A comparative study of three ultrasound techniques for liver fibrosis staging.

The aim of this study is to assess the agreement and performance of visual transient elastography (ViTE), sound touch elastography (STE), and sound touch quantification (STQ) for liver fibrosis staging using transient elastography (TE) as a standard. We finally enrolled 252 subjects with chronic liver disease (CLD) who underwent ViTE, STE, STQ, and TE examinations simultaneously in our hospital from October 2022 to July 2023. We evaluated the correlation and agreement between various technologies. And also evaluated the performances and optimal cutoffs of ViTE, STE, and STQ . The correlation coefficients of ViTE and TE, STE and TE, STQ and TE were 0.863, 0.709, and 0.727, respectively. The ICC among ViTE, STE, STQ, and TE was 0.911. The area under the receiver operating characteristics (AUROCs) of ViTE, STE, and STQ for detection of TE of ≥5 kPa, ≥10 kPa, ≥15 kPa, and ≥20 kPa were 0.867, 0.771, 0.804; 0.972, 0.935, 0.933; 0.998, 0.973, 0.968; and 1.000, 0.960, 0.954, respectively. The AUROCs of ViTE for detection of lower stages (TE≥5 kPa and ≥10 kPa) were significantly higher than STE and STQ in the overall cohort (ViTE vs. STE: Z  = 2.766, for TE ≥5 kPa; ViTE vs. STE: Z  = 2.145, ; ViTE vs. STQ: Z  = 2.587, for TE ≥10 kPa) (all P < 0.05). These methods all have coincided with performance in more advanced stages (TE ≥15 kPa and ≥20 kPa) (all P  > 0.05). These methods showed excellent correlation and agreement. ViTE performance in more advanced fibrosis differentiation is comparable to the STE and STQ while ViTE is more accurate than STE and STQ to identify patients with mild CLD stage, and can more effectively rule out compensated advanced CLD.

Efficient macrocyclization facilitated by skeleton preorganization.

Reported here is the efficient macrocyclization facilitated by skeleton preorganization. A pyridylcarbazole macrocycle and a phenylpyridylcarbazole macrocycle was synthesized in yield up to 75%. Single-crystal structures and theoretic computation uncovered that the skeleton preorganization promoted the formation of cyclization-favorable conformation of noncyclic precursors via π⋯π interactions. This result provided a new approach for the efficient syntheses of macrocycles.

Lower expression of PDZRN3 induces endometrial carcinoma progression via the activation of canonical Wnt signaling.

Endometrial carcinoma (EC) exhibits an extremely malignant biological behavior and has a high mortality rate. EC has recently become one of the most lethal cancers in women worldwide. E3 ubiquitin ligases play an important role in the biological function of healthy cells but can also contribute to tumorigenesis and cancer development. PDZ Domain Containing Ring Finger 3 (PDZRN3) is associated with cell differentiation and its structure includes the E3 ubiquitin ligase. However, the effects of PDZRN3 in EC remain unclear. Reverse transcription-quantitative PCR was used to detect the expression levels of PDZRN3 in EC cells, and the role of PDZRN3 in EC progression was determined using western blotting, MTT, colony formation, Transwell, subcutaneous tumor formation and pulmonary metastasis assays. A multi-pathway reporter arrays and western blotting were performed to investigate the potential biological mechanisms of PDZRN3 in EC. The present study demonstrated that PDZRN3 served an essential role in metastasis and proliferation of EC. PDZRN3 expression was lower in EC tissues compared with that in normal endometrial tissues. Low expression level of PDZRN3 in EC was correlated with certain clinicopathological features of patients with EC, such as the age of the patients, the tumor grade and the tumor subtype. The invasive and proliferative activities of EC cells with low expression of PDZRN3 were more potent than those of EC cells with high expression of PDZRN3, which was confirmed by in vivo and in vitro experiments. Furthermore, lower expression of PDZRN3 promoted metastasis and proliferation via activation of the canonical Wnt signaling pathway. The present study demonstrated that decreased PDZRN3 expression promoted metastasis and proliferation in EC cells via activation of the canonical Wnt signaling pathway, highlighting a potential biological therapeutic target for the management of EC.

TTLL12 expression in ovarian cancer correlates with a poor outcome.

The tubulin-tyrosine ligase (TTLL) family is involved in the progression of many cancers. Tubulin-tyrosine ligase-like protein 12 (TTLL12), a member of the TTLL family, has functions of histone methylation and affects the activities of tubulin tyrosine ligase, which are often observed abnormally in many cancers. Recently, a TTLL12 isoform was reported as abnormal in many cancer cells, but the potential role of TTLL12 in ovarian cancer (OC) is still unknown. In this study, we used quantitative real-time RT-PCR and western blot to determine the expressions of TTLL12 in ovarian cancer cells and tissues and also performed immunohistochemical staining to examine the TTLL12 expression levels in 72 OC tissues and their matched adjacent normal ovarian tissues (ANOTs), to further explore the potential clinical features. The results showed that the TTLL12 expression level in OC tissues was significantly increased when compared to the ANOTs. In addition, TTLL12 expression was also remarkably upregulated in OC cell lines compared to the normal ovarian cell line. Furthermore, we found that the TTLL12 level was significantly associated with the clinical features of the FIGO stage (P=0.001) and peritoneal cytology (P=0.042). Moreover, TTLL12 is thought to be an independent risk factor for the overall survival (OS, P=0.022) and disease-free survival (DFS, P=0.040) of OC patients. In conclusion, this study identified TTLL12 as a potential molecular marker for predicting the invasion and progression of OC.