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An eco-friendly superabsorbent composites of xanthan gum-g-polyacrylic acid/semi-coke (XG-g-PAA/SC) were fabricated via grafting of polyacrylic acid onto the XG in the presence of SC. The obtained products were characterized in combination with Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and scanning electron microscopy (SEM). The result indicated that the SC interacted with the polymeric network by hydrogen bond or electrostatic interaction. The swelling ratio of the best sample XG-g-PAA/SC (15 wt%) in distilled water and 0.9 wt% NaCl solution was 410.8 and 61.5 g/g by optimizing the polymerization conditions. In addition, compared with the blank sample (only containing soil), it can be found that adding a certain amount of XG-g-PAA/SC can significantly improve the soil water retention efficiency, which can be further proved by the results of plant pot experiment. Based on the above excellent swelling capacity, water holding capacity and plant growth promoting performance, it can be inferred that the XG-g-PAA/SC is expected to become a water retaining agent or soil regulator for plant growth.

A hybrid fluorescent pigment composed of fluorescent yellow X-10GFF (FY-10G) and palygorskite (PLG) was prepared by semi-dry grinding. The effects of the physically adsorbed water content and grinding time on the environmental stability of FY-10G/PLG hybrid fluorescent pigments in terms of acid, ethanol and ultraviolet irradiation are discussed in detail. The incorporated FY-10 G molecules are mainly trapped on the external surface and the groove of PLG. Due to the host–guest interaction between PAL and FY-10G, the emission spectrum of the FY-10G/PLG hybrids shifts to a greater wavelength compared with that of FY-10G, but the physically adsorbed water content and grinding time have no effect on the position of the emission spectrum except for its intensity. A larger, physically adsorbed water content and appropriate grinding time may effectively prevent the aggregation and breakage of the bundles of PLG and facilitate FY-10 G molecules to enter into the groove of PAL. This increases the environmental stability of the as-prepared hybrid pigments.

Idiopathic pulmonary fibrosis (IPF) is the most common type of idiopathic interstitial pneumonia and has one of the poorest prognosis. However, the molecular mechanisms underlying IPF progression remain largely unknown. In this study, we determined that IL-24, an IL-20 subfamily cytokine member, was increased both in the serum of IPF patients and the bronchoalveolar lavage fluid (BALF) of mice following bleomycin (BLM)-induced pulmonary fibrosis. As a result, IL-24 deficiency protected mice from BLM-induced lung injury and fibrosis. Specifically, loss of IL-24 significantly attenuated transforming growth factor β1 (TGF-β1) production and reduced M2 macrophage infiltration in the lung of BLM-induced mice. Mechanistically, IL-24 alone did not show a perceptible impact on the induction of M2 macrophages, but it synergized with IL-4 to promote M2 program in macrophages. IL-24 suppressed IL-4-induced expression of suppressor of cytokine signaling 1 (SOCS1) and SOCS3, through which it enhanced signal transducer and activator of transcription 6/peroxisome proliferator-activated receptor gamma (STAT6/PPARγ) signaling, thereby promoting IL-4-induced production of M2 macrophages. Collectively, our data support that IL-24 synergizes with IL-4 to promote macrophage M2 program contributing to the development of pulmonary fibrosis.

A series of porous quaternized silicate (QS) adsorbents with superior adsorption capabilities for anionic dye Congo Red (CR) were prepared by synchronous inorganic and organic functionalization of natural low-grade palygorskite (Pal) via a facile one-pot hydrothermal process. The Pal and its associated minerals were restructured as new porous silicate adsorbents under the action of the inorganic salts of sodium silicate and magnesium sulfate, and simultaneously the quaternary ammonium groups were in-situ introduced into the silicates using cetyltrimethylammonium bromide (CTAB) or dodecyltrimethylammonium bromide (DTAB) as donors of quaternary ammonium groups. The adsorption capacities of the QS adsorbents enhanced as the increment of quaternization degree until equilibrium is reached. The silicate adsorbents with the organification degree of 16.46% (for CTA-QS-1.2) and 13.32% (for DTA-QS-1.2) showed the best adsorption capacities of 664.29 ± 3.92 mg/g and 684.01 ± 8.50 mg/g for CR, respectively, which are far away higher than that of raw Pal (51.22 ± 2.85 mg/g), the magnesium silicate adsorbents without quaternization (78.69 ± 0.54 mg/g), and the CTAB-modified Pal prepared by commonly used method (145.10 ± 3.61 mg/g). The fitting results of thermodynamics and kinetic models revealed that the adsorption process of the silicate adsorbents for CR obeys Freundlich and pseudo-second-order models very well, which suggests a chemical interaction and multilayer adsorption mechanism. In addition, the electrostatic attraction and hydrogen-bonding interaction contribute more to the adsorption capability than specific surface area. This paper provides a new route to fabricate high-efficient silicate adsorbent by restructure of naturally abundant low-cost Pal clay for deep decontamination of anionic dye-polluted water.

The 'repurposed drug,' disulfiram (DSF), is an inexpensive FDA-approved anti-alcoholism drug with multi-target anti-cancer effect. However, the use of DSF in clinical settings remains limited due to its high instability in blood. In the present study, we created nanostructured lipid carriers (NLC) encapsulated DSF modified with d-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E-TPGS). A spherical shape, superior drug encapsulation (80.7%), and decreased crystallinity of DSF were confirmed with results obtained from TEM, XRD, and DSC analysis. Addition of TPGS considerably improved the physicochemical stability profile of NLC-encapsulated DSF under the different conditions tested here. Furthermore, TPGS-DSF-NLCs outperformed unmodified DSF-NLCs and the free DSF solution by having significantly higher cytotoxicity, lower IC50 value (4T1: 263.2 nM and MCF-7: 279.9 nM), and an enhanced cellular uptake in MCF7 and 4T1 cell lines. In vivo anti-tumor analysis in 4T1 murine xenograft model mice revealed a significant (p-value 0.05) decrease in tumor volume and higher tumor growth inhibition rate (48.24%) with TPGS-DSF-NLC treatment as compared to both the free DSF solution (8.49%) and DSF-NLC formulations (29.2%). Histopathology analysis of tumor tissues further confirmed a noticeably higher anti-tumor activity of TPGS-DSF-NLC through augmented cell necrosis in solid tumors. Hence, the present study established that addition of TPGS can synergize the anti-cancer activity of NLC-encapsulated DSF formulations, and thus, offer a promising anti-cancer delivery system for DSF.

Charge heterogeneity is an important aspect of research into the development of monoclonal antibody drugs. In the present study, charge variants were separated into four fractions using weak cation exchange chromatography and were thoroughly analyzed using liquid chromatography-mass spectrometry at multiple levels. Molecular weight analysis of intact antibody and subunits confirmed the presence of heavy-chain leader sequences, light-chain leader sequences, dehydration, and cysteinylation. Peptide mapping of the fractions using different enzymes further localized the modified sites. Modified proportions identified at peptide level were compared with the purity detected by imaged capillary isoelectric focusing, the results showed that basic variant 1 consisted of cysteinylation and dehydration of asparagine, and basic variant 2 fully accounted for the N-terminal leader sequence of the heavy chain. About 14.8% of the acidic variant can be explained by N-terminal leader sequences in the light chain, and 18% of the acidic variant was demonstrated to be deamidation of asparagine in the heavy chain. There was approximately 54.2% of the acidic variant still cannot be explained. It was hypothesized that those acidic variants that have not yet been identified are an ensemble of molecules with slight molecular weight differences or the same molecular weight but different structures.

Liposomes carrying MBD2 siRNA protect mice against BLM-induced lung injury and fibrosis by targeting macrophage M2 program., Despite past extensive studies, the mechanisms underlying pulmonary fibrosis (PF) still remain poorly understood. Here, we demonstrated that lungs originating from different types of patients with PF, including coronavirus disease 2019, systemic sclerosis–associated interstitial lung disease, and idiopathic PF, and from mice following bleomycin (BLM)–induced PF are characterized by the altered methyl-CpG–binding domain 2 (MBD2) expression in macrophages. Depletion of Mbd2 in macrophages protected mice against BLM-induced PF. Mbd2 deficiency significantly attenuated transforming growth factor–β1 (TGF-β1) production and reduced M2 macrophage accumulation in the lung following BLM induction. Mechanistically, Mbd2 selectively bound to the Ship promoter in macrophages, by which it repressed Ship expression and enhanced PI3K/Akt signaling to promote the macrophage M2 program. Therefore, intratracheal administration of liposomes loaded with Mbd2 siRNA protected mice from BLM-induced lung injuries and fibrosis. Together, our data support the possibility that MBD2 could be a viable target against PF in clinical settings.

This study discusses the hydrochemical components of glacier snow meltwater using the correlation analysis, factor analysis, enrichment factor, and the Gibbs diagram. Water samples were collected from June to September in 2016 and 2017. The results obtained the monthly changes for anions and cations in Yuzhufeng (YZG) and Jianggudiru Glacier (JGG) were notably, with highest concentration of ions recorded in September. The effect of seasonal variation on the chemical characteristics of glacier snow meltwater was determined by studying the interaction between the glacier snow meltwater and the control source. The change of hydrochemical characteristics and hydrological cycle is positive in cold areas under the climate warming. The hydrochemical characteristics of glacier snow meltwater in study area were mainly contributed by crustal sources such as evaporates and carbonate rocks. Certainly, a small part of human input cannot be ignored. There was a close relationship between temperature and hydrochemical characteristics, and the relationship between meteorological factors and other ions except K+ was not clear. It is concluded that the water chemistry of glacier snow meltwater in the Alpine region is mainly controlled by the temperature factor-led ablation.

Objective: We hypothesize that functional wrist motion is lost in the arthritic wrist due to a combination of mechanical incongruity & pain. Restoration of functional motion is achieved through elimination of pain generators and reestablishment of adequate freedom of motion through a three dimensional[for full text, please go to the a.m. URL], 14th Triennial Congress of the International Federation of Societies for Surgery of the Hand (IFSSH), 11th Triennial Congress of the International Federation of Societies for Hand Therapy (IFSHT), 11th Triennial Congress of the International Federation of Societies for Hand Therapy (IFSHT)

Disorder of lipid metabolism is closely related to the incidence of Alzheimer's disease (AD). Regulation of lipid disorder is one of the important mechanisms of drug therapy for AD. In this study, serum lipidomics study based on an online liquid extraction surface analysis coupled to direct infusion mass spectrometry (Online-LESA-direct infusion MS) was established and applied to assess the efficacy of Ding-Zhi-Xiao-Wan (DZXW) for treating AD in rats by regulating lipid metabolism disorders. Dried serum spot (DSS) samples of 10 health control (HG), 10 AD, 10 DZXW, and 10 donepezil rats were directly detected by Online-LESA-direct infusion MS without prior treatments. And the acquired data was analyzed by multivariate statistical analyses such as PCA and PLS-DA to identify potential lipid biomarkers in serum. By this method, 15 compounds were screened and identified, belonging to phosphatidylcholines (PCs), sphingomyelins (SMs) and lysophosphatides (LPCs), which were considered as potential lipid biomarkers with AD mechanisms. Among them, the levels of PCs and SMs were markedly declined, and the levels of LPCs were increased in the AD group. Moreover, compared with administrating donepezil, the observed PCs and SMs were more up-regulation to normal levels with the treatment of DZXW in AD rats, which indicated that DZXW can play a better role in the treatment of AD by regulating lipid metabolism. And the results of the study also showed that the Online-LESA-direct infusion MS on DSS analytical strategy has a potential to become a high-throughput analysis method for large-scale clinical diagnostics analysis.

Palygorskite/carbon composites were constructed by using the spent bleaching earth after bleaching of animal fat as feedstock via one-step calcination and deemed to be adsorbents for the efficient removal of methyl violet. And continuous cyclic adsorption of methyl violet using the obtained palygorskite/carbon composites was emphatically evaluated by continuous adsorption-calcination process in this study. The results unveiled that the formed carbon species were closely anchored on the palygorskite surface, and the as-prepared palygorskite/carbon composites always exhibited a high adsorption capacity for methyl violet though the calcination temperature, initial pH, initial concentration of dye and contact time varied. By a simple thermal regeneration process, the exhausted adsorbents were recycled repeatedly for methyl violet removal. Interestingly, no obvious decrease in the adsorption capacity of the palygorskite/carbon composites prepared at 300 °C was detected after ten times cycles calcination. It developed a novel avenue to fully utilize spent bleaching earth and exhausted palygorskite/carbon composites.

The comprehensive characterization of metabolome and lipidome to reveal unknown pathological conditions, are being used to investigate the molecular mechanisms of cancer, especially in the field of early diagnosis, treatment, and prognosis. The multidrug resistance (MDR) of tumor cells limits the therapeutic effect of anti-cancer drugs and is the main obstacle for chemotherapy. Here, we adopted a methyl-tert-butyl ether (MTBE)-based extraction method to simultaneously extract small polar molecules and lipophilic metabolites for nontargeted metabolomics of multidrug-resistant breast cancer cell line MCF-7/ADR and its parental cell line MCF-7/S by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Distinctly different metabolic features were shown between MCF-7/ADR cells and MCF-7/S on the basis of multivariate analyses. 17 potential biomarkers were identified. And these potential biomarkers were mainly correlated with cell membrane lipids composition, cell signaling regulated by lipids, and anti-oxidation ability. The studies of cellular ultrastructure and morphology by in situ atomic force microscopy (AFM) also demonstrated the cellular membrane changed along with the MDR. We expect that this study could provide a new method for monitoring drug resistance during clinical chemotherapy and be useful for the development of drugs to overcome the MDR.

Rheumatoid arthritis (RA) is characterized by synovial inflammation and hyperplasia, autoantibody production, cartilage and bone destruction, and systemic features including cardiovascular, pulmona...

Recent studies have investigated the potential of type 1 diabetes mellitus–related autoantigens, such as heat shock protein 60, to induce immunological tolerance or to suppress the immune response. A functional 24-residue peptide derived from heat shock protein 60 (P277) has shown anti-type 1 diabetes mellitus potential in experimental animals and in clinical studies, but it also carries a potential atherogenic effect. In this study, we have modified P277 to retain an anti-type 1 diabetes mellitus effect and minimize the atherogenic potential by replacing the P277 B epitope with another diabetes-associated autoantigen, insulinoma antigen-2 (IA-2), to create the fusion peptide IA-2-P2. In streptozotocin-induced diabetic C57BL/6J mice, the IA-2-P2 peptide displayed similar anti-diabetic effects to the control P277 peptide. Also, the IA-2-P2 peptide did not show atherogenic activity in a rabbit model. Our findings indicate the potential of IA-2-P2 as a promising vaccine against type 1 diabetes mellitus.

Escherichia coli (E. coli) commonly reside in human intestine and most E. coli strains are harmless, but some serotypes cause serious food poisoning. This study identified and molecularly characterized blaSHV genes from 490 E. coli strains with multi-drug resistance in a hospital population. PCR and molecular cloning and southern blot were performed to assess functions and localizations of this resistant E. coli gene and the pulsed-field gel electrophoresis (PFGE) was utilized to demonstrate the clonal relatedness of the positive E. coli strains. The data showed that 4 of these 490 E. coli strains (4/499, 0.8%) carried blaSHV genes that included EC D2485 (blaSHV-5), EC D2487 (blaSHV-5), EC D2684 (blaSHV-11) and EC D2616 (blaSHV-195, a novel blaSHV). Analysis of blaSHV open-reading frame showed that blaSHV-5 had a high hydrolysis activity to the broad-spectrum penicillin (ampicillin or piperacillin), ceftazidime, ceftriaxone, cefotaxime and aztreonam. blaSHV-195 and blaSHV-11 had similar resistant characteristics with high hydrolysis activities to ampicillin and piperacillin, but low activities to cephalosporins. Moreover, the two blaSHV-5 genes were located on a transferable plasmid (23kb), whereas the other two blaSHV variants (blaSHV-11 and blaSHV-195) seemed to be located in the chromosomal material. Both EC D2485 and EC D2487 clones isolated in 2010 had the same DNA finger printing profile and they might be the siblings of clonal dissemination. The data from the current study suggest that the novel blaSHV and clonal dissemination may be developed, although blaSHV genes were infrequently identified in this hospital population. The results of the work demonstrate the necessity for molecular surveillance in tracking blaSHV-producing strains in large teaching hospital settings and emphasize the need for epidemiological monitoring.

Though great progress on the adsorbents of heavy metal ions has been made in recent years, it is still challenging to develop economic, high-efficient and eco-friendly adsorbents. Herein, a series of MgO/palygorskite (MgO/Pal) composites with robust adsorption performance toward Zn(II) and Cd(II) were successfully prepared by a facile and industrially feasible precipitation-calcinations process using environmentally benign natural palygorskite (Pal) and Mg(II)-rich brine as the raw materials. The XRD, TG and SEM analyses confirm that MgO species was formed and uniformly distributed on the surface of Pal nanorods. The resultant MgO/Pal adsorbent exhibited high adsorption capacities of 841 and 669 mg/g for Zn(II) and Cd(II) ions, respectively. About 98.79% of Zn(II) and 98.69% of Cd(II) were removed from 200 mg/L of the initial solution by only using 1 g/L of the adsorbent. The spent MgO/Pal adsorbent can be regenerated by a simple one-step calcinations process, and the regenerated adsorbent can remove 99.5% of cationic dyes from 100 mg/L of the initial dye solution. The adsorption process obeys Langmuir isotherm model and pseudo-second-order kinetic model, which suggest the monolayer adsorption of Zn(II) and Cd(II) onto the composite. The chemo-adsorption process including phase transformation and precipitation is mainly responsible for the enhanced adsorption capacities. In a word, the composites are made from naturally available matters, which can serve as promising adsorbents for high-efficient removal of toxic metal ions from polluted water.

Multifunctional nanomedicines with active targeting and stimuli-responsive drug release function utilizing pathophysiological features of the disease are regarded as an effective strategy for treatment of rheumatoid arthritis (RA). Under the inflammatory environment of RA, activated macrophages revealed increased expression of folate receptor and elevated intracellular reactive oxygen species (ROS) level. In this study, we successfully conjugated folate to polyethylene glycol 100 monostearate as film-forming material and further prepared methotrexate (MTX) and catalase (CAT) co-encapsulated liposomes, herein, shortened to FOL-MTX&amp, CAT-L, that could actively target to activated macrophages. Thereafter, elevated intracellular hydrogen peroxide, the main source of ROS, diffused into liposomes and encapsulated CAT catalyzed the decomposition of hydrogen peroxide into oxygen and water. Continuous oxygen-generation inside liposomes would eventually disorganize its structure and release the encapsulated MTX. We characterized the in vitro drug release, cellular uptake and cytotoxicity studies as well as in vivo pharmacokinetics, biodistribution, therapeutic efficacy and safety studies of FOL-MTX&amp, CAT-L. In vitro results revealed that FOL-MTX&amp, CAT-L possessed sufficient ROS-sensitive drug release, displayed an improved cellular uptake through folate-mediated endocytosis and exhibited a higher cytotoxic effect on activated RAW264.7 cells. Moreover, in vivo results showed prolonged blood circulation time of PEGylated liposomes, enhanced accumulation of MTX in inflamed joints of collagen-induced arthritis (CIA) mice, reinforced therapeutic efficacy and minimal toxicity toward major organs. These results imply that FOL-MTX&amp, CAT-L may be used as an effective nanomedicine system for RA treatment.

A novel microsphere adsorbent based upon carboxymethyl cellulose sodium/prussian blue composite loaded with Lanthanum(III) (CMC/PB-La) was successfully synthesized via electrostatic ejection device for removal of cesium from contaminated water, and characterized by FT-IR, SEM, EDX and XPS. Influencing factors to adsorption cesium were investigated, including solution pH, adsorbent dosage, contact time, initial concentration, temperature and competing ions. Linear Freundlich isotherm was fitted satisfactorily to the adsorption data, and the adsorption kinetic data was fitted well with pseudo-second-order model. Moreover, the results of γ-irradiation experiments indicate that CMC/PB-La has good radiation stability.

A hierarchical mesoporous hybrid Zn-silicate adsorbent with superior adsorption performance for aureomycin (AMC) and tetracycline (TC) has been successfully synthesized by employing an “all-into-one” strategy and one-pot hydrothermal reaction, using naturally abundant, low-cost red palygorskite clay (RPAL), sodium silicate and zinc salts as raw materials. The morphologies and crystal forms of the Zn-silicates can be tuned by altering the dosage of Zn2+ ions. Low-crystalline sheet-like Zn-silicates were formed at the Si/Zn ratio of 3:1 and 2:1, and zinc orthosilicates were obtained at the Si/Zn ratio of 1:1 and 1:2. A systematic study on their adsorption abilities for the antibiotics AMC and TC indicates that the sheet-like Zn-silicate has higher adsorption capacity for AMC and TC than zinc orthosilicate, and the Zn-silicate with Si/Zn ratio of 3:1 has the best adsorption capacity of 384 mg/g for AMC and 337 mg/g for TC, which is obviously higher than that of RPAL (154 mg/g for AMC and 140 mg/g for TC). The adsorption properties are dependent on the pore size and surface charges, instead of specific surface area. The average pore sizes of 10.62–11.50 nm and the negative surface charge (−42.54 mV) resulting from the –Si(M)O− groups are beneficial to the adsorption for both AMC and TC. The adsorption process mainly involves with monolayer coverage, and chemo-adsorption plays a key role for the enhanced adsorption capacity. The results suggest that the Zn-silicates derived from natural abundant clay mineral have superior performance, and could be candidates to remove AMC and TC from the wastewater with high amounts of AMC and TC.

Replication of the 3.2-kb hepatitis B virus (HBV) genome is driven by the covalently closed circular (ccc) DNA in the nucleus, from which four classes of co-terminal RNAs are transcribed. Genome replication requires just the 3.5-kb pregenomic RNA, which is terminally redundant. Cloning the full-length HBV genome into a vector disrupts its continuity, thus preventing genome replication at the step of pregenomic RNA transcription. This can be overcome by converting the monomeric construct into a tandem dimer, yet the need to ligate two molecules of the HBV genome with vector DNA makes it inefficient and even unsuccessful. To overcome this problem we partially digested the monomeric construct with the unique restriction enzyme used for cloning, and dephosphorylated the linearized monomer before its ligation with another copy of the HBV genome. Alternatively, the monomer was linearized at another unique restriction site inside the HBV genome, followed by its dephosphorylation and ligation with another copy of the HBV genome linearized at the same site. These approaches of two-way molecular ligation greatly improved the efficiency of dimer formation with about 50% of the bacterial colonies screened harboring tandem dimers.

Human heat shock protein 60 (Hsp60), is an endogenous β-cells autoantigen, it could postpone the onset of insulitis and sooner type 1 diabetes mellitus. P277 is one of Hsp65 determinants at position 437-469 of amino acids cascaded. Meanwhile, it's already well-known that there were several better anti-diabetic B epitopes, such as insulinoma antigen-2 (IA-2). Currently, fusion protein IA2P2 has constructed in order to enhance its pharmacological efficacy. In addition, added homologous bacterial-derived Hsp65 and His tag were beneficial to protein immunogenicity and purification separately. So, finally we examined a fusion protein His-Hsp65-6IA2P2 could regulate Th2 immune response and reduce natural diabetic incidence in NOD mice. We constructed two express vector pET28a-His-Hsp65-6P277 and pET28a-His-Hsp65-6IA2P2. After purification, we observed that triple intranasal administration of these two fusion protein in 4-week-old NOD mice maintained normal blood glucose and weight, with a lower diabetic or insulitis incidence. Consistent with induced splenic T cells proliferation and tolerance, His-Hsp65-6IA2P2-treated mice performed reduced IFN-γ and increased IL-10 level. In conclusion, we suggested that fusion protein His-Hsp65-6IA2P2 could be reconstructed and purified successively. Furthermore, nasal administration of this fusion protein could rebalance T cells population and prevent T1DM.

As promising eco-friendly materials, natural silicates have received great attention as abundant, low-cost, non-toxic, stable, and environmentally benign adsorbents. Inspired by the idea of “from nature, for nature”, a series of highly efficient hybrid silicate adsorbents were synthesized via a simple one-step hydrothermal process, using naturally abundant low-grade palygorskite (PAL) as the initial material in the presence of sodium silicate (SS), magnesium sulfate (MS), and monochloroacetic acid (MCA). As expected, the PAL crystal and the associated minerals were restructured as amorphous and multi-porous Mg, Al-silicates, while the active COOH groups were simultaneously introduced into the silicate to form a hybrid adsorbent with a specific surface area of 410.61 m2/g (compared to 52.87 m2/g for raw PAL). The hybrid silicate adsorbent showed excellent adsorption capabilities for the antibiotics chlortetracycline (CTC) (329.84 mg/g) and oxytetracycline (OTC) (207.47 mg/g), which were enhanced by 218.9% and 107.9%, respectively, in contrast to that of raw PAL. The adsorption of the hybrid adsorbent for CTC and OTC was pH-dependent, and the pH values of 3.56–7.82 (for CTC) and 3.45–7.57 (for OTC) favored the adsorption. The dynamic adsorption process was well described by a pseudo second-order model, which suggested that chemical adsorption was the prominent driving force. The thermodynamic adsorption pattern agreed well with the Redlich–Peterson model, revealing that the heterogeneous surface was the main adsorption site and that removal of antibiotics occurred mainly by multi-layer adsorption.

Gene immunotherapy has been developed as a promising strategy for inhibition of tumor growth. In the study, mannosylated protamine sulphate (MPS) was used as a novel DNA vaccine carrier to enhance transfection efficiency and anti-tumor immune responses. Anti-GRP DNA vaccine (pGRP) was selected as a model gene and condensed by MPS to form MPS/pGRP nanoparticles. The cellular uptake and transfection efficiency of MPS/pGRP nanoparticles in macrophages were evaluated. The effect of the nanoparticles in enhancing GRP-specific humoral immune response was then evaluated by nasal vaccination of nanoparticles in mice. The results demonstrated that both the cellular uptake and transfection efficiency of MPS nanoparticles in macrophages were higher than those of protamine nanoparticles. MPS/pGRP nanoparticles stimulated the production of higher titers (3.9×10(3)) of specific antibodies against GRP than those of protamine/pGRP nanoparticles (6.4×10(2), p

The aim of this study was to analyze the molecular epidemiologic characteristics of Acinetobacter baumannii. A total of 398 isolates were collected in 7 regions of South China from January to June of 2012. Drug sensitivity was tested toward 15 commonly used antibiotics; thus, 146 multi-drug-resistant strains (resistant to more than 7 drugs) were identified, representing 36.7% of all isolates. Pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) were used for molecular subtyping. According to the PFGE results (with a cutoff of 70% similarity for the DNA electrophoretic bands), 146 strains were subdivided into 15 clusters, with cluster A being the largest (33.6%, distributed in all districts except Jiaxing). Cluster B was also widespread and included 14.4% of all strains. In addition, MLST results revealed 11 sequence types (ST), with ST208 being the most prevalent, followed by ST191 and ST729. Furthermore, 4 novel alleles and 6 novel STs were identified. Our results showed that multi-drug-resistant A. baumannii in South China shares the origin with other widespread strains in other countries. The nosocomial infections caused by A. baumannii have been severe in South China. Continuous monitoring and judicious antibiotic use are required.

Palygorskite (PAL) has been widely used for adsorption removal of dyes from wastewater, but the dye-loaded PAL is usually discharged as solid waste because it is hardly regeneratable by conventional elution processes. As the aim was to efficiently utilize the dye-loaded PAL waste, we employed a facile one-pot hydrothermal process to transform the spent methyl violet (MV)-loaded PAL into multifunctional ternary palygorskite/carbon/Ag nanoparticles (PAL/C/AgNPs) nanocomposites in the assistance of AgNO3. The MV-loaded PAL serves as a carbon precursor, reducer of Ag(I) and supporter of the in situ formed AgNPs. Structure characterizations confirmed that the MV dye was transformed into carbon species, and AgNPs were formed on the PAL with good dispersion, and the addition of Ag(I) ions promoted carbonization of the MV molecules. The as-prepared nanocomposites exhibited excellent adsorption and catalytic performance. Adsorption evaluation showed that the nanocomposite prepared at 5 mass% of AgNO3 dosage gives the best adsorption properties, and 99.2% of methylene blue (MB), 86.9% of MV, 68.7% of chlortetracycline hydrochloride (CTC) and 46.2% of tetracyclines (TC) were rapidly removed from 100 mg L−1 of the aqueous solution using 0.5 g L−1 of the adsorbent. The removal ratio increased with increasing dosage of adsorbent, and the minimum usage amounts of adsorbent for the thorough removal of MB, MV, CTC and TC molecules were 1.0 g L−1, 1.2 g L−1, 3.5 g L−1 and 4.5 g L−1, respectively. Moreover, the nanocomposites could rapidly catalyze the conversion of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP) within 6.5 min with a catalytic rate constant of 0.0120 s−1, and the catalytic activity is still retained after 8 cycles of reuse. In addition, the nanocomposite can be re-generated into new adsorbents by the same hydrothermal process after adsorption of organic matters, which open a new sustainable avenue to efficiently utilize waste dye-loaded PAL and develop new adsorption and catalysis materials.

Acid leaching of clay minerals provides a simple and industrially efficient route to produce active silica materials with different morphologies and functions on a large scale, but the generated acid leachate rich in metal ions has become a source of hazardous waste. Therefore, methods to treat or reuse it harmlessly become an emerging challenge. Here, a sustainable method to reuse the metal ions (i.e., Fe(II), Fe(III), Mg(II), and Al(III)) in the waste acid leachate of three representative clay minerals (palygorskite (Pal), montmorillonite (MMT) and nontronite (NNT)) for synthesizing 2D layered double hydroxide (LDH) was reported. The obtained Pal-LDH, MMT-LDH and NNT-LDH adsorbents can adsorb 127.16 ± 1.49 mg/g, 134.56 ± 3.49 mg/g and 123.20 ± 4.11 mg/g of Congo red (CR), respectively. The subsequent calcination treatment of LDH adsorbed CR produces three magnetic layered double oxides (LDO) with a 2D nano-layered shape and positive surface charges: Pal-LDO, MMT-LDO and NNT-LDO. The Pal-LDO adsorbent exhibits high adsorption capacities of 538.39 ± 4.23 mg/g for dye CR and 626.91 ± 4.89 mg/g for antibiotic tetracycline (TC). Using the adsorbent concentration of 0.50 g/L, the CR in the initial 100 mg/L dye solutions is removed completely. After adsorption, the adsorbent is easily recycled by exposing it to a magnetic field, regenerated by one-step calcination treatment and reused for the next adsorption cycle. After reuse 3 times, the resulting adsorbent still displays a good adsorption capacity of 350.67 ± 3.21 mg/g for the CR dye. Therefore, this study provides a new and universal approach to reuse the waste acid leachate of clay minerals and develop new recyclable adsorbents for the efficient decontamination of organic contaminants from wastewater.

Multidrug resistance (MDR) has seriously affected or hindered the effect of chemotherapy. Ursolic acid (UA) as a natural compound exhibits a number of potential biological effects including antitumor. Searching for the reversal agents from the natural products has been an effective strategy recently applied in overcoming the MDR. So in this study, the reversal effect of UA on the MDR and involved mechanisms were investigated via a multidrug-resistant MCF-7/ADR cells model and ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analytical methods. The synergistic effects were yielded by the combination of UA and Dox based on the investigation of the intracellular accumulation, the P-glycoprotein (P-gp) mediated transport, the energy metabolism including glycolysis, tricarboxylic acid (TCA) cycle, and glutamine metabolism as well as related amino acid metabolism. Obtained results showed that the UA could increase amount of doxorubicin (Dox) entering the cell to accumulate in nuclei, decrease the efflux ratio of digoxin comparable to the effects of the known inhibitor verapamil by acting as a P-gp substrate, decrease the content of intracellular alanine, lactate, pyruvate, glucose, α-ketoglutarate, glutamate, glutamine, aspartate, serine, and glycine. Taken together, inhibition of P-gp function and disruption of the metabolism of energy and related amino acids could be the key mechanisms by which UA could reverse the MDR. The findings also indicated that UA could be a potential alternative adjuvant antitumour herbal medicine to resensitize cells with MDR to chemotherapeutic agents.

Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as a hepatitis B virus (HBV) receptor, and its overexpression in HepG2 cell lines leads to efficient secretion of hepatitis B e antigen (HBeAg) following challenge with a large dose of cell culture-derived HBV (cHBV) particles. However, NTCP-reconstituted HepG2 cells are inefficiently infected by patient serum-derived HBV (sHBV) and release very little hepatitis B surface antigen (HBsAg) following cHBV infection, unlike differentiated HepaRG cells, which are naturally susceptible to both cHBV and sHBV particles. Here, we investigated whether NTCP could explain the different behaviors of the two cell types. Endogenous NTCP protein from differentiated HepaRG cells was unglycosylated despite wild-type coding sequence. HepaRG cells stably transfected with an epitope-tagged NTCP expression construct displayed higher sHBV but not cHBV susceptibility than cells transfected with the null mutant. Tagged NTCP introduced to both HepG2 and HepaRG cells was glycosylated, with N5 and N11 being sites of N-linked glycosylation. Mutating N5, N11, or both did not alter cell surface availability of NTCP or its subcellular localization, with both the singly glycosylated and nonglycosylated forms still capable of mediating cHBV infection in HepG2 cells. In conclusion, nonglycosylated NTCP is expressed by differentiated HepaRG cells and capable of mediating cHBV infection in HepG2 cells, but it cannot explain differential susceptibility of HepaRG and HepG2/NTCP cells to cHBV versus sHBV infection and different HBsAg/HBeAg ratios following cHBV infection. The responsible host factor(s) remains to be identified. IMPORTANCE HBV can infect differentiated HepaRG cells and also HepG2 cells overexpressing NTCP, the currently accepted HBV receptor. However, HepG2/NTCP cells remain poorly susceptible to patient serum-derived HBV particles and release very little hepatitis B surface antigen following infection by cell culture-derived HBV. We found differentiated HepaRG cells expressed nonglycosylated NTCP despite a wild-type coding sequence. NTCP introduced to HepG2 cells was glycosylated at two N-linked glycosylation sites, but mutating either or both sites failed to prevent infection by cell culture-derived HBV or to confer susceptibility to serum-derived HBV. Overexpressing NTCP in HepRG cells did not increase infection by cell culture-derived HBV or distort the ratio between the two viral antigens. These findings suggest that host factors unique to HepaRG cells are required for efficient infection by serum-derived HBV, and factors other than NTCP contribute to balanced viral antigen production following infection by cell culture-derived HBV.

RATIONALE Multidrug resistance (MDR) occurs frequently and is a major challenge in tumor treatment. The lipid composition in the cell membrane and the redox balance are closely associated with the development of MDR. Liquid extraction surface analysis in combination with mass spectrometry (LESA-MS) has the characteristics of minimal sample preparation, rapid analysis, high sensitivity and high throughput, and has obtained wide applications. METHODS LESA-MS was employed to in situ determine the lipids and other specific metabolites of intact MCF-7/ADR cells (adriamycin-resistant breast cancer cells) and its parental MCF-7/S cells grown on a glass slide. In situ atomic force microscopy was used to observe the morphology of tumor cells before and after extraction. Multivariate statistical analysis was used to investigate the potential lipid biomarkers correlated with the MDR. Moreover, the cell membrane fluidity and potential were determined. RESULTS The changes in the level of the lipids were closely correlated with the multidrug resistance of MCF-7/S cells. Moreover, lower cell membrane fluidity and higher cell membrane potential were observed and thus demonstrated the changes in the cell membrane induced by multidrug resistance. Also, the ratios of GSH/GSSG, ATP/ADP and ATP/AMP were significantly higher in MCF-7/ADR cells relative to MCF-7/S cells. CONCLUSIONS Lower cell membrane fluidity and higher cell membrane potential caused by the changes in lipid compositions, enhanced anti-oxidative ability and energy generation were involved in the development of the MDR. The specific alterations identified in this study may provide more information for overcoming MDR.

As the materials of “green 21st century material worlds”, natural silicates have received unprecedented attention by virtue of their abundance, low-cost, stability, and non-toxic and eco-friendly nature compared to other synthetic materials. With the aim to develop a new hybrid silicate adsorbent with improved adsorption properties, the naturally abundant palygorskite (PAL) was functionalized with glycine (GLY) via a simple one-step hydrothermal process and used for capturing Pb(II) ions from aqueous solution. The main reaction parameters, e.g., the pH values of the reaction medium, solid-to-liquid ratio, reaction time and dosage of GLY, were systematically optimized, and the as-prepared adsorbent was characterized using X-ray diffraction (XRD), field-emission scanning electron microscopy (FESEM), transmittance electronic microscopy (TEM) and Fourier transform infrared spectroscopy (FTIR) techniques. The results reveal that the PAL crystal was converted to a hybrid silicate material with the assistance of GLY, and simultaneously the functional groups were introduced during the hydrothermal reaction, which caused an evident enhancement in the adsorption capacity of PAL for Pb(II) ions from 55.76 mg g−1 to 123.24 mg g−1. Almost 99.60% of Pb(II) could be captured and removed from a 40 mg L−1 Pb(II) solution using the as-prepared GLY-PAL silicate adsorbent, which is obviously higher than the 83.85% achieved by raw PAL. The intensified complexation of the functional groups on the silicate with Pb(II), the electrostatic attraction and the pore adsorption are responsible for the enhancement in the adsorption capability.

The purpose of this study was to prepare and investigate long circulating polyelectrolyte nanoparticles (PENPs) based on hydrochloride chitosan (HCS) and hyaluronic acid (HA) coated by methoxy poly(ethylene glycol) (mPEG). Mitoxantrone hydrochloride (MTO) was selected as a model drug. TEM showed that MTO-loaded PENPs (MTO-PENPs) were spherical but MTO-loaded PENPs coated by mPEG (MTO-mPEG-PENPs) had a slightly rough morphology with an average hydrodynamic diameter around 200-240nm. The EE of MTO-mPEG-PENPs and MTO-PENPs were 99.02% and 98.33%, respectively. DSC thermograms showed MTO existed at the molecular level inside the MTO-mPEG-PENPs. Drug release studies revealed MTO-mPEG-PENPs offered better control over the release of drug than uncoated counterparts. Observations of the pharmacokinetic study reveal that MTO-mPEG-PENPs exhibited significant prolongation in blood circulation of drug compared to MTO-PENPs and MTO solution in rats after intravenous administration. The MRT of MTO increased from 117.83min (MTO solutions) and 162.34min (MTO-PENPs) to 344.42min (MTO-mPEG-PENPs). The AUC of MTO in MTO-mPEG-PENPs increased 2.52-fold and 3.41-fold compared to MTO-PENPs and MTO solution, respectively. In conclusion, mPEG coated PENPs based on HCS/HA could present a workable strategy for long-circulating systemic delivery of drugs.

In order to research hydro-geochemistry characteristic and environmental significance of river and spring water, 68 samples were collected in different ablation periods (initial ablation period; ablation period; end ablation period) in Hulugou river basin. The results showed that the chemical type of the river and spring in different ablation period was SO4 2−–Ca2+–Mg2+ type in Hulugou River Basin. Compared with water samples in different ablation, the order of the total ionic concentration was the initial ablation period > the end ablation period > ablation period, with the mean was 238.29, 237.19 and 178.19 mg/L, respectively. From the analysis of ionic sources, which indicated the chemical composition of river and spring water was controlled by crustal materials during the different ablation period in the Hulugou River Basin. And the dominant processes were water–rock intersection, especially the weathering and dissolution of dolomite. Meanwhile, the results of enrichment factor also confirmed that most of the ions influenced by local soil source in study area. But the ratios of NO3 −, SO4 2− and Cl− to Na+ also confirmed that anthropogenic also influenced the water chemistry in study area. The results are also helpful for further understanding the hydro-geochemistry characteristic in different ablation period in the alpine regions of western China and providing scientific basis for further study on hydro-geochemistry.

Many Pseudomonas aeruginosa virulence traits that contribute to human infections are accepted as being associated with its environmental lifestyle. Therefore, identifying the molecular mechanisms that govern the lifestyle choice is of high significance. We previously reported that a mutation in suhB results in a decrease in swimming motility and increased biofilm formation compared to the wild-type strain. Yet, little is known about how this occurs. In this study, we demonstrated that SuhB inversely regulates motility and biofilm formation through the GacA-RsmY/Z-RsmA cascade. Mutations in gacA or the two small RNAs rsmY/rsmZ, or overproduction of the RsmA protein essentially rescued the motility defect of the suhB mutant. Additionally, we identified a c-di-GMP mediated mechanism for SuhB regulation of motility and biofilm formation. We showed that the ΔsuhB mutant displayed elevated levels of c-di-GMP, and the ΔsuhB motility and biofilm phenotypes could be switched by artificially decreasing c-di-GMP levels. Further experiments led to the identification of the diguanylate cyclase GcbA responsible for regulating the c-di-GMP concentration in ΔsuhB and hence the switch between planktonic and surface-associated growth. Together, our results demonstrate a novel mechanism for SuhB regulation of the lifestyle transition via the Gac/Rsm and c-di-GMP signaling networks in P. aeruginosa.

This study aimed to identify and characterize mutations in the hepatitis B virus (HBV) genome associated with advanced liver diseases. The 3.2-kb HBV genome of the C2 subgenotype was amplified from sera of 18 cirrhotic Korean patients with (10) or without (8) hepatocellular carcinoma (HCC), and two clones per patient were characterized by transient transfection experiments in human hepatoma cells. While A1762T/G1764A core promoter mutations were highly prevalent in both groups, the G1896A precore mutation to abolish hepatitis B e antigen (HBeAg) expression was more common in HCC clones (55% vs. 20%). High replication capacity was mostly found in HCC clones and associated with core promoter mutations, whereas more non-HCC clones harbored a nonfunctional core gene (34% vs. 8%). Large in-frame deletions in the preS region were found in 60% of HCC clones and 38% of non-HCC clones. They removed the first 11 residues of large envelope protein or impaired small envelope protein expression, or deleted a neutralizing epitope in the preS2 domain. Additional point mutations prevented middle envelope protein expression, or caused nonsense mutations in the preS or S region to truncate large and/or small envelope protein. Consequently, many clones were unable to express or secrete hepatitis B surface antigen (HBsAg). In conclusion, mutations associated with the advanced stage of chronic HBV infection are complex and diverse. Host immune pressure most likely selected for mutations in the HBV genome to abolish or reduce HBeAg or HBsAg production, to enhance genome replication, or to escape neutralizing antibodies. Some of these mutations may contribute to liver cirrhosis or HCC development.

Hepatitis B virus (HBV) transcribes two subsets of 3.5-kb RNAs: precore RNA for hepatitis B e antigen (HBeAg) expression, and pregenomic RNA for core and P protein translation as well as genome replication. HBeAg expression could be prevented by mutations in the precore region, while an upstream open reading frame (uORF) has been proposed as a negative regulator of core protein translation. We employed replication competent HBV DNA constructs and transient transfection experiments in Huh7 cells to verify the uORF effect and to explore the alternative function of precore RNA. Optimized Kozak sequence for the uORF or extra ATG codons as present in some HBV genotypes reduced core protein expression. G1896A nonsense mutation promoted more efficient core protein expression than mutated precore ATG, while a +1 frameshift mutation was ineffective. In conclusion, various HBeAg-negative precore mutations and mutations affecting uORF differentially regulate core protein expression and genome replication.

Background: Although the predictive value of the excision repair cross-complementing group 1 (ERCC1) C118T polymorphism in clinical outcomes of patients with colorectal cancer (CRC) receiving oxaliplatin-based chemotherapy has been evaluated in numerous published studies, the conclusions are conflicting. Therefore, we performed the present meta-analysis to determine the precise role of the ERCC1 C118T polymorphism in this clinical situation and help optimize individual chemotherapy. Materials and Methods: A multiple search strategy was used to identify eligible studies. Pooled odds ratios (ORs) and their 95% confidence intervals (CIs) were used to estimate objective response and oxaliplatin-induced toxicity, with hazard ratios (HRs) with 95%CIs for progression-free survival (PFS) and overall survival (OS). Results: A total of 22 studies including 2,846 CRC patients were eligible in the analysis. Overall, no significant correlation was found between the ERCC1 C118T polymorphism and objective response to oxaliplatin-based chemotherapy, in all patients or in the Asian and Caucasian subgroups. However, the pooled analysis showed that the PFS and OS were significantly shorter in patients who carried T/T or T/C genotypes of ERCC1 C118T as compared to the C/C genotype. On stratified analysis by ethnicity, the ERCC1 118T allele was associated with a favorable prognosis in Caucasians (PFS, HR=0.58, 95%CI: 0.24-1.44; OS, HR=0.38, 95%CI: 0.22-0.64) but an unfavorable prognosis in Asians (PFS, HR=2.49, 95%CI: 1.87-3.33; OS, HR=2.63, 95%CI: 1.87-3.69) based on a dominant model. In addition, we failed to find a statistically significant impact of ERCC1 C118T polymorphism on oxaliplatin-induced toxicity. Conclusions: The ERCC1 C118T polymorphism may have prognostic value in patients with CRC undergoing oxaliplatin-based chemotherapy.

Renal fibrosis is a common progressive kidney disease, and there is a lack of efficient treatment for the condition. In this study, we designed a kidney-specific nanocomplex by forming coordination-driven assembly from catechol-derived low molecular weight chitosan (HCA-Chi), metal ions and active drug molecules. The coordination activities of various metals and ligands, cytotoxicity, immunogenicity and biodistribution of HCA-Chi were investigated. Autofluorescent doxorubicin (DOX) was selected to fabricate HCA-Chi-Cu-DOX ternary nanocomplex for investigating cellular uptake behavior, transmembrane and targeting properties. The nanodevice demonstrated satisfactory stability under normal physiological conditions and pH-responsive drug release in acidic environments. Uptake of HCA-Chi-Cu-DOX by HK-2 cells was dependent on exposure time, concentration, and temperature, and was inhibited by blockers of megalin receptor. Tissue distribution showed that HCA-Chi-Cu-DOX nanocomplex was specifically accumulated in kidney with a renal relative uptake rate (r(e)) of 25.6. When active anti-fibrosis compound emodin was installed in HCA-Chi-Zn-emodin and intravenously injected to the ureter obstructed mice, obvious attenuation of fibrotic progression was exhibited. It was concluded that HCA-Chi coordination-driven nanocomplex showed special renal targeting capacity and could be utilized to develop drug delivery systems for treating renal fibrosis.

Palygorskite (Pal) is a natural abundant environment-friendly adsorbent that has shown high efficiency to decontaminate dye in water. However, the dye removal results in transformation of Pal to a very stable Maya Blue-like structure or waste Pal clay (WPal), which could not be easily regenerated by a commonly used desorption process. This paper presents a use of WPal as the precursor material to synthesize a highly-efficient mesoporous silicate/carbon composite adsorbent. The composite adsorbent has a large specific surface area (427.9 m2·g−1), a high negative potential (−40.6 mV) and a mesoporous size (3.48 nm). This adsorbent shows almost complete removal of tetracycline (TC), crystal violet (CV) and methylene blue (MB) (initial concentration, 200 mg·L−1) with the optimal adsorption capacities of 319.8 mg·g−1, 244.4 mg·g−1 and 281.7 mg·g−1, respectively. The active -Si-O− adsorption sites produced by the breaking of inert Si-O-Si (or M) bonds and the electrostatic interactions of negatively charged adsorbents to adsorbates play a major role in the adsorption process. Adsorption capacities of the developed composite are significantly higher than that of Pal, WPal and hydrothermally treated WPal (HWPal). Results demonstrate that the composite adsorbents have high potential in decontamination of organics in water efficiently.

This study was designed to explore if hepatitis B virus (HBV) may be transmitted via breast milk through mother-to-child transmission (MTCT), and assay the immunoprophylaxis efficacy after passive-active immunization.From year 2008 to 2012, 67,720 pregnant women were screened and 1186 HBsAg-carrier mothers and their infants aged 8-12 months were followed in multi-centers of China, among whom HBV markers (HBsAg, HBsAb, HBeAg, HBeAb and HBcAb) and HBV-DNA were measured.HBsAg positive rate of pregnant women was 6.7% (4533/67,720) and infants' immunoprophylaxis failure rate was 3.3% (39/1186). Immunoprophylaxis failure infants were all born to mothers of HBeAg positive and HBV-DNA6 log10 copies/ml. Among infants of HBeAg positive mothers, HBV infection rate was 9.0% and HBsAg positive rate was 8.3% in breast-feeding group versus 9.2% in formula-feeding group, P=0.761. Occurrence of perinatal HBV infection was indicated in uterus or during delivery. Different feeding patterns had no effects on HBsAb conversion of infants with the implementation of immunization.HBsAg prevalence rate of pregnant women enrolled was 6.7% and immunoprophylaxis failure rate of infants was 3.3%, while the infection rate reached 9.0% in infants of HBeAg positive mothers. Breast feeding did not increase the occurrence of HBV MTCT.

Refractory leukemia remains the most common therapeutic problem in clinical treatment of leukemia. The key therapy of refractory leukemia is to kill, thoroughly, the minimal residual disease and leukemia stem cells in the highly vascularized red marrow areas. In this study, two new conjugates, alendronate-polyethylene glycol (100) monostearate and folate-polyethylene glycol (100) monostearate, were synthesized to develop a multistep targeting nanostructured lipid carriers by enhancing drug transport to the high bone turnover areas adjacent to the red marrow and targeting the minimal residual disease and leukemia stem cells. This dual targeting system demonstrated a great binding affinity to hydroxyapatite, a model component of bone minerals, and higher cell uptake (in the form of carriers but not drug) and cytotoxicity in the K562 cell line, a leukemia cell line with overexpressed folate receptors, were observed in vitro compared to unmodified carriers, especially when the cells were pretreated and the receptors were up-regulated by all-trans retinoic acid. The comodel test of K562 cells and HA showed that this dual targeting system could desorb from bone surface and be taken up by leukemia cells. For the in vivo study, this dual targeting system exhibited a significant increase in plasma half-life and could specifically accumulate in the bone tissue of rats or mice after intravenous injection. Ex vivo imaging of mice femurs and confocal laser scanning microscope imaging of mice femur slices further confirmed that this dual targeting system could favorably deposit to the osteoblast-enriched areas of high bone turnover in regions of trabecular bone surrounded by red marrow. In vivo antitumor activity in K562/BALB/c-nu leukemia mice showed that the treatment of this dual targeting system significantly reduced the white blood cell (WBC) number in peripheral blood and bone marrow to the normal level. In conclusion, this dual targeting system could precisely target to the regions where the minimal residual disease and leukemia stem cells are located and then be specifically uptaken in large amounts, which is a valuable target for refractory leukemia therapy.

Cigarette smoke can cause cellular oxidative stress that contributes to various adverse health effects associated with smoke exposure, partially due to reactive oxygen species (ROS) present in cigarette smoke. Reduction of abundant ROS in the cigarette mainstream smoke (MSS) is of importance for human health. In this work, a simple, rapid, and reliable fluorescence evaluation of scavenging efficiency of antioxidants as potential filter additives against ROS in cigarette smoke is reported. This method was based on the combination of model glass reactor and a fluorescence assay of ROS in cigarette smoke using dihydrorhodamine 6 G (DHR-6 G). The antioxidant was added into a glass reactor attached to cigarette filter, which simplified the preparation of combined filter containing additives. The ROS scavenging efficiency of antioxidants was then determined using spectrofluorimetry by the change in fluorescence intensity of whole smoke-bubbled solutions before and after addition of antioxidants into the glass r...

A mesoporous hybrid silicate microsphere with superior adsorption performance has been successfully synthesized by employing an “all-into-one” strategy and a simple one-pot hydrothermal process using naturally abundant low-grade red palygorskite (PAL) clay as raw material in the presence of non-toxic SiO32− and Mg2+ ions. As is expected, both the PAL and associated minerals transformed into a new amorphous mesoporous hybrid silicate microsphere without using any additional pore-forming template. The mesoporous silicate microsphere shows a large pore size of 37.74 nm, high specific surface area of 489.81 m2/g (only 54.67 m2/g for raw PAL) and negative surface potential of −43.3 mV, and its maximum adsorption capabilities for Methylene bule (MB) and Crystal violet (CV) reach 407.95 mg/g and 397.22 mg/g, respectively. Meanwhile, 99.8% of MB (only 53% for raw PAL) and 99.7% of CV (only 43% for raw PAL) were sucessfully removed from 200 mg/L of initial dye solution by only using 1 g/L of the adsorbent. In addition, the spent adsorbent can be easily regenerated and repeatly reused for muptiple cycles. The study on adsorption mechanism revealed that electrostatic attraction, hydrogen bonding and chemical complexing interactions are the main factors contributed to the high dye adsorption.

Specific and effective delivery of DNA vaccines into dendritic cells (DCs) to express antigens is a precondition for induction of immune responses. Construction of a new DNA vaccine delivery system with the ability of programmed gene transfection may achieve this objective. In this study, we successfully integrated dendritic lipopeptide, charge-reversible polymer, and APC-targeted material into DNA vaccine delivery system through layer-by-layer (LBL) assembly. By the means of adjusting the weight ratios and concentration ratios of components, stable complexes were formulated with a particle size of 256.8 ± 10.7 nm and zeta potential of 25.1 ± 2.3 mV. Moreover, this DNA vaccine delivery system could achieve specific delivery into DCs, high transfection efficiency and low cytotoxicity, holding great promise for immunotherapy.

Cell culture (cc)-derived hepatitis B virus (HBV) can infect differentiated HepaRG cells, but efficient infection requires addition of polyethylene glycol (PEG) during inoculation. Identification of sodium taurocholate cotransporting polypeptide (NTCP) as an HBV receptor enabled ccHBV infection of NTCP reconstituted HepG2 cells, although very little hepatitis B surface antigen (HBsAg) is produced. We found infection by patient serum-derived HBV (sHBV), which required purification of viral particles through ultracentrifugation or PEG precipitation, was PEG independent and much more efficient in HepaRG cells than in HepG2/NTCP cells. In contrast to hepatitis B e antigen (HBeAg), HBsAg was not a reliable marker of productive sHBV infection at early time points. A low HBsAg/HBeAg ratio by ccHBV-infected HepG2/NTCP cells was attributable to dimethyl sulfoxide (DMSO) in culture medium, NTCP overexpression, and HBV genotype D. HepG2/NTCP cells released more viral antigens than HepG2 cells after HBV genome delivery by adeno-associated virus, and stable expression of NTCP in a ccHBV producing cell line increased viral mRNAs, proteins, replicative DNA, and covalently closed circular DNA. NTCP protein expression in HepG2/NTCP cells, despite being driven by the cytomegalovirus promoter, was markedly increased by DMSO treatment. This at least partly explains ability of DMSO to promote ccHBV infection in such cell lines. In conclusion, NTCP appeared inefficient to mediate infection by serum-derived HBV. It could promote HBV RNA transcription while inhibiting HBsAg secretion. Efficient PEG-independent sHBV infection of HepaRG cells permits comparative studies of diverse clinical HBV isolates and will help identify additional factors on virion surface promoting attachment to hepatocytes. IMPORTANCE Currently in vitro infection with hepatitis B virus (HBV) depends on cell culture-derived HBV inoculated in the presence of polyethylene glycol. We found patient serum-derived HBV could efficiently infect differentiated HepaRG cells independent of polyethylene glycol, which represents a more physiological infection system. Serum-derived HBV has poor infectivity in HepG2 cells reconstituted with sodium taurocholate cotransporting polypeptide (NTCP), the currently accepted HBV receptor. Moreover, HepG2/NTCP cells secreted very little hepatitis B surface antigen after infection with cell culture-derived HBV, which was attributed to NTCP overexpression, genotype D virus, and dimethyl sulfoxide added to culture medium. NTCP could promote HBV RNA transcription, protein expression, and DNA replication in HepG2 cells stably transfected with HBV DNA, while dimethyl sulfoxide could increase NTCP protein level despite transcriptional control by a cytomegalovirus promoter. Therefore, this study revealed several unusual features of NTCP as an HBV receptor and established conditions for efficient serum virus infection in vitro .

Although anticancer drug resistance has been linked to high expression of P-glycoprotein and the enhanced DNA repair ability, the biochemical process and the underlying mechanisms of drug resistance are not clear. In order to clarify the biochemical mechanisms of drug resistance during anticancer drug treatment, we studied the metabolomics of MCF-7/S and MCF-7/Adr cell lines, the COC1 and COC1/DDP cell lines, including the metabolic pathways of multidrug-resistant tumor cells and the changes of endogenous substances in cells. The intracellular metabolites were profiled using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). In this study, 24 biomarkers in MCF-7/Adr cells and 15 biomarkers in COC1/DDP cells that are involved in some important metabolic pathways were putatively identified. Several metabolic pathways are changed in tumor cells showing drug resistance, such as protein synthesis pathways, cysteine synthesis, the glutamine metabolic pathway, and the ammonia cycle; the first of these are involved in the synthesis of some important proteins including membrane proteins, multidrug resistance-associated proteins, and P-glycoprotein (P-gp). Proteins related to drug resistance were overexpressed in multidrug-resistant tumor cells. These proteins depended on energy and play important roles in the emergence of drug resistance. The changes in glutathione and cysteine metabolic pathways showed that the cells can activate related metabolic pathways and reduce the cell apoptosis when they encounter oxidative damage. These findings indicate that drug resistance is likely associated with increased P-gp synthesis and reduced apoptosis of tumor cells. Graphical Abstract Drug resistance was charactered in the changing of genomics and proteomics. Like enhancing DNA repair, reducing uptake, high P-g protein expression. Here, we studied the changes of metabolite pathway which could be also play an imported role in drug resistance.

Combination therapy has been developed as a promising therapeutic approach for hepatocellular carcinoma therapy. Here we report a low toxicity and high performance nanoparticle system that was self-assembled from a poly(ethylenimine)-glycyrrhetinic acid (PEI-GA) amphiphilic copolymer as a versatile gene/drug dual delivery nanoplatform. PEI-GA was synthesized by chemical conjugation of hydrophobic GA moieties to the hydrophilic PEI backbone via an acylation reaction. The PEI-GA nanocarrier could encapsulate doxorubicin (DOX) efficiently with loading level about 12% and further condense DNA to form PEI-GA/DOX/DNA complexes to codeliver drug and gene. The diameter of the complexes is 102 ± 19 nm with zeta potential of 19.6 ± 0.2 mV. Furthermore, the complexes possess liver cancer targeting ability and could promote liver cancer HepG2 cell internalization. Apoptosis of cells could be induced by chemotherapy of DOX, and PI3K/Akt/mTOR signaling pathway acts a beneficial effect on the modulation of autophagy. Here, it is revealed that utilizing PEI-GA/DOX/shAkt1 complexes results in effective autophagy and apoptosis, which are useful to cause cell death. The induction of superfluous autophagy is reported to induce type-II cell death and also could increase the sensity of chemotherapy to tumor cells. In this case, combining autophagy and apoptosis is meaningful for oncotherapy. In this study, PEI-GA/DOX/shAkt1 has demonstrated favorable tumor target ability, little side effects, and ideal antitumor efficacy.