TIPE1‐mediated autophagy suppression promotes nasopharyngeal carcinoma cell proliferation via the AMPK/mTOR signalling pathway

Recent studies have shown that tumour necrosis factor‐α–induced protein 8 like‐1(TIPE1) plays distinct roles in different cancers. TIPE1 inhibits tumour proliferation and metastasis in a variety of tumours but acts as an oncogene in cervical cancer. The role of TIPE1 in nasopharyngeal carcinoma (NPC) remains unknown. Interestingly, TIPE1 expression was remarkably increased in NPC tissue samples compared to adjacent normal nasopharyngeal epithelial tissue samples in our study. TIPE1 expression was positively correlated with that of the proliferation marker Ki67 and negatively correlated with patient lifespan. In vitro, TIPE1 inhibited autophagy and induced cell proliferation in TIPE1‐overexpressing CNE‐1 and CNE‐2Z cells. In addition, knocking down TIPE1 expression promoted autophagy and decreased proliferation, whereas overexpressing TIPE1 increased the levels of pmTOR, pS6 and P62 and decreased the level of pAMPK and the LC3B. Furthermore, the decrease in autophagy was remarkably rescued in TIPE1‐overexpressing CNE‐1 and CNE‐2Z cells treated with the AMPK activator AICAR. In addition, TIPE1 promoted tumour growth in BALB/c nude mice. Taken together, results indicate that TIPE1 promotes NPC progression by inhibiting autophagy and inducing cell proliferation via the AMPK/mTOR signalling pathway. Thus, TIPE1 could potentially be used as a valuable diagnostic and prognostic biomarker for NPC.     

The Water-Soluble Pool in Biochar Dominates Maize Plant Growth Promotion Under Biochar Amendment

Although amending biochar into agricultural soils has been regarded as an effective measure to improve crop productivity, it remains unclear why biochar increases crop yield. The objective of this study was to compare the relative contribution of different biochar components in crop growth promotion. Three biochar components were separated: (i) water-soluble biochar extract (BE), (ii) mineral nutrients from biochar ash (BA), and (iii) washed biochar residue (WB). Two soils (Anthrosol and Primosol) with distinctly different organic carbon content, soil texture and land use were amended with the three biochar components and their effects on maize (Zea mays L.) growth were tested in a pot experiment. We hypothesized that (1) plant grown in the Anthrosol benefitted more from the water-soluble compounds of biochar than from its mineral nutrients or washed residue, since the soil is already fertile and has a good structure; (2) plant grown in the Primosol benefitted more from the mineral nutrients of biochar and its washed residual, since the soil is nutrient-poor and has a poor structure. The addition of biochar and its three components increased maize aboveground biomass for both soils. In the Anthrosol, BE, BA, and WB increased the aboveground biomass by 41.6%, 32.7%, and 27.1%; in the Primosol, they increased the aboveground biomass by 41.3%, 24.4%, and 18.2%, respectively. BE had the highest plant growth-promoting effect compared to the other two biochar components, which was regardless of soil condition. In addition, the biomass, total volume, surface area, and number of maize root tips under BE amendment were significantly enhanced, particularly the fine roots (< 0.2 mm in diameter). And a strong positive correlation was observed between maize aboveground biomass and the total length of the fine roots. The results demonstrated that the water-soluble compounds present in biochar, in addition to the mineral nutrients and the washed biochar residue, dominate the plant growth promotion under both soil conditions.

     

Nanoscale mapping and organization analysis of target proteins on cancer cells from B-cell lymphoma patients

CD20, a membrane protein highly expressed on most B-cell lymphomas, is an effective target demonstrated in clinical practice for treating B-cell non-Hodgkin's lymphoma (NHL). Rituximab is a monoclonal antibody against CD20. In this work, we applied atomic force microscopy (AFM) to map the nanoscale distribution of CD20 molecules on the surface of cancer cells from clinical B-cell NHL patients under the assistance of ROR1 fluorescence recognition (ROR1 is a specific cell surface marker exclusively expressed on cancer cells). First, the ROR1 fluorescence labeling experiments showed that ROR1 was expressed on cancer cells from B-cell lymphoma patients, but not on normal cells from healthy volunteers. Next, under the guidance of ROR1 fluorescence, the rituximab-conjugated AFM tips were moved to cancer cells to image the cellular morphologies and detect the CD20-rituximab interactions on the cell surfaces. The distribution maps of CD20 on cancer cells were constructed by obtaining arrays of (16×16) force curves in local areas (500×500 nm²) on the cell surfaces. The experimental results provide a new approach to directly investigate the nanoscale distribution of target protein on single clinical cancer cells.     

Tuning of emission: Synthesis, structure and photophysical properties of imidazole, oxazole and thiazole-based iridium (III) complexes

Three new iridium (III) complexes with two cyclometalated C^∧N ligands (imidazole, oxazole and thiazole-based, respectively) and one acetylacetone (acac) ancillary ligand have been synthesized and fully characterized. The structure of the thiazole-based complex has been determined by single crystal X-ray diffraction analysis. The Ir center was located in a distorted octahedral environment by three chelating ligands with the N-N in the trans and C-C in the cis configuration. By changing the hetero-atom of C^∧N ligands the order S, O and N, a marked and systematic hypsochromic shift of the maximum emission peak of the complexes was realized. The imidazole-based complex emits at a wavelength of 500 nm, which is in the blue to green region. The tuning of emission wavelengths is consistent with the variation of the energy gap estimated from electrochemistry results. An electroluminescent device using the thiazole-based complex as a dopant in the emitting layer has been fabricated. A highly efficient yellow emission with a maximum luminous efficiency of 9.8 cd/A at a current density of 24.2 mA/cm² and a maximum brightness of 7985 cd/m² at 19.6 V has been achieved.     

Decline in topsoil microbial quotient, fungal abundance and C utilization efficiency of rice paddies under heavy metal pollution across South China

Agricultural soils have been increasingly subject to heavy metal pollution worldwide. However, the impacts on soil microbial community structure and activity of field soils have been not yet well characterized. Topsoil samples were collected from heavy metal polluted (PS) and their background (BGS) fields of rice paddies in four sites across South China in 2009. Changes with metal pollution relative to the BGS in the size and community structure of soil microorganisms were examined with multiple microbiological assays of biomass carbon (MBC) and nitrogen (MBN) measurement, plate counting of culturable colonies and phospholipids fatty acids (PLFAs) analysis along with denaturing gradient gel electrophoresis (DGGE) profile of 16S rRNA and 18S rRNA gene and real-time PCR assay. In addition, a 7-day lab incubation under constantly 25°C was conducted to further track the changes in metabolic activity. While the decrease under metal pollution in MBC and MBN, as well as in culturable population size, total PLFA contents and DGGE band numbers of bacteria were not significantly and consistently seen, a significant reduction was indeed observed under metal pollution in microbial quotient, in culturable fungal population size and in ratio of fungal to bacterial PLFAs consistently across the sites by an extent ranging from 6% to 74%. Moreover, a consistently significant increase in metabolic quotient was observed by up to 68% under pollution across the sites. These observations supported a shift of microbial community with decline in its abundance, decrease in fungal proportion and thus in C utilization efficiency under pollution in the soils. In addition, ratios of microbial quotient, of fungal to bacterial and qCO(2) are proved better indicative of heavy metal impacts on microbial community structure and activity. The potential effects of these changes on C cycling and CO(2) production in the polluted rice paddies deserve further field studies.     

Dynamic Model for Characterizing Contractile Behaviors and Mechanical Properties of a Cardiomyocyte

Studies on the contractile dynamics of heart cells have attracted broad attention for the development of both heart disease therapies and cardiomyocyte-actuated micro-robotics. In this study, a linear dynamic model of a single cardiomyocyte cell was proposed at the subcellular scale to characterize the contractile behaviors of heart cells, with system parameters representing the mechanical properties of the subcellular components of living cardiomyocytes. The system parameters of the dynamic model were identified with the cellular beating pattern measured by a scanning ion conductance microscope. The experiments were implemented with cardiomyocytes in one control group and two experimental groups with the drugs cytochalasin-D or nocodazole, to identify the system parameters of the model based on scanning ion conductance microscope measurements, measurement of the cellular Young’s modulus with atomic force microscopy indentation, measurement of cellular contraction forces using the micro-pillar technique, and immunofluorescence staining and imaging of the cytoskeleton. The proposed mathematical model was both indirectly and qualitatively verified by the variation in cytoskeleton, beating amplitude, and contractility of cardiomyocytes among the control and the experimental groups, as well as directly and quantitatively validated by the simulation and the significant consistency of 90.5% in the comparison between the ratios of the Young’s modulus and the equivalent comprehensive cellular elasticities of cells in the experimental groups to those in the control group. Apart from mechanical properties (mass, elasticity, and viscosity) of subcellular structures, other properties of cardiomyocytes have also been studied, such as the properties of the relative action potential pattern and cellular beating frequency. This work has potential implications for research on cytobiology, drug screening, mechanisms of the heart, and cardiomyocyte-based bio-syncretic robotics.     

Allosteric activation via kinetic control: potassium accelerates a conformational change in IMP dehydrogenase

Allosteric activators are generally believed to shift the equilibrium distribution of enzyme conformations to favor a catalytically productive structure; the kinetics of conformational exchange is seldom addressed. Several observations suggested that the usual allosteric mechanism might not apply to the activation of IMP dehydrogenase (IMPDH) by monovalent cations. Therefore, we investigated the mechanism of K(+) activation in IMPDH by delineating the kinetic mechanism in the absence of monovalent cations. Surprisingly, the K(+) dependence of k(cat) derives from the rate of flap closure, which increases by ≥65-fold in the presence of K(+). We performed both alchemical free energy simulations and potential of mean force calculations using the orthogonal space random walk strategy to computationally analyze how K(+) accelerates this conformational change. The simulations recapitulate the preference of IMPDH for K(+), validating the computational models. When K(+) is replaced with a dummy ion, the residues of the K(+) binding site relax into ordered secondary structure, creating a barrier to conformational exchange. K(+) mobilizes these residues by providing alternate interactions for the main chain carbonyls. Potential of mean force calculations indicate that K(+) changes the shape of the energy well, shrinking the reaction coordinate by shifting the closed conformation toward the open state. This work suggests that allosteric regulation can be under kinetic as well as thermodynamic control.     

复提霉素的研究

综述复提霉素的研究情况,报导提取工艺的改进。     

植被恢复对退化红壤表层土壤颗粒中有机碳和Pb、Cd分布的影响

采用原状土壤水稳性团聚体分离方法提取不同粒径的土壤颗粒,测定其有机碳及重金属元素Pb、Cd的含量,研究了退化红壤在植被恢复下表层(0～10cm和10～20cm)土壤颗粒中有机碳与重金属分布及其关系.这些土壤颗粒中有机碳和重金属元素Pb、Cd的含量范围分别介于7.5～15g/kg,11～20mg/kg和20～70μg/kg,且粒组间有显著差异.尽管所测组分的含量以＜0.002mm粒组中最高,但2～0.25mm的粒组占其总量的50%左右,其次约20%存在于0.25～0.02mm粒组中.以土壤粒组中分量而言,有机碳和所测的重金属元素间有密切的依存关系.与荒地相比,植被恢复措施降低了各土层2～0.25mm粒组中Pb的含量和分量,但提高了0～10cm土层Cd的含量和分量.在所研究的几种处理中,玉米-包菜处理显著地促进了有机碳和重金属在各颗粒粒组中的均衡分布.因此,退化红壤植被恢复措施改变了上壤颗粒中有机碳和重金属的分布,因而可能影响着土壤环境中有机碳和重金属的形态及其活性.对于这些措施下土壤环境中有机碳和重金属的生物有效性机制尚需进一步研究.