NR3C2 inhibits the proliferation of colorectal cancer via regulating glucose metabolism and phosphorylating AMPK.

We aim to investigate the roles and mechanisms of NR3C2 in colorectal cancer (CRC). The expression of NR3C2 in CRC tumours and paired paracancerous tissues of 71 CRC patients and five CRC cell lines was detected by western blotting, immunohistochemistry and real-time reverse-transcription PCR. Moreover, NR3C2 was overexpressed or knocked down in CRC cells by lentiviral vector transfection. The proliferation of cells was measured by MTT, colony formation assay and flow cytometry. Glucose metabolism was assessed by detecting lactate production, glucose consumption and ATP production. Western blotting and real-time reverse-transcription PCR were used to detect the expression of AMPK, LDHA and HK2. The expression of NR3C2 was significantly decreased in CRC tumours compared to paracancerous tissues, which was correlated with distant metastasis, poor prognosis and advanced stages of CRC patients. Overexpressing NR3C2 suppressed the proliferation and promoted the G2/M cell cycle arrest of CRC cells. Furthermore, NR3C2 inhibited glucose metabolism by decreasing the expression of HK2 and LDHA. The phosphorylation of AMPK was also downregulated in CRC cells overexpressing NR3C2. This study demonstrated that NR3C2 inhibited the proliferation of CRC by inhibiting glucose metabolism and phosphorylation of AMPK which may serve as a therapeutic target for CRC.

Eosinophils protect against pulmonary hypertension through 14-HDHA and 17-HDHA.

BACKGROUND: Pulmonary hypertension (PH) is a life-threatening disease featuring pulmonary vessel remodelling and perivascular inflammation. The effect, if any, of eosinophils (EOS) on the development of PH remains unclear. METHODS: EOS infiltration and chemotaxis were investigated in peripheral blood and lung tissues from pulmonary arterial hypertension (PAH) patients without allergic history and from sugen/hypoxia-induced PH mice. The role of EOS deficiency in PH development was investigated using GATA1-deletion (ΔdblGATA) mice and anti-interleukin 5 antibody-treated mice and rats. Ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was conducted to identify the critical oxylipin molecule(s) produced by EOS. Culture supernatants and lysates of EOS were collected to explore the mechanisms in co-culture cell experiments. RESULTS: There was a lower percentage of EOS in peripheral blood but higher infiltration in lung tissues from PAH patients and PH mice. PAH/PH lungs showed increased EOS-related chemokine expression, mainly C-C motif chemokine ligand 11 derived from adventitial fibroblasts. EOS deficiency aggravated PH in rodents, accompanied by increased neutrophil and monocyte/macrophage infiltration. EOS highly expressed arachidonate 15-lipoxygenase (ALOX15). 14-hydroxy docosahexaenoic acid (14-HDHA) and 17-HDHA were critical downstream oxylipins produced by EOS, which showed anti-inflammatory effects on recruitment of neutrophils and monocytes/macrophages through N-formyl peptide receptor 2. They also repressed pulmonary artery smooth muscle cell (PASMC) proliferation by activating peroxisome proliferator-activated receptor γ and blunting Stat3 phosphorylation. CONCLUSIONS: In PH development without external stimuli, peripheral blood exhibits a low EOS level. EOS play a protective role by suppressing perivascular inflammation and maintaining PASMC homeostasis via 14/17-HDHA.

One-Step Fabrication of a Multifunctional Aggregation-Induced Emission Nanoaggregate for Targeted Cell Imaging and Enzyme-Triggered Cancer Chemotherapy.

A novel multifunctional aggregation-induced emission (AIE) nanoaggregate for targeted imaging and enzyme-triggered chemotherapy was successfully fabricated via a one-step assembly. In this system, a quaternary ammonium-modified tetraphenylethene derivative (QA-TPE) acted as the AIE fluorophore as well as the chemotherapeutic agent, and a water-soluble acidic polysaccharide, hyaluronic acid (HA) acted as the aggregation-inducing scaffold, AIE turn-on agent, and targeting agent for CD44 receptor-mediated cancer cells. More importantly, HA endowed the QA-TPE/HA nanoaggregate both good biocompatibility and hysteretic chemotherapy activity, which were achieved by controlling the release of QA-TPE using the endogenous HAase in CD44 receptor-mediated cancer cells.

Identification of polymer materials using laser-induced breakdown spectroscopy combined with artificial neural networks.

A combination of laser-induced breakdown spectroscopy (LIBS) and artificial neural networks (ANNs) has been used for the identification of polymer materials, including polypropylene (PP), polyvinyl chloride (PVC), polytetrafluoroethylene (PTFE), polyoxymethylene (POM), polyethylene (PE), polyamide or nylon (PA), polycarbonate (PC) and poly(methyl methacrylate) (PMMA). After optimization of the experimental setup and the spectrum acquisition protocol, successful identification rates between 81 and 100% were achieved using spectral features gathered from single spectra without averaging (1 second acquisition time) over a wide spectral range (240-820 nm). Furthermore, ten different materials based on PVC were tested using the identification procedure. Correct identifications were obtained as well. Sorting of the materials into sub-categories of PVC materials according to their charges (concentration in trace elements such as Ca) was performed. The demonstrated capacities fit, in practice, the needs of plastic-waste sorting and of producing high-grade recycled plastic materials.

Nonlinear X-shaped waves by second-harmonic generation with collimated femtosecond pulses.

Nonlinear X-shaped angle-wavelength spectrum of the generated second-harmonic wave is observed for a collimated femtosecond pulse of a large beam waist, where the spatiotemporal balance is originated from mutual coupling of the effective nonlinear Kerr effects, pulse frequency chirp, and negative phase shift from cascaded quadratic processes with appropriate phase mismatch.