Liver Type 1 innate lymphoid cells (ILCs) comprise conventional natural killer (cNK) cells and ILC1s. The main functions of Type 1 ILCs not only include directly killing target cells but also regulating the local immune microenvironment of the liver through the secretion of cytokines. Uncovering the intricate mechanisms by which transcriptional factors regulate and influence the functions of Type 1 ILCs, particularly within the context of liver tumors, presents a significant opportunity to amplify the effectiveness of immunotherapies against liver malignancies. Using Ncr1-drived conditional knockout mouse model, our study reveals the regulatory role of Prdm1 in shaping the composition and maturation of liver Type 1 ILCs. Notably, Prdm1 regulates the ratio between NK cells and ILC1s, promoting a shift in the balance towards the direction of NK cells. Although Prdm1 did not affect the killing function of cNK cells in an in vivo cytotoxicity model, a significant increase in cancer metastasis was observed in Prdm1 knockout mice. IFN-γ, granzyme B, and perforin secretion decreased significantly in Prdm1 deficient Type 1 ILCs. scRNA sequencing data also provided evidence that Prdm1 sustains functional subsets of liver type 1 ILCs and facilitates communications between Type 1 ILCs and macrophages. The present study unveiled a novel regulatory mechanism of Prdm1 in liver Type 1 ILCs, showing promising potential for developing innovative immune therapy strategies against liver cancer.
Natural killer (NK) cells demonstrate potent cytotoxic activities and the capacity to secrete cytokines. Their distinctive capability to trigger cell death, bypassing the need for major histocompatibility complex recognition, opens promising avenues for their use in clinical settings such as allogeneic transplantation and tumor immunotherapy. Although the ability of NK cells to kill hematological tumors has been widely recognized, their effectiveness in treating solid tumors is not as pronounced. The intricate interplay of NK cells with the tumor microenvironment, specifically in the context of solid malignancies, has been noted to attenuate the anti-cancer prowess of NK cells and foster the ability of malignant cells to elude immune surveillance. Successful NK cell-centered immunotherapy hinges on obtaining a substantial quantity of NK cells with potent tumor-killing capabilities. However, the current challenge lies in the limited ex vivo expansion of NK cells and the inefficiency of gene introduction methods. Induced pluripotent stem cells (iPSCs) are multipotent stem cells with relatively easier gene transfection capability and theoretically unlimited proliferation potential. NK cells derived from iPSCs circumvent the challenge of difficult genetic modification in NK cells, offering various potential strategies to counteract the immune suppression induced by the tumor microenvironment.
Commercial block not only serves as a public space for the consumption, entertainment, and recreation of residents but also witnesses the history of urban commercial development. With the urban development and the improvement of people's living standards, most commercial blocks are faced with such problems as traffic congestion, simple commercial form, and unreasonable spatial layout. By taking the commercial block of Huaihe Commercial Pedestrian Street as an example and combining the axis and viewshed analysis method of space syntax theory, this article has analyzed the space and quantified the relevant data to analyze the spatial layout relationships of commercial blocks. As the outcomes, this article summarizes the strategies for optimizing the traffic space, scenic space, and commercial space of commercial blocks, hoping to facilitate the commercial block space layout optimization in the era of stock.
The outbreak of COVID-19 in December 2019 sent tens of thousands of people into panic; For sudden outbreak, due to the variability and immune virus, in view of the research and development will be to contain virus vaccine, so the country should not only possess strong vaccine research and development team and scientific research ability, and more need a kind of epidemic development simulation platform, the simulationof the real effective epidemic trends, provide high quality data for prevention and research department reference value; In this paper, the minimum deviation is sought through Logistics prediction model to improve the reliability and authenticity of epidemic simulation and prediction data. Real-time communication is completed by combining big data technology Spark training model and Kafka, and the simple and intuitive H5 realistic visual interface is adopted.
Degree management is considered the kernel of the Degree Informationization Construction. With the continue population and development of information and technology, the government put great emphasis on college graduation student, effective and standard graduate student degree management system has been the mainstream direction of college graduation management system, as well as thenecessary means and effective ways to educate college graduation student. Firstly, this paper introduced the application status of graduate comprehensive information management system at home and abroad. Citing Anhui University of technology’s graduation student education, we have analysised and researched the reality problems and emergency situations in the process of degree management, proposing reasonable solutions. Next, basing on Anhui University of Technology graduation degree management rules and degree management requirements, we designed graduation comprehensive information management system—degeree management software. The system has been devided five subsystem: thesis proposal management subsystem, mid-term examination subsystem, degree management subsystem,scientific information subsystem and fostering plan subsystem. Lastly, this paper not only introduced the test cases of the system but also summarized the system and put forward the prospect. This system is based on B/S(Browse/Server) and used OOD(Object-Oriented Design) method. In addition, software reuse and MVC(Model + View + Hibernate) pattern has been used in the paper. The degeree management software has improved the development efficiency greatly and reduced the development cost.Users can learn and master the software by its simple interactive inference.
Group 1 innate lymphoid cells (ILCs) comprise conventional natural killer (cNK) cells and type 1 innate lymphoid cells (ILC1s). The main functions of liver cNK cells and ILC1s not only include directly killing target cells but also regulating local immune microenvironment of the liver through the secretion of cytokines. Uncovering the intricate mechanisms by which transcriptional factors regulate and influence the functions of liver cNK cells and ILC1s, particularly within the context of liver tumors, presents a significant opportunity to amplify the effectiveness of immunotherapies against liver malignancies. Using Ncr1-drived conditional knockout mouse model, our study reveals the regulatory role of Prdm1 in shaping the composition and maturation of cNK cells. Although Prdm1 did not affect the killing function of cNK cells in an in vivo cytotoxicity model, a significant increase in cancer metastasis was observed in Prdm1 knockout mice. Interferon- gamma (IFN-γ), granzyme B, and perforin secretion decreased significantly in Prdm1 deficient cNK cells and liver ILC1s. scRNA sequencing data also provided evidences that Prdm1 maintains functional subsets of cNK cells and liver ILC1s and facilitates communications between cNK cells, liver ILC1s and macrophages. The present study unveiled a novel regulatory mechanism of Prdm1 in cNK cells and liver ILC1s, showing promising potential for developing innovative immune therapy strategies against liver cancer.
Group 1 innate lymphoid cells (ILCs) comprise conventional natural killer (cNK) cells and type 1 innate lymphoid cells (ILC1s). The main functions of liver cNK cells and ILC1s not only include directly killing target cells but also regulating local immune microenvironment of the liver through the secretion of cytokines. Uncovering the intricate mechanisms by which transcriptional factors regulate and influence the functions of liver cNK cells and ILC1s, particularly within the context of liver tumors, presents a significant opportunity to amplify the effectiveness of immunotherapies against liver malignancies. Using Ncr1-drived conditional knockout mouse model, our study reveals the regulatory role of Prdm1 in shaping the composition and maturation of cNK cells. Although Prdm1 did not affect the killing function of cNK cells in an in vivo cytotoxicity model, a significant increase in cancer metastasis was observed in Prdm1 knockout mice. Interferon- gamma (IFN-γ), granzyme B, and perforin secretion decreased significantly in Prdm1 deficient cNK cells and liver ILC1s. scRNA sequencing data also provided evidences that Prdm1 maintains functional subsets of cNK cells and liver ILC1s and facilitates communications between cNK cells, liver ILC1s and macrophages. The present study unveiled a novel regulatory mechanism of Prdm1 in cNK cells and liver ILC1s, showing promising potential for developing innovative immune therapy strategies against liver cancer.
TiCN/Ti reinforced layers were fabricated on titanium alloy by the laser cladding method, aiming at improving its surface properties. Ti and TiCN powders of size 60 and 3 µm, respectively, were mixed in a certain ratio, prepasted on a Ti-6Al-4V substrate, and irradiated with a pulsed YAG laser in nitrogen atmosphere. The temperature field was calculated with a semi-infinite model. The calculated results show that the laser scanning velocity should be in the range of 1.0 to 3.0 mm/s; the best value for metting the substrate and realizing the cladding process is about 1.4 mm/s. The cladded samples were analyzed with x-ray diffraction, optical microscope observation, and a microhardness test. The results indicate that the composition of the cladding layer changes with the ratio of Ti to TiCN. The optimum Ti:TiCN mass ratio is about 15:85. The optical micrograph revealed a TiCN film thickness about 100 µm. The hardness was increased from 330 HV in the substrate to nearly 1500 HV in the modified layers, due to the presence of the hard TiCN phase. It is found that the proper laser scanning velocity to obtain high cladding quality is about 1.5 mm/s, which agrees with the calculated result of 1.4 mm/s.
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