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Mitochondria-associated membranes (MAMs), physical connection sites between the endoplasmic reticulum (ER) and the outer mitochondrial membrane (OMM), are involved in numerous cellular processes, such as calcium ion transport, lipid metabolism, autophagy, ER stress, mitochondria morphology, and apoptosis. Autophagy is a highly conserved intracellular process in which cellular contents are delivered by double-membrane vesicles, called autophagosomes, to the lysosomes for destruction and recycling. Autophagy, typically triggered by stress, eliminates damaged or redundant protein molecules and organelles to maintain regular cellular activity. Dysfunction of MAMs or autophagy is intimately associated with various diseases, including aging, cardiovascular, infections, cancer, multiple toxic agents, and some genetic disorders. Increasing evidence has shown that MAMs play a significant role in autophagy development and maturation. In our study, we concentrated on two opposing functions of MAMs in autophagy: facilitating the formation of autophagosomes and inhibiting autophagy. We recognized the link between MAMs and autophagy in the occurrence and progression of the diseases and therefore collated and summarized the existing intrinsic molecular mechanisms. Furthermore, we draw attention to several crucial data and open issues in the area that may be helpful for further study.

With rapid development of artificial intelligence and Chinese information processing technology, research related to natural language processing have reached the level of semantic understanding gradually, while Chinese Shallow Semantic Parsing is the key technique in the semantic understanding field. In this paper, a further improvement is conducted on the basic model of Chinese semantic role labeling for linear classification based on conditional random fields. In this paper, a method of combination of linguistic clues, combining with the existing linear sequence labeling algorithm and integrating some multilevel linguistic clues, such as morphology is related to syntax, in the model training to reconstruct and improve the Chinese semantic role labeling model of linear sequence. Through the experimental comparison and linguistic assistant analysis, this paper puts forward a targeted improvement method to significantly improve the accuracy of model labeling and proves that the integration of related linguistic clues in the semantic role labeling model based on linear sequence can improve the effect of model labeling.

The influence of hyperlipidemia on titanium implant osseointegration and the underlying mechanisms is not well understood. This study investigates the changes in osseointegration and explores the potential mechanisms in hyperlipidemia conditions. In vivo, specialized titanium implants were implanted in the femurs of diet-induced or genetic hyperlipidemia mice. In vitro, primary murine osteoblasts were cultured on the titanium surface in high-fat medium. Results showed that hyperlipidemia led to poor osseointegration in both types of mice in vivo, and high-fat medium impaired the osteogenic differentiation of primary osteoblasts on the titanium surface in vitro. In addition, high-fat medium caused significant overproduction of reactive oxygen species (ROS) and inhibition of the Wnt/β-catenin pathway in osteoblasts. Both N-acetyl-L-cysteine (NAC, an ROS antagonist) and Wnt3a (an activator of the Wnt/β-catenin pathway) attenuated the poor osteogenic ability of osteoblasts. In addition, NAC reactivated the Wnt/β-catenin pathway in osteoblasts under high-fat stimulation. These results demonstrate that hyperlipidemia impairs osseointegration via the ROS/Wnt/β-catenin pathway and provide support for the ROS or Wnt/β-catenin pathway as a promising therapeutic target for the development of novel drugs or implant materials to improve the osseointegration of implants in hyperlipidemic patients.

Background Type 2 diabetes mellitus (T2DM) has a harmful effect on the stability and osseointegration of dental implants. T2DM induces mitochondrial damage by inhibiting AMPK signaling, resulting in oxidative stress and poor osteogenesis in the peri-implant bone area. Genipin is a major component of gardenia fruits with strong antioxidant, anti-inflammation, and antidiabetic actions, and it also can activate mitochondrial quality control via the AMPK pathway. The purpose of this study was to investigate the effects of genipin and insulin treatment on implant osseointegration in T2DM rats and explore the underlying mechanisms. Methods Streptozotocin-induced diabetic rats received implant surgery in their femurs and were then assigned to five groups that were subjected to different treatments for three months: control group, T2DM group, insulin-treated T2DM group (10 IU/kg), genipin-treated T2DM group (50 mg/kg), and the genipin and insulin combination-treated T2DM group. Then, we regularly assessed the weight and glucose levels of the animals. Rats were euthanized at 3 months after the implantation procedure, and the femora were harvested for microscopic computerized tomography analysis, biomechanical tests, and different histomorphometric assessment. Results The results indicated that the highest blood glucose and oxidative stress levels were measured for the T2DM group, resulting in the poorest osseointegration. The combination-treated T2DM group mitigated hyperglycemia and normalized, reactivated AMPK signaling, and alleviated oxidative stress as well as reversed the negative effect of osseointegration. There were beneficial changes observed in the T2DM-genipin and T2DM-insulin groups, but these were less in comparison to the combination treatment group. Conclusion Our study suggests that treatment with genipin in combination with insulin could be an effective method for promoting implant osseointegration in T2DM rats, which may be related to AMPK signaling.

With the rapid development of 5G+ information intelligence, higher requirements are put forward for accurate and efficient semantic annotation methods. Semantic role annotation for any single method at present has its obvious and complementary advantages and disadvantages. Therefore, this paper attempts to introduce the above three mainstream and stable annotation methods into each task of semantic role annotation, and designs a Chinese semantic role annotation that integrates multi-method. This method integrates the statistical-based linear sequence method, the rule-based hierarchical tree method and the most advanced deep learning in the four processing modules of semantic role annotation. Multi-level linguistic features are introduced into the feature arrangement of the model to realize the mutual combination of multiple modules. Experiments show that the modular fusion of steps and methods effectively improves the annotation performance of each step of annotation.

In this article, based on the collaborative deep learning (CDL) and convolutional matrix factorisation (ConvMF), the language model BERT is used to replace the traditional word vector construction method, and the bidirectional long–short time memory network Bi-LSTM is used to construct an improved collaborative filtering model BMF, which not only solves the phenomenon of ‘polysemy’, but also alleviates the problem of sparse scoring matrix data. Experiments show that the proposed model is effective and superior to CDL and ConvMF. The trained MSE value is 1.031, which is 9.7% lower than ConvMF.

Periodontitis can cause damage to dental support tissue and affect the function of periodontal ligament cells. Rutin, a common flavonoid, plays a key role in anti-inflammatory responses, tissue repair and bone development. The purpose of this study was to investigate the effects of rutin on the oxidative stress, proliferation, and osteogenic differentiation of human periodontal ligament stem cells (PDLSCs) in an inflammatory environment and the underlying mechanism. Lipopolysaccharide (LPS) was used to stimulate PDLSCs to mimic an inflammatory environment model. Reactive oxygen species (ROS) levels were detected by the dichlorodihydrofluorescein diacetate (DCFH-DA) probe and the oxidative stress factors were tested by an oxidative stress factor detection kit. Moreover, the proliferation of PDLSCs was evaluated by cell counting kit-8 (CCK-8) assay. In addition, the osteogenic differentiation of PDLSCs was determined by alkaline phosphatase (ALP) staining, ALP activity test, alizarin red staining, and alizarin red semi-quantitative analysis. Furthermore, the protein levels of AKT and p-AKT were detected by Western blot. The results showed that rutin inhibited the release of ROS and increased the secretion of oxidative stress factors [superoxide dismutase (SOD) and glutathione (GSH)] and promoted the proliferation of PDLSCs in an inflammatory environment. Moreover, rutin upregulated ALP activity and enhanced the number of mineralized nodules. Conversely, the use of LY294002 (an inhibitor of PI3K) blocked the activation of the PI3K/AKT signaling pathway and prevented the beneficial effects of rutin. In conclusion, rutin promoted the antioxidative stress ability, proliferation and osteogenic differentiation of PDLSCs through PI3K/AKT signaling pathway in LPS-induced inflammatory environment.

Mitochondria-associated membranes (MAMs) are structural and functional connection sites between the endoplasmic reticulum (ER) and mitochondria dynamically connected by many molecules. The MAMs mainly rely on these molecules for their various functions, and protein complexes are the most important ones. Here, we focus on the intrinsic protein complexes involved in MAMs of mammalians. Additionally, we summarized some critical information that may be useful for future research.

Answer extraction is an important part of the field of automatic question answering (QA). The traditional answer extraction method relies heavily on contextual semantics, which makes the extraction process consume a lot of time and manpower. Aiming at the question of answer extraction, a method based on the bidirectional long-term memory network conditional random field (Bi-LSTM-CRF) is proposed. This question is extracted in parts from the answer segment. Extract the entity that contains the answer, and then extract the final answer from it. On a valid data set, the accuracy of the experimental results can reach more than 0.6050.

Both human periodontal ligament stem cells (hPDLSCs) and human gingival mesenchymal stem cells (hGMSCs) are candidate seed cells for bone tissue engineering, but the osteo‐differentiation ability of the latter is weaker than the former, and the mechanisms are unknown. To explore the potential regulation of mRNAs and long non‐coding RNAs (lncRNAs), this study obtained the gene expression profiles of hPDLSCs and hGMSCs in both undifferentiated and osteo‐differentiated conditions by microarray assay and then analysed the common and specific differentially expressed mRNAs and lncRNAs in hPDLSCs and hGMSCs through bioinformatics method. The results showed that 275 mRNAs and 126 lncRNAs displayed similar changing patterns in hPDLSCs and hGMSCs after osteogenic induction, which may regulate the osteo‐differentiation in both types of cells. In addition, the expression of 223 mRNAs and 238 lncRNAs altered only in hPDLSCs after osteogenic induction, and 177 mRNAs and 170 lncRNAs changed only in hGMSCs. These cell‐specific differentially expressed mRNAs and lncRNAs could underlie the different osteo‐differentiation potentials of hPDLSCs and hGMSCs. Finally, dickkopf Wnt signalling pathway inhibitor 1 (DKK1) was proved to be one regulator for the weaker osteo‐differentiation ability of hGMSCs through validation experiments. We hope these results help to reveal new mRNAs‐lncRNAs‐based molecular mechanism for osteo‐differentiation of hPDLSCs and hGMSCs and provide clues on strategies for improving stem cell–mediated bone regeneration.

With the development of social media, the development of large-scale social media has become the main platform for public opinion today. Visual analysis of public opinion for keywords under specific conditions uses data mining technology, data cleaning technology and data visualization technology. Through keyword reviews and content mining under specific conditions, discrete data is denoised, cleaned, keyword events and geographic information of interest are extracted. Through the visual expression of the geographical distribution of the focus area, the tag cloud and the geographical map are combined to obtain the public opinion dynamics of keyword events, which opens up ideas for the visualization of public opinion analysis of keywords under specific conditions.

Text to SQL technology is to convert natural language problems into corresponding SQL statements to help users query massive data from the database. This paper introduces the construction of text to SQL data set, the analysis of various technologies of the task model and the application fields based on the technology. It is found that the current model still has a lot of room for improvement for wikisql, spider and other large-scale annotation data sets, while there is little research on Chinese text to SQL technology. Finally, it summarizes some problems that should be paid attention to in future research.

As reported in our previous study, cinaciguat can improve implant osseointegration in type 2 diabetes mellitus (T2DM) rats by reactivating type 2 cGMP-dependent protein kinase (PKG2), but the downstream mechanisms remain unclear. In the present study, we investigated the favorable effect of cinaciguat on primary rat osteoblast, which was cultivated on titanium disc under vitro T2DM conditions (25 mM glucose and 200 μM palmitate), and clarified the therapeutic mechanism by proteomic analysis. The results demonstrated that T2DM medium caused significant downregulation of PKG2 and induced obvious osteoblast dysfunction. And overexpression of PKG2 by lentivirus and cinaciguat could promote cell proliferation, adhesion, and differentiation, leading to decreased osteoblasts injury. Besides, proteomic analysis revealed the interaction between PKG2 and phospholipase Cβ1 (PLCβ1) in the cinaciguat addition group, and we further verified that upregulated PKG2 by cinaciguat could inhibit the activation of PLCβ1, then relieve intracellular calcium overload, and suppress endoplasmic reticulum (ER) stress to ameliorate osteoblast functions under T2DM condition. Collectively, these findings provided the first detailed mechanisms responsible for cinaciguat provided a favorable effect on promoting osseointegration in T2DM and demonstrated a new insight that diabetes mellitus-induced the aberrations in PKG2-PLCβ1-Ca2+-ER stress pathway was one underlying mechanism for poor osseointegration.

Background: Type 2 diabetes mellitus (T2DM) has a harmful effect on the stability and osseointegration of dental implants. T2DM induces mitochondrial damage by inhibiting AMPK signaling, resulting in oxidative stress and poor osteogenesis in the peri-implant bone area. Genipin is a major component of gardenia fruits with strong antioxidant, anti-inflammation, and anti-diabetic actions, and it also can activate mitochondrial quality control via the AMPK pathway. The purpose of this study was to investigate the effects of genipin and insulin treatment on implant osseointegration in T2DM rats and explore the underlying mechanisms. Methods: Streptozotocin-induced diabetic rats received implant surgery in their femurs, and were then assigned to five groups that were subjected to different treatments for three months: control group, T2DM group, insulin-treated T2DM group (10 IU/kg), genipin-treated T2DM group (50 mg/kg), and the genipin and insulin combination-treated T2DM group. Then, we regularly assessed the weight and glucose levels of the animals. Rats were euthanized at three months after the implantation procedure, and the femora were harvested for microscopic computerized tomography analysis, biomechanical tests, and different histomorphometric assessment. Results: The results indicated that the highest blood glucose and oxidative stress levels were measured for the T2DM group, resulting in the poorest osseointegration. The combination-treated T2DM group mitigated hyperglycemia and normalized, reactivated AMPK signaling, and alleviated oxidative stress as well as reversed the negative effect of osseointegration. There were beneficial changes observed in the T2DM-genipin and T2DM-insulin groups, but these were less in comparison to the combination treatment group. Conclusion: Our study suggests that treatment with genipin in combination with insulin could be an effective method for promoting implant osseointegration in T2DM rats, which may be related to AMPK signaling.

Due to the existing single machine translation model for named entity markup is too rough and not detailed to meet the requirements. This paper proposes an integrated analysis of lexical and syntactic integration of named entity information to improve the performance of Tibetan-Chinese machine translation. Experiments show that the performance of the model is better than that of the model based on independent integration and the model based on independent grammar. In the stage of syntactic analysis, the combination of named entity information and comprehensive information can improve the performance of syntactic analysis.

One potential solution to the problem of information overload is the recommendation system, and the main task of recommendation system based on user portrait is to combine user and product, by mapping user portrait and product portrait, combining association rule mining and reordering algorithm, a personalized product recommendation list is obtained. Not only can help users find valuable information for themselves, but also can make the information displayed in front of interested users, so as to achieve a win-win situation between information consumers and information producers.

Diabetes-induced advanced glycation end products (AGEs) overproduction would result in compromised osseointegration of titanium implant and high rate of implantation failure. 1α,25-dihydroxyvitamin D3 (1,25VD3) plays a vital role in osteogenesis, whereas its effects on the osseointegration and the underlying mechanism are unclear. The purpose of this study was to investigate that 1,25VD3 might promote the defensive ability of osseointegration through suppressing AGEs/RAGE in type 2 diabetes mellitus. In animal study, streptozotocin-induced diabetic rats accepted implant surgery, with or without 1,25VD3 intervention for 12 weeks. After killing, the serum AGEs level, bone microarchitecture and biomechanical index of rats were measured systematically. In vitro study, osteoblasts differentiation capacity was analyzed by alizarin red staining, alkaline phosphatase assay and Western blotting, after treatment with BSA, AGEs, AGEs with RAGE inhibitor and AGEs with 1,25VD3. And the expression of RAGE protein was detected to explore the mechanism. Results showed that 1,25VD3 could reverse the impaired osseointegration and mechanical strength, which possibly resulted from the increased AGEs. Moreover, 1,25VD3 could ameliorate AGEs-induced damage of cell osteogenic differentiation, as well as downregulating the RAGE expression. These data may provide a theoretical basis that 1,25VD3 could work as an adjuvant treatment against poor osseointegration in patients with type 2 diabetes mellitus.

The influence of hyperlipidemia on titanium implant osseointegration and the underlying mechanisms remain elusive. Here, we studied the effects of hyperlipidemia on osseointegration and the related mechanisms. In vivo, specialized titanium implants were implanted in the femurs of diet-induced or genetic hyperlipidemia mice. In vitro, primary murine osteoblasts were cultured on titanium surface. Results showed that hyperlipidemia led to poor bone formation on bone-implant interface in two types of mice in vivo. In vitro, high-fat medium caused significant overproduction of reactive oxygen species (ROS) and inhibiting of Wnt/β-catenin pathway in osteoblasts on titanium surface, inducing obvious cell dysfunction. Both N-acetyl-L-cysteine(NAC, a ROS antagonist) and Wnt3a(an activator of Wnt/β-catenin pathway) could effectively attenuated the poor osteogenic ability of osteoblasts. Besides, NAC reactivated the Wnt/β-catenin pathway in osteoblasts under high-fat stimulation. Our results suggested that the cellular oxidative stress leads to osteoblasts dysfunction via the Wnt/β-catenin pathway, which plays a critical role in the compromised implant osseointegration under hyperlipidemia conditions. These results demonstrated new insights into the negative effect of hyperlipidemia on osseointegration and also provided ROS or Wnt/β-catenin pathway as promising therapeutic targets for developing novel implant materials to accelerate the osseointegration of implants in hyperlipidemia patients.

Type 2 diabetes mellitus (T2DM) is considered to compromise implant osseointegration. Protein tyrosine phosphatase non-receptor type 2 (PTPN2) regulates glucose metabolism, systemic inflammation, and bone regeneration. This study aimed to investigate the role of PTPN2 in implant osseointegration in T2DM and explore the potential mechanisms. Streptozotocin-induced diabetic rats received implant surgery, with or without local overexpression of PTPN2 for three months, and implant osseointegration was examined by histological evaluation, micro-CT analysis, pull-out test, and scanning electron microscope. Rat bone marrow stem cells (RBMSCs) were isolated and exposed to high glucose, and osteogenic differentiation was evaluated by alizarin red staining, ALP assay, and Western blot analysis. Overexpression of PTPN2 could improve impaired implant osseointegration in T2DM rats and promote osteogenic differentiation of RBMSCs in high glucose. In addition, p-ERK level in RBMSCs was increased in high glucose and decreased after PTPN2 overexpression. These results suggest that PTPN2 promotes implant osseointegration in T2DM rats and enhances osteogenesis of RBMSCs in high glucose medium via inducing the dephosphorylation of ERK. PTPN2 may be a novel target for the therapy of impaired implant osseointegration in T2DM patients. Impact statement Using both in vivo and in vitro approaches, we made important findings that PTPN2 promoted implant osseointegration in T2DM rats and enhanced osteogenesis of RBMSCs in high glucose medium. The positive effects of PTPN2 on osteogenesis are related to the dephosphorylation of ERK and the inhibition of MAPK/ERK pathway. PTPN2 may be a novel target for the therapy of impaired implant osseointegration in T2DM patients.

Objectives Peripheral nerve injuries are a common occurrence, resulting in considerable patient suffering; it also represents a major economic burden on society. To improve treatment options following peripheral nerve injuries, scientists aim to find a way to promote Schwann cell (SC) myelination to help nerves to carry out their functions effectively. In this study, we investigated myelination ability of SCs, regulated by co-culture with adipose-derived stem cells (ASCs) or low-intensity pulsed ultrasound (LIPUS), and synergistic effects of combined treatments. Materials and methods Schwann cells were co-cultured with or without ASCs, and either left untreated or treated with LIPUS for 10 min/d for 1, 4 or 7 days. Effects of LIPUS and ASC co-culture on pro-myelination indicators of SCs were analysed by real-time PCR (RT-PCR), Western blotting and immunofluorescence staining (IF). Results Our results indicate that ASC-SC co-culture and LIPUS, together or individually, promoted mRNA levels of epidermal growth factor receptor 3 (EGFR3/ErbB3), neuregulin1 (NRG1), early growth response protein 2 (Egr2/Krox20) and myelin basic protein (MBP), with corresponding increases in protein levels of ErbB3, NRG1 and Krox20. Interestingly, combination of ASC-SC co-culture and LIPUS displayed the most remarkable effects. Conclusion We demonstrated that ASCs upregulated pro-myelination indicators of SCs by indirect contact (through co-culture) and that effects could be potentiated by LIPUS. We conclude that LIPUS, as a mechanical stress, may have potential in nerve regeneration with potential clinical relevance.

Information extraction is to extract the required specific entity, event, relationship and other information from a large number of texts and store it in a structured form, which occupies an important position in the field of natural language. Information extraction helps people get the information they need efficiently, avoids a lot of complicated work, and saves manpower and material resources. In this paper, named entity recognition and so on are described and summarized in detail, as well as the prospect of information extraction.

Tyrosine‐protein phosphatase non‐receptor type 2 (PTPN2) is an important protection factor for diabetes and periodontitis, but the underlying mechanism remains elusive. This study aimed to identify the substrate of PTPN2 in mediating beneficial effects of 25‐Hydroxyvitamin D3 (25(OH)2D3) on diabetic periodontitis. 25(OH)2D3 photo‐affinity probe was synthesized with the minimalist linker and its efficacy to inhibit alveolar bone loss, and inflammation was evaluated in diabetic periodontitis mice. The probe was used to pull down the lysates of primary gingival fibroblasts. We identified PTPN2 as a direct target of 25(OH)2D3, which effectively inhibited inflammation and bone resorption in diabetic periodontitis mice. In addition, we found that colony‐stimulating factor 1 receptor (CSF1R) rather than JAK/STAT was the substrate of PTPN2 to regulate bone resorption. PTPN2 direct interacted with CSF1R and dephosphorylated Tyr807 residue. In conclusion, PTPN2 dephosphorylates CSF1R at Y807 site and inhibits alveolar bone resorption in diabetic periodontitis mice. PTPN2 and CSF1R are potential targets for the therapy of diabetic periodontitis or other bone loss‐related diseases.

The osseointegration process of implant is seriously impaired in type 2 diabetes mellitus (T2DM) that causes high failure rate, and insufficiency exists in current insulin therapy, creating a demand for new bone-synergistic agent. Cinaciguat, a novel type of soluble guanylate cyclase (sGC) activator, plays a vital role in glucose metabolism, inflammation control and bone regeneration. We hypothesized that the combined application of cinaciguat and insulin could reverse poor implant osseointegration in diabetes. To test this hypothesis, streptozotocin-induced diabetic rats were placed implants in the femur, and divided into five groups: control, T2DM, cinaciguat-treated T2DM (7 μg/kg), insulin-treated T2DM (12 IU/kg), cinaciguat plus insulin combination-treated T2DM (7 μg/kg and 12 IU/kg respectively), according to different treatment received. The weight and glucose levels of rats were evaluated at fixed times, and plasma level of cyclic guanosine monophosphate (cGMP) was determined before euthanasia. Three months after therapy, the femurs were isolated for pull-out test, environmental scanning electron microscope observation, microscopic computerized tomography evaluation and various histology analysis. Results revealed that diabetic rats showed the highest blood glucose level and lowest cGMP content, which led to the worst structural damage and least osseointegration. Combined treatment could attenuate the diabetes induced hyperglycemia to be normal, restore the cGMP content, protein kinase G II (PKG II) expression, phosphodiesterase-5 (PDE5) activity and ameliorate the mechanical strength, the impaired bone microarchitecture and osseointegration to the highest level. Meanwhile, monotreatment (insulin or cinaciguat) also showed restorative effect, but less. Our findings demonstrated that the cGMP/PKG II signaling pathway activated by cinaciguat mediated the favorable effects of the combined application on improving implant fixation under T2DM condition.