Table2_Does the scarcity of urban space resources make the quality of underground space planning more sustainable? A case study of 40 urban underground space master plans in China.DOCX

The international community has reached a consensus on promoting the sustainable development of global cities. As an important and irreversible space resource in a city, the development and utilization of urban underground space should follow the principle of sustainability and emphasize scientific and forward-looking planning. At present, most cities have formulated urban underground space master plans. However, due to the lack of an effective evaluation method, the plan quality is uneven, which directly affects the sustainability of underground space development and utilization. This paper proposes a set of sustainability evaluation framework of underground space planning based on relevant planning standards and plan quality evaluation protocol, and makes a comparative analysis of the 40 urban underground space master plans formulated in China from 2004 to 2020. The research found that the planning documents generally reflected the problem of emphasizing design strategies and engineering technology while neglecting implementation and humanistic care; administrative region, population density, land price and other variables closely related to the scarcity of urban space resources are the main factors affecting the quality of urban underground space planning. The conclusions of this paper can aid planners and researchers to identify the problems and influencing factors of underground space planning related to sustainability, and summarize the methods to improve the quality of underground space planning.</p

Table4_Does the scarcity of urban space resources make the quality of underground space planning more sustainable? A case study of 40 urban underground space master plans in China.DOCX

The international community has reached a consensus on promoting the sustainable development of global cities. As an important and irreversible space resource in a city, the development and utilization of urban underground space should follow the principle of sustainability and emphasize scientific and forward-looking planning. At present, most cities have formulated urban underground space master plans. However, due to the lack of an effective evaluation method, the plan quality is uneven, which directly affects the sustainability of underground space development and utilization. This paper proposes a set of sustainability evaluation framework of underground space planning based on relevant planning standards and plan quality evaluation protocol, and makes a comparative analysis of the 40 urban underground space master plans formulated in China from 2004 to 2020. The research found that the planning documents generally reflected the problem of emphasizing design strategies and engineering technology while neglecting implementation and humanistic care; administrative region, population density, land price and other variables closely related to the scarcity of urban space resources are the main factors affecting the quality of urban underground space planning. The conclusions of this paper can aid planners and researchers to identify the problems and influencing factors of underground space planning related to sustainability, and summarize the methods to improve the quality of underground space planning.</p

Table1_Does the scarcity of urban space resources make the quality of underground space planning more sustainable? A case study of 40 urban underground space master plans in China.XLSX

The international community has reached a consensus on promoting the sustainable development of global cities. As an important and irreversible space resource in a city, the development and utilization of urban underground space should follow the principle of sustainability and emphasize scientific and forward-looking planning. At present, most cities have formulated urban underground space master plans. However, due to the lack of an effective evaluation method, the plan quality is uneven, which directly affects the sustainability of underground space development and utilization. This paper proposes a set of sustainability evaluation framework of underground space planning based on relevant planning standards and plan quality evaluation protocol, and makes a comparative analysis of the 40 urban underground space master plans formulated in China from 2004 to 2020. The research found that the planning documents generally reflected the problem of emphasizing design strategies and engineering technology while neglecting implementation and humanistic care; administrative region, population density, land price and other variables closely related to the scarcity of urban space resources are the main factors affecting the quality of urban underground space planning. The conclusions of this paper can aid planners and researchers to identify the problems and influencing factors of underground space planning related to sustainability, and summarize the methods to improve the quality of underground space planning.</p

Table3_Does the scarcity of urban space resources make the quality of underground space planning more sustainable? A case study of 40 urban underground space master plans in China.XLSX

The international community has reached a consensus on promoting the sustainable development of global cities. As an important and irreversible space resource in a city, the development and utilization of urban underground space should follow the principle of sustainability and emphasize scientific and forward-looking planning. At present, most cities have formulated urban underground space master plans. However, due to the lack of an effective evaluation method, the plan quality is uneven, which directly affects the sustainability of underground space development and utilization. This paper proposes a set of sustainability evaluation framework of underground space planning based on relevant planning standards and plan quality evaluation protocol, and makes a comparative analysis of the 40 urban underground space master plans formulated in China from 2004 to 2020. The research found that the planning documents generally reflected the problem of emphasizing design strategies and engineering technology while neglecting implementation and humanistic care; administrative region, population density, land price and other variables closely related to the scarcity of urban space resources are the main factors affecting the quality of urban underground space planning. The conclusions of this paper can aid planners and researchers to identify the problems and influencing factors of underground space planning related to sustainability, and summarize the methods to improve the quality of underground space planning.</p

Additional file 7: of Circular RNA circTADA2A promotes osteosarcoma progression and metastasis by sponging miR-203a-3p and regulating CREB3 expression

Figure S7. The mRNA, protein levels of some genes and MMP activity in different stable OS cells. a Sh-circTADA2A with or without CREB3 overexpression was transfected into OS cells, followed by qRT-PCR detection on CREB3, c-Jun, mmp9 and Bcl-2. The histograms show the relative alteration in mRNA levels. b & c Cells were stably transfected with sh-circTADA2A and N.C. (or CREB3). The relative protein levels of CREB3, c-Jun, Bcl-2, mmp9, mmp2, E-cadherin, N-cadherin and Vimentin were analyzed and bands are shown in Fig. 7. d Mmp2 and mmp9 activity in different stable OS cells was evaluated by a zymography assay. Data are from three independent experiments (mean ± SEM) (a-c) or are representative of three independent experiments with similar results (d) (*P < 0.01 vs control or as indicated by Student’s t-test). (TIF 1683 kb

Additional file 3: of Circular RNA circTADA2A promotes osteosarcoma progression and metastasis by sponging miR-203a-3p and regulating CREB3 expression

Figure S2. The transfection effects of miR-203a-3p. a & b The miR-203a-3p alteration of both HOS and 143B cells stably transfected with N.C. sponge or miR-203a-3p sponge or N.C. or pre-miR-203a-3p was determined by qRT-PCR. Histograms show the fold-change in miR-203a-3p expression. c Zymography assay demonstrated the activity of mmp2 and mmp9 in both stable HOS and 143B cells. Data are from three independent experiments (mean ± SEM) (a and b) or are representative of three independent experiments with similar results (c) (*P < 0.01 vs control or as indicated by Student’s t-test). (TIF 986 kb

Additional file 1: of Circular RNA circTADA2A promotes osteosarcoma progression and metastasis by sponging miR-203a-3p and regulating CREB3 expression

Figure S1. The effects of knocking down several microRNAs on the apoptosis of OS cells. a HOS and 143B cells were transfected with various microRNA mimics or mimics N.C. After 48 h, apoptotic cells were detected by flow cytometry with Annexin V-FITC/PI staining. Histograms are shown in Fig. 3. b Schematic illustration shows the complementary sequence between miR-203a-3p and circTADA2A. CircTADA2A Mut1, Mut2 and Co-Mut sequences are shown in lowercase letters. Data are representative of three independent experiments with similar results (a). (TIF 2763 kb

Additional file 6: of Circular RNA circTADA2A promotes osteosarcoma progression and metastasis by sponging miR-203a-3p and regulating CREB3 expression

Figure S5. CREB3 functions as a driver gene in Osteosarcoma. a HOS and 143B cells were transfected with si-SFRP1 (or si-TYMS or si-LMNB2 or si-SLC25A23 or si-HMGN2 or si-CREB3 or N.C.). After 48 h, the apoptosis rate of OS cells with knockdown of certain genes was determined by apoptosis assay with Annexin V-FITC/PI staining. Histograms are shown in Fig. 6f. b OS cells including U2OS, SJSA-1 and MG63 were transfected with si-CREB3, and then an apoptosis assay was performed with Annexin V-FITC/PI after 48 h. c Cells were transfected with si-CREB3, followed by evaluation of the migration and invasion abilities by Transwell migration and Matrigel invasion assays. d Wound-healing assay demonstrated the alteration of cell migration rates with the silence of CREB3. e Colony formation assay demonstrated the capacity of proliferation in OS cells. f Cell viability of OS cells under the effect of si-CREB3 after 24 h, 48 h and 72 h were examined by CCK-8 assay. g BALB/c-nu (n = 6) mice were respectively subcutaneously injected with 143B cells stably transfected with N.C. and sh-CREB3. Representative images of tumors after 30 days are shown. Data are from three independent experiments (mean ± SEM) (b-f) or are representative of three independent experiments with similar results (a) (*P < 0.01 vs control or as indicated Student’s t-test). (TIF 6952 kb

Additional file 5: of Circular RNA circTADA2A promotes osteosarcoma progression and metastasis by sponging miR-203a-3p and regulating CREB3 expression

Figure S4. Bioinformatic analysis of RNA sequencing. a Circos plots show the expressed genes in chromosomes. Outer: chromosomes; inner: plus strand (red) and minus strand (green). b Go analysis of differentially expressed genes were shown. c & d KEGG analysis of differentially expressed genes. (TIF 2356 kb

DataSheet_1_Administration of SB239063 Ameliorates Ovariectomy-Induced Bone Loss via Suppressing Osteoclastogenesis in Mice.pdf

Activation of osteoclast formation and function is crucial for the development of osteolytic diseases such as osteoporosis. RANKL (receptor activator of nuclear factor-κB ligand) activates NF-κB (nuclear factor κB), MAPK (mitogen-activated protein kinase), and NFATc1 (nuclear factor of activated T-cells, cytoplasmic 1) signaling pathways to induce osteoclastogenesis. In this study, we demonstrated that SB239063, a p38-specific inhibitor, suppressed osteoclastogenesis and bone resorption via inhibiting phosphorylation of MEF2C (myocyte enhancer factor 2C) and subsequently leading to MEF2C degradation by ubiquitination. Knockdown of MEF2C impaired osteoclast formation due to decreased c-Fos expression. Furthermore, MEF2C can directly bind to the promoter region of c-Fos to initiate its transcription. Interestingly, overexpression of either MEF2C or c-Fos can partially rescue the inhibitory effect of SB239063 on osteoclastogenesis. In addition, in vivo data proved that SB239063 also played a preventive role in both LPS (lipopolysaccharide)- and OVX (ovariectomy)-induced bone loss in mice. In conclusion, our results show that SB239063 can be a potential therapy for osteolytic diseases, and a novel p38/MEF2C/c-Fos axis is essential for osteoclastogenesis.</p