A Concrete Core Void Imaging Approach and Parameter Analysis of Concrete-Filled Steel Tube Members Using Travel Time Tomography: Multi-Physics Simulations and Experimental Studies.

Concrete-filled steel tube (CFST) members have been widely used in civil engineering due to their advanced mechanical properties. However, internal defects such as the concrete core voids and interface debonding in CFST structures are likely to weaken their load-carrying capacity and stiffness, which affects the safety and serviceability. Visualizing the inner defects of the concrete cores in CFST members is a critical requirement and a challenging task due to the obvious difference in the material mechanical parameters of the concrete core and steel tube in CFST members.

Clinical implications of additional chromosomal abnormalities in adult acute myeloid leukemia with inv (16)/t(16;16)/CBFB::MYH11.

Objectives: This study assesses the clinical significance of additional cytogenetic abnormalities (ACAs) and/or the deletion of 3'CBFB (3'CBFB) resulting in unbalanced CBFB::MYH11 fusion in acute myeloid leukemia (AML) with inv (16)/t(16;16)/CBFB::MYH11.

Methods: We retrospectively evaluated the clinicopathologic features of 47 adult de novo AML with inv (16)/t(16;16)/CBFB::MYH11 fusion. There were 44 balanced and 3 unbalanced CBFB::MYH11 fusions.

Chromatin reconstruction during mouse terminal erythropoiesis.

Mammalian terminal erythropoiesis involves chromatin and nuclear condensation followed by enucleation. Late-stage erythroblasts undergo caspase-mediated nuclear opening that is important for nuclear condensation through partial histone release. It remains unknown the dynamic changes of three-dimensional (3D) genomic organization during terminal erythropoiesis.

Bone marrow-confined IL-6 signaling mediates the progression of myelodysplastic syndromes to acute myeloid leukemia.

Myelodysplastic syndromes (MDS) are age-related myeloid neoplasms with increased risk of progression to acute myeloid leukemia (AML). The mechanisms of transformation of MDS to AML are poorly understood, especially in relation to the aging microenvironment. We previously established an mDia1/miR-146a double knockout (DKO) mouse model phenocopying MDS.

SAF-189s, a potent new-generation ROS1 inhibitor, is active against crizotinib-resistant ROS1 mutant-driven tumors.

The ROS1 fusion kinase is an attractive antitumor target. Though with significant clinical efficacy, the well-known first-generation ROS1 inhibitor (ROS1i) crizotinib inevitably developed acquired resistance due to secondary point mutations in the ROS1 kinase. Novel ROS1is effective against mutations conferring secondary crizotinib resistance, especially G2032R, are urgently needed.

Farnesoid X Receptor Constructs an Immunosuppressive Microenvironment and Sensitizes FXRPD-L1 NSCLC to Anti-PD-1 Immunotherapy.

The farnesoid X receptor (FXR) regulates inflammation and immune responses in a subset of immune-mediated diseases. We previously reported that FXR expression promotes tumor cell proliferation in non-small cell lung cancer (NSCLC). Here we study the relevance of FXR to the immune microenvironment of NSCLC.

Discovery of 2,4-diarylaminopyrimidines bearing a resorcinol motif as novel ALK inhibitors to overcome the G1202R resistant mutation.

To address drug resistance caused by ALK kinase mutations, especially the most refractory and predominant mutation G1202R for the second-generation ALK inhibitor, a series of new diarylaminopyrimidine analogues were designed by incorporating a resorcinol moiety (A-ring) to interact the ALK kinase domain where the G1202R is located. Compound 12d turns out as the most potent with IC values of 1.7, 3.

An orally available tyrosine kinase ALK and RET dual inhibitor bearing the tetracyclic benzo[b]carbazolone core.

Our early structure-activity relationship study has identified benzo[b]carbazolone 6 as a high potency orally bioavailable ALK inhibitor. Further lead profiling disclosed that 6 is active against both ALK resistant and hot spot-activating mutants, and is also highly potent against RET kinase. Tumor stasis and partial tumor regression were achieved with 6 in both NIH/3T3-EML4-ALK and NIH/3T3-EML4-ALK L1196M xenograft models.

Cyclophilin A promotes human hepatocellular carcinoma cell metastasis via regulation of MMP3 and MMP9.

Cyclophilin A (CypA) is a member of peptidyl prolyl isomerases (PPIases), which catalyze the cis/trans isomerization of prolyl peptide bonds on the NH-terminal side of Pro residues in peptide chains. Altered expression of CypA has been reported in hepatocellular carcinoma (HCC), but the biological functions of CypA in HCC remain unknown. We found that the level of CypA expression correlated with the metastatic capability of two HCC cell lines, MHCC97-L and MHCC97-H.