Application of Mesoporous Carbon-Based Highly Dispersed K-O2 Strong Lewis Base in the Efficient Catalysis of Methanol and Ethylene Carbonate.

As an atom-economical reaction, the direct generation of dimethyl carbonate (DMC) and ethylene glycol (EG) via the transesterification of CH3OH and ethylene carbonate (EC) has several promising applications, but the exploration of carriers with high specific surface areas and novel heterogeneous catalysts with more basic sites remains a long-standing research challenge. For this purpose, herein, a nitrogen-doped mesoporous carbon (NMC, 439 m2/g) based K-O2 Lewis base catalyst (K-O2/NMC) with well-dispersed strongly basic sites (2.23 mmol/g, 84.5%) was designed and synthesized. The compositions and structures of NMC and K-O2/NMC were comprehensively investigated via Fourier transform infrared spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, scanning electron microscopy, transmission electron microscopy, N2 adsorption-desorption, CO2 temperature-programmed desorption, and contact angle measurements. The optimal structural configuration and electron cloud distribution of the K-O2/NMC catalyst were simulated using first-principles calculations. The electron transfer predominantly manifested as a flow from K-O to C-O/C-N, and the interatomic interactions between each atom were enhanced and exhibited a tendency for a more stable state after redistribution. Furthermore, the adsorption energies (Eads) of CH3OH at K-O-O and K-O-N sites were -1.4185 eV and -1.3377 eV, respectively, and the O atom in CH3OH exhibited a stronger adsorption tendency for the K atom at the K-O-O site. Under the optimal conditions, the EC conversion, DMC/EG selectivity, and turnover number/frequency were 80.9%, 98.6%/99.4%, and 40.5/60.8 h-1, respectively, with a reaction rate constant (k) of 0.1005 mol/(L·min). Results showed that the heterogeneous K-O2/NMC catalyst prepared herein greatly reduced the reaction cost while guaranteeing the catalytic effect, and the whole system required a lower reaction temperature (65 °C), a shorter reaction time (40 min), and a lower catalyst amount (2.0 wt % of EC). Therefore, K-O2/NMC can be used as a catalyst in different transesterification reactions.

Deep learning models for predicting the survival of patients with medulloblastoma based on a surveillance, epidemiology, and end results analysis.

Medulloblastoma is a malignant neuroepithelial tumor of the central nervous system. Accurate prediction of prognosis is essential for therapeutic decisions in medulloblastoma patients. We analyzed data from 2,322 medulloblastoma patients using the SEER database and randomly divided the dataset into training and testing datasets in a 7:3 ratio. We chose three models to build, one based on neural networks (DeepSurv), one based on ensemble learning that Random Survival Forest (RSF), and a typical Cox Proportional-hazards (CoxPH) model. The DeepSurv model outperformed the RSF and classic CoxPH models with C-indexes of 0.751 and 0.763 for the training and test datasets. Additionally, the DeepSurv model showed better accuracy in predicting 1-, 3-, and 5-year survival rates (AUC: 0.767-0.793). Therefore, our prediction model based on deep learning algorithms can more accurately predict the survival rate and survival period of medulloblastoma compared to other models.

A polyetheretherketone framework removable partial denture for a 6-year-old child with nonsyndromic oligodontia made using glass-ceramic hemispheres to enhance retention: A clinical report.

A 6-year-old child with nonsyndromic oligodontia in the mixed dentition received a removable dental prosthesis with a polyetheretherketone framework and artificial gingiva, restoring esthetics and function. Computer-aided design and computer-aided manufacturing hemispherical glass-ceramic attachments were added to the teeth under the guidance of acid-etching and bonding guides to obtain an undercut area. The bonding and cementation of the attachments and the prosthesis delivery were completed in a single visit. This method offers a suitable prosthodontic treatment option for treating children with oligodontia in the mixed dentition.

Accuracy of the novel digital non-cross-arch surgical guides with integration of tooth undercut retention and screw-bone support for implant placement in mandibular free-end.

BACKGROUND: Large cross-arch free-end surgical guides can obscure the visual field, compromising surgical accuracy due to insufficient stability at the free-end. This in vitro study aims to evaluate the accuracy of novel digital non-cross-arch surgical guides designed for implant placement at the mandibular free-end, incorporating tooth undercut retention and screw-bone support. MATERIALS AND METHODS: A mandibular dental model lacking left molars was utilized to fabricate unilateral (cross-arch) tooth-supported surgical guides (GT I, n = 20). Subsequently, two additional types of surgical guides were fabricated: GT II (covering two teeth, n = 20) and GT III (covering three teeth, n = 20). These novel surgical guides were designed to utilize the undercut of the supporting teeth for retention and enhance stability with screw-bone support at the guide's free-end. Furthermore, 60 identical guiding blocks were assembled on the three types of surgical guides to facilitate the implants' insertion. On a phantom head, 120 implant replicas were placed at the Federal Dentaire Internationale (FDI) teeth positions #36 and #37 on the dental model, employing a combination of surgical guides and guiding blocks. To assess accuracy, planned and placed implant positions were compared using intraoral optical scanning. Discrepancies in angulation and linear deviations, including the coronal/apical 3D deviations, lateral deviation as well as depth deviation, were measured. Statistical analysis was performed using two-way ANOVA and Bonferroni test (α = 0.05). RESULTS: GT I exhibited significantly largest discrepancies, including angular and linear deviations at the crest and apex at every implant site. Especially in depth, at implant site #36, the mean deviation value of GT I (0.27 ± 0.13 mm) was twice as large as GT III (0.13 ± 0.07 mm), and almost twice as large as GT II (0.14 ± 0.08 mm). However, at implant site #37, this deviation increased to almost a five-fold relationship between GT I (0.63 ± 0.12 mm) and II (0.14 ± 0.09 mm), as well as between GT I and III (0.13 ± 0.09 mm). No significant discrepancies existed between the novel surgical guides at either implant site #36 or #37. CONCLUSION: This study provides a practical protocol for enhancing accuracy of implant placement and reducing the size of free-end surgical guides used at mandibular molar sites.

Identifying global research trends on inflammation associated with traumatic brain injury by bibliometric and visualized analysis.

Background: Traumatic brain injury (TBI) is a catastrophic disease involving complex inflammatory processes. This study aimed to quantitatively analyze and visualize the global research trends on inflammation associated with TBI. Methods: All publications concerning TBI and inflammation published from 2007 to 2021 were retrieved from the Web of Science Core Collection database. Key visualization and statistical analysis were calculated and evaluated using VOSviewer, CiteSpace, R package "bibliometrix," and an online bibliometric analysis platform. Results: From 2007 to 2021, 15,138 authors from 2860 institutions in 77 countries/regions published 3154 articles on inflammation associated with TBI in 786 academic journals. The research output has significantly increased over the years despite a minor fluctuation. Among the countries, the United States showed the highest output (43.50%) with the most total citations (62,791). The author with the most published articles was Cox CS (30 articles with h-index = 20), and the most popular journal in the field was the Journal of Neurotrauma (190 papers, cited 6433 times). The high-frequency keywords were "post-traumatic brain injury," "brain edema," and "glial activation." Moreover, high-frequency keywords analysis indicated that various inflammatory cells contributed to neuroinflammation, neuroprotection, and oxidative stress after TBI. Conclusion: This study revealed the research trends, hotspots, and emerging topics in inflammation associated with TBI by quantitative and visualized analysis. The current research focuses on the crosstalk between various inflammatory cells and the brain and the associated mechanisms. This study presents the research landscape and inspires future research on inflammation associated with TBI.

Function of Long Noncoding RNAs in Glioma Progression and Treatment Based on the Wnt/ß-Catenin and PI3K/AKT Signaling Pathways.

Gliomas are a deadly primary malignant tumor of the central nervous system, with glioblastoma (GBM) representing the most aggressive type. The clinical prognosis of GBM patients remains bleak despite the availability of multiple options for therapy, which has needed us to explore new therapeutic methods to face the rapid progression, short survival, and therapy resistance of glioblastomas. As the Human Genome Project advances, long noncoding RNAs (lncRNAs) have attracted the attention of researchers and clinicians in cancer research. Numerous studies have found aberrant expression of signaling pathways in glioma cells. For example, lncRNAs not only play an integral role in the drug resistance process by regulating the Wnt/ß-catenin or PI3K/Akt signaling but are also involved in a variety of malignant biological behaviors such as glioma proliferation, migration, invasion, and tumor apoptosis. Therefore, the present review systematically assesses the existing research evidence on the malignant progression and drug resistance of glioma, focusing on the critical role and potential function of lncRNAs in the Wnt/ß-catenin and PI3K/Akt classical pathways to promote and encourage further research in this field.

Evaluation of automated detection of head position on lateral cephalometric radiographs based on deep learning techniques.

BACKGROUND: Lateral cephalometric radiograph (LCR) is crucial to diagnosis and treatment planning of maxillofacial diseases, but inappropriate head position, which reduces the accuracy of cephalometric measurements, can be challenging to detect for clinicians. This non-interventional retrospective study aims to develop two deep learning (DL) systems to efficiently, accurately, and instantly detect the head position on LCRs. METHODS: LCRs from 13 centers were reviewed and a total of 3000 radiographs were collected and divided into 2400 cases (80.0 %) in the training set and 600 cases (20.0 %) in the validation set. Another 300 cases were selected independently as the test set. All the images were evaluated and landmarked by two board-certified orthodontists as references. The head position of the LCR was classified by the angle between the Frankfort Horizontal (FH) plane and the true horizontal (HOR) plane, and a value within - 3°- 3° was considered normal. The YOLOv3 model based on the traditional fixed-point method and the modified ResNet50 model featuring a non-linear mapping residual network were constructed and evaluated. Heatmap was generated to visualize the performances. RESULTS: The modified ResNet50 model showed a superior classification accuracy of 96.0 %, higher than 93.5 % of the YOLOv3 model. The sensitivity&recall and specificity of the modified ResNet50 model were 0.959, 0.969, and those of the YOLOv3 model were 0.846, 0.916. The area under the curve (AUC) values of the modified ResNet50 and the YOLOv3 model were 0.985 ± 0.04 and 0.942 ± 0.042, respectively. Saliency maps demonstrated that the modified ResNet50 model considered the alignment of cervical vertebras, not just the periorbital and perinasal areas, as the YOLOv3 model did. CONCLUSIONS: The modified ResNet50 model outperformed the YOLOv3 model in classifying head position on LCRs and showed promising potential in facilitating making accurate diagnoses and optimal treatment plans.

Light-triggered photosynthetic engineered bacteria for enhanced-photodynamic therapy by relieving tumor hypoxic microenvironment.

Background: Singlet oxygen (1O2) has received considerable research attention in photodynamic therapy (PDT) due to its cytotoxic solid features. However, the inherent hypoxic state of the tumor microenvironment (TME) leads to the meager 1O2 quantum yield of inorganic PDT reagents, and their application in vivo remains elusive. Methods: We developed a novel strategy to fabricate active photosynthetic bacteria/photosensitizer/photothermal agent hybrids for photosynthetic tumor oxygenation and PDT and PTT tumor therapy under different laser irradiation sources. Photosynthetic bacteria combined with Ce6 photosensitizer and Au NPs photothermal agent, the obtained Bac@Au-Ce6 effectively targets tumor tissues and further enhances the tumor accumulation of Au-Ce6. Results: The results showed that the Au-Ce6-loaded engineered bacteria (Bac@Au-Ce6) maintained the photosynthetic properties of Syne. After i.v. injection, Bac@Au-Ce6 efficiently aggregates at tumor sites due to the tumor-targeting ability of active Syne. With 660 nm laser irradiation at the tumor site, the photoautotrophic Syne undergoes sustained photosynthetic O2 release and immediately activates O2 to 1O2 via a loaded photosensitizer. PTT was subsequently imparted by 808 laser irradiations to enhance tumor killing further. Conclusions: This work provides a new platform for engineering bacteria-mediated photosynthesis to promote PDT combined with PTT multi-faceted anti-tumor.

The mechanical properties, tribological behaviors and color stability of a feldspar nanoceramics strengthening extrinsic stain for high-translucent zirconia.

The present work is aimed to explore the mechanical properties, tribological behaviors and color stability of nanoceramics and microceramics strengthened extrinsic stain coatings (NS and MS) upon high-translucent zirconia (TZ). The Na-rich feldspar ceramics component, microstructure and particle size of NS and MS were verified. The mechanical properties including elastic modulus and hardness of NS were enhanced compared to MS. Reciprocating wear tests under a ball-on-plate configuration manifested that the reduced coefficient of friction, wear depth and wear volume loss of NS was evaluated after 1 × 10 4 cycles and the wear scar morphology of NS characterized by microcracks while MS featured more delamination and wear debris. Post toothbrushing simulation revealed that the color stability of extrinsic stain coatings was elevated with the addition of feldspar nanoceramics. The feldspar nanoceramics strengthening extrinsic stain exhibited enhanced elastic modulus, hardness, wear resistance and color stability, especially for TZ.

Functionalized Cortical Bone-Inspired Composites Adapt to the Mechanical and Biological Properties of the Edentulous Area to Resist Fretting Wear.

Dental implants with long-term success of osseointegration have always been the goal, however, difficulties exist. The accumulation of fretting damage at the implant-bone interface often gets overlooked. Commonly used titanium is approximately 7-fold harder and stiffer than cortical bone. Stress shielding caused by the mismatching of the elastic modulus aggravates fretting at the interface, which is accompanied by the risk of the formation of proinflammatory metal debris and implant loosening. Thus, the authors explore functionalized cortical bone-inspired composites (FCBIC) with a hierarchical structure at multiple scales, that exhibit good mechanical and biological adaptivity with cortical bone. The design is inspired by nature, combining brittle minerals with organic molecules to maintain machinability, which helps to acquire excellent energy-dissipating capability. It therefore has the comparable hardness and elastic modulus, strength, and elastic-plastic deformation to cortical bone. Meanwhile, this cortical bone analogy exhibits excellent osteoinduction and osseointegration abilities. These two properties also facilitate each other to resist fretting wear, and therefore improve the success rate of implantation. Based on these results, the biological-mechanical co-operation coefficient is proposed to describe the coupling between these two factors for designing the optimized dental implants.

A chairside digital radiographic guide for registering digital casts to cone beam computed tomography scans with strong metallic artifacts.

Accurate registration of digital casts and cone beam computed tomography (CBCT) scans with strong metallic artifacts is essential for the accuracy of guided implant surgery. This article describes a procedure for mapping digital casts onto CBCT scans containing significant scatter artifacts in the virtual implant planning stage. The technique uses a chairside segmented occlusal wing-like radiographic guide, which is constructed of digital splints fabricated using a desktop 3-dimensional printer and composite resin spheres as markers to accurately superimpose the bimaxillary digital scans onto the CBCT scans in a single procedure. This cost-effective technique is timesaving for clinicians and patients, and the digital information for implant planning can be collected in a single visit.

Identification and validation of oxidative stress and immune-related hub genes in Alzheimer's disease through bioinformatics analysis.

Alzheimer's disease (AD) is the leading cause of dementia in aged population. Oxidative stress and neuroinflammation play important roles in the pathogenesis of AD. Investigation of hub genes for the development of potential therapeutic targets and candidate biomarkers is warranted. The differentially expressed genes (DEGs) in AD were screened in GSE48350 dataset. The differentially expressed oxidative stress genes (DEOSGs) were analyzed by intersection of DEGs and oxidative stress-related genes. The immune-related DEOSGs and hub genes were identified by weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) analysis, respectively. Enrichment analysis was performed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. The diagnostic value of hub genes was assessed by receiver operating characteristic analysis and validated in GSE1297. The mRNA expression of diagnostic genes was determined by qRT-PCR analysis. Finally, we constructed the drug, transcription factors (TFs), and microRNA network of the diagnostic genes. A total of 1160 DEGs (259 up-regulated and 901 down-regulated) were screened in GSE48350. Among them 111 DEOSGs were identified in AD. Thereafter, we identified significant difference of infiltrated immune cells (effector memory CD8 T cell, activated B cell, memory B cell, natural killer cell, CD56 bright natural killer cell, natural killer T cell, plasmacytoid dendritic cell, and neutrophil) between AD and control samples. 27 gene modules were obtained through WGCNA and turquoise module was the most relevant module. We obtained 66 immune-related DEOSGs by intersecting turquoise module with the DEOSGs and identified 15 hub genes through PPI analysis. Among them, 9 hub genes (CCK, CNR1, GAD1, GAP43, NEFL, NPY, PENK, SST, and TAC1) were identified with good diagnostic values and verified in GSE1297. qRT-PCR analysis revealed the downregulation of SST, NPY, GAP43, CCK, and PENK and upregulation of NEFL in AD. Finally, we identified 76 therapeutic agents, 152 miRNAs targets, and 91 TFs regulatory networks. Our study identified 9 key genes associated with oxidative stress and immune reaction in AD pathogenesis. The findings may help to provide promising candidate biomarkers and therapeutic targets for AD.

Mechanical stability of angulated zirconia abutments supporting maxillary anterior single crowns on narrow-diameter implants.

OBJECTIVES: To investigate the fracture strength of angulated hybrid abutments supporting anterior single crowns on narrow-diameter implants (NDIs). MATERIAL AND METHODS: Zirconia abutment with angulations of labial inclination 0° (TZ0Z), 15° (TZ15Z), 30° (TZ30Z) and palatal inclination 15° (TZ - 15Z) was designed on 3.3-mm titanium-zirconium (Ti-Zr) NDIs. Titanium abutment connected with Ti-Zr implant (TZ0T) and 0° zirconia abutment connected with pure titanium (Ti) implant (T0Z) were control groups. Thirty-six un-restored abutments and 36 abutments restored with highly translucent zirconia (HTZ) crowns were tested. Failure loads were compared among 6 groups, and bending moments were calculated for comparison between un-restored and restored abutments. RESULTS: Failure loads of un-restored abutments were affected by the abutment angle. Sixty-seven percent samples in TZ30Z and 83% samples in TZ - 15Z group fractured at the thinnest part of the zirconia abutment and exhibited lower failure load (p < .05). Failure loads of restored abutments were close to or exceeded the maximum bite force of anterior teeth, and no differences were found among six groups (p > .05). Except TZ15Z and TZ0T group, the bending moment increased with the crown construction, especially for TZ30Z and TZ - 15Z groups (p < .001). CONCLUSIONS: The fracture strength of hybrid abutments restored with HTZ crown on Ti-Zr NDIs exceeded the bite forces of anterior teeth for all the groups and were not affected by the abutment angle. CLINICAL RELEVANCE: In terms of fracture strength, Ti-Zr NDIs combined with angulated hybrid abutments and HTZ crowns can be used in the anterior region.

circTOP2A functions as a ceRNA to promote glioma progression by upregulating RPN2.

Competing endogenous RNA (ceRNA)-mediated signaling pathway dysregulation provides great insight into comprehensively understanding the molecular mechanism and combined targeted therapy for glioblastoma. circRNA is characterized by high stability, tissue/developmental stage-specific expression and abundance in brain and plays significant roles in the initiation and progression of cancer. Our previous published data have demonstrated that RPN2 was significantly upregulated in glioma and promoted tumor progression via the activation of the Wnt/ß-catenin pathway. Furthermore, we proved that miR-422a regulated the Wnt/ß-catenin signaling pathway by directly targeting RPN2. In this study, based on the glioblastoma microarray profiles, we identified the upstream circTOP2A, which completely bound to miR-422a and was co-expressed with the RPN2. circTOP2A was significantly overexpressed in glioma and conferred a poor prognosis. circTOP2A could regulate RPN2 expression by sponging miR-422a, verified by western blot, dual-luciferase reporter gene assay, and RNA pull-down assay. Functional assays including CCK8, transwell and FITC-annexin V were performed to explore the RPN2-mediated role of the circTOP2A effect on the glioma malignant phenotype. Additionally, TOP/FOP and immunofluorescence analysis were used to confirm that sh-circTOP2A could suppress the Wnt/ß-catenin pathway partly through RPN2. Finally, a tumor xenograft model was applied to validate the biological function of circTOP2A in vivo. Taken together, our findings reveal the critical role of circTOP2A in promoting glioma proliferation and invasion via a ceRNA mechanism and provide an exploitable biomarker and therapeutic target for glioma patients.

The lipid-lowering drug fenofibrate combined with si-HOTAIR can effectively inhibit the proliferation of gliomas.

BACKGROUND: Fenofibrate is a fibric acid derivative known to have a lipid-lowering effect. Although fenofibrate-induced peroxisome proliferator-activated receptor alpha (PPARα) transcription activation has been shown to play an important role in the malignant progression of gliomas, the underlying mechanisms are poorly understood. METHODS: In this study, we analyzed TCGA database and found that there was a significant negative correlation between the long noncoding RNA (lncRNA) HOTAIR and PPARα. Then, we explored the molecular mechanism by which lncRNA HOTAIR regulates PPARα in cell lines in vitro and in a nude mouse glioma model in vivo and explored the effect of the combined application of HOTAIR knockdown and fenofibrate treatment on glioma invasion. RESULTS: For the first time, it was shown that after knockdown of the expression of HOTAIR in gliomas, the expression of PPARα was significantly upregulated, and the invasion and proliferation ability of gliomas were obviously inhibited. Then, glioma cells were treated with both the PPARα agonist fenofibrate and si-HOTAIR, and the results showed that the proliferation and invasion of glioma cells were significantly inhibited. CONCLUSIONS: Our results suggest that HOTAIR can negatively regulate the expression of PPARα and that the combination of fenofibrate and si-HOTAIR treatment can significantly inhibit the progression of gliomas. This introduces new ideas for the treatment of gliomas.

Discovery and optimization of selective RET inhibitors via scaffold hopping.

Aberrant alterations of rearranged during transfection (RET) have been identified as actionable drivers of multiple cancers, including thyroid carcinoma and lung cancer. Currently, several approved multikinase inhibitors such as vandetanib and cabozantinib demonstrate clinical activity in patients with RET-rearranged or RET-mutant cancers. However, the observed response rates are only modest and the 'off-target' toxicities resulted from the inhibition of other kinases is also a concern. Herein, we designed and synthesized a series of RET inhibitors based on the structure of selective RET inhibitor BLU-667 and investigated their biological activities. We identified compound 9 as a novel potent and selective RET inhibitor with improved drug-like properties. Compound 9 exhibits a selective inhibitory profile with an inhibitory concentration 50 (IC50) of 1.29 nM for RET and 1.97 (RET V804M) or 0.99 (RET M918T) for mutant RETs. The proliferation of Ba/F3 cells transformed with NSCLC related KIF5B-RET fusion was effectively suppressed by compound 9 (IC50 = 19 nM). Additionally, compound 9 displayed less 'off-target' effects than BLU-667. In mouse xenograft models, compound 9 repressed tumor growth driven by KIF5B-RET-Ba/F3 cells in a dose-dependent manner. Based on its exceptional kinase selectivity, good potency and high exposure in tumor tissues, compound 9 represents a promising lead for the discovery of RET directed therapeutic agents and the study of RET-driven tumor biology.

MicroRNA­301a/ZNRF3/wnt/ß­catenin signal regulatory crosstalk mediates glioma progression.

MicroRNA (miR)­mediated mRNA and multiple signaling pathway dysregulations have been extensively implicated in several cancer types, including gliomas. Although previous studies have reported that miR­301a acts as an oncogene, the underlying mechanisms of miR­301a in the initiation and progression of glioma remain unknown. The present study aimed to investigate the involvement of miR­301a­mediated signaling pathway dysregulation in glioma. The results identified that miR­301a was significantly upregulated in gliomas and was associated with a poor prognosis based on The Cancer Genome Atlas and Chinese Glioma Genome Atlas databases. Moreover, zinc and ring finger 3 (ZNRF3) exerted a critical role in the miR­301a­mediated effects on the malignant phenotype, such as by affecting proliferation and apoptosis. Mechanistically, the TOP/FOP luciferase assay, western blotting and immunofluorescence results demonstrated that miR­301a knockdown inhibited the wnt/ß­catenin signaling pathway, at least partially via ZNRF3, while ZNRF3 was a direct functional target of miR­301a, as indicated by luciferase reporter assay and western blot analysis. Furthermore, ZNRF3 could in turn repress miR­301a expression, which was dependent on the wnt pathway. Collectively, the present study identified a novel miR­301a/ZNRF3/wnt/ß­catenin signaling feedback loop that serves critical roles in glioma tumorigenesis, and that may represent a potential therapeutic target.

RPN2 is targeted by miR-181c and mediates glioma progression and temozolomide sensitivity via the wnt/ß-catenin signaling pathway.

Accumulating evidence indicates that the dysregulation of the miRNAs/mRNA-mediated carcinogenic signaling pathway network is intimately involved in glioma initiation and progression. In the present study, by performing experiments and bioinformatics analysis, we found that RPN2 was markedly elevated in glioma specimens compared with normal controls, and its upregulation was significantly linked to WHO grade and poor prognosis. Knockdown of RPN2 inhibited tumor proliferation and invasion, promoted apoptosis, and enhanced temozolomide (TMZ) sensitivity in vitro and in vivo. Mechanistic investigation revealed that RPN2 deletion repressed ß-catenin/Tcf-4 transcription activity partly through functional activation of glycogen synthase kinase-3ß (GSK-3ß). Furthermore, we showed that RPN2 is a direct functional target of miR-181c. Ectopic miR-181c expression suppressed ß-catenin/Tcf-4 activity, while restoration of RPN2 partly reversed this inhibitory effect mediated by miR-181c, implying a molecular mechanism in which TMZ sensitivity is mediated by miR-181c. Taken together, our data revealed a new miR-181c/RPN2/wnt/ß-catenin signaling axis that plays significant roles in glioma tumorigenesis and TMZ resistance, and it represents a potential therapeutic target, especially in GBM.

MicroRNA­422a functions as a tumor suppressor in glioma by regulating the Wnt/ß­catenin signaling pathway via RPN2.

MicroRNAs (miRs), which act as crucial regulators of oncogenes and tumor suppressors, have been confirmed to play a significant role in the initiation and progression of various malignancies, including glioma. The present study analyzed the expression and roles of miR­422a in glioma, and reverse transcription­quantitative PCR confirmed that miR­422a expression was significantly lower in glioblastoma multiforme (GBM) samples and cell lines compared with the low­grade glioma samples and the H4 cell line, respectively. miR­422a overexpression suppressed proliferation and invasion, and induced apoptosis in LN229 and U87 cell lines. Luciferase reporter assay, western blotting and RNA immunoprecipitation analysis revealed that ribophorin II (RPN2) is a direct functional target of miR­422a. Additionally, the overexpression of RPN2 partially reversed the miR­422a­mediated inhibitory effect on the malignant phenotype. Mechanistic investigation demonstrated that the upregulation of miR­422a inhibited ß­catenin/transcription factor 4 transcriptional activity, at least partially through RPN2, as indicated by in vitro and in vivo experiments. Furthermore, RPN2 expression was inversely correlated with miR­422a expression in GBM specimens and predicted patient survival in the Chinese Glioma Genome Atlas, UALCAN, Gene Expression Profiling Interactive Analysis databases. In conclusion, the present data reveal a new miR­422a/RPN2/Wnt/ß­catenin signaling axis that plays critical roles in glioma tumorigenesis, and it represents a potential therapeutic target for GBM.

[A technique to design the framework of removable partial denture by multi-stage expert system].

This study aims to apply a new expert system to design removable partial denture (RPD) framework. The RPD design is completed in three steps, namely, "selecting missing teeth", "selecting abutment condition", and "selecting personalized clasp". The system can help auxiliary dentists develop personalized treatment plans to reduce their clinical workload. It can also generate a dental preparation guideline for clinical preparation, which can prevent tooth preparation mistakes. By generating the standard electronic drawings of the framework design, the system can reduce the inconvenience caused by manual drawing, thereby facilitating dentist-technician communication and reducing the rate of remade.