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Nicotinic acid adenosine dinucleotide phosphate (NAADP) is a Ca2+-mobilizing second messenger that regulates a wide range of biological activities. However, the mechanism of its biogenesis remains controversial. CD38 is the only enzyme known to catalyze NAADP synthesis from NADP and nicotinic acid. CD38-mediated catalysis requires an acidic pH, suggesting that NAADP may be produced in acidic endolysosomes, but this hypothesis is untested. In this study, using human cell lines, we specifically directed CD38 to the endolysosomal system and assessed cellular NAADP production. First, we found that nanobodies targeting various epitopes on the C-terminal domain of CD38 could bind to cell surface–localized CD38 and induce its endocytosis. We also found that CD38 internalization occurred via a clathrin-dependent pathway, delivered CD38 to the endolysosome, and elevated intracellular NAADP levels. We also created a CD38 variant for lysosome-specific expression, which not only withstood the degradative environment in the lysosome, but was also much more active than WT CD38 in elevating cellular NAADP levels. Supplementing CD38-expressing cells with nicotinic acid substantially increased cellular NAADP levels. These results demonstrate that endolysosomal CD38 can produce NAADP in human cells. They further suggest that CD38's compartmentalization to the lysosome may allow for its regulation via substrate access, rather than enzyme activation, thereby providing a reliable mechanism for regulating cellular NAADP production.

ROOT UV-B SENSITIVE4 (RUS4) encodes a Domain of Unknown Function647 (DUF647) protein, whose function is poorly understood. We have previously shown the artificial microRNA knockdown Arabidopsis RUS4 plants, referred to as amiR-RUS4, have severely reduced male fertility with a defect in anther dehiscence. Here, we show that amiR-RUS4 plants are also defective in pollen maturation and germination. Promoter-reporter analysis shows that RUS4 is highly expressed in tapetal layer, developing microspores, mature and germinating pollen, strongly suggesting its role in the process of pollen maturation. As the translational RUS4-GFP fusion protein has been localized to the chloroplasts where the first step of jasmonic acid (JA) biosynthesis takes place, leading to the hypothesis that RUS4 may be involved in JA-mediated stamen development. We show that expression of several JA metabolic genes increased markedly in flower buds of the amiR-RUS4 plants compared to that of the wild-type. We further show that transcript abundance of a clade of the JA-responsive MYB transcript factor genes, especially MYB108, reduced significantly in stamens of amiR-RUS4 plants relative to the wild-type; these MYB transcript factors have been shown to be required for JA-mediated stamen and pollen maturation. Our data suggest that RUS4 may play a role in coordinating anther dehiscence and pollen maturation by affecting the expression of JA-related genes.

CXC195 showed strong protective effects in neuronal apoptosis by exerting its antioxidant activity. However, the anti-cancer effects of CXC195 is still with limited acquaintance. Here, we investigated the role of CXC195 in lipopolysaccharide (LPS)-induced human hepatocellular carcinoma (HCC) cells lines (HepG2) and the possible signaling pathways. CXC195 exhibited significant anti-proliferative effect and induced cell cycle arrest in LPS-induced HepG2 cells. In addition, CXC195 suppressed the release of pro-inflammatory mediators in LPS-induced HepG2 cells, including TNF-α, iNOS, IL-1β, IL-6, CC chemokine ligand (CCL)-2, CCL-22 and epidermal growth factor receptor (EGFR). Moreover, CXC195 inhibited the expressions and interactions of TLR4, MyD88 and TAK1, NF-κB translocation to nucleus and its DNA binding activity, phosphorylation of ERK1/2, p38 and JNK. Our results suggested that treatment with CXC195 could attenuate the TLR4-mediated proliferation and inflammatory response in LPS-induced HepG2 cells, thus might be beneficial for the treatment of HCC.

Nicotinic acid adenosine dinucleotide phosphate (NAADP) is a Ca(2+)-mobilizing second messenger that regulates a wide range of biological activities. However, the mechanism of its biogenesis remains controversial. CD38 is the only enzyme known to catalyze NAADP synthesis from NADP and nicotinic acid. CD38-mediated catalysis requires an acidic pH, suggesting that NAADP may be produced in acidic endolysosomes, but this hypothesis is untested. In this study, using human cell lines, we specifically directed CD38 to the endolysosomal system and assessed cellular NAADP production. First, we found that nanobodies targeting various epitopes on the C-terminal domain of CD38 could bind to cell surface–localized CD38 and induce its endocytosis. We also found that CD38 internalization occurred via a clathrin-dependent pathway, delivered CD38 to the endolysosome, and elevated intracellular NAADP levels. We also created a CD38 variant for lysosome-specific expression, which not only withstood the degradative environment in the lysosome, but was also much more active than WT CD38 in elevating cellular NAADP levels. Supplementing CD38-expressing cells with nicotinic acid substantially increased cellular NAADP levels. These results demonstrate that endolysosomal CD38 can produce NAADP in human cells. They further suggest that CD38's compartmentalization to the lysosome may allow for its regulation via substrate access, rather than enzyme activation, thereby providing a reliable mechanism for regulating cellular NAADP production.

The magnetoresistance (MR) of A/B granular mixture is investigated as a function of B content. A and B are both half-metallic materials, but have opposite spin polarization. The correlation of the angles between magnetic moments of neighboring grains is taken into account. Using Monte Carlo simulations, we model the granular mixture as a random resistor network. The variation of magnetoresistance with B content is calculated. The appearance of MR valley may be attributed to two kinds of materials with the opposite sign of spin polarizations. But in a granular mixture, little inverse magnetoresistance could be observed. Calculated results are consistent with the experiment as well. When there is a large difference between resistances of distinct contact barriers, a weak peak will appear in the magnetoresistance curve. Percolation effect is the probable origin of this weak peak.

The transport properties of ultrasonic-treated CrO 2 particles are studied. The experimental results indicate that the ultrasonic treatment not only leads to an increase in the resistivity, but also reduces the saturation magnetization of CrO 2 powders. These modifications are attributed to a change in the surface state of the CrO 2 particles. Furthermore, a modified surface state can yield a decreasing magnetoresistance of CrO 2 granular compacts. XPS analysis provides supports that the surface nature of CrO 2 particles is altered after ultrasonic treatment. The reduced saturation magnetization is related to the existence of a magnetic dead layer, which is estimated to be of a few nanometers thick. This work reveals that our ultrasonic technique is a method to control magnetotransport of granular materials by altering the surface state of the particles.

We present a study on temperature dependence of impedance spectra of the cold-pressed chromium dioxide (CrO 2 )–titanic dioxide (TiO 2 ) composite over the temperature range of 77–300 K, and over the frequency range of 40 Hz–500 kHz. The microstructure of the sample is analyzed using transmission electron microscopy (TEM), SEM and X-ray diffraction (XRD). The impedance spectra exhibit a strong dependence upon temperature. By evaluating the ac electricity behavior of the composite, we find the experimental data are successfully described by a power-law behavior σ ac = A ( T ) ω s , in which the frequency exponent s shows slightly greater than a universal value (0≤ s ≤1), and rises approximately linearly with temperature over a broad range of low temperature.

We study the dependence of resistivity ρ on graphite volume fraction p in Fe 3 O 4 /C magnetic composite. The measured percolation threshold, p c was determined to be 0.212 and 0.231 at 300 and 77 K, respectively. The difference in values of p c can be attributed to the variation in the value of ρ Fe 3 O 4 / ρ c . Experimental results indicate that the conductivity exhibits non-universal critical behavior. The non-universal critical exponent t is 3.88±0.20 (300 K) and 3.18±0.26 (77 K), which may be related to cavities in powder composite. Transport mechanisms were also discussed with temperature dependence of resistance and I–V characteristics. It is considered that decreasing electrical transport at 77 K leads likely to low critical exponent t in contrast to 300 K.

We report a study of enhanced negative magnetoresistence (MR) in Fe3O4/graphite powder composite. In the vicinity of percolation region, the experiment exhibits that the enhanced MR reaches –32% at the temperature of 77 K with an applied field of 6.5 kOe. The high MR value is due to the enhanced spin-dependent scattering on the surface of Fe3O4 particles. Simultaneously, it is also found that the composite exhibits an adjustable MR from negative to positive with the variation of graphite concentration. This switch effect is ascribed to the transition of MR mechanism.

This letter presents an experimental study of the correlation between low field magnetoresistance (MR) and percolation process, and the dependence of conductance on temperature between 77 and 300 K in the CrO 2 –TiO 2 composites. We also discuss the conduction mechanisms of the composites and conclude that the conductance is mainly attributed to higher-order hopping at higher temperature.

Impedance spectroscopy is used to evaluate the contributions of grain and grain boundary resistance to conduction process and magnetoresistance (MR) in CrO 2 –TiO 2 granular composites. It is found that there is a transition from two semicircles to a single semicircle in the Nyquist plot with increasing CrO 2 concentration. The resistivities of grain and grain boundary reveal very similar percolation processes, but their critical behaviors display slight differences in the conductance critical exponent. The fittings to experimental data indicate the critical exponents t gb =2.42±0.15, and t g =1.65±0.23, for grain boundaries and grains, respectively. The ratio γ g = ρ g / ρ gb depends strongly on CrO 2 concentration. In particular, in the conductance percolation region, we find that the ratio γ g exhibits a switch point from γ g γ g >1, which may have a great influence on MR. The maximum of MR at 77 K appears close to percolation threshold x c , and reaches −9.1% at 6 kOe, which is attributed to the cluster microstructure and the ratio γ g of the composite. As a result, the effective grain boundaries play an important role in manipulating MR in the CrO 2 composite.

Granular CrO 2 /polystyrene composites were prepared by evaporating polystyrene solution. The composites consisting of the acicular half-metallic CrO 2 particles encapsulated properly with a thin layer of insulating polymer can exhibit a large enhancement in room temperature magnetoresistance (MR), up to −8.2% at a low field of 6.5 kOe. The microstructures and thermal behaviors of the composite are analyzed by XRD, SEM, TGA and DSC. The temperature dependence of the electrical resistance is studied at the temperature range (77–298 K). We also argue that the influence of polymer on room temperature MR is more significant than that at low temperature, which may be mainly attributed to spin-dependent tunneling between particles.