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Background Periodontal ligament stem cells (PDLSCs) are considered as candidate cells for the regeneration of periodontal and alveolar bone tissues. Antisense to the cerebellar degeneration-related protein 1 transcript (CDR1as), which is a newly discovered circular RNA (circRNA), has been reported to act as an miR-7 sponge and to be involved in many biological processes. Here, we investigated the potential roles of CDR1as and miR-7 in the osteogenic differentiation of PDLSCs. Methods The expression pattern of CDR1as and miR-7 in PDLSCs during osteogenesis was detected by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Then we overexpressed or knocked down CDR1as or miR-7 to confirm whether they were involved in the regulation of osteoblast differentiation in PDLSCs. Alkaline phosphatase (ALP) and alizarin red S (ARS) staining were used to detect the activity of osteoblasts and mineral deposition. Furthermore, a dual luciferase reporter assay was conducted to analyze the binding of miR-7 to growth differentiation factor (GDF)5. To further verify the role of CDR1as in osteoblast differentiation, we conducted animal experiments in vivo. New bone formation in specimens was analyzed by microcomputed tomography (micro-CT), hematoxylin and eosin staining, and immunofluorescence staining. Results We observed that CDR1as was significantly upregulated during the osteogenic differentiation, whereas miR-7 was significantly downregulated. Moreover, knockdown of CDR1as and overexpression of miR-7 inhibited the ALP activity, ARS staining, and expression of osteogenic genes. Overexpression of miR-7 significantly reduced the activity of luciferase reporter vectors containing the wild-type, but not the mutant, 3’ untranslated region (UTR) sequence of GDF5. Furthermore, knockdown of GDF5 partially reversed the effects of miR-7 inhibitor on osteoblast differentiation. Downregulation of CDR1as or GDF5 subsequently inhibited phosphorylation of Smad1/5/8 and p38 mitogen-activated protein kinases (MAPK), while upregulation of miR-7 decreased the level of phosphorylated Smad1/5/8 and p38 MAPK. In vivo, CDR1as knockdown lead to less bone formation compared with the control group as revealed by micro-CT and the histological analysis. Conclusions Our results demonstrated that CDR1as acts as a miR-7 inhibitor, triggering the upregulation of GDF5 and subsequent Smad1/5/8 and p38 MAPK phosphorylation to promote osteogenic differentiation of PDLSCs. This study provides a novel understanding of the mechanisms of osteogenic differentiation, and suggests a potential method for promoting bone formation.

Osteoporosis is a prevalent metabolic bone disease characterized by low bone mineral density and degenerative disorders of bone tissues. Previous studies showed the abnormal osteogenic differentiation of endogenous bone marrow mesenchymal stem cells (BMSCs) contributes to the development of osteoporosis. However, the underlying mechanisms by which BMSCs undergo osteogenic differentiation remain largely unexplored. Recently, long non-coding RNAs have been discovered to play important roles in regulating BMSC osteogenesis. In this study, we first showed MIR22HG , which has been demonstrated to be involved in the progression of several cancer types, played an important role in regulating BMSC osteogenesis. We found the expression of MIR22HG was significantly decreased in mouse BMSCs from the osteoporotic mice and it was upregulated during the osteogenic differentiation of human BMSCs. Overexpression of MIR22HG in human BMSCs enhanced osteogenic differentiation, whereas MIR22HG knockdown inhibited osteogenic differentiation both in vitro and in vivo. Mechanistically, MIR22HG promoted osteogenic differentiation by downregulating phosphatase and tensin homolog (PTEN) and therefore activating AKT signaling. Moreover, we found MIR22HG overexpression promoted osteoclastogenesis of RAW264.7 cells, which indicated that MIR22HG played a significant role in bone metabolism and could be a therapeutic target for osteoporosis and other bone-related diseases.

Osteoclastogenesis in alveolar bone induced by compression stress triggers orthodontic tooth movement. Compression stress also stimulates angiogenesis, which is essential for osteoclastogenesis. However, the effects of osteoclastogenesis induced by compression on angiogenesis are poorly understood. In vivo , we found the markers of angiogenesis increased during orthodontic bone remodeling. In vitro , osteoclast-derived exosomes increased proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs), as well as expression of vascular endothelial growth factor and CD31. The promotive effects of exosomes derived from compressed osteoclasts were greater than those derived from osteoclasts without compression. Next, we analyzed changes in the microRNA transcriptome after compression stress and focused on microRNA146a-5p (miR-146a), which was significantly decreased by compression. Transfection of an inhibitor of miR-146a stimulated angiogenesis of HUVECs while miR-146a mimics repressed angiogenesis. Adiponectin (ADP) was confirmed to be a target of miR-146a by dual luciferase reporter assay. In HUVECs treated with exosomes, we detected increased ADP which promoted angiogenesis. Knockdown of ADP in HUVECs reduced the promotive effects of exosomes. Our results demonstrate that the decreased miR-146a observed in osteoclasts after compression promotes angiogenesis by targeting ADP, suggesting a novel method to interfere with bone remodeling induced by compression stress.

Circular RNAs (circRNAs), which are produced by back-splicing events in genes, have emerged as factors in gene regulation and normal cellular homeostasis. They play an important role not only in normal development of tissues and organs, but also in disease pathogenesis and cell differentiation. However, the role of circRNAs in bone marrow stem cells (BMSCs) undergoing osteoblast differentiation remains largely unknown. We performed microarray analysis to determine the expression profiles of circRNAs during osteoblast differentiation. In total, 3938 circRNAs were upregulated and 1505 were downregulated in BMSCs at day 7 (D7) compared with day 0 (D0). About 95% of the differentially expressed circRNAs were derived from protein coding genes, and functional annotation analysis showed that the parental genes of differentially expressed circRNAs were enriched in osteogenesis-associated terms. We also analyzed the microRNA (miRNA) transcriptome since circRNAs have been suggested to interact with miRNAs. We then selected the circRNAs that were negatively correlated with miRNAs and possessed miRNA response elements to construct a circRNA-miRNA interaction network. Analysis of the hub nodes in the networks showed that the top five nodes were miRNAs. Some circRNAs were linked to miRNAs with osteogenic roles, indicating that these circRNAs potentially function in osteogenic differentiation of BMSCs. Moreover, we validated the expression of one hub miRNA, miR-199b-5p, and its linked circIGSF11. Silencing of circIGSF11 promoted osteoblast differentiation and increased the expression of miR-199b-5p. Our study suggests that circRNA-miRNA interaction actively contributes to the osteogenic differentiation of human BMSCs, suggesting potential avenues for further study.

As United States Food and Drug Administration-approved implantable material, carbon fiber-reinforced polyetheretherketone (CFRPEEK) possesses an adjustable elastic modulus similar to cortical bone and is a prime candidate to replace surgical metallic implants. The bioinertness and inferior osteogenic properties of CFRPEEK, however, limit its clinical application as orthopedic/dental implants. In this study, CFRPEEK-nanohydroxyapatite ternary composites (PEEK/n-HA/CF) with variable surface roughness have been successfully fabricated. The effect of surface roughness on their in vitro cellular responses of osteoblast-like MG-63 cells (attachment, proliferation, apoptosis, and differentiation) and in vivo osseointegration is evaluated. The results show that the hydrophilicity and the amount of Ca ions on the surface are significantly improved as the surface roughness of composite increases. In cell culture tests, the results reveal that the cell proliferation rate and the extent of osteogenic differentiation of cells are a function of the size of surface roughness. The composite with moderate surface roughness significantly increases cell attachment/proliferation and promotes the production of alkaline phosphatase (ALP) activity and calcium nodule formation compared with the other groups. More importantly, the PEEK/n-HA/CF implant with appropriate surface roughness exhibits remarkably enhanced bioactivity and osseointegration in vivo in the animal experiment. These findings will provide critical guidance for the design of CFRPEEK-based implants with optimal roughness to regulate cellular behaviors, and to enhance biocompability and osseointegration. Meanwhile, the PEEK/n-HA/CF ternary composite with optimal surface roughness might hold great potential as bioactive biomaterial for bone grafting and tissue engineering applications.

The non-parallel least squares support matrix machine (NPLSSMM), extending the original model with a non-parallel one, provides an enhanced framework to utilize the structural information of matrix data. However, its least squares loss makes it sensitive to imperfectly labeled data. To address this limitation, this paper proposes a correntropy-based non-parallel least squares support matrix machine (C-NPLSSMM). By incorporating correntropy, a symmetric and bounded similarity measure, into the loss function design, C-NPLSSMM adaptively adjusts the classification model to match the underlying structure of matrix data while mitigating the impact of mislabeled samples. Theoretical analysis is conducted to reveal the intrinsic relationship between C-NPLSSMM and the original NPLSSMM. Specifically, when the kernel size of correntropy loss is large enough, C-NPLSSMM degenerates into NPLSSMM, ensuring consistency with the original formulation. Experimental results on publicly available image and electroencephalogram datasets demonstrate that C-NPLSSMM achieves higher classification accuracy than other competitive methods in most cases.

The cultivated/domesticated peach (Prunus persica var. persica; Rosaceae, subgenus Amygdalus; synonym: Amygdalus persica) originated in China, but its wild ancestor, as well as where, when, and under what circumstances the peach was domesticated, is poorly known. Five populations of archaeological peach stones recovered from Zhejiang Province, China, document peach use and evolution beginning ca. 8000 BP. The majority of the archaeological sites from which the earliest peach stones have been recovered are from the Yangzi River valley, indicating that this is where early selection for favorable peach varieties likely took place. Furthermore, peach stone morphology through time is consistent with the hypothesis that an unknown wild P. persica was the ancestor of the cultivated peach. The oldest archaeological peach stones are from the Kuahuqiao (8000-7000 BP) and Tianluoshan (7000-6500 BP) sites and both stone samples segregate into two size groups, suggesting early selection of preferred types. The first peach stones in China most similar to modern cultivated forms are from the Liangzhu culture (ca. 5300 to 4300 BP), where the peach stones are significantly larger and more compressed than earlier stones. Similar peach stones are reported from Japan much earlier (6700-6400 BP). This large, compressed-stone peach was introduced to Japan and indicates a yet unidentified source population in China that was similar to the Liangzhu culture peach. This study proposes that the lower Yangzi River valley is a region, if not the region, of early peach selection and domestication and that the process began at least 7500 years ago.

Background Orthodontic treatment was found to have an impact on the quantity and constitution of subgingival microbiota. However, contradictory findings regarding the effects of fixed appliances on microbial changes were reported. The aim of this systematic review was to investigate the microbial changes in subgingival plaques of orthodontic patients. Methods The PubMed, Cochrane Library, and EMBASE databases were searched up to November 20, 2016. Longitudinal studies observing microbial changes in subgingival plaques at different time points of orthodontic treatment are included. The methodological quality of the included studies was assessed by Methodological index for non-randomized studies (MINORS). The studies that reported the frequency of subgingival periodontopathogens were used for quantitative analysis. Other studies were analysed qualitatively to describe the microbial changes during orthodontic treatment. Results Thirteen studies were selected, including two controlled clinical trials, three cohort studies and eight self-controlled studies. Four periodontopathogens, including Aggregatibacter actinomycetemcomitans ( Aa ), Porphyromonas gingivalis ( Pg ), Prevotella intermedia ( Pi ) and Tannerella forsythia ( Tf ), were analysed. Following orthodontic appliance placement, the frequencies of Pg and Aa showed no significant change ( P  = 0.97 and P  = 0.77), whereas the frequency of Tf significantly increased ( P <  0.01) during short-term observation (0–3 months). The frequency of Pi showed a tooth-specific difference, as it presented no significant difference ( P  = 0.25) at the site of the first molar but was significantly increased ( P  = 0.01) at the incisor. During long-term observation (> = 6 months), two studies reported that the levels of subgingival periodontopathogens exhibited a transient increase but decreased to the pretreatment levels afterwards. After removal of the orthodontic appliance, the four periodontopathogens showed no significant difference compared with before removal. Conclusion The levels of subgingival pathogens presented temporary increases after orthodontic appliance placement, and appeared to return to pretreatment levels several months later. This indicates that orthodontic treatment might not permanently induce periodontal disease by affecting the level of subgingival periodontal pathogen levels. Further studies of high methodological quality are required to provide more reliable evidence regarding this issue.

Poor soil structure and aeration in coastal saline-alkaline lands severely constrain crop productivity. This study evaluated the efficacy of aerated drip irrigation in improving tomato (Solanum lycopersicum L.) cultivation under these conditions. A field experiment compared aerated (A1) and non-aerated (A0) irrigation across three water levels: severe deficit (W1, 0.6 Ep), mild deficit (W2, 0.8 Ep), and full irrigation (W3, 1.0 Ep), where Ep represents cumulative pan evaporation. Relative to conventional irrigation, aeration significantly improved plant performance by promoting root development, which supported enhanced canopy growth and a higher net photosynthetic rate. The A1W3 treatment produced the highest yield (1561.6 g plant⁻¹), a 22.70% increase over the non‑aerated full irrigation control, while also improving fruit quality attributes including lycopene and vitamin C contents. Principal component analysis identified A1W3 as the most effective strategy under our experimental conditions for integrated yield and quality. These results indicate that aerated drip irrigation offers a practical approach to enhance tomato production in marginal coastal regions.

Background The mammalian target of rapamycin (mTOR) pathway plays a significant role in osteogenic differentiation and bone maintenance. As the only known endogenous inhibitor of mTOR function, DEP domain containing mTOR interacting protein (DEPTOR) is potentially involved in stem cell differentiation, although the pathophysiological significance and its molecular mechanisms remain unclear. The present study aimed to elucidate the effects of DEPTOR on the progress of osteoporosis and investigate the underlying molecular mechanisms of osteogenic regulation. Methods An ovariectomy mouse model with decreased bone formation and osteogenic induction with bone marrow mesenchymal stem cells (BMSCs) were used to investigate the relationship between DEPTOR and osteogenic events. A loss-of-function investigation was then performed to explore the role of DEPTOR in the osteogenic differentiation of BMSCs both in vitro and in vivo. Finally, long noncoding RNA (lncRNA) and mRNA sequences were investigated to reveal the underlying mechanisms of DEPTOR in osteogenic regulation. RNA interference, western blotting, and chromatin immunoprecipitation assays were performed for further mechanistic determination. Results The results indicated that DEPTOR contributes to the progress of osteoporosis, and higher expression of Deptor was observed in osteoporotic bones. The expression of DEPTOR was reduced during the osteogenic differentiation of BMSCs, and knockdown of DEPTOR promoted BMSC osteogenesis in vitro and in vivo. lncRNA and mRNA sequences indicated that knockdown of DEPTOR upregulated the expression of maternally expressed 3 (nonprotein coding) ( MEG3 ), which subsequently activated bone morphogenetic protein 4 (BMP4) signaling. Furthermore, DEPTOR could bind to a specific region (− 1000 bp ~ 0) of the MEG3 promoter to regulate its transcription, and inhibition of MEG3 reduced BMP4 activation triggered by DEPTOR knockdown. Conclusions Taken together, our study revealed a novel function of DEPTOR in osteogenic differentiation by inhibiting MEG3-mediated activation of BMP4 signaling, which suggested that DEPTOR could be a therapeutic target for bone loss diseases and skeletal tissue regeneration.