Circ_0027791 contributes to the growth and immune evasion of hepatocellular carcinoma via the miR-496/programmed cell death ligand 1 axis in an m6A-dependent manner.

Emerging evidence indicates the critical roles of circular RNAs in the development of multiple cancers, containing hepatocellular carcinoma (HCC). Herein, our present research reported the biological function and mechanism of circ_0027791 in HCC progression. Circ_0027791, microRNA-496 (miR-496), programmed cell death ligand 1 (PDL1), and methyltransferase-like 3 (METTL3) levels were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Cell viability, proliferation, invasion, and sphere formation ability were detected using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, 5-ethynyl-2'-deoxyuridine, transwell, and sphere formation assays. Macrophage polarization was detected using flow cytometry assay. To understand the role of circ_0027791 during the immune escape, HCC cells were cocultured with peripheral blood mononuclear cells or cytokine-induced killer (CIK) cells in vitro. A xenograft mouse model was applied to assess the function of circ_0027791 in vivo. After prediction using circinteractome and miRDB, the binding between miR-496 and circ_0027791 or PDL1 was validated based on a dual-luciferase reporter assay. Interaction between METTL3 and circ_0027791 was determined using methylated RNA immunoprecipitation (MeRIP)-qPCR, RIP-qPCR, and RNA pull-down assays. Circ_0027791, PDL1, and METTL3 expression were upregulated, and miR-496 was decreased in HCC patients and cells. Moreover, circ_0027791 knockdown might repress proliferation, invasion, sphere formation, M2 macrophage polarization, and antitumor immune response. Circ_0027791 knockdown repressed HCC tumor growth in vivo. In mechanism, circ_0027791 functioned as a sponge for miR-496 to increase PDL1 expression. In addition, METTL3 mediated the m6A methylation of circ_0027791 and stabilized its expression. METTL3-induced circ_0027791 facilitated HCC cell progression partly regulating the miR-496/PDL1 axis, which provided a new prognostic and therapeutic marker for HCC.

TruScreen detection of cervical tissues for high-risk human papillomavirus-infected women during the COVID-19 pandemic.

Aims: To evaluate the efficacy of TruScreen (TS01) for high-risk human papillomavirus (HR-HPV) women compared with other methods in reducing colposcopy referral rates in hospitals. Methods: A single-center, prospective, case-control study was conducted from December 2019 to June 2020. Results: Among 139 (46.2%) HR-HPV-positive patients, 58 were CIN1, 52 were CIN2-3 and 29 had cervical cancer (n = 29). The sensitivity and specificity of detecting CIN2+ by TS01, colposcopy and HPV16/18 testing were 96.3% and 46.4%, 85.2% and 40.5% and 59.3% and 74.1%, respectively. The highest sensitivity was 96.3% at HPV16/18 and TS01 (each positive results), and the highest specificity was 83.6% at HPV16/18 and TS01 (both positive) for CIN2+ compared with the other methods. Conclusion: TS01 is a noninvasive screening method and can be used to diagnose cervical lesions quickly. It is especially suitable as triage tool for HR-HPV-positive women facing SARS-CoV-2 exposure and infection risks in hospital.

Cytotoxic polyprenylated phloroglucinol derivatives from Hypericum elodeoides Choisy modulating the transactivation of RXRα.

Hyperelodione D (1), an undescribed polyprenylated phloroglucinol derivative possessing 6/6/5/5 fused tetracyclic core, together with hyperelodiones E-F (2-3), two unreported analogues bearing 6/5/5 fused tricyclic structure, were isolated from Hypericum elodeoides Choisy. Their planar structures were elucidated by spectroscopic analysis (HRESIMS, 1D and 2D NMR) and their absolute configurations were determined by comparison of experimental and calculated ECD data. The cytotoxicity and retinoid X receptor-α (RXRα) related activities of the isolates were evaluated and the plausible biogenetic pathways of 1-3 were proposed.

Serum sCD14 as a Biomarker for Significant Liver Inflammation in Chronic Hepatitis B Patients with Normal or Mildly Elevated ALT.

BACKGROUND: CD14 is a pattern recognition receptor constitutively expressed in different types of immune cells, either in a membrane-anchored (mCD14) or in a soluble (sCD14) form. This study investigated whether hepatic CD14 expression levels were correlated with the grades of liver inflammation as well as the potential usefulness of serum sCD14 as a biomarker for predicting liver inflammation in chronic hepatitis B (CHB) patients with normal or mildly elevated ALT. METHODS: A total of 216 treatment-naive CHB patients with normal or mildly elevated ALT who underwent liver biopsy were recruited. Hepatic expression level of CD14 was measured using immunohistochemistry and real-time PCR. Serum sCD14 concentrations were determined with an enzyme-linked immunosorbent assay. Correlations between hepatic CD14, serum sCD14, and liver inflammation grade were analyzed. Univariate and multivariate analysis were performed to identify significant liver inflammation-associated factors. The receiver operating characteristic curve was used to assess the discriminating power of serum sCD14 to significant liver inflammation in CHB patients with normal or mildly elevated ALT. RESULTS: Both hepatic expression levels of CD14 and serum sCD14 concentrations significantly increased with the aggravation of liver inflammation. Moreover, hepatic expression levels of CD14, serum sCD14 concentrations, and liver inflammation grades were positively correlated with each other. Three parameters including alkaline phosphatase (ALP), neutrophil, and sCD14 were identified as independent predictors of significant liver inflammation. Subsequently, a diagnostic equation named model-sCD14 was developed incorporating sCD14 and other variables (ALP and neutrophils) with p < 0.05 in multivariate logistic analysis. The area under receiver operating characteristic curve (AUC) of sCD14 for predicting significant liver inflammation was 0.788 and the optimal cutoff was 27.14 ng/mL, with a sensitivity of 66.67%, a specificity of 81.70%, positive predictive value of 60.01%, and negative predictive value of 85.62%. When sCD14 was replaced by model-sCD14, the AUC value increased from 0.788 to 0.843 (z = 2.311, p = 0.021), with sensitivity of 77.78%, specificity of 77.12%, positive predictive value of 58.33%, and negative predictive value of 89.39%. CONCLUSIONS: Serum sCD4 has the potential to discriminate significant liver inflammation from CHB patients with normal or mildly increased ALT levels.

Medulloblastoma exome sequencing uncovers subtype-specific somatic mutations.

Medulloblastomas are the most common malignant brain tumours in children. Identifying and understanding the genetic events that drive these tumours is critical for the development of more effective diagnostic, prognostic and therapeutic strategies. Recently, our group and others described distinct molecular subtypes of medulloblastoma on the basis of transcriptional and copy number profiles. Here we use whole-exome hybrid capture and deep sequencing to identify somatic mutations across the coding regions of 92 primary medulloblastoma/normal pairs. Overall, medulloblastomas have low mutation rates consistent with other paediatric tumours, with a median of 0.35 non-silent mutations per megabase. We identified twelve genes mutated at statistically significant frequencies, including previously known mutated genes in medulloblastoma such as CTNNB1, PTCH1, MLL2, SMARCA4 and TP53. Recurrent somatic mutations were newly identified in an RNA helicase gene, DDX3X, often concurrent with CTNNB1 mutations, and in the nuclear co-repressor (N-CoR) complex genes GPS2, BCOR and LDB1. We show that mutant DDX3X potentiates transactivation of a TCF promoter and enhances cell viability in combination with mutant, but not wild-type, ß-catenin. Together, our study reveals the alteration of WNT, hedgehog, histone methyltransferase and now N-CoR pathways across medulloblastomas and within specific subtypes of this disease, and nominates the RNA helicase DDX3X as a component of pathogenic ß-catenin signalling in medulloblastoma.

α5-GABAA receptors negatively regulate MYC-amplified medulloblastoma growth.

Neural tumors often express neurotransmitter receptors as markers of their developmental lineage. Although these receptors have been well characterized in electrophysiological, developmental and pharmacological settings, their importance in the maintenance and progression of brain tumors and, importantly, the effect of their targeting in brain cancers remains obscure. Here, we demonstrate high levels of GABRA5, which encodes the α5-subunit of the GABAA receptor complex, in aggressive MYC-driven, "Group 3" medulloblastomas. We hypothesized that modulation of α5-GABAA receptors alters medulloblastoma cell survival and monitored biological and electrophysiological responses of GABRA5-expressing medulloblastoma cells upon pharmacological targeting of the GABAA receptor. While antagonists, inverse agonists and non-specific positive allosteric modulators had limited effects on medulloblastoma cells, a highly specific and potent α5-GABAA receptor agonist, QHii066, resulted in marked membrane depolarization and a significant decrease in cell survival. This effect was GABRA5 dependent and mediated through the induction of apoptosis as well as accumulation of cells in S and G2 phases of the cell cycle. Chemical genomic profiling of QHii066-treated medulloblastoma cells confirmed inhibition of MYC-related transcriptional activity and revealed an enrichment of HOXA5 target gene expression. siRNA-mediated knockdown of HOXA5 markedly blunted the response of medulloblastoma cells to QHii066. Furthermore, QHii066 sensitized GABRA5 positive medulloblastoma cells to radiation and chemotherapy consistent with the role of HOXA5 in directly regulating p53 expression and inducing apoptosis. Thus, our results provide novel insights into the synthetic lethal nature of α5-GABAA receptor activation in MYC-driven/Group 3 medulloblastomas and propose its targeting as a novel strategy for the management of this highly aggressive tumor.

Distribution, enrichment mechanisms, and health risk assessment of high-fluorine groundwater in the Yudong Plain, Henan Province, China.

The Yudong Plain is in the eastern part of Henan Province, China, where there is little rain and high evaporation. Compared to other areas in Henan Province, the groundwater fluorine content is generally high, which affects the health of residents. Based on the systematic analysis of water chemistry data of shallow and mid-depth groundwater samples in the Yudong Plain, the causes of shallow and mid-depth high-fluorine groundwater in the Yudong Plain were explored using mathematical statistics, spatial interpolation, and ion ratios. The results show that the fluorine contents of both shallow and mid-depth groundwater in the study area are high. The shallow samples had fluorine contents ranging from 0.1 to 4.89 mg/L, with an exceedance rate of 48% and an average content of 1.15 mg/L. The fluorine content of mid-depth samples ranged from 0.14 to 3.32 mg/L, with an exceedance rate of 68% and an average content of 1.33 mg/L. The shallow high-fluorine groundwater is mainly distributed in the central low-lying area, and its main hydrochemical type is HCO3-Na·Mg; the mid-depth high-fluorine groundwater is mainly distributed in strips in the north and east of the study area, and its main water chemistry type is HCO3-Na. Fluorine enrichment in shallow groundwater in the study area is controlled by rock weathering, evaporation concentration, and competitive adsorption, while leaching and dissolution of fluorine-containing minerals in sedimentary strata are the main factors influencing fluorine enrichment in mid-depth groundwater. The results of the human health risk assessment (HRA) showed that the mean non-carcinogenic hazard quotients (HQs) in shallow groundwater were 0.95, 0.64, 0.57, and 0.55 for infants, children, teenagers, and adults, respectively, while the mean non-carcinogenic HQs in mid-depth groundwater were 1.11, 0.74, 0.66, and 0.63, respectively. The study provides a scientific basis for the rational development and use of groundwater in the area and offers theoretical support for the prevention and control of groundwater pollution.

Occurrence, distribution, and ecological risk assessment of pharmaceuticals and personal care products in the surface water of the middle and lower reaches of the Yellow River (Henan section).

Pharmaceuticals and personal care products (PPCPs) are commonly seen emerging organic contaminants in aquatic environments. The transects for the occurrence and distribution of 24 PPCPs along the middle and lower reaches of the Yellow River (Henan section) were investigated in this study. All 24 targeted compounds were detected in surface water, with concentrations in the range from not detected (ND) to 527.4 ng/L. Among these PPCPs, caffeine is found to have the highest concentration and its detection frequency is 100%. The total PPCP concentration ranged from 136 ng/L to 916 ng/L (median, 319.5 ng/L). Spatial analysis showed that the pollution level of PPCPs in the trunk stream was lower than that in most tributaries in the middle and lower reaches of the Yellow River (Henan section). The ecotoxicological risk assessment indicated that norfloxacin, azithromycin, estrone, and triclosan posed high risks to aquatic organisms (RQ > 1), roxithromycin and oxytetracycline imposed moderate risks (0.1 ≤ RQ < 1), and the tributary Jindi River had the highest mixed risk (MRQ = 222).

Low Serum Soluble Transferrin Receptor Levels Are Associated with Poor Prognosis in Patients with Hepatitis B Virus-Related Acute-on-Chronic Liver Failure.

Iron metabolism disorder is closely related to acute-on-chronic liver failure (ACLF). This study was conducted to analyze the serum levels of soluble transferrin receptor (sTfR) in hepatitis B virus (HBV)-related ACLF and to evaluate the predictive value of sTfR for the short-term prognosis of HBV-ACLF. A total of 359 patients, including 139 with HBV-ACLF, 103 with chronic hepatitis B (CHB), and 117 healthy controls (HCs), participated in this study. We measured serum levels of ferritin, transferrin, and sTfR using nephelometry and performed data analysis using SPSS software. Ferritin levels were significantly higher in HBV-ACLF patients (both P < 0.001), while transferrin and sTfR were significantly lower (all P < 0.001) than in patients with CHB and HCs. Spearman correlation analysis demonstrated that serum sTfR significantly correlated with the alanine aminotransferase (ALT) (r = -0.366, P < 0.001), aspartate aminotransferase (AST) (r = -0.322, P < 0.001), total bilirubin (TBIL) (r = -0.222, P = 0.009), alpha fetoprotein (AFP) (r = 0.329, P < 0.001), prothrombin time-international normalization ratio (PT-INR) (r = -0.428, P < 0.001), and model for end-stage liver disease (MELD) (r = -0.459, P < 0.001). Nonsurviving HBV-ACLF patients who died within 30 days had much lower serum sTfR levels than surviving patients (P < 0.001). Logistic regression analysis showed that decreased serum sTfR levels were independently associated with 30-day mortality in patients with HBV-ACLF (P = 0.003). Receiver operating characteristic (ROC) curve analysis for predicting 30-day mortality showed that the area under the curve (AUC) for serum sTfR was 0.813 (95% CI: 0.738-0.874, P < 0.001). This was similar to that of the MELD score (AUC = 0.812, 95% CI: 0.737-0.873, P < 0.001). Serum sTfR combined with MELD score significantly improved the predictive capacity for 30-day mortality in patients with HBV-ACLF (AUC = 0.871, 95% CI: 0.803-0.922, P < 0.001). Kaplan-Meier analysis revealed that the overall cumulative 30-day mortality rate was significantly higher in patients with serum sTfR levels ≤ 0.55 mg/L compared to those with serum sTfR levels > 0.55 mg/L (P < 0.001).

Occurrence, distribution, and ecological risk assessment of artificial sweeteners in surface and ground waters of the middle and lower reaches of the Yellow River (Henan section, China).

As a new class of water contaminants, artificial sweeteners (ASs) have attracted much attention due to their environmental persistence and potential adverse effects to human and the environment. This study systematically investigated the occurrence and distribution of four commonly used ASs in the effluent of wastewater treatment plants (WWTPs), surface water and groundwater in the middle and lower reaches of the Yellow River (Henan section). Sucralose (SUC) was dominant in WWTP effluents and had the highest mass loading. Acesulfame (ACE), cyclamate (CYC), saccharin (SAC), and SUC were consistently detected in surface water at concentrations ranging from 1.364 ng/L (CYC) to 7786 ng/L (ACE). Spatial analysis showed that the pollution level of ASs in the trunk stream was lower than that in most tributaries. The total concentrations of ASs detected in surface water ranged between 308.7 and 10,498 ng/L, while in groundwater, the total concentration of ASs detected was between ND-4863 ng/L. ACE and SUC are the main pollutants in surface water and groundwater within this survey area. The risk assessment showed that the risks of the four target ASs to aquatic organisms were negligible (risk quotient (RQ) values < 0.1), and the maximum risk quotient of the mixtures (MRQ) values of all rivers were all much less than 0.1.

Adsorption-desorption characteristics of typical heavy metal pollutants in submerged zone sediments: a case study of the Jialu section in Zhengzhou, China.

In recent years, the accumulation ability of heavy metals in sediment has become a key indicator for sediment pollution prevention and control. The adsorption-desorption processes of typical heavy metal pollutants in sediments under different conditions were explored and relied in this article. In addition, different binary competitive adsorption systems were designed to study the competitive adsorption properties of heavy metal contaminants, The quasi-secondary kinetic model simulated the adsorption kinetic process. The sediment adsorption rates for heavy metals were (in descending order) Cu, Pb, Cd, Zn. The Elovich equation simulated the desorption kinetics process better, and the sediment desorption rates for heavy metals were (in descending order) Cd, Cu, Zn, Pb. The average free adsorption energy E of heavy metals was within the range of 8-16 kJ∙mol-1. After the removal of organic matter, the ability of the sediment to sequester heavy metals decreases, The binary competitive adsorption results showed that the presence of interfering ions had the greatest effect on Cd and the least effect on Pb. The adsorption and desorption of the four heavy metals by the sediments in the submerged zone increased with the increase of temperature, and the ratio of desorption to adsorption also increased therewith: the adsorptions of heavy metals by the sediments were all spontaneous processes (under heat absorption reactions). The presence of organic matter can increase the ability of the sediment to sequester Cd, Pb, Cu, and Zn. Additionally, heavy metals exhibited significant selective adsorption properties.

Spatial distribution of heavy metal contaminants: The effects of water-sediment regulation in the Henan section of the Yellow River.

Water-sediment regulation (WSR) affects sediment transport in the middle and lower reaches of the Yellow River through periodic interception of sediment by dams and alteration of downstream flow rates, which leads to redistribution and recycling of elements. In this study, based on the evaluation of seven heavy metals (V, Cr, Ni, Co, Cu, Zn, and Cd) in water, sediment and suspended particulate matter (SPM) in the Henan section of the Yellow River, the effects of WSR on the redistribution and risk of release of metals to the downstream aquatic environment were investigated, and the range of impact and pollution sources were determined. Dissolved metals were well below guideline values for water quality, but Cd, Cr, and Cu were enriched in the sediments, especially in the reservoir, and the pollution load index (PLI) results indicated that the contamination in the study area remained very low. The level of contamination was decreased, and metals migrated downstream after WSR. The chemical speciation of metals indicates that anthropogenic input of metals occurs in upstream tributaries, and the risk of release of metals in the sediments increases after WSR, but the spatial distribution of the risk is more homogeneous. The distribution coefficient explains the distribution pattern of pollution, where SPM carries pollutants to the downstream while formed surface sediments through natural deposition during the sand-discharge stage. Based on geological and field investigations, upstream gold mining and downstream riverbank cultivation activities in the study area are potential sources of Cu and Cd pollution. These findings are crucial to the better understanding of patterns of metal release from artificial impoundments in river systems and provide a theoretical basis for ecological development in the Yellow River Basin.

Minimizing buried interfacial defects for efficient inverted perovskite solar cells.

Controlling the perovskite morphology and defects at the buried perovskite-substrate interface is challenging for inverted perovskite solar cells. In this work, we report an amphiphilic molecular hole transporter, (2-(4-(bis(4-methoxyphenyl)amino)phenyl)-1-cyanovinyl)phosphonic acid, that features a multifunctional cyanovinyl phosphonic acid group and forms a superwetting underlayer for perovskite deposition, which enables high-quality perovskite films with minimized defects at the buried interface. The resulting perovskite film has a photoluminescence quantum yield of 17% and a Shockley-Read-Hall lifetime of nearly 7 microseconds and achieved a certified power conversion efficiency (PCE) of 25.4% with an open-circuit voltage of 1.21 volts and a fill factor of 84.7%. In addition, 1-square centimeter cells and 10-square centimeter minimodules show PCEs of 23.4 and 22.0%, respectively. Encapsulated modules exhibited high stability under both operational and damp heat test conditions.

Heavy-Metal Speciation Distribution and Adsorption Characteristics of Cr (VI) in the Soil within Sewage Irrigation Areas.

While sewage irrigation relieves water shortages in Northern China, its excessive application triggers a series of environmental problems, such as heavy-metal pollution. Soil profile and river sediment profile samples from the sewage irrigation area (SIA) were collected by selecting the farmlands in which sewage irrigation activity has been reported since the 1960s, around Huiji River (HJR) and Huafei River (HFR) in Kaifeng, Henan Province, China, as research areas. In this study, the total amount of heavy metals (Cr, Cd, Pb, Mn, Zn, and Ni) and the heavy-metal speciation analysis using the modified BCR sequential extraction method were used to evaluate the impacts of wastewater on agricultural soils and the potential risk. Furthermore, the least contaminated Cr (VI) was selected for the study of adsorption characteristics to determine the environmental capacity of soils for heavy metals when the composition of wastewater changes under long-term effluent irrigation conditions. The results show that: (1) the concentrations of heavy metals in soil continuously decreased with depth, while the opposite was observed in sediment, reflecting the continuous improvement in water quality over the historical period; (2) In the topsoil, the mean concentrations (mg·kg−1) in rank order are as follows: Mn (588.68) > Zn (284.21) > Pb (99.76) > Cr (76.84) > Ni (34.71) > Cd (3.25), where Cd exceeded the control value by 3.15 times around HFR, and sediment samples also showed higher heavy metal concentrations in HFR than in HJR; (3) Speciation distribution and risk assessment code (RAC) indicate that Mn and Cd were at medium risk and that Cd warrants attention due to its being a non-essential toxic element in humans; (4) The adsorption rates of soil in various layers in different profiles within SIAs for Cr (VI) gradually increased with the increasing initial content of Cr (VI). Among the three isothermal adsorption models, the fit result obtained by the Langmuir equation was superior to those obtained by the Freundlich equation and the linear equation.

Suppression of Nrdp1 toxicity by Parkin in Drosophila models.

Nrdp1 is a RING finger ubiquitin E3 ligase that interacts with Parkin, and promotes the degradation of Parkin, a causative protein for early onset Autosomal Recessive Juvenile Parkinsonism (AR-JP). To investigate if Nrdp1 plays a role in the pathogenesis of Parkinson's disease, we generated transgenic Drosophila that expressed Drosophila Nrdp1 (dNrdp1) and dNrdp1(D56V), an aspartic acid to valine mutant at residue 56 that disrupts its ring finger domain, resulting in impaired capacity to degrade its substrate ErbB3. Our data show that a pan-neuronal expression of transgenic dNrdp1 but not dNrdp1(D56V) mutant leads to the loss of dopaminergic neurons in brains, resulting in reduction of dopamine production. These flies also manifested decreased flight ability. Co-expression of human Parkin (hParkin) provides protection against toxicity induced by over-expression of dNrdp1, reversing the effects of dNrdp1 on death of dopaminergic neurons, reduction of dopamine production, and decreased flight ability. Taken together, we conclude that Nrdp1 plays a role in neurodegeneration and could be potentially targeted as a therapeutic strategy for Parkinson's disease.

Occurrence, sources and fate of pharmaceuticals and personal care products and artificial sweeteners in groundwater.

Groundwater is considered as the main source for supplying the public drinking water in many countries and regions; however, pharmaceuticals and personal care products (PPCPs) and artificial sweeteners (ASs) found in groundwater can exert harmful effects on human health and aquatic ecosystems, and therefore, they are of persistent concern. The recent data on the occurrence of a series of PPCPs (including antibiotics, excitants and lipid regulators) and ASs often detected in groundwater are reviewed, in which the PPCPs and ASs occur in groundwater at the concentration from several nanograms to several micrograms per litre. In addition, the spatio-temporal distribution characteristics of PPCPs and ASs are discussed and the main sources and possibly pollution pathways of PPCPs and ASs in groundwater are summarised and analysed. Additionally, the adsorption, migration and degradation of PPCPs and ASs in underground environments are evaluated. Due to the long residence time in groundwater, pollutants are likely to threaten the freshwater body for decades under certain conditions. Therefore, according to the current level of pollution, it is necessary to improve and enhance the supervision on PPCP and AS pollutants and prevent and control groundwater pollution.

The diagnostic value of miR-145 and miR-205 in patients with cervical cancer.

OBJECTIVE: To investigate the diagnostic value of miRNA-145 (miR-145) and miRNA-205 (miR-205) in cervical cancer patients. METHODS: Cervical tissue samples were collected from 144 patients diagnosed with and suspected to have cervical cancer in our hospital. Confirmed by pathology, 84 samples were obtained from cervical cancer patients and 60 samples were from patients with cervical intraepithelial neoplasia. Meanwhile, 30 patients with cervicitis were also selected, and the expression levels of miR-145, miR-205 and human papillomavirus (HPV) were detected in cervical lesions and normal cervical tissue. RESULTS: In comparison to normal cervical tissue, cervicitis and cervical intraepithelial neoplasia groups, the relative expression level of miR-145 was significantly lower, whereas the relative expression level of miR-205 was notably higher in the cervical cancer group, respectively (P<0.001). The area under the receiver operating characteristic (ROC) curve of miR-145 for diagnosis of cervical cancer in patients was 0.878, of which the sensitivity and the specificity were 0.905 and 0.822, respectively. The area under the ROC curve of miR-205 was 0.881, of which the sensitivity and the specificity was 0.869 and 0.889, respectively. Among all patients, the relative expression level of miR-145 was significantly lower while the relative expression level of miR-205 was considerably higher in HPV-positive patients than those of HPV-negative groups (P<0.001). Parauterine invasion, FIGO stage III-IV and lymphatic metastasis were considered as independent factors that affect the expression of miR-145. FIGO stage III-IV and lymphatic metastasis were independent factors affecting the expression of miR-205. CONCLUSION: The low expression level of miR-145 and the high expression level of miR-205 in patients with cervical cancer demonstrate a certain diagnostic value in cervical cancer. The expression level of miR-145 and miR-205 is correlated with HPV infection and cervical tumor malignancy.

AHNAK suppresses ovarian cancer progression through the Wnt/ß-catenin signaling pathway.

Globally, ovarian cancer is the 2nd most frequent cause of gynecologic-associated cancer fatalities among women. It has an unfavorable prognosis. There is a need to elucidate on the mechanisms involved in ovarian cancer progression and to identify novel cancer targets. We investigated and verified AHNAK contents in ovarian cancer tissues and corresponding healthy tissues. Then, we overexpressed AHNAK in vitro and in vivo to establish the roles of AHNAK in ovarian cancer cell proliferation and metastasis. Finally, we evaluated the possible molecular mechanisms underlying. We established that AHNAK was downregulated in ovarian cancer. Elevated AHNAK contents in ovarian cancer cell lines remarkably repressed ovarian cancer cell growth, along with metastasis in vitro, as well as in vivo. Moreover, AHNAK suppressed the progress of ovarian cancer partly via dampening the Canonical Wnt cascade. Therefore, AHNAK may be a biomarker and treatment target for ovarian cancer.

Silencing of hsa_circ_0009035 Suppresses Cervical Cancer Progression and Enhances Radiosensitivity through MicroRNA 889-3p-Dependent Regulation of HOXB7.

Circular RNAs (circRNAs), a novel type of endogenous noncoding RNAs, have been identified as critical regulators in human carcinogenesis. Here, we investigated the precise actions of hsa_circ_0009035 in the progression and radioresistance of cervical cancer (CC). The levels of hsa_circ_0009035, microRNA 889-3p (miR-889-3p), and homeobox B7 (HOXB7) were detected by quantitative real-time PCR (qRT-PCR) or Western blotting. RNase R and actinomycin D assays were used to assess the stability of hsa_circ_0009035. Cell proliferation, cell cycle progression, apoptosis, migration, and invasion were gauged with Cell Counting Kit-8 (CCK-8), flow cytometry, and transwell assays. Cell colony formation and survival were determined by the colony formation assay. Targeted correlations among hsa_circ_0009035, miR-889-3p, and HOXB7 were examined by the dual-luciferase reporter, RNA immunoprecipitation (RIP), or RNA pulldown assay. Animal studies were performed to evaluate the impact of hsa_circ_0009035 on tumor growth. We found that hsa_circ_0009035 was highly expressed in CC tissues and cells, and it was associated with the radioresistance of CC patients. Moreover, the silencing of hsa_circ_0009035 inhibited CC cell proliferation, migration, invasion, and it enhanced apoptosis and radiosensitivity in vitro and weakened tumor growth in vivo. Mechanistically, hsa_circ_0009035 directly targeted miR-889-3p by binding to miR-889-3p, and hsa_circ_0009035 modulated HOXB7 expression through miR-889-3p. HOXB7 was a functional target of miR-889-3p in regulating CC progression and radioresistance in vitro, and hsa_circ_0009035 modulated CC progression and radioresistance in vitro by miR-889-3p. Our current study first identified hsa_circ_0009035 as an important regulator of CC progression and radioresistance at least in part through targeting the miR-889-3p/HOXB7 axis, highlighting its significance as a potential therapeutic target for CC treatment.

Analysis of spatial-temporal distributions of nitrate-N concentration in Shitoukoumen catchment in northeast China.

This article discusses the generation and migration process of nitrate-N pollution in shallow groundwater caused by agricultural nonpoint source pollution in the catchment area of Shitoukoumen Reservoir in northeast China. By monitoring the shallow groundwater nitrate-N in the low-water period, the normal season, and high-flow period in the study area for a year, it was found that the nitrate-N concentration in the shallow groundwater of this area had a seasonal variation in both spatial and time distribution. In the time distribution, the peak value appeared in July, the high-flow period, and the valley value appeared in April, the low-water period, and showed a significant correlation with the time distribution of fertilization rate and rainfall. In the spatial distribution of nitrate-N pollution, when the distribution in shallow groundwater was analyzed separately in the three different periods (low-water period, the normal season, and high-flow period) and the discipline transference and enrichment of nitrate-N pollution in shallow groundwater was determined, this indicated that the region in the southeast study area where runoff conditions were better was less contaminated, and the region where runoff conditions were poor, as well as the region along the river were seriously polluted. The nitrate-N concentration in shallow groundwater was distributed mainly along the path of groundwater flow and was excreted in the drainage region. This showed that the spatial distribution of nitrate-N concentration in the shallow groundwater of the entire region was mainly controlled by the groundwater flow system. At the same time, in the middle and lower reaches of the study area, the seasonal changes in the recharged-excreted relationship between groundwater and river caused seasonal differences in the spatial distribution of nitrate-N pollution in groundwater. The combined effects of the groundwater mobility and the surface river resulted in a poor correlation between the groundwater nitrate-N concentration and land-use types. Only in the plain area where there was little influence from groundwater runoff and the surface river did the groundwater nitrate-N concentration correlate with land-use types. The spatial and time distribution of nitrate-N concentration in the shallow groundwater of the study area was impacted by agricultural nonpoint source pollution, the groundwater flow system, and the surface river and formed a concentration response system which uses basins as a unit.