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IntroductionNitrogen (N) and phosphorus (P) enrichment due to anthropogenic activities can significantly affect soil N transformations in forest ecosystems. However, the effects of N and P additions on nitrification and denitrification processes in Metasequoia glyptostroboides plantations, and economically important forest type in China, remain poorly understood.MethodsThis study investigated the responses of soil nitrification and denitrification rates, as well as the abundances of nitrifiers and denitrifiers, to different levels of N and P additions in a 6-year nutrient addition experiment in a M. glyptostroboides plantation.ResultsStepwise multiple regression analysis was used to identify the main predictors of nitrification and denitrification rates. The results showed that moderate N addition (N2 treatment, 2.4 mol·m-2) stimulated nitrification rates and abundances of ammonia-oxidizing archaea (AOA) and bacteria (AOB), while excessive N and P additions inhibited denitrification rates and reduced the abundance of nirS-type denitrifiers. AOB abundance was the main predictor of nitrification rates under N additions, whereas microbial biomass carbon and nirS gene abundance were the key factors controlling denitrification rates. Under P additions, tree growth parameters (diameter at breast height and crown base height) and AOB abundance were the primary predictors of nitrification and denitrification rates.DiscussionOur study reveals complex interactions among nutrient inputs, plant growth, soil properties, and microbial communities in regulating soil N transformations in plantation forests. This study also offers valuable insights for formulating effective nutrient management strategies to enhance the growth and health of M. glyptostroboides plantations under scenarios of increasing elevated nutrient deposition.

Mycoplasma hyopneumoniae is a highly contagious pathogen causing porcine enzootic pneumonia, which elicits prolonged inflammatory response modulated by pattern recognition receptors (PRRs). Although significant advances have been achieved in understanding the Toll-Like receptors that recognize M. hyopneumoniae, the role of nucleotide-binding oligomerization domain 1 (NOD1) in M. hyopneumoniae infected cells remains poorly understood. This study revealed that M. hyopneumoniae activates the NOD1-RIP2 pathway and is co-localized with host NOD1 during infection. siRNA knockdown of NOD1 significantly impaired the TRIF and MYD88 pathway and blocked the activation of TNF-α. In contrast, NOD1 overexpression significantly suppressed M. hyopneumoniae proliferation. Furthermore, we for the first time investigated the interaction between M. hyopneumoniae mhp390 and NOD1 receptor, and the results suggested that mhp390 and NOD1 are possibly involved in the recognition of M. hyopneumoniae. These findings may improve our understanding of the interaction between PRRs and M. hyopneumoniae and the function of NOD1 in host defense against M. hyopneumoniae infection.

Growing evidence has shown the oncogenic function of matrix metallopeptidase 7 (MMP7) in various tumors. However, no systemic pan-cancer analysis on the association between MMP7 and different cancers based on big clinical data is available. TIMER2, GEPIA2, UALCAN, cBioPortal, String, Metascape, and other web databases were searched in the present study. Generally, MMP7 expression is significantly upregulated in most The Cancer Genome Atlas (TCGA) cancer types compared to the paired normal controls, yet is downregulated in tumor tissues of invasive breast carcinoma (BRCA), kidney chromophobe (KICH), kidney renal clear cell carcinoma (KIRC), liver hepatocellular carcinoma (LIHC), and skin cutaneous melanoma (SKCM). MMP7 protein expression is notably higher in the primary tumor tissues of colon cancer, lung adenocarcinoma (LUAD), and uterine corpus endometrial carcinoma (UCEC) than in normal tissues and is significantly lower in the primary tumor tissues of breast cancer, clear cell renal carcinoma, and ovarian cancer. Furthermore, MMP7 expression is strongly associated with pathological stages, clinical outcomes, tumor mutational burden (TMB), and microsatellite instability (TSI). Gene amplification was detected in most TCGA cancer types. In addition, the missense mutation is the primary type of MMP7 genetic alteration in tumors. Significant positive correlations between MMP7 expression and cancer-associated fibroblasts (CAFs) have been demonstrated in most TCGA cancers. MMP7 expression was also found to be positively correlated with infiltration of dendritic cells and macrophages in some specific tumor types. Functional enrichment analysis by the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and gene ontology (GO) methods revealed that RNA processing and DNA damage checkpoints might reveal the pathogenetic mechanisms of MMP7. This pan-cancer analysis provides a clear panorama for the tumorigenic roles of MMP7 across different cancer types. Moreover, MMP7 could be a potential drug therapeutic target in such cancers.

The Exocrine Differentiation and Proliferation Factor (EXDPF) gene could promote exocrine while inhibit endocrine functions. Although it is well known that ovary is an endocrine organ, the functions of EXDPF in ovarian cancer development is still unknown. This study demonstrated that EXDPF gene is significantly higher expressed in ovarian tumors compared to normal ovarian tissue controls. EXDPF DNA amplification was exhibited in lots of human tumors including 7.19% of ovarian tumors. Also, high expression of EXDPF positively correlated with poor overall survival (OS) of ovarian cancer patients. EXDPF expression could be universally detected in most epithelial ovarian cancer cells (SKOV3, IGROV1, MACS, HO8910PM, ES2, COV362 and A2780) tested in this study. Knock-down of EXDPF by siRNA delivered by plasmid or lentivirus largely inhibited ovarian cancer cells, IGROV1 and SKOV3 proliferation, migration and tumorigenesis in vitro and/or in vivo. Knock-down of EXDPF sensitized SKOV3 cells to the treatment of the front-line drug, paclitaxel. Mechanism study showed that EXDPF enhanced DNA replication pathway to promote ovarian cancer tumorigenesis. In conclusion, this study demonstrated that EXDPF could be a potential therapeutic target as a pro-oncogene of ovarian cancer.

Novel inhibitors are urgently needed for use as targeted therapies to improve the overall survival (OS) of patients with ovarian cancer. Here, we show that cell division cycle 25B (CDC25B) is over-expressed in ovarian tumors and associated with poor patient prognosis. All previously reported CDC25B inhibitors have been identified by their ability to reversibly inhibit the catalytic dephosphorylation activity of CDC25B in vitro; however, none of these compounds have entered clinical trials for ovarian cancer therapy. In this study, we synthesized a novel small molecule compound, WG-391D, that potently down-regulates CDC25B expression without affecting its catalytic dephosphorylation activity. The inhibition of CDC25B by WG-391D is irreversible, and WG-391D should therefore exhibit potent antitumor activity against ovarian cancer. WG-391D induces cell cycle progression arrest at the G2/M phase. Half maximal inhibitory concentration (IC50) values of WG-391D for inhibition of the proliferation and migration of eight representative ovarian cancer cell lines (SKOV3, ES2, OVCAR8, OVTOKO, A2780, IGROV1, HO8910PM, and MCAS) and five primary ovarian tumor cell lines (GFY004, GFY005, CZ001, CZ006, and CZ008) were lower than 10 and 1 μM, respectively. WG-391D inhibited tumor growth in nude mice inoculated with SKOV3 cells or a patient-derived xenograft (PDX). The underlying mechanisms were associated with the down-regulation of CDC25B and subsequent inactivation of cell division cycle 2 (CDC2) and the serine/threonine kinase, AKT. In conclusion, this study demonstrates that WG-391D exhibits strong antitumor activity against ovarian cancer and indicates that the down-regulation of CDC25B by inhibitors could provide a rationale for ovarian cancer therapy.