Nitrogen-Doped and Sulfonated Carbon Dots as a Multifunctional Additive to Realize Highly Reversible Aqueous Zinc-Ion Batteries.

Aqueous zinc-ion batteries (ZIBs) using the Zn metal anode have been considered as one of the next-generation commercial batteries with high security, robust capacity, and low price. However, parasitic reactions, notorious dendrites and limited lifespan still hamper their practical applications. Herein, an eco-friendly nitrogen-doped and sulfonated carbon dots (NSCDs) is designed as a multifunctional additive for the cheap aqueous ZnSO4 electrolyte, which can overcome the above difficulties effectively. The abundant polar groups (-COOH, -OH, -NH2 , and -SO3 H) on the CDs surfaces can regulate the solvation structure of Zn2+ through decreasing the coordinated active H2 O molecules, and thus redistribute Zn2+ deposition to avoid side reactions. Some of the negatively charged NSCDs are adsorbed on Zn anode surface to isolate the H2 O/SO4 2- corrosion through the electrostatic shielding effect. The synergistic effect of the doped nitrogen species and the surface sulfonic groups can induce a uniform electrolyte flux and a homogeneous Zn plating with a (002) texture. As a result, the excellent cycle life (4000 h) and Coulombic efficiency (99.5%) of the optimized ZIBs are realized in typical ZnSO4 electrolytes with only 0.1 mg mL-1 of NSCDs additive.

Combination of co-crystal and nanocrystal techniques to improve the solubility and dissolution rate of poorly soluble drugs.

PURPOSE: Solubility and dissolution rate are essential for the oral absorption and bioavailability of poorly soluble drugs. The aim of this study was to prepare nano-co-crystals by combination of nanocrystal and co-crystal technologies, and investigate its effect, in situ, on increased kinetic solubility and dissolution rate. METHODS: Co-crystals of itraconazole-fumaric acid, itraconazole-succinic acid, indomethacin-saccharin and indomethacin-nicotinamide were prepared and nano-sized by wet milling. The particle size and solid state of the co-crystals were characterized by optical microscope, LD, PCS, DSC and XRPD before and after milling. RESULTS: 300-450 nm sized nano-co-crystals with a stable physical solid state were successfully prepared. Nano-co-crystals exhibited a lower crystallinity reduction than nanocrystals after wet milling. The particle size effect on the kinetic solubility of co-crystals was analysed for macro-, micro- and nano-co-crystals with in situ kinetic solubility studies. The maximum kinetic solubility of nano-co-crystals increased with excess conditions until a plateau. The highest increase was obtained with itraconazole-succinic acid nano-co-crystals with a kinetic solubility of 263.5 ± 3.9 µg/mL which was 51.5 and 6.6 times higher than the solubility of raw itraconazole and itraconazole-succinic acid co-crystal. CONCLUSIONS: The synergistic effect of nanocrystals and co-crystals with regard to increased kinetic solubility and dissolution rate was proven. The combination of the advantages of nanocrystals and co-crystals is a promising formulation strategy to increase both the solubility and dissolution rate of poorly soluble drugs.

Incorporation of itraconazole nano-co-crystals into multiparticulate oral dosage forms.

Limited research has been performed on the downstream processing of nano-co-crystal suspensions into solid oral dosage forms. The objectives of this study were to evaluate the impact of three downstream processes (wet granulation, spray granulation and bead layering) on the performance of itraconazole-succinic acid (ITZ-SUC) nano-co-crystal suspension. An optimized ITZ-SUC nano-co-crystal suspension mixed with HPMC E5 was utilized for the downstream processing. The suspension was converted in the solid state either by wet or spray granulation (with microcrystalline cellulose or lactose as substrates) or by layering onto microcrystalline cellulose and sugar beads. The multiparticulate solid dosage forms were characterized by optical microscopy, differential scanning calorimeter (DSC), X-ray powder diffraction (XRPD) and in situ dissolution studies. Spray granulation and bead layering resulted in less particle aggregation, a faster dissolution rate, and higher kinetic solubility when compared to wet granulation. ITZ-SUC nano-co-crystals spray granulated with lactose resulted in higher kinetic solubility profiles compared to microcrystalline cellulose granules. The type of bead core had no impact on the dissolution behavior. A slower dissolution and decreased kinetic solubility were observed with increasing drug loading for sprayed granules when microcrystalline cellulose was used as substrate. All dosage forms were stable under accelerated storage conditions (40 °C/75% RH) when blistered. Nano-co-crystals incorporated in granules were less stable than layered beads under non-blistered condition. Nano-co-crystals layered sugar beads are an interesting alternative to amorphous solid dispersion; a comparable kinetic solubility but a faster drug release were achieved. This study identified bead layering as a superior downstream process approach for incorporating ITZ-SUC nano-co-crystals into an oral solid dosage form without compromising drug dissolution.

In-Situ Growth of Mn3 O4 Nanoparticles on Nitrogen-Doped Carbon Dots-Derived Carbon Skeleton as Cathode Materials for Aqueous Zinc Ion Batteries.

Mn3 O4 is a promising cathode material for aqueous zinc ion batteries (ZIBs) which is a new type of low cost, eco-friendly, high security energy storage system, while those previously reported electrochemical capacities of Mn3 O4 are far from its theoretical value. In this work, Mn3 O4 nanoparticles and nitrogen-doped carbon dots (NCDs) are synthesized together through an in-situ hydrothermal route, and then calcined to be a nanocomposite in which Mn3 O4 nanoparticles are anchored on a nitrogen-doped carbon skeleton (designated as Mn3 O4 /NCDs). Although the carbon content is only 3.9 wt.% in the Mn3 O4 /NCDs, the NCDs-derived carbon skeleton provides an electrically conductive network and a stable structure. Such a special nanocomposite has a large specific surface area, plenty of active sites, excellent hydrophilicity and good electronic conductivity. Owing to these structural merits, the Mn3 O4 /NCDs electrode exhibits a preeminent specific capacity of 443.6 mAh g-1 and 123.3 mAh g-1 at current densities of 0.1 and 1.5 A g-1 in ZIBs, respectively, which are far beyond the bare Mn3 O4 nanoparticles synthesized under the similar condition. The electrochemical measurement results prove that carbon dots, as a new type of carbon nanomaterials, have strong ability to modify and improve the performance of existing electrode materials, which may push these electrode materials forward to practical applications.

Kinetic solubility improvement and influence of polymers on controlled supersaturation of itraconazole-succinic acid nano-co-crystals.

Nano-co-crystals enhance the solubility and dissolution rate of poorly soluble drugs. The objective of this study was to obtain a better understanding of the dissolution process of nano-co-crystals and of the precipitation inhibition by various polymers. Itraconazole-succinic acid (ITZ-SUC) nano-co-crystal was chosen as model drug formulation to investigate the supersaturation and precipitation inhibition capabilities of various polymers (HPMC E5, HPMC E50, HPMCAS, HPC-SSL, PVPK30 and PVPVA64). The kinetic concentration-time profiles of nano-co-crystal were measured under non-sink conditions with in situ UV-VIS spectroscopy. HPMC E5 performed best by achieving the greatest extended supersaturation/precipitation inhibition. The precipitation inhibition capacity of HPMC E5 was proportional to its concentration. The maximum achievable supersaturation was proportional to the dissolution rate which can be modulated by the rate of supersaturation generation (i.e., addition rate or dose). Supersaturation could be prolonged significantly resulting in 2-5-fold increased area under the dissolution curves compared to nano-co-crystals alone. This effect was limited by a critical excess of undissolved particles with high specific surface area which acted as crystallization seeds resulting in faster precipitation. The study highlighted that a faster dissolution rate and the use of precipitation inhibitors were two key factors determining the extent and time of supersaturation of nano-co-crystals.

Denitrifying anaerobic methane oxidation process responses to the addition of growth factor betaine in the MFC-granular sludge coupling system: Enhancing mechanism and metagenomic analysis.

To solve the problem of the slow growth of denitrifying anaerobic methane oxidation (DAMO) bacteria during the enrichment process, betaine was added as a growth factor and its influence on the mechanism of DAMO process along with the metagenomic analysis of the process in a MFC-granular sludge coupling system was explored. When the addition of betaine was increased to 0.5 g/L and 1.0 g/L, the NO3--N removal increased to 210 mg/L. Also, the increasing betaine dosage in 1st to 4th chambers resulted in a significant increase in dissolved methane concentration which reached a maximum value of 16.6 ± 1.19 mg/L. When the dosage of betaine was increased from 0 g/L to 1.0 g/L, the dominant bacterial phyla in the 1st to 4th chambers changed to Proteobacteria (20.8-50.7%) from Euryarchaeota (42.0-54.1%) and Methanothrix which was significantly decreased by 17.9-37.4%. There was a slight decline in the DAMO microorganism abundance, possibly due to the increased methyl donors limiting the DAMO microorganism growth. Denitrification metabolism pathway module (increased from 0.10% to 0.15%) of Nitrogen metabolism and Formaldehyde assimilation, and serine pathway of Methane metabolism presented an ascendant trend with the increased betaine dosage as determined by the metagenomics analysis of KEGG metabolism pathway.

[Effects of PES and 2,4-DCP on the Extracellular Polymeric Substances and Microbial Community of Anaerobic Granular Sludge].

The effects of polyether sulfone (PES) microplastics and 2,4-dichlorophenol (2,4-DCP) on the loosely-bound extracellular polymeric substances (LB-EPS) and tightly-bound EPS (TB-EPS) of anaerobic granular sludge were investigated. In addition, high-throughput sequencing technology was used to analyze the changes in the microbial community and gene functions in the anaerobic granular sludge. The results revealed that the chemical oxygen demand (COD) removal rates of the 2,4-DCP and PES+2,4-DCP experimental groups were 35% and 37%, which were 57% and 55% lower than that of the blank control group, while the COD removal rates of the PES experimental group remained around 90%. After the addition of the PES microplastics and 2,4-DCP, the protein and polysaccharide contents in the LB-EPS decreased compared with the control group, and the polysaccharide content in TB-EPS increased the least. In presence of the PES microplastics and 2,4-DCP, the activity of coenzyme F420 was inhibited. Through high-throughput sequencing, the microbial richness and diversity of the anaerobic granular sludge in the experimental group were reduced with the addition of the PES microplastics or 2,4-DCP. In the control group and the experimental group, the dominant bacteria at the phylum level were Proteobacteria (13.45%-44.47%), Firmicutes (6.86%-21.67%), and Actinobacteria (3.16%-18.11%). The abundance of ß-Proteobacteria in the PES+2,4-DCP experimental group was reduced by 15.28%, while the abundance of γ-Proteobacteria increased by 28.44% compared with the control group. Based on the phylogenetic investigation of the communities using the reconstruction of unobserved states (PICRUSt) analysis, it was found that in the experimental group with the PES microplastics or 2,4-DCP, the genes related to the sludge energy metabolism function were 0.25%-0.72% more than the control group; therefore, the abundance of genes related to the transport function group decreased significantly.

Enzymatic preparation of manno-oligosaccharides from locust bean gum and palm kernel cake, and investigations into its prebiotic activity

BACKGROUND: Manno-oligosaccharides (MOS) is known as a kind of prebiotics. Mannanase plays a key role for the degradation of mannan to produce MOS. In this study, the mannanases of glycoside hydrolase (GH) families 5 Man5HJ14 and GH26 ManAJB13 were employed to prepare MOS from locust bean gum (LBG) and palm kernel cake (PKC). The prebiotic activity and utilization of MOS were assessed in vitro using the probiotic Lactobacillus plantarum strain. RESULTS: Galactomannan from LBG was converted to MOS ranging in size from mannose up to mannoheptose by Man5HJ14 and ManAJB13. Mannoheptose was got from the hydrolysates produced by Man5HJ14, which mannohexaose was obtained from LBG hydrolyzed by ManAJB13. However, the same components of MOS ranging in size from mannose up to mannotetrose were observed between PKC hydrolyzed by the mannanases mentioned above. MOS stability was not affected by high-temperature and high-pressure condition at their natural pH. Based on in vitro growth study, all MOS from LBG and PKC was effective in promoting the growth of L. plantarum CICC 24202, with the strain preferring to use mannose to mannotriose, rather than above mannotetrose. CONCLUSIONS: The effect of mannanases and mannan difference on MOS composition was studied. All of MOS hydrolysates showed the stability in adversity condition and prebiotic activity of L. plantarum, which would have potential application in the biotechnological applications.

Thermo-Electric Properties of Cu and Ni Nanoparticles Packed Beds.

The hot-wire method and the four-probe resistivity method are applied to probe the thermal conductivity (k) and the electric conductivity (σ) of Cu and Ni nanoparticle packed beds (NPBs). A fitting method based on classical physical theory is devised to separate ke (electronic thermal conductivity) and kp (phonon thermal conductivity) from k at room temperature. Results turn out that kp only accounts for a small proportion of k (4-20%); the proportion decreases with increasing porosity or temperature. Most importantly, this fitting method provides a simple way to separate ke and kp from k at room temperature. The Wiedemann-Franz law is checked and is found to be unsuitable for NPBs. The Lorenz number (L) is calculated from measurements of ke, k, and σ. Results turn out that L is found to be 50-60 times that of the bulk. With a Seebeck coefficient (S) measured, the thermoelectric property of NPBs is also calculated. We find that the NPB possess an advantage in thermoelectric property than bulk, the thermoelectric figure of merit (ZT) of Ni (Cu) NPBs can be 20.17 (1.87) times that of bulk Ni (Cu). The effect of porosity on ZT is also discussed, and results show that a NPB with a small porosity is more preferable as a thermoelectric material. With a small porosity, ZT can be even 1.73 times that of a large porosity. Although metals are not good thermoelectric material, the method in this paper supplies a way to improve the thermoelectric property of other thermoelectric materials.

Reducing Interstitial Fluid Pressure and Inhibiting Pulmonary Metastasis of Breast Cancer by Gelatin Modified Cationic Lipid Nanoparticles.

Interstitial fluid pressure (IFP) in tumor is much higher than that in normal tissue, and it constitutes a great obstacle for the delivery of antitumor drugs, thus becoming a potential target for cancer therapy. In this study, cationic nanostructured lipid carriers (NLCs) were modified by low molecular weight gelatin to achieve the desirable reduction of tumor IFP and improve the drug delivery. In this way, the chemotherapy of formulations on tumor proliferation and pulmonary metastasis was further improved. The nanoparticles were used to load three drugs, docetaxel (DTX), quercetin (Qu), and imatinib (IMA), with high encapsulation efficiency of 89.54%, 96.45%, and 60.13%, respectively. GNP-DTX/Qu/IMA nanoparticles exhibited an enzyme-sensitive drug release behavior, and the release rate could be mediated by matrix metalloproteinases (MMP-9). Cellular uptake and MTT assays showed that the obtained GNP-DTX/Qu/IMA could be internalized into human breast 4T1 cells effectively and exhibited the strongest cytotoxicity. Moreover, GNP-DTX/Qu/IMA demonstrated obvious advantages in inducing apoptosis and mediating the expression of apoptosis-related proteins (Caspase 3, Caspase 9, and bcl-2). In the wound-healing assay, GNP-DTX/Qu/IMA exhibited evidently inhibition of cell migration. The benefits of tumor IFP reduction induced by GNP-DTX/Qu/IMA were further proved after a continuous administration to 4T1 tumor-bearing mice. Finally, in the in vivo antitumor assays, GNP-DTX/Qu/IMA displayed stronger antitumor efficiency as well as suppression on pulmonary metastasis. In conclusion, the GNP-DTX/Qu/IMA system might be a promising strategy for metastatic breast cancer treatment.

Multifunctional Nanoparticles Loading with Docetaxel and GDC0941 for Reversing Multidrug Resistance Mediated by PI3K/Akt Signal Pathway.

The polylactic-co-glycolic acid polyethylene glycol conjugated with cell penetrating peptide R7 (PLGA-PEG-R7)/polysulfadimethoxine-folate nanoparticles loaded with docetaxel (DTX) and GDC0941 (R7/PSD-Fol NPs) were prepared to overcome multidrug resistance (MDR) and enhance the antitumor activity. First, polysulfadimethoxine-folate was synthesized to construct the R7/PSD-Fol NPs. The R7/PSD-Fol NPs were prepared with the abilities of effective entrapment and drug loading. Due to the pH-sensitive effect of PSD-folate, the releasing of DTX and GDC0941 from the R7/PSD-Fol NPs was lower in pH 7.4 buffer solution than that in pH 5.0 buffer solution. The half maximal inhibitory concentration (IC50) of MCF-7 and resistant to doxorubicin (MCF-7/Adr) cells illustrated the cytotoxicity of R7/PSD-Fol nanoparticles by using the MTT method. The uptake of R7/PSD-Fol NPs was visualized by using the fluorescence of Rh-123 to detect the targeting effect of folate on the surface of R7/PSD-Fol NPs. The results of the cell apoptosis and the depolarization of mitochondrial membrane potential (MMP) were adopted to show the cytotoxicity of the R7/PSD-Fol NPs on MCF-7/Adr cells. The Western blot revealed the inhibition of PI3K/Akt pathway in MCF-7/Adr cells induced by R7/PSD-Fol NPs. Finally, both in vivo distribution and in vivo antitumor showed the R7/PSD-Fol NPs displayed the better distribution at tumor site and the stronger suppression of tumor growth in the tumor bearing nude mice compared with control group. It was concluded that R7/PSD-Fol NPs loaded with DTX and GDC0941 could overcome MDR and enhance the antitumor effect further.

Hyaluronic acid-coated cationic nanostructured lipid carriers for oral vincristine sulfate delivery.

The goal of this research is to structure a hyaluronic acid modified nanostructured lipid carrier (HA-NLCs) for vincristine sulfate (VCR) delivery, and detect its efficiency to improve the oral bioavailability. Emulsion solvent evaporation method was used to prepare the HA-NLCs nanoparticles. The particle size, zeta potential and entrapment efficiency of VCR-NLCs and HA-NLCs were 187 ± 3.52 nm, -8.61 ± 1.29 mV, 33.12 ± 1.16% and 192 ± 4.41 nm, -32.82 ± 2.64 mV, 34.41 ± 2.21%, respectively. HA-NLCs could significantly improve the cellular uptake efficiency and cytotoxicity in MCF-7 cells than other VCR formulations. The expressions of apoptosis related protein Caspase-3, Caspase-9, Bax and Bcl-2 were estimated by western blot assay in MCF-7 cells, and HA-NLCs exhibited the strongest effect in promoting cell apoptosis. The pharmacokinetics of HA-NLCs was evaluated in Sprague-Dawley male rats and the relative oral bioavailability of HA-NLCs and VCR-NLCs was improved about 1.8-fold and two-fold compared with VCR solution, respectively. Therefore, these results indicated that HA-NLCs could significantly improve the oral bioavailability and was a promising vehicle for the oral delivery of VCR.

Optical phase retrieval using conical refraction in structured media.

We propose a method of optical phase retrieval based on the conical refraction imaging in structured media. We show that a multilayered dielectric photonic crystal functioning as a conically refractive flat lens can be used to reconstruct phase information of complex optical signals. Our method enables a single simultaneous measurement of multiple images on the same image plane and allows a rapid stable recovery of the optical phase. The planar geometry of the proposed device is compatible with current nano-fabrication techniques and, therefore, can find broad applications in optical signal processing and imaging.

Influence of Nanopore Shapes on Thermal Conductivity of Two-Dimensional Nanoporous Material.

The influence of nanopore shapes on the electronic thermal conductivity (ETC) was studied in this paper. It turns out that with same porosity, the ETC will be quite different for different nanopore shapes, caused by the different channel width for different nanopore shapes. With same channel width, the influence of different nanopore shapes can be approximately omitted if the nanopore is small enough (smaller than 0.5 times EMFP in this paper). The ETC anisotropy was discovered for triangle nanopores at a large porosity with a large nanopore size, while there is a similar ETC for small pore size. It confirmed that the structure difference for small pore size may not be seen by electrons in their moving.

Identification and Characterization of a New 7-Aminocephalosporanic Acid Deacetylase from Thermophilic Bacterium Alicyclobacillus tengchongensis.

UNLABELLED: Deacetylation of 7-aminocephalosporanic acid (7-ACA) at position C-3 provides valuable starting material for producing semisynthetic ß-lactam antibiotics. However, few enzymes have been characterized in this process before now. Comparative analysis of the genome of the thermophilic bacterium Alicyclobacillus tengchongensis revealed a hypothetical protein (EstD1) with typical esterase features. The EstD1 protein was functionally cloned, expressed, and purified from Escherichia coli BL21(DE3). It indeed displayed esterase activity, with optimal activity at around 65°C and pH 8.5, with a preference for esters with short-chain acyl esters (C2 to C4). Sequence alignment revealed that EstD1 is an SGNH hydrolase with the putative catalytic triad Ser15, Asp191, and His194, which belongs to carbohydrate esterase family 12. EstD1 can hydrolyze acetate at the C-3 position of 7-aminocephalosporanic acid (7-ACA) to form deacetyl-7-ACA, which is an important starting material for producing semisynthetic ß-lactam antibiotics. EstD1 retained more than 50% of its initial activity when incubated at pH values ranging from 4 to 11 at 65°C for 1 h. To the best of our knowledge, this enzyme is a new SGNH hydrolase identified from thermophiles that is able to hydrolyze 7-ACA. IMPORTANCE: Deacetyl cephalosporins are highly valuable building blocks for the industrial production of various kinds of semisynthetic ß-lactam antibiotics. These compounds are derived mainly from 7-ACA, which is obtained by chemical or enzymatic processes from cephalosporin C. Enzymatic transformation of 7-ACA is the main method because of the adverse effects chemical deacylation brought to the environment. SGNH hydrolases are widely distributed in plants. However, the tools for identifying and characterizing SGNH hydrolases from bacteria, especially from thermophiles, are rather limited. Here, our work demonstrates that EstD1 belongs to the SGNH family and can hydrolyze acetate at the C-3 position of 7-ACA. Moreover, this study can enrich our understanding of the functions of these enzymes from this family.

Zeroth-order transmission resonance in hyperbolic metamaterials.

We present a new approach to subwavelength optical confinement, based on hyperbolic media in planar Fabry-Perot geometry. Unlike higher-order resonance modes in indefinite metamaterial cavities, the predicted resonance corresponds to 0th-order mode and can be observed in planar systems. Our approach combines subwavelength light confinement with strong radiative coupling, enabling a practical planar design of nanolasers and subwavelength waveguides.

Synthesis and antiproliferative evaluation of certain 4-anilino-8-methoxy-2-phenylquinoline and 4-anilino-8-hydroxy-2-phenylquinoline derivatives.

The present report describes the synthesis and antiproliferative evaluation of certain 4-anilino-8-methoxy-2-phenylquinoline and 4-anilino-8-hydroxy-2-phenylquinoline derivatives. The antiproliferative activity of 4'-COMe-substituted derivatives decreased in an order of 6-OMe (1, 3.89 microM) > 8-OMe (8, 10.47 microM) > 8-OH (9, 14.45 microM), indicating that the position of substitution at the quinoline ring is crucial. For 3'-COMe derivatives, the antiproliferative activity of 8-OH (11, 1.20 microM) is more potent than its 8-OMe counterpart (10, 8.91 microM), indicating that a H-bonding donating substituent is more favorable than that of a H-bonding accepting group. Comparison of 8-OH derivatives, the antiproliferative effect of COMe (11) is more potent than its oxime derivative (15a, 2.88 microM), which in turn is more potent than the methyloxime counterpart (15b, 5.50 microM). Compound 11 is especially active against the growth of certain solid cancer cells such as HCT-116 (colon cancer), MCF7, and MDA-MB-435 (breast cancer) with GI50 values of 0.07, <0.01, and <0.01 microM, respectively. Flow cytometric analyses revealed that growth inhibition by 11 and 15a was due to accumulation in S-phase. This result is interesting because 2-phenylquinolone derivatives have been reported to be antimitotic agents which induced cell cycle arrest in G2/M phase.