A Sub-Aperture Overlapping Imaging Method for Circular Synthetic Aperture Radar Carried by a Small Rotor Unmanned Aerial Vehicle.

Circular synthetic aperture radar (CSAR) can obtain higher image resolution and more target information using 360° observation of the target. Due to the anisotropy of target scattering characteristics in the actual scene, the sub-aperture imaging method is usually used for CSAR imaging. However, the uniformly divided overlapping sub-aperture CSAR imaging algorithm only considers phase compensation, ignoring the effect of target scattering characteristics on echo amplitude. In CSAR imaging scenarios carried by small rotor unmanned aerial vehicles (SRUAVs), the size of the observed scene cannot be ignored compared to the distance between the target and the antenna and the effect of the anisotropy of the target scattered energy on the echo amplitude should be considered. In this paper, a sub-aperture CSAR imaging method based on adaptive overlapping sub-aperture is proposed. First, the boundary points of the sub-aperture are determined by analyzing the correlation coefficient and the variation coefficient of the energy function. Next, the overlapping sub-aperture division schemes are automatically generated by screening and combining the boundary points. The sub-aperture images are then generated by a Back Projection (BP) algorithm. Finally, sub-aperture image registration and incoherent superposition are used to generate the final CSAR image. Verified by the CSAR field echo data, the proposed method can realize imaging of the original echo data without the Inertial Navigation System (INS) and Global Positioning System (GPS) observation data. Compared with the CSAR full-aperture BP imaging algorithm, the entropy of the image generated by the proposed method increased by 66.77%. Compared with the sub-aperture CSAR imaging algorithm, the entropy of the image generated by the proposed method was improved by 11.12%, retaining more details of the target, improving the target contour features, and enhancing the focusing effect.

Influence of the type of carrier on ferromagnetism in a Si semiconductor implanted with Cu ions.

Silicon semiconductor samples implanted with Cu ions and samples co-implanted with Cu- and N-ions were prepared by MEVVA and the Kaufman technique. None of the samples showed evidence of secondary phases. The initially n-type Si matrix, when implanted with Cu ions, changed to a p-type semiconductor, and the Cu ions existed as local Cu2+ cations in the p-type environment. As a result, none of the Cu-implanted samples were ferromagnetic at room temperature. The co-implanted samples, on the other hand, showed room-temperature ferromagnetism because the introduction of N ions made the carrier type change from p-type to n-type which is favorable for the appearance of Cu2+. First principles calculations were applied to understand the experimental phenomena. The formation energy was reduced by implanting N ions, and was decreased effectively with the increase in ratio of N to Cu ions. The density of states and spin density of states indicated that the hybridization of s, p and d electrons induced ferromagnetism at 0 K. Particularly, we proposed possible exchange interactions between the Cu2+-N-(N4+)-Cu2+ ions to explain the ferromagnetism mechanism.

17ß-estradiol regulates the expression of apolipoprotein M through estrogen receptor α-specific binding motif in its promoter.

BACKGROUND: We have previously demonstrated that estrogen could significantly enhance expression of apolipoprotein M (apoM), whereas the molecular basis of its mechanism is not fully elucidated yet. To further investigate the mechanism behind the estrogen induced up-regulation of apoM expression. RESULTS: Our results demonstrated either free 17ß-estradiol (E2) or membrane-impermeable bovine serum albumin-conjugated E2 (E2-BSA) could modulate human apoM gene expression via the estrogen receptor alpha (ER-α) pathway in the HepG2 cells. Moreover, experiments with the luciferase activity analysis of truncated apoM promoters could demonstrate that a regulatory region (from-1580 to -1575 bp (-GGTCA-)) upstream of the transcriptional start site of apoM gene was essential for the basal transcriptional activity that regulated by the ER-α. With the applications of an electrophoresis mobility shift assay and a chromatin immunoprecipitation assay, we could successfully identify a specific ER-α binding element in the apoM promoter region. CONCULSION: In summary, the present study indicates that 17ß-estradiol induced up-regulation of apoM in HepG2 cells is through an ER-α-dependent pathway involving ER-α binding element in the promoter of the apoM gene.

Hyperglycemia-induced downregulation of apolipoprotein M expression is not via the hexosamine pathway.

BACKGROUND: We previously demonstrated that hyperglycemia could suppress apolipoprotein M (apoM) synthesis both in vivo and in vitro; however, the mechanism of hyperglycemia-induced downregulation of apoM expression is unknown yet. METHODS: In the present study we further examined if hexosamine pathway, one of the most important pathways of glucose turnover, being involved in modulating apoM expression in the hyperglycemia condition. We examined the effect of glucosamine, a prominent component of hexosamine pathway and intracellular mediator of insulin resistance, on apoM expression in HepG2 cells and in rat's models. In the present study we also determined apolipoprotein A1 (apoA1) as a control gene. RESULTS: Our results demonstrated that glucosamine could even up-regulate both apoM and apoA1 expressions in HepG2 cell cultures. The glucosamine induced upregulation of apoM expression could be blocked by addition of azaserine, an inhibitor of hexosamine pathway. Moreover, intravenous infusion of glucosamine could enhance hepatic apoM expression in rats, although serum apoM levels were not significantly influences. CONCLUSIONS: It is concluded that both exogenous and endogenous glucosamine were essential for the over-expression of apoM, which may suggest that the increased intracellular content of glucosamine does not be responsible for the depressed apoM expression at hyperglycemia condition.

Increased mRNA levels of apolipoprotein M and apolipoprotein AI in the placental tissues with fetal macrosomia.

PURPOSE: The present study examined mRNA levels of apolipoprotein M (apoM) and apolipoprotein AI (apoAI) in the term placental tissues obtained from 37 women with normal birth weight neonates and from 37 women with macrosomic neonates (birth body weight ≥4,000 g), and further discussed possible clinical significance of these observations. METHODS: The mRNA levels of apoM and apoAI in the placental tissues were determined by the real time RT-PCR, which demonstrated that both apoM and apoAI mRNA levels were significantly higher in the placentas from macrosomia than those from normal birth. Moreover, we analyzed the overexpressions of apoM and apoAI with the clinical data. Meanwhile we examined several known risk factors of macrosomia including the mRNA levels of insulin-like growth factor I (IGF-I), IGF-II, insulin-like growth factor I receptor (IGF-IR) and IGF-IIR. RESULTS: It demonstrated that apoM expression was significantly positively correlated to the placental weight, fetal birth weight, pregestational body mass index (BMI), weight gain during pregnancy, maternal weight, maternal BMI and the mRNA levels of IGF-IR as well as IGF-IIR. The apoAI mRNA level was statistically significantly correlated to the placental weight, fetal birth weight, IGF-I and IGF-IR mRNA levels. CONCLUSIONS: Binary logistic regression analysis suggested that both apoM and apoAI mRNA may considered as independent risk factors for macrosomia. The clinical significance needs further investigation.

Palmitic acid suppresses apolipoprotein M gene expression via the pathway of PPARß/δ in HepG2 cells.

It has been demonstrated that apolipoprotein M (APOM) is a vasculoprotective constituent of high density lipoprotein (HDL), which could be related to the anti-atherosclerotic property of HDL. Investigation of regulation of APOM expression is of important for further exploring its pathophysiological function in vivo. Our previous studies indicated that expression of APOM could be regulated by platelet activating factor (PAF), transforming growth factors (TGF), insulin-like growth factor (IGF), leptin, hyperglycemia and etc., in vivo and/or in vitro. In the present study, we demonstrated that palmitic acid could significantly inhibit APOM gene expression in HepG2 cells. Further study indicated neither PI-3 kinase (PI3K) inhibitor LY294002 nor protein kinase C (PKC) inhibitor GFX could abolish palmitic acid induced down-regulation of APOM expression. In contrast, the peroxisome proliferator-activated receptor beta/delta (PPARß/δ) antagonist GSK3787 could totally reverse the palmitic acid-induced down-regulation of APOM expression, which clearly demonstrates that down-regulation of APOM expression induced by palmitic acid is mediated via the PPARß/δ pathway.

Decreased activities of apolipoprotein m promoter are associated with the susceptibility to coronary artery diseases.

The present study investigated the correlation among genetic polymorphisms of the proximal promoter region of apolipoprotein M (apoM) gene, the polymorphisms in relation to apoM expressions and the susceptibility to coronary artery diseases (CAD) in a Han Chinese population. Four common polymorphic sites, i.e., T-1628G, C-1065A, T-855C and T-778C, were confirmed, and a new deletion mutation C-724del was found, in 206 CAD patients and 209 non-CAD patients using direct DNA sequencing analyses. Occurrences of alleles T-1628G, T-855C and C-724del were significantly higher in CAD patients compared to non-CAD patients. Moreover we examined all these polymorphisms in relation to apoM expression by applying luciferase reporter assay. It demonstrated that constructs -855C and 724del showed obvious decreased luciferase activities, i.e., (0.93±0.15 vs. 2.11±0.15; P=0.012) and (1.13±0.25 vs. 2.11±0.15; P=0.009) respectively, which indicates these two polymorphisms could confer decreased apoM expressions. Meanwhile the occurrences of these two SNP were also significantly higher in the CAD patients than in non-CAD patients. It is therefore reasonable to speculate that down-regulated apoM expressions in relation to these polymorphisms may affect HDL and cholesterol metabolism in vivo and further influence the susceptibility to CAD, although the underlying mechanisms need further investigation.

Rosiglitazone enhances apolipoprotein M (Apom) expression in rat's liver.

Apolipoprotein M (APOM) has been suggested as a vasculoprotective constituent of high density lipoprotein (HDL), which plays a crucial role behind the mechanism of HDL-mediated anti-atherosclerosis. Previous studies demonstrated that insulin resistance could associate with decreased APOM expressions. In agreement with our previous reports, here, we further confirmed that the insulin sensitivity was also reduced in rats treated with high concentrations of glucose; such effect could be reversed by administration of rosiglitazone, a peroxisome proliferator-activated receptor-γ (PPARγ). The present study shows that Apom expression is significantly affected by either rosiglitazone or hyperglycemia alone without cross interaction with each other, which indicates that the pathway of Apom expression regulating by hyperglycemia might be differed from that by rosiglitazone. Further study indicated that hyperglycemia could significantly inhibit mRNA levels of Lxrb (P=0.0002), small heterodimer partner 1 (Shp1) (P<0.0001), liver receptor homologue-1 (Lrh1) (P=0.0012), ATP-binding cassette transporter 1 (Abca1) (P=0.0012) and Pparb/d (P=0.0043). Two-way ANOVA analysis demonstrated that the interactions between rosiglitazone and infusion of 25% glucose solution on Shp1 (P=0.0054) and Abca1 (4E, P=0.0004) mRNA expression was statistically significant. It is concluded that rosiglitazone could increase Apom expression, of which the detailed mechanism needs to be further investigated. The downregulation of Apom by hyperglycemia might be mainly through decreasing expression of Pparg and followed by inhibiting Lxrb in rats.

Surufatinib-induced renal thrombotic microangiopathy: first case report and review of literature.

Angiogenesis inhibitors such as tyrosine kinase inhibitors (TKIs) are common therapeutics currently used to treat oncologic disease. Surufatinib is a novel, small-molecule multiple receptor TKI approved by the National Medical Products Administration (NMPA) for the treatment of progressive, advanced, and well-differentiated pancreatic and extrapancreatic neuroendocrine tumours (NETs). Thrombotic microangiopathy (TMA) is a well-documented complication of TKIs targeting the VEGF-A/VEGFR2 signalling pathway. Here, we describe a 43-year-old female patient with biopsy-proven TMA and nephrotic syndrome due to surufatinib treatment for adenoid cystic carcinoma. Histological lesions included glomerular endothelial swelling, widening of subendothelial spaces, mesangiolysis, and double contour, which caused nephrotic proteinuria. Effective management was achieved by drug withdrawal and oral anti-hypertensive regents. The management of surufatinib-related nephrotoxicity without compromising its anticancer effects is challenging. Hypertension and proteinuria must be closely monitored during drug use to reduce or stop the dose in a timely manner before severe nephrotoxicity occurs.

In-frame deletion of SMC5 related with the phenotype of primordial dwarfism, chromosomal instability and insulin resistance.

BACKGROUND: SMC5/6 complex plays a vital role in maintaining genome stability, yet the relationship with human diseases has not been described. METHODS: SMC5 variation was identified through whole-exome sequencing (WES) and verified by Sanger sequencing. Immunoprecipitation, cytogenetic analysis, fluorescence activated cell sorting (FACS) and electron microscopy were used to elucidate the cellular consequences of patient's cells. smc5 knockout (KO) zebrafish and Smc5K371del knock-in mouse models were generated by CRISPR-Cas9. RNA-seq, quantitative real-time PCR (qPCR), western blot, microquantitative computed tomography (microCT) and histology were used to explore phenotypic characteristics and potential mechanisms of the animal models. The effects of Smc5 knockdown on mitotic clonal expansion (MCE) during adipogenesis were investigated through Oil Red O staining, proliferation and apoptosis assays in vitro. RESULTS: We identified a homozygous in-frame deletion of Arg372 in SMC5, one of the core subunits of the SMC5/6 complex, from an adult patient with microcephalic primordial dwarfism, chromosomal instability and insulin resistance. SMC5 mutation disrupted its interaction with its interacting protein NSMCE2, leading to defects in DNA repair and chromosomal instability in patient fibroblasts. Smc5 KO zebrafish showed microcephaly, short length and disturbed glucose metabolism. Smc5 depletion triggers a p53-related apoptosis, as concomitant deletion of the p53 rescued growth defects phenotype in zebrafish. An smc5K371del knock-in mouse model exhibited high mortality, severe growth restriction and fat loss. In 3T3-L1 cells, the knockdown of smc5 results in impaired MCE, a crucial step in adipogenesis. This finding implies that defective cell survival and differentiation is an important mechanism linking growth disorders and metabolic homeostasis imbalance.

Lessons from 17ß-HSD3 deficiency: Clinical spectrum and complex molecular basis in Chinese patients.

17ß-Hydroxysteroid dehydrogenase type 3 (17ß-HSD3) deficiency is rarely reported in Chinese patients with 46, XY disorders of sexual development (DSD). Seven subjects with 17ß-HSD3 deficiency were identified from 206 Chinese 46, XY DSD patients using targeted next-generation sequencing (NGS). Serum AD and T levels were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). In silico and functional studies were performed to evaluate the enzymatic activity impairment of HSD17B3 variants. A minigene assay was performed in an exonic splicing variant. Our results showed that four novel and five reported HSD17B3 variants were identified in 7 unrelated patients. The patients showed cryptic presentation during childhood and classical virilization after puberty with T/AD ratio< 0.4. A heterozygous large deletion from the 5'UTR to exon 1 was identified in a patient with a monoallelic variant of p.N130S. Although predicted to be 'likely pathogenic', only p. S232P and p. S160F drastically reduced the enzymatic activity of 17ß-HSD3. A previously reported 'missense' variant c 0.277 G>A (p. E93K) was revealed to have no impact on enzyme activity but resulted in aberrant splicing of exon 3 and was reclassified as an exonic splicing variant. In our study, one nonsense, one exonic splicing, one deletion, one large deletion and five missense variants were detected in patients with 17ß-HSD3 deficiency, expanding the clinical and molecular profile of this disorder. In silico analysis should be cautiously interpreted when the heredity pattern and functional study are inconsistent.

Rare Variant in Metallothionein 1E Increases the Risk of Type 2 Diabetes in a Chinese Population.

OBJECTIVE: To uncover novel targets for the treatment of type 2 diabetes (T2D) by investigating rare variants with large effects in monogenic forms of the disease. RESEARCH DESIGN AND METHODS: We performed whole-exome sequencing in a family with diabetes. We validated the identified gene using Sanger sequencing in additional families and diabetes- and community-based cohorts. Wild-type and variant gene transgenic mouse models were used to study the gene function. RESULTS: Our analysis revealed a rare variant of the metallothionein 1E (MT1E) gene, p.C36Y, in a three-generation family with diabetes. This risk allele was associated with T2D or prediabetes in a community-based cohort. MT1E p.C36 carriers had higher HbA1c levels and greater BMI than those carrying the wild-type allele. Mice with forced expression of MT1E p.C36Y demonstrated increased weight gain, elevated postchallenge serum glucose and liver enzyme levels, and hepatic steatosis, similar to the phenotypes observed in human carriers of MT1E p.C36Y. In contrast, mice with forced expression of MT1E p.C36C displayed reduced weight and lower serum glucose and serum triglyceride levels. Forced expression of wild-type and variant MT1E demonstrated differential expression of genes related to lipid metabolism. CONCLUSIONS: Our results suggest that MT1E could be a promising target for drug development, because forced expression of MT1E p.C36C stabilized glucose metabolism and reduced body weight, whereas MT1E p.C36Y expression had the opposite effect. These findings highlight the importance of considering the impact of rare variants in the development of new T2D treatments.

Estrogen upregulates hepatic apolipoprotein M expression via the estrogen receptor.

Apolipoprotein M (apoM) is present predominantly in high-density lipoprotein (HDL) in human plasma, thus possibly involved in the regulation of HDL metabolism and the process of atherosclerosis. Although estrogen replacement therapy increases serum levels of apoAI and HDL, it does not seem to reduce the cardiovascular risk in postmenopausal women. Therefore, we investigated the effects of estrogen on apoM expression in vitro and in vivo. HepG2 cells were incubated with different concentrations of estrogen with or without the estrogen receptor antagonist, fulvestrant, and apoM expression in the cells was determined. Hepatic apoM expression and serum levels of apoM were also determined in normal and in ovariectomized rats treated with either placebo or estradiol benzoate, using sham operated rats as controls. Estrogen significantly increased mRNA levels of apoM and apoAI in HepG2 cell cultures in a dose- and time-dependent manner; the upregulation of both apolipoproteins was fully abolished by addition of estrogen receptor antagonist. In normal rats, estrogen treatment led to an increase in plasma lipid levels including HDL cholesterol, a marked upregulation of apoM mRNA and a significant increase in serum levels of apoM. The same pattern of regulation was found in ovariectomized rats treated with estrogen. Thus, estrogen upregulates apoM expression both in vivo and in vitro by mechanism(s) involving the estrogen receptor.

ABCA1 upregulating apolipoproein M expression mediates via the RXR/LXR pathway in HepG2 cells.

We have previously reported that liver X receptor (LXR) agonist, TO901317, could significantly inhibit hepatic apolipoprotein M (apoM) expression. It has been reported that TO901317 could activate the ATP-binding cassette transporter A1 (ABCA1) that mediates cholesterol efflux to the lipid-poor apoAI, which is an essential step for the high-density lipoprotein (HDL) formation. It is unknown if ABCA1 may regulate hepatic apoM expression. In the present study, HepG2 cells were cultured with the synthetic LXR agonists, TO901317 or GW3965 in the presence or absence of ABCA1 antagonist, disodium 4,4'-diisothiocyanatostilbene- 2,2'-disulfonate (DIDS). The mRNA levels of ABCA1, apoM and liver receptor homolog-1 (LRH-1) determined by the real-time RT-PCR. It demonstrated that both TO901317 and GW3965 could significantly enhance ABCA1 expression, and simultaneously, inhibit LRH1 expression. However, TO901317 alone could significantly inhibit apoM expression, while GW3965 alone did not influence apoM expression. ABCA1 antagonist, DIDS, have no effects on GW3965 induced upregulation of ABCA1 and downregulation of LRH1. However, apoM mRNA level was significantly decreased when the cells cultured with GW3965 together with DIDS. The present study demonstrated that apoM expression could be elevated by ABCA1 via the RXR/LXR pathway and LRH1 does not involve in the regulation of apoM by the activation of ABCA1, although the direct regulative pathway(s) between ABCA1 and apoM gene is still unknown yet. The detailed mechanism needs further investigation.

Association Between Single Nucleotide Polymorphisms of miRNAs and Gastric Cancer: A Scoping Review.

Background: Gastric cancer (GC) is the third leading cause of cancer-related mortality worldwide, and single nucleotide polymorphisms (SNPs) in microRNAs (miRNAs) are believed to affect the occurrence and progression of cancer by altering the expression and biological functions of miRNAs. Methods: The present scoping review was designed to evaluate and discuss microRNA SNPs (miR-SNPs) that have been found to be associated with GC in the following two contexts: (1) the biological effects on GC based on SNP localization; and (2) the associations between miRNA-SNPs and clinical factors (susceptibility, tumor size, metastasis, overall survival, and prognosis) of GC. Results and Conclusions: Information on miRNAs was collected, including the SNPs, their proven target genes, and the possible impact of the SNPs on GC outcome. Our findings suggest an etiological or modifying role for multiple miRNA SNPs (miR-499, miR-146a, miR-149, miR-148, miR-27a, miR-608, miR-196a-2) in GC and its progression. The findings of this study reinforce the multiple roles of miRNA SNPs in GC.

Role of DTL in Hepatocellular Carcinoma and Its Impact on the Tumor Microenvironment.

Background: The crucial role of DTL has been previously implicated in genomic stability; however, its prognostic value and its relation with tumor immunity in hepatocellular carcinoma (HCC) remain to be further explored. Methods: Transcriptional and mutational datasets as well as clinical information were retrieved from the GEO, ICGC, and TCGA databases. Differentially expressed genes (DEGs) were obtained from the comparison of DTLhigh and DTLlow expression groups of the TCGA-HCC cohort. Those genes were under KEGG and gene ontology (GO) analyses to decipher the influence of the DTL gene on the biological behavior of HCC tumor cells. The survival status and mutational characteristics of patients according to DTL levels were depicted and analyzed. The DTL overexpression in HCC and its impact on prognosis were further confirmed by a cohort of 114 HCC patients (validation cohort). The TIMER, GEPIA, and TISIDB databases were adopted to investigate the potential relations between DTL levels and the status of immune cells, as well as immune cell infiltrations. Results: The DTL gene is overexpressed in tumor tissues compared with distant non-malignant liver tissues, and DTL overexpression in HCC would enhance the HCC cells in the activities of cell cycle and division. HCC patients with high DTL expression have unfavorable clinical outcomes and harbor more somatic mutations than those with low DTL expression, and multivariate analysis also revealed that DTL overexpression could act as an independent biomarker for prognosis. Moreover, the DTL gene was positively linked to marker sets of infiltrating activated CD8+ and CD4+ T cells; however, these cells demonstrated to be functionally exhausted. Conclusions: Patients with a DTL overexpression phenotype in HCC have poorer prognosis than those in the DTLlow group due to the role of the DTL gene in the process of pro-cell proliferation, accompanied by the immunosuppressive microenvironment and T cell exhaustion.

MAFG-AS1 is a prognostic biomarker and facilitates prostate cancer progression.

Long Noncoding RNAs (LncRNAs) have recently been identified as key regulator in tumor progression. The LncRNA MAFG-AS1 has been reported to facilitate the progression of multiple cancers, however, its role in prostate cancer is still unknown. Here, we reported that MAFG-AS1 was upregulated in prostate cancer. Importantly, high expression of MAFG-AS1 indicated advanced stage prostate cancer. Univariate and Multivariate Cox regression analyses showed that high MAFG-AS1 expression was independently correlated with poor progression-free interval (PFI). According to the result of The Cancer Genome Atlas (TCGA) database and tissue microarray, high MAFG-AS1 expression indicated a poor prognosis in prostate cancer patients. In addition, gene functional enrichment analysis revealed that MAFG-AS1 may be involved in ribosome biogenesis, ribonucleoprotein complex subunit organization, ribonucleoprotein complex assembly, rRNA metabolic process, structural constituent of ribosome, and ribonucleoprotein complex binding. Furthermore, MAFG-AS1 knockdown by siRNA markedly impaired prostate cancer cell proliferation, migration, and invasion.

ELK1-mediated YTHDF1 drives prostate cancer progression by facilitating the translation of Polo-like kinase 1 in an m6A dependent manner.

Background: N6-methyladenosine (m6A) is one of the most prevalent mRNA modifications in mammals, and it regulates the fate of modified RNA transcripts. In the current study, we aimed to elucidate the role of YTH m6A RNA-binding protein 1 (YTHDF1), a "reader" of m6A modification, in prostate cancer tumorigenesis. Methods: We employed a multi-omics approach to detect the direct target of YTHDF1 upon manipulation of YTHDF1 expression in prostate cancer cells. Expression of YTHDF1 was also evaluated in human prostate tumors and either adjacent or paired normal tissues. Additionally, in vivo tumor growth and metastasis experimental assays were performed to evaluate the role of YTHDF1 in tumorigenesis. Finally, luciferase reporter assays and Chromatin immunoprecipitation (ChIP) were conducted to elucidate the transcriptional regulators of YTHDF1. Results: We demonstrated that polo-like kinase 1 (PLK1) is a direct target of YTHDF1. YTHDF1 facilitated the translation efficiency of PLK1 in an m6A-dependent manner by identifying the m6A-modified PLK1 mRNA and subsequently promoted the hyperactivation of the PI3K/AKT signaling pathway. Moreover, our results indicated that YTHDF1 was upregulated in prostate cancer tissue and that high YTHDF1 expression was associated with adverse prognosis in patients with prostate cancer. Furthermore, upregulation of YTHDF1 promoted prostate cancer tumorigenesis and metastasis in vitro and in vivo. Additionally, dysregulation of ETS transcription factor ELK1 activated the transcription of YTHDF1 by directly binding to its promoter region. Conclusions: Collectively, our findings suggest that the ELK1/YTHDF1/PLK1/PI3K/AKT axis is critical for prostate cancer progression and may serve as a potential therapeutic target for prostate cancer treatment.

E2F transcription factor 2-activated DLEU2 contributes to prostate tumorigenesis by upregulating serum and glucocorticoid-induced protein kinase 1.

Long noncoding RNAs (lncRNAs) participate in biological processes in multiple types of tumors. However, the regulatory patterns of lncRNAs in prostate cancer remain largely unclear. Here, we evaluated the expression and roles of the lncRNA DLEU2 in prostate cancer. Our results showed that DLEU2 was upregulated in advanced prostate cancer tissues. Patients with prostate cancer displaying high expression of DLEU2 had a poor prognosis. Moreover, we demonstrated that overexpression of DLEU2 facilitated the proliferation, migration, and invasion of prostate cancer in vitro. Mechanistically, DLEU2 promoted serum and glucocorticoid-induced protein kinase 1 (SGK1) expression by acting as an miR-582-5p sponge, and the transcription of DLEU2 was activated by the dysregulation of E2F transcription factor 2 (E2F2) expression in prostate cancer. Furthermore, knockdown of DLEU2 attenuated prostate cancer tumorigenesis in vivo. Notably, these findings suggested that E2F2-activated DLEU2 may function as a competing endogenous RNA to facilitate prostate cancer progression by targeting the miR-582-5p/SGK1 axis.

Mutation Screening and Functional Study of SLC26A4 in Chinese Patients with Congenital Hypothyroidism

Objective: Defects in the human solute carrier family 26 member 4 (SLC26A4) gene are reported to be one of the causes of congenital hypothyroidism (CH). We aimed to identify SLC26A4 mutations in Chinese patients with CH and analyze the function of the mutations. Methods: Patients with primary CH were screened for 21 CH candidate genes mutations by targeted next-generation sequencing. All the exons and exon-intron boundaries of SLC26A4 were identified and analyzed. The function of six missense mutation in SLC26A4 were further investigated in vitro. Results: Among 273 patients with CH, seven distinct SLC26A4 heterozygous mutations (p.S49R, p.I363L, p.R409H, p.T485M, p.D661E, p.H723R, c.919-2A>G) were identified in 10 patients (3.66%, 10/273). In vitro experiments showed that mutation p.I363L, p.R409H, p.H723R affect the membrane location and ion transport of SLC26A4, while p.S49R did not. Mutation p.T485M and p.D661E only affected ion transport, but had no effect on the membrane location. Conclusion: The prevalence of SLC26A4 mutations was 3.66% in Chinese patients with CH. Five mutations (p.I363L, p.R409H, p.T485M, p.D661E and p.H723R) impaired the membrane location or ion transport function of SLC26A4, suggesting important roles for Ile363, Arg409, Thr485, Asp661, and His723 residues in SLC26A4 function. As all variants identified were heterozygous, the pathogenesis of these patients cannot be explained, and the pathogenesis of these patients needs further study.