To investigate the effect and mechanism of TC2N in skin cutaneous melanoma（SKCM）.

Using the Human Protein Atlas（HPA）and The Cancer Genome Atlas（TCGA）databases to analyze the expression and correlation of clinicopathologic feature of TC2N in SKCM. Human melanoma A375 cells were used to construct an overexpression cell model of TC2N. CCK-8 assay method was used to detect the effect of TC2N on cell proliferation. Cutaneous melanin xenograft model was constructed in TC2N knockout mice, and the tumor growth was observed and measured. Based on the animal model, the expression of Ki67 was detected in transplanted tumor by immunohistochemistry to analyze the proliferation of tumor cells. In addition, Gene Set Enrichment Analysis（GSEA）was performed to investigate the correlation between TC2N expression and ERK/MAPK signaling pathway. RT-qPCR and Western blot assay were used to detect mRNA and protein expression levels of related genes（CyclinD1, c-Myc, CDK2 and CyclinE1 in vitro and in vivo）.

Compared with normal skin tissues, the expression level of TC2N protein in SKCM tissues was higher, which was significantly associated with clinicopathological stages and lymphatic node metastasis in patients with SKCM（P<0.05）. In vitro cell experiments demonstrated that the proliferation ability of A375 cells were significantly increased after TC2N overexpression（P<0.05）. The results of skin melanin xenograft model of knockout mouse revealed that compared with TC2N^＋/＋ mice, the tumor weight and tumor volume of TC2N^-/- mice were significantly decreased（P<0.05）, suggesting that TC2N knockout significantly inhibited the growth of SKCM. GSEA enrichment analysis indicated that TC2N was significantly correlated with MAPK signaling pathway（P<0.01）, and TC2N was positively correlated with ERK/MAPK downstream gene expression（all P<0.01）. Experiments in vivo and in vitro showed TC2N expression significantly promoted the expression of ERK and p-ERK, and exerted effect on the mRNA and protein expression levels of ERK-related molecues, CyclinD1, c-Myc, CDK2 and CyclinE1（P<0.01）.

TC2N gene may promote the growth of cutaneous melanoma through activating ERK/MAPK signaling pathway.

To explore the male reproductive toxicity in rats caused by single or combined exposure to noise and carbon monoxide（CO）in closed cabin, and evaluate the joint effects and associated signal pathways.

Fifty male SD rats were randomly divided into blank control group, restraint group（negative control group）, noise exposure group, CO exposure group and combined group（n=10）. According to the poisoning procedure, the rats were fixed in the oral and nasal toxic cup and placed in the chamber and they were poisoned for 2 h per day for 30 consecutive days. The sperm quality, including sperm motility and sperm density, was analyzed after exposure, and the apoptosis of testicular cells was determined by TUNEL staining. The testicular tissues were harvested for circRNA sequencing, and the sequencing data were analyzed by bioinformatics enrichment.

After exposure to noise and CO, the semen density of the noise group and combine group was decreased significantly（P<0.05）. The sperm motility was obviously lower in the CO group than the negative control group（P<0.05）, and more serious decline was observed in the combined group（P<0.05）. Morphological study showed that there were a few vacuoles in the testis of rats exposed to noise or CO and much more vacuoles in the testis of rats exposed to combination. Obvious pathological damage was found in the testis of rats combined exposed to noise and CO, and the cells in the seminiferous tubules were in a disordered arrangement. The number of apoptotic cells was increased in the noise and CO group, and the number was the largest in the combined group. The results of sequencing analysis suggested that key circRNA and their regulated key molecules might be involved in the reproductive damage effects of noise and CO exposure on rat testes, including Smc4, Sycp1, Sycp3, Spag17, Mns1, Top2a and Rock1, which played important roles in meiosis, spermatogenesis, cell cycle and apoptosis pathways.

Combined exposure to noise and CO shows typical joint effect on male reproductive damages, which are associated with circRNAs regulation.

Non‐small cell lung cancer (NSCLC), including the lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) subtypes, is a malignant tumor type with a poor 5‐year survival rate. The identification of new powerful diagnostic biomarkers, prognostic biomarkers, and potential therapeutic targets in NSCLC is urgently required.

The UCSC Xena, UALCAN, and GEO databases were used to screen and analyze differentially expressed genes, regulatory modes, and genetic/epigenetic alterations in NSCLC. The UCSC Xena database, GEO database, tissue microarray, and immunohistochemistry staining analyses were used to evaluate the diagnostic and prognostic values. Gain‐of‐function assays were performed to examine the roles. The ESTIMATE, TIMER, Linked Omics, STRING, and DAVID algorithms were used to analyze potential molecular mechanisms.

NR3C2 was identified as a potentially important molecule in NSCLC. NR3C2 is expressed at low levels in NSCLC, LUAD, and LUSC tissues, which is significantly related to the clinical indexes of these patients. Receiver operating characteristic curve analysis suggests that the altered NR3C2 expression patterns have diagnostic value in NSCLC, LUAD, and especially LUSC patients. Decreased NR3C2 expression levels can help predict poor prognosis in NSCLC and LUAD patients but not in LUSC patients. These results have been confirmed both with database analysis and real‐world clinical samples on a tissue microarray. Copy number variation contributes to low NR3C2 expression levels in NSCLC and LUAD, while promoter DNA methylation is involved in its downregulation in LUSC. Two NR3C2 promoter methylation sites have high sensitivity and specificity for LUSC diagnosis with clinical application potential. NR3C2 may be a key participant in NSCLC development and progression and is closely associated with the tumor microenvironment and immune cell infiltration. NR3C2 co‐expressed genes are involved in many cancer‐related signaling pathways, further supporting a potentially significant role of NR3C2 in NSCLC.

NR3C2 is a novel potential diagnostic and prognostic biomarker and therapeutic target in NSCLC.