Ursodeoxycholic acid loaded dual-modified graphene oxide nanocomposite alleviates cholestatic liver injury through inhibiting hepatocyte apoptosis.

Ursodeoxycholic acid (UDCA) is the preferred treatment for various types of cholestasis, however, its effectiveness is limited because of its insolubility in water. We used polyethylene glycol (PEG) and cationic polymer polyethylenimine (PEI) to double-modify graphite oxide (PPG) as a drug delivery system. UDCA was successfully loaded onto PPG through intermolecular interactions to form UDCA-PPG nanoparticles. UDCA-PPG nanoparticles not only improve the solubility and dispersibility of UDCA, but also have good biocompatibility and stability, which significantly improve the delivery rate of UDCA. The results indicated that UDCA-PPG significantly reduced ROS levels, promoted cell proliferation, protected mitochondrial membrane potential, reduced DNA damage and reduced apoptosis in the DCA-induced cell model. In a mouse cholestasis model established by bile duct ligation (BDL), UDCA-PPG improved liver necrosis, fibrosis, and mitochondrial damage and reduced serum ALT and AST levels, which were superior to those in the UDCA-treated group. UDCA-PPG reduced the expression of the apoptosis-related proteins, Caspase-3 and Bax, increased the expression of Bcl-2, and reduced the expression of the oxidative stress-related proteins, NQO and HO-1, as well as the autophagy-related proteins LC3, p62 and p-p62. Therefore, UDCA-PPG can enhance the therapeutic effect of UDCA in cholestasis, by significantly improving drug dispersibility and stability, extending circulation time in vivo, promoting absorption, decreasing ROS levels, enhancing autophagy flow and inhibiting apoptosis via the Bcl-2/Bax signaling pathway.

Effect of Butyl Paraben on Oxidative Stress in the Liver of Mauremys sinensis.

Butyl paraben (BuP) has been widely used as a preservative in the cosmetics, food, and medicine industries. Recently, it has become a new pollutant and has attracted much attention. In order to evaluate the toxic effect of BuP on aquatic animals, Chinese striped-neck turtles (Mauremys sinensis) were exposed to BuP solutions with different concentrations of 0, 5, 50, 500, and 5000 µg/L for 20 weeks. The results showed that with an increase in BuP concentration, the activity of antioxidant enzymes (SOD, CAT and GSH-PX) in liver decreased. The expression of key genes in the Nrf2-Keap1 signal pathways first increased and then decreased, while the expression of the HSP70 and HSP90 genes increased. In addition, the liver had an inflammatory reaction. The expression of the BAFF and IL-6 genes increased and then decreased with an increase in BuP concentration, while the expression of P50 and P65 increased significantly. Oxidative stress induced apoptosis, and the expression of pro-apoptosis genes (BAX, cytc, Caspase3 and Caspase9) increased, while the expression of the anti-apoptosis gene Bcl2 decreased. The results provide an important reference for the comprehensive ecological and health risk assessment of environmental BuP.

A Volume Self-Regulation MoS2 Superstructure Cathode for Stable and High Mass-Loaded Zn-Ion Storage.

Engineering multifunctional superstructure cathodes to conquer the critical issue of sluggish kinetics and large volume changes associated with divalent Zn-ion intercalation reactions is highly desirable for boosting practical Zn-ion battery applications. Herein, it is demonstrated that a MoS2/C19H42N+ (CTAB) superstructure can be rationally designed as a stable and high-rate cathode. Incorporation of soft organic CTAB into a rigid MoS2 host forming the superlattice structure not only effectively initiates and smooths Zn2+ transport paths by significantly expanding the MoS2 interlayer spacing (1.0 nm) but also endows structural stability to accommodate Zn2+ storage with expansion along the MoS2 in-plane, while synchronous shrinkage along the superlattice interlayer achieves volume self-regulation of the whole cathode, as evidenced by in situ synchrotron X-ray diffraction and substantial ex situ characterizations. Consequently, the optimized superlattice cathode delivers high-rate performance, long-term cycling stability (∼92.8% capacity retention at 10 A g-1 after 2100 cycles), and favorable flexibility in a pouch cell. Moreover, a decent areal capacity (0.87 mAh cm-2) is achieved even after a 10-fold increase of loading mass (∼11.5 mg cm-2), which is of great significance for practical applications. This work highlights the design of multifunctional superlattice electrodes for high-performance aqueous batteries.

Proton-Dominated Reversible Aqueous Zinc Batteries with an Ultraflat Long Discharge Plateau.

Aqueous zinc batteries (AZBs) are considered promising candidates for large-scale energy storage systems because of their low cost and high safety. However, currently developed AZB cathodes always suffer from the intense charge repulsion of multivalent-ion and complex multiphase electrochemistry, resulting in an insufficient cycling life and impracticable high-sloping discharge profile. Herein, we found that the synthesized ultrathin Bi2O2Se nanosheets can effectively activate stable protons storage in AZBs rather than large zinc ions. This proton-dominated cathode provides an ultraflat discharge plateau (72% capacity proportion) and exhibits long-term cyclability as 90.64% capacity retention after 2300 cycles at 1 A g-1. Further in situ synchrotron X-ray diffraction, ex situ X-ray photoelectronic spectroscopy, and density functional theory confirm the energy storage mechanism regarding the highly reversible proton insertion/extraction process. Benefiting from the proton-dominated fast dynamics, reliable energy supply (>81.5% discharge plateau capacity proportion) is demonstrated at a high rate of up to 10 A g-1 and in the frozen electrolyte below -15 °C. This work provides a potential design of high-performance electrode materials for AZBs.

Observed equilibrium partition and second-order kinetic interaction of quantum dot nanoparticles in saturated porous media.

This study integrated batch experiments and theoretical calculations to understand the equilibrium adsorption and kinetic interaction of CdSeS/ZnS alloyed quantum dots nanoparticles (QDNPs) in sand porous media under different ionic strengths (ISs; 0.001-0.2 M NaCl). Our experimental results showed that equilibrium was reached for QDNP concentration between solid phase and bulk solution due to reversible adsorption of the QDNPs on sand surfaces. Derjaguin-Landau-Verwey-Overbeek (DLVO) interaction energy calculations showed that the repulsive energy barriers were low and primary energy wells were shallow (i.e., comparable to the average kinetic energy of a colloid) at all tested solution ISs. Hence, the QDNPs could mobilize into and simultaneously escape from the primary wells by Brownian diffusion, resulting in the reversible adsorption. Additional batch experiments confirmed that a fraction of adsorbed QDNPs was released even without any perturbation of system conditions. The release was more evident at a lower IS because the primary energy wells spanned more narrowly at low ISs and thus the nanoparticles have a higher possibility to escape out. The batch kinetic experiments showed that the adsorption of QDNPs followed first- and second-order kinetic interactions at low and high ISs, respectively. These results indicate that the well-known colloid filtration theory that assumes irreversible first-order kinetics for colloid deposition is not suitable for describing the QDNP adsorption. The findings in our work can aid better description and prediction of fate and transport of QDNPs in subsurface environments.

Nucleus-Targeted Photosensitizer Nanoparticles for Photothermal and Photodynamic Therapy of Breast Carcinoma.

PURPOSE: The near-infrared fluorescent dye indocyanine green (ICG) has shown great potential in the photodynamic therapy (PDT) and photothermal therapy (PTT) of cancer. However, its disadvantages of instability in aqueous solution, short half-life, and non-targeting accumulation limit the effectiveness of ICG PDT/PTT. To overcome the disadvantages of ICG in tumor treatment, we designed PEGylated-human serum albumin (PHSA)-ICG-TAT. In this nanoparticle, PEG4000, the HSA package, and nuclear targeting peptide TAT (human immunodeficiency virus 1 [HIV-1]-transactivator protein) were used to improve the water solubility of ICG, prolong the life span of ICG in vivo, and target the nuclei of tumor cells, respectively. METHODS: The PHSA-ICG-TAT was characterized in terms of morphology and size, ultraviolet spectrum, dispersion stability, singlet oxygen and cellular uptake, and colocalization using transmission electron microscopy and dynamic light scattering, and fluorescence assay, respectively. Subsequently, the anti-tumor effect of PHSA-ICG-TAT was investigated via in vitro and in vivo experiments, including cell viability, apoptosis, comet assays, histopathology, and inhibition curves. RESULTS: The designed ICG-loaded nanoparticle had a higher cell uptake rate and stronger PDT/PTT effect than free ICG. The metabolism of PHSA-ICG-TAT in normal mice revealed that there was no perceptible toxicity. In vivo imaging of mice showed that PHSA-ICG-TAT had a good targeting effect on tumors. PHSA-ICG-TAT was used for the phototherapy of tumors, and significantly suppressed the tumor growth. The tumor tissue sections showed that the cell gap and morphology of the tumor tissue had been obviously altered after treatment with PHSA-ICG-TAT. CONCLUSION: These results indicate that the PHSA-ICG-TAT had a significant therapeutic effect against tumors.

Hydrogen-rich water attenuates the radiotoxicity induced by tritium exposure in vitro and in vivo.

Radionuclide tritium is widely used in the nuclear energy production industry and creates a threat to human health through radiation exposure. Herein, the radioactive elimination and radioprotective effect of hydrogen-rich water (HRW), a potential antioxidant with various medical applications, on tritiated water (HTO) exposure, was studied in vitro and in vivo. Results showed that intragastric administration of HRW effectively promoted the elimination of urinary tritium, decreased the level of serum tritium and tissue-bound tritium (OBT), and attenuated the genetic damage of blood cells in mice exposed to HTO (18.5 MBq/kg). Pretreatment with HRW effectively reduces tritium accumulation in HTO-treated human blood B lymphocyte AHH-1 cells. In addition, the anti-oxidative properties of HRW could attenuate the increased intracellular ROS (such as O2•-, •OH and ONOO-), resulting in reversing the exhaustion of cellular endogenous antioxidants (reduced GSH and SOD), decreasing lipid peroxidation (MDA), relieving DNA oxidative damage, and depressing cell apoptosis and cytotoxicity induced by HTO exposure. In conclusion, HRW is expected to be an effective radioactive elimination agent through the competition effect of isotope exchange or a radioprotective agent by scavenging free radicals induced by HTO exposure.

Methods and Influencing Factors for the Simple and Rapid Identification of Depleted Uranium Weapon Use under Battlefield Conditions.

The purpose of this paper is to explore how to rapidly and easily identify depleted uranium (DU) samples under battlefield conditions and to study the factors that influence their measurement. The air-absorbed dose rate and surface contamination levels for DU samples of 2-330 g were measured using a patrol instrument and portable energy spectrometer. The results were analyzed in accordance with IAEA standards for judging radioactive substances. The energy spectra of 5-g quantities of DU samples were analyzed using a high-purity germanium gamma spectrometer, and the uranium content of 100 mg DU samples was determined with an inductively coupled plasma mass spectrometer to clarify the type and composition of the uranium. The same batches of DU samples were identified using a portable gamma-ray spectrometer. We added 0-5 g environmental soil powders at different proportions. After sealing, the spectra were collected with a detection distance of 1-5 cm for 10 min. The activities of U and U nuclides in the samples were detected with an NaI(TI) scintillation detector. The U and U mass abundances in samples were calculated from measured specific activities. The sample was determined to contain DU if the U to U ratio was below 0.00723. It is found that for detecting DU materials with a low activity, surface contamination level measurements are more effective than calculating the air-absorbed external irradiation dose rate. Hence, for low-activity samples suspected to be radioactive, a radiometer with a high sensitivity for surface contamination is recommended, and the optimal measurement distance is 1-3 cm. Under all detection conditions, U can be identified using a portable gamma spectrometer, whereas U can only be detected under certain conditions. If these nuclides can be detected simultaneously, a U to U ratio of below 0.00723 indicates the presence of DU. The main factors affecting this identification include the sample mass, sample purity, measurement distance, and measurement time. For the rapid identification of DU with a portable gamma-ray spectrometer, the mass of uranium in the sample must be more than 1 g, the measuring distance needs to be less than 1 cm, and the measuring time must be 1-10 min. It is feasible to use a portable gamma-ray spectrometer to rapidly identify the types and composition of nuclides in DU samples. The detection of U activity is a precondition for the identification of DU.

Removal of hexavalent chromium from aqueous solution by fabricating novel heteroaggregates of montmorillonite microparticles with nanoscale zero-valent iron.

This study fabricated novel heteroaggregates of montmorillonite (Mt) microparticles with nanoscale zero-valent iron (nZVI) (Mt-nZVI) and examined the removal of Cr(VI) by the Mt-nZVI through batch experiments. Spherical nZVI particles were synthesized by the liquid phase reduction method, which were then attached on the flat Mt surfaces in monolayer. The fabricated Mt-nZVI had similar removal efficiency for Cr(VI) compared to the monodispersed nZVI particles, but was much greater than that of nZVI aggregates. The removal efficiency of Mt-nZVI increased with decreasing its dosage and increasing initial Cr(VI) concentration, whereas had insignificant change with solution pH. The removal of Cr(VI) by Mt-nZVI was well described by the pseudo second-order kinetics and the Langmuir equilibrium model. The removal was spontaneous and exothermic, which was mainly due to chemsorption rather than intra-particle diffusion according to calculation of change in free energy and enthalpy and Weber-Morris model simulations. X-ray diffraction and X-ray photoelectron spectroscopy analysis revealed that the adsorption was likely due to reduction of Cr(VI) to Cr(III) by Fe(0) and co-precipitation in the form of oxide-hydroxide of Fe(III) and Cr(III). The fabricated Mt-nZVI showed the promise for in-situ soil remediation due to both high removal efficiency and great mobility in porous media.

Bombyx mori monocarboxylate transporter 9 (BmMCT9) is involved in the transport of uric acid in silkworm integument.

In Bombyx mori, there are more than 30 mutant strains exhibiting the translucent larval skin resulting from a decrease in the uric acid content in epidermal cell. Of these, the Chinese translucent (oc) mutant presents a moderately translucent larval skin. Previously, we narrowed the region linked to the oc phenotype to approximately 234 kb by positional cloning, and found that BmMCT9 was severely suppressed in the mutant. Here, we analyzed the mutation and potential molecular function of BmMCT9. Sequence analysis showed that a 2,624-bp fragment of BmMCT9 promoter region was replaced by a 22-bp sequence in the mutant. Luciferase reporter gene assay confirmed that BmMCT9 promoter activity in the mutant was significantly lower than that in the wild type. Knockdown of BmMCT9 caused a translucent phenotype in the first-instar silkworm larvae. Immunoblotting analysis showed that BmMCT9 expression was severely reduced in the mutant than in the wild type, and immunofluorescence showed that BmMCT9 existed mainly within the cytoplasm of epidermal cells. Together, our results suggest that reduced levels of BmMCT9 were responsible for the translucent phenotype of oc mutant, and that BmMCT9 might function in intracellular vesicles facing the cytoplasm including urate granules in silkworm integument.

Proteomic Analysis of Larval Integument in a Dominant Obese Translucent (Obs) Silkworm Mutant.

The dominant obese translucent (Obs) mutant of the silkworm (Bombyx mori) results in a short and stout larval body, translucent phenotype, and abnormal pigmentation in the integument. The Obs mutant also displays deficiency in ecdysis and metamorphosis. In the present study, to gain an understanding of multiple Obs phenotypes, we investigated the phenotypes of Obs and performed a comparative analysis of the larval integument proteomes of Obs and normal silkworms. The phenotypic analysis revealed that the Obs larvae were indeed short and fat, and that chitin and uric acid content were lower but melanin content was higher in the Obs mutant. Proteomic analysis revealed that 244 proteins were significantly differentially expressed between Obs and normal silkworms, some of which were involved in uric acid metabolism and melanin pigmentation. Twenty-six proteins were annotated as cuticular proteins, including RR motif-rich cuticular proteins (CPR), glycine-rich cuticular protein (CPG), hypothetical cuticular protein (CPH), cuticular protein analogous to peritrophins (CPAPs), and the chitin_bind_3 motif proteins, and accounted for over 84% of the abundance of the total significantly differentially expressed proteins. Moreover, 22 of the 26 cuticular proteins were downregulated in the Obs mutant. Comparative proteomic analysis suggested that the multiple phenotypes of the Obs mutant might be related to changes in the expression of proteins that participate in cuticular formation, uric acid metabolism, and melanin pigmentation. These results could lay a basis for further identification of the gene responsible for the Obs mutant. The data have been deposited to ProteomeXchange with identifier PXD010998.

First-principle atomistic thermodynamic study on the early-stage corrosion of NiCr alloy under fluoride salt environment.

The atomic morphology change in the NiCr alloy surface induced by fluorine-chemisorption was investigated by the ab initio atomistic thermodynamic method to elucidate early-stage corrosion processes of nickel-based alloys in strong oxidizing environment. The surface phase diagrams of Cr-doped Ni(111) surface as a function of fluorine chemical potential were obtained to track the surface structures that are most likely to be fostered in various temperature and pressure conditions. The adsorption of fluorine on the top site of Cr in the alloy surface was the most energetically favorable one. With increasing fluorine chemical potential, more fluorine atoms started to agglomerate in the trapping sink of Cr. Fluorine-fluorine repulsion interaction coupled with strong F-Cr bonding could facilitate a decided morphology modification of the metal substrate. Moreover, an insight into the desorption pathways for potential species revealed that in the presence of fluorine, the dissociation of Cr predominantly stems from the relatively easy desorption in the form of CrF2/CrF3 molecules from the non-passivated Ni-based alloy surface.

Analysis of digital gene expression profiling in the gonad of male silkworms (Bombyx mori) under fluoride stress.

Fluorine is an essential element, but excessive fluoride can cause serious effects on the respiratory, digestive, and reproductive systems. Fluorine has been suggested to cause reproductive toxicity in vertebrates, but its potential to reproductively affect invertebrates remains unknown. In the present study, the lepidopteran model insect Bombyx mori was used to assess the reproductive toxicity of NaF. The underlying molecular mechanisms were explored by RNA sequencing, and we investigated the testes transcriptomic profile of B. mori treated with NaF via a digital gene expression (DGE) analysis. Among 520 candidate genes, 297 and 223 were identified as significantly upregulated or downregulated, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were carried out on all genes to determine their biological functions and associated processes. The results indicated that numerous differentially expressed genes are involved in the stress response, detoxification, antibacterial, transport, oxidative phosphorylation, and ribosome. The reliability of the data was confirmed by a quantitative real-time polymerase chain reaction (qRT-PCR) analysis. The changed Glutathione S-transferase (GST) activity and glutathione (GSH) content in the NaF-treated groups were increased and reduced respectively. This study reveals that using RNA-sequencing for the transcriptome profiling of B. mori testes can lead to better comprehension of the male reproductive toxicity effects of NaF. Furthermore, we expect that these results will aid future molecular studies on the reproductive toxicity of NaF in other species.

[Expression and characterization of juvenile hormone binding protein Bmtol gene in silkworm, Bombyx mori].

The head of the silkworm is a nerve center and a sense organ, contains antennaes and sensory hair, feels the outside signal, and responds to the external signal delivered to the brain. Juvenile hormone is mainly synthesized and secreted by corpora allata, and it needs to be played with the aid of the hormone binding protein, because the juvenile hormone binding protein is the carrier of juvenile hormone transport and plays a functional in vivo, they have an extremely important function in insects. The objective of this study is to screened and identify a novel BmTOL proteins that it has a conserved structure of the juvenile hormone binding protein family by SilkDB and NCBI database. Its coding gene number is BGIBMGA003404 (GenBank Accession No. KY681053). We also expressed the recombinant protein using the prokaryotic expression system, and then successfully purified the recombinant protein by Ni-NTA chromatography column to generate the polyclonal antibodies. The expression patterns analysis in various tissues showed that both in transcriptional and protein levels Bmtol was higher expressed in head. Furthermore, the expression level of Bmtol gene was higher in newly exuviated silkworm, and expression level of Bmtol gene was lower from at 3 days 5th instar to 7 days pupa, began to increase after the moth. Immunohistochemistry showed that BmTOL protein was localized in the cortex, antennaes and brain of the head, It may be related to the information transmission of the head, and provides an important source of information for the growth and development of silkworm.