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Current thrombolytic agents generally possess low specificity and pose a high risk of intracranial hemorrhage. Here, various generations of multiarm polylactic acid-polyglutamic acid peptide dendrimers were synthesized, and then nattokinase-combining magnetic Fe

Metal diborides are a class of ceramic materials with crystal structures consisting of hexagonal sheets of boron atoms alternating with planes of metal atoms held together with mixed character ionic/covalent bonds. Many of the metal diborides are ultrahigh-temperature ceramics such as HfB2, TaB2, and ZrB2, which have melting points above 3000 °C, high mechanical hardness and strength at high temperatures, and high chemical resistance, while MgB2 is a superconductor with a transition temperature of 39 K. Here, we demonstrate that this diverse family of non-van der Waals (vdW) materials can be processed into stable dispersions of quasi-two-dimensional (2D) nanosheets using ultrasonication-assisted exfoliation. We generate quasi-2D nanosheets of the metal diborides AlB2, CrB2, HfB2, MgB2, NbB2, TaB2, TiB2, and ZrB2 and use electron and scanning probe microscopy techniques to characterize their structures, morphologies, and compositions. The exfoliated layers have a distribution of lateral dimensions from tens of nanometers up to several micrometers and a distribution of thicknesses from as low as 2–3 nm up to tens of nanometers, all while retaining their hexagonal atomic structure and chemical composition. We exploit the convenient solution-phase dispersions of exfoliated CrB2 nanosheets to incorporate them directly into polymer composites. In contrast to the hard and brittle bulk CrB2, we find that CrB2 nanocomposites remain very flexible and simultaneously provide increases in the elastic modulus and the ultimate tensile strength of the polymer. The successful liquid-phase production of quasi-2D metal diborides enables their processing using scalable low-temperature solution-phase methods, extending their use to previously unexplored applications, and reveals a new family of non-vdW materials that can be efficiently exfoliated into quasi-2D forms.

This study used constitutive CD226 gene knockout (KO) mice as a model to investigate the functions and mechanisms of CD226 in megakaryocyte (MK) maturation and platelet activation. Although CD226 deficiency did not cause MK polyploidization or platelet granule abnormalities, increased MK counts were detected in the femora bone marrow (BM) and spleen of CD226 KO mice. Particularly, CD226 KO mice have a more extensive membrane system in MKs and platelets than wild-type (WT) mice. We also demonstrated that CD226 KO mice displayed increased platelet counts, shortened bleeding time, and enhanced platelet aggregation. CD226 KO platelets had an increased mature platelet ratio compared to the control platelets. In addition, the observed reduction in bleeding time may be due to decreased nitric oxide (NO) production in the platelets. Platelet-specific CD226-deficient mice showed similar increased MK counts, shortened bleeding time, enhanced platelet aggregation, and decreased NO production in platelets. Furthermore, we performed middle cerebral artery occlusion-reperfusion surgery on WT and CD226 KO mice to explore the potential effect of CD226 on acute ischemia-reperfusion injury; the results revealed that CD226 deficiency led to significantly increased infarct area. Thus, CD226 is a promising candidate for the treatment of thrombotic disorders.

Background Chromosomal rearrangements in addition to t(15;17) have been reported in 25-40% of APL patients, with a large predominance of trisomy 8. Other abnormalities are far less frequent, particularly as ider(17), and the prognostic significance is still unclear. Case presentation We present the case of a patient with t(15;17)(q22;q21), der(15)t(15;17) and ider(17)(q10)t(15;17)(q22;q21). In particular, the RT-PCR result for PML-RARA of this patient was a false negative and mutational analysis of AML-related genes showed SNP rs2454206 in the TET2 gene and yielded negative findings in other genes including AML1, ASXL1, CEBPA, DNMT3A, FLT3, KIT, NPM1, TP53, and U2AF1. After the early usage of arsenic trioxide combinated with ATRA and vigorous supportive treatment to maintain PLT ≥30×109/L and FIB >1500 mg/L, this patient was under MMR and HCR without any clinical symptoms or signs until now. Conclusion False negative reslults of RT-PCR analysis for PML-RARA are rare in APL and ider(17) is even more infrequent. To our knowledge, this is the first reported case of APL with ider(17) and false negative RT-PCR analysis results. The role of ider(17) in APL is still an ongoing investigation and limited by the small number of published cases. The patient reported here benefited from vigorous supportive treatment during the combination of ATRA and arsenic trioxide in induction chemotherapy and the clinical outcome was favorable.

A label-free, sensitive, simple and general colorimetric method was reported to monitor S1 nuclease activity based on protamine-assisted aggregation of gold nanoparticles (AuNPs). Here, protamine, a linear polycation, was used as a medium for causing the aggregation of negatively charged AuNPs by electrostatic interactions, resulting in changes in the surface plasmon resonance (SPR) absorption bands as well as the color of AuNPs. Here, the AuNPs were employed as an indicator to detect the level of S1 nuclease in the solution. Substrate DNA could be cleaved into small fragments by the specific S1 nuclease, which effectively prevents the electrostatic interaction between DNA and protamine and thus facilitates the interaction between protamine and AuNPs. The quantitative analysis of S1 nuclease activity can be performed via directly measuring the changes in the absorption spectra of the AuNPs. Using S1 nuclease as a model analyte, the limit of detection was estimated to be 1.0 × 10-4 U mL-1. Furthermore, the proposed concept has been successfully applied in S1 nuclease analysis of serum samples, offering an ultrasensitive strategy for the speedy detection of the nuclease activity and providing a new avenue for high-throughput screening of nucleases and drugs with potential inhibition properties.

Platelet-rich plasma (PRP) is a platelet-based application used to treat osteoarthritis (OA) clinically. The co-stimulatory molecule CD226 is expressed in T cells, NK cells, and also platelets. However, exact effects of CD226 on platelets and whether its expression level influences PRP efficacy are largely unknown. Here, CD226fl/flPF4-Cre mice were obtained from mating CD226 fl/fl mice with PF4-Cre mice. Blood samples and washed platelets were collected from the mice eyeballs to undergo routine blood tests and transmission electron microscopy. Differentially expressed proteins were detected by iTRAQ-based proteomics analysis. Animal OA models were established through surgical destabilization of the medial meniscus (DMM) for C57BL/6 wildtype mice, followed by PRP injection to evaluate the effects of platelet CD226 on PRP efficacy. The results showed that deletion of platelet CD226 increased the number of megakaryocytes (MKs) in bone marrow (BM) but reduced MKs in spleen, combined with significantly decreased platelet amounts, α-granule secretion, and reduced immature platelets; indicating that absence of platelet CD226 may disrupt MK/platelet homeostasis and arrested platelet release from MKs. Sequencing analysis showed abnormal ribosomal functions and much downregulated proteins in the absence of platelet CD226. Autophagy-related proteins were also reduced in the CD226-absent MKs/platelets. Moreover, deletion of platelet CD226 diminished the protective effects of PRP on DMM-induced cartilage lesions in mice, and PDGF restored it. Therefore, deficiency of platelet CD226 inhibited platelet maturation, secretion, and normal ribosomal functions, which may lead to depressed PRP efficacy on OA, suggesting that CD226 is required to regulate platelet growth, functions, and its application.

Effective control of a fly ash/polymer interface is often hindered by poor compatibility. Advanced surface modification of fly ash by using corrosive microorganisms is proposed in this study. Microbial adhesion and catabolism of corrosive microorganisms resulted in a lipophilic surface and a cellular structure of fly ash, which contribute to the compatibility between fly ash and polymers. The mechanisms of corrosive microorganisms modifying the fly ash were revealed by X-ray photoelectron spectroscopy. Owing to the favorable interface bonding between modified fly ash and rubber, the fluororubber compounds achieved a favorable tensile strength exceeding 10.0 MPa. The reinforcement effect, which was almost identical to that of medium thermal black, indicates that microbial modification can be used to treat fly ash and other similar inorganic particles.

Polysaccharides purified from natural herbs possess immunoregulatory functions, while the efficacy of natural polysaccharides on cancer treatment remains unreliable, likely due to their low prescribed doses and fast clearances in clinical settings. In this study, gold nanocomposites containing Ganoderma lucidum polysaccharide (GLP-Au) efficiently induced dendritic cell (DC) activation, evident by the increase of CD80/CD86/CD40/MHCII, decrease of phagocytic ability and acid phosphatase activity, and increased cytokine transcription. GLP-Au significantly promoted the proliferation of CD4+ and CD8+ T cells in splenocytes. DC/T cell co-culture study proved that GLP-Au activation on DC directly resulted in T cell proliferation. GLP-Au exhibited strong inhibitory effects on 4T1 tumor growth and pulmonary metastasis when combined with doxorubicin. GLP-Au recovered body weight loss by doxorubicin and increased the percentage of CD4+/CD44+ memory T cells. This work suggests that polysaccharides from natural herbs can be incorporated into nanocomposites with immunoregulatory characteristics for enhanced efficacy on tumor therapy.

Carbamates weaken the luminol-H$_{2}$O$_{2}$ chemiluminescence (CL) catalyzed by sodium copper chlorophyll (SCC). The capacity to inhibit the CL of three carbamates is in the order of carbaryl (CBL) \textgreater carbofuran (CBF) \textgreater metolcarb (MTC). Mechanisms of carbamates inhibiting SCC-luminol-H$_{2}$O$_{2}$ CL are investigated using fluorescence quenching and quantum chemistry simulations for the first time in this work. Carbamate-SCC interactions studied using fluorescence spectroscopy show that with the increasing concentration of the SCC, the fluorescence of carbamate is quenched regularly, and the quenching mechanism is a static quenching process. Binding constants ($K_{B})$ of the three carbamates with SCC are CBL (4.39 x 10$^{5})$ > CBF (1.46 x 10$^{4})$ > MTC (2.16 x 10$^{3}$ L/mol), which is completely harmonious with the capacity to inhibit CL of the carbamates. Furthermore, the carbamate-SCC interaction energies from quantum chemistry simulations are CBL-porphyrin copper (PPCu) (-30.1), CBF-PPCu (-21.0), and MTC-PPCu (-19.9 kJ/mol), which is also identical to their inhibiting capacity. This provides further evidence that the formation of carbamate-SCC complexes reduces the SCC catalytic activity and the CL intensity decreases. In addition, a novel flow injection chemiluminescence method for the determination of carbamate was established based on carbamate inhibiting CL of the SCC-luminol-H$_{2}$O$_{2}$ CL system under alkaline conditions. This work may contribute to the study of the mechanism of CL inhibition using fluorescence quenching and quantum chemistry calculation methods.

BackgroundOsteosarcoma (OS) is a highly malignant and aggressive bone tumor. This study was performed to explore the mechanisms of HuR (human antigen R) in the progression of OS.MethodsHuR expression levels in OS tissues and cells were detected by immunohistochemistry and western blotting. HuR siRNA was transfected into SJSA-1 OS cells to downregulate HuR expression, and then cell proliferation, migration, and epithelial-mesenchymal transition (EMT) were evaluated. RNA immunoprecipitation was performed to determine the association of the long non-coding RNA (lncRNA) XIST and argonaute RISC catalytic component (AGO) 2 with HuR. Fluorescence in situ hybridization analysis was performed to detect the expression of lncRNA XIST. Western blotting and immunofluorescence assays were performed to observe AGO2 expression after HuR or/and lncRNA XIST knockdown.ResultsKnockdown of HuR repressed OS cell migration and EMT. AGO2 was identified as a target of HuR and silencing of HuR decreased AGO2 expression. The lncRNA XIST was associated with HuR-mediated AGO2 suppression. Moreover, knockdown of AGO2 significantly inhibited cell proliferation, migration, and EMT in OS.ConclusionOur findings indicate that HuR knockdown suppresses OS cell EMT by regulating lncRNA XIST/AGO2 signaling.

A label-free colorimetric method based on exonuclease I (Exo I)-assisted signal amplification with protamine as a medium was developed for analysis of kanamycin. In this study, a double-stranded DNA (dsDNA) probe was tailored by manipulating an aptamer and its complementary DNA (cDNA) ensuring detection of target with high selectivity and excellent sensitivity. Herein, protamine could not only combine with negatively charged gold nanoparticles but also interaction with polyanion DNA. Upon addition of target kanamycin, the target-aptamer complex was formed and the cDNA was released. Thus, both aptamer and cDNA could be digested by Exo I, and the captured kanamycin was liberated for triggering target recycling and signal amplification. Under optimized conditions, the proposed colorimetric method realized a low detection limit of 2.8 × 10−14 M along with a wide linear range plus excellent selectivity. Our strategy exhibited enormous potentials for fabricate various kinds of biosensors based on target-induced aptamer configuration changes.

Rationale: Cardiotoxic β 1 adrenergic receptor (β 1 AR)-CaMKII (calmodulin-dependent kinase II) signaling is a major and critical feature associated with development of heart failure. SAP97 (synapse-associated protein 97) is a multifunctional scaffold protein that binds directly to the C-terminus of β 1 AR and organizes a receptor signalosome. Objective: We aim to elucidate the dynamics of β 1 AR-SAP97 signalosome and its potential role in chronic cardiotoxic β 1 AR-CaMKII signaling that contributes to development of heart failure. Methods and Results: The integrity of cardiac β 1 AR-SAP97 complex was examined in heart failure. Cardiac-specific deletion of SAP97 was developed to examine β 1 AR signaling in aging mice, after chronic adrenergic stimulation, and in pressure overload hypertrophic heart failure. We show that the β 1 AR-SAP97 signaling complex is reduced in heart failure. Cardiac-specific deletion of SAP97 yields an aging-dependent cardiomyopathy and exacerbates cardiac dysfunction induced by chronic adrenergic stimulation and pressure overload, which are associated with elevated CaMKII activity. Loss of SAP97 promotes PKA (protein kinase A)-dependent association of β 1 AR with arrestin2 and CaMKII and turns on an Epac (exchange protein directly activated by cAMP)-dependent activation of CaMKII, which drives detrimental functional and structural remodeling in myocardium. Moreover, we have identified that GRK5 (G-protein receptor kinase-5) is necessary to promote agonist-induced dissociation of SAP97 from β 1 AR. Cardiac deletion of GRK5 prevents adrenergic-induced dissociation of β 1 AR-SAP97 complex and increases in CaMKII activity in hearts. Conclusions: These data reveal a critical role of SAP97 in maintaining the integrity of cardiac β 1 AR signaling and a detrimental cardiac GRK5-CaMKII axis that can be potentially targeted in heart failure therapy. Graphical Abstract: A graphical abstract is available for this article.

Considerable effort has been made to develop nanocarriers for controlled drug delivery over the last decade, while it remains unclear how the strength of adverse drug effect will be altered when a drug is loaded on the nanocarrier. Drug-induced phospholipidosis (DIP) is characterized with excessive accumulation of phospholipids in cells and is common for cationic amphiphilic drugs (CAD). Previously, we have reported that PEGylated graphene oxide (PEG-GO) loaded with several CAD can potentiate DIP. In current study, we extended our study on newly identified phospholipidosis (PLD) inducers that had been identified from the Library of Pharmacologically Active Compounds (LOPAC), to investigate if PEO-GO loaded with these CAD can alter DIP. Twenty-two CAD were respectively loaded on PEG-GO and incubated with RAW264.7, a macrophage cell line. The results showed that when a CAD was loaded on PEG-GO, its strength of PLD induction can be enhanced, unchanged or attenuated. PEG-GO loaded with Ifenprodil exhibited the highest PEG-GO potentiation effect compared to Ifenprodil treatment alone in RAW264.7 cells, and this effect was confirmed in human hepatocellular carcinoma HepG2, another cell line model for PLD induction. Primary hepatocyte culture and spheroids mimicking in vivo conditions were used to further validate nanocarrier potentiation on DIP by Ifenprodil. Stronger phospholipid accumulation was found in PEG-GO/Ifenprodil treated hepatocytes or spheroids than Ifenprodil treatment alone. Therefore, evidences were provided by us that nanocarriers may increase the adverse drug effects and guidance by regulatory agencies need to be drafted for the safe use of nanotechnology in drug delivery.

Foams offer extremely large surface area per unit mass, making them competitive material for heat exchangers and energy storage systems. Understanding the influence of foam characteristics, i.e., size, distribution and concentration of pores, ligament defects as well as foam architecture, on thermal transport is important when designing the foam-based devices. In this article, we present the effective thermal conductivity of open-cell polyurethane (PU) foam (20 PPI) with ~10 μm thick nickel coating measured by transient plane source (TPS) method. A calibration methodology for TPS method is developed to obtain accurate measurements. A finite element model and thermal resistance model are developed for the heat transfer in metal coated foams occurring near room temperature. For precisely modeling the foam architecture topology, an X-Ray tomography is employed. The developed models are used to investigate how the Ni coating thickness affects the effective thermal conductivity. Lastly, we discuss how the model assumptions are related to the discrepancy between the model predictions and measurements for the polymer-metal foams.

Denitrification in electroactive constructed wetland (EW) systems is constrained by the carbon source and the carbon/nitrogen (C/N) ratio (the COD/TN ratio). In this study, wastewater with a high C/N from a brewery was added to wastewater with a low C/N (dairy wastewater) in an EW system, and the pollutant removal, bioelectricity generation, transformations of dissolved organic matter, and microbial community structures were evaluated. The results showed that the average removal rates of ammonium nitrogen, total nitrogen, and chemical oxygen demand from the wastewater mixture were 6.40%, 46.44%, and 23.85% higher than those from the wastewater with a low C/N, respectively. Dissimilatory nitrate reduction to ammonium was effectively inhibited, and the NH4+-N removal was 25.52% higher, when the wastewater mixture was used instead of the high C/N wastewater. Similarly, the output voltage was significantly increased, and the internal resistance of the device was reduced, for the wastewater mixture. The structure of the microbial community improved, the relative abundance of electrochemically active bacteria was higher, and the protein-like and humic-like components were lower, in the mixture treatment than in the individual treatment. The results show that the nitrogen removal and biopower generation improved in an EW system when high C/N wastewater was used as the carbon source.

Tandem reactions of methyl pyropheophorbide a with paraformaldehyde, reactive methylene compounds, and/or ammonium acetate provided novel pyrido[2,3-n]chlorophylls in good yields as the first examples of pyridine fused chlorophyll a derivatives, which displayed near-infrared absorptions (748–766 nm) with unusually broadened Q bands and small electrochemical HOMO-LUMO gaps (1.89–2.02 eV).

A novel hybrid Anderson-type polyoxometalate, {[(CH 3 ) 3 N(CH 2 ) 2 OH] 2 }[H 0.2 K 0.2 Na 2.6 (H 2 O) 6 ][IMo 6 O 24 ] (Abbreviated as (ChO) 2 K 0.2 Na 2.6 IMo 6 ) was synthesized in a deep eutectic solvent and characterized by XRD, FT-IR, thermal analysis, electrochemical measurements and inductively-coupled plasma, atomic emission spectrometer (ICP-AES). This hybrid polyoxometalate was used as a catalyst in ionic liquids (ILs) for desulfurization of model diesel. The catalyst (ChO) 2 K 0.2 Na 2.6 IMo 6 in the extraction and catalytic oxidative desulfurization (ECODS) system, containing H 2 O 2 and 1-octyl-3-methylimidazolium tetrafluoroborate (OmimBF 4 ), displayed so high activity that the removal of DBT can reach 100% at 60 °C in 60 min. Sulfur removal for S-compounds was in the following order: DBT > 4,6-DMDBT > BT. The desulfurization system shows so good stability that it can be recycled 20 times without noticeable decrease in activity.

To clone and characterize the squalene synthase from Siraitia grosvenorii (SgSQS). The gene encoding SgSQS was cloned. SgSQS has 417 amino acid residues with an pI of 7.3. There are 32 phosphorylation sites in its sequence: S48 as well as S196 play important roles in regulation of enzyme activity. The enzyme is a monomeric protein with a cave-like active center formed by α helixes and has two transmembrane domains at its C-terminus. SgSQS mRNA expression in stem and root were about twice as much as that in leaf and peel. Full-length SgSQS with measurable catalytic activity was expressed in Escherichia coli. SgSQS activity was optimal at 37 °C and pH 7.5 respectively. SgSQS gene was cloned, and the molecular structure and biochemical function of SgSQS were characterized.

Accurate analysis of prostate cancer specific biomarkers plays an important role in the early diagnosis of prostate cancer. Traditional colorimetric lateral flow assay (LFA) has the limitations of low detection sensitivity and qualitative or semiquantitative detection. In this study, we developed a novel surface-enhanced Raman scattering (SERS)-based competitive LFA for the rapid and highly sensitive quantitative evaluation of prostate cancer antigen 3 (PCA3) mimic DNA. Herein, the competitive hybridization interaction with capture DNA between target PCA3 mimic DNA and reporter DNA-labeled SERS nanotags results in a change in the amount of SERS nanotags on the test line. The quantitative analysis of target PCA3 mimic DNA was realized by monitoring the Raman peak intensity of SERS nanotags on the test line. The limit of detection of PCA3 mimic DNA was estimated to be 3 fM, which is about three orders of magnitude more sensitive than that of a commercially available kit. By combining the outstanding characteristics of the well-established SERS-based competitive strategy and LFA platform, our design has strong potential for the early diagnosis of prostate cancer and other diseases.

In this study, we observed that deletion of CD226 on regulatory T cells (Tregs) precedes renal fibrosis in a mouse unilateral ureteral obstruction (UUO) model. First, we generated Treg-specific CD226 gene knockout mice (CD226fl/fl Foxp3YFP-Cre). Next, CD226fl/fl Foxp3YFP-Cre mice and Foxp3YFP-Cre control mice were subjected to UUO surgery. Pathologic analysis and Sirius red and Masson's trichrome staining showed that the kidneys of CD226fl/fl Foxp3YFP-Cre mice following UUO showed much more severe interstitial fibrosis than Foxp3YFP-Cre control mice at days 10 and 20. Additionally, CD226fl/fl Foxp3YFP-Cre mice showed increased fibronectin expression, as demonstrated by immunohistochemistry (IHC) staining. Although Treg cell-restricted CD226 deficiency showed increased Foxp3+ expression, expression of the cell surface functional molecule CD103 was significantly reduced, indicating impaired homeostasis in the Tregs of CD226fl/fl Foxp3YFP-Cre mice. To better understand CD226 function, RNA sequencing (RNA-Seq) analysis was conducted in Tregs isolated from CD226fl/fl Foxp3YFP-Cre and Foxp3YFP-Cre mice. RNA-Seq data showed that the helper T cell (Th) 2-related cytokines IL-4 and IL-10 were significantly up-regulated in CD226 deficient Tregs. In addition, mRNA analysis of kidney samples from the mice following UUO by qPCR also showed increased IL-4 and IL-10 expression in CD226fl/fl Foxp3YFP-Cre mice, as well as elevated TGF-β1 levels, indicating that CD226 deficiency in Tregs resulted in the acquisition of the ability to produce Th2 cytokines. Finally, we found that microRNA-340 (miR-340), which was down-regulated in Tregs isolated from CD226fl/fl Foxp3YFP-Cre mice, directly regulated IL-4 gene expression in vitro. These data suggest that the promotion of CD226 signaling on Tregs is a therapeutic target for renal disease.

Cardiac troponin I (cTnI) was considered as the “gold standard” for acute myocardial infarction (AMI) diagnosis owing to its superior cardiac specificity for cardiac damage and showing little or no changes in patients with a skeletal muscle disease or trauma. Herein, a new signal amplification surface-enhanced Raman scattering (SERS) platform was developed for recognition and detection of cTnI by using gold nanoparticles (AuNPs), graphene oxide (GO) and magnetic beads (MB). Here, antibody/Raman reporter labeled AuNP–functionalized GO were employed as both SERS nanotags and signal amplification carriers. Monoclonal antibody modified MB were applied as the capture probe and separation agents. In the presence of cTnI, sandwich type immunocomplexes, “capture probe/target/SERS nanotags”, were formed through antibody–antigen–antibody interactions. Due to the strong SERS enhancement ability of the designed GO/AuNP complexes and a high binding chance between cTnI and the GO/AuNP complexes, the proposed SERS-based immunoassay could selectively detect cTnI with a high sensitivity (detection limit of 5 pg mL−1) and a good linearity was obtained in a range of 0.01–1000 ng mL−1. In addition, this method was also successfully applied for detecting cTnI in serum substitute media with a similar linear range. Furthermore, this strategy can be constructed with different kinds of antibodies and Raman reporters, and thus can be easily used for simultaneous detection of multiple biomarkers. Therefore, this proposed SERS-based signal amplification technique shows strong potential for the clinical diagnosis of AMI disease.

Thrombotic complications turn into the second leading cause of death in colon cancer patients due to the hypercoagulable state caused by malignancy. Therefore, it is necessary to treat colon cancer and its thrombosis complications simultaneously. Herein, a nano polymer conjugate based on disulfide cross-linked low-generation peptide dendrimers was developed to treat colon cancer and its thrombotic complications. First, two-generation polyglutamic acid dendrimer was bonded to nattokinase (NK) and then cross-linkers containing disulfide linkages were used to obtain polymer conjugates (NK-G2)n. Then doxorubicin (Dox) was encapsulated. The system can release drugs sequentially due to the dissociation of the polymer conjugates. In vitro thrombolytic experiments exhibited a significant thrombolysis ability of (NK-G2)n. The toxicity and cellular uptake tests on HCT116 cells showed that Dox loaded polymer conjugates had good endocytosis ability and anti-cancer effect. Therefore, this drug delivery system will be a promising strategy to the combined treatment of colon cancer and thrombotic complications.

For aqueous two-phase extraction (ATPE), adsorbents such as primary secondary amine (PSA) are usually used to remove fat and protein in meat samples. However, it was determined that PSA adsorbed approximately 5% of measured sulfonamides (SAs), which is the reason for the low recovery rate. To overcome this adverse PSA effect, a solid phase extraction (SPE) method was used for purification and enrichment after the formation of aqueous two-phase. Based on these, A new aqueous two-phase sample pretreatment method with solid phase extraction (ATP-SPE) to detect sulfonamides in fish meat is proposed. Fluorescence quenching showed that for 6 SAs, hydrogen bonding and van der Waals force played the major role in the binding reaction with fish serum albumin protein. In addition, in the 80% ACN aqueous solution, a slow protein denaturation took place and the drugs bound with the protein were released, which is more conducive to the aqueous two-phase extraction. In order to obtain better separation effect, the factors for synthesis of hydrophobic-lyophobic balance (HLB) packing for SPE were explored. Stirring speed is the most important factor affecting the particle size of microspheres. After purification and enrichment by SPE, samples were directly analyzed by HPLC. The analytical process was validated in the fish sample matrix by the analysis of spiked blank samples. The mean recoveries of this method were 80.1–95.1% with RSD values of 1.37–3.95%. The detection limits were 5.8–11.7 ng/g. The new ATP-SPE pretreatment method provides a new way for better recovery of veterinary drugs in meat products.

Accurate tumor margin demarcation in situ remains a paramount challenge. Herein, a NanoFlare (also known as spherical-nucleic-acid technology) based strategy is reported for in situ tumor margin delineation by transforming and amplifying the pathophysiological redox signals of tumor microenvironment. The NanoFlare designed (named AuNS-ASON) is based on gold nanostar (AuNS) coated with a dense shell of disulfide bridge-inserted and cyanine dyes-labeled antisense oligonucleotides (ASON) targeting survivin mRNA. The unique anisotropic ASON-spike nanostructure endows the AuNS-ASON with universal cellular internalization of tumor cells, while the disulfide bridge inserted confers response specificity toward redox activation. In vitro experiments demonstrate that the AuNS-ASON can discriminate tumor cells rapidly with activated fluorescence signals (>100-fold) in 2 h, and further achieve synergistic gene/photothermal tumor cells ablation upon near-infrared laser irradiation. Remarkably, in situ tumor margin delineation with high accuracy and outstanding spatial resolution (

Metal nanoparticles or metal-based compounds have drawn attention in various fields ranging from industry to medicine because of their unique physicochemical properties. Bismuth (Bi) compounds and nanomaterials have been commonly used in alloys, electronic industry, batteries, and as flame retardants as well as for anti- Helicobacter pylori therapy, while the nanomaterial form has great potential for computed tomography imaging and thermotherapy, both of which will be introduced in this review. Although Bi was used for several decades, there is a lack of detailed information concerning their toxicity and mechanisms on human health. We described the toxicity of Bi on the kidney that seemed to be relatively known by researchers, while the mechanisms remain unclear. Recently, our group has found that Bi compounds, including bismuth nitrate (BN) and Bi nanomaterials, can induce autophagy in kidney cells. We also extended our findings by selecting five Bi compounds, and the results showed that BN, bismuth oxychloride, bismuth citrate, colloidal bismuth subcitrate, and Bi nanomaterials all induced slight cytotoxicity accompanied with autophagy. Although the role of autophagy in Bi-induced cytotoxicity and kidney injury is under investigation by us, autophagy may help with the exploration of the mechanisms of nephrotoxicity by Bi.

Bismuth is widely used in metallurgy, cosmetic industry, and medical diagnosis and recently, bismuth nanoparticles (NPs) (BiNP) have been made and proved to be excellent CT imaging agents. Previously, we have synthesized bovine serum albumin based BiNP for imaging purpose but we found a temporary kidney injury by BiNP. Due to the reported adverse events of bismuth on human health, we extended our studies on the mechanisms for BiNP induced nephrotoxicity. Blood biochemical analysis indicated the increase in creatinine (CREA) and blood urea nitrogen (BUN), and intraluminal cast formation with cell apoptosis/necrosis was evident in proximal convoluted tubules (PCTs) of mice. BiNP induced acute kidney injury (AKI) was associated with an increase in LC3II, while the autophagic flux indicator p62 remained unchanged. Chloroquine and rapamycin were used to evaluate the role of autophagy in AKI caused by BiNP. Results showed that BiNP induced AKI was further attenuated by rapamycin, while AKI became severe when chloroquine was applied. In vitro studies further proved BiNP induced autophagy in human embryonic kidney cells 293, presented as autophagic vacuole (AV) formation along with increased levels of autophagy-related proteins including LC3II, Beclin1, and Atg12. Specifically, reactive oxygen species (ROS) generated by BiNP could be the major inducer of autophagy, because ROS blockage attenuated autophagy. Autophagy induced by BiNP was primarily regulated by AMPK/mTOR signal pathway and partially regulated by Akt/mTOR. Our study provides fundamental theory to better understand bismuth induced nephrotoxicity for better clinical application of bismuth related compounds.

A simple, environmentally friendly and high efficient extraction method was proposed for the determination of five phthalates in aquatic products by gas chromatography combined with mass spectrometry detector (GC-MS). When this method was adopted, samples were pretreated by modified QuEChERS(quick, easy, cheap, effective, rugged and safe) method. An environmentally friendly extractant(ethanol aqueous solution) replaced toxic acetonitrile for extracting phthalates in the protein-matrix samples. Fluorescence quenching spectra of bovine serum albumin(BSA) with phthalates show that there was a high-affinity interaction between phthalate and protein, decreasing the extraction efficiency of phthalates from fish samples. However, in the 80%(volume fraction, φ) ethanol aqueous solution, a slow but full protein denaturation takes place, which would cause the unfolding of protein and the release of phthalates. Meanwhile, the fat-soluble impurities are extracted less in φ(ethanol) 80% aqueous solution than in either φ(ethanol) 100% or hydrophobic solvents in the liquid-liquid extraction procedure. Therefore the purification steps were greatly simplified. Overall recoveries were 81.77%–90.5% with limits of detection between 2.53 and 9.61 μg/L, and relative standard deviation values at 1.15%–4.85%. The proposed approach was satisfactorily applied to the determination of phthalates in real aquatic products, such as fish, shrimp and oyster.

Zero-current ion-flux has a great influence on the characteristics of the ion-selective electrodes. In this work the improvement of analytical performance of all-solid-state Pb2+-selective membrane electrodes was demonstrated by adjusting the transmembrane ion flux. The study is focused on the relationship between the conditioning solution and the linear working range of the obtained electrodes for different sample matrixes. Results show that the electrode with appropriate conditioning keeps good reproducibility within linear working range. The utility of the electrode has been tested by successfully determining Pb2+ concentration in real water samples. (c) 2012 Elsevier B.V. All rights reserved.

Polysaccharides from different types of natural herbs have not been compared with each other to determine their differential potencies on innate immune response, such as maturation of dendritic cells (DC). In addition, the role of endocytosis of polysaccharides in DC maturation has not been explored previously. Polysaccharides isolated from Astragalus membranaceus (APS), Ganoderma lucidum (GLP) and Radix ophiopogonis (OGP) were characterized and applied in bone marrow derived DC. Compared to immature DC, three polysaccharides with immunoactivities showed elongated dendrites, decreased phagocytic abilities, phenotypic changes (CD40/MHCII/CD80/CD86) and increased level of nitric oxide (NO) in a dose dependent manner. Interestingly, blockage of NO by iNOS inhibitor slightly decreased CD40 and MHCII but not CD80/CD86 expression induced by polysaccharides, indicating that NO was partially involved in DC maturation. In addition, GLP can enter cells in a dose and time dependent manner, shown as punctate distribution in the cytoplasm. Endocytic inhibitors sodium azide and brefeldinA that were demonstrated to inhibit cellular uptake of GLP can block phenotypic maturation of DC. Taken together, these results suggested that polysaccharides from natural herbs are effective immunostimulators with variable potencies ranking as GLP>APS>OGP, and the increase of NO level as well as the increase in polysaccharide endocytosis could be the novel strategies for improved innate response and immunotherapy.

A new solid-contact Ag+-selective electrode was prepared with 9,10,12,13,24,25-hexahydro-5H,15H,23H-dibenzo[b,q][1,7,10,13,19,4,16]-entathiadiazacyclodocosine-6,16(7H,17H)-dione as ionophore, and alpha,omega-dihexylsexithiophene (DH-6T) ion-to-electron transducer. The sensor exhibited a working concentration range of 10(-8) to 10(-3) mol/L, with a near-Nemstian slope of 55.1 +/- 0.2 mV/dec and detection limit of 1.7 x 10(-9) mol/L. The fabricated electrodes demonstrated excellent selectivity over the most common monovalent and divalent cations.

A novel method was developed using molecular imprinting technology (MIT) coupled with flow-injection chemiluminescence (FI-CL) for highly sensitive detection of phenformin hydrochloride (PH). The phenformin imprinted polymer was synthesized with methacrylic acid (MAA) as a functional monomer and ethylene glycol dimethacrylate (EGDMA) as a cross-linker. Newly synthesized molecularly imprinted polymer (MIP) particles were packed into a column as a selective recognition element for determination of PH. A CL method for the determination of PH was developed based on the CL reaction of PH with N-bromosuccinimide sensitized by eosin Y in basic media. The optimization of detection conditions was investigated. The CL intensity responded linearly to the concentration of PH in the range 0.09-2.0 µg/mL, with a correlation coefficient of 0.9920. The detection limit was 0.031 µg/mL. The relative standard deviation for the determination of 1.0 µg/mL PH solution was 1.0% (n = 11). The method was applied to the determination of PH in urine samples, with satisfactory results.

In this work, a novel all-solid-state polymeric membrane Pb2+-selective electrode was developed by using for the first time poly(2-methoxy-5-(2'-ethylhexyloxy)-p-phenylene vinylene) (MEH-PPV) as solid contact. To demonstrate the ion-to-electron transducing ability of MEH-PPV, chronopotentiometry and electrochemical impedance spectroscopy measurements were carried out. The proposed electrodes showed a Nernstian response of 29.1 mV decade(-1) and a lower detection limit of subnanomolar level. No water film was observed with the conventional plasticized PVC membrane. This work demonstrates a new strategy for the fabrication of robust potentiometric ion sensors. (C) 2011 Elsevier B.V. All rights reserved.

In recent years, there has been a pronounced interest in solid-contact ion-selective electrodes (SC-ISEs), with emphasis on the use of conducting polymers as ion-to-electron transducer. In this work, a ladder conjugated polymer, thieno[3,2-b]thiophene (LCPT), was investigated in fabricating Cu2+-selective electrodes for the first time. The resulting electrodes were characterized by electrochemical impedance spectroscopy (EIS), chronopotentiometry, and the water layer test. Results proved that the active LCPT facilitates the ion-to-electron transduction, and avoids the detrimental aqueous layer formed at the interface of SC-ISEs. (C) 2013 Shun-Yang Yu and Tao Xiong. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

The morphology of 2D cell colonies has been studied to understand tumor metastasis in the past decades. However, 2D cell cultures are lacking many features of 3D tissues, and their physiological behaviors are quite different from solid tumors in vivo. In this work, we studied the multi-cellular tumor spheroid (MCTS) spreading on the substrate, which keeps parts of 3D tissue characteristics and facilitates cell tracking through 2D imaging. By using a high content imaging system (HCS), we tracked multiple spheroids in one single 96-well plate for 36 h. An automated algorithm based on Otsu's method was developed to investigate the morphological details of spheroids through the quantification of radius length and its coefficients of variation. Spheroid spreading is altered by the PIP-platin, which was a novel platinum based drug previously reported by us with an inhibitory effect on cell migration. All parameters showed dose dependent decreases when PIP-platin concentration increased, indicating the inhibition of spheroid expansion by this compound. To investigate the surface roughness of spheroids affected by the drug, we applied the Fourier parameter β and the normalized standard deviation of the radius STD r / [Formula: see text], which were found inversely proportional to the concentrations of PIP-platin. Particularly at the low drug concentrations, the indices of contour roughness appeared to be more sensitive than spheroid sizes, which could be the potential morphological markers for high content screening of drugs.

The binding reaction between 10-hydroxycamptothecin (10-HCPT) and human serum albumins (HSA) is studied by means of fluorescence spectroscopy, UV-Vis absorption spectrum, 1H NMR spectrum, and molecular simulation. The results indicate that the binding reaction of 10-HCPT and HSA is a single static quenching process, and the binding equilibrium constant for 10-HCPT binding with HSA is estimated K0= 4.93×104 L · mol−1 at 25 °C with the molar ratio of 1:1. The distance (r) and energy transfer efficiency (E) between donor (HSA) and acceptor (10-HCPT) are obtained as follows, r =3.51 nm; E =0.27. The enthalpy change (ΔH⦵) and entropy change (ΔS⦵) are calculated at different temperatures, and the hydrophobic force and shidipole force are the functions in the reaction. The results show that 10-HCPT binds within the subdomain II A of HSA by the hydrophobic force, and the 10-OH and 20-OH of 10-HCPT bind with both residue Leu-238 of HSA and Ala 291 of HSA by hydrogen bonds.

Norbornene polymerizations proceeded in toluene with bis(β-ketoamino)nickel(II) {Ni[CH3C(O)CHC(NR)CH3]2 [R = phenyl (1) or naphthyl (2)]} complexes as the catalyst precursors and the organo-Lewis compound tris(pentafluorophenyl)borane [B(C6F5)3] as a unique cocatalyst. The polymerization conditions, such as the cocatalyst/catalyst ratio (B/Ni), catalyst concentration, monomer/catalyst ratio (norbornene/Ni), polymerization temperature, and polymerization time, were studied in detail. Both bis(β-ketoamino)nickel(II)/B(C6F5)3 catalytic systems showed noticeably high conversions and activities. The polymerization activities were up to 3.64 × 107 g of polymer/mol of Ni h for complex 1/(B(C6F5)3 and 3.80 × 107 g of polymer/mol of Ni h for complex 2/B(C6F5)3, and very high conversions of 90–95% were maintained; both polymerizations provided high-molecular-weight polynorbornenes with molecular weight distributions (weight-average molecular weight/number-average molecular weight) of 2.5–3.0. The achieved polynorbornenes were confirmed to be vinyl-addition and atactic polymers through the analysis of Fourier transform infrared, 1H NMR, and 13C NMR spectra, and the thermogravimetric analysis results showed that the polynorbornenes exhibited good thermal stability (decomposition temperature > 410 °C). © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 4733–4743, 2007

Styrene (St) was polymerized in toluene solution by using bis(β-ketoamino)nickel(II) complex as the catalyst precursor and methylaluminoxane (MAO) as the cocatalyst. The polymerization conditions, such as Al : Ni ratio, monomer concentration, reaction temperature, and polymerization time, were studied in detail. Both of the bis(β-ketoamino)nickel(II)/MAO catalytic systems exhibited higher activity for polymerization of styrene, and polymerization gave moderate molecular weight of polystyrene with relatively narrow molecular weight distribution (Mw/Mn < 1.6). The obtained polymer was confirmed to be atactic polystyrene by analyzing the stereo-triad distributions mm, mr, and rr of aromatic carbon C1 in NMR spectrum of the polymer. The mechanism of the polymerization was also discussed and a metal–carbon coordination mechanism was proposed. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007

Background Mechanical strain plays a great role in growth and differentiation of osteoblast. A previous study indicated that integrin-β (β1, β5) mediated osteoblast proliferation promoted by mechanical tensile strain. However, the involvement of integrin-β in osteoblastic differentiation and extracellular matrix (ECM) formation induced by mechanical tensile strain, remains unclear. Results After transfection with integrin-β1 siRNA or integrin-β5 siRNA, mouse MC3T3-E1 preosteoblasts were cultured in cell culture dishes and stimulated with mechanical tensile strain of 2500 microstrain (με) at 0.5 Hz applied once a day for 1 h over 3 or 5 consecutive days. The cyclic tensile strain promoted osteoblastic differentiation of MC3T3-E1 cells. Transfection with integrin-β1 siRNA attenuated the osteoblastic diffenentiation induced by the tensile strain. By contrast, transfection with integrin-β5 siRNA had little effect on the osteoblastic differentiation induced by the strain. At the same time, the result of ECM formation promoted by the strain, was similar to the osteoblastic differentiation. Conclusion Integrin-β1 mediates osteoblast differentiation and osteoblastic ECM formation promoted by cyclic tensile strain, and integrin-β5 is not involved in the osteoblasts response to the tensile strain. Electronic supplementary material The online version of this article (doi:10.1186/s40659-015-0014-y) contains supplementary material, which is available to authorized users.

Pyrroloquinoline quinone (PQQ) is an antioxidant that also stimulates nerve growth factor (NGF) synthesis and secretion. In an earlier pilot study in our laboratory, Schwann cell growth was accelerated, and NGF mRNA expression and NGF secretion were promoted. The present study was designed to explore the possible nerve-inducing effect of PQQ on a nerve tube model over a 1-cm segmental deficit. An 8-mm sciatic nerve deficit was created in a rat model and bridged by a 1-cm silicone tube. Then,10 mul of 0.03 mmol/l PQQ were perfused into the silicone chamber in the PQQ group. The same volume of normal saline was delivered in the control group. Each animal underwent functional observation (SFI) at 2-week intervals and electrophysiological studies at 4-week intervals for 12 weeks. Histological and morphometrical analyses were performed at the end of the experiment, 12 weeks after tube implantation. Using a digital image-analysis system, thickness of the myelin sheath was measured, and total numbers of regenerated axons were counted. There was a significant difference in SFI, electrophysiological index (motor-nerve conduct velocity and amplitude of activity potential), and morphometrical results (regenerated axon number and thickness of myelin sheath) in nerve regeneration between the PQQ group and controls (P < 0.05). More mature, high-density, newly regenerated nerve was observed in the PQQ group. We conclude that PQQ is a potent enhancer for the regeneration of peripheral nerves.

We present a new method of chemical quantification utilizing thermal analysis for the detection of relative humidity. By measuring the temperature change of a hydrophilically-modified temperature sensing element vs. a hydrophobically-modified reference element, the total heat from chemical interactions in the sensing element can be measured and used to calculate a change in relative humidity. We have probed the concept by assuming constant temperature streams, and having constant reference humidity (~0% in this case). The concept has been probed with the two methods presented here: (1) a thermistor-based method and (2) a thermographic method. For the first method, a hydrophilically-modified thermistor was used, and a detection range of 0–75% relative humidity was demonstrated. For the second method, a hydrophilically-modified disposable surface (sensing element) and thermal camera were used, and thermal signatures for different relative humidity were demonstrated. These new methods offer opportunities in either chemically harsh environments or in rapidly changing environments. For sensing humidity in a chemically harsh environment, a hydrophilically-modified thermistor can provide a sensing method, eliminating the exposure of metallic contacts, which can be easily corroded by the environment. On the other hand, the thermographic method can be applied with a disposable non-contact sensing element, which is a low-cost upkeep option in environments where damage or fouling is inevitable. In addition, for environments that are rapidly changing, the thermographic method could potentially provide a very rapid humidity measurement as the chemical interactions are rapid and their changes are easily quantified.

The petroleum ether extract of puccoon has been separated with thin-layer chromatography (TLC) and three compounds have been isolated. The structures of the compounds have been identified by spectroscopic methods as β,β-dimethyl-acrylshikonin, acetylshikonin and shikonin. Their antioxidant properties in lard have been tested with the oxidative stability instrument (OSI). The raw extracts and pure compounds all have obvious antioxidant activity, and all have some synergistic effects with d,l -α-tocopherol (Ve) and butylatedhydroxytoluene (BHT). They all show antioxidant properties in lard containing Fe 3+ , and all show synergistic effects with Ve and citric acid (CA) with different degrees. In the concentration range of 0.01–0.06%, antioxidant activity of Ve and BHT, on OSI at 100°C, increases with increase of concentration, but much less than acetylshikonin, shikonin and β,β-dimethyl-acrylshikonin.

The interference effects of major matrix elements, contained in gold ores (silicate-, oxide-, sulfide-, bismuth- and tellurium-ores) for the determination of gold by electrothermal atomic absorption spectrometry (ETAAS), were studied. Samples of five one-component (Cu, Mo, Ni, Pd and V) and 12 two-component chemical modifiers composed from above five one-component modifiers were compared for their anti-interference effects on the major matrix elements (Al, As, Bi, Ca, Cu, Fe, Mg, Mn, Pb, Sb, Te and Zn) in gold ores. A chemical-modifier solution composed of 1000 mg l−1 each of Ni and V showed the best performance. Gold in five decoppered copper oxide ores was determined by ETAAS with the help of the Ni/V chemical modifier without matrix pre-separation. The relative standard deviation was 3.9% (n=9) for 0.47 mg l−1 gold. The recoveries of added gold (50 mg l−1) were 93–102%. The characteristic mass was 12.8 pg.

A new matrix modifier composed of calcium and chromium[VI] was proposed for the determination of tributyltin (TBT) in toluene extract from sea water containing sediment by graphite furnace atomic absorption spectrometry (GFAAS). Fourteen inorganic and organic compounds (barium, calcium, chromium[VI], lanthanum, magnesium, nickel, palladium, strontium, calcium-chromium[VI], calcium-strontium, nickel isocaprylate, 5%-, 10%-aqueous solution of ascorbic acid and toluene-saturated solution of ascorbic acid) as a matrix modifier were comparatively studied and a matrix modifier composed from 5 microg of calcium and 1 microg of chromium[VI] was found to give the best performance. The interference effects of co-existing elements in sea water containing sediment (aluminium, iron, magnesium, sodium and strontium) were studied. TBT in eight toluene extracts was determined by GFAAS with the proposed matrix modifier. The relative standard deviation was 3.0% for 63 ng ml(-1) of TBT (n = 11). The recoveries were 88-104%. The characteristic mass was 7 pg. The linearity range was 0-250 ng mg(-1).

A matrix modifier composed of nickel and zirconium, and a graphite tube treated with zirconium solution were proposed for the determination of boron in cobalt-based alloys by graphite furnace-atomic absorption spectrometry. The effects of this matrix modifier and the treated graphite tube were studied, and the combination of 60 mug of nickel and 20 mug of zirconium as matrix modifier, and a graphite tube soaked with 10 g 1(-1) of zirconium solution were found to give the highest analytical sensitivity. The interference effects of major components (cobalt) and eight minor components (chromium, nickel, tungsten, iron, tantalum, molybdenum, titanium, aluminium and manganese) were studied. Boron in four cobalt-based alloys was determined by graphite furnace-atomic absorption spectrometry employing the proposed matrix modifier and the treated graphite tube, without the preseparation of matrix. The relative standard deviation was 3.3% for 0.048% of boron. A characteristic mass was 500 pg.

A nickel/palladium matrix modifier was proposed for the determination of selenium and tellurium in nickel and nickel/iron-based alloys by graphite furnace atomic absorption spectrometry without preseparation of the matrix. The effect of this matrix modifier was studied and it was found that a composition of 3000 mg/1 of nickel and 100 mg/1 of palladium gave the optimal effect. The interference effects of major matrix (nickel and iron) and minor matrix (chromium, cobalt, aluminium, molybdenum, titanium, niobium and tantalum) compounds were studied. Selenium and tellurium in a standard nickel/iron-based alloy and five nickel-based alloys were determined. The relative standard deviations were 4.4% for 11.0 μg/g of selenium and 4.9% for 2.1 μg/g of tellurium. The characteristic masses were 19 pg for selenium and 17 pg for tellurium. The recoveries of these elements were better than 85% for 10 ng/ml of selenium and 5 ng/ml of tellurium. The linearity ranges were 0–60 μg/l for selenium ( r = 0.9999) and 0–20 μg/g for tellurium ( r = 0.9993).