EMP2 re-expression inhibits growth and enhances radiosensitivity in nasopharyngeal carcinoma.

Although radiation therapy is the primary treatment for nasopharyngeal carcinoma, radioresistance remains a major obstacle to successful treatment in many cases, and the exact underlying molecular mechanisms are still ill-defined. EMP2, epithelial membrane protein-2, was a recently identified potential oncogene involved in multiple biological processes including cell migration and cell proliferation. This study was to explore the potential relationship between EMP2 expression, nasopharyngeal carcinoma genesis, and radioresistance. EMP2 expression status in 98 nasopharyngeal carcinoma clinical samples was examined by immunohistochemical staining. As a result, most of the nasopharyngeal carcinoma tumor samples were weakly or negatively stained, while paired adjacent normal tissues were moderately or strongly stained. Moreover, patients with higher expression of EMP2 had significant longer survival times. EMP2 re-expression suppresses cell growth, induces S-phase cell cycle arrest, and promotes radiosensitivity and apoptosis in nasopharyngeal carcinoma cells. These results support that loss of EMP2 is common, and its re-expression may serve as an approach to enhance radiation sensitivity in nasopharyngeal carcinoma.

Sema3A Inhibits Osteolytic Bone Metastasis of Non-small Cell Lung Cancer.

BACKGROUND: Osteolytic bone metastasis is a common complication of Non-Small Cell Lung Cancer (NSCLC), resulting in bone pain, hypercalcemia, and fractures that severely reduce the quality of life and survival time of patients. Semaphorins 3A (Sema3A) is one of the isoforms of the Semaphorins family, which is important in a variety of physiological and pathological processes, such as angiogenesis, immune regulation, and tumorigenesis. However, the role of Sema3A in the development of osteolytic bone metastasis in NSCLC is unknown. METHODS: In this study, we established in vitro models simulating NSCLC cells in regulating the differentiation and maturation of osteoblast and osteoclast precursors and observed the differentiation of osteoblasts and osteoclasts. RESULTS: The results demonstrated that the expression of Sema3A inhibited the proliferation, migration, and invasion of NSCLC cells, as well as promoted the differentiation of osteoblasts and inhibited the differentiation of osteoclasts, suggesting that Sema3A can inhibit the occurrence and development of osteolytic bone metastasis of NSCLC. CONCLUSION: This study provides a new idea for the clinical treatment of osteolytic bone metastasis in NSCLC.

Dual blockchain-based data sharing mechanism with privacy protection for medical internet of things.

In the period of big data, the Medical Internet of Things (MIoT) serves as a critical technology for modern medical data collection. Through medical devices and sensors, it enables real-time collection of a large amount of patients' physiological parameters and health data. However, these data are often generated in a high-speed, large-scale, and diverse manner, requiring integration with traditional medical systems, which further exacerbates the phenomenon of scattered and heterogeneous medical data. Additionally, the privacy and security requirements for the devices and sensor data involved in the MIoT are more stringent. Therefore, when designing a medical data sharing mechanism, the data privacy protection capability of the mechanism must be fully considered. This paper proposes an alliance chain medical data sharing mechanism based on a dual-chain structure to achieve secure sharing of medical data among entities such as medical institutions, research institutions, and cloud privacy centers, and at the same time provide privacy protection functions to achieve a balanced combination of privacy protection capability and data accessibility of medical data. First, a knowledge technology based on ciphertext policy attribute encryption with zero-knowledge concise non-interactive argumentation is used, combined with the data sharing structure of the federation chain, to ensure the integrity and privacy-protecting capability of medical data. Second, the approach employs certificate-based signing and proxy re-encryption technology, ensuring that entities can decrypt and verify medical data at the cloud privacy center using this methodology, consequently addressing the confidentiality concerns surrounding medical data. Third, an efficient and secure key identity-based encryption protocol is used to ensure the legitimacy of user identity and improve the security of medical data. Finally, the theoretical and practical performance analysis proves that the mechanism is feasible and efficient compared with other existing mechanisms.

Unraveling the impact of lanthanum on methane consuming microbial communities in rice field soils.

The discovery of the lanthanide requiring enzymes in microbes was a significant scientific discovery that opened a whole new avenue of biotechnological research of this important group of metals. However, the ecological impact of lanthanides on microbial communities utilizing methane (CH4) remains largely unexplored. In this study, a laboratory microcosm model experiment was performed using rice field soils with different pH origins (5.76, 7.2, and 8.36) and different concentrations of La3+ in the form of lanthanum chloride (LaCl3). Results clearly showed that CH4 consumption was inhibited by the addition of La3+ but that the response depended on the soil origin and pH. 16S rRNA gene sequencing revealed the genus Methylobacter, Methylosarcina, and Methylocystis as key players in CH4 consumption under La3+ addition. We suggest that the soil microbiome involved in CH4 consumption can generally tolerate addition of high concentrations of La3+, and adjustments in community composition ensured ecosystem functionality over time. As La3+ concentrations increase, the way that the soil microbiome reacts may not only differ within the same environment but also vary when comparing different environments, underscoring the need for further research into this subject.

Semaphorin 3F induces colorectal cancer cell chemosensitivity by promoting P27 nuclear export.

Colorectal adenocarcinoma (CRC) is the third most common malignancy worldwide. Metastatic CRC has a poor prognosis because of chemotherapy resistance. Our previous study demonstrated that semaphorin 3F (SEMA3F) signaling may contribute to reversing chemotherapy resistance in CRC cells by reducing E-cadherin and integrin αvß3 expression levels. Another study showed that upregulation of p27 significantly increase the expression of E-cadherin and integrin. This study aimed to evaluate the effect of SEMA3F on P27 and whether it can reverse resistance in CRC cells. We compared the chemosensitivity of human colorectal cancer cell lines with different SEMA3F expression levels to 5-Fu through cell experiment and animal experiment. Then the interaction between SEMA3F and p27 and its possible mechanism were explored by Western Blot, immunofluorescence and immunocoprecipitation. We also compared the disease-free survival of 118 CRC patients with high or low expression of SEMA3F.The results showed that overexpresstion of SEMA3F enhanced the chemotherapy sensitivity and apoptosis of CRC cells in vitro and in vivo. Among 118 postoperative CRC specimens, the disease-free survival of patients with positive SEMA3F expression was significantly longer than that with negative SEMA3F expression after adjuvant treatment. Upregulation of SEMA3F in multicellular spheroid culture (MSC) could increase p27 phosphorylation at serine 10 (Ser10), subsequently promote the cytosolic translocation of P27. Overall, our results reveal a novel molecular mechanism: SEMA3F mediates the degradation of p27 and regulates its subcellular localization to enhance chemosensitivity to 5-Fu in CRC cells, rather than inhibits p27 expression.

Flexural Performance and Toughness Characteristics of Geogrid-Reinforced Pervious Concrete with Different Aggregate Sizes.

Pervious concrete is an environmentally friendly paving material to reduce surface runoff in urban construction. However, due to low flexural strength and cracking susceptibility caused by the high porosity, pervious concrete is only used in low-volume traffic roadways and parking lots for current service. This study investigated the permeability, strength, and flexural performance of pervious concrete with different coarse aggregate size, geogrid position, and geogrid layer number. Test results indicate that the geogrid placed at an appropriate position in pervious concrete improved the permeability and compressive strength. Four-point bending tests were conducted in the laboratory to evaluate the flexural performance and toughness characteristics of pervious concrete beam. Meanwhile, this study also proposed a new evaluation method to distinguish the contribution of geogrids and concrete mixture to the flexural toughness of pervious concrete beam at the pre-peak and post-peak stages by two toughness indices. Test results indicate that geogrids improved the flexural strength, deformability, and energy absorption capability of pervious concrete beam. The geogrids placed at both one-third and two-thirds of the heights of pervious concrete beam resulted in the optimum flexural performance. Besides, the small size (5-10 mm) aggregates were conducive to providing high flexural strength for the geogrid-reinforced pervious concrete beam, while the large size (10-15 mm) aggregates played a significant role in obtaining noteworthy post-cracking performance.

ZBTB7 evokes 5-fluorouracil resistance in colorectal cancer through the NF­κB signaling pathway.

Zinc finger and BTB domain containing 7A (ZBTB7), a POZ/BTB and Krüppel erythroid myeloid oncogenic factor, is critical for the tumorigenicity and progression of various cancer types. ZBTB7 has been reported to promote the cell proliferation of colorectal cancers (CRC). However, the function of ZBTB7 to 5-fluorouracil (5­FU) resistance has not yet been studied. In the current study, ZBTB7 expression and function in 5­FU resistance in CRC were investigated using with multidisciplinary approaches, including western blot analysis, Transwell assay, CCK8 and a tumor xenograft model. Overexpression of ZBTB7 was increased the level of proteins associated with cell invasion and epithelial-mesenchymal transition. ZBTB7 inhibition attenuated the invasion and enhanced the apoptosis of CRC cells. IC50 values and cell viability were significantly reduced in cells with short hairpin RNA (shRNA)-mediated ZBTB7 depletion compared with the control group. 5­FU administration decreased viability to a greater extent in the ZBTB7-shRNA group compared with the control, which was dose- and time-dependent. Analysis of gene expression omnibus data demonstrated that ZBTB7 mediated 5­FU resistance, potentially through nuclear factor (NF)-κB signaling. NF­κB inhibitor SN50 reversed ZBTB7-induced resistance in CRC. Collectively, the findings demonstrated that ZBTB7 mediated 5­FU resistance in CRC cells through NF­κB signaling. Thus, targeting ZBTB7 and NF­κB signaling may be an effective strategy to reverse 5­FU resistance in CRC.

RNA interference of Biot2 induces G1 phase arrest and apoptosis in mouse colorectal cancer cell line.

Biot2 is a tumor-associated antigen, and it is a novel gene (GenBank EF100607) that was first identified with the SEREX technique and named by our laboratory. It is highly expressed in cancer cells and testis, with low or no expression in normal tissues. In our previous study, RNA interference of human Biot2 can inhibit tumor cell growth, and it is associated with poor prognosis of patients in clinical study; however, the mechanism of Biot2 that effects tumor growth is not yet clear. Here, in this study, we explore further the mechanism of Biot2 by silencing Biot2 in CT26 cells. It provides some theoretical basis for Biot2 as a new target for gene therapy. In CT26 cells, the expression of Biot2 was downregulated by Biot2-shRNA. It also promoted G1 phase arrest, the expression of p16 and p21, and cell apoptosis. In the mouse model, the tumor volume and the expression of PCNA of the Biot2-shRNA group significantly decreased. These results suggest that silencing Biot2 in CT26 cells by RNA interference can inhibit cell growth in vitro and in vivo. It also induces cell cycle arrest in the G1 phase and apoptosis throughout regulation of p16 and p21. Taken together, our data demonstrate that Biot2 can be a potential target of gene therapy.

Phosphorylation and changes in the distribution of nucleolin promote tumor metastasis via the PI3K/Akt pathway in colorectal carcinoma.

Here, we investigated the molecular mechanism underlying the changes in the distribution of nucleolin. Our study identified PI3K/Akt signaling as an essential pathway regulating the distribution of nucleolin. Furthermore, nucleolin can interact with phospho-PI3K-p55, and changes in the distribution of nucleolin were related to its phosphorylation. Subsequently, we analyzed the correlation of VEGF and nucleolin, and found that distribution of nucleolin related to metastatic potential. Finally, blocking cell surface nucleolin influences the process of epithelial-mesenchymal transitions. This indicates that nucleolin may be a novel cancer therapy target and a predictive marker for tumor migration in colorectal carcinoma.