Design and Synthesis of c-Met and HDAC Dual Inhibitors for the Treatment of Breast Cancer.

In recent years, it has been proposed that c-mesenchymal-to-epithelial transition factor (c-Met) and histone deacetylase (HDAC) dual inhibition is a promising cancer treatment strategy. Herein, a series of c-Met/HDAC dual inhibitors were designed and synthesized given their synergistic anticancer effect in breast cancer cells. Compound exhibited excellent inhibitory activity against c-Met (IC = 28.

Dual inhibitors of DNMT and HDAC induce viral mimicry to induce antitumour immunity in breast cancer.

The existing conventional treatments for breast cancer, including immune checkpoint blockade, exhibit limited effects in some cancers, particularly triple-negative breast cancer. Epigenetic alterations, specifically DNMT and HDAC alterations, are implicated in breast cancer pathogenesis. We demonstrated that DNMTs and HDACs are overexpressed and positively correlated in breast cancer.

Design, synthesis, and evaluation of VHL-based EZH2 degraders for breast cancer.

EZH2 (enhancer of zeste homolog 2) is one of the most important histone methyltransferases (HMTs), and overexpression of EZH2 can lead to proliferation, migration and angiogenesis of tumor cells. But most of EZH2 inhibitors are only effective against some hematologic malignancies and have poor efficacy against solid tumors. Here, we report the design, synthesis, and evaluation of highly potent proteolysis targeting chimeric (PROTACs) small molecules targeting EZH2.

Design, optimization, and characterization of an XY nanopositioning stage with multi-level spatial flexure hinges for high-precision large-stroke motion guidance.

Establishing a novel design and accurate analytical models for XY nanopositioning stages based on voice coil motor (VCM) actuators is critical to achieving an optimal working performance. To overcome the existing design challenges of 2-degree-of-freedom guiding mechanisms, a four-layer structure composed of L-shaped spatial double parallelogram flexure mechanisms was proposed for the magnetic stage, which exhibits light weight and inhibits parasitic and decoupled motions. The guiding mechanisms were modeled by the compliance matrix method.

Efficacy and safety of low dose aspirin plus clopidogrel in the treatment of elderly patients with symptomatic intracranial artery stenosis.

Background: As one of the most common causes of stroke, symptomatic intracranial artery stenosis (sICAS) is a great threat to public health, and its financial burden is substantial, with annual direct high medical costs particularly in China. Currently, the long-term use of conventional dual antiplatelet therapy (DAPT) as the primary modality of treatment for sICAS decreases the risk of stroke recurrence but increases the risk of bleeding. We aimed to evaluate the efficacy and safety of low dose aspirin plus clopidogrel for the treatment of sICAS in the elderly population.

Computational mining of GeH-based Janus III-VI van der Waals heterostructures for solar cell applications.

The asymmetrical group III-VI monolayer Janus MXY (M = Al, Ga, In; X ≠ Y = S, Se, Te) have attracted widespread attention due to their significant optical absorption properties, which are the potential building blocks for van der Waals (vdW) heterostructure solar cells. In this study, we unraveled an InSTe/GeH vdW heterostructure as a candidate for solar cells by screening the Janus MXY and GeH monolayers on lattice mismatches and electronic band structures based on first-principles calculations. The results highlight that the InSTe/GeH vdW heterostructure exhibits a type-II band gap of 1.

Responses of Bacterial Community Structure, Diversity, and Chemical Properties in the Rhizosphere Soil on Fruiting-Body Formation of .

Mycorrhiza helper bacteria (MHB) play an important role in driving mycorrhizal formation. There are few reports on the relationship between bacteria and fruiting growths. Taking mycorrhizal rhizosphere soil from sporocarps of the S.

Case Study of a MEMS Snap-Through Actuator: Modeling and Fabrication Considerations.

MEMS actuators rely on the deformation of silicon structures. Using dimensions smaller than dozens of micrometers reveals that the micro-electro-mechanical systems (MEMS) actuators are affected by fabrication inaccuracies, leading to hardly predictable forces and/or actuation results. In this paper, MEMS bistable buckled beam actuators are presented.

Design, synthesis and anti-tumor evaluation of 1,2,4-triazol-3-one derivatives and pyridazinone derivatives as novel CXCR2 antagonists.

Chemokine receptor 2 (CXCR2) is the receptor of glutamic acid-leucine-arginine sequence-contained chemokines CXCs (ELR CXCs). In recent years, CXCR2-target treatment strategy has come a long way in cancer therapy. CXCR2 antagonists could block CXCLs/CXCR2 axis, and are widely used in regulating immune cell migration, tumor metastasis, apoptosis and angiogenesis.

Synthesis of α-Amino Tertiary Alkylperoxides by Lewis Acid-Catalyzed Peroxidation of 1,3,5-Triazines.

α-Substituted peroxides have been found in natural products and are widely used as anti-malarial agents. Zn(OTf) -catalyzed peroxidation of 1,3,5-triazines has been developed, accessing diversely substituted α-amino tertiary alkylperoxides with high efficiency. Mechanistic investigations and useful synthetic application of the products have also been presented.

Discovery of the PARP (poly ADP-ribose polymerase) inhibitor 2-(1-(4,4-difluorocyclohexyl)piperidin-4-yl)-1H-benzo[d]imidazole-4-carboxamide for the treatment of cancer.

In this work, two series of cyclic amine-containing benzimidazole carboxamide derivatives were designed and synthesized as potent anticancer agents. PARP1/2 inhibitory activity assays indicated that most of the compounds showed significant activity. The in vitro antiproliferative activity of these compounds was investigated against four human cancer cell lines (MDA-MB-436, MDA-MB-231, MCF-7 and CAPAN-1), and several compounds exhibited strong cytotoxicity to tumor cells.

Design, synthesis and evaluation of novel ErbB/HDAC multitargeted inhibitors with selectivity in EGFR mutant cell lines.

Acquired resistance leads to the failure of EGFR TKIs in NSCLC treatment. A novel series of hydroxamic acid-containing 4-aminoquinazoline derivatives as irreversible ErbB/HDAC multitargeted inhibitors for NSCLC therapy had been designed and synthesized, which displayed weak anti-proliferative activity in several EGFR wild-type cancer cell lines (NCI-H838, SK-BR-3, A549, A431) yet retained moderate activity to EGFR resistance mutation harboring NCI-H1975 cells. The mechanistic studies revealed that the representative compound 11e was able to inhibit the phosphorylation of EGFR, up-regulate hyperacetylation of histone H3 and even reduce the expression of EGFR and Akt in NCI-H1975 cells.

Cost-effectiveness analysis of etanercept plus methotrexate vs triple therapy in treating Chinese rheumatoid arthritis patients.

Objective: This study aimed to explore the cost-effectiveness of etanercept plus methotrexate (ETN+MTX) compared to triple disease-modifying anti-rheumatic drugs (DMARDs) in treating Chinese rheumatoid arthritis (RA) patients.

Methods: The 134 Chinese RA patients who were about to initiate ETN+MTX or triple DMARDs therapy based on treat-to-target strategy were consecutively recruited and categorized into ETN+MTX group (N = 49) or triple DMARDs group (N = 85). Treatment efficacy was assessed at month 3 (M3)/M6/M9/M12 after initiation of treatment.

A Novel, Portable and Fast Moisture Content Measuring Method for Grains Based on an Ultra-Wideband (UWB) Radar Module and the Mode Matching Method.

To perform fast and portable grain moisture measurements under field conditions, a novel moisture sensor was designed, which consisted of a coaxial waveguide, a circular waveguide, and an isolation layer. The electromagnetic characteristics of the sensor were simulated and measured. The analytical model, which represented the relationship between the reflection coefficient of the sensor and the complex permittivity of grain, was established by using the mode matching method.

Clinical efficacy and safety of gemcitabine plus nedaplatin in the treatment of advanced nasopharyngeal carcinoma.

Objective: The purpose was to explore the clinical effects and safety of gemcitabine plus nedaplatin in the treatment of advanced nasopharyngeal carcinoma.

Materials And Methods: From March 2014 to August 2015, we recruited 63 advanced nasopharyngeal carcinoma patients in our hospital. Moreover, the 62 cases were randomly divided into control group (n = 31) and treatment group (n = 32).

[CT/MRI image characteristics of iliopsoas bursitis in avascular necrosis of femoral head].

Objective: To investigate the spectrum of CT and MR imaging and surgical operation findings in iliopsoas bursitis in patients with avascular necrosis of femoral head so as to enhance the diagnostic ability.

Methods: A total of 1,415 patients with avascular necrosis of the femoral head were analyzed retrospectively; of them, 15 patients were complicated by iliopsoas bursitis surgically or aspiration of synovial fluid between May 2005 and May 2007. Fifteen cases were all necrosis of the bilateral femoral head and 17 hips were combined with iliopsoas bursitis.