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Abstract Purpose The purpose of this study was to compare the learning in the implant dentistry hands-on course to that of the flipped classroom (FC) and the traditional lecture cohorts (control). Materials and methods In this study,80 students were enrolled for the first time in an implant dentistry program. Subsequently, they were divided into two groups. The first, the FC group, which had free access to a video with a PowerPoint presentation on the Chaoxing-WHU-MOOC platform about the implant placement on first molar sites before class. The second, the control group, which attended a didactic lecture describing implant practice on the first molar site via a bidirectional multimedia interactive teaching demonstration and then operated on a simulation model. Cone beam computed tomography (CBCT) and the deviation gauge were utilized to analyze the accuracy of the implant placement in the students’ models. An online satisfaction questionnaire was distributed to both groups one week after the class. Results The linear deviation of the CBCT examination did not show any statistical difference between the two groups concerning cervical, apex, and angular. A significant buccal deviation was observed in the control group compared with the FC group (mean: 0.7436 mm vs. 0.2875 mm, p = 0.0035), according to the restoration-level deviation gauge. A total of 74.36% of students in the FC group placed implant within 0.5 mm buccal-to-lingual deviations, but only 41.03% of students in the control group reached within 0.5 mm buccal-to-lingual deviation ranges. Additionally, 91.67% of the students in the FC group and 97.5% of the students in the control group were satisfied with the practical implant class. Conclusion FC was more effective than a didactic lecture for implant dentistry practical skill acquisition.

Abstract Bone substitute material implantation has become an important treatment strategy for the repair of oral and maxillofacial bone defects. Recent studies have shown that appropriate inflammatory and immune cells are essential factors in the process of osteoinduction of bone substitute materials. Previous studies have mainly focused on innate immune cells such as macrophages. In our previous work, we found that T lymphocytes, as adaptive immune cells, are also essential in the osteoinduction procedure. As the most important antigen-presenting cell, whether dendritic cells (DCs) can recognize non-antigen biomaterials and participate in osteoinduction was still unclear. In this study, we found that surgical trauma associated with materials implantation induces necrocytosis, and this causes the release of high mobility group protein-1 (HMGB1), which is adsorbed on the surface of bone substitute materials. Subsequently, HMGB1-adsorbed materials were recognized by the TLR4-MYD88-NFκB signal axis of dendritic cells, and the inflammatory response was activated. Finally, activated DCs release regeneration-related chemokines, recruit mesenchymal stem cells, and initiate the osteoinduction process. This study sheds light on the immune-regeneration process after bone substitute materials implantation, points out a potential direction for the development of bone substitute materials, and provides guidance for the development of clinical surgical methods.

Abstract Studies in neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease and Amyotrophic lateral sclerosis, Huntington’s disease, and so on, have suggested that inflammation is not only a result of neurodegeneration but also a crucial player in this process. Protein aggregates which are very common pathological phenomenon in neurodegeneration can induce neuroinflammation which further aggravates protein aggregation and neurodegeneration. Actually, inflammation even happens earlier than protein aggregation. Neuroinflammation induced by genetic variations in CNS cells or by peripheral immune cells may induce protein deposition in some susceptible population. Numerous signaling pathways and a range of CNS cells have been suggested to be involved in the pathogenesis of neurodegeneration, although they are still far from being completely understood. Due to the limited success of traditional treatment methods, blocking or enhancing inflammatory signaling pathways involved in neurodegeneration are considered to be promising strategies for the therapy of neurodegenerative diseases, and many of them have got exciting results in animal models or clinical trials. Some of them, although very few, have been approved by FDA for clinical usage. Here we comprehensively review the factors affecting neuroinflammation and the major inflammatory signaling pathways involved in the pathogenicity of neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and Amyotrophic lateral sclerosis. We also summarize the current strategies, both in animal models and in the clinic, for the treatment of neurodegenerative diseases.

This study employs deep learning and artificial intelligence (AI) clustering analysis techniques to evaluate the suitability of integrated rural land for three industries. Diverse datasets pertaining to rural development, encompassing land use, agricultural production, and rural tourism, are gathered and harmoniously amalgamated. An innovative land suitability assessment model, merging ResNet-50 with the k-means algorithm, is devised. Specifically, ResNet-50 is harnessed for the classification and recognition of rural land-use images, thus deriving feature vectors for each sample. These feature vectors are subsequently fed into the k-means algorithm to cluster samples with akin land-use patterns. The ensuing examination of land use composition within each cluster facilitates the evaluation of rural land’s suitability for three-industry integration. Experimental scrutiny discloses that this study achieves an accuracy rate of 88.3% in rural land-use classification and recognition, outperforming alternative algorithms by at least 3.1%. Furthermore, it yields an average intersection over union (IoU) of 67.29%. Remarkably, the k-means algorithm exhibits superior clustering outcomes. Consequently, the model introduces herein demonstrated substantial enhancements in rural land-use classification and recognition accuracy, average IoU, and clustering performance. It offers an innovative tool for policymakers to advance rural industry integration, fostering economic diversification. Additionally, this model aids decision-makers in identifying prospective opportunities and challenges, thus facilitating the formulation of forward-thinking and viable rural development strategies.

FAM76B has been reported to be a nuclear speckle-localized protein with unknown function. In this study, FAM76B was first demonstrated to inhibit the NF-κB-mediated inflammatory pathway by affecting the translocation of hnRNPA2B1 in vitro. We further showed that FAM76B suppressed inflammation in vivo using a traumatic brain injury (TBI) mouse model. Lastly, FAM76B was shown to interact with hnRNPA2B1 in human tissues taken from patients with acute, organizing, and chronic TBI, and with different neurodegenerative diseases. The results suggested that FAM76B mediated neuroinflammation via influencing the translocation of hnRNPA2B1 in vivo during TBI repair and neurodegenerative diseases. In summary, we for the first time demonstrated the role of FAM76B in regulating inflammation and further showed that FAM76B could regulate the NF-κB-mediated inflammatory pathway by affecting hnRNPA2B1 translocation, which provides new information for studying the mechanism of inflammation regulation.

Disruption of colonic homeostasis caused by aberrant M1/M2 macrophage polarization contributes to the development of inflammatory bowel disease (IBD). Lycium barbarum polysaccharide (LBP) is the primary active constituent of traditional Chinese herbal Lycium barbarum L., which has been widely demonstrated to have important functions in regulating immune activity and anti-inflammatory. Thus, LBP may protect against IBD. To test this hypothesis, the DSS-induced colitis model was established in mice, then the mice were treated with LBP. The results indicated that LBP attenuated the weight loss, colon shortening, disease activity index (DAI), and histopathological scores of colon tissues in colitis mice, suggesting that LBP could protect against IBD. Besides, LBP decreased the number of M1 macrophages and the protein level of Nitric oxide synthase 2(NOS2) as a marker of M1 macrophages and enhanced the number of M2 macrophages and the protein level of Arginase 1(Arg-1) as a marker of M2 macrophages in colon tissues from mice with colitis, suggesting that LBP may protect against IBD by regulating macrophage polarization. Next, the mechanistic studies in RAW264.7 cells showed that LBP inhibited M1-like phenotype by inhibiting the phosphorylation of STAT1, and promoted M2-like phenotype by promoting the phosphorylation of STAT6. Finally, immunofluorescence double-staining results of colon tissues showed that LBP regulated STAT1 and STAT6 pathways in vivo. The results in the study demonstrated that LBP could protect against IBD by regulating macrophage polarization through the STAT1 and STAT6 pathways.

IntroductionIt is necessary to explore a noninvasive method to stratify head and neck squamous cell carcinoma (HNSCC)’s prognosis and to seek new indicators for individualized precision treatment. As a vital inflammatory cytokine, IL1B might drive a new tumor subtype that could be reflected in overall survival (OS) and predicted using the radiomics method.MethodsA total of 139 patients with RNA-Seq data from The Cancer Genome Atlas (TCGA) and matched CECT data from The Cancer Image Archive (TCIA) were included in the analysis. The prognostic value of IL1B expression in patients with HNSCC was analyzed using Kaplan-Meier analysis, Cox regression analysis and subgroup analysis. Furthermore, the molecular function of IL1B on HNSCC was explored using function enrichment and immunocytes infiltration analyses. Radiomic features were extracted with PyRadiomics and processed using max-relevance minredundancy, recursive feature elimination, and gradient boosting machine algorithm to construct aradiomics model for predicting IL1B expression. The area under the receiver operating characteristic curve (AUC), calibration curve, precision recall (PR) curve, and decision curve analysis (DCA) curve were used to examine the performance of the model.ResultsIncreased IL1B expression in patients with HNSCC indicated a poor prognosis (hazard ratio [HR] = 1.56, P = 0.003) and was harmful in patients who underwent radiotherapy (HR = 1.87, P = 0.007) or chemotherapy (HR = 2.514, P < 0.001). Shape_Sphericity, glszm_SmallAreaEmphasis, and firstorder_Kurtosis were included in the radiomics model (AUC: training cohort, 0.861; validation cohort, 0.703). The calibration curves, PR curves and DCA showed good diagnostic effect of the model. The rad-score was close related to IL1B (P = 4.490*10-9), and shared the same corelated trend to EMT-related genes with IL1B. A higher rad-score was associated with worse overall survival (P = 0.041).DiscussionThe CECT-based radiomics model provides preoperative IL1B expression predictionand offers non-invasive instructions for the prognosis and individualized treatment of patients withHNSCC.

Glioma is a common intracranial malignant tumor with high mortality and high recurrence rate. In recent years, increasing evidence has demonstrated that circular RNAs (circRNAs) are potential biomarkers and therapeutic targets for many tumors. However, the role of circRNAs in glioma remains unclear. In this study, we found that circRNA-0002109 was highly expressed in glioma tissues and cell lines. Downregulation of circRNA-0002109 expression inhibited the proliferation, migration, and invasion of glioma cells and inhibited the malignant progression of tumors in vivo. Investigations into the relevant mechanisms showed that circRNA-0002109 upregulated the expression of EMP2 through endogenous competitive binding of microRNA-129-5P (miR-129-5P), which partially alleviated the inhibitory effect of miR-129-5P on epithelial membrane protein-2 (EMP2) and ultimately promoted the malignant development of glioma. Our results indicate that circRNA-0002109 plays an important role in the proliferation, invasion, and migration of glioma cells by regulating the miR-129-5P/EMP2 axis, which provides a new potential therapeutic target for glioma.

Chimeric antigen receptor T cell (CAR-T) therapy has been shown to be an effective strategy for combatting non-solid tumors; however, CAR-T therapy is still a challenge for solid tumors, such as glioblastoma. To improve CAR-T therapy for glioblastoma, a new TanCAR, comprising the tandem arrangement of IL13 (4MS) and EphA2 scFv, was generated and validated in vitro and in vivo. In vitro, the novel TanCAR-redirected T cells killed glioblastoma tumor cells by recognizing either IL-13 receptor α2 (IL13Rα2) or EphA2 alone or together upon simultaneous encounter of both targets, but did not kill normal cells bearing only the IL13Rα1/IL4Rα receptor. As further proof of principle, the novel TanCAR was tested in a subcutaneous glioma xenograft mouse model. The results indicated that the novel TanCAR-redirected T cells produced greater glioma tumor regression than single CAR-T cells. Thus, the novel TanCAR-redirected T cells kill gliomas more efficiently and selectively than a single IL13 CAR or EphA2 scFv CAR, with the potential for preventing antigen escape and reduced off-target cytotoxicity.

Abstract Background This study aimed to investigate the clinical characteristics and early soft tissue response to zirconium oxide (Zr) and titanium (Ti) healing abutments in dogs. Methods Eight implants (four at each hemi-mandible) were inserted after bilateral mandibular third and fourth premolars and first molar extraction in dogs. Then, two Zr and two Ti healing abutments were connected to each unilateral mandible eight weeks later. The ligation method was used to create a peri-implant mucositis model and the 24 abutments were divided into four groups: Zr or Ti healing abutments with ligation (ZrL, TiL) or non-ligation (ZrN, TiN). The clinical indices, peri-implant crevicular fluid (PICF), and inflammatory cytokines (TNF-α and IL-1β) were measured and analyzed on days 0 and 28. The dogs were then sacrificed on day 28, soft tissues around the implants were harvested, and inflammation infiltration was tested by immunohistochemistry. Normal distribution test and two-way analysis of variance was used to analyze the data. Results The results showed that the clinical indices were similar for Zr and Ti healing abutments. There was significantly more PICF in the ZrL and TiL groups compared to in the ZrN and TiN groups. The TNF-α levels in PICF were significantly different between ZrL and ZrN groups on day 28. And the TNF-α levels in PICF were significantly higher in TiL group on day 28 than that on day 0. However, the number of inflammatory cells was not significantly different between the groups as measured by immunohistochemistry. Conclusions These data indicate that soft tissue responses to Zr healing abutments with peri-implant mucositis were comparable to those of Ti healing abutments in vivo, providing a theoretical foundation for the clinical application of Zr abutments.

Abstract Mineralized tissue regeneration is an important and challenging part of the field of tissue engineering and regeneration. At present, autograft harvest procedures may cause secondary trauma to patients, while bone scaffold materials lack osteogenic activity, resulting in a limited application. Loaded with osteogenic induction growth factor can improve the osteoinductive performance of bone graft, but the explosive release of growth factor may also cause side effects. In this study, we innovatively used platelet-rich fibrin (PRF)-modified bone scaffolds (Bio-Oss®) to replace autograft, and used cytokine (BMP-2) to enhance osteogenesis. Encouragingly, this mixture, which we named “Autograft Mimic (AGM)”, has multiple functions and advantages. (1) The fiber network provided by PRF binds the entire bone scaffold together, thereby shaping the bone grafts and maintaining the space of the defect area. (2) The sustained release of BMP-2 from bone graft promoted bone regeneration continuously. (3) AGM recruited bone marrow mesenchymal stem cells (BMSCs) and promote their proliferation, migration, and osteogenic differentiation. Thus, AGM developed in this study can improve osteogenesis, and provide new guidance for the development of clinical bone grafts.

Heat stress (HS) is directly correlated with mammary gland dysfunction and the hypothalamic-pituitary-mammary gland (HPM) axis is involved in regulating stress responses and lactation in dairy cows. Circular RNAs (circRNAs) play major roles in regulating transcription and post-transcription but their expression in the HPM axis of dairy cows under HS is still unclear. In the present study, we performed RNA sequencing to identify diferentially expressed (DE) circRNAs, DE microRNAs(miRNAs) and DEmRNAs, and performed bioinformatics analysis on those in HPM axis-related tissues of heat-stressed and normal cows. A total of 1680, 1112 and 521 DEcircRNAs, 120, 493 and 108 DEmiRNAs, 274, 6475 and 3134 DEmRNAs were identified in the hypothalamic, pituitary, and mammary gland tissues, respectively. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses indicated that the MAPK signaling pathway is potentially a key pathway. Competitive endogenous RNA (ceRNA) networks related to HS response and lactation regulation were established in three tissues. In conclusion, our results indicate that HS induces differential circRNA expression profiles in HPM axis-related tissues, and the predicted ceRNA network provides a molecular basis for regulating the stress response and lactation regulation in heat-stressed dairy cows.

The purpose of this paper is to explore the spatial heterogeneity of internal migration in China and to discuss the influence of economic, social and environmental characteristics on this demographic process. The overall results suggest that migration in China occurred from inland to coastal areas and from rural areas to urban areas. By stepwise regression, we identified that 9 out of 15 factors with potential influence on internal migration were retained, and the multicollinearity among them was reduced. In addition, we used the OLS and GWR regression analysis to discuss the global and local effects of relevant factors on internal migration. Economic scale (GDP), population concentration (population density) and demographic dividend (labour force proportion) were the three main driving forces of internal migration. In turn, internal migration further widened the gap of economic scale, population agglomeration and demographic dividend between counties and cities. Internal migration in southern coastal areas of China was most affected by economic aspects and demographic dividend. In the central China, the population was more concentrated in high-density cities, while in the eastern regions, areas with high level of education were conducive to immigration, thus forming talent reserve highlands. In the west, areas with highly educated level faced out-migration, which might cause brain drain and widen further the gap in talent reserves between the east and the west in China. From the perspective of location, the net immigration of the provincial capital was accompanied by the net immigration of the surrounding area, which was conducive to the formation of city clusters or urban sprawl. On the other side, the net immigration in prefecture-level cities often meant the net out-migration in surrounding areas. The correlation is particularly strong in eastern coastal provinces.

Background: Matrix metalloproteinase 12 (MMP12), a member of MMPs, can take lots of roles including extracellular matrix component degradation, viral infection, inflammation, tissue remodeling and tumorigenesis. To explore the transcriptional regulation of MMP12 gene, a sensitive luciferase reporter HEK293 cell line for endogenous MMP12 promoter was generated by CRISPR/Cas9 technology. Results: The HEK293-MMP12-T2A-luciferase-KI cell line was successfully established by CRISPR/Cas9 technology. The sequencing results indicated that one allele of the genome was proven to have a site-directed insertion of luciferase gene and another allele of the genome was confirmed to have additional 48 bp insertion in this cell line. The cell line was further demonstrated to be a sensitive reporter of the endogenous MMP12 promoter by applying transcription factors STAT3, AP-1 and SP-1 to the cell line. The reporter cell line was then screened with bioactive small molecule library, and a small molecule Tanshinone I was found to significantly inhibit the transcriptional activity of MMP12 gene in HEK293-MMP12-T2A-luciferase-KI cell line by luciferase activity assay, which was further confirmed to inhibit the expression of MMP12 mRNA in wild-type HEK293 cells. Conclusions: This novel luciferase knock-in reporter system will be helpful for investigating the transcriptional regulation of MMP12 gene and screening the drugs targeting MMP12 gene.How to cite: Du C, Wu Y, Ju Y, et al. The luciferase reporter system of the MMP12 endogenous promoter for investigating transcriptional regulation of the human MMP12 gene. Electron J Biotechnol 2020;43. https://doi.org/10.1016/j.ejbt.2019.12.003. Keywords: Cancer research, Cell line, Cell–cell interactions, Cell–extracellular matrix interactions, CRISPR/Cas9, Knock-in, Luciferase, Matrix metalloproteinases, MMP12, Transcriptional regulation, Zinc-dependent endopeptidase

It is foreseeable that the next few decades will be the golden age of high-speed rail (HSR) development, with many new construction plans emerging. The construction of the HSR will inevitably cause an impact on the economic spatial structure of urban agglomeration, but it is still unclear whether the impacts differ between economically developed and developing areas. How and to what extent do such differences exist? Based on the modified gravity model, this paper employs a social network analysis method and selects the Yangtze River Delta and Sichuan-Chongqing (Chuanyu) urban agglomeration as the research area to analyze the differences. The main conclusions are as follows. With the construction of HSR: (1) The network density and the average economic connection of urban agglomerations have shown a trend of gradual increase. (2) The number of core areas in developed regions has gradually increased, but there were no changes in the center of developing regions. (3) In developed regions, the new metropolitan areas are the cities that have benefited the most from the HSR construction. In developing regions, the central city with difficult topography benefits the most. (4) The network structure of developed regions tends to be more balanced. The edge cities in developing regions are getting farther from the center.

Global urbanization has brought about a significant transition to rural areas. With the development of remote sensing technologies, land use/land cover (LULC) datasets allow users to analyze the changes in global rural settlements. However, few studies have examined the performances of the LULC datasets in mapping rural settlements. Taking China as the study area, this research selected eight of the latest LULC datasets (ESRI Land Cover, WSF, ESA WorldCover, GHS-BUILT-S2, GISD30, GISA2.0, GLC30, and GAIA) to compare their accuracy for rural settlement detection. Spatial stratified sampling was used for collecting and sampling rural settlements. We conducted omission tests, area comparison, and pixel-based accuracy tests for comparison. The results show that: (1) the performances of the 10 m resolution datasets are better than those of the 30 m resolution datasets in almost all scenarios. (2) the mapping of villages in Western China is a challenge for all datasets. (3) GHS-BUILT-S2 performs the best in almost every scenario, and can allow users to adjust the threshold value for determining a proper range of rural settlement size; ESRI outperforms any other dataset in detecting the existence of rural settlements, but it dramatically overestimates the area of rural settlements. (4) GISD30 is the best among the 30 m resolution datasets, notably in the Pearl River Delta. Finally, we provide useful suggestions on ideal map selection in various regions and scenarios.

Elastomeric membranes are frequently used in several emerging fields such as soft robotics and flexible electronics. For convenience of the structural design, it is very attractive to find simple analytical solutions to well describe their elastic deformations in response to external loadings. However, both the material/geometrical nonlinearity and the deformation inhomogeneity due to boundary constraints make it much challenging to get an exact analytical solution. In this paper, we focus on the inflation of a pre-stretched elastomeric circular membrane under uniform pressure, and derive an approximate analytical solution of the pressure–volume curve based upon a reasonable assumption on the shape of the inflated membrane. Such an explicit expression enables us to quantitatively design the material and geometrical parameters of the pre-stretched membrane to generate a target pressure–volume curve with prescribed peak point and initial slope. This work would be of help in the simplified mechanical design of structures involving elastomeric membranes.

IFT20 is a subunit of the intraflagellar transport (IFT) system essential for the formation and function of cilia. Besides predominant research in the cilia field, some IFT subunits perform extraciliary roles in non-ciliated cancer cells. However, the specific roles of IFT subunits in tumorigenesis remain unknown. Here, we found that knockout of IFT20 in mouse breast cancer cells lacking primary cilia promoted epithelial mesenchymal transitions (EMTs), active lamellipodia formation, and cell migration. IFT20 localized at the trans-Golgi and trans-Golgi network (TGN), and displayed vesicular co-distributions with Rab8a, the marker of TGN-to-plasma membrane vesicular trafficking. Proximity-dependent biotin identification (BioID) and colocalization analyzes showed that Numb and Ctnnal1, whose depletion promoted cell migration, co-localized with IFT20 at the trans-Golgi/TGN or intracellular transport vesicles. Furthermore, Strep-Tactin pulldown assays revealed an interaction between IFT20 and Ctnnal1 or Numb. Loss of IFT20 lowered the expression of actin-associated Tagln2, whose knockdown promoted cell migration. Thus, the extraciliary function of ITF20 in breast cancer cell was associated with the negative regulation of migration.

Heterogeneity of fibroblasts directly affects the outcome of tissue regeneration; however, whether bioactive ceramics regulate bone regeneration through fibroblasts is unclear. Ectopic bone formation model with biphasic calcium phosphate (BCP) implantation was used to investigate the temporal and spatial distribution of fibroblasts around ceramics. The effect of BCP on L929 fibroblasts was evaluated by EdU assay, transwell assay, and qRT-PCR. Further, the effect of its conditioned medium on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) was confirmed by ALP staining. SEM and XRD results showed that BCP contained abundant micro- and macro-pores and consisted of hydrogen-apatite (HA) and β-tricalcium phosphate (β-TCP) phases. Subsequently, BCP implanted into mice muscle successfully induced osteoblasts and bone formation. Fibroblasts labelled by vimentin gathered around BCP at 7 days and peaked at 14 days post implantation. In vitro, BCP inhibited proliferation of L929 fibroblast but promoted its migration. Moreover, expression of Col1a1, Bmp2, and Igf1 in L929 treated by BCP increased significantly while expression of Tgfb1 and Acta did not change. ALP staining further showed conditioned media from L929 fibroblasts treated by BCP could enhance osteogenic differentiation of BMSCs. In conclusion, fibroblasts mediate ectopic bone formation of calcium phosphate ceramics.

How to achieve the sustainable and coordinated development of the ecological environment, the economy and tourism has already received much attention. In this paper, a comprehensive evaluation index system of the ecological environment, the economy and tourism is established, and the coupling degrees and coordination degrees of the three subsystems of 31 provinces in China from 2003 to 2017 are calculated. The results show that the average coupling degree and average coordination degree have fluctuating upward trends during the period of 2003-2017. According to the spatial distribution of the coupling degrees and coordination degrees, the coastal provinces and Chongqing, with their high ecological environment pressure and good economic development, have low coupling and extremely high coordination levels. The vast central and western provinces with good ecological environment protection and economic backwardness have high coupling and low coordination development level. From the perspective of coordinated development, only seven of the western provinces and three middle-eastern provinces possess basic coordinated development of the ecological environment, the economy and tourism. The remaining 21 provinces are over-utilizing or sacrificing their ecological environments, among which eleven eastern provinces have an advanced economy or advanced tourism and five southwestern provinces with high tourism resource endowments have an advanced tourism.

Due to the rapid economic growth and the heavy reliance on fossil fuels, China has become one of the countries with the highest sulfur dioxide (SO2) emissions, which pose a severe challenge to human health and the sustainable development of social economy. In order to cope with the serious problem of SO2 pollution, this study attempts to explore the spatial temporal variations of industrial SO2 emissions in China utilizing the Defense Meteorological Satellite Program's Operational Linescan System (DMSP-OLS) nighttime stable light (NSL) data. We first explored the relationship between the NSL data and the statistical industrial SO2 emissions at the provincial level, and confirmed that there was a positive correlation between these two datasets. Consequently, 17 linear regression models were established based on the NSL data and the provincial statistical emissions to model the spatial-temporal dynamics of China's industrial SO2 emissions from 1997 to 2013. Next, the NSL-based estimated results were evaluated utilizing the prefectural statistical industrial SO2 emissions and emission inventory data, respectively. Finally, the distribution of China's industrial SO2 emissions at 1 km spatial resolution were estimated, and the temporal and spatial dynamics were explored from multiple scales (national scale, regional scale and scale of urban agglomeration). The results show that: (1) The NSL data can be successfully applied to estimate the dynamic changes of China's industrial SO2 emissions. The coefficient of determination (R2) values of the NSL-based estimation results in most years were greater than 0.6, and the relative error (RE) values were less than 10%, when validated by the prefectural statistical SO2 emissions. Moreover, compared with the inventory emissions, the adjusted coefficient of determination (Adj.R-Square) reached 0.61, with the significance at the 0.001 level. (2) During the observation period, the temporal and spatial dynamics of industrial SO2 emissions varied greatly in different regions. The high growth type was largely distributed in China's Western region, Central region, and Shandong Peninsula, while the no-obvious-growth type was concentrated in Western region, Beijing-Tianjin-Tangshan and Middle south of Liaoning. The high grade of industrial SO2 emissions was mostly concentrated in China's Eastern region, Western region, Shanghai-Nanjing-Hangzhou and Shandong Peninsula, while the low grade mainly concentrated in China's Western region, Middle south of Liaoning and Beijing-Tianjin-Tangshan. These results of our research can not only enhance the understanding of the spatial-temporal dynamics of industrial SO2 emissions in China, but also offer some scientific references for formulating feasible industrial SO2 emission reduction policies.

Periodontal tissue engineering is a possible strategy for regeneration of human periodontal ligaments (PDLs) around dental implants. The aim of this study was to investigate the feasibility of three-dimensional polyglycolic acid (PGA) fibre mesh as a scaffold for human PDL cells in periodontal tissue engineering with a nude mouse model. Human PDL cells at a density of 2 × 107/mL were seeded onto porous PGA scaffolds. After seven days of incubation in vitro, the PGA–cell constructs and cell-free scaffolds were subcutaneously implanted on the back of BALB/c-nu mice bilaterally. The mice were sacrificed in batches at 2, 4, 6 and 8 weeks after implantation, and the harvests were examined histologically. In our study, PGA scaffolds promoted mRNA expression of collagen type I, collagen type III and fibronectin in PDL cells. Masson's trichrome staining showed that after two weeks, the implants were well vascularised in vivo. Fluorescence microscopy indicated that the newly formed tissues were derived from the GFP-labelled human PDL cells. Our study suggested that the delivery of PDL cells via a non-woven PGA mesh might serve as a viable approach to promote periodontal tissue regeneration.

Abstract We performed a meta-analysis aimed to assess the clinical results after transalveolar sinus floor lift without bone grafting in the atrophic maxilla. A systematic electronic literature search was conducted in PubMed, Embase and The Cochrane Library, followed by a manual search. Two reviewers independently extracted study data and conducted quality assessments. Ten non-controlled studies including 1484 implants and eight controlled studies (5 RCTs and 3 prospective studies) including 817 implants (451 implants in the non-graft group) were enrolled in this study. The survival rate of implants via the graft-free method was 98% (95%CI 96% to 100%). There was no significant difference in the survival rate between the non-graft group and the graft group (RR: 1.02; p = 0.18). No statistically significant difference in marginal bone loss was detected between the groups at 12 months (0.57, p = 0.07) or 36 months (0.05, p = 0.61). The endo-sinus bone gain in the non-graft group was significantly lower than in the graft group at 12 months (−1.10, p = 0.0001) and 36 months (−0.74, p = 0.02). Hence, the available evidence suggests that predictable results could be acquired through transalveolar sinus floor lift without bone grafting, while there may be a trend toward more endo-sinus bone gain with bone grafts.

The purpose of this paper is to simulate the future runoff change of the Yellow River Basin under the combined effect of land use and climate change based on Cellular automata (CA)-Markov and Soil & Water Assessment Tool (SWAT). The changes in the average runoff, high extreme runoff and intra-annual runoff distribution in the middle of the 21st century are analyzed. The following conclusions are obtained: (1) Compared with the base period (1970–1990), the average runoff of Tangnaihai, Toudaoguai, Sanmenxia and Lijin hydrological stations in the future period (2040–2060) all shows an increasing trend, and the probability of flood disaster also tends to increase; (2) Land use/cover change (LUCC) under the status quo continuation scenario will increase the possibility of future flood disasters; (3) The spring runoff proportion of the four hydrological stations in the future period shows a decreasing trend, which increases the risk of drought in spring. The winter runoff proportion tends to increase; (4) The monthly runoff proportion of the four hydrological stations in the future period tends to decrease in April, May, June, July and October. The monthly runoff proportion tends to increase in January, February, August, September and December.

Computer aided modeling and simulation of nanomaterials can describe the correlation between the material’s microstructure and its macroscopic properties quantitatively. In this paper, we propose an integrated modeling, simulation, and visualization approach for designing nanomaterials. Firstly, a fast parametric modeling method for important nanomaterials such as graphene, nanotubes, and MOFs is proposed; secondly, the material model could be edited adaptively without affecting the validity of the model on the physical level; thirdly a preliminary calculation for nanomaterials’ energy is implemented based on the theory of surface fitting; finally, an integrated framework of nanomaterials modeling, simulation, and visualization is designed and implemented. Experimental results show that the proposed approach is feasible and effective.

Human FAM76B (hFAM76B) is a 39 kDa protein that contains homopolymeric histidine tracts, a targeting signal for nuclear speckles. FAM76B is highly conserved among different species, suggesting that it may play an important physiological role in normal cellular functions. However, a lack of appropriate tools has hampered study of this potentially important protein. To facilitate research into the biological function(s) of FAM76B, murine monoclonal antibodies (MAbs) against hFAM76B were generated by using purified, prokaryotically expressed hFAM76B protein. Six strains of MAbs specific for hFAM76B were obtained and characterized. The specificity of MAbs was validated by using FAM76B-/- HEK 293 cell line. Double immunofluorescence followed by laser confocal microscopy confirmed the nuclear speckle localization of hFAM76B, and the specific domains recognized by different MAbs were further elucidated by Western blot. Due to the high conservation of protein sequences between mouse and human FAM76B, MAbs against hFAM76B were shown to react with mouse FAM76B (mFAM76B) specifically. Lastly, FAM76B was found to be expressed in the normal tissues of most human organs, though to different extents. The MAbs produced in this study should provide a useful tool for investigating the biological function(s) of FAM76B.

ZFN technology is a powerful research tool and has been used for genome editing in cells lines, animals and plants. The generation of functional ZFNs for particular targets in mammalian genome is still challenging for an average research group. The modular-assembly method is relatively fast, easy-to-practice but has a high failure rate. Some recent studies suggested that a ZFP with low binding activity might be able to form a working ZFN pair with another binding active half-ZFP. In order to unveil the potential ZFP candidates among those with low binding activities, this paper established a highly sensitive mammalian cell-based transcriptional reporter system to assess the DNA binding activities of ZFPs by inserting multiple copies of ZFN target sequence fragment (TSF) of an interested gene (e. g., hPGRN or hVEGF). Our results showed that this system increased the screening sensitivity up to 50-fold and markedly amplified the differences in the binding activities between different ZFPs. We also found that the targeted chromosomal gene repair efficiency of each hPGRN or hVEGF ZFN pair was in proportion with the combination of the binding activities of the ZFL (Left zinc finger) and ZFR (Right zinc finger). A hPGRN ZFR with low binding ability was able to form a biological active ZFN if combined with a hPGRN ZFL with relatively high binding ability. Lastly, site-specific genome editing by hPGRN ZFNs generated by this system was confirmed by sequencing, and the PGRN knock-out cell line showed significantly decreased cell growth compared with the control. Our system will provide a valuable tool for further optimizing the nucleases with regard to specificity and cytotoxicity.

Purpose: To review experimental peri-implantitis studies using rat models and summarize different peri-implantitis induction techniques and evaluate their effectiveness. Materials and Methods: Electronic searches were conducted by two independent examiners to address the following issues. Meta-analyses explored the marginal bone loss (MBL) of four types of peri-implantitis induction methods in rats. The detailed induction tactics--such as the implant design, implant size, surgical process, time cost, induction methods, and endpoint measurements--were summarized. Results: Of the 18 included studies, 38.9% of the studies placed implants at the maxillary first molar, and 44.4% placed them at the alveolar ridge region anterior to the maxillary first molar. As for the induction method, the numbers of published studies on ligature methods, bacterial inoculation, and bacterial lipopolysaccharide inoculation were equally high among all selected studies. The total implant survival rate at the end was 160 out of 213 implants (75.11%). Eight studies with high pooled heterogeneity (I2 = 98, P < .01) in the meta-analysis reported an overall MBL (µ-CT) of 0.47 mm (95% CI = 0.14 to 0.81). A subgroup analysis estimated an MBL of 0.31 mm (95% CI = 0.12 to 0.50) for bacterial inoculation and 0.66 mm (95% CI = 0.07 to 1.26) for the ligature method. Histopathologic analysis revealed that peri-implantitis in rats was similar to peri-implantitis lesions in humans. Conclusions: Implant placement at the maxillary first molar with bacterial inoculation and the silk ligature method to build peri-implantitis rat models is reliable to use for research on peri-implantitis. [ABSTRACT FROM AUTHOR]

Disruption of colonic homeostasis caused by aberrant M1/M2 macrophage polarization contributes to the development of inflammatory bowel disease (IBD). Lycium barbarum polysaccharide (LBP) is the primary active constituent of traditional Chinese herbal Lycium barbarum L., which has been widely demonstrated to have important functions in regulating immune activity and anti-inflammatory. Thus, LBP may protect against IBD. To test this hypothesis, the DSS-induced colitis model was established in mice, then the mice were treated with LBP. The results indicated that LBP attenuated the weight loss, colon shortening, disease activity index (DAI), and histopathological scores of colon tissues in colitis mice, suggesting that LBP could protect against IBD. Besides, LBP decreased the number of M1 macrophages and the protein level of Nitric oxide synthase 2(NOS2) as a marker of M1 macrophages and enhanced the number of M2 macrophages and the protein level of Arginase 1(Arg-1) as a marker of M2 macrophages in colon tissues from mice with colitis, suggesting that LBP may protect against IBD by regulating macrophage polarization. Next, the mechanistic studies in RAW264.7 cells showed that LBP inhibited M1-like phenotype by inhibiting the phosphorylation of STAT1, and promoted M2-like phenotype by promoting the phosphorylation of STAT6. Finally, immunofluorescence double-staining results of colon tissues showed that LBP regulated STAT1 and STAT6 pathways in vivo. The results in the study demonstrated that LBP could protect against IBD by regulating macrophage polarization through the STAT1 and STAT6 pathways. [ABSTRACT FROM AUTHOR]