Identification of a lncRNA/circRNA-miRNA-mRNA network in Nasopharyngeal Carcinoma by deep sequencing and bioinformatics analysis.

Background: Accumulating evidence indicates that non-coding RNAs (ncRNA), including long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), can function as competitive endogenous RNAs (ceRNAs) by binding to microRNAs (miRNAs) and regulating host gene expression at the transcriptional or post-transcriptional level. Dysregulation in ceRNA network regulation has been implicated in the occurrence and development of cancer. However, the lncRNA/circRNA-miRNA-mRNA regulatory network is still lacking in nasopharyngeal carcinoma (NPC). Methods: Differentially expressed genes (DEGs) were obtained from our previous sequencing data and Gene Expression Omnibus (GEO). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) were used to explore the biological functions of these common DEGs. Through a series of bioinformatic analyses, the lncRNA/circRNA-miRNA-mRNA network was established. In additional, the external data GSE102349 was used to test the prognostic value of the hub mRNAs through the Kaplan-Meier method. Results: We successfully constructed a lncRNA/circRNA-miRNA-mRNA network in NPC, consisting of 16 lncRNAs, 6 miRNAs, 3 circRNAs and 10 mRNAs and found that three genes (TOP2A, ZWINT, TTK) were significantly associated with overall survival time (OS) in patients. Conclusion: The regulatory network revealed in this study may help comprehensively elucidate the ceRNA mechanisms driving NPC, and provide novel candidate biomarkers for evaluating the prognosis of NPC.

Research progress on the multi-omics and survival status of circulating tumor cells.

In the dynamic process of metastasis, circulating tumor cells (CTCs) emanate from the primary solid tumor and subsequently acquire the capacity to disengage from the basement membrane, facilitating their infiltration into the vascular system via the interstitial tissue. Given the pivotal role of CTCs in the intricate hematogenous metastasis, they have emerged as an essential resource for a deeper comprehension of cancer metastasis while also serving as a cornerstone for the development of new indicators for early cancer screening and new therapeutic targets. In the epoch of precision medicine, as CTC enrichment and separation technologies continually advance and reach full fruition, the domain of CTC research has transcended the mere straightforward detection and quantification. The rapid advancement of CTC analysis platforms has presented a compelling opportunity for in-depth exploration of CTCs within the bloodstream. Here, we provide an overview of the current status and research significance of multi-omics studies on CTCs, including genomics, transcriptomics, proteomics, and metabolomics. These studies have contributed to uncovering the unique heterogeneity of CTCs and identifying potential metastatic targets as well as specific recognition sites. We also review the impact of various states of CTCs in the bloodstream on their metastatic potential, such as clustered CTCs, interactions with other blood components, and the phenotypic states of CTCs after undergoing epithelial-mesenchymal transition (EMT). Within this context, we also discuss the therapeutic implications and potential of CTCs.

Identification of a Difluorinated Alkoxy Sulfonyl Chloride as a Novel Antitumor Agent for Hepatocellular Carcinoma through Activating Fumarate Hydratase Activity.

Fenofibrate is known as a lipid-lowering drug. Although previous studies have reported that fenofibrate exhibits potential antitumor activities, IC50 values of fenofibrate could be as high as 200 µM. Therefore, we investigated the antitumor activities of six synthesized fenofibrate derivatives. We discovered that one compound, SIOC-XJC-SF02, showed significant antiproliferative activity on human hepatocellular carcinoma (HCC) HCCLM3 cells and HepG2 cells (the IC50 values were 4.011 µM and 10.908 µM, respectively). We also found this compound could inhibit the migration of human HCC cells. Transmission electron microscope and flow cytometry assays demonstrated that this compound could induce apoptosis of human HCC cells. The potential binding sites of this compound acting on human HCC cells were identified by mass spectrometry-cellular thermal shift assay (MS-CETSA). Molecular docking, Western blot, and enzyme activity assay-validated binding sites in human HCC cells. The results showed that fumarate hydratase may be a potential binding site of this compound, exerting antitumor effects. A xenograft model in nude mice demonstrated the anti-liver cancer activity and the mechanism of action of this compound. These findings indicated that the antitumor effect of this compound may act via activating fumarate hydratase, and this compound may be a promising antitumor candidate for further investigation.

Altered Cerebellar-Cerebral Circuits in Patients With Type 2 Diabetes Mellitus.

The role of the cerebellum in type 2 diabetes mellitus (T2DM) has been receiving increased attention. However, the functional connectivity (FC) between the cerebellar subregions and the cerebral cortex has not been investigated in T2DM. Therefore, the purpose of this study was to investigate cerebellar-cerebral FC and the relationship between FC and clinical/cognitive variables in patients with T2DM. A total of 34 patients with T2DM and 30 healthy controls were recruited for this study to receive a neuropsychological assessment and undergo resting-state FC. We selected four subregions of the cerebellum (bilateral lobules IX, right and left Crus I/II, and left lobule VI) as regions of interest (ROIs) to examine the differences in cerebellar-cerebral circuits in patients with T2DM compared to healthy controls. Correlation analysis was performed to examine the relationship between FC and clinical/cognitive variables in the patients. Compared to healthy controls, patients with T2DM showed significantly decreased cerebellar-cerebral FC in the default-mode network (DMN), executive control network (ECN), and visuospatial network (VSN). In the T2DM group, the FC between the left cerebellar lobule VI and the right precuneus was negatively correlated with the Trail Making Test A (TMT-A) score (r = -0.430, P = 0.013), after a Bonferroni correction. In conclusion, patients with T2DM have altered FC between the cerebellar subregions and the cerebral networks involved in cognitive and emotional processing. This suggests that a range of cerebellar-cerebral circuits may be involved in the neuropathology of T2DM cognitive dysfunction.

The generalized Phillips-Twomey method for NMR relaxation time inversion.

The inversion of NMR relaxation time involves the Fredholm integral equation of the first kind. Due to its ill-posedness, numerical solutions to this type of equations are often found much less accurate and bear little resemblance to the true solution. There has been a strong interest in finding a well-posed method for this ill-posed problem since 1950s. In this paper, we prove the existence, the uniqueness, the stability and the convergence of the generalized Phillips-Twomey regularization method for solving this type of equations. Numerical simulations and core analyses arising from NMR transverse relaxation time inversion are conducted to show the effectiveness of the generalized Phillips-Twomey method. Both the simulation results and the core analyses agree well with the model and the realities.

Rapid determination of fluid viscosity using low-field two-dimensional NMR.

The rapid prediction of fluid viscosity, especially the fluid in heavy-oil petroleum reservoirs, is of great importance for oil exploration and transportation. We suggest a new method for rapid prediction of fluid viscosity using two-dimensional (2D) NMR relaxation time distributions. DEFIR, Driven-Equilibrium Fast-Inversion Recovery, a new pulse sequence for rapid measurement of 2D relaxation times, is proposed. The 2D relation between the ratio of transverse relaxation time to longitudinal relaxation time (T1/T2) and T1 distribution of fluid are obtained by means of DEFIR with only two one-dimensional measurements. The measurement speed of DEFIR pulse sequence over 2 times as fast as that of the traditional 2D method. Using Bloembergen theory, the relation between the distributions and fluid viscosity is found. Precise method for viscosity prediction is then established. Finally, we apply this method to a down-hole NMR fluid analysis system and realized on-site and on-line prediction of viscosity for formation fluids. The results demonstrated that the new method for viscosity prediction is efficient and accurate.

Phase Correction-Adaptive Line Enhancement for Noise Reduction of Low-Field NMR.

The amplitude of low-field nuclear magnetic resonance (NMR) is weak, and the echo is buried in the noise. The reduction of noise is critical to accurately extract echo amplitude. Phase correction-adaptive line enhancement (PC-ALE) is proposed to noise suppression based on the principle of ALE and NMR spin-echo characteristics. The echo amplitude is calculated after two-stage processes; phase shift from time-delay and filter tap would be compensated effectively in frequency domain. Simulation and experiments show that PC-ALE has prominent performance on noise suppression, envelope recovery, as well as the correction of the phase shift. The amplitude from the method of sample average nearby the middle of the echo is more accurate than the maximum peak when the PC-ALE is applied to noise suppression of spin-echo.