Rational Exploration of Novel SDHI Fungicide through an Amide-β-ketonitrile Bioisosteric Replacement Strategy.

The identification of succinate dehydrogenase inhibitor (SDHI) fungicides bearing a novel scaffold is of great importance to control pathogenic fungi. Difluoromethyl-pyrazole β-ketonitrile derivatives were rationally designed through an innovative amide-β-ketonitrile bioisosteric replacement strategy and evaluated for their antifungal activities. In preliminary fungicidal screening, our new β-ketonitrile compounds showed outstanding in vitro activity.

Reversible Regulation of Succinate Dehydrogenase by Tools of Photopharmacology.

Succinate dehydrogenase (SDH) is extremely important in metabolic function and biological processes. Modulation of SDH has been reported to be a promising therapeutic target to SDH mutations. Current measures for the regulation of SDH are scarce, and precise and reversible modulation of SDH still remains challenging.

A novel ETV6-miR-429-CRKL regulatory circuitry contributes to aggressiveness of hepatocellular carcinoma.

Background: Tumor metastasis is one of the main causes of the high mortality of hepatocellular carcinoma (HCC). E-Twenty Six variant gene 6 (ETV6) is a strong transcriptional repressor, associated with the development and progression of tumors. However, the exact role and underlying mechanism of ETV6 in HCC remain unclear.

Annexin A5 regulates hepatocarcinoma malignancy via CRKI/II-DOCK180-RAC1 integrin and MEK-ERK pathways.

As a calcium-dependent phospholipid binding annexin protein, annexin A5 (Anxa5) links to the progression, metastasis, survival, and prognosis of a variety of cancers. Current work showed ANXA5 overexpression was positively correlated with the upregulations of CRKI/II and RAC1 in hepatocarcinoma (HCC) patients' tissues, which potentially enhanced the clinical progression and lymphatic metastasis of HCC. The role and action mechanism of ANXA5 in hepatocarcinoma was then investigated using a hepatocarcinoma Hca-P cell line, an ideal and well-established murine cell model with 100% inducible tumorigenicity of implanted mice with low (~25%) lymph node metastatic (LNM) rate.

Anxa5 mediates the in vitro malignant behaviours of murine hepatocarcinoma Hca-F cells with high lymph node metastasis potential preferentially via ERK2/p-ERK2/c-Jun/p-c-Jun(Ser73) and E-cadherin.

Objective: Annexin A5 (Anxa5) is associated with the progression of some cancers, while its role and regulation mechanism in tumor lymphatic metastasis is rarely reported. This study aims to investigate the influence of Anxa5 knockdown on the malignant behaviours of murine hepatocarcinoma Hca-F cell line with high lymph node metastatic (LNM) potential and the underlying regulation mechanism.

Methods: RNA interfering was performed to silence Anxa5 in Hca-F.

ANXA5 level is linked to in vitro and in vivo tumor malignancy and lymphatic metastasis of murine hepatocarcinoma cell.

Aim: To investigate ANXA5 overexpression on in vitro and in vivo malignancies of murine Hca-P cells.

Materials & Methods: Hca-P with low lymph node metastasis (LNM) potential was used as cell model. TEM, CCK-8 and Boyden transwell assays were performed for in vitro Hca-P behaviors.

CRKL knockdown promotes in vitro proliferation, migration and invasion, in vivo tumor malignancy and lymph node metastasis of murine hepatocarcinoma Hca-P cells.

Our previous study (Biomed Pharmacother 2015;69:11) demonstrated that the over-expression of CRKL, a chicken tumor virus number 10 regulator of kinase-like protein, suppresses in vitro proliferation, invasion and migration of murine hepatocarcinoma Hca-P cell, a murine HCC cell with lymph node metastatic (LNM) rate of ∼25%. In current work, we investigated the effects of CRKL knockdown on the in vitro cell proliferation, migration and invasion, and on the in vivo tumor malignancy and LNM rate and level for Hca-P cells. Western blotting assay indicated that CRKL was down-regulated by ∼90% in a monoclonal CrkL-shRNA-transfected Hca-P cells.

Experimental observation of classical subwavelength interference with a pseudothermal light source.

We report the experimental observation of classical subwavelength double slit interference with a pseudothermal light source. The experimental results are in good agreement with the theoretical simulation using the second order correlation function for the thermal light.