet for 11 weeks and sacrificed for analyzing periodontitis,systemic inflammation,and atherosclerosis.Controls did not develop periodontitis or systemic inflammation and had minimal lipid deposition in the aortas,but mice receiving ligature or ligature/P.g.LPS showed severe periodontitis,systemic inflammation,and aortic plaque formation.The aortic plaque contained abundant macrophages and cells expressing both endothelial and mesenchymal cell markers.The severity of periodontitis was slightly higher in mice receiving ligature/P.g.LPS than ligature alone,and the magnitude of systemic inflammation and aortic plaque formation were also notably greater in the mice with ligature/P.g.LPS.These observations indicate that the development of atherosclerosis is due to systemic inflammation caused by severe periodontitis.In vitro,P.g.LPS enhanced the secretion of pro-inflammatory cytokines from macrophages and increased the adhesion of monocytes to endothelial cells by upregulating the expression of adhesion molecules from endothelial cells.Moreover,secretory proteins,such as TNF-α,from macrophages induced endothelial–mesenchymal transitions of the endothelial cells.Taken together,systemic inflammation induced by severe periodontitis might exacerbate atherosclerosis via,in part,causing aberrant functions of vascular endothelial cells and the activation of macrophages in mice.展开更多
Mesenchymal stem cells （MSCs） have been identified and isolated from dental tissues, including stem cells from apical papilla, which demonstrated the ability to differentiate into dentin-forming odontoblasts. The hi...Mesenchymal stem cells （MSCs） have been identified and isolated from dental tissues, including stem cells from apical papilla, which demonstrated the ability to differentiate into dentin-forming odontoblasts. The histone demethylase KDM6B （also known as JMJD3） was shown to play a key role in promoting osteogenic commitment by removing epigenetic marks H3K27me3 from the promoters of osteogenic genes. Whether KDM6B is involved in odontogenic differentiation of dental MSCs, however, is not known. Here, we explored the role of KDM6B in dental MSC fate determination into the odontogenic lineage. Using shRNA-expressing lentivirus, we performed KDM6B knockdown in dental MSCs and observed that KDM6B depletion leads to a significant reduction in alkaline phosphate （ALP） activity and in formation of mineralized nodules assessed by Alizarin Red staining. Additionally, mRNA expression of odontogenic marker gene SP7 （osterix, OSX）, as well as extracellular matrix genes BGLAP （osteoclacin, OCN） and SPP1 （osteopontin, OPN）, was suppressed by KDM6B depletion. When KDM6B was overexpressed in KDM6B-knockdown MSCs, odontogenic differentiation was restored, further confirming the facilitating role of KDM6B in odontogenic commitment. Mechanistically, KDM6B was recruited to bone morphogenic protein 2 （BMP2） promoters and the subsequent removal of silencing H3K27me3 marks led to the activation of this odontogenic master transcription gene. Taken together, our results demonstrated the critical role of a histone demethylase in the epigenetic regulation of odontogenic differentiation of dental MSCs. KDM6B may present as a potential therapeutic target in the regeneration of tooth structures and the repair of craniofacial defects.展开更多
Both microstrueture and mechanical properties of low alloy steels treated by quenching and partitioning （Q＆P） process were examined. The mixed microstructure of martensite and large-fractioned retained austenite （...Both microstrueture and mechanical properties of low alloy steels treated by quenching and partitioning （Q＆P） process were examined. The mixed microstructure of martensite and large-fractioned retained austenite （about 27.3%） was characterized and analyzed, excellent combinations of total elongation of 19% and tensile strength of 1 835 MPa were obtained, and three-stage work hardening behavior was demonstrated during tensile test. The en hanced mechanical properties and work hardening behavior were explained based on the transformation induced plas ticity effect of large fractioned austenite.展开更多
Mesenchymal stem cells （MSCs） are characterized by their self-renewing capacity and differentiation potential into multiple tissues. Thus, management of the differentiation capacities of MSCs is important for MSC-ba...Mesenchymal stem cells （MSCs） are characterized by their self-renewing capacity and differentiation potential into multiple tissues. Thus, management of the differentiation capacities of MSCs is important for MSC-based regenerative medicine, such as craniofacial bone regeneration, and in new treatments for metabolic bone diseases, such as osteoporosis. In recent years, histone modification has been a growing topic in the field of MSC lineage specification, in which the Su（var）3-9, enhancer-of-zeste, trithorax （SET） domain-containing family and the Jumonji C （JmjC） domain-containing family represent the major histone lysine methyltransferases （KMTs） and histone lysine demethylases （KDMs）, respectively. In this review, we summarize the current understanding of the epigenetic mechanisms by which SET domain-containine KMTs and JmiC domain-containinlz KDMs balance the osteogenic and adipogenic differentiation of MSCs.展开更多
RNA sequencing(RNAseq)can reveal gene fusions,splicing variants,mutations/indels in addition to differential gene expression,thus providing a more complete genetic picture than DNA sequencing.This most widely used tec...RNA sequencing(RNAseq)can reveal gene fusions,splicing variants,mutations/indels in addition to differential gene expression,thus providing a more complete genetic picture than DNA sequencing.This most widely used technology in genomics tool box has evolved from classic bulk RNA sequencing(RNAseq),popular single cell RNA sequencing(scRNAseq)to newly emerged spatial RNA sequencing(spRNAseq).Bulk RNAseq studies average global gene expression,scRNAseq investigates single cell RNA biology up to 20,000 individual cells simultaneously,while spRNAseq has ability to dissect RNA activities spatially,representing next generation of RNA sequencing.This article highlights these technologies,characteristic features and suitable applications in precision oncology.展开更多
Aim To determine how SDF-1α/CXCR4 activates nuclear factor-kappa B （NF-κB） and promotes oral squamous cell carcinoma （OSCC） invasion.Methodology A lentivirus-based knockdown approach was utilized to deplete gene...Aim To determine how SDF-1α/CXCR4 activates nuclear factor-kappa B （NF-κB） and promotes oral squamous cell carcinoma （OSCC） invasion.Methodology A lentivirus-based knockdown approach was utilized to deplete gene expression. NF-κB activation was evaluated by Western blot analysis and electrophoretic mobility shift （EMSA）. Results We show that the activation of NF-κB by CXCR4 occurs through the Carma3/Bcl10/Maltl （CBM） complex in OSCC. We found that loss of components of the CBM complex in HNSCC can inhibit SDF-1α induced phosphorylation and degradation of IκBα, while TNFα induced IKK activation remains unchanged. Further, we identified a role for novel and atypical, but not classical, PKCs in activating IKK through CXCR4. Importantly, inhibition of the CBM complex leads to a significant decrease in SDF-1α mediated invasion of OSCC. Conclusion The CBM complex plays a critical role in CXCR4-induced NF-κB activation in OSCC. Targeting molecular components of the NF-κB signaling pathway may provide an important therapeutic opportunity in controlling the progression and metastasis of OSCC mediated by SDF-1α.展开更多
A duplex ultrafine microstructure in a medium manganese steel （0.2C-5Mn） was produced by austenite re- verted transformation annealing （ART-annealing）. The microstructural evolution during annealing was examined b...A duplex ultrafine microstructure in a medium manganese steel （0.2C-5Mn） was produced by austenite re- verted transformation annealing （ART-annealing）. The microstructural evolution during annealing was examined by scanning electron microscopy （SEM）, transmission electron microscopy （TEM） and X-ray diffraction （XRD）. Based on the microstructure examination, it was found that some M3C type carbides appeared in the martensitic matrix at the beginning of the ART-annealing. But with further increasing annealing time, these carbides would be dissolved and finally disappeared. Meanwhile, the austenite lath was developed in the ART-annealing process and the volume fraction of austenite increosed with the increase of the annealing time, which resulted in a duplex microstructure con- sisting of ultrafine-grained ferrite and large fraction of reverted austenite after long time annealing. The mechanical property examinations by uniaxial tensile tests showed that ART-annealing （6 h, 650 ℃） resulted in a superhigh product of strength to elongation up to 42 GPa ·%.展开更多
Head and neck squamous cell carcinoma(HNSCC),an aggressive malignancy,is characterized by high morbidity and low survival rates with limited therapeutic options outside of regional surgery,conventional cytotoxic chemo...Head and neck squamous cell carcinoma(HNSCC),an aggressive malignancy,is characterized by high morbidity and low survival rates with limited therapeutic options outside of regional surgery,conventional cytotoxic chemotherapy,and irradiation.Increasing studies have supported the synergistic role of the tumor microenvironment(TME)in cancer advancement.The immune system,in particular,plays a key role in surveillance against the initiation,development,and progression of HNSCC.The understanding of how neoplastic cells evolve and evade the immune system whether through self-immunogenicity manipulation,or expression of immunosuppressive mediators,provides the foundation for the development of advanced therapies.Furthermore,the crosstalk between cancer cells and the host immune system have a detrimental effect on the TME promoting angiogenesis,proliferation,and metastasis.This review provides a recent insight into the role of the key inflammatory cells infiltrating the TME,with a focus on reviewing immunological principles related to HNSCC,as cancer immunosurveillance and immune escape,including a brief overview of current immunotherapeutic strategies and ongoing clinical trials.展开更多
The microstructural evolutions of the cold rolled Fe-0.1C-5Mn steel during intercritical annealing were ex- amined using combined advanced techniques. It was demonstrated that intercritical annealing results in an ult...The microstructural evolutions of the cold rolled Fe-0.1C-5Mn steel during intercritical annealing were ex- amined using combined advanced techniques. It was demonstrated that intercritical annealing results in an ultrafine granular ferrite and austenite duplex structure in cold rolled 0.1C-5Mn steel. The strong partitioning of manganese and carbon elements from ferrite to austenite was found during intercritical annealing by scanning transmission elec- tron microscopy （STEM） and X-ray diffraction （XRD）. Strong effects of boundary characters on the austenite for- mation were indicated by austenite fast nucleation and growth in the high angle boundaries but sluggish nucleation and growth in the low angle boundaries. The ultrafine grained duplex structure in 0.1C-5Mn was resulted from the the sluggish Mn-diffusion and the extra high Gibbs free energy of ferrite phase. Based on the analysis of the micro- structure evolution, it was pointed out that the intercritical annealing of the medium Mn steels could be applied to fabricate an ultrafine duplex grained microstructure, which would be a promising approach to develop the 3rd genera- tion austomobile steels with excellent combination of strength and ductility.展开更多
AFF1 and AFF4 belong to the AFF （AF4/FMR2） family of proteins, which function as scaffolding proteins linking two different transcription elongation factors, positive elongation factor b （P-TEFb） and ELL1/2, in su...AFF1 and AFF4 belong to the AFF （AF4/FMR2） family of proteins, which function as scaffolding proteins linking two different transcription elongation factors, positive elongation factor b （P-TEFb） and ELL1/2, in super elongation complexes （SECs）. Both AFF1 and AFF4 regulate gene transcription through elongation and chromatln remodeling. However, their function in the osteogenic differentiation of mesenchymal stem cells （MSCs） is unknown. In this study, we show that small interfering RNA （siRNA）-mediated depletion of AFF1 in human MSCs leads to increased alkaline phosphatase （ALP） activity, enhanced mineralization and upregulated expression of osteogenic-related genes. On the contrary, depletion of AFF4 significantly inhibits the osteogenic potential of MSCs. In addition, we confirm that overexpression of AFF1 and AFF4 differentially affects osteogenic differentiation in vitro and MSC-mediated bone formation in vivo. Mechanistically, we find that AFFI regulates the expression of DKK1 via binding to its promoter region. Depletion of DKK1 in HA-AFFl-overexpressing MSCs abrogates the impairment of osteogenic differentiation. Moreover, we detect that AFF4 is enriched in the promoter region of ID1. AFF4 knockdown blunts the BRE luciferase activity, SP7 expression and ALP activity induced by BMP2 treatment. In conclusion, our data indicate that AFF1 and AFF4 differentially regulate the osteogenic differentiation of human MSCs.AFF1 and AFF4 belong to the AFF （AF4/FMR2） family of proteins, which function as scaffolding proteins linking two different transcription elongation factors, positive elongation factor b （P-TEFb） and ELL1/2, in super elongation complexes （SECs）. Both AFFI and AFF4 regulate gene transcription through elongation and chromatln remodeling. However, their function in the osteogenic differentiation of mesenchymal stem cells （MSCs） is unknown. In this study, we show that small interfering RNA （siRNA）-mediated depletion of AFF1 in human MSCs leads to increased alkaline phosphatase （ALP） activity, enhanced mineralization and upregulated expression of osteogenic-related genes. On the contrary, depletion of AFF4 significantly inhibits the osteogenic potential of MSCs. In addition, we confirm that overexpression of AFF1 and AFF4 differentially affects osteogenic differentiation in vitro and MSC-mediated bone formation in vivo. Mechanistically, we find that AFFI regulates the expression of DKK1 via binding to its promoter region. Depletion of DKK1 in HA-AFFl-overexpressing MSCs abrogates the impairment of osteogenic differentiation. Moreover, we detect that AFF4 is enriched in the promoter region of ID1. AFF4 knockdown blunts the BRE luciferase activity, SP7 expression and ALP activity induced by BMP2 treatment. In conclusion, our data indicate that AFF1 and AFF4 differentially regulate the osteogenic differentiation of human MSCs.展开更多
Mesenchymal stem cell （MSC）-mediated therapy has been shown to be clinically effective in regenerating tissue defects. For improved regenerative therapy, it is critical to isolate homogenous populations of MSCs with...Mesenchymal stem cell （MSC）-mediated therapy has been shown to be clinically effective in regenerating tissue defects. For improved regenerative therapy, it is critical to isolate homogenous populations of MSCs with high capacity to differentiate into appropriate tissues. The utilization of stem cell surface antigens provides a means to identify MSCs from various tissues. However, few surface markers that consistently isolate highly regenerative MSCs have been validated, making it challenging for routine clinical applications and making it all the more imperative to identify reliable surface markers. In this study, we used three surface marker combinations： CD51/CD140a, CD271, and STRO-1/CD146 for the isolation of homogenous populations of dental mesenchymal stem cells （DMSCs） from heterogeneous periodontal ligament cells （PDLCs）. Fluorescence-activated cell sorting analysis revealed that 24% of PDLCs were CD51＋/CD140a＋, 0.8% were CD271＋, and 2.4% were STRO-1＋/CD146＋. Sorted cell populations were further assessed for their multipotent properties by inducing osteogenic and chondrogenic differentiation. All three subsets of isolated DMSCs exhibited differentiation capacity into osteogenic and chondrogenic lineages but with varying degrees. CD271＋ DMSCs demonstrated the greatest osteogenic potential with strong induction of osteogenic markers such as DLX5, RUNX2, and BGLAP. Our study provides evidence that surface marker combinations used in this study are sufficient markers for the isolation of DMSCs from PDLCs. These results provide important insight into using specific surface markers for identifying homogenous populations of DMSCs for their improved utilization in regenerative medicine.展开更多
The austenite transformation behavior and mechanical properties of medium manganese steel subjected to tensile strain were studied by electron backscatter diffraction,X-ray diffraction and tensile tests.The results sh...The austenite transformation behavior and mechanical properties of medium manganese steel subjected to tensile strain were studied by electron backscatter diffraction,X-ray diffraction and tensile tests.The results show that the austenite phases are mainly distributed on the grain boundary in the duplex microstructure of austenite and ferrite,and it is easy for the big-size austenite to transform at small beginning tension strain following the mechanisms of both austenite (fcc)→ε- martensite (hcp)→α-martensite (bcc)and austenite (fcc)→α-martensite (bcc).Both yield strength and tensile strength increase with the increase in pre-strain,and the total elongation decreases,while the value of pre-strain plus total elongation almost keeps constant.During tensile deformation,transformation from austenite into martensite improves work-hardening rate remarkably.展开更多
Osteoporosis is a highly prevalent public health burden associated with an increased risk of bone fracture, particularly in aging women. Estrogen, an important medicinal component for the preventative and therapeutic ...Osteoporosis is a highly prevalent public health burden associated with an increased risk of bone fracture, particularly in aging women. Estrogen, an important medicinal component for the preventative and therapeutic treatment of postmenopausal osteoporosis, induces osteogenesis by activating the estrogen receptor signaling pathway and upregulating the expression of osteogenic genes, such as bone morphogenetic proteins(BMPs). The epigenetic regulation of estrogen-mediated osteogenesis,however, is still unclear. In this report, we found that estrogen significantly induced the expression of lysine-specific demethylase 6B(KDM6B) and that KDM6B depletion by shRNAs led to a significant reduction in the osteogenic potential of DMSCs.Mechanistically, upon estrogen stimulation, estrogen receptor-α(ERα) was recruited to the KDM6B promoter, directly enhancing KDM6B expression. Subsequently, KDM6B was recruited to the BMP2 and HOXC6 promoters, resulting in the removal of H3K27me3 marks and activating the transcription of BMP2 and HOXC6, the master genes of osteogenic differentiation. Furthermore, we found that estrogen enhanced DMSC osteogenesis during calvarial bone regeneration and that estrogen’s pro-osteogenic effect was dependent on KDM6B in vivo. Taken together, our results demonstrate the vital role of the ERα/KDM6B regulatory axis in the epigenetic regulation of the estrogen-dependent osteogenic response.展开更多
The aim of the present real time in vivo micro-computed tomography （pCT） and histologic experiment was to assess the efficacy of guided bone regeneration （GBR） around standardized calvarial critical size defects ...The aim of the present real time in vivo micro-computed tomography （pCT） and histologic experiment was to assess the efficacy of guided bone regeneration （GBR） around standardized calvarial critical size defects （CSD） using bone marrow-derived mesenchymal stem cells （BMSCs）, and collagen membrane （CM） with and without tricalcium phosphate （TCP） graft material. In the calvaria of nine female Sprague-Dawley rats, full-thickness CSD （diameter 4.6 mm） were created under general anesthesia. Treatment-wise, rats were divided into three groups. In group 1, CSD was covered with a resorbable CM; in group 2, BMSCs were filled in CSD and covered with CM; and in group 3, TCP soaked in BMSCs was placed in CSD and covered with CM. All defects were closed using resorbable sutures. Bone volume and bone mineral density of newly formed bone （NFB） and remaining TCP particles and rate of new bone formation was determined at baseline, 2, 4, 6, and 10 weeks using in vivo pCT. At the lOth week, the rats were killed and calvarial segments were assessed histologically. The results showed that the hardness of NFB was similar to that of the native bone in groups I and 2 as compared to the NFB in group 3. Likewise, values for the modulus of elasticity were also significantly higher in group 3 compared to groups 1 and 2. This suggests that TCP when used in combination with BMSCs and without CM was unable to form bone of significant strength that could possibly provide mechanical ＂lock＂ between the natural bone and NFB. The use of BMSCs as adjuncts to conventional GBR initiated new bone formation as early as 2 weeks of treatment compared to when GBR is attempted without adiunct BMSC therapy.展开更多
The dislocation pipe diffusion of Mn during annealing of 5Mn steel was experimentally investigated using transmission electron microscopy （TEM）. Many dislocations existed inside the ferrite and terminated at the α/...The dislocation pipe diffusion of Mn during annealing of 5Mn steel was experimentally investigated using transmission electron microscopy （TEM）. Many dislocations existed inside the ferrite and terminated at the α/γin- terface of the sample after intercritieal annealing at 650 ℃ for 1 min. Line scans of Mn distribution demonstrated a high Mn concentration in austenite and Mn enrichment at dislocations, indicating that the dislocation pipe diffusion of Mn during intercritical annealing occurred in addition to the γ/α interface diffusion. In-situ TEM observations at 500 ℃revealed that due to Ostwald ripening, large cementite precipitates grew while small cementite precipitates dissolved via Mn diffusion along the dislocations between them.展开更多
Mesenchymal stem cells （MSCs） are a promising tool in regenerative medicine due to their capacity to differentiate into multiple lineages. In addition to MSCs isolated from bone marrow （BMSCs）, adult MSCs are isol...Mesenchymal stem cells （MSCs） are a promising tool in regenerative medicine due to their capacity to differentiate into multiple lineages. In addition to MSCs isolated from bone marrow （BMSCs）, adult MSCs are isolated from craniofacial tissues including dental pulp tissues （DPs） using various stem cell surface markers. However, there has been a lack of consensus on a set of surface makers that are reproducibly effective at isolating putative multipotent dental mesenchymal stem cel^s （~M^Cs）. II1 ~his stucly, we used clif^et（~nt combinations of surface markers （CD51/CD140a, CD271, and STRO-1/CD146） to isolate homogeneous populations of DMSCs from heterogeneous dental pulp cells （DPCs） obtained from DP and compared their capacity to undergo multilineage differentiation. Fluorescence-activated cell sorting revealed that 27.3% of DPCs were CD51＋/CD140a＋, 10.6% were CD271＋, and 0.3% were STRO-1＋/CD146＋. Under odontogenic conditions, all three subsets of isolated DMSCs exhibited differentiation capacity into odontogenic lineages. Among these isolated subsets of DMSCs, CD271＋ DMSCs demonstrated the greatest odontogenic potential. While all three combinations of surface markers in this study successfully isolated DMSCs from DPCs, the single CD271 marker presents the most effective stem cell surface marker for identification of DMSCs with high odontogenic potential. Isolated CD271＋ DMSCs could potentially be utilized for future clinical applications in dentistry and regenerative medicine.展开更多
Aging of craniofacial skeleton significantly impairs the repair and regeneration of trauma-induced bony defects,and complicates dental treatment outcomes.Age-related alveolar bone loss could be attributed to decreased...Aging of craniofacial skeleton significantly impairs the repair and regeneration of trauma-induced bony defects,and complicates dental treatment outcomes.Age-related alveolar bone loss could be attributed to decreased progenitor pool through senescence,imbalance in bone metabolism and bone-fat ratio.Mesenchymal stem cells isolated from oral bones(OMSCs)have distinct lineage propensities and characteristics compared to MSCs from long bones,and are more suited for craniofacial regeneration.However,the effect of epigenetic modifications regulating OMSC differentiation and senescence in aging has not yet been investigated.In this study,we found that the histone demethylase KDM4B plays an essential role in regulating the osteogenesis of OMSCs and oral bone aging.Loss of KDM4B in OMSCs leads to inhibition of osteogenesis.Moreover,KDM4B loss promoted adipogenesis and OMSC senescence which further impairs bone-fat balance in the mandible.Together,our data suggest that KDM4B may underpin the molecular mechanisms of OMSC fate determination and alveolar bone homeostasis in skeletal aging,and present as a promising therapeutic target for addressing craniofacial skeletal defects associated with age-related deteriorations.展开更多
Optical spectroscopy devices are being developed and tested for the screening and diagnosis of oral precancer and cancer lesions. This study reports a device that uses white light for detection of suspicious lesions a...Optical spectroscopy devices are being developed and tested for the screening and diagnosis of oral precancer and cancer lesions. This study reports a device that uses white light for detection of suspicious lesions and green–amber light at 545 nm that detect tissue vascularity on patients with several suspicious oral lesions. The clinical grading of vascularity was compared to the histological grading of the biopsied lesions using specific biomarkers. Such a device, in the hands of dentists and other health professionals, could greatly increase the number of oral cancerous lesions detected in early phase. The purpose of this study is to correlate the clinical grading of tissue vascularity in several oral suspicious lesions using the IdentafiH system with the histological grading of the biopsied lesions using specific vascular markers. Twenty-one patients with various oral lesions were enrolled in the study. The lesions were visualized using IdentafiH device with white light illumination, followed by visualization of tissue autofluorescence and tissue reflectance. Tissue biopsied was obtained from the all lesions and both histopathological and immunohistochemical studies using a vascular endothelial biomarker（CD34） were performed on these tissue samples. The clinical vascular grading using the green–amber light at 545 nm and the expression pattern and intensity of staining for CD34 in the different biopsies varied depending on lesions, grading ranged from 1 to3. The increase in vascularity was observed in abnormal tissues when compared to normal mucosa, but this increase was not limited to carcinoma only as hyperkeratosis and other oral diseases, such as lichen planus, also showed increase in vascularity. Optical spectroscopy is a promising technology for the detection of oral mucosal abnormalities; however, further investigations with a larger population group is required to evaluate the usefulness of these devices in differentiating benign lesions from potentially malignant lesions.展开更多
Mesenchymal stem cells(MSCs)derived from human embryonic stem cells(hESCs)have significant potential for cell-mediated bone regeneration.Our recent study revealed that inhibiting the epigenetic regulator EZH2 plays a ...Mesenchymal stem cells(MSCs)derived from human embryonic stem cells(hESCs)have significant potential for cell-mediated bone regeneration.Our recent study revealed that inhibiting the epigenetic regulator EZH2 plays a key role in promoting the mesodermal differentiation of hESCs.In this study,an epigenome-wide analysis of hESCs and MSCs revealed that growth differentiation factor 6(GDF6),which is involved in bone formation,was the most upregulated gene associated with MSCs compared to hESCs.Furthermore,we identified GDF6 as a repressive target of EZH2 and found that ectopic GDF6 selectively promoted hESC differentiation towards the mesodermal lineage and enriched the MSC population.Our results provide molecular insights governing the mesenchymal commitment of hESCs and identify an inducing factor that offers strong promise for the future of regenerative medicine.展开更多
A combined process of hot-deformation plus two-step quenching and partitioning （HDQP） treatment was applied to a low carbon 20Si2CrNi3MoV steel, and transmission electron microscopy （TEM）, scanning electron micros...A combined process of hot-deformation plus two-step quenching and partitioning （HDQP） treatment was applied to a low carbon 20Si2CrNi3MoV steel, and transmission electron microscopy （TEM）, scanning electron microscopy （SEM）, X-ray diffraction （XRD）, Vickers hardness and tension test were used to characterize the microstructure and mechanical properties. More stable retained austen ite due to fine microstructures and typical curved micromorphology is obtained, and the newly-treated steel obtains more retained austenite because of the effect of hot deformation. The retained austenite fraction increases and then decreases with the increasing quenching temperature from 200 to 350 ℃. The maximum retained austenite fraction （18.3 % ） and elongation （15 % ） are obtained to enhance the ductility.展开更多
基金supported, in part, by the research funds awarded from the UCLA Chancellor’s Office (N.-H.P.)NIH/NIDCR DE 023348 (R.H.K. and N.-H.P.)NIH/NHLBI HL30568 (K.I.B.)
文摘Growing evidence suggests close associations between periodontitis and atherosclerosis.To further understand the pathological relationships of these associations,we developed periodontitis with ligature placement around maxillary molars or ligature placement in conjunction with Porphyromonas gingivalis lipopolysaccharide injection at the ligature sites (ligature/P.g.LPS) in Apolipoprotein E knock out mice and studied the atherogenesis process in these animals.The mice were fed with high fat diet for 11 weeks and sacrificed for analyzing periodontitis,systemic inflammation,and atherosclerosis.Controls did not develop periodontitis or systemic inflammation and had minimal lipid deposition in the aortas,but mice receiving ligature or ligature/P.g.LPS showed severe periodontitis,systemic inflammation,and aortic plaque formation.The aortic plaque contained abundant macrophages and cells expressing both endothelial and mesenchymal cell markers.The severity of periodontitis was slightly higher in mice receiving ligature/P.g.LPS than ligature alone,and the magnitude of systemic inflammation and aortic plaque formation were also notably greater in the mice with ligature/P.g.LPS.These observations indicate that the development of atherosclerosis is due to systemic inflammation caused by severe periodontitis.In vitro,P.g.LPS enhanced the secretion of pro-inflammatory cytokines from macrophages and increased the adhesion of monocytes to endothelial cells by upregulating the expression of adhesion molecules from endothelial cells.Moreover,secretory proteins,such as TNF-α,from macrophages induced endothelial–mesenchymal transitions of the endothelial cells.Taken together,systemic inflammation induced by severe periodontitis might exacerbate atherosclerosis via,in part,causing aberrant functions of vascular endothelial cells and the activation of macrophages in mice.
文摘Mesenchymal stem cells （MSCs） have been identified and isolated from dental tissues, including stem cells from apical papilla, which demonstrated the ability to differentiate into dentin-forming odontoblasts. The histone demethylase KDM6B （also known as JMJD3） was shown to play a key role in promoting osteogenic commitment by removing epigenetic marks H3K27me3 from the promoters of osteogenic genes. Whether KDM6B is involved in odontogenic differentiation of dental MSCs, however, is not known. Here, we explored the role of KDM6B in dental MSC fate determination into the odontogenic lineage. Using shRNA-expressing lentivirus, we performed KDM6B knockdown in dental MSCs and observed that KDM6B depletion leads to a significant reduction in alkaline phosphate （ALP） activity and in formation of mineralized nodules assessed by Alizarin Red staining. Additionally, mRNA expression of odontogenic marker gene SP7 （osterix, OSX）, as well as extracellular matrix genes BGLAP （osteoclacin, OCN） and SPP1 （osteopontin, OPN）, was suppressed by KDM6B depletion. When KDM6B was overexpressed in KDM6B-knockdown MSCs, odontogenic differentiation was restored, further confirming the facilitating role of KDM6B in odontogenic commitment. Mechanistically, KDM6B was recruited to bone morphogenic protein 2 （BMP2） promoters and the subsequent removal of silencing H3K27me3 marks led to the activation of this odontogenic master transcription gene. Taken together, our results demonstrated the critical role of a histone demethylase in the epigenetic regulation of odontogenic differentiation of dental MSCs. KDM6B may present as a potential therapeutic target in the regeneration of tooth structures and the repair of craniofacial defects.
基金Item Sponsored by Youth Science Funds of China(51101036)National Basic Research Program of China(2010CB630803)National Key Technology Support Program of China(2013BAE07B05)
文摘Both microstrueture and mechanical properties of low alloy steels treated by quenching and partitioning （Q＆P） process were examined. The mixed microstructure of martensite and large-fractioned retained austenite （about 27.3%） was characterized and analyzed, excellent combinations of total elongation of 19% and tensile strength of 1 835 MPa were obtained, and three-stage work hardening behavior was demonstrated during tensile test. The en hanced mechanical properties and work hardening behavior were explained based on the transformation induced plas ticity effect of large fractioned austenite.
基金supported by the National Institute of Dental and Craniofacial Research grants, K08DE024603-02, DE019412, and DE01651a grant from 111 Project of MOE, Chinasupported by Open Fund of State Key Laboratory of Oral Diseases, Sichuan University
文摘Mesenchymal stem cells （MSCs） are characterized by their self-renewing capacity and differentiation potential into multiple tissues. Thus, management of the differentiation capacities of MSCs is important for MSC-based regenerative medicine, such as craniofacial bone regeneration, and in new treatments for metabolic bone diseases, such as osteoporosis. In recent years, histone modification has been a growing topic in the field of MSC lineage specification, in which the Su（var）3-9, enhancer-of-zeste, trithorax （SET） domain-containing family and the Jumonji C （JmjC） domain-containing family represent the major histone lysine methyltransferases （KMTs） and histone lysine demethylases （KDMs）, respectively. In this review, we summarize the current understanding of the epigenetic mechanisms by which SET domain-containine KMTs and JmiC domain-containinlz KDMs balance the osteogenic and adipogenic differentiation of MSCs.
基金This work was supported by NIH/NIDCR grants R01DE029173 and R01DE030445 and NIH/NCI grant R01CA236878.
文摘RNA sequencing(RNAseq)can reveal gene fusions,splicing variants,mutations/indels in addition to differential gene expression,thus providing a more complete genetic picture than DNA sequencing.This most widely used technology in genomics tool box has evolved from classic bulk RNA sequencing(RNAseq),popular single cell RNA sequencing(scRNAseq)to newly emerged spatial RNA sequencing(spRNAseq).Bulk RNAseq studies average global gene expression,scRNAseq investigates single cell RNA biology up to 20,000 individual cells simultaneously,while spRNAseq has ability to dissect RNA activities spatially,representing next generation of RNA sequencing.This article highlights these technologies,characteristic features and suitable applications in precision oncology.
基金supported by the grants DE13848 and DE15964 from National Institute of Dental and Craniofacial Research, National Institute of Health, USA
文摘Aim To determine how SDF-1α/CXCR4 activates nuclear factor-kappa B （NF-κB） and promotes oral squamous cell carcinoma （OSCC） invasion.Methodology A lentivirus-based knockdown approach was utilized to deplete gene expression. NF-κB activation was evaluated by Western blot analysis and electrophoretic mobility shift （EMSA）. Results We show that the activation of NF-κB by CXCR4 occurs through the Carma3/Bcl10/Maltl （CBM） complex in OSCC. We found that loss of components of the CBM complex in HNSCC can inhibit SDF-1α induced phosphorylation and degradation of IκBα, while TNFα induced IKK activation remains unchanged. Further, we identified a role for novel and atypical, but not classical, PKCs in activating IKK through CXCR4. Importantly, inhibition of the CBM complex leads to a significant decrease in SDF-1α mediated invasion of OSCC. Conclusion The CBM complex plays a critical role in CXCR4-induced NF-κB activation in OSCC. Targeting molecular components of the NF-κB signaling pathway may provide an important therapeutic opportunity in controlling the progression and metastasis of OSCC mediated by SDF-1α.
基金Sponsored by National Natural Science Foundation of China(51371057,11172187)National Basic Research Program(973 Program)of China(2010CB630803)Program for New Century Excellent Talents in University of China(NCET-12-0372)
文摘A duplex ultrafine microstructure in a medium manganese steel （0.2C-5Mn） was produced by austenite re- verted transformation annealing （ART-annealing）. The microstructural evolution during annealing was examined by scanning electron microscopy （SEM）, transmission electron microscopy （TEM） and X-ray diffraction （XRD）. Based on the microstructure examination, it was found that some M3C type carbides appeared in the martensitic matrix at the beginning of the ART-annealing. But with further increasing annealing time, these carbides would be dissolved and finally disappeared. Meanwhile, the austenite lath was developed in the ART-annealing process and the volume fraction of austenite increosed with the increase of the annealing time, which resulted in a duplex microstructure con- sisting of ultrafine-grained ferrite and large fraction of reverted austenite after long time annealing. The mechanical property examinations by uniaxial tensile tests showed that ART-annealing （6 h, 650 ℃） resulted in a superhigh product of strength to elongation up to 42 GPa ·%.
基金supported by the NIH Grants R01DE029173,R01DE030445,and R01CA236878。
文摘Head and neck squamous cell carcinoma(HNSCC),an aggressive malignancy,is characterized by high morbidity and low survival rates with limited therapeutic options outside of regional surgery,conventional cytotoxic chemotherapy,and irradiation.Increasing studies have supported the synergistic role of the tumor microenvironment(TME)in cancer advancement.The immune system,in particular,plays a key role in surveillance against the initiation,development,and progression of HNSCC.The understanding of how neoplastic cells evolve and evade the immune system whether through self-immunogenicity manipulation,or expression of immunosuppressive mediators,provides the foundation for the development of advanced therapies.Furthermore,the crosstalk between cancer cells and the host immune system have a detrimental effect on the TME promoting angiogenesis,proliferation,and metastasis.This review provides a recent insight into the role of the key inflammatory cells infiltrating the TME,with a focus on reviewing immunological principles related to HNSCC,as cancer immunosurveillance and immune escape,including a brief overview of current immunotherapeutic strategies and ongoing clinical trials.
基金Item Sponsored by National Natural Science Foundation of China(51371057)National Basic Research Program of China(2010CB630803)
文摘The microstructural evolutions of the cold rolled Fe-0.1C-5Mn steel during intercritical annealing were ex- amined using combined advanced techniques. It was demonstrated that intercritical annealing results in an ultrafine granular ferrite and austenite duplex structure in cold rolled 0.1C-5Mn steel. The strong partitioning of manganese and carbon elements from ferrite to austenite was found during intercritical annealing by scanning transmission elec- tron microscopy （STEM） and X-ray diffraction （XRD）. Strong effects of boundary characters on the austenite for- mation were indicated by austenite fast nucleation and growth in the high angle boundaries but sluggish nucleation and growth in the low angle boundaries. The ultrafine grained duplex structure in 0.1C-5Mn was resulted from the the sluggish Mn-diffusion and the extra high Gibbs free energy of ferrite phase. Based on the analysis of the micro- structure evolution, it was pointed out that the intercritical annealing of the medium Mn steels could be applied to fabricate an ultrafine duplex grained microstructure, which would be a promising approach to develop the 3rd genera- tion austomobile steels with excellent combination of strength and ductility.
基金supported by grants from the National Natural Science Foundation of China(NSFC,81722014,81571001,81500354,and 81621062)Sichuan Province Science and Technology Innovation Team Program(2017TD0016)State Key Laboratory of Oral Diseases(SKLOD201704)
文摘AFF1 and AFF4 belong to the AFF （AF4/FMR2） family of proteins, which function as scaffolding proteins linking two different transcription elongation factors, positive elongation factor b （P-TEFb） and ELL1/2, in super elongation complexes （SECs）. Both AFF1 and AFF4 regulate gene transcription through elongation and chromatln remodeling. However, their function in the osteogenic differentiation of mesenchymal stem cells （MSCs） is unknown. In this study, we show that small interfering RNA （siRNA）-mediated depletion of AFF1 in human MSCs leads to increased alkaline phosphatase （ALP） activity, enhanced mineralization and upregulated expression of osteogenic-related genes. On the contrary, depletion of AFF4 significantly inhibits the osteogenic potential of MSCs. In addition, we confirm that overexpression of AFF1 and AFF4 differentially affects osteogenic differentiation in vitro and MSC-mediated bone formation in vivo. Mechanistically, we find that AFFI regulates the expression of DKK1 via binding to its promoter region. Depletion of DKK1 in HA-AFFl-overexpressing MSCs abrogates the impairment of osteogenic differentiation. Moreover, we detect that AFF4 is enriched in the promoter region of ID1. AFF4 knockdown blunts the BRE luciferase activity, SP7 expression and ALP activity induced by BMP2 treatment. In conclusion, our data indicate that AFF1 and AFF4 differentially regulate the osteogenic differentiation of human MSCs.AFF1 and AFF4 belong to the AFF （AF4/FMR2） family of proteins, which function as scaffolding proteins linking two different transcription elongation factors, positive elongation factor b （P-TEFb） and ELL1/2, in super elongation complexes （SECs）. Both AFFI and AFF4 regulate gene transcription through elongation and chromatln remodeling. However, their function in the osteogenic differentiation of mesenchymal stem cells （MSCs） is unknown. In this study, we show that small interfering RNA （siRNA）-mediated depletion of AFF1 in human MSCs leads to increased alkaline phosphatase （ALP） activity, enhanced mineralization and upregulated expression of osteogenic-related genes. On the contrary, depletion of AFF4 significantly inhibits the osteogenic potential of MSCs. In addition, we confirm that overexpression of AFF1 and AFF4 differentially affects osteogenic differentiation in vitro and MSC-mediated bone formation in vivo. Mechanistically, we find that AFFI regulates the expression of DKK1 via binding to its promoter region. Depletion of DKK1 in HA-AFFl-overexpressing MSCs abrogates the impairment of osteogenic differentiation. Moreover, we detect that AFF4 is enriched in the promoter region of ID1. AFF4 knockdown blunts the BRE luciferase activity, SP7 expression and ALP activity induced by BMP2 treatment. In conclusion, our data indicate that AFF1 and AFF4 differentially regulate the osteogenic differentiation of human MSCs.
基金supported by National Institute of Dental and Craniofacial Research grant T90DE022734
文摘Mesenchymal stem cell （MSC）-mediated therapy has been shown to be clinically effective in regenerating tissue defects. For improved regenerative therapy, it is critical to isolate homogenous populations of MSCs with high capacity to differentiate into appropriate tissues. The utilization of stem cell surface antigens provides a means to identify MSCs from various tissues. However, few surface markers that consistently isolate highly regenerative MSCs have been validated, making it challenging for routine clinical applications and making it all the more imperative to identify reliable surface markers. In this study, we used three surface marker combinations： CD51/CD140a, CD271, and STRO-1/CD146 for the isolation of homogenous populations of dental mesenchymal stem cells （DMSCs） from heterogeneous periodontal ligament cells （PDLCs）. Fluorescence-activated cell sorting analysis revealed that 24% of PDLCs were CD51＋/CD140a＋, 0.8% were CD271＋, and 2.4% were STRO-1＋/CD146＋. Sorted cell populations were further assessed for their multipotent properties by inducing osteogenic and chondrogenic differentiation. All three subsets of isolated DMSCs exhibited differentiation capacity into osteogenic and chondrogenic lineages but with varying degrees. CD271＋ DMSCs demonstrated the greatest osteogenic potential with strong induction of osteogenic markers such as DLX5, RUNX2, and BGLAP. Our study provides evidence that surface marker combinations used in this study are sufficient markers for the isolation of DMSCs from PDLCs. These results provide important insight into using specific surface markers for identifying homogenous populations of DMSCs for their improved utilization in regenerative medicine.
文摘The austenite transformation behavior and mechanical properties of medium manganese steel subjected to tensile strain were studied by electron backscatter diffraction,X-ray diffraction and tensile tests.The results show that the austenite phases are mainly distributed on the grain boundary in the duplex microstructure of austenite and ferrite,and it is easy for the big-size austenite to transform at small beginning tension strain following the mechanisms of both austenite (fcc)→ε- martensite (hcp)→α-martensite (bcc)and austenite (fcc)→α-martensite (bcc).Both yield strength and tensile strength increase with the increase in pre-strain,and the total elongation decreases,while the value of pre-strain plus total elongation almost keeps constant.During tensile deformation,transformation from austenite into martensite improves work-hardening rate remarkably.
基金supported by NIH/NIDCR grants K08DE024603, R01DE16513, and R01DE024828
文摘Osteoporosis is a highly prevalent public health burden associated with an increased risk of bone fracture, particularly in aging women. Estrogen, an important medicinal component for the preventative and therapeutic treatment of postmenopausal osteoporosis, induces osteogenesis by activating the estrogen receptor signaling pathway and upregulating the expression of osteogenic genes, such as bone morphogenetic proteins(BMPs). The epigenetic regulation of estrogen-mediated osteogenesis,however, is still unclear. In this report, we found that estrogen significantly induced the expression of lysine-specific demethylase 6B(KDM6B) and that KDM6B depletion by shRNAs led to a significant reduction in the osteogenic potential of DMSCs.Mechanistically, upon estrogen stimulation, estrogen receptor-α(ERα) was recruited to the KDM6B promoter, directly enhancing KDM6B expression. Subsequently, KDM6B was recruited to the BMP2 and HOXC6 promoters, resulting in the removal of H3K27me3 marks and activating the transcription of BMP2 and HOXC6, the master genes of osteogenic differentiation. Furthermore, we found that estrogen enhanced DMSC osteogenesis during calvarial bone regeneration and that estrogen’s pro-osteogenic effect was dependent on KDM6B in vivo. Taken together, our results demonstrate the vital role of the ERα/KDM6B regulatory axis in the epigenetic regulation of the estrogen-dependent osteogenic response.
基金King Saud University,through Vice Deanship of Research Chairs
文摘The aim of the present real time in vivo micro-computed tomography （pCT） and histologic experiment was to assess the efficacy of guided bone regeneration （GBR） around standardized calvarial critical size defects （CSD） using bone marrow-derived mesenchymal stem cells （BMSCs）, and collagen membrane （CM） with and without tricalcium phosphate （TCP） graft material. In the calvaria of nine female Sprague-Dawley rats, full-thickness CSD （diameter 4.6 mm） were created under general anesthesia. Treatment-wise, rats were divided into three groups. In group 1, CSD was covered with a resorbable CM; in group 2, BMSCs were filled in CSD and covered with CM; and in group 3, TCP soaked in BMSCs was placed in CSD and covered with CM. All defects were closed using resorbable sutures. Bone volume and bone mineral density of newly formed bone （NFB） and remaining TCP particles and rate of new bone formation was determined at baseline, 2, 4, 6, and 10 weeks using in vivo pCT. At the lOth week, the rats were killed and calvarial segments were assessed histologically. The results showed that the hardness of NFB was similar to that of the native bone in groups I and 2 as compared to the NFB in group 3. Likewise, values for the modulus of elasticity were also significantly higher in group 3 compared to groups 1 and 2. This suggests that TCP when used in combination with BMSCs and without CM was unable to form bone of significant strength that could possibly provide mechanical ＂lock＂ between the natural bone and NFB. The use of BMSCs as adjuncts to conventional GBR initiated new bone formation as early as 2 weeks of treatment compared to when GBR is attempted without adiunct BMSC therapy.
基金Item Sponsored by National Key Research and Development Program of China(2016YFB0700402)National Basic Research Program of China(2010CB630800,2015CB921700)+1 种基金National Natural Science Foundation of China(51671112,51471096,51390471,11374174)Tsinghua University Initiative Scientific Research Program(20141081200,20131089311)
文摘The dislocation pipe diffusion of Mn during annealing of 5Mn steel was experimentally investigated using transmission electron microscopy （TEM）. Many dislocations existed inside the ferrite and terminated at the α/γin- terface of the sample after intercritieal annealing at 650 ℃ for 1 min. Line scans of Mn distribution demonstrated a high Mn concentration in austenite and Mn enrichment at dislocations, indicating that the dislocation pipe diffusion of Mn during intercritical annealing occurred in addition to the γ/α interface diffusion. In-situ TEM observations at 500 ℃revealed that due to Ostwald ripening, large cementite precipitates grew while small cementite precipitates dissolved via Mn diffusion along the dislocations between them.
基金supported by National Institute of Dental and Craniofacial Research grant T90DE022734
文摘Mesenchymal stem cells （MSCs） are a promising tool in regenerative medicine due to their capacity to differentiate into multiple lineages. In addition to MSCs isolated from bone marrow （BMSCs）, adult MSCs are isolated from craniofacial tissues including dental pulp tissues （DPs） using various stem cell surface markers. However, there has been a lack of consensus on a set of surface makers that are reproducibly effective at isolating putative multipotent dental mesenchymal stem cel^s （~M^Cs）. II1 ~his stucly, we used clif^et（~nt combinations of surface markers （CD51/CD140a, CD271, and STRO-1/CD146） to isolate homogeneous populations of DMSCs from heterogeneous dental pulp cells （DPCs） obtained from DP and compared their capacity to undergo multilineage differentiation. Fluorescence-activated cell sorting revealed that 27.3% of DPCs were CD51＋/CD140a＋, 10.6% were CD271＋, and 0.3% were STRO-1＋/CD146＋. Under odontogenic conditions, all three subsets of isolated DMSCs exhibited differentiation capacity into odontogenic lineages. Among these isolated subsets of DMSCs, CD271＋ DMSCs demonstrated the greatest odontogenic potential. While all three combinations of surface markers in this study successfully isolated DMSCs from DPCs, the single CD271 marker presents the most effective stem cell surface marker for identification of DMSCs with high odontogenic potential. Isolated CD271＋ DMSCs could potentially be utilized for future clinical applications in dentistry and regenerative medicine.
基金supported by NIH/NIDCR grants R01DE028260 and R01DE024828。
文摘Aging of craniofacial skeleton significantly impairs the repair and regeneration of trauma-induced bony defects,and complicates dental treatment outcomes.Age-related alveolar bone loss could be attributed to decreased progenitor pool through senescence,imbalance in bone metabolism and bone-fat ratio.Mesenchymal stem cells isolated from oral bones(OMSCs)have distinct lineage propensities and characteristics compared to MSCs from long bones,and are more suited for craniofacial regeneration.However,the effect of epigenetic modifications regulating OMSC differentiation and senescence in aging has not yet been investigated.In this study,we found that the histone demethylase KDM4B plays an essential role in regulating the osteogenesis of OMSCs and oral bone aging.Loss of KDM4B in OMSCs leads to inhibition of osteogenesis.Moreover,KDM4B loss promoted adipogenesis and OMSC senescence which further impairs bone-fat balance in the mandible.Together,our data suggest that KDM4B may underpin the molecular mechanisms of OMSC fate determination and alveolar bone homeostasis in skeletal aging,and present as a promising therapeutic target for addressing craniofacial skeletal defects associated with age-related deteriorations.
文摘Optical spectroscopy devices are being developed and tested for the screening and diagnosis of oral precancer and cancer lesions. This study reports a device that uses white light for detection of suspicious lesions and green–amber light at 545 nm that detect tissue vascularity on patients with several suspicious oral lesions. The clinical grading of vascularity was compared to the histological grading of the biopsied lesions using specific biomarkers. Such a device, in the hands of dentists and other health professionals, could greatly increase the number of oral cancerous lesions detected in early phase. The purpose of this study is to correlate the clinical grading of tissue vascularity in several oral suspicious lesions using the IdentafiH system with the histological grading of the biopsied lesions using specific vascular markers. Twenty-one patients with various oral lesions were enrolled in the study. The lesions were visualized using IdentafiH device with white light illumination, followed by visualization of tissue autofluorescence and tissue reflectance. Tissue biopsied was obtained from the all lesions and both histopathological and immunohistochemical studies using a vascular endothelial biomarker（CD34） were performed on these tissue samples. The clinical vascular grading using the green–amber light at 545 nm and the expression pattern and intensity of staining for CD34 in the different biopsies varied depending on lesions, grading ranged from 1 to3. The increase in vascularity was observed in abnormal tissues when compared to normal mucosa, but this increase was not limited to carcinoma only as hyperkeratosis and other oral diseases, such as lichen planus, also showed increase in vascularity. Optical spectroscopy is a promising technology for the detection of oral mucosal abnormalities; however, further investigations with a larger population group is required to evaluate the usefulness of these devices in differentiating benign lesions from potentially malignant lesions.
基金the NIH/NIDCR grant R01DE16513(C.Y.W.),NIH/NIDCR K08DE024603(C.H.)the Shapiro family Charitable Funds.The Flow cytometry was performed in the UCLA Flow Cytometry Core Facility that is supported by NIH awards P30CA016042 and 5P30AI028697.
文摘Mesenchymal stem cells(MSCs)derived from human embryonic stem cells(hESCs)have significant potential for cell-mediated bone regeneration.Our recent study revealed that inhibiting the epigenetic regulator EZH2 plays a key role in promoting the mesodermal differentiation of hESCs.In this study,an epigenome-wide analysis of hESCs and MSCs revealed that growth differentiation factor 6(GDF6),which is involved in bone formation,was the most upregulated gene associated with MSCs compared to hESCs.Furthermore,we identified GDF6 as a repressive target of EZH2 and found that ectopic GDF6 selectively promoted hESC differentiation towards the mesodermal lineage and enriched the MSC population.Our results provide molecular insights governing the mesenchymal commitment of hESCs and identify an inducing factor that offers strong promise for the future of regenerative medicine.
基金supported by the National Key Research and Development Plan(Nos.2017YFB0304401 and 2016YFB0101605)the Major State Basic Research Development Program of China(973Program)(No.2010CB630803)
文摘A combined process of hot-deformation plus two-step quenching and partitioning （HDQP） treatment was applied to a low carbon 20Si2CrNi3MoV steel, and transmission electron microscopy （TEM）, scanning electron microscopy （SEM）, X-ray diffraction （XRD）, Vickers hardness and tension test were used to characterize the microstructure and mechanical properties. More stable retained austen ite due to fine microstructures and typical curved micromorphology is obtained, and the newly-treated steel obtains more retained austenite because of the effect of hot deformation. The retained austenite fraction increases and then decreases with the increasing quenching temperature from 200 to 350 ℃. The maximum retained austenite fraction （18.3 % ） and elongation （15 % ） are obtained to enhance the ductility.
