A pan-cancer analysis of the prognosis and immune infiltration of eEF1A2 and its potential function in thyroid carcinoma.

Purpose: Eukaryotic translation elongation factor 1α2 (eEF1A2) promotes tumour progression in various cancers. We performed a pan-cancer analysis of eEF1A2 and explored its role in thyroid carcinoma (THCA). Methods: Databases from The Cancer Genome Atlas (TCGA), the University of Alabama at Birmingham Cancer data analysis Portal (UALCAN), and the Human Protein Atlas (HPA) were used to investigate the differential expression of eEF1A2 in pan-cancer. The pathological stage, prognostic characteristics, tumour microenvironment (TME), tumour mutational burden (TMB), and microsatellite instability (MSI) were analysed in diverse tumours with different expression levels of eEF1A2. The expression levels in papillary thyroid carcinoma (PTC) and its specific role in cell proliferation, migration, invasion, and cell glycolysis in PTC cells were verified by quantitative real time polymerase chain reaction (qRT-PCR), immunohistochemistry, cell counting kit-8, colony formation, wound healing, Transwell assay, and lactate acid and glucose assays.Results:eEF1A2 was differentially expressed in various malignant tumour tissues compared to control tissues and was associated with poor pathological stage and prognosis in most types of tumours. Moreover, eEF1A2 expression closely correlated with the infiltration of immunosuppressive cells, TMB, and MSI in some tumour types. Expression of eEF1A2 in PTC is higher than the para-carcinoma, and eEF1A2 downregulation suppressed TPC-1 and BCPAP cell proliferation, migration, invasion, and glycolysis. Conclusion: Our study suggests that the expression of eEF1A2 is related to the prognosis and immune infiltration of some tumours and may be a predictor of prognosis and immunotherapy. eEF1A2 could promote malignant behaviour of PTC cells.

Transcription factor FOXP4 inversely governs tumor suppressor genes and contributes to thyroid cancer progression.

Objective: In recent decades, thyroid cancer (TC) has exhibited a rising incidence pattern. Elevated levels of the transcription factor FOXP4 have been strongly linked to the progression of diverse tumors; nevertheless, its specific role in thyroid cancer remains underexplored. The primary objective of this study was to elucidate the functions of FOXP4 and its associated target gene, FBXW7, in the context of thyroid cancer. Methods: FOXP4 and FBXW7 expression levels in TC tissues and cell lines were assessed through immunohistochemistry and RT-qPCR analyses. The functional aspects of FOXP4, including its effects on cell proliferation, migration capabilities, cell cycle regulation, and epithelial-mesenchymal transition (EMT), were investigated. Furthermore, the interaction between FOXP4 and FBXW7 was confirmed using chromatin immunoprecipitation (ChIP) assays. The impact of FBXW7 on FOXP4-mediated cellular phenotypes was subsequently examined. Additionally, the in vivo role of FOXP4 and FBXW7 in tumor growth was elucidated through the establishment of a murine tumor model. Results: Elevated levels of FOXP4 were observed in papillary carcinoma tissues, and patients exhibiting high FBXW7 levels showed a more favorable prognosis. KTC-1 cells displayed a concomitant increase in FOXP4 expression and decrease in FBXW7 expression. FOXP4 overexpression in these cells enhanced cell proliferation, migration capabilities, and EMT. The interaction between the FOXP4 protein and the FBXW7 promoter was confirmed, and the effects of FOXP4 were mitigated upon overexpression of FBXW7. Furthermore, knockdown of FOXP4 led to decelerated growth of transplanted tumors and increased FBXW7 levels within the tumors. Conclusion: The findings of the current study underscore the regulatory role of FOXP4 in the transcription of FBXW7 and establish a clear link between aberrations in FBXW7 expression and the manifestation of malignant phenotypes in highly aggressive TC cells.

The essential role of forkhead box P4 (FOXP4) in thyroid cancer: a study related to The Cancer Genome Atlas and experimental data.

Objective: Thyroid cancer (THCA) is the most common endocrine cancer in the world. Although most patients with THCA have a good prognosis, the prognosis of those with THCA who have an extra-glandular invasion, vascular invasion, and distant metastasis is poor. Therefore, it is very important to find potential biomarkers that can effectively predict the prognosis and progression of highly aggressive THCAs. It has been identified that forkhead box P4 (FOXP4) may be a new biomarker for the proliferation and prognosis for tumor diagnosis. However, the expression and function of FOXP4 in THCA remain to be determined. Methods: In the present study, the function of FOXP4 in cells was investigated through the comprehensive analysis of data in The Cancer Genome Atlas and combined with experiments including immunohistochemistry (IHC), colony formation, Cell Counting Kit-8 assay, wound scratch healing, and transwell invasion assay. Results: In the present study, relevant bioinformatic data showed that FOXP4 was highly expressed in THCA, which was consistent with the results of the IHC and cell experiments. Meanwhile, 10 FOXP4-related hub genes were identified as potential diagnostic genes for THCA. It was found in further experiments that FOXP4 was located in the nucleus of THCA cells, and the expression of FOXP4 in the nucleus was higher than that in the cytoplasm. FOXP4 knockdown inhibited in vitro proliferation of the THCA cells, whereas overexpression promoted the proliferation and migration of THCA cells. Furthermore, deficiency of FOXP4 induced cell-cycle arrest. Conclusion: FOXP4 might be a potential target for diagnosing and treating THCA.

Influenza A virus NS1 protein represses antiviral immune response by hijacking NF-κB to mediate transcription of type III IFN.

Background: Non-structural protein 1 (NS1), one of the viral proteins of influenza A viruses (IAVs), plays a crucial role in evading host antiviral immune response. It is known that the IAV NS1 protein regulates the antiviral genes response mainly through several different molecular mechanisms in cytoplasm. Current evidence suggests that NS1 represses the transcription of IFNB1 gene by inhibiting the recruitment of Pol II to its exons and promoters in infected cells. However, IAV NS1 whether can utilize a common mechanism to antagonize antiviral response by interacting with cellular DNA and immune-related transcription factors in the nucleus, is not yet clear. Methods: Chromatin immunoprecipitation and sequencing (ChIP-seq) was used to determine genome-wide transcriptional DNA-binding sites for NS1 and NF-κB in viral infection. Next, we used ChIP-reChIP, luciferase reporter assay and secreted embryonic alkaline phosphatase (SEAP) assay to provide information on the dynamic binding of NS1 and NF-κB to chromatin. RNA sequencing (RNA-seq) transcriptomic analyses were used to explore the critical role of NS1 and NF-κB in IAV infection as well as the detailed processes governing host antiviral response. Results: Herein, NS1 was found to co-localize with NF-κB using ChIP-seq. ChIP-reChIP and luciferase reporter assay confirmed the co-localization of NS1 and NF-κB at type III IFN genes, such as IFNL1, IFNL2, and IFNL3. We discovered that NS1 disturbed binding manners of NF-κB to inhibit IFNL1 expression. NS1 hijacked NF-κB from a typical IFNL1 promoter to the exon-intron region of IFNL1 and decreased the enrichment of RNA polymerase II and H3K27ac, a chromatin accessibility marker, in the promoter region of IFNL1 during IAV infection, consequently reducing IFNL1 gene expression. NS1 deletion enhanced the enrichment of RNA polymerase II at the IFNL1 promoter and promoted its expression. Conclusion: Overall, NS1 hijacked NF-κB to prevent its interaction with the IFNL1 promoter and restricted the open chromatin architecture of the promoter, thereby abating antiviral gene expression.

[Pollution Characteristics and Risk Assessment of Nutrients and Heavy Metals in Sediments of the Fuhe River Influenced Area, Baiyangdian Lake].

Based on the flow direction of the Fuhe River into Baiyangdian Lake, the impacted area of the Fuhe River was divided into 6 subareas, and sediments from 48 sites were collected in November 2020. The characteristics and risks of sediment nutrients and heavy metal pollution in these six subareas were investigated. The results showed that the average ω(TN), ω(TP), and ω(TOC) were 1841 mg·kg-1, 769 mg·kg-1, and 1.77%, respectively. The major heavy metals were Cd, Cu, Zn, Hg, and Pb, which were 3.73, 1.50, 1.42, 1.31, and 1.31 times the soil background values for Hebei Province, respectively. The TP and heavy metal (Cd, Cu, Zn, Hg, and Pb) content showed a decreasing trend from the Fuhe River estuary to the downstream Zaolinzhuang, whereas the TN and TOC content showed no marked trends. TN, TP, TOC, and heavy metals (Cd, Cu, Zn, Hg, and Pb) were enriched in surface sediments (0-10 cm). The TP content in the surface sediments (0-10 cm) of the Fuhe River estuary, Fuhe River estuary-Nanliuzhuang, and Nanliuzhuang subareas were heavily polluted; the Wangjiazhai and Guangdian subareas were moderately polluted; and the Zaolinzhuang subarea was slightly polluted. Cd and Hg were the major contributors to heavy metal pollution, which were at considerable risk and moderate risk levels, respectively. The heavy metals in surface sediments (0-10 cm) of the Fuhe River estuary, Fuhe River estuary-Nanliuzhuang, and Nanliuzhuang subareas were at a considerable risk level, and the sediments below 30 cm presented a low risk level. The leaching concentrations of heavy metals in sediments from the subarea of severe ecological risk level were far less than the identification standard values of leaching toxicity, suggesting that the sediments can be treated as general waste after dredging.

[Correlation of single nucleotide polymorphisms of the osteopontin gene with astheozoospermia].

OBJECTIVE: To investigate the correlation of the single nucleotide polymorphisms (SNP) rs1126772, rs117291487, rs11730582, rs142608941 and rs6813526 of the osteopontin (OPN) gene with the risk of asthenozoospermia (AZS). METHODS: We included 135 AZS patients in the AZS group and another 239 fertile men as normal controls. Using the SNaPshot technique, we genotyped the rs1126772, rs117291487, rs11730582, rs142608941 and rs6813526 polymorphisms of the OPN gene in all the subjects and analyzed the correlation of the five SNPs with AZS. RESULTS: The GA genotype and A allele of the OPN gene rs1126772 were found to be correlated with the risk of AZS (GA vs AA: OR = 0.55, 95% CI: 0.35－0.86, P = 0.009; A vs G: OR = 0.64, 95% CI: 0.46－0.89, P = 0.007), and so was the CT genotype and T allele at the RS11730582 locus (CT vs TT: OR = 0.526, 95% CI: 0.34－0.82, P = 0.009; T vs C: OR = 0.60, 95% CI: 0.44－0.83, P = 0.002). Haplotype analysis showed that the AATCT haplotype decreased the risk of AZS (AATCT: OR = 0.61, 95% CI: 0.42－0.88, P = 0.008) . CONCLUSIONS: The polymorphisms of the OPN gene RS1126772 and RS11730582 may reduce the risk of AZS.

[Identification of Dredging Depths Based on Sediment Vertical Distribution Profiles of Total Nitrogen and Total Phosphorus and Their Adsorption-desorption Equilibria].

A dredging demonstration project in the Baiyangdian Lake included open waters and fishing ponds to reduce the internal release of nitrogen and phosphorus from bottom sediments. The dredging depth design was determined by both the sediment vertical distribution profile of total nitrogen and phosphorus, and the sediment adsorption-desorption equilibrium method. The determined dredging depths were very similar and coincident. The dredging depth for the demonstration area of open waters in Nanliuzhuang was identified as(50±10) cm; and the dredging depths for fishing ponds were(30±10) cm in both the Nanliuzhuang and Caiputai demonstration areas. The equilibrium nitrogen(NH4+-N) and phosphorus(SRP) concentrations at zero net sorption or desorption(ENC0 and EPC0) were significantly positively correlated with both exchangeable and total nitrogen and phosphorus in the sediments. The total nitrogen and phosphorus in the sediments were also used to predict the risk of their release from the bottom sediments to the overlying water column. The sediment layers with ENC0 and EPC0 values greater than the NH4+-N and SRP in the overlying water column indicated the sediments act as a source of dissolved nitrogen and phosphorus to the overlying water column in the Nanliuzhuang and Caiputai demonstration areas. Accordingly, the sediment layers with both total nitrogen concentrations greater than 750 mg·kg-1 and total phosphorus concentrations greater than 500 mg·kg-1 should be identified as dredging layers.

Evolution of Superconducting Properties in Fe1.1Se0.8Te0.2 Films Before and After Structure Avalanche.

By preparing a series of high-quality Fe1.1Se0.8Te0.2 films on the CaF2 substrate via pulsed laser deposition, we reveal the evolution of the structure as well as the superconductivity with the film thickness. We have found that there exists a threshold thickness above which the critical temperature Tc reaches its optimal value of 23.18 K with large activation energy, promising for high-field technological applications. Most importantly, the thick films have been found in a metastable state due to the fragile balance between the increased strain energy and the large compressive stress. Once the balance is broken by an external perturbation, a unique structure avalanche happens with a large part of the film exfoliated from the substrate and curves out. The exfoliated part of the film remains a single phase, with its lattice parameter and Tc recovering the bulk values. Our results clearly demonstrate the close relation between the compressive stress of the film/substrate interface and the high critical temperature observed in FeSeTe films. Moreover, this also provides an efficient way to fabricate free-standing single-phase FeSeTe crystals in the phase-separation regime.

Association of interleukin-27 gene polymorphisms with susceptibility to HIV infection and disease progression.

Interleukin-27 (IL-27) gene polymorphisms are linked to infectious disease susceptibility and IL-27 plasma level is associated with HIV infection. Therefore, we aimed to investigate the association between IL-27 polymorphisms and susceptibility to HIV infection and disease progression. A total of 300 patients with HIV infection (48 long-term nonprogressors and 252 typical progressors) and 300 healthy controls were genotyped for three IL-27 polymorphisms, rs17855750, rs181206, rs40837 which were performed by using multiple single nucleotide primer extension technique. Significant association was found between IL-27 rs40837 polymorphisms with susceptibility to HIV infection (AG vs AA: adjusted OR = 1.60, 95% CI, 1.11-2.30, P = 0.012; AG+GG vs AA: adjusted OR = 1.44, 95% CI, 1.02-2.03, P = 0.038) and disease progression (LTNP: AG vs AA: adjusted OR = 2.33, 95% CI, 1.13-4.80, P = 0.021; TP: AG vs AA: adjusted OR = 1.50, 95% CI, 1.04-2.24, P = 0.030). Serum IL-27 levels were significantly lower in cases compared to controls (P < 0.001). There were lower serum IL-27 levels in TPs than in LTNPs (P < 0.001). We further found that LTNPs with rs40837 AG or GG genotype had lower serum IL-27 levels than with AA genotype (P < 0.05). The CD4+ T counts in cases were significantly lower than controls (P < 0.001). In contrast, individuals with rs40837 AG genotype had lower CD4+ T counts than with AA genotype in cases (P < 0.05). In addition, CD4+ T counts in TPs were significantly lower than LTNPs (P < 0.001). IL-27 rs40837 polymorphism might influence the susceptibility to HIV infection and disease progression probably by regulating the level of serum IL-27 or the quantity of CD4+ T.

[Asthenozoospermia is not correlated with 3' UTR polymorphisms of the GRP78 gene].

OBJECTIVE: To investigate the correlation of the single nucleotide polymorphisms (SNPs) rs12009, rs1140763 and rs16927997 in the 3'-untranslated region (3'UTR) of the glucose-regulated protein 78 (GRP78) gene with the risk of male asthenozoospermia (AZS). METHODS: We included 400 AZS patients in the AZS group and another 400 fertile men as normal controls. Using the SNaPshot technique, we genotyped the rs12009, rs1140763 and rs16927997 polymorphisms in the 3'UTR of the GRP78 gene in all the male subjects and analyzed the association of the three SNPs with AZS. RESULTS: The percentage of progressively motile sperm was significantly lower in the AZS group than in the normal controls (ï¼»20.09 ± 8.18ï¼½ % vs ï¼»57.16 ± 13.45ï¼½ %, P <0.01). Three genotypes of CC, CT and TT and 2 alleles of C and T were found in rs12009 and rs1140763 of the GRP78 gene, and another three genotypes of GG, GA and AA and two alleles of G and A were observed in rs16927997. There were no statistically significant differences between the control and AZS groups in the frequencies of the C and T alleles in rs12009 (44.3% vs 47.3% and 55.7% vs 52.7%, P >0.05) or rs1140763 (50.0% vs 52.0% and 50.0% vs 48.0%, P >0.05) or those of the G and A alleles in rs16927997 (6.0% vs 4.4% and 94.0% vs 95.6%, P >0.05), nor in the genotypes and allele frequencies of the 3 polymorphisms (P >0.05). Furthermore, three haplotypes of C-C-A, T-C-G and T-T-A were observed in the male subjects but showed no evident correlation between the AZS and normal control groups. CONCLUSIONS: The polymorphisms in the 3'UTR of the GRP78 gene are not correlated with the risk of male asthenozoospermia.