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Abstract Background Increasing evidence proves that RBP7 plays a significant role in breast cancer (BC). The present study was aimed to investigate the mechanism of RBP7. Methods Western Blotting and qRT-PCR were performed for evaluating the expression levels. CCK8, colony forming, xenograft mouse model, wound healing and transwell assays were conducted to examine cell ability of proliferation, invasion and migration. Nile red staining and Oil red O staining were used for testing the lipid. Results RBP7 was related to overall survival (OS) in patients with HR + BC. RBP7 protein was significantly decreased in HR + BC tissues and cells. RBP7 suppressed HR + BC cell proliferation in vitro and in vivo, and inhibited migration and invasion. RBP7 reduced fatty acid in HR + BC cells by inhibiting the AKT/SREBP1 pathway. Conclusions RBP7 may function as a tumor suppressor in HR + BC by inhibiting the AKT/SREBP1 pathway and reducing fatty acid.

AbstractSaccharum species are of great importance as fruit crops due to their economic and food value. S. fulvum is a wild relative of sugarcane that has a wide geographic distribution and is well-adapted to various environmental conditions. It exhibits high resistance to pests, diseases, drought, cold, and degraded soils, making it a valuable resource for sugarcane research. Here, we report the chloroplast genome of S. fulvum. This chloroplast genome was 141,151 bp in length with a GC content of 38.41%. The large single-copy, small single-copy, and inverted repeat regions were 83,030 bp, 12,533 bp, and 22,794 bp in length, respectively. The chloroplast genome contained 111 different genes, including 77 protein-coding genes, 4 rRNA genes, and 30 tRNA genes. Phylogenetic analysis indicated that S. fulvum was closely related to S. narenga. This study not only enriches the genome information of Saccharum, but also will be useful for the evolutionary study of the family Poaceae.

Monocyte/macrophages constitute a significant population of tumor-infiltrating immune cells and play a crucial role in tumor growth, invasion, and metastasis. B7-H3, has immune regulatory functions, however, it is unclear whether B7-H3 expressed on monocyte/macrophages plays a significance role in tumor progression. We found B7-H3 was high-expressed on monocyte/macrophages in tumor microenvironment compared with adjacent tissues in lung cancer, and its expression level was positively correlated with the number of monocyte/macrophages. Furthermore, the expression of B7-H3 was related to clinical stage and lymph node metastasis. Moreover, miR-29a-3p negatively regulated B7-H3, and the expression of B7-H3 on THP-1-derived macrophages was regulated by secreting exosomes containing miR-29a-3p. In addition, knockdown of B7-H3 promoted macrophage apoptosis under hypoxia. Mechanistically, B7-H3 enhanced the antiapoptotic ability of macrophage by up-regulating HIF-1ɑ via activating NF-κB. Taken together, these results imply that B7-H3 as a therapeutic target could hold promise for enhancing anti-tumor immune responses in individuals diagnosed with lung cancer.

Abstract Aerobic glycolysis has been shown to play a key role in tumor cell proliferation and metastasis. However, how it is directly regulated is largely unknown. Here, we found that HES1 expression was significantly higher in CRC tissues than that in adjacent normal tissues. Moreover, high HES1 expression is associated with poor survival in CRC patients. HES1 knockdown markedly inhibited cell growth and metastasis both in vitro and in vivo. Additionally, silencing of HES1 suppressed aerobic glycolysis of CRC cells. Mechanistic studies revealed that HES1 knockdown decreased the expression of GLUT1, a key gene of aerobic glycolysis, in CRC cells. GLUT1 overexpression abolished the effects of HES1 knockdown on cell aerobic glycolysis, proliferation, migration and invasion. ChIP-PCR and dual-luciferase reporter gene assay showed that HES1 directly bound the promoter of IGF2BP2 and promoted IGF2BP2 expression. Furthermore, our data indicated that IGF2BP2 recognized and bound the m6A site in the GLUT1 mRNA and enhanced its stability. Taken together, our findings suggest that HES1 has a significant promotion effect on CRC aerobic glycolysis and progression by enhancing the stability of m6A-modified GLUT1 mRNA in an IGF2BP2-dependent manner, which may become a viable therapeutic target for the treatment of CRC in humans. The mechanism of HES1 regulating glycolysis in CRC.

Abstract. Background:. Cancer stem-like cells (CSCs) are a small subset of cells in tumors that exhibit self-renewal and differentiation properties. CSCs play a vital role in tumor formation, progression, relapse, and therapeutic resistance. B7-H3, an immunoregulatory protein, has many protumor functions. However, little is known about the mechanism underlying the role of B7-H3 in regulating gastric cancer (GC) stemness. Our study aimed to explore the impacts of B7-H3 on GC stemness and its underlying mechanism. Methods:. GC stemness influenced by B7-H3 was detected both in vitro and in vivo. The expression of stemness-related markers was examined by reverse transcription quantitative polymerase chain reaction, Western blotting, and flow cytometry. Sphere formation assay was used to detect the sphere-forming ability. The underlying regulatory mechanism of B7-H3 on the stemness of GC was investigated by mass spectrometry and subsequent validation experiments. The signaling pathway (Protein kinase B [Akt]/Nuclear factor erythroid 2-related factor 2 [Nrf2] pathway) of B7-H3 on the regulation of glutathione (GSH) metabolism was examined by Western blotting assay. Multi-color immunohistochemistry (mIHC) was used to detect the expression of B7-H3, cluster of differentiation 44 (CD44), and Nrf2 on human GC tissues. Student's t-test was used to compare the difference between two groups. Pearson correlation analysis was used to analyze the relationship between two molecules. The Kaplan-Meier method was used for survival analysis. Results:. B7-H3 knockdown suppressed the stemness of GC cells both in vitro and in vivo. Mass spectrometric analysis showed the downregulation of GSH metabolism in short hairpin B7-H3 GC cells, which was further confirmed by the experimental results. Meanwhile, stemness characteristics in B7-H3 overexpressing cells were suppressed after the inhibition of GSH metabolism. Furthermore, Western blotting suggested that B7-H3-induced activation of GSH metabolism occurred through the AKT/Nrf2 pathway, and inhibition of AKT signaling pathway could suppress not only GSH metabolism but also GC stemness. mIHC showed that B7-H3 was highly expressed in GC tissues and was positively correlated with the expression of CD44 and Nrf2. Importantly, GC patients with high expression of B7-H3, CD44, and Nrf2 had worse prognosis (P = 0.02). Conclusions:. B7-H3 has a regulatory effect on GC stemness and the regulatory effect is achieved through the AKT/Nrf2/GSH pathway. Inhibiting B7-H3 expression may be a new therapeutic strategy against GC.

B7-H6 is a novel immune checkpoint molecule that triggers NK cell cytotoxicity, but the role of N-glycosylation in B7-H6 is poorly understood. We here identified the existence of N-glycosylation of B7-H6 in different cell lines and exogenous expression cells by PNGase F digestion and tunicamycin blockage. Subsequently, we demonstrated that B7-H6 contains 6 functional N-linked glycosylation sites by single site mutation and electrophoresis. Phylogenetical and structural analysis revealed that N43 and N208 glycan are conserved in jawed vertebrates and may thus contribute more to the biological functions. We further demonstrated that N43 and N208 glycosylation are essential for B7-H6 to trigger NK cell activation. Mechanistically, we found that N43 and N208 glycan contributed to the stability and membrane expression of B7-H6 protein. Lack of N208 glycosylation led to membrane B7-H6 shedding, while N43 mutation resulted in impaired B7-H6/NKp30 binding affinity. Together, our findings highlight the significance of N-linked glycosylation in B7-H6 biological functions and suggest potential targets for modulating NK cell-mediated immunity.

Abstract Background Genetic background plays an important role in the occurrence and development of gastric cancer (GC). With the application of genome-wide association study (GWAS), an increasing number of tumor susceptibility genes in gastric cancer have been discovered. While little of them can be further applicated in clinical diagnosis and treatment due to the lack of in-depth analysis. Methods A GWAS of peripheral blood leukocytes from GC patients was performed to identify and obtain genetic background data. In combination with a clinical investigation, key SNP mutations and mutated genes were screened. Via in vitro and in vivo experiments, the function of the mutated gene was verified in GC. Via a combination of molecular function studies and amino acid network analysis, co-mutations were discovered and further identified as potential therapeutic targets. Results At the genetic level, the G allele of rs104886038 in DHCR7 was a protective factor identified by the GWAS. Clinical investigation showed that patients with the rs104886038 A/G genotype, age ≥ 60, smoking ≥ 10 cigarettes/day, heavy drinking and H. pylori infection were independent risk factors for GC, with odds ratios of 12.33 (95% CI, 2.10 ~ 72.54), 20.42 (95% CI, 2.46 ~ 169.83), and 11.39 (95% CI, 1.82 ~ 71.21), respectively. Then molecular function studies indicated that DHCR7 regulated cell proliferation, migration, and invasion as well as apoptosis resistance via cellular cholesterol biosynthesis pathway. Further amino acid network analysis based on the predicted structure of DHCR7 and experimental verification indicated that rs104886035 and rs104886038 co-mutation reduced the stability of DHCR7 and induced its degradation. DHCR7 mutation suppressed the malignant behaviour of GC cells and induced apoptosis via inhibition on cell cholesterol biosynthesis. Conclusion In this work, we provided a comprehensive multi-dimensional analysis strategy which can be applied to in-depth exploration of GWAS data. DHCR7 and its mutation sites identified by this strategy are potential theratic targets of GC via inhibition of cholesterol biosynthesis.

Abstract Colorectal cancer (CRC) is the third most common malignancy worldwide. Circular RNAs (circRNAs) have been reported to play critical regulatory roles in tumorigenesis, serving as tumor biomarkers and therapeutic targets. However, the contributions of circRNAs to CRC tumorigenesis are unclear. In our study, high expression of circLDLR was found in CRC tissues and cells and was closely associated with the malignant progression and poor prognosis of CRC patients. We demonstrated that circLDLR boosts growth and metastasis of CRC cells in vitro and in vivo, and modulates cholesterol levels in vitro. Mechanistically, we showed that circLDLR competitively binds to miR-30a-3p and prevents it from reducing the SOAT1 level, facilitating the malignant progression of CRC. In sum, our findings illustrate that circLDLR participates in CRC tumorigenesis and metastasis via the miR-30a-3p/SOAT1 axis, serving as a potential biomarker and therapeutic target in CRC.

In the neuroendocrine system, corticotropin-releasing hormone (CRH) plays an important role in the hypothalamic–pituitary–adrenal/interrenal (HPA/HPI) axis. It exerts its effects by activating CRHRs, which belong to the class B G protein-coupled receptor family. Two characteristic genes of CRHR1 subtypes in the Larimichthys crocea genome were identified: LcCRHR1-1 and LcCRHR1-2. Alignments indicated that they were highly homologous to known and validated teleost CRHR1s. The CDS sequences of the two receptors were cloned into the pEGFP-N1 plasmid, and membrane localization of the fusion expressing LcCRHR1-1-EGFP and LcCRHR1-2-EGFP was revealed in HEK293 cells. Treatment with LcCRH could lead to two receptors internalization and trigger a significant increase in the secondary messenger cAMP and Ca2+ and mitogen-activated protein kinase phosphorylation in an LcCRH dose-dependent manner. Based on quantitative real-time PCR, LcCRHR1s were expressed in all examined tissues and highly expressed in the brain and ovaries. Furthermore, immunohistochemical findings showed the specific localization of CRHR1s in ovarian follicle cells. Collectively, our study identified two CRH receptors in L. crocea and suggested that the CRH/CRHR1 system is potentially involved in the neuroendocrine regulation of reproduction in this marine fish.

B7 homolog 3 (B7‐H3) plays an important role in tumor biology, but the molecular mechanism underlying the role of B7‐H3 in tumor metastasis remains unclear. In this article, our analysis of The Cancer Genome Atlas database suggested that B7‐H3 expression is associated with poor prognosis of patients with clear cell renal cell carcinoma (ccRCC). B7‐H3 knockdown affected the expression of metastasis‐related genes and significantly suppressed the metastasis of ccRCC cells, but it had no significant effect on the proliferation of ccRCC cells. Database analysis revealed a strong positive correlation between B7‐H3 and fibronectin (FN) in ccRCC cells, and further study also confirmed that FN interacts with B7‐H3. Silencing FN expression inhibited the migration and invasion of ccRCC cells, whereas exogenous FN promoted the migration and invasion of ccRCC cells, which was accompanied by activation of kinases [namely, phosphorylated (p)‐phosphoinositide 3‐kinase, p‐protein kinase B, p‐p38 and p‐extracellular regulated protein kinase]. B7‐H3 knockdown abolished the prometastatic effect of FN. In conclusion, our data suggest that B7‐H3 binds to exogenous FN and promotes the metastasis of ccRCC cells.

Abstract Background Encouraged by the goal of developing an effective treatment strategy for prostate cancer, this study explored the mechanism involved in metformin-mediated inhibition of AR-negative prostate cancer. Methods Cell behaviors of DU145 and PC3 cells were determined by CCK8 test, colony formation experiment and scratch test. Flow cytometry was used to detect cell cycle distribution. Cell autophagy was induced with metformin, and an autophagy inhibitor, 3-MA, was used to assess the level of autophagy. Detection of LC3B by immunofluorescence was conducted to determine autophagy level. Cell proliferation, autophagy and cell cycle were examined by performing Western blot. DU145 and PC3 cell lines were transfected with AMPK siRNA targeting AMPK-α1 and AMPK-α2. Tumor formation experiment was carried out to evaluate the anti-prostate cancer effect of metformin in vivo. Results The inhibitory effect of metformin on the proliferation of prostate cancer cell lines was confirmed in this study, and the mechanism of such an effect was related to autophagy and the block of cell cycle at G0/G1 phase. Metformin also induced the activation of AMPK, markedly promoted expression of LC3II, and down-regulated the expression of p62/SQSTM1. Animal experiments showed that the tumor volume of metformin group was smaller, meanwhile, the levels of p-AMPK (Thr172) and LC3B were up-regulated and the Ki-67 level was down-regulated, without abnormalities in biochemical indicators. Conclusion This study found that autophagy induction might be the mechanism through which metformin suppressed the growth of AR-negative prostate cancer. Moreover, the activation of AMPK/autophagy pathway might be a therapeutically effective for treating AR-negative prostate cancer in the future.

Abstract Emerging evidence suggests that cellular senescence induced by chemotherapy has been recognized as a new weapon for cancer therapy. This study aimed to research novel functions of B7-H3 in cellular senescence induced by a low dose of doxorubicin (DOX) in colorectal cancer (CRC). Here, our results demonstrated that B7-H3 knockdown promoted, while B7-H3 overexpression inhibited, DOX-induced cellular senescence. B7-H3 knockdown dramatically enhanced the growth arrest of CRC cells after low-dose DOX treatment, but B7-H3 overexpression had the opposite effect. By RNA-seq analysis and western blot, we showed that B7-H3 prevented cellular senescence and growth arrest through the AKT/TM4SF1/SIRT1 pathway. Blocking the AKT/TM4SF1/SIRT1 pathway dramatically reversed B7-H3-induced resistance to cellular senescence. More importantly, B7-H3 inhibited DOX-induced cellular senescence of CRC cells in vivo. Therefore, targeting B7-H3 or the B7-H3/AKT/TM4SF1/SIRT1 pathway might be a new strategy for promoting cellular senescence-like growth arrest during drug treatment in CRC.

Objective: Several reports have proposed that lncRNAs, as potential biomarkers, participate in the progression and growth of malignant tumors. HIF1A-AS2 is a novel lncRNA and potential biomarker, involved in the genesis and development of carcinomas. However, the molecular mechanism of HIF1A-AS2 in renal carcinoma is unclear. Methods: The relative expression levels of HIF1A-AS2 and miR-30a-5p were detected using RT-qPCR in renal carcinoma tissues and cell lines. Using loss-of-function and overexpression, the biological effects of HIF1A-AS2 and miR-30a-5p in kidney carcinoma progression were characterized. Dual luciferase reporter gene analysis and Western blot were used to detect the potential mechanism of HIF1A-AS2 in renal carcinomas. Results: HIF1A-AS2 was upregulated in kidney carcinoma tissues when compared with para-carcinoma tissues (P < 0.05). In addition, tumor size, tumor node mestastasis stage and differentiation were identified as being closely associated with HIF1A-AS2 expression (P < 0.05). Knockdown or overexpression of HIF1A-AS2 either restrained or promoted the malignant phenotype and WNT/β-catenin signaling in renal carcinoma cells (P < 0.05). MiR-30a-5p was downregulated in renal cancers and partially reversed HIF1A-AS2 functions in malignant renal tumor cells. HIF1A-AS2 acted as a microRNA sponge that actively regulated the relative expression of SOX4 in sponging miR-30a-5p and subsequently increased the malignant phenotypes of renal carcinomas. HIF1A-AS2 showed a carcinogenic effect and miR-30a-5p acted as an antagonist of the anti-oncogene effects in the pathogenesis of renal carcinomas. Conclusions: The HIF1A-AS2-miR-30a-5p-SOX4 axis was associated with the malignant progression and development of renal carcinoma. The relative expression of HIF1A-AS2 was negatively correlated with the expression of miR-30a-5p, and was closely correlated with SOX4 mRNA levels in renal cancers.

Abstract Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) play critical roles in human diseases. We aimed to clarify the role of lncRNA X-inactive specific transcript (XIST)/miR-149-3p/forkhead box P3 (FOXP3) axis in ovarian cancer (OC) cell growth. XIST, miR-149-3p and FOXP3 expression in OC tissues and cell lines was assessed, and the predictive role of XIST in prognosis of OC patients was analyzed. The OC cell lines were screened and accordingly treated with silenced/overexpressed XIST plasmid or miR-149-3p mimic/inhibitor, and then the proliferation, invasion, migration, colony formation ability, apoptosis, and cell cycle distribution of OC cells were measured. Effect of altered XIST and miR-149-3p on tumor growth in vivo was observed. Online website prediction and dual luciferase reporter gene were implemented to detect the targeting relationship of lncRNA XIST, miR-149-3p, and FOXP3. XIST and FOXP3 were upregulated, whereas miR-149-3p was downregulated in OC tissues and cells. High XIST expression indicated a poor prognosis of OC. Inhibition of XIST or elevation of miR-149-3p repressed proliferation, invasion, migration, and colony formation ability, and promoted apoptosis and cell cycle arrest of HO-8910 cells. In SKOV3 cells upon treatment of overexpressed XIST or reduction of miR-149-3p, there exhibited an opposite tendency. Based on online website prediction, dual luciferase reporter gene, and RNA pull-down assays, we found that there was a negative relationship between XIST and miR-149-3p, and miR-149-3p downregulated FOXP3 expression. This study highlights that knockdown of XIST elevates miR-149-3p expression to suppress malignant behaviors of OC cells, thereby inhibiting OC development.

Renal carcinoma (RCC) is widely accepted as a malignant tumour of urinary system. Long intergenic non-coding RNA 1939 (LINC01939) is a novel lncRNA which was found to be down-regulated in RCC. Thus, we set out to explore the effect and regulation mechanism of LINC01939 in RCC. LINC01939 and miR-154 in RCC tissues and cell lines were detected using qRT-PCR assay. To examine cellular viability of ACHN and CAKI-1 cells, cell counting kit-8 (CCK-8) assay was exploited here. Flow cytometric analysis was conducted to examine apoptosis. Cell mobility was valued through wound healing assays. Western blotting was applied for examination of proteins related to proliferation, apoptosis, migration and Wnt/β-catenin/Notch. LINC01939 was down-regulated in RCC tissues. LINC01939 overexpression impeded proliferation and migration, and induced apoptosis. Further study found that the overexpression of LINC01939 strongly suppressed miR-154 expression. Then, the inhibiting effect of overexpressed LINC01939 on proliferation and mobility and the promoting role of LINC01939 in apoptosis were abolished by the combination of miR-154 mimic. Finally, we found that overexpressed LINC01939 inactivated Wnt/β-catenin and Notch through suppressing miR-154. Up-regulation of LINC01939 inhibited proliferation and migration of RCC cells by down-regulating miR-154.

Elaeocarpus decipiens F. B. Forbes and Hemsl is an evergreen tree native to East Asia. Here, we sequenced and reported the complete chloroplast genome of E. decipiens for the first time. In the present work, the complete chloroplast (cp) genome sequence of E. decipiens was characterized by Illumina pair-end sequencing. The genome was 158,148 bp in total length, including a large single-copy (LSC) region of 85,702 bp, a small single-copy (SSC) region of 17,672 bp, and a pair of invert repeats (IR) regions of 27,387 bp. The plastid genome contained 142 genes including 97 protein-coding genes, 37 tRNA genes, and eight rRNA genes. Phylogenetic analysis based on 13 chloroplast genomes indicates that E. decipiens is closely related to Elaeocarpus bracean in Elaeocarpacea.

Background: B7-H3 is an important immunomodulatory molecule, and clinical studies have confirmed that its expression level is closely correlated with prostate cancer prognosis. However, the mechanism of its biological action is unclear. Methods: An engineered cell line overexpressing B7-H3 was constructed. Cell apoptosis, growth and proliferation assays in vitro and an animal model in vivo were performed to analyze the role and possible mechanism of B7-H3 in promoting prostate cancer progression. Results: Compared with the control cell line (Mock-RM-1), the B7-H3-overexpressing prostate cancer cell line (B7-H3-RM-1) showed no significant growth differences in vitro , whereas the in vivo tumorigenesis rate of B7-H3-RM-1 was significantly higher than that of Mock-RM-1. These results suggest that B7-H3indirectly, rather than directly, promotes prostate cancer progression. Further analysis revealed that significantly higher levels of myeloid-derived suppressor cells (MDSCs) accumulated in vivo in B7-H3-RM-1 tumor-bearing mice than in Mock-RM-1 mice. In vitro and in vivo experiments showed that B7-H3-RM-1 cells significantly antagonized MDSC apoptosis. To further confirm the role of MDSCs in B7-H3-mediated prostate cancer progression, model mice were pretreated with cyclophosphamide before inoculation to clear immune cells and achieve myelo suppression. The results showed no significant differences in tumor growth between the B7-H3-RM-1 group and the Mock-RM-1 group. Conclusions: We found, for the first time, that B7-H3 can antagonize MDSC apoptosis, leading to MDSC accumulation in the tumor microenvironment and thereby promoting prostate cancer progression.

Objective: Cancer-associated fibroblasts (CAFs) were associated with tumor progression in the tumor microenvironment (TME). However, their immunosuppressive roles in protecting cancer cells from the attack by cytotoxic T lymphocytes (CTLs) are not fully clear. In this study, we investigated whether and how CAFs regulate tumor-infiltrating lymphocytes as well as their role in tumor immunosuppression.Methods: Eighty-three cases of ovarian cancer and 10 controls were analyzed for CAFs and CD8+ tumor-infiltrating lymphocytes by gene array and immunohistochemistry. We evaluated presenilin 1 (PS1) expression in CAFs, CTL penetration, tumor burden, dendritic cell function, and migration of tumor-infiltrating lymphocytes and their function in vivo and in vitro after silencing PS1. In addition, the pathway via which PS1 affects the TME was also evaluated.Results: PS1 was highly expressed in CAFs, and its silencing significantly promoted CD8+ CTL proliferation and penetration in multiple ovarian models (p < 0.05), resulting in tumor regression and growth inhibition. Interleukin (IL)-1β was identified as a major immune inhibitor in the TME, and it was significantly decreased after PS1 silencing (p < 0.05), which was regulated by the WNT/β-catenin pathway. It was also showed that high expression of IL-1β in CAFs inhibits CTL penetration significantly (p < 0.05).Conclusion: Highly expressed PS1 in CAFs plays a crucial role in regulating tumor-infiltrating lymphocyte populations in the TME via the WNT/β-catenin pathway. Targeting PS1 may retrieve functional CTLs in the TME and improve the efficacy of current immunotherapies.

Background. Several efforts have been made to find out a valuable marker to assist the diagnosis and differentiation of gangrenous/perforated appendicitis. We aimed to determine the diagnostic capacity of soluble B7H3 (sB7H3) in acute appendicitis (AA) and its accuracy as a predictor of the severity of appendicitis. Methods. 182 children were allocated into four groups as follows: control group (CG, 90), simple appendicitis (SA, 12), purulent appendicitis (PA, 49), and gangrenous appendicitis (GA, 31). Prior to appendectomy, blood was collected and sent for analysis of routine examination and cytokines (sB7H3 and TNF-α). We compared values of all measured parameters according to histological findings. Furthermore, we assigned AA patients into the nonperforated appendicitis group and the perforated appendicitis group. The diagnostic effects of significant markers were assessed by ROC curves. Results. Only the levels of CRP, FIB, and sB7H3 had a remarkable rising trend in AA-based groups, while differences in the levels of CRP and FIB between simple appendicitis and purulent appendicitis were not statistically significant. In addition, sB7H3 was found as the only marker in children with AA, which was markedly associated with the degree of histological findings of the appendix. Furthermore, sB7H3 had a high diagnostic value in predicting AA and complex appendicitis (PA+GA) in children. However, the diagnostic performance of sB7H3 for distinguishing PA from GA was not remarkable. Additionally, only the levels of CRP and sB7H3 were statistically different between the nonperforated appendicitis group and the perforated appendicitis group. The diagnostic performance of CRP and sB7H3 could not merely predict perforation of AA in children; however, the diagnostic performance was improved after combination. Conclusions. sB7H3 could be used as a valuable marker to predict the presence of AA and complex AA in children. However, the diagnostic value of sB7H3 to predict gangrenous/perforated appendicitis was not found to be remarkable. The combination of sB7H3 and CRP might improve the prediction of perforated appendicitis.

The immunoregulatory protein B7-H3, a member of the B7 family, has been confirmed to be highly expressed in colon cancer. However, the exact influence of B7-H3 on the features and antitumor ability of γδT cells in colon cancer remains unknown. In the present study, we investigated that the proportions of B7-H3+ γδT cells were distinctly increased in the peripheral blood and tumor tissues of colon cancer patients. B7-H3 blockade or knockdown promoted proliferation, inhibited cell apoptosis and induced the expression of activation markers (CD25 and CD69) on Vδ2 T cells. In contrast, treatment with the B7-H3 agonist 4H7 had the opposite effect. Furthermore, B7-H3 suppressed IFN-γ expression by inhibiting T-bet in Vδ2 T cells. Moreover, B7-H3 mediated the inhibition of Vδ2 T cell cytotoxicity via the downregulation of IFN-γ and perforin/granzyme B expression. More importantly, blocking the B7-H3 function significantly enhanced the cytotoxicity of Vδ2 T cells against colon cancer cells in vivo. Therefore, the inhibition or blockade of B7-H3 is a potential immunotherapeutic approach for colon cancer.

Abstract Background B7-H3, a member of the B7 family of the Ig superfamily of proteins, has been detected in the epididymis, which is a storage organ related to sperm maturation. However, the characteristics of its expression in different regions of the epididymis remain unknown. Our aim was to investigate the expression of B7-H3 in the caput, corpus, and cauda of the epididymis. Methods We extracted epididymis specimens from adult male C57BL/6 mice. The expression of B7-H3 was then measured with immunohistochemistry, enzyme-linked immunosorbent assay (ELISA) and western blotting. Results B7-H3 protein was predominantly detected on the membrane and in the cytoplasm of the principal cells in the epididymis. Moreover, the level of B7-H3 in the corpus of the mouse epididymis was significantly higher than that in the caput (p 0.05). Conclusions The caput, corpus, and cauda of the mouse epididymis all expressed B7-H3 protein. However, the levels of B7-H3 were different in the three regions of the epididymis.

Activated hepatic stellate cells (aHSCs) are now established as a central driver of fibrosis in human liver injury. In the presence of chronic or repeated injury, fibrosis, cirrhosis, and hepatocellular carcinoma (HCC) can occur, so there is interest in down-regulating aHSCs activity in order to treat these diseases. Here, we report that Vγ9Vδ2 T cells are reduced in patients with liver cirrhosis, stimulating us to investigate possible interactions between Vγ9Vδ2 T cells and aHSCs. We find that Vγ9Vδ2 T cells kill aHSCs and killing is enhanced when aHSCs are pretreated with BPH-1236, a lipophilic analog of the bone resorption drug zoledronate. Cytotoxicity is mediated by direct cell-to-cell contact as shown by Transwell experiments and atomic force microscopy, with BPH-1236 increasing the adhesion between aHSCs and Vγ9Vδ2 T cells. Mechanistically, BPH-1236 functions by inhibiting farnesyl diphosphate synthase, leading to accumulation of the phosphoantigen isopentenyl diphosphate and recognition by Vγ9Vδ2 T cells. The cytolytic process is largely dependent on the perforin/granzyme B pathway. In a Rag2−/−γc−/− immune-deficient mouse model, we find that Vγ9Vδ2 T cells home-in to the liver, and when accompanied by BPH-1236, kill not only orthotopic aHSCs but also orthotopic HCC tumors. Collectively, our results provide the first proof-of-concept of a novel immunotherapeutic strategy for the treatment of fibrosis–cirrhosis–HCC diseases using adoptively transferred Vγ9Vδ2 T cells, combined with a lipophilic bisphosphonate.

T cell immunoglobulin-3 (TIM-3) has been established as a negative regulatory molecule and plays a critical role in immune tolerance. TIM-3 is upregulated in exhausted CD8(+) T cells in both chronic infection and tumor. However, the nature of TIM-3(+)CD4(+) T cells in the tumor microenvironment is unclear. This study is to characterize TIM-3 expressing lymphocytes within human lung cancer tissues and establish clinical significance of TIM-3 expression in lung cancer progression.A total of 51 human lung cancer tissue specimens were obtained from pathologically confirmed and newly diagnosed non-small cell lung cancer (NSCLC) patients. Leukocytes from tumor tissues, distal normal lung tissues, and peripheral blood mononuclear cells (PBMC) were analyzed for TIM-3 surface expression by flow cytometry. TIM-3 expression on tumor-infiltrating lymphocytes (TILs) was correlated with clinicopathological parameters.TIM-3 is highly upregulated on both CD4(+) and CD8(+) TILs from human lung cancer tissues but negligibly expressed on T cells from patients' peripheral blood. Frequencies of IFN-γ(+) cells were reduced in TIM-3(+)CD8(+) TILs compared to TIM-3(-)CD8(+) TILs. However, the level of TIM-3 expression on CD8(+) TILs failed to associate with any clinical pathological parameter. Interestingly, we found that approximately 70% of TIM-3(+)CD4(+) TILs expressed FOXP3 and about 60% of FOXP3(+) TILs were TIM-3(+). Importantly, TIM-3 expression on CD4(+) T cells correlated with poor clinicopathological parameters of NSCLC such as nodal metastasis and advanced cancer stages. Our study reveals a new role of TIM-3 as an important immune regulator in the tumor microenvironment via its predominant expression in regulatory T cells.

In the title compound, C18H21N3O6, the dihedral angle between the two aromatic rings is 61.1 (1)°. The crystal structure is stabilized by intermolecular O—H...O hydrogen bonds. An intramolecular O—H...O hydrogen bonds is also present.

B7-H3, a recently identified B7 family member, has different isoforms in human and mouse. Mouse B7-H3 gene has only one isoform (2IgB7-H3) with two Ig-like domains, whereas human B7-H3 has two isoforms (2IgB7-H3 and 4IgB7-H3). In this study a systematic genomic survey across various species from teleost fishes to mammals revealed that 4IgB7-H3 isoform also appeared in pigs, guinea pigs, cows, dogs, African elephants, pandas, megabats and higher primate animals, which resulted from tandem exon duplication. Further sequence analysis indicated that this duplication generated a new conserved region in the first IgC domain, which might disable 4IgB7-H3 from releasing soluble form, while 2IgB7-H3 presented both membrane and soluble forms. Through three-dimensional (3D) structure modeling and fusion-protein binding assays, we discovered that the duplicated isoform had a different structure and might bind to another potential receptor on activated T cells. In T cell proliferation assay, human 2IgB7-H3 (h2IgB7-H3) and mouse B7-H3 (mB7-H3) both increased T cell proliferation and IL-2, IFN-γ production, whereas human 4IgB7-H3 (h4IgB7-H3) reduced cytokine production and T cell proliferation compared to control. Furthermore, both h2IgB7-H3 and mB7-H3 upregulated the function of lipopolysacharide (LPS)-activated monocyte in vitro. Taken together, our data implied that during the evolution of vertebrates, B7-H3 exon duplication contributed to the generation of a new 4IgB7-H3 isoform in many mammalian species, which have carried out distinct functions in the immune responses.

This article presents an effective method for improving the structure and performance of coal rock masses, thereby facilitating coalbed methane extraction -- the grouting solidification technique. A systematic review is conducted on grouting solidification materials, process methods, evaluation techniques, and other related aspects. In conclusion, it is emphasized that the grouting solidification technique requires further refinement in its system, and its continued significance in the dynamically evolving energy and coal industry is underscored. This is crucial for ensuring the efficient development and sustainable utilization of coal and coalbed methane resources. [ABSTRACT FROM AUTHOR]

Colon cancer is one of the most common malignant tumors in the human body, ranking second as a gastrointestinal tumor. It has a high incidence in Europe, America and China and more than 1 million new cases of colon cancer are reported worldwide each year. The incidence of colon cancer in China has increased from 12/0.1 million in the early 1970s to 56/0.1 million at present with an annual growth rate of 4.2%, which far exceeds the international level (2%). Rhotekin (RTKN) 2, a Rho-guanosine triphosphatase (GTPase) effector, has been reported to be anti-apoptotic. However, the molecular mechanism underlying the biological function of RTKN2 in colon cancer remains unknown. The present study investigated whether the mRNA expression level of RTKN2 was markedly higher in 30 human colon cancer specimens compared with adjacent non-cancerous tissues. The results showed that the protein expression level of RTKN2 was significantly higher in SW480 and HCT116 cells, compared with HIEC cells. Knockdown of RTKN2 in the SW480 and HCT116 colon cancer cells, by lentivirus-mediated RNA interference led to the notable inhibition of cell proliferation and cell cycle progression, by reducing the expression levels of the PCDA, Cyclin D1 and c-myc cell cycle-associated proteins. The inhibitory effect of RTKN2 silencing on the proliferation of colon cancer cells may be partially realized by inhibiting the Wnt/β-catenin signaling pathway. Furthermore, the silencing of RTKN2 in the cells induced apoptosis by reducing the expression level of Bax and increasing the expression level of Bcl2. These results show that RTKN2 is involved in the carcinogenesis and progression of human colon cancer, indicating that RTKN2 may be a molecular target in colon cancer therapy. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study is to explore the correlations of interleukin 36 (IL-36) and Soluble B7-H3 (sB7-H3) levels in bronchoalveolar lavage fluid (BALF) with clinical characteristics and laboratory findings.Methods: A total of 35 children with M. pneumnoiae pneumonia (MPP) and 15 control subjects were enrolled. BALF concentrations of sB7-H3 and IL-36 were detected using enzyme-linked immunosorbent assays and clinical profiles of children with MPP were obtained.Results: Children with MPP had significantly higher levels of sB7-H3 and IL-36 compared to control subjects (both P < 0.05). Meanwhile, children with pleural effusion had significantly higher levels of sB7-H3 and IL-36 compared to children without pleural effusion (both P < 0.05). BALF concentration of sB7-H3 was strongly associated with concentration of IL-36 (r = 0.796, P < 0.0001) and sB7-H3 was correlated with duration of fever (r = 0.427, P = 0.11) and length of stay (r = 0.345, P = 0.043). Both concentrations of sB7-H3 and IL-36 were significantly decreased in convalescent phase after treatment (both P < 0.05).Conclusion: Both soluble B7-H3 and IL-36 may play an important role in pathogenesis of M. pneumoniae infection and sB7-H3 could be useful as a prognostic predictor or biomarker of MPP. [ABSTRACT FROM AUTHOR]

Background: As a kind of versatility of cytokines, overexpression of macrophage migration inhibitory factor (MIF) and vascular endothelial growth factor-C (VEGF-C) have been reported in a wide variety of tumors. However, the correlation and mechanism between MIF and VEGF-C are still not clear. As an important signal transduction system, MAPK signaling pathways participate in a variety of biological behavior of cells. The purposes of this study are to study the relationship between MIF and VEGF-C and discuss the role of MAPK signal pathway in the relationship. Methods: In this study, we first knocked down the MIF using small interfering RNA (siRNA) and built the stable low expression MIF breast cancer cells (siRNA-MIF-MCF-7) and the negative control cells (siRNA-NC-MCF-7). And then, we evaluated the expression of MIF using Western blot to confirm the effect of transfection. Using real-time fluorescent quantitative polymerase chain reaction and enzyme-linked immunosorbent experiment, we respectively examined the different expression of VEGF-C between siRNA-MIF-MCF-7 and siRNA-NC-MCF-7 and breast cancer cells MCF-7. Moreover, we investigated the expression of p38 MAPK, P-p38 MAPK, p44/42 MAPK, and P-p44/42 MAPK in the three kinds of cells by Western blot to analyze the regulatory mechanism to VEGF-C. Results: We found that MIF siRNA markedly reduced the expression of MIF. And the expression level of VEGF-C, p38 MAPK, P-p38-MAPK, p44/42-MAPK, and P-p44/42 MAPK in siRNA-MIF-MCF-7 cells had different degree of decrease compared with siRNA-NC-MCF-7 cells and MCF-7 cells. Conclusions: These results suggest that MIF can regulate the expression of VEGF-C in breast cancer cells. And its regulatory mechanism may work by activating the MAPK signaling pathway. [ABSTRACT FROM AUTHOR]

An elevated number of myeloid-derived suppressor cells (MDSCs) in tumor-bearing hosts has been recognized as a crucial mediator of tumor progression due to the cells potent ability to suppress antitumor immunity. Cluster of differentiation (CD) 40, as a suppressive phenotype expressed in MDSCs, is essential for MDSC-mediated immune suppression and the expansion of T regulatory cells. However, whether CD40 exerts a direct effect on the accumulation of MDSCs remains unclear. In the present study, CD40 was observed to be highly expressed on the MDSCs obtained from mice bearing gastric tumors. Notably, a significant decrease in the level of CD40 expression was observed in addition to an increased number of MDSCs during tumor progression. Further analysis revealed that the MDSC levels were found to positively correlate with tumor progression and that CD40 expression levels inversely correlate with the accumulation of MDSCs. To confirm the potent correlation between CD40 expression and the accumulation of MDSCs, the apoptosis of the MDSCs was detected using agonistic anti-CD40 treatment. The results indicated that CD40 activation induces apoptosis in MDSCs and that the downregulation of CD40 expression may contribute to MDSC accumulation by facilitating MDSC resistance to apoptosis. Thus, these observations provide a novel mechanism to improve our understanding of the involvement of CD40 in MDSC accumulation during cancer development. [ABSTRACT FROM AUTHOR]

As to the uncertainty relations between soil organic matter content and spectral characteristics, at first, based on the objective function that sum of squares of generalized weighted grey distance is minimum, this paper proposes a new self-iteration grey clustering model whose classification standard is unknown. It then establishes a grey clustering estimating model of soil organic matter content based on hyper-spectral data, and then applies the model to Hengshan County of Shanxi Province. The results show that the self-iteration grey clustering model can not only make full use of the intrinsic information of clustering object indicators but also utilize expert knowledge and experience, and overcome the subjectivity of determining classification standards and weights. The average whitening and grey prediction accuracy of test sample is 93.088% and 99.192% respectively. The example shows that the presented model is valid. [ABSTRACT FROM AUTHOR]

Abstract: Cancer stem–like cells are enriched in CD133-positive (CD133+) colorectal cancer (CRC) cells. To date, the biological significance of CD133 expression in cancer stem–like cells is still unknown. B7-H3, a costimulatory molecule, plays a pivotal role in tumor immune escape by inhibiting the functions of T cells. To identify a new marker to predict the tumor grade of CRC, we analyzed the expression of B7-H3 and CD133 in colorectal tumor samples, and their clinical significance was determined. By using a series of techniques including pathologic tissue microarray technology, immunohistochemistry, and immunofluorescent staining, we found B7-H3 was expressed in 56.73% of the CRC cases (59/104) sampled; CD133 was detected in 26.92% of the CRC cases (28/104) sampled. Further analysis indicated that 22 of these CD133+ samples expressed B7-H3. We also found coexpression of CD133 and B7-H3 in tumor tissue samples (r = 0.321, P < 0.01). Moreover, in contrast to individual CD133 or B7-H3 expression, the coexpression of B7-H3 and CD133 was evidently associated with the depth of tumor invasion, lymphatic metastasis, distant metastasis, and Dukes' stage, suggesting it is a valuable biomarker for the progression of CRC. Indeed, the patients with coexpression of B7-H3 and CD133 had a poorer survival than the other patients (P < 0.05). In summary, our results reveal that B7-H3 was aberrantly expressed in CD133+ CRC cells, and the expression level was closely associated with tumor progression. [Copyright &y& Elsevier]

Purpose – This paper attempts to establish the grey GM(0,N) estimation model of the soil organic matter content spectral inversion under the uncertainties between soil organic matter contents and spectral characteristics and the theory of grey system. Design/methodology/approach – At first, based on the uncertainty of the relationship between the soil organic matter content and spectral characteristics, using the ordered grey accumulation generation and grey GM(0, N) model to establish hyper-spectral grey estimation model of soil organic matter content. Second, the presented model is used to estimate soil organic matter of Hengshan County in Shanxi province in the last part of the paper. Findings – The results are convincing: not only that soil organic matter content spectral inversion grey GM(0, N) model based on the ordered grey accumulation generation theory is valid, but also the model's prediction accuracy is higher, with the sample's average prediction accuracy being 93.662 per cent. Practical implications – The method exposed in the paper can be used on soil organic matter content hyper-spectral inversion and even for other similar forecast problems. Originality/value – The paper succeeds in realising both prediction pattern and application of soil organic matter content hyper-spectral inversion by using the newest developed theories: grey GM(0, N) model based on the ordered grey accumulation generation. [ABSTRACT FROM AUTHOR]

CD83 is commonly known as a specific marker for mature dendritic cells. It has been shown to be important for CD4+ T-cell development in the thymus. However, its function in the peripheral immune system remains enigmatic. Here, we show that CD83 inhibits proliferation and production of IL-2 and IFN-γ by T cells, and the inhibitory effect of CD83 is mediated by monocytes. Prostaglandin E2 (PGE2), but not IL-10 or TGF-β, was up-regulated specifically by CD83 in monocytes. Consistent with high levels of PGE2, expression of COX-2 also was increased upon CD83 treatment. NF-κB activation also is required for induction of PGE2 by CD83. Finally, application of the COX-2-selective inhibitor NS-398 fully prevented CD83-triggered inhibition of T-cell responses. Our study establishes an immune-regulatory mechanism by CD83 via stimulation of PGE2 production in monocytes. [ABSTRACT FROM AUTHOR]

Expression of membrane CD276 (mB7-H3) has been reported on dendritic cells (DCs), monocytes, activated T cells, and various carcinoma cells. However, reports concerning its in vivo function have been inconsistent. Moreover, whether there is a soluble form of this protein is not known. In this study, using a sensitive dual monoclonal antibody sandwich enzyme-linked immunosorbent assay (ELISA) to detect the soluble form of B7-H3 (sB7-H3), we demonstrated the release of sB7-H3 by monocytes, DCs, activated T cells, and various mB7-H3+ but not mB7-H3– carcinoma cells. Release from cells was blocked by addition of a matrix metalloproteinase inhibitor (MMPI), which concomitantly caused the accumulation of B7-H3 on the cell surface. To determine the level of circulating sB7-H3, more than 200 serum samples were included in the study. The results indicated that sB7-H3 was present at high levels in all serum samples. Western blotting of sB7-H3 from cell culture supernatants or sera of healthy donors indicated that the molecular size was approximately 16 kDa. Soluble B7-H3 was able to bind to the B7-H3 receptor (B7-H3R) on activated T cells, which showed that sB7-H3 is a functionally active form. These results indicate that release of sB7-H3 from the cell surface is mediated by a matrix metalloproteinase and probably regulates B7-H3R/B7-H3 interactions in vivo. Cleavage of sB7-H3 to an active soluble form would alter both proximal and distal cellular responses. [ABSTRACT FROM AUTHOR]

Objective: To investigate risk factors affecting short-term functional prognosis after discharge in patients with acute cerebral infarction and explore the correlation between relevant factors and National Institutes of Health Stroke Scale (NIHSS) scores. Methods: A retrospective analysis of 4,048 patients with acute cerebral infarction hospitalised between January 2014 and November 2018 in Department of Neurology, Renqiu Kangji Xintu Hospital, Hebei were conducted. The enrolled patients, including 2,506 men and 1,542 women, were divided into mild (n=3,696), moderate (n=278) and severe groups (n=74) based on NIHSS score. Baseline data (gender, history of hypertension, diabetes, hyperlipidaemia, drinking, cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, lipoprotein (a), urea nitrogen, creatinine) were compared among the three groups, and the relationship between relevant factors and NIHSS scores was studied. Results: Through single factor regression analysis, it was found that age, history of stroke, atrial fibrillation, coronary heart disease, antiplatelet medication usage, systolic blood pressure and uric acid were risk factors for the moderate group. Multivariate logistic regression analysis showed that, after adjusting for confounding factors, age, history of stroke and systolic blood pressure (P<0.01) were independent risk factors for the moderate group. Age (OR=1.089;, history of stroke, atrial fibrillation, diastolic blood pressure, fasting plasma glucose and uric acid (P<0.05) were independent risk factors for the severe group. Conclusion: Age, history of stroke, atrial fibrillation, systolic and diastolic blood pressure, fasting plasma glucose and uric acid levels are independent risk factors affecting the short-term post-discharge functional prognosis of patients with acute cerebral infarction and are related to the NIHSS scores of these patients after discharge. [ABSTRACT FROM AUTHOR]

IL-33 released by epithelial cells and immune cells functions as an alarmin and can induce both type 1 and type 2 immune responses. However, the role of IL-33 release in tumor development is still not clear. In this study, we examined the function of released IL-33 in murine hepatocellular carcinoma (HCC) models by hydrodynamically injecting either IL-33-expressing tumor cells or IL-33-expressing plasmids into the liver of tumor-bearing mice. Tumor growth was greatly inhibited by IL-33 release. This antitumor effect of IL-33 was dependent on suppression of tumorigenicity 2 (ST2) because it was diminished in ST2-/- mice. Moreover, HCC patients with high IL-33 expression have prolonged overall survival compared with the patients with low IL-33 expression. Further study showed that there were increased percentages and numbers of activated and effector CD4+ and CD8+ T cells in both spleen and liver in IL-33-expressing tumor-bearing mice. Moreover, IFN-γ production of the CD4+ and CD8+ T cells was upregulated in both spleen and liver by IL-33. The cytotoxicity of CTLs from IL-33-expressing mice was also enhanced. In vitro rIL-33 treatment could preferentially expand CD8+ T cells and promote CD4+ and CD8+ T cell activation and IFN-γ production. Depletion of CD4+ and CD8+ T cells diminished the antitumor activity of IL-33, suggesting that the antitumor function of released IL-33 was mediated by both CD4+ and CD8+ T cells. Taken together, we demonstrated in murine HCC models that IL-33 release could inhibit tumor development through its interaction with ST2 to promote antitumor CD4+ and CD8+ T cell responses. [ABSTRACT FROM AUTHOR]

Cancer stem-like cells are enriched in CD133-positive (CD133(+)) colorectal cancer (CRC) cells. To date, the biological significance of CD133 expression in cancer stem-like cells is still unknown. B7-H3, a costimulatory molecule, plays a pivotal role in tumor immune escape by inhibiting the functions of T cells. To identify a new marker to predict the tumor grade of CRC, we analyzed the expression of B7-H3 and CD133 in colorectal tumor samples, and their clinical significance was determined. By using a series of techniques including pathologic tissue microarray technology, immunohistochemistry, and immunofluorescent staining, we found B7-H3 was expressed in 56.73% of the CRC cases (59/104) sampled; CD133 was detected in 26.92% of the CRC cases (28/104) sampled. Further analysis indicated that 22 of these CD133(+) samples expressed B7-H3. We also found coexpression of CD133 and B7-H3 in tumor tissue samples (r = 0.321, P < 0.01). Moreover, in contrast to individual CD133 or B7-H3 expression, the coexpression of B7-H3 and CD133 was evidently associated with the depth of tumor invasion, lymphatic metastasis, distant metastasis, and Dukes' stage, suggesting it is a valuable biomarker for the progression of CRC. Indeed, the patients with coexpression of B7-H3 and CD133 had a poorer survival than the other patients (P < 0.05). In summary, our results reveal that B7-H3 was aberrantly expressed in CD133(+) CRC cells, and the expression level was closely associated with tumor progression., (Copyright © 2014 Elsevier Inc. All rights reserved.)