Semaphorin 4D promotes bone invasion in head and neck squamous cell carcinoma

Head and neck squamous cell carcinomas (HNSCCs) frequently invade the bones of the facial skeleton. Semaphorin 4D (Sema4D) is an axon guidance molecule produced by oligodendrocytes. Sema4D was also identified in the bone microenvironment and many cancer tissues including HNSCC. To date, however, the role of Sema4D in cancer-associated bone disease is still unknown. This is the first study to demonstrate the role of Sema4D in bone invasion of cancer. In the clinical tissue samples of bone lesion of HNSCC, Sema4D was detected at high levels, and its expression was correlated with insulin-like growth factor-I (IGF-I) expression. In vitro experiments showed that IGF-I regulates Sema4D expression and Sema4D increased proliferation, migration and invasion in HNSCC cells. Sema4D also regulated the expression of receptor activator of nuclear factor κβ ligand (RANKL) in osteoblasts, and this stimulated osteoclastgenesis. Furthermore, knockdown of Sema4D in HNSCC cells inhibited tumor growth and decreased the number of osteoclasts in a mouse xenograft model. Taken together, IGF-I-driven production of Sema4D in HNSCCs promotes osteoclastogenesis and bone invasion

Analysis of Blockchain Consensus Protocols

The thesis delivers analyses of multiple types of blockchain systems. We narrow our analysis scope down to consensus algorithms. Specifically, we identify four mainstream types of protocols, from the old-fashioned to the most popular ones: Byzantine fault-tolerant consensus, Nakamoto consensus, (natural) DAG-based protocols, and parallel-chain based protocols. In each type, we analyse one of the top-ranked projects. Our instances include the dBFT protocol in NEO, the proof of authority in Ethereum (Geth), the Tangle network in IOTA, and the weak consensus in Sphinx. Our discussion covers their major properties of security, scalability, and decentralization

Temporal heterogeneity.

The 14th Five-Year Plan stated that China should accelerate green development and promote a comprehensive green transition in economic and social development. As China’s economic growth slows, green development becomes greatly significant for the high-quality development of the economy. Based on China’s provincial panel data from 2005 to 2021, this study applies fixed effects model and mediating effect model to explore the influence of the government environmental investment on green development. The results indicate that (1) the government environmental investment was conducive to green development, but such effect weakened with time. (2) The government environmental investment indirectly promoted green development through the application of green patents and economic agglomeration. (3) The promotional effect of the government environmental investment varied according to region and time. Specifically, investment exerted the most significant effect on the green development of eastern China, which became more evident after 2015. The government should promote green development by implementing long-term assessment and accountability mechanisms, expanding the scale of economic agglomeration, improving the efficiency of the application of green patents, and improving the accuracy of environmental investment.</div

Results of descriptive statistics.

The 14th Five-Year Plan stated that China should accelerate green development and promote a comprehensive green transition in economic and social development. As China’s economic growth slows, green development becomes greatly significant for the high-quality development of the economy. Based on China’s provincial panel data from 2005 to 2021, this study applies fixed effects model and mediating effect model to explore the influence of the government environmental investment on green development. The results indicate that (1) the government environmental investment was conducive to green development, but such effect weakened with time. (2) The government environmental investment indirectly promoted green development through the application of green patents and economic agglomeration. (3) The promotional effect of the government environmental investment varied according to region and time. Specifically, investment exerted the most significant effect on the green development of eastern China, which became more evident after 2015. The government should promote green development by implementing long-term assessment and accountability mechanisms, expanding the scale of economic agglomeration, improving the efficiency of the application of green patents, and improving the accuracy of environmental investment.</div

Robustness test.

The 14th Five-Year Plan stated that China should accelerate green development and promote a comprehensive green transition in economic and social development. As China’s economic growth slows, green development becomes greatly significant for the high-quality development of the economy. Based on China’s provincial panel data from 2005 to 2021, this study applies fixed effects model and mediating effect model to explore the influence of the government environmental investment on green development. The results indicate that (1) the government environmental investment was conducive to green development, but such effect weakened with time. (2) The government environmental investment indirectly promoted green development through the application of green patents and economic agglomeration. (3) The promotional effect of the government environmental investment varied according to region and time. Specifically, investment exerted the most significant effect on the green development of eastern China, which became more evident after 2015. The government should promote green development by implementing long-term assessment and accountability mechanisms, expanding the scale of economic agglomeration, improving the efficiency of the application of green patents, and improving the accuracy of environmental investment.</div

Results of benchmark model.

The 14th Five-Year Plan stated that China should accelerate green development and promote a comprehensive green transition in economic and social development. As China’s economic growth slows, green development becomes greatly significant for the high-quality development of the economy. Based on China’s provincial panel data from 2005 to 2021, this study applies fixed effects model and mediating effect model to explore the influence of the government environmental investment on green development. The results indicate that (1) the government environmental investment was conducive to green development, but such effect weakened with time. (2) The government environmental investment indirectly promoted green development through the application of green patents and economic agglomeration. (3) The promotional effect of the government environmental investment varied according to region and time. Specifically, investment exerted the most significant effect on the green development of eastern China, which became more evident after 2015. The government should promote green development by implementing long-term assessment and accountability mechanisms, expanding the scale of economic agglomeration, improving the efficiency of the application of green patents, and improving the accuracy of environmental investment.</div

Regional heterogeneity.

The 14th Five-Year Plan stated that China should accelerate green development and promote a comprehensive green transition in economic and social development. As China’s economic growth slows, green development becomes greatly significant for the high-quality development of the economy. Based on China’s provincial panel data from 2005 to 2021, this study applies fixed effects model and mediating effect model to explore the influence of the government environmental investment on green development. The results indicate that (1) the government environmental investment was conducive to green development, but such effect weakened with time. (2) The government environmental investment indirectly promoted green development through the application of green patents and economic agglomeration. (3) The promotional effect of the government environmental investment varied according to region and time. Specifically, investment exerted the most significant effect on the green development of eastern China, which became more evident after 2015. The government should promote green development by implementing long-term assessment and accountability mechanisms, expanding the scale of economic agglomeration, improving the efficiency of the application of green patents, and improving the accuracy of environmental investment.</div

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The 14th Five-Year Plan stated that China should accelerate green development and promote a comprehensive green transition in economic and social development. As China’s economic growth slows, green development becomes greatly significant for the high-quality development of the economy. Based on China’s provincial panel data from 2005 to 2021, this study applies fixed effects model and mediating effect model to explore the influence of the government environmental investment on green development. The results indicate that (1) the government environmental investment was conducive to green development, but such effect weakened with time. (2) The government environmental investment indirectly promoted green development through the application of green patents and economic agglomeration. (3) The promotional effect of the government environmental investment varied according to region and time. Specifically, investment exerted the most significant effect on the green development of eastern China, which became more evident after 2015. The government should promote green development by implementing long-term assessment and accountability mechanisms, expanding the scale of economic agglomeration, improving the efficiency of the application of green patents, and improving the accuracy of environmental investment.</div

Results of mediating effect model.

The 14th Five-Year Plan stated that China should accelerate green development and promote a comprehensive green transition in economic and social development. As China’s economic growth slows, green development becomes greatly significant for the high-quality development of the economy. Based on China’s provincial panel data from 2005 to 2021, this study applies fixed effects model and mediating effect model to explore the influence of the government environmental investment on green development. The results indicate that (1) the government environmental investment was conducive to green development, but such effect weakened with time. (2) The government environmental investment indirectly promoted green development through the application of green patents and economic agglomeration. (3) The promotional effect of the government environmental investment varied according to region and time. Specifically, investment exerted the most significant effect on the green development of eastern China, which became more evident after 2015. The government should promote green development by implementing long-term assessment and accountability mechanisms, expanding the scale of economic agglomeration, improving the efficiency of the application of green patents, and improving the accuracy of environmental investment.</div

Table S2. Fabrics and water contents of peridotites in the Neotethyan Luobusa ophiolite, Southern Tibet: Implications for mantle recycling in suprasubduction zones

Table S2. Major oxide concentration in spinel from peridotite core samples in the Luobusa ophiolite