Neutral ceramidase activity inhibition is involved in palmitate-induced apoptosis in INS-1 cells.

Neutral ceramidase (NCDase) is a class of ceramidases, a key enzyme in ceramide degradation. Recently, it was observed that NCDase activity was suppressed by saturated fatty acids to increase ceramide content in rat muscle. However, little is known about its changes in activity and roles in palmitate (Palm)-induced lipotoxicity in pancreatic ß cells. Here, we demonstrated that Palm treatment significantly down-regulated NCDase activity, mRNA and protein levels in rat INS-1 cells. In addition, Palm caused a significant accumulation of ceramide, while SPH level remained unchanged, suggesting that inhibition of NCDase activity led to no change of SPH level after treatment with Palm for 24 h. Furthermore, NCDase overexpression significantly reduced Palm-induced apoptosis in INS-1 cells. Conversely, NCDase siRNA knockdown markedly exacerbated Palm-induced apoptosis. In conclusion, Palm treatment suppressed the activity of NCDase and down-regulated its mRNA and protein expression. Furthermore, NCDase inhibition was involved in Palm-induced apoptosis by blocking ceramide degradation in INS-1 cells.

915 nm Light-Triggered Photodynamic Therapy and MR/CT Dual-Modal Imaging of Tumor Based on the Nonstoichiometric Na0.52 YbF3.52 :Er Upconversion Nanoprobes.

Lanthanide (Ln(3+) )-doped upconversion nanoparticles (UCNPs) as a new generation of multimodal bioprobes have attracted great interest for theranostic purpose. Herein, red emitting nonstoichiometric Na0.52 YbF3.52 :Er UCNPs of high luminescence intensity and color purity are synthesized via a facile solvothermal method. The red UC emission from the present nanophosphors is three times more intense than the well-known green emission from the ≈30 nm sized hexagonal-phase NaYF4 :Yb,Er UCNPs. By utilizing Na0.52 YbF3.52 :Er@SrF2 UCNPs as multifunctional nanoplatforms, highly efficient in vitro and in vivo 915 nm light-triggered photodynamic therapies are realized for the first time, with dramatically diminished overheating yet similar therapeutic effects in comparison to those triggered by 980 nm light. Moreover, by virtue of the high transverse relaxivity (r 2 ) and the strong X-ray attenuation ability of Yb(3+) ions, these UCNPs also demonstrate good performances as contrast agents for high contrast magnetic resonance and X-ray computed tomography dual-modal imaging. Our research shows the great potential of the red emitting Na0.52 YbF3.52 :Er UCNPs for multimodal imaging-guided photodynamic therapy of tumors.

Heme oxygenase-1 enhances autophagy in podocytes as a protective mechanism against high glucose-induced apoptosis.

Injury and loss of podocytes play vital roles in diabetic nephropathy progression. Emerging evidence suggests autophagy, which is induced by multiple stressors including hyperglycemia, plays a protective role. Meanwhile, heme oxygenase-1 (HO-1) possesses powerful anti-apoptotic properties. Therefore, we investigated the impact of autophagy on podocyte apoptosis under diabetic conditions and its association with HO-1. Mouse podocytes were cultured in vitro; apoptosis was detected by flow cytometry. Transmission electron microscopy and biochemical autophagic flux assays were used to measure the autophagy markers microtubule-associated protein 1 light chain 3-II (LC3-II) and beclin-1. LC3-II and beclin-1 expression peaked 12-24h after exposing podocytes to high glucose. Inhibition of autophagy with 3-methyladenine or Beclin-1 siRNAs or Atg 5 siRNAs sensitized cells to apoptosis, suggesting autophagy is a survival mechanism. HO-1 inactivation inhibited autophagy, which aggravated podocyte injury in vitro. Hemin-induced autophagy also protected podocytes from hyperglycemia in vitro and was abrogated by HO-1 siRNA. Adenosine monophosphate-activated protein kinase phosphorylation was higher in hemin-treated and lower in HO-1 siRNA-treated podocytes. Suppression of AMPK activity reversed HO-1-mediated Beclin-1 upregulation and autophagy, indicating HO-1-mediated autophagy is AMPK dependent. These findings suggest HO-1 induction and regulation of autophagy are potential therapeutic targets for diabetic nephropathy.

Cationic and anionic defect decoration of CoO through Cu dopants and oxygen vacancy for a High­Performance supercapacitor.

CoO has attracted increasing attention as an electrochemical energy storage owing to its excellent redox activity and high theoretical specific capacitance. However, its low inherent electrical conductivity results in sluggish reaction kinetics, and the poor rate capability of CoO limits its widespread applications. Herein, a multiple-defect strategy of engineering oxygen vacancies and Cu-ion dopants into the low-crystalline CoO nanowires (Ov-Cu-CoO) is successfully applied. Because of the advantage of the dual defect synergetic effect, the electronic structure and charge distribution are effectively modulated, thus enhancing the electrical conductivity and enriched redox chemistry. The obtained Ov-Cu-CoO electrode exhibits a high specific capacity of 1388.6 F⋅g-1 at a current density of 1 A⋅g-1, an ultrahigh rate performance (81.2% of the capacitance retained at 20 A⋅g-1) and excellent cycling stability (101.1% after 10,000 cycles). Moreover, an asymmetric supercapacitor device with Ov-Cu-CoO as the positive electrode having a high energy density of 44.1 W⋅h⋅kg-1 at a power density of 800 W⋅kg-1, and can still remain 27.2 W⋅h⋅kg-1 at a power density of 16 kW⋅kg-1. This study demonstrates an effective strategy to enhance electrochemical performance of CoO that can be easy applied to other transition metal oxides.

The three-dimensional coordination network in poly[di-µ3-cyanido-µ5-[5-(pyridin-4-yl)tetrazolato]-tricopper(I)].

In the title three-dimensional tetrazolate-based coordination polymer, poly[bis(µ(3)-cyanido-κ(3)N:C:C)[µ(5)-5-(pyridin-4-yl)tetrazolato-κ(5)N:N':N'':N''':N'''']tricopper(I)], [Cu(3)(C(6)H(4)N(5))(CN)(2)](n), there are two types of coordinated Cu(I) atoms. One type exhibits a tetrahedral environment and the other, residing on a twofold axis, adopts a trigonal coordination environment. The closest Cu···Cu distance is only 2.531 (2) Å, involving a bridging cyanide C atom. All four tetrazolate and the pyridine N atom of the 4-(pyridin-4-yl)-1H-tetrazolate anion are coordinated to these Cu(I) atoms and exhibit a µ(5)-bridging mode. The three-dimensional coordination network can be topologically simplified as a rarely observed (3,3,4,5)-connected network with the Schläfli symbol (4.6.8(4))(2).(4(2).6.8(7)).(6.8(2))(3).

Black 3D-TiO2 Nanotube Arrays on Ti Meshes for Boosted Photoelectrochemical Water Splitting.

Black 3D-TiO2 nanotube arrays are successfully fabricated on the Ti meshes through a facile electrochemical reduction method. The optimized black 3D-TiO2 nanotubes arrays yield a maximal photocurrent density of 1.6 mA/cm2 at 0.22 V vs. Ag/AgCl with Faradic efficiency of 100%, which is about four times larger than that of the pristine 3D-TiO2 NTAs (0.4 mA/cm2). Such boosted PEC water splitting activity primarily originates from the introduction of the oxygen vacancies, which results in the bandgap shrinkage of the 3D-TiO2 NTAs, boosting the utilization efficiency of visible light including the incident, reflected and/or refracted visible light captured by the 3D configuration. Moreover, the oxygen vacancies (Ti3+) can work as electron donors, which leads to the enhanced electronic conductivity and upward shift of the Fermi energy level, and thereby facilitating the transfer and separation of the photogenerated charge carrier at the semiconductor-electrolyte interface. This work offers a new opportunity to promote the PEC water splitting activity of TiO2-based photoelectrodes.

Benzene-1,3,5-tricarb-oxy-lic acid-5-(pyridin-1-ium-3-yl)-5H-1,2,3,4-tetra-zol-5-ide (1/1).

The asymmetric unit of the title compound, C(6)H(5)N(5)·C(9)H(6)O(6), comprises a full mol-ecule each of neutral trimesic acid (tma) and zwitterionic 5-(pyridin-1-ium-3-yl)-5H-1,2,3,4-tetra-zol-5-ide (ptz). The components are linked into a two-dimensional layer by a combination of O-H⋯O, O-H⋯N, N-H⋯O and N-H⋯N hydrogen bonds parallel to the (10[Formula: see text]) plane. Layers comprising alternating rows of tma and ptz are linked into a three-dimensional network by C-H⋯O and π-π inter-actions between tma and tetra-zolate rings [centroid-centroid distance = 3.763 (2) Å], and between pyridinium and tetra-zolate rings [centroid-centroid distance = 3.745 (2) Å].

Dysregulation of lncRNAs GM5524 and GM15645 involved in high­glucose­induced podocyte apoptosis and autophagy in diabetic nephropathy.

Diabetic nephropathy (DN) is an important microvascular complication of diabetes, and one of the leading causes of end­stage kidney disease. However, the mechanism of the DN pathogenic process remains unclear. Recently, long non­coding (lnc)RNA dysregulation has been regarded to cause the occurrence and development of various human diseases, although the functions of lncRNAs in human DN are poorly understood. The authors' previous study using microarray analysis identified hundreds of dysregulated lncRNAs in DN, although the functions of these lncRNAs were not demonstrated. Out of those dysregulated lncRNAs, Gm5524 was significantly upregulated in response to DN, while Gm15645 was significantly downregulated in response to DN. In the present study, this result was further validated by reverse transcription­quantitative polymerase chain reaction assays, and downregulating or overexpressing Gm5524 and Gm15645 in mouse podocytes. Notably, knockdown of Gm5524 and overexpression of Gm15645 induced mouse podocyte apoptosis and decreased cell autophagy in high­glucose culture conditions. In conclusion, the results of the present study revealed the roles of lncRNAs Gm5524 and Gm15645 in high­glucose induced podocyte apoptosis and autophagy during DN, which may further the understanding of the involvement of lncRNAs in DN, and provide a potential novel therapeutic target for this disease.

Neodymium-doped NaHoF4 nanoparticles as near-infrared luminescent/T2-weighted MR dual-modal imaging agents in vivo.

The achievement of efficient near-infrared (NIR) luminescence of lanthanide ions in a paramagnetic nanoparticle (NP) host is highly desirable to optimize the performance of multimodal bioprobes. Herein, we present a facile coprecipitation method to prepare highly uniform NaHoF4:Nd3+ nanoplates. Upon NIR excitation at 785 nm, efficient NIR luminescence of Nd3+ can be obtained from the paramagnetic NaHoF4 hosts. More interestingly, due to energy transfer from the excited state of Nd3+ to the adjacent Ho3+, NIR emission at around 1200 nm from Ho3+ ions is also observed. The r2 value of NaHoF4:Nd3+ NPs reaches 143.7 s-1 mM-1 at a high magnetic field of 11.7 T. By modifying with hydrophilic alpha-cyclodextrin, the NaHoF4:Nd3+ NPs were further successfully applied for the NIR luminescent/T2-weighted MR dual-modal in vivo imaging of nude mice, high contrast NIR imaging of the liver and T2-weighted MR imaging of stem cells in the mouse brain using the NaHoF4:Nd3+ NPs as multimodal bioprobes.

Microarray analysis of long noncoding RNA expression patterns in diabetic nephropathy.

AIMS: Long noncoding RNAs (lncRNAs) are implicated in various biological processes and human diseases. Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD). We explored the potential functions of lncRNAs in DN. METHODS: We established a mouse model of DN and compared lncRNA expression patterns between DN model and db/m control mouse kidney tissues using microarray analysis. lncRNA function was predicted by gene ontology enrichment and KEGG pathway analyses of lncRNAs-coexpressed mRNAs. Quantitative reverse-transcription PCR was used for validation. Cis- and trans-regulation analyses were conducted to reveal potential relationships between lncRNAs and their target genes. RESULTS: In DN, 311 lncRNAs were dysregulated. LncRNA-coexpressed mRNAs were mainly targeted to golgi apparatus (ontology: cellular component), catalytic activity (ontology: molecular function), and mitotic nuclear division (ontology: biological process), and were mostly enriched in glutathione metabolism signaling. One hundred forty-seven lncRNAs were regarded as cis-regulatory. Several groups of lncRNAs may participate in biological pathways related to DN via trans-regulation of protein-coding genes. CONCLUSION: Hundreds of lncRNAs are dysregulated in DN. These lncRNAs might be involved in the pathogenesis of DN by modulating multiple molecular pathways. Our findings provide potential candidate biomarkers for predicting or diagnosing DN.

Resveratrol protects podocytes against apoptosis via stimulation of autophagy in a mouse model of diabetic nephropathy.

Podocyte apoptosis coincides with albuminuria onset and precedes podocytopenia in diabetic nephropathy. However, there is a lack of effective therapeutic drugs to protect podocytes from apoptosis. Here, we demonstrated that resveratrol relieved a series of indicators of diabetic nephropathy and attenuated apoptosis of podocytes in db/db diabetic model mice. In addition, resveratrol induced autophagy in both db/db mice and human podocytes. Furthermore, inhibition of autophagy by 3-methyladenine (3-MA) and autophagy gene 5 (Atg5) short hairpin RNA (shRNA) reversed the protective effects of resveratrol on podocytes. Finally, we found that resveratrol might regulate autophagy and apoptosis in db/db mice and podocytes through the suppression of microRNA-383-5p (miR-383-5p). Together, our results indicate that resveratrol effectively attenuates high glucose-induced apoptosis via the activation of autophagy in db/db mice and podocytes, which involves miR-383-5p. Thus, this study reveals a new possible strategy to treat diabetic nephropathy.

Effects of diet-induced hypercholesterolemia on testosterone-regulated protein expression in mice liver.

We report here testosterone deficiency in diet-induced hypercholesterolemic mice. We attempted to compare the liver protein profiles between hypercholesterolemic and normal mice by using the technology of proteomics. Protein extractions from mice livers were separated by two-dimensional electrophoresis and the gels were analysed with image analysis software 2D Elite 4.0. The differentially expressed proteins were identified primarily by comparing with reference gel images in the SWISS 2DPAGE database and then confirmed by peptide mass fingerprinting. Sixteen differentially expressed protein spots (>2-fold) were detected and 8 of which were identified as major urinary proteins, carbonic anhydrase III, and glutathione S-transferase P2, which are known to be regulated by androgens. The expression of these three proteins was statistically lower in the livers of hypercholesterolemic mice. Meanwhile, the testosterone levels in serum, testis, and liver were lower in hypercholesterolemic mice than those in normal mice, when human chorionic gonadotrophin was injected intramuscularly. These results suggest a testosterone deficiency in diet-induced hypercholesterolemic mice.

Low-dose cytokine-induced neutral ceramidase secretion from INS-1 cells via exosomes and its anti-apoptotic effect.

It has been reported that the effect of inflammatory cytokines on ß-cell destruction in type 1 diabetes is concentration-dependent. However, the underlying mechanisms remain unclear. In the present study, we found that a high concentration of cytokines promoted apoptosis in the rat ß-cell line INS-1, whereas a low concentration of cytokines had no effect. We also found that cytokines at a low concentration stimulated neutral ceramidase (NCDase) release via exosomes from INS-1 cells, whereas cytokines at a high concentration inhibited NCDase release. Furthermore, the results showed that the NCDase-containing exosomes isolated from the culture medium of INS-1 cells treated with cytokines at a low concentration inhibited apoptosis induced by a high concentration of cytokines. Finally, the results also showed that the protective action of NCDase in the exosomes on apoptosis was mediated by the generation of sphingosine 1-phosphate (S1P) and its interaction with S1P receptor 2. Taken together, these findings revealed a novel NCDase-S1P-phosphate-S1P receptor 2-dependent mechanism by which a low level of inflammatory cytokines protects pancreatic ß-cells from apoptosis induced by a high level of inflammatory cytokines.

Three-dimensional Ni/SnOx/C hybrid nanostructured arrays for lithium-ion microbattery anodes with enhanced areal capacity.

The areal capacity of lithium-ion microbatteies (LIMBs) can be potentially increased by adopting a three-dimensional (3D) architectured electrode. Herein, we report the novel 3D Ni/SnOx/C hybrid nanostructured arrays that were built directly on current collectors via a facile hydrothermal method followed by a calcination-reduction process. Branched SnO2 nanorods grew uniformly on Ni2(OH)2CO3 nanowall arrays, resulting in the formation of precursors with a 3D interconnected architecture. By using ethylene glycol as the reducing agent, the glucose-coated SnO2/Ni2(OH)2CO3 precursors were evolved into an interesting 3D Ni/SnOx/C hybrid nanostructured arrays within the calcination treatment. Compared to conventional 2D SnOx/C nanorod arrays, the electrode of 3D Ni/SnOx/C hybrid nanostructured arrays exhibited enhanced lithium storage capacity per unit area, preferable rate capability and improved cycling performance when tested for LIMBs. The superior performance might be attributed to the open-up Ni frameworks that can not only serve as effective channels for electrons transport and Li+ diffusion but also help to accommodate the large volume changes upon lithiation/delithiation.

A novel evolution strategy to fabricate a 3D hierarchical interconnected core-shell Ni/MnO2 hybrid for Li-ion batteries.

A novel evolution strategy has been put forward to build a 3D interconnected core-shell Ni/MnO(2) hybrid on a current collector, which demonstrated stable cyclic performance and good rate capabilities when applied as the anode for Li-ion batteries.