p-Phenylenediamine Antioxidants in PM2.5: The Underestimated Urban Air Pollutants.

The wide use and continuous abrasion of rubber-related products appears to be leading to an incredible release of p-phenylenediamine (PPD) antioxidants in the environment. However, no related research has been conducted on the pollution characteristics and potential health risks of PM2.5-bound PPDs. We report for the first time the ubiquitous distributions of six emerging PPDs and a quinone derivative, N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPDQ), in PM2.5 from urban areas of China. Atmospheric contamination levels of PM2.5-bound PPDs were found to be mostly in pg m-3 amounts between 2018 and 2019. Urban vehicle rubber tire abrasion was found to probably contribute to the PPDs in PM2.5 and accounted for their significant spatiotemporal-dependent concentration variations. Furthermore, 6PPDQ, an emerging oxidation product of 6PPD in the environment, was first quantified (pg m-3) with a total detection rate of 81% in the urban PM2.5, demonstrating its broad existence. On the basis of the determined ambient concentrations, the annual intakes of PPDs and 6PPDQ for adults were not low, indicating their possible human health risks induced by long-term exposure. This study confirms the widespread occurrence of PPDs and 6PPDQ in PM2.5, showing that the pollution of such compounds in urban air should not be underestimated.

LTBP3 Pathogenic Variants Predispose Individuals to Thoracic Aortic Aneurysms and Dissections.

The major diseases affecting the thoracic aorta are aneurysms and acute dissections, and pathogenic variants in 11 genes are confirmed to lead to heritable thoracic aortic disease. However, many families in which multiple members have thoracic aortic disease do not have alterations in the known aortopathy genes. Genes highly expressed in the aorta were assessed for rare variants in exome sequencing data from such families, and compound rare heterozygous variants (p.Pro45Argfs∗25 and p.Glu750∗) in LTBP3 were identified in affected members of one family. A homozygous variant (p.Asn678_Gly681delinsThrCys) that introduces an additional cysteine into an epidermal growth factor (EGF)-like domain in the corresponding protein, latent TGF-ß binding protein (LTBP-3), was identified in a second family. Individuals with compound heterozygous or homozygous variants in these families have aneurysms and dissections of the thoracic aorta, as well as aneurysms of the abdominal aorta and other arteries, along with dental abnormalities and short stature. Heterozygous carriers of the p.Asn678_Gly681delinsThrCys variant have later onset of thoracic aortic disease, as well as dental abnormalities. In these families, LTBP3 variants segregated with thoracic aortic disease with a combined LOD score of 3.9. Additionally, heterozygous rare LTBP3 variants were found in individuals with early onset of acute aortic dissections, and some of these variants disrupted LTBP-3 levels or EGF-like domains. When compared to wild-type mice, Ltbp3-/- mice have enlarged aortic roots and ascending aortas. In summary, homozygous LTBP3 pathogenic variants predispose individuals to thoracic aortic aneurysms and dissections, along with the previously described skeletal and dental abnormalities.

Dual-ligand functionalized carbon nanodots as green fluorescent nanosensors for cellular dual receptor-mediated targeted imaging.

The conjugation of ligands to nanoparticles as drug delivery systems that target specific cells is a promising approach for the delivery of therapeutic agents to tumor cells. Herein, we prepared green-emission fluorescent carbon nanodots (CNDs) by a facile hydrothermal method with d-(+)-glucosamine hydrochloride and l-aspartic acid as the precursors, then covalently conjugated with folate (FA), polyethyleneimine (PEI) and hyaluronic acid (HA) to develop dual ligand-decorated nanocarriers (FA-PEI-HA-CNDs) for the targeted imaging of cancer cells. FA-PEI-HA-CNDs integrated the excellent fluorescence property of CNDs, and can be used for the real-time and noninvasive location tracking of cancer cells. The cellular uptake study demonstrated that FA-PEI-HA-CNDs markedly improved the internalization efficiency in A-549 cells via folate/CD44 receptor-mediated endocytosis in comparison with that of the A549 cells pretreated with excess FA, HA, and FA and HA. Therefore, these dual folate/CD44 receptor-targeted CNDs (FA-PEI-HA-CNDs) show promising potential for cancer detection, drug delivery, and individualized treatment as performance platforms.

High-efficient nickel-doped lignin carbon dots as a fluorescent and smartphone-assisted sensing platform for sequential detection of Cr(VI) and ascorbic acid.

Using lignin as a raw material to prepare fluorescent nanomaterials represents a significant pathway toward the high-value utilization of waste biomass. In this study, Ni-doped lignin carbon dots (Ni-LCDs) were rapidly synthesized with a yield of 63.22 % and a quantum yield of 8.25 % using a green and simple hydrothermal method. Exploiting the inner filter effect (IFE), Cr(VI) effectively quenched the fluorescence of the Ni-LCDs, while the potent reducing agent ascorbic acid (AA) restored the quenched fluorescence, thus establishing a highly sensitive fluorescence switch sensor platform for the sequential detection of Cr(VI) and AA. Importantly, the integration of a smartphone facilitated the portability of Cr(VI) and AA detection, enabling on-site, in-situ, and real-time monitoring. Ultimately, the developed fluorescence and smartphone-assisted sensing platform was successfully applied to detect Cr(VI) in actual water samples and AA in various fruits. This study not only presents an efficient method for the conversion and utilization of waste lignin but also broadens the application scope of the CDs in the field of smart sensors.

MnO2 nanosheets anchored with polypyrrole nanoparticles as a multifunctional platform for combined photothermal/photodynamic therapy of tumors.

Herein, PPy@MnO2 nanocomposites were first harvested by anchoring MnO2 nanosheets on polypyrrole (PPy) nanoparticles via an in situ redox reaction, then polyethylene glycol (PEG) modifier and methylene blue (MB) photosensitizer were linked through electrostatic interactions to obtain PPy@MnO2-PEG-MB nanoarchitectures. PPy nanoparticles ensure photothermal therapy (PTT) ability and MnO2 nanosheets ameliorate tumor hypoxia for enhanced photodynamic therapy (PDT). Therefore, a multifunctional nanotherapeutic system was constructed for the combined PTT/PDT of tumors. For extracellular photothermal properties, the optimal temperature elevation was 52.6 °C with 54.4% photothermal conversion efficiency. The extracellular PDT ability was measured by detecting 1O2 generation; more 1O2 was produced under acidic conditions in the presence of H2O2 (a simulated tumor microenvironment). The effective cellular uptake of the nanotherapeutic system in HeLa cells was observed by confocal laser scanning microscopy (CLSM). CLSM also indicated that more 1O2 was generated by the nanotherapeutic system as compared to free MB in HeLa cells, confirming the amelioration of tumor hypoxia by MnO2 nanosheets. MTT assays demonstrated that the nanotherapeutic system possessed superior biocompatibility without laser irradiation, and the lowest cell viabilities for single PTT and PDT groups were 13.78%, 38.82% respectively, while there was only 1.29% cell viability in the combined PTT and PDT group. These results suggest that the strategy of assembling PPy with MnO2 for a multifunctional PTT and enhanced PDT nanoplatform was realized, and opens up an unimpeded approach for integrating photothermal reduction materials with MnO2 for use in synergistic PTT and PDT.

One-Step Synthesis of Label-Free Ratiometric Fluorescence Carbon Dots for the Detection of Silver Ions and Glutathione and Cellular Imaging Applications.

The construction of ratiometric fluorescence assay has displayed fantastic advantages in improving semi-quantitative visualization capability by presenting successive color changes. Herein, long-wavelength emission nitrogen-doped carbon dots (N-CDs) were developed for intrinsic ratiometric detection of silver ions (Ag+) and glutathione (GSH), accompanied by visualization fluorescence variation of orange and green. The label-free N-CDs were favorably obtained through one-step hydrothermal synthesis and displayed single long-wavelength emission at 618 nm under the excitation wavelength of 478 nm. Interestingly, a ratio rising peak emerges at 532 nm and the emission at 618 nm decreases with the introduction of Ag+, which exhibits ratiometric fluorescence emission characteristics ( I618nm/ I532nm) in the range of 0-140 µM with significant fluorescence varying from orange to green. Furthermore, the fluorescence of CDs@Ag(I) can be effectively ratiometric recovered by virtue of a specific reaction of GSH with Ag+, which is accompanied by the fluorescence of the solution returning from green to orange. In addition, the N-CDs hold excellent biocompatibility which can be implemented as the visualization biosensing platform for intracellular determination of Ag+ and GSH, demonstrating that proposed N-CDs have tremendous potential in biological systems.

[Effect of calcium on proliferation, migration and osteogenic differentiation of human dental follicle cells].

PURPOSE: To determine the role of Ca2+ in proliferation,migration and osteogenic differentiation of human dental follicle cells(hDFCs). METHODS: hDFCs were isolated and cultured. The source of hDFCs was detected by immunofluorescence staining. Osteogenesis and adipogenic differentiation of hDFCs was detected by alizarin red staining and oil red O staining, to identify its multi-directional differentiation ability. A series of Ca2+ solutions with different concentrations was prepared, CCK8 assay was used to detect the proliferative abilities at 1, 3, 5, and 7 d；migratory ability of 24 h was detected by Transwell assay. Calcium nodules were detected by semiquantitative analysis of alizarin red staining. mRNA expression of osteogenic differentiation related genes was examined by real-time quantitative polymerase chain reaction (RT-qPCR).Statistical analysis was performed using SPSS 17.0 software package. RESULTS: Compared with the control group, 3,4 and 5 mmol/L Ca2+ significantly promoted proliferation of hDFCs at 3, 5 and 7 d (P<0.05). 3, 4, 5 and 6 mmol/L Ca2+ significantly promoted the migration of hDFCs at 24 h(P<0.01). High concentration of Ca2+ had no significant effect on its proliferation and migration. The results of alizarin red staining showed that when Ca2+ concentration reached 4 mmol/L, formation of mineralized nodules were increased(P<0.01), and Ca2+ concentration-dependent. RT-qPCR results showed that Ca2+ up-regulated the expression of RUNX2 and OCN in osteogenic differentiation genes (P<0.01). CONCLUSIONS: Low Ca2+ concentration is beneficial to proliferation and migration, and high Ca2+ concentration is beneficial to osteogenic differentiation of human dental follicle cells.

Electrochemical sensor for sensitive detection of triclosan based on graphene/palladium nanoparticles hybrids.

In this paper, poly (diallyldimethylammonium chloride) functionalized graphene/palladium nanoparticles (PDDA-Gr/PdNPs) have been successfully synthesized through a simple one-pot method with the use of PDDA as stabilizing agents. The electrochemical response of triclosan on the PDDA-Gr/PdNPs modified glassy carbon electrode (GCE) is greatly enhanced comparing to the PDDA-Gr/GCE or the bare GCE. It is suggested that the nanocomposite exhibited good electron transfer ability and catalytic activity. Under the optimal conditions, the oxidation current increased linearly with the concentration of triclosan in the range of 9.0nM to 20.0µM. The detection limit was estimated to be 3.5nM (S/N=3). Besides, the electrochemical sensor presented superior reproducibility, excellent anti-interference performance and long-term stability. What is more, the method is promising for the determination of trace amounts of triclosan in water samples.

A novel proposal of a simplified bacterial gene set and the neo-construction of a general minimized metabolic network.

A minimal gene set (MGS) is critical for the assembly of a minimal artificial cell. We have developed a proposal of simplifying bacterial gene set to approximate a bacterial MGS by the following procedure. First, we base our simplified bacterial gene set (SBGS) on experimentally determined essential genes to ensure that the genes included in the SBGS are critical. Second, we introduced a half-retaining strategy to extract persistent essential genes to ensure stability. Third, we constructed a viable metabolic network to supplement SBGS. The proposed SBGS includes 327 genes and required 431 reactions. This report describes an SBGS that preserves both self-replication and self-maintenance systems. In the minimized metabolic network, we identified five novel hub metabolites and confirmed 20 known hubs. Highly essential genes were found to distribute the connecting metabolites into more reactions. Based on our SBGS, we expanded the pool of targets for designing broad-spectrum antibacterial drugs to reduce pathogen resistance. We also suggested a rough semi-de novo strategy to synthesize an artificial cell, with potential applications in industry.

A high performance nonenzymatic electrochemical glucose sensor based on polyvinylpyrrolidone-graphene nanosheets-nickel nanoparticles-chitosan nanocomposite.

In this report, a new nanocomposite was successfully synthesized by chemical deposition of nickel nanoparticles (NiNPs) on polyvinylpyrrolidone (PVP) stabilized graphene nanosheets (GNs) with chitosan (CS) as the protective coating. The as obtained nanocomposite (PVP-GNs-NiNPs-CS) was characterized by X-ray photoelectron spectroscopy (XPS) and transmission electron microscopy (TEM). Benefiting from the synergistic effect of GNs (large surface area and high conductivity), NiNPs (high electrocatalytic activity towards the glucose oxidation) and CS (good film-forming and antifouling ability), a nonenzymatic electrochemical glucose sensor was established. The nanocomposite displays greatly enhanced electrocatalytic activity towards the glucose oxidation in NaOH solution. The PVP-GNs-NiNPs-CS based electrochemical glucose sensor demonstrates good sensitivity, wide linear range (0.1 µM-0.5 mM), outstanding detection limit (30 nM), attractive selectivity, good reproducibility, high stability as well as prominent feasibility for the real sample analysis. The proposed experiment might open up a new possibility for widespread use of non-enzymatic sensors for monitoring blood glucose owing to its advantages of low cost, simple preparation and excellent properties for glucose detection.

Facile synthesis of nitrogen-doped carbon dots for Fe(3+) sensing and cellular imaging.

A fast and facile approach to synthesize highly nitrogen (N)-doped carbon dots (N-CDs) by microwave-assisted pyrolysis of chitosan, acetic acid and 1,2-ethylenediamine as the carbon source, condensation agent and N-dopant, respectively, is reported. The obtained N-CDs are fully characterized by elemental analysis, transmission electron microscopy, high-resolution transmission electron microscopy, Fourier transform infrared spectroscopy, Raman spectroscopy, X-ray diffraction pattern, X-ray photoelectron spectroscopy, UV-vis absorption, and photoluminescence spectroscopy. Doping N heteroatoms benefits the generation of N-CDs with stronger fluorescence emission. As the emission of N-CDs is efficiently quenched by Fe(3+), the as-prepared N-CDs are employed as a highly sensitive and selective probe for Fe(3+) detection. The detection limit can reach as low as 10 ppb, and the linear range is 0.010-1.8 ppm Fe(3+). The as-synthesized N-CDs have been successfully applied for cell imaging and detecting Fe(3+) in biosystem.

Grass height and transmission ecology of Echinococcus multilocularis in Tibetan communities, China.

BACKGROUND: Alveolar echinococcosis is a major zoonosis of public health significance in western China. Overgrazing was recently assumed as a potential risk factor for transmission of alveolar echinococcosis. The research was designed to further test the overgrazing hypothesis by investigating how overgrazing influenced the burrow density of intermediate host small mammals and how the burrow density of small mammals was associated with dog Echinococcus multilocularis infection. METHODS: The study sites were chosen by previous studies which found areas where the alveolar echinococcosis was prevalent. The data, including grass height, burrow density of intermediate host small mammals, dog and fox fecal samples as well as Global Positioning System (GPS) position, were collected from field investigations in Shiqu County, Sichuan Province, China. The fecal samples were analyzed using copro-PCR. The worms, teeth, bones and hairs in the fecal samples were visually examined. Single factor and multifactor analyses tools including chi square and generalized linear models were applied to these data. RESULTS: By using grass height as a proxy of grazing pressure in the homogenous pasture, this study found that taller grass in the pasture led to lower small mammals' burrow density (chi(2) = 4.670, P = 0.031, coefficient = -1.570). The Echinococcus multilocularis worm burden in dogs was statistically significantly related to the maximum density of the intermediate host Ochotona spp. (chi(2) = 5.250, P = 0.022, coefficient = 0.028). The prevalence in owned dogs was positively correlated to the number of stray dogs seen within a 200 meter radius (Wald chi(2) = 8.375, P = 0.004, odds ratio = 1.198). CONCLUSIONS: Our findings support the hypothesis that overgrazing promotes transmission of alveolar echinococcosis and confirm the role of stray dogs in the transmission of alveolar echinococcosis.