2-bromoacetamide exposure impairs oocyte maturation in mice and humans primarily via disrupting the cytoskeleton.

2-bromoacetamide (BAcAm) is an emerging class of unregulated disinfection by-products (DBPs), with potent cytogenetic and developmental toxicity in animals. However, whether BAcAm exerts toxic effects on mammalian oocyte quality remains to be elucidate. In this research, we investigated the effect of BAcAm on mouse and human oocyte maturation with an in vitro culture system. Our results revealed that BAcAm exposure hindered the extrusion of the first polar body, disrupted the spindle organization and reduced the competence of embryo development after fertilization in the mouse oocytes. Results of single-cell RNA sequencing (scRNA-seq) showed that 605 differentially expressed genes (DEGs) were identified in the BAcAm exposed mouse oocytes, among which 366 were up-regulated and 239 were down-regulated. Gene Ontology (GO) analysis further revealed that DEGs were mainly enriched in mitochondrial functions, oxidative stress, cytoskeleton, endoplasmic reticulum (ER), Golgi and protein synthesis, DNA damage and apoptosis. We then conducted further tests in these aspects and discovered that BAcAm exposure principally perturbed the function of microtubule and actin cytoskeleton. This finding was confirmed in human oocytes. Overall, our data suggest that BAcAm exposure disturbs the cytoskeleton function, thus impairing oocyte maturation. These data, for the first time, provide a comprehensive view for the toxic effects of BAcAm on oocyte maturation.

Ribosome ADP-ribosylation: A mechanism for maintaining protein homeostasis in cancers.

A recent study suggests that ribosome MARylation in cancers maintains proteostasis by reducing protein synthesis and preventing toxic protein aggregation. Mechanistically, NMNAT-2 is a cytosolic NAD+ synthase that supports the catalytic activity of PARP-16, which mediates ribosomal proteins MARylation. Ribosomal protein MARylation regulates polysomes assembly or function through the 3'-untranslated region (3'-UTR) stem-loop secondary structures in mRNAs, resulting in reduced protein synthesis and preventing toxic protein aggregation, thus supporting the growth of cancer cells during accelerated cell growth. When PARP-16 or NMNAT-2 is deleted, the stem-loop element in the 3'-UTRs of mRNAs increases polysome loading, enhances protein synthesis, promotes toxic protein aggregation, leading to inhibited cancer cell growth. Collectively, ribosome MARylation provides us with an exciting and scientific direction for us to understand cancers.

The role of metal ions in the Golgi apparatus.

The Golgi apparatus is a membrane-bound organelle that functions as a central role in the secretory pathway. Since the discovery of the Golgi apparatus, its structure and function have attracted ever-increasing attention from researchers. Recently, it has been demonstrated that metal ions are necessary for the Golgi apparatus to maintain its proper structure and functions. Given that metal ions play an important role in various biological processes, their abnormal homeostasis is related to many diseases. Therefore, in this paper, we reviewed the uptake and release mechanisms of the Golgi apparatus Ca2+ , Cu, and Zn2+ . Furthermore, we describe the diseases associated with Golgi apparatus Ca2+ , Cu, and Zn2+ imbalance.

M6 A modification: A mechanism for protecting hematopoietic development in mammals.

N6 -methyladenosine (m6 A) is one of the most common internal modifications in messenger RNA, which is necessary for cell physiological activities. A recent study shows that during mammalian hematopoietic development, loss of m6 A modification leads to the aberrant production of double-stranded RNA, which results in the abnormal activation of innate immune response, and ultimately leads to hematopoietic failure. Accordingly, m6 A modification provide us an attractive direction for us to understand mammalian hematopoietic development and innate immune response.

Comparison of Model-Free and Model-Based Dynamic Contrast-Enhanced Magnetic Resonance Imaging Pharmacokinetic Parameters for Predicting Breast Cancers' Response to Neoadjuvant Chemotherapy.

OBJECTIVE: To prospectively compare the performance of model-based and model-free dynamic contrast-enhanced (DCE) pharmacokinetic parameters in monitoring breast cancers' early response to neoadjuvant chemotherapy (NACT). METHODS: Sixty patients, with 61 pathology-proven breast cancers, were examined using DCE magnetic resonance imaging before, after the first cycle, and after full cycles of NACT. Both model-based (Ktrans and others) and model-free parameters, mainly time-intensity curve (TIC), were measured. According to Miller-Payne grading, patients were divided into response and nonresponse group. Mann-Whitney U test, Fisher exact test, multivariate logistic regression, and receiver operating characteristic curve were used in analysis. RESULTS: After the first cycle, among all the parameters, Ktrans and TIC were strongly associated with tumors' early response. There was no significant difference between the areas under receiver operating characteristic curve of Ktrans and TIC (0.768, 0.852, respectively). CONCLUSIONS: Model-based and model-free DCE parameters, especially Ktrans and TIC, have similar performance in predicting the efficacy of NACT for breast cancers.

Elicitation context does not drive F0 lowering following voiced stops: Evidence from French and Italian.

Consonant-intrinsic F0 (CF0) effects are mainly the result of raising F0 following voiceless obstruents, rather than of lowering F0 following voiced obstruents. However, there are also documented instances where lowered F0 following voiced obstruents is enhanced. Given that both voicing and F0 are affected by prosodic context, it is possible that CF0 is lowered in some contexts but not others. This possibility is investigated by examining CF0 in French and Italian in isolated citation forms. Results are comparable to carrier-phrase contexts, where no F0 lowering after voiced obstruents is observed. Possible sources of the apparent cross-linguistic differences are discussed.

CircRNA hsa_circRNA_101996 increases cervical cancer proliferation and invasion through activating TPX2 expression by restraining miR-8075.

In recent years, circular RNAs have been shown to serve as essential regulators in several human cancers. Nevertheless, the function and mechanism of CircRNA in cervical cancer remain elusive. In the present study, we showed that hsa_circRNA_101996 was highly expressed in cervical cancer tissues compared with matched normal tissues by bioinformatics analysis. We showed that the expression level of hsa_circRNA_101996 in cervical cancer tissues was positively correlated with TNM stage, tumor size, and lymph node metastasis. Moreover, higher levels of hsa_circRNA_101996 were related to poor outcomes of cervical cancer patients. We found that knockdown of hsa_circRNA_101996 significantly inhibited the proliferation, cell cycle, migration, and invasion of cervical cancer cells. Mechanistically, we demonstrated that hsa_circRNA_101996 served as a sponge of miR-8075, which targeted TPX2 in cervical cancer cells. We showed that miR-8075 that was downregulated in cervical cancer tissues repressed cervical cancer cell proliferation, migration, and invasion. Furthermore, we validated that upregulation of TPX2 by hsa_circRNA_101996-mediated inhibition of miR-8075 contributed to cervical cancer proliferation, migration, and invasion. Taken together, our findings revealed a novel mechanism that hsa_circRNA_101996-miR-8075-TPX2 network promoted cervical cancer progression.

The effect of bisphenol a exposure onto endothelial and decidualized stromal cells on regulation of the invasion ability of trophoblastic spheroids in in vitro co-culture model.

Bisphenol A (BPA) is a kind of environmental endocrine disruptors (EEDs) that interfere embryo implantation. Trophoblast invasion plays a crucial role during embryo implantation. In this study, the effects of BPA on invasion ability of human trophoblastic Jeg-3 spheroids and regulation of endothelial and stromal cells on trophoblastic spheroids invasion, and its possible mechanism were investigated. The results showed that BPA at 10 and 100 µM can inhibit the attachment of Jeg-3 spheroid onto Ishikawa cells. BPA at 1-100 µM also activate ERE-Luc reporter expression in the transfected cells, which was through the ERα, but not ERß or GPR30 binding. Endothelial receptivity ability was harmed by BPA treatment since receptivity markers of LIF, EGF, MUC1 and integrin αVß3 were decreased after BPA treatment. The invasion ability of trophoblastic spheroids generated from Jeg-3 cell line was inhibited by BPA and this effect was mediated through canonical ERs pathway and MMP2/MMP9 down-regulation and TIMP1/PAI-1 up-regulation. Besides, BPA treated decidualized stromal cells suppressed Jeg-3 spheroid outgrowth and invasion in co-culture assay. Our study would give a better understanding on the possible mechanism of BPA effect on human embryo implantation process.

Intravoxel Incoherent Motion Diffusion-Weighted Imaging Versus Dynamic Contrast-Enhanced Magnetic Resonance Imaging: Comparison of the Diagnostic Performance of Perfusion-Related Parameters in Breast.

OBJECTIVE: The aim of this study was to investigate the diagnostic performance of the perfusion-related parameters of intravoxel incoherent motion (IVIM) imaging for breast lesions, compared with dynamic contrast-enhanced magnetic resonance imaging (DCE MRI). METHODS: Fifty-nine patients with both IVIM imaging and subsequent DCE MRI were enrolled. Perfusion-related parameters of IVIM imaging (perfusion fraction, f; pseudo-diffusion coefficient, D*), as well as model-based and model-free parameters of DCE MRI, were measured. Receiver operating characteristic curve analysis and correlations between the IVIM and DCE MRI parameters were performed. RESULTS: Thirty-one malignant and 35 benign lesions were pathologically proved. The area under the receiver operating characteristic curves (AUC) of D* plus f (AUCf+D*) was 0.834. The combined AUC of all model-based DCE MRI parameters (AUCmodel-based) was 0.904. The combined AUC of all model-free DCE MRI parameters (AUCmodel-free) was 0.876. AUCf+D* had no significant difference with either AUCmodel-based or AUCmodel-free. No significant correlation was found between f or D* and DCE-derived parameters. CONCLUSIONS: Intravoxel incoherent motion imaging has the same value in differentiating malignant and benign breast lesions, compared with DCE MRI, in terms of perfusion-related parameters.

Hypoxia inhibits pulmonary artery endothelial cell apoptosis via the e-selectin/biliverdin reductase pathway.

Hypoxia-induced inhibition of apoptosis in pulmonary artery endothelial cells (PAECs) has an important role in pulmonary arterial remodeling leading to aggravated hypoxic pulmonary arterial hypertension. However, the mechanisms involved in the hypoxia-induced inhibition of PAEC apoptosis have not been elucidated. e-selectin and biliverdin reductase (BVR) have been reported to contribute to the cascade of apoptosis in several cell lines but not in PAECs. In the present study, we show that the expression of e-selectin and BVR was both up-regulated by hypoxia in PAECs. Moreover, hypoxia attenuated the decreased cell survival and apoptotic protein expression, and increased DNA fragmentation induced by serum deprivation in the PAECs, which was mediated by the e-selectin/BVR pathway. In addition, by examining the mitochondrial membrane potential and mitochondrial membrane proteins (Bcl-2 and BAX), we show that the mitochondrial-dependent apoptosis pathway was necessary for the e-selectin/BVR pathway inducing the anti-apoptotic effect of hypoxia in PAECs. Taken all together, our data show that the e-selectin/BVR pathway participates in the inhibitory process of hypoxia in PAEC apoptosis which is mediated by the mitochondrial-dependent apoptosis pathway.

Serum levels of TSP-1, NF-κB and TGF-ß1 in polycystic ovarian syndrome (PCOS) patients in northern China suggest PCOS is associated with chronic inflammation.

OBJECTIVE: The objective of this study was to determine the levels of thrombospondin-1 (TSP-1), transforming growth factor-ß1 (TGF-ß1) and nuclear factor kappaß (NF-κß) in polycystic ovarian syndrome (PCOS) patients with and without insulin resistance and after treatment with cyproterone acetate/ethinyloestradiol with or without concomitant metformin. DESIGN: Prospective. PATIENTS: Patients with PCOS and healthy women were recruited. Patients were subdivided into obese and nonobese based on body mass index. Patients with PCOS were also grouped according to homoeostasis model assessment-insulin resistance (HOMA-IR) ≥ 2·69 or <2·69, and by PCOS phenotype. Patients with PCOS-IR were treated with a 6-month course of cyproterone acetate/ethinyloestradiol with or without concomitant metformin. MEASUREMENTS: Inflammatory markers were examined at baseline, and after 6 months of treatment. RESULTS: A total of 445 women with PCOS (mean age 25·9 ± 2·7 years; 298 obese, 147 nonobese) and 213 normal controls (mean age 24·9 ± 3·0 years) were included. Regardless of obesity status, testosterone, free androgen index (FAI), luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratio, HOMA-IR, TSP-1 and NF-κB in the PCOS groups were significantly higher than in the control group, whereas TSP-1 was lower in the PCOS groups (all, P < 0·05). Patients with PCOS without IR had lower TSP-1 levels than control patients (P < 0·05). Treatment with cyproterone acetate/ethinyloestradiol with addition of metformin reduced the level of NF-κB, TGF-ß1 and HOMA-IR and increased the level of TSP-1. CONCLUSIONS: These results support the association between PCOS and chronic inflammation.

Apparent diffusion coefficient reproducibility of the pancreas measured at different MR scanners using diffusion-weighted imaging.

PURPOSE: To evaluate the reproducibility of the pancreatic apparent diffusion coefficient (ADC) measured at different MR scanners. MATERIALS AND METHODS: Twenty-four healthy volunteers underwent three consecutive diffusion-weighted imaging (DWI) at a GE 1.5 Tesla (T), a Siemens 1.5 T and a Philips 3.0 T (session 1), and imaged again using the same protocol at the same GE 1.5 T (session 2) 12 days later. The ADC values of pancreas were measured at all three MR scanners. Paired-sample t-test and the Bland-Altman method were used for ADC data analysis. RESULTS: The individual mean ADC values of pancreatic head, body, and tail (in 10(-3) mm(2)/s) measured at GE 1.5 T (2.24, 2.01, 1.88 for observer 1 and 2.23, 2.00, 1.92 for observer 2) and Siemens 1.5 T (2.24, 2.04, 1.84 for observer 1 and 2.20, 1.98, 1.84 for observer 2) were significantly higher than those at Philips 3.0 T (2.06, 1.80, 1.56 for observer 1 and 2.02, 1.79, 1.60 for observer 2) (P = 0.000-0.008). There was no significant difference of ADC values either between GE 1.5 T and Siemens 1.5 T (P = 0.115-0.966), or between imaging session 1 and 2 at GE 1.5 T (P = 0.072-0.938). The range of mean difference ± limits of agreement (in 10(-3) mm(2)/s) was -0.07-0.04 ± 0.39-0.53 between two 1.5 T scanners, and -0.04-0.04 ± 0.24-0.47 between two imaging sessions at GE 1.5 T. CONCLUSION: The measured ADC values of pancreas are affected by the field strength of scanner, but show good reproducibility between different MR systems with same field strength and at the same MR system over time.

Carbonized cellulose microspheres loaded with Pd NPs as catalyst in p-nitrophenol reduction and Suzuki-Miyaura coupling reaction.

Catalytic reduction of p-nitrophenol is usually carried out using transition metal nanoparticles such as gold, palladium, silver, and copper, especially palladium nanoparticles (Pd NPs), which are characterized by fast reaction rate, high turnover frequency, good selectivity, and high yield. However, the aggregation and precipitation of the metals lead to the decomposition of the catalyst, which results in a significant reduction of the catalytic activity. Therefore, the preparation of homogeneous stabilized palladium nanoparticles catalysts has been widely studied. Stabilized palladium nanoparticles mainly use synthetic polymers. Cellulose microspheres, as a natural polymer material with low-cost and porous fiber network structure, are excellent carriers for stabilizing metal nanoparticles. Cellulose microspheres impregnated with palladium metal nanoparticles were carbonized to have a larger specific surface area and highly dispersed palladium nanoparticles, which exhibited excellent catalytic activity in the catalytic reduction of p-nitrophenol. In this work, the cellulose carbon-based microspheres palladium (Pd@CCM) catalysts were designed and characterized by SEM, TEM, EDS, XRD, FTIR, XPS, TGA, BET, and so on. Furthermore, the catalytic performance of Pd@CCM catalysts was investigated via p-nitrophenol reduction, which showed high catalytic activity. This catalyst also exhibited excellent catalytic performance in the Suzuki-Miyaura coupling reaction. Linking aromatic monomer and benzene through Suzuki-Miyaura coupling was presented as an effective route to obtaining biaryls, and the synthesis method is low-cost and simple. In addition, Pd@CCM showed desirable recyclability while maintaining its catalytic activity even after five recycles. This work is highly suggestive of the design and application of the heterogeneous catalyst.

Diffusion-weighted, intravoxel incoherent motion, and diffusion kurtosis tensor MR imaging in chronic kidney diseases: Correlations with histology.

OBJECTIVES: To probe the correlations of parameters derived from standard DWI and its extending models including intravoxel incoherent motion (IVIM), diffusion tensor imaging (DTI), and diffusion kurtosis imaging (DKI) with the pathological and functional alterations in CKD. MATERIAL AND METHODS: Seventy-nine CKD patients with renal biopsy and 10 volunteers were performed with DWI, IVIM, diffusion kurtosis tensor imaging (DKTI) scanning. Correlations between imaging results and the pathological damage [glomerulosclerosis index (GSI) and tubulointerstitial fibrosis index (TBI)], as well as eGFR, 24 h urinary protein and Scr) were evaluated.CKD patients were divided into 2 groups: group 1: both GSI and TBI scores <2 points (61 cases); group 2: both GSI and TBI scores ≥2 points (18 cases). RESULTS: There were significant difference in cortical and medullary MD, and cortical D among 3 groups and between group 1 and 2. Cortical and medullary MD, cortical D, and medullary FA were negatively correlated with GSI score (r = -0.322 to -0.386, P < 0.05). Cortical and medullary MD and D, medullary FA were also negatively correlated with TBI score (r = -0.257 to -0.395, P < 0.05). These parameters were all correlated with eGFR and Scr. Cortical MD and D showed the highest AUC of 0.790 and 0.745 in discriminating mild and moderate-severe glomerulosclerosis and tubular interstitial fibrosis, respectively. CONCLUSIONS: The corrected diffusion-related indices, including cortical and medullary D and MD, as well as medullary FA were superior to ADC, perfusion-related and kurtosis indices for evaluating the severity of renal pathology and function in CKD patients.

Quantitative apparent diffusion coefficient metrics for MRI-only suspicious breast lesions: any added clinical value?

Background: Suspicious breast lesions [Breast Imaging Reporting and Data System (BI-RADS) category 4 or 5] detected only by magnetic resonance imaging (MRI) and invisible on other initial imaging modalities (MRI-only lesions) are usually small and poorly characterized in previous literature, thus making diagnosis and management difficult. This study aimed to investigate the clinical significance of quantitative apparent diffusion coefficient (ADC) metrics derived from conventional diffusion-weighted imaging (DWI) on evaluating MRI-only lesions. Methods: A total of 90 suspicious MRI-only lesions were evaluated, including 51 malignant and 39 benign lesions. Morphological and kinetic characteristics of all lesions (termed BI-RADS parameters) were described according to the BI-RADS lexicon on dynamic contrast-enhanced (DCE) imaging. Minimum, maximum, and mean ADC values (ADCmin, ADCmax, ADCmean) were obtained by measuring the ADC map of DWI. ADCheterogeneity was then obtained by the following formula: ADCheterogeneity = (ADCmax - ADCmin)/ADCmean. Diagnostic performance of these parameters was assessed and compared using the receiver operating characteristic (ROC) curve. Results: Of the 90 MRI-only lesions, there were 45 masses and 45 non-mass lesions. Among BI-RADS parameters, only two different kinetic patterns were significantly different between benign and malignant groups (P=0.005 and P<0.001, respectively). The area under the ROC curve (AUC) of combined significant ADC parameters (ADCmin, ADCmean, and ADCmax, all P≤0.001) was significantly higher than that of the two different kinetic patterns (P=0.006 for both). For MRI-only masses, only ADCmean and ADCmax, among all BI-RADS and ADC parameters, had diagnostic value (combined AUC =0.833). For non-mass lesions, size, distribution, ADCmin, and ADCmean were significantly different between benign and malignant groups (P=0.004, P<0.001, P=0.001, and P<0.001, respectively). In addition, ADCmean had the highest diagnostic performance among all ADC parameters, regardless of mass or non-mass (AUC =0.825 and 0.812, respectively). ADCheterogeneity showed no significant differences, no matter in mass or non-mass groups (P=0.62 and 0.43, respectively). Conclusions: In differentiating MRI-only suspicious lesions, quantitative ADC metrics generally performed better than BI-RADS parameters, and ADCmean is still the best ADC parameter to distinguish MRI-only lesions.

Golgi stress response: A regulatory mechanism of Golgi function.

The organelle of eukaryotes is a finely regulated system. Once disturbed, it activates the specific autoregulatory systems, namely, organelle autoregulation. Among which, the Golgi stress response accounts for one. When the abundance and capacity of the Golgi apparatus are insufficient compared with cellular demand, the Golgi stress response is activated to enhance the function of the Golgi apparatus. Although the molecular mechanism of the Golgi stress response has not been well characterized yet, it seems to be an important part of the mammalian stress response. In this review, we discuss the current status of research on the six pathways of the mammalian Golgi stress response (the TFE3, heat shock protein 47, CREB3, E26 transformation specific, proteoglycan, and mucin pathways), which regulate the general function of the Golgi apparatus, anti-apoptosis, pro-apoptosis, proteoglycan glycosylation, and mucin glycosylation, respectively.

Mitochondrial iron metabolism and its role in diseases.

Iron is one of the most important elements for life, but excess iron is toxic. Intracellularly, mitochondria are the center of iron utilization requiring sufficient amounts to maintain normal physiologic function. Accordingly, disruption of iron homeostasis could seriously impact mitochondrial function leading to impaired energy state and potential disease development. In this review, we discuss mechanisms of iron metabolism including transport, processing, heme synthesis, iron-sulfur cluster biogenesis and storage. We highlight the vital role of mitochondrial iron in pathologic states including neurodegenerative disorders and sideroblastic anemia.

Sarcopenia as a predictor of initial administration dose of afatinib in patients with advanced non-small cell lung cancer.

BACKGROUND: Sarcopenia has recently emerged as a new condition with increasing importance in lung cancer patients. The aim of this study was to investigate the influence of sarcopenia on tolerance and efficacy of afatinib. METHODS: We retrospectively evaluated 35 patients with epidermal growth factor receptor (EGFR) mutant advanced non-small cell lung cancer (NSCLC) treated with first-line afatinib. Skeletal muscle area (SMA) was measured at the third lumbar vertebra using routine conducted computed tomography (CT) images for evaluation of disease burden. Sarcopenia was defined as skeletal muscle index (SMI = SMA/height2 ) ≤38.5 cm2 /m2 for women and ≤52.4 cm2 /m2 for men based on previous criteria. Fisher's exact tests, Kaplan-Meier method, and logistic regression modeling were used. RESULTS: The median age at diagnosis was 65 years (range,39-84 years). A total of 24 (68.6%) patients were diagnosed with sarcopenia. The most frequent adverse events (AEs) related to afatinib were diarrhea (94.3%) followed by rash (77.1%) and paronychia (60%). Overall, 19 (54.3%) patients had dose reduction. Sarcopenic patients had a significantly higher rate of grade ≥ 2 diarrhea (75.0 vs. 27.3%, p = 0.011) and toxicity-related dose reduction (75.0 vs. 9.1%, p = 0.001). Multivariate analysis also showed that sarcopenia (odds ratio [OR] 51.7, 95% confidence interval [CI]: 2.4-1081.3, p = 0.01) was an independent risk factor for dose reduction of afatinib. The median progression-free survival (PFS) for afatinib was 12.0 months (95% CI: 10.6-13.4). Both dose reduction and sarcopenia did not affect therapeutic efficacy. CONCLUSIONS: Toxicity-related dose reduction is common with initiation of afatinib 40 mg/day. Sarcopenic patients might begin treatment with a low dose of afatinib according to tolerance.

Application of diffusion kurtosis tensor MR imaging in characterization of renal cell carcinomas with different pathological types and grades.

BACKGROUND: To probe the feasibility and reproducibility of diffusion kurtosis tensor imaging (DKTI) in renal cell carcinoma (RCC) and to apply DKTI in distinguishing the subtypes of RCC and the grades of clear cell RCC (CCRCC). METHODS: Thirty-eight patients with pathologically confirmed RCCs [CCRCC for 30 tumors, papillary RCC (PRCC) for 5 tumors and chromophobic RCC (CRCC) for 3 tumors] were involved in the study. Diffusion kurtosis tensor MR imaging were performed with 3 b-values (0, 500, 1000s/mm2) and 30 diffusion directions. The mean kurtosis (MK), axial kurtosis (Ka), radial kurtosis (Kr) values and mean diffusity (MD) for RCC and contralateral normal parenchyma were acquired. The inter-observer agreements of all DKTI metrics of contralateral renal cortex and medulla were evaluated using Bland-Altman plots. Statistical comparisons with DKTI metrics of 3 RCC subtypes and between low-grade (Furman grade I ~ II, 22 cases) and high-grade (Furman grade III ~ IV, 8 cases) CCRCC were performed with ANOVA test and Student t test separately. Receiver operating characteristic (ROC) curve analyses were used to compare the diagnostic efficacy of DKTI metrics for predicting nuclear grades of CCRCC. Correlations between DKTI metrics and nuclear grades were also evaluated with Spearman correlation analysis. RESULTS: Inter-observer measurements for each metric showed great reproducibility with excellent ICCs ranging from 0.81 to 0.87. There were significant differences between the DKTI metrics of RCCs and contralateral renal parenchyma, also among the subtypes of RCC. MK and Ka values of CRCC were significantly higher than those of CCRCC and PRCC. Statistical difference of the MK, Ka, Kr and MD values were also obtained between CCRCC with high- and low-grades. MK values were more effective for distinguishing between low- and high- grade CCRCC (area under the ROC curve: 0.949). A threshold value of 0.851 permitted distinction with high sensitivity (90.9%) and specificity (87.5%). CONCLUSION: Our preliminary results suggest a possible role of DKTI in differentiating CRCC from CCRCC and PRCC. MK, the principle DKTI metric might be a surrogate biomarker to predict nuclear grades of CCRCC. TRIAL REGISTRATION: ChiCTC, ChiCTR-DOD-17010833, Registered 10 March, 2017, retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=17559 .

Circular RNA circRNA_101996 promoted cervical cancer development by regulating miR-1236-3p/TRIM37 axis.

Circular RNAs (circRNAs) appear to be significant modulators in various physiological processes. Recently, it is found that circRNA_101996 exerts important roles in various cancers. Our previous studies showed that circRNA_101996 promoted cervical cancer growth and metastasis by regulating miR-8075/TPX2. However, the potential regulatory role of circRNA_101996 in cervical cancer still needs further investigation. Our results in this study suggested that circRNA_101996 was over-expressed in cervical cancer patients. circRNA_101996 up-regulation remarkably assisted cell proliferation, cell cycle progression, and cell migration in cervical cancer, while circRNA_101996 knockdown exerted the inverse effects. The molecular investigations indicated that circRNA_101996 could increase the expression level of miR-1236-3p, tripartite motif-containing 37 (TRIM37), through binding to miR-1236-3p and reducing its expression. Moreover, in vivo results demonstrated that circRNA_101996 shRNA can function as a tumor suppressor through down-regulating TRIM37 in cervical cancer. In conclusion, our data indicated that circRNA_101996/miR-1236-3p/TRIM37 axis accelerated cervical cancer development, providing novel insights into cervical cancer diagnosis and treatment.